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Gandelsman E, Grin L, Wainstock T, Berkovitz Shperling R, Scherbina E, Saar-Ryss B. Risk of adverse pregnancy outcomes after abnormal hysterosalpingography. HUM FERTIL 2025; 28:2431109. [PMID: 39804029 DOI: 10.1080/14647273.2024.2431109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2024] [Accepted: 11/13/2024] [Indexed: 01/30/2025]
Abstract
OBJECTIVE To investigate the association between an abnormal hysterosalpingogram (HSG) and obstetrical and neonatal outcomes. DESIGN A retrospective cohort study comparing outcomes between women with normal versus abnormal tubal patency and uterine cavity on HSG. RESULTS Among 2181 women included in the study, 494 (22.6%) had an abnormal HSG. Of these, 207 (42%) presented with uterine abnormalities, 336 (68%) with tubal abnormalities and 49 (10%) with both. The study identified 232 clinical pregnancies in the abnormal HSG group and 814 pregnancies in controls. Women with abnormal HSG showed higher rates of preterm labour (PTL) compared to controls (13.6% vs. 7.7%, p < 0.05, n = 1687). Multivariate analysis revealed that any HSG abnormality was associated with an increased risk of PTL (aOR 2.39, 1.04-5.51). When analysing by type of abnormality, uterine abnormalities increased the risk of preeclampsia (aOR 2.86, 1.06-7.7) and low birthweight (aOR 2.31, 1.0-5.35), while tubal abnormalities were specifically associated with increased risk of PTL (aOR 3.87, 1.63-9.19). CONCLUSION An abnormal HSG study was associated with adverse obstetrical outcomes. Specifically, uterine abnormalities increased the risk of preeclampsia and birthweight below 10th percentile, while tubal abnormalities were associated with a heightened risk of PTL.
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Affiliation(s)
- Erika Gandelsman
- Department of Obstetrics and Gynecology, Hillel Yaffe Medical Center, Hadera, Israel
- Ruth and Bruce Rappaport School of Medicine, Technion, Haifa, Israel
| | - Leonti Grin
- Assisted Reproductive Technologies Unit, Department of Obstetrics and Gynecology, Barzilai University Medical Center, Ashkelon, Israel
| | - Tamar Wainstock
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Roza Berkovitz Shperling
- Department of Obstetrics and Gynecology, Lis Maternity and Women's Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
- Faculty of Medical Health Sciences, Tel Aviv University, Tel Aviv, Israel
| | - Elena Scherbina
- Assisted Reproductive Technologies Unit, Department of Obstetrics and Gynecology, Barzilai University Medical Center, Ashkelon, Israel
| | - Bozhena Saar-Ryss
- Assisted Reproductive Technologies Unit, Department of Obstetrics and Gynecology, Barzilai University Medical Center, Ashkelon, Israel
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Wulff SM, Jorsal MJ, Kooij I, Krog H, Bentin-Ley U, Blomberg Jensen M, Yahyavi SK. Phosphate concentrations in follicular fluid during assisted reproductive treatment: relevance for ovarian function and fertility outcomes. Reprod Biol Endocrinol 2025; 23:69. [PMID: 40369590 PMCID: PMC12076920 DOI: 10.1186/s12958-025-01408-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2025] [Accepted: 04/29/2025] [Indexed: 05/16/2025] Open
Abstract
BACKGROUND The role of follicular fluid phosphate for reproductive health and oocyte maturation is unclear. This study investigates the relationship between follicular fluid vs serum phosphate concentrations and the possible link with sex steroids during in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) at a Danish fertility clinic. METHODS A prospective cohort of infertile women who attended Danfert Fertility clinic (Copenhagen, Denmark) and received IVF or ICSI treatment between June 2015 and February 2017. Correlation analyses were performed with Spearman's Rank or Pearson's correlation, while categorical variables were analyzed with Chi-squared test. RESULTS In total, 110 participants were included in the study, and 33 of these achieved a live birth. Phosphate concentrations were higher in the follicular fluid compared to corresponding serum samples (1.16 mmol/L vs. 1.06 mmol/L, p = 0.002) and there was a positive correlation between serum and follicular fluid phosphate concentrations (r = 0.43, p = 0.007). A positive trend was also found for calcium concentrations, though not statistically significant (r = 0.31, p = 0.060). Correlation analysis also showed a positive correlation between concentrations of phosphate and calcium in follicular fluid (r = 0.41, p < 0.001). A positive correlation was observed between concentrations of phosphate and testosterone in follicular fluid (r = 0.34, p < 0.001). When stratified into tertiles, we found no significant differences between live birth rates in follicular fluid phosphate (p = 0.624), calcium (p = 0.207), or testosterone (p = 0.841). CONCLUSIONS This study found that follicular fluid phosphate concentrations are higher than serum phosphate concentrations, suggesting possible local regulation. However, no significant association was found between follicular phosphate and ART outcomes. Further research is needed to explore its potential role in reproductive physiology. CLINICAL TRIAL Clinicaltrials.gov (NCT02437578; registration date 2015/04/16).
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Affiliation(s)
- Signe Marie Wulff
- Department of Endocrinology and Internal Medicine, Division of Translational Endocrinology, Copenhagen University Hospital - Herlev, Gentofte, Denmark
| | - Mads Joon Jorsal
- Department of Endocrinology and Internal Medicine, Division of Translational Endocrinology, Copenhagen University Hospital - Herlev, Gentofte, Denmark
| | - Ireen Kooij
- Department of Endocrinology and Internal Medicine, Division of Translational Endocrinology, Copenhagen University Hospital - Herlev, Gentofte, Denmark
| | - Hans Krog
- TFP Danfert Fertility, Seedorffs Vaenge, Seedorffs Vaenge 2, 2000, Frederiksberg, Denmark
| | - Ursula Bentin-Ley
- TFP Danfert Fertility, Seedorffs Vaenge, Seedorffs Vaenge 2, 2000, Frederiksberg, Denmark
| | - Martin Blomberg Jensen
- Department of Endocrinology and Internal Medicine, Division of Translational Endocrinology, Copenhagen University Hospital - Herlev, Gentofte, Denmark.
- Department of Clinical Medicine, Copenhagen University Hospital, Copenhagen, Denmark.
| | - Sam Kafai Yahyavi
- Department of Endocrinology and Internal Medicine, Division of Translational Endocrinology, Copenhagen University Hospital - Herlev, Gentofte, Denmark.
- Department of Growth and Reproduction, Group of Skeletal, Mineral and Gonadal Endocrinology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
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Qi X, Ji H, Bianchi E, Hall SJ, Avellino G, Berg W, Bearelly P, Sigman M, Wu Z, Spade DJ. Downregulation of spermatogenesis-associated transcripts in the spermatozoa of idiopathic infertile men. Andrology 2025. [PMID: 40346865 DOI: 10.1111/andr.70060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2025] [Revised: 04/11/2025] [Accepted: 04/28/2025] [Indexed: 05/12/2025]
Abstract
BACKGROUND Approximately half of male factor infertility cases are idiopathic, indicating a need for new methods to supplement male fertility assessment. OBJECTIVES The objective of this study was to identify differences in the sperm transcriptomes of men with different clinical fertility status. We hypothesized that sperm mRNA profiling could distinguish men presenting for fertility assessment from proven fertile men. MATERIALS AND METHODS We compared two groups of study participants: men who presented for infertility assessment (n = 53, "infertility"), and men without a history of infertility who had fathered a child and were presenting for vasectomy (n = 14, "proven fertile" control). Study participants provided a semen sample for semen analysis and sperm mRNA sequencing. Differentially abundant genes were identified, and a gene expression summary score was constructed to test the ability of RNA-seq data to differentiate between study populations. RESULTS The semen parameter that best differentiated between study populations was motility (area under the ROC curve = 0.746). In RNA-seq analysis, 1885 total differentially abundant transcripts were identified (q < 0.05, fold difference ≥ 2), 1004 (53.3%) of which were downregulated in infertility study participants. The Gene Ontology term, spermatogenesis, was enriched, with 40 out of 44 differentially abundant genes downregulated in infertility study participants. A gene expression summary score consisting of 100 upregulated and 100 downregulated genes was able to differentiate between the two groups of study participants. DISCUSSION Sperm mRNAs differed between proven fertile and infertility study men. Known fertility-associated genes, including PRM1 and PRM2, and potentially novel fertility markers, including HOOK1 and SPATA6, were downregulated in infertility study samples. Future studies should test these results for reproducibility and test whether novel biomarker candidates can provide mechanistic information about etiologies of idiopathic male infertility. CONCLUSION Our results support the hypothesis that sperm mRNA abundance differs by clinical fertility status.
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Affiliation(s)
- Xinran Qi
- Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island, USA
| | - Han Ji
- Department of Biostatistics, Brown University, Providence, Rhode Island, USA
| | - Enrica Bianchi
- Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island, USA
| | - Susan J Hall
- Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island, USA
| | - Gabriella Avellino
- Department of Surgery, Division of Urology, Brown University, Providence, Rhode Island, USA
| | - William Berg
- Department of Surgery, Division of Urology, Brown University, Providence, Rhode Island, USA
| | - Priyanka Bearelly
- Department of Surgery, Division of Urology, Brown University, Providence, Rhode Island, USA
| | - Mark Sigman
- Department of Surgery, Division of Urology, Brown University, Providence, Rhode Island, USA
| | - Zhijin Wu
- Department of Biostatistics, Brown University, Providence, Rhode Island, USA
| | - Daniel J Spade
- Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island, USA
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Wang Y, Tian Y, Zhou F, Zhong Z. The association between the triglyceride-glucose index with all-cause and cardiovascular mortality within the infertility population. PLoS One 2025; 20:e0320526. [PMID: 40333798 PMCID: PMC12057929 DOI: 10.1371/journal.pone.0320526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2024] [Accepted: 02/19/2025] [Indexed: 05/09/2025] Open
Abstract
BACKGROUND The relationship between triglyceride-glucose (TyG) index and all-cause or cardiovascular mortality among infertile women remains unclear. In this study, we intended to utilize a national cohort from National Health and Nutrition Examination Survey (NHANES) to check the association between them. METHODS Ten datasets from the NHANES database spanning almost 20 years were used as the data source and were combined within National Death Index for mortality follow-up. Multiple-variable Cox proportionate hazards regression models and three others were employed in this study to for assessing relationships among TyG index levels with all-cause and cardiovascular mortality. SPSS (version 29.0) and online websites were utilized for conducting the primary statistical analyses. RESULTS 1,450 female participants were identified in this study. The samples were classified based on TyG index quartiles (7.05-11.95). The TyG index had a mean of 8.58±0.66. Participants with higher TyG indices were older-aged, had greater body mass index (BMI), and a stronger likelihood of having hypertension and diabetes (P < 0.05). Participants whose TyG indices were higher were older in age, along with increased BMI, and blood pressure along with diabetes (P < 0.05). Significant positive associations were observed among the TyG index and total mortality in the crude model (HR: 1.81, 95% CI: 1.27-2.58). Correlation persisted in Model 2 (following the adjustment of age and race) and Model 3 (following the adjustment of age, race, BMI, education, family poverty income ratio, smoking and drinking habits, menstrual regularity, hypertension, and diabetes). The TyG index did not affect the cardiovascular mortality in infertile women. CONCLUSION TyG index levels were in positive association with all-cause mortality within the female infertile population.
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Affiliation(s)
- Yuhan Wang
- Department of Reproductive Endocrinology, Center for Reproductive Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China
| | - Yishu Tian
- Department of Ultrasound Medicine, Center for Reproductive Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China
| | - Feifei Zhou
- Department of Reproductive Endocrinology, Center for Reproductive Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China
| | - Zixing Zhong
- Department of Obstetrics, Center for Reproductive Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China
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Hu K, Ma S, Li R, Zhou Y. Breaking barriers: A triumph in pregnancy for a patient with Sjögren syndrome: A case report. Medicine (Baltimore) 2025; 104:e42326. [PMID: 40324234 PMCID: PMC12055138 DOI: 10.1097/md.0000000000042326] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2024] [Accepted: 04/15/2025] [Indexed: 05/07/2025] Open
Abstract
RATIONALE Sjögren syndrome (SS) is a systemic autoimmune disease with a variety of clinical presentations. Successful pregnancies and deliveries among these patients remain challenging. This manuscript describes a case report of diagnosis, detailed clinical management, and successful pregnancy and delivery of a patient of SS, which treated by immunosuppressive agents, especially cyclosporine A (CsA) and assisted reproductive technology. PATIENT CONCERNS A 31-year-old female had been experiencing persistent infertility with a 5-year-long history. However, the results indicated that patent fallopian tubes, an ovulatory cycle, and normal semen analysis. DIAGNOSES After obtaining clinical manifestations, medical history, and the serum biochemical and salivary gland histopathology examination results, main causes such as tubal factor, impaired endometrial function, endocrine dysfunctions and male factors were excluded, and the final diagnosis was SS-induced autoimmune infertility. INTERVENTIONS The patient was treated with immunosuppressive agents and assisted reproductive technology. After 5 failed attempts of assisted reproductive technology treatment and treatment with 3 immunosuppressive agents, the application of a relatively potent immunosuppressive agent CsA was finally used and a high-quality frozen-thawed blastocyst embryo was transferred. OUTCOMES A clinical pregnancy was confirmed. The newborn was delivered by elective cesarean section and showed normal development over the 1-year follow-up. LESSONS The accurate diagnosis of autoimmune infertility requires a combination of clinical presentation, medical history, and biochemical findings, and, if available, histopathology examinations. The role of immunosuppressive agents, especially CsA is crucial for the clinical management of autoimmune infertility.
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Affiliation(s)
- Kaiyue Hu
- Department of Reproductive Medicine, Luoyang Maternal and Child Health Hospital, Luoyang, China
- Luoyang Branch of the National Center for Assisted Reproduction and Eugenics, Luoyang, China
- Key Laboratory of Reproduction and Genetics, Luoyang, China
- Institute of Reproductive Medicine, Luoyang, China
| | - Shuxia Ma
- Department of Reproductive Medicine, Luoyang Maternal and Child Health Hospital, Luoyang, China
- Luoyang Branch of the National Center for Assisted Reproduction and Eugenics, Luoyang, China
- Key Laboratory of Reproduction and Genetics, Luoyang, China
- Institute of Reproductive Medicine, Luoyang, China
| | - Ruirui Li
- Department of Reproductive Medicine, Luoyang Maternal and Child Health Hospital, Luoyang, China
- Luoyang Branch of the National Center for Assisted Reproduction and Eugenics, Luoyang, China
- Key Laboratory of Reproduction and Genetics, Luoyang, China
- Institute of Reproductive Medicine, Luoyang, China
| | - Ying Zhou
- Department of Reproductive Medicine, Luoyang Maternal and Child Health Hospital, Luoyang, China
- Luoyang Branch of the National Center for Assisted Reproduction and Eugenics, Luoyang, China
- Key Laboratory of Reproduction and Genetics, Luoyang, China
- Institute of Reproductive Medicine, Luoyang, China
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Wehrli L, Altevogt H, Brenker C, Zufferey F, Rossier MF, Strünker T, Nef S, Rahban R. The major phytocannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), affect the function of CatSper calcium channels in human sperm. Hum Reprod 2025; 40:796-807. [PMID: 40078063 PMCID: PMC12046078 DOI: 10.1093/humrep/deaf020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 12/19/2024] [Indexed: 03/14/2025] Open
Abstract
STUDY QUESTION Do the main psychoactive phytocannabinoid delta-9-tetrahydrocannabinol (THC) and its non-psychoactive analog cannabidiol (CBD) affect human sperm function? SUMMARY ANSWER THC and CBD affect the sperm-specific Ca2+ channel CatSper, suppress activation of the channel by progesterone (P4) and prostaglandin E1 (PGE1), and THC also alters human sperm function in vitro. WHAT IS KNOWN ALREADY Marijuana (Cannabis sativa) is one of the most commonly used recreational drugs worldwide. Although the effects of phytocannabinoids on semen parameters have been studied, there is no evidence of a direct impact of THC and CBD on human sperm. STUDY DESIGN, SIZE, DURATION We investigated the effects of the major psychoactive phytocannabinoid, THC, its non-psychoactive analog, CBD, and their major metabolites on Ca2+ influx via CatSper in human spermatozoa. THC and CBD were selected to further evaluate their action on P4-, PGE1-, and pH-induced activation of CatSper. The effects of THC and CBD on sperm motility, penetration into viscous media, and acrosome reaction (AR) were also assessed. PARTICIPANTS/MATERIALS, SETTING, METHODS The effects of phytocannabinoids on CatSper activity were investigated on semen samples from healthy volunteers and men with homozygous deletion of the CATSPER2 gene using kinetic Ca2+ fluorimetry and patch-clamp recordings. Motility was assessed by computer-assisted sperm analysis (CASA). Sperm penetration into viscous media was assessed using a modified Kremer test. The AR was evaluated by flow cytometry using Pisum sativum agglutinin-stained spermatozoa. MAIN RESULTS AND THE ROLE OF CHANCE Both THC and CBD increased the intracellular calcium concentration with CBD inducing a greater increase compared to THC. These Ca2+ signals were abolished in men with homozygous deletion of the CATSPER2 gene demonstrating that they are mediated through CatSper. THC suppressed the P4- and the PGE1-induced Ca2+ increase with a half-maximal inhibitory concentration (IC50) of 1.88 ± 1.15 µM and 0.98 ± 1.10, respectively. CBD also suppressed the P4- and PGE1-induced Ca2+ signal with an IC50 of 2.47 ± 1.12 µM and 6.14 ± 1.08 µM, respectively. The P4 and PGE1 responses were also suppressed by THC and CBD metabolites, yet with greatly reduced potency and/or efficacy. THC and CBD were found to inhibit the Ca2+ influx evoked by intracellular alkalization via NH4Cl, with THC featuring a higher potency compared to CBD. In conclusion, THC and CBD inhibit both the ligand-dependent and -independent activation of CatSper in a dose-dependent manner. This indicates that these phytocannabinoids are genuine CatSper inhibitors rather than P4 and PGE1 antagonists. Finally, THC, but not CBD, impaired sperm hyperactivation and penetration into viscous media and induced a small increase in AR. LIMITATIONS, REASONS FOR CAUTION Future studies are needed to assess whether cannabis consumption can affect fertility since this study was in vitro. WIDER IMPLICATIONS OF THE FINDINGS The action of THC and CBD on CatSper in human sperm may interfere with the fertilization process, but the impact on fertility remains to be elucidated. THC inhibits the P4 and the PGE1 response more potently than CBD and most previously described CatSper inhibitors. THC can be used as a starting point for the development of non-hormonal contraceptives targeting CatSper. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the Swiss Center for Applied Human Toxicology (SCAHT), the Département de l'Instruction Publique (DIP) of the State of Geneva and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation). The authors declare that no conflicts of interest have been identified that might affect the impartiality of the research reported. TRIAL REGISTRATION NUMBER N/A.
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Affiliation(s)
- Lydia Wehrli
- Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland
- Swiss Centre for Applied Human Toxicology (SCAHT), Basel, Switzerland
| | - Hannah Altevogt
- Centre of Reproductive Medicine and Andrology, University Hospital Münster, University of Münster, Münster, Germany
| | - Christoph Brenker
- Centre of Reproductive Medicine and Andrology, University Hospital Münster, University of Münster, Münster, Germany
| | - Fanny Zufferey
- Swiss Centre for Applied Human Toxicology (SCAHT), Basel, Switzerland
- Service of Clinical Chemistry and Toxicology, Central Institute of Hospitals, Hospital of Valais, Sion, Switzerland
| | - Michel F Rossier
- Swiss Centre for Applied Human Toxicology (SCAHT), Basel, Switzerland
- Service of Clinical Chemistry and Toxicology, Central Institute of Hospitals, Hospital of Valais, Sion, Switzerland
- Department of Internal Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | - Timo Strünker
- Centre of Reproductive Medicine and Andrology, University Hospital Münster, University of Münster, Münster, Germany
| | - Serge Nef
- Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland
- Swiss Centre for Applied Human Toxicology (SCAHT), Basel, Switzerland
| | - Rita Rahban
- Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland
- Swiss Centre for Applied Human Toxicology (SCAHT), Basel, Switzerland
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Zhe J, Zheng D. The correlation between uric acid to high-density lipoprotein cholesterol ratio and the prevalence of female infertility. J Obstet Gynaecol Res 2025; 51:e16309. [PMID: 40355124 DOI: 10.1111/jog.16309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2024] [Accepted: 04/21/2025] [Indexed: 05/14/2025]
Abstract
AIM The relationship between uric acid to high-density lipoprotein (HDL) cholesterol ratio (UHR) and female infertility remains unclear. The aim of our study was to explore the correlation between UHR and fertility in US adults. METHODS Data from the National Health and Nutrition Examination Survey from 2013 to 2018 was analyzed in this study. UHR was considered the independent variable, and female infertility was the dependent variable. Multivariable logistic regression and smooth curve fitting were conducted to evaluate the correlation between UHR and infertility. Subgroup and sensitivity analyses were utilized to assess the stability of the findings. RESULTS UHR in transform and female infertility proved to have a positive relationship in logistic regression models, and this relationship remained significant after adjusting for all possible confounding factors (odds ratio [OR] = 1.86, 95% confidence interval: 1.28-2.69, p = 0.001). When UHR was split into four quartile groups, individuals in Tertiles 2, 3, and 4 separately had a 1.84, 1.86, and 2.02 times greater incidence of female infertility than those in Tertile 1. A positive linear relationship between UHR and female infertility incidence was demonstrated using smooth curve fitting. The results of the subgroup analysis revealed consistent correlations and no difference in the UHR index and infertility subgroups (p for interaction tests >0.05). CONCLUSION This national study identified the association between a higher prevalence of female infertility and an elevated UHR. The findings suggested that UHR levels could be useful in predicting the incidence of infertility. The management of UHR should be given more consideration.
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Affiliation(s)
- Jing Zhe
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Guiyang Maternal and Child Health Care Hospital, Guiyang Children's Hospital, Guiyang, Guizhou, China
| | - Dan Zheng
- Department of Maternity Health Care, Guiyang Maternal and Child Health Care Hospital, Guiyang Children's Hospital, Guiyang, Guizhou, China
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Navapour L, Mogharrab N, Parvin A, Rezaei Arablouydareh S, Movahedpour A, Jebraeily M, Taheri-Anganeh M, Ghasemnejad-Berenji H. Identification of high-risk non-synonymous SNPs (nsSNPs) in DNAH1 and DNAH17 genes associated with male infertility: a bioinformatics analysis. J Appl Genet 2025; 66:333-346. [PMID: 38874855 DOI: 10.1007/s13353-024-00884-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Revised: 06/04/2024] [Accepted: 06/05/2024] [Indexed: 06/15/2024]
Abstract
Male infertility is a significant reproductive issue affecting a considerable number of couples worldwide. While there are various causes of male infertility, genetic factors play a crucial role in its development. We focused on identifying and analyzing the high-risk nsSNPs in DNAH1 and DNAH17 genes, which encode proteins involved in sperm motility. A total of 20 nsSNPs for DNAH1 and 10 nsSNPs for DNAH17 were analyzed using various bioinformatics tools including SIFT, PolyPhen-2, CADD, PhD-SNPg, VEST-4, and MutPred2. As a result, V1287G, L2071R, R2356W, R3169C, R3229C, E3284K, R4096L, R4133C, and A4174T in DNAH1 gene and C1803Y, C1829Y, R1903C, and L3595P in DNAH17 gene were identified as high-risk nsSNPs. These nsSNPs were predicted to decrease protein stability, and almost all were found in highly conserved amino acid positions. Additionally, 4 nsSNPs were observed to alter post-translational modification status. Furthermore, the interaction network analysis revealed that DNAH1 and DNAH17 interact with DNAH2, DNAH3, DNAH5, DNAH7, DNAH8, DNAI2, DNAL1, CFAP70, DNAI3, DNAI4, ODAD1, and DNAI7, demonstrating the importance of DNAH1 and DNAH17 proteins in the overall functioning of the sperm motility machinery. Taken together, these findings revealed the detrimental effects of identified high-risk nsSNPs on protein structure and function and highlighted their potential relevance to male infertility. Further studies are warranted to validate these findings and to elucidate the underlying mechanisms.
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Affiliation(s)
- Leila Navapour
- Reproductive Health Research Center, Clinical Research Institute, Urmia University of Medical Sciences, Urmia, Iran
| | - Navid Mogharrab
- Biophysics and Computational Biology Laboratory (BCBL), Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran
| | - Ali Parvin
- Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran
| | - Sahar Rezaei Arablouydareh
- Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Mohamad Jebraeily
- Department of Health Information Technology, School of Allied Medical Sciences, Urmia University of Medical Sciences, Urmia, Iran
| | - Mortaza Taheri-Anganeh
- Cellular and Molecular Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran.
| | - Hojat Ghasemnejad-Berenji
- Reproductive Health Research Center, Clinical Research Institute, Urmia University of Medical Sciences, Urmia, Iran.
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Ouadrhiri M, Rochdi C, Archou R, Touil D, Boucetta M, Amazian K, Mamouni N. Knowledge gaps among healthcare professionals regarding infertility: Exploring educational needs in primary healthcare setting-Morocco. JOURNAL OF EDUCATION AND HEALTH PROMOTION 2025; 14:145. [PMID: 40400612 PMCID: PMC12094433 DOI: 10.4103/jehp.jehp_421_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Accepted: 08/02/2024] [Indexed: 05/23/2025]
Abstract
BACKGROUND The role of healthcare professionals (HCPs) is paramount in improving fertility awareness and practices. This study aimed to explore the level of infertility knowledge among primary care providers in Fez-Meknes, Morocco. MATERIALS AND METHODS A cross-sectional study was carried out in July-September 2023 concerning HCPs practicing in primary care establishments employing a snowball sampling technique. The questionnaire was designed and validated by an expert panel of sexual and reproductive health (SRH). It was consisted of 14 items concerning infertility knowledge and gives a score between 0 and 14. The basic infertility knowledge score (BIKS) was obtained to assess HCPs knowledge level. RESULTS 641 HCPs were included; they had low level about basic knowledge of infertility. The total BIKS average of HCPs was found to be "05.08 ± 01.99". The mean nurses' score was "5.11 ± 2.02" and midwives' score was "5.03±;1.93". Three-quarters (75.4%) of respondents scored <7 to the 14 questions. Almost 60% did not know neither the meaning of primary infertility nor secondary infertility; just 27.9% reported that infertility is considered a disease by the WHO, and only 9% recognized the prevalence of infertility in Morocco. Education level and practicing setting were significantly associated with correct responses, 10-3 and 0,02, respectively. CONCLUSION The finding of our survey asserts that nurses and midwives in primary healthcare lack basic knowledge about infertility. It is essential to provide them an appropriate education to assist Moroccan couple who are seeking their parental project as part of the promotion of SHR for all.
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Affiliation(s)
- Meriem Ouadrhiri
- Biomedical and Translational Research Laboratory, Faculty of Medicine and Pharmacy, Sidi Mohammed Ben Abdellah University, Fez, Morocco
- Laboratory of Health Sciences, Care and Techniques, Higher Institute of Nursing Professions and Health Techniques, Fez, Morocco
| | - Chaymae Rochdi
- Maternal-Child and Mental Health Research Laboratory, Faculty of Medicine and Pharmcy, Mohammed First University, Oujda, Morocco
| | - Rachida Archou
- Laboratory of Health Sciences, Care and Techniques, Higher Institute of Nursing Professions and Health Techniques, Fez, Morocco
- Clinical Neuroscience Laboratory, Faculty of Medicine and Pharmacy, Sidi Mohammed Ben Abdellah University, Fez, Morocco
| | - Driss Touil
- Laboratory of Health Sciences, Care and Techniques, Higher Institute of Nursing Professions and Health Techniques, Fez, Morocco
- Biology and Health Laboratory: Cognitive-Behavioral Neurosciences and Applied Nutrition Unit, Department of Biology, Faculty of Sciences, Ibn Tofail University, Kenitra, Morocco
| | - Mustapha Boucetta
- Laboratory of Health Sciences, Care and Techniques, Higher Institute of Nursing Professions and Health Techniques, Fez, Morocco
- Clinical Neuroscience Laboratory, Faculty of Medicine and Pharmacy, Sidi Mohammed Ben Abdellah University, Fez, Morocco
| | - Kamelia Amazian
- Laboratory of Health Sciences, Care and Techniques, Higher Institute of Nursing Professions and Health Techniques, Fez, Morocco
- Human Pathology, Biomedicine and Environment Laboratory, Faculty of Medicine and Pharmacy, Sidi Mohammed Ben Abdellah University, Fez, Morocco
| | - Nisrine Mamouni
- Biomedical and Translational Research Laboratory, Faculty of Medicine and Pharmacy, Sidi Mohammed Ben Abdellah University, Fez, Morocco
- Obstetrics and Gynaecology Service, Hassan II University Hospital, Fez, Morocco
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Kusuma B, Harzif AK, Maidarti M, Saroyo YB, Winarto H, Meutia AP. Infertility misperception and improper health-seeking behavior between urban and rural areas. PLoS One 2025; 20:e0312456. [PMID: 40273033 PMCID: PMC12021135 DOI: 10.1371/journal.pone.0312456] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Accepted: 10/07/2024] [Indexed: 04/26/2025] Open
Abstract
OBJECTIVES The prevalence of infertility among reproductive-age couples in Indonesia is around 10-15%. Lack of understanding, misleading myths, and negative attitudes could result in improper behavior. This study aims to reveal the discrepancy between perception and behavior towards infertility in urban and rural areas in Indonesia. MATERIALS AND METHODS A cross-sectional study using an internet-based questionnaire was given to 408 individuals, divided into two groups, Java and outside Java, representing urban and rural populations. The study included Indonesian citizens over 18 who were willing to participate, encompassing individuals of both genders, regardless of their fertility status. All participants completed the questionnaire from October 2020 to April 2021. RESULTS Half of the respondents from both groups consider infertility a disease. All respondents have excellent access to information. Although more than 80% of subjects from each group had been exposed to infertility information, a better understanding was observed in the urban community. Most subjects answered that smoking is the leading risk factor for infertility, followed by stress and advanced age. More respondents in rural areas have the wrong perception that stress causes infertility. Furthermore, they seek unwarranted advice, as 19.5% came to midwives and only 9.1% came to general practitioners. This study showed that 35.6% of subjects in the urban group and 41.6% in the rural group are considered late to seek healthcare assistance. Most respondents from both groups accept using Assisted Reproductive Technology and fertility-enhancing drugs as treatment options. CONCLUSION Infertility misconceptions are more prevalent in rural groups than in urban groups. Fertility education among both groups needs to be improved to optimize the chance of conceiving and having a healthy baby.
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Affiliation(s)
- Berli Kusuma
- Department of Obstetrics and Gynecology, Faculty of Medicine Universitas Indonesia - dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia
| | - Achmad Kemal Harzif
- Reproductive Immunoendocrinology Division, Department of Obstetrics and Gynecology, Faculty of Medicine Universitas Indonesia - dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia
- Human Reproduction, Infertility, and Family Planning Cluster, Indonesia Reproductive Medicine Research and Training Center, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
| | - Mila Maidarti
- Reproductive Immunoendocrinology Division, Department of Obstetrics and Gynecology, Faculty of Medicine Universitas Indonesia - dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia
- Human Reproduction, Infertility, and Family Planning Cluster, Indonesia Reproductive Medicine Research and Training Center, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
| | - Yudianto Budi Saroyo
- Department of Obstetrics and Gynecology, Faculty of Medicine Universitas Indonesia - dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia
| | - Hariyono Winarto
- Department of Obstetrics and Gynecology, Faculty of Medicine Universitas Indonesia - dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia
| | - Alfa Putri Meutia
- Department of Obstetrics and Gynecology, Faculty of Medicine Universitas Indonesia - dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia
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11
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Sethi S, Andrabi W, Mitra K, Rajender S. Case Report: A homozygous mutation in the SPAG17 gene in a case with oligoasthenoteratozoospermic infertility. FRONTIERS IN REPRODUCTIVE HEALTH 2025; 7:1554027. [PMID: 40330001 PMCID: PMC12053157 DOI: 10.3389/frph.2025.1554027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2024] [Accepted: 03/31/2025] [Indexed: 05/08/2025] Open
Abstract
Background Defects in sperm size and form, known as teratozoospermia, can adversely impair sperm motility and its ability to fertilize an oocyte. Teratozoospermia has been most often linked with genetic abnormalities with close to 100 genes known. Objective The primary objective of this study was to investigate the genetic basis of oligoasthenoteratozoospermic infertility in an infertile man. Methods We performed the whole exome sequencing, followed by in silico filtration of observed genetic variations. Filtered rare variants were assessed for their pathogenic nature on the basis of scores assigned by various in-silico tools and their biological relevance to sperm structural development. The potential pathogenic mutation was validated by Sanger sequencing. Results Our study identified a homozygous substitution, c.4511A > G, in the SPAG17 gene as a potential pathogenic mutation associated with oligoasthenoteratozoospermic infertility in the case under investigation. The mutation resulted in the substitution of asparagine with serine at the 1504th amino acid position in a protein of 2,223 amino acids. This mutation shows a minor allele frequency of 0.0004671 in the gnomAD database. ACMG classification suggested this mutation to be likely pathogenic. Conclusion Our study identified a homozygous likely pathogenic mutation (c.4511A > G, Asn1504Ser) in the SPAG17 gene that explains oligoasthenoteratozoospermic infertility in the present case.
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Affiliation(s)
- Shruti Sethi
- Division of Endocrinology, Central Drug Research Institute, Lucknow, India
- Academy of Scientific and Industrial Research (AcSIR), Ghaziabad, India
| | | | - Kalyan Mitra
- Division of Endocrinology, Central Drug Research Institute, Lucknow, India
- Academy of Scientific and Industrial Research (AcSIR), Ghaziabad, India
| | - Singh Rajender
- Division of Endocrinology, Central Drug Research Institute, Lucknow, India
- Academy of Scientific and Industrial Research (AcSIR), Ghaziabad, India
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12
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Göhring D, Goeckenjan M, Göhring I, Lange V, Sauter J, Kreßner-Kiel D, Schmidt AH, Croy I. Primary infertile couples share more HLA alleles than expected by chance. Eur J Obstet Gynecol Reprod Biol 2025; 308:47-53. [PMID: 40010160 DOI: 10.1016/j.ejogrb.2025.02.053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Revised: 01/14/2025] [Accepted: 02/23/2025] [Indexed: 02/28/2025]
Abstract
OBJECTIVE To examine whether the rate of HLA similarity among 609 primarily infertile couples is higher than would be expected by chance. DESIGN Clinical Trial. SUBJECTS 609 primary infertile couples (mean age women: 34.35 years, men: 37.59 years) were recruited before undergoing IVF or ICSI therapy. Couples with former pregnancies, tubal factor, azoospermia or donor therapies were excluded. INTERVENTION For each of the partners, exons encoding the corresponding antigen recognition sites of HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 were sequenced by using next-generation sequencing. HLA similarity between partners was determined based on the probability of homozygous offspring and the observed probability of heterozygous offspring in the sample of primary infertile couples was comparted to the probability for random pairing using bootstrapping. MAIN OUTCOME MEASURES HLA similarity of infertile couples compared to randomly assigned couples. RESULTS In each of the loci, infertile pairs shared more alleles than expected by chance. This result was significant for all HLA class 2 loci (-DRB1, -DQB1, -DPB1), as well as for the HLA class I locus -C, while HLA-A and -B showed a nonsignificant trend towards higher similarity. CONCLUSION These data suggest that HLA similarity between couples relates to primary infertility.
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Affiliation(s)
- David Göhring
- Department of Gynecology and Obstetrics, TU Dresden, Fetscherstr. 74, 01307 Dresden, Germany; Kinderwunschpraxis Dres. Göhring, Hagellocher Weg 63, 72072 Tübingen, Germany.
| | - Maren Goeckenjan
- Department of Gynecology and Obstetrics, TU Dresden, Fetscherstr. 74, 01307 Dresden, Germany
| | - Inés Göhring
- Kinderwunschpraxis Dres. Göhring, Hagellocher Weg 63, 72072 Tübingen, Germany
| | - Vinzenz Lange
- DKMS Life Science Lab, St. Petersburger Straße 2, 01069 Dresden, Germany
| | - Jürgen Sauter
- DKMS German Bone Marrow Donor Center, Kressbach 1, 72072 Tübingen, Germany
| | - Denise Kreßner-Kiel
- Department of Psychotherapy and Psychosomatic Medicine, Faculty of Medicine, TU Dresden, Fetscherstr. 74, 01307 Dresden, Germany
| | - Alexander H Schmidt
- DKMS Life Science Lab, St. Petersburger Straße 2, 01069 Dresden, Germany; DKMS German Bone Marrow Donor Center, Kressbach 1, 72072 Tübingen, Germany
| | - Ilona Croy
- Department of Psychotherapy and Psychosomatic Medicine, Faculty of Medicine, TU Dresden, Fetscherstr. 74, 01307 Dresden, Germany; Department of Clinical Psychology, Friedrich-Schiller-University Jena, Am Steiger 3, 07743 Jena, Germany
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Yao MWM, Nguyen ET, Retzloff MG, Gago LA, Nichols JE, Payne JF, Ripps BA, Opsahl M, Groll J, Beesley R, Neal G, Adams J, Nowak L, Swanson T, Chen X. Machine learning center-specific models show improved IVF live birth predictions over US national registry-based model. Nat Commun 2025; 16:3661. [PMID: 40246850 PMCID: PMC12006386 DOI: 10.1038/s41467-025-58744-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Accepted: 04/02/2025] [Indexed: 04/19/2025] Open
Abstract
Expanding in vitro fertilization (IVF) access requires improved patient counseling and affordability via cost-success transparency. Clinicians ask how two types of live birth prediction (LBP) models perform: machine learning, center-specific (MLCS) models and the multicenter, US national registry-based model produced by Society for Assisted Reproductive Technology (SART). In a retrospective model validation study, we tested whether MLCS performs better than SART using 4635 patients' first-IVF cycle data from 6 centers. MLCS significantly improved minimization of false positives and negatives overall (precision recall area-under-the-curve) and at the 50% LBP threshold (F1 score) compared to SART (p < 0.05). To contextualize, MLCS more appropriately assigned 23% and 11% of all patients to LBP ≥ 50% and LBP ≥ 75% whereas SART gave lower LBPs. Here, we show MLCS improves model metrics relevant for clinical utility - personalizing prognostic counseling and cost-success transparency - and is externally validated. We recommend evaluating MLCS in a larger sample of fertility centers.
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Affiliation(s)
| | | | | | | | - John E Nichols
- Piedmont Reproductive Endocrinology Group, Greenville, SC, USA
| | - John F Payne
- Piedmont Reproductive Endocrinology Group, Greenville, SC, USA
| | | | | | | | | | - Gregory Neal
- Fertility Center of San Antonio, San Antonio, TX, USA
| | - Jaye Adams
- Fertility Center of San Antonio, San Antonio, TX, USA
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Ghosh S, Biswas M. Co-administration of atorvastatin with piperine induces reproductive toxicity in male Wistar rats through oxidative stress induction and downregulation of StAR, CYP11a1, 3βHSD and 17βHSD genes. Reprod Toxicol 2025; 135:108919. [PMID: 40246250 DOI: 10.1016/j.reprotox.2025.108919] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2025] [Revised: 03/19/2025] [Accepted: 04/14/2025] [Indexed: 04/19/2025]
Abstract
Atorvastatin is a statin group of medicine that inhibits biosynthesis of cholesterol and mainly prescribed for treating cardiovascular diseases. Black pepper is a one of the mostly used spices that contains an alkaloid called piperine in its fruits which is known to cause male reproductive toxicity. Both atorvastatin and black pepper (piperine) are randomly consumed by the patients of chronic hyperlipidemia and it is important to know the synergistic effects of atorvastatin and piperine on male fertility parameters. Twenty rats were taken for the study and divided into four groups each containing five rats. Group I served as a control, group II animals are treated with atorvastatin (ATR) (8mg/kg BW), group III animals received piperine (PIP) (10mg/kg BW) and group IV animals were co-administered with piperine (10mg/kg BW) and atorvastatin (8mg/kg BW). All treatments were done by using water suspension of atorvastatin and piperine and using oral gavage for consecutive 28 days and thereafter assessed for gravimetric and histomorphometry analysis, sperm motility and morphology, ROS generation, anti-oxidant enzymes, serum testosterone quantification, qRTPCR (StAR, CYP11a1, 3βHSD and 17βHSD genes) and toluidine blue staining for analyzing chromatin integrity of spermatozoa. The results showed that co-administration of ATR+PIP significantly reduced body weight, changed in GSI also found. Activities of major two antioxidant enzymes (SOD and Catalase) were found to reduce whereas levels of TBARS and ROS in testicular tissues increased significantly. The study found that combined administration of atorvastatin and piperine negatively impacted male fertility potential, causing reproductive toxicity.
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Affiliation(s)
- Sanjib Ghosh
- Endocrinology Laboratory, Department of Zoology, University of Kalyani, West Bengal, India; Department of Zoology (PG Studies), Rishi Bankim Chandra College, West Bengal, India
| | - Maharaj Biswas
- Endocrinology Laboratory, Department of Zoology, University of Kalyani, West Bengal, India.
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15
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G M, M S. Comparative Analysis of Hysterosalpingography and Diagnostic Hysteroscopy Findings in Infertility Evaluation. Cureus 2025; 17:e81789. [PMID: 40330349 PMCID: PMC12054333 DOI: 10.7759/cureus.81789] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/06/2025] [Indexed: 05/08/2025] Open
Abstract
Introduction Infertility affects most of the women of reproductive age, with uterine and tubal factors contributing significantly. Hysterosalpingography (HSG) and diagnostic hysteroscopy are widely used modalities in infertility evaluation. This study compares the findings of HSG and hysteroscopy to assess their diagnostic accuracy and utility in clinical management. Materials and methods A retrospective comparative observational study was conducted at Adichunchungiri Hospital, Karnataka, over six months (April-September 2024). Thirty-nine women aged 23-36 years with primary or secondary infertility underwent both HSG and diagnostic hysteroscopy. HSG assessed tubal patency and gross uterine abnormalities, while hysteroscopy provided direct visualization of intrauterine pathologies. Statistical analysis included sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), with hysteroscopy considered the gold standard for intrauterine pathology. Results Bilateral tubal patency was observed in 59% of cases on both HSG and hysteroscopy. HSG demonstrated a sensitivity of 95.83% and specificity of 92.31% for tubal patency. However, hysteroscopy detected additional findings like hydrosalpinx (10.26%), fimbrial cysts (5.13%), and uterine adhesions (7.69%), which were missed by HSG. For uterine abnormalities, HSG had a sensitivity of 70% and specificity of 85.71%, while hysteroscopy provided superior detection of fibroids and septate uterus. Notably, hysteroscopy influenced management decisions, guiding surgical interventions or assisted reproductive techniques in selected cases. Conclusion While HSG remains effective for screening tubal patency, diagnostic hysteroscopy offers superior detection of intrauterine pathologies, impacting treatment strategies. Combining both modalities enhances diagnostic accuracy in infertility evaluation.
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Affiliation(s)
- Mahendra G
- Obstetrics and Gynecology, Adichunchanagiri Institute of Medical Sciences, BG Nagara, IND
| | - Sahana M
- Obstetrics and Gynecology, Adichunchanagiri Medical College Bellur Mandya, Mandya, IND
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16
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Zhu J, Zhu Q, Li X, Shen T, Shi X, Zhao T. Systemic lupus erythematosus and male reproductive health: A systematic review and meta-analysis. Autoimmun Rev 2025; 24:103742. [PMID: 39788440 DOI: 10.1016/j.autrev.2025.103742] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 01/06/2025] [Accepted: 01/06/2025] [Indexed: 01/12/2025]
Abstract
OBJECTIVE Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect various organs. Male SLE patients often face reproductive health challenges, but research on male sexual and reproductive health in SLE remains limited. This systematic review and meta-analysis aimed to explore the effects of SLE and its related factors on male sexual function and reproductive health. METHODS The PubMed, Cochrane library, Embase, Web of Science, Wanfang Data, and China National Knowledge Infrastructure (CNKI) databases were examined from January 2000 to December 2024. Data extraction and quality assessment were performed by two reviewers. Meta-analysis was carried out using Review Manager 5.3 software, and the risk of bias was assessed using the AHRQ checklist. The following outcomes were evaluated: sexual function, reproductive hormones and fertility. RESULTS In the literature search, 5002 articles were identified, of which 9 studies met the inclusion criteria. Meta-analysis showed a significantly higher incidence of erectile dysfunction (ED) in SLE patients (OR = 7.44; 95 % CI = 5.00 to 11.06, p < 0.001). SLE patients also had higher levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) compared to controls (FSH: MD = 4.02; 95 % CI = 1.47 to 6.57; p = 0.002; LH: MD = 2.21; 95 % CI = 1.10 to 3.32; p < 0.001). Semen analysis showed a significant decrease in sperm count in SLE patients (MD = -0.54; 95 % CI = -0.86 to -0.22; p < 0.001). CONCLUSIONS Male SLE patients are more likely to have problems with sexual function, reproductive hormones and sperm quality. These findings emphasize the need for increased clinical awareness and interventions focused on male sexual and reproductive health in SLE patients.
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Affiliation(s)
- Jie Zhu
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), 310053 Hangzhou, China
| | - Qingmiao Zhu
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, 310053 Hangzhou, China
| | - Xiaolong Li
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, 310053 Hangzhou, China
| | - Tianshu Shen
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, 310053 Hangzhou, China
| | - Xiaowei Shi
- Key Laboratory of Chinese medicine rheumatology of Zhejiang Province, Research Institute of Chinese Medical Clinical Foundation and Immunology, College of Basic Medical Science, Zhejiang Chinese Medical University, 310053 Hangzhou, China.
| | - Ting Zhao
- Key Laboratory of Chinese medicine rheumatology of Zhejiang Province, Research Institute of Chinese Medical Clinical Foundation and Immunology, College of Basic Medical Science, Zhejiang Chinese Medical University, 310053 Hangzhou, China.
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17
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Peterlin B, Peterlin A. Carrier screening and pregnancy. Best Pract Res Clin Obstet Gynaecol 2025; 100:102601. [PMID: 40120478 DOI: 10.1016/j.bpobgyn.2025.102601] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Revised: 11/19/2024] [Accepted: 02/24/2025] [Indexed: 03/25/2025]
Abstract
Recessive genetic conditions impose a significant burden, often leading to severe childhood disorders, many of which remain untreatable. It is estimated that 1-2 % of couples are at risk of having an affected child in the general population, with the risk being significantly higher in consanguineous couples. Understanding the increased risk of having a child with a recessive disorder empowers prospective parents to make informed reproductive choices. With technological advancements, genetic screening has evolved beyond identifying only a few common conditions. Expanded carrier screening (ESC) now offers a single test that covers a comprehensive list of recessive disorders, addressing those that contribute most significantly to the burden of these conditions within specific populations. ESC is recommended for all couples planning a pregnancy, with particular emphasis on consanguineous couples or those who are subfertile. To ensure responsible use of ESC, clinical service delivery should adopt a multidisciplinary approach, providing couples with the information they need to make voluntary, informed decisions. This includes access to high-quality genetic testing, genetic counseling, and psychosocial support. National professional societies and governments play a crucial role in shaping guidelines, policies, oversight, and funding to guarantee equitable access to high-quality ESC services.
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Affiliation(s)
- Borut Peterlin
- Clinical Institute of Genomic Medicine, University Medical Center Ljubljana, Slovenia.
| | - Ana Peterlin
- Clinical Institute of Genomic Medicine, University Medical Center Ljubljana, Slovenia; Institute of Histology and Embryology, Medical Faculty Ljubljana, Slovenia.
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18
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Pónusz-Kovács D, Csákvári T, Sántics-Kajos LF, Elmer D, Pónusz R, Kovács B, Várnagy Á, Kovács K, Bódis J, Boncz I. Epidemiological disease burden and annual, nationwide health insurance treatment cost of female infertility based on real-world health insurance claims data in Hungary. BMC Health Serv Res 2025; 25:336. [PMID: 40038705 PMCID: PMC11881250 DOI: 10.1186/s12913-025-12348-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Accepted: 01/28/2025] [Indexed: 03/06/2025] Open
Abstract
BACKGROUND Infertility affects more than 50 million couples worldwide, resulting in a significant burden on individuals and society. Its prevalence ranges from 8-12% among developed countries. The growing number of patients poses an increasing challenge to the healthcare system and its funding. Our quantitative, descriptive, and cross-sectional study aimed to analyze the prevalence and annual nationwide health insurance treatment cost of female infertility in Hungary in 2019. METHODS We used claims data obtained from the Hungarian National Health Insurance Fund Administration (NHFIA). The number of patients, total and age-specific prevalence, annual health insurance expenditure, and the distribution of costs by age group were evaluated. Infertility was determined according to the World Health Organization International Classification of Diseases codes (N.97.0, N97.1, N97.2, N97.3, N97.4, N97.8, and N97.9) and the utilization of each healthcare service type. During the study descriptive statistics, correlation analysis and t-test were used. RESULTS In 2019, the NHIFA spent a total of 7.2 billion HUF (22.2 million EUR) on female infertility treatment in Hungary (33,151 women in outpatient care). The most significant costs were related to inpatient care (4.1 billion HUF, 12.7 million EUR). The highest number of patients and prevalence (650.4 per 100,000 women) were found in outpatient care. In inpatient care, the prevalence is substantially lower (206.7 per 100,000 women). Regardless of its type, female infertility mainly affects patients in the 30-39 years age group (number of patients: 18,156 women). The average annual health insurance expenditure per capita was 1,083 EUR. CONCLUSIONS Reproductive health education, prevention, and medical screening play inevitable roles in the early stages of reproductive life to reduce the risk of infertility and decrease treatment costs.
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Affiliation(s)
- Dalma Pónusz-Kovács
- Faculty of Health Sciences, Institute for Health Insurance, University of Pécs, 7621 Vörösmarty Utca 3, Pécs, Hungary.
- National Laboratory On Human Reproduction, University of Pécs, 7624 Ifjúság Utca 20, Pécs, Hungary.
| | - Tímea Csákvári
- Faculty of Health Sciences, Institute for Health Insurance, University of Pécs, 7621 Vörösmarty Utca 3, Pécs, Hungary
- National Laboratory On Human Reproduction, University of Pécs, 7624 Ifjúság Utca 20, Pécs, Hungary
| | - Luca Fanni Sántics-Kajos
- Faculty of Health Sciences, Institute for Health Insurance, University of Pécs, 7621 Vörösmarty Utca 3, Pécs, Hungary
- National Laboratory On Human Reproduction, University of Pécs, 7624 Ifjúság Utca 20, Pécs, Hungary
| | - Diána Elmer
- Faculty of Health Sciences, Institute for Health Insurance, University of Pécs, 7621 Vörösmarty Utca 3, Pécs, Hungary
- National Laboratory On Human Reproduction, University of Pécs, 7624 Ifjúság Utca 20, Pécs, Hungary
| | - Róbert Pónusz
- Faculty of Health Sciences, Institute for Health Insurance, University of Pécs, 7621 Vörösmarty Utca 3, Pécs, Hungary
- National Laboratory On Human Reproduction, University of Pécs, 7624 Ifjúság Utca 20, Pécs, Hungary
| | - Bettina Kovács
- Faculty of Health Sciences, Institute for Health Insurance, University of Pécs, 7621 Vörösmarty Utca 3, Pécs, Hungary
| | - Ákos Várnagy
- National Laboratory On Human Reproduction, University of Pécs, 7624 Ifjúság Utca 20, Pécs, Hungary
- Department of Obstetrics and Gynecology, Medical School, Clinical Center, University of Pécs, 7624 Édesanyák Útja 17, Pécs, Hungary
| | - Kálmán Kovács
- National Laboratory On Human Reproduction, University of Pécs, 7624 Ifjúság Utca 20, Pécs, Hungary
- Department of Obstetrics and Gynecology, Medical School, Clinical Center, University of Pécs, 7624 Édesanyák Útja 17, Pécs, Hungary
| | - József Bódis
- Faculty of Health Sciences, Institute for Health Insurance, University of Pécs, 7621 Vörösmarty Utca 3, Pécs, Hungary
- National Laboratory On Human Reproduction, University of Pécs, 7624 Ifjúság Utca 20, Pécs, Hungary
- Department of Obstetrics and Gynecology, Medical School, Clinical Center, University of Pécs, 7624 Édesanyák Útja 17, Pécs, Hungary
| | - Imre Boncz
- Faculty of Health Sciences, Institute for Health Insurance, University of Pécs, 7621 Vörösmarty Utca 3, Pécs, Hungary
- National Laboratory On Human Reproduction, University of Pécs, 7624 Ifjúság Utca 20, Pécs, Hungary
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Sadeghpour S, Sedgi FM, Daneghian S, Adabi SB, Behroozi-Lak T, Pashaei M, RasouIi J, Valizadeh R, Ghasemnejad‐Berenji H. Associations of dietary inflammatory indices (DII and E-DII) with sperm parameters. Clin Exp Reprod Med 2025; 52:79-86. [PMID: 39084681 PMCID: PMC11900668 DOI: 10.5653/cerm.2024.06982] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Revised: 06/04/2024] [Accepted: 06/09/2024] [Indexed: 08/02/2024] Open
Abstract
OBJECTIVE This study aimed to explore the ambiguous link between dietary inflammatory indices and sperm parameters. Specifically, it investigated the associations between the dietary inflammatory index (DII) and the energy-adjusted dietary inflammatory index (E-DII) with sperm motility, morphology, and count in men undergoing routine semen analysis. METHODS A cross-sectional study was conducted with 144 men enrolled, where semen samples were collected and evaluated according to the 2010 World Health Organization guidelines. Dietary data were gathered using a 147-item semi-quantitative food frequency questionnaire developed by the researchers. Pearson correlation analysis was employed to assess the relationships of the DII and E-DII with sperm parameters. RESULTS The mean DII and E-DII scores were 1.23±1.1 and 0.49±0.43, respectively. The mean values for sperm motility, morphology, and count were 43.08%±19.30%, 78.03%±26.99%, and 48.12±44.41 million, respectively. Both motility (r=-0.353) and count (r=-0.348) were found to be inversely and significantly correlated with DII. Similarly, Pearson correlation tests revealed strong and significant inverse correlations of motility (r=-0.389) and count (r=-0.372) with E-DII. CONCLUSION The findings suggest that a diet with a higher anti-inflammatory potential may be associated with increased sperm count and motility, but not with changes in morphology. Further research is necessary to confirm these findings, elucidate the underlying mechanisms, and identify dietary modifications that could improve male fertility.
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Affiliation(s)
- Sonia Sadeghpour
- Reproductive Health Research Center, Clinical Research Institute, Urmia University of Medical Sciences, Urmia, Iran
- Department of Obstetrics and Gynecology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Fatemeh Maleki Sedgi
- Department of Nutrition, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Sevana Daneghian
- Department of Nutrition, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Somayyeh Barania Adabi
- Department of Nutrition, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Tahereh Behroozi-Lak
- Reproductive Health Research Center, Clinical Research Institute, Urmia University of Medical Sciences, Urmia, Iran
| | - Mohammadreza Pashaei
- Department of Internal Medicine, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Javad RasouIi
- Department of Biostatistics and Epidemiology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Rohollah Valizadeh
- Department of Biostatistics and Epidemiology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Hojat Ghasemnejad‐Berenji
- Reproductive Health Research Center, Clinical Research Institute, Urmia University of Medical Sciences, Urmia, Iran
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Feng Y, Liu W, Dong J, Lu F, Wu C, Shao Q, Duan A, Yang X, Sun R, Sha Y, Wu S, Wei X. Genetic Underpinnings of Oligoasthenoteratozoospermia. Clin Genet 2025; 107:243-260. [PMID: 39780539 DOI: 10.1111/cge.14652] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Revised: 11/07/2024] [Accepted: 11/10/2024] [Indexed: 01/11/2025]
Abstract
Oligoasthenoteratozoospermia (OAT) is a frequent but severe type of male infertility. As one of the most multifaceted male infertility resulting from sperm problems, its genetic etiology remains unknown in most cases. In this review, we systematically sort out the latest literature on clinical reports and animal models leading to OAT, summarise the expression profiles of causative genes for OAT, and highlight the important role of the protein transport system during spermiogenesis, spermatid cell-specific genes, Golgi and acrosome-related genes, manchette-related genes, HTCA-related genes, and axoneme-related genes in OAT development. These causative genes would be instrumental in genetic etiological screening, genetic counseling, and pre-implantation genetic testing of patients with clinical OAT.
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Affiliation(s)
- Yanting Feng
- School of Medicine, Yunnan University, Kunming, Yunnan, China
| | - Wensheng Liu
- Department of Reproductive Medicine, NHC Key Laboratory of Healthy Birth and Birth Defect Prevention in Western China, First People's Hospital of Yunnan Province, Kunming, China
- The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China
| | - Junbo Dong
- School of Medicine, Yunnan University, Kunming, Yunnan, China
| | - Fei Lu
- School of Medicine, Yunnan University, Kunming, Yunnan, China
| | - Chunyan Wu
- School of Medicine, Yunnan University, Kunming, Yunnan, China
| | - Qingting Shao
- School of Medicine, Yunnan University, Kunming, Yunnan, China
| | - Aizhu Duan
- School of Medicine, Yunnan University, Kunming, Yunnan, China
| | - Xinjie Yang
- School of Medicine, Yunnan University, Kunming, Yunnan, China
| | - Ruipeng Sun
- School of Medicine, Yunnan University, Kunming, Yunnan, China
| | - Yanwei Sha
- Department of Andrology, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, China
- Fujian Provincial Key Laboratory of Reproductive Health Research, School of Medicine, Xiamen University, Xiamen, Fujian, China
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, Fujian, China
| | - Shihao Wu
- School of Medicine, Yunnan University, Kunming, Yunnan, China
| | - Xiaoli Wei
- School of Medicine, Yunnan University, Kunming, Yunnan, China
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21
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Kristensen TS, Foldager A, Laursen ASD, Mikkelsen EM. Sexually transmitted infections (Chlamydia trachomatis, genital HSV, and HPV) and female fertility: A scoping review. SEXUAL & REPRODUCTIVE HEALTHCARE 2025; 43:101067. [PMID: 39889622 DOI: 10.1016/j.srhc.2025.101067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2024] [Revised: 11/02/2024] [Accepted: 01/09/2025] [Indexed: 02/03/2025]
Abstract
More than one million sexually transmitted infections (STIs) are acquired every day worldwide. They are commonly caused by Chlamydia trachomatis (CT), herpes simplex virus (HSV), or human papillomavirus (HPV) and are suggested to contribute to female infertility. This scoping review aims to map and summarize existing literature on the association between a pre-pregnancy infection with CT, genital HSV, or HPV and female fertility. We searched two databases (PubMed, Embase) to identify published literature on the association between CT, genital HSV, or HPV infection and female fertility. We included full-text articles, published from 2002 to 2022, on pre-pregnancy infection with either CT, genital HSV, or HPV within a population of women of reproductive age. The study endpoint was either pregnancy, time-to-pregnancy, or infertility. The included studies were evaluated according to the Critical Appraisal Tool by Joanna Briggs Institute. Eight studies were eligible for the review. All of them investigated the association between a CT infection and fertility, while none of them investigated infections with genital HSV or HPV. Three studies found that a CT infection was associated with poorer female fertility, and one study found a similar association in a subgroup analysis of women with a pregnancy intention. Four studies indicated no association, although methodological differences between the studies preclude firm conclusions. This review revealed sparse literature investigating the association between CT, HPV, and HSV and subsequent female fertility. Prospective cohort studies with preconception assessments of these STIs are needed to determine the relation between STIs and subsequent fertility.
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Affiliation(s)
- Trine S Kristensen
- Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Olof Palmes Allé 43-45, 8200 Aarhus N, Denmark.
| | - Amalie Foldager
- Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Olof Palmes Allé 43-45, 8200 Aarhus N, Denmark
| | - Anne Sofie D Laursen
- Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Olof Palmes Allé 43-45, 8200 Aarhus N, Denmark.
| | - Ellen M Mikkelsen
- Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Olof Palmes Allé 43-45, 8200 Aarhus N, Denmark.
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22
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Juel Mortensen L, Lorenzen M, Andreassen CH, Bentin-Ley U, Krog H, Juul A, Blomberg Jensen M. Soluble luteinizing hormone receptor in follicular fluid and the association with reproductive function during IVF and ICSI. Reprod Biol 2025; 25:100988. [PMID: 39642780 DOI: 10.1016/j.repbio.2024.100988] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Revised: 10/21/2024] [Accepted: 11/26/2024] [Indexed: 12/09/2024]
Abstract
The need for assisted reproductive technology (ART) has increased worldwide, leaving a negative impact on both physical and emotional health of the individual as well as on society depending on child births, thus biomarkers that can increase the success of ART are warranted. The luteinizing hormone/choriogonadotropin receptor (LHCGR) is released into blood and follicular fluid, and the level of soluble LHCGR (sLHCGR) in serum has previously been suggested to predict chances of pregnancy and live birth rate after ART. We aimed to investigate whether sLHCGR originates from the ovary and if serum or follicular fluid sLHCGR can predict the likelihood of pregnancy or live birth. A total of 133 women referred to a fertility clinic were included in the study, in total 203 trials of ART were performed. sLHCGR was analyzed in 170 follicular fluid samples and 75 serum samples. Interestingly, serum levels of sLHCGR were higher than follicular fluid levels (0.51 vs. 0.31 pmol/mL, p = 0.020) and a positive correlation in the two compartments was identified (r2 0.770, p < 0.0001), suggesting an extragonadal origin of sLHCGR. Follicular levels of sLHCGR were associated with follicular SHBG and free testosterone. Follicular/serum-ratio of sLHCGR was inversely associated with both serum- and follicular AMH. However, no association was found between sLHCGR and antral follicle count, which questions a link with folliculogenesis. Neither serum nor follicular fluid sLHCGR levels could predict pregnancy or live births in this cohort. Further studies are needed to clarify the role of sLHCGR in the ovaries.
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Affiliation(s)
- Li Juel Mortensen
- Group of Skeletal, Mineral, and Gonadal Endocrinology, Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; Department of Growth and Reproduction, and International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Denmark.
| | - Mette Lorenzen
- Group of Skeletal, Mineral, and Gonadal Endocrinology, Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; Division of Translational Endocrinology, Department of Endocrinology and Internal Medicine, Copenhagen University Hospital, Herlev-Gentofte, Denmark
| | - Christine Hjorth Andreassen
- Group of Skeletal, Mineral, and Gonadal Endocrinology, Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; Division of Translational Endocrinology, Department of Endocrinology and Internal Medicine, Copenhagen University Hospital, Herlev-Gentofte, Denmark
| | | | - Hans Krog
- TFP Danfert Fertility, Seedorffs Vaenge 2, Frederiksberg, Denmark
| | - Anders Juul
- Department of Growth and Reproduction, and International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Martin Blomberg Jensen
- Group of Skeletal, Mineral, and Gonadal Endocrinology, Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; Division of Translational Endocrinology, Department of Endocrinology and Internal Medicine, Copenhagen University Hospital, Herlev-Gentofte, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
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23
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Li X, Zhang J, Chun, Ling X, Luan T. Association between the composite dietary antioxidant index and risk of infertility: Evidence from NHANES 2013-2020 and a Mendelian randomization study. Int J Gynaecol Obstet 2025; 168:1264-1275. [PMID: 39422585 DOI: 10.1002/ijgo.15942] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Accepted: 09/17/2024] [Indexed: 10/19/2024]
Abstract
OBJECTIVE The Composite Dietary Antioxidant Index (CDAI) measures the antioxidant capacity of the diet, which is believed to provide protection against various diseases, including depression, osteoporosis, and papillomavirus infection, by neutralizing harmful oxidative stress. However, the relationship between CDAI and infertility is not well understood. This research aims to explore the potential correlations between CDAI and the risk of infertility. METHODS This research harnessed data from the National Health and Nutrition Examination Survey (NHANES) to execute a cross-sectional analysis involving 8263 US women aged 20-45. Each participant was subjected to two distinct 24-h dietary recall interviews. We calculated the CDAI using average daily antioxidant intake. Infertility was assessed using a standardized questionnaire. The association between CDAI and infertility was examined using weighted multiple logistic regression models, while nonlinear correlations were explored through restricted cubic splines. To affirm the robustness of our findings, sensitivity and subgroup analyses were performed using unweighted logistic regression. Additionally, to ascertain the causal influence of circulating antioxidant levels on infertility, a two-sample univariable Mendelian randomization (MR) analysis was conducted, using the inverse variance weighted (IVW) method as the primary analytic approach. RESULTS Participants who were infertile exhibited lower CDAI levels compared to their fertile counterparts. When confounding variables were accounted for in the multivariate weighted logistic regression model, an inverse relationship was observed between CDAI and infertility, with the odds ratio for the highest versus lowest quartile being 0.55 (0.33-0.90, P = 0.02). However, the IVW method indicated that genetically predicted elevated levels of CDAI did not significantly correlate with infertility. CONCLUSION Cross-sectional observational studies indicate that antioxidants from diets might diminish infertility risks. However, findings from MR studies do not confirm a causal connection. Additional prospective research is required to elucidate this association further.
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Affiliation(s)
- Xin Li
- Department of Reproductive Medicine, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, China
| | - JuanJuan Zhang
- Department of Reproductive Medicine, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, China
| | - Chun
- Department of Reproductive Medicine, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, China
| | - Xiufeng Ling
- Department of Reproductive Medicine, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, China
| | - Ting Luan
- Department of Obstetrics and Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, China
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24
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Wang H, Jiang B. Assessing and projecting the global impacts of female infertility: a 1990-2040 analysis from the Global Burden of Disease study. Sex Health 2025; 22:SH24237. [PMID: 40048314 DOI: 10.1071/sh24237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Accepted: 02/16/2025] [Indexed: 05/08/2025]
Abstract
Background This study aims to assess the global burden of female infertility from 1990 to 2040. Methods Data on disability-adjusted life years associated with female infertility were sourced from the Global Burden of Disease 2021 study. Generalized additive models were utilized to predict trends for the period spanning from 2022 to 2040. Results The global burden of female infertility is expected to increase significantly, with the age-standardized disability-adjusted life year rate projected to reach 19.92 (95% uncertainty interval (UI): 18.52, 21.33) by 2040. The projected estimated annual percentage change (EAPC) for the age-standardized disability-adjusted life year rate from 2022 to 2040 is expected to be 1.42, with a 95% confidence interval (CI) of 1.3951-1.4418. This is in contrast to the EAPC of 0.71 (95% CI: 0.5391-0.8789) observed from 1990 to 2021. Central sub-Saharan Africa is projected to have the highest age-standardized rate at 29.37 (95% UI: 24.58-34.16), whereas Australasia is expected to have the lowest at 0.78 (95% UI: 0.72-0.84). Age-specific projections show a consistent decline in infertility rates across all age groups. Countries such as Kenya, Chad and Peru exhibit EAPCs exceeding 9.00, whereas Mali and South Africa show significant negative EAPCs. Correlation analysis indicates that regions with a higher sociodemographic index generally have lower female infertility burdens, with notable trends observed in Europe and Asia. Conclusion The projected global burden of female infertility is expected to increase significantly from 2021 to 2040, with notable regional disparities. Central sub-Saharan Africa and south Asia are anticipated to experience higher burdens, whereas overall rates are projected to decrease across different age groups.
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Affiliation(s)
- Hanjin Wang
- Four Gynecological Wards, Women and Children's Hospital of Ningbo University, Ningbo 315000, Zhejiang, China
| | - Bengui Jiang
- Four Gynecological Wards, Women and Children's Hospital of Ningbo University, Ningbo 315000, Zhejiang, China
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25
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Moosazadeh M, Bordbari AH, Hashemi SM, Ghasemi Tirtashi M, Kargar-Soleimanabad S. The association between age at menarche and infertility: a systematic review and meta-analysis of observational studies. Contracept Reprod Med 2025; 10:15. [PMID: 39994726 PMCID: PMC11853611 DOI: 10.1186/s40834-025-00346-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Accepted: 02/19/2025] [Indexed: 02/26/2025] Open
Abstract
OBJECTIVE Both early and late age at menarche have been associated with various health issues and may influence the risk of infertility. This present study investigated the relationship between age at menarche and infertility risk. METHODS This study follows PRISMA guidelines. Databases including PubMed, Scopus, Web of Science, Embase, and Cochrane were searched in December 2024. Odds ratios with 95% confidence intervals were estimated using a random-effects model. Heterogeneity was assessed with the I2 index and chi-square, and publication bias was evaluated using Egger's test and a funnel plot. Sensitivity analysis and meta-regression examined study impact and variable influence on heterogeneity. RESULTS Out of 7,267 articles screened, 18 primary studies were included, yielding 21 pieces of evidence. The odds ratio (OR) for infertility in the late menarche group compared to the normal menarche group was 1.44 (95% CI: 0.98-2.10), while the OR for the early menarche group versus the normal menarche group was 0.98 (95% CI: 0.68-1.42). Additionally, the OR for infertility in the early menarche group compared to the late menarche group was 0.77 (95% CI: 0.55-1.06). For primary infertility, the OR for the late menarche group relative to the normal menarche group was 1.98 (95% CI: 1.02-3.85), whereas the OR for the early menarche group compared to the late menarche group was 0.59 (95% CI: 0.36-0.97). CONCLUSION Although the overall meta-analysis lacked statistical significance, subgroup analysis revealed a notable association between late menarche and primary infertility. Women with late menarche had higher odds of infertility, supporting a dose-responsive relationship. The observed 44% increase in infertility odds highlights late menarche as a potential risk factor, warranting further investigation into its implications for reproductive health.
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Affiliation(s)
- Mahmood Moosazadeh
- Gastrointestinal Cancer Research Center, Non-Communicable Disease Institute, Mazandaran University of Medical Sciences, Sari, Iran
| | - Amir-Hassan Bordbari
- Student Research Committee, School of Medicine, Mazandaran University of Medical Sciences, Farah Abad Road, P.O. Box: 48471-91628, Sari, Iran.
| | - Seyyed Mohammad Hashemi
- Student Research Committee, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Maliheh Ghasemi Tirtashi
- Department of Obstetrics and Gynecology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Saeed Kargar-Soleimanabad
- Student Research Committee, School of Medicine, Mazandaran University of Medical Sciences, Farah Abad Road, P.O. Box: 48471-91628, Sari, Iran
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26
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Ding J. Mendelian randomization reveals causal relationships between cytokines and male reproductive diseases. J Reprod Immunol 2025; 169:104465. [PMID: 40023096 DOI: 10.1016/j.jri.2025.104465] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Revised: 02/21/2025] [Accepted: 02/24/2025] [Indexed: 03/04/2025]
Abstract
This study aims to explore the causal links between cytokines and four male reproductive disorders, namely abnormal spermatozoa (AS), male infertility, erectile dysfunction (ED), and hyperplasia of prostate (HP), employing a two-sample Mendelian randomization (MR) approach. Genetic associations with male reproductive diseases were derived from the IEU OpenGWAS project, with cytokine data from two GWASs focused on the human proteome and cytokines. Estimations were derived using inverse variance weighting, MR-Egger regression, weighted median, weighted model, and simple mode. Furthermore, the robustness of the findings was evaluated through Cochran's Q-test, MR-Egger regression, and leave-one-out sensitivity analysis. Fifteen unique cytokines were identified as having causal relationships with the risk of four male reproductive disorders. Specifically, for AS, interleukin-22 (IL-22), IL-12, and macrophage migration inhibitory factor were negatively correlated with AS, while tumor necrosis factor β levels were positively correlated with AS. In the context of male infertility, IL-2 receptor antagonist levels, IL-34, and granulocyte-colony stimulating factor levels were positively linked to male infertility, whereas IL-21 showed a negative relationship. Regarding ED, IL-19, IL-1β, and eotaxin levels were negatively associated with ED risk, while macrophage inflammatory protein 1β (MIP-1β) levels and interferon gamma-induced protein 10 levels were positively associated. As for HP, stromal-cell-derived factor 1α levels and MIP-1α levels revealed negative associations with HP. In conclusion, this MR analysis revealed that several cytokines were causally associated with male reproductive diseases and could be valuable in offering new insights for further mechanistic and clinical investigations of cytokines-associated male reproductive diseases.
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Affiliation(s)
- Jie Ding
- Department of Reproductive Medicine, The Affiliated Hospital of Chongqing Population and Family Planning Science and Technology Research Institute, Chongqing 400020, China.
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27
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Jiang S, Chen Z, Li L. Assessing vitamin D's impact on pregnancy success: a predictive model for assisted reproductive technology outcomes. FRONTIERS IN REPRODUCTIVE HEALTH 2025; 7:1510484. [PMID: 40040781 PMCID: PMC11876408 DOI: 10.3389/frph.2025.1510484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Accepted: 01/23/2025] [Indexed: 03/06/2025] Open
Abstract
Objective To investigate the correlation between vitamin D levels and clinical pregnancy rates in infertile women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) procedures and to assess the utility of vitamin D levels in developing a predictive model for assisted reproductive technology (ART) outcomes. Methods A total of 188 infertile patients receiving their initial IVF or ICSI treatment at our reproductive center between June 2020 and July 2021 were selected for data collection. Vitamin D levels and other relevant ART-related factors were used to construct a predictive model. Result The multivariate regression analysis revealed that several independent variables significantly impacted ART pregnancy outcomes, including infertility age, vitamin D level, reproductive anti-Müllerian hormone, antral follicle count, Gn dose, daily endometrial thickness after human chorionic gonadotropin (HCG) administration, and number of retrieved eggs. The area under the receiver operating characteristic curve for this comprehensive model was 75.34%, with a standard error of 0.045 and p-value of 0.003 (95% confidence interval 0.712-0965). Furthermore, the multivariate regression analysis identified specific independent variables that might influence vitamin D levels, such as the number of embryos obtained, daily endometrial thickness after HCG administration, and clinical pregnancy. Conclusion The developed predictive model integrating serum 25-Hydroxyvitamin D level and ART-related factors holds significant clinical value in forecasting pregnancy outcomes.
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Affiliation(s)
- Songwei Jiang
- Reproductive Center, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Zushun Chen
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Liuming Li
- Reproductive Center, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
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28
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Bao Z, Zhang Y, Zhou J, Dai Z. Association between atherogenic index of plasma and infertility: a cross-sectional study based on U.S. women. Lipids Health Dis 2025; 24:51. [PMID: 39953566 PMCID: PMC11829380 DOI: 10.1186/s12944-025-02469-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2024] [Accepted: 02/06/2025] [Indexed: 02/17/2025] Open
Abstract
BACKGROUND A wealth of evidence indicates that dyslipidemia is associated with endothelial dysfunction, oxidative stress, and inflammation, each of which can impair reproductive function and lead to infertility. The Atherogenic Index of Plasma (AIP) is an innovative lipid biomarker that combines the triglyceride to high-density lipoprotein cholesterol (HDL-C) ratio, providing a more in-depth evaluation of lipid metabolism. This biomarker synthesizes discrete lipid disruptions into a single value, surpassing isolated lipid indicators' diagnostic value. The primary goal of our study was to explore the link between AIP and the incidence of infertility. METHODS Data from the National Health and Nutrition Examination Survey (NHANES) spanning 2013-2018 were subjected to cross-sectional examination. The AIP is determined through the logarithmic transformation (base 10) of the triglyceride-to-HDL-C ratio. To uncover the connection between AIP and infertility, a suite of analytical techniques was employed, encompassing weighted multiple logistic regression, stratified analyses, spline curve modeling, and determination of cutoff values. RESULTS Among the 1,191 participants, with a weighted mean age of 31.89 years, 12.09% were diagnosed as infertile. The multivariate-adjusted odds ratios for infertility occurrence across the AIP quartiles were 1.00 (reference), 1.96 (95% CI: 1.10-3.49), 2.62 (95% CI: 1.48-4.63), and 2.38 (95% CI: 1.31-4.32), respectively. Subgroup examinations suggest that the association between AIP and infertility remains robust and is not substantially altered by factors including age, marital status, economic status, tobacco use, alcohol intake, and body mass index. Curve fitting and threshold analyses have indicated a positive nonlinear relationship between AIP and infertility, as well as a relatively stable incidence of infertility within the AIP range from -0.21 to 0.22. CONCLUSIONS Incorporating an assessment of AIP into the clinical evaluation could potentially refine the accuracy of risk estimation for infertility patients.
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Affiliation(s)
- Zihong Bao
- Department of Infectious Diseases, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650000, China
| | - Yanmei Zhang
- Department of Infectious Diseases, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650000, China
| | - Ju Zhou
- Department of Infectious Diseases, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650000, China
| | - Zhikun Dai
- Shantou University Medical College, Shantou, Guangdong, 515041, China.
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Xu Y, Wang H, Li H, Wei C, Zhu Z, Zhao Y, Zhu J, Lei M, Sun Y, Yang Q. Nicotinamide Riboside Supplementation Alleviates Testicular Aging Induced by Disruption of Qprt-Dependent NAD + De Novo Synthesis in Mice. Aging Cell 2025:e70004. [PMID: 39902575 DOI: 10.1111/acel.70004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 12/21/2024] [Accepted: 01/09/2025] [Indexed: 02/05/2025] Open
Abstract
Recent studies have shown that disruptions in the nicotinamide adenine dinucleotide (NAD+) de novo synthesis pathway accelerate ovarian aging, yet its role in spermatogenesis remains largely unknown. In this study, we investigated the impact of the NAD+ de novo synthesis pathway on spermatogenesis by generating Qprt-deficient mice using CRISPR-Cas9 to target quinolinate phosphoribosyl transferase (Qprt), a key enzyme predominantly expressed in spermatocytes. Our results revealed that the deletion of Qprt did not affect NAD+ levels or spermatogenesis in the testes of 3-month-old mice. However, from 6 months of age onward, Qprt-deficient mice exhibited significantly reduced NAD+ levels in the testes compared to wild-type (WT) controls, along with a notable decrease in germ cell numbers and increased apoptosis. Additionally, these mice demonstrated mitochondrial dysfunction in spermatocytes, impaired progression through prophase I of meiosis, defective double-strand break (DSB) repair, and abnormal meiotic sex chromosome inactivation. Importantly, supplementation with the NAD+ precursor nicotinamide riboside (NR) in Qprt-deficient mice restored NAD+ levels and rescued the spermatogenic defects. These findings underscore the critical role of NAD+ de novo synthesis in maintaining NAD+ homeostasis and highlight its importance in meiotic recombination and meiotic sex chromosome inactivation in spermatogenesis.
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Affiliation(s)
- Yining Xu
- Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Henan Provincial Obstetrical and Gynecological Diseases (Reproductive Medicine) Clinical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Huan Wang
- Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Henan Provincial Obstetrical and Gynecological Diseases (Reproductive Medicine) Clinical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Hui Li
- Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Henan Provincial Obstetrical and Gynecological Diseases (Reproductive Medicine) Clinical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Chenlu Wei
- Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Henan Provincial Obstetrical and Gynecological Diseases (Reproductive Medicine) Clinical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhenye Zhu
- Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Henan Provincial Obstetrical and Gynecological Diseases (Reproductive Medicine) Clinical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yanqing Zhao
- Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Henan Provincial Obstetrical and Gynecological Diseases (Reproductive Medicine) Clinical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jiajia Zhu
- Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Henan Provincial Obstetrical and Gynecological Diseases (Reproductive Medicine) Clinical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Min Lei
- Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Henan Provincial Obstetrical and Gynecological Diseases (Reproductive Medicine) Clinical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yingpu Sun
- Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Henan Provincial Obstetrical and Gynecological Diseases (Reproductive Medicine) Clinical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Qingling Yang
- Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Henan Provincial Obstetrical and Gynecological Diseases (Reproductive Medicine) Clinical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Li X, Lu J, Sun Q, Zhang J, Zhao C, Ling X. The association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and risk of infertility among US adults: A cross-sectional NHANES study. Eur J Obstet Gynecol Reprod Biol 2025; 305:356-364. [PMID: 39746223 DOI: 10.1016/j.ejogrb.2024.12.041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Revised: 12/12/2024] [Accepted: 12/22/2024] [Indexed: 01/04/2025]
Abstract
BACKGROUND Infertility affects millions worldwide, with a significant proportion of cases remaining unexplained. Recent evidence suggests a potential link between lipid metabolism and reproductive health, prompting investigations into novel biomarkers like the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) for assessing infertility risk. METHODS This study utilized data from the National Health and Nutrition Examination Survey (NHANES) to conduct a cross-sectional analysis of 5,524 women aged 20-45 in the United States. NHHR was calculated from lipid profiles, and infertility was determined via the Reproductive Health Questionnaire. Multivariate logistic regression and restricted cubic spline (RCS) analyses were performed to examine the relationship between NHHR and infertility, adjusting for confounding factors such as age, BMI (body mass index), and lifestyle habits. RESULTS The study found a nonlinear association between NHHR and infertility risk, with the risk peaking in the second and third quartiles of NHHR levels. Notably, women in the higher NHHR quartiles exhibited a 2.15 to 2.36 odds ratio for infertility compared to those in the lowest quartile, suggesting a significant increase in risk. Subgroup analyses revealed that this association was particularly strong in younger women and those with a higher BMI. Moreover, the RCS analysis confirmed the nonlinear pattern of the relationship, highlighting a more pronounced risk at moderate NHHR levels, which plateaued or varied at higher levels. The interaction analyses further suggested that the relationship between NHHR and infertility risk could be influenced by age and BMI, pointing to differential effects in various subpopulations. CONCLUSIONS Elevated NHHR levels are associated with increased infertility risk, especially in specific subgroups, suggesting a complex link between lipid metabolism and reproductive health. Further research is needed to validate these findings and explore the potential of NHHR as a biomarker for infertility risk.
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Affiliation(s)
- Xin Li
- Department of Reproductive Medicine, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, PR China; Department of Obstetrics and Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital Nanjing, PR China
| | - Jueyun Lu
- Department of Reproductive Medicine, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, PR China; Department of Obstetrics and Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital Nanjing, PR China
| | - Qixi Sun
- Department of Reproductive Medicine, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, PR China; Department of Obstetrics and Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital Nanjing, PR China
| | - JuanJuan Zhang
- Department of Reproductive Medicine, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, PR China; Department of Obstetrics and Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital Nanjing, PR China.
| | - Chun Zhao
- Department of Reproductive Medicine, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, PR China; Department of Obstetrics and Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital Nanjing, PR China.
| | - Xiufeng Ling
- Department of Reproductive Medicine, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, PR China; Department of Obstetrics and Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital Nanjing, PR China.
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Saponara S, Angioni S, Parry JP, Pacheco LA, Carugno J, Moawad N, Haimovich S, Lasmar RB, Dealberti D, Aksakal E, Urman B, Nappi L, Vitale SG. The Pivotal role of hysteroscopy in diagnosing subtle uterine lesions in infertile patients: Seeing the unseen can make the difference. Eur J Obstet Gynecol Reprod Biol 2025; 305:132-141. [PMID: 39701007 DOI: 10.1016/j.ejogrb.2024.12.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 12/01/2024] [Accepted: 12/08/2024] [Indexed: 12/21/2024]
Abstract
BACKGROUND Subtle uterine lesions are abnormal intracavitary conditions that, while not causing significant anatomical changes, can adversely impact fertility. Identifying these "subtle" lesions is challenging due to arbitrary interpretation, varied management strategies, unclear clinical significance, and insufficient clinician training in recognizing them. Hysteroscopy offers direct visualization and the capacity to obtain targeted biopsies, making it an invaluable tool for the diagnosis and treatment of these often overlooked conditions. PURPOSE The lack of standardized and universally accepted terminology complicates the diagnosis and treatment of subtle uterine pathologies. A thorough understanding of how to identify and effectively manage these lesions is essential for the treatment of infertile patients. This review summarizes the critical and evolving subtle uterine lesions that clinicians frequently overlook during hysteroscopic procedures, highlighting the importance of accurate identification and its potential to improve reproductive outcomes. METHODS This literature review followed the Scale for the Quality Assessment of Narrative Review Articles (SANRA) guidelines. All articles discussing infertility-related issues and subtle lesions diagnosable with hysteroscopy were deemed eligible for inclusion. RESULTS We identified several subtle uterine lesions that are often overlooked during routine hysteroscopic evaluations but can adversely impact fertility. These include morphological abnormalities such as the T-shaped uterus, cystic lesions of the uterine wall, adenomyosis, cervicitis, cervical and tubal endometriosis, and endometrial conditions such as chronic endometritis, thin endometrium and endometrial calcifications. CONCLUSIONS Effective diagnosis and treatment of subtle uterine lesions is essential to fertility care. Knowing which lesions are commonly missed and understanding their endoscopic features and potential clinical implications, is crucial for enhancing the diagnostic capacity of hysteroscopy. This, in turn, may improve reproductive outcomes and the overall quality of care of infertile patients.
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Affiliation(s)
- Stefania Saponara
- Division of Gynecology and Obstetrics, Department of Surgical Sciences, University of Cagliari, Cagliari, Italy.
| | - Stefano Angioni
- Division of Gynecology and Obstetrics, Department of Surgical Sciences, University of Cagliari, Cagliari, Italy
| | | | - Luis Alonso Pacheco
- Centro Gutenberg, Unidad de Endoscopia Ginecológica, Hospital Xanit Internacional, Málaga, Spain
| | - Jose Carugno
- Minimally Invasive Gynecology Unit, Obstetrics, Gynecology and Reproductive Sciences Department, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Nash Moawad
- Division of Minimally Invasive Gynecologic Surgery, Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville, FL
| | - Sergio Haimovich
- Department of Obstetrics and Gynecology, Laniado University Hospital, Netanya, Israel; Adelson School of Medicine, Ariel University, Ariel, Israel
| | - Ricardo Bassil Lasmar
- Department of Surgery and Specialized, Faculty of Medicine, Universidade Federal Fluminense, UFF, Niterói 24020-141, RJ, Brazil
| | - Davide Dealberti
- Department of Obstetrics and Gynecology, "SS Antonio e Biagio Hospital", Alessandria, Italy
| | - Ece Aksakal
- Obstetrics and Gynecology, American Hospital, Bodrum, Turkey
| | - Bulent Urman
- Department of Obstetrics and Gynecology, Koc University School of Medicine, Istanbul, Turkey
| | - Luigi Nappi
- Department of Medical and Surgical Sciences, Institute of Obstetrics and Gynecology, University of Foggia, Foggia, Italy
| | - Salvatore Giovanni Vitale
- Division of Gynecology and Obstetrics, Department of Surgical Sciences, University of Cagliari, Cagliari, Italy
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Kong X, Liu Z, Huang C, Hu X, Mo M, Zhang H, Zeng Y. How to estimate the probability of a live birth after one or more complete IVF cycles? the development of a novel model in a single-center. BMC Pregnancy Childbirth 2025; 25:86. [PMID: 39885409 PMCID: PMC11780784 DOI: 10.1186/s12884-024-07017-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2023] [Accepted: 11/27/2024] [Indexed: 02/01/2025] Open
Abstract
OBJECTIVE To develop a predictive tool in the form of a Nomogram based on the Cox regression model, which incorporates the impact of the length of treatment cycles on the outcome of live birth, to evaluate the probability of infertile couples having a live birth after one or more complete cycles of In Vitro Fertilization (IVF), and to provide patients with a risk assessment that is easy to understand and visualize. METHODS A retrospective study for establishing a prediction model was conducted in the reproductive center of Shenzhen Zhongshan Obstetrics & Gynecology Hospital (formerly Shenzhen Zhongshan Urology Hospital). A total of 4413 patients who completed ovarian stimulation treatment and reached the trigger were involved. 70% of the patients were randomly placed into the training set (n = 3089) and the remaining 30% of the patients were placed into the validation set (n = 1324) randomly. Live birth rate (LBR) and cumulative LBR (CLBR) were calculated for one retrieval cycle and the subsequent five frozen embryo transfer (FET) cycles. Proportional Hazards (PH) Assumption test was used for selecting the parameter in the predictive model. A Cox regression model was built based on the basis of training set, and ROC curves were used to test the specificity and sensitivity of the prediction model. Subsequently, the validation set was applied to verify the validity of the model. Finally, for a more intuitive assessment of the CLBR more intuitively for clinicians and patients, a Nomogram model was established based on predictive model. By calculating the scores of the model, the clinicians could more effectively predict the probability for an individual patient to obtain at least one live birth. RESULTS In the fresh embryo transfer cycle, the LBR was 38.7%. In the first to fifth FET cycle, the optimal estimate and conservative estimate CLBRs were 59.95%, 65.41%, 66.35%, 66.58%, 66.61% and 56.81%, 60.84%, 61.50%, 61.66%, 61.68%, respectively. Based on PH test results, the potential predictive factors for live birth were insemination method, infertility factors, serum progesterone level (R = 0.043, p = 0.059), and luteinizing hormone level (R = 0.015, p = 0.499) on the day initiated with gonadotropin, basal follicle-stimulating hormone (R = -0.042, p = 0.069) and BMI (R = -0.035, p = 0.123). We used ROC curve to test the predictive power of the model. The AUC was 0.782 (p < 0.01, 95% CI: 0.764-0.801). Then the model was verified using the validation data. The AUC was 0.801 (p < 0.01, 95% CI: 0.774-0.828). A Nomogram model was built based on potential predictive factors that might influence the event of a live birth. CONCLUSIONS The Cox regression and Nomogram prediction models effectively predicted the probability of infertile couples having a live birth. Therefore, this model could assist clinicians with making clinical decisions and providing guidance for patients. TRIAL REGISTRATION N/A.
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Affiliation(s)
- Xiangyi Kong
- Reproductive Center of Shenzhen Zhongshan Obstetrics and Gynecology Hospital Formerly Reproductive Center of Shenzhen Zhongshan Urology Hospital, Shenzhen, Guangdong Province, China
| | - Zhiqiang Liu
- Reproductive Center of Shenzhen Zhongshan Obstetrics and Gynecology Hospital Formerly Reproductive Center of Shenzhen Zhongshan Urology Hospital, Shenzhen, Guangdong Province, China
| | - Chunyu Huang
- Reproductive Center of Shenzhen Zhongshan Obstetrics and Gynecology Hospital Formerly Reproductive Center of Shenzhen Zhongshan Urology Hospital, Shenzhen, Guangdong Province, China
| | - Xiuyu Hu
- Reproductive Center of Shenzhen Zhongshan Obstetrics and Gynecology Hospital Formerly Reproductive Center of Shenzhen Zhongshan Urology Hospital, Shenzhen, Guangdong Province, China
| | - Meilan Mo
- Reproductive Center of Shenzhen Zhongshan Obstetrics and Gynecology Hospital Formerly Reproductive Center of Shenzhen Zhongshan Urology Hospital, Shenzhen, Guangdong Province, China
| | - Hongzhan Zhang
- Reproductive Center of Shenzhen Zhongshan Obstetrics and Gynecology Hospital Formerly Reproductive Center of Shenzhen Zhongshan Urology Hospital, Shenzhen, Guangdong Province, China.
| | - Yong Zeng
- Reproductive Center of Shenzhen Zhongshan Obstetrics and Gynecology Hospital Formerly Reproductive Center of Shenzhen Zhongshan Urology Hospital, Shenzhen, Guangdong Province, China
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Amodio G, Giacomini G, Boeri L, Raffo M, Cilio S, Pozzi E, Belladelli F, Negri F, Ferrara AM, d'Arma A, Santoni de Sio FR, Pagliardini L, Papaleo E, Ventimiglia E, Alfano M, Montorsi F, Salonia A, Gregori S. Specific types of male infertility are correlated with T cell exhaustion or senescence signatures. Nat Commun 2025; 16:971. [PMID: 39856063 PMCID: PMC11759947 DOI: 10.1038/s41467-025-56193-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Accepted: 01/10/2025] [Indexed: 01/27/2025] Open
Abstract
The association between male infertility and health status has yet to be unraveled. Here, by combining multiparameter phenotyping and scRNA-seq, we delineate the immune status of infertile men both at the semen and systemic levels. We first observe that young infertile men have a pro-inflammatory milieu with increased frequency of myeloid cells and inflammatory mediators in the seminal fluid and the peripheral blood, which are immune alterations typically observed in healthy elderly men. Transcriptomic profiling confirms the upregulation of genes associated with the interferon-gamma and -alpha responses in peripheral blood T cells of infertile men with oligo-astheno-teratozoospermia or non-obstructive azoospermia, with distinct T cell signatures of exhaustion and senescence discriminating the two infertile conditions. These findings provide evidence that subtypes of male infertility are characterized by specific immune signatures and unravel the potential link between infertility and the risk of developing secondary diseases.
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Affiliation(s)
- Giada Amodio
- San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS Ospedale San Raffaele, Milan, Italy
| | - Giorgia Giacomini
- San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS Ospedale San Raffaele, Milan, Italy
| | - Luca Boeri
- IRCCS Fondazione Ca' Granda Ospedale Maggiore Policlinico, Department of Urology, Milan, Italy
| | - Massimiliano Raffo
- Division of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele, Milan, Italy
- University Vita-Salute San Raffaele, Milan, Italy
| | - Simone Cilio
- Division of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele, Milan, Italy
- Department of Neurosciences, Reproductive Sciences and Odontostomatology, Urology Unit, University of Naples "Federico II", Naples, Italy
| | - Edoardo Pozzi
- Division of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele, Milan, Italy
- University Vita-Salute San Raffaele, Milan, Italy
| | - Federico Belladelli
- Division of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele, Milan, Italy
- University Vita-Salute San Raffaele, Milan, Italy
| | - Fausto Negri
- Division of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele, Milan, Italy
- University Vita-Salute San Raffaele, Milan, Italy
| | - Anna Maria Ferrara
- Division of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele, Milan, Italy
| | - Alessia d'Arma
- Division of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele, Milan, Italy
| | | | - Luca Pagliardini
- Reproductive Sciences Laboratory, Obstetrics and Gynaecology Unit, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Enrico Papaleo
- Reproductive Sciences Laboratory, Obstetrics and Gynaecology Unit, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Eugenio Ventimiglia
- Division of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele, Milan, Italy
| | - Massimo Alfano
- Division of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele, Milan, Italy
| | - Francesco Montorsi
- Division of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele, Milan, Italy
- University Vita-Salute San Raffaele, Milan, Italy
| | - Andrea Salonia
- Division of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele, Milan, Italy.
- University Vita-Salute San Raffaele, Milan, Italy.
| | - Silvia Gregori
- San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS Ospedale San Raffaele, Milan, Italy.
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Ombelet W, Van Blerkom J, Boshoff G, Huyser C, Lopes F, Nargund G, Sallam H, Vanmechelen K, Campo R. Now is the time to introduce new innovative assisted reproduction methods to implement accessible, affordable, and demonstrably successful advanced infertility services in resource-poor countries. Hum Reprod Open 2025; 2025:hoaf001. [PMID: 39935763 PMCID: PMC11810638 DOI: 10.1093/hropen/hoaf001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 12/02/2024] [Indexed: 02/13/2025] Open
Abstract
Nearly 200 million people worldwide suffer from infertility. Disparities exist between developed and developing countries due to differences in the availability of infertility care, different reimbursement policies and socio-cultural differences surrounding procreation. In low- and middle-income countries, specialized infertility centres are either scarce or non-existent, mostly in private settings, and accessible only to the fortunate few who can afford them. The success and sustainability of ARTs will depend on our ability to optimize these techniques in terms of availability, affordability, and effectiveness. A low-cost, simplified IVF system has been developed and shown to be safe, cost-effective, and widely applicable to low-resource settings. Combined with inexpensive mild ovarian stimulation protocols, this could become a truly effective means of treating infertility and performing assisted reproduction at affordable prices, but only if such programmes are sincerely desired and supported by all relevant stakeholders. A receptive political, governmental, and clinical community is essential.
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Affiliation(s)
- Willem Ombelet
- The Walking Egg Non-Profit Organization, Genk, Belgium
- Faculty of Medicine and Life Sciences, LCRC, University of Hasselt, Diepenbeek, Belgium
| | - Jonathan Van Blerkom
- Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO, USA
| | - Gerhard Boshoff
- Faculty of Medicine and Life Sciences, LCRC, University of Hasselt, Diepenbeek, Belgium
- Department of Obstetrics and Gynaecology, University of Pretoria, Pretoria, South Africa
| | - Carin Huyser
- Department of Obstetrics and Gynaecology, University of Pretoria, Pretoria, South Africa
| | | | | | - Hassan Sallam
- Department of Reproductive Medicine, Alexandria University Faculty of Medicine, Alexandria, Egypt
| | | | - Rudi Campo
- The Walking Egg Non-Profit Organization, Genk, Belgium
- Life Expert Centre, Leuven, Belgium
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Zhang W, He J, Zhao F, Pan J, Wen J, Jiang L, Zhang M. Exploring the link between exposure to volatile organic chemicals and incidence of infertility:A cross-sectional study. Heliyon 2025; 11:e40902. [PMID: 39802009 PMCID: PMC11721247 DOI: 10.1016/j.heliyon.2024.e40902] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Revised: 11/14/2024] [Accepted: 12/02/2024] [Indexed: 01/16/2025] Open
Abstract
Background Growing evidence suggests that environmental pollutants exert a detrimental impact on female fertility. Among these pollutants, volatile organic compounds (VOCs), easily encountered in the environment, have garnered significant attention as prevalent airborne contaminants. Nevertheless, a definitive consensus regarding the association between VOCs and the incidence of infertility remains elusive. Method Conducted as a cross-sectional study, this research utilized data from three survey cycles of the NHANES program spanning from 2013 to 2018. The objective was to delve into the relationship between volatile organic compounds and the prevalence of infertility. The definition of infertility relied upon information derived from the reproductive health questionnaire. In order to comprehensively explore this relationship, various analytical models, including logistic regression, weighted quantile sum (WQS), and Bayesian kernel-machine regression (BKMR), were employed. Result A total of 1098 participants, 120 in the infertility group and 978 in the control group, were included. All 15 volatile organic compounds showed higher concentrations in the infertility group's urine. Multivariate regression revealed that the highest AMCC (N-acetyl-S-(N-methylcarbamoyl)-L-cysteine) and CYMA (2-hydroxyethyl mercapturic acid) quartiles associated with significant infertility increases, approximately 191 % and 128 %, respectively, versus the lowest quartile (OR for AMCC = 2.91; 95%CI: 1.33, 6.37; OR for CYMA = 2.28; 95%CI: 1.01, 5.15). This emphasizes AMCC and CYMA's role in infertility, supported by WQS and BKMR studies. Inflammation mediates AMCC's impact on infertility, enhancing our understanding of volatile organic compounds and reproductive health. Conclusion The study highlights the correlation between VOCs exposure, notably AMCC and CYMA, and infertility. It identifies inflammation as a mediating factor connecting AMCC to infertility.
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Affiliation(s)
- Wen Zhang
- Department of Neurosurgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, PR China
- Department of Nephrology, Yiyang Central Hospital affiliated, University of South China, Yiyang, Hunan, PR China
| | - Jiarong He
- Department of Neurosurgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, PR China
| | - Fang Zhao
- Department of Rheumatology, The First Hospital and Institute of Innovation and Applied Research in Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, PR China
| | - Jing Pan
- Department of Nephrology, Hengyang Central Hospital, University of South China, Hengyang, Hunan, PR China
| | - Jiefu Wen
- Department of Nephrology, Yiyang Central Hospital affiliated, University of South China, Yiyang, Hunan, PR China
| | - Lijun Jiang
- Department of Orthopedics, Yiyang Central Hospital affiliated, University of South China, Yiyang, Hunan, PR China
| | - Mingming Zhang
- Department of Neurosurgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, PR China
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Jeremic A, Vasiljevic M, Mikovic Z, Bukumiric Z, Simic P, Stanisavljevic T, Simic T, Djukic T. Oxidative Homeostasis in Follicular Fluid and Embryo Quality-A Pilot Study. Int J Mol Sci 2025; 26:388. [PMID: 39796245 PMCID: PMC11721896 DOI: 10.3390/ijms26010388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Revised: 01/01/2025] [Accepted: 01/02/2025] [Indexed: 01/13/2025] Open
Abstract
The objective of this study was to measure the different redox biomarker levels within the follicular fluid (FF) and evaluate correlations with embryo quality using the one follicle-one oocyte/embryo approach. The prospective study included 54 women (average age 34.6 ± 3.0 years). Out of the 235 mature metaphase II cells that underwent intracytoplasmic sperm injection, fertilization was achieved in 177 cells, producing 92 Grade I embryos, 26 Grade II embryos, 39 Grade III embryos, and 20 Grade IV embryos. The activities of antioxidant enzymes, superoxide dismutase, glutathione peroxidase, and glutathione transferase were significantly higher in the group consisting of lower-quality (Grades II-IV) embryos in comparison with top-quality (Grade I) embryos (p = 0.011; p = 0.021; p = 0.008, respectively). The concentration of oxidative stress markers, malondialdehyde, 8-hydroxy-2'-deoxyguanosine, and thiol groups was significantly increased in the group with lower-quality embryos (Grades II-IV) compared to top-quality embryos (0.027; 0.018; 0.021, respectively). Furthermore, a significant positive correlation between each oxidative marker and the activities of antioxidant enzymes was observed (p < 0.001). According to our findings, the best embryos and, consequently, better in vitro fertilization outcomes are linked to low levels of oxidative stress and low antioxidant enzyme activity.
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Affiliation(s)
- Ana Jeremic
- University Clinic for Gynecology and Obstetrics “Narodni Front”, 11000 Belgrade, Serbia; (A.J.); (M.V.); (Z.M.); (P.S.)
| | - Mladenko Vasiljevic
- University Clinic for Gynecology and Obstetrics “Narodni Front”, 11000 Belgrade, Serbia; (A.J.); (M.V.); (Z.M.); (P.S.)
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (Z.B.); (T.S.)
| | - Zeljko Mikovic
- University Clinic for Gynecology and Obstetrics “Narodni Front”, 11000 Belgrade, Serbia; (A.J.); (M.V.); (Z.M.); (P.S.)
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (Z.B.); (T.S.)
| | - Zoran Bukumiric
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (Z.B.); (T.S.)
- Institute of Medical Statistics and Informatics, 11000 Belgrade, Serbia
| | - Petar Simic
- University Clinic for Gynecology and Obstetrics “Narodni Front”, 11000 Belgrade, Serbia; (A.J.); (M.V.); (Z.M.); (P.S.)
| | - Tamara Stanisavljevic
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (Z.B.); (T.S.)
- Institute of Medical and Clinical Biochemistry, 11000 Belgrade, Serbia
- Center of Excellence for Redox Medicine, 11000 Belgrade, Serbia
| | - Tatjana Simic
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (Z.B.); (T.S.)
- Institute of Medical and Clinical Biochemistry, 11000 Belgrade, Serbia
- Center of Excellence for Redox Medicine, 11000 Belgrade, Serbia
- Serbian Academy of Sciences and Arts, 11000 Belgrade, Serbia
| | - Tatjana Djukic
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (Z.B.); (T.S.)
- Institute of Medical and Clinical Biochemistry, 11000 Belgrade, Serbia
- Center of Excellence for Redox Medicine, 11000 Belgrade, Serbia
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Ernst A, Brix N, Gaml‐Sørensen A, Arendt LH, Toft G, Tøttenborg SS, Hougaard KS, Bonde JPE, Ramlau‐Hansen CH. Parental age at birth and biomarkers of fecundity in young Danish men. Andrology 2025; 13:89-100. [PMID: 37750236 PMCID: PMC11635595 DOI: 10.1111/andr.13536] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Revised: 08/16/2023] [Accepted: 09/12/2023] [Indexed: 09/27/2023]
Abstract
BACKGROUND High parental age is associated with adverse birth and genetic outcomes, but little is known about fecundity in male offspring. OBJECTIVES We investigated if high parental age at birth was associated with biomarkers of male fecundity in a large population-based sample of young men. MATERIALS AND METHODS We conducted a study of 1057 men from the Fetal Programming of Semen Quality (FEPOS) cohort, a sub-cohort of sons born 1998-2000 into the Danish National Birth Cohort. Semen characteristics and reproductive hormone concentrations were measured in samples provided by the men 2017-2019. Testis volume was determined by self-measurement. Data on the parental age was drawn from registers. Adjusted relative difference in percentage with 95% confidence intervals were estimated for each outcome according to pre-specified maternal and paternal age groups (< 30 (reference), 30-34 and ≥ 35) as well as for combinations of parental age groups, using multivariable negative binomial regression models. RESULTS We did not observe consistent associations between parental age and biomarkers of fecundity, although sons of mothers ≥ 35 years had lower sperm concentration (-15% (95% CI: -30, 3)) and total sperm count (-10% (95% CI: -25, 9)). The analysis with parental age combinations showed lower sperm concentration with high age of the parents (both ≥ 35 years: -27%, 95% CI: -40, -19) when compared to the reference where both parents were below 30 years. DISCUSSION AND CONCLUSION We found no strong association between higher parental age and biomarkers of fecundity in young men. However, we cannot exclude poorer semen characteristics in sons born by older mothers or with high age of both parents.
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Affiliation(s)
- Andreas Ernst
- Research Unit for Epidemiology, Department of Public HealthAarhus UniversityAarhusDenmark
- Department of UrologyAarhus University HospitalAarhusDenmark
| | - Nis Brix
- Research Unit for Epidemiology, Department of Public HealthAarhus UniversityAarhusDenmark
- Department of Clinical GeneticsAarhus University HospitalAarhusDenmark
| | - Anne Gaml‐Sørensen
- Research Unit for Epidemiology, Department of Public HealthAarhus UniversityAarhusDenmark
| | - Linn Håkonsen Arendt
- Research Unit for Epidemiology, Department of Public HealthAarhus UniversityAarhusDenmark
| | - Gunnar Toft
- Steno Diabetes Center AarhusAarhus University HospitalAarhusDenmark
| | - Sandra Søgaard Tøttenborg
- Department of Occupational and Environmental MedicineCopenhagen University Hospital‐Bispebjerg and FrederiksbergCopenhagenDenmark
- Department of Public HealthUniversity of CopenhagenCopenhagenDenmark
| | - Karin Søring Hougaard
- Department of Public HealthUniversity of CopenhagenCopenhagenDenmark
- National Research Centre for the Working EnvironmentCopenhagenDenmark
| | - Jens Peter Ellekilde Bonde
- Department of Occupational and Environmental MedicineCopenhagen University Hospital‐Bispebjerg and FrederiksbergCopenhagenDenmark
- Department of Public HealthUniversity of CopenhagenCopenhagenDenmark
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Ntais C, Artsita M, Talias MA, Fanourgiakis J, Kontodimopoulos N. Assessing Willingness to Pay for IVF Among Infertile Women in Greece: A Single-Center Case Study. Health Sci Rep 2025; 8:e70402. [PMID: 39872911 PMCID: PMC11770250 DOI: 10.1002/hsr2.70402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Revised: 01/07/2025] [Accepted: 01/13/2025] [Indexed: 01/30/2025] Open
Abstract
Background and Aims In recent years, In Vitro fertilization (IVF) science has grown by leaps and bounds in the field of assisted reproduction, helping millions of couples worldwide. The aim of this study is to examine the extent to which infertile women are willing to pay for IVF services in Greece. Methods Through the distribution of questionnaires, willingness to pay (WTP) is recorded according to IVF success rates, and the relationship between WTP and the respondents' demographic characteristics is analyzed. Subjects were divided into two groups according to age and were given a hypothetical scenario, according to the contingent valuation approach. Results The majority of women were reluctant to pay the amount of money corresponding to the average cost of an IVF cycle in Greece. In particular, participants replied that the amount they would be willing to pay is only one-third of the indicative amount of €6000. Moreover, WTP is not influenced by the professional status or educational level of the participating women. Conclusion This study highlights the financial barriers many couples face when pursuing assisted reproduction. If the average cost of IVF were lower, infertile women would be willing to undergo more IVF cycles if necessary. This finding has important implications for the valuation of IVF services and the development of pricing policies to enhance affordability and accessibility. Policymakers must consider reforms that balance the cost of IVF with its societal benefits. By incorporating this aspect into pricing and policy decisions, Greece can improve the accessibility of IVF services and ensure equitable treatment opportunities for all concerned individuals.
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Affiliation(s)
- Christos Ntais
- Epidemiology Program, School of Science and TechnologyHellenic Open UniversityPatrasGreece
- Healthcare Management Program, School of Economics & ManagementOpen University of CyprusNicosiaCyprus
| | - Mary Artsita
- Healthcare Management Program, School of Social SciencesHellenic Open UniversityPatrasGreece
| | - Michael A. Talias
- Healthcare Management Program, School of Economics & ManagementOpen University of CyprusNicosiaCyprus
| | - John Fanourgiakis
- Healthcare Management Program, School of Social SciencesHellenic Open UniversityPatrasGreece
- Department of Management Science and TechnologyHellenic Mediterranean UniversityAgios NikolaosCreteGreece
| | - Nikolaos Kontodimopoulos
- Healthcare Management Program, School of Social SciencesHellenic Open UniversityPatrasGreece
- Department of Economics and Sustainable DevelopmentHarokopio UniversityAthensGreece
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Hall-Clifford R, Hamdan ZA, Bergenfeld I, Bawadi H, Mowla W, Hamdaneh J, Salem HA, Clark CJ. "Infertility frightened me": Violence among infertile couples in Jordan. WOMEN'S HEALTH (LONDON, ENGLAND) 2025; 21:17455057251322815. [PMID: 40014755 PMCID: PMC11869262 DOI: 10.1177/17455057251322815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 01/10/2025] [Accepted: 02/06/2025] [Indexed: 03/01/2025]
Abstract
BACKGROUND Women in couples experiencing infertility are at heightened risk for intimate partner violence (IPV) from husbands and domestic violence (DV) from family. Couples experiencing infertility in Jordan, a patriarchal culture with high rates of IPV and DV, are particularly vulnerable. This article explores the gendered similarities and differences in the experiences of mental health, social support, exclusion, and IPV. OBJECTIVES The objectives of this study are to understand both men and women's perspectives on their experiences of infertility and to develop intervention strategies to reduce IPV among married couples experiencing infertility. DESIGN This study is a descriptive, observational study. METHODS Through quantitative surveys and in-depth qualitative interviews, we examined key themes including: challenges to mental health and well-being; reproductive health and fertility care-seeking; experiences of shame, isolation, and discrimination; coping skills; sources of support; and challenges within spousal and family relationships. RESULTS In this article, we analyze primary areas of gender discordance and discuss how gendered experiences can shape implementation of psychosocial support intervention programs to prevent IPV. Our findings provide important insight into facilitators and barriers to prevention of IPV in this vulnerable group. CONCLUSION We conclude that providing both women and men with culturally appropriate support during fertility treatment-seeking can improve psychosocial health and couple functioning and ultimately to reduce the occurrence of IPV in this vulnerable population.
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Affiliation(s)
- Rachel Hall-Clifford
- Center for the Study of Human Health, Department of Sociology, Hubert Department of Global Health, Emory University, Atlanta, GA, USA
| | - Zaid Al Hamdan
- School of Nursing and Health Management, Jordan University of Science and Technology, Irbid, Jordan
| | - Irina Bergenfeld
- Rollins School of Public Health, Hubert Department of Global Health, Emory University, Atlanta, USA
| | - Hala Bawadi
- School of Midwifery and Maternity, University of Jordan, Amman, Jordan
| | - Wardha Mowla
- Rollins School of Public Health, Hubert Department of Global Health, Emory University, Atlanta, USA
| | - Jehan Hamdaneh
- Department of Obstetrics and Gynecology, Director of the In Vitro Fertilization Center, King Abdullah University Hospital, Irbid, Jordan
| | | | - Cari Jo Clark
- Rollins School of Public Health, Hubert Department of Global Health, Emory University, Atlanta, USA
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Gadapani Pathak B, Mburu G, Habib N, Kabra R, Kiarie J, Chowdhury R, Dhabhai N, Mazumder S. Quality of life and its determinants in women with delayed conception in low-mid socioeconomic neighbourhoods of Northern India: a cross-sectional study. BMJ PUBLIC HEALTH 2025; 3:e001740. [PMID: 40260127 PMCID: PMC12010299 DOI: 10.1136/bmjph-2024-001740] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Accepted: 04/02/2025] [Indexed: 04/23/2025]
Abstract
Background The inability to conceive or delay in conception has negative and multidimensional effects on health and well-being, daily functioning and societal interactions. This study assesses the impact of delayed conception on quality of life (QoL) among Indian women with delayed conception and evaluates the Fertility Quality of Life (FertiQoL) questionnaire's reliability and construct validity in this population. Methodology A cross-sectional study of 1530 women aged 18-30, who had not conceived over a period of 18 months, was conducted in low-to-mid-socioeconomic neighbourhoods in Delhi, India. The 24-item core module of the FertiQoL questionnaire was used to assess participants' QoL. Researchers analysed data to identify factors associated with QoL scores and evaluated FertiQoL's internal consistency and validity. Data were collected between July 2020 and August 2021. Result The average FertiQoL score was 31.71 out of 100, indicating a moderately low QoL. Among the subscales, emotional (mean: 29.0) and mind-body domains (mean: 25.4) scored the lowest, while the relational domain scored the highest (mean: 50.7). Factors negatively associated with QoL included a longer duration of delayed conception (β=-0.3, 95% CI: -0.5 to -0.1), husbands fathering children with other partners (β=-1.1, 95% CI: -1.7 to -0.38), domestic violence-emotional (β=-3.5, 95% CI: -4.5 to -2.4), verbal (β=-3.2, 95% CI: -4.7 to -1.7), physical abuse by family (β=-3.6, 95% CI: -5.5 to -1.6), lack of financial support (β=-3.2, 95% CI: -5.2 to -1.2), social pressures (β=-1.6, 95% CI: -2.3 to -0.9) and physical health issues (β=-0.9, 95% CI: -1.7 to -0.2). The FertiQoL tool demonstrated acceptable reliability (Cronbach's alpha=0.64) and good construct validity (confirmatory factor analysis), confirming its utility in this population. Conclusion Indian women experiencing delayed conception have reduced QoL, particularly in emotional and mind-body domains, due to various psychosocial and socioeconomic challenges. The FertiQoL questionnaire proved to be a reliable and valid tool for assessing QoL in this context. Psychosocial interventions addressing emotional, social and economic stressors are urgently needed to improve their well-being. Future research should include men to better understand the holistic challenges faced by couples struggling to conceive.
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Affiliation(s)
- Barsha Gadapani Pathak
- Society for Applied Studies, New Delhi, New Delhi, India
- Centre for International Health, Faculty of Medicine, University of Bergen, Bergen, Norway
| | - Gitau Mburu
- UNDP-UNFPA-UNICEF-WHO-World Bank Special Program of Research, Development and Research Training in Human Reproduction (HRP), Department of Sexual and Reproductive Health and Research, World Health Organization, Geneva, Switzerland
| | - Ndema Habib
- UNDP-UNFPA-UNICEF-WHO-World Bank Special Program of Research, Development and Research Training in Human Reproduction (HRP), Department of Sexual and Reproductive Health and Research, World Health Organization, Geneva, Switzerland
| | - Rita Kabra
- UNDP-UNFPA-UNICEF-WHO-World Bank Special Program of Research, Development and Research Training in Human Reproduction (HRP), Department of Sexual and Reproductive Health and Research, World Health Organization, Geneva, Switzerland
| | - James Kiarie
- UNDP-UNFPA-UNICEF-WHO-World Bank Special Program of Research, Development and Research Training in Human Reproduction (HRP), Department of Sexual and Reproductive Health and Research, World Health Organization, Geneva, Switzerland
| | | | - Neeta Dhabhai
- Society for Applied Studies, New Delhi, New Delhi, India
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Baazeem A, Alqurashi TMM, Alharbi YHH, Aldahhas RAD, Fatani MHA. Consumption of folk medicine in men-seeking treatment for infertility. Urol Ann 2025; 17:48-51. [PMID: 40051996 PMCID: PMC11881943 DOI: 10.4103/ua.ua_34_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Accepted: 10/06/2024] [Indexed: 03/09/2025] Open
Abstract
Background Male infertility is a major health problem that can have a tremendous negative impact on the affected individuals and couples. The use of folk medicine is common practice in the Middle Eastern region, especially before seeking conventional medical treatment. Unfortunately, some of these remedies might be potentially harmful. This study aims to assess the use of folk medicine before formal medical evaluation by a male infertility specialist among men in couples with subfertility in Saudi Arabia. Materials and Methods A retrospective study of prospectively documented data was conducted among male patients who presented for evaluation of their infertility at one center in Jeddah, Saudi Arabia, from May 1, 2020, to April 30, 2021, to assess the prevalence of the use of traditional medicine among these patients. Results The total number of patients who visited the center for infertility assessment during the specified period was of 427. Most patients had primary infertility (64.4%). Table 1 summarizes the demographic data of the patient population. About 55.3% of the patients were 40 years old or less. Patients who consumed some form of alternative medicine are 38.9%. A clinical varicocele was detected in 57.8% of these men. Patients who use alternative medicine had significantly lower semen concentration and estradiol levels (P = 0.02 similarly). Conclusion About 38.9% of patients who attended our clinic were using some alternative medicine. Furthermore, patients who use alternative medicine had significantly less sperm motility and progressive motility.
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Affiliation(s)
- Abdulaziz Baazeem
- Department of Surgery, College of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
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Sun F, Li X, Kang L, Wang Y, Li H, Zhu H. Case report: Carcinosarcoma of uterus in nulliparous women. Front Oncol 2024; 14:1472416. [PMID: 39723383 PMCID: PMC11668669 DOI: 10.3389/fonc.2024.1472416] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Accepted: 11/22/2024] [Indexed: 12/28/2024] Open
Abstract
Background Uterine carcinosarcoma (UCS), or malignant mixed Müllerian tumor, is a cancer that include both carcinomatous and sarcomatous components, resembling endometrial carcinoma. A 55-year-old woman was admitted to the hospital with postmenopausal vaginal bleeding. Gross examination of the specimen revealed brittle tissue in the fundus and the left wall of the endometrium. Postoperative pathology revealed a mixture of well-differentiated endometrioid adenocarcinoma and osteosarcoma. The patient was never given birth, which may be relevant to the diagnosis. Literature review suggests that being nulliparous may be a significant risk factor for developing uterine carcinosarcoma. Case description In December 2023, a 55-year-old female patient was admitted to the hospital with postmenopausal vaginal bleeding. Hysteroscopic surgery was performed, and the postoperative pathology showed endometrial cancer accompanied by ossified tissue with necrosis. The immunohistochemical results indicated positive Estrogen receptors (ER), positive Progesterone receptors (PR), ki67 positivity at 70%, negative PTEN, mutated positive p53, focal positive Pax-8, positive SATB2, positive Cytokeratin 7 (CK7), positive EMA and positive Vimentin (Vim). The patient was diagnosed with Uterine carcinosarcoma. On December 18, 2023, the patient underwent partial vaginal resection, bilateral salpingo-oophorectomy, pelvic lymph node dissection, and a sub-extensive laparoscopic hysterectomy. Postoperatively, the patients received radiotherapy and four cycles of chemotherapy in the DC regimen. As of July 2024, laboratory and impact test results showed no tumor recurrence. The patient's disease-free survival (DFS) was seven months. Conclusion The rate of childless in patients with uterine carcinosarcoma is at a high level.
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Affiliation(s)
| | | | | | | | - Hongyu Li
- *Correspondence: Hongyu Li, ; Hai Zhu,
| | - Hai Zhu
- *Correspondence: Hongyu Li, ; Hai Zhu,
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Dreischor F, Dancet EAF, Lambalk CB, van Lunsen HW, Besselink D, van Disseldorp J, Boxmeer J, Brinkhuis EA, Cohlen BJ, Hoek A, de Hundt M, Janssen CAH, Lambers M, Maas J, Nap A, Perquin D, Verberg M, Verhoeve HR, Visser J, van der Voet L, Mochtar MH, Goddijn M, Laan E, van Wely M, Custers IM. The web-based Pleasure&Pregnancy programme in the treatment of unexplained infertility: a randomized controlled trial. Hum Reprod 2024; 39:2711-2721. [PMID: 39352942 PMCID: PMC11630088 DOI: 10.1093/humrep/deae220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Revised: 07/22/2024] [Indexed: 10/04/2024] Open
Abstract
STUDY QUESTION Does offering the Pleasure&Pregnancy (P&P) programme rather than expectant management improve naturally conceived ongoing pregnancy rates in couples diagnosed with unexplained infertility? SUMMARY ANSWER The P&P programme had no effect on the ongoing pregnancy rates of couples with unexplained infertility. WHAT IS KNOWN ALREADY Underpowered studies suggested that face-to-face interventions targeting sexual health may increase pregnancy rates. The impact of an eHealth sexual health programme had yet to be evaluated by a large randomized controlled trial. STUDY DESIGN, SIZE, DURATION This is a nationwide multi-centre, unblinded, randomized controlled superiority trial (web-based randomization programme, 1:1 allocation ratio). This RCT intended to recruit 1164 couples within 3 years but was put on hold after having included 700 couples over 5 years (2016-2021). The web-based P&P programme contains psychosexual information and couple communication, mindfulness and sensate focus exercises aiming to help maintain or improve sexual health, mainly pleasure, and hence increase pregnancy rates. The P&P programme additionally offers information on the biology of conception and enables couples to interact online with peers and via email with coaches. PARTICIPANTS/MATERIALS, SETTING, METHODS Heterosexual couples with unexplained infertility and a Hunault-prognosis of at least 30% chance of naturally conceiving a live-born child within 12 months were included, after their diagnostic work-up in 41 Dutch secondary and tertiary fertility centres. The primary outcome was an ongoing pregnancy, defined as a viable intrauterine pregnancy of at least 12 weeks duration confirmed by an ultrasound scan, conceived naturally within 6 months after randomization. Secondary outcomes were time to pregnancy, live birth, sexual health, and personal and relational well-being at baseline and after 3 and 6 months. The primary analyses were according to intention-to-treat principles. We calculated relative risks (RRs, pregnancy rates) and a risk difference (RD, pregnancy rates), Kaplan-Meier survival curves (live birth over time), and time, group, and interactive effects with mixed models analyses (sexual health and well-being). MAIN RESULTS AND THE ROLE OF CHANCE Totals of 352 (one withdrawal) and 348 (three withdrawals) couples were allocated to, respectively the P&P group and the expectant management group. Web-based tracking of the intervention group showed a high attrition rate (57% of couples) and limited engagement (i.e. median of 16 visits and 33 min total visitation time per couple). Intention-to-treat analyses showed that 19.4% (n = 68/351) of the P&P group and 22.6% (n = 78/345) of the expectant management group achieved a naturally conceived ongoing pregnancy (RR = 0.86; 95% CI = 0.64-1.15, RD = -3.24%; 95% CI -9.28 to 2.81). The time to pregnancy did not differ between the groups (Log rank = 0.23). Live birth occurred in 18.8% (n = 66/351) of the couples of the P&P group and 22.3% (n = 77/345) of the couples of the expectant management group (RR = 0.84; 95% CI = 0.63-1.1). Intercourse frequency decreased equally over time in both groups. Sexual pleasure, orgasm, and satisfaction of women of the P&P group improved while these outcomes remained stable in the expectant management group. Male orgasm, intercourse satisfaction, and overall satisfaction decreased over time with no differences between groups. The intervention did not affect personal and relational well-being. Non-compliance by prematurely starting medically assisted reproduction, and clinical loss to follow-up were, respectively, 15.1% and 1.4% for the complete study population. Per protocol analysis for the primary outcome did not indicate a difference between the groups. Comparing the most engaged users with the expectant management group added that coital frequency decreased less, and that male sexual desire improved in the intervention group. LIMITATIONS, REASONS FOR CAUTION The intended sample size of 1164 was not reached because of a slow recruitment rate. The achieved sample size was, however, large enough to exclude an improvement of more than 8% of the P&P programme on our primary outcome. WIDER IMPLICATIONS OF THE FINDINGS The P&P programme should not be offered to increase natural pregnancy rates but may be considered to improve sexual health. The attrition from and limited engagement with the P&P programme is in line with research on other eHealth programmes and underlines the importance of a user experience study. STUDY FUNDING/COMPETING INTEREST(S) Funded by The Netherlands Organisation for Health Research and Development (ZonMw, reference: 843001605) and Flanders Research Foundation. C.B.L. is editor-in-chief of Human Reproduction. H.W.L. received royalties or licences from Prometheus Publishers Springer Media Thieme Verlag. J.B. received support from MercK for attending the ESHRE course 'The ESHRE guideline on ovarian stimulation, do we have agreement?' J.v.D. reports consulting fees and lecture payments from Ferring, not related to the presented work, and support for attending ESHRE from Goodlife and for attending NFI Riga from Merck. A.H. reports consulting fees by Ferring Pharmaceutical company, The Netherlands, paid to institution UMCG, not related to the presented work. H.V. reports consulting fees from Ferring Pharmaceutical company, The Netherlands, and he is a member of the ESHRE guideline development group unexplained infertility and Chair of the Dutch guideline on unexplained infertility (unpaid). M.G. declares unrestricted research and educational grants from Ferring not related to the presented work, paid to their institution VU Medical Centre. The other authors have no conflicts to declare. TRIAL REGISTRATION NUMBER NTR5709. TRIAL REGISTRATION DATE 4 February 2016. DATE OF FIRST PATIENT’S ENROLMENT 27 June 2016.
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Affiliation(s)
- F Dreischor
- Department of Obstetrics and Gynaecology, Centre for Reproductive Medicine, Amsterdam UMC Location AMC, University of Amsterdam, Amsterdam, The Netherlands
| | - E A F Dancet
- Department of Public Health and Primary Care, KU Leuven-University of Leuven, Leuven, Belgium
| | - C B Lambalk
- Division of Reproductive Medicine, Department of Obstetrics & Gynaecology, Amsterdam UMC Location VUMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - H W van Lunsen
- Sexology and Psychosomatic Obstetrics and Gynaecology, Amsterdam UMC Location AMC, Amsterdam, The Netherlands
| | - D Besselink
- Radboudumc, Department of Obstetrics & Gynaecology, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - J van Disseldorp
- Department of Obstetrics and Gynaecology, Sint Antonius Ziekenhuis, Nieuwegein, The Netherlands
| | - J Boxmeer
- Department of Gynaecology, Reinier de Graaf Gasthuis, Delft, The Netherlands
| | - E A Brinkhuis
- Department of Obstetrics and Gynaecology, Meander MC, Amersfoort, The Netherlands
| | - B J Cohlen
- Isala Fertility Centre, Isala Clinics, Zwolle, The Netherlands
| | - A Hoek
- Department of Obstetrics and Gynaecology, Section Reproductive Medicine, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands
| | - M de Hundt
- Department of Obstetrics and Gynaecology, Noordwest Ziekenhuisgroep, Alkmaar, The Netherlands
| | - C A H Janssen
- Department of Obstetrics and Gynaecology, Groene Hart Ziekenhuis, Gouda, The Netherlands
| | - M Lambers
- Department of Obstetrics and Gynaecology, Dijklander Ziekenhuis, Hoorn, The Netherlands
| | - J Maas
- Department of Obstetrics and Gynaecology, Maastricht UMC+, Maastricht, The Netherlands
- Maastricht University GROW School for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands
| | - A Nap
- Radboudumc, Department of Obstetrics & Gynaecology, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - D Perquin
- Department of Obstetrics and Gynaecology, Medical Centre Leeuwarden, Leeuwarden, The Netherlands
| | - M Verberg
- Fertility Clinic Twente, Twente, The Netherlands
| | - H R Verhoeve
- Department of Obstetrics and Gynaecology, OLVG, Amsterdam, The Netherlands
| | - J Visser
- Department of Obstetrics and Gynaecology, Amphia Ziekenhuis, Breda, The Netherlands
| | - L van der Voet
- Department of Obstetrics and Gynaecology, Deventer Hospital, Deventer, The Netherlands
| | - M H Mochtar
- Department of Obstetrics and Gynaecology, Centre for Reproductive Medicine, Amsterdam UMC Location AMC, University of Amsterdam, Amsterdam, The Netherlands
- Reproduction and Development Research Institute, Amsterdam, The Netherlands
| | - M Goddijn
- Department of Obstetrics and Gynaecology, Centre for Reproductive Medicine, Amsterdam UMC Location AMC, University of Amsterdam, Amsterdam, The Netherlands
- Division of Reproductive Medicine, Department of Obstetrics & Gynaecology, Amsterdam UMC Location VUMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
- Reproduction and Development Research Institute, Amsterdam, The Netherlands
| | - E Laan
- Sexology and Psychosomatic Obstetrics and Gynaecology, Amsterdam UMC Location AMC, Amsterdam, The Netherlands
| | - M van Wely
- Department of Obstetrics and Gynaecology, Centre for Reproductive Medicine, Amsterdam UMC Location AMC, University of Amsterdam, Amsterdam, The Netherlands
- Reproduction and Development Research Institute, Amsterdam, The Netherlands
| | - I M Custers
- Department of Obstetrics and Gynaecology, Centre for Reproductive Medicine, Amsterdam UMC Location AMC, University of Amsterdam, Amsterdam, The Netherlands
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Chen Y, Sun T, Liu C, Gu L, Yuan P. In silico approach uncovers the shared genetic landscape of type 2 diabetes mellitus and asthenozoospermia. Syst Biol Reprod Med 2024; 70:272-288. [PMID: 39292564 DOI: 10.1080/19396368.2024.2395545] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Revised: 07/14/2024] [Accepted: 08/10/2024] [Indexed: 09/20/2024]
Abstract
Asthenozoospermia (AZS) is one of the most common types of male infertility. Current evidence revealed that type 2 diabetes mellitus (T2DM) is closely associated with declining semen quality, especially for poor sperm motility. This study aimed to uncover the genetic interrelationships and important biomarkers between AZS and T2DM. Transcriptome data regarding AZS and T2DM were downloaded from the Gene Expression Omnibus (GEO) database. We performed GO and pathway analysis, and protein-protein interaction (PPI) network construction for T2DM-related differentially expressed genes (DMRGs). Moreover, we calculated receiver operator characteristic (ROC) curve and conducted external independent validation. Expression of hub DMRGs was assessed for patients using the qPCR method. MiRNA interaction and immune infiltration were subsequently characterized. A total of 554 overlapping DMRGs were identified between the AZS/T2DM and healthy groups. These overlapping DMRG participated in the DNA damage-, energy metabolism-, and immune-related biological pathways. Module function analysis discovered that the top three PPI modules were tightly correlated with DNA damage-related processes. After external validation in other independent datasets, two hub DMRGs (TBC1D12 and SCG5) were obtained. ROC analysis revealed that TBC1D12 and SCG5 had good diagnostic performance (area under the curve > 0.75). Immune infiltration profile showed that the level of T cell co-stimulation and CD8+_T_cells were negatively related to the hub DMRGs expression. Mirna interaction analysis showed 15 significant hub DMRGs-miRNA interactions. The qPCR results showed that expression of TBC1D12 and SCG5 were significantly different between sperm samples from diabetic patients with AZS and controls. The present study revealed molecular signatures and critical pathways between the AZS and T2DM, and identified two hub DMRGs of TBC1D12 and SCG5. The data would provide novel understandings of shared pathogenic mechanisms in T2DM-associated AZS.
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Affiliation(s)
- Yinwei Chen
- Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Taotao Sun
- Department of Urology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Chang Liu
- Reproductive Medicine Center, Department of Obstetrics and Gynecology, West China Second Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Longjie Gu
- Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Penghui Yuan
- Department of Urology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
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45
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Lôbo ADOM, Morbach V, Kelly FA, de Moraes FCA. Association between ovarian tumors and exposure to assisted reproductive technologies and ovarian stimulation: a systematic review and meta-analysis. Arch Gynecol Obstet 2024; 310:2753-2765. [PMID: 39412534 DOI: 10.1007/s00404-024-07763-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Accepted: 09/27/2024] [Indexed: 12/18/2024]
Abstract
INTRODUCTION The question of whether assisted reproductive technologies (ART) and ovulation induction are related to a higher incidence of ovarian tumors (OTs) is still controversial in the literature. METHODS We performed a comprehensive search of PubMed, Embase, and Web of Science databases for case-control and cohort studies that investigated ART and ovulation induction exposure as risk factors for OT in infertile women. Odds ratios (OR) with 95% confidence intervals (CI) were employed for all endpoints. RESULTS A total of nine case-control and twelve cohort studies were included, encompassing 439,477 women. ART was not associated with a higher risk of OTs (OR 1.05; 95% CI 0.86-1.29; p = 0.64; I2 = 36%), nor when considering only borderline OTs (OR 1.13; 95% CI 0.84-1.51; p = 0.42; I2 = 31%). In a subgroup analysis by study type, the risk difference of OTs remained non-significant for case-control (OR 1.12; 95% CI 0.70-1.78; p = 0.65; I2 = 60%) and cohort studies (OR 1.05; 95% CI 0.87-1.27; p = 0.60; I2 = 1%). For borderline OTs, the difference between groups was also non-significant for case-control studies (OR 1.44; 95% CI 0.73-2.87; p = 0.30; I2 = 40%) and cohort studies (OR 1.00; 95% CI 0.75-1.34; p = 0.99; I2 = 24%). CONCLUSION In this systematic review and meta-analysis, ART exposure in infertile women was not associated with a higher risk of OTs in general or borderline tumors, even when accounting for study type differences.
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Affiliation(s)
- Artur de Oliveira Macena Lôbo
- Center of Medical Sciences, Federal University of Pernambuco, Av. da Engenharia, 531-611, Recife, Pernambuco, 50670-901, Brazil.
| | - Victória Morbach
- Department of Medicine, Feevale University, Novo Hamburgo, Rio Grande do Sul, 93510-235, Brazil
| | - Francinny Alves Kelly
- Department of Hypertension, Dante Pazzanese Institute of Cardiology, São Paulo, São Paulo, 04012-909, Brazil
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Skowrońska M, Pawłowski M, Buczyńska A, Wiatr A, Dyszkiewicz A, Wenta A, Gryko K, Zbucka-Krętowska M, Milewski R. The Relationship Between Body Composition Parameters and the Intake of Selected Nutrients, and Serum Anti-Müllerian Hormone (AMH) Levels in the Context of Ovulatory Infertility. Nutrients 2024; 16:4149. [PMID: 39683543 DOI: 10.3390/nu16234149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Revised: 11/26/2024] [Accepted: 11/28/2024] [Indexed: 12/18/2024] Open
Abstract
Background/Objective: The aim of this study was to outline the relationships between selected parameters connected with lifestyle and serum anti-Müllerian hormone (AMH) levels, i.e., a marker of ovarian reserve. By examining AMH levels in connection with nutrient intake and body composition parameters, this study aimed to provide a preliminary background for further studies focused on establishing dietary and lifestyle recommendations that could lead to improvements in fertility outcomes. Methods: The research involved 28 women, aged 26 to 42-both with and without ovulatory infertility-who were patients of the Reproductive Health Clinic at the Medical University of Białystok. The participants underwent a number of tests consisting of hormonal profiling, including AMH measurements, body composition analyses, and dietary assessments based on a 3-day food diary. Results: The findings of the study indicate that certain lifestyle factors are associated with changes in AMH levels. Most importantly, the multivariate linear regression model designed in the study shows that age, waist-to-hip ratio (WHR), as well as the intake of sucrose, iodine, and erucic acid explain variations in serum AMH levels. These results support the hypothesis that modifiable lifestyle factors can influence AMH levels, and thus ovarian reserve. Conclusions: The study underscores the potential for targeted lifestyle interventions to support fertility and calls for further research in the form of prospective studies performed in larger groups of patients to substantiate these associations and inform fertility care strategies. Based on the preliminary results of this study, certain dietary ideas that could positively influence fertility have been proposed, focused on the normalization of body weight and the reduction in excess fat tissue.
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Affiliation(s)
| | - Michał Pawłowski
- Department of Biostatistics and Medical Informatics, Medical University of Bialystok, 15-295 Bialystok, Poland
| | - Angelika Buczyńska
- Clinical Research Center, Medical University of Bialystok, 15-276 Bialystok, Poland
| | - Aleksandra Wiatr
- Clinical Research Center, Medical University of Bialystok, 15-276 Bialystok, Poland
| | - Aleksandra Dyszkiewicz
- Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, 15-276 Bialystok, Poland
| | - Aleksandra Wenta
- Department of Gynecological Endocrinology and Adolescent Gynecology, Medical University of Bialystok, 15-276 Bialystok, Poland
| | - Kamila Gryko
- Department of Gynecological Endocrinology and Adolescent Gynecology, Medical University of Bialystok, 15-276 Bialystok, Poland
| | - Monika Zbucka-Krętowska
- Department of Gynecological Endocrinology and Adolescent Gynecology, Medical University of Bialystok, 15-276 Bialystok, Poland
| | - Robert Milewski
- Department of Biostatistics and Medical Informatics, Medical University of Bialystok, 15-295 Bialystok, Poland
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Hamroun S, Couderc M, Flipo RM, Sellam J, Richez C, Dernis E, Frazier A, Gossec L, Gervais E, Marotte H, Dunogeant L, Lukas C, Deroux A, Guettrot-Imbert G, Le Guern V, Costedoat-Chalumeau N, Molto A. NSAID exposure delays time-to-pregnancy in patients with spondyloarthritis: an analysis of the GR2 prospective cohort. RMD Open 2024; 10:e004745. [PMID: 39615886 PMCID: PMC11624830 DOI: 10.1136/rmdopen-2024-004745] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Accepted: 10/26/2024] [Indexed: 12/06/2024] Open
Abstract
BACKGROUND The impact of disease activity and treatment on fertility outcomes in patients with spondyloarthritis (SpA) has been little explored. This study aimed to describe median time to pregnancy (TTP) in women with SpA and the factors influencing TTP in this population. METHODS This prospective observational multicentre (63 centres) French cohort (GR2 study-NCT02450396) included consecutive women with a diagnosis of SpA (according to their rheumatologist) who wanted to become pregnant between 2015 and 2021. TTP (in months) was the main outcome criterion, prospectively calculated from the date of study inclusion to the date of conception. Data on demographics, disease characteristics, disease activity, severity and treatment were prospectively collected at inclusion and each year thereafter until pregnancy occurred. TTP and its associated factors were estimated by survival analysis (Shared Frailty Cox models), with a random centre effect and multiple imputation to address missing data. RESULTS We analysed 88 women included before conception. Among them, 56 (63.6%) became pregnant during follow-up. Median TTP was 16.1 (95% CI (12.2 to 25.3)) months. Mean preconceptional Bath Ankylosing Spondylitis Disease Activity Index at inclusion was 2.9 (±SD 2.1). Patients were treated with TNF inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), conventional synthetic disease-modifying antirheumatic drugs and glucocorticoids in 61 (69.3%), 23 (26.1%), 12 (13.6%) and 8 (9.1%) cases, respectively. The multivariate model found a significant association between TTP and age (HR) (per year) 1.22 95% CI (1.08 to 1.40); p<0.001) and the use of NSAIDs during preconception (HR 3.01 95% CI (2.15 to 3.85); p=0.01). CONCLUSION Age and NSAID use during preconception were significantly associated with a longer TTP, after adjustment for other confounding factors. These findings warrant caution in the use of NSAIDs in SpA patients trying to conceive.
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Affiliation(s)
- Sabrina Hamroun
- Rheumatology Department, HP center, Paris, France
- Université Paris Cité, Paris, France
| | - Marion Couderc
- Rheumatology, University Hospital Centre, Clermont-Ferrand, France
- Inserm/Imost UMR1240, Clermont Auvergne University, Clermont-Ferrand, France
| | - René-Marc Flipo
- Université Lille 2 Droit et Santé BU Santé Learning Centre, Lille, France
| | - Jérémie Sellam
- Rheumatology, INSERM UMRS_938, Sorbonnes Université UPMC Univ Paris 06, St-Antoine Hospital, DHU i2B, Paris, France
| | - Christophe Richez
- Service de Rhumatologie, Hôpital Pellegrin, CHU de Bordeaux, Bordeaux, France
- UMR CNRS 5164, Université de Bordeaux Collège Sciences de la Santé, Bordeaux, France
| | | | - Aline Frazier
- Service de rhumatologie, AP-HP, Hôpital Laribosière, Paris, France
| | - Laure Gossec
- INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Sorbonne Universite, Paris, France
- Rheumatology Department, APHP, Hopital Universitaire Pitie Salpetriere, Paris, France
| | | | - Hubert Marotte
- Rhumatologie, CHU Saint-Etienne, Saint-Etienne, France
- SAINBIOSE, INSERM U1059, University of Lyon, Saint-Etienne, France
| | - Laetitia Dunogeant
- Rheumatology and Internal Medicine Department, Pays d’Aix Hospital, Aix-en-Provence, France
| | - Cédric Lukas
- Rheumatology, University Hospital Lapeyronie, Montpellier, France
- EA2415, Montpellier University, Montpellier, France
| | - Alban Deroux
- Internal Medicine Department, Grenoble, Grenoble, France
| | | | | | | | - Anna Molto
- Rheumatology, Hospital Cochin, Paris, France
- INSERM U1153, CRESS - Université Paris-Cité, Paris, France
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48
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Grande G. Human Infertility and Reproductive Endocrinology. Life (Basel) 2024; 14:1550. [PMID: 39768258 PMCID: PMC11677894 DOI: 10.3390/life14121550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Accepted: 11/15/2024] [Indexed: 01/11/2025] Open
Abstract
One of the biggest problems facing modern medicine is infertility [...].
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Affiliation(s)
- Giuseppe Grande
- Unit of Andrology and Reproductive Medicine, Department of Medicine, University of Padua, Via Giustiniani 2, 35128 Padua, Italy
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49
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Aikawa S, Hiraoka T, Matsuo M, Fukui Y, Fujita H, Saito-Fujita T, Shimizu-Hirota R, Takeda N, Hiratsuka D, He X, Ishizawa C, Iida R, Akaeda S, Harada M, Wada-Hiraike O, Ikawa M, Osuga Y, Hirota Y. Spatiotemporal functions of leukemia inhibitory factor in embryo attachment and implantation chamber formation. Cell Death Discov 2024; 10:481. [PMID: 39587062 PMCID: PMC11589870 DOI: 10.1038/s41420-024-02228-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2024] [Revised: 10/22/2024] [Accepted: 10/24/2024] [Indexed: 11/27/2024] Open
Abstract
Embryo implantation is crucial for successful pregnancy, requiring appropriate uterine responses to implantation-competent blastocysts. Molecular communication at the maternal-fetal junction governs this process. Leukemia inhibitory factor (Lif) plays a pivotal role in implantation across species. Lif is abundantly expressed in the glandular epithelium during blastocyst-receptive phase and is induced in the stroma surrounding attached blastocysts. While diminished Lif expression leads to infertility, its influence on peri-implantation uteri remains unclear. Therefore, we investigated the role of Lif in uterine physiology using its uterine-specific knockout (uKO) and uterine epithelial-specific KO (eKO) in mice. Lif eKO and uKO mice displayed infertility owing to failed embryo attachment. Recombinant Lif supplementation rescued the reproductive phenotype of Lif eKO mice, but not Lif uKO mice; however, recombinant Lif injection rescued embryo attachment in Lif uKO mice. RNA-seq analysis indicated that Lif governs uterine epithelial genes, but not embryonic genes, to facilitate embryo attachment via activating nuclear Stat3. Concordantly, three-dimensional imaging of the uterine epithelium revealed that luminal closure and crypt formation are regulated by the uterine Lif-Stat3 axis as well as the presence of blastocysts. Collectively, our findings shed light on previously unknown mechanism on how Lif influences uterine functions molecularly and physiologically during early pregnancy.
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Affiliation(s)
- Shizu Aikawa
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Takehiro Hiraoka
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
- Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan
| | - Mitsunori Matsuo
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yamato Fukui
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hidetoshi Fujita
- Department of Biomedical Engineering, Osaka Institute of Technology, Osaka, Japan
| | - Tomoko Saito-Fujita
- Division of Cancer Biology, The Cancer Institute of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Ryoko Shimizu-Hirota
- Department of Internal Medicine, Center for Preventive Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Norihiko Takeda
- Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Daiki Hiratsuka
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Xueting He
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Chihiro Ishizawa
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Rei Iida
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Shun Akaeda
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Miyuki Harada
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Osamu Wada-Hiraike
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Masahito Ikawa
- Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan
| | - Yutaka Osuga
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yasushi Hirota
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
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50
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Babakhanzadeh E, Hoseininasab FA, Khodadadian A, Nazari M, Hajati R, Ghafouri-Fard S. Circular RNAs: novel noncoding players in male infertility. Hereditas 2024; 161:46. [PMID: 39551760 PMCID: PMC11572108 DOI: 10.1186/s41065-024-00346-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Accepted: 11/05/2024] [Indexed: 11/19/2024] Open
Abstract
Infertility is a global problem being associated with emotional and financial burden. Recent studies have shown contribution of a group of non-coding RNAs, namely circular RNAs (circRNAs) to the etiology of some infertility conditions. CircRNA are transcribed from exons and form a circular RNA molecule, being abundant in eukaryotes. Traditionally classified as non-coding RNA, these transcripts are endogenously produced through either non-canonical back-splicing or linear splicing, typically produced from precursor messenger ribonucleic acid (pre-mRNA). While during the canonical splicing process the 3' end of the exon is joined to the 5' end of the succeeding exon to form linear mRNA, during backsplicing, the 3' end to the 5' end of the same exon is joined to make a circular molecule. circRNAs are involved in the regulation of several aspects of spermatogenesis. They appear to influence how stem germ cells grow and divide during the sperm production process. Malfunctions in circRNA activity could contribute to male infertility issues stemming from abnormalities in spermatogenesis. In the current review, we highlight the exciting potential of circRNAs as key players in the male fertility.
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Affiliation(s)
- Emad Babakhanzadeh
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | | | - Ali Khodadadian
- Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Majid Nazari
- Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Reza Hajati
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Soudeh Ghafouri-Fard
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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