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Yano Maher JC, Zelinski MB, Oktay KH, Duncan FE, Segars JH, Lujan ME, Lou H, Yun BH, Hanfling SN, Schwartz LE, Laronda MM, Halvorson LM, O'Neill KE, Gomez-Lobo V. Classification system of human ovarian follicle morphology: recommendations of the National Institute of Child Health and Human Development - sponsored ovarian nomenclature workshop. Fertil Steril 2025; 123:761-778. [PMID: 39549739 PMCID: PMC12045743 DOI: 10.1016/j.fertnstert.2024.11.016] [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: 09/05/2024] [Revised: 11/01/2024] [Accepted: 11/11/2024] [Indexed: 11/18/2024]
Abstract
OBJECTIVE To develop a consensus on histologic human ovarian follicle staging nomenclature, provide guidelines for follicle density calculation, and assess changes due to fixation to enhance communication among clinicians and ovarian biology researchers to gain a deeper understanding of human fertility. SETTING Beginning in March 2021, the Ovarian Nomenclature Workshop's Follicle Classification Working Subgroup was organized by the Pediatric and Adolescent Gynecology program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. METHODS After the initial workshop held in May 2021, a Follicle Working Subgroup comprised of experts in reproductive endocrinology and ovarian biology held multiple meetings to develop the human follicle classification system and reported to the collective group during two follow up workshops. RESULTS The Follicle Working Subgroup recommends consolidation and expansion of the current classification systems to include six stages of normal preantral follicles, five stages of normal antral follicles, as well as categories of corpus lutea, abnormal preantral follicles, abnormal antral follicles, and other distinct follicle types. The new preantral staging added intermediate stages (primordial, transitional primordial, primary, transitional primary, secondary, and multilayer ovarian follicles). The antral follicle staging includes early, preselection, selection, dominance, and preovulatory follicles. Abnormal preantral follicles include those with an abnormal oocyte, granulosa cells, or both. We suggest a uniform way of calculating the mean follicle density in the number of follicles/mm2. CONCLUSION To establish a consensus in human ovarian follicle terminology, the Ovarian Follicle Working Subgroup of the National Institute of Child Health and Human Development Ovarian Nomenclature Workshop standardized follicle staging nomenclature and follicle density calculating systems so consistent common language can be used among ovarian biology researchers and clinicians.
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Affiliation(s)
- Jacqueline C Yano Maher
- Division of Pediatric and Adolescent Gynecology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
| | - Mary B Zelinski
- Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Beaverton, Oregon; Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, Oregon
| | - Kutluk H Oktay
- Laboratory of Molecular Reproduction and Fertility Preservation, Yale School of Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, New Haven, Connecticut
| | - Francesca E Duncan
- Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - James H Segars
- Division of Reproductive Science and Women's Health Research, Johns Hopkins University, Baltimore, Maryland
| | - Marla E Lujan
- Division of Nutritional Sciences, College of Human Ecology, Cornell University, Ithaca, New York
| | - Hong Lou
- Division of Pediatric and Adolescent Gynecology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
| | - Bo Hyon Yun
- Division of Pediatric and Adolescent Gynecology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland; Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, South Korea
| | - Sarina N Hanfling
- Division of Pediatric and Adolescent Gynecology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
| | - Lauren E Schwartz
- Division of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Monica M Laronda
- Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; Stanley Manne Children's Research Institute, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois; Division of Endocrinology, Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Lisa M Halvorson
- Gynecologic Health and Disease Branch, Division of Extramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
| | - Kathleen E O'Neill
- Division of Reproductive Endocrinology and Infertility, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Veronica Gomez-Lobo
- Division of Pediatric and Adolescent Gynecology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
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Yan L, Tu W, Zhao X, Wan H, Wu J, Zhao Y, Wu J, Sun Y, Zhu L, Qin Y, Hu L, Yang H, Ke Q, Zhang W, Luo W, Xiao Z, Chen X, Wu Q, He B, Teng M, Dai S, Zhai J, Wu H, Yang X, Guo F, Wang H. Stem cell transplantation extends the reproductive life span of naturally aging cynomolgus monkeys. Cell Discov 2024; 10:111. [PMID: 39496598 PMCID: PMC11535534 DOI: 10.1038/s41421-024-00726-4] [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: 12/18/2023] [Accepted: 08/03/2024] [Indexed: 11/06/2024] Open
Abstract
The ovary is crucial for female reproduction and health, as it generates oocytes and secretes sex hormones. Transplantation of mesenchymal stem cells (MSCs) has been shown to alleviate pathological ovarian aging. However, it is unclear whether MSCs could benefit the naturally aging ovary. In this study, we first examined the dynamics of ovarian reserve of Chinese women during perimenopause. Using a naturally aging cynomolgus monkey (Macaca fascicularis) model, we found that transplanting human embryonic stem cells-derived MSC-like cells, which we called M cells, into the aging ovaries significantly decreased ovarian fibrosis and DNA damage, enhanced secretion of sex hormones and improved fertility. Encouragingly, a healthy baby monkey was born after M-cell transplantation. Moreover, single-cell RNA sequencing analysis and in vitro functional validation suggested that apoptosis, oxidative damage, inflammation, and fibrosis were mitigated in granulosa cells and stromal cells following M-cell transplantation. Altogether, these findings demonstrate the beneficial effects of M-cell transplantation on aging ovaries and expand our understanding of the molecular mechanisms underlying ovarian aging and stem cell-based alleviation of this process.
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Affiliation(s)
- Long Yan
- Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
- University of Chinese Academy of Sciences, Beijing, China
- Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China
- Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China
| | - Wan Tu
- Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
- University of Chinese Academy of Sciences, Beijing, China
- Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China
- Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China
| | - Xuehan Zhao
- Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
- Department of Human Reproductive Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Beijing Maternal and Child Health Care Hospital, Beijing, China
| | - Haifeng Wan
- Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
- University of Chinese Academy of Sciences, Beijing, China
- Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China
- Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China
| | - Jiaqi Wu
- Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
- Department of Human Reproductive Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Beijing Maternal and Child Health Care Hospital, Beijing, China
| | - Yan Zhao
- Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
- University of Chinese Academy of Sciences, Beijing, China
- Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China
- Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China
| | - Jun Wu
- Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
- Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China
- Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China
- National Stem Cell Resource Center, Chinese Academy of Sciences, Beijing, China
| | - Yingpu Sun
- Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Lan Zhu
- Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Yingying Qin
- State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, Shandong, China
| | - Linli Hu
- Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Hua Yang
- Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Qiong Ke
- The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Wenzhe Zhang
- State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, Shandong, China
- Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Wei Luo
- State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, Shandong, China
- Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Zhenyu Xiao
- Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China
- School of Life Science, Beijing Institute of Technology, Beijing, China
| | - Xueyu Chen
- Laboratory of Neonatology, Department of Neonatology, Affiliated Shenzhen Maternity & Child Healthcare Hospital, Southern Medical University, Shenzhen, Guangdong, China
| | - Qiqian Wu
- Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
- University of Chinese Academy of Sciences, Beijing, China
- Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China
- Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China
| | - Beijia He
- Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
- University of Chinese Academy of Sciences, Beijing, China
- Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China
- Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China
| | - Man Teng
- Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
- University of Chinese Academy of Sciences, Beijing, China
- Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China
- Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China
| | - Shanjun Dai
- Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Jinglei Zhai
- Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
- University of Chinese Academy of Sciences, Beijing, China
- Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China
- Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China
| | - Hao Wu
- Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
- Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China
- Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China
| | - Xiaokui Yang
- Department of Human Reproductive Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Beijing Maternal and Child Health Care Hospital, Beijing, China
| | - Fan Guo
- Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
- University of Chinese Academy of Sciences, Beijing, China
- Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China
- Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China
| | - Hongmei Wang
- Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
- University of Chinese Academy of Sciences, Beijing, China.
- Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China.
- Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China.
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3
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Haig D. Germline ecology: Managed herds, tolerated flocks, and pest control. J Hered 2024; 115:643-659. [PMID: 38447039 DOI: 10.1093/jhered/esae004] [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: 08/13/2023] [Accepted: 03/04/2024] [Indexed: 03/08/2024] Open
Abstract
Multicopy sequences evolve adaptations for increasing their copy number within nuclei. The activities of multicopy sequences under constraints imposed by cellular and organismal selection result in a rich intranuclear ecology in germline cells. Mitochondrial and ribosomal DNA are managed as domestic herds subject to selective breeding by the genes of the single-copy genome. Transposable elements lead a peripatetic existence in which they must continually move to new sites to keep ahead of inactivating mutations at old sites and undergo exponential outbreaks when the production of new copies exceeds the rate of inactivation of old copies. Centromeres become populated by repeats that do little harm. Organisms with late sequestration of germ cells tend to evolve more "junk" in their genomes than organisms with early sequestration of germ cells.
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Affiliation(s)
- David Haig
- Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA, United States
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Wang Q, Tang X, Lv X, Meng X, Geng L, Zhong Z, Ding Y, Li T, Wan Q. Age at menarche and risk of ovarian hyperstimulation syndrome in women undergoing IVF/ICSI cycles: a retrospective cohort study. BMJ Open 2024; 14:e076867. [PMID: 38365296 PMCID: PMC10875511 DOI: 10.1136/bmjopen-2023-076867] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Accepted: 01/08/2024] [Indexed: 02/18/2024] Open
Abstract
OBJECTIVES We aimed to explore the association between age at menarche (AAM) and ovarian hyperstimulation syndrome (OHSS) in fresh in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) cycles. DESIGN A retrospective cohort study. SETTING Data were collected from a large obstetrics and gynaecology hospital in Sichuan, China. PARTICIPANTS This study included 17 419 eligible women aged ≤40 years who underwent the first IVF/ICSI cycles from January 2015 to December 2021. Women were divided into three groups according to their AAM: ≤12 years (n=5781), 13-14 years (n=9469) and ≥15 years (n=2169). RESULTS The means of age at recruitment and AAM were 30.4 years and 13.1 years, respectively. Restricted cubic spline models suggested that early menarche age increased the risk of OHSS. The multivariable logistic analysis showed that women with menarche age ≤12 years were more likely to suffer from OHSS (OR 1.321, 95% CI 1.113 to 1.567) compared with those aged 13-14 years among the whole cohort. This significant relationship remained in women administered with different ovarian stimulation protocols and gonadotrophin doses. When stratified by female age, this correlation was presented only in patients aged ≤30 years (OR 1.362, 95% CI 1.094 to 1.694). And the mediation analysis showed that the relationship between AAM and OHSS was totally mediated by antral follicle counts (AFC). CONCLUSION Menarche age earlier than 12 years may increase the OHSS risk in women aged ≤30 years through the mediation of AFC. More prospective studies are required to verify the results.
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Affiliation(s)
- Qiaofeng Wang
- Sichuan University West China Second University Hospital, Chengdu, Sichuan, China
- Chongqing University Three Gorges Hospital, Wanzhou, Chongqing, China
- School of Public Health, Chongqing Medical University, Chongqing, China
| | - Xiaojun Tang
- School of Public Health, Chongqing Medical University, Chongqing, China
| | - Xingyu Lv
- Department of Gynecology and Obstetrics, Chengdu Jinjiang Hospital for Women's and Children's Health, Chengdu, Sichuan, China
| | - Xiangqian Meng
- Department of Gynecology and Obstetrics, Chengdu Jinjiang Hospital for Women's and Children's Health, Chengdu, Sichuan, China
| | - Lihong Geng
- Department of Gynecology and Obstetrics, Chengdu Jinjiang Hospital for Women's and Children's Health, Chengdu, Sichuan, China
| | - Zhaohui Zhong
- School of Public Health, Chongqing Medical University, Chongqing, China
| | - Yubin Ding
- School of Public Health, Chongqing Medical University, Chongqing, China
- Department of Pharmacology, Academician Workstation, Changsha Medical University, Changsha, China
| | - Tian Li
- Department of Reproductive Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Qi Wan
- Sichuan University West China Second University Hospital, Chengdu, Sichuan, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University West China Second University Hospital, Chengdu, Sichuan, China
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Hassan J, Knuus K, Lahtinen A, Rooda I, Otala M, Tuuri T, Gidlöf S, Edlund E, Menezes J, Malmros J, Byström P, Sundin M, Langenskiöld C, Vogt H, Frisk P, Petersen C, Damdimopoulou P, Jahnukainen K. Reference standards for follicular density in ovarian cortex from birth to sexual maturity. Reprod Biomed Online 2023; 47:103287. [PMID: 37603956 DOI: 10.1016/j.rbmo.2023.103287] [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: 03/17/2023] [Revised: 06/15/2023] [Accepted: 07/11/2023] [Indexed: 08/23/2023]
Abstract
RESEARCH QUESTION Are age-normalized reference values for human ovarian cortical follicular density adequate for tissue quality control in fertility preservation? DESIGN Published quantitative data on the number of follicles in samples without known ovarian pathology were converted into cortical densities to create reference values. Next, a sample cohort of 126 girls (age 1-24 years, mean ± SD 11 ± 6) with cancer, severe haematological disease or Turner syndrome were used to calculate Z-scores for cortical follicular density based on the reference values. RESULTS No difference was observed between Z-scores in samples from untreated patients (0.3 ± 3.5, n = 30) and patients treated with (0.5 ± 2.9, n = 48) and without (0.1 ± 1.3, n = 6) alkylating chemotherapy. Z-scores were not correlated with increasing cumulative exposure to cytostatics. Nevertheless, Z-scores in young treated patients (0-2 years -2.1 ± 3.1, n = 10, P = 0.04) were significantly lower than Z-scores in older treated patients (11-19 years, 2 ± 1.9, n = 15). Samples from patients with Turner syndrome differed significantly from samples from untreated patients (-5.2 ± 5.1, n = 24, P = 0.003), and a Z-score of -1.7 was identified as a cut-off showing good diagnostic value for identification of patients with Turner syndrome with reduced ovarian reserve. When this cut-off was applied to other patients, analysis showed that those with indications for reduced ovarian reserve (n = 15) were significantly younger (5.9 ± 4.2 versus 10.7 ± 5.9 years, P = 0.004) and, when untreated, more often had non-malignant haematologic diseases compared with those with normal ovarian reserve (n = 24, 100% versus 19%, P = 0.009). CONCLUSION Z-scores allow the estimation of genetic- and treatment-related effects on follicular density in cortical tissue from young patients stored for fertility preservation. Understanding the quality of cryopreserved tissue facilitates its use during patient counselling. More research is needed regarding the cytostatic effects found in this study.
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Affiliation(s)
- Jasmin Hassan
- Department of Clinical Science, Intervention and Technology, Division of Obstetrics and Gynaecology, Karolinska Institutet, Stockholm, Sweden; Department of Gynaecology and Reproductive Medicine, Karolinska University Hospital, Stockholm, Sweden.
| | - Katri Knuus
- Department of Obstetrics and Gynaecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
| | - Atte Lahtinen
- Applied Tumour Genomics Research Programme, Faculty of Medicine, University of Helsinki, Finland; Department of Medical and Clinical Genetics, Medicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Ilmatar Rooda
- Department of Clinical Science, Intervention and Technology, Division of Obstetrics and Gynaecology, Karolinska Institutet, Stockholm, Sweden; Department of Gynaecology and Reproductive Medicine, Karolinska University Hospital, Stockholm, Sweden
| | - Marjut Otala
- University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Timo Tuuri
- Department of Obstetrics and Gynaecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
| | - Sebastian Gidlöf
- Department of Clinical Science, Intervention and Technology, Division of Obstetrics and Gynaecology, Karolinska Institutet, Stockholm, Sweden; Department of Gynaecology and Reproductive Medicine, Karolinska University Hospital, Stockholm, Sweden; Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden
| | - Erik Edlund
- Department of Gynaecology and Reproductive Medicine, Karolinska University Hospital, Stockholm, Sweden
| | - Judith Menezes
- Department of Gynaecology and Reproductive Medicine, Karolinska University Hospital, Stockholm, Sweden
| | - Johan Malmros
- Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden; Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden
| | - Petra Byström
- Department of Clinical Science, Intervention and Technology, Division of Paediatrics, Karolinska Institutet, Stockholm, Sweden; Section of Paediatric Haematology, Immunology and HCT, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden
| | - Mikael Sundin
- Department of Clinical Science, Intervention and Technology, Division of Paediatrics, Karolinska Institutet, Stockholm, Sweden; Section of Paediatric Haematology, Immunology and HCT, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden
| | - Cecilia Langenskiöld
- Department of Paediatric Oncology, Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Hartmut Vogt
- Crown Princess Victoria's Child and Youth Hospital, Linköping, Sweden; Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health, Linköping University, Linköping, Sweden
| | - Per Frisk
- Department of Women's and Children's Health, Uppsala University Children's Hospital, Uppsala, Sweden
| | - Cecilia Petersen
- NORDFERTIL Research Lab Stockholm, Department of Women's and Children's Health, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden; Department of Paediatric Oncology, Karolinska University Hospital, Stockholm, Sweden
| | - Pauliina Damdimopoulou
- Department of Clinical Science, Intervention and Technology, Division of Obstetrics and Gynaecology, Karolinska Institutet, Stockholm, Sweden; Department of Gynaecology and Reproductive Medicine, Karolinska University Hospital, Stockholm, Sweden
| | - Kirsi Jahnukainen
- NORDFERTIL Research Lab Stockholm, Department of Women's and Children's Health, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden; Children's Hospital, Paediatric Research Centre, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
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Davis SR, Pinkerton J, Santoro N, Simoncini T. Menopause-Biology, consequences, supportive care, and therapeutic options. Cell 2023; 186:4038-4058. [PMID: 37678251 DOI: 10.1016/j.cell.2023.08.016] [Citation(s) in RCA: 40] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2023] [Revised: 07/06/2023] [Accepted: 08/15/2023] [Indexed: 09/09/2023]
Abstract
Menopause is the cessation of ovarian function, with loss of reproductive hormone production and irreversible loss of fertility. It is a natural part of reproductive aging. The physiology of the menopause is complex and incompletely understood. Globally, menopause occurs around the age of 49 years, with geographic and ethnic variation. The hormonal changes of the menopause transition may result in both symptoms and long-term systemic effects, predominantly adverse effects on cardiometabolic and musculoskeletal health. The most effective treatment for bothersome menopausal symptoms is evidence-based, menopausal hormone therapy (MHT), which reduces bone loss and may have cardiometabolic benefits. Evidence-based non-hormonal interventions are also available for symptom relief. Treatment should be individualized with shared decision-making. Most MHT regimens are not regulator approved for perimenopausal women. Studies that include perimenopausal women are needed to determine the efficacy and safety of treatment options. Further research is crucial to improve menopause care, along with research to guide policy and clinical practice.
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Affiliation(s)
- Susan R Davis
- Women's Health Research Program, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC 3004, Australia; Department of Endocrinology and Diabetes, Alfred Health, Commercial Rd., Melbourne, VIC 3004, Australia.
| | - JoAnn Pinkerton
- Department of Obstetrics and Gynecology, Division of Midlife Health, The University of Virginia Health System, Charlottesville, VA, USA
| | | | - Tommaso Simoncini
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
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7
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Mohammad H, S JC, Haripriya G, Maskeri D, K P, Priya P. Model of Anti-Mullerian Hormone Over Age to Predict Menopause in Polycystic Ovary Syndrome and Eumenorrheic Women: A Study on Southern Indian Population. Cureus 2023; 15:e43419. [PMID: 37706124 PMCID: PMC10496936 DOI: 10.7759/cureus.43419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/13/2023] [Indexed: 09/15/2023] Open
Abstract
Introduction Anti-mullerian hormone (AMH) is a member of the transforming growth factor β family and is a marker of ovarian reserve; it is produced by the granulosa cells of developing preantral and early antral ovarian follicles. AMH concentration decreases with increasing age. Its concentration is increased relatively in those with polycystic ovary syndrome (PCOS) than eumenorrheic women. Objectives In this research, using a model of AMH over age, the age of menopause is predicted in PCOS and eumenorrheic women. Study design The study subjects were classified into two groups. Group 1 included PCOS subjects. Group 2 included eumenorrheic women. General profiles such as age, BMI, and hormonal parameters such as AMH were measured. Based on the exponential functional dependence of AMH over age, a model was proposed, and the value of exponential constants such as log βo and β1 were calculated using least square approximation. An arbitrary value of 0.2 ng/mL for AMH was taken as a cut-off value to predict the age of menopause in both groups. Outcome measures We predicted the age of menopause using a model of AMH over age by the least square approximation technique. Results The age prediction for menopause using the least squares model of AMH over age showed that in group 1 patients with PCOS, menopause is projected to occur at around 54.7 years, while in group 2 with eumenorrheic women, it is expected to happen at approximately 45.2 years. Conclusion Data demonstrates that serum AMH concentration declines over time, and predicting the age of menopause reflects sustained reproductive life span in PCOS subjects.
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Affiliation(s)
| | - Janaki C S
- Anatomy, Bharath Medical College and Hospital, Chennai, IND
| | | | | | - Prabhu K
- Anatomy, Sree Balaji Medical College and Hospital, Chennai, IND
| | - Padma Priya
- Microbiology, Bharath Medical College, Chennai, IND
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Stovezky YR, Romanski PA, Bortoletto P, Spandorfer SD. Antimüllerian hormone is not associated with embryo ploidy in patients with and without infertility undergoing in vitro fertilization with preimplantation genetic testing. Fertil Steril 2023; 119:444-453. [PMID: 36423663 DOI: 10.1016/j.fertnstert.2022.11.018] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Revised: 11/17/2022] [Accepted: 11/18/2022] [Indexed: 11/23/2022]
Abstract
OBJECTIVE To assess the association between antimüllerian hormone (AMH) and embryo ploidy rates in 2 cohorts of patients undergoing in vitro fertilization (IVF) with trophectoderm biopsy for preimplantation genetic testing for aneuploidy (PGT-A): the general population of women pursuing IVF with PGT-A (Infertile cohort) and women pursuing IVF with preimplantation genetic testing for monogenic disorders (PGT-M) owing to the risk of hereditary monogenic diseases (Non-infertile cohort). DESIGN Retrospective cohort study. SETTING Academic center. PATIENT(S) Patients undergoing their first cycle of IVF with trophectoderm biopsy and PGT-A or PGT-A and PGT-M in our center between March 2012 and June 2020. Patients of advanced maternal age according to the Bologna criteria (age ≥40 years) and patients who underwent fresh embryo transfers were excluded. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Proportion of euploid, mosaic, and aneuploid embryos per cycle. RESULT(S) "Infertile" (n = 926) and "Non-infertile" (n = 214) patients were stratified on the basis of AMH levels, with low-AMH defined as <1.1 ng/mL in accordance with the Bologna criteria. Age-adjusted regression models showed no relationship between AMH classification and proportion of euploid, mosaic, and aneuploid embryos in the Infertile or Non-infertile cohorts. In the Infertile cohort, no association between AMH classification and embryo ploidy rates was identified in a subgroup analysis of patients aged <35 years, 35-37 years, and 38-39 years. These findings persisted in a sensitivity analysis of infertile patients stratified into AMH (ng/mL) quartile categories. CONCLUSION(S) No association was found between AMH and the proportion of euploid, mosaic, or aneuploid embryos in 2 large cohorts of patients undergoing IVF with PGT-A (Infertile patients) or PGT-A and PGT-M (Non-infertile patients), suggesting that a quantitative depletion of ovarian reserve does not predict the ploidy status of the embryo cohort.
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Affiliation(s)
- Yael R Stovezky
- Weill Medical College of Cornell University, New York, New York.
| | - Phillip A Romanski
- The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical Center, New York, New York
| | - Pietro Bortoletto
- The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical Center, New York, New York
| | - Steven D Spandorfer
- The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical Center, New York, New York
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9
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Kelsey T. Models and Biomarkers for Ovarian Ageing. Subcell Biochem 2023; 103:185-199. [PMID: 37120469 DOI: 10.1007/978-3-031-26576-1_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/01/2023]
Abstract
The human ovarian reserve is defined by the number of non-growing follicles (NGFs) in the ovary, with the age-related decline in NGF population determining age at menopause for healthy women. In this chapter, the concept of ovarian reserve is explored in detail, with a sequence of models described that in principle allow any individual to be compared to the general population. As there is no current technology that can count the NGFs in a living ovary, we move our focus to biomarkers for the ovarian reserve. Using serum analysis and ultrasound it is possible to measure anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), and ovarian volume (OV) and to count numbers of antral follicles (AFC). These are compared, with ovarian volume being the closest to a true biomarker for a wide range of ages and with AMH and AFC being the most popular for post-pubertal and pre-menopausal ages. The study of genetic and subcellular biomarkers for the ovarian reserve has produced less concrete results. Recent advances are described and compared in terms of limitations and potential. The chapter concludes with an overview of the future study indicated by our current knowledge and by current controversy in the field.
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Affiliation(s)
- Tom Kelsey
- School of Computer Science, University of St Andrews, St Andrews, UK.
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10
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Ovarian Reserve Disorders, Can We Prevent Them? A Review. Int J Mol Sci 2022; 23:ijms232315426. [PMID: 36499748 PMCID: PMC9737352 DOI: 10.3390/ijms232315426] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Revised: 11/28/2022] [Accepted: 11/29/2022] [Indexed: 12/12/2022] Open
Abstract
The ovarian reserve is finite and begins declining from its peak at mid-gestation until only residual follicles remain as women approach menopause. Reduced ovarian reserve, or its extreme form, premature ovarian insufficiency, stems from multiple factors, including developmental, genetic, environmental exposures, autoimmune disease, or medical/surgical treatment. In many cases, the cause remains unknown and resulting infertility is not ultimately addressed by assisted reproductive technologies. Deciphering the mechanisms that underlie disorders of ovarian reserve could improve the outcomes for patients struggling with infertility, but these disorders are diverse and can be categorized in multiple ways. In this review, we will explore the topic from a perspective that emphasizes the prevention or mitigation of ovarian damage. The most desirable mode of fertoprotection is primary prevention (intervening before ablative influence occurs), as identifying toxic influences and deciphering the mechanisms by which they exert their effect can reduce or eliminate exposure and damage. Secondary prevention in the form of screening is not recommended broadly. Nevertheless, in some instances where a known genetic background exists in discrete families, screening is advised. As part of prenatal care, screening panels include some genetic diseases that can lead to infertility or subfertility. In these patients, early diagnosis could enable fertility preservation or changes in family-building plans. Finally, Tertiary Prevention (managing disease post-diagnosis) is critical. Reduced ovarian reserve has a major influence on physiology beyond fertility, including delayed/absent puberty or premature menopause. In these instances, proper diagnosis and medical therapy can reduce adverse effects. Here, we elaborate on these modes of prevention as well as proposed mechanisms that underlie ovarian reserve disorders.
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de Guzman GS, Manalo EM. Assessment of the knowledge, attitudes, and perceptions of Filipino obstetrics and gynecology residents on fertility preservation: A cross-sectional study. Ann Med Surg (Lond) 2022; 84:104934. [DOI: 10.1016/j.amsu.2022.104934] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2022] [Revised: 10/26/2022] [Accepted: 11/12/2022] [Indexed: 11/19/2022] Open
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12
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Labrosse J, Grynberg M. Fertility of tomorrow: are there any restrictions left ? ANNALES D'ENDOCRINOLOGIE 2022; 83:207-209. [DOI: 10.1016/j.ando.2022.04.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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13
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Bühler N. The making of 'old eggs': the science of reproductive ageing between fertility and anti-ageing technologies. REPRODUCTIVE BIOMEDICINE & SOCIETY ONLINE 2022; 14:169-181. [PMID: 35024473 PMCID: PMC8732751 DOI: 10.1016/j.rbms.2021.07.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Revised: 05/09/2021] [Accepted: 07/29/2021] [Indexed: 06/14/2023]
Abstract
This article proposes going back in the history of reproductive medicine to shed light on the role of assisted reproductive technology (ART) in the making of 'old eggs'. Focusing on two key technologies - egg donation and cytoplasmic transfer - both of which contributed significantly to the production of scientific knowledge about reproductive ageing, the article suggests that ART can be analysed as 'in-vivo models' playing a pivotal role in the shift from age as a demographic variable to ageing understood in biological terms. It will shed light on the role of ART in locating age in the eggs and producing a cellular understanding of fertility decline. It argues that ART not only offers new means of reconfiguring the biological clock by extending fertility, but also reconfigures the biology of reproductive ageing itself. This becomes both the target and the means for new technological interventions, imaginaries and norms, anchored in women's bodies and a more plastic biology, and thereby illuminates hitherto underexplored aspects of the encounter between the science and technology of reproduction and anti-ageing.
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14
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Intrinsic innervation of the ovary and its variations in the rat senescence process. J Mol Histol 2022; 53:347-356. [PMID: 35217964 PMCID: PMC9117379 DOI: 10.1007/s10735-022-10069-7] [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: 06/26/2021] [Accepted: 02/20/2022] [Indexed: 11/03/2022]
Abstract
Ovarian functions decrease with perimenopause. The ovary has extrinsic innervation, but the neural influence on ovarian functions and dysfunction is not well-studied. The present study aimed to biochemically and morphometrically characterize the intrinsic neurons in ovaries from young adult, middle-aged, and senescent Long Evans CII-ZV rats (3, 12, and 15 months old, respectively). Ovaries were extracted from four rats of each age group (n = 12 total), cryopreserved, and processed for immunofluorescence studies with the primary NeuN/β-tubulin and NeuN/tyrosine hydroxylase (TH) antibodies. The soma area and number of intrinsic neurons in the ovarian stroma, surrounding follicles, corpus luteum, or cyst were evaluated. The intrinsic neurons were grouped in cluster-like shapes in ovarian structures. In senescent rats, the intrinsic neurons were mainly localized in the ovarian stroma and around the cysts. The number of neurons was lower in senescent rats than in young adult rats (p < 0.05), but the soma size was larger than in young adult rats. Immunoreactivity to TH indicated the presence of noradrenergic neurons in the ovary with the same characteristics as NeuN/β-tubulin, which indicates that they are part of the same neuronal group. Taken together, the findings indicate that the intrinsic neurons may be related to the loss of ovarian functions associated with aging.
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Essentiality of Trace Elements in Pregnancy, Fertility, and Gynecologic Cancers-A State-of-the-Art Review. Nutrients 2021; 14:nu14010185. [PMID: 35011060 PMCID: PMC8746721 DOI: 10.3390/nu14010185] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 12/23/2021] [Accepted: 12/28/2021] [Indexed: 12/18/2022] Open
Abstract
Gynecological neoplasms pose a serious threat to women's health. It is estimated that in 2020, there were nearly 1.3 million new cases worldwide, from which almost 50% ended in death. The most commonly diagnosed are cervical and endometrial cancers; when it comes to infertility, it affects ~48.5 million couples worldwide and the number is continually rising. Ageing of the population, environmental factors such as dietary habits, environmental pollutants and increasing prevalence of risk factors may affect the reproductive potential in women. Therefore, in order to identify potential risk factors for these issues, attention has been drawn to trace elements. Trace mineral imbalances can be caused by a variety of causes, starting with hereditary diseases, finishing with an incorrect diet or exposure to polluted air or water. In this review, we aimed to summarize the current knowledge regarding trace elements imbalances in the case of gynecologic cancers as well as female fertility and during pregnancy.
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The Use of Androgen Priming in Women with Reduced Ovarian Reserve Undergoing Assisted Reproductive Technology. Semin Reprod Med 2021; 39:207-219. [PMID: 34500477 DOI: 10.1055/s-0041-1735646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Androgen priming with either dehydroepiandrosterone (DHEA) or testosterone has been suggested as an adjunct to improve in vitro fertilization (IVF) outcomes in women with diminished ovarian reserve (DOR). Numerous studies have investigated the effects of both DHEA and testosterone on IVF outcome. The results were inconsistent, and the quality of most studies is substandard. Meta-analyses have consistently reported that DHEA does appear to significantly improve IVF outcome in women with predicted or proven poor ovarian response (POR), but these have included some normal responders and/or nonrandomized studies. Our meta-analyses including randomized controlled trials (RCTs) incorporating only women with DOR or POR suggest that DHEA confers no benefit. While meta-analyses of RCTs on the use of testosterone in women with DOR or POR showed an improved IVF outcome, most studies included are of low quality with high risk of bias. When analysis of data from studies of only low-risk bias was performed, such a benefit with testosterone was not observed. Although recruitment may well be a challenge, a large, well-designed RCT is, however, still warranted to investigate whether or not androgen priming with either DHEA or testosterone should be recommended as an adjuvant treatment for women with DOR or POR undergoing IVF.
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17
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Tsai HW, Liao PF, Li CJ, Lin LT, Wen ZH, Tsui KH. High serum anti-Müllerian hormone concentrations have a negative impact on fertilization and embryo development rates. Reprod Biomed Online 2021; 44:171-176. [PMID: 34801403 DOI: 10.1016/j.rbmo.2021.08.016] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 07/06/2021] [Accepted: 08/17/2021] [Indexed: 10/20/2022]
Abstract
RESEARCH QUESTION What is the impact of high serum anti-Müllerian hormone (AMH) concentrations on fertilization and embryo development among infertile women undergoing treatment with assisted reproductive technology (ART)? DESIGN Retrospective study of 1036 infertile women undergoing ART; women were divided into three groups according to serum AMH concentrations: AMH <1.1 ng/ml, 1.1-5.0 ng/ml and >5.0 ng/ml. The fertilization and embryo development rates of patients with different AMH concentrations and after stratification according to age were compared. RESULTS Women with high AMH concentrations were younger and had higher testosterone concentrations (0.4 ± 0.13 versus 0.3 ± 0.12 versus 0.3 ± 0.08 µg/dl, P < 0.001) than women with low AMH concentrations. However, analysis of the embryo development rate showed negative outcomes for women with high AMH concentrations, including a poor fertilization rate (76.3 ± 17.36 versus 82.1 ± 19.15 versus 82.4 ± 25.38, P = 0.003), and poor day 3 embryo development rate (55.6 ± 23.88 versus 62.6 ± 26.52 versus 62.8 ± 32.65, P = 0.014). Multivariate linear regression analysis showed significantly negative correlations of the AMH concentrations with the fertilization rate (P < 0.001) and day 3 embryo development rate (P = 0.006). Subgroup analysis showed that age 30 years or younger had a significant negative correlation with AMH and the embryo development rate, including the fertilization rate (P < 0.001) and day 3 embryo development rate (P = 0.037). CONCLUSION These results suggest that high serum AMH concentrations, contributing to a hyperandrogenic environment and leading to decreased oocyte developmental competence, may have a negative impact on fertilization and the early stage of embryo development in women undergoing treatment with ART.
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Affiliation(s)
- Hsiao-Wen Tsai
- Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; School of Medicine, Department of Obstetrics and Gynecology, National Yang-Ming University, Taipei, Taiwan; Institute of BioPharmaceutical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | - Pei-Fen Liao
- Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Chia-Jung Li
- Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Institute of BioPharmaceutical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | - Li-Te Lin
- Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Institute of BioPharmaceutical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | - Zhi-Hong Wen
- Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | - Kuan-Hao Tsui
- Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Institute of BioPharmaceutical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
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18
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Llarena N, Hine C. Reproductive Longevity and Aging: Geroscience Approaches to Maintain Long-Term Ovarian Fitness. J Gerontol A Biol Sci Med Sci 2021; 76:1551-1560. [PMID: 32808646 PMCID: PMC8361335 DOI: 10.1093/gerona/glaa204] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Indexed: 11/12/2022] Open
Abstract
Increases in delayed childbearing worldwide have elicited the need for a better understanding of the biological underpinnings and implications of age-related infertility. In women 35 years and older the incidences of infertility, aneuploidy, and birth defects dramatically increase. These outcomes are a result of age-related declines in both ovarian reserve and oocyte quality. In addition to waning reproductive function, the decline in estrogen secretion at menopause contributes to multisystem aging and the initiation of frailty. Both reproductive and hormonal ovarian function are limited by the primordial follicle pool, which is established in utero and declines irreversibly until menopause. Because ovarian function is dependent on the primordial follicle pool, an understanding of the mechanisms that regulate follicular growth and maintenance of the primordial follicle pool is critical for the development of interventions to prolong the reproductive life span. Multiple pathways related to aging and nutrient-sensing converge in the mammalian ovary to regulate quiescence or activation of primordial follicles. The PI3K/PTEN/AKT/FOXO3 and associated TSC/mTOR pathways are central to the regulation of the primordial follicle pool; however, aging-associated systems such as the insulin-like growth factor-1/growth hormone pathway, and transsulfuration/hydrogen sulfide pathways may also play a role. Additionally, sirtuins aid in maintaining developmental metabolic competence and chromosomal integrity of the oocyte. Here we review the pathways that regulate ovarian reserve and oocyte quality, and discuss geroscience interventions that leverage our understanding of these pathways to promote reproductive longevity.
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Affiliation(s)
- Natalia Llarena
- Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic Lerner Research Institute, Ohio
- Reproductive Endocrinology and Infertility, Cleveland Clinic Women’s Health Institute, Ohio
| | - Christopher Hine
- Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic Lerner Research Institute, Ohio
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19
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Grynberg M, Labrosse J, Bennani Smires B, Sifer C, Peigne M, Sonigo C. Could hormonal and follicular rearrangements explain timely menopause in unilaterally oophorectomized women? Hum Reprod 2021; 36:1941-1947. [PMID: 34037751 DOI: 10.1093/humrep/deab132] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Revised: 04/26/2021] [Indexed: 11/13/2022] Open
Abstract
STUDY QUESTION Does unilateral oophorectomy modify the relationship between serum anti-Müllerian hormone (AMH) levels and antral follicle count (AFC)? SUMMARY ANSWER No altered 'per-ovary' and 'per-follicle' AMH production and antral follicle distribution was evident in unilaterally oophorectomized women compared to matched controls. WHAT IS KNOWN ALREADY The age of menopause onset is relatively unchanged in patients having undergone unilateral oophorectomy. Mechanisms that occur to preserve and maintain ovarian function in this context remain to be elucidated. STUDY DESIGN, SIZE, DURATION Forty-one infertile women, with no polycystic ovary syndrome (PCOS) and no endometriosis, aged 19-42 years old, having undergone unilateral oophorectomy (One Ovary group; average time since surgery: 23.8 ± 2.2 months) were retrospectively age-matched (±1 year) with 205 infertile women having two intact ovaries and similar clinical features (Control group). PARTICIPANTS/MATERIALS, SETTING, METHODS Serum AMH levels, 3-4 mm AFC, 5-12 mm AFC, and total AFC (3-12 mm) were assessed on cycle Day 3 in both groups. Hormonal and ultrasonographic measurements obtained from patients in the Control group (i.e. having two ovaries) were divided by two to be compared with measurements obtained from patients of the One Ovary group (i.e. having one single remaining ovary). To estimate per-follicle AMH production, we calculated the ratio between serum AMH levels over 3-4 mm AFC, 5-12 mm AFC, and total AFC (3-12 mm), and the strength of the correlation between serum AMH levels and total AFC. The main outcome measure was to assess Day 3 AMH/Day 3 AFC ratio and hormonal-follicular correlation. MAIN RESULTS AND THE ROLE OF CHANCE As expected, before correction, mean serum AMH levels (1.46 ± 0.2 vs 2.77 ± 0.1 ng/ml, P < 0.001) and total AFC (7.3 ± 0.6 vs 15.1 ± 0.4 follicles, P < 0.0001) were lower in the One Ovary group compared to the Control group, respectively. Yet, after correction, per-ovary AMH levels (1.46 ± 0.2 vs 1.39 ± 0.1 ng/ml) and total AFC (7.3 ± 0.6 vs 7.5 ± 0.2 follicles) values were comparable between the two groups. Consistently, per-follicle AMH levels (3-4 mm, 5-12 mm, and total) were not significantly different between the two groups (0.39 ± 0.05 vs 0.37 ± 0.02 ng/ml/follicle; 0.69 ± 0.12 vs 0.59 ± 0.05 ng/ml/follicle, and 0.23 ± 0.03 vs 0.19 ± 0.01 ng/ml/follicle; respectively). In addition, the prevalence of 3-4 mm follicles was comparable between the two groups (66.7% for One Ovary group vs 58.8% for Control group, respectively). Finally, the correlation between serum AMH levels and total AFC was similar for patients in the One Ovary group (r = 0.70; P < 0.0001) compared to those in the Control group (r = 0.68; P < 0.0001). LIMITATIONS/REASONS FOR CAUTION The retrospective character of the analysis might lead to potential bias. WIDER IMPLICATIONS OF THE FINDINGS The present investigation did not provide evidence of altered 'per-ovary' and 'per-follicle' AMH production and antral follicle distribution in unilaterally oophorectomized women compared to matched controls. Further studies are warranted to support the hypothesis that follicle-sparing mechanisms are clearly at stake in remaining ovaries after unilateral oophorectomy to explain their long-lasting function and timely menopausal onset. STUDY FUNDING/COMPETING INTEREST(S) The authors have no funding or competing interests to declare. TRIAL REGISTRATION NUMBER N/A.
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Affiliation(s)
- M Grynberg
- AP-HP, Department of Reproductive Medicine & Fertility Preservation, Hôpital Antoine Béclère, Clamart, France.,AP-HP, Department of Reproductive Medicine & Fertility Preservation, Hôpital Jean Verdier, Bondy, France.,University Paris-Sud, Clamart, France
| | - J Labrosse
- AP-HP, Department of Reproductive Medicine & Fertility Preservation, Hôpital Jean Verdier, Bondy, France
| | - B Bennani Smires
- Department of Cytogenetic and Reproductive Biology, Hôpital Jean Verdier, Bondy, France
| | - C Sifer
- Department of Cytogenetic and Reproductive Biology, Hôpital Jean Verdier, Bondy, France
| | - M Peigne
- AP-HP, Department of Reproductive Medicine & Fertility Preservation, Hôpital Jean Verdier, Bondy, France
| | - C Sonigo
- AP-HP, Department of Reproductive Medicine & Fertility Preservation, Hôpital Antoine Béclère, Clamart, France.,University Paris-Sud, Clamart, France
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Ovarian follicular waves during the menstrual cycle: physiologic insights into novel approaches for ovarian stimulation. Fertil Steril 2021; 114:443-457. [PMID: 32912608 DOI: 10.1016/j.fertnstert.2020.07.008] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Revised: 07/07/2020] [Accepted: 07/07/2020] [Indexed: 12/11/2022]
Abstract
Elucidation of multiple waves of antral ovarian follicular development during the menstrual cycle has challenged traditional concepts of female reproductive physiology and foundations of assisted reproductive therapies. Approximately two-thirds of women develop two follicle waves throughout an interovulatory interval and the remainder exhibit three waves of follicle development. Major and minor waves of follicle development have been observed. Major waves are those in which a dominant follicle develops; dominant follicles either regress or ovulate. In minor waves, physiologic selection of a dominant follicle is not manifest. Knowledge of waves of antral follicular development has led to the global adoption of novel ovarian stimulation strategies in which stimulation can be initiated at various times throughout the cycle. Random-start and luteal-phase ovarian stimulation regimens have had important clinical applications for women requiring urgent oocyte or embryo cryopreservation for fertility preservation prior to chemotherapy. Ovarian stimulation twice in the same cycle, referred to as double stimulation, may be used to optimize clinical outcomes in women with a poor ovarian response to stimulation as well as in those requiring fertility preservation before chemotherapy.
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21
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Girsh E, Harlev A, Grin L. IN-VITRO ACTIVATION OF OVARIAN FOLLICULAR RESIDUAL RESERVE. REPRODUCTIVE MEDICINE 2020. [DOI: 10.37800/rm2020-1-34] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
The newly developed in-vitro activation (IVA) method provides a novel fertility treatment for patients with premature ovarian insufficiency. The IVA method pretends to promote growth of residual ovarian follicles at early stages of their development. Based on preliminary data, poor ovarian response (POR) patients with decreased ovarian reserve (DOR) who have multiple secondary follicles, IVA is a promising technique to promote growth of secondary follicle as well.
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22
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Gebel J, Tuppi M, Sänger N, Schumacher B, Dötsch V. DNA Damaged Induced Cell Death in Oocytes. Molecules 2020; 25:molecules25235714. [PMID: 33287328 PMCID: PMC7730327 DOI: 10.3390/molecules25235714] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Revised: 11/25/2020] [Accepted: 11/30/2020] [Indexed: 12/19/2022] Open
Abstract
The production of haploid gametes through meiosis is central to the principle of sexual reproduction. The genetic diversity is further enhanced by exchange of genetic material between homologous chromosomes by the crossover mechanism. This mechanism not only requires correct pairing of homologous chromosomes but also efficient repair of the induced DNA double-strand breaks. Oocytes have evolved a unique quality control system that eliminates cells if chromosomes do not correctly align or if DNA repair is not possible. Central to this monitoring system that is conserved from nematodes and fruit fly to humans is the p53 protein family, and in vertebrates in particular p63. In mammals, oocytes are stored for a long time in the prophase of meiosis I which, in humans, can last more than 50 years. During the entire time of this arrest phase, the DNA damage checkpoint remains active. The treatment of female cancer patients with DNA damaging irradiation or chemotherapeutics activates this checkpoint and results in elimination of the oocyte pool causing premature menopause and infertility. Here, we review the molecular mechanisms of this quality control system and discuss potential therapeutic intervention for the preservation of the oocyte pool during chemotherapy.
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Affiliation(s)
- Jakob Gebel
- Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University, 60438 Frankfurt, Germany; (J.G.); (M.T.)
| | - Marcel Tuppi
- Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University, 60438 Frankfurt, Germany; (J.G.); (M.T.)
| | - Nicole Sänger
- Department for Gynecological Endocrinology and Reproductive Medicine, University Hospital of Bonn, Venusberg-Campus 1, 53217 Bonn, Germany;
| | - Björn Schumacher
- Institute for Genome Stability in Aging and Disease, Cologne Cluster of Excellence in Cellular Stress Responses in Aging-Associated Diseases (CECAD) Research Center, and Center for Molecular Medicine, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany;
| | - Volker Dötsch
- Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University, 60438 Frankfurt, Germany; (J.G.); (M.T.)
- Correspondence: ; Tel.: +49-69-798-29631
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Sarma UC, Winship AL, Hutt KJ. Comparison of methods for quantifying primordial follicles in the mouse ovary. J Ovarian Res 2020; 13:121. [PMID: 33054849 PMCID: PMC7560236 DOI: 10.1186/s13048-020-00724-6] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Accepted: 10/01/2020] [Indexed: 12/29/2022] Open
Abstract
Background Accurate evaluation of primordial follicle numbers in mouse ovaries is an essential endpoint for studies investigating how endogenous and exogenous insults, such as maternal aging and chemotherapy, impact the ovarian reserve. In this study, we compared and contrasted two methods for counting healthy primordial follicles following exposure to cyclophosphamide (75 mg/kg), a well-established model of follicle depletion. The first was the fractionator/optical dissector technique, an unbiased, assumption-free stereological approach for quantification of primordial follicle numbers. While accurate, highly reproducible and sensitive, this method relies on specialist microscopy equipment and software, requires specific fixation, embedding and sectioning parameters to be followed, and is largely a manual process that is tedious and time-consuming. The second method was the more widely used serial section and direct count approach, which is relatively quick and easy. We also compared the impacts of different fixatives, embedding material and section thickness on the overall results for each method. Results Direct counts resulted in primordial follicle numbers that were significantly lower than those obtained by stereology, irrespective of fixation and embedding material. When applied to formalin fixed tissue, the direct count method did not detect differences in follicle numbers between saline and cyclophosphamide treated groups to the same degree of sensitivity as the gold standard stereology method (referred to as the Reference standard). However, when Bouin’s fixative was used, direct counts and stereology were comparable in their ability to detect follicle depletion caused by cyclophosphamide. Conclusions This work indicates that the direct count method can produce similar results to stereology when Bouin’s fixative is used instead of formalin. The findings presented here will assist others to select the most appropriate experimental approach for accurate follicle enumeration, depending on whether the primary objective of the study is to determine absolute primordial follicle numbers or relative differences between groups.
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Affiliation(s)
- Urooza C Sarma
- Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Level 3, Building 76, 19 Innovation walk, Clayton, VIC, 3800, Australia.,Department of Anatomy and Developmental Biology, Monash University, Level 3, Building 76, 19 Innovation walk, Clayton, VIC, 3800, Australia
| | - Amy L Winship
- Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Level 3, Building 76, 19 Innovation walk, Clayton, VIC, 3800, Australia.,Department of Anatomy and Developmental Biology, Monash University, Level 3, Building 76, 19 Innovation walk, Clayton, VIC, 3800, Australia
| | - Karla J Hutt
- Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Level 3, Building 76, 19 Innovation walk, Clayton, VIC, 3800, Australia. .,Department of Anatomy and Developmental Biology, Monash University, Level 3, Building 76, 19 Innovation walk, Clayton, VIC, 3800, Australia.
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Ortega MT, Carlson L, McGrath JA, Kangarloo T, Adams JM, Sluss PM, Lambert-Messerlian G, Shaw ND. AMH is Higher Across the Menstrual Cycle in Early Postmenarchal Girls than in Ovulatory Women. J Clin Endocrinol Metab 2020; 105:dgaa059. [PMID: 32016427 PMCID: PMC7082083 DOI: 10.1210/clinem/dgaa059] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2019] [Accepted: 02/03/2020] [Indexed: 01/02/2023]
Abstract
CONTEXT Adolescents have more small, growing follicles and larger ovaries than normal women and are prone to anovulatory cycles (ANOV). It is unknown if a higher antral follicle count (AFC) per se contributes to ANOV in early postmenarchal girls. OBJECTIVE To determine the relationship between AMH (an AFC biomarker), other reproductive hormones, and ANOV in postmenarchal girls and to compare AMH in girls and regularly cycling adults. METHODS A total of 23 girls (1.7 ± 0.2 years postmenarche) and 32 historic adult controls (≤34 years) underwent serial hormone measurements during 1 to 2 menstrual cycles. Girls also had pelvic ultrasounds. AMH was measured 5 times/subject using the Ansh ultrasensitive ELISA. RESULTS Girls had higher AMH than women (5.2 ± 0.3 vs. 3.3 ± 0.4 ng/mL; P < 0.01) and girls with more ovulatory (OV) cycles tended to have lower AMH than those with ANOV (2 OV 4.5 ± 0.2, 1 OV 5.7 ± 1.1, 0 OV 6.8 ± 1.1 ng/mL; P = 0.1). In girls, AMH correlated with natural-log (ln) transformed LH (r = 0.5, P = 0.01), ln_androstenedione (r = 0.6, P = 0.003), ln_testosterone (r = 0.5, P = 0.02), and ovarian volume (r = 0.7, P < 0.01) but not with FSH, estradiol, P4, or body mass index. In women, AMH correlated with estradiol and P4 (both r = -0.4, P ≤ 0.03) but not with ln_LH or body mass index. CONCLUSIONS In postmenarchal girls, AMH is higher than in ovulatory women and is associated with LH, androgens, and a propensity for anovulatory cycles. The cause of the transient increase in AMH and AFC during late puberty and the steps underlying the transition to a mature ovary deserve further study.
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Affiliation(s)
- Madison T Ortega
- Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA
| | - Lauren Carlson
- Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA
| | | | - Tairmae Kangarloo
- Reproductive Endocrine Unit, Massachusetts General Hospital, Boston, MA, USA
| | - Judith Mary Adams
- Reproductive Endocrine Unit, Massachusetts General Hospital, Boston, MA, USA
| | - Patrick M Sluss
- Department of Pathology, Massachusetts General Hospital, Boston, MA, USA
| | - Geralyn Lambert-Messerlian
- Department of Pathology, Women and Infants Hospital and the Alpert Medical School of Brown University, RI, USA
| | - Natalie D Shaw
- Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA
- Reproductive Endocrine Unit, Massachusetts General Hospital, Boston, MA, USA
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Baerwald A, Vanden Brink H, Lee C, Hunter C, Turner K, Chizen D. Endometrial development during the transition to menopause: preliminary associations with follicular dynamics. Climacteric 2020; 23:288-297. [PMID: 32077310 DOI: 10.1080/13697137.2020.1721455] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Objective: This study aimed to test the hypothesis that the development of functional luteal phase dominant follicles (LPDFs) is associated with increased endometrial growth as women transition to menopause.Methods: Endometrial thickness (ET), follicle development, and hormone production were characterized in ovulatory women of mid-reproductive age (MRA; 18-35 years, n = 10) and advanced reproductive age (ARA; 45-55 years, n = 16). Transvaginal ultrasonography was conducted every 1-3 days during one interovulatory interval to quantify ET and the diameters of follicles ≥2 mm. Blood was drawn at each visit to measure progesterone, estradiol, inhibin A, follicle stimulating hormone, and luteinizing hormone.Results: In the MRA group, ET was lower (8.87 vs. 10.1 mm) in women with typical versus no LPDFs, in association with greater luteal phase estradiol (91.1 vs. 48.8 ng/l). In the ARA group, luteal phase endometrial growth was greater (12.0 vs. 10.4 mm) in women with typical versus no LPDFs, in association with lower progesterone (10.7 vs. 13.8 μg/l; LPDF effect p < 0.1) and inhibin A (35.6 vs. 51.17 ng/l; p < 0.10).Conclusions: Preliminary findings suggest that ET may be increased in women who develop LPDFs, in association with reduced luteal phase progesterone and inhibin A, during the transition to menopause. Continued research is required to confirm these findings.
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Affiliation(s)
- A Baerwald
- Department of Academic Family Medicine, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada
| | - H Vanden Brink
- Department of Obstetrics, Gynecology and Reproductive Sciences, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada
| | - C Lee
- Department of Mathematics and Statistics, University of Calgary, Calgary, AB, Canada
| | - C Hunter
- Department of Obstetrics, Gynecology and Reproductive Sciences, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada
| | - K Turner
- Department of Obstetrics, Gynecology and Reproductive Sciences, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada
| | - D Chizen
- Department of Obstetrics, Gynecology and Reproductive Sciences, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada
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Premature ovarian insufficiency (POI) and autoimmunity-an update appraisal. J Assist Reprod Genet 2019; 36:2207-2215. [PMID: 31440958 DOI: 10.1007/s10815-019-01572-0] [Citation(s) in RCA: 89] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2019] [Accepted: 08/16/2019] [Indexed: 12/11/2022] Open
Abstract
PURPOSE Primary ovarian insufficiency (POI) represents ovarian dysfunction related to very early aging of the ovaries. While the cause of POI in a majority of clinical cases remains undefined, autoimmunity is responsible for approximately 4-30% of POI cases. In the present paper, we aim to provide a critical appraisal and update review on the role of autoimmunity in POI patients. METHODS A literature review was conducted for all relevant articles reporting on POI and autoimmunity. PubMed/MEDLINE and the Cochrane library were searched for the best available evidence on this topic. RESULTS Patients with POI and coexisting autoimmunity are indistinguishable from those with negative autoimmune screen with regard to age of onset, prevalence of primary amenorrhea, or their endocrine profiles. A specific noninvasive reliable diagnostic test for the diagnosis of an autoimmune etiology is lacking; therefore, patients should be screened for the most common autoantibodies, i.e., steroid cell antibodies, anti-ovarian antibodies, and anti-thyroid antibodies. Moreover, treatment strategies to POI infertility are lacking and controversial. CONCLUSIONS Nowadays, guidelines for the treatment of autoimmune POI are not available. Moreover, since diagnostic and treatment strategies to POI infertility are still lacking and controversial, further large clinical studies are needed to investigate the true impact of autoimmunity on POI and to identify the selected groups of patients who are most likely to benefit from immunossuprresive treatment.
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Shtaut MI, Kurilo LF. Composition of Somatic and Germ Cells of Human Gonads in Prenatal and Postnatal Periods. Russ J Dev Biol 2019. [DOI: 10.1134/s1062360419020061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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Richardson A, Mascarenhas M, Balen A. Is a woman's chronological age or 'ovarian age' more important in determining perinatal outcome after assisted reproductive treatment? HUM FERTIL 2019; 24:144-150. [PMID: 31038011 DOI: 10.1080/14647273.2019.1597987] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Ovarian reserve (OR) decreases as women get older but there is considerable variation in the rate at which this occurs. Older women are at increased risk of complications during pregnancy. The aim of the study was to determine whether poor OR influences perinatal outcomes independent of age. All fresh IVF/ICSI cycles in which a single embryo was transferred between 1 January 2010 and 31 December 2016 were reviewed. An anti-Müllerian hormone (AMH) concentration of ≤5.4 pmol/l was considered poor and 5.41-24.99 pmol/l normal. Data were collected regarding cycle outcome, congenital anomalies, gestational age at delivery and birth weight. A total of 1520 women were included, of whom 1197 had normal OR and the remaining 323 had poor OR. Once pregnant, after adjusting for maternal age, women with poor OR (n = 109) were no more likely to experience a biochemical pregnancy or miscarriage (41.3% versus 41.6%, p = 0.809) than women with normal OR (n = 596). There were no significant differences in rates of congenital anomalies (1.8% versus 1.2%, p = 0.636), birth weight (3272 ± 630.7 g versus 3376.4 ± 576.3 g, p = 0.216) or gestational age at delivery (38.9 ± 2.3 weeks versus 39.1 ± 2.1 weeks, p = 0.517) between women with normal or poor OR. OR does not appear to affect pregnancy loss rates, incidence of congenital anomalies, birth weight, or gestational age at delivery after adjusting for maternal age.
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Affiliation(s)
- Alison Richardson
- Leeds Fertility, Seacroft Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Mariano Mascarenhas
- Leeds Fertility, Seacroft Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Adam Balen
- Leeds Fertility, Seacroft Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, UK
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Evaluation of the Second Follicular Wave Phenomenon in Natural Cycle Assisted Reproduction: A Key Option for Poor Responders through Luteal Phase Oocyte Retrieval. ACTA ACUST UNITED AC 2019; 55:medicina55030068. [PMID: 30875815 PMCID: PMC6473900 DOI: 10.3390/medicina55030068] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2018] [Revised: 01/08/2019] [Accepted: 03/06/2019] [Indexed: 12/24/2022]
Abstract
Background: Emergence of Luteal Phase Oocyte Retrieval (LuPOR) may revolutionize the practice regarding the time-sensitive nature of poor responders ascertaining a higher number of oocytes, in a shorter amount of time. This may be especially important in view of employing the approach of natural cycles for Poor Responders. We suggest the acronym LuPOR describing the clinical practice of luteal phase oocyte retrieval. The aim of the study is to offer insight regarding the identity of LuPOR, and highlight how this practice may improve management of the special subgroup of poor responders. Materials and Methods: The present retrospective observational clinical study includes the collection and statistical analysis of data from 136 poor responders who underwent follicular oocyte retrieval (FoPOR) and subsequent LuPOR in natural cycles, during their In Vitro Fertilization (IVF) treatment, from the time period of 2015 to 2018. All 136 participants were diagnosed with poor ovarian reserve (POR) according to Bologna criteria. The 272 cycles were categorized as follows: 136 natural cycles with only FoPORs (Control Group) and 136 natural cycles including both FoPORs and LuPORs. Results: Our primary results indicate no statistically significant differences with regards to the mean number of oocytes, the maturation status, and fertilization rate between FoPOR and LuPOR in natural cycles. Secondarily, we demonstrate a statistically significant higher yield of oocytes (2.50 ± 0.78 vs. 1.25 ± 0.53), better oocyte maturity status (1.93 ± 0.69 vs. 0.95 ± 0.59) and higher fertilization rate (1.31 ± 0.87 vs. 0.61 ± 0.60) in natural cycles including both FoPOR and LuPOR, when compared to cycles including only FoPOR. Conclusion: Our study may contribute towards the establishment of an efficient poor responders’ management through the natural cycle approach, paving a novel clinical practice and ascertaining the opportunity to employ oocytes and embryos originating from a luteal phase follicular wave.
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30
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Intergenerational response of steroidogenesis-related genes to maternal malnutrition. J Dev Orig Health Dis 2019; 10:587-594. [PMID: 30789120 DOI: 10.1017/s2040174419000060] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
We sought to examine whether rat maternal food restriction (MFR) affects the expression of steroidogenesis-related genes Cyp19, Cyp17a1, Insl3 and Gdf-9 in the ovaries of offspring from the first (FRG1) and second (FRG2) generations at pre-pubertal age (week 4) and during adulthood (week 8). At week 4, MFR significantly increased the expression of RNAs for all analyzed genes in both FRG1 and FRG2 females, which may indicate that MFR affects the onset of the reproductive lifespan, by inducing early pubertal onset. At week 8, the Cyp19 gene was still upregulated in MRF-subjected animals (Cyp19: P=0.0049 and P=0.0508 in FRG1 and FRG2, respectively), but MFR induced a significant decrease in Cyp17 and Gdf-9 gene expression in the offspring of both FRG1 and FRG2 females when compared with the controls (Cyp17: P=0.0018 and P=0.0016, respectively; Gdf-9: P=0.0047 and P=0.0023, respectively). This suggests that females at week 8, which should normally be in their optimal reproductive capacity, experience premature ovarian aging. At week 4, the activation of Cyp19 and Cyp17 was higher in the FRG1 ovaries than in the FRG2 ovaries, whereas the extent of Insl3 and Gdf-9 activation was lower in the FRG1 ovaries. This may indicate that FRG2 females were more vulnerable to MFR than their mothers (FRG1) and grandmothers, which is consistent with the 'predictive adaptive response' hypothesis. Our findings reveal that MFR may induce intergenerational ovarian changes as an adaptive response to ensure reproductive success before death.
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Muzii L, Di Tucci C, Di Feliciantonio M, Galati G, Pecorella I, Radicioni A, Anzuini A, Piccioni MG, Patacchiola F, Benedetti Panici P. Ovarian Reserve Reduction With Surgery Is Not Correlated With the Amount of Ovarian Tissue Inadvertently Excised at Laparoscopic Surgery for Endometriomas. Reprod Sci 2019; 26:1493-1498. [DOI: 10.1177/1933719119828055] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
The aim of the present study was to evaluate the effect of laparoscopic cystectomy on ovarian reserve by means of anti-Müllerian hormone (AMH) serial measurements and to compare AMH values with the number of inadvertently removed follicles in histological specimens. Fifty-two women were enrolled: 34 patients with endometriomas (group 1) and 18 patients with other benign ovarian cysts (group 2). All patients underwent laparoscopic cystectomy performed by a single experienced surgeon. The AMH was measured before, and 1, 3, and 6 months after cystectomy in group 1, and before and 6 months after surgery in group 2. Preoperative AMH levels (mean [standard deviation, SD]) in group 1 (3.39 [2.43] ng/mL) were not significantly different from group 2 (3.74 [2.57] ng/mL; P = .68). In group 1, a significant decrease in AMH levels of 43.4% was observed at 1 month (1.93 [1.36]; P = .003), and of 63.1% at 3 months (1.25 [1.00]; P = .007) postoperatively. The AMH increased not significantly between the third and sixth months in group 1 (+9.4%). Six months after surgery, AMH was reduced by 59.3% compared to baseline values in group 1 ( P = .012), and by 29.5% in group 2 ( P = .200). A significant difference in the AMH decrease was present between bilateral and monolateral endometriomas ( P = .006). There was no correlation between the reduction rate of AMH and the number of follicles inadvertently removed in patients with endometriomas ( P = .669). In conclusion, AMH decreases significantly after surgical excision of ovarian endometriomas. The postoperative decrease does not appear to correlate with the amount of ovarian tissue inadvertently excised with the endometrioma wall.
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Affiliation(s)
- Ludovico Muzii
- Department of Obstetrics and Gynecology, “Sapienza” University of Rome, Rome, Italy
| | - Chiara Di Tucci
- Department of Obstetrics and Gynecology, “Sapienza” University of Rome, Rome, Italy
| | | | - Giulia Galati
- Department of Obstetrics and Gynecology, “Sapienza” University of Rome, Rome, Italy
| | - Irene Pecorella
- Department of Pathology, “Sapienza” University of Rome, Rome, Italy
| | - Antonio Radicioni
- Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, “Sapienza” University of Rome, Rome, Italy
| | - Antonella Anzuini
- Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, “Sapienza” University of Rome, Rome, Italy
| | | | - Felice Patacchiola
- Department of Life, Health and Environmental Sciences, University of L’Aquila, L’Aquila, Italy
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Uliani RC, Conley AJ, Corbin CJ, Friso AM, Maciel LFS, Alvarenga MA. Anti-Müllerian hormone and ovarian aging in mares. J Endocrinol 2019; 240:147-156. [PMID: 30400031 DOI: 10.1530/joe-18-0391] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2018] [Accepted: 10/26/2018] [Indexed: 12/31/2022]
Abstract
Anti-Müllerian hormone (AMH) is used as a marker of follicle population numbers and potential fertility in several species including horses but limited data exist across the lifespan. No one has decreased ovarian reserve experimentally to investigate whether a corresponding, quantitative decrease in AMH results. Concentrations of AMH across the lifespan were compiled from 1101 equine females sampled from birth to >33 years of age. Young and old mares (averaging 6 and 19 years) were hemi-ovariectomized and circulating AMH was assessed before and daily thereafter for 15 days. The remaining ovary was removed later and blood was drawn again before and after this second surgery for AMH determination. Polynomial regression analysis and analysis of mares grouped by 5-year intervals of age demonstrated AMH concentrations to be higher in mares aged 5-10 and 10-15 years than 0-5 years of age and lower in mares after 20 years of age. There was high variability in AMH concentrations among neonatal fillies, some of which had concentrations typical of males. Hemi-ovariectomy was followed by a decrease of AMH, almost exactly halving concentrations in intact mares. Concentrations of AMH had returned to intact levels in old mares before complete ovariectomy, as if exhibiting ovarian compensatory hypertrophy, but recovery of AMH was not evident in young mares. AMH may reflect ovarian senescence in mares after 20 years of age but is too variable to do so in the first two decades of life. The ovarian endocrine response to hemi-ovariectomy in mares appears to change with age.
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Affiliation(s)
- Renata C Uliani
- Department of Animal Reproduction, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Alan J Conley
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California Davis, Davis, California, USA
| | - C Jo Corbin
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California Davis, Davis, California, USA
| | - Aimê M Friso
- Department of Animal Reproduction, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Luciana F S Maciel
- Department of Animal Reproduction, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Marco A Alvarenga
- Department of Animal Reproduction, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
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Links between age at menarche, antral follicle count, and body mass index in African American and European American women. Fertil Steril 2019; 111:122-131. [PMID: 30611402 DOI: 10.1016/j.fertnstert.2018.09.007] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Revised: 08/14/2018] [Accepted: 09/07/2018] [Indexed: 01/21/2023]
Abstract
OBJECTIVE To examine the relationships between age at menarche, antral follicle count (AFC), and body mass index (BMI) in a multi-ethnic population of women. DESIGN Community-based, cross-sectional study. SETTING Academic setting. PATIENT(S) A total of 245 African American women and 273 European American women, aged 25-45 years, with regular menstrual cycles and no reproductive disorders. The ethnicity of these women was self-reported and genetically validated. INTERVENTION(S) The AFCs were measured by transvaginal ultrasound during the early follicular phase. Anthropometric measurements were taken, and age at menarche was gathered by questionnaire. MAIN OUTCOME MEASURE(S) Determination of the associations between age of menarche and adult AFC and BMI. RESULT(S) Earlier age of menarche was associated with both higher BMIs and higher AFCs in adulthood, with control for female age. The antral follicle difference between early (<12 years) vs. late (≥15 years) initiation of menarche in both white and black women was +3.81 and +3.34 follicles, respectively, which is equivalent to an approximately 20% difference in AFC. CONCLUSION(S) This study provides the first evidence that timing of menarche may influence AFC. Because of limited studies on African American women, this work provides additional needed data and may enhance our ability to prospectively screen and better treat various diseases associated with the female reproductive lifespan.
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Seneda MM, Morotti F, Zangirolamo AF, da Silva NC, Sanches TK, Blaschi W, Barreiros TRR. Antral follicle population in prepubertal and pubertal heifers. Reprod Fertil Dev 2019; 31:10-16. [PMID: 32188538 DOI: 10.1071/rd18344] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
The antral follicle count (AFC) is an important tool in the selection of bovine females destined for biotechnology. However, little is known about AFC in prepubertal and pubertal heifers. Some challenges inherent to the physiology of young females must be considered to achieve efficient rates with different procedures, such as ovum pick-up and IVF. This paper covers some important topics about ovarian physiology related to the population of antral follicles and reproductive efficiency in young female cattle.
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Affiliation(s)
- M M Seneda
- Universidade Estadual de Londrina, Laboratório de Reprodução Animal, Departamento de Clínicas Veterinárias - Centro de Ciências Agrárias - Universidade Estadual de Londrina, Londrina, Parana, Brazil
| | - F Morotti
- Universidade Estadual de Londrina, Laboratório de Reprodução Animal, Departamento de Clínicas Veterinárias - Centro de Ciências Agrárias - Universidade Estadual de Londrina, Londrina, Parana, Brazil
| | - A F Zangirolamo
- Universidade Estadual de Londrina, Laboratório de Reprodução Animal, Departamento de Clínicas Veterinárias - Centro de Ciências Agrárias - Universidade Estadual de Londrina, Londrina, Parana, Brazil
| | - N C da Silva
- Universidade Estadual de Londrina, Laboratório de Reprodução Animal, Departamento de Clínicas Veterinárias - Centro de Ciências Agrárias - Universidade Estadual de Londrina, Londrina, Parana, Brazil
| | - T K Sanches
- Universidade Estadual de Londrina, Laboratório de Reprodução Animal, Departamento de Clínicas Veterinárias - Centro de Ciências Agrárias - Universidade Estadual de Londrina, Londrina, Parana, Brazil
| | - W Blaschi
- Universidade Estadual do Norte do Paraná, Laboratório de Biotecnologia da Reprodução Animal, Departamento de Veterinária e Produção Animal, Rodovia BR - 369, Km 54, Vila Maria, Bandeirantes, Parana 86360-000, Brazil
| | - T R R Barreiros
- Universidade Estadual do Norte do Paraná, Laboratório de Biotecnologia da Reprodução Animal, Departamento de Veterinária e Produção Animal, Rodovia BR - 369, Km 54, Vila Maria, Bandeirantes, Parana 86360-000, Brazil
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Chen P, Li T, Jia L, Fang C, Liang X. Should all embryos be cultured to blastocyst for advanced maternal age women with low ovarian reserve: a single center retrospective study. Gynecol Endocrinol 2018; 34:761-765. [PMID: 29544364 DOI: 10.1080/09513590.2018.1450379] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/17/2022] Open
Abstract
The purpose of this study is to determine whether all-blastocyst-culture can benefit advanced maternal age (AMA) patients with low ovarian reserve. We retrospectively analyze AMA patients with low ovarian reserve undergoing IVF/ICSI in Reproductive Medicine Research Center of the Sixth Affiliated Hospital of Sun Yat-sen University from May 2016 to August 2017. We divide them into group A (all-blastocyst-culture) and group B (none-blastocystculture) based on different culture approach of D3 transferrable embryo. We compared the cumulative biochemical pregnancy rate and cumulative clinical pregnancy rate between them. A total of 261 eligible patients are included, with 151 in group A and 110 in group B. The basic conditions of the two groups show no difference. Cumulative biochemical pregnancy rate/clinical pregnancy rate in group A is higher than that of group B, though not statistically significant (p > .05). After removing patients canceling embryo transfer due to failure in blastocyst culture, the cumulative biochemical pregnancy rate/clinical pregnancy rate in group A is significantly higher than group B (p < .05). Multivariate analysis showed that female age and the number of D3 transferrable embryo are risk factors for the failure of blastocyst culture (OR = 0.672 and 2.270, 95%CI 0.511-0.883 and 1.203-4.284, p = .004 and p = .011, respectively). Hence, we drew to conclusion that all-blastocyst-culture will not adversely affect the pregnancy outcome of AMA patients with low ovarian reserve.
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Affiliation(s)
- Panyu Chen
- a Reproductive Medicine Research Center , The 6th Affiliated Hospital of Sun Yat-sen University , Guangzhou , China
| | - Tingting Li
- a Reproductive Medicine Research Center , The 6th Affiliated Hospital of Sun Yat-sen University , Guangzhou , China
| | - Lei Jia
- a Reproductive Medicine Research Center , The 6th Affiliated Hospital of Sun Yat-sen University , Guangzhou , China
| | - Cong Fang
- a Reproductive Medicine Research Center , The 6th Affiliated Hospital of Sun Yat-sen University , Guangzhou , China
| | - Xiaoyan Liang
- a Reproductive Medicine Research Center , The 6th Affiliated Hospital of Sun Yat-sen University , Guangzhou , China
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Fritz R, Jindal S. Reproductive aging and elective fertility preservation. J Ovarian Res 2018; 11:66. [PMID: 30098598 PMCID: PMC6087539 DOI: 10.1186/s13048-018-0438-4] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2018] [Accepted: 08/02/2018] [Indexed: 01/05/2023] Open
Abstract
Reproductive aging is a natural process that occurs in all women, eventually leading to reproductive senescence and menopause. Over the past half century there has been a trend towards delayed motherhood. Postponing reproduction can increase the chance of a woman remaining involuntarily childless as well as an increase in pregnancy complications in those that do achieve pregnancy at advanced maternal age. Despite the well-documented decrease in fecundity that occurs as a woman ages, reproductive aged women frequently overestimate the age at which a significant decline in fertility occurs and overestimate the success of assisted reproductive technologies (ART) to circumvent infertility. Oocyte cryopreservation enables women to achieve genetically related offspring in the event that they desire to postpone their childbearing to an age after which a significant decline in fertility occurs or in circumstances in which their reproductive potential is compromised due to medical pathology. Available success rates and safety data following oocyte cryopreservation have been reassuring and is not considered experimental according to the American Society for Reproductive Medicine and the European Society for Human Reproduction and Embryology. This review article will focus on an evidence-based discussion relating to reproductive aging and oocyte cryopreservation.
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Affiliation(s)
- Rani Fritz
- Department of Obstetrics, Gynecology & Women’s Health, Albert Einstein College of Medicine/Montefiore Medical Center, Minneapolis, USA
| | - Sangita Jindal
- Department of Obstetrics, Gynecology & Women’s Health, Albert Einstein College of Medicine/Montefiore Medical Center, Minneapolis, USA
- Montefiore’s Institute for Reproductive Medicine and Health, New York, USA
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Fritz R, Klugman S, Lieman H, Schulkin J, Taouk L, Castleberry N, Buyuk E. Counseling patients on reproductive aging and elective fertility preservation-a survey of obstetricians and gynecologists' experience, approach, and knowledge. J Assist Reprod Genet 2018; 35:1613-1621. [PMID: 30073435 DOI: 10.1007/s10815-018-1273-7] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2018] [Accepted: 07/17/2018] [Indexed: 01/25/2023] Open
Abstract
PURPOSE What are the experience, approach, and knowledge of US Obstetricians and Gynecologists' (ob-gyn) towards counseling patients on reproductive aging (RA) and elective fertility preservation (EFP). METHODS A cross-sectional survey emailed by the American College of Obstetricians and Gynecologists (ACOG) to 5000 ACOG fellows consisting of 9 demographic and 28 questions relating to counseling patients on RA and EFP. RESULTS Seven hundred and eighty-four responders completed the survey. Although 82.8% agreed that conversations relating to RA should take place with patients desiring future childbearing and delaying due to social reasons, only 27.6% stated that they frequently counsel these women aged 18-34 years old, compared to 75.8% aged 35-44 years old (P < 0.01). Limited time (75.8%) and limited knowledge (41.4%) were amongst the most frequent reported barriers towards counseling patients on RA. Fifty-eight percent stated that they have been asked about EFP by patients. Although 74.8% agreed that conversations should take place related to EFP in women desiring future childbearing and delaying due to social reasons, only 27.6% stated that they frequently counsel these patients on EFP (P < 0.01). Limited time (75%) and limited knowledge (59.9%) were amongst the most frequent barriers towards counseling on EFP. CONCLUSIONS In the USA, methods to improve patient counseling and provider knowledge on RA and EFP are warranted and further studies are needed to address optimal methods to improve counseling and knowledge related to these topics.
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Affiliation(s)
- Rani Fritz
- Montefiore Institute for Reproductive Medicine and Health, Department of Obstetrics, Gynecology & Women's Health, Albert Einstein College of Medicine / Montefiore Medical Center, Bronx, NY, 10461, USA
| | - Susan Klugman
- Montefiore Institute for Reproductive Medicine and Health, Department of Obstetrics, Gynecology & Women's Health, Albert Einstein College of Medicine / Montefiore Medical Center, Bronx, NY, 10461, USA
| | - Harry Lieman
- Montefiore Institute for Reproductive Medicine and Health, Department of Obstetrics, Gynecology & Women's Health, Albert Einstein College of Medicine / Montefiore Medical Center, Bronx, NY, 10461, USA
| | - Jay Schulkin
- Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, 98195, USA
| | - Laura Taouk
- Research Department, The American College of Obstetricians and Gynecologists (ACOG), Washington, DC, 20024, USA
| | - Neko Castleberry
- Research Department, The American College of Obstetricians and Gynecologists (ACOG), Washington, DC, 20024, USA
| | - Erkan Buyuk
- Montefiore Institute for Reproductive Medicine and Health, Department of Obstetrics, Gynecology & Women's Health, Albert Einstein College of Medicine / Montefiore Medical Center, Bronx, NY, 10461, USA.
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Jiang X, Yan J, Sheng Y, Sun M, Cui L, Chen ZJ. Low anti-Müllerian hormone concentration is associated with increased risk of embryonic aneuploidy in women of advanced age. Reprod Biomed Online 2018; 37:178-183. [PMID: 29724534 DOI: 10.1016/j.rbmo.2018.04.039] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2017] [Revised: 03/28/2018] [Accepted: 04/04/2018] [Indexed: 01/09/2023]
Abstract
RESEARCH QUESTION Does an association exist between serum anti-Müllerian hormone (AMH) level, the marker of biological ovarian age, and embryonic aneuploidy risk in recurrent spontaneous miscarriage (RSM) patients of reproductive age? DESIGN This retrospective study included a total of 422 IVF cycles of 394 unexplained RSM patients undergoing preimplantation genetic testing for aneuploidy (PGT-A), enrolled from January 2014 to December 2016. Subjects were divided into three groups according to the 25th (1.50 ng/ml) and 75th (5.60 ng/ml) percentiles of AMH level (Group 1: low AMH <1.50 ng/ml [N = 107], Group 2: normal AMH 1.50- < 5.60 ng/ml [N = 210] and Group 3: high AMH ≥ 5.60 ng/ml [N = 105]). RESULTS There was a significant difference in embryonic aneuploid rate between AMH groups (66.7% versus 42.9% versus 50.0%, Groups 1 to 3, respectively, P = 0.006). It was significantly higher in the low AMH group (Group 1) compared with that in the normal AMH group (Group 2, P1vs2 = 0.002) and high AMH group (Group 3, P1vs3 = 0.015). After age stratification, embryonic aneuploidy rate was still significantly different among AMH groups with a similar trend in women ≥35 years old (68.2% versus 54.4% versus 51.0%, P = 0.038, P1vs2 = 0.025, P1vs3 = 0.035), but not in young subjects. CONCLUSIONS These findings indicate that low AMH level was associated with increased risk of embryo aneuploidy only in women of advanced age. Maternal diminished ovarian reserve along with oocyte ageing may contribute to impaired chromosomal competence of the embryo.
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Affiliation(s)
- Xiao Jiang
- Centre for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250001, China; The Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, 250001, China; National Research Centre for Assisted Reproductive Technology and Reproductive Genetics, Jinan, 250001, China
| | - Junhao Yan
- Centre for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250001, China; The Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, 250001, China; National Research Centre for Assisted Reproductive Technology and Reproductive Genetics, Jinan, 250001, China
| | - Yan Sheng
- Centre for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250001, China; The Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, 250001, China; National Research Centre for Assisted Reproductive Technology and Reproductive Genetics, Jinan, 250001, China
| | - Mei Sun
- Centre for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250001, China; The Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, 250001, China; National Research Centre for Assisted Reproductive Technology and Reproductive Genetics, Jinan, 250001, China
| | - Linlin Cui
- Centre for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250001, China; The Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, 250001, China; National Research Centre for Assisted Reproductive Technology and Reproductive Genetics, Jinan, 250001, China.
| | - Zi-Jiang Chen
- Centre for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250001, China; The Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, 250001, China; National Research Centre for Assisted Reproductive Technology and Reproductive Genetics, Jinan, 250001, China; Centre for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200000, China; Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, 200000, China.
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Abstract
Osteoporosis is the most common bone metabolic disease with a very high morbidity, and women usually got a higher risk of osteoporosis than men. The high incidence rate of osteoporosis in women was mainly caused by (1) women having fewer skeletons and bone mass, (2) pregnancy consuming a large amount of calcium and other nutrients, and most importantly (3) the cease of estrogen secretion by ovaries after menopause. Along with ovarian aging, the follicle pool gradually declines and the oocyte quality reduced, accompanied with decline in serum estrogen. Estrogen deficiency plays an important role in the pathogenesis of postmenopausal osteoporosis; it is mainly a result of the recognition that estrogen regulates bone remodeling by modulating the production of cytokines and growth factors from bone marrow and bone cells. This review will summarize current knowledge concerning ovarian aging and postmenopause osteoporosis and also discuss clinical treatment and new ideas of drug development for osteoporosis.
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Affiliation(s)
- Liyuan Li
- MOE Key Laboratory of Protein Sciences, School of Pharmaceutical Sciences, Tsinghua University, Beijing, China
| | - Zhao Wang
- School of Pharmaceutical Sciences, Tsinghua University, Beijing, China.
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40
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Abstract
The concept of the ovarian continuum can be understood as a process that occurs during a woman's lifetime and begins during intrauterine life with fertilization. Women start their reproductive years with approximately five hundred thousand follicles containing oocytes, of which only around five hundred will be released during ovulation. Ovulation has been recognized as an event linked with reproduction; however, recent evidence supports the role of ovulation as a sign of health. The use of biomarkers that help women recognize ovulation enables them to identify their health status. This knowledge helps medical healthcare providers in the prevention, diagnosis, and treatment of different pathologies related with endocrine disorders, gynecological abnormalities, autoimmune, genetic, and neoplastic diseases, as well as pregnancy-related issues. The knowledge of the ovarian continuum and the use of biomarkers to recognize ovulation should be considered a powerful tool for women and medical professionals. Summary The ovarian continuum is a process that occurs during a woman's lifetime. It begins during intrauterine life with fertilization and ends with menopause. This process can be greatly affected by different conditions such as changes in hormonal levels and illnesses. Therefore, understanding and promoting the knowledge and use of biomarkers of ovulation in women is a key aspect to consider when evaluating their health status. The knowledge and education about the ovarian continuum should be taken into account as a powerful tool for women and medical professionals.
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Affiliation(s)
- Pilar Vigil
- Biomedical Division, Reproductive Health Research Institute (RHRI), Santiago, Chile.,Pontificia Universidad Católica de Chile, Vicerrectoría de Comunicaciones, Santiago, Chile
| | - Carolina Lyon
- Biomedical Division, Reproductive Health Research Institute (RHRI), Santiago, Chile
| | - Betsi Flores
- Biomedical Division, Reproductive Health Research Institute (RHRI), Santiago, Chile
| | - Hernán Rioseco
- Biomedical Division, Reproductive Health Research Institute (RHRI), Santiago, Chile
| | - Felipe Serrano
- Biomedical Division, Reproductive Health Research Institute (RHRI), Santiago, Chile
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Milman LW, Senapati S, Sammel MD, Cameron KD, Gracia C. Assessing reproductive choices of women and the likelihood of oocyte cryopreservation in the era of elective oocyte freezing. Fertil Steril 2017; 107:1214-1222.e3. [PMID: 28476182 DOI: 10.1016/j.fertnstert.2017.03.010] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2016] [Revised: 02/26/2017] [Accepted: 03/06/2017] [Indexed: 11/30/2022]
Abstract
OBJECTIVE To assess reproductive choices of reproductive-age women in the United States and factors that influence consideration of elective egg freezing (EF). DESIGN Cross-sectional internet-based survey. SETTING Not applicable. PATIENTS One thousand women aged 21-45 years. INTERVENTION(S) An anonymous 63-item self-administered questionnaire was distributed to a representative cross-section of women aged 21-45 years, stratified by age <35 years. One-half of the sample had at least one child, and the other one-half did not. All of the participants were interested in having children. MAIN OUTCOME MEASURE(S) Ordinal logistic regression was performed to characterize the association of population characteristics and reproductive knowledge with likelihood to consider EF. Willingness to pay was assessed with the use of a linear prediction model that calculated dollar amounts at varying success rates. RESULT(S) Overall, 87.2% of the sample reported awareness of EF for fertility preservation and 25% would consider this option, yet only 29.8% knew what the EF process entails. Once informed of the process, 30% of women changed their level of consideration. In a multivariable model, Asian race, single status, and infertility increased the likelihood of considering EF. Women likely to consider egg freezing would be willing to pay $3,811.55 (95% confidence interval $2,862.66-$4,760.44). If the total cost were $10,000, 91% of the cohort would accept at minimum a 50% chance of successful delivery. CONCLUSION(S) This study is one of the largest cohorts of reproductive-age women in the United States addressing reproductive choices and factors associated with the importance of having a biologically related child and the likelihood of considering EF to preserve fertility. This study provides important insight into the willingness to pay for this elective endeavor.
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Affiliation(s)
- Lauren W Milman
- Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Suneeta Senapati
- Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania.
| | - Mary D Sammel
- Center for Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Katherine D Cameron
- Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Clarisa Gracia
- Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania
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Gebel J, Tuppi M, Krauskopf K, Coutandin D, Pitzius S, Kehrloesser S, Osterburg C, Dötsch V. Control mechanisms in germ cells mediated by p53 family proteins. J Cell Sci 2017:jcs.204859. [PMID: 28794013 DOI: 10.1242/jcs.204859] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Germ cells are totipotent and, in principle, immortal as they are the source for new germ cells in each generation. This very special role requires tight quality control systems. The p53 protein family constitutes one of the most important quality surveillance systems in cells. Whereas p53 has become famous for its role as the guardian of the genome in its function as the most important somatic tumor suppressor, p63 has been nicknamed 'guardian of the female germ line'. p63 is strongly expressed in resting oocytes and responsible for eliminating those that carry DNA double-strand breaks. The third family member, p73, acts later during oocyte and embryo development by ensuring correct assembly of the spindle assembly checkpoint. In addition to its role in the female germ line, p73 regulates cell-cell contacts between developing sperm cells and supporting somatic cells in the male germ line. Here, we review the involvement of the p53 protein family in the development of germ cells with a focus on quality control in the female germ line and discuss medical implications for cancer patients.
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Affiliation(s)
- Jakob Gebel
- Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University, Max von Laue-Str. 9, Frankfurt am Main 60438, Germany
| | - Marcel Tuppi
- Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University, Max von Laue-Str. 9, Frankfurt am Main 60438, Germany
| | - Katharina Krauskopf
- Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University, Max von Laue-Str. 9, Frankfurt am Main 60438, Germany
| | - Daniel Coutandin
- Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University, Max von Laue-Str. 9, Frankfurt am Main 60438, Germany
| | - Susanne Pitzius
- Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University, Max von Laue-Str. 9, Frankfurt am Main 60438, Germany
| | - Sebastian Kehrloesser
- Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University, Max von Laue-Str. 9, Frankfurt am Main 60438, Germany
| | - Christian Osterburg
- Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University, Max von Laue-Str. 9, Frankfurt am Main 60438, Germany
| | - Volker Dötsch
- Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University, Max von Laue-Str. 9, Frankfurt am Main 60438, Germany
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Abstract
Recently, the existence of a mechanism for neo-oogenesis in the ovaries of adult mammals has generated much controversy within reproductive biology. This mechanism, which proposes that the ovary has cells capable of renewing the follicular reserve, has been described for various species of mammals. The first evidence was found in prosimians and humans. However, these findings were not considered relevant because the predominant dogma for reproductive biology at the time was that of Zuckerman. This dogma states that female mammals are born with finite numbers of oocytes that decline throughout postnatal life. Currently, the concept of neo-oogenesis has gained momentum due to the discovery of cells with mitotic activity in adult ovaries of various mammalian species (mice, humans, rhesus monkeys, domestic animals such as pigs, and wild animals such as bats). Despite these reports, the concept of neo-oogenesis has not been widely accepted by the scientific community, generating much criticism and speculation about its accuracy because it has been impossible to reproduce some evidence. This controversy has led to the creation of two positions: one in favour of neo-oogenesis and the other against it. Various animal models have been used in support of both camps, including both classic laboratory animals and domestic and wild animals. The aim of this review is to critically present the current literature on the subject and to evaluate the arguments pro and contra neo-oogenesis in mammals.
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García-Guerra A, Motta JCL, Melo LF, Kirkpatrick BW, Wiltbank MC. Ovulation rate, antral follicle count, and circulating anti-Müllerian hormone in Trio allele carriers, a novel high fecundity bovine genotype. Theriogenology 2017; 101:81-90. [PMID: 28708520 DOI: 10.1016/j.theriogenology.2017.05.026] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2017] [Revised: 05/29/2017] [Accepted: 05/30/2017] [Indexed: 12/24/2022]
Abstract
High fecundity genotypes in sheep are a valuable model to study the physiological mechanisms underlying follicle selection and the control of ovulation rate. Similar genotypes in cattle had not been described until the recent identification of a major bovine allele, termed Trio, which had a large effect on ovulation rate. The present study was designed to evaluate ovulation rate, antral follicle count (AFC), circulating ant-müllerian hormone (AMH), and the association among these measures in unstimulated and superstimulated Trio carrier cattle. We hypothesized that AFC and AMH would be variable among individual cows but would be similar between Trio carriers and non-carrier control cows and that there would be no association between these measures of follicle numbers and ovulation rate. In experiment 1, ovulation rate was determined during 4 consecutive estrous cycles in Trio carriers (n = 34) and non-carrier controls (n = 27). Ovulation rate, on average, was greater (P < 0.01) in Trio carriers (3.5 ± 0.2) compared to non-carrier controls (1.1 ± 0.1) with ∼70% of carrier cycles (n = 136) having 3-4 ovulations while only ∼5% had single ovulations. In contrast, non-carrier cycles (n = 108) were mostly single ovulation (89%) with none having more than two ovulations. In experiment 2, AFC, determined at wave emergence, was not different (P = 0.54) between Trio carriers (24.5 ± 1.3; n = 45) and non-carrier controls (23.1 ± 0.9; n = 37), and no correlation was found between AFC and mean ovulation rate in either genotype (r = -0.009 and r = -0.07; P > 0.70, respectively). In Experiment 3, circulating AMH was also not different between genotypes (P = 0.65) while correlations were found between AFC and AMH in Trio carriers (r = 0.43; P = 0.05; n = 27) and non-carrier controls (r = 0.78; P < 0.01; n = 19). In experiment 4, AFC and AMH were determined in Trio-carriers (n = 9) in relation to a synchronized follicular wave which was unstimulated or stimulated with exogenous FSH. Stimulation with FSH increased ovulation rate, compared to unstimulated Trio carriers, however no association was found between AFC or AMH and ovulation rate regardless of whether superstimulation with exogenous FSH was used. In conclusion, the novel high fecundity bovine genotype Trio, results in consistent multiple ovulations despite having similar AFC and AMH. Therefore, our results suggest that differences in antral follicle numbers during the final stages of follicle development are not a key component of the mechanism underlying multiple ovulations in Trio carriers.
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Affiliation(s)
- Alvaro García-Guerra
- Department of Dairy Science, University of Wisconsin-Madison, 1675 Observatory Drive, Madison, WI, United States; Endocrinology and Reproductive Physiology Program, University of Wisconsin-Madison, Madison, WI, United States
| | - Jéssica C L Motta
- Department of Dairy Science, University of Wisconsin-Madison, 1675 Observatory Drive, Madison, WI, United States
| | - Leonardo F Melo
- Department of Dairy Science, University of Wisconsin-Madison, 1675 Observatory Drive, Madison, WI, United States; Department of Animal Science, University of São Paulo, Piracicaba, São Paulo, Brazil
| | - Brian W Kirkpatrick
- Department of Dairy Science, University of Wisconsin-Madison, 1675 Observatory Drive, Madison, WI, United States; Department of Animal Science, University of Wisconsin-Madison, 1675 Observatory Drive, Madison, WI, United States
| | - Milo C Wiltbank
- Department of Dairy Science, University of Wisconsin-Madison, 1675 Observatory Drive, Madison, WI, United States; Endocrinology and Reproductive Physiology Program, University of Wisconsin-Madison, Madison, WI, United States.
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Ovarian features in white-tailed deer (Odocoileus virginianus) fawns and does. PLoS One 2017; 12:e0177357. [PMID: 28542265 PMCID: PMC5444630 DOI: 10.1371/journal.pone.0177357] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2016] [Accepted: 04/12/2017] [Indexed: 01/01/2023] Open
Abstract
The knowledge about ovarian reserve is essential to determine the reproductive potential and to improve the methods of fertility control for overpopulated species, such as white-tailed deer (Odocoileus virginianus). The goal of this study was to evaluate the effect of age on the female reproductive tract of white-tailed deer, focusing on ovarian features. Genital tracts from 8 prepubertal and 10 pubertal females were used to characterize the preantral follicle population and density, morphology, distribution of follicular classes; stromal cell density; and apoptosis in the ovary. In addition, uterus and ovary weights and dimensions were recorded; and the number and the size of antral follicles and corpus luteum in the ovary were quantified. Overall, fawns had a greater (P < 0.05) preantral follicle population, percentage of normal follicles, and preantral follicle density than does. The mean stromal cell density in ovaries of fawns and does differed among animals but not between age groups. The apoptotic signaling did not differ (P > 0.05) between the ovaries of fawns and does. However, apoptotic ovarian cells negatively (P < 0.001) affected the preantral follicle morphology and density, and conversely, a positive correlation was observed with stromal cell density. As expected, the uteri and ovaries were larger (P < 0.002) and heavier (P < 0.001) in does than in fawns. In conclusion, this study has shown, for the first time, the preantral follicle population and distribution of classes, rate of morphologically normal follicles, and density of preantral follicles and stromal cells in white- tailed deer. Therefore, the findings herein described lead to a better understanding of the white-tailed deer ovarian biology, facilitating the development of new methods of fertility control.
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Tsikouras P, Manav B, Koukouli Z, Trypsiannis G, Galazios G, Souftas D, Souftas V. Ovarian reserve after fibroid embolization in premenopausal women. MINIM INVASIV THER 2017. [DOI: 10.1080/13645706.2017.1292919] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Affiliation(s)
- Panagiotis Tsikouras
- Department of Obstetrics and Gynaecology, Democritus University of Thrace, Alexandroupolis, Greece
| | - Bachar Manav
- Department of Obstetrics and Gynaecology, Democritus University of Thrace, Alexandroupolis, Greece
| | - Zacharoula Koukouli
- Department of Obstetrics and Gynaecology, Democritus University of Thrace, Alexandroupolis, Greece
| | - Grigorios Trypsiannis
- Department of Medical Statistics, Medical Faculty, Democritus University of Thrace, Alexandroupolis, Greece
| | - Georgios Galazios
- Department of Obstetrics and Gynaecology, Democritus University of Thrace, Alexandroupolis, Greece
| | - Dimitrios Souftas
- Department of Social Administration, Democritus University of Thrace, Alexandroupolis, Greece
| | - Vasileios Souftas
- Department of Radiology and Medical Imaging, Democritus University of Thrace, Alexandroupolis, Greece
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Bukovsky A. Novel Immunological Aspects for the Treatment of Age-induced Ovarian and Testicular Infertility, Other Functional Diseases, and Early and Advanced Cancer Immunotherapy. Hum Reprod 2016. [DOI: 10.1002/9781118849613.ch4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Affiliation(s)
- Antonin Bukovsky
- The Laboratory of Reproductive Biology BIOCEV, Institute of Biotechnology; Academy of Sciences of the Czech Republic; Prague Czech Republic
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Bukovsky A. Involvement of blood mononuclear cells in the infertility, age-associated diseases and cancer treatment. World J Stem Cells 2016; 8:399-427. [PMID: 28074124 PMCID: PMC5183987 DOI: 10.4252/wjsc.v8.i12.399] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2016] [Revised: 08/19/2016] [Accepted: 09/21/2016] [Indexed: 02/06/2023] Open
Abstract
Blood mononuclear cells consist of T cells and monocyte derived cells. Beside immunity, the blood mononuclear cells belong to the complex tissue control system (TCS), where they exhibit morphostatic function by stimulating proliferation of tissue stem cells followed by cellular differentiation, that is stopped after attaining the proper functional stage, which differs among various tissue types. Therefore, the term immune and morphostatic system (IMS) should be implied. The TCS-mediated morphostasis also consists of vascular pericytes controlled by autonomic innervation, which is regulating the quantity of distinct tissues in vivo. Lack of proper differentiation of tissue cells by TCS causes either tissue underdevelopment, e.g., muscular dystrophy, or degenerative functional failures, e.g., type 1 diabetes and age-associated diseases. With the gradual IMS regression after 35 years of age the gonadal infertility develops, followed by a growing incidence of age-associated diseases and cancers. Without restoring an altered TCS function in a degenerative disease, the implantation of tissue-specific stem cells alone by regenerative medicine can not be successful. Transfused young blood could temporarily restore fertility to enable parenthood. The young blood could also temporarily alleviate aging diseases, and this can be extended by substances inducing IMS regeneration, like the honey bee propolis. The local and/or systemic use of honey bee propolis stopped hair and teeth loss, regressed varicose veins, improved altered hearing, and lowered high blood pressure and sugar levels. Complete regression of stage IV ovarian cancer with liver metastases after a simple elaborated immunotherapy is also reported.
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Affiliation(s)
- Antonin Bukovsky
- Antonin Bukovsky, Laboratory of Reproductive Biology BIOCEV, Institute of Biotechnology Czech Academy of Sciences, 25250 Vestec, Czech Republic
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Jin H, Won M, Park SE, Lee S, Park M, Bae J. FOXL2 Is an Essential Activator of SF-1-Induced Transcriptional Regulation of Anti-Müllerian Hormone in Human Granulosa Cells. PLoS One 2016; 11:e0159112. [PMID: 27414805 PMCID: PMC4944948 DOI: 10.1371/journal.pone.0159112] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2016] [Accepted: 06/27/2016] [Indexed: 11/17/2022] Open
Abstract
Anti-Müllerian hormone (AMH) is required for proper sexual differentiation by regulating the regression of the Müllerian ducts in males. Recent studies indicate that AMH could be an important factor for maintaining the ovarian reserve. However, the mechanisms of AMH regulation in the ovary are largely unknown. Here, we provide evidence that AMH is an ovarian target gene of steroidogenic factor-1 (SF-1), an orphan nuclear receptor required for proper follicle development. FOXL2 is an evolutionally conserved transcription factor, and its mutations cause blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES), wherein affected females display eyelid defects and premature ovarian failure (POF). Notably, we found that functional FOXL2 is essential for SF-1-induced AMH regulation, via protein-protein interactions between FOXL2 and SF-1. A BPES-inducing mutant of FOXL2 (290-291delCA) was unable to interact with SF-1 and failed to mediate the association between SF-1 and the AMH promoter. Therefore, this study identified a novel regulatory circuit for ovarian AMH production; specifically, through the coordinated interplay between FOXL2 and SF-1 that could control ovarian follicle development.
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Affiliation(s)
- Hanyong Jin
- School of Pharmacy, Chung-Ang University, Seoul, Korea
| | - Miae Won
- Department of Pharmacy, CHA University, Seongnam, Korea
| | - Si Eun Park
- School of Pharmacy, Chung-Ang University, Seoul, Korea
| | - Seunghwa Lee
- Department of Life Science, Chung-Ang University, Seoul, Korea
| | - Mira Park
- School of Pharmacy, Chung-Ang University, Seoul, Korea
| | - Jeehyeon Bae
- School of Pharmacy, Chung-Ang University, Seoul, Korea
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Iwata H. Age-associated events in bovine oocytes and possible countermeasures. Reprod Med Biol 2016; 15:155-164. [PMID: 29259432 PMCID: PMC5715852 DOI: 10.1007/s12522-015-0233-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2015] [Accepted: 12/19/2015] [Indexed: 01/31/2023] Open
Abstract
Maternal aging profoundly affects oocyte quality. This has become common knowledge in industrialized countries and extensive studies addressing the causes and possible countermeasures against age-associated deterioration of oocytes suggest that mitochondrial dysfunction is a causal factor in infertility. However, almost all studies addressing age-associated events in oocytes have used mice as an animal model, and the reproductive life of mice is very short, making it difficult to study the gradual decline in fertility observed in humans. In the present review, age-associated changes in the quality and quantity of bovine oocytes and possible countermeasures related to mitochondrial quality control are introduced.
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Affiliation(s)
- Hisataka Iwata
- Tokyo University of AgricultureFunako 1737243‐034AtsugiKanagawaJapan
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