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Chen Y, Waseem S, Luo L. Advances in the diagnosis and management of endometriosis: A comprehensive review. Pathol Res Pract 2025; 266:155813. [PMID: 39808858 DOI: 10.1016/j.prp.2025.155813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Revised: 11/11/2024] [Accepted: 01/03/2025] [Indexed: 01/16/2025]
Abstract
Endometriosis is a prevalent gynecological condition characterized by the presence of endometrial-like tissue outside the uterus, leading to chronic pelvic pain and infertility. This review aims to shed light on the latest advancements in diagnosing and managing endometriosis. It offers insight into the condition's pathogenesis, clinical symptoms, diagnostic techniques, and available treatment approaches. Furthermore, the article emphasizes innovative technologies and novel therapeutic strategies that promise to enhance patient outcomes significantly. This review aspires to empower clinicians to deliver the highest quality care to their patients affected by this challenging condition by consolidating the current understanding of endometriosis.
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Affiliation(s)
- Yingying Chen
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China
| | - Shanza Waseem
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China; Department of Gynecology and Obstetrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second Hospital, Sichuan University, Chengdu, Sichuan Province 610041, China
| | - Li Luo
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China.
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Nezhat FR, Cathcart AM, Nezhat CH, Nezhat CR. Pathophysiology and Clinical Implications of Ovarian Endometriomas. Obstet Gynecol 2024; 143:759-766. [PMID: 38626453 PMCID: PMC11090516 DOI: 10.1097/aog.0000000000005587] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Revised: 03/12/2024] [Accepted: 03/14/2024] [Indexed: 04/18/2024]
Abstract
Ovarian endometriomas affect many patients with endometriosis and have significant effects on quality of life, fertility, and risk of malignancy. Endometriomas range from small (1-3 cm), densely fibrotic cysts to large (20 cm or greater) cysts with varying degrees of fibrosis. Endometriomas are hypothesized to form from endometriotic invasion or metaplasia of functional cysts or alternatively from ovarian surface endometriosis that bleeds into the ovarian cortex. Different mechanisms of endometrioma formation may help explain the phenotypic variability observed among endometriomas. Laparoscopic surgery is the preferred first-line modality of diagnosis and treatment of endometriomas. Ovarian cystectomy is preferred over cyst ablation or sclerotherapy for enabling pathologic diagnosis, improving symptoms, preventing recurrence, and optimizing fertility outcomes. Cystectomy for small, densely adherent endometriomas is made challenging by dense fibrosis of the cyst capsule obliterating the plane with normal ovarian cortex, whereas cystectomy for large endometriomas can carry unique challenges as a result of adhesions between the cyst and pelvic structures. Preoperative and postoperative hormonal suppression can improve operative outcomes and decrease the risk of endometrioma recurrence. Whether the optimal management, fertility consequences, and malignant potential of endometriomas vary on the basis of size and phenotype remains to be fully explored.
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Affiliation(s)
- Farr R Nezhat
- Weill Cornell Medical College, Cornell University, New York, and NYU Long Island School of Medicine, Mineola, New York; the Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, Oregon; the Atlanta Center for Minimally Invasive Surgery and Reproductive Medicine, Atlanta, Georgia; and the Center for Special Minimally Invasive and Robotic Surgery, and Stanford University Medical Center, Palo Alto, and the University of California, San Francisco, San Francisco, California
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Management of Ovarian Endometrioma in Asymptomatic Reproductive Age Women. CURRENT OBSTETRICS AND GYNECOLOGY REPORTS 2021. [DOI: 10.1007/s13669-021-00311-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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Wang L, Jiang YJ. Rupture of ovarian endometriotic cyst complicated with endometriosis: A case report. World J Clin Cases 2021; 9:8524-8530. [PMID: 34754863 PMCID: PMC8554428 DOI: 10.12998/wjcc.v9.i28.8524] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Revised: 06/30/2021] [Accepted: 08/02/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Endometriosis (EMs), an estrogen-dependent disease, refers to the appearance of mucosa-covered endometrial tissues (glandular and interstitial) growing in the uterine cavity outside the uterine myometrium. It is commonly seen in women aged 25 to 45, with an incidence of approximately 10%-15%.
CASE SUMMARY A 35-year-old unmarried female who denied a history of sex with an intact hymen had multiple dysmenorrhea and pain in the left lower abdomen that recurred during menstruation. Ultrasound examination revealed a dark cystic area measuring 4.9 cm × 4.6 cm on the left side with poor light transmittance, which suggested a left endometriotic cyst. The patient was treated with pain medications (four capsules t.i.d., p.o.). After one month, computed tomography of the abdomen and pelvis revealed a low-density focus measuring approximately 38 mm in diameter, a blurred mesentery fat plane in the pelvic cavity, and pelvic effusion. Ultrasound showed a complex echo density measuring 5.2 cm × 3.0 cm × 4.2 cm in the left ovarian area and a fluid sonolucent area with a depth of 2.0 cm in the pelvic cavity. Left ovarian cystectomy, electrocautery for endometriotic lesions, myomectomy, and pelvic adhesion lysis were performed under laparoscopy. The postoperative diagnosis was left ovarian chocolate cyst rupture and EMs (stage III, ovarian type, peritoneal type).
CONCLUSION Laparoscopic surgery can safely control the symptoms of EMs and effectively eradicate the disease.
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Affiliation(s)
- Lu Wang
- Department of Gynecology, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310005, Zhejiang Province, China
| | - Yan-Jiao Jiang
- Department of Gynecology, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310005, Zhejiang Province, China
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Alborzi S, Askary E, Keramati P, Moradi Alamdarloo S, Poordast T, Ashraf MA, Shomali Z, Namavar Jahromi B, Zahiri Sorouri Z. Assisted reproductive technique outcomes in patients with endometrioma undergoing sclerotherapy vs laparoscopic cystectomy: Prospective cross-sectional study. Reprod Med Biol 2021; 20:313-320. [PMID: 34262399 PMCID: PMC8254172 DOI: 10.1002/rmb2.12386] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Revised: 04/11/2021] [Accepted: 04/13/2021] [Indexed: 12/02/2022] Open
Abstract
PURPOSE The authors compared assisted reproductive technique (ART) outcomes and the recurrence rate of endometrioma in the infertile patients undergoing sclerotherapy vs laparoscopic ovarian cystectomy. METHODS In this prospective cross-sectional study, a total of 101 infertile patients, with unilateral endometriomas, were divided into two groups. The first group (n = 57) underwent ART after 1 year of unsuccessful spontaneous pregnancy after laparoscopic ovarian cystectomy; the second group (n = 44) had ethanol sclerotherapy (EST) at the time of oocyte retrieval. The authors measured the number of oocytes, clinical pregnancy rate (CPR), live birth rate (LBR), complication, and recurrence of endometriomas as the primary and secondary outcomes. RESULTS The two groups had no significant differences in baseline characteristics and ovarian stimulation markers and also total number of oocytes. 42.1% and 34.1% of the patients (n = 24 and 15) had clinical pregnancy, and 38.6% and 29.5% (n = 22 and 13) had live birth following ART cycles in the surgery group and sclerotherapy group (P = .41, 0.34). The recurrence rates were 14.0% and 34.1% in the surgery and sclerotherapy groups (P = .017, X 2 = 5.67). CONCLUSIONS Ethanol sclerotherapy can be a good alternative to surgery concerning the treatment of endometrioma; however, the recurrence of the disease in this group is significantly higher.
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Affiliation(s)
- Saeed Alborzi
- Department of Obstetrics and GynecologyLaparoscopy Research CenterSchool of MedicineShiraz University of Medical SciencesShirazIran
| | - Elham Askary
- Department of Obstetrics and GynecologyInfertility Research CenterSchool of MedicineShiraz University of Medical SciencesShirazIran
| | - Pegah Keramati
- Department of Obstetrics and GynecologySchool of MedicineShiraz University of Medical SciencesShirazIran
| | - Shaghayegh Moradi Alamdarloo
- Department of Obstetrics and GynecologyInfertility Research CenterSchool of MedicineShiraz University of Medical SciencesShirazIran
| | - Tahereh Poordast
- Department of Obstetrics and GynecologyInfertility Research CenterSchool of MedicineShiraz University of Medical SciencesShirazIran
| | - Mohammad Ali Ashraf
- Department of Obstetrics and GynecologySchool of MedicineShiraz University of Medical SciencesShirazIran
| | - Zahra Shomali
- Department of Obstetrics and GynecologySchool of MedicineShiraz University of Medical SciencesShirazIran
| | - Behieh Namavar Jahromi
- Department of Obstetrics and GynecologyLaparoscopy Research CenterSchool of MedicineShiraz University of Medical SciencesShirazIran
| | - Ziba Zahiri Sorouri
- Department of Obstetrics and GynecologyLaparoscopy Research CenterSchool of MedicineGuilan University of Medical SciencesRashtIran
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Ding S, Yu Q, Wang J, Zhu L, Li T, Guo X, Zhang X. Activation of ATF3/AP-1 signaling pathway is required for P2X3-induced endometriosis pain. Hum Reprod 2021; 35:1130-1144. [PMID: 32303740 DOI: 10.1093/humrep/deaa061] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2019] [Revised: 02/26/2020] [Indexed: 12/22/2022] Open
Abstract
STUDY QUESTION Does P2X ligand-gated ion channel 3 (P2X3) play a role in endometriosis pain? SUMMARY ANSWER Upregulation of P2X3 in dorsal root ganglia (DRG) tissues via the activating transcription factor 3 (ATF3)/activator protein (AP)-1 pathway contributed to endometriosis-associated hyperalgesia, which could be attenuated by the chitosan oligosaccharide stearic acid (CSOSA)/liposomes (LPs)/SP600125 delivery system. WHAT IS KNOWN ALREADY Infiltrating nerve fibers and elevated nociceptors in endometriotic lesions are associated with endometriosis pain. P2X3 has been demonstrated to play an important role in neuropathic pain. STUDY DESIGN, SIZE, DURATION A rat model of endometriosis was used to investigate the signaling pathways involved in P2X3-induced pain. PARTICIPANTS/MATERIALS, SETTING, METHODS Degrees of hyperalgesia, endogenous adenosine 5'-triphosphate (ATP) contents and P2X3 expression levels in endometriotic lesions and DRG tissues were detected in a rat model of endometriosis. The expression levels of ATF3 and P2X3 were measured using qRT-PCR, western blot analysis and immunofluorescence analysis after adenosine 5'-diphosphate (ADP) exposure in DRG cells. Plasmids encoding ATF3 and its siRNA were used to investigate the role of ATF3 on ADP-induced P2X3 upregulation. The activity of ATF binding to the P2X3 promoter was evaluated by using chromatin immunoprecipitation (CHIP) and luciferase assays. SP600125, an inhibitor of c-JUN N-terminal kinase, was wrapped in CSOSA/LPs delivery system and its inhibitory effects on ADP-induced upregulation of P2X3 in DRG cells and endometriosis-induced hyperalgesia in rats were tested. MAIN RESULTS AND THE ROLE OF CHANCE The concentrations of endogenous ATP and expression levels of P2X3 were significantly increased in both endometriotic lesions and DRG tissues in endometriosis rat models and were found to be positively correlated with the severity of hyperalgesia. In DRG cells, P2X3 expression levels were elevated by ADP stimulation, but dramatically inhibited by blocking ATF3 with its siRNA and SP600125. CHIP and luciferase assay showed that ADP increased the binding of ATF3 to the P2X3 promoter, resulting in an increase in P2X3 expression levels. In the CSOSA/LPs/SP600125 delivery system, the drug could be effectively concentrated in endometriotic lesions, and it could alleviate endometriosis-induced hyperalgesia, reduce the size of endometriotic lesions and attenuate upregulated P2X3 expression levels in endometriosis rat models. LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION Changes in the sensitivity and function of P2X3 caused by endometriosis need to be further investigated. WIDER IMPLICATIONS OF THE FINDINGS This study indicates that ATP and the P2X3 receptor are involved in endometriosis pain, thus providing a novel therapeutic approach for the treatment of endometriosis pain by targeting the P2X3 receptor. STUDY FUNDING/COMPETING INTEREST(S) This work was funded by National Key R&D Program of China (Grant No. 2017YFC1001202) and National Natural Science Foundation of China (Grant Nos. 81974225, 81671429 and 81471433). There are no competing interests.
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Affiliation(s)
- Shaojie Ding
- Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang, P.R. China
| | - Qin Yu
- Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang, P.R. China
| | - Jianzhang Wang
- Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang, P.R. China
| | - Libo Zhu
- Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang, P.R. China
| | - Tiantian Li
- Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang, P.R. China
| | - Xinyue Guo
- Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang, P.R. China
| | - Xinmei Zhang
- Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang, P.R. China
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A National Survey of Umbilical Endometriosis in Japan. J Minim Invasive Gynecol 2020; 27:80-87. [DOI: 10.1016/j.jmig.2019.02.021] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2018] [Revised: 02/03/2019] [Accepted: 02/13/2019] [Indexed: 12/30/2022]
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Streuli I, Benard J, Hugon-Rodin J, Chapron C, Santulli P, Pluchino N. Shedding light on the fertility preservation debate in women with endometriosis: a swot analysis. Eur J Obstet Gynecol Reprod Biol 2018; 229:172-178. [DOI: 10.1016/j.ejogrb.2018.08.577] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2018] [Revised: 08/17/2018] [Accepted: 08/20/2018] [Indexed: 01/21/2023]
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Harada T, Momoeda M. Evaluation of an ultra-low-dose oral contraceptive for dysmenorrhea: a placebo-controlled, double-blind, randomized trial. Fertil Steril 2016; 106:1807-1814. [PMID: 27717552 DOI: 10.1016/j.fertnstert.2016.08.051] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2016] [Revised: 08/31/2016] [Accepted: 08/31/2016] [Indexed: 10/20/2022]
Abstract
OBJECTIVE To evaluate the efficacy and safety of an ultra-low-dose oral contraceptive (NPC-01; 0.02 mg ethinyl estradiol and 1 mg norethisterone) in subjects with dysmenorrhea. DESIGN Placebo-controlled, double-blind, randomized trial. SETTING Clinical trial sites. PATIENT(S) Two hundred fifteen subjects with dysmenorrhea. INTERVENTION(S) Subjects were randomly assigned to receive NPC-01, placebo, or IKH-01 (0.035 mg ethinyl estradiol and 1 mg norethisterone) for four cycles. MAIN OUTCOME MEASURE(S) Total dysmenorrhea score (verbal rating scale) assessing pain on the basis of limited ability to work and need for analgesics. RESULT(S) The reductions of total dysmenorrhea score and visual analog scale score after the treatment were significantly higher in the NPC-01 group than in the placebo group. Furthermore, the efficacy of NPC-01 was comparable to that of IKH-01. The overall incidence of side effects was significantly higher in the NPC-01 group than in the placebo group. All side effects that occurred in the NPC-01 group were previously reported in patients receiving IKH-01. No serious side effects occurred. CONCLUSION(S) The ultra-low-dose contraceptive NPC-01 relieved dysmenorrhea as effectively as IKH-01. Thus, NPC-01 could represent a new option for long-term treatment of dysmenorrhea. CLINICAL TRIAL IDENTIFICATION NUMBER NCT01129102.
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Affiliation(s)
- Tasuku Harada
- Department of Obstetrics and Gynecology, Tottori University School of Medicine, Tottori, Japan.
| | - Mikio Momoeda
- Department of Integrated Women's Health, St. Luke's International Hospital, Tokyo, Japan
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10
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Laschke MW, Menger MD. The gut microbiota: a puppet master in the pathogenesis of endometriosis? Am J Obstet Gynecol 2016; 215:68.e1-4. [PMID: 26901277 DOI: 10.1016/j.ajog.2016.02.036] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2015] [Revised: 02/01/2016] [Accepted: 02/13/2016] [Indexed: 02/08/2023]
Abstract
Endometriosis is a frequent gynecologic disease with a complex, multifactorial cause. It is characterized by the cyclic estrogen-driven proliferation and bleeding of endometriotic lesions (ie, ectopic endometrial glands and stroma) outside the uterus. These lesions induce a chronic activation of the innate immune system within the peritoneal cavity that is associated with the release of various inflammatory cytokines and angiogenic growth factors into the peritoneal fluid. This stimulates angiogenesis and the further spread of the lesions and triggers the typical pain that is symptomatic of the disease. Moreover, circulating stem and progenitor cells are recruited into the ectopic endometrial tissue and contribute to its growth and vascularization. In recent years, an increasing number of studies have indicated that the gut microbiota is not only essential for a physiologic gastrointestinal function but acts as a central regulator of a variety of inflammatory and proliferative conditions. Besides, the gut flora affects estrogen metabolism and stem-cell homeostasis. Based on these findings, we hypothesize that the gut microbiota may be involved crucially in the onset and progression of endometriosis. In the future, this novel view of the pathogenesis of endometriosis may be verified by analysis of the development of endometriotic lesions in animal models with a defined composition of the gut microbiota and by investigation of the microbiota of patients with endometriosis with modern next-generation sequencing tools. This could open the door for completely new preventive, diagnostic, and therapeutic approaches for endometriosis.
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Abdominal Wall Endometrioma after Laparoscopic Operation of Uterine Endometriosis. Case Rep Surg 2016; 2016:5843179. [PMID: 27340586 PMCID: PMC4906174 DOI: 10.1155/2016/5843179] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2015] [Accepted: 04/06/2016] [Indexed: 11/17/2022] Open
Abstract
Endometriosis is presence of functional endometrium outside of uterine cavum. As a pluripotent tissue, endometrium has the possibility of implanting itself almost everywhere; even implantation in abdominal wall was described, but it is not common site. This case report presents implantation of functional endometrium in abdominal wall, inside scar tissue, and after insertion of a laparoscopic trocar port. Final diagnosis was confirmed by pathohistological examination.
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Takaesu Y, Nishi H, Kojima J, Sasaki T, Nagamitsu Y, Kato R, Isaka K. Dienogest compared with gonadotropin-releasing hormone agonist after conservative surgery for endometriosis. J Obstet Gynaecol Res 2016; 42:1152-8. [DOI: 10.1111/jog.13023] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2015] [Revised: 02/14/2016] [Accepted: 03/11/2016] [Indexed: 12/17/2022]
Affiliation(s)
- Yotaro Takaesu
- Department of Obstetrics and Gynecology; Tokyo Medical University; Tokyo Japan
- St. John's Society Sakuramachi Hospital; Tokyo Japan
| | - Hirotaka Nishi
- Department of Obstetrics and Gynecology; Tokyo Medical University; Tokyo Japan
| | - Junya Kojima
- Department of Obstetrics and Gynecology; Tokyo Medical University; Tokyo Japan
| | - Toru Sasaki
- Department of Obstetrics and Gynecology; Tokyo Medical University; Tokyo Japan
| | - Yuzo Nagamitsu
- Department of Obstetrics and Gynecology; Tokyo Medical University; Tokyo Japan
| | - Rina Kato
- Department of Obstetrics and Gynecology; Tokyo Medical University; Tokyo Japan
| | - Keiichi Isaka
- Department of Obstetrics and Gynecology; Tokyo Medical University; Tokyo Japan
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A systematic review of ultrasonography-guided transvaginal aspiration of recurrent ovarian endometrioma. Int J Gynaecol Obstet 2016; 134:3-7. [DOI: 10.1016/j.ijgo.2015.10.021] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2015] [Revised: 10/23/2015] [Accepted: 02/29/2016] [Indexed: 12/19/2022]
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14
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Clinical management of endometriosis-associated infertility. Reprod Med Biol 2016; 15:217-225. [PMID: 29259439 DOI: 10.1007/s12522-016-0237-9] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2015] [Accepted: 02/01/2016] [Indexed: 12/19/2022] Open
Abstract
Endometriosis is a common chronic benign disease that affects reproductive age women and causes chronic pelvic pain and infertility. Despite its prevalence, the exact mechanisms of the pathogenesis of endometriosis-associated infertility are unknown, and precise standards of management have not yet been established. Medical and surgical treatments for endometriosis have different effects on the chance of conception, either spontaneously or via assisted reproductive technologies (ART). In this manuscript, we review the literature from years 1979 to 2015 to report on the proposed mechanism of endometriosis-associated infertility, the staging system of endometriosis for pregnancy outcomes and the current management of patients with endometriosis-associated infertility.
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Abstract
Endometriosis is a disease characterized by the growth of endometrial tissue outside the uterus and is associated with chronic pelvic pain. Peritoneal fluid (PF) of women with endometriosis is a dynamic milieu and is rich in inflammatory markers, pain-inducing prostaglandins prostaglandin E2 and prostaglandin F2α, and lipid peroxides; and the endometriotic tissue is innervated with nociceptors. Our clinical study showed that the abundance of oxidatively modified lipoproteins in the PF of women with endometriosis and the ability of antioxidant supplementation to alleviate endometriosis-associated pain. We hypothesized that oxidatively modified lipoproteins present in the PF are the major source of nociceptive molecules that play a key role in endometriosis-associated pain. In this study, PF obtained from women with endometriosis or control women were used for (1) the detection of lipoprotein-derived oxidation-sensitive pain molecules, (2) the ability of such molecules to induce nociception, and (3) the ability of antioxidants to suppress this nociception. LC-MS/MS showed the generation of eicosanoids by oxidized-lipoproteins to be similar to that seen in the PF. Oxidatively modified lipoproteins induced hypothermia (intracerebroventricular) in CD-1 mice and nociception in the Hargreaves paw withdrawal latency assay in Sprague-Dawley rats. Antioxidants, vitamin E and N-acetylcysteine, and the nonsteroidal anti-inflammatory drug indomethacin suppressed the pain-inducing ability of oxidatively modified lipoproteins. Treatment of human endometrial cells with oxidatively modified lipoproteins or PF from women with endometriosis showed upregulation of similar genes belonging to opioid and inflammatory pathways. Our finding that oxidatively modified lipoproteins can induce nociception has a broader impact not only on the treatment of endometriosis-associated pain but also on other diseases associated with chronic pain.
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Koga K, Takamura M, Fujii T, Osuga Y. Prevention of the recurrence of symptom and lesions after conservative surgery for endometriosis. Fertil Steril 2015; 104:793-801. [DOI: 10.1016/j.fertnstert.2015.08.026] [Citation(s) in RCA: 93] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2015] [Revised: 08/20/2015] [Accepted: 08/24/2015] [Indexed: 01/02/2023]
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Nezhat FR, Apostol R, Nezhat C, Pejovic T. New insights in the pathophysiology of ovarian cancer and implications for screening and prevention. Am J Obstet Gynecol 2015; 213:262-7. [PMID: 25818671 DOI: 10.1016/j.ajog.2015.03.044] [Citation(s) in RCA: 105] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2014] [Revised: 01/31/2015] [Accepted: 03/20/2015] [Indexed: 11/30/2022]
Abstract
Despite advances in medicine, ovarian cancer remains the deadliest of the gynecological malignancies. Herein we present the latest information on the pathophysiology of ovarian cancer and its significance for ovarian cancer screening and prevention. A new paradigm for ovarian cancer pathogenesis presupposes 2 distinct types of ovarian epithelial carcinoma with distinct molecular profiles: type I and type II carcinomas. Type I tumors include endometrioid, clear-cell carcinoma, and low-grade serous carcinoma and mostly arise via defined sequence either from endometriosis or from borderline serous tumors, mostly presenting in an early stage. More frequent type II carcinomas are usually high-grade serous tumors, and recent evidence suggests that the majority arise from the fimbriated end of the fallopian tube. Subsequently, high-grade serous carcinomas usually present at advanced stages, likely as a consequence of the rapid peritoneal seeding from the open ends of the fallopian tubes. On the other hand, careful clinical evaluation should be performed along with risk stratification and targeted treatment of women with premalignant conditions leading to type I cancers, most notably endometriosis and endometriomas. Although the chance of malignant transformation is low, an understanding of this link offers a possibility of prevention and early intervention. This new evidence explains difficulties in ovarian cancer screening and helps in forming new recommendations for ovarian cancer risk evaluation and prophylactic treatments.
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MESH Headings
- Adenocarcinoma, Clear Cell/classification
- Adenocarcinoma, Clear Cell/pathology
- Adenocarcinoma, Clear Cell/prevention & control
- Carcinoma, Endometrioid/classification
- Carcinoma, Endometrioid/pathology
- Carcinoma, Endometrioid/prevention & control
- Early Detection of Cancer
- Endometriosis/surgery
- Fallopian Tubes
- Female
- Humans
- Neoplasm Grading
- Neoplasms, Cystic, Mucinous, and Serous/classification
- Neoplasms, Cystic, Mucinous, and Serous/pathology
- Neoplasms, Cystic, Mucinous, and Serous/prevention & control
- Ovarian Diseases/surgery
- Ovarian Neoplasms/classification
- Ovarian Neoplasms/pathology
- Ovarian Neoplasms/prevention & control
- Ovariectomy
- Precancerous Conditions/surgery
- Salpingectomy
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Affiliation(s)
- Farr R Nezhat
- Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Mount Sinai Roosevelt, Division of Minimally Invasive Gynecologic Surgery, Winthrop University Hospital, State University of New York at Stony Brook, College of Medicine, New York, NY.
| | - Radu Apostol
- Department of Obstetrics and Gynecology, Division of Minimally Invasive Gynecologic Surgery, Mount Sinai-St. Luke's and Roosevelt Hospital System, New York, NY
| | - Camran Nezhat
- Center for Special Minimally Invasive and Robotic Surgery, Palo Alto, CA
| | - Tanja Pejovic
- Division of Gynecologic Oncology, Oregon Health and Science University, Portland, OR
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Yun BH, Jeon YE, Chon SJ, Park JH, Seo SK, Cho S, Choi YS, Lee JS, Lee BS. The Prognostic Value of Individual Adhesion Scores from the Revised American Fertility Society Classification System for Recurrent Endometriosis. Yonsei Med J 2015; 56:1079-86. [PMID: 26069133 PMCID: PMC4479838 DOI: 10.3349/ymj.2015.56.4.1079] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
PURPOSE This study aimed to evaluate the prognostic value of each component of the revised American Fertility Society (rAFS) classification system for the first recurrence of endometriosis after conservative laparoscopy. MATERIALS AND METHODS As this was a retrospective cohort study, data were collected by reviewing medical records. A total of 379 women ages 18 to 49 years were included. Women who underwent conservative laparoscopy with histologic confirmation of endometriosis at Gangnam Severance Hospital between March 2003 and May 2010 were included. Individual components of the rAFS classification system as well as preoperative serum CA-125 levels were retrospectively analyzed to assess their prognostic values for recurrence of endometriosis. RESULTS Of 379 patients, 80 (21.2%) were found to have recurrence of endometriosis. The median duration of follow-up was 19.0 months, and the mean age at the time of surgery was 31.8±6.7 years. In endometriosis of advanced stage, younger age at the time of surgery, bilateral ovarian cysts at the time of diagnosis, a rAFS ovarian adhesion score >24, and complete cul-de-sac obliteration were independent risk factors of poor outcomes, and a rAFS ovarian adhesion score >24 had the highest risk of recurrence [hazard ratio=2.948 (95% CI: 1.116-7.789), p=0.029]. CONCLUSION Our results suggest that of the rAFS adnexal adhesion scores, the ovarian adhesion score rather than the tubal adhesion score was associated with a significantly increased risk of recurrent endometriosis. The preoperative serum CA-125 level may be also a significant prognostic factor for recurrence, as known. However, it seemed to only have borderline significance in affecting recurrence in the current study.
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Affiliation(s)
- Bo Hyon Yun
- Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.; Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea
| | - Young Eun Jeon
- Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea.; Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Seung Joo Chon
- Department of Obstetrics and Gynecology, Gil Hospital, Graduate School of Medicine, Gachon University of Medicine and Science, Incheon, Korea
| | - Joo Hyun Park
- Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea.; Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Seok Kyo Seo
- Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.; Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea
| | - SiHyun Cho
- Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea.; Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Young Sik Choi
- Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.; Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea
| | - Ji Sung Lee
- Department of Obstetrics and Gynecology, Gil Hospital, Graduate School of Medicine, Gachon University of Medicine and Science, Incheon, Korea.
| | - Byung Seok Lee
- Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.; Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea.
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A randomized study comparing the side effects and hormonal status of triptorelin and leuprorelin following conservative laparoscopic surgery for ovarian endometriosis in Chinese women. Eur J Obstet Gynecol Reprod Biol 2014; 183:164-8. [PMID: 25461372 DOI: 10.1016/j.ejogrb.2014.10.022] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2014] [Revised: 10/01/2014] [Accepted: 10/22/2014] [Indexed: 11/23/2022]
Abstract
OBJECTIVES Different gonadotropin-releasing-hormone agonist (GnRH-a) formulations with different potency and associated side effects, therefore, different compliance and persistence of therapy. This study was to evaluate the difference of hormonal profile and side effects due to hypoestrogenic status after treatment of leuprorelin and triptorelin in Chinese women with ovarian endometrioma after conservative surgical treatment. STUDY DESIGN A total of 302 women underwent laparoscopic excision of ovarian endometriomas with rASRM III and IV were enrolled in the study.Subjects were randomized into two groups with use of a random table. Twenty two patients dropped out during the study. Thus 142 patients had three doses of i.m. leuprorelin (group A) and 138 patients had three doses of i.m. triptorelin(group B) at 4 weeks intervals after surgical treatment. Menopausal symptoms were evalutaed using a questionnaire and serum sex hormonal levels were also measured during the follow-up. RESULTS At week 4 after the treatment, most of the patients in leuprorelin group have no obvious side effects. After 9 weeks, bone pain, hot flashes and sweating, and irregular bleeding were the main side effects and showed no difference between the groups. Anxiety, depression, vaginal dryness, headache, and acne rates were all significantly higher in triptorelin group than in leuprorelin group. A significant difference in FSH (p=0.003), LH (p=0.026) and E2 (p=0.002) levels between the groups were observed after 21 days of the GnRHa treatment. The FSH (p=0.021) and E2 (p=0.033) levels remained higher in the leuprorelin group than the triptorelin group after six weeks of treatment, but the difference of LH(p=0.917) level was no longer discernible. CONCLUSION Leuprorelin in down-regulating the pituitary-ovarian function was more moderate, and the hormonal levels decrease progressively and gradually, therefore, with lower rate of menopausal symptoms. Leuprorelin acetate maybe better tolerated than triptorelin.
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Somigliana E, Vercellini P, Vigano P, Benaglia L, Busnelli A, Fedele L. Postoperative medical therapy after surgical treatment of endometriosis: from adjuvant therapy to tertiary prevention. J Minim Invasive Gynecol 2013; 21:328-34. [PMID: 24157566 DOI: 10.1016/j.jmig.2013.10.007] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2013] [Revised: 10/15/2013] [Accepted: 10/15/2013] [Indexed: 01/03/2023]
Abstract
The high rate of disease recurrence after surgery is critical and frustrating for women with endometriosis. Adjuvant treatments using a 3- to 6-months course of hormone therapy after surgery have been extensively investigated during the last 2 decades; however, results have been unsatisfactory, primarily because the benefits of hormone therapy rapidly vanish once treatment is discontinued. The protective effect is limited to the period of use. Accordingly, it is recognized that suppressive hormone therapy after surgery markedly prevents recurrent episodes only if given over the long term. The emerging view is that estroprogestins do not ameliorate the effects of surgery but demonstrate tertiary prevention of the disease. They prevent ovulation and reduce retrograde menstrual flow, two crucial events in the pathogenesis of endometriosis. The available literature strongly supports the benefits of prolonged administration of estroprogestins after surgery in preventing recurrence of endometriomas and dysmenorrhea. In contrast, data on dyspareunia and nonmenstrual pelvic pain remain scanty and unconvincing, and there is no information about recurrence of other forms of endometriosis such as peritoneal implants and adhesions. Overall, estroprogestin therapy after surgery to treat endometriosis should be recommended in women who do not seek to become pregnant. Further evidence is warranted to better delineate the beneficial effects of this emerging but convincing strategy.
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Affiliation(s)
| | - Paolo Vercellini
- Fondazione Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy; Università degli Studi di Milano, Milan, Italy
| | - Paola Vigano
- Obstetrics and Gynecology Unit, Scientific Institute San Raffaele, Milan, Italy
| | - Laura Benaglia
- Fondazione Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | - Andrea Busnelli
- Fondazione Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy; Università degli Studi di Milano, Milan, Italy
| | - Luigi Fedele
- Fondazione Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy; Università degli Studi di Milano, Milan, Italy
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