Premature Ovarian Failure

In: Clinical Journal of Obstetrics and Gynecology · 2025 · vol. 8(3) , pp. 061–068 · doi:10.29328/journal.cjog.1001189 · W4412383234
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This review synthesizes epidemiological, genetic, immunological, and environmental factors contributing to premature ovarian failure, highlighting chemotherapy, endometriosis, and genetic mutations as key influences.

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This structured literature review synthesizes epidemiological, genetic, immunological, and environmental factors contributing to premature ovarian failure (POF), with emphasis on regional disparities, occupational exposures, iatrogenic effects (especially chemotherapy), and fertility preservation strategies, and it also addresses the occurrence and recurrence of “endometrosis.” Across reported literature, POF prevalence varies globally and is estimated to affect about 1% of women under 40, with key genetic contributions including FMR1 and BMP15 mutations and associations with autoimmune diseases; chemotherapy and ovarian cyst surgery are identified as major contributors to reduced ovarian reserve. The authors note limitations typical of a review synthesis, including reliance on heterogeneous published reports and the need for further genomic studies to clarify rare mutations and their effects. Relevance to endometriosis: the review specifically addresses “endometrosis” in the context of POF occurrence and recurrence and also cites ovarian-reserve impacts of endometriosis, though its main focus is the multifactorial causes and risk factors of premature ovarian failure.

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Abstract

Objective: To provide a rigorous, multidisciplinary synthesis of the epidemiological, genetic, immunological, and environmental factors contributing to Premature Ovarian Failure (POF), with particular attention to regional disparities, occupational exposures, the impact of chemotherapy, the occurrence and recurrence of endometrosis, and emerging fertility preservation strategies. Design: A structured literature review with an emphasis on recent advances in genetic and immunological understanding. Setting: Academic research and clinical insights from multidisciplinary contributors. Patients: Individuals diagnosed with POF as reported in the literature. Interventions: Review of literature concerning epidemiology, genetic mutations, immunological disorders, and surgical outcomes linked to POF. Main outcome measures: Identification of both established and emerging risk factors, validation of genetic and immunological markers, and clarification of diagnostic and preventive clinical approaches. Results: The prevalence of POF varies globally, affecting 1% of women under 40. Genetic factors, particularly mutations in the FMR1 and BMP15 genes, play a significant role, alongside autoimmune diseases. Chemotherapy is a leading iatrogenic cause, while endometriosis and ovarian cyst surgeries significantly contribute to diminished ovarian reserve. Conclusion: POF is a multifactorial condition with rising incidence in specific subgroups. Improved early detection, standardized biomarker use, and expanded access to fertility preservation are essential. Targeted genomic and occupational risk screening may enable personalized interventions. Further genomic studies are needed to elucidate rare mutations and their impact.
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Abstract

Objective: To provide a rigorous, multidisciplinary synthesis of the epidemiological, genetic, immunological, and environmental factors contributing to Premature Ovarian Failure (POF), with particular attention to regional disparities, occupational exposures, the impact of chemotherapy, the occurrence and recurrence of endometrosis, and emerging fertility preservation strategies. Design: A structured literature review with an emphasis on recent advances in genetic and immunological understanding. Setting: Academic research and clinical insights from multidisciplinary contributors. Patients: Individuals diagnosed with POF as reported in the literature. Interventions: Review of literature concerning epidemiology, genetic mutations, immunological disorders, and surgical outcomes linked to POF. Main outcome measures: Identification of both established and emerging risk factors, validation of genetic and immunological markers, and clarification of diagnostic and preventive clinical approaches.

Results

The prevalence of POF varies globally, affecting 1% of women under 40. Genetic factors, particularly mutations in the FMR1 and BMP15 genes, play a significant role, alongside autoimmune diseases. Chemotherapy is a leading iatrogenic cause, while endometriosis and ovarian cyst surgeries significantly contribute to diminished ovarian reserve.

Conclusion

POF is a multifactorial condition with rising incidence in specific subgroups. Improved early detection, standardized biomarker use, and expanded access to fertility preservation are essential. Targeted genomic and occupational risk screening may enable personalized interventions. Further genomic studies are needed to elucidate rare mutations and their impact. Article Details Copyright (c) 2025 Bulletti FM, et al. This work is licensed under a Creative Commons Attribution 4.0 International License. Nelson LM. Clinical practice. Primary ovarian insufficiency. N Engl J Med. 2009;360(6):606–614. Available from: https://doi.org/10.1056/nejmcp0808697 nejm.org+9nejm.org+9europepmc.org+9 Chapman C, Cree L, Shelling AN. The genetics of premature ovarian failure: current perspectives. Int J Womens Health. 2015;7:799–810. Available from: https://doi.org/10.2147/ijwh.s64024 Coulam CB, Adamson SC. Premature ovarian failure: evidence for a genetic basis. Hum Reprod Update. 1996;2(6):482–490. 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BMP15 mutations associated with primary ovarian insufficiency cause a defective production of bioactive protein. Hum Mutat. 2009;30(5):804–810. Available from: https://doi.org/10.1002/humu.20961 Nash Z, Davies M. Premature ovarian insufficiency. BMJ. 2024;384. Available from: https://doi.org/10.1136/bmj-2023-077469 Bakalov VK, Anasti JN, Calis KA, Vanderhoof VH, Premkumar A, Chen S, et al. Autoimmune oophoritis as a mechanism of follicular dysfunction in women with 46,XX spontaneous premature ovarian failure. Fertil Steril. 2005;84(4):958–965. Available from: https://doi.org/10.1016/j.fertnstert.2005.04.060 Meirow D. Reproduction post-chemotherapy in young cancer patients. Mol Cell Endocrinol. 2000;169(1–2):123–131. Available from: https://doi.org/10.1016/S0303-7207(00)00365-8 journals.sagepub.com+8rep.bioscientifica.com+8journals.scholarsportal.info+8 Somigliana E, Vercellini P, Pasinato L. Endometriosis and ovarian reserve: a dangerous association. Endocrine. 2003;23(2–3):187–192. Practice Committee of the American Society for Reproductive Medicine. Evidence‑based outcomes after oocyte cryopreservation for donor oocyte in vitro fertilization and planned oocyte cryopreservation: a guideline. Fertil Steril. 2021;116(1):36–47. Available from: https://doi.org/10.1016/j.fertnstert.2021.02.024 Ter Welle-Butalid ME, Derhaag JG, van Bree BE, Vriens IJH, Goddijn M, Balkenende EME, et al. Outcomes of female fertility preservation with cryopreservation of oocytes or embryos in the Netherlands: a population‑based study. Hum Reprod. 2024;39(12):2693–2701. Available from: https://doi.org/10.1093/humrep/deae243 Kasaven LS, Jones BP, Heath CR, Odia R, Green J, Petrie A, et al. Reproductive outcomes from ten years of elective oocyte cryopreservation. Arch Gynecol Obstet. 2022;306:1753–1760. Available from: https://doi.org/10.1007/s00404-022-06711-0 Walker Z, Lanes A, Ginsburg E. Oocyte cryopreservation review: outcomes of medical oocyte cryopreservation and planned oocyte cryopreservation. Reprod Biol Endocrinol. 2022;20:10. Available from: https://doi.org/10.1186/s12958-021-00884-0 Milachich T, Shterev A. Are there optimal numbers of oocytes, spermatozoa, and embryos in assisted reproduction? JBRA Assist Reprod. 2016;20(3):142–149. Available from: https://doi.org/10.5935/1518-0557.20160032 Sermondade N, Pasquier M, Ahdad‑Yata N, Fraison E, Grynberg M. Searching for the optimal number of oocytes to reach a live birth after in vitro fertilization: a systematic review with meta-analysis. F&S Rev. 2023;4(2):101–115. Available from: https://doi.org/10.1016/j.xfnr.2023.03.002 Goldman RH, Racowsky C, Farland LV, Munné S, Ribustello L, Fox JH. Predicting the likelihood of live birth for elective oocyte cryopreservation: a counseling tool for physicians and patients. Hum Reprod. 2017;32(4):853–859. 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endometriosis

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