Anti-Müllerian hormone: an ovarian reserve marker in primary ovarian insufficiency

Abstract Study question To address whether there was a correlation between thyroid parameters and primary ovarian insufficiency. Summary answer Thyroid dysfunction was related with bPOI and LOR. What is known already In our daily clinical work, there seems to be a link between thyroid disease and POI. A recent study reported that subclinical hypothyroidism was associated with lower ovarian reserve during later reproductive age. Animal studies demonstrated that thyroid hormones played important roles in ovarian functions, and both maternal hypothyroidism and hyperthyroidism were related with reduced primordial, primary and secondary follicle number in rats. However, others reported that thyroid autoimmunity (TAI) and hypothyroidism were not associated with DOR. In all, accumulative animal and epidemiological studies indicated the connection between thyroid function and ovarian reserve, but the results were still inconsistent. Study design, size, duration This is a cross-sectional study with consecutive women performed ovarian reserve assessment and thyroid test in the Second Hospital of Zhejiang University School of Medicine from April 2016 to March 2019. A total of 2109 women were included, with 111 with bPOI and 1771 without bPOI. To exclude the influence of age the participants were categorized into low ovarian reserve (LOR) and non-LOR groups based on age-specific AMH, including 78 LOR and 2031 non-LOR. Participants/materials, setting, methods At the outpatient, a doctor carried out an interview, recorded age, body mass index (BMI), past history, and current treatment, and made a diagnosis. Serum AMH, FSH, TPOAb, TgAb, Tg, TT3, FT3, TT4, FT4, and TSH levels were measured with electrochemiluminescence method. Main results and the role of chance TT3, FT3, FT4 was significantly positively correlated with serum AMH level. Further logistic regression analysis found that abnormal TT3, FT3 and TT4 levels were related to increased risks of bPOI and LOR. Chi-square analysis also proved that the incidence of abnormal TT3, FT3 and TT4 increased significantly in women with bPOI or LOR. The incidence of bPOI and LOR increased significantly in women with 2 or 3 abnormal thyroid hormones. The above analyses demonstrate in multiple aspects that thyroid dysfunction is related with decreased ovarian reserve. Limitations, reasons for caution Since this is a retrospective cross-sectional study, we only got the correlation between factors, and we could not achieve causal relationship. Further prospective cohort or randomized controlled trial (RCT) studies are required to make the results more robust. Wider implications of the findings: The present study demonstrated that thyroid dysfunction was related with bPOI and LOR. It might be thyroid hormones, not TSH or thyroid antibodies, played the major role in ovarian reserve impairment. The treatment of euthyroxine may improve the ovarian reserve function. Trial registration number Not applicable

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Diminished ovarian reserve and primary ovarian insufficiency in two women with celiac disease. Is there a link?

Maturitas ◽

10.1016/j.maturitas.2017.03.156 ◽

2017 ◽

Vol 100 ◽

pp. 163

Author(s):

Pantelis Messaropoulos ◽

Vassilia Hatzidakis ◽

Christina Tzouma ◽

Maria Oikonomou ◽

Spyridoula Neofytou ◽

...

Keyword(s):

Celiac Disease ◽

Ovarian Reserve ◽

Primary Ovarian Insufficiency ◽

Diminished Ovarian Reserve ◽

Ovarian Insufficiency

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AMH/MIS as a contraceptive that protects the ovarian reserve during chemotherapy

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1620729114 ◽

2017 ◽

Vol 114 (9) ◽

pp. E1688-E1697 ◽

Cited By ~ 60

Author(s):

Motohiro Kano ◽

Amanda E. Sosulski ◽

LiHua Zhang ◽

Hatice D. Saatcioglu ◽

Dan Wang ◽

...

Keyword(s):

Ovarian Reserve ◽

Primordial Follicle ◽

Primary Ovarian Insufficiency ◽

Negative Regulator ◽

Ovarian Insufficiency ◽

Gene Therapy Vector ◽

Primordial Follicles ◽

Primordial Follicle Activation ◽

Virus Serotype ◽

Follicle Activation

The ovarian reserve represents the stock of quiescent primordial follicles in the ovary which is gradually depleted during a woman’s reproductive lifespan, resulting in menopause. Müllerian inhibiting substance (MIS) (or anti-Müllerian hormone/AMH), which is produced by granulosa cells of growing follicles, has been proposed as a negative regulator of primordial follicle activation. Here we show that long-term parenteral administration of superphysiological doses of MIS, using either an adeno-associated virus serotype 9 (AAV9) gene therapy vector or recombinant protein, resulted in a complete arrest of folliculogenesis in mice. The ovaries of MIS-treated mice were smaller than those in controls and did not contain growing follicles but retained a normal ovarian reserve. When mice treated with AAV9/MIS were paired with male breeders, they exhibited complete and permanent contraception for their entire reproductive lifespan, disrupted vaginal cycling, and hypergonadotropic hypogonadism. However, when ovaries from AAV9-MIS–treated mice were transplanted orthotopically into normal recipient mice, or when treatment with the protein was discontinued, folliculogenesis resumed, suggesting reversibility. One of the important causes of primary ovarian insufficiency is chemotherapy-induced primordial follicle depletion, which has been proposed to be mediated in part by increased activation. To test the hypothesis that MIS could prevent chemotherapy-induced overactivation, mice were given carboplatin, doxorubicin, or cyclophosphamide and were cotreated with AAV9-MIS, recombinant MIS protein, or vehicle controls. We found significantly more primordial follicles in MIS-treated animals than in controls. Thus treatment with MIS may provide a method of contraception with the unique characteristic of blocking primordial follicle activation that could be exploited to prevent the primary ovarian insufficiency often associated with chemotherapy.

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Onco-fertility and personalized testing for potential for loss of ovarian reserve in patients undergoing chemotherapy: proposed next steps for development of genetic testing to predict changes in ovarian reserve

Fertility Research and Practice ◽

10.1186/s40738-021-00105-7 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Bei Sun ◽

John Yeh

Keyword(s):

Genetic Testing ◽

Genetic Markers ◽

Ovarian Reserve ◽

Genetic Variants ◽

Reproductive Potential ◽

Ovarian Failure ◽

Primary Ovarian Insufficiency ◽

Reproductive Age ◽

Ovarian Insufficiency ◽

Ovarian Damage

AbstractWomen of reproductive age undergoing chemotherapy face the risk of irreversible ovarian insufficiency. Current methods of ovarian reserve testing do not accurately predict future reproductive potential for patients undergoing chemotherapy. Genetic markers that more accurately predict the reproductive potential of each patient undergoing chemotherapy would be critical tools that would be useful for evidence-based fertility preservation counselling. To assess the possible approaches to take to develop personalized genetic testing for these patients, we review current literature regarding mechanisms of ovarian damage due to chemotherapy and genetic variants associated with both the damage mechanisms and primary ovarian insufficiency. The medical literature point to a number of genetic variants associated with mechanisms of ovarian damage and primary ovarian insufficiency. Those variants that appear at a higher frequency, with known pathways, may be considered as potential genetic markers for predictive ovarian reserve testing. We propose developing personalized testing of the potential for loss of ovarian function for patients with cancer, prior to chemotherapy treatment. There are advantages of using genetic markers complementary to the current ovarian reserve markers of AMH, antral follicle count and day 3 FSH as predictors of preservation of fertility after chemotherapy. Genetic markers will help identify upstream pathways leading to high risk of ovarian failure not detected by present clinical markers. Their predictive value is mechanism-based and will encourage research towards understanding the multiple pathways contributing to ovarian failure after chemotherapy.

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Limited Value of Ovarian Function Markers following Orthotopic Transplantation of Ovarian Tissue after Gonadotoxic Treatment

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2010-2188 ◽

2011 ◽

Vol 96 (4) ◽

pp. 1136-1144 ◽

Cited By ~ 45

Author(s):

Femi Janse ◽

Jacques Donnez ◽

Ellen Anckaert ◽

Frank H. de Jong ◽

Bart C. J. M. Fauser ◽

...

Keyword(s):

Ovarian Reserve ◽

Ovarian Function ◽

Ovarian Tissue ◽

Graft Function ◽

Primary Ovarian Insufficiency ◽

Inhibin B ◽

University Hospital ◽

Ovarian Insufficiency ◽

Orthotopic Transplantation ◽

Ovarian Transplantation

Abstract Context: In young women, some treatments for cancer or other conditions (such as sickle cell anemia) may give rise to primary ovarian insufficiency. Ovarian transplantation is one of the available options for fertility preservation, with highly variable pregnancy rates. Objective: The objective of the study was to investigate markers of ovarian reserve and ovarian function in women up to 7 yr after orthotopic ovarian transplantation. Secondary objectives were to assess the relationship between markers of ovarian reserve and pregnancy rate along with the duration of ovarian function. Design: This was a prospective cohort study in 10 women, with a mean follow-up of 2.5 yr. Setting: The study was conducted at a university hospital in Brussels, Belgium. Patients: Patients included 10 women who were about to receive or had previously received gonadotoxic treatment. In seven women cryopreservation of ovarian tissue was performed before starting treatment. Subsequently autografts were orthotopically transplanted in these women. Three women, who had already developed primary ovarian insufficiency due to treatment, underwent orthotopic transplantation of ovarian allograft tissue originating from their human leukocyte antigen-compatible sisters. Main Outcome Measures: Serum concentrations of FSH, LH, estradiol, inhibin B, and anti-Müllerian hormone (AMH) were measured. Results: On average, first menses took place after 4.7 months. Duration of graft functioning varied from 2 to more than 60 months. FSH concentrations remained elevated, whereas estradiol levels normalized and AMH was low to undetectable. Inhibin B varied among women and was not associated with the duration of ovarian function (hazard ratio 0.966, 95% confidence interval 0.881–1.059). Two spontaneous pregnancies occurred. Endocrine characteristics were not significantly different in these women. Conclusions: Low AMH and inhibin B concentrations may suggest decreased ovarian reserve in women after ovarian transplantation. AMH and inhibin B levels may not be associated with the duration of ovarian graft function or probability to achieve a pregnancy.

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