AMH Regulation by Steroids in the Mammalian Testis: Underlying Mechanisms and Clinical Implications.

Anti-Müllerian hormone (AMH) is a distinctive biomarker of the immature Sertoli cell. AMH expression, triggered by specific transcription factors upon fetal Sertoli cells differentiation independently of gonadotropins or sex steroids, drives Müllerian duct regression in the male, preventing the development of the uterus and Fallopian tubes. AMH continues to be highly expressed by Sertoli until the onset of puberty, when it is downregulated to low adult levels. FSH increases testicular AMH output by promoting immature Sertoli cell proliferation and individual cell expression. AMH secretion also showcases a differential regulation exerted by intratesticular levels of androgens and estrogens. In the fetus and the newborn, Sertoli cells do not express the androgen receptor, and the high androgen concentrations do not affect AMH expression. Conversely, estrogens can stimulate AMH production because estrogen receptors are present in Sertoli cells and aromatase is stimulated by FSH. During childhood, sex steroids levels are very low and do not play a physiological role on AMH production. However, hyperestrogenic states upregulate AMH expression. During puberty, testosterone inhibition of AMH expression overrides stimulation by estrogens and FSH. The direct effects of sex steroids on AMH transcription are mediated by androgen receptor and estrogen receptor α action on AMH promoter sequences. A modest estrogen action is also mediated by the membrane G-coupled estrogen receptor GPER. The understanding of these complex regulatory mechanisms helps in the interpretation of serum AMH levels found in physiological or pathological conditions, which underscores the importance of serum AMH as a biomarker of intratesticular steroid concentrations.

Role of AMH in Prediction of Menopause.

Anti-Müllerian Hormone (AMH) is produced by small antral follicles and has evolved over the past three decades as an assumed potential marker of the number of follicles in the human ovaries, also known as ovarian reserve. This quantitative measure, given the gradual decline over time and its non-replenishable feature, could be the dreamed marker for predicting the final exhaustion of ovarian storage: the post-menopause. This introductory chapter summarizes current knowledge with regard to the contribution of serum AMH measurements to predict age of normal menopause and critically discuss its potential in this regard. Furthermore, its predictive role in the context of menopause in association with several frequently occurring fertility disorders such as premature menopause, polycystic ovarian syndrome and endometriosis are discussed. Overall, while ovarian reserve markers including AMH are unmistakably related to age at menopause, they are insufficiently precise to inform on an individual's journey of ovarian aging.

Translational Physiology of Anti-Müllerian Hormone: Clinical Applications in Female Fertility Preservation and Cancer Treatment.

Background: Whilst the ability of AMH to induce the regression of the Müllerian ducts in the male fetus is well appreciated, AMH has additional biological actions in relation to steroid biosynthesis and ovarian follicle dynamics. An understanding of the physiology of AMH illuminates the potential therapeutic utility of AMH to protect the ovarian reserve during chemotherapy and in the treatment of female malignancies. The translation of the biological actions of AMH into clinical applications is an emerging focus of research, with promising preliminary results. Objective and Rationale: Studies indicate AMH restrains primordial follicle development, thus administration of AMH during chemotherapy may protect the ovarian reserve by preventing the mass activation of primordial follicles. As AMH induces regression of tissues expressing the AMH receptor (AMHRII), administration of AMH may inhibit growth of malignancies expressing AMHR II. This review evaluates the biological actions of AMH in females and appraises human clinical applications. Search Methods: A comprehensive search of the Medline and EMBASE databases seeking articles related to the physiological functions and therapeutic applications of AMH was conducted in July 2021. The search was limited to studies published in English. Outcomes: AMH regulates primordial follicle recruitment and moderates sex steroid production through the inhibition of transcription of enzymes in the steroid biosynthetic pathway, primarily aromatase and 17α-hydroxylase/17,20-lyase. Preliminary data indicates that administration of AMH to mice during chemotherapy conveys a degree of protection to the ovarian reserve. Administration of AMH at the time of ovarian tissue grafting has the potential to restrain uncontrolled primordial follicle growth during revascularization. Numerous studies demonstrate AMH induced regression of AMHR II expressing malignancies. As this action occurs via a different mechanism to traditional chemotherapeutic agents, AMH has the capacity to inhibit proliferation of chemo-resistant ovarian cancer cells and cancer stem cells. Wider Implications: To date, AMH has not been administered to humans. Data identified in this review suggests administration of AMH would be safe and well tolerated. Administration of AMH during chemotherapy may provide a synchronistic benefit to women with an AMHR II expressing malignancy, protecting the ovarian reserve whilst the cancer is treated by dual mechanisms.

Anti-Müllerian Hormone Accelerates Pathological Process of Insulin Resistance in Polycystic Ovary Syndrome Patients.

Insulin resistance (IR) is one of the most common features of polycystic ovary syndrome (PCOS), which is related to obesity. Whether increased anti-Müllerian hormone (AMH) levels in PCOS are involved in the pathogenesis of insulin resistance remains unclear. We investigated serum levels of leptin and AMH along with basic clinical and metabolic parameters in 114 PCOS patients and 181 non-PCOS women. PCOS patients presented higher fasting blood glucose, insulin concentrations and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) in addition to body mass index (BMI), lipids profiles and hormone levels. HOMA-IR showed a positive correlation with BMI, AMH, leptin, and low-density lipoprotein-cholesterol (LDL-c) levels. Interestingly, AMH is strongly positively correlated with HOMA-IR and insulin concentrations for 1st and 2nd hours of glucose treatment after fasting. Among PCOS women with BMI≥25 kg/m2, high AMH level group showed an increased HOMA-IR when compared to normal AMH level. However, among PCOS women with normal BMI, women with high AMH presented an elevated fasting insulin levels but not HOMA-IR when compared to normal AMH group. In vitro treatment of isolated islet cells with high concentration of leptin (200 ng/ml) or high leptin plus high concentration of AMH (1 ng/ml) significantly enhanced insulin secretion. Importantly, co-treatment of AMH plus leptin upregulates the expression of pro-apoptotic proteins, such as Bax, caspase-3, and caspase-8 after incubating with a high level of glucose. These results suggest that AMH may involve in the pathological process of pancreatic ß-cells in obese PCOS women.

Anti-Mullerian Hormone and Macrophage Migration Inhibitory Factor Determine the Reproductive Health of Ladakhi Women Residing at 3,500 m.

Shaw, Snigdha, Himashree Gidugu, Gopinath Bhaumik, Maramreddy Prasanna Kumar Reddy, Usha Panjwani, and Dishari Ghosh. Anti-Mullerian hormone and macrophage migration inhibitory factor determine the reproductive health of Ladakhi women residing at 3,500 m. High Alt Med Biol. 22:317-326, 2021. Background: Reproductive health of Ladakhi high-altitude (HA) native females was investigated for the first time in this study. Available literature suggest that, female reproductive cycle and hormonal profile varies in different HA populations due to heterogeneity. Although these studies illustrate some progress on the role of HA hypoxia, it still leaves scope for evaluation of the remaining mechanisms involved in the maintenance of reproductive health in this contemporary population. Materials and Methods: Menstrual details, phasic variations in circulatory steroid hormones, and gonadotropins along with oxytocin in sea level (SL) and HA (∼3,500 m) native females of India were assessed. Moreover, ovarian reserve marker anti-Mullerian hormone (AMH) and proinflammatory cytokine macrophage migration inhibitory factor (MIF) were measured. Results: A difference in Ladakhi women was registered compared to SL, regarding luteinizing hormone (LH) (2.6 mIU/ml vs. 4.4 mIU/ml, p < 0.05) and progesterone (P) (4.1 ng/ml vs. 9.4 ng/ml, p < 0.05) levels in their luteal phase. Reduced LH might contribute to poor development of the ovarian corpus luteum, subsequently diminish P level. Decreased AMH level in three age groups: 21-30 years (1.4 ng/ml vs. 3.2 ng/ml, p < 0.01), 31-40 years (0.6 ng/ml vs. 2.1 ng/ml, p < 0.01), and >40 years (0.4 ng/ml vs. 1.7 ng/ml, p < 0.01) of Ladakhi women were recorded than their SL counterpart. Elevated oxytocin (83.5 ng/ml vs. 76.3 ng/ml, p < 0.05) and MIF levels (70.2 ng/ml vs. 49.7 ng/ml, p < 0.01) along with low P and AMH levels delineated the reason for recorded early menopause (43.9 years), shorter reproductive span (∼29 years), and history of miscarriage in HA dwellers compared to SL. Conclusion: Therefore, the findings insinuated that the response of the reproductive system to hypoxia in Ladakhi women differs from SL women, and the adaptive response in these women might be in favor of their reproductive health.

Increased Body Mass Index Is Associated With A Nondilutional Reduction in Antimüllerian Hormone.

CONTEXT: Controversy exists regarding if and how body mass index (BMI) impacts antimüllerian hormone (AMH) in women with and without polycystic ovary syndrome (PCOS). Understanding the BMI-AMH relationship has critical implications for clinical interpretation of laboratory values and could illuminate underlying ovarian physiology. OBJECTIVE: To test the hypotheses that (1) BMI is associated with reduced AMH in PCOS and ovulatory controls (OVAs) and (2) the reduction in AMH is not accounted for by dilutional effects. DESIGN/SETTING: Multicenter cohort. PARTICIPANTS: Women aged 25 to 40 years from 2 clinical populations: 640 with PCOS, 921 women as OVAs. MAIN OUTCOME MEASURES: Ovarian reserve indices: AMH, antral follicle count (AFC), and AMH to AFC ratio (AMH/AFC) as a marker of per-follicle AMH production. RESULTS: In both cohorts, increasing BMI and waist circumference were associated with reductions in AMH and AMH/AFC, after adjusting for age, race, smoking, and site in multivariate regression models. Increasing BMI was associated with reduced AFC in PCOS but not OVAs. Body surface area (BSA), which unlike BMI is strongly proportional to plasma volume, was added to investigate a potential dilutive effect of body size on AMH concentrations. After controlling for BSA, BMI retained independent associations with AMH in both cohorts; BSA no longer associated with AMH. CONCLUSIONS: In an adjusted analysis, BMI, but not BSA, was associated with reduced AMH; these data do not support a role for hemodilution in mediating the relationship between increased body size and reduced AMH. Decreased AMH production by the follicle unit may be responsible for reduced AMH with increasing BMI.

Anti-Müllerian hormone (Amh/amh) plays dual roles in maintaining gonadal homeostasis and gametogenesis in zebrafish.

Anti-Müllerian hormone (AMH/Amh) plays a role in gonadal differentiation and function across vertebrates. In zebrafish we demonstrated that Amh deficiency caused severe gonadal dysgenesis and dysfunction. The mutant gonads showed extreme hypertrophy with accumulation of early germ cells in both sexes, namely spermatogonia in the testis and primary growth oocytes in the ovary. In amh mutant females, the folliculogenesis was normal in young fish but receded progressively in adults, which was accompanied by progressive decrease in follicle-stimulating hormone (fshb) expression. Interestingly the expression of fshb increased in the pituitary of juvenile amh mutant males but decreased in adults. The upregulation of fshb in mutant male juveniles was likely one of the mechanisms for triggering gonadal hypergrowth, whereas the downregulation of fshb in adults might involve a negative feedback by gonadal inhibin. Further analysis using mutants of fshb and growth differentiation factor 9 (gdf9) provided evidence for a role of FSH in triggering ovarian hypertrophy in young female amh mutant as well. In summary, the present study provided comprehensive genetic evidence for dual roles of Amh in controlling zebrafish gonadal homeostasis and gametogenesis in both sexes. Amh suppresses proliferation or accumulation of early germ cells (spermatogonia in testis and primary growth oocytes in ovary) while promoting their exit to advanced stages, and its action may involve both endocrine and paracrine pathways.

Age effect on in vitro fertilization pregnancy mediated by anti-Mullerian hormone (AMH) and modified by follicle stimulating hormone (FSH).

BACKGROUND: Both follicle stimulating hormone (FSH) and anti-mullerian hormone (AMH) are widely used to assess the ovarian reserve in women for in vitro fertilization (IVF). However, studies also showed that both AMH and FSH are significantly associated with age: as age increases, AMH decreases and FSH increases. This study aims to investigate the mechanism of age effect on IVF live birth rate, particularly through mediation and interaction by AMH and FSH. METHODS: We conducted a retrospective cohort study of 13970 IVF cycles collected by eIVF from 2010 to 2016. A series of logistic mixed models were used to estimate the association of live birth and AMH (or FSH). The mediation effects and proportion mediated, were quantified by our previously proposed mediation analyses. We further investigated the FSH-modified mediation effects on live birth rate through AMH, accounting for the nonlinear age effect. RESULTS: Our analyses showed that age effect on live birth was mediated more by AMH than by FSH (18 vs. 6%). The mediation effect through AMH can be further modified by FSH level regardless of women's age. CONCLUSIONS: In summary, mediation model provides a new perspective elucidating the mechanism of IVF successful rate by age. The majority of the age effect on live birth rate remained unexplained by AMH and FSH, suggesting its importance and independent role in IVF.

Anti-Müllerian hormone as a qualitative marker - or just quantity?

PURPOSE OF REVIEW: In this review, we will summarize research looking into anti-Müllerian hormone (AMH) as a measure of oocyte quality. RECENT FINDINGS: AMH is a key factor involved in embryogenesis but also in the development of early follicles. Owing to its relatively small inter and intracycle variability, it has become a widely used method of ovarian reserve testing. In the realm of assisted reproductive technology, it has demonstrated a reliable ability to gauge the number of oocytes obtained during an in-vitro fertilization cycle. For these purposes, AMH is a readily measured quantitative tool. However, its qualitative role is as yet undefined. SUMMARY: Although levels of this hormone have been associated with fertilization, blastulation, implantation, and clinical pregnancy rates, there is no clear link with live-birth rates. Furthermore, AMH levels do not appear to correspond with risk of fetal trisomy. AMH does show significant predictive value for the risk of premature ovarian insufficiency and time to onset of menopause.

Endometriosis reduces ovarian response in controlled ovarian hyperstimulation independent of AMH, AFC, and women's age measured by follicular output rate (FORT) and number of oocytes retrieved.

PURPOSE: To determine the influence of endometriosis on the ovarian response during controlled ovarian hyperstimulation measured by number of oocytes retrieved and the follicular output rate (FORT). METHODS: A retrospective, single center study included 96 women, who underwent ICSI treatments for male factor infertility according to World Health Organisation between 2016 until 2018. A total of 96 patients were included in the study with 205 fresh ICSI cycles. The study group included 26 patients with endometriosis after surgical and medical treatment; the control group included 70 patients without endometriosis. The women with endometriosis underwent 47 and the control group 158 ICSI cycles. Women underwent fresh intracytoplasmatic sperm injection cycles after controlled ovarian hyperstimulation following a GnRH-antagonist protocol. The FORT was calculated as the ratio of pre-ovulatory follicle count × 100/small antral follicle count at baseline. RESULTS: A lower number of retrieved oocytes (5.89 vs. 7.25, p = 0.045), lower FORT (75.67 vs. 94.63, p = 0.046), lower number of metaphase II oocytes (4.87 vs. 6.04, p = 0.046), and lower fertilization rate after intracytoplasmatic sperm injection (40.61 vs. 57.76, p = 0.003) were found in women with endometriosis compared to women without endometriosis. The number of oocyctes retrieved was 0.71 lower in the group with endometriosis than in the group without (p = 0.026). The FORT was 24.55% lower in the group with endometriosis (p = 0.025). CONCLUSIONS: Endometriosis reduces the FORT and the number of metaphase-II oocytes after controlled ovarian hyperstimulation independly of women's age, antral follicle count and anti-Müllerian hormone.

Association of birth weight with functional ovarian reserve during menacme estimated by serum concentration of anti-Müllerian hormone.

To investigate the relationship of birth weight (BW) of females born at full term with functional ovarian reserve (FOR) during menacme, based on serum level of anti-Müllerian hormone (AMH), among women who were 34-35 years old. This prospective birth cohort study assessed all women who were born in Ribeirão Preto City, State of São Paulo (Brazil) between June 1, 1978 and May 31, 1979. The primary endpoint was serum AMH, a marker of FOR, and its correlation with the BW of females classified as small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational (LGA). We included 274 women in this study, 19 were SGA, 238 were AGA, and 17 were LGA. The average of AMH concentration was not significantly different (p = 0.11) among women in the SGA group (2.14 ng/mL), AGA group (2.13 ng/mL), and LGA group (2.57 ng/mL). An analysis of variance indicated that the three groups also had no significant differences in the percentage of women who had adequate AMH levels (1 ng/mL; p = 0.11). There were no significant differences in the serum concentrations of AMH among 34 and 35 year-old women who were born at full term and classified as SGA, AGA, and LGA. Our sample size allowed detection of major differences between these groups (effect size of 0.8). Association of birth weight of females born at full term with functional ovarian reserve during menacme estimated by serum concentration of anti-Müllerian hormone.

The role of anti-Müllerian hormone in prediction of pregnancy in young and older women with unexplained infertility undergoing intrauterine insemination.

BACKGROUND: Serum anti-Müllerian hormone (AMH) level is considered to be a reliable marker of ovarian reserve. However, there are conflicting reports on the role of AMH level in predicting pregnancy after intrauterine insemination (IUI) cycles. The aim of this study is to investigate the clinical value of AMH in predicting pregnancy in younger and older women with unexplained infertility undergoing gonadotropin stimulation and IUI. METHODS: The medical records of 84 women who underwent first gonadotropin-stimulated IUI cycle owing to unexplained infertility were retrospectively evaluated. The relation of AMH levels with clinical pregnancy rate was analyzed. RESULTS: The overall clinical pregnancy rate was 19%. There was no significant difference in AMH levels between the pregnant and nonpregnant women (2.0 ± 1.0 vs 2.8 ± 2.0 ng/mL, respectively, p = 0.250). A further analysis according to age also failed to reveal significant differences in AMH levels between pregnant and nonpregnant women for both the younger (<35 years, n = 61) and the older (≥35 years, n = 23) subgroups (p = 0.714 and 0.532, respectively). Post-hoc power analysis showed a power of 0.80 with a 5% level of significance and a 0.8 effect size. CONCLUSION: These findings indicate that AMH levels cannot predict pregnancy in women with unexplained infertility undergoing gonadotropin-stimulated IUI cycle. In addition, AMH is not a strong predictive factor for pregnancy either in younger or older women.

Inferior fertility and higher concentrations of anti-Müllerian hormone in dairy cows with longer anogenital distance.

Anogenital distance (AGD), which is an indicator of prenatal androgen exposure, has been reported to have high variability and negative association with fertility in dairy cows. Prenatal exposure to androgens could influence the development of primordial follicles and size of ovarian reserve, which is related to reproduction. However, the relationship between AGD and size of ovarian reserve has not been studied. Therefore, the present study was conducted to determine the association between AGD and circulating anti-Müllerian hormone (AMH), as an indirect marker of ovarian reserve, and to evaluate serum AMH concentration and reproductive performance in dairy cows with short and long AGD. Anogenital distance was measured 28 to 32 d postpartum, and based on the median of AGD, cows were divided into 2 subsets including short (n = 43) and long (n = 43) AGD groups. Afterward, serum AMH was evaluated on the day of estrus in cows that were estrus-synchronized. Furthermore, reproductive data of dairy cows during the previous lactation period were collected from the herd database. Concentrations of serum AMH tended to be positively associated with length of AGD, and there was a tendency for higher serum AMH concentrations in the long (634.89 ± 74.52 pg/mL) than short (451.39 ± 45.92 pg/mL) AGD group (0.05

0.05). Calving to conception interval was prolonged in long (194.30 ± 17.12 d) than short (147.14 ± 13.11 d) AGD cows (P ≤ 0.05). In conclusion, the present study revealed elevated serum AMH concentrations and poor reproductive performance in cows with longer AGD compared with cows with shorter AGD.

Insuficiencia ovárica prematura / Premature ovarian insufficiency

RESUMEN La insuficiencia ovárica prematura es la pérdida de la función ovárica antes de los 40 años de edad. Se caracteriza por hipogonadismo hipergonadotrófico y amenorrea u oligomenorrea. Su etiología es multifactorial, pudiendo deberse a causas iatrogénicas, genéticas, metabólicas, autoinmunes y ambientales; siendo de origen idiopático en el 90 % de los casos. Su incidencia es de 1 cada 100 mujeres menores de 40 años y 1 cada 1000 mujeres menores de 30 años. En la actualidad no existe un único marcador que se pueda utilizar para calcular la reserva ovárica; sin embargo, en los últimos años la hormona antimülleriana ha demostrado presentar algunas ventajas respecto a los biomarcadores clásicamente utilizados. Además, diversos estudios indican que existe una correlación positiva entre los niveles de esta hormona y el recuento de folículos antrales, que es, por el momento, el método más confiable para evaluar reserva ovárica debido a las actuales dificultades técnicas para la determinación de hormona antimülleriana.

ABSTRACT Premature ovarian insufficiency, the loss of ovarian function before the age of 40 years, is characterized by hipergonadotrofic hipogonadism and amenorrhea or oligomenorrhea. The etiology is multifactorial, and can be due to genetic, metabolic, autoimmune, environmental or iatrogenic causes, being idiopathic 90% of cases. Currently there is not a single marker that can be used for estimate ovarian reserve in this patients; however, in recent years antimüllerian hormone has proved to have some advantages over other classical biomarkers. Moreover, several studies indicate a positive correlation between antimüllerian hormone concentration and antral follicle count, considered nowadays the most reliable method for ovarian reserve estimation.

Genome-wide association study of anti-Müllerian hormone levels in pre-menopausal women of late reproductive age and relationship with genetic determinants of reproductive lifespan.

Anti-Müllerian hormone (AMH) is required for sexual differentiation in the fetus, and in adult females AMH is produced by growing ovarian follicles. Consequently, AMH levels are correlated with ovarian reserve, declining towards menopause when the oocyte pool is exhausted. A previous genome-wide association study identified three genetic variants in and around the AMH gene that explained 25% of variation in AMH levels in adolescent males but did not identify any genetic associations reaching genome-wide significance in adolescent females. To explore the role of genetic variation in determining AMH levels in women of late reproductive age, we carried out a genome-wide meta-analysis in 3344 pre-menopausal women from five cohorts (median age 44-48 years at blood draw). A single genetic variant, rs16991615, previously associated with age at menopause, reached genome-wide significance at P = 3.48 × 10-10, with a per allele difference in age-adjusted inverse normal AMH of 0.26 standard deviations (SD) (95% confidence interval (CI) [0.18,0.34]). We investigated whether genetic determinants of female reproductive lifespan were more generally associated with pre-menopausal AMH levels. Genetically-predicted age at menarche had no robust association but genetically-predicted age at menopause was associated with lower AMH levels by 0.18 SD (95% CI [0.14,0.21]) in age-adjusted inverse normal AMH per one-year earlier age at menopause. Our findings provide genetic support for the well-established use of AMH as a marker of ovarian reserve.

Anti Müllerian Hormone: More than a biomarker of female reproductive function.

Anti-Müllerian hormone (AMH), known for its role during sexual differentiation, is a dimeric glycoprotein that belongs to the transforming growth factor-ß (TGF-ß) family. AMH has recently been identified as a reliable marker of ovarian reserve that can help predict early ovarian follicle loss and menopause onset. AMH levels also reflect the effects of damaging gynecologic surgeries or gonadotoxic treatments such as chemotherapy on ovarian reserve. Furthermore, AMH participates in the diagnosis of certain diseases such as granulosa cell tumors or Polycystic Ovary Syndrome (PCOS). Currently used to establish patient profiles and predict ovarian response to stimulation, its role in ART techniques is crucial. Nevertheless, AMH appears to be a weak independent predictor of qualitative outcomes such as implantation, pregnancy, and live birth. As the reliability and reproducibility of AMH dosage have raised many doubts due to different existing standards and thresholds, an international consensus is still expected to improve AMH measurement and interpretation.

AMH prevents primordial ovarian follicle loss and fertility alteration in cyclophosphamide-treated mice.

The follicular ovarian reserve, constituted by primordial follicles (PMFs), is established early in life, then keeps declining regularly along reproductive life. The maintenance of a normal female reproductive function implies the presence of a vast amount of dormant PMFs. This process involves a continuous repression of PMF activation into early growing follicle through the balance between factors activating the initiation of follicular growth, mainly actors of the PI3K signaling pathway, and inhibiting factors such as anti-Müllerian hormone (AMH). Any disruption of this balance may induce follicle depletion and subsequent infertility. It has been recently proposed that cyclophosphamide (Cy), an alkylating agent commonly used for treating breast cancer, triggers PMF activation, further leading to premature ovarian insufficiency. Preventing chemotherapy-induced ovarian dysfunction might represent an interesting option for preserving optimal chances of natural or medically assisted conceptions after healing. The aim of the present study was to evaluate, in a model of Cy-treated pubertal mice, whether AMH administration might restrain PMF depletion. The counting of the total PMF number within mouse ovaries showed that recombinant AMH prevented Cy-induced PMF loss. Western blot analysis revealed activation of PI3K signaling pathway after Cy administration. After AMH injection, FOXO3A phosphorylation, a main actor of PMF activation, was significantly decreased. Taken together, these results support a protective role of AMH against Cy-induced follicular loss. We also provide evidence for a possible role of autophagy in the preservation of follicular pool reserve. Therefore, concomitant recombinant AMH administration during chemotherapy might offer a new option for preserving young patients' fertility.-Sonigo, C., Beau, I., Grynberg, M., Binart, N. AMH prevents primordial ovarian follicle loss and fertility alteration in cyclophosphamide-treated mice.