Population-based anti-Müllerian hormone reference intervals help define gonadal status in the bitch.

OBJECTIVE: To establish statistically valid, population-based reference intervals (RIs) for canine anti-Müllerian hormone (AMH) and define changes in AMH and inhibin-B in bitches during breeding cycles. METHODS: A homologous canine ELISA was used to measure AMH in serum samples (collected between May 2019 and July 2024) from 102 intact and 78 reportedly ovariohysterectomized (OVH) bitches and 8 bitches before and after ovariohysterectomy, and in longitudinal samples from 24 bitches undergoing breeding management. Established 95% RIs were used in a retrospective assessment of 3,193 clinical submissions. Cyclic variation of AMH and inhibin-B (heterologous ELISA) were regressed with time and normalized to the rise in progesterone in samples from breeding bitches. RESULTS: Intact and OVH RIs for AMH were calculated with and without inclusion of 7 samples from reportedly OVH bitches that had AMH concentrations in the intact RI. Anti-Müllerian hormone and inhibin-B were positively correlated, and AMH was 3 times higher in proestrus than in estrus. Retrospectively, of 3,193 samples submitted for clinical AMH testing, 41% to 56% were in or above the intact AMH interval, 37% to 44% were within the OVH interval, and < 10% were inconclusive, depending on how RIs were defined. CONCLUSIONS: Statistically valid, population-based RIs establish a sound basis for interpreting results of clinical submissions requesting AMH to assess gonadal status in the bitch. CLINICAL RELEVANCE: Confirmation of cyclic variation in AMH (and, for the first time, inhibin-B) reaffirms proestrus as the optimum time to draw samples, and ≤ 10% of samples submitted for determination of gonadal status are expected to fall in an inconclusive AMH RI.

Impact of Periconceptional and Gestational Vitamin D3 Restriction on Fetal Folliculogenesis and Anti-Mullerian Hormone Secretion Using Sheep as a Model.

Ovarian reserve is a reflection of the overall female reproductive potential. Vitamin D status has been suspected to influence fetal development and female fertility. As maternal diet during pregnancy can affect fetal development and future fertility, we hypothesised that periconceptional and gestational Vitamin D restriction could affect folliculogenesis and AMH secretion in the offspring. Nineteen sexually mature Welsh mountain ewes were randomly assigned to Vitamin D3 deficient (VDD, n = 10) and Vitamin D3 control (VDC, n = 9) diets from 17 days (d) before mating, up to 127-130 days of gestation, when fetal ovaries were collected (3 from VDC and 6 from VDD). Serum 25(OH)D3 concentrations were lower in VDD compared with VDC (p < 0.05). Relative to total follicle number, the percentage of primordial follicles was higher (p < 0.05), while the percentage of primary follicles was lower (p < 0.05) in VDD group compared with VDC group fetal ovaries. The integrated density value and percentage of affected area in TUNEL staining in VDD group did not vary from VDC group fetal ovaries (p > 0.05). Relative expression of AMH mRNA and AMH protein in VDD fetal ovaries were not statistically different compared with controls (p > 0.05). The relative expression of VDR mRNA were lower in VDD compared with VDC group fetal ovaries (p < 0.05). These data indicate that maternal Vitamin D dietary restriction is associated with ovarian tissue stemness and increased primordial follicle number but does not promote normal follicle recruitment or development in sheep fetal ovaries.

Comparing Serum AMH, InhB, Testosterone Levels and Finger Length Ratio (2D/4D) of Male Children with Specific Learning Disorder and Controls.

Introduction: It has been suggested that inhibin B (InhB), Anti-Müllerian hormone (Müllerian-inhibiting substance, AMH) levels, and 2D/4D finger length ratios are related to sex differences in neurodevelopmental disorders. The aim of this study is to investigate the role of InhB, AMH levels, and 2D/4D finger length ratios in male children with specific learning disorder (SLD). Methods: The study included 38 male children diagnosed with SLD and 38 males of similar ages without SLD as the control group. Tests used in the evaluation were the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version, Specific learning disorder clinical observation battery, Wechsler Intelligence Scale for Children-Revised (WISC-R), and Conners' Parent Rating Scale. Revised: Short Form. Serum AMH, InhB, and Testosterone levels were measured using an enzyme-linked immunosorbent assay. Results: Male children diagnosed with SLD demonstrated significantly higher levels of serum InhB compared to controls (t= 2.59 p=0.009); both groups had similar levels of serum testosterone and AMH. The 2D/4D finger ratios in the SLD group were found to be lower than those in the control group (t= 2.92 p= 0.005). Serum InhB levels were positively correlated with WISC-R verbal scores (p= 0.003). Conclusion: Our findings suggest that serum InhB levels and the 2D/4D ratio, which is an indicator of prenatal testosterone exposure, may play a role in the male predominance of SLD.

Effect of AMH on primordial follicle populations in mouse ovaries and human pre-pubertal ovarian xenografts during doxorubicin treatment.

Introduction: Survival rates of the childhood cancer patients are improving, however cancer treatments such as chemotherapy may lead to infertility due to loss of the primordial follicle (PMF) reserve. Doxorubicin (DXR) is a gonadotoxic chemotherapy agent commonly used in childhood cancers. Anti-Müllerian Hormone (AMH) has been reported to have a protective effect on the mouse ovarian reserve against DXR in vivo. However, whether AMH can prevent PMF loss in conjunction with DXR in human ovarian tissue in vivo has not been determined. Methods: In order to investigate this, we first established an optimum dose of DXR that induced PMF loss in cultured mouse ovaries and investigated the efficacy of AMH on reducing DXR-induced PMF loss in mice in vitro. Second, we investigated the effects of DXR on pre-pubertal human ovarian tissue and the ability of AMH to prevent DXR-induced damage comparing using a mouse xenograft model with different transplantation sites. Results: Mouse ovaries treated with DXR in vitro and in vivo had reduced PMF populations and damaged follicle health. We did not observe effect of DXR-induced PMF loss or damage to follicle/stromal health in human ovarian cortex, this might have been due to an insufficient dose or duration of DXR. Although AMH does not prevent DXR-induced PMF loss in pre-pubertal and adult mouse ovaries, in mouse ovaries treated with higher concentration of AMH in vitro, DXR did not cause a significant loss in PMFs. This is the first study to illustrate an effect of AMH on DXR-induced PMF loss on pre-pubertal mouse ovaries. However, more experiments with higher doses of AMH and larger sample size are needed to confirm this finding. Discussion: We did not observe that AMH could prevent DXR-induced PMF loss in mouse ovaries in vivo. Further studies are warranted to investigate whether AMH has a protective effect against DXR in xenotransplanted human ovarian tissue. Thus, to obtain robust evidence about the potential of AMH in fertility preservation during chemotherapy treatment, alternative AMH administration strategies need to be explored alongside DXR administration to fully interrogate the effect of DXR and AMH on human xenografted tissues.

Evaluation of ovarian reserve and the assisted reproductive technology (ART) cycles' outcome as well as the relapse rate within one year after ART in women with multiple sclerosis: a case-control study.

OBJECTIVE: To compare the ovarian reserve and the results of infertility treatment, as well as to investigate the relapse rate in the first year after the assisted reproductive technology (ART) cycle in patients with multiple sclerosis (MS) referred to Royan Institute. MATERIALS AND METHODS: This retrospective study was carried out to evaluate all women diagnosed with MS and referred to Royan Institute for assessment and treatment of possible infertility between 2011 and 2022. The control group consisted of randomly selected healthy women with tubal factor infertility who were referred for treatment during the same time period and matched in terms of age. A comparison was made between groups in terms of ovarian reserve and infertility treatment outcomes. Additionally, patients with MS who met the criteria were monitored via telephone to evaluate the symptoms, disability and relapse rate both pre- and post-ART. RESULTS: Over the course of a decade, the database documented a total of 60 cases diagnosed with MS. Upon examination of the records, it was found that in 27 patients only admission was done without any hormonal assessment or infertility treatment cycle and 5 patients proceeded with the intrauterine insemination cycle. Eventually, 28 women with MS underwent the ART cycle and all of them were treated with interferon beta, glatiramer acetate, or some oral disease modifying therapies. No statistically significant difference in terms of the basal levels of luteinizing hormone, follicle-stimulating hormone and anti-Müllerian hormone was found between the MS and control groups (P > 0.05). Two groups were comparable in terms of menstrual status. The study revealed that both groups exhibited similarities in terms of the controlled ovarian stimulation protocol and duration, the dosage of gonadotropin administered, as well as the ovarian response type, clinical pregnancy rate, and live birth rate (P > 0.05). After follow up, only 2 patients (9.5%) reported relapse of symptoms within one year after ART. CONCLUSION: The ovarian reserve and ovarian stimulation cycle and pregnancy outcomes following the ART cycle in MS patients were similar to the age-matched control group. The relapse rate of multiple sclerosis did not show a significant increase within a year following the ART cycle.

Potential damage to ovarian reserve from laparoscopic electrocoagulation in endometriomas and benign ovarian cysts: a systematic review and meta-analysis.

PURPOSE: Laparoscopic cystectomy for ovarian endometriomas and benign ovarian cysts is often conducted through hemostatic methods, with bipolar electrocoagulation as a common approach. This study evaluated the impact of electrocoagulation, primarily through bipolar energy, versus nonthermal hemostatic methods on ovarian reserve in patients undergoing laparoscopic cystectomy for ovarian endometriomas and benign ovarian cysts. METHODS: A systematic review with meta-analysis was conducted by searching the Cochrane Library, PubMed, EMBASE, and Web of Science databases. Randomized controlled trials (RCTs) comparing the impact of nonthermal hemostatic methods and electrocoagulation on the ovarian reserve during laparoscopic cystectomy were included. The Cochrane Risk of Bias Tool for Randomized Controlled Trials (ROB 2.0) was utilized to assess the quality of the included studies. The meta-analysis included 13 RCTs involving 1043 patients. Postoperative serum anti-Müllerian hormone (AMH) levels and antral follicle counts (AFCs) were analyzed using Review Manager ver. 5.4. RESULTS: Compared with the bipolar group, patients with endometriomas in the nonthermal hemostatic group exhibited significantly higher postoperative AMH levels at 1, 3, 6, and 12 months. Conversely, no significant differences in AMH levels were observed in patients with benign ovarian cysts. Similarly, AFCs showed no significant differences, except for lower postoperative AFCs in patients with endometrioma in the electrocoagulation group. CONCLUSION: Nonthermal hemostatic methods are associated with more effective preservation of the ovarian reserve compared with bipolar electrocoagulation in laparoscopic cystectomy for ovarian endometriomas. However, no significant impact of bipolar electrocoagulation on the ovarian reserve was observed in patients with benign ovarian cysts. TRIAL REGISTRATION: Registered in PROSPERO on April 10, 2023; ID # CRD42023413158.

The Association of AMH Level with the Number and Quality of Oocytes in Women Undergoing IVF/ICSI: A Single-Center Study.

Background: The recognized role of Anti-Müllerian hormone (AMH) as a marker for women's biological age and ovarian reserve prompts debate on its efficacy in predicting oocyte quality during IVF/ICSI. Recent findings challenging this view compelled us to conduct this study to examine the correlation between AMH levels and quantity/quality of oocytes in IVF/ICSI procedures. Methods: The data were collected retrospectively from the medical records of 320 women between 25-42 years old. The included patients were divided into two groups: the high AMH group (>1.1 ng/ml) and the low AMH (=<1.1 ng/ml) group. The high AMH group comprised 213 patients, while the low AMH group consisted of 107 patients. Spearman's correlation coefficient and Multinomial logistic regression were computed to assess the relationships between different variables. Results: Significant positive correlations were detected between AMH level and the number of aspirated follicles (rho=0.741, p<0.001), retrieved oocytes (rho=0.659, p<0.001), M2 oocytes (rho=0.624, p<0.001), grade A embryos (rho=0.419, p<0.001), and grade AB embryos (rho=0.446, p<0.001. In contrast, AMH levels had negative associations with the number and duration of cycles (p<0.05). AMH emerged as a statistically significant independent predictor of the number of M2 oocytes. Conclusions: Serum AMH level could represent the quantity and quality of oocytes following IVF/ICSI treatments. Future studies should aim to delve deeper into the correlations between AMH levels and both the quality and quantity of embryos. Additionally, it would be beneficial to consider the influence of sperm factors, as well as assess pregnancy rates.

Safety and efficacy of allogenic human amniotic epithelial cells transplantation via ovarian artery in patients with premature ovarian failure: a single-arm, phase 1 clinical trial.

Background: Premature ovarian failure (POF) is a prevalent and severe condition that impairs female health but there is currently no effective treatment available to restore ovarian function. Human amniotic epithelial cells (hAECs) exhibit ovarian protection in pre-clinical models. Thus, we conducted a single-arm, phase 1 clinical trial to assess the safety and efficacy of allogenic hAECs in treating POF. Methods: A total of 35 patients received 6 × 107 hAECs via ovarian artery and completed a five-month follow-up from December 30, 2020 to January 31, 2022. The follow-up assessments were conducted at various intervals after hAECs treatment, including one month (Visit-1, V-1), three months (Visit-2, V-2), and five months (Visit-3, V-3) post-treatment. The primary endpoints were incidence of adverse events (AEs), and clinically significant laboratory abnormalities. Secondary endpoints included evaluation of transvaginal ultrasound results, sex hormone levels, Menopausal Quality of Life (MENQOL) questionnaire, as well as reproductive indicators. This trial was registered at www.clinicaltrials.gov as NCT02912104. Findings: No serious AEs were observed throughout the five-month follow-up period. The most common AE was hematoma (7/35, 20.00%), and other AEs include pelvic pain (4/35, 11.43%), fever (2/35, 5.71%), anaphylaxis (2/35, 5.71%), and hepatotoxicity (1/35, 2.86%). After hAECs transplantation (hAECT), significant improvements were observed in the levels of endometrial thickness, left ovarian volume, sex hormones (follicle-stimulating hormone (FSH) and estradiol (E2)), and MENQOL scores in all patients during the five-month follow-up period. Among them, 13 participants (37.14%) experienced spontaneous menstrual bleeding, and 20.00% (7/35) reported more than one regular menstrual bleeding post-hAECT. In this response group, significant improvements were observed in endometrial thickness, left ovarian volume, levels of FSH, E2, anti-Müllerian hormone (AMH), and MENQOL scores one month after hAECT in comparison to pre-hAECT. Interpretation: hAECT via ovarian artery is safe, well-tolerated and temporarily ameliorates endometrial thickness, ovarian size, hormone levels, and menopausal symptoms in POF patients. Further randomized controlled trial of hAECs with longer follow-up period and a larger sample size is warranted. Funding: National Natural Science Foundation of China (No. 82271664), the Interdisciplinary Program of Shanghai Jiao Tong University (YG2022ZD028), the Shanghai Municipal Health Committee (202240345), Shanghai Key Laboratory of Embryo Original Diseases (No. Shelab2022ZD01), Shanghai Municipal Education Commission (No. 20152236), and National Key Research and Development Program of China (No. 2018YFC1004802), Shanghai Clinical Research Center for Cell Therapy, China (No. 23J41900100).

Placental expressions of Anti-Mullerian hormone/Receptor, vascular endothelial growth factor and related microRNAs in patients with preeclampsia: a case control study.

Anti-Mullerian hormone (AMH) has been implicated in the pathogenesis of preeclampsia. The present study was primarily designed to determine the placental tissue AMH, Anti-Mullerian hormone Receptor II (AMHRII), vascular endothelial growth factor (VEGF) and microRNA (miRNA) 26a/126/155/210 expressions and serum miRNA 26a/126/155/210 levels in patients with preeclampsia to examine their potential role in the pathogenesis of preeclampsia. Placental tissue samples from patients with preeclampsia (n = 20) and control subjects (n = 20) were examined by immunohistochemical staining and quantitative polymerase chain reaction (qPCR) for AMH, AMHRII, VEGF mRNA expression levels and miRNA 26a/126/155/210 expressions. Serum levels of miRNA 26a/126/155/210 were measured by qPCR. Patients with preeclampsia had lower AMH/AMHRII immunostaining, particularly in syncytiotrophoblastic cells compared to control subjects (p < 0.05). The relative mRNA expressions of AMH/AMHRII were increased (1.535 ± 0.121 and 1.155 ± 0.049 fold, p < 0.0002 and p < 0.033, respectively) and the relative mRNA expression of VEGF was decreased (4.878 ± 0.331 fold, p < 0.0002) in patients with preeclampsia compared to control subjects. The miR-26a expression was increased and miR-126 expression was decreased in serum samples of patients with preeclampsia compared to control subjects (p < 0.0002). miR-155 and miR-210 expressions were increased in serum and placental tissue samples of patients with preeclampsia compared to control subjects (p < 0.0002). In conclusion, reduced placental tissue immunostaining of AMH/AMHRII along with increased AMH/AMHRII mRNA expressions may indicate posttranscriptional dysregulation. Robust increase in expressions of hypoxia/inflammation-related miRNAs particularly miR-155 and miR-210 might have a role in this mechanistic pathway. Increased serum levels of miR 26a, 155 and 210 are potential early diagnostic markers for preeclampsia.

Dehydroepiandrosterone supplementation improves diminished ovarian reserve clinical and in silico studies.

The therapeutic role of dehydroepiandrosterone (DHEA) supplementation among infertile women with diminished ovarian reserve (DOR) is still unclear. Objective evaluation of different ovarian reserve tests (ORTs) such as serum anti-Mullerian hormone (AMH), serum follicle stimulating hormone (FSH), and antral follicle count (AFC) in women with diminished ovarian reserve is required. This is a cross-sectional study performed in Mosul city, Iraq, with 122 infertile women who had been diagnosed with DOR. The enrolled women's age ranged from 18 to 45 years old (mean age of 29.46 ± 2.64 years). The ages of the enrolled women ranged from 18 to 45 years (mean age of 29.46 ± 2.64 years). To assess the influence of DHEA supplements (25 mg, three times/day for 12 weeks) across different age groups, the women were initially divided into three groups (18 to 27 years old, 28 to 37 years old, and ≥ 38 years old). Significant differences were noticed in AMH, FSH, level and AFC before and after DHEA supplementation. (AMH: 0.64 ± 0.82 vs. 1.98 ± 1.32, AFC: 2.86 ± 0.64 vs. 5.82 ± 2.42, and FSH: 12.44 ± 3.85 vs. 8.12 ± 4.64), statistically obvious significant differences regarding the results of AMH (p < 0.001), AFC (p < 0.001), and FSH (p < 0.001). DHEA supplementations improved the ovarian reserve of the enrolled women, which was more evident in younger women (<38 years old) than older women (≥38 years old). The AMH serum levels and AFC value can be considered the best, most reliable and significant OR parameters. However, large randomized multicenter studies are required to confirm the available results and data.

[Resveratrol enhances the local antioxidant ability of the ovary in rats with polycystic ovary syndrome].

OBJECTIVE: To investigate the effects of resveratrol (RSV) on ovarian morphology, plasma anti-Müllerian hormone (AMH) and insulin-like growth factor 1 levels (IGF-1), and oxidative stress parameters in rats with polycystic ovary syndrome (PCOS). METHODS: Forty-six rats were randomly divided into a normal control (n = 12), a PCOS model control (n = 12), a rosiglitazone (RSG, n = 11), and an RSV group (n = 11). The PCOS model was established in the latter three groups by rejection of epidehydroandrosterone. The rats in the normal control and PCOS model control groups were treated by gavage of normal saline and those in the RSG and RSV groups by intragastric administration of RSG at 10 mg/(kg·d) and RSV at 3.0 mg/(kg·d), respectively. After 4 weeks of treatment, the ovarian histology was observed under the light microscope, the levels of plasma AMH and IGF-1 measured by ELISA, and the activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) in the ovarian tissue detected using the Ellman, Sun and AEBI methods, respectively. RESULTS: After a 4-week treatment, statistically significant differences were observed in the above indicators between the normal control and PCOS model control groups (P<0.05). The rats treated with RSG and RSV also showed significant differences in these parameters from the model controls (P<0.05). CONCLUSION: RSV can enhance the local antioxidant capacity of the ovary, reduce the levels of AMH and IGF-1, and improve the morphology of the ovarian tissue in rats with PCOS, indicating its potential value in the treatment of PCOS.

Associations of bisphenol and phthalate exposure and anti-Müllerian hormone levels in women of reproductive age.

Background: In women, exposure to endocrine disrupting chemicals might accelerate the depletion of the ovarian reserve and might be associated with accelerative reproductive aging and fertility. We examined the longitudinal associations of exposure to bisphenols and phthalates with anti-Müllerian hormone concentrations. Methods: Pregnant women of 18 years or older that resided in Rotterdam between 2002 and 2006 were eligible for participation in this longitudinal prospective cohort study. We measured urinary bisphenol and phthalate concentration at three time-points in pregnancy among 1405 women, of whom 1322 women had serum Anti-Müllerian Hormone (AMH) measurements 6 and/or 9 years postpartum. We performed linear regression models to assess the association of urinary bisphenol and phthalate metabolites with AMH after 6 and 9 years, and linear mixed-effect model to assess the association with AMH over time. Models were adjusted for sociodemographic and lifestyle factors. Findings: In our multivariable linear regression models we observed associations of higher urinary pregnancy-averaged mono-isobutyl phthalate (mIBP), mono-(2-ethyl-5-oxohexyl) phthalate (mEOHP), and monobenzyl phthalate (mBzBP) with lower serum AMH after both 6 and 9 years. However, these associations did not remain after adjustment for multiple testing. No significant associations of bisphenol A with AMH were present in our study sample. In our linear mixed-effects models, higher mIBP, mono-(2-ethyl-5-hydroxyhexyl) phthalate (mEHHP), mEOHP, and mBzBP were associated with lower overall AMH levels (differences -0.07 (95% CI -0.13, -0.02), -0.09 (-0.15, -0.02), -0.08 (95% CI -0.14, -0.02), and -0.08 (-0.13, -0.03) µg/L per doubling in mIBP, mEHHP, mEOHP, and mBzBP respectively) (all False Discovery Rate adjusted p-values < 0.05). Interpretation: We identify decreases in indices of ovarian reserve in relationship to prenatal phthalate exposures. Studies are needed replicating our results among large multi-ethnic non-pregnant populations and assessing transgenerational effects of exposure on ovarian reserve. Funding: This study was supported by the Erasmus Medical Center and Erasmus University Rotterdam, the Netherlands Organisation for Health Research and Development, the European Research Council, the Dutch Heart Foundation, the Dutch Diabetes Foundation, the European Union's Horizon 2020 Research and Innovation Program, the National Institutes of Health, Ansh Labs Webster, and the Royal Netherlands Academy of Arts and Sciences.

Dissecting the shared genetic architecture between anti-Müllerian hormone and age at menopause based on genome-wide association study.

BACKGROUND: While the phenotypic association between anti-Müllerian hormoneand age at menopause has been widely studied, the role of anti-Müllerian hormone in predicting the age at menopause is currently controversial, and the genetic architecture or causal relationships underlying these 2 traits is not well understood. AIM: We aimed to explore the shared genetic architecture between anti-Müllerian hormone and age at menopause, to identify shared pleiotropic loci and genes, and to investigate causal association and potential causal mediators. STUDY DESIGN: Using summary statistics from publicly available genome-wide association studies on anti-Müllerian hormone (N=7049) and age at menopause (N=201,323) in Europeans, we investigated the global genetic architecture between anti-Müllerian hormone and age at menopause through linkage disequilibrium score regression. We employed pleiotropic analysis under composite null hypothesis, Functional Mapping and Annotation of Genetic Associations, multimarker analysis of GenoMic annotation, and colocalization analysis to identify loci and genes with pleiotropic effects. Tissue enrichment analysis based on Genotype-Tissue Expression data was conducted using the Linkage Disequilibrium Score for the specific expression of genes analysis. Functional genes that were shared were additionally identified through summary data-based Mendelian randomization. The relationship between anti-Müllerian hormone and age at menopause was examined through 2-sample Mendelian randomization, and potential mediators were further explored using colocalization and metabolite-mediated analysis. RESULTS: A positive genetic association (correlation coefficient=0.88, P=1.33×10-5) was observed between anti-Müllerian hormone and age at menopause. By using pleiotropic analysis under composite null hypothesis and Functional Mapping and Annotation of Genetic Associations, 42 significant pleiotropic loci were identified that were associated with anti-Müllerian hormone and age at menopause, and 10 of these (rs10734411, rs61913600, rs2277339, rs75770066, rs28416520, rs9796, rs11668344, rs403727, rs6011452, and rs62237617) had colocalized loci. Additionally, 245 significant pleiotropic genes were identified by multimarker analysis of GenoMic annotation. Genetic associations between anti-Müllerian hormone and age at menopause were markedly concentrated in various tissues including whole blood, brain, heart, liver, muscle, pancreas, and kidneys. Further, summary data-based Mendelian randomization analysis revealed 9 genes that may have a causative effect on both anti-Müllerian hormone and age at menopause. A potential causal effect of age at menopause on anti-Müllerian hormone was suggested by 2-sample Mendelian randomization analysis, with very-low-density lipoprotein identified as a potential mediator. CONCLUSION: Our study revealed a shared genetic architecture between anti-Müllerian hormone and age at menopause, providing a basis for experimental investigations and individual therapies to enhance reproductive outcomes. Furthermore, our findings emphasized that relying solely on anti-Müllerian hormone is not sufficient for accurately predicting the age at menopause, and a combination of other factors needs to be considered. Exploring new therapeutics aimed at delaying at the onset of menopause holds promise, particularly when targeting shared genes based on their shared genetic architecture.

Effect of Combined Low Dose Human Gonadotropic Hormone , Follicle Stimulating Hormone, and Testosterone Therapy (LFT Regimen) Versus Conventional High Dose Human Gonadotropic Hormone and Follicle Stimulating Hormone on Spermatogenesis and Biomarkers in Men With Hypogonadotropic Hypogonadism.

OBJECTIVE: In male congenital hypogonadotropic hypogonadism (CHH), it was observed that lower dose human gonadotropic hormone (hCG) can maintain normal intratesticular testosterone levels. We propose this study to compare the low-dose hCG, follicle stimulating hormone (FSH), and Testosterone (T) [LFT Regimen] to conventional treatment to induce virilization and fertility. DESIGN: This open-label randomized pilot study was conducted from June 2020 to December 2021. SUBJECTS AND OUTCOME MEASURES: CHH were randomly assigned to either the LFT regimen (Group A)-low-dose hCG (500U thrice per week), FSH (150U thrice per week), and T(100 mg biweekly) or conventional therapy(GroupB) with high hCG dose(2000U thrice per week) and the same FSH dose. The hCG dosage was titrated to reduce anti-mullerian hormone (AMH) by 50% and normalization of plasma T in groups A and B, respectively. The primary objective was to compare the percentage of individuals who achieved spermatogenesis between the two groups. RESULTS: Out of 30 patients, 23 (76·7%) subjects achieved spermatogenesis, and the median time was 12 (9-14·9) months. There was no difference in achieving spermatogenesis between the two groups (64·3% vs 7·5%,P = 0·204), and even the median time for spermatogenesis was similar (15months vs 12months,P = 0·248). Both groups had nonsignificant median plasma AMH at spermatogenesis, [6·6 ng/ml (3·3-9·76) vs4·41 ng/ml (2·3-6·47), P = 0·298]. Similarly, the median plasma Inhibin B at spermatogenesis between groups were comparable [152·4 pg/ml (101·7-198·0) vs49·1 pg/ml (128·7-237·3), P = 0·488]. CONCLUSIONS: A reasonable approach to induce fertility in male CHH is to initiate combination therapy using FSH, low-dose hCG targeting AMH <6·9 ng/ml, along with T to achieve normal range. Monitoring AMH could serve as a proxy indicator of spermatogenesis.

Altered ovarian reserve in Ewe lambs exposed to a glyphosate-based herbicide.

Glyphosate-based herbicides (GBHs) are considered endocrine disruptors that affect the female reproductive tract of rats and ewe lambs. The present study aimed to investigate the impact of neonatal exposure to a low dose of a GBH on the ovarian follicular reserve of ewe lambs and the response to a gonadotropic stimulus with porcine FSH (pFSH). To this end, ewe lambs were orally exposed to an environmentally relevant GBH dose (1 mg/kg/day) or vehicle (Control) from postnatal day (PND) 1 to PND14, and then some received pFSH (50 mg/day) between PND41 and 43. The ovaries were dissected, and follicular types and gene expression were assessed via RT-PCR. The treatments did not affect the body weight of animals, but pFSH increased ovarian weight, not observed in GBH-exposed lambs. GBH-exposed lambs showed decreased Estrogen receptor-alpha (56%), Progesterone receptor (75%), Activin receptor II (ACVRII) (85%), and Bone morphogenetic protein 15 (BMP15) (88%) mRNA levels. Control lambs treated with pFSH exhibited downregulation of Follistatin (81%), ACVRII (77%), BMP15 (93%), and FSH receptor (FSHr) (72%). GBH-exposed lambs treated with pFSH displayed reduced ACVRII (68%), BMP15 (81%), and FSHr (50%). GBH-exposed lambs also exhibited decreased Anti-Müllerian hormone expression in primordial and antral follicles (27%) and (54%) respectively) and reduced Bone morphogenetic protein 4 (31%) expression in primordial follicles. Results suggest that GBH disrupts key follicular development molecules and interferes with pFSH action in ovarian receptors, decreasing the ovarian reserve. Future studies should explore whether this decreased ovarian reserve impairs adult ovarian function and its response to superovulation stimuli.

Reproductive outcome after in vitro fertilization in endometriosis - key factors and implications.

Endometriosis is a benign chronic disease with a major impact on a woman's quality of life, mainly due to painful physical symptoms. Endometriosis is also a common cause of infertility caused by low ovarian reserve, distorted pelvic anatomy, and severe local inflammation with a direct negative impact on the quality of oocytes, embryos, and endometrium. We conducted a retrospective study between January 2019 and December 2023, including women with a history of surgery for endometriosis who underwent in vitro fertilization (IVF) to achieve pregnancy. Their reproductive outcome was compared with a group of patients with documented tubal obstruction. The aim of our study was to identify the factors associated with a positive impact on the pregnancy rate, specifically age, anti-Mullerian hormone (AMH), ovarian stimulation protocol, and types of gonadotropins used. We analyzed a group of 175 patients with endometriosis compared with 189 patients with tubal obstruction. The average age was similar between the two groups but with a difference in the average AMH value (1.63 ± 1.09 ng/mL vs. 2.55 ± 1.67 ng/mL). The most utilized ovarian stimulation protocol in both groups was the short gonadotropin-releasing hormone (GnRH) antagonist. The clinical pregnancy rate was 27.2% in the endometriosis group and 54.7% in the tubal obstruction group. Our study revealed that treatment with corifollitropin alfa in the endometriosis group was associated with a higher clinical pregnancy rate. AMH and age proved to be significant independent factors for the reproductive outcome.

Prevalence and correlates of diagnosed and probable polycystic ovary syndrome (PCOS) in a cohort of parous women.

OBJECTIVES: To assess correlates of diagnosed and probable polycystic ovary syndrome (PCOS) among parous women. METHODS: This study includes 557 women recruited from multi-specialty clinics in eastern Massachusetts. We categorized women as "diagnosed PCOS" based on medical records and self-reported clinician-diagnoses. Next, we constructed a category of "probable PCOS" for women without a diagnosis but with ≥2 of the following: ovulatory dysfunction (cycle length<21 or ≥35 days), hyperandrogenism (free testosterone>75th percentile), or elevated anti-Müllerian hormone (>75th percentile). We classified the remaining as "no PCOS," and compared characteristics across groups. RESULTS: 9.7% had diagnosed and 9.2% had probable PCOS. The frequency of irregular cycles was similar for diagnosed and probable PCOS. Free testosterone and AMH were higher for probable than diagnosed PCOS. Frequency of irregular cycles and both hormones were higher for the two PCOS groups vs. the no PCOS group. Obesity prevalence for diagnosed PCOS was twice that of probable PCOS (43.9% vs. 19.6%), yet the two groups had similar HbA1c and adiponectin. CONCLUSIONS: Women with probable PCOS are leaner but have comparable glycemic traits to those with a formal diagnosis, highlighting the importance of assessing biochemical profiles among women with irregular cycles, even in the absence of overweight/obesity.

Association of Anti-Müllerian Hormone on Oocyte Maturation, Fertilization, and Pregnancy Rates in Patients under Assisted Reproductive Technology Cycles: A Cross-Sectional Study.

BACKGROUND: Ovarian reserve is one of the most important factors that influences the success of assisted reproductive technology (ART). Recently, the role of anti-müllerian hormone (AMH) in ART has been investigated as a marker for the prediction of ovarian response. We aim to examine this relationship within a large Iranian population. MATERIALS AND METHODS: In this cross-sectional study, we obtained data from 1000 infertile couples who referred to the Research and Clinical Centre of Yazd Infertility Clinic for in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). Serum AMH levels, oocyte count, numbers of fertilised oocytes, endometrial thickness, and percentage of mature oocytes were measured. The relationship between AMH serum levels and the number and quality of oocytes and embryos in ART cycles was analysed. RESULTS: In the linear regression model, the log of the variables total dose of gonadotropin, two pronuclei (2PN), log oestradiol, total embryos, duration of stimulation, number of embryos transferred, protocol, and cause of infertility were significant predictors of log AMH. CONCLUSION: There appears to be a relationship between serum AMH levels in the early follicular phase and ovarian reserve. Higher serum AMH levels were also associated with shorter ART cycles.

Temperature-Dependent Sex Determination in Crocodilians and Climate Challenges.

The sex of crocodilians is determined by the temperature to which the eggs, and hence the developing embryo are exposed during critical periods of development. Temperature-dependent sex determination is a process that occurs in all crocodilians and numerous other reptile taxa. The study of artificial incubation temperatures in different species of crocodiles and alligators has determined the specific temperature ranges that result in altered sex ratios. It has also revealed the precise temperature thresholds at which an equal number of males and females are generated, as well as the specific developmental period during which the sex of the hatchlings may be shifted. This review will examine the molecular basis of the sex-determination mechanism in crocodilians elucidated during recent decades. It will focus on the many patterns and theories associated with this process. Additionally, we will examine the consequences that arise after hatching due to changes in incubation temperatures, as well as the potential benefits and dangers of a changing climate for crocodilians who display sex determination based on temperature.

Anti-Müllerian hormone a surrogate of follicular fluid oxidative stress in polycystic ovary syndrome?

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women at childbearing age. Anti-Müllerian hormone (AMH) is a widely accepted sensitive marker of ovarian reserve, which has been suggested that could also act as biomarker of ovarian morphology for PCOS diagnosis. Oxidative stress (OS) is known to be associated and have a negative impact factor in several reproductive conditions, including PCOS. However, the relationship between circulating AMH and OS within the follicular fluid (FF), and its potential impact on in vitro fertilization (IVF) outcomes of women with PCOS, remains largely unexplored. A total of 84 women, with PCOS (n = 30) or ovulatory controls (n = 54), were enrolled in this study. Women underwent individualized controlled ovarian stimulation for oocyte retrieval. Blood and FF obtained from mature follicles were collected at the time of oocyte retrieval, for measuring total testosterone, ∆4-androstenedione, progesterone, sex hormone binding globulin (SHBG) and AMH. OS in the FF was assessed by measuring total antioxidant capacity (TAC) through the ferric reducing antioxidant power (FRAP) and lipid peroxidation (LPO) by quantification of malondialdehyde (MDA) levels. Our results demonstrated that women with PCOS had significantly higher plasma levels of AMH, ∆4-androstenedione, total testosterone and a free androgen index (FAI) than observed in non-PCOS controls. In women with PCOS, total testosterone and AMH levels in the FF were also higher, while TAC was lower compared to non-PCOS. Furthermore, circulating AMH levels were positively correlated with ∆4-androstenedione, albeit negatively correlated with TAC. In this study we demonstrated that the susceptibility to OS, as assessed by the total antioxidant capacity in the FF, is higher in women with PCOS and inversely related to AMH levels. This study results lead us to forge the reasonable hypothesis that the greater susceptibility to OS within the follicle microenvironment is potentially at the end of a roadway that starts with elevated ∆4-androstenedione and AMH within the FF, which in turn are mirrored by circulating AMH and androgen levels. Thus, suggesting that circulating AMH levels could act as a surrogate biomarker of follicular fluid oxidative stress in women with PCOS.