anti-Müllerian Hormone Research Articles

Identify high-risk DOR women ≤ 35 years old following assisted reproduction technology through cutoffs of anti-mullerian hormone and antral follicle counts

BackgroundFemales with diminished ovarian reserve (DOR) have significantly lower cumulative live birth rates (CLBRs) than females with normal ovarian reserve. A subset of young infertile patients, whose ovarian reserve is declining but has not yet met the POSEIDON criteria for DOR, has not received the attention it merited. These individuals have not been identified in a timely manner prior to the initiation of assisted reproductive technology (ART), leading to suboptimal clinical pregnancy outcomes. We categorized this overlooked cohort as the “high-risk DOR” group.ObjectiveThe primary aim of this study was to identify high-risk DOR patients through anti-Mullerian hormone (AMH) and antral follicle counts (AFCs).MethodsA total of 10037 young women (≤ 35 years old) who underwent their first initial oocyte aspiration cycle at a single reproductive medicine center were included and further classified into three groups, based on the thresholds for AMH and AFC established through receiver operating characteristic (ROC) analysis and in alignment with the POSEIDON criteria. Two ROC analyses were performed to identify the cutoff values of AMH and AFC to obtain one viable embryo (one top-quality embryo or one viable blastocyst). The cutoffs of ROC were measured by sensitivity and specificity. The primary outcome was the cumulative live birth rate (CLBR) per oocyte aspiration cycle. The secondary outcomes included the number of oocytes retrieved and the number of viable embryos formed. Pearson’s chi-square tests were conducted to compare the clinical outcomes among the three groups. Furthermore, univariate logistic regression analyses were performed to investigate the associations between ovarian reserve and clinical outcomes. All of the above comparisons between the high-risk DOR and NOR were further confirmed by propensity score matching (PSM) (1:1 nearest-neighbor matching, with a caliper width of 0.02).ResultsAccording to the ROC analyses and POSEIDON criteria, the present study identified a population of high-risk DOR patients (1.20 ng/mL < AMH values < 2.50 ng/mL, with 6 ≤ AFC ≤ 10; n = 682), and their outcomes were further compared to those of DOR patients (positive control, AMH values ≤ 1.2 ng/mL, and/or AFC ≤ 5; n = 1153) and of NOR patients (negative control, 2.5 ng/mL ≤ AMH values ≤ 5.5 ng/mL, and 11 ≤ AFC ≤ 20; n = 2649). Patients in the high-risk DOR group had significantly lower CLBRs than those in the NOR group (p < 0.001) but higher CLBRs than those in the DOR group (p < 0.001). Logistic regression further demonstrated that high-risk DOR was associated with a lower likelihood of cumulative live birth chance (OR 0.401, 95% CI: 0.332–0.486, p < 0.001) than NOR was, with a greater likelihood of cumulative live birth chance (OR 1.911, 95% CI:1.558–2.344, p < 0.001) than DOR was. To investigate the effects of embryo development stage, the outcomes of D3 embryos and blastocysts were analyzed separately. Significant differences in pregnancy outcomes were detected only in D3 embryo ET cycles among the three groups (high-risk DOR vs. NOR, all p < 0.05; DOR vs. NOR, all p < 0.05). DOR/high-risk DOR did not influence the pregnancy loss rates or pregnancy outcomes (clinical pregnancy rates and ongoing pregnancy rates) per positive HCG cycle (all p > 0.05). After PSM, the differences in ovarian response and pregnancy outcomes between the high-risk DOR and NOR groups were consistent with the results before PSM.Conclusion(s)Our study revealed that the CLBR of the high-risk DOR patients was significantly lower than that of females with normal ovarian reserve and greater than that of females with DOR. The values of AMH ranging from 1.2 to 2.5 and AFC ranging from 6 to 10 appeared to constitute meaningful thresholds in females with mildly reduced ovarian reserve.

Key predictors of fertility: Exploring the role of Vitamin-D

Background &amp; Objectives: The relationship of Vitamin-D (VD) with Luteinizing Hormone (LH), Follicle stimulating Hormone (FSH) and Anti Mullerian Hormone (AMH) is recognized. This study was conducted to determine whether VD is a predictor of fertility and investigate its relationship with female reproductive hormones and markers of ovarian reserve in female population of Karachi. Methods: A cross-sectional study was performed from July 2020 to June 2022 at the Aga Khan University Hospital (AKUH) with recruitment of 135 fertile and infertile subjects. VD, AMH, FSH and LH levels were estimated by ‘Enzyme Linked Immunosorbent assay (ELISA)’. By applying binary logistic regression, variables with p-value &lt; 0.25 in univariate analysis were used for multivariate regression model and adjusted odds ratios were computed. In multivariate analysis, significance was p-value ≤ 0.05. Results: VD deficiency was observed in all infertile female subjects. In univariate regression analysis, FSH, LH, LH/FSH ratio and VD levels turned out to be significant. The Multivariate analysis represented that for every one ng/mL increase in VD level, the odds of fertility were expected to be 50.154 times higher with p-value &lt; 0.001. The positive correlation of VD with FSH was significant. Conclusion: VD deficiency was prevalent in all infertile female subjects. VD levels were strong predictor of fertility in the study population. The significant association of VD with FSH explained the indirect effect of VD on follicular development and ovarian functions however no relationship of VD with ovarian reserve was exhibited. Note: AI assisted technologies were used in the preparation of the manuscripts, to improve readability and language. doi: https://doi.org/10.12669/pjms.40.10.9774 How to cite this: Salahuddin H, Zaki S, Ashraf M, Rehana Rehman4. Key predictors of fertility: Exploring the role of Vitamin-D. Pak J Med Sci. 2024;40(10):2363-2367. doi: https://doi.org/10.12669/pjms.40.10.9774 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Anti-Müllerian Hormone Serum Levels as Biomarker of Ovarian Reserve in Adult Women with Juvenile Idiopathic Arthritis Treated with csDMARDs and/or bDMARDs: A Pilot Study

Background/Objectives: Juvenile idiopathic arthritis (JIA) is a chronic childhood disease that often persists into the reproductive years. JIA may impact long-term fertility due to the prolonged exposure to immunosuppressive therapies. Methods: A total of 35 adult JIA female patients of childbearing age and 20 age-matched healthy controls were studied to test their anti-Müllerian hormone (AMH) serum levels as a biomarker of ovarian reserve. Demographic characteristics, disease duration, previous and current treatments, disease activity (DAS44), and a health assessment questionnaire (HAQ) were recorded. Results: JIA patients had a mean age of 22.3 ± 2.9 years, a disease duration of 12.3 ± 6.1 years, and a DAS44 of 1.24 ± 0.61. No differences were found in AMH serum levels between JIA and controls (5.78 ± 2.37 ng/mL vs. 6.60 ± 2.68 ng/mL, respectively; p = 0.17). Among the patients, 22 (62.9%) were receiving a stable dose of methotrexate (MTX) and 19 (54.3%) a dose of TNFα inhibitors. No difference in AMH serum levels was observed between JIA patients who were or were not exposed to MTX (p = 0.29) or to TNFα inhibitors (p = 0.50). Conclusions: Ovarian reserve as assessed by AMH serum levels appears to be comparable between those with JIA and age-matched controls and does not appear to be influenced by disease characteristics or prior/concomitant exposure to immunosuppressive drugs.

Associations of AMH in mid-reproductive years with bone mineral density and turnover markers in mid-life.

Concentration of circulating anti-Müllerian hormone (AMH) predicts short-term (3-5 years) bone loss around menopause. Whether AMH during mid-reproductive years predicts bone health over a decade later is unknown. To study the association of AMH levels in mid-reproductive years with bone density and turnover biomarkers measured after ∼14 years of follow-up. We assessed plasma AMH in 2003-2006 (mean 37.0 years, SD 5.1) among 450 parous women (71% White) in a US longitudinal cohort, and bone mineral density (BMD; spine, hip, and femoral neck, measured by dual-energy X-ray absorptiometry) in 2017-2021 (mean 51.0 years, SD 5.1). Secondary outcomes were plasma levels of procollagen type I N-propeptide (PINP) and C-terminal telopeptide I (CTX-I). In linear regression models adjusted for demographics and lifestyle, compared to women with AMH >3.5 ng/mL, those with AMH <1.0 ng/mL had lower BMD (g/cm2) at follow-up (beta [95% CI]: spine: -0.06 [-0.10, -0.02]; hip: -0.05 [-0.08, -0.02]; femoral neck: -0.03 [-0.06, 0.00]) and higher bone turnover markers (beta [95% CI]: PINP: 0.36 SD [0.10, 0.63]; CTX-I: 0.34 SD [0.07, 0.60]). The association of AMH with spine BMD was more pronounced among post-menopausal women, in contrast to associations with bone turnover markers which were more pronounced among women who had not yet reached menopause. The associations between AMH and BMD were primarily mediated by menopausal status at follow-up. Lower AMH during mid-reproductive years is associated with lower BMD and higher bone turnover 14 years later. Ovarian reserve during mid-reproductive years may be a valuable predictor of long-term bone health.

Comparison of fresh and frozen-thawed embryo transfer cycles in patients with low oocyte retrieval

Objective: To explore the choice of embryo transfer schemes for patients with low oocyte retrieval (≤ 3 oocytes). Methods: A retrospective analysis was conducted on patients with oocyte yields ≤ 3 undergoing in vitro fertilization and embryo transfer (IVF-ET) and frozen embryo transfer (FET) at the Maternity &amp; Child Care Center of Qinhuangdao Reproductive Medicine Department from January 2018 to December 2022. The data included 202 fresh cycles, with 104 cycles in Group-A and 98 cycles in Group-B. Additionally, 87 cycles involved the transfer of frozen embryos from fresh cycles that could not be transplanted for various reasons, with 31 cycles in Group-C and 56 cycles in Group-D. General patient information, embryo transfer details, and clinical pregnancy outcomes in both fresh and frozen cycles were statistically analyzed. Results: No significant differences were observed between Groups A and C in age, anti-Müllerian hormone (AMH), basal follicle-stimulating hormone (bFSH), body mass index (BMI), duration of infertility, the proportion of patients with diminished ovarian reserve (DOR), oocyte retrieval count, usable embryo count, or the number of transplanted embryos (all p&gt; 0.05). Advanced age was a risk factor for a decreased pregnancy rate, and FET significantly increased the pregnancy rate (p&lt; 0.05, respectively). Conclusion: For patients under 35 years old with low oocyte retrieval, it is recommended to freeze all embryos when available and then proceed with FET. For patients aged 35 and above, without reducing the pregnancy rate, fresh embryo transfer is recommended to minimize treatment cycle frequency and economic expenses. doi: https://doi.org/10.12669/pjms.40.10.9269 How to cite this: Shi H, Song Q, Liu J, Li C, Liu R. Comparison of fresh and frozen-thawed embryo transfer cycles in patients with low oocyte retrieval. Pak J Med Sci. 2024;40(10):2251-2255. doi: https://doi.org/10.12669/pjms.40.10.9269 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Evaluation of Biochemical Serum Markers for the Diagnosis of Polycystic Ovary Syndrome (PCOS) in Obese Women in Kazakhstan: Is Anti-Müllerian Hormone a Potential Marker?

Background: Polycystic Ovarian Syndrome (PCOS) is a common endocrine condition that affects 8-13% of women of reproductive age. In Kazakhstan, the prevalence of this syndrome is particularly high compared with other countries and the global average. Currently, the diagnosis of PCOS is based on internationally established Rotterdam criteria, using hyperandrogenism as a key parameter. These criteria are applied to diagnose PCOS in all female patients, although obese patients may have excess testosterone produced by adipose tissue. To avoid possible misdiagnosis, an additional criterion, especially for the diagnosis of PCOS in obese women, could be considered. The aim of this study was to identify whether anti-Müllerian hormone (AMH) or other biochemical criteria can be used for this purpose. Methods: A total of 138 women were recruited for this study and grouped into control (n = 46), obese subjects without PCOS (n = 67), and obese patients with PCOS (n = 25). The health status, anthropometric parameters, and serum indicators for glucose, glycosylated hemoglobin, and hormone levels were examined for all subjects. Statistical data were analyzed using GraphPad Prism 10 software for interpretation of the data. Results: Serum AMH, testosterone, and LH were positively correlated in obese PCOS patients, while AMH and FSH were negatively correlated. Compared with other biochemical indicators, the serum AMH and testosterone levels in obese PCOS patients were significantly higher than those in non-PCOS patients (regardless of obesity), and AMH was also positively correlated with testosterone. Conclusions: AMH appears to be a reliable criterion in addition to testosterone for the diagnosis of PCOS in obese women.

Factors affecting the outcomes of in vitro fertilization in women with endometriosis: Preliminary data from Vietnam

Objectives: This study aimed to assess the efficacy of in vitro fertilization (IVF) in patients with endometriosis and identify related factors that may influence treatment outcomes. Methods: This retrospective descriptive study was conducted between November 2018 and November 2022. The study group comprised individuals who were diagnosed with endometriosis (endometrioma and/or adenomyosis) indicated for in vitro fertilization. The control group (129 patients with 249 cycles), which included patients without endometriosis and had an equivalent mean age as the study group patients. Results: In the endometriosis group, the quantities of retrieved oocytes and Anti-Müllerian Hormone (AMH) were reduced compared to the control group. The overall dose of gonadotropin and the duration of ovarian stimulation were significantly higher than the control group. The endometriosis group exhibited a Metaphase II (MII) oocyte rate of 82.3% and an oocyte fertilization rate of 82.2%. However, in patients with endometriosis, the rates of implantation, clinical pregnancy, and ongoing pregnancy were significantly lower than in patients without endometriosis. Besides, the clinical pregnancy rate of women with endometriosis was remarkably higher in the groups with maternal age ⩽35 years, a ratio of Follicle-stimulating Hormone to Luteinizing Hormone (FSH/LH) ⩽1.5, and over 10 retrieved oocytes. Conclusion: Endometriosis was associated with a decreased rate of implantation, clinical pregnancy, and ongoing pregnancy after in vitro fertilization treatment compared with patients without endometriosis. In vitro fertilization outcomes in patients with endometriosis were influenced by maternal age ⩽35 years, FSH/LH ratio ⩽1.5, and number of retrieved oocytes over 10.

Evaluation of Anogenital Distance and Anti-Müllerian Hormone Plasmatic Concentration as Potential Phenotypes to Predict Reproductive Performance in Holstein Heifers.

Anogenital distance (AGD) is a marker of the degree of prenatal exposure to androgens in multiple species, and it has been suggested that there is an inverse association between AGD and fertility. Therefore, the aim of this study was to determine the usefulness of AGD and anti-Müllerian hormone (AMH) concentrations, an indirect marker of the follicular population, as predictors of future reproductive potential in Holstein cattle. The AGD was measured in 566 females from 9 dairy farms in Galicia (Spain). A group of 172 females underwent a second measurement 9 months after. Additionally, data on the age at first insemination (1stAI age), number of AI (AI-PREG), age at first pregnancy (1stPREG age), age at first calving (1stCAL age), and calving-pregnancy (CAL-PREG) and calving-calving (CAL-CAL) intervals were collected. Blood samples were collected from 80 heifers to determine AMH concentrations. Our results showed that AGD varied minimally with age, and that cows with short AGD had earlier 1stAI age, 1stPREG age, and 1stCAL age (p < 0.05) than cows with long AGD. No significant differences were observed for the CAL-PREG and CAL-CAL intervals. Additionally, no significant association was found between AMH concentration and AGD or reproductive parameters. Consequently, the results suggest the possibility of using AGD as a marker of future reproductive performance in Holstein heifers. However, there was insufficient evidence to associate AMH concentrations and reproductive performance, underlining the need for further studies with larger sample sizes.

Delayed endometrial preparation for the induction of luteolysis as a potential factor for improved reproductive performance in Angus beef heifers with high antral follicle counts.

Antral Follicle Count (AFC) and anti-Müllerian hormone (AMH) concentrations are reflective for ovarian reserve and have been associated with improved reproductive performance in cattle. Key events for regulation of uterine receptivity are orchestrated by progesterone. As progesterone concentrations are greater in animals with high than low AFC, we tested the hypothesis, if the resulting improved uterine environment will lead to improved conceptus elongation and endometrial response to interferon tau. For four years, 10 heifers with lowest and highest AFC, respectively, were selected from 120 heifers. Reproductive tracts and blood samples for progesterone and AMH analysis were collected after synchronization and insemination. For a recovered conceptus, length was determined, and interferon tau (IFNT) transcript abundance was analyzed. Endometrial transcript abundance of interferon-stimulated gene 15 (ISG15) and oxytocin receptor (OXTR) were analyzed. Progesterone concentrations did not differ between Low and High AFC Group (P= 0.1). A difference in conceptus length was not observed. Endometrial abundance of ISG15 did not differ between Pregnant Low and High AFC heifers. Abundance of OXTR was greater in Open Low AFC than Open High AFC heifers (P< 0.01). Interaction of AMH and Pregnancy Status was determined, with greater AMH in Pregnant than Open High AFC heifers (P< 0.05). Improved uterine environment in High vs. Low AFC heifers did not result in longer conceptuses or improved endometrial response. As the increase in OXTR transcript abundance was only detected in Low AFC heifers, reported differences in reproductive performance might be associated with earlier initiation of luteolysis.

Exenatide improves cisplatin induced ovarian damage through NLRP3, Nrf-2, and TLR4 pathways.

Cisplatin (CP) toxicity causes ovarian damage by oxidative stress, inflammation and fibrosis. The aim of the present study is to investigate the possible beneficial effects of exenatide on the experimental ovarian damage model produced by CP. For 14 rats, CP was administered by intraperitoneally (i.p) twice a week for 5 weeks. No drug was administered to the remainder of rats (n = 7) (Group 0). The rats taken CP were divided into two groups. Group 1 rats (n = 7) were given 1 mL/kg/day saline i.p., and Group 2 rats (n = 7) was given with 20 μg/kg/day exenatide. The number of primordial, primary, secondary, and tertiary follicle was significantly lower in Group1 compared with Group 0 and Group 2. The ovarian fibrosis percent was significantly higher in Group 1 than Group 0 and 2. The plasma anti-Mullerian hormone value was lower in Group1compared with Group 0 and 2. Over Nuclear factor-erythroid factor 2-related factor 2 level, Over Toll-like receptor 4 level and over nucleotide-binding domain leucine-rich repeat and pyrin domain containing receptor 3 were higher in Group 1 compared with Group 0 and 2. Exenatide has possible beneficial effect on ovarian damage induced by CP by anti-inflammatory actions and can be a promising candidate for ovarian damage caused by CP.

The Effectiveness of Letrozole Alone or in Combination with Methotrexate in the Management of Ectopic Pregnancy, A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis aimed to investigate the effect of letrozole alone or in combination with Methotrexate on the management of ectopic pregnancy. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were applied for reporting. The EMBASE, PubMed, Scopus, and Web of Science databases were searched for relevant studies focused on women diagnosed with ectopic pregnancy and managed non-surgically with letrozole alone or in combination with methotrexate (MTX) until April 2024. The success rate, laboratory findings, and complications were analyzed and reported. Meta-analysis was done using RevMan 5.4.1 software. Out of 129 unique studies obtained, 7 of them were found eligible for final review; of which, 3 were nonrandomized prospective cohort studies, 2 were randomized clinical trials, and 2 study were case studies. In 5 studies letrozole was used as monotherapy. While in another study letrozole was used with MTX. The meta-analysis showed a significantly lower level of β-HCG in the letrozole group compared to MTX, 7days after initiation of treatment (Fixed effect model, MD = -92.22, 95%CI: [-159.39, -25.04], P = 0.007, I2 = 0%). There was no significant difference in the level of anti-mullerian hormone (AMH) between groups (Fixed effect model, MD = 0.18, 95%CI: [-0.09, 0.45], P = 0.20, I2 = 0%). Success rate, platelet count, and level of liver enzymes seemed to be better or similar among patients receiving Letrozole compared to patients receiving Methotrexate. Letrozole exhibits potential as a therapeutic option for ectopic pregnancies; however, further randomized clinical trials are necessary to establish strong evidence.

Korelasi Vitamin D terhadap Kadar Antimullerian Hormone pada Pasien Sindroma Ovarium Polikistik dengan Obesitas di Kota Palembang

Polycystic Ovary Syndrome (PCOS) is one of the most common endocrine system disorders affecting women of reproductive age. One of the biomarkers for the diagnosis of PCOS is Anti Mullerian Hormone (AMH). Meanwhile, women with PCOS are at higher risk for vitamin D deficiency. The research aims to examine vitamin D and AMH for PCOS women with obesity. PCOS or also known as hyperandrogenic anovulation (HA), or Stein-Leventhal syndrome, is one of the most common endocrine system disorders affecting women of reproductive age. This study was analytic with a cross-sectional approach. The subjects were women with PCOS who went to Dr. M. Hoesin Sriwijaya University (n=30). Inclusion criteria were patients diagnosed with PCOS using Rotterdam, patients who had not received therapy for insulin resistance, and were obese. The exclusion criteria were that the patient couldn’t fulfill Rotterdam criteria and/or option not to participate in this study. The results were that most patients experienced oligomenorrhea (76.7%), the age mean was 31.17 years, and the BMI mean was 33.4 kg/m2. The Spearman correlation test showed a negative correlation between AMH and Vitamin D (p=0.011, correlation coefficient=-0.458). There was no correlation between BMI and vitamin D in PCOS patients, but there was a negative correlation between AMH and vitamin D levels.

Antioxidant activity of self-nanoemulsifying drug delivery system (SNEDDS) of Curcuma longa in polycystic ovary syndrome rat model

Purpose: To investigate the effect of SNEDDS containing Curcuma longa extract on hormonal and histological improvement of polycystic ovary syndrome (PCOS) rat model. Method: A total of 36 female Wistar rats, aged between 8 and 10 weeks, were randomly divided into 6 groups, including control (normal rats), PCOS (untreated PCOS rats), PCOS + M (treated with 20 mg/kg bw/day metformin), PCOS + SC25, PCOS + SC50, and PCOS + SC100 (treated with Curcuma longa extract at 25, 50, and 100 mg/kg/day with SNEDDS, respectively). This study used a posttest-only control group design. The rats were euthanized on day 15, and blood samples were taken to examine malondialdehyde (MDA) and anti-mullerian hormone (AMH) levels. Ovarian tissue was prepared on a histological slide, and various follicles were observed. Data was analyzed using analysis of variance (ANOVA) and Kruskal-Wallis tests. Results: Curcuma longa extract, at 50 and 100 mg/kg, incorporated in SNEDDS resulted in a significant reduction in the corpus luteum number and width of the granulosa layer (p &lt; 0.05). Also, Curcuma longa significantly reduced malondialdehyde (MDA), anti-mullerian hormone (AMH), preantral follicles, and follicular cysts (p &lt; 0.05). Conclusion: Curcuma longa extract in SNEDDS reduces MDA and AMH levels and improves the histology of the ovaries in PCOS model rats. There is a need to conduct further studies of C. longa extract or isolates in SNEDDS using human cell lines of PCOS model.

Pathohistological Findings after Bilateral Ovariectomy in Mares with Behavioral Problems

Behavioral problems in reproductively healthy mares are a challenging issue that is successfully treated with bilateral ovariectomy (BO). This laparoscopic procedure represents an alternative to conservative treatment for mares not intended for breeding and results in high owner satisfaction regarding behavioral improvement. However, a pathohistological explanation to justify surgical ovarian removal regarding animal welfare is lacking. Therefore, the objective of this study was to pathohistologically evaluate bilaterally removed, clinically unremarkable ovaries of mares with behavioral problems (bOE, n = 20) and to compare them with pathohistologically confirmed granulosa cell tumors of mares with neoplastic ovaries (GCT-uOE, n = 10). A complete data set including preliminary presentation, clinical examination, and serum anti-Müllerian hormone (AMH) and testosterone was further analyzed in both groups. Both hormones were significantly higher in GCT-uOE compared with bOE. Immunohistochemical expression of Ki-67, AMH, aromatase, epidermal growth factor receptor, calretinin, and epithelial cadherin in granulosa cells of large follicular structures in bOE did not differ from neoplastic granulosa cells in GCT-uOE. Ultrasonographically nondetectable early neoplastic changes were pathohistologically evaluated in 15% of mares and anovulatory-like follicles in 30% of mares in bOE and might be one explanation for the high success rate of BO in 85% of bOE in this study.

Functional hypothalamic amenorrhoea and polycystic ovarian morphology: a narrative review about an intriguing association.

Functional hypothalamic amenorrhoea (FHA) is responsible for 20-35% of all cases of secondary amenorrhoea and, thus, is the second most common cause of secondary amenorrhoea after polycystic ovary syndrome (PCOS). A high number of patients with FHA reveal polycystic ovarian morphology (PCOM) on ultrasound. The combination of amenorrhoea and PCOM can lead to confusion. First, amenorrhoeic women with PCOM fulfil the revised Rotterdam criteria and, thus, can easily be misdiagnosed with PCOS. Moreover, it has been claimed that some women with FHA and concomitant PCOM differ from those without PCOM in terms of endocrine regulation and metabolic traits. The main focus of this article was on studies about FHA, which differentiated between patients with or without PCOM. The aim was to estimate the prevalence of PCOM and to look if it has an impact on pathophysiologic, diagnostic and therapeutic issues as well as on long-term consequences. Peer review original and review articles were selected from PubMed searches for this review. Searches were performed using the search terms 'polycystic AND functional hypothalamic amenorrhoea'. The reference lists of publications found were searched for relevant additional studies. The inclusion criteria for publications were: English language, patients' age ≥ 18 years, year of publication >1980, original studies, validated diagnosis of FHA, and validated diagnosis of PCOM using transvaginal ultrasound. The prevalence of PCOM in women with FHA varied from 41.9% to 46.7%, which is higher than in healthy non-PCOS controls. Hypothetically, the high prevalence might be due to a mixture of silent PCOM, as in the general population, and pre-existing PCOS. Several differences in metabolic and hormonal parameters were found between FHA-PCOM and FHA-non-PCOM patients. While oestrogen deficiency is common to both groups of patients, FHA-PCOM patients have a higher BMI, higher levels of anti-Müllerian hormone (AMH) and testosterone, a higher increase in LH in the course of a GnRH test, and lower sex hormone binding globulin (SHBG) levels than FHA-non-PCOM patients. The differential diagnosis between FHA-PCOM and PCOS, especially PCOS phenotype D (PCOM and oligo-/anovulation without hyperandrogenism), can be challenging. Several parameters have been suggested, which are helpful though not absolutely reliable. They include the typical causes for FHA (excessive exercise, energy deficit, and/or psychological stress), the serum levels of LH, testosterone, and SHBG, as well as the progestin challenge test. Whether FHA-PCOM has a different risk profile for long-term consequences concerning patients' metabolic and cardiovascular situation as well as their bone mass, is unclear. Concerning therapeutic aspects, there are only few data about FHA-PCOM compared to FHA-non-PCOM. To treat anovulation, the use of pulsatile GnRH treatment seems to be equally effective in both groups. Similar to FHA-non-PCOM patients, pulsatile GnRH therapy would be more efficient than exogenous gonadotropins in FHA-PCOM patients. Women with FHA-PCOM present a special sub-population of FHA patients. The diagnostic pitfall of FHA-PCOM should be emphasized in clinical guidelines about FHA and PCOS. The fact that almost half of the women with FHA have an ovarian follicle excess (i.e. PCOM) in face of low gonadotropin serum levels suggests that the intra-ovarian regulation of folliculogenesis is subject to individual variations, for unknown reasons, either genetic or epigenetic. Further studies are needed to investigate this hypothesis. Not applicable.

Anti-Müllerian hormone as a diagnostic marker for testicular degeneration in dogs: insights from cryptorchid models.

The increasing prevalence of infertility in male dogs in clinical practice mirrors current trends seen in human medicine. Acquired infertility is notably more common in dogs compared to congenital causes, with conditions such as testicular degeneration leading to irreversible loss of fertility. Current diagnostic methods for testicular degeneration, such as histopathological and cytological examinations, rely on testicular biopsy or fine needle aspiration, making them less feasible for routine use. Anti-Müllerian hormone (AMH), produced by Sertoli cells, has emerged as a potential alternative biomarker for testicular health, which can be measured in serum. This study evaluates AMH as a potential marker for testicular degeneration, using cryptorchid dogs as models for impaired fertility and altered testicular histology. The relationship between serum AMH levels and AMH tissue expression with impaired spermatogenesis and altered histology was investigated. Serum AMH levels were determined in intact, cryptorchid, and castrated individuals using an immuno-enzymatic ELISA kit and compared between subgroups based on testicular location. Tissue AMH immuno-expression was differentially quantified in two regions of interest (ROIs), the interstitial space and the seminiferous tubule, in both descended and retained gonads. Furthermore, testicles were analyzed using histomorphometric analysis in seminiferous tubules, while spermatogenesis was evaluated using the Johnsen score. Serum AMH levels were positively correlated with AMH expression assessed in both interstitial space (ρ = 0.494, p ≤ 0.01) and seminiferous tubules (ρ = 0.610, p ≤ 0.001). Conversely, serum AMH levels showed a negative correlation with the seminiferous tubule area (ρ = -0.435, p ≤ 0.05). Smaller seminiferous tubule areas were linked to increased AMH reactivity in both seminiferous tubules (ρ = -0.774, p ≤ 0.001) and interstitial space (ρ = -0.725, p ≤ 0.001). Additionally, lower Johnsen scores were associated with higher serum AMH levels (ρ = -0.537, p ≤ 0.01) and elevated AMH expression in both seminiferous tubules (ρ = -0.756, p ≤ 0.001) and interstitial space (ρ = -0.679, p ≤ 0.001). Our results suggest that higher serum levels and tissue expression of AMH are linked to smaller seminiferous tubules and poorer Johnsen scores, reflecting degenerative changes and Sertoli cell dysfunction in retained testicles. Given the similarities in the mechanisms that increase AMH levels in both cryptorchid and non-cryptorchid testicles affected by testicular degeneration, this study recommends using AMH as a marker for diagnosing testicular degeneration in dogs.

Experience of using transvaginal sclerotherapy in the treatment of ovarian endometriomas

BACKGROUND: Ethanol sclerotherapy is an effective and a safe surgical treatment method for ovarian endometrioma (OMA). Destruction with 95% ethanol solution of the capsule allows minimal impact on the ovarian reserve. However, this method should be thoroughly evaluated for the possibility to be used more frequently in practice. AIM: To determine the indications for the use of transvaginal sclerotherapy in surgical treatment of OMA. MATERIAL AND METHODS: Between October 2021 and October 2023, 17 patients with OMA were operated at the Moscow Regional Research Institute of Obstetrics and Gynecology, with sclerotherapy performed by transvaginal access. Clinical manifestations included pelvic pain (76.4%), dysmenorrhea (82.3%), dyspareunia (47.0%), bowel symptoms (35.3%), polymenorrhea (47.0%), and infertility (64.7%). Eleven (64.7%) of the patients had been previously operated because of ОМА. RESULTS: Postoperative anti-Mullerian hormone (AMH) levels were slightly reduced (mean difference before and after the surgery was 0.47 ng/ml). The mean antral follicle count in the both ovaries were 10.8 before surgery and 8.6 after surgery. The volume of the ovary decreased from 2 to 6 times after sclerotherapy of the endometrioma. Symptoms recurred in four women. Six (35.2%) recurrences of endometrioma were noted with ultrasound control after 3, 6, and 12 months postoperatively. Endometrioid detritus in the cyst capsule was not detected in 64.8% of cases. CONCLUSION: Preliminary results indicates the use of sclerotherapy by transvaginal access with ultrasound control for the treatment of endometriomas in women of reproductive age and patients planning pregnancy by ART with any level of ovarian reserve and recurrent, previously histologically confirmed, symptomatic endometriomas in women of reproductive age with no plans for pregnancy presently with a reduced ovarian reserve (AMH 1.2 ng/ml) and with any level of ovarian reserve but with symptomatic endometrioma in the preserved ovary. Transvaginal access is applicable for symptomatic endometriomas in women who had undergone several operations in the past.

INCIDENCE, SOCIODEMOGRAPHIC, AND CLINICAL CHARACTERISTICS OF ANOVULATORY INFERTILITY AMONG WOMEN PRESENTING TO A SECONDARY CARE HOSPITAL OF NORTH INDIA

Objectives: The objective of the study was to assess the incidence and factors associated with anovulatory infertility among reproductive-age women. Methods: The study was an observational cross-sectional study conducted in the Department of Obstetrics and Gynecology of a secondary care hospital of Prayagraj, Uttar Pradesh over a period of 20 months, from October 2020 to May 2022. A consecutive sampling method was used to recruit a total of 100 women presenting with a complaint of inability to conceive even after regular intercourse over the past 1 year into the present research. Based on the detailed physical and clinical examination as well as laboratory findings, the final diagnosis of the cause and the nature of the infertility (primary/secondary) were established. Results: Among the 100 patients, 22 were found to have anovulatory infertility. The mean age was 28.68±3.71 years. Majority (50%) belonged to the upper socioeconomic class the mean weight of patients was 55.91±5.66 kg and the mean body mass index was 22.85±2.21 kg/m2. Majority presented with normal menstruation, followed by oligomenorrhoea (45.5%). 81.8% of the participants had hirsutism. The mean follicle-stimulating hormone of patients was 6.30±1.87 IU/mL, the mean luteinizing hormone was 6.04±1.83 IU/mL, mean estradiol was 45.00±6.50 pg/mL, mean anti-mullerian hormone was 6.94±2.13 ng/mL, mean total cholesterol was 76.21±16.86 ng/dL, mean thyroid stimulating hormone was 2.63±0.98 mIU/L and mean prolactin was 15.94±4.94 ng/mL. About 86.4% had primary infertility, the most common cause being polycystic ovarian syndrome (PCOS, 63.6%). This was followed by hyperprolactinemia (13.6%) and hypothyroidism (9.2%). Secondary anovulation associated with obesity was identified in 13.6% of the patients. Conclusion: The incidence of anovulatory infertility was 22%, with the majority being primary infertility due to PCOS, followed by hyperprolactinemia, and hypothyroidism.

8303 Analysis of Over 2.2 Million Anti-Mullerian Hormone Patient Results Across Lifespan From Birth to Over 80 Years Using a Lab Developed Chemiluminescent Immunoassay

Abstract Disclosure: C. Cheng: None. D. Alfego: None. K.Y. Chun: None. Introduction: Anti-Mullerian hormone (AMH) is a glycoprotein produced by granulosa cells of the ovarian follicle in females and by Sertoli cells of the testes in males. AMH is best known to correlate with ovarian reserve in females. As such, AMH is among the most frequently ordered tests in reproductive age females. The clinical utility of AMH beyond ovarian reserve assessment, especially in males, pediatric and postmenopausal populations, is less commonly examined. As a national reference laboratory that serves approximately 50% of providers across the country, our large database provides an opportunity to examine the clinical utility of AMH testing in other areas of health besides fertility. Objective: To examine AMH test utilization across lifespan of males and females in the US. Methods: Retrospective AMH tests performed at Labcorp® endocrine specialty lab from year 2012 to 2023 of 2,229,845 female patients and 10,362 male patients have been analyzed. Patients with unspecified sex were excluded. Serum AMH levels from birth to 80 plus years for males vs females were compared. For clinical utility assessments, female results are separated into four age groups: pediatric (age 0-17), adult (age 18-39), perimenopausal (age 40-59), and postmenopausal (age &amp;gt;60), and males into pediatric (age 0-17), adult (age 18-59), and older adult (age &amp;gt;60). ICD-10 codes associated with testing order were reviewed for each subgroup based on age and sex Results: In postmenopausal females, AMH is most frequently ordered for evaluation of ovarian cancer, whereas menstrual disorders and PCOS make up the most frequent clinical entities associated with AMH orders in females &amp;lt;18 years. Fertility testing is the most common ICD-10 associated with AMH orders, particularly in reproductive age and perimenopausal females. The most common ICD-10s associated with AMH in pediatric males include delayed puberty, hypoplasia of penis, and childhood short stature. In the adult and older adult male groups, AMH is surprisingly found to also most commonly associate with fertility testing and hypogonadism, although the clinical significance of post pubertal AMH is less defined. Conclusion: AMH testing has most often been used for female fertility testing, but our data show that significant fraction (10-20%) of AMH testing is used to evaluate and manage other suspected endocrine disorders and malignancies including intersex conditions at birth, pubertal development disorder, polycystic ovarian syndrome, male gonadal disfunction at all ages and granulosa cell tumors. Analysis of our large database underscores a need for clinical study to better define AMH levels that are relevant for non-fertility-related conditions. Presentation: 6/2/2024

7222 Structural and Mechanistic Studies of the Bioactive Anti-Müllerian Hormone Procomplex

Abstract Disclosure: J.A. Howard: None. L. Hok: None. N.J. Sanford: None. R.L. Cate: None. K. Hart: Employee; Self; Regeneron Pharmaceuticals. E. Leach: None. D. Pepin: None. P.K. Donahoe: None. T.B. Thompson: Advisory Board Member; Self; Oviva Therapeutics, Keros Therapeutics. The Anti-Mullerian hormone (AMH), a divergent member of the TGF-beta signaling superfamily, plays crucial roles in reproductive development and maintenance. Owing to its key role as a negative feedback regulator in folliculogenesis, AMH has garnered significant interest for therapeutic applications in contraception and oncofertility. The bioactive form of AMH is a noncovalent complex, comprising the TGFβ-like signaling domain and a dimeric prodomain whose structure remains largely unexplored. The prodomain component is necessary for the dimerization and secretion of the signaling domain, shuttling the ligand to autocrine, paracrine, and endocrine targets. In contrast, the structure and biochemistry of this domain remain poorly characterized, and its role in enhancing AMH signaling remains unclear. This gap in understanding significantly limits the enhancement and wider application of AMH-based protein therapeutics. Molecular modeling unveiled an unexpected AMH prodomain structure: an N-terminal dimerizing domain (NTD) linked to a novel C-terminal binding domain (CTD). This atypical design was affirmed by both small-angle X-ray scattering and negative-stain EM. The CTD introduces a unique TGFβ superfamily fold consisting of a four-helix bundle and an unstructured binding “belt”. The more prodomain-like NTD does not interact with the signaling ligand, nor does it consistently interact with the CTD. Both domains exhibit high levels of interspecies conservation as well as disease-causing mutations, such as those found in PMDS, PCOS, and POI. Using single-particle Cryo-EM we have elucidated the molecular mechanisms of the interaction between the AMH prodomain and signaling domain bound by mAb 6E11. Our 3.2Å cryo-EM structure confirmed the predicted architecture and binding function of the CTD and demonstrated a new dimension of conformational plasticity within the signaling ligand. We observed movements up to 5Å at the fingertips and 10Å in the outer helices of the CTD. More unexpectedly, the conformation of the AMH signaling ligand in the procomplex form is far more open and extended than has been observed in any other structure of a TGF-beta superfamily ligand, including the AMH ligand bound to its receptor AMHR2. We see that transitioning from a prodomain-bound to a receptor-bound state involves significant conformational remodeling of the signaling domain. This reorganization supports a conformational shift mechanism for AMH signaling in which bivalent binding of AMHR2 at the cell surface induces a &amp;gt;15Å and 38° closing of the ligand fingertips, leading to prodomain displacement and subsequent recruitment of type I receptors. Our findings correct earlier structural misconceptions and build a comprehensive model for interpreting existing functional data. This structure provides a foundation for understanding AMH dysregulation and developing advanced AMH therapeutics. Presentation: 6/1/2024