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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.

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Anti-Müllerian hormone (AMH) has become a pivotal subject in the study of testicular descent, maturation, integrity, and male fertility. Recent studies explored its roles and implications across various domestic species. A prominent approach involved the understanding of the modulation of AMH in reproductive disorders, including cryptorchidism. While substantial findings have been reported in dogs, ruminants, swine, and horses, data on AMH in feline cryptorchidism remains limited. Here, we aimed to bridge this gap by comparing AMH serum levels among cryptorchid, healthy intact, and castrated tomcats, employing an enzyme-linked immunosorbent assay (ELISA) kit for quantification. In addition, AMH expression in retained and descended testes was evaluated through immunohistochemistry, with positive staining quantified via pixel analysis in two distinct regions of interest: the seminiferous tubule and the interstitial space. Furthermore, tissue samples were subjected to histological evaluation and morphometric analysis, which included the calculation of seminiferous tubule areas (STA) and assessment of Johnsen scores. Thus, the relationship between AMH expression, altered testicular histology, and impaired spermatogenesis could be examined. The expression of AMH in retained and descended testes, was investigated, and the relationship between AMH expression, altered testicular histology, and impaired spermatogenesis was examined. Mean serum AMH levels differed significantly (P < 0.001) across the different groups being 15.35 ± 4.66 ng/mL (mean ± SD) in healthy intact tomcats (n = 15), 25.55 ± 2.86 ng/mL (mean ± SD) in cryptorchids (n = 10) and below 0.015 ng/mL in castrated cats (n = 10). STAs and Johnsen scores were significantly reduced in retained testes when compared to descended gonads (P < 0.01). Furthermore, serum AMH was negatively correlated with both the STA (ρ = -0.725, P < 0.001) and the Johnsen scores (ρ = -0.699, P < 0.001), suggesting its potential value for tissue integrity and spermatogenesis evaluation. In addition, positive immunostaining was significantly higher in retained testes (P < 0.05), especially in the interstitial space (P < 0.01), suggesting an involvement of the Leydig cells. Additionally, the increased interstitial expression was linked to the degree of tissue degeneration and the impaired spermatogenesis being negatively corelated with both Johnsen scores (ρ = -0.309, P < 0.01) and STA (ρ = -0.208, P < 0.05). Our findings underscore the potential of AMH in assessing testicular health and reveal possible interspecific differences, stressing the need for further investigation in cats.

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OBJECTIVE: To evaluate the association between sleep quality and ovarian reserve among women of reproductive age. DESIGN: Cross-sectional study SETTING: Not applicable. PATIENTS: A total of 1070 female participants aged 20-40 years enrolled from February 2023 to January 2024. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: A questionnaire was administered to the participants to collect baseline information related to reproductive and lifestyle factors. Pittsburgh Sleep Quality Index (PSQI) was used to measure sleep quality. Assessment was conducted on ovarian reserve, including total antral follicle count (AFC), anti-Müllerian hormone (AMH) level, and basal sex hormone level. RESULTS: The study sample of 1070 women had a mean age of 31.67 ± 4.41 years. A total of 314 participants (29.35%) were classified under the poor sleep group (PSQI score > 5).Significant differences were observed in the follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), testosterone(T),AFC, and AMH between the two groups (P < 0.05). The poor sleep group exhibited significantly lower levels of AMH and AFC (P < 0.01). The FSH levels in the poor sleep group were higher (P < 0.01).After the adjustment for confounding factors, multivariate regression analysis results indicated that the per-unit increase in PSQI score was associated with increased odds of diminished ovarian reserve (adjusted odds ratio [AOR] of 1.28 for AMH < 1.1 ng/ml, 95% confidence interval [CI]: 1.20- 1.37; AFC < 7, AOR: 1.34 ,95% CI: 1.25- 1.43;FSH ≥10mIU/mL,AOR:1.16 ,95%CI 1.08-1.25;AMH < 1.1 ng/ml or AFC < 7 or FSH ≥10mIU/mL, AOR: 1.29, 95%CI:1.22- 1.37). Compared with the PSQI ≤ 5 group, subjects with PSQI > 5 had increased odds of diminished ovarian reserve (odds ratio [OR]: 3.80, 95% CI: 2.82- 5.13; AOR: 4.43, 95% CI: 3.22-6.14). After stratification by age and body mass index (BMI), compared with the PSQI ≤ 5 group, all subgroups of the PSQI > 5 group had increased odds of diminished ovarian reserve, especially <35-year-old and BMI ≤ 18.4 kg/m2 subgroups. CONCLUSIONS: Poor sleep quality is associated with diminished ovarian reserve in women of reproductive age.

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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.

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In recent years several studies established the diagnostic value of anti-Müllerian hormone (AMH) in companion animals. However, less is known about physiological AMH concentrations in young individuals highlighting the necessity to apply the diagnostic findings to this group. The aim of this study was to determine the AMH values of healthy male and female dogs between the age of 8 and 48 weeks, tomcats under 8 weeks and up to 48 weeks of age and queens between 2 to 12 weeks of age. In total, 96 blood samples were collected. Anti-Müllerian hormone was measured in all samples and testosterone was measured in the oldest age group of the males in both species. The hormones were analyzed using a human based chemiluminescence immune assay. Overall, AMH concentrations were higher in males than in females (p < 0.001). According to the AMH concentration there was no difference in males, but queens had significant higher AMH concentrations than bitches (p < 0.001). AMH remained high in males up to week 24 and decreased significantly thereafter (tomcats: p = 0.015; male dogs: p = 0.013), which correlated with an increase in testosterone levels for male dogs only. In bitches, AMH remained below the detection limit until the week 16 and slightly increased subsequently. In queens, AMH was detectable from the beginning with a significant increase in the older age group (p = 0.003). Half of the cats in the older age group even approached the chemiluminescence immune assay's upper limit. The results show that female cats secrete AMH much earlier than female dogs in which AMH secretion begins just shortly before the start of the puberty. In the male animals, the decrease in AMH concentration around puberty was similar in dogs and cats, but a correlation with the increase of testosterone was only observed in dogs. Further research is required to determine the origin of the high AMH concentrations in female kittens and the lack of correlation between testosterone and AMH concentrations in male kittens.

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Purpose: Female childhood cancer survivors (CCSs) risk infertility due to gonadotoxic chemotherapy/radiation. Anti-Müllerian hormone (AMH) helps evaluate ovarian reserve, and the 2020 Oncofertility Pediatric Initiative Network (O-PIN) risk stratification is utilized to counsel risk of gonadal dysfunction/infertility. This study analyzed how AMH levels after cancer treatment differ with age and correlate AMH with O-PIN risk level and clinical outcomes. Methods: A literature review and mega-analysis of individual patient data were performed. Females ages 0-20 years at the time of cancer diagnosis with AMH values post-treatment were included. AMH outcomes were compared by O-PIN risk stratification, age at diagnosis, cyclophosphamide equivalent dose (CED), and hematopoietic stem cell transplant (HSCT). Multivariable random effects mixed models correlated AMH with diminished ovarian reserve (DOR), premature ovarian insufficiency (POI), and pregnancy. Results: In 13 studies with 608 CCSs, the median age (years) at diagnosis was 12.0 (interquartile range [IQR] 5.2-16.2) and 21.1 (IQR 17.1-30.0) at AMH measurement. AMH values were higher with time since treatment and correlated with the O-PIN risk level. Patients with HSCT had very low/undetectable AMH levels regardless of CED; when stratified by CED, AMH levels were lower if treated peripubertally or older. AMH was detectable in 54% (34/63) of patients with POI on hormone replacement. Pregnancy did not correspond to the gonadotoxicity risk level (p = 0.70). Conclusion: This study supports utilizing the O-PIN risk stratification system in estimating risk of DOR in CCSs and its categorization by pubertal status. AMH levels may return over time even after receiving the highest risk therapy. These findings may help counsel cancer patients pre- and post-therapy.

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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.

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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.

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Objective: Ovarian reserve and hence ovarian response has a key role in assisted reproductive technology and predicting response to gonadotrophins in controlled ovarian hyperstimulation. Various tools, namely follicle-stimulating hormone (FSH), anti-Mullerian hormone (AMH), antral follicle count (AFC), estradiol, etc., have been studied to discover the best determinant of ovarian reserve. The aim of our study is to correlate different reproductive hormones with age of women to estimate ovarian reserve and to evaluate reliable marker for aiding infertility treatment. Materials and Methods: It is an observational study performed for 6 months, with 88 women (aged 21-39 years) having a complaint of infertility, enrolled in the infertility clinic of a tertiary care hospital. Baseline scan for AFC was done for every patient and their blood was sent for serum FSH, AMH analysis. Statistical procedures were employed to determine the association between age and reproductive hormones (i.e. FSH and AMH) as independent variables and AFC as a dependent variable. Results: A strong negative correlation was noted between FSH and AMH and between age and AMH (r = -0.492 and r = -0.498, respectively). A weak negative correlation was seen between AMH and total AFC (r = -0.241). A moderate positive correlation was seen on comparing age and FSH (r = 0.331), whereas no correlation was seen on comparing FSH with AFC and AMH with AFC. The presence of ovarian cyst did not affect AMH or AFC but reduced FSH values significantly. Conclusion: In the quest to determine a panel test for ovarian reserve testing we conclude, FSH and AFC should perform fairly in poor resource and low socioeconomic setting. The combination of FSH with AMH and AFC might aid in better determination of ovarian reserve in tertiary centers with available resources.

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OBJECTIVE: To evaluate the correlation between serum anti-Müllerian hormone (AMH) and the number of oocytes retrieved after controlled ovarian stimulation for in vitro fertilization treatments and determine cut-off values predictive of poor and high response to stimulation. METHODS: It was performed a retrospective observational study that included 1003 cycles of controlled ovarian stimulation carried between February 2017 and December 2023 at a Medically Assisted Procreation Centre. The exclusion criteria were the following: serum AMH levels obtained more than 6 months prior to the start of the ovarian stimulation, the presence of a single ovary, non-Caucasian ethnicity, a controlled ovarian stimulation cycle performed for the purpose of oocyte donation or fertility preservation, a documented diagnosis of endometriosis, a documented history of ovarian surgery and the absence of essential data for the study in the medical records (absence of the number of oocytes obtained or the AMH value). Poor response to stimulation was defined as ≤ 3 oocytes retrieved, and high response was defined as > 15 oocytes. The correlation between variables was calculated using Spearman's correlation test and cut-off values were determined using ROC (Receiver Operating Characteristic) curves. RESULTS: AMH exhibited a significantly positive correlation with the number of oocytes retrieved (Spearman's correlation coefficient = 0.60, p<0.01). The predictive cut-off for poor ovarian response was 0.72 ng/mL (specificity of 95.13%, sensitivity of 43.23%), and the predictive cut-off for high ovarian response was 4.77 ng/mL (specificity of 89.86%, sensitivity of 38.22%). CONCLUSIONS: Serum AMH proved to be a good predictor of the ovarian response to controlled ovarian stimulation for in vitro fertilization treatments, which makes it useful in supporting clinical decision-making. However, it should not be used as an absolute discriminator of poor or high ovarian response.

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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.

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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).

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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PURPOSE: To evaluate the predictive value of serum AMH for clinical pregnancy in non-infertile population undergoing intrauterine insemination with donor sperm (ds-IUI). METHODS: This multicenter prospective study (ClinicalTrials.gov ID: NCT06263192) recruited all non-infertile women undergoing ds-IUI from June 2020 to December 2022 in three different fertility clinics in Spain and Chile. Indications for ds-IUI included severe oligoasthenoteratozoospermia, female partner, or single status. Clinical pregnancy rates were compared between women with AMH ≥ 1.1 and < 1.1 ng/mL. The main outcome measure was the cumulative clinical pregnancy rate after up to 4 ds-IUI cycles. RESULTS: A total of 458 ds-IUI cycles were performed among 245 patients, of whom 108 (44.08%) achieved clinical pregnancy within 4 cycles, 60.2% of these occurring in the first attempt and 84.2% after two attempts. We found no significant differences in AMH levels or other parameters (such as age, BMI, FSH, AFC) between women who became pregnant and those who did not. Cumulative pregnancy rates and logistic regression analysis revealed that AMH ≥ 1.1 ng/mL was not predictive of ds-IUI success. While a high positive correlation was observed between AFC and AMH (r = 0.67, p < 0.001), ROC curve analyses indicated that neither of these ovarian reserve markers accurately forecasts cumulative ds-IUI outcomes in non-infertile women. CONCLUSIONS: The findings of this multicenter study suggest that AMH is not a reliable predictor of pregnancy in non-infertile women undergoing ds-IUI. Even women with low AMH levels can achieve successful pregnancy outcomes, supporting the notion that diminished ovarian reserve should not restrict access to ds-IUI treatments in eligible non-infertile women.

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