anti-Müllerian Hormone Concentrations Research Articles

Ovarian reserve in children with juvenile idiopathic arthritis using biologic disease-modifying anti-rheumatic drugs.

The aim of the study is to assess the effect of juvenile idiopathic arthritis (JIA) and biologic disease-modifying anti-rheumatic drugs (bDMARDs) on ovarian reserve in children. A cross-sectional study was performed from March 2021 to March 2022 and included 81 patients with JIA and 49 healthy children. Serum anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol levels were analyzed using electrochemiluminescence methods. The mean of current age (13.5 ± 3.2 vs. 14.4 ± 2.4years), height standard deviation score (SDS) (- 0.35 ± 1.18 vs. - 0.44 ± 0.94), body mass index SDS (0.12 ± 1.33 vs. 0.25 ± 1.28), and the median weight SDS (- 0.13 (- 2.27-3.23) vs. - 0.52 (- 3.4-3.3)) were similar in JIA patients and controls (p > 0.05). Patients with JIA were divided into two groups according to their treatment regimens: treated with methotrexate (MTX) (biologic naive) (n = 32) and treated with MTX plus bDMARDs (n = 49). No significant differences were detected between the 3 groups regarding menarche age, menstrual cycle length, and flow duration (for all p > 0.05). The median serum concentration of AMH was 2.94 (1.12-7.88) ng/ml in the control group, 3.02 (0.36-8.54) ng/ml in the biologic naïve group, and 3.01 (0.99-8.26) ng/ml in the MTX plus bDMARD group. There were no significant differences between 3 groups according to serum AMH, FSH, LH, and estradiol levels (p > 0.05). Biologic DMARDs are reassuring in terms of ovarian reserve in girls with JIA and demonstrate that AMH is unaffected by treatment. Prospective studies with larger sample sizes are needed to confirm our findings and to evaluate the impact on the future fertility of patients. Key Points • Although biologic disease-modifying anti-rheumatic drugs (bDMARDs) are being game-changing treatment options in juvenile idiopathic arthritis, their effect on fertility and ovarian reserve is one of the most discussed issues. • In addition to treatment used, autoimmune diseases might also have a negative effect on fertility. • In this cross-sectional study, we found that anti-Mullerian hormone level of patients who were on bDMARDs, patients who were on methotrexate, and healthy controls were similar. • Our results suggest that bDMARDs are reassuring in terms of ovarian reserve in girls with JIA and demonstrate that AMH is unaffected by treatment.

Evaluation of the ovarian reserve in women and adolescent girls with Hashimoto's thyroiditis by serum anti-Müllerian hormone level: A systematic review and meta-analysis

ObjectivesSeveral researchers performed case-control studies to explore the relationship between Hashimoto's thyroiditis(HT) and ovarian reserve using anti-Müllerian hormone(AMH) in adolescent girls and women. But the results among these studies are inconsistent and the relationship between HT and ovarian reserve is still controversial. The study aimed to conduct the meta analysis of case-control studies to confirm the relationship between HT and ovarian reserve using AMH. Methods6 electronic databases including PubMed, EMBASE, the Cochrane Library, China National Knowledge Internet(CNKI), SinoMed and Wanfang were searched from inception to December 2021. Endnote X7.0 software was applied to managing all the relevant records. Then data extraction and evaluation of methodological quality of included studies were conducted after two-step selection.Review manager 5.4 version software and Stata 12.0 version software were used to perform all statistical analyses. Results10 case-control studies involving 1202 individuals were included in the present study. The preliminary results revealed AMH values were significantly higher in adolescent girls with euthyroid HT compared with healthy adolescent girls(MD = 1.97; 95%CI, 1.43–2.51; P < 0.001; I2 = 0%). The pooled results in the subgroup of female adults with euthyroid HT showed AMH values were not significantly different between patients with HT and healthy women(MD = −0.21; 95%CI, −0.51-0.09; P = 0.18; I2 = 38%). The pooled results in the two subgroups of female adults with subclinical hypothyroidism and overt hypothyroidism both showed AMH values were significantly lower in the HT group compared with healthy women [(MD = −0.60; 95%CI, −0.86 to −0.34; P < 0.001; I2 = 0%), (MD = −1.34; 95%CI, −1.94 to −0.74; P < 0.001; I2 = 65%)]. ConclusionsOvarian reserve evaluated by serum AMH concentration is affected by female adults with subclinical hypothyroidism and overt hypothyroidism. The AMH level was significantly higher in euthyroid adolescent girls.

Model of Anti-Mullerian Hormone Over Age to Predict Menopause in Polycystic Ovary Syndrome and Eumenorrheic Women: A Study on Southern Indian Population.

Introduction Anti-mullerian hormone (AMH) is a member of the transforming growth factor β family and is a marker of ovarian reserve; it is produced by the granulosa cells of developing preantral and early antral ovarian follicles. AMH concentration decreases with increasing age. Its concentration is increased relatively in those with polycystic ovary syndrome (PCOS) than eumenorrheic women. Objectives In this research, using a model of AMH over age, the age of menopause is predicted in PCOS and eumenorrheic women. Study design The study subjects were classified into two groups. Group 1 included PCOS subjects. Group 2 included eumenorrheic women. General profiles such as age, BMI, and hormonal parameters such as AMH were measured. Based on the exponential functional dependence of AMH over age, a model was proposed, and the value of exponential constants such as log βo and β1 were calculated using least square approximation. An arbitrary value of 0.2 ng/mL for AMH was taken as a cut-off value to predict the age of menopause in both groups. Outcome measures We predicted the age of menopause using a model of AMH over age by the least square approximation technique. Results The age prediction for menopause using the least squares model of AMH over age showed that in group 1 patients with PCOS, menopause is projected to occur at around 54.7 years, while in group 2 with eumenorrheic women, it is expected to happen at approximately 45.2 years. Conclusion Data demonstrates that serum AMH concentration declines over time, and predicting the age of menopause reflects sustained reproductive life span in PCOS subjects.

The role of anti-Mullerian hormone and other correlates in patients with polycystic ovary syndrome

ABSTRACT Background Anti-Müllerian hormone (AMH) has recently emerged as a promising biomarker for the detection of polycystic ovarian morphology. In polycystic ovary syndrome (PCOS), an elevated level of AMH has been suggested to add value to the Rotterdam criteria in cases of diagnostic uncertainty. In this study, we evaluated the correlation between AMH and PCOS, and the potential role of AMH in PCOS diagnosis. Methods A case-control study was performed on a total of 200 females, 100 of which were diagnosed with PCOS as per Rotterdam revised criteria (2003) and 100 as the control (non-PCOS group). Patient medical records were therefore retrieved for clinical, biochemical and ultrasound markers for PCOS diagnosis. Sensitivity, specificity, area under receiver operating characteristic (AUROC) curve, and multivariate linear regression models were applied to analyze our data. Results Mean serum levels of LH and AMH, and LH/FSH ratio were significantly different between compared groups. In the PCOS group, the mean serum AMH level was 6.78 ng/mL and LH/FSH ratio was 1.53 while those of controls were 2.73 ng/mL and 0.53, respectively (p < .001). The most suitable compromise between 81% specificity and 79% sensitivity was obtained with a cutoff value of 3.75 ng/mL (26.78 pmol/L) serum AMH concentration for PCOS prediction, with an AUROC curve of 0.9691. Conclusion Serum AMH cutoff level of 3.75 ng/mL was identified as a convenient gauge for the prediction of PCOS and an adjuvant to the Rotterdam criteria.

Effect of a GnRH Antagonist on Anti-Müllerian Hormone and Follicular Population in Anestrous Bitches.

The objective of this study was to describe the effect of the third-generation GnRH antagonist, acyline, on ovarian follicular population and serum anti-Müllerian hormone (AMH) concentrations in female dogs. Four late anestrous bitches were administered 330 μg/kg SC acyline every 10 days for 60 days and followed up for 45 days. Blood samples were drawn on days -1, 15, 30, 45, 60, 75, 90 and 105 for AMH determination. Then, the females were ovariectomized and the excised ovaries were gross and histologically evaluated. The total ovarian follicles were counted. None of the female dogs presented estrus during treatment. Only one bitch presented an ovulatory estrus 20 days after treatment. The total number of ovarian follicles in these bitches was 96,200.10 ± 26,125.12, with 84.13%, 11.36%, 7.8% and 0.01% corresponding to primordial, primary, secondary and antral structures, respectively. Pretreatment AMH concentrations were 0.62 ± 0.17 ng/mL. This hormone varied throughout the study period (p < 0.01), diminishing to nadir values during treatment to then rapidly recover after its effect (0.2 ± 0.05 vs. 0.67 ± 0.22 ng/mL; p < 0.01). Acyline rapidly and reversibly prevented the initiation of cycling without affecting follicle count but diminishing serum AMH concentrations.

Effects of chronic urticaria on ovarian reserve

Aims: To evaluate the ovarian reserve in women with chronic urticaria (CU).&#x0D; Methods: Thirty women with CU and twenty nine healthy controls were enrolled in this study. Serum levels of anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), estradiol (E2), and luteinizing hormone (LH) were measured on cycle day 2. All patients underwent transvaginal ultrasonographic examination on the second day of their menstrual cycle to assess Antral Follicle Count (AFC) and ovarian volume (OV). The disease activity of CU was measured with the urticaria control test (UCT) and urticaria activity score (UAS).&#x0D; Results: Women with CU had significantly lower concentrations of AMH, AFC, and E2 than controls. Additionally, total AFC and ovarian volume were significantly lower in women with CU than in the control group. UAS and UCT were positively associated with FSH and negatively associated with AMH, AFC, and OV.&#x0D; Conclusion: This is the first prospective controlled study to examine ovarian reserve in women with CU. In this study, we found that ovarian reserve was significantly reduced in women with CU. CU may negatively affect the ovarian reserve but the mechanism of this effect is unclear.

Studying the Effect of Curcumin (Standard &amp; Supplements) and Zinc on the Concentrations of Glucose, Insulin, HOMA-IR, and Anti-Mullerian Hormone in PCOS-Model Rats

Studying the Effect of Curcumin (Standard &amp; Supplements) and Zinc on the Concentrations of Glucose, Insulin, HOMA-IR, and Anti-Mullerian Hormone in PCOS-Model Rats

The Value of Anti-Müllerian Hormone in Predicting Ovulation Induced by Aromatase Inhibitors in Women With Polycystic Ovary Syndrome

ObjectivesThis study aimed to evaluate the value of anti-Müllerian hormone (AMH) in predicting ovulation induced by aromatase inhibitors (AI) and pregnancy outcomes in women with polycystic ovary syndrome (PCOS). MethodsFrom January 2018 to December 2020, this prospective cohort study enrolled women with PCOS aged between 18 and 45 years who underwent ovulation induction using AI protocol and intrauterine insemination (IUI) for infertility at a Center for Reproductive Endocrinology and Infertility, University Hospital. Receiver operating characteristic curves were used to estimate the chance of ovulation responses and pregnancy outcomes. ResultsIn total, 64% of 65 women with PCOS were recruited following AI treatment, and the clinical pregnancy rate was 19.4% following IUI. Patients who experienced ovulation had a lower mean serum AMH concentration than non-responders (7.11 ng/mL vs. 8.95 ng/mL, respectively), but the difference was not statistically significant. Between the pregnancy and non-pregnancy groups, statistically significant differences in AMH concentrations were observed (8.71 ng/mL vs. 6.73 ng/mL, respectively, P = 0.040). The area under the curve of the receiver operating characteristic for non-ovulation prediction was 0.445, 95% CI (0.284–0.606) with P = 0.467, and for clinical pregnancy was 0.735, 95% CI (0.561–0.910) with P = 0.104. ConclusionsIn women with PCOS, the AMH level does not predict ovarian responsiveness to AI treatment, but it does predict the success of IUI cycles.

Long-term exposure to air pollution and anti-mullerian hormone rate of decline: a population-based cohort study in Tehran, Iran.

Anti-mullerian hormone (AMH) concentration is a marker of ovarian reserve that decreases with age. However, a decrease in AMH may occur more rapidly under the influence of environmental factors. The present study investigated the association between long-term exposure to ambient air pollutants with serum concentrations of AMH and the AMH rate of decline. This study included 806 women with median age of 43years (interquartile range: 38-48) participating in the Tehran Lipid and Glucose Study (TLGS) that were followed from 2005 to 2017. The AMH concentration and the demographic, anthropometric, and personal health parameters of the study participants were obtained from the TLGS cohort database. Air pollutant data were collected from the monitoring stations and the individual exposures were estimated by previously developed land use regression (LUR) models. Multiple linear regression analysis was used to estimate linear relationships between the air pollutant exposures and serum concentration of AMH and with the AMH declination rate. The results show no statistically significant associations between exposures to any of the air pollutants (including PM10, PM2.5, SO2, NO, NO2, NOX, and benzene, toluene, ethylbenzene, p-xylene, m-xylene, o-xylene (BTEX), and total BTEX) with serum concentration of AMH. Compared to the first tertile, no statistically significant associations were observed between the second or third tertiles of air pollutants, with the AMH rate of decline. In this study, we did not find significant association between air pollution and AMH in middle age women in Tehran, Iran. Future work may study such associations in younger women.

Contemporary Anti-Retroviral Drugs (ARVDs) Disrupt Follicular Development in Female Wistar Rats.

There are genuine concerns that long-term use of anti-retroviral drugs may be associated with reproductive complications in females. This study aimed to ascertain the effect of highly active anti-retroviral drugs on the ovarian reserve and reproductive potential of female Wistar rats and by extension to HIV-positive human females. A total of 25 female Wistar rats, weighing between 140g and 162g, were randomly allotted into non-intervention and intervention groups, receiving the anti-retroviral drugs, Efavirenz (EFV), Tenofovir Disoproxil Fumarate (TDF), Lamivudine (3TC), and a fixed-dose combination (FDC). The dosage was administered orally at 8 am daily for 4 weeks. Serum concentrations of anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinising hormone (LH), and estradiol were measured using standard biochemical techniques (ELISA). Follicular counts were made on fixed ovarian tissue from the sacrificed rats. The mean AMH level for the control group and the EFV, TDF, 3TC, and FDC groups were 11.20, 6.75, 7.30, 8.27, and 6.60 pmol/L, respectively. The EFV and FDC groups had the lowest AMH, compared to the other groups, but there was no statistically significant difference in AMH across the groups. The mean count of antral follicles was significantly lower in the group that received EFV when compared to the other groups. The corpus luteal count was significantly higher in the control group than in the intervention groups. The study demonstrated a disruption in the reproductive hormones of female Wistar rats receiving anti-retroviral regimens containing EFV. Clinical studies are required to determine if these changes are seen in women receiving EFV-based treatment, as this may compromise reproductive function and predispose them to early menopause.

Effects of postpartum diseases on antral follicle count and serum concentration of Anti-Müllerian hormone in dairy cows

The antral follicle count (AFC) and Anti-Müllerian hormone (AMH) concentration are validated markers for ovarian reserve in cattle, but their use as fertility markers is controverse. Here we assessed the effects of postpartum diseases on AFC and AMH concentration, as well as the influence of parity and breed on these parameters. Cows (n = 513, mostly Holstein Friesian and Brown Swiss, parity 3.0 ± 1.8) underwent a single ultrasonography examination 28–56 days after parturition and categorized as having low (n ≤ 15 follicles), intermediate (n = 16–24 follicles), or high (n ≥ 25 follicles) AFC based on objective video analysis of recorded sequences. Blood samples for AMH determination were collected at the time of examination and animals divided into low (< 0.05 ng/ml) and high AMH (≥ 0.05 ng/ml) group, respectively. No effects of postpartum diseases or breed on either AFC or AMH groups could be observed. There was a strong interaction between parity and AFC, primiparous cows having less follicles (13.6 ± 6.2 vs. 17.1 ± 7.0, P < 0.001) than pluriparous cows. The AFC did not affect reproductive parameters or productivity of the cows. In comparison, pluriparous cows with high AMH concentration had shorter calving to first service (86.0 ± 37.6 vs. 97.1 ± 46.7 days, P < 0.05) and calving to conception (123.8 ± 51.9 vs. 135.8 ± 54.4 days, P < 0.05) intervals, but lower milk yield (8440.3 ± 2292.9 vs. 8927.9 ± 2192.5 kg, P < 0.05) compared to cows with low AMH. In conclusion, no effect of postpartum diseases on AFC or AMH concentration of dairy cows could be observed. However, an interaction between parity and AFC, as well as associations of AMH with fertility and productivity in pluriparous cows, were demonstrated.

Ovarian reserve in patients with systemic sclerosis

Objective. To evaluate the ovarian reserve in women with systemic sclerosis (SSc) and to analyze the relationship of the concentration of anti-Müllerian hormone (AMH) with the main manifestations of the disease and therapy. Material and methods. The study included 74 SSc patients aged 18 to 40 years; the control group consisted of 32 healthy women, matched by age. The concentration of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, estradiol (E2) and testosterone was determined by enzyme immunoassay (ELISA), AMH quantitatively using standard chemiluminescent analysis on paramagnetic particles in blood serum. The AMG level of 1.0– 10.6 ng/ml was taken as normative values. Values &lt;1.0 were regarded as a decrease in ovarian reserve. Results. In patients with SSD, the levels of AMH and testosterone were significantly lower than 1.4 [0.5; 2.3] and 0.45 [0.2; 0.96], respectively, versus 2.4 [1.8; 3.3] (p=0.002) and 1.6 [0.97; 2.5] (p=0.0001) in the control. The concentration of prolactin and E2 was recorded higher with SSDs – 22.23 [14.08; 31.18] and 140.2 [102.43; 179.74], respectively, against 10.2 [7.11; 16.68] (p=0.000002) and 95.3 [64.50; 130.0] (p=0.002) in the control. A decrease in the ovarian reserve by the level of AMH was significantly more often detected in patients with SSD in 43% versus 9.4% in the control (p=0.002). The risk of AMH reduction in patients with SSD was 7 times higher compared to the control (OR=7.030; 95% CI: 1.97–25.11). The levels of the hormones studied were comparable in patients with low and normal ovarian reserve. Diffuse form (46.9%) and subacute course of the disease (53.1%) were more often detected in patients with SSD and with low ovarian reserve compared to those with normal ovarian reserve (23.8% (p=0.033); 23.4% (p=0.004)). The frequency of organ lesions of SSDs, immunological disorders, inflammatory markers, and the lipid spectrum in the groups did not differ depending on the level of AMH. There were also no differences in the regimens and doses of treatment with basic anti-inflammatory drugs and glucocorticoids. Menstrual cycle disorders were noted by 31% of patients with SSD versus 6.2% in the control (p=0.004). Premature ovarian insufficiency (POI) was detected in 6.8% of patients with SSD and none in the control group (p=0.02). Patients with SSD and POI did not differ in age, duration of illness, clinical manifestations and therapy of them without POI.Conclusion. The concentration of AMH and testosterone was significantly lower in patients with. A decrease in ovarian reserve was significantly more often detected in women with SSs. Low ovarian reserve was more often detected in patients with diffuse form and subacute course of the disease. POI was more often observed in the group of SSc.

The optimal time for laparoscopic excision of ovarian endometrioma: a prospective randomized controlled trial

ObjectiveThis study aimed to explore the optimal time of laparoscopic cystectomy for unilateral ovarian endometrioma patients and evaluate the influence on ovarian reserve.Materials and methodsThis prospective randomized controlled study included 88 women with unilateral ovarian endometrioma at a tertiary teaching hospital. All patients received their first identified diagnosis of ovarian endometrioma by ultrasound (> 4 cm and ≤ 10 cm) and were administered an oral contraceptive pill (OC) for one cycle before laparoscopy. They were randomly divided into two groups: laparoscopy at the late luteal phase (group LLP) (n = 44) (termination of OC for two days) and laparoscopy at the early follicular phase (group EFP) (n = 44) (day 3 after menstruation). Basic clinical characteristics were recorded. Serum Anti-Müllerian hormone (AMH) levels were measured at various times to predict ovarian reserve. Serum levels of Anti-Müllerian hormone (AMH) were measured at several time sites to predict the ovarian reserve; AMH and leukocyte esterase (LE) levels of the endometrioma wall were measured.ResultsBefore surgery, serum AMH levels decreased in both groups from preoperative to one week and six months postoperatively. In contrast, the difference values of group EFP were larger than those of group LLP at postoperative one week and postoperative six months (1.87 ± 0.97 vs. 1.31 ± 0.93, P = 0.07; 1.91 ± 1.06 vs. 1.54 ± 0.93, P = 0.001). The mean rates of postoperative serum AMH decline were 37.92% and 46.34% in group EFP, significantly higher than those in group LLP (25.83% vs. 31.43%, P < 0.001). Ovarian endometrioma wall AMH of group LLP was significantly lower than that of group EFP ([22.86 ± 3.74] vs. [31.02 ± 5.23], P < 0.001). Meanwhile, ovarian endometrioma LE concentration of group LLP was significantly higher than that of group EFP ([482.83 ± 115.88] vs. [371.68 ± 84.49], P<0.001). There was also a significant inverse correlation between leukocyte esterase and AMH concentration in an ovarian endometrioma cyst wall (r=-0.564, P<0.001).Conclusion(s)The optimal time for laparoscopic cystectomy for patients with first identified unilateral ovarian endometrioma is the late luteal phase, which reduces ovarian tissue loss and preserves ovarian reserve effectively and safely.

P-684 Subclinical hypothyroidism and ovarian reserve indices in women with normogonadotropic anovulation

Abstract Study question Does subclinical hypothyroidism (SCH) affect ovarian reserve indices in women with Polycystic Ovary syndrome (PCOS) or other forms of Hypothalamic-Pituitary-Ovarian Axis Dysfunction (HPOD)? Summary answer SCH increases Anti-Müllerian hormone (AMH) concentration, but has no influence on Follicle-stimulating hormone (FSH). What is known already In PCOS, anovulation is caused by the arrest of growing follicles due to increased frequency and amplitude of luteinizing hormone (LH) pulses, resulting in increased number of pre-antral and antral follicles, and concentration of AMH. In other cases of HPOD, the causes of anovulation are more diverse and have not yet been clearly identified. Thyroid hormones can modify the function of the HPO axis, affecting the maturation of follicles. While overt hypothyroidism is treated to improve ovulation and fertility, the effect of subclinical hypothyroidism (SCH) and the presence of circulating antithyroid antibodies (ATA) on ovarian function is uncertain. Study design, size, duration A prospective cohort tertiary single-center study (consent no. 1072.6120.172.2022) included women aged 18-45, examined due to menstrual disorders and/or infertility, from July to August 2022. Only women without previously diagnosed thyroid dysfunction were included. All enrolled women gave informed written consent to participate in the study. Participants/materials, setting, methods Women underwent routine gynecological examination and pelvic ultrasound. Blood sample was tested for AMH, FSH, Luteinizing hormone (LH), Thyroid-stimulating hormone (TSH), anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-TG) antibodies concentrations. The Rotterdam-ESHRE-ASRM criteria were used to diagnose PCOS and its phenotypes. HPOD was diagnosed according to WHO classification. SCH was defined as TSH &amp;gt; 2.5 uIU/ml with normal thyroid function. The above parameters within subpopulations were calculated using regression analysis, Kruskal-Wallis and post-hoc tests. Main results and the role of chance The study included 51 euthyroid women aged 18-40. PCOS was diagnosed in 42/51 (82.35%) women, including PCOS-A phenotype in 31/51 (60.78%), PCOS-B in 5/51 (9.8%), PCOS-D in 6/51 (11.76%) women, and HPOD in 9/51 (17.65%) women. There was a significant positive correlation between the concentration of TSH and AMH in the studied population - with the increase of TSH value, the concentration of AMH increased (r = 0.4, p = 0.0035). The mean AMH concentration significantly differed between the groups and equaled to 55.4, 39.4, 31.1, 24.0 pmol/l in PCOS-A, PCOS-B, PCOS-D and HPOD (p = 0.05), respectively. The mean anti-TPO concentration was significantly different between the groups and was equal to 18.2, 19.0, 14.6, 10.9 U/ml in PCOS-A, PCOS-B, PCOS-D and HPOD (p = 0.05), respectively. There was no significant difference in FSH, LH, TSH, anti-TG concentrations between the groups. Limitations, reasons for caution The limitations of the study are small study group and single-center nature. Wider implications of the findings SCH increases the concentration of AMH, which in PCOS may exacerbate the symptoms of anovulation. Whether treatment of subclinical hypothyroidism affects ovarian reserve indices and improves ovarian function remain a subject of further research. Trial registration number 1072.6120.172.2022

P-477 Bidirectional association between ovarian reserve and spontaneous miscarriage: findings from the clinical IVF data to epidemiological evidence and genetic links

Abstract Study question To determine whether the association between ovarian reserve and spontaneous miscarriage risk is bidirectional and caused by shared genetic risk loci. Summary answer Bidirectional association between ovarian reserve and spontaneous miscarriage was observed. This may be attributed to five shared risk genes (SYCP2L, TP63, GSPT1, RIF1, and PRRC2A). What is known already Previous studies have shown that women with lower serum anti-Müllerian hormone (AMH) had an increased risk of embryo aneuploidy or spontaneous miscarriage risk, compared to women with higher AMH concentration, although not all studies agree. The most recent meta-analysis postulated that the association between diminished ovarian reserve (DOR) and miscarriage may be not causal, but that the two occurrences merely share a common cause, such as other systematic clinical conditions or past exposure. Inspired by this hypothesis, we conducted the present analyses to clarify this bidirectional association between DOR and miscarriage and further elucidate plausible mechanisms by using genetic data. Study design, size, duration There were four data sources. 1) The Clinical IVF data were retrospectively collected from an academically affiliated Reproductive Medicine Center (17,786 cycles included). 2) We further analyzed data from the UK Biobank (UKB) which is a large-scale, population-based, prospective cohort study (35,316 white women included). 3) The GWAS summary statistics for age at natural menopause (ANM) and spontaneous miscarriage were obtained from published GWAS studies. 4) The individual-level genotype data were also extracted from UKB. Participants/materials, setting, methods There were four analysis modules, 1) IVF data to test the association of ovarian reserve and miscarriage risk by using logistic regression models, 2) UKB data to test the association of spontaneous miscarriage history and ANM by using linear regression models, 3) GWAS summary data to test the overall genetic enrichment between miscarriage and ANM by plotting Q-Q plot, and 4) individual-level genotype data to identify specific shared genes by using ‘pleio’ R package. Main results and the role of chance In the analysis of clinical data, the risk of miscarriage was 1.5 (95% CI: 1.22-1.85, p &amp;lt; 0.001) times in the group with AMH&amp;lt;1.1 ng/ml, compared to the group with AMH &amp;gt; =1.1 ng/ml after adjustment. In the analysis of UK Biobank data, one more spontaneous miscarriage history would lead to 0.02 (95% CI: 0.00-0.03, p = 0.032) years earlier in the standardized ANM after adjustment. Participants with &amp;gt; =2 spontaneous miscarriage history would have 0.05 (95% CI:0.01-0.08, p = 0.011) years earlier in standardized ANM, compared with participants with &amp;lt; =1 spontaneous miscarriage. In the analysis of GWAS summary statistics, we found that there were 11,736,532 single nucleotide polymorphisms (SNPs) tested by both GWAS studies of ANM and miscarriage. In the stratified conditional Q-Q plot, successive leftward deflections did not show which suggested that an overall genetic overlap between miscarriage and ANM was not observed. In the analysis of the individual-level genotype data, we identified five shared genetic risk loci that affect both miscarriage and menopause. They were all novel risk genes for spontaneous miscarriage. Of these five genes, SYCP2L, TP63, GSPT1, and RIF1 were associated with congenital malformations and PRRC2A was associated with autoimmune disease, which are factors that possibly play a role in the occurrence of miscarriage. Limitations, reasons for caution The UKB epidemiology data and genetic data were restricted to participants of European ancestry. Further studies are needed in non-white populations. Second, the predictive value of GWAS summary data for miscarriage may be limited which results in a null finding in the conditional Q-Q plot. Wider implications of the findings Our findings could be of interest to IVF clinicians in patient counseling regarding the prognosis of IVF treatment and genetic counseling for miscarriage. Our findings encourage further research focus on the shared genetic architecture and common pathophysiological basis of diminished ovarian reserve and miscarriage which may bring new therapeutic opportunities. Trial registration number not applicable

Anti-Müllerian hormone levels in serum and testes of male dogs: relations with neuter status and bilateral abdominal cryptorchidism

Anti-Müllerian hormone (AMH) analysis has contributed to new information in the reproductive endocrinology of domestic animals, due to clinically available diagnostic tools. An accurate and rapid diagnostic method to distinguish between neutered and bilateral abdominal cryptorchid dogs is needed in veterinary practice. Therefore, this study uses an enzyme-linked immunosorbent assay to evaluate the clinical relevance of AMH analysis in peripheral blood as a diagnostic tool for dogs with suspected bilateral abdominal cryptorchidism. The possible alteration of the AMH localization in testicular tissue caused by this pathologic condition was also investigated using immunohistochemistry. Male dogs were divided into three groups of healthy intact (n = 14), healthy castrated (n = 14), and bilateral abdominal cryptorchid (n = 14) dogs. The results demonstrated a higher level of serum AMH in the cryptorchid group compared to the intact group (P < 0.01), while serum AMH levels of all castrated dogs were below the limit of detection (<0.05 ng/mL). Moreover, the percentage of positive AMH immunostaining of the intact group was less than that of the cryptorchid group (P < 0.01). A significantly positive correlation was found between serum AMH concentration and localization in testicular tissues (r = 0.93, P < 0.01). Our findings suggest that AMH levels in the peripheral blood could be used as an alternative and rapid screening method for detecting dogs with abdominal cryptorchidism.

Effect of actinomycin D on ovarian reserve in low-risk gestational trophoblastic neoplasia

ObjectiveThis study aimed to explore the single-agent chemotherapy actinomycin D on ovarian reserve by measuring the anti-Mullerian hormone (AMH) levels before, during, and after chemotherapy.MethodsThis study recruited premenopausal women aged...

AMH as part of the diagnostic PCOS workup in large epidemiological studies.

Previous studies have shown good correlation between polycystic ovarian morphology (PCOM) and serum anti-Müllerian hormone (AMH) levels. We evaluated the utility of AMH as a surrogate for PCOM as a part of the polycystic ovary syndrome (PCOS) diagnosis by describing how the use of different AMH cut-off values would change the prevalence of PCOS. A general population-based birth cohort study. Anti-Müllerian hormone concentrations were measured from serum samples taken at age 31 years (n = 2917) using the electrochemiluminescence immunoassay (Elecsys). Anti-Müllerian hormone data were combined with data on oligo/amenorrhoea and hyperandrogenism to identify women with PCOS. The addition of AMH as a surrogate marker for PCOM increased the number of women fulfilling at least two PCOS features in accordance with the Rotterdam criteria. The prevalence of PCOS was 5.9% when using the AMH cut-off based on the 97.5% quartile (10.35 ng/mL) and 13.6% when using the recently proposed cut-off of 3.2 ng/mL. When using the latter cut-off value, the distribution of PCOS phenotypes A, B, C, and D was 23.9%, 4.7%, 36.6%, and 34.8%, respectively. Compared with the controls, all PCOS groups with different AMH concentration cut-offs showed significantly elevated testosterone (T), free androgen index (FAI), luteinizing hormone (LH), LH/follicle-stimulating hormone (FSH) ratio, body mass index (BMI), waist circumference, and homoeostatic model assessment of insulin resistance (HOMA-IR) values, as well as significantly decreased sex hormone-binding globulin (SHBG) values. Anti-Müllerian hormone could be useful surrogate for PCOM in large data sets, where transvaginal ultrasound is not feasible, to aid the capturing of women with typical PCOS characteristics. Anti-Müllerian hormone measurement from archived samples enables retrospective PCOS diagnosis when combined with oligo/amenorrhoea or hyperandrogenism.

AMHconverter: an online tool for converting results between the different anti-Müllerian hormone assays of Roche Elecsys®, Beckman Access, and Kangrun.

The anti-Müllerian hormone (AMH) is gaining attention as a key factor in determining ovarian reserve and polycystic ovarian syndrome, and its clinical applications are becoming more widespread worldwide. To identify the most accurate formula for converting AMH assay results between different platforms, so that the developed AMH converter can be used to reduce the need for multiple AMH tests at different hospitals. Assuming that the Beckman Access, Kangrun, and Roche Elecsys® AMH assays fit a linear relationship from the lowest to the highest concentration (a global relationship), we used Passing-Bablok regression to determine the conversion equation between each two assays. When the relationship between two AMH assays was a local one, spline regression was used. Bland-Altman plots were drawn to check systemic bias and heterogeneity of variance across different ranges of values. The fitting effects of the models were evaluated using the squared coefficient of determination (r2), adjusted r2, root mean square error (RMSE), Akaike information criterion (AIC), and corrected AIC. The coefficient of variance for multiple controls in the Kangrun, Roche, and Beckman assays was lower than 5%, and the bias of multiple controls was lower than 7%. A global linear relationship was observed between the Kangrun and Roche assays, with the intercept being zero, for which Passing-Bablok regression was employed for data conversion between the two platforms. For the other two pairs of platforms, i.e., Roche and Kangrun or Beckman and Kangrun, spline regression was applied, with the intercepts not including zero. The six corresponding formulas were developed into an online AMH converter (http://121.43.113.123:8006/). This is the first time Passing-Bablok plus spline regression has been used to convert AMH concentrations from one assay to another. The formulas have been developed into an online tool, which makes them convenient to use in practical applications.

Plasma-free metanephrines, nerve growth factor, and renalase significance in patients with PCOS.

Polycystic ovarian syndrome (PCOS) is a common heterogeneous condition with probably multifactorial genesis. Animal studies have proven the essential role of the sympathetic nervous system in the syndrome development, while human studies are still contradictory. The present study aims to investigate the possible influence of plasma-free metanephrine (MN), and normetanephrine (NMN), nerve growth factor (NGF), and renalase (RNL) on the hormonal and metabolic parameters in women with PCOS and healthy controls. Fifty patients with PCOS and 30 healthy women participated in the study. The plasma-free MN and NMN, NGF, RNL, anti-Mullerian hormone (AMH), gonadotropin, androgen levels, and metabolic parameters were investigated. Plasma-free NMN and NGF concentrations were increased in PCOS individuals, while RNL levels were decreased compared to healthy volunteers. Increased plasma-free NMN (OR = 1.0213 [95%CI 1.0064-1.0364], p = 0.005) and NGF (OR = 1.0078 [95%CI 1.0001-1.0155], p = 0.046) but not MN or RNL levels were associated with a higher risk of PCOS after adjustment for age. Plasma-free NMN levels were positively associated with the LH (r = +0.253; p = 0.039). androstenedione (r = +0.265; p = 0.029), 17-OH progesterone (r = +0.285; p = 0.024), NGF (r = +0.320; p = 0.008), and AMH (r = +0.417; p < 0.001) concentrations of the investigated women. RNL levels were inversely related to the BMI (r = -0.245; p = 0.029), HOMA-IR (r = -0.250; p = 0.030), free testosterone (r = -0.303; p = 0.006) levels. systolic (r = -0.294; p = 0.008) and diastolic (r = -0.342; p = 0.002) blood pressure. Increased sympathetic noradrenergic activity and NGF synthesis might be related to the increased AMH and delta-4 androgen levels in a subgroup of PCOS patients. RNL levels might influence the metabolic status of PCOS patients. Further studies are needed to explore the significance of adrenal medullar and autonomic dysfunction for developing different PCOS phenotypes and their subsequent cardiovascular complications.