anti-Müllerian Hormone Decline Research Articles

The effect of dienogest treatment on anti-Mullerian hormone in patients with endometrioma: a 12-month follow-up study.

To assess the effect of dienogest treatment on endometrioma (OMA) size, serum anti-Mullerian hormone (AMH) levels and associated pain over a 12-month follow-up period. A longitudinal cohort study of 104 patients with OMA who were treated with dienogest, between January 2017 and January 2020. Of the included patients, each had a 12-month follow-up period with transvaginal or pelvic ultrasound and measurement of serum AMH concentration at the sixth and twelfth months of follow-up. The alteration in OMA size in the sixth and twelfth months of treatment was the primary outcome measure and the alteration in AMH concentration over the same period was the secondary outcome measure. The only exclusion criterion was having surgical intervention for OMA during the follow-up period (n=44). In patients with bilateral OMA (n=21), the change in size of the largest OMA was considered in the analysis. A total of 60 patients with a mean ± standard deviation (SD) age of 31.5±8.0 years were included. The mean ± SD OMA size on the day the dienogest was started was 46.3±17.4 mm and the mean AMH level was 3.6±2.4 ng/mL. After six months, the mean OMA size had decreased to 38.6±14.0 mm, with a median difference of 7.8 mm [95% confidence interval (CI): 3.0 to 12.6; p=0.003]. The mean AMH level was 3.3±2.7 ng/mL at 6 months follow-up (95% CI: -0.2 to 0.8; p=0.23) and the average difference was 0.3 ng/mL. At the 12th-month visit, when compared with the beginning of the treatment, OMA size had again significantly decreased by a median of -8.9 mm (95% CI: -2.9 to -14.9; p=0.005), and the decline in median AMH was also significant (-0.9 ng/mL, 95% CI: -0.1 to -1.7; p=0.045). The initial mean ± SD visual analog scale pain score at the commencement of dienogest treatment was 6.3±3.4. The mean values at the sixth and twelfth months of dienogest therapy were 1.08±1.8 and 0.75±1.5, respectively (both p<0.001 compared to baseline). At the sixth and twelfth months of dienogest treatment a significant decrease in OMA size and reported pain scores were observed, whereas the AMH concentrations did not change significantly.

Heavy Metals and Trajectories of Anti-Müllerian Hormone During the Menopausal Transition.

Experimental and epidemiological studies have linked metals with women's reproductive aging, but the mechanisms are not well understood. Disrupted ovarian folliculogenesis and diminished ovarian reserve could be a pathway through which metals impact reproductive hormones and outcomes. The study aimed to evaluate the associations of heavy metals with anti-Müllerian hormone (AMH), a marker of ovarian reserve. The study included 549 women from the Study of Women's Health Across the Nation with 2252 repeated AMH measurements from 10 to 0 years before the final menstrual period (FMP). Serum AMH concentrations were measured using picoAMH ELISA. Urinary concentrations of arsenic, cadmium, mercury, and lead were measured using high-resolution inductively coupled plasma mass spectrometry. Multivariable linear mixed regressions modeled AMH as a function of time before the FMP interaction terms between metals and time to the FMP were also included. Adjusting for confounders, compared with those in the lowest tertile, women in the highest tertile of urinary arsenic or mercury concentrations had lower AMH concentrations at the FMP (percent change: -32.1%; 95% CI, -52.9 to -2.2, P-trend = .03 for arsenic; percent change: -40.7%; 95% CI, -58.9 to -14.5, P-trend = .005 for mercury). Higher cadmium and mercury were also associated with accelerated rates of decline in AMH over time (percent change per year: -9.0%; 95% CI, -15.5 to -1.9, P-trend = .01 for cadmium; -7.3%; 95% CI, -14.0 to -0.1, P-trend = .04 for mercury). Heavy metals including arsenic, cadmium, and mercury may act as ovarian toxicants by diminishing ovarian reserve in women approaching the FMP.

Efficacy of Ethanol Sclerotherapy Versus Laparoscopic Excision in the Treatment of Ovarian Endometrioma.

The purpose of this study was to examine the recurrence rates of ovarian endometrioma, dysmenorrhea, dyspareunia, and related complications between sclerotherapy and laparoscopic ovarian cystectomy in individuals aged 25 to 38. Eighty-eight women participated in this retrospective, single-center study between January 2020 and February 2022. Patients received either laparoscopy or sclerotherapy, depending on the opinion of the pertinent physician. In this study, the following parameters were retrospectively analyzed in follow-up visits 2, 6 and 12months after sclerotherapy and laparoscopy: dysmenorrhea and dyspareunia by visual analog scale, complications following the intervention, and serial pelvic sonograms for endometrioma cyst recurrence. Moreover, serum Anti-Müllerian hormone (AMH) level before and 6months after sclerotherapy/surgery were analyzed. The collected data were then analyzed using R software. The results demonstrate the efficiency of both sclerotherapy and laparoscopic techniques in reducing endometrioma-related dysmenorrhea and dyspareunia over a 12-month period. There was no statistically significant difference in the occurrence of complications and recurrence rate between these two therapies, and both are equally beneficial. Also, the rate of AMH decline after laparoscopy was higher than sclerotherapy; however there was not a statistically significant change in serum level of AMH in laparoscopy compared to the sclerotherapy after 6months. Considering all the data, it appears that sclerotherapy, with its lower cost, shorter hospital stay, and quicker return to activities, can be a laparoscopic alternative to endometrioma cyst removal. More studies are required.

'Age specific variations in ovarian reserves in healthy fertile and infertile women: A cross sectional study.

Ovarian reserve tests are valuable for evaluation of female fertility, and to formulate appropriate treatment strategies for infertile women. Antral follicle count (AFC) and Anti-Mullerian hormone (AMH) are most reliable markers of ovarian reserve which are related inversely to age. There are many factors that affect ovarian reserve like race, ethnicity, fertility status, BMI or any chronic illness. We conducted this study to find outage specific nomograms for AMH and AFC among fertile and Infertile Indian women, to find out any variations between fertile and Infertile ovarian reserves at various centiles, to define the age cut-off of decline in AMH and AFC among fertile and Infertile Indian women and to find correlation between AMH and AFC. It was a prospective cross sectional single centre study conducted at a tertiary hospital of northern India from March 2017 to February 2022. Fertile healthy women were recruited from family planning clinic, oocyte donors and subfertile women from Gynaecology and ART clinic. AMH was done using ELISA, Beckmann Coulter Gen II assay and AFC was done using TVS with high frequency probe (9.0 MHZ, Voluson,S-6, GE Healthcare, USA) by trained personnel. R Statistical Programming Language was used for statistical modelling and visualization. Age-specific AFC centile chart and AMH centile chart were generated using GAMLSS (Generalized Additive Models for Location Scale and Shape) package available in R Statistical Computing Language. A Non-linear decline in ovarian reserves among fertile, while linear among infertile women was seen. Centiles defined for both groups with a faster decline in infertile women. Age cut off for decline in AMH and AFC in fertile women approximately 31 years using ROC analysis and Age cut off for decline in AMH and AFC in infertile women is approximately 34 years. There seems to be a good correlation between AFC and AMH. We need to counsel women to consider child bearing well before ovarian reserves decline (31-34 years).

Rapid Ovarian Reserve Decline in a Woman with Pericentric Inv(9) Variant

Inv(9) is one of the most common chromosomal variants and is generally considered to be a variant of no clinical significance. We describe a case of a 35-year-old woman with a normal baseline fertility workup who presented to a university-affiliated fertility clinic after eight months of attempting conception. She underwent a rapid decline in anti-Mullerian hormone (AMH) from 10.0 ng/mL to 0.5 mg/mL and cycle day 3 (CD3) antral follicle count (AFC) from 58 to 4 total follicles during 18 months of follow-up. Her karyotype demonstrated a reportedly benign 46XX, Inv(9)(p11q13) variant. During follow-up and fertility treatment, she achieved pregnancy three times, but they all ended in chemical pregnancies. A systematic review of the literature identified 24 publications evaluating the association between infertility or recurrent pregnancy loss (RPL) and Inv(9). We report the prevalence of Inv(9) in women with infertility and the prevalence of infertility or RPL in women with Inv(9) mutation. Although Inv(9) has previously been considered to be a normal variant, several publications support the possible correlation between Inv(9) with reproductive failure. There has been limited literature regarding this association, and future studies should consider higher-resolution genomic detection methods to identify Inv(9)-related chromosomal rearrangements in couples presenting with infertility.

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-622 Age-specific reference intervals for anti-müllerian hormone in Mexico: A population-based study. implications for Latin America

Abstract Study question To determine the age-specific normal range of antimullerian hormone (AMH) levels in a female Latin American population. Summary answer Age-related nomograms for general population for the 3rd-97th percentiles were produced. These nomograms could provide a reference guide for clinicians to consult women with infertility. What is known already The variation of AMH levels among different races and ethnicities has been well documented (Seifer et al., 2009). Despite the wide use of AMH measurements in clinical assessment of ovarian reserve, a population-based estimate for its reference range in Latin America is not available. Study design, size, duration A longitudinal, observational, retrospective, real-world study was carried out, including all AMH measurements performed from January 2017 to December 2018 at a large clinical laboratory network in the Mexico City area, encompassing 35 locations. A total of 6444 AMH measurements were included. Participants/materials, setting, methods AMH was assayed using either the cobas or ELISA methodologies. All AMH measurements from women 25-45 years were included. The Kolmogorov-Smirnov test was used to confirm that AMH levels between patients assayed with cobas were comparable to those assayed with ELISA at every age. Main results and the role of chance In total, 6444 measurements were identified and available for analysis. Age-related normograms for the 3rd, 10th, 25th, 50th, 75th, 90th, and 97th percentiles of AMH were produced. The overall rate of AMH decline accelerated after 40 years of age. In women 25-30 years, 11.4% (63/554) had an AMH &amp;lt;1.0ng/mL. In women 30-35 years, 18.6% (276/1484) had an AMH &amp;lt;1.0ng/mL. In women 35-40 yeras, 35.8% (830/2319) had an AMH &amp;lt;1.0ng/mL. In women 40-45 years, 58.0% (1120/1932) had an AMH &amp;lt;1.0ng/mL. Limitations, reasons for caution The lack of medical history for patients precluded identification and exclusión of patients with iatrogenically abnormal AMH levels (e.g. due to oophorectomy). Patients undergoing measurement of AMH were primarily referred through fertility clinics, limiting the potential for extrapolation to the general population. Wider implications of the findings The study reports age-specific AMH levels drawn from a large sample of women around Mexico City. The study includes the largest dataset to date. Latin American patients considering fertility preservation should be aware of the high prevalence of diminished ovarian reserve in this large cohort, including among women 35-39. Trial registration number Not Applicable

Impact of immune checkpoint inhibition on ovarian reserve in patients with melanoma enrolled in the ECOG-ACRIN E1609 adjuvant trial.

12013 Background: Immunotherapy with immune checkpoint inhibition (ICI) is being widely adopted in the treatment of patients with a wide range of malignancies. However, we have no data on how these therapies influence fertility or ability to undergo fertility treatments after therapy. Within the melanoma community numerous women of childbearing age have been treated with ICI including ipilimumab, nivolumab and pembrolizumab. Anti-mullerian hormone (AMH) is a biomarker of ovarian reserve and a predictor of response to fertility treatments, including in vitro fertilization (IVF). In women under the age of 35 who have no reproductive pathology, AMH should be detectable and remain relatively stable over time. Above the age of 35 AMH decline accelerates as the number of eggs decreases more rapidly due to normal ovarian aging. Methods: Pre and post-treatment samples from women aged 20-35 whose melanoma was treated with 3 mg/kg ipilimumab (57%) or 10 mg/kg ipilimumab (43%) in the adjuvant setting on trial ECOG-ACRIN E1609 were analyzed in collaboration with the BWH Reproductive Endocrine Laboratory. Serum samples were tested for luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol, AMH and prolactin. Results: Samples from E1609 were available from 28 female patients with a median age of 28 (min 20, max 35). The median time between samples was 8.0 months (min 0.7, max 16.4). 53% of patients had stage IIIB melanoma, 43% stage IIIC and one patient had M1a disease. AMH, estradiol and LH significantly decreased after treatment (p &lt; 0.001, p = 0.016, p = 0.012, respectively) (Figure 1); there was no significant difference in the level of FSH and prolactin before and after the treatment (p = 0.68, p = 0.12, respectively). The median AMH was 4.24 ng/mL in the pre-treatment group and 3.51 in the post-treatment group. Conclusions: In this study of young women treated with ipilimumab there was a significant decrease in AMH before and after ICI therapy suggesting that ovarian reserve and possibly female fertility may be impacted by immune checkpoint inhibition. Further investigation is needed to look at PD-1 inhibition and combination immunotherapy effects on ovarian reserve and female fertility. In addition, there is a similar need to examine ICI effects on male fertility.

Low ovarian reserve and risk of miscarriage in pregnancies derived from assisted reproductive technology.

Do low levels of anti-Müllerian hormone (AMH) or antral follicle count (AFC) properly predict miscarriage in young women conceiving with ART? Low ovarian reserve, as indicated by AMH or AFC, is not associated with miscarriage in young women conceiving with ART. Presently, the impact of low ovarian reserve on the risk of miscarriage remains controversial. Some studies have reported an association between serum AMH levels and AFC and miscarriage, but others have failed to confirm these findings. The main limitation that undermines the reliability and consistency of the results is the confounding effect of female age. Indeed, after 35 years of age, on the one hand, the risk of miscarriage starts increasing because of impaired oocyte quality while, on the other, the physiological decline in AMH and AFC levels continues, thus hampering the possibility to properly explore the real effects of reduced ovarian reserve. Indeed, the two processes, i.e. the gradual loss of resting primordial follicles and the loss of oocyte quality, progress in parallel. In other words, the older the woman becomes, the higher is the risk of miscarriage, but one cannot distinguish between the effects of biological aging on oocyte quality and those mediated by a lower ovarian reserve. The present retrospective monocentric cohort study was carried out at Fondazione IRCSS Ca Granda Ospedale Maggiore Policlinico, Milan. All women referred to the ART Unit between 2014 and 2021 and who underwent either conventional IVF (c-IVF), ICSI, or IUI were reviewed. Only women younger than 35 were eligible because, up to this age, the risk of miscarriage is steady and not strictly related to age. Women younger than 35 who achieved a singleton clinical pregnancy with c-IVF, ICSI, or IUI were selected. Women with patent causes of recurrent miscarriage were excluded, as well as those undergoing pregnancy termination for fetal or medical causes. Women who did and did not have a pregnancy loss before 20 weeks' gestation were compared. Detailed information was obtained from charts of the consulting patients. ART procedures were performed according to the standardized policy of our Unit. All women underwent serum AMH measurement and a transvaginal assessment of AFC prior to initiation of treatment. AMH levels were measured by a commercially available ELISA assay. To assess AFC, all identifiable antral follicles 2-10 mm in diameter at ultrasound were recorded. The primary outcome was the risk of miscarriage for women with serum AMH levels below 5 pmol/l. There were 538 women were included, of whom 92 (17%) had a miscarriage. The areas under the ROC curves for prediction of miscarriage based on AMH levels and AFC were 0.51 (95% CI: 0.45-0.58) and 0.52 (95% CI: 0.45-0.59), respectively. The odds ratio (OR) of miscarriage for women with serum AMH levels below 5.0 pmol/l was 1.10 (95% CI: 0.51-2.36); the adjusted OR was 1.12 (95% CI: 0.51-2.45). Analyses were repeated considering other thresholds for AMH (2.9, 3.6 and 7.9 pmol/l) and for AFC (thresholds of 7 and 10). No associations emerged. The retrospective design of the study hampered the collection of more precise but potentially relevant clinical information of the couples. We did not exclude women suffering from PCOS, a condition possibly associated with miscarriage. Moreover, the baseline characteristics of women who did and did not have a miscarriage differed in some characteristics. Thus, we adjusted the OR using a multivariate analysis, but we cannot fully exclude residual confounding effects. Finally, our results cannot be inferred to women older than 35. The mechanisms causing premature exhaustion of ovarian reserve may be different in younger and older women and this may lead to a different impact on the risk of miscarriage. Women embarking on ART with low ovarian reserve should be informed of their likely poor response to ovarian stimulation but can be reassured that, if conception occurs, their risk of miscarriage is not increased. This study was partially funded by Italian Ministry of Health-Current research IRCCS. E.S. reports grants from Ferring and honoraria for lectures from Merck-Serono and Gedeon-Richter. All the other authors do not have any competing interest to declare. N/A.

Characteristics of patients with stage III and IV ovarian endometriomas and trends in postoperative anti-Mullerian hormone changes.

This study aimed to investigate the manifestations of postoperative Anti-Mullerian hormone (AMH) changes in patients with stage III and IV ovarian endometriomas. Trends in postoperative AMH were categorized and described, and the risk factors for postoperative AMH decline were screened using dichotomous logistic regression. The overall trend of postoperative AMH decreased, with a more significant decrease in stage IV than stage III cases. Elevated preoperative CA-125 levels, a history of caesarean section, and abortion were independent risk factors for postoperative AMH decline. There is a general trend toward decreasing AMH levels after surgery, but each case may also show a different elevation.

Impact of Anti-HER2 Therapy Alone and With Weekly Paclitaxel on the Ovarian Reserve of Young Women With HER2-Positive Breast Cancer.

The potential gonadotoxicity of anti-HER2 agents remains largely unknown, and limited, conflicting evidence exists for taxanes. Antimüllerian hormone (AMH) is an established biomarker of ovarian reserve that may aid in quantifying anticancer treatment-induced gonadotoxicity. The present biomarker analysis of the randomized phase III neoadjuvant NeoALTTO trial included premenopausal women aged ≤45 years at diagnosis of HER2-positive early breast cancer with available frozen serum samples at baseline (ie, before anticancer treatments), at week 2 (ie, the "biological window" of anti-HER2 therapy alone), and/or at the time of surgery (ie, after completing paclitaxel + anti-HER2 therapy, before starting adjuvant chemotherapy). The present analysis included 130 patients with a median age of 38 years (interquartile ratio [IQR], age 33-42 years). AMH values at the 3 time points differed significantly (P<.001). At baseline, median AMH levels were 1.29 ng/mL (IQR, 0.56-2.62 ng/mL). At week 2, a small but significant reduction in AMH levels was observed (median, 1.10 ng/mL; IQR, 0.45-2.09 ng/mL; P<.001). At surgery, a larger significant decline in AMH levels was observed (median, 0.01 ng/mL; IQR, 0.01-0.03 ng/mL; P<.001). Although the type of anti-HER2 treatment (trastuzumab and/or lapatinib) did not seem to impact the results, age and pretreatment ovarian reserve had a major influence on treatment-induced gonadotoxicity risk. This NeoALTTO biomarker analysis showed that anti-HER2 therapies alone had limited gonadotoxicity but that the addition of weekly paclitaxel resulted in marked AMH decline with possible negative implications for subsequent ovarian function and fertility.

Impact of anti-HER2 therapy alone and in association with weekly paclitaxel on the ovarian reserve of young women with HER2-positive early breast cancer: Biomarker analysis of the NeoALTTO trial.

12084 Background: The potential gonadotoxicity of anti-HER2 agents remains largely unknown and limited conflicting evidence exists for taxanes. Anti-Mullerian hormone (AMH) is an established biomarker of ovarian reserve; its measurement during systemic therapies may aid in indicating gonadotoxicity, in the diagnosis and prediction of primary ovarian insufficiency (POI). The present analysis explored for the first time the impact of anti-HER2 therapy alone and then combined with weekly paclitaxel on ovarian reserve measured by AMH levels in breast cancer (BC) patients not previously exposed to anthracycline and cyclophosphamide. Methods: This biomarker analysis of the NeoALTTO (NCT00553358) randomized phase III neoadjuvant trial included premenopausal women aged ≤45 years at diagnosis of HER2-positive early BC with available frozen serum samples at baseline (i.e. before administering any anticancer treatment), at week 2 (i.e. “biological window” of anti-HER2 therapy alone) and/or at the time of surgery (i.e. after completion of paclitaxel plus anti-HER2 therapy and before starting adjuvant chemotherapy). Central AMH testing was performed with the Roche Elecsysâ AMH Plus assay (LoD = 0.01 ng/ml). AMH levels during anti-HER2 therapy alone and then combined with paclitaxel were assessed as a measure of treatment acute gonadotoxicity. The impact of different anti-HER2 agents, patients’ age, and baseline AMH levels on treatment gonadotoxicity were also investigated. Results: The present analysis included 130 patients with a median age of 38 years (IQR: 33-42 years). AMH values at the 3 time points differed significantly from each other (p &lt; 0.001). At baseline, median AMH levels were 1.29 ng/mL (IQR 0.56 – 2.62 ng/mL). At week 2, a small but significant reduction in AMH levels was observed (median value: 1.10 ng/mL, IQR 0.45 – 2.09 ng/mL, p &lt; 0.001). At surgery, there was a larger significant decline in AMH levels (median value: 0.01 ng/mL, IQR 0.01 – 0.03 ng/mL, p &lt; 0.001). There was no significant difference between treatment arms (trastuzumab vs. lapatinib vs. trastuzumab plus lapatinib) in the degree of reduction in AMH levels at week 2 (p = 0.763) and at surgery (p = 0.700). Age and pre-treatment ovarian reserve had a major influence on treatment-induced gonadotoxicity risk, with older age and lower AMH levels at diagnosis being associated with a greater negative impact. Conclusions: This biomarker analysis of the NeoALTTO trial showed for the first time that anti-HER2 therapies alone had limited gonadotoxicity but the addition of weekly paclitaxel resulted in marked AMH decline which likely has implications for subsequent ovarian function and fertility. These data highlight the importance of oncofertility counselling among all premenopausal women with HER2-positive BC receiving systemic anticancer treatments. Clinical trial information: NCT00553358.

Reliability of AMH and AFC measurements and their correlation: a large multicenter study.

Anti-Müllerian hormone (AMH) and antral follicle count (AFC) are correlated with the ovarian response, but their reliability and reproducibility are questionable. This large multicenter study describes their distribution, inter-cycle and inter-center variability, and their correlation. A total of 25,854 IVF cycles among 15,219 patients were selected in 12 ART centers. Statistical distribution of AMH and AFC was studied by using the Kolmogorov-Smirnov test and Shapiro goodness of fit test. The reproducibility of AFC and AMH was measured using a mixed model regressing the logarithmic transformation of AFC with age. The distribution of AMH and AFC was characterized by a wide dispersion of values, twice more important for AFC, and a logarithmic distribution. The faster decline in AMH than in AFC with age suggests that their correlation changes with age. AMH and AFC showed a very low proportion of concordance in the range of expected poor responders according to Bologna cutoffs. The heterogeneity for AMH and AFC across centers was small, but much larger across patients within each center. Concerning the patients with several successive cycles, the reproducibility for AMH seemed much better than for AFC. Comparing respective performances of AMH and AFC for the prediction of ovarian response depended on the local conditions for measuring these indicators and on the reproducibility of results improved over time. Distribution of AMH and AFC was characterized by the wide dispersion of values, and a logarithmic distribution. Establishing cutoffs or a direct relationship AMH/AFC without considering age seems hazardous. Correlation between AMH and AFC was very poor in the range of poor responders.

Risk Factors for Anti Mullerian Hormone Decline after Laparoscopic Excision of Endometrioma: A Prospective Study.

Background:Laparoscopic excision of ovarian endometrioma is believed to decrease the ovarian reserve, but the risk factors of declining ovarian reserve are not well studied. This study aimed to determine the risk factors of anti mullerian hormone (AMH) decline after laparoscopic surgery of endometrioma.Materials and Methods:This prospective study was recruited in Yas and Arash Hospitals affiliated to Tehran University of Medical Sciences from 2020 to 2021. Women between 18-45 years with ovarian endometriomas with a diameter greater than 3 centimeters who were candidates for laparoscopy were included. AMH, luteinizing hormone (LH), and follicular stimulating hormone (FSH) as well as cancer antigen 125 (CA125) and cancer antigen 19-9 (CA19-9) were obtained and compared pre and postoperatively. Indeed, the relation of AMH decline rate and the demographic, symptoms and endometrioma characteristics were investigated either.Results:In this study, 100 women were recruited. The mean ± SD age of the participants was 29.08 ± 4.6. AMH (P<0.000) and LH (P=0.013) declined significantly postoperatively. Whereas, no significant difference was observed between pre and postoperative FSH (P=0.520). AMH decline rate was 30.07 ± 2.30% and didn’t have significant relation with the demographic characteristics, preoperative AMH, and the amount of CA125. Otherwise in the multivariate analysys, CA125 (P=0.160) and the grade of endometriosis (P=0.05) had significant correlation with AMH decline rate.Conclusion:Ovarian reserve decline after laparoscopic excision of endometrioma. Otherwise, there may no specific risk factor to predict the degree of ovarian reserve decline. Therefore, the selection of patients for laparoscopic excision of endometrioma should be taken more cautiously as the ovarian reserve diminishes even in the patients with the lowest risks.

The Effect of Laparoscopic Endometrioma Surgery on Anti-Müllerian Hormone: A Systematic Review of the Literature and Meta-Analysis.

ObjectiveThis study aimed to assess the effect of endometrioma surgery on ovarian reserve by measuring anti-Müllerian hormone (AMH) levels.MethodsThis systematic review and meta-analysis included observational studies and randomized clinical trials published in English referenced in MEDLINE, SCOPUS and Cochrane (1982-2019). We included studies that reported AMH levels in the pre and post-operative period of patients undergoing laparoscopic surgery for endometrioma. Preoperative AMH was defined as the baseline AMH; short term AMH was measured no later than a month after surgery; medium term AMH was measured between one and six months after surgery; and long-term AMH was measured six or more months after surgery.ResultsThirty-six studies met the inclusion criteria. A significant decrease was observed in short, medium and long-term post-operative AMH levels when compared with baseline AMH. However, there were no differences between short and long-term post-operative AMH levels, suggesting a non-significant recovery after one year of follow-up. A significant decrease in post-operative AMH was observed in bilateral endometriomas compared with unilateral cases. In addition, patients with endometriomas presented a significant decline in post-operative AMH compared with patients with other benign ovarian conditions. The decrease in post-operative AMH was significantly greater in bilateral cystectomy when compared with vaporization with bipolar energy or laser. We also observed a greater decrease in post-operative AMH with bipolar energy hemostasis compared with suture and hemostatic agents. These results should be taken with caution due to the high heterogeneity of the studies analyzed.ConclusionsEndometrioma surgery has a deleterious effect on short, medium, and long-term post-operative AMH levels. Bilateral endometriomas and endometriomas greater than 7 cm have been associated with greater decreases in AMH. The mechanical resection of healthy tissue and the inflammatory damage on the ovarian cortex might explain the diminishing of ovarian reserve.

The relation of Anti-Mullerian Hormone with final Menstrual period and menopausal symptoms in the menopausal transition

Objective: To determine the role of anti- mullerian hormone (AMH), menstrual hormones and symptoms in predicting final menstrual period (FMP) in menopausal transition (MT). Material and Methods: Eighty-two women aged 37-50 years in MT with any degree of menopausal symptoms were included in this prospective study. At the beginning and at the end of two years; serum AMH and menstrual hormone (Follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol) levels were measured, Menopause Rating Scale (MRS) scores were recorded, then compared. The cut-off of initial AMH level to detect FMP was calculated. Results: Of the 82 patients that were followed for two years, thirty six were in early MT, forty-six were in late MT at the initial. At the end of two years, 15.8 % (13/82) of patients were found to have reached menopause. The rate of AMH decline in two years did not differ significantly between patients who had and did not go through menopause. According to ROC analysis, in patients with menopause the optimal threshold value of baseline AMH to predict FMP over the next 12 months was 0.085 ng/ml (area under curve :0.873, 95% CI: 0.726-0.948, p&lt;.001). There was a significant positive correlation between AMH change rate and MRS score change in two years (r=0.462, p&lt;0.001). A significant negative correlation was observed between baseline AMH levels and second year MRS scores (r=- 0.56, p&lt;0.001). Multivariate regression analysis showed no significant independent effect of age, BMI, baseline AMH level, FSH, estradiol, baseline MRS score on AMH change. Conclusion: In MT, serum AMH level and menopausal symptom scores can help predict FMP and assist in the appropriate management of the MT period to provide women with a long-term healthy life.

Does the Anti-Mullerian Hormone Decline Rate Improve the Prediction of Age at Menopause?

ObjectivesThere are controversial studies investigating whether multiple anti-Mullerian hormone (AMH) measurements can improve the individualized prediction of age at menopause in the general population. This study aimed to reexplore the additive role of the AMH decline rate in single AMH measurement for improving the prediction of age at physiological menopause, based on two common statistical models for analysis of time-to-event data, including time-dependent Cox regression and Cox proportional-hazards regression models.MethodsA total of 901 eligible women, aged 18–50 years, were recruited from the Tehran Lipid and Glucose Study (TLGS) population and followed up every 3 years for 18 years. The serum AMH level was measured at the time of recruitment and twice after recruitment within 6-year intervals using the Gen II AMH assay. The added value of repeated AMH measurements for the prediction of age at menopause was explored using two different statistical approaches. In the first approach, a time-dependent Cox model was plotted, with all three AMH measurements as time-varying predictors and the baseline age and logarithm of annual AMH decline as time-invariant predictors. In the second approach, a Cox proportional-hazards model was fitted to the baseline data, and improvement of the complex model, which included repeated AMH measurements and the logarithm of the AMH annual decline rate, was assessed using the C-statistic.ResultsThe time-dependent Cox model showed that each unit increase in the AMH level could reduce the risk of menopause by 87%. The Cox proportional-hazards model also improved the prediction of age at menopause by 3%, according to the C-statistic. The subgroup analysis for the prediction of early menopause revealed that the risk of early menopause increased by 10.8 with each unit increase in the AMH annual decline rate.ConclusionThis study confirmed that multiple AMH measurements could improve the individual predictions of the risk of at physiological menopause compared to single AMH measurements. Different alternative statistical approaches can also offer the same interpretations if the essential assumptions are met.

P–462 First live birth after fertility preservation using vitrified oocytes in a woman with mosaic Turner syndrome

Abstract Study question Is oocyte vitrification an option for preserving the fertility of women diagnosed with Turner syndrome (TS)? Summary answer We report the first live birth achieved using cryopreserved oocytes in a woman diagnosed with mosaic Turner syndrome. What is known already Women with TS are at extremely high risk for premature ovarian insufficiency (POI) and infertility. Although the desire of becoming parents may be fulfilled through egg donation or adoption, fertility preservation using ovarian tissue cryopreservation or oocyte vitrification has been offered to adolescents with TS before complete exhaustion of their follicular stockpile. However, women with TS exhibit higher rates of pregnancy loss and obstetric complications, and the feasibility of fertility preservation in TS is hampered by the reduced follicular pool and by concerns about the X chromosomal content of oocytes and follicular cells. Study design, size, duration Case report in a university hospital. Participants/materials, setting, methods A 25-year-old woman with Turner syndrome mosaicism (45,X0[14]/46,XX[86]) was referred for fertility preservation (FP) counseling. Serum antimüllerian hormone (AMH) level was normal (6.4 µg/L). In view of parenthood postponement and because of the unpredictable rate of follicle loss, the woman underwent two cycles of ovarian stimulation using recombinant follicle stimulating hormone (rFSH), 200–250 IU/day for 8 resp. 12 days, in a GnRH antagonist protocol. Main results and the role of chance In total, 29 metaphase II oocytes (MII) were vitrified. Five years later, the patient returned to the clinic with a desire for pregnancy. Because of evidence of considerable AMH decline (–56% in an interval of four years), the patient was advised to utilize her cryopreserved oocytes for in-vitro fertilization with preimplantation genetic testing for aneuploidy screening (PGT-A). All 29 MII oocytes were thawed; 26 oocytes survived (89.7%) and were inseminated using intracytoplasmic sperm injection (ICSI). Thirteen oocytes were fertilized normally. Three good quality blastocysts ensued and were vitrified after trophectoderm biopsy for PGT-A using array-CGH. Two blastocysts were found euploid. One was thawed and transferred into the uterus using a HRT priming protocol. An uneventful pregnancy occurred. The patient delivered a healthy baby girl weighing 3490 g at 40 weeks of gestation. Limitations, reasons for caution Cryopreservation of oocytes and/or ovarian tissue in selected postmenarchal girls or young women with Turner syndrome is an investigational FP approach that may result in genetic parenthood. The feasibility of FP in TS individuals is limited to those with evidence of ovarian function, before POI occurs. Wider implications of the findings: Cryopreservation of mature oocytes after ovarian stimulation is a realistic option for FP in selected postmenarchal individuals with mosaic TS. Whether PGT-A may reduce the risk of pregnancy loss in TS has to be confirmed by further studies. Trial registration number Not applicable

Effects of environmental, social and surgical factors on ovarian reserve: Implications for age-relative female fertility.

ObjectiveTo investigate new risk factors for female fertility by analyzing the effects of environmental, social, and surgical factors on antral follicle counts (AFC) and anti‐Müllerian hormone (AMH) levels.MethodsA total of 1513 women aged 20–47 years who underwent in vitro fertilization/intracytoplasmic injection treatment in Southwest Hospital from December 2017 to December 2019 were included. Women were assessed for AFC and AMH levels, and completed a questionnaire. Ordinal logistic regression analyses with generalized linear mixed models were used to calculate the adjusted odds ratio (OR) for diminished ovarian reserve.ResultsAdnexal surgery was the only risk factor associated with low AFC in women aged 20–30 years. Younger age at menarche, alcohol drinking, and adnexal surgery are three independent risk factors for AMH decline in women aged 20–30 years. Intense exercise, sleep quality, and adnexal surgery are three independent risk factors for a low AFC in women aged 31–36 years. Alcohol drinking and adnexal surgery are two independent risk factors for AMH decline in women aged 31–36 years.ConclusionWith age, female fertility becomes sensitive to high‐intensity exercise and poor sleep quality. Adnexal surgery and alcohol drinking are two important risk factors for female fertility in women under age 37 years.

Serum metabolomics study of women with different annual decline rates of anti-Müllerian hormone: an untargeted gas chromatography-mass spectrometry-based study.

Which metabolites are associated with varying rates of ovarian aging, measured as annual decline rates of anti-Müllerian hormone (AMH) concentrations? Higher serum concentrations of metabolites of phosphate, N-acetyl-d-glucosamine, branched chained amino acids (BCAAs), proline, urea and pyroglutamic acid were associated with higher odds of fast annual decline rate of AMH. Age-related rate of ovarian follicular loss varies among women, and the factors underlying such inter-individual variations are mainly unknown. The rate of ovarian aging is clinically important due to its effects on both reproduction and health of women. Metabolomics, a global investigation of metabolites in biological samples, provides an opportunity to study metabolites or metabolic pathways in relation to a physiological/pathophysiological condition. To date, no metabolomics study has been conducted regarding the differences in the rates of ovarian follicular loss. This prospective study was conducted on 186 reproductive-aged women with regular menstrual cycles and history of natural fertility, randomly selected using random case selection option in SPSS from the Tehran Lipid and Glucose Study. AMH concentrations were measured at baseline (1999-2001) and the fifth follow-up examination (2014-2017), after a median follow-up of 16 years, by immunoassay using Gen II kit. The annual decline rate of AMH was calculated by dividing the AMH decline rate by the follow-up duration (percent/year). The women were categorized based on the tertiles of the annual decline rates. Untargeted metabolomics analysis of the fasting-serum samples collected during the second follow-up examination cycle (2005-2008) was performed using gas chromatography-mass spectrometry. A combination of univariate and multivariate approaches was used to investigate the associations between metabolites and the annual decline rates of AMH. After adjusting the baseline values of age, AMH and BMI, 29 metabolites were positively correlated with the annual AMH decline rates. The comparisons among the tertiles of the annual decline rate of AMH revealed an increase in the relative abundance of 15 metabolites in the women with a fast decline (tertile 3), compared to those with a slow decline (tertile 1). There was no distinct separation between women with slow and fast decline rates while considering 41 metabolites simultaneously using the principal component analysis and the partial least-squares discriminant analysis models. The odds of fast AMH decline was increased with higher serum metabolites of phosphate, N-acetyl-d-glucosamine, BCAAs, proline, urea and pyroglutamic acid. Amino sugar and nucleotide sugar metabolism, BCAAs metabolism and aminoacyl tRNA biosynthesis were among the most significant pathways associated with the fast decline rate of AMH. Estimating the annual decline rates of AMH using the only two measures of AMH is the main limitation of the study which assumes a linear fixed reduction in AMH during the study. Since using the two-time points did not account for the variability in the decline rate of AMH, the annual decline rates estimated in this study may not accurately show the trend of the reduction in AMH. In addition, despite the longitudinal nature of the study and statistical adjustment of the participants' ages, it is difficult to distinguish the AMH-related metabolites observed in this study can accelerate ovarian aging or they are reflections of different rates of the aging process. Some metabolite features related to the decline rates of AMH have been suggested in this study; further prospective studies with multiple measurements of AMH are needed to confirm the findings of this study and to better understand the molecular process underlying variations in ovarian aging. This study, as a part of PhD thesis of Ms Nazanin Moslehi, was supported by Shahid Beheshti University of Medical Sciences (10522-4). There were no competing interests. N/A.