anti-Müllerian Hormone Decrease Research Articles

Risk factors associated with changes in serum anti-Müllerian hormone levels before and after laparoscopic cystectomy for endometrioma.

The objective of our study was to investigate the risk factors for a decrease in ovarian reserve in patients with endometriomas after standardized laparoscopic procedures and evaluation to provide corresponding clinical guidance for patients with fertility requirements. Anti-Müllerian hormone (AMH) levels and other clinical data from 233 patients with endometriomas and 57 patients with non-endometrioma ovarian cysts admitted to the Peking Union Medical College Hospital between January 2018 and September 2023 were prospectively analysed. The pretreatment AMH levels of the study groups were compared to assess the impact of endometrioma on ovarian reserve, and the decrease in AMH after treatment was analysed to determine potential risk factors contributing to this change. Pretreatment AMH levels did not significantly differ between patients with endometriomas and those with non-endometrioma ovarian cysts. Within the endometrioma group, older age, higher body mass index (BMI), and shorter menstrual cycles were found to be associated with decreased AMH levels prior to treatment (p<0.05). Participants presenting with bilateral cysts, advanced surgical staging, or a completely enclosed Douglas pouch demonstrated significantly lower levels of AMH prior to treatment compared to those without these conditions (p<0.05). Furthermore, their AMH levels further declined within one year after undergoing laparoscopic cystectomy (p<0.05). However, there was no difference in AMH levels after surgery between patients who successfully became pregnant and those who did not (p>0.05). Laparoscopic removal of endometriomas can adversely affect ovarian reserve, especially during bilateral cysts removal and when patients are diagnosed as having a higher stage of endometriosis, further impacting ovarian function. It should be noted that a decrease in AMH levels may not necessarily indicate an absolute decline in fertility. Therefore, it is crucial to conduct thorough patient evaluations and provide comprehensive patient education to offer appropriate guidance for fertility preservation.

Serum anti-müllerian hormone (AMH) concentration during pregnancy: a longitudinal study.

A prospective longitudinal cohort study aimed to longitudinally examine the kinetics of Anti-müllerian hormone (AMH) during the first two trimesters of pregnancy. Pregnant women with stored 1st trimester serum samples were recruited at 24-28 weeks gestation during their gestational diabetes testing, where they provided an additional serum sample. The samples were analysed for AMH, oestradiol and progesterone concentrations. A decrease in serum AMH was observed in 40 out of 45 (88.9%) (95% CI 75.9% to 96.3%) of the participants in this study. The median serum AMH concentration was 10.9 pmol/L in the 1st trimester and 6.5 pmol/L during the 2nd trimester, with a significantly different distribution of the values between the 1st and the 2nd trimester AMH samples (p<0.001). The median percentage of AMH difference of -39.8%. This study demonstrated a significant decrease in serum AMH levels from the 1st to the 2nd trimester of pregnancy. The absolute decrease in AMH levels seems to be positively associated with 1st trimester AMH levels, whereas the percentage of AMH difference is not. Further studies are required to elucidate the potential physiological mechanisms of this finding.

Age-related changes in serum anti-Müllerian hormone in women of reproductive age in Kenya

Background. Anti-Müllerian hormone (AMH) is produced by the granulosa cells of ovarian antral follicles and plays a role in therecruitment of dominant follicles during folliculogenesis. The serum level of AMH is proportional to the number of developing folliclesin the ovaries and reflects ovarian reserve. Nomograms of AMH variation with age exist from Caucasian populations, but there are none drawn from local African data.Objectives. To establish age-specific median serum AMH levels in an unselected East African population of women of reproductive age.Methods. We retrospectively analysed data on 1 718 women who underwent AMH testing using the Beckman Coulter AMH Gen IIenzyme-linked immunosorbent assay during the period 2015 - 2019 at Aga Khan University Hospital, Nairobi, Kenya. Age-specific median AMH levels were derived and presented in 5-year age bands. AMH levels were then log-transformed and, using linear regression in a natural spline function, presented on a scatter plot to demonstrate variation across reproductive age.Results. The median (interquartile range (IQR)) age of women who were tested for AMH was 38 (19 - 49) years. For the study population, the median (IQR) serum AMH level was 0.87 (0.01 - 17.10) ng/mL. The AMH concentration was inversely related to age, with a progressive decline whereby an increase of 1 year resulted in a corresponding decrease in AMH of 0.18 ng/mL. The proportion of women with decreased ovarian reserve increased exponentially with age from 14.9% in those aged 20 - 24 years to 48.7% at 35 - 39 years.Conclusion. From a large dataset of mainly black African women, this study confirms that serum AMH declines with advancing age,as reported elsewhere in Caucasian populations. There was, however, a higher than expected number of women with diminished ovarian reserve for age. Future studies prospectively exploring ovarian reserve in the general population could unravel underlying biological, reproductive and environmental factors that may influence AMH levels and reproductive capacity in this indigenous population.

Anti-Müllerian Hormone Levels among Female Firefighters.

Female firefighters have occupational exposures which may negatively impact their reproductive health. Anti-müllerian hormone (AMH) is a clinical marker of ovarian reserve. We investigated whether AMH levels differed in female firefighters compared to non-firefighters and whether there was a dose-dependent relationship between years of firefighting and AMH levels. Female firefighters from a pre-existing cohort completed a cross-sectional survey regarding their occupational and health history and were asked to recruit a non-firefighter friend or relative. All participants provided a dried blood spot (DBS) for AMH analysis. Linear regression was used to assess the relationship between firefighting status and AMH levels. Among firefighters, the influence of firefighting-related exposures was evaluated. Firefighters (n = 106) and non-firefighters (n = 58) had similar age and BMI. Firefighters had a lower mean AMH compared to non-firefighters (2.93 ng/mL vs. 4.37 ng/mL). In multivariable adjusted models, firefighters had a 33% lower AMH value than non-firefighters (−33.38%∆ (95% CI: −54.97, −1.43)). Years of firefighting was not associated with a decrease in AMH. Firefighters in this study had lower AMH levels than non-firefighters. More research is needed to understand the mechanisms by which firefighting could reduce AMH and affect fertility.

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.

P–450 Effects of rheumatoid arthritis and methotrexate therapy on ovarian reserve in infertile women

Abstract Study question Do patients with infertility and rheumatoid arthritis (RA) treated with methotrexate (MTX) have ovarian reserve alterations? Summary answer Women with infertility and RA treated with MTX were found to have statistically significant decrease of ovarian reserve. What is known already Rheumatoid arthritis (RA) is one of the most prominent inflammatory diseases affecting women of child-bearing age [Brouwer J. et al, 2014]. RA and its treatment may interfere with the female reproductive physiology. The vast majority of patients with RA are treated with methotrexate (MTX) which is a folate antagonist that inhibits DNA synthesis. MTX, which is the anchor drug in RA, targets actively proliferating cells including the oocytes and granulosa cells which may impair the ovarian reserve [Min Tun Kyaw et al, 2020]. Study design, size, duration A prospective case-control study that enrolled 72 female patients with infertility was conducted in the 2-year time period of September 2018 to October 2020. Participants/materials, setting, methods The main group comprised 32 patients with infertility and RA; the control group consisted of 40 women with infertility only. Patients with RA were stratified into subgroups based on whether or not they received MTX. To investigate ovarian reserve measurement of serum anti-Müllerian hormone (AMH) was used. The level of AMH was evaluated concerning RA duration and activity, as well as the age at initiation of MTX therapy, dosage, and treatment duration. Main results and the role of chance The mean age of the study population was 36±3 years. The duration of RA was 4 [3; 11] years. The low disease activity based on DAS28-ESR (disease activity score based on 28 joints using the erythrocyte sedimentation rate) prevailed(56.2%). In the main group 19(59.4%) women received MTX therapy. The MTX dosage was 15 [15;20]mg /wk, the duration of MTX therapy by the day of inclusion in the study was 18.7[1; 15]months. The AMH level was significantly lower in the main group (2.1 n /ml vs 2.73ng /ml, p = 0.043). The number of patients with decreased ovarian reserve (AMH level&amp;lt;1.0ng/ml) significantly prevailed in the group of patients with RA (25% vs 5%, p = 0.015). When assessing the AMH level in patients with RA who received MTX (n = 19) and patients in the control group, there was a tendency towards a decrease in the indicator in the first subgroup, but no statistically difference was found (p = 0.074). Correlation analysis of the dependence of AMH level on the patient age showed the most significant decrease in AMH in the patients with RA receiving MTX compared to the patients with RA who did not, and compared to all patients with RA regardless of the therapy received (rs=–0.563)(p &amp;lt; 0.05). Limitations, reasons for caution The lack of statistically significant data in certain cases may be due to the small sample size. Wider implications of the findings: RA and MTX administration are associated with a significant decrease in AMH levels. The age of initiation of the therapy is negatively correlated with the AMH level. In this regard, patients with already compromised reproductive function who are planning to receive MTX should be advised to preserve the genetic material. Trial registration number 567890

P-450 Effects of rheumatoid arthritis and methotrexate therapy on ovarian reserve in infertile women

Abstract Study question Do patients with infertility and rheumatoid arthritis (RA) treated with methotrexate (MTX) have ovarian reserve alterations? Summary answer Women with infertility and RA treated with MTX were found to have statistically significant decrease of ovarian reserve. What is known already Rheumatoid arthritis (RA) is one of the most prominent inflammatory diseases affecting women of child-bearing age [Brouwer J. et al, 2014]. RA and its treatment may interfere with the female reproductive physiology. The vast majority of patients with RA are treated with methotrexate (MTX) which is a folate antagonist that inhibits DNA synthesis. MTX, which is the anchor drug in RA, targets actively proliferating cells including the oocytes and granulosa cells which may impair the ovarian reserve [Min Tun Kyaw et al, 2020]. Study design, size, duration A prospective case-control study that enrolled 72 female patients with infertility was conducted in the 2-year time period of September 2018 to October 2020. Participants/materials, setting, methods The main group comprised 32 patients with infertility and RA; the control group consisted of 40 women with infertility only. Patients with RA were stratified into subgroups based on whether or not they received MTX. To investigate ovarian reserve measurement of serum anti-Müllerian hormone (AMH) was used. The level of AMH was evaluated concerning RA duration and activity, as well as the age at initiation of MTX therapy, dosage, and treatment duration. Main results and the role of chance The mean age of the study population was 36±3 years. The duration of RA was 4 [3;11] years. The low disease activity based on DAS28-ESR (disease activity score based on 28 joints using the erythrocyte sedimentation rate) prevailed(56.2%). In the main group 19(59.4%) women received MTX therapy. The MTX dosage was 15 [15;20]mg /wk, the duration of MTX therapy by the day of inclusion in the study was 18.7[1;15]months. The AMH level was significantly lower in the main group (2.1 n /ml vs 2.73ng /ml, p = 0.043). The number of patients with decreased ovarian reserve (AMH level&amp;lt;1.0ng/ml) significantly prevailed in the group of patients with RA (25% vs 5%, p = 0.015). When assessing the AMH level in patients with RA who received MTX (n = 19) and patients in the control group, there was a tendency towards a decrease in the indicator in the first subgroup, but no statistically difference was found (p = 0.074). Correlation analysis of the dependence of AMH level on the patient age showed the most significant decrease in AMH in the patients with RA receiving MTX compared to the patients with RA who did not, and compared to all patients with RA regardless of the therapy received (rs=-0.563)(p &amp;lt; 0.05). Limitations, reasons for caution The lack of statistically significant data in certain cases may be due to the small sample size. Wider implications of the findings RA and MTX administration are associated with a significant decrease in AMH levels. The age of initiation of the therapy is negatively correlated with the AMH level. In this regard, patients with already compromised reproductive function who are planning to receive MTX should be advised to preserve the genetic material. Trial registration number 567890

Deletion of Gremlin-2 alters estrous cyclicity and disrupts female fertility in mice†.

Members of the differential screening-selected gene aberrative in neuroblastoma (DAN) protein family are developmentally conserved extracellular binding proteins that antagonize bone morphogenetic protein (BMP) signaling. This protein family includes the Gremlin proteins, GREM1 and GREM2, which have key functions during embryogenesis and adult physiology. While BMPs play essential roles in ovarian follicle development, the role of the DAN family in female reproductive physiology is less understood. We generated mice null for Grem2 to determine its role in female reproduction in addition to screening patients with primary ovarian insufficiency (POI) for variants in GREM2. Grem2-/- mice are viable, but female Grem2-/- mice have diminished fecundity and irregular estrous cycles. This is accompanied by significantly reduced production of ovarian anti-Müllerian hormone (AMH) from small growing follicles, leading to a significant decrease in serum AMH. Surprisingly, as AMH is a well-established marker of the ovarian reserve, morphometric analysis of ovarian follicles showed maintenance of primordial follicles in Grem2-/- mice like wild-type (WT) littermates. While Grem2 mRNA transcripts were not detected in the pituitary, Grem2 is expressed in hypothalami of WT female mice, suggesting the potential for dysfunction in multiple tissues composing the hypothalamic-pituitary-ovarian axis that contribute to the subfertility phenotype. Additionally, screening 106 women with POI identified one individual with a heterozygous variant in GREM2 that lies within the predicted BMP-GREM2 interface. In total, these data suggest that Grem2 is necessary for female fecundity by playing a novel role in regulating the HPO axis and contributing to female reproductive disease.

Association between arthritis treatments and ovarian reserve: a prospective study

Research questionHow do anti-Müllerian hormone (AMH) concentrations in women with and without arthritis compare? Is there an association between AMH and arthritis drug regimen? DesignIn this prospective cohort study, AMH was measured at two time points (T0 and T1) in 129 premenopausal women with arthritis. AMH at T0 was compared with that from a bank of serum samples from 198 premenopausal women without arthritis. Primary outcomes were: (i) diminished ovarian reserve (DOR) (AMH <1.1 ng/ml) and (ii) annual rate of AMH decrease. Univariate, multivariable and Firth logistic regression identified variables associated with annual AMH decrease in excess of the 75th percentile. ResultsMedian time between T0 and T1 was 1.72 years. At time T0, median age-adjusted AMH in women with arthritis was significantly lower than that of women without arthritis (median 2.21 ng/ml versus 2.78 ng/ml; P = 0.009). Women with arthritis at highest risk for DOR had a history of tubal sterilization or were over the age of 35. Those with highest odds of having an annual AMH decrease in excess of the 75th percentile (over 28% decrease per year) were those: over the age of 35 or who sought care for infertility. Women with arthritis taking methotrexate alone (OR 0.08, 95% CI 0.01–0.67) or methotrexate plus tumour necrosis factor-alpha antagonists (OR 0.13, 95% CI 0.02–0.89) were less likely to be in the highest quartile of annual AMH decrease than women with arthritis not taking medication. ConclusionsWomen with arthritis had lower AMH than healthy controls. Long-term methotrexate use was not associated with an annual AMH decrease.

After cyclophosphamide exposure, granulosa cells recover their anti-müllerian hormone-producing ability but not their numbers.

Anti‐müllerian hormone (AMH) produced by granulosa cells (GCs), reserves the ovarian follicle pool for future recruitment and ovulation. However, women who have undergone cyclophosphamide (Cy) treatment have decreased AMH levels due to damaged GCs. This study establishes flow cytometry protocols for identification of GCs and investigates the cause of the Cy‐induced AMH decrease by analyzing the number of GCs and their AMH production at the single cell level. Over 2 weeks, C57BL/6 mice were intraperitoneally injected 6 times with 100 mg/kg Cy and sacrificed either immediately or 4 weeks after Cy treatment. Twenty‐four hours post‐Cy exposure, a decrease in serum AMH levels was seen due to a reduction in the number of follicle‐stimulating hormone receptor (FSHR)+AMH+ GCs and their ability to produce AMH. However, 4 weeks after Cy treatment, serum AMH levels were still decreased due to the decreased number of FSHR+AMH+ GCs, however, their AMH‐producing ability was unaltered. Consistently, in vitro, Cy‐induced low AMH production in FSHR+AMH+ hGL5 cells (immortalized human GCs) was restored 24 h after Cy treatment, although their numbers remained decreased. Thus, the surviving GCs after Cy exposure had intact AMH‐producing ability. In future, an effort to minimize GC death by Cy treatment is required, while maintaining its therapeutic effects.

Comparison of the therapeutic efficacy and ovarian reserve between catheter-directed sclerotherapy and surgical excision for ovarian endometrioma.

To compare the efficacies of catheter-directed sclerotherapy (CDS) with 99% ethanol and surgery for ovarian endometrioma and their impact on the ovarian reserve. From January 2011 to June 2019, 71 patients who underwent surgical excision (n = 51) or CDS (n = 20) for symptomatic ovarian endometriomas were reviewed. To analyze the effect on the ovarian reserve, serum anti-Müllerian hormone (AMH) levels were compared before and after the procedure. Symptoms, serum cancer antigen 125 (CA-125), lesion size, recurrence, hospitalization, and complications were reviewed retrospectively. During a mean follow-up of 22.3months (range, 6 to 94months), no significant difference in symptom relief was found between CDS and surgery (95.0% [19/20] and 92.2% [47/51], respectively, p > 0.999). The hospital stay was shorter with CDS than with surgery (2.6 ± 0.6days and 4.1 ± 0.5days, respectively, p < 0.001). There was no significant difference in serum AMH levels before and after CDS (2.3 (interquartile range (IQR) 1.1-5.3) ng/mL and 2.6 (IQR 0.9-4.9) ng/mL, respectively, p = 0.243), but there was a significant decrease in serum AMH in the surgery group (3.0 (IQR 1.3-5.5) ng/mL and 1.6 (IQR 0.7-3.2) ng/mL, respectively, p < 0.001). CA-125 decreased in both CDS and surgery groups (p = 0.001 and < 0.001, respectively). Two minor complications occurred in the surgery group, while no complication was observed in the CDS group. The therapeutic efficacy of CDS appears to be comparable to that of surgical resection for ovarian endometrioma. Ovarian function was well-preserved, and a shorter hospital stay was required in patients who underwent CDS. • There was no significant difference in symptom relief between CDS and surgery (95.0% [19/20], 92.2% [47/51], respectively, p >0.999). • No significant difference in serum AMH levels was seen before and after CDS (2.3 (1.1, 5.3)* ng/mL, 2.6 (0.9, 4.9)* ng/mL, respectively, p = 0.243), whereas serum AMH levels significantly decreased after surgical resection (3.0 (1.3, 5.5)* ng/mL, 1.6 (0.7, 3.2)* ng/mL, respectively, p <0.001). *Median (25 quartiles, 75 quartiles) • The hospitalization period was shorter with CDS than with surgery (2.6 ± 0.6 days, 4.1 ± 0.5 days, respectively, p <0.001).

Improvement of anti-Müllerian hormone and oxidative stress through regular exercise in Chinese women with polycystic ovary syndrome.

Structured exercise is shown to be one of the most effective lifestyle interventions for women with polycystic ovary syndrome (PCOS). Anti-Müllerian hormone (AMH) has been proposed as a marker of ovarian dysfunction, and oxidative stress plays an important role in the development of PCOS. We sought to investigate whether there was any effect of aerobic exercise on AMH levels and oxidative stress in Chinese PCOS women. Thirty-eight PCOS women were enrolled and divided into two groups. The exercise group carried out a 12-week exercise program, while the control group maintained their normal lifestyle. All women underwent blood tests and cardiopulmonary exercise tests (CPETs) at enrollment and at 12-week follow-up. At baseline, there was no statistically significant difference between the two groups in clinical characteristics, AMH, oxidative biomarkers, and CPET parameters. After 12weeks, body mass index (BMI) and cardiovascular fitness indexes of the exercise group were improved. We also found a decrease in AMH (P= 0.021) and malondialdehyde (MDA) (P= 0.002) and an increase in superoxide dismutase (SOD) (P= 0.009) and total antioxidant capacity (TAC) (P= 0.012) in the exercise group, while there was no change in the control group. Moreover, the change of AMH was positively associated with the change of MDA (r = 0.23, P= 0.003) in the exercise group. Our findings demonstrated that 12weeks of aerobic exercise produced beneficial effects on BMI, cardiovascular fitness, AMH, and oxidative stress in PCOS women. Favorable modification of oxidative stress might thus be an effective method for improvement of AMH in these women, which deserves further exploration in the future.

Impact of ABVD chemotherapy on ovarian reserve after fertility preservation in reproductive-aged women with Hodgkin lymphoma.

How is ovarian reserve affected by chemotherapy in patients with Hodgkin lymphoma (HL) who undergo fertility preservation (FP)? A retrospective study was conducted by reviewing medical records of 105 HL patients referred to the FP unit before starting adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy. Ovarian reserve was evaluated before chemotherapy and at the last follow-up using anti-Müllerian hormone (AMH) and antral follicle count (AFC) measurements. The decrease in AMH was compared with that expected from normograms. AMH was compared between patients who underwent cryopreservation of ovarian tissue and those who underwent cryopreservation of mature oocytes. After ABVD, 15% of patients required hematopoietic stem cell transplantation. At a median follow-up of 33months, the median decrease in AMH was 0.88ng/mL, which was significantly greater than that of the general population of this age group (p< 0.001). Of the 82 women who only had ABVD, 38 underwent FP by cryopreservation of mature oocytes and 44 underwent cryopreservation of the ovarian cortex. There was no significant difference in AMH or AFC at the last follow-up between FP techniques. Although ABVD is considered to be of low gonadotoxic risk, the decrease in AMH was greater than expected for patients' age, and 15% of patients needed more aggressive therapy during follow-up. Type of FP was not associated with decline in ovarian reserve. Reproductive-aged women with HL should have the opportunity for FP counseling before starting treatment.

Ovarian Reserve Reduction With Surgery Is Not Correlated With the Amount of Ovarian Tissue Inadvertently Excised at Laparoscopic Surgery for Endometriomas.

The aim of the present study was to evaluate the effect of laparoscopic cystectomy on ovarian reserve by means of anti-Müllerian hormone (AMH) serial measurements and to compare AMH values with the number of inadvertently removed follicles in histological specimens. Fifty-two women were enrolled: 34 patients with endometriomas (group 1) and 18 patients with other benign ovarian cysts (group 2). All patients underwent laparoscopic cystectomy performed by a single experienced surgeon. The AMH was measured before, and 1, 3, and 6 months after cystectomy in group 1, and before and 6 months after surgery in group 2. Preoperative AMH levels (mean [standard deviation, SD]) in group 1 (3.39 [2.43] ng/mL) were not significantly different from group 2 (3.74 [2.57] ng/mL; P = .68). In group 1, a significant decrease in AMH levels of 43.4% was observed at 1 month (1.93 [1.36]; P = .003), and of 63.1% at 3 months (1.25 [1.00]; P = .007) postoperatively. The AMH increased not significantly between the third and sixth months in group 1 (+9.4%). Six months after surgery, AMH was reduced by 59.3% compared to baseline values in group 1 (P = .012), and by 29.5% in group 2 (P = .200). A significant difference in the AMH decrease was present between bilateral and monolateral endometriomas (P = .006). There was no correlation between the reduction rate of AMH and the number of follicles inadvertently removed in patients with endometriomas (P = .669). In conclusion, AMH decreases significantly after surgical excision of ovarian endometriomas. The postoperative decrease does not appear to correlate with the amount of ovarian tissue inadvertently excised with the endometrioma wall.

Changes in Anti-Müllerian Hormone and Inhibin B in Children Treated for Cancer.

Purpose: Diminished reproductive function can be a major late effect of childhood cancer treatment. This study evaluates the changes, and occurrence of possible recovery, in gonadal function markers in children treated for cancer. Methods: Gonadal function markers were measured before (T0), directly after (T1), and 1 year after (T2) end of treatment of childhood cancer. Anti-Müllerian hormone (AMH) was measured in girls and inhibin B in boys and compared to reference populations. Repeated measures analysis of variance and t-tests were employed for data analysis. Results: Baseline gonadal function markers (T0) at diagnosis were available in 129 girls and 150 boys. Paired gonadal function markers were available in 49 girls and 54 boys for T0-T1, and in 27 girls and 32 boys for T1-T2. Gonadal function markers were significantly lower than the reference population at each time point (p < 0.001). Post-menarcheal girls showed a decrease in AMH between T0 and T1 (standard deviation scores [SDS] -0.72 to -1.32, p = 0.007), and in the boys cohort, a decrease in inhibin B (SDS -1.14 to -1.43, p = 0.045) was observed. Impaired gonadal function levels (<5th percentile) at T1 were observed in 15 of 27 (56%) girls and in 15 of 32 (47%) boys. However, gonadal function had recovered at T2 in seven girls and six boys. Conclusion: Our data suggest that gonadal function is already compromised at diagnosis and is further decreased by childhood cancer treatment. Nevertheless, about half of the children with gonadal impairment recovered over time. Evaluation of gonadal function markers before 1 year after end of treatment may therefore be unreliable.

Characterization of intra- and interpatient variability and trajectory of ovarian reserve measures in 121,737 women

Measures of ovarian reserve including basal antral follicle count (BAFC), follicle-stimulating hormone (FSH), and anti-Müllerian hormone (AMH) are routinely utilized to counsel women undergoing fertility treatment or preservation. These measures also help in personalizing clinical protocols to minimize risks and optimize success rates, however, no large-scale study has been performed interrogating intra- or inter-individual variability in these metrics. To characterize variability and trajectory of ovarian reserve measures among a spectrum of women. We included 152,858 FSH, 330,266 BAFC, and 79,565 AMH measurements from 121,737 women at 13 fertility clinics (2000-2017). The mean number of FSH, BAFC, and AMH measurements per woman was 2.6, 3.1, and 1.3, respectively. Women were classified as UnknownFecundity if they used a sperm donor and had a female partner or no partner. Others were defined as FertilityTreatment or subgrouped based on diagnosis. We evaluated intra-individual variability of measurements within 3 months using the coefficient of variation (CV; standard deviation/mean) and used Kruskal-Wallis and Mann-Whitney Wilcoxon tests for difference of means between groups. We evaluated the relationship with age using a Generalized Estimating Equations (GEE) model with Poisson family (BAFC) or with Gaussian family (FSH, AMH), controlling for clinic and diagnosis. For trajectory models, we used GEE models controlling baseline age, clinic, and diagnosis. We also tested for interactions between time, age, and diagnosis. The intra-individual CV increased significantly with age for all three metrics, regardless of patient type. We saw greater variation in BAFC and AMH for FertilityTreatment, while FSH variation was greater for UnknownFecundity. For each metric within the FertilityTreatment diagnoses, the greatest variation was seen with diminished ovarian reserve (DOR), while the least was with polycystic ovary syndrome (PCOS). We next examined inter-individual variability among different patient groups. When we controlled for age and clinic, BAFC and AMH in UnknownFecundity, MaleFactor, TubalFactor, and UterineFactor both had similar values. Compared with UnknownFecundity, statistically significant differences in BAFC and AMH were found in DOR (BAFC 45% lower, AMH 1.3 ng/mL lower), Endometriosis (16% lower, 0.8 ng/mL lower), PCOS (50% higher, 3.3 ng/mL higher), and OvulatoryDysfunction (31% higher, 1.95 ng/mL higher). In contrast, for FSH, we only found differences in DOR (1.6 IU higher) and PCOS (1.4 IU lower), while UnknownFecundity was similar to other diagnoses in the FertilityTreatment group. Finally, we studied intra-individual rate of change of these metrics over time using trajectory modeling. We found that the rate of change increased with age, starting at age 30.0 for BAFC, 29.1 for AMH, and 25.9 for FSH. For subtypes, we found that the rate of change for FSH increased at a slower rate for PCOS and UnknownFecundity, compared with other diagnoses. Interestingly, we found that DOR patients had a slower rate of decrease in AMH compared with other patients. We found significant differences in variability and trajectory of ovarian reserve measures among women and at different ages. These findings underscore the importance of taking multiple factors into account when leveraging these markers in counseling and decision-making.

A Single Radioactive Iodine Treatment Has a Deleterious Effect on Ovarian Reserve in Women with Thyroid Cancer: Results of a Prospective Pilot Study.

Women of reproductive age with differentiated thyroid cancer (DTC) often need radioactive iodine (RAI) treatment after surgery. In contrast to the well-documented effect of RAI on testicular function, the potential negative effects of this treatment on ovarian reserve have been largely dismissed. The objective of this pilot study was to examine the possibility that RAI treatment is deleterious to the ovarian reserve by prospectively measuring the concentration of anti-Müllerian hormone (AMH) after RAI treatment. Thirty premenopausal women (Mage = 34 years; range 20-45 years) with a new diagnosis of DTC scheduled to undergo RAI ablation were recruited for this study. All of them had TNM stage 1 disease (T1-3, N0, or N1, M0), and were scheduled to receive RAI activities ranging from 30 to 150 mCi. AMH was measured at baseline and at 3, 6, 9, and 12 months after the administration of RAI. Of the 30 women, only 24 returned after the baseline assessment. RAI treatment resulted in a significant decrease in AMH concentrations at three months, from 3.25 ± 2.75 to 1.9 ± 1.74 ng/mL (p < 0.0001). Only partial recovery was subsequently documented. Eighty-two percent of subjects had final values below baseline levels, such that at one year, serum AMH was still 32% lower than prior to treatment (2.36 ± 1.88 ng/mL; p < 0.005). The only two continuous variables that correlated with the extent of AMH reduction at three months were the woman's age (r = 0.51; p = 0.02) and the age at menarche (r = 0.48; p = 0.03). Importantly, the RAI dose was not associated with the extent of AMH reduction and neither were smoking or the use of birth control pills. Older subjects (≥35 years) were significantly more likely to experience a marked AMH reduction at three months (63.7 ± 18.5% vs. 33.1 ± 29.2%; p = 0.01). The only predictor of recovery after one year was the extent of AMH decrease at three months: the lower the decline, the higher the chances for recovery. RAI in DTC has a rapid and profound effect on ovarian reserve, with only a partial recovery potential. In an era of declining human fertility, it is of relevance to recognize the potentially adverse effect of RAI in women of reproductive age. AMH measurement may be useful as a tool in this decision-making process.

Ovarian aging is associated with gray matter volume and disability in women with MS.

To determine if ovarian aging as measured by levels of anti-Müllerian hormone (AMH) is associated with pattern of multiple sclerosis (MS) progression in women. Women with MS and healthy controls were included from a longitudinal research cohort with up to 10 years follow-up. Plasma AMH levels were measured by ELISA for baseline and years 3, 5, and 8-10. Mixed effects logistic and linear regression models were employed, with adjustments for age, disease duration, and other covariables as appropriate. AMH levels were similar (0.98-fold difference, 95% confidence interval [CI] 0.69-1.37, p = 0.87) in women with MS (n = 412, mean age 42.6 years) and healthy controls (n = 180, mean age 44 years). In a multivariable model of women with MS, including adjustments for age, body mass index, and disease duration, 10-fold lower AMH level was associated with 0.43-higher Expanded Disability Status Scale (EDSS) score (95% CI 0.15-0.70, p = 0.003), 0.25-unit worse MS Functional Composite z score (95% CI -0.40 to -0.10, p = 0.0015), and 7.44 mm3 lower cortical gray matter volume (95% CI -14.6 to -0.30; p = 0.041) at baseline. In a multivariable random-intercept-random-slope model using all observations over time, 10-fold decrease in AMH was associated with a 0.27 increase in EDSS (95% CI 0.11-0.43, p = 0.006) and 5.48 mm3 (95% CI 11.3-0.33, p = 0.065) and 4.55 mm3 (95% CI 9.33-0.23, p = 0.062) decreases in total gray and cortical gray matter, respectively. As a marker of ovarian aging, lower AMH levels were associated with greater disability and gray matter loss in women with MS independent of chronological age and disease duration.

Usefulness of hemostatic sealants for minimizing ovarian damage during laparoscopic cystectomy for endometriosis.

We aimed to evaluate the impact of topical hemostatic sealants and bipolar coagulation during laparoscopic ovarian endometriotic cyst resection on ovarian reserve by comparing the rates of decrease in anti-Müllerian hormone (AMH). A randomized prospective data collection was made on women aged 19-45 years who planned to have laparoscopic ovarian cystectomy at one of two institutions (n = 80), Kangbuk Samsung Hospital, Seoul, Korea or National Health Insurance Service Ilsan Hospital, Goyang, Korea, from January 2014 to April 2016. Patients were randomly divided into two groups treated with either a topical hemostatic sealant or bipolar coagulation for hemostasis. The hemostatic group was randomized to the FloSeal or TachoSil subgroups. Preoperative and 3-month postoperative AMH levels were checked and the rates of decrease of AMH were compared. All patients enrolled were treated with dienogest (Visanne) for 6-12 months. None were lost to follow-up at postoperative 3 months, but about one-third of the patients had been lost to follow-up by 6-12 months. AMH was significantly decreased in both groups 3 months postoperatively; however, the rate of decrease in the bipolar coagulation group was greater than that in the hemostatic sealant group, 41.9% (interquartile range [IQR], 22.29-65.24) versus 18.1% (IQR, 10.94-29.90), P = 0.007. Between the two hemostatic subgroups, there was no significant difference in AMH decrease rate, 14.95% (IQR, 11.34-21.21) versus 18.1% (IQR 9.76-40.70), P = 0.204. Hemostatic sealants may be an alternative to bipolar coagulation for preservation of ovarian reserve after laparoscopic ovarian cystectomy for endometriosis.

Fertility Preservation in Endometriosis Patients: Anti-Müllerian Hormone Is a Reliable Marker of the Ovarian Follicle Density.

To analyze the ovarian reserve via measurement of follicular density and anti-Müllerian hormone (AMH) in endometriosis patients participating to a clinical program of cortical ovarian cryopreservation. Retrospective analysis of serum AMH levels and prospective investigation of ovarian follicle number. University Hospital. Two hundred and two women with endometriosis and 400 controls. Blood samples and ovarian biopsies. Correlation of serum AMH levels and the number of non-growing follicles in the biopsied cortical tissues in endometriosis and control subjects, including age, type of AMH kit, and the laboratory performing the analysis as covariates. AMH levels were shown to decrease with age in untreated endometriosis patients (P < 1.0 × 10-5) but they were significantly lower in endometriosis compared to controls only in patients over 36 years old (P = 2.7 × 10-4). The AMH decrease was faster in endometriosis compared to controls (beta = 0.27, P = 4.0 × 10-4). Primordial follicle number decreased with the reduction of AMH levels in both cases and controls (beta = 0.3; P = 0.04). AMH is a reliable marker of ovarian reserve in endometriosis patients, and it can predict follicular density in women undergoing ovarian tissue cryopreservation.