Baseline anti-Müllerian Hormone Research Articles

The Effect of Coenzyme Q10 Pretreatment on Ovarian Reserve in Women Undergoing Hysterectomy with Bilateral Salpingectomy: A Randomized, Double-Blind, Placebo-Controlled Trial.

The effect of diminished ovarian reserves after undergoing hysterectomies with bilateral salpingectomies is one of the health concerns among reproductive-age women with benign gynecologic diseases. Coenzyme Q10 (CoQ10), an antioxidant, is crucial in mitochondrial energy production, improving oocyte quality and quantity. This study compares the benefit of a 14-day preoperative (CoQ10) versus placebo on ovarian reserve by measuring anti-mullerian hormone (AMH) in women undergoing hysterectomy with bilateral salpingectomy. A double-blinded, randomised, placebo-controlled trial was conducted. Forty-four women with benign gynecologic diseases were randomised to receive either oral CoQ10 300 mg per day or placebo for 14 days before undergoing hysterectomy with bilateral salpingectomy. Serum AMH levels were collected for analysis before taking CoQ10 and 6 weeks postoperatively in each group. The baseline demographic, clinical characteristics, and baseline AMH levels were comparable between the groups (1.47(0.45,2.49) vs.1.29 (0.47,2.11), p=0.763). The serum AMH levels after the surgery were significantly decreased from pre-operative levels (median 0.99 (0.37,1.63) vs 1.34 (0.57,2.30)), p= 0.001. However, there was no significant difference in the AMH change between the CoQ10 group and the placebo group (AMH per cent change -28.2% (64.09, -4.81) vs -20.07% (-61.51, -2.92)), p= 0.99, respectively. Age, gynecologic disease, operative time, and blood loss were not significantly associated with the AMH change. There were no significant side effects or adverse operative outcomes among coQ10 users. In conclusion, Hysterectomy with bilateral salpingectomy led to a significantly decreased AMH level. However, pretreatment with CoQ10 for two weeks was ineffective in protecting an ovarian reserve.

Age and serum Anti-Mullerian Hormone (AMH) levels as predictors of time to return of menses after chemotherapy.

Chemotherapeutic agents result in the loss of growing follicles, which can manifest as amenorrhoea. Alkylating chemotherapy (AC) is known to be more gonadotoxic than non-alkylating chemotherapy (NAC). Anti-Mullerian Hormone (AMH), an indirect marker of ovarian reserve, and age have been investigated as predictors of ovarian function after chemotherapy, however little is known about the time to return of menses. This study aimed to assess how patient age and baseline serum AMH levels at cancer diagnosis affect the time to return of menses post-chemotherapy. This retrospective cohort study examined oncology patients (n=67) who underwent chemotherapy and were treated through the Reproductive Services Unit of two institutions in Melbourne, Australia. Primary outcomes included correlation between age and baseline AMH with time to return of menses after chemotherapy. Secondary outcomes include the change in AMH levels at 6- and 12-months post-completion of chemotherapy. Pairwise correlation of pre-chemotherapy AMH level and time to return of menses demonstrated statistical significance (Spearman's coefficient, ρ = -0.40) for patients who underwent AC. This analysis in breast cancer patients who underwent AC displayed a negative correlation, however, was not statistically significant. No association was found between age and time to return of menses for all cancer (NAC or AC) or breast cancer patients who underwent AC. Higher AMH level prior to AC was associated with an earlier return of menses after chemotherapy. Age at the commencement of chemotherapy was not associated with return of menses. Further prospective research is required to assess post-chemotherapy recovery of AMH.

P-709 A retrospective cohort study of the stability of ovarian reserve in women with Turner Syndrome (TS) and spontaneous menstruation

Abstract Study question What is the stability of ovarian reserve, as measured by anti-Müllerian hormone (AMH), over time in women with TS and spontaneous menstruation beyond age 16? Summary answer Ovarian reserve, as measured by AMH, is stable over time in adult (>16 years) women with TS and spontaneous menstruation. What is known already TS is associated with gonadal dysgenesis and premature ovarian insufficiency (POI). In a minority of TS women, ovarian function is maintained with ongoing menstruation and the possibility of achieving spontaneous pregnancy. There is uncertainty as to the role of fertility preservation in this population. The 2016 Clinical practice guidelines for the care of girls and women with TS recommend counselling women with TS that their probability to conceive spontaneously decreases rapidly with age. However, the natural history of AMH over time in this sub-population has not been reported. Study design, size, duration Retrospective cohort study of patients attending the TS clinic at University College London Hospital between December 2020 and December 2022. This time interval was chosen to ensure that the entire UCLH TS cohort was screened, even if one year of annual follow-up was missed during COVID-19. Clinical records were reviewed to identify adult patients (>16years old) with spontaneous menstruation at any time and at least one measurement of AMH. Participants/materials, setting, methods To assess the stability of the AMH values, the rate of change was calculated using the formula: ratechangeAMH = (lastAMH-baselineAMH)/(time in months between readings). The distribution of the rate of change in the PCOS and non-PCOS groups was then compared using a non-parametric Mann-Whitney test: a regression analysis was performed with the outcome as the ratechangeAMH and the explanatory variables being baseline AMH and age at baseline AMH. Main results and the role of chance 55 patients were identified, median age 25.9 (range 16 to 41).Their karyotypes were 45X (n = 2) 45X/46XX mosaic (n = 28), 45X/47XXX mosaic (n = 11), and other (n = 14). The number of AMH measurements varied from 1-10 and the longest duration of AMH follow-up was 11 years. A subgroup of 9 patients met diagnostic criteria for PCOS. Median AMH for the 45X/46XX group was 21.25pmol/L (range 0.45-59.36), for the 45X group the median was 1.39pmol/L (range 0.20-2.57), in the 47XXX mosaic group the median was 5.05pmol/L (range 0.70-13.97) and in the other group the median was 9.35pmol/L (0.20-54.40). There was a significantly higher mean AMH, adjusted for age and baseline AMH, in the PCOS group than non PCOS group, mean 26.83 vs 16.23 pmol/L (p < 0.01). Overall, the mean rate of change of AMH was +0.0386pmol/L per month 95%CI [-0.0454, +0.1227] and the median was 0.0000pmol/L per month. In the PCOS group, the mean rate of change was +0.0034 pmol/L per month, median 0.0000pmol/L per month. Regression analyses determined that neither age or baseline AMH had a significant impact on the rate of change. Only one patient in the cohort went onto develop POI during the period of follow up. Limitations, reasons for caution The average age of this cohort at the end of the reported follow up period is 25.9. Ongoing prospective follow up is needed to assess the stability of ovarian reserve into the later part of the typical reproductive window to confirm ongoing stability and assess age reated decline. Wider implications of the findings These findings question the necessity and efficacy of fertility preservation in this subset of TS patients as ovarian reserve is stable over time. Until further data is available, we advocate offering observation with annual AMH masurement rather than immediate recourse to fertility preservation. Trial registration number Not applicable

O-226 Effects of preventive uterine artery occlusion during laparoscopic myomectomy on ovarian reserve markers: a randomized controlled trial

Abstract Study question Does definitive occlusion of uterine arteries have a short or long term impact on anti-Müllerian hormone (AMH) levels in reproductive age women undergoing laparoscopic myomectomy? Summary answer Preventive uterine artery occlusion during laparoscopic myomectomy does not impact AMH levels in reproductive age women. What is known already Uterine leiomyoma are the most common benign tumours in women of reproductive age. For symptomatic women willing to retain their uterus, especially for a future pregnancy, the current gold standard is the myomectomy for subserous/intramural leiomyoma. Temporary or definitive occlusion of uterine arteries can be performed to control bleeding during surgery but its impact on ovarian reserve markers is still unknown. A single randomized trial with a one-year follow-up demonstrated that temporary bilateral uterine artery occlusion during laparoscopic myomectomy slightly decreased AMH levels at day-2 after surgery but has no impact thereafter 3, 6 and 12 months postoperatively. Study design, size, duration We conducted a randomized controlled trial with a two-year follow-up evaluating the effect of definitive occlusion of uterine arteries on ovarian reserve via sequential measures of anti-Müllerian hormone (AMH) levels. Fifty-eight women with symptomatic leiomyoma type FIGO 3-6 scheduled for laparoscopic myomectomy at were included between July 2015 and October 2021. Participants/materials, setting, methods Patients were randomized into: the intervention group (laparoscopic myomectomy with preventive occlusion of uterine arteries) and the control group (laparoscopic myomectomy without occlusion of uterine arteries) ). AMH evaluated at T0 and followed at 1 month (T1), 3 months (T3), 6 months (T6), 12 months (T12) and 24 months (T24) after surgery. Intraoperative blood loss, leiomyoma recurrence and adenomyosis occurrence were also evaluated comparing pre- and post-operative findings. Finally, pregnancies and live births were monitored. Main results and the role of chance Women in both groups did not differ in their baseline characteristics in terms of age, body mass index, ethnicity, parity, wish to become pregnant, hormonal treatment, leiomyoma number and size, baseline haemoglobin levels, bleeding symptoms baseline AMH levels and antral follicular count (AFC). The mean operative time was similar in between both groups. Mean blood loss during surgery was on average 138 (±104)ml in the intervention group versus 436 (±498)ml in controls (p < 0.001). The difference in haemoglobin between before and after surgery was significantly higher in the control group 21.8 (±12.7)g/l compared with the intervention group 14.8 (±8.9)g/l (p = 0.02). Regarding clinical symptoms, most patients had decreased menstrual flow at the last follow-up visit (24 months) compared to baseline in both group improvement of dysmenorrhea followed the same trend with a reduction in pain levels in both groups. Risk of leiomyoma recurrence was found similar between both groups. Most importantly, AMH levels were similar between groups at all times (T1, T3, T6, T12 and T24) and non-inferiority of preventive occlusion was demonstrated with a non-inferiority margin of -3.5pmol/L (0.5 ng/ml). The pregnancy rate was not different between groups. Limitations, reasons for caution Our sample size was calculated to detect a clinically relevant difference of at least two-third of the standard deviation in AMH levels, but we cannot exclude a smaller impact on AMH with a different sample size. Wider implications of the findings Preventive uterine artery occlusion during laparoscopic myomectomy does not impact ovarian reserve markers and can be safely used to control perioperative bleeding. Trial registration number NCT02563392

(106) OVARIAN RESERVE AFTER LAPAROSCOPIC CYSTECTOMY OF ENDOMETRIOTIC CYSTS AND OTHER BENIGN CYSTS: 36-MONTHS FOLLOW-UP STUDY

Abstract Introduction There is a growing body of evidence that ovarian cystectomy may negatively impact ovarian reserve. It is unclear whether there are any differences in the long-term effect of ovarian reserve after ovarian cystectomy between women with endometrioma and those with other benign ovarian cysts. Although several studies have shown that AMH reduction is milder in nonendometriotic benign ovarian cysts compared with endometriomas, further studies are necessary because long-term studies are lacking. Objective The aim of this study was to compare the long-term effects of laparoscopic cystectomy for endometriotic cysts and other benign cysts on ovarian reserve. Methods A total of 165 women aged 20-40 years who underwent laparoscopic cystectomy for endometriotic cysts (Endometrioma group, n=96) and other benign cysts (Non-endometrioma group, n=69) were included in this retrospective study. Ovarian reserve was measured by serum anti-Müllerian hormone (AMH) and compared before surgery and at 6, 12, 24 and 36 months after surgery. Results Baseline AMH levels were lower in the endometrioma group compared with the non-endometrioma group without statistical significance (4.43±3.52 ng/mL vs. 4.95±3.59 ng/mL; p =0.378). AMH levels of 6, 12, 24, and 36 months after surgery was significantly decreased when compared with preoperative levels in the endometrioma group. Decline of the AMH levels was statistically significant at 6 months and 24 months but not at 12 and 36 months in the non-endometrioma group. There was no further significant decrease in the AMH levels after 6 months of surgery in both groups. Decline of AMH levels at 6, 12, 24, and 36 months after surgery from preoperative levels was significantly larger in the endometrioma group compared with the non-endometrioma group. Conclusions Laparoscopic ovarian cystectomy reduced ovarian reserve irrespective of the type of cysts. Surgical excision of endometriotic cysts has a more detrimental and persistent damage on ovarian reserve compared with other benign ovarian cysts. After 6 months of surgery, no further significant fall in AMH levels was observed in the 36-month follow-up. Disclosure No.

The impact of treatment for childhood classical Hodgkin lymphoma according to the EuroNet-PHL-C2 protocol on serum anti-Müllerian Hormone.

What is the impact of the EuroNet-PHL-C2 treatment protocol for children with classical Hodgkin lymphoma (cHL) on gonadal function in girls, based on assessment of serum anti-Müllerian hormone (AMH)? Serum AMH levels decreased after induction chemotherapy and increased during subsequent treatment and 2 years of follow-up, with lowest levels in patients treated for advanced stage cHL. Treatment for cHL, particularly alkylating agents and pelvic irradiation, can be gonadotoxic and result in premature reduction of primordial follicles in females. The current EuroNet-PHL-C2 trial aims to reduce the use of radiotherapy in standard childhood cHL treatment, by intensifying chemotherapy. This study aims to assess the gonadotoxic effect of the EuroNet-PHL-C2 protocol. This international, prospective, multicenter cohort study is embedded in the EuroNet-PHL-C2 trial, an European phase-3 treatment study evaluating the efficacy of standard cHL treatment with OEPA-COPDAC-28 (OEPA: vincristine, etoposide, prednisone, and doxorubicin; COPDAC-28: cyclophosphamide, vincristine, prednisone, and dacarbazine) versus intensified OEPA-DECOPDAC-21 (DECOPDAC-21: COPDAC with additional doxorubicin and etoposide and 25% more cyclophosphamide) in a randomized setting. Participants were recruited between January 2017 and September 2021. Female patients aged ≤18 years, treated according to the EuroNet-PHL-C2 protocol for cHL were recruited across 18 sites in the Netherlands, Belgium, Germany, Austria, and Czech Republic. All parents and patients (aged ≥12 years old) provided written informed consent. Serum AMH levels and menstrual cycle characteristics were evaluated over time (at diagnosis, one to three times during treatment and 2 up to 5 years post-diagnosis) and compared between treatment-levels (TL1, TL2, and TL3) and treatment-arms (OEPA-COPDAC-28 and OEPA-DECOPDAC-21). Serum samples obtained from patients after receiving pelvic radiotherapy were excluded from the main analyses. A total of 104 females, with median age at diagnosis of 15.6 years (IQR 13.7; 17.0), were included in the analysis. Ninety-nine were (post)pubertal. Eighteen girls were diagnosed with an early stage of cHL (TL1) and 86 with intermediate or advanced stage disease (50 TL2 and 36 TL3, 66% received COPDAC-28 and 34% DECOPDAC-21). Five patients received pelvic radiotherapy. Median AMH level at diagnosis was 1.7 µg/l (IQR 0.9; 2.7). After two courses of OEPA chemotherapy, AMH levels decreased substantially in all patients (98% <0.5 µg/l), followed by a significant increase during the consolidation treatment and follow-up. After 2 years, 68% of patients reached their baseline AMH value, with overall median recovery of 129% (IQR 75.0; 208.9) compared to baseline measurement. Five patients (7%) had AMH <0.5 µg/l. In patients treated for advanced stage disease, AMH levels remained significantly lower compared to early- or intermediate stage disease, with median serum AMH of 1.3 µg/l (IQR 0.8; 2.1) after 2 years. Patients who received DECOPDAC-21 consolidation had lower AMH levels during treatment than patients receiving COPDAC-28, but the difference was no longer statistically significant at 2 years post-diagnosis. Of the 35 postmenarchal girls who did not receive hormonal co-treatment, 19 (54%) experienced treatment-induced amenorrhea, two girls had persisting amenorrhea after 2 years. The studied population comprises young girls with diagnosis of cHL often concurring with pubertal transition, during which AMH levels naturally rise. There was no control population, while the interpretation of AMH as a biomarker during childhood is complex. The state of cHL disease may affect AMH levels at diagnosis, potentially complicating assessment of AMH recovery as a comparison with baseline AMH. The current analysis included data up to 2-5 years post-diagnosis. The current PANCARE guideline advises to use the cyclophosphamide-equivalent dose score (CED-score, as an estimation of cumulative alkylating agent exposure) with a cut-off of 6000 mg/m2 to identify females aged <25 years at high risk of infertility. All treatment-arms of the EuroNet-PHL-C2 protocol remain below this cut-off, and based on this guideline, girls treated for cHL should therefore be considered low-risk of infertility. However, although we observed an increase in AMH after chemotherapy, it should be noted that not all girls recovered to pre-treatment AMH levels, particularly those treated for advanced stages of cHL. It remains unclear how our measurements relate to age-specific expected AMH levels and patterns. Additional (long-term) data are needed to explore clinical reproductive outcomes of survivors treated according to the EuroNet-PHL-C2 protocol. The fertility add-on study was funded by the Dutch charity foundation KiKa (project 257) that funds research on all forms of childhood cancer. C.M-K., D.K., W.H.W., D.H., M.C., A.U., and A.B. were involved in the development of the EuroNet-PHL-C2 regimen. The other authors indicated no potential conflicts of interest. N/A.

Resumption of ovulation in anovulatory women with PCOS and obesity is associated with reduction of 11β-hydroxyandrostenedione concentrations.

Is resumption of ovulation after a 6-month lifestyle intervention in women with PCOS and obesity associated with differential changes in endocrine and metabolic parameters (weight, insulin resistance, anti-Müllerian hormone (AMH), and androgens) compared to women with PCOS who remained anovulatory? Resumption of ovulation after a 6-month lifestyle intervention in women with PCOS and obesity is associated with changes in serum 11β-hydroxyandrostenedione (11OHA4) concentrations. Lifestyle interventions have been shown to reduce clinical and biochemical hyperandrogenism in women with PCOS. Weight loss of 5-10% may reverse anovulatory status, thereby increasing natural conception rates. However, the mechanisms underlying why some women with PCOS remain anovulatory and others resume ovulation after weight loss are unclear. Reproductive characteristics at baseline and a greater degree of change in endocrine and metabolic features with lifestyle intervention may be crucial for ovulatory response. We used data and samples originating from an earlier randomized controlled trial (RCT), which examined the efficacy of a 6-month lifestyle intervention prior to infertility treatment compared to prompt infertility treatment on live birth rate in women with obesity. A total of 577 women with obesity (BMI > 29 kg/m2) were randomized between 2009 and 2012. Anovulatory women with PCOS who were allocated to the intervention arm of the original RCT (n = 95) were included in the current analysis. We defined women as having resumed ovulation (RO+) based on the following criteria: spontaneous pregnancy; or assignment to expectant management; or IUI in natural cycles as the treatment strategy after lifestyle intervention. Steroid hormones were measured using liquid chromatography tandem mass spectrometry. Generalized estimating equations with adjustment for baseline measures and interaction between group and time was used to examine differences in changes of endocrine and metabolic parameters between RO+ (n = 34) and persistently anovulatory women (RO-, n = 61) at 3 and 6 months after intervention. At baseline, the mean ± SD age was 27.5 ± 3.6 years in the RO+ group and 27.9 ± 4.1 years in the RO- group (P = 0.65), and the mean ± SD weights were 101.2 ± 9.5 kg and 105.0 ± 14.6 kg, respectively (P = 0.13). Baseline AMH concentrations showed significant differences between RO+ and RO- women (median and interquartile range [IQR] 4.7 [3.2; 8.3] versus 7.2 [5.3; 10.8] ng/ml, respectively). Baseline androgen concentrations did not differ between the two groups. During and after lifestyle intervention, both groups showed weight loss; changes in 11OHA4 were significantly different between the RO+ and RO groups (P-value for interaction = 0.03). There was a similar trend for SHBG (interaction P-value = 0.07), and DHEA-S (interaction P-value = 0.06), with the most pronounced differences observed in the first 3 months. Other parameters, such as AMH and FAI, decreased over time but with no difference between the groups. No high-resolution transvaginal ultrasonography was used to confirm ovulatory status at the end of the lifestyle program. The small sample size may limit the robustness of the results. Reduction of androgen concentrations during and after lifestyle intervention is associated with recovery of ovulatory cycles. If our results are confirmed in other studies, androgen concentrations could be monitored during lifestyle intervention to provide individualized recommendations on the timing of resumption of ovulation in anovulatory women with PCOS and obesity. The study was supported by a grant from ZonMw, the Dutch Organization for Health Research and Development (50-50110-96-518). The Department of Obstetrics and Gynecology of the UMCG received an unrestricted educational grant from Ferring Pharmaceuticals BV, The Netherlands. A.H. reports consultancy for the development and implementation of a lifestyle App MyFertiCoach developed by Ferring Pharmaceutical Company. All other authors have no conflicts to declare. The LIFEstyle RCT was registered at the Dutch trial registry (NTR 1530).

Pharmacological Protection of Ovaries During Program Drug Chemotherapy in Classical Hodgkin Lymphoma and Non-Hodgkin Lymphoma Patients

Aim. To assess the efficacy of ovarian protection and options for fertility preservation with the use of gonadotropin-releasing hormone agonists (a-GnRH) in patients with classical Hodgkin lymphoma (cHL) and non-Hodgkin lymphomas (NHLs) during program drug chemotherapy.&#x0D; Materials &amp; Methods. The study enrolled 247 female patients (187 with cHL and 60 with NHLs) undergoing program drug chemotherapy from 2019 to 2023. The patients were aged 13–42 years (median 24 years). Prior to chemotherapy and after it was completed, the serum anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), and estradiol levels were measured. Besides, antral follicle count was estimated by pelvic ultrasound. To provide ovarian protection during chemotherapy, a-GnRH was administered to 67 (27 %) out of 247 patients. Ovarian reserve was assessed based on ultrasound and AMH, FSH, and estradiol levels in 2–3 months after completing the program of drug chemotherapy or after spontaneous menstrual recovery.&#x0D; Results. Menstrual cycle recovered in 194 (78.5 %) out of 247 patients, regardless of lymphoid malignancy variant. Among them, there were 79.7 % (n = 149) of cHL patients and 75 % (n = 45) of NHL patients. Accordingly, ovarian function was lost in 20.3 % (n = 38) of cHL patients and 25 % (n = 15) of NHL patients. Predictors of ovarian function recovery appeared to be age ≤ 28 years and AMH level &gt; 2.45 ng/mL. Pharmacological protection of ovaries did not impact the probability of menstrual cycle recovery. Regardless of immunomorphological variant of lymphoid malignancy, a regular menstrual cycle was completely restored in 48 (71.6 %) out of 67 a-GnRH recipients and in 146 (81.1 %) out of 180 patients without a-GnRH treatment.&#x0D; Conclusion. Most of cHL and NHL patients of early reproductive age (≤ 30 years) have a fair chance of menstrual cycle recovery after completing the program drug chemotherapy similar to BEACOPP, EACODD(PP)-14, R-CHOP, R-Da-EPOCH and other regimens. Ovarian reserve cannot be preserved by means of a-GnRH administration during chemotherapy. High baseline FSH and low baseline AMH levels indirectly indicate evidence of impaired ovarian reserve. Patients belonging to this category are those who, if intensive combined cytostatic therapy regimens are planned, should undergo prior oocyte/embryo retrieval with subsequent cryopreservation due to the risk of premature loss of ovarian function.

Antimüllerian hormone level predicts ovulation in women with polycystic ovary syndrome treated with clomiphene and metformin

ObjectiveTo describe serum anti-Müllerian hormone (AMH) concentrations in a large, well-phenotyped cohort of women with polycystic ovary syndrome (PCOS) and evaluate whether AMH predicts successful ovulation induction (OI) in women treated with clomiphene and metformin. DesignSecondary analysis of randomized controlled trial Subjects333 women with anovulatory infertility attributed to PCOS who participated in thedouble blind randomized trial entitled The Pregnancy in Polycystic Ovary Syndrome I (PPCOSI) study (registration number NCT00068861) who had serum samples from baselinelaboratory testing available for further serum analysis were studied. Main Outcome MeasuresThe association between baseline AMH concentration in each of the three treatment groups and ovulation rates, pregnancy rates and live birth rates were assessed. Results322 individuals had a baseline AMH concentration available, of which the mean AMH was 11.7 ± 8.3 ng/mL with a range from 0.1 to 43.0 ng/mL. With each unit (1 ng/mL) increase in baseline AMH, the odds of ovulation decreased by 10 percent (OR 0.90, 95% CI 0.86-0.93); this effect did not differ by treatment group. Women with a high baseline AMH concentration (>8 ng/mL) were significantly less likely to ovulate compared to those with a normal baseline AMH concentration (<4 ng/mL) (OR 0.23, 95% CI 0.05-0.68). This remained statistically significant when controlling for confounders, including age, body mass index, time in study, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) score (p=0.008). Ovulation occurred even at very high AMH concentrations; there was no maximum level noted at which no ovulation events occurred. Baseline AMH concentration was not associated with pregnancy or live birth rates when controlling for confounders (p=0.947 and p=0.848, respectively). ConclusionThese AMH values of well-phenotyped individuals with PCOS adds to the literature and will aid in identifying AMH criteria for the diagnosis of PCOS. In women with infertility and PCOS, a higher AMH concentration was associated with reduced odds of ovulation with OI with clomiphene, clomiphene+metformin and metformin.

Elevated Anti-Müllerian Hormone as a Prognostic Factor for Poor Outcomes of In Vitro Fertilization in Women with Polycystic Ovary Syndrome.

Women with polycystic ovary syndrome (PCOS) tend to have elevated anti-Müllerian hormone (AMH) levels, which appear to correlate with disease severity and pregnancy outcomes. This was a retrospective observational study designed to assess the relationship between circulating AMH levels and in vitro fertilization (IVF) outcomes. The study involved 150 women with PCOS who underwent IVF treatments. The women's IVF cycles were allocated into three subgroups according to AMH levels: 'low' (AMH < 3.7 ng/mL; n = 49), 'middle' (AMH 3.7-7.4 ng/mL; n = 94), and 'high' (AMH > 7.4 ng/mL; n = 56). All pregnancy-related outcomes (positive beta human chorionic gonadotropin (βHCG), clinical pregnancy rate, live birth rate, and cumulative live birth rate) were greater in women's IVF cycles with 'low' AMH when compared to those with 'middle' or 'high' AMH (p < 0.05). AMH levels below 3.7 ng/mL were found to be associated with lower oocyte immaturity rate and better pregnancy outcomes, although baseline AMH was not shown to have any significant predictive power for live birth and cumulative live birth in the multivariable logistic regression analysis after adjusting for possible confounders nor in the ROC analyses. In summary, the current study lays the groundwork to validate high AMH levels as a poor prognostic factor for pregnancy outcomes after IVF in women with PCOS.

Impact of baseline luteinizing hormone (LH) level and anti-Müllerian hormone (AMH) on pregnancy outcomes in polycystic ovary syndrome (PCOS) patients undergoing IVF/ICSI cycle in antagonist protocol

Introduction: Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder often associated with infertility. There are several factors that could impair the pregnancy outcomes of PCOS patients. The latter endocrine profile along with high baseline luteinizing hormone (LH), high LH/follicle-stimulating hormone ratio, as well as high anti-Müllerian hormone (AMH) levels appear detrimental for patients undergoing In vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). The objective of this study is to evaluate the impact of baseline LH and AMH levels on pregnancy outcomes in PCOS patients performing IVF/ICSI cycles in an antagonist protocol. Materials and methods: The current investigation is a retrospective cohort study conducted at IVF Tiziri Center in Algiers on PCOS patients undergoing IVF/ICSI from January 2017 to March 2021. According to the Rotterdam criteria, patients aged between 23 and 42 years were divided into 2 groups: group 1 (G1) =91 patients; group 2 (G2) =100 all patients had an LH level &gt;10 IU/L. Both groups had AMH levels &gt;5 ng/mL. Controlled ovarian stimulation was done with a fixed antagonist protocol, as for the ovulation it was triggered with human chorionic gonadotropin or gonadotropin-releasing hormone agonist. Fresh and frozen embryo transfers were, thereafter, evaluated. Concerning the statistical analysis, it was done with SPSS software. Results: The mean LH level was 15.16±7.08 for G1 versus 5.7±1.86 for G2 (P=10−6), mean LH/follicle-stimulating hormone ratio 2.71±1.36 in G1 versus 1.05±0.44 (P=10−6) and mean AMH level was 9.27±3.90 for G1 versus 7.53±2.76 for G2 with (P&lt;10−3). The mean follicles over 11 mm in diameter, estradiol (E2) level, and progesterone level on the trigger day did not differ significantly between G1 and G2. Also, the mean of oocytes and metaphase II oocytes retrieved fertilization, and blastulation rate were similar for both groups. The pregnancy rate for G1 was 40.6% versus 54% (P&gt;0.05); the ongoing pregnancy rate (OPR) was 28.6% in G1 versus 47% in G2 (P=0.078); and the miscarriage rate was 32.4% for G1 versus 12.9 for G2 (P=0.072). A univariate analysis was performed with all confounder factors supposed to impact pregnancy outcomes: AMH level did not impact pregnancy outcomes, whereas LH level &lt;11 IU/L has been determined as a threshold impacting positively on OPR with odds ratio=2.01 (95% CI: 1.05–3.87). After a multivariate logistic regression including con-founders, 3 factors significantly influence OPR: LH, E2, and infertility with known etiology. Conclusion: The high baseline LH level impairs pregnancy outcomes in PCOs patients undergoing an antagonist protocol IVF/ICSI cycle. The identification of PCOS patients by their endocrine profile enables the establishment of a prognosis for council patients and a plan for an individualized therapeutic strategy.

Does the addition of metformin to carboplatin treatment decreases ovarian reserve damage associated with carboplatin usage?

BackgroundWe aimed to determine whether adding metformin to carboplatin treatment would reduce the damage to ovarian reserve associated with carboplatin use.MethodsWe included 35 adult female non-pregnant albino Wistar rats approximately three months old, weighing 220–310 g. The rats were divided into five groups of seven rats according to the treatment they received. Carboplatin and salin was given to Group 2, and carboplatin plus metformin was given to Group 3. Group 4 was administered only metformin. Group 5 was administered only salin. Carboplatin was given to Groups 2 and 3 as a single dose on the 15th day, while metformin was given to Groups 3 and 4 during the 28-day experiment. After oophorectomy, histopathologic analyses of primordial, primary, secondary, and tertiary Graff follicles according to the epithelial cells surrounding the oocyte and total follicular number were conducted per section. Serum Anti-Mullerian Hormone (AMH), tissue catalase, and malonyl dialdehyde levels were measured and compared within each group.ResultsThe baseline and 15th-day serum AMH values of the menstrual cycle were compared among the groups, and no statistically significant differences were observed (p > 0.05). Group 3, which was given both carboplatin and metformin, had statistically significantly higher 28th-day AMH levels than Group 2, which was given only carboplatin and saline (p < 0.001). The number of primordial follicles in Group 3 was found to be statistically significantly higher than in Group 2 (p < 0.001). Tissue catalase enzyme levels in Group 3 were statistically significantly higher than in Group 2 (p < 0.001). Tissue malondialdehyde levels in Group 2 were statistically significantly higher than tissue malondialdehyde levels in Groups 3 and 4 (p < 0.001).ConclusionsMetformin may attenuate carboplatin-induced ovarian damage, possibly through its antioxidative effects.

Assessment of the ovarian reserve in patients with beta-thalassemia major: a prospective longitudinal study

Repeated blood transfusions in women with beta-thalassemia major (BTM) may lead to iron overload and increase oxidative stress, consequently resulting in ovarian damage. The aim was to evaluate alterations in ovarian reserve in transfusion-dependent BTM patients over a time period of one year and to compare levels of anti-Mullerian hormone (AMH) in women with BTM and their healthy peers. This longitudinal prospective study was conducted in women with transfusion-dependent BTM at a tertiary level hospital. The hospital database was interogated for women diagnosed with BTM between 1996 and 2021. AMH levels were assessed at baseline and one year later. Forty-one women with BTM were identified, of whom 25 (60.9%) had amenorrhea and 16 (39.1%) had normal cycles. The mean AMH level of all women was 2.7±1.8 ng/mL at baseline, significantly lower than the age-matched nomogram value of 4.0±0.4 ng/mL for a healthy population (p=0.001). The baseline AMH level of patients with amenorrhea were significantly lower than patients with normal menstrual cycles (2.1±1.8 vs. 3.6±1.5 ng/mL, p=0.009). After one-year follow-up, there was a trend towards a decrease in the AMH levels of patients with normal menstrual cycles. Serum AMH values are decreased in patients with transfusion-dependent BTM. BTM patients should be educated about the possible effects of repeated blood transfusions on fertility.

Anti-Müllerian hormone predicts positive sperm retrieval in men with idiopathic non-obstructive azoospermia-findings from a multi-centric cross-sectional study.

Is it possible to identify a reliable marker of successful sperm retrieval (+SR) in men with idiopathic non-obstructive azoospermia (iNOA) undergoing microdissection testicular sperm extraction (mTESE)? A higher likelihood of +SR during mTESE is observed in men with iNOA and lower preoperative serum anti-Müllerian hormone (AMH) levels, with good predictive accuracy achieved using an AMH threshold of <4 ng/ml. AMH has been previously linked to +SR in men with iNOA undergoing mTESE prior to ART. A multi-centre cross-sectional study was carried out with a cohort of 117 men with iNOA undergoing mTESE at three tertiary-referral centres. Data from 117 consecutive white-European men with iNOA presenting for primary couple's infertility associated with a pure male factor at three centres were analysed. Descriptive statistics was applied to compare patients with negative (-SR) versus +SR at mTESE. Multivariate logistic regression models were fitted to predict +SR at mTESE, after adjusting for possible confounders. Diagnostic accuracy of the factors associated with +SR was assessed. Decision curve analyses were used to display the clinical benefit. Overall, 60 (51.3%) men had an -SR and 57 (48.7%) had a +SR at mTESE. Patients with +SR had lower levels of baseline AMH (P = 0.005) and higher levels of estradiol (E2) (P = 0.01). At multivariate logistic regression analysis, lower levels of AMH (odds ratio: 0.79; 95% CI: 0.64-0.93, P = 0.03) were associated with +SR at mTESE, after adjusting for possible confounders (e.g. age, mean testicular volume, FSH, and E2). A threshold of AMH <4 ng/ml achieved the highest accuracy for +SR at mTESE, with an AUC of 70.3% (95% CI: 59.8-80.7). Decision curve analysis displayed the net clinical benefit of using an AMH <4 ng/ml threshold. There is a need for external validation in even larger cohorts, across different centres and ethnicities. Systematic reviews and meta-analysis to provide high level of evidence are lacking in the context of AMH and SR rates in men with iNOA. Current findings suggest that slightly more than one in two men with iNOA had -SR at mTESE. Overall, men with iNOA with lower levels of AMH had a significantly higher percentage of successful SR at surgery. A threshold of <4 ng/ml for circulating AMH ensured satisfactory sensitivity, specificity, and positive predictive values in the context of +SR at mTESE. This work was supported by voluntary donations from the Urological Research Institute (URI). All authors declare no conflict of interest. N/A.

Magnetic resonance guided high intensity focused ultrasound for uterine fibroids and adenomyosis has no effect on ovarian reserve

Introduction Uterine fibroids are the most common benign tumors in healthy women. High Intensity Focused Ultrasound (HIFU) is a modern, noninvasive thermal ablation method for treating uterine fibroids. There is increasing evidence that ultrasound guided HIFU (US-HIFU) has no adverse impact on ovarian reserve but little data exists on magnetic resonance guided HIFU (MR-HIFU). There are different options to estimate ovarian reserve, perhaps the most reliable being the measurement of serum Anti-Müllerian hormone (AMH). Material and methods Seventy-four (74) premenopausal women with serum AMH 0.1 ug/L or over, aged 24–48 and with fibroids or adenomyosis treated with MR-HIFU were enrolled in our study. AMH levels were analyzed before and 3 months after the MR-HIFU treatment. Correlations between AMH level changes and position of fibroids, fibroid volume, non-perfused volume ratio, and treatment energies were studied. Results The median AMH level before the HIFU treatment was 1.20 (range: 0.1–7.75 ug/L) and after the treatment 1.23 (range: 0.1–8.51 ug/L). No significant change was detected (p = .90). The patients were divided in three subgroups depending on the baseline AMH levels. The changes were not significant in any of the subgroups. Neither did the location of the treated fibroid affect the change of AMH levels nor the total energy used during treatment. Conclusions MR-HIFU does not compromise the ovarian reserve. Neither the location of the treated fibroid nor the total energy used during MR-HIFU had any effect on the change of AMH levels.

O-014 An expected benefit analysis of using an interpretable machine learning model for gonadotropin starting dose selection during ovarian stimulation

Abstract Study question What is the expected benefit of using a machine learning model for predicting the optimal starting dose of gonadotropin during ovarian stimulation? Summary answer Patients who had an optimal starting gonadotropin dose had improved outcomes and used significantly less total FSH compared to propensity matched patients who did not. What is known already The relationship between the starting dose of follicle-stimulating hormones (FSH) and ovarian response is complex. In general, too little starting FSH may lead to inadequate follicle recruitment, while too much may lead to excessive response. In completed cycles, there exists conflicting evidence of whether higher doses are beneficial or detrimental to the number of oocytes retrieved. The field of assisted reproduction has begun to apply machine learning techniques to clinical decision support for ovarian stimulation, but no studies have specifically investigated optimizing starting FSH dose selection. Study design, size, duration We performed a retrospective analysis of patients undergoing autologous, non-cancelled IVF cycles from 2014 - 2020 (n = 18,591) at three different IVF clinics in the United States. The primary outcomes were the average number of MIIs, 2PNs, and usable blastocysts in relation to starting and total doses of FSH. Participants/materials, setting, methods A K-nearest neighbor similarity model was trained on all cycles and used to identify the 100 most similar patients to a patient-of-interest using age, BMI, baseline anti-mullerian hormone (AMH), and baseline antral follicle count (AFC). For each patient, a patient-specific dose response curve was created by fitting a constrained second order polynomial to the number of MII oocytes relative to the starting dose of FSH across all of the neighbors. Main results and the role of chance For each patient, their individual dose response curve was used to determine if there was an optimal dose that maximizes the prediction of MIIs (called dose-responsive patients), or if the dose response curve shows no optimal dose (called non-responsive patients). 30% of cycles were identified as dose-responsive, 64% were identified as non-responsive, and 6% were inconclusive and excluded from analysis. Dose-responsive patients who received an optimal starting dose had, on average, 1.5 more MIIs, 1.0 more 2PNs, and 0.5 more usable blastocysts using 10 IU’s less of starting FSH and 195 IU’s less of total FSH compared to propensity-matched patients with non-optimal doses. Non-responsive patients who received a low starting dose had, on average, 0.3 more MIIs, 0.4 more 2PNs, and 0.3 more usable blastocysts using 150 IU’s less of FSH and 1375 IU’s less of total FSH compared to propensity-matched patients with a high starting dose. Limitations, reasons for caution The primary limitation is the retrospective nature of this study. Further, our calculations of starting FSH combined the contribution of pure FSH plus the FSH component of FSH/LH medication, rather than evaluating each separately. We also did not differentiate between types of protocols, as the majority were antagonist cycles. Wider implications of the findings Our results suggest that a patient similarity model for selecting starting FSH can help increase MII outcomes while reducing the amount of FSH given to a patient. Future work will include continuing to increase the diversity of our dataset and performing validation studies to show improved outcomes with model use. Trial registration number Not applicable

Circulating anti-Müllerian hormone levels and markers of subclinical cardiovascular disease in middle-aged and older men

ContextRecent research suggests that higher circulating anti-Müllerian hormone (AMH) levels are associated with less frequent occurrence of (subclinical) cardiovascular disease (CVD) in women, but evidence in men is limited. ObjectiveWe investigated whether circulating AMH levels are associated with measures of subclinical CVD in middle-aged and older men. DesignProspective cohort study with a median follow-up time of 8.7 years. Serum AMH was measured at baseline. We assessed both cross-sectional and longitudinal associations using linear regression models adjusted for confounders. SettingDutch middle-aged and older men from the community. Participants394 men (aged 40–80 years) with an available AMH measurement at baseline. Main outcome measuresAt baseline (2001−2002): carotid intima-media thickness (CIMT), pulse wave velocity (PWV), abdominal aortic diameter, and Framingham risk score (FRS) predictions. At follow-up (2010−2011): CIMT, mean carotid aortic plaque score, PWV, and FRS predictions. All outcomes were transformed using rank-based inverse normal transformation to meet the normality assumption. ResultsHigher AMH levels were associated with lower CIMT at baseline (β = −0.04; 95%CI = 0.07, −0.01), but not with the other measures of subclinical CVD at baseline. Longitudinal analyses suggested that higher baseline AMH levels were associated with lower mean plaque scores at follow-up (β = −0.03, 95%CI = −0.07, 0.00), but not with the other follow-up outcomes. ConclusionsOur results suggest that AMH is associated with current CIMT and future carotid aortic plaque burden in men, implying that circulating AMH levels are potentially associated with local atherosclerosis rather than with total aortic stiffness.

Ovarian reserve in premenopausal women with breast cancer

BackgroundAs a special reproductive hormone and ovarian reserve indicator, the role of anti-Müllerian hormone (AMH) in premenopausal women with breast cancer deserves further study. MethodsWe conducted an in-depth analysis of the data from the EGOFACT study (NCT02518191), a phase Ⅲ, randomized, controlled trial involving premenopausal female breast cancer patients in two parallel groups: chemotherapy with or without gonadotropin-releasing hormone analogs (GnRHa). Three hundred thirty premenopausal women aged 25–49 years with operable stage I to III breast cancer were included in this study. The characteristics of ovarian reserve changes marked by AMH in the EGOFACT study and the factors affecting ovarian function in premenopausal women with breast cancer were analyzed. ResultsThe AMH level of the chemotherapy alone group decreased gradually within one year, while the AMH level of the GnRHa group was significantly higher as early as 6 months after chemotherapy and recovered to close to the baseline level 12 months after chemotherapy (F = 34.991, P < 0.001). Correlation analysis showed that the factors affecting AMH levels mainly included age, menarche age, body mass index (BMI), reproductive history, baseline follicle stimulating hormone (FSH) level, pathological stage and GnRHa application, but they had different effects on the incidence of premature ovarian insufficiency (POI) at different periods. Multivariate logistic regression analysis showed that menarche age younger than 14 years (OR 0.470 [0.259, 0.852], P = 0.013), baseline AMH level higher than 0.5 ng/mL (OR 9.590 [3.366, 27.320], P < 0.001), pathological stage Ⅰ(OR 0.315 [0.124, 0.798], P = 0.015) and GnRHa application (OR 0.090 [0.045, 0.183], P < 0.001) were independent factors conducive to protection of ovarian reserve, as well as to recovery of ovarian reserve. ConclusionsAge, menarche age, baseline AMH level, and GnRHa application are the most important influencing factors for ovarian reserve in premenopausal women with breast cancer. Trial registrationClinicalTrials.gov, NCT02518191, registered on Aug 5, 2015.

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.

The level of vitamin D in follicular fluid and ovarian reserve in an in vitro fertilization program: A pilot study.

The level of vitamin D in follicular fluid (FF) according to the ovarian reserve has never been investigated, and the effect of FF vitamin D on the outcome of assisted reproductive technology (ART) remains controversial. The aim of this study is to evaluate the association between FF vitamin D levels and baseline anti-Müllerian hormone (AMH) / ART outcomes. Forty-seven patients who underwent controlled ovarian stimulation at the fertility clinic of an academic tertiary care center were enrolled for a prospective observational study. FF was collected from the first aspirated leading follicle of each ovary and assayed by an enzyme-linked immunosorbent assay. Multivariable linear regression analysis was used to assess the association between baseline AMH and FF vitamin D levels with adjustment for basal FSH and serum vitamin D levels. Both the AMH and serum vitamin D were significant predictors for FF vitamin D. The estimated marginal mean of FF vitamin D level was higher in women with decreased ovarian reserve (DOR) than those with normal ovarian reserve (24.1 ± 2.1 vs. 18.8 ± 1.4 ng/ml, p = 0.048). However, FF vitamin D did not demonstrate any significant associations with cycle outcomes, including fertilization rate and the number and proportion of good embryos at day three. We observed significantly higher FF vitamin D levels in women with DOR. However, FF vitamin D did not demonstrate any significant associations with the outcome of ART. A larger prospective study is needed to investigate the effect of FF vitamin D on the clinical pregnancy rate and live birth rate.