Baseline anti-Mullerian Hormone Levels Research Articles

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.
 Materials & 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.
 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 > 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.
 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.

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.

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 < 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 < 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 < 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.

Abstract PD5-05: 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

Abstract Background: Knowledge regarding risk of treatment-induced premature ovarian insufficiency (POI) is crucial for appropriate oncofertility counseling. While the gonadotoxicity of anthracycline- and cyclophosphamide-based chemotherapy (CT) in young breast cancer (BC) patients (pts) is well established, the impact 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 measurements during systemic therapies may aid in diagnosis and prediction of POI. The NeoALTTO trial represented a unique setting to explore the acute gonadotoxicity of anti-HER2 therapy alone and in combination with weekly paclitaxel in pts not previously exposed to any other potentially gonadotoxic anticancer treatment. Methods: NeoALTTO (NCT00553358) is a multicenter, open-label, randomized phase III neoadjuvant trial in HER2-positive early BC pts randomized to receive lapatinib (L), trastuzumab (T), or their combination (L+T) alone for 6 weeks followed by the addition of paclitaxel for 12 weeks before surgery.The present analysis included only premenopausal women aged ≤45 years 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 surgery (i.e. after completion of paclitaxel plus anti-HER2 therapy). Central AMH testing was performed at Erasme Hospital (Brussels, Belgium) with the Roche Elecsys® AMH Plus assay (LoD=0.010 ng/ml). AMH levels during anti-HER2 therapy alone and then combined with paclitaxel were assessed as a measure of treatment impact on ovarian reserve. The impact of different anti-HER2 agents (T and/or L), pts’ age and baseline AMH levels on treatment gonadotoxicity were also investigated. Results: The present analysis included 130 pts with a median age of 38 years (IQR: 33-42 years), of whom 86 (66.2%) were ≤40 years. 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<0.001; median cumulative decrease: -12.5%, IQR -37.6% - 12.4%). At surgery, there was a large significant decline in AMH levels (median value: 0.01 ng/mL, IQR 0.01 - 0.03 ng/mL, p<0.001; median cumulative decrease: -99.9%, IQR -100.0% - -98.7%). Type of anti-HER2 treatment (L vs. L vs. T+L) did not impact the results: there was no significant difference between treatment arms in degree of reduction in AMH levels at week 2 (p=0.763) or at surgery (p=0.700). Age and pre-treatment ovarian reserve had a major impact on treatment-induced gonadotoxicity risk, with a more profound decrease in AMH levels observed for older pts (p<0.001) and those with lower baseline AMH levels (p<0.001). Among pts aged <35 years, there was no significant difference in AMH levels between those with (n=7) or without (n=35) a subsequent pregnancy at baseline (p=0.316), week 2 (p=0.463) or at surgery (p=0.610). Conclusions: This biomarker analysis of the NeoALTTO trial showed for the first time the potential acute gonadal damage induced by anti-HER2 therapies alone and with the addition of weekly paclitaxel. We observed a small but significant reduction in AMH levels during T and/or L alone and then a profound reduction to almost undetectable levels following the addition of weekly paclitaxel, without differences by specific anti-HER2 regimen. Age and pre-treatment AMH levels strongly impacted gonadotoxicity risk. While this analysis is limited by lack of AMH measurement in longer term follow-up, findings have important implications for future research and oncofertility counseling of premenopausal women with HER2-positive BC. Citation Format: Matteo Lambertini, Marcello Ceppi, Richard A. Anderson, David A. Cameron, Marco Bruzzone, Maria Alice Franzoi, Claudia Massarotti, Sarra El-Abed, Yingbo Wang, Christophe Lecocq, Paolo Nuciforo, Rebecca Rolyance, Lajos Pusztai, Joohyuk Sohn, Jacopo Ligato, Maria Maddalena Latocca, Luca Arecco, Barbara Pistilli, Kathryn J. Ruddy, Alberto Ballestrero, Lucia Del Mastro, Fedro A. Peccatori, Ann H. Partridge, Cristina Saura, Michael Untch, Martine Piccart, Serena Di Cosimo, Evandro de Azambuja, Isabelle Demeestere. 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 [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD5-05.

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

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

Effect of Laparoscopic Ovarian Cystectomy on Ovarian Reserve in Benign Ovarian Cysts.

Background:Laparoscopic cystectomy is one of the common modes of treatment for benign ovarian cysts. The data related to the effect of cystectomy on ovarian reserve are limited.Aim:The aim of this study was to investigate the effect of laparoscopic ovarian cystectomy on anti-Mullerian hormone (AMH) levels in benign ovarian cysts.Settings and Design:It was a prospective clinical study conducted in a tertiary care hospital from March 2017 to August 2018.Materials and Methods:Seventy-two benign ovarian cyst patients who were admitted for cystectomy were enrolled in the study. Serum AMH levels were estimated in all the patients at baseline, 1 week, and 3 months after cystectomy.Statistical Analysis:Paired t-test was used to assess the differences in AMH levels before and after laparoscopic cystectomy.Results:AMH was significantly reduced after 1 week (P < 0.05) and 3 months (P < 0.05) of cystectomy compared to preoperative levels in both endometriotic and nonendometriotic cysts. The percentage of reduction in the AMH values measured on the 7th postoperative day was found to be greater with endometriotic cysts (54%) followed by mucinous cystadenoma (32%). On day 90, greater recoveries of the AMH values to the baseline AMH levels were observed with cystic teratoma (83% of the baseline AMH levels).Conclusions:Laparoscopic ovarian cystectomy reduces AMH levels immediately after surgery, and improvement in AMH level was observed after 3 months.

Significant Post-Chemotherapy Decrease of Ovarian Reserve in Iranian Women With Breast Cancer

Fertility preservation counseling has a high priority in young breast cancer (BC) patients. Cytotoxic chemicals used for chemotherapy in these patients increased the risk of premature ovarian failure. This study evaluated the anti-mullerian hormone (AMH) level at the time of diagnosis and within a month after the end of chemotherapy, while predicting the time of the return of ovarian function in BC cases (n=46) younger than 46 years for the first time in Iran. Cases were selected from those attending the breast oncology clinic of the two hospitals with a newly diagnosed in situ or invasive BC. The present study results showed AMH levels were significantly decreased in almost all women within a month after chemotherapy. It seems that the need for fertility preservation depends on patient age and baseline AMH level, but counseling should be offered by the clinician in young breast cancer patients.

Effect of Hysterectomy on Ovarian Reserve in the Early Postoperative Period Based on the Type of Surgery.

ObjectivesThis study aimed to evaluate the influence of simple hysterectomy on the ovarian reserve based on the type of surgery.MethodsEighty-six premenopausal women between 31 and 48 years who underwent hysterectomy for benign gynecologic disease without additional adnexal surgery at a university hospital participated in this study. Seventy-one patients underwent laparoscopy-assisted vaginal hysterectomy (LAVH), and 15 patients underwent abdominal hysterectomy (AH). Blood samples were obtained from all study participants on preoperative day and 3 days after the operation to determine the anti-Müllerian hormone (AMH) levels.ResultsThe postoperative reduction of the mean serum AMH level in the LAVH group (0.42 ± 0.76 ng/mL) was greater than that in the AH group, although the difference was not statistically significant (0.01 ± 0.60 ng/mL) (P = 0.053). The mean baseline AMH level (2.59 ± 2.33 ng/mL) was significantly reduced to 2.24 ± 2.08 ng/mL at 3 days after hysterectomy, and the mean rate of decline of AMH levels after surgery was 13.61% ± 30.81%. In subgroup analysis based on the type of surgery, the mean serum AMH level decreased significantly after surgery in the LAVH group, but no significant changes were found in serum AMH levels before and after the surgery in the AH group.ConclusionsThese preliminary results suggest that simple hysterectomy affects the early postoperative decline of ovarian reserve, and these results might vary depending on the type of surgery.

Changes in serum markers of patients with PCOS during consecutive clomiphene stimulation cycles: a retrospective study

BackgroundA retrospective case-control study was performed to evaluate whether PCOS-specific serum markers would change in women with polycystic ovary syndrome (PCOS) during the course of two consecutive cycles of clomiphene citrate (CC)-stimulation, which did not lead to a pregnancy.MethodsAnovulatory PCOS patients who underwent two consecutive CC-cycles (n = 41) and anovulatory PCOS controls who chose an observational approach for two months (n = 24) were included in the study. The main outcome measures were levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), anti-Mullerian hormone (AMH), total testosterone, androstenedione, and sexual hormone binding globulin (SHBG).ResultsIn the control group, PCOS-specific serum parameters did not change during two months (p > 0.05). In the CC-group, there were decreases in LH (11.8 ± 4.9 mU/mL vs. 10.9 ± 4.0 mU/mL; p = 0.029), the LH:FSH ratio (2.1 ± 0.8 mU/mL vs. 1.8 ± 0.5 mU/mL; p = 0.007), and AMH (8.08 ± 4.27 ng/mL vs. 7.17 ± 3.37 ng/mL; p = 0.011), as well as an increase in SHBG (46.0 ± 20.2 nmol/L vs. 51.2 ± 21.0 nmol/L; p < 0.001). A higher age and lower baseline total testosterone and AMH levels were predictive of an AMH decline (p < 0.05).ConclusionTwo cycles of CC-stimulation that did not lead to a pregnancy were accompanied by mean LH, AMH, and LH:FSH ratio declines and an SHBG increase. The clinical significance seems of minor relevance.

Association of progesterone production with serum anti-Müllerian hormone levels in assisted reproductive technology cycles with corifollitropin alfa.

The use of corifollitropin alfa (CA) in assisted reproductive technology (ART) cycles is dependent on the antral follicle count and body weight of patients. The present study investigated the safety and efficacy of using 100μg of CA in predicted excessive responders based on serum anti-Mullerian hormone (AMH) level. The results of 381 ART cycles stimulated by CA versus daily recombinant follicle-stimulation hormone (rFSH) in patients with low (<1.0 ng/mL; n = 38 vs. n = 90), moderate (1.0–3.36 ng/mL; n = 38 vs. n = 95), and high (> 3.36 ng/mL; n = 48 vs. n = 72) serum AMH levels, were analyzed. Pregnancy and live birth rates did not significantly differ between CA and daily rFSH groups. In the patients with high AMH levels, serum progesterone (P4) levels on the day of human chorionic gonadotropin (hCG) injection were significantly lower in the CA group than in the rFSH group (0.93 ± 0.55 vs. 1.16 ± 0.64 ng/mL). Furthermore, serum P4 levels on the day of hCG injection were negatively correlated with baseline AMH levels in the CA group, but not in the rFSH group, in the patients with high AMH levels. In conclusion, the use of 100 μg of CA in patients with high AMH levels is safe and effective and is associated with a lower P4 level on the day of hCG injection compared with the use of daily rFSH.

Serum anti-mullerian hormone and all-cause mortality in men.

Several studies have examined an association of anti-mullerian hormone to various risk factors for mortality, however, to the best of our knowledge, no study has reported a direct relationship between anti-mullerian hormone and all-cause mortality. Therefore, we examined the relationship between baseline anti-mullerian hormone levels and subsequent all-cause mortality in men during median follow-up of 9.4 (range = 0-13) years. We used the continuous National Health and Nutrition Examination Surveys from 1999-2004 combined with National Death Index for vital status information through December 2011. Cox proportional hazard models were fit to estimate hazard ratios for all-cause mortality. Models were adjusted for age, ethnic background, body mass index, hypertension, diabetes, smoking status, c-reactive protein, total cholesterol, estimated glomerular filtration rate, serum estradiol, testosterone, sex hormone binding globulin, and androstenedione. Of the 989 men, 30 % were older than 65 years, 51 % were Caucasians, 33 % had hypertension, 27 % were active smokers, and 11 % had diabetes. Mean serum anti-mullerian hormone level of the population was 7.2 (6.3) ng/mL. During the 8943 person-years of follow-up, 164 (17 %) men died. In unadjusted analysis, each unit increase in serum anti-mullerian hormone level was associated with a 13 % lower risk of death (HR = 0.87; 95 %CI = 0.83-0.92). In multivariable models, the inverse association between serum anti-mullerian hormone levels and mortality remained significant (HR = 0.94; 95 %CI = 0.90-0.98) and was independent of confounding variables. Similarly, individuals in the highest quartile had significantly lower risk of death as compared to individuals in the lowest quartile (unadjusted HR = 0.13, 95 %CI = 0.07-0.25; adjusted HR = 0.36, 95 %CI = 0.16-0.81). We found an independent and inverse association between serum anti-mullerian hormone levels and all-cause mortality in men. The mechanism underlying this association is unknown. Further studies are needed to validate our findings in men and to examine this association in women.

The Possibly Reversible Isotretinoin Effect of Decreased Ovarian Reserve in Sprague-Dawley Albinos: Part I, Biochemical Analyses

Background: The study aims to determine the detrimental effects of 7.5 mg/kg/day isotretinoin treatment on the anti-Mullerian hormone (AMH) levels in an experimental study to see whether the effects on ovarian reserve are reversible. Methods: Blood was sampled in 16 Sprague-Dawley albinos before any treatment to see baseline AMH levels. Then, the rats were randomly divided into 2 groups. Control group received only 1.0 ml soybean oil per oral for 30 days, whereas the study group received 7.5 mg/kg/day isotretinoin suspended in soybean oil. AMH levels were measured at the 30th day - immediately after the last medication - and on 60th day - 1 month after the last medication. Results: The mean values of AMH levels were 8.16 ± 1.47, 6.95 ± 1.87, 6.27 ± 0.71 and 8.20 ± 1.48, 6.56 ± 1.45, 7.07 ± 0.96 ng/ml before, immediately after and 1 month after the last medication in the control and isotretinoin treatment group, respectively. The mean AMH levels significantly decreased (p = 0.02) immediately after isotretinoin administration. The mean AMH levels 1 month after the last dose of isotretinoin therapy were higher than the levels immediately after the medication; however, the difference was not statistically significant. Conclusion: This study indicates that exposure to isotretinoin is responsible for decreased AMH levels in experimental rat model and this effect seems to be reversible.

Fertility Preservation Decisions Among Newly Diagnosed Oncology Patients

To evaluate fertility preservation decisions and compare controlled ovarian stimulation (COS) and assisted reproductive technology (ART) outcomes between newly diagnosed cancer patients and age-matched healthy controls. Our retrospective study was conducted at Columbia University's Center for Women's Reproductive Care between 2005 and 2012. Forty-nine women elected to undergo ART with COS for either oocyte or embryo cryopreservation before commencement of cancer therapy. Demographic and descriptive characteristics were collected from the cohort of patients. Treatment outcomes were compared with randomly selected, healthy, age-matched controls undergoing ART with COS during the same time period. Single women began fertility preservation cycles in half the time of married women (10.4 vs. 22.9 d). All 21 married women chose embryo cryopreservation, whereas 17 of the 28 (61%) single women chose embryo over oocyte cryopreservation. Baseline anti-Mullerian hormone levels and body mass indices were similar among fertility preservation patients and controls. Despite elevated baseline estradiol (E2) levels and luteal phase cycle starts in some cycles to avoid delay of cancer treatment, no significant differences were noted when comparing days of stimulation, total gonadotropins prescribed, numbers of oocytes and mature oocytes retrieved, fertilization rate, or cancellation rate to controls. Our experience shows that, with appropriate counseling and multidisciplinary care, newly diagnosed cancer patients desiring fertility preservation experience similar outcomes as age-matched healthy controls. These women can pursue oocyte or embryo cryopreservation with likely minimal disruption to the flow of their oncologic care.

Lack of Serum anti-Mullerian hormone responses after recombinant human chorionic gonadotropin stimulation in women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is an anovulatory disorder characterized by excess androgen production and increased LH secretion. Serum anti-Mullerian hormone (AMH) is also elevated in this disorder. Women with PCOS exhibit a positive correlation between AMH and LH levels and recent in vitro data demonstrate that LH can directly stimulate AMH production by granulosa cells from women with PCOS. The objective of the study was to directly test whether LH increases AMH production in women with PCOS in vivo by assessing responses after recombinant human chorionic gonadotropin (r-hCG) stimulation. This was a prospective study. The study was conducted at a research center at an academic medical center. Women with PCOS (n = 28) and normal controls (n = 29) participated in the study. Blood samples were obtained before and 24 hours after iv administration of 25 μg r-hCG. Basal and stimulated serum AMH, androstenedione, T, and 17-hydroxyprogesterone levels were measured. Baseline AMH levels in women with PCOS were greater than in normal controls and correlated with levels of LH as well as androstenedione, T, and 17-hydroxyprogesterone. A rise of serum AMH levels was not observed after r-hCG administration in women with PCOS or normal ovaries. These findings are in contrast to in vitro evidence demonstrating that AMH secretion by granulosa cells of PCOS women in response to LH stimulation and suggest AMH regulation in vivo is complex and that the elevated serum AMH in women with PCOS is not a direct effect of the excess LH production characteristic of PCOS.

Role of baseline antral follicle count and anti-Mullerian hormone in the index stimulation cycle of IVF treatment in predicting outcome of subsequent frozen-thawed embryo transfers

This retrospective cohort study aims at determining whether baseline antral follicle count (AFC) and serum anti-Mullerian hormone (AMH) level in the index stimulation cycle predict live-birth outcome in subsequent frozen-thawed embryo transfer (FET) cycles. We studied 500 women undergoing the first IVF cycle who had embryo(s) cryopreserved. The main outcome measures were live-birth in the first FET cycle and cumulative live-birth in all the FETs combined after the same stimulation cycle. Our results showed that baseline AFC and AMH level on the day before ovarian stimulation showed significant correlation. In the first FET cycle, AFC and AMH level were significantly higher in subjects attaining live-birth in the first FET cycle or cumulative live-birth from all FETs than those who did not. Both AMH and AFC were insignificant predictors of live-birth in the first FET cycle or cumulative live-birth after adjusting for age. The areas under the ROC curves for AMH, AFC and age were 0.654, 0.625 and 0.628, respectively, for predicting cumulative live-birth. In conclusion, we reported for the first time that baseline AFC and AMH in the index stimulation cycle have only modest predictive performance on cumulative live-birth in subsequent FET cycles.

Role of Baseline Antral Follicle Count and Anti-Mullerian Hormone in Prediction of Cumulative Live Birth in the First In Vitro Fertilisation Cycle: A Retrospective Cohort Analysis

ObjectiveThis retrospective study determined for the first time the role of baseline antral follicle count (AFC) and serum anti-Mullerian hormone (AMH) level in the first in-vitro fertilisation (IVF) cycle in predicting cumulative live birth from one stimulation cycle.MethodsWe studied 1,156 women (median age 35 years) undergoing the first IVF cycle. Baseline AFC and AMH level on the day before ovarian stimulation were analysed. The main outcome measure was cumulative live birth in the fresh plus all the frozen embryo transfers after the same stimulation cycle.ResultsSerum AMH was significantly correlated with AFC. Both AMH and AFC showed significant correlation with age and ovarian response in the stimulated cycle and total number of transferrable embryos. Baseline AFC and serum AMH were significantly higher in subjects attaining a live birth than those who did not in the fresh stimulated cycle, as well as those attaining cumulative live birth. There was a significant trend of higher cumulative live birth rate in women with higher AMH or AFC. However, logistic regression revealed that both AMH and AFC were not significant predictors of cumulative live birth after adjusting for age and number of embryos available for transfer. Considering only one single predictor, the areas under the ROC curves for AMH (0.646, 95% CI 0.616–0.675) and age (0.648, 95% CI 0.618–0.677) were slightly higher than that for AFC (0.617, 95% CI 0.587–0.647) in predicting cumulative live birth. However, a model combining AMH (with or without AFC) and age of the women only classified an addition of less than 2% of subjects correctly compared to the model with age alone.ConclusionBaseline AFC and serum AMH have only modest predictive performance on the occurrence of cumulative live birth, and may not give additional value on top of the women's age.

Follicular fluid antimullerian hormone (AMH) does not predict IVF outcomes in polycystic ovary syndrome patients

Abstract Introduction AMH, is a member of the transforming growth factor (TGF-β) produced by granulosa cells with the highest expression being in small antral follicles. Our objective is to evaluate the predictive value of follicular AMH levels as an indicator of IVF outcomes in PCOS patients. Material and methods A total of 63 patients undergoing the IVF trail were recruited for this prospective case-control study. The patients were classified into three groups: Group I: 43 patients with Polycystic ovary syndrome (PCOS). Group II: 20 normo-ovulatory patients were recruited for the IVF trail because of the male infertility factor (control group). Group III: consists of 33 patients from group I recruited to determine the effect of controlled ovarian hyperstimulation (COH) on serum AMH levels. Serum AMH levels were performed on day 3 of the menstrual cycle whereas the follicular fluid AMH level has been evaluated at the time of oocyte retrieval by enzyme linked immune-sorbent assay (AMH Gen II ELISA kit, Beckman Coulter, Inc. USA). AMH concentrations were adjusted to its protein content, to avoid possible bias due to FF volume variability. The relationship between follicular fluid AMH (FF AMH) levels and the number of oocytes retrieved, number of mature oocytes, number of embryos, fertilization and clinical pregnancy rate were assessed. The demographic data were similar between two groups as regards age and BMI. Results Both serum AMH levels and FF AMH levels were significantly higher in PCOS patients than in the controls, the values for serum levels were (5.07 ± 3.39 ng/ml, 3.07 ± 2.09 ng/ml) respectively and for follicular fluid levels were (67 ± 50.7 ng/g∗, 38.5 ± 44.4 ng/g) respectively. Serum AMH levels showed a positive correlation with oocytes retrieved and mature oocyte number, but there was no significant correlation with good quality embryo number, fertilization rate or clinical pregnancy rate in PCOS patients. On the other hand FF AMH levels do not show correlation with any of the IVF outcomes mentioned above in PCOS patients. Interestingly, the interval change in serum AMH levels between baseline AMH levels and levels after COH had a significant predictive value of pregnancy. Conclusions Serum AMH levels can predict the number of the retrieved oocytes and mature oocytes, whereas FF AMH may not be a valuable predictor for IVF outcomes in PCOS patients.

Anti-Mullerian Hormone as a Predictor of Time to Menopause in Late Reproductive Age Women

Anti-mullerian hormone (AMH) has emerged as a marker of ovarian reserve and a possible surrogate measure of reproductive aging. The aim of the study was to evaluate the predictive value of AMH levels in determining the median time to menopause for late reproductive age women and the predictive ability of AMH compared to FSH and inhibin b. A 14-yr follow-up in the Penn Ovarian Aging Study, 1996-2010, was conducted for a randomly identified population-based cohort. A total of 401 late reproductive age women participated in the study. Observed time to menopause was measured. All participants were premenopausal, with a mean (SD) age of 41.47 (3.52) yr and a median AMH level of 0.68 ng/ml at baseline. AMH strongly predicted time to menopause; age further improved predictions. Among women with a baseline AMH level below 0.20 ng/ml, the median time to menopause was 5.99 yr [95% confidence interval (CI), 4.20-6.33] in the 45- to 48-yr age group and 9.94 yr (95% CI, 3.31-12.73) in the 35- to 39-yr age group. With higher baseline AMH levels above 1.50 ng/ml, the median time to menopause was 6.23 yr in the oldest age group and more than 13.01 yr in the youngest age group. Smoking significantly reduced the time to menopause (hazard ratio, 1.61; 95% CI, 1.19-2.19; P = 0.002). AMH was a stronger predictor of time to menopause than FSH or inhibin b. AMH is a strong predictor of median time to menopause in late reproductive age women. Age and smoking are significant and independent contributors to the predictions of AMH.

Endometrin vs. progesterone in oil for luteal phase support with in vitro fertilization

OBJECTIVE: To evaluate clinical pregnancy rates and implantation rates in IVF cycles with a vaginal progesterone insert (Endometrin) compared to progesterone in oil for luteal phase support.DESIGN: Retrospective case control study.MATERIALS AND METHODS: From May 2007 through February 2010, all fresh non-donor IVF cycles were reviewed for the use of Endometrin starting the day after oocyte retrieval. For each subject using Endometrin, two control subjects were found that were matched by age and baseline AMH (Anti Mullerian Hormone) levels. Twenty seven subjects were identified that had matched controls. T test, chi square, and poisson regression were used to compare baseline characteristics where appropriate. Clinical pregnancy rates were compared using logistic regression, while implantation rates were compared using linear regression. For both comparisons, regression analysis was performed while controlling for age, AMH level, number of embryos transferred, and stage of embryos at transfer (cleavage vs blastocyst).Tabled 1Endometrin vs. IM ProgesteroneEndometrin (n=27)IM Progesterone (n=54)p valueAge (mean ± SD)35.0 ± 4.134.9 ± 4.00.97AMH (mean ± SD)3.3 ± 3.93.3 ± 3.80.90# Embryos transferred (mean ± SD)2.4 ± 0.932.9 ± 0.890.2% Blastocysts51.948.10.75Clinical pregnancy rate66.7%63.0%0.45Implantation rate (mean ± SD)46.0% ± 43.2%34.8% ± 33.1%0.15 Open table in a new tab CONCLUSION: Endometrin appears to have similar efficacy for luteal phase support compared to IM progesterone. Endometrin is an effective mode of progesterone delivery with a more patient-friendly approach. OBJECTIVE: To evaluate clinical pregnancy rates and implantation rates in IVF cycles with a vaginal progesterone insert (Endometrin) compared to progesterone in oil for luteal phase support. DESIGN: Retrospective case control study. MATERIALS AND METHODS: From May 2007 through February 2010, all fresh non-donor IVF cycles were reviewed for the use of Endometrin starting the day after oocyte retrieval. For each subject using Endometrin, two control subjects were found that were matched by age and baseline AMH (Anti Mullerian Hormone) levels. Twenty seven subjects were identified that had matched controls. T test, chi square, and poisson regression were used to compare baseline characteristics where appropriate. Clinical pregnancy rates were compared using logistic regression, while implantation rates were compared using linear regression. For both comparisons, regression analysis was performed while controlling for age, AMH level, number of embryos transferred, and stage of embryos at transfer (cleavage vs blastocyst). CONCLUSION: Endometrin appears to have similar efficacy for luteal phase support compared to IM progesterone. Endometrin is an effective mode of progesterone delivery with a more patient-friendly approach.

Effect of cell cycle specificity of chemotherapeutic agents on the gonadal functions of a pediatric cancer population: role of anti-mullerian hormone (AMH)

OBJECTIVE: The objectives of the study are to 1) determine whether AMH levels could be used to quantify gonadal damage inflicted by gonadotoxic chemotherapy and 2) to examine the effect of cell cycle specificity of the chemotherapeutic agents on the gonadal reserve as evidenced by the post-treatment AMH assay.DESIGN: Cohort study.MATERIALS AND METHODS: Baseline blood samples were obtained from 34 cancer patients (group I: 27 males and 7 females) and 10 normal controls (group II: 7 males and 3 females). Group I was composed of patients treated with chemotherapy for hematological, musculoskeletal and soft tissue cancers in 18,6 and 10 patients, respectively. Patients were followed until the completion of chemotherapy (range1-3 years). A second blood sample was collected at the completion of chemotherapy. AMH assay was completed using a commercially available kit.RESULTS: Using Spearman correlation, baseline AMH levels were significantly correlated with age of the study population (R=0.41, P=0.007). Patients and controls were comparable regarding their age at the initiation of chemotherapy. Baseline AMH levels were comparable between patients and controls irrespective of gender, age, pubertal status and type of malignancy (Boys7.83±4.75ng/ml vs 17.24±7.77 ng/ml; P=0.056) and (Girls 1.53±1.39 ng/ml vs 1.86±0.55 ng/ml; P=0.12)}. Post-chemotherapy AMH levels were not significantly different from baseline in boys (9.86±7.30 ng/ml vs 7.83±4.75 ng/ml, P=0.28). On the other side, post-chemotherapy AMH levels were significantly lower from baseline in girls (0.81±1.11 ng/ml vs 1.53±1.39 ng/ml, P=0.02). In boys and girls there was no significant reduction of post-chemotherapy AMH levels in subjects who received cell cycle specific chemotherapy. Similarly, there was no significant reduction of post-chemotherapy AMH levels in male subjects who received cell cycle non specific chemotherapy, P=0.06. On the contrary, girls who received cell cycle non specific chemotherapy showed significantly lower AMH levels compared to baseline (0.22 0.35 ng/ml vs 1.28 ±1.43 ng/ml; P=0.01).CONCLUSIONS: AMH assay is a sensitive marker for ovarian functions before and after puberty in patients at risk of gonadal damage secondary to chemotherapy. Ovarian reserve appears to be more sensitive to the insult of cell cycle non specific chemotherapeutic agents than the testicular reserve. AMH assay could be added to the initial work up of all patients undergoing chemotherapy to assess the damage to their reproductive potential. OBJECTIVE: The objectives of the study are to 1) determine whether AMH levels could be used to quantify gonadal damage inflicted by gonadotoxic chemotherapy and 2) to examine the effect of cell cycle specificity of the chemotherapeutic agents on the gonadal reserve as evidenced by the post-treatment AMH assay. DESIGN: Cohort study. MATERIALS AND METHODS: Baseline blood samples were obtained from 34 cancer patients (group I: 27 males and 7 females) and 10 normal controls (group II: 7 males and 3 females). Group I was composed of patients treated with chemotherapy for hematological, musculoskeletal and soft tissue cancers in 18,6 and 10 patients, respectively. Patients were followed until the completion of chemotherapy (range1-3 years). A second blood sample was collected at the completion of chemotherapy. AMH assay was completed using a commercially available kit. RESULTS: Using Spearman correlation, baseline AMH levels were significantly correlated with age of the study population (R=0.41, P=0.007). Patients and controls were comparable regarding their age at the initiation of chemotherapy. Baseline AMH levels were comparable between patients and controls irrespective of gender, age, pubertal status and type of malignancy (Boys7.83±4.75ng/ml vs 17.24±7.77 ng/ml; P=0.056) and (Girls 1.53±1.39 ng/ml vs 1.86±0.55 ng/ml; P=0.12)}. Post-chemotherapy AMH levels were not significantly different from baseline in boys (9.86±7.30 ng/ml vs 7.83±4.75 ng/ml, P=0.28). On the other side, post-chemotherapy AMH levels were significantly lower from baseline in girls (0.81±1.11 ng/ml vs 1.53±1.39 ng/ml, P=0.02). In boys and girls there was no significant reduction of post-chemotherapy AMH levels in subjects who received cell cycle specific chemotherapy. Similarly, there was no significant reduction of post-chemotherapy AMH levels in male subjects who received cell cycle non specific chemotherapy, P=0.06. On the contrary, girls who received cell cycle non specific chemotherapy showed significantly lower AMH levels compared to baseline (0.22 0.35 ng/ml vs 1.28 ±1.43 ng/ml; P=0.01). CONCLUSIONS: AMH assay is a sensitive marker for ovarian functions before and after puberty in patients at risk of gonadal damage secondary to chemotherapy. Ovarian reserve appears to be more sensitive to the insult of cell cycle non specific chemotherapeutic agents than the testicular reserve. AMH assay could be added to the initial work up of all patients undergoing chemotherapy to assess the damage to their reproductive potential.