Lower anti-Müllerian Hormone Levels Research Articles

Low concentration of circulating antimüllerian hormone is not predictive of reduced fecundability in young healthy women: a prospective cohort study

To evaluate whether circulating levels of antimüllerian hormone (AMH) predict fecundability in young healthy women. Prospective cohort study. General community. A total of 186 couples who intended to discontinue contraception to become pregnant were followed until pregnancy or for six menstrual cycles. None. Fecundability was evaluated by the monthly probability of conceiving (i.e., fecundability ratio [FR]). In addition, circulating levels of LH, FSH, T, and sex hormone-binding globulin (SHBG) were evaluated in 158 of 186 women. Fifty-nine percent of couples conceived during the study period. Compared to the reference group of women with medium AMH (AMH quintiles 2-4), fecundability did not differ significantly in women with low AMH (AMH quintile 1) (FR 0.81; 95% confidence interval [CI] 0.44-1.40). In contrast, women with high AMH (AMH quintile 5) had reduced fecundability (FR 0.62; 95% CI 0.39-0.99) after adjustment for covariates (woman's age, body mass index [BMI], smoking, diseases affecting fecundability, and oligozoospermia). Irregular menstrual cycles were more prevalent in women with high AMH compared with women with low or medium AMH levels, and they had higher levels of LH (geometric mean: 8.4 vs. 5.3 IU/L) and LH:FSH ratio (2.4 vs. 1.8). After exclusion of women with irregular cycles, women with high AMH still had reduced fecundability (FR 0.48; 95% CI 0.27-0.85) and elevated LH:FSH ratio (2.4 vs. 1.7). Low AMH in healthy women in their mid-20s did not predict reduced fecundability. Even after exclusion of women with irregular cycles, the probability of conceiving was reduced in women with high AMH.

Among patients of similar ages, a low serum anti-mullerian hormone(AMH) does not predict a higher incidence of aneuploidy in embryos tested with comprehensive chromosomal screening (CCS)

Serum AMH levels have been studied as predictors of ovarian response to exogenous gonadotropins as well as pregnancy rates among patients undergoing IVF. The purpose of this study was to determine whether low serum AMH levels prognosticate the aneuploidy rate in embryos, further defining its role as a marker of oocyte quantity and/or quality.

Endocrine late sequelae in long-term survivors of childhood non-Hodgkin lymphoma

Aim of this study was to investigate the long-term endocrine effects of treatment of childhood non-Hodgkin lymphoma (NHL). A single-center cohort of 84 survivors (22 females) was included in this retrospective study. Median age was 21 years (9-40 years) and time after cessation of therapy 12 years (4-30 years). Height, weight, percentage fat, lean body mass (LBM), bone mineral content (BMC), bone mineral density of total body (BMD(TB)) and bone mineral density of lumbar spine (BMD(LS)) were measured. Thyroid-stimulating hormone (TSH), free thyroxin (fT4), insulin-like growth factor-1 (IGF-1), inhibin B and anti-müllerian hormone (AMH) levels were measured. Results were compared with Dutch controls. Height was lower in survivors [mean standard deviation score (SDS) -0.36, P = 0.002], but further analysis showed that shorter stature was already present at diagnosis (mean SDS -0.28, P = 0.023). Body mass index, percentage fat, BMC, BMD(TB) and BMD(LS) were not different from controls. LBM was lower in survivors (mean SDS -0.47, P = 0.008). TSH, fT4 and IGF-1 were normal in all survivors. Three of 20 adult females had low AMH levels and 23 of 42 adult males had low inhibin B levels. Twelve years after cessation of treatment, NHL survivors did not develop adiposity, osteoporosis or thyroid disease. Male survivors may be at risk for infertility.

Circulating antimüllerian hormone levels in boys decline during early puberty and correlate with inhibin B

To investigate peripheral levels of inhibin B and antimüllerian hormone (AMH) in boys during peripuberty and in patients with congenital hypogonadotropic hypogonadism (HH). Randomized, placebo-controlled trial (peripubertal boys); and cross-sectional clinical study (males with HH). University central hospital. Twenty-eight peripubertal boys with idiopathic short stature (ISS), 19 males with Kallmann syndrome. Letrozole (2.5 mg/day) or placebo in boys with ISS for 2 years. Longitudinal follow-up observation of serum AMH and its relationship with inhibin B during early puberty and the influence of high (letrozole-treated boys) and low (males with HH) gonadotropin exposure on circulating AMH. In boys with ISS receiving placebo, the decrease in AMH levels and the increase in inhibin B levels were correlated. The serum AMH level had already declined before a clinically significant increase in testis volume or serum testosterone occurred. Letrozole did not appear to modulate the decline in AMH. The AMH levels were lower in boys and young adults with Kallmann syndrome and prepubertal testes (mean: 20.9 ± 4.7 ng/mL, n = 6) as compared with prepubertal ISS boys (102.3 ± 11.9 ng/mL). The gonadotropin-mediated early pubertal increase in inhibin B is tightly coupled to decrease in AMH levels and may reflect androgen-mediated differentiation of Sertoli cells. Profound gonadotropin deficiency is associated with low AMH levels, suggesting impaired development of the Sertoli cell population.

Anti-Mullerian hormone as a predictor of follicular reserve in ovarian insufficiency: special emphasis on FSH-resistant ovaries

Anti-Müllerian hormone (AMH) is secreted by ovarian granulosa cells and its serum levels reflect ovarian follicle reserve. The main objective of this study was to test the use of AMH assay in identifying women with primary amenorrhea (PA) and existing follicles and to study follicle phase dependent AMH secretion. Serum levels of AMH were measured in subjects with FSH-resistant ovaries (FSHRO, n= 12), primary ovarian insufficiency (POI) with PA (n= 11) or secondary amenorrhea (SA n= 20) of unknown etiology, and controls (n= 23), and in Turner syndrome (TS) [45,X (n= 18), mosaicism (n= 7), structural X chromosome abnormalities (SCA, n= 10)], and healthy controls (n= 34). Serum levels of AMH in women with FSHRO were comparable with those in control women (2.76 ± 2.37 versus 3.77 ± 2.36 ng/ml) and significantly higher than in women with PA (0.05 ± 0.04 ng/ml; P < 0.001) or SA of unknown origin (0.12 ± 0.20 ng/ml; P < 0.001). TS girls/women with 45,X or SCA had low serum AMH levels (0.13 ± 0.09 and 0.27 ± 0.19 ng/ml) compared with their controls (3.34 ± 2.23 ng/ml) or subjects with mosaicism (2.33 ± 2.81 ng/ml). AMH expression was detected in granulosa cells of women with FSHRO but not in any of the 45,X fetal ovarian specimens. A serum AMH assay could be used to identify patients with decreasing ovarian reserves and POI. Moreover, our results support the notion that AMH is secreted mainly by small non-selected follicles, since follicular granulosa cells were AMH-positive and serum AMH levels were normal/low normal in women with FSHRO, who lack follicle development beyond the small antral stage.

The Anti Mullerian Hormone- A Novel Marker for Assessing the Ovarian Reserve in Women with Regular Menstrual Cycles

Ovarian Reserve (OR) is a term which describes the functional potential of the ovary, which constitutes the size of the ovarian follicle pool and reflects the number and quality of the oocytes which are within it. Assessment of the OR helps in reflecting the reproductive potential of women. Various markers are available for assessing the OR and the best marker is the Anti Mullerian Hormone (AMH) which reflects the ovarian follicular pool in the ovary. In this study, the serum level of AMH/MIS(Mullerian Inhibiting Substance)was estimated to assess the ovarian reserve in both fertile and infertile women. To assess the ovarian reserve in women of the fertile and subfertile groups with regular cycles, who were in the age range of 26 -33yrs, by estimating the level of AMH and those of other hormones like FSH and E2 and also to calculate the ovarian volume and the Antral follicular count by an ultrasonographic method. Thirty fertile and thirty sub fertile women whose ages ranged from 26-33yrs were included as group 1 and group 2 respectively. The hormones like AMH ,FSH and oestradiol were assayed. Measurement of the ovarian volume and the antral follicular count by doing a transvaginal ultrasonogram, was done in all the subjects who were involved in both the groups. The correlation test was studied between the variables and the test of significance of the variables between the 2 groups was also analyzed by the Statistical Package Of Social Sciences (SPSS). The Antral Follicular Count (AFC) and the ovarian volume were negatively correlated with the age. The ovarian volume was positively correlated with the AFC. The FSH negatively correlated with the AFC. The Anti Mullerian Hormone negatively correlated with the age, and it positively correlated with the AFC. The mean values of AFC, FSH, and AMH were also statistically significant between the two groups. AMH can be considered as a marker for assessing the ovarian reserve, as it is cycle independent as compared to the other hormones. The women in the subfertile group with low levels of AMH should be insisted to proceed for ART as early as possible.

Anti-Müllerian hormone in women with polycystic ovary syndrome

Objective The aim of this study is to investigate the relationship between anti-Mullerian hormone (AMH) and parameters related to polycystic ovary syndrome (PCOS). Methods We measured serum AMH levels in 100 women with PCOS by Rotterdam European Society for Human Reproduction and Embryology criteria. We conducted somatometry, blood test and transvaginal or transrectal ultrasound test. We compared and analyzed AMH and parameters in terms of insulin resistance according to PCOS related phenotypes. We divided phenotypes into four groups by polycystic ovarian morphology (PCOM) and hyperandrogenemia (total testosterone [TT], free testosterone [fT]). Results AMH levels ranged from 4.1 to 21.0 ng/mL and the mean level was 10.4 ± 4.1 ng/mL. Signifi cant differences in parameters of insulin resistance were not observed among low (4 to 8 ng/mL), moderate (8 to 12 ng/mL), and high (>12 ng/mL) levels of AMH. Significant differences in AMH were not observed among groups according to PCOS related phenotypes. Weight, body mass index, waist-hip ratio, TT, fT, sex hormone binding globulin, 2-hour insulin and homeostasis model assessment of insulin resistance index were different signifi cantly according to PCOS related phenotypes. TT, ovarian volume and follicle number were positively correlated with AMH.

P5-14-05: Anti-Müllerian Hormone (AMH) Levels in Premenopausal Breast Cancer Patients Treated with Adjuvant Chemotherapy – A Translational Research Project of the SUCCESS Study.

Abstract Background: Premenopausal women undergoing chemotherapy are at risk of premature ovarian failure and long term side-effects caused by premature menopause. However, knowledge about the rate of ovarian failure and potential markers to evaluate the ovarian reserve is limited, especially in the context of modern chemotherapy concepts. Therefore, Anti-Müllerian hormone (AMH) was measured at before, immediately after and 2 years after chemotherapy in premenopausal patients of the SUCCESS study. Materials and Methods: The German SUCCESS trial is a multicenter phase III study comparing FEC-Docetaxel vs. FEC-Docetaxel+Gemcitabine as adjuvant treatment in patients with node positive or high risk node negative primary breast cancer. Blood samples were taken prior to and 4 weeks after last cycle of adjuvant chemotherapy, as well as after 2 years of follow up. We retrospecitvely identified 170 patients stratified premenopausal and aged 40 years or younger at trial entry, who received 3cycles of FEC (500/100/500mg/m2) q3w followed by 3 cycles of docetaxel (100mg/m2) q3w as one of the most commonly used chemotherapy regimens in Europe. Serum AMH levels were evaluated in a central laboratory by a manual immunoassay AMH DSL ELISA (Diagnostic Systems Laboratories, Webster, USA). Results: Median age within this subgroup was 36 years (21-40 years). 48% of the patients had a tumor stage pT1 and 54% were node positive. 69% were hormone receptor positive and 29% Her2 positive. Median serum AMH level before adjuvant chemotherapy was 1.32 ng/ml (range &amp;lt;0.1−11.32). Immediately after chemotherapy AMH levels dropped in 96% of the patients below the threshold of detection (&amp;lt;0.1 ng/ml, range &amp;lt;0.1−3.9ng/ml). No association to classical prognostic markers, such as tumor stage, lymph node involvement, etc. was observed. After a follow up period of 2 years, serum was available from 95 patients. 76% of those patients showed no evidence of ovarian function indicated by AMH (&amp;lt;0.1 ng/ml, range &amp;lt;0.1−1.43ng/ml). AMH levels prior to and 2 years after chemotherapy were significantly correlated with older age, with a reduction of 0.14 ng/ml per life year (p=0.0025) and 0.01 ng/ml (p=0.017) respectively. 12 patients (7%) received optional gonadotropin-releasing hormone (GnRH) agonists during chemotherapy. These patients presented significantly higher AMH levels (+ 0.18 ng/ml; p=0.01) 2 years after cytotoxic treatment. Conclusion: In this retrospective analysis premenopausal patients showed a high rate of ***f ovarian insufficiency reflected by low serum AMH levels immediately after cytotoxic treatment and after 2 years of follow up. GnRH agonists given as ovarian protectants during chemotherapy may have an influence on serum AMH 2 years after chemotherapy. Further data from prospective trials with longer follow up are needed to evaluate the role of serum AMH as a predictor of ovarian failure in breast cancer patients exposed to chemotherapy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-14-05.

Ovarian reserve diminished by oral cyclophosphamide therapy for granulomatosis with polyangiitis (Wegener's)

Standard treatment for severe granulomatosis with polyangiitis (Wegener's) (GPA) is daily oral cyclophosphamide (CYC), a cytotoxic agent associated with ovarian failure. In this study, we assessed the rate of diminished ovarian reserve in women with GPA who received CYC versus methotrexate (MTX). Patients in the Wegener's Granulomatosis Etanercept Trial received either daily CYC or weekly MTX and were randomized to etanercept or placebo. For all women ages <50 years, plasma samples taken at baseline or early in the study were evaluated against samples taken later in the study to compare levels of anti-Müllerian hormone (AMH) and follicle-stimulating hormone (FSH), endocrine markers of remaining egg supply. Diminished ovarian reserve was defined as an AMH level of <1.0 ng/ml. Of 42 women in this analysis (mean age 35 years), 24 had CYC exposure prior to enrollment and 28 received the drug during the study. At study entry, women with prior CYC exposure had significantly lower AMH, higher FSH, and a higher rate of early menstruation cessation. For women with normal baseline ovarian function, 6 of 8 who received CYC during the trial developed diminished ovarian reserve, compared to 0 of 4 who did not receive CYC (P < 0.05). Changes in AMH correlated inversely with cumulative CYC dose (P < 0.01), with a 0.74 ng/ml decline in AMH level for each 10 gm of CYC. Daily oral CYC, even when administered for less than 6 months, causes diminished ovarian reserve, as indicated by low AMH levels. These data highlight the need for alternative treatments for GPA in women of childbearing age.

Endocrine Late Sequelae in Long-Term Survivors of Childhood Non-Hodgkin Lymphoma

Abstract 5215 Introduction.Currently, the 5-year survival for childhood NHL is ∼80%. Because of this high survival rate and since treatment is administered in a growing and developing individual, long-term side effects are an important issue. Studies on endocrine long-term effects in survivors of childhood non-Hodgkin lymphoma (NHL) are scarce and often limited by small sample sizes, or by the fact that data of NHL survivors have been combined with that of survivors of other malignancies. Aim of this study was to investigate the long-term endocrine effects of treatment for childhood NHL. Methods.A single centre cohort of 84 survivors (22 females) was included in this retrospective study. Median age was 21 yrs (9–40 yrs) and time after cessation of therapy 12 yrs (4–30 yrs). Height, weight, percentage fat, lean body mass (LBM), bone mineral content (BMC), bone mineral density of total body (BMDTB) and lumbar spine (BMDLS) were measured. Bone mineral apparent density of the lumbar spine (BMADLS) was calculated to correct for bone size. Thyroid stimulating hormone (TSH), free thyroxin (fT4), insulin-like growth factor-1 (IGF-1), Inhibin-B and anti-müllerian hormone (AMH) levels were measured. Results were compared with Dutch controls. Results.Height was lower in survivors at follow-up (mean SDS −0.36, P=0.002), but further analysis showed that shorter stature was already present at diagnosis (mean SDS −0.28, P=0.023). BMI, percentage fat, BMC, BMDTB, BMDLS and BMADLS were not different from controls. LBM was lower in survivors (mean SDS −0.47, P=0.008). TSH, fT4 and IGF-1 were normal in all survivors. Three out of 20 adult females had low AMH levels and 55% (23/42) of adult males had low Inhibin-B levels. Conclusion.Twelve years after cessation of therapy, survivors of NHL did not develope adiposity, osteopenia or osteoporosis or thyroid disease. Male NHL survivors seem to be at risk for infertility. Disclosures:No relevant conflicts of interest to declare.

Early menopause in mothers of children with Down syndrome?

To investigate whether having a Down syndrome pregnancy at a relatively young age is associated with lower ovarian reserve as reflected by lower antimüllerian hormone (AMH) levels and the occurrence of earlier menopause. Retrospective, case control study. Not applicable. Two hundred twenty mothers (118 trisomy cases, 102 controls). Questionnaire and serum AMH measurement. Serum AMH levels and menopause, defined as not having a menstrual cycle for at least 1 year. The participant response rate was 93%. After applying the exclusion criteria, 144 women were evaluable (73 trisomy cases, and 71 controls). The baseline characteristics of the women were not statistically significantly different. More women with a Down syndrome pregnancy had an AMH level below 0.5 μg/L, a difference that was statistically significant. Eleven women (15.1%) in the Down syndrome group had reached menopause compared with 9 (12.7%) of the controls. Women who have had a Down syndrome pregnancy at a younger age show signs of limited ovarian reserve, as evidenced by their frequently having lower AMH levels. The study has found no obvious signs of early menopause thus far. Whether their age at menopause is within the normal range remains to be determined.

Postnatal Developmental Changes in the Pituitary-Ovarian Axis in Preterm and Term Infant Girls

Postnatal pituitary-testicular activation in infant boys is well characterized. However, the ovarian response to pituitary activation in infancy is less well understood. The aim of the study was to compare postnatal developmental changes in the pituitary-ovarian axis in preterm and term infant girls. Sixty-three infant girls, divided into three groups according to gestational age (GA) [i.e. full term (FT; n = 29; GA, 37-42 wk), near term (NT; n = 17; GA, 34-37 wk), and preterm (PT; n = 17; GA, 24-34 wk)] were examined monthly from 1 wk (D7) to 6 months (M1-M6) of age and reexamined at the corrected age of 14 months (cM14). We performed a longitudinal follow-up of urinary FSH and serum anti-Müllerian hormone (AMH) levels and the number of follicles in transabdominal ovarian ultrasonography. The postnatal FSH surge was stronger and more prolonged in NT and PT girls than in FT girls (P ≤ 0.001). Increased folliculogenesis and a rise in AMH levels were observed in all three groups after the FSH surge. In NT and PT girls, follicular development was delayed in comparison with FT girls, and a decrease in high FSH levels around the 40th postmenstrual week was temporally associated with the appearance of antral follicles in ultrasonography and an increase in AMH levels. The postnatal FSH surge results in transient ovarian stimulation in term and preterm girls. A delay in ovarian folliculogenesis shown in ovarian ultrasonography and by low serum AMH levels may provide an explanation for the exaggerated FSH surge in NT and PT girls.

The role of anti-müllerian hormone in the classification of anovulation

The role of anti-müllerian hormone in the classification of anovulation

Age as determinant of in vitro fertilization (IVF) outcome with extremely low anti- müllerian hormone (AMH)

Though widely considered a contraindication to IVF, we reported robust pregnancy rates with AMH at < 0.1 (undetectable) to 0.4 ng/mL, though AMH = 1.05ng/mL separates lower and higher pregnancy chances (Fertil Steril 2010;94:2824-7). We here investigated if significance of AMH changes with age. Cohort study. We assessed 254 IVF cycle outcomes with AMH < 0.4 ng/mL in 128 women: Patient age 40.8 ± 4.1 (SD) years; follicle stimulating hormone (FSH) 15.7 ± 11.1 mIU/mL; AMH 0.2 ± 0.1 ng/mL. All women with diminished ovarian reserve are prior to IVF supplemented with dehydroepiandrosterone (DHEA, 25 mg p. o. TID) for at least 6 weeks. Ovarian stimulation involved microdose agonist, daily FSH (450-600 IU) and human menopausal gonadotropin (hMG, 150 IU). Ovulation was triggered with human chorionic gonadotropin (10,000 IU). Twenty clinical pregnancies were recorded (7.9% per cycle start [95% CI 4.9%-11.9%]; 15.6% cumulative [9.8%-23.1%]); resulting in 13 live births in 12 women (11 singletons and a pair of twins); eight miscarried. Eight deliveries occurred after first (6.3% per cycle start), 4 after subsequent IVF cycles (3.2%). 70 women ≤ 42 years presented with 16 clinical pregnancies that resulted in 10 deliveries (14.3%), while 58 patients above age 42 presented with four clinical pregnancies that resulted in two deliveries (3.4%), representing a significantly reduced pregnancy chance and delivery rate versus age ≤ 42 years (P=0.013; P=0.036). These data confirm our prior publications suggesting surprisingly robust pregnancy chances, even at undetectable to extremely low AMH levels. They, however, significantly decline above age 42. Since patients were supplemented with DHEA, here reported outcomes may not be universally applicable. Even extremely low AMH can, however, no longer be considered an absolute contraindication for IVF.

Live birth chances in women with extremely low-serum anti-Mullerian hormone levels

To determine whether women with extremely low-serum anti-Mullerian hormone (AMH) levels (<0.1-0.4 ng/ml) still demonstrate live birth potential with assisted reproduction and whether such potential is age dependent. Between January 2006 and October 2009, 128 consecutive infertility patients with AMH ≤0.4 ng/ml were retrospectively evaluated for pregnancy chances and live birth rates after IVF. Patients presented at a mean (±SD) age of 40.8 ± 4.1 years, with mean (±SD) baseline FSH of 15.7 ± 11.1 mIU/ml and mean (±SD) AMH of 0.2 ± 0.1 ng/ml. One hundred and twenty-eight women underwent a total of 254 IVF cycles. Twenty clinical pregnancies were recorded (7.9% per cycle start [95% confidence interval (CI): 4.9-11.9%]; 15.6% cumulative [CI: 9.8-23.1%]). These pregnancies resulted in 13 live births in 12 women (i.e. 11 singletons and a pair of twins) and 8 patients miscarried. Eight deliveries occurred after the first cycle (6.3% per cycle start) and four after subsequent IVF cycles (3.2%). When evaluated according to female age, 70 women ≤42 years presented with 16 clinical pregnancies that resulted in 10 deliveries (14.3%), while 58 patients >42 years presented with four clinical pregnancies that resulted in 2 deliveries (3.4%), representing a reduced pregnancy chance (P = 0.013) and delivery rate (P = 0.036) versus age ≤42 years. With extremely low-serum AMH levels, moderate, but reasonable pregnancy and live birth rates are still possible. Extremely low AMH levels do not seem to represent an appropriate marker for withholding fertility treatment.

Elevated anti‐Müllerian hormone (AMH) and inhibin B levels in prepubertal girls with type 1 diabetes mellitus

Elevated anti-Müllerian hormone (AMH) and adrenal androgen levels have been observed during childhood in girls at risk of developing polycystic ovarian syndrome (PCOS). The aim of this study was to evaluate ovarian function and adrenal steroid levels in prepubertal girls with type 1 diabetes mellitus (T1D). Cross-sectional study. PATIENTS/MEASUREMENTS: We evaluated hormonal and ultrasonographic characteristics in girls with T1D (N = 73) and compared them to characteristics found in a control group of healthy girls (N = 86). Data are reported as geometric means (95% CI). Prepubertal girls with T1D had higher levels of AMH (29·1 pmol/l (23·2-36·3) vs 20·9 pmol/l (16·6-26·1), P = 0·038), inhibin B (arithmetic mean: 16·7 pg/ml (11·6-21·7) vs 11·7 pg/ml (10·0-13·5), P = 0·044) and dehydroepiandrosterone sulphate (DHEAS) (0·3 nmol/l (0·2-0·6) vs 0·2 nmol/l (0·1-0·3)) than controls (P = 0·045). During puberty, decreasing AMH levels were observed in girls with T1D only (P < 0·0001). Girls with T1D in Tanner stages 4-5 had lower AMH levels than their paired healthy controls (10·1 pmol/l (7·4-13·9) vs 15·7 pmol/l (11·6-21·3), respectively, P = 0·047). Our observations indicate that prepubertal girls with T1D may exhibit similar endocrine findings to those of other girls at risk of developing PCOS. The elevated levels of AMH and inhibin B suggest that higher numbers of follicles are present in the ovary during childhood in these patients and that insulin treatment may act as a local growth factor. In addition, AMH levels differed in prepubertal and pubertal girls, suggesting that the effect of T1D on ovarian folliculogenesis changes once gonadotrophin levels rise during puberty.

Evaluation of Chemotherapy-Induced Ovarian Failure by Sequential Anti-Müllerian Hormone Dosage.

AbstractAbstract 3813 Background.Chemotherapy-induced ovarian failure is one of the most challenging side effects for female patients with lymphoma. For a given patient, it remains difficult to predict if ovarian failure will recover or lead to sterility. Anti-Müllerian Hormone (AMH) reflects primordial follicle depletion and may predict ovarian function recovery. In this study, we prospectively assessed AMH levels during and after treatment of young female patients with lymphoma. Methods.Patients diagnosed with any type of lymphoma and aged below 36 years were eligible. AMH level was measured before chemotherapy, 2 weeks after initiating chemotherapy, 2 weeks before last chemotherapy and every 3 months during 2 years. Median AMH levels at each time point were compared according to the type of chemotherapy regimen (ABVD versus alkylating containing regimen -excluding Dacarbazine-). Results.From April 2004 to May 2010, 100 patients from 7 centers were enrolled of whom 80 are currently evaluable. Diagnosis was Hodgkin lymphoma (n= 65) or non-Hodgkin lymphoma (n=15). Median age was 25 years old (range: 17–36). Forty-eight patients (60.8%) had extended disease and 32 (62%) had at least one risk factor according to validated prognostic score. Chemotherapy regimen consisted of: ABVD (n=51), BEACOPP (n=5), CHOP or CHOP-like (n=11), CHOP followed by BEAM high dose therapy and autologous stem cell transplantation (ASCT) (n=3), or various salvage (MINE or IGEV) followed by BEAM and ASCT (n=10). The median follow up after chemotherapy was 18 months (range 3 – 24 months). The median number of cycles of ABVD was 6 (range: 2–8) whereas for the other regimen, the median cumulative dose of alkylating agents was: cyclophosphamide, 4.5 g/m2; procarbazine, 5.6 g/m2; ifosfamide, 15 g/m2 and melphalan, 140 mg/m2. Baseline AMH was 15 pMol/L (range 4–73). As soon as 2 weeks after chemotherapy, all chemotherapy regimen induced a significant decrease of AMH levels: 5 pMol/L(range 3–45). AMH recovery was significantly different for patients treated with or without alkylating agents (p=0.01) at 6 months (3 v 13 pMol/L) and 12 months (3 v 19 pMol/L) after last chemotherapy. Moreover, at 2 years, patients treated with BEACOPP had persistently low AMH levels (≤3 pMol/L) whereas patients treated with CHOP or CHOP like regimen showed an increasing of AMH levels to 6 (3-34) pMol/L at 1 year after chemotherapy. Patients who underwent ASCT had lower AMH levels than patients treated by alkylating agents without ASCT, yet non significant at 1 year (p=0.09). Three pregnancies were reported 7, 16 and 24 months after last chemotherapy (two patients treated with ABVD and one with CHOP). Conclusion. Sequential AMH profiles during and after chemotherapy were divers. Different AMH profiles were observed for ABVD compared to alkylating-based regimen and also among alkylating-based regimen. AMH recovery started at 6 months after ABVD, at 1 year after CHOP regimen and later for other regimen. Longer clinical follow-up will confirm if no or delayed AMH recovery recovery always reflects severe ovarian failure and will help guiding our decisions of ovarian cryopreservation in the future according to the planned chemotherapy regimen. Disclosures:No relevant conflicts of interest to declare.

Association of insulin resistance with anti‐Mullerian hormone levels in women without polycystic ovary syndrome (PCOS)

To explore the relationship of insulin resistance (IR) and adipokines (leptin, adiponectin, RBP4) to anti-Mullerian hormone (AMH) levels in women without polycystic ovary syndrome (PCOS). We recruited 120 healthy, reproductive age women without PCOS. An overnight fasting blood draw, anthropometric measurements, analyses of serum levels of AMH, adipokines (leptin, adiponectin and RBP4) and total testosterone, a homeostasis model assessment for insulin resistance (HOMA-IR) and a transvaginal ultrasound scan were performed between the third and fifth day of their spontaneous menstrual cycles. Higher HOMA-IR levels were associated with lower levels of AMH. After adjustment for age, serum AMH levels negatively correlated with insulin, fasting glucose, HOMA-IR and RBP4. However, a positive correlation was identified between serum AMH and adiponectin. A final multiple stepwise linear regression demonstrated that HOMA-IR was independently associated with AMH. An independent relationship exists between HOMA-IR and AMH in women without PCOS, possibly due to the effect of abnormal insulin action on AMH secretion by granulosa cells.

Anti-Müllerian hormone and inhibin B variability during normal menstrual cycles

To describe anti-Müllerian hormone (AMH) variation across normal menstrual cycles. Cohort study. Academic environment. Twenty regularly menstruating women. Serum AMH and inhibin B assayed daily during one normal menstrual cycle. Intracycle variability of AMH and inhibin B. Data were classified into quartiles of AMH area-under-the-curve (AUCs). Mean AMH AUC was 15.7 ng/mL for quartile 1 versus 43.5, 80.9 and 144.9 ng/mL for quartiles 2, 3, and 4. Mean AMH levels (ng/mL) were 0.67, 1.71, 3.02, and 5.33, respectively. There was no variation in quartile 1 AMH rate of change from stochastic modeling, but in quartiles 2 to 4, there were increased rates of change in days 2 to 7. Women in quartile 1 had the lowest mean inhibin B (24.2 pg/mL vs. 44.3, 43.2, and 42.2 pg/mL), and had shorter menstrual cycles (24.6 days) than women in quartiles 3 and 4 (28.2 and 28.4 days). There were two menstrual cycle patterns of AMH. The "aging ovary" pattern included low AMH levels with little variation, lower inhibin B, and shorter cycle lengths. The "younger ovary" pattern included higher AMH levels with significant variation days 2 to 7, suggesting that for women with AMH>1 ng/mL, the interpretation of AMH levels is contingent upon the day of the menstrual cycle on which the specimen is obtained.

How predictive of basic pregnancy potential are extremly low levels of anti-müllerian hormone (AMH)?

OBJECTIVE: Anti-Müllerian hormone (AMH) is increasingly a tool of ovarian reserve assessment, exceeding follicle stimulating hormone (FSH) in specificity. It, however, loses predictive value at very low levels. Whether very low AMH levels can discriminate who may, or may not, conceive and should, or should not, be treated was investigated. DESIGN: Cohort study. MATERIALS AND METHODS: Of 249 consecutive women with initial AMH ≤ 1.2ng/ml and (diminished ovarian reserve, DOR) during 2007/8, 229 qualified for analysis. They were divided into AMH <0.1 ng/ml; 0.11-0.4 ng/ml; 0.41-0.8 ng/ml; 0.81-1.2 ng/ml and pregnancy rates were determined. Since most women received dehydroepiandrosterone (DHEA), data do not reflect unsupplemented patients. RESULTS: Mean age 37.0 ± 5.6 years; mean BMI 25.7 ±6.4. Confirming DOR, mean follicle stimulating hormone (FSH) was 12.5 mIU/mL (95% CI 11.0-14.1); mean AMH 0.3 ng/mL (95% CI 0.3-0.4). 181 (73.3%) of patients were Caucasian, 32 (13.0% African American and 34 (13.8%) Asian. Independent of time and length of treatment, 19 women (9.5%) had conceived by time of analysis. Pregnancies occurred at all AMH levels, but likelihood of pregnancy was below 5% at AMH ≤ 0.4 ng/ml, and increased significantly (p =0.01) between 0.41-0.80 ng/mL and again (p=0.001) at AMH 0.81-1.2 ng/mL. Women who conceived had significantly higher AMH levels than those who did not (p=0.001). CONCLUSIONS: AMH, indeed, loses predictive value at low levels. Pregnancies occur even in absence of detectable AMH. Chances are, however, low at AMH under 0.4 ng/ml. AMH, thus, does not allow discrimination between who should, or should not, be entered into fertility treatment. While encouraging treatment attempts at even very low AMH levels, these data should be considered with caution since they mostly involve DHEA supplemented women, and do not discriminate for length and/or form of treatment.