Serum anti-Müllerian hormone and estradiol levels as predictors of ovarian hyperstimulation syndrome in assisted reproduction technology cycles

BACKGROUND: Anti-Müllerian hormone (AMH) is reported to be a reliable marker of the ovarian response to controlled ovarian stimulation (COS). The objective of this study is to determine whether the serum AMH level can predict ovarian hyperstimulation syndrome (OHSS) prior to selection of COS protocols. METHODS: A cohort of 262 IVF cycles was investigated prospectively, in order to evaluate the predictive value for OHSS by means of certain risk factors, including age, body mass index (BMI), serum estradiol (E2) level, number of retrieved oocytes and basal serum AMH level. RESULTS: The basal serum AMH level predicted OHSS better than age and BMI with a sensitivity of 90.5% and specificity of 81.3%. Both the basal serum AMH level (odds ratio: 1.7856, P = 0.0003) and serum E2 level on the day of HCG administration (odds ratio: 1.0005, P = 0.0455) proved to be significant predictors of OHSS by logistic regression analysis. However, age (odds ratio: 0.9346, P = 0.049) was the only significant factor for prediction of clinical pregnancy. CONCLUSIONS: The basal serum AMH level could be utilized effectively to predict OHSS and thus to direct the selection of mild COS protocols.     

Anti-Müllerian hormone and anti-Müllerian hormone type II receptor polymorphisms are associated with follicular phase estradiol levels in normo-ovulatory women

BACKGROUND: In mice, anti-Müllerian hormone (AMH) inhibits primordial follicle recruitment and decreases FSH sensitivity. Little is known about the role of AMH in human ovarian physiology. We hypothesize that in women AMH has a similar role in ovarian function as in mice and investigated this using a genetic approach. METHODS: The association of the AMH Ile(49)Ser and the AMH type II receptor (AMHR2) -482 A > G polymorphisms with menstrual cycle characteristics was studied in a Dutch (n = 32) and a German (n = 21) cohort of normo-ovulatory women. RESULTS: Carriers of the AMH Ser(49) allele had higher serum estradiol (E(2)) levels on menstrual cycle day 3 when compared with non-carriers in the Dutch cohort (P = 0.012) and in the combined Dutch and German cohort (P = 0.03). Carriers of the AMHR2 -482G allele also had higher follicular phase E(2) levels when compared with non-carriers in the Dutch cohort (P = 0.028), the German cohort (P = 0.048) and hence also the combined cohort (P = 0.012). Women carrying both AMH Ser(49) and AMHR2 -482G alleles had highest E(2) levels (P = 0.001). For both polymorphisms no association with serum AMH or FSH levels was observed. CONCLUSIONS: Polymorphisms in the AMH and AMHR2 genes are associated with follicular phase E(2) levels, suggesting a role for AMH in the regulation of FSH sensitivity in the human ovary.     

Depletion of ovarian reserve in young women after treatment for cancer in childhood: detection by anti-Müllerian hormone, inhibin B and ovarian ultrasound

BACKGROUND: Treatment of cancer during childhood may result in loss of primordial follicles from the ovary. METHODS: Ten cancer survivors and 11 controls with regular menstrual cycles, in addition to 10 cancer survivors and 10 controls taking the combined oral contraceptive pill (COCP) were recruited. Subjects were investigated on days 3-5 of a menstrual cycle, or week 3 of COCP administration before and 24 h after administration of 225 IU FSH. RESULTS: Serum FSH levels were elevated in cancer survivors with regular menstrual cycles (7.5 +/- 1.4 versus 4.2 +/- 0.3 IU/l; P = 0.02), while anti-Müllerian hormone (AMH) levels were lower (13.0 +/- 3.0 versus 21.0 +/- 3.4 pmol/l; P < 0.05). Other hormone levels were unchanged. Ovarian volume was smaller in cancer survivors than controls (3.0 +/- 0.5 versus 5.0 +/- 0.8 ml; P < 0.05), but antral follicle count (AFC) was similar. During COCP administration, inhibin B remained undetectable in six cancer survivors after FSH administration, whereas all controls showed a rise in inhibin B levels. The AFC was lower in cancer survivors than in controls (4.2 +/- 0.8 versus 7.2 +/- 0.8; P = 0.02). Ovarian volume was low in both groups, but did not differ between them. CONCLUSIONS: The study results demonstrate both hormonal and biophysical evidence of partial loss of the ovarian reserve in young cancer survivors. This was detected both in women with normal menstrual cycles and during COCP administration.     

Serum anti-Müllerian hormone and inhibin B levels at ovulation triggering day can predict the number of immature oocytes retrieved in in vitro fertilization cycles

The aim of this study was to investigate whether serum levels of anti-Müllerian hormone (AMH) and inhibin B at ovulation triggering day correlate with the number of immature oocytes obtained from stimulated in vitro fertilization (IVF) cycles. Fifty-nine consecutive cycles of ovarian hyperstimulation and IVF were selected from 45 women who had tubal (n=18) or unexplained infertility (n=27) and obtained at least one oocyte. Serum levels of AMH and inhibin B at ovulation triggering day were measured by enzyme-linked immunosorbent assay (ELISA). Univariate analysis and multiple regressions revealed that serum AMH or inhibin B levels were significantly correlated with immature oocyte count and the correlation coefficients were higher compared to the mature oocyte count. Serum AMH and inhibin B levels on triggering day seems to be more closely related with the immature oocyte count and thus could be good predictors to determine the immature oocyte count in IVF cycle.     

Serum anti-Müllerian hormone (AMH) levels are differentially modulated by both serum gonadotropins and not only by serum follicle stimulating hormone (FSH) levels

It is generally accepted that serum AMH levels are thought to reflect the size of the ovarian follicle pool. Therefore, an inverse correlation between serum AMH and Follicle Stimulating Hormone (FSH) levels has been noted in older women with abnormal or exhausted follicular development, such as menopause, leading to the use of serum AMH as a marker of ovarian reserve. In clinical practice the use of serum AMH for the assessment of ovarian reserve has been expanding to women irrespective of age, such as women in early menopause or women undergoing ovarian stimulation for in vitro fertilization (IVF).To our knowledge, this opinion article aims to show that serum AMH levels are differentially modulated by both serum gonadotropins, depending on the degree of ovarian reserve. For instance, in conditions of increased LH and normal to low FSH such as young PCOS women with hyperandrogenemia, serum AMH levels are increased and tend to be associated to serum LH, while in conditions of increased FSH such as premature ovarian failure, serum AMH levels are decreased and tend to be associated to serum FSH.The evidence that supports the theory of a link between AMH and LH in PCOS comes from both in vitro and in vivo experiments. Serum AMH levels have been directly linked to serum LH levels in the most severe forms of PCOS. LH has also been shown in vitro to directly increase serum AMH levels in PCOS derived granulosa cells. Finally, hyperandrogenism, obesity, insulin resistance and OCs administration, indirectly affect serum AMH levels, by modulating serum LH.Concerning PCOS, the correlation between AMH and LH can be used in the future for the assessment of the severity of PCOS, of the amelioration of PCOS under OCs treatment, as well as of the efficacy of infertility treatment in clomiphene resistant PCOS women.Apart from PCOS, the clinical implications of this theoretical approach might become important in a variety of medical conditions. For instance, serum AMH levels might be used in the future as a marker of cysts formation in the ovaries as well as of ovarian endometriosis, or as a marker of ovarian response to treatment of ovarian cysts or ovarian endometriosis by oral contraceptives, etc. Additionally, in infertile women with hypothalamic amenorrhea, serum AMH levels might be used for the assessment of ovarian recovery under treatment.     

Anti-Müllerian hormone measurement on any day of the menstrual cycle strongly predicts ovarian response in assisted reproductive technology

BACKGROUND: Recently, a new marker, the anti-Müllerian hormone (AMH), has been evaluated as a marker of ovarian response. Serum AMH levels have been measured at frequent time-points during the menstrual cycle, suggesting the complete absence of fluctuation. The aim of this study was to evaluate whether serum AMH measurement on any day of the menstrual cycle could predict ovarian response in women undergoing assisted reproductive technology (ART). METHODS: This study included 48 women attending the IVF/ICSI programme. Blood withdrawal for AMH measurement was performed in all the patients independently of the day of the menstrual cycle. RESULTS: Women in the lowest AMH quartile (<0.4 ng/ml) were older and required a higher dose of recombinant FSH than women in the highest quartile (>7 ng/ml). All the cancelled cycles due to absent response were in the group of the lowest AMH quartile, whereas the cancelled cycles due to risk of ovarian hyperstimulation syndrome (OHSS) were in the group of the highest AMH quartile. This study demonstrated a strong correlation between serum AMH levels and ovarian response to gonadotrophin stimulation. CONCLUSION: For the first time, clinicians may have a reliable serum marker of ovarian response that can be measured independently of the day of the menstrual cycle.     

Serum anti-Müllerian hormone and FSH: prediction of live birth and extremes of response in stimulated cycles--implications for individualization of therapy

BACKGROUND: Serum concentrations of anti-Müllerian hormone (AMH) correlate with oocyte yield in assisted reproduction treatment (ART) cycles, however, performance of AMH for prediction of live birth is unknown. METHODS: A total of 340 first cycle IVF/ICSI patients (median age 34.0 years, inter-quartile range 31.0-37.0 years), had basal plasma AMH and FSH measured and their predictive values for live birth and oocyte yield compared. RESULTS: AMH predicts live birth [contribution to variance (CTV) 3.84%, P < 0.001] and oocyte yield (r = 0.71, P < 0.0001, CTV 7.3%, P < 0.0001). Compared with age and FSH, AMH performs better in prediction of live births [area under receiver operating characteristic curve (AUC) 0.62, 95% CI 0.55-0.68; FSH AUC 0.42, 95% CI 0.35-0.49; age AUC 0.48, 95% CI 0.41-0.55, P = 0.0028] and excessive response to ovarian stimulation (AMH AUC 0.90, 95% CI 0.83-0.96; FSH AUC 0.32, 95% CI 0.23-0.40; age AUC 0.57, 95% CI 0.43-0.71, P < 0.001). AMH prediction of oocyte yield is independent of age (r = -0.28, P < 0.0001, CTV 1.4%, P = 0.006), however, a significant negative interaction (CTV 3.6%, P < 0.0001) exists. AMH demonstrates improved differential distributions for non-, poor, normal and excessive ovarian responses relative to FSH and age. CONCLUSIONS: Plasma AMH is a superior predictor of live birth and anticipated oocyte yield compared with FSH and age, facilitating individualization of therapy prior to first ART cycle.