The influence of circulating anti-Mullerian hormone on ovarian responsiveness to ovulation induction with gonadotrophins in women with polycystic ovarian syndrome: a pilot study

Background: Women with polycystic ovarian syndrome (PCOS) are known to have elevated circulating Anti-Mullerian hormone (AMH), which has been found to desensitize ovarian follicles to follicle stimulating hormone (FSH). The purpose of this study was to investigate the impact of high circulating AMH on ovarian responsiveness to ovulation induction with gonadotrophins in PCOS women. Methods: This prospective observational pilot study was conducted in two collaborating Fertility Centres in the UK and Egypt. The study included 20 consecutive anovulatory women with PCOS who underwent 34 cycles of human menopausal gonadotrophin (hMG) ovarian stimulation using chronic low-dose step up protocol. Blood samples were collected for the measurement of serum AMH concentrations in the early follicular (day 2-3) phase in all cycles of hMG treatment. The serum levels of AMH were compared between cycles with good vs. poor response. The good response rates and the total dose and duration of hMG treatment were compared between cycles with high vs. low serum AMH concentrations. Results: Cycles with poor response (no or delayed ovulation requiring >20 days of hMG treatment) had significantly (p = .007) higher median{range} serum AMH concentration (6.5{3.2-13.4}ng/ml) compared to that (4.0 {2.2-10.2}ng/ml) of cycles with good response (ovulation within 20 days of hMG treatment). ROC curve showed AMH to be a useful predictor of poor response to hMG stimulation (AUC, 0.772; P = 0.007). Using a cut-off level of 4.7 ng/ml, AMH had a sensitivity of 100% and specificity of 58% in predicting poor response. The good response rate was significantly (p < .001) greater in cycles with lower AMH (< 4.7 ng/ml) compared to that in those with AMH > = 4.7 ng/ml (100% vs. 35%, respectively). All cycles with markedly raised serum AMH levels (> 10.2 ng/ml) were associated with poor response. Cycles with high AMH (> = 4.7 ng/ml) required significantly (p < .001) greater amounts (median {range}, 1087{450-1650}IU) and longer duration (20{12-30}days) of hMG stimulation than cycles with lower AMH (525 {225-900}IU and 8{6-14} days). Conclusions: PCOS women with markedly raised circulating AMH seem to be resistant to hMG ovulation induction and may require a higher starting dose.