Predictors of response to ovulation induction using letrozole in women with polycystic ovary syndrome

Abstract

Background This study aimed to evaluate the predictive value of the initial screening characteristics of women with anovulatory polycystic ovary syndrome (PCOS) who did or did not respond to 2.5 mg letrozole (LET). Methods The clinical and laboratory characteristics of women with PCOS who underwent LET treatment were evaluated. Women with PCOS were stratified according to their responses to LET (2.5 mg). The potential predictors of their responses to LET were estimated using logistic regression analysis. Results Our retrospective study included 214 eligible patients with a response to 2.5 mg LET (n = 131) or no response to 2.5 mg LET (n = 83). PCOS patients who responded to 2.5 mg LET showed better outcomes than those who did not (2.5 mg LET) for pregnancy rate, live birth rate, pregnancy rate per patient, and live birth rate per patient. Logistic regression analyses showed that late menarche (odds ratio [OR], 1.79 [95% confidence intervals (CI), 1.22–2.64], P = 0.003), and increased anti-müllerian hormone (AMH) (OR, 1.12 [95% CI, 1.02–1.23], P = 0.02), baseline luteinizing hormone (LH)/ follicle stimulating hormone (FSH) (OR, 3.73 [95% CI, 2.12–6.64], P < 0.001), and free androgen index (FAI) (OR, 1.37 [95% CI, 1.16–1.64], P < 0.001) were associated with a higher possibility of no response to 2.5 mg LET. Conclusions PCOS patients with an increased LH/FSH ratio, AMH, FAI, and late menarche may need an increased dosage of LET for a treatment response, which could be helpful in designing a personalized treatment strategy.

Anti-Mullerian Hormone and Fertility Treatment Decisions in Polycystic Ovary Syndrome: A Literature Review

“…A high pre-treatment AMH merits initiating OI with higher doses of CC or LET than used in ovulatory women. [ 50 51 52 53 54 ] Alternatively, gonadotropins may be more effective in inducing ovulation in such women. In the context of IUI, very high levels of AMH >10 ng/ml may predict a poor response even with gonadotropins.…”

“…[ 52 ] A small retrospective study further reported an AMH level of 9.78 as the discriminatory level beyond which cumulative ovulation rates were significantly lower. [ 53 ] Finally, in a large cohort study of women with PCOS using Gen II AMH assay, it was noted that women with higher AMH levels needed higher doses of CC or LET to achieve ovulation and the chances of ovulation reduced with increasing levels of AMH. [ 54 ] In vitro studies involving human granulosa cells suggest that the probable underlying mechanism is related to high AMH, as high AMH inhibits aromatase activity and reduces follicular sensitivity to FSH.…”

Development and validation of a prediction model for suboptimal ovarian response in polycystic ovary syndrome (PCOS) patients undergoing GnRH-antagonist protocol in IVF/ICSI cycles

“…The association between ovarian reserve markers such as age, AMH, and bFSH and the ovarian response has been reported in patients with normal ovarian reserve [ 23 ].In addition, many studies have uncovered the remarkable precision of ovarian reserve markers in predicting poor ovarian response [ 24 ] and have established mathematical models to forecast ovarian sensitivity [ 25 , 26 ]. In infertile PCOS women receiving letrozole for ovulation induction, increased levels of baseline LH/FSH ratio, AMH, and free androgen index were found to be negatively associated with response to letrozole treatment [ 27 ]. Moreover, PCOS individuals with significantly higher circulating AMH levels were more likely to be resistant to exogenous Gn ovulation induction and required a higher starting dosage [ 28 ].…”