Letrozole May Improve Outcomes After Frozen Embryo Transfer in Women With PCOS

Letrozole treatment may significantly improve live birth rate compared with artificial-cycle frozen embryo transfer (FET) in women with polycystic ovary syndrome (PCOS), according to study results published in Fertility and Sterility.

There are limited data regarding the optimal means of endometrial preparation for women with ovulatory dysfunction, such as PCOS. While artificial-cycle FET is the most frequently used regimen in these patients, it is expensive and may be associated with side effects. Letrozole is an aromatase inhibitor that maintains normal central feedback and generally leads to mono-ovulatory cycles.

The goal of this study was to assess pregnancy outcomes after artificial-cycle FET compared with FET with letrozole in women with PCOS.

The study included women with infertility and PCOS undergoing their first FET cycles between January 2011 and December 2016. Letrozole was given orally for 5 days, initiating on day 3 of spontaneous menses or withdrawal bleeding. In the artificial-cycle FET group, oral 17β-E₂ was given 3 times daily, initiating on day 2 or 3 of a menstrual cycle.

The primary outcome was live birth rate (live born baby after ≥24 gestational weeks) with artificial-cycle FET compared with FET with letrozole. Secondary outcomes included pregnancy rate, cancellation rate, endometrial thickness, and pregnancy loss rate.

Of 2664 patients fulfilling the inclusion criteria, 1571 were treated with letrozole and 1093 women underwent hormone replacement therapy. The groups were similar regarding age, body mass index, duration of infertility, obstetric history, antral follicle count, and smoking habits. Insufficient endometrial thickness was the main reason for cancellation in both groups, with similar cancellation rates in the 2 study groups (P =.576).

In the crude analysis, live birth rate/embryo transfer was 54.4% after FET with letrozole and 50.7% with artificial-cycle FET (P =.100). While the rates of clinical or biochemical pregnancy and implantation were similar between the groups, the miscarriage rate was significantly lower in the letrozole group (9.1% vs 17%; P <.001).

After adjustment for possible confounders, the miscarriage rate remained consistently lower in the group of women receiving letrozole (adjusted odds ratio, 0.51; 95% CI, 0.35-0.74). In addition, after correcting for confounders, the live birth rate was significantly higher with letrozole compared with artificial-cycle FET (adjusted odds ratio, 1.33; 95% CI, 1.09-1.61).

The researchers acknowledged that the study had several limitations, including the retrospective nature and possible biases of the statistical models used.

“These findings imply that letrozole use for [endometrial preparation] might be a potentially better alternative to [artificial cycle] in women with PCOS. Prospective randomized trials need to be conducted to assess the efficacy of letrozole as a method of [endometrial preparation] for FET,” concluded the investigators.

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Reference

Zhang J, Liu H, Wang Y, et al. Letrozole use during frozen embryo transfer cycles in women with polycystic ovary syndrome [published online May 21, 2019]. Fertil Steril. doi:10.1016/j.fertnstert.2019.04.014