Letrozole supplementation during controlled ovarian stimulation in expected high responders: a pilot randomized controlled study.

backgroundAlmost all of the previous studies related with co-administration of letrozole in IVF cycles were performed in poor responders and letrozole may reduce the total gonadotropin dose required for ovarian stimulation, and the pregnancy rate did not decrease in poor responders. This study aimed to assess whether high responders co-treatment with letrozole reduced supraphysiological late follicular phase estradiol levels and the incidence of premature progesterone elevated at the end of the follicular phase, thereby impacting positively on endometrial receptivity.

methodsA randomized parallel controlled study in a university-affiliated center include 130 high responders between October 2015 and August 2016. The patients were randomized on the first stimulation day of the IVF cycle and from stimulation day 5 receive letrozole (group A) or without letrozole treatment (group B).

resultsAlthough estradiol levels were significantly lower in the letrozole group (group A) (P < 0.001), progesterone elevation (> 1.5 ng/mL was considered as a rise) on the day of hCG triggering (15.4, 7.7%) was not statistically significant (P = 0.170). RecFSH, the recovery rate of eggs, the high-quality embryo rate, and the thickness of endometrium (P = 0.776) were similar between the letrozole group(group A) and control groups (group B). Clinical pregnancy rates were 53.1% (26/49) and 72.9% (35/48) in the letrozole and control groups, respectively, with a statistical significance (P = 0.043).Live birth rates were 42.9% (21/49) and 62.5% (30/48),showed a marginally significant difference (P = 0.053). The miscarriage rate did not significantly differ between the two groups.

conclusionsIn this pilot study, letrozole supplementation could not reduce the incidence of premature progesterone rise during the late follicular phase in stimulated in vitro fertilization cycles in expected high responders, producing a harmful effect on the pregnancy outcome.

trial registrationChina Clinical Trial Registration Center: ChiCTR-IPR-15006211 URL of the trial registry record: http://www.chictr.org.cn/showproj.aspx?proj=10731 . Trial registration date: 8 April, 2015. Date of first patient's enrolment: 5 October, 2015.