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

Xiaoyi Yang,Fei Gong,Ge Lin,Guangxiu Lu

doi:10.1186/s12958-019-0483-x

Abstract

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.

Highlights

Almost all of the previous studies related with co-administration of letrozole in in vitro fertilization (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
Whether it is gonadotropin-releasing hormone (GnRH) agonist or GnRH antagonist used for pituitary downregulation, the progesterone levels of more than 1.5 ng/mL on the day of human chorionic gonadotropin administration in IVF-stimulated cycles were associated with lower pregnancy rates [5,6,7]
This study aimed to assess whether co-treatment with letrozole reduced supraphysiological late follicular phase E2 levels and the incidence of premature progesterone elevated at the end of the follicular phase, thereby impacting positively on endometrial receptivity

Summary

Introduction

Almost 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. Increased serum progesterone levels in the late follicular phase are associated with reduced implantation rate [4]. Whether it is gonadotropin-releasing hormone (GnRH) agonist or GnRH antagonist used for pituitary downregulation, the progesterone levels of more than 1.5 ng/mL on the day of human chorionic gonadotropin (hCG) administration in IVF-stimulated cycles were associated with lower pregnancy rates [5,6,7]. Analysis of more than 60,000 cycles showed that serum E2 levels and the number of mature oocytes collected on the day of hCG administration showed a statistical relationship with elevated progesterone and was associated with a lower pregnancy rate [10]

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