A randomized clinical trial comparing the effects of transdermal and oral estrogen on clinical outcomes in patients undergoing frozen-thawed embryo transfer

Abstract

Although there are studies comparing the effect of true natural and modified natural cycle on clinical outcome, with the exception of a study of donation cycles with fresh embryo transfer (Madero et al., 2016), there is only one randomized clinical trial (RCT) study in the literature comparing the effect of two different routes of the artificial cycle, oral and transdermal estrogen. However, the number of patients included in this study is very limited, only 45 patients in each arm (R. Davar et al., 2016). In our RCT, a total of 267 patients were included, the largest one comparing the efficiency of transdermal and oral estrogen. Randomized Controlled Trial. This randomized controlled trial was undertaken in Assisted Reproductive Technologies and Genetics Center at Istanbul Memorial Hospital between May 2017 and October 2017 (ClinicalTrials.gov identifier:NCT03155048).The primary outcome measure was endometrial thickness on the day of progesterone administration and secondary outcome measure was clinical outcome. A total of 267 patients undergoing FET cycles with oral (n=137) and transdermal patch (n=130) were evaluated. Oral estrogen or transdermal patch was started from the second day of menstruation after basal ultrasonography to rule out the presence of ovarian cysts. USG scan was repeated on 11th day of cycle to measure endometrial thickness. If the endometrial thickness was more than 7 mm, estrogen treatment was continued to day 15. USG was repeated and progesteron vaginal gel replacement, twice a day, was started. First, separate generalized linear mixed models (GLMMs) were conducted to evaluate if there was any difference between the type of estrogen used and patient specific variables including age, AMH, BMI and endometrial thickness. Second, separate GLMMs with logit link were conducted to analyze the factors. When patient specific variables were analysed using generalized linear mixed models (GLMMs), the results showed that the generated model was not statistically significant in AMH (0.977), BMI (0.891), endometrial thickness (0.651) and age (0.216). Furthermore ongoing pregnancy rates were analysed using the same model and we found no difference in the ongoing pregnancy rate between the oral and transdermal routes. No significant difference in clinical outcomes between transdermal estrogen and oral estrogen in PCOS patients undergoing FET cycle was found. Transdermal estrogen can be used as it has the advantages of being more patient-friendly, less stressful, cost effective and avoids the first-pass hepatic metabolism.