Oral estradiol hemihydrate and estradiol valerate show similar clinical outcomes in IVF setting

The regulation of estrogen levels is essential to control uterine receptivity for implantation. Endometrial thickness increases throughout the follicular phase under the influence of estrogen. Following adequate estrogen priming of the endometrium, progesterone prepares the endometrium for implantation. Estrogen enables contraction of spiral arteries resulting in hypoxia in the functional layers and promotes endometrial proliferation. Since exogenous administration of estrogen is required to increase the serum estrogen within a required range, it is important to be selective and understand the nature of such estrogen interventions. The pharmacological and clinical similarities or dissimilarities need good quality clinical validations.

The common forms in current use are estradiol valerate and micronized estrogens. One of them, estradiol valerate, has been regularly employed in IVF. Monitoring endometrial thickness in cycles using a HRT protocol provides the best model to study and compare the different estrogen compounds because the endometrium in these cycles is completely under the control of exogenously administered drugs. The aim of study by Manish Banker et al was to analyze retrospectively if oral estradiol hemihydrate and estradiol valerate are equally efficacious or dissimilar when used in a HRT protocol. Endometrial thickness and implantation rate (IR), were analyzed as primary outcomes. Secondary outcome measures included in the study were clinical pregnancy rate, abortion rate, live birth rate, and ectopic pregnancy. This study compared the clinical efficacy of two estrogen products in IVF treatment.

In this study, retrospective in nature, authors compare the efficacy of oral estradiol hemihydrate with estradiol valerate in HRT cycles in 2,529 Indian women, undergoing treatment at a center in India between Jan 2017 and May 2019.

The results primarily indicate that between the estradiol valerate and estradiol hemihydrate treatment groups, the implantation rate (IR) was 47.42% and 49.07%, respectively (P value 0.284), and the endometrial thickness (mean ± SEM in mm) that was achieved was 9:25 ± 0:038 mm and 9:57 ± 0:058 mm (P value < 0.001), respectively. There were no significant differences observed in the secondary outcome measures including clinical pregnancy rate, abortion rate, ectopic pregnancy, and live birth rate.

Study indicated that treatments with either estradiol valerate or estradiol hemihydrate improved the endometrial receptivity, indicated by increase in endometrial thickness. The endometrial thickness achieved by both compounds is adequate though there is a significant increase (of 0.351 mm; P < 0:0001) in thickness in the hemihydrate group. Although statistically significant, the difference in endometrial thickness between the two treatment groups is minimal (0.351 mm), both above 9 mm, and hence should not translate into any clinically significant difference. The implantation rate measured as the proportion of gestational sacs observed on sonography to the number of embryos transferred did not significantly differ between the two treatment groups. These primary results suggest that estradiol hemihydrate is not inferior to estradiol valerate in terms of efficacy.

Although it is a retrospective real-life data analysis of the two different preparations of estradiol, this is the first study where the two oral estradiol compounds have been compared for their clinical effects across various treatments in ART involving HRT cycles. The results of this large study (n = 2476) show that there is no significant difference between these two different forms of estradiol in terms of efficacy in endometrial preparation (measured as endometrial thickness) and the clinical outcomes (measured as implantation rates, clinical pregnancy rates, abortion rates, and live birth rates).

Source: Manish Banker, Parul Arora, Jwal Banker; Hindawi International Journal of Reproductive Medicine https://doi.org/10.1155/2021/3153307