Comparing Ovulation Outcomes of Letrozole-Tamoxifen-Estradiolwith and without Vitamin E in Infertile Women with PolycysticOvary Syndrome: A Double-Blind, Randomized Clinical Trial.

Abstract

Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder and a leading cause of anovulatory infertility. This study evaluated whether adding vitamin E to a regimen of letrozole, tamoxifen, and estradiol improves ovulation outcomes in infertile women with PCOS.

Materials and methods: In a double-blind, randomized clinical trial conducted in Jahrom, Iran (December 2023-August 2024), 90 infertile women with PCOS were randomly assigned to two groups. Group A (n=45) received letrozole, tamoxifen, estradiol, and vitamin E, while group B (n=45) received the same regimen without vitamin E. The primary outcome was pregnancy rate; secondary outcomes included follicle size, count, and endometrial thickness, measured on cycle days 3, 7, and 12. Data were analyzed using Chi-square, Fisher's exact, and t tests (Stata 14).

Results: Baseline characteristics including age (mean: 31.21 ± 6.31 Y), BMI (24.96 ± 3.45 kg/m²), and infertility duration (3.48 ± 2.70 Y) were similar between groups (P>0.05). On day 7, the vitamin E group showed significantly larger follicles (14.15 ± 0.36 mm vs. 10.90 ± 0.68 mm), more follicles (5.16 ± 0.36 vs. 3.73 ± 0.83), and thicker endometrium (7.16 ± 0.36 mm vs. 5.16 ± 0.36 mm). These advantages persisted on day 12, including improved follicular maturity and endometrial thickness. Although the pregnancy rate was higher in the vitamin E group (11.1% vs. 6.7%), the difference was not statistically significant (P=0.457). Adverse effects, including ovarian hyperstimulation syndrome (OHSS) and irregular bleeding, did not differ significantly (P=0.553).

Conclusion: The results indicate that the addition of vitamin E to the letrozole-tamoxifen-estradiol protocol might be associated with improved ovulatory outcomes in women with PCOS. Nevertheless, no significant effect on pregnancy rates was observed. These findings highlight the potential adjunctive role of vitamin E in ovulation induction among women with PCOS, although further large-scale randomized trials are needed to confirm its clinical relevance (number registration: IRCT20150407021653N20).