Impact of letrozole on prevention of early-onset ovarian hyperstimulation syndrome in GnRH antagonist protocol: A Randomized Controlled Trial

Background: Letrozole is an aromatase inhibitor that decreases the risk of Ovarian Hyperstimulation Syndrome (OHSS) in assisted reproductive technology. We aimed to evaluate the clinical outcomes of high-risk patients undergoing different Intracytoplasmic Sperm Injection (ICSI) protocols, one with letrozole and one without. Patients and Methods: This RCT was done at the assisted reproduction unit, Ain Shams University Maternity Hospital, from February 2022 to May 2023. A total of 170 infertile women with polycystic ovarian syndrome were enrolled and divided into two equal groups; the study group consisted of 85 women who received controlled ovarian stimulation with a conventional antagonist protocol and letrozole, and the control group consisted of 85 women who received controlled ovarian stimulation with a conventional GnRH antagonist protocol and a placebo. Results: Letrozole could not decrease the incidence of total early-onset ovarian hyperstimulation syndrome compared with placebo treatment. Conversely, letrozole significantly reduced the severity and grades of early-onset OHSS in the study group. Letrozole significantly lowered the number of retrieved oocytes, which, according to our study results, was the only independent risk factor for OHSS. Letrozole also decreased estrogen on the day of the trigger injection. Also, letrozole did not affect biochemical/clinical pregnancy rates, total gonadotropin dose needed for induction of ovulation, endometrial thickness on the day of trigger, or embryos transferred per cycle. Conclusion: In high-risk, PCO infertile women undergoing ICSI, letrozole had no role in the prevention of the development of early-onset ovarian hyperstimulation syndrome. But it decreases its severity if occurred.