A drop in serum estradiol levels during GnRH antagonist cotreatment in cycles stimulated with gonadotropins is associated with lower cumulative live birth rates

Over the last decades, the gonadotropin-releasing hormone (GnRH) antagonist protocol has become widely used for prevention of premature luteinizing hormone surge during ovarian stimulation with exogenous gonadotropins. Literature has shown its efficacy and safety, while maintaining similar live birth rates compared to agonist protocols. Clinicians occasionally notice a drop in serum estradiol levels after GnRH antagonist initiation. This study aimed to analyze the impact of a drop in serum estradiol levels after the administration of a GnRH antagonist on clinical outcomes in in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles. The results showed that estradiol drop was related to lower ongoing pregnancy, live birth and cumulative live birth rates. Estradiol drop was less frequent in cycles using gonadotropins containing luteinizing hormone (LH) activity and cycles with a drop showed a larger decrease in serum LH after the first GnRH antagonist administration, resulting in lower serum values on the day of ovulation triggering. These findings suggest that future prospective research could focus on potential optimization of luteinizing hormone (LH) levels and this study might also add to the discussion that estradiol monitoring could be useful in detecting cycles with an increased risk of less favorable outcomes.