Prolonged pituitary downregulation with gonadotropin-releasing hormone agonist improves the live-birth rate: a retrospective cohort study comparing 3 different protocols

Background: The long protocol has been recognized as the gold standard in controlled ovarian hyperstimulation (COH). However, the full dose of gonadotropin-releasing hormone agonist (GnRH- a) under the prolonged protocol has become increasingly popular in China. This study sought to compare pregnancy outcomes among the following 3 groups: a long protocol group, and 2 types of improved prolonged protocol groups. Methods: A retrospective cohort study was conducted of 550 patients undergoing fresh embryo transfer (ET). Patients were treated either with the improved prolonged protocol in the follicular phase (Group 1; n=288) or the mid-luteal phase (Group 2; n=143), or the long protocol (Group 3; n=119). The clinical and laboratory outcomes of the 3 groups were compared. Results: The general characteristics of the women in the 3 groups were comparable. On the day on which gonadotropin (Gn) was first administered and on the day on which human chorionic gonadotropin (hCG) was administered, the luteinizing hormone (LH) levels of patients in both Groups 1 and 2 were lower than those of patients in Group 3. The number of oocytes retrieved, fertilized, and cleaved, and the number of high-quality embryos in the 3 procedures were similar. However, the number of transferred embryos, the rate of blastocyst progression, and the rate of implantation differed. The clinical pregnancy rates (CPRs) were significantly higher in the prolonged protocol groups (62.5% and 61.5%) than the long protocol group (48.7%). Further, statistically significant differences in the live-birth rates (LBRs) (56.9% vs. 57.3% vs. 42.9%) were observed. However, no differences in early abortion rates were found. Conclusions: As a result of pituitary downregulation with GnRH-a, the prolonged groups had better CPRs and LBRs than the long protocol group. The prolonged protocol in the mid-luteal phase was equally effective as that in the early follicular phase in fresh in-vitro fertilization (IVF)/intracytoplasmic sperm injection-embryo transfer ( ICSI-ET) cycles. High LH levels on the day of hCG may be a predictor of adverse clinical outcomes.