Delaying the initiation of progesterone supplementation results in decreased pregnancy rates after in vitro fertilization: A randomized, prospective study

Objective: To compare IVF outcome between two protocols for luteal phase supplementation, one beginning on day 3 after oocyte retrieval and the other beginning on day 6 after retrieval. Design: Prospective, randomized study. Setting: University-based assisted reproductive technology center. Patient(s): One hundred twenty-six consecutive patients undergoing IVF between January and July 2000. Intervention(s): Patients were randomized to begin luteal phase support using vaginal progesterone beginning either on day 3 after oocyte retrieval or on day 6 after oocyte retrieval. Main Outcome Measure(s): Clinical pregnancy rates and implantation rates. Result(s): All patients randomized underwent transfer. There were no differences in age, oocytes retrieved, or embryos transferred between the two groups. Those patients receiving luteal phase support with progesterone beginning on day 6 after retrieval had a significantly lower clinical pregnancy rate per transfer compared with those beginning support on day 3 after retrieval (44.8% vs. 61.0%, respectively). This difference in pregnancy rates was greater in those patients undergoing a luteal gonadotropin releasing hormone (GnRH) agonist down-regulation protocol (47.5% vs. 71.4%, day 6 vs. day 3, respectively). Beginning support on day 6 also significantly decreased implantation rates in the GnRH agonist group (21.0% vs. 34.0%, day 6 vs. day 3, respectively). Conclusion(s): Pregnancy rates are significantly decreased by initiating luteal-phase progesterone supplementation on day 6 after oocyte retrieval during in vitro fertilization cycles.