Delaying the initiation of progesterone supplementation results in decreased pregnancy rates following in vitro fertilization: a randomized, prospective study.

Abstract

Objective: To compare in vitro fertilization outcome between two protocols for luteal phase progesterone supplementation: one beginning on day 3 following retrieval and the other beginning on day 6 following retrieval. Design: Prospective, randomized study. Materials/Methods: 126 consecutive patients undergoing IVF at our institution between January and July 2000 were randomized to receive one of two luteal phase progesterone supplementation protocols. All patients underwent ovarian hyperstimulation using a luteal GnRH-agonist protocol, a ‘stop’ GnRH-agonist protocol, or a GnRH agonist microdose flare protocol, depending on individual patient characteristics. Patients began using 200 mg micronized progesterone vaginally TID beginning the morning of either day 3 following oocyte retrieval or beginning on day 6 following oocyte retrieval. All patients continued progesterone supplementation daily until a negative serum pregnancy test, or, if the patient became pregnant, until 10 weeks of gestation. Clinical pregnancy and implantation rates were compared. Results: All patients undergoing randomization received an embryo transfer. There were no differences in patient age, BMI, oocytes retrieved, or number of embryos transferred between the two groups. Those patients beginning progesterone support on day 6 following retrieval had a significantly lower pregnancy rate compared to those beginning on day 3 following retrieval (44.8% vs. 61.0%, p < 0.05). This difference in pregnancy rates was greater in those patients undergoing a luteal GnRH-agonist downregulation protocol (47.5% vs. 71.4%, day 6 vs. day 3, P = 0.03). Beginning progesterone on day 6 also significantly decreased implantation rates in the GnRH-agonist group (21.0% vs. 34.0%, day 6 vs. day 3, P = 0.02). Conclusions: Pregnancy rates are significantly decreased by initiating luteal phase supplementation later than day 3 following retrieval during IVF cycles. Despite elevated progesterone levels at the time of embryo transfer, progesterone supplementation should continue to be initiated at this time. Efforts to simplify medication regimens or to decrease treatment costs by decreasing the duration of progesterone supplementation should not be undertaken.