Luteal Phase Support in Infertility Treatment: a Meta-analysis of the Randomized Trials

Background: The addition of GnRH agonist to the treatment regimen in women undergoing IVF cycles is thought to create a luteal phase defect. In an attempt to correct for this, many practitioners supplement with a variety of steroid hormones in the luteal phase.

Methods: To determine whether luteal phase support increases reproductive success in modern IVF cycles, a systematic review of the literature was performed. Meta-analyses were conducted when multiple homogeneous studies addressed a single issue. Only randomized controlled trials were included in the data analysis. The efficacy of supplementation, as well as the optimal route, formulation, dose, and length of administration were queried.

Results: Luteal supplementation with either i.m. hCG or i.m. progesterone significantly improved fertility outcomes compared with no treatment. When comparing i.m. progesterone with i.m. hCG, no fertility differences were found. Intramuscular progesterone conferred the most benefit compared with oral or vaginal use. Addition of oral estrogen to progesterone also improved implantation rates.

Conclusion: Given the increased risk of ovarian hyperstimulation syndrome associated with hCG use, i.m. progesterone is favoured for luteal phase supplementation with the addition of estrogen.