Progesterone Supplementation for Luteal Support: Efficacy and Patient Experiences With Vaginal Inserts (Endometrin®) Versus Intramuscular Injection

Abstract

BACKGROUND: Progesterone is administered to counteract luteal phase defects that may occur during stimulated in vitro fertilization (IVF) cycles. Several routes of progesterone administration are available, although no single method is considered the standard of care. Comparative data are needed to establish a preferred mode of progesterone supplementation. OBJECTIVE(S): To evaluate the efficacy, tolerability, and patient experiences with luteal support using progesterone vaginal inserts (PVI; Endometrin ) vs intramuscular injection of progesterone in oil (PIO) for women undergoing IVF cycles. MATERIALS AND METHOD(S): Women (aged 18 to 42 years) with a documented history of infertility who were suitable candidates for IVF were enrolled in 1 of 2 multicenter, open-label, exploratory studies. The 2 study designs were similar, with the exception of gonadotropin-releasing hormone (GnRH) antagonist use in the first study and only women with polycystic ovary syndrome (PCOS) were included in the second study. Participating centers followed standard IVF protocols. Prior to ovarian stimulation with menotropins for injection (Menopur ) or follitropin beta injection (Follistim AQ ), women were randomized to luteal support with either PVI or PIO. Biochemical, clinical, and ongoing pregnancy (defined as a positive human chorionic gonadotropin serum pregnancy test, presence of a gestational sac, and fetal heart movements, respectively) was assessed. Patients’ experiences were evaluated through a questionnaire administered at the time of the first pregnancy test and at the final study visit. RESULT(S): The combined intent-to-treat population (all randomized patients who received at least 1 dose of study medication) included 137 women treated with PVI and 138 women treated with PIO. The mean number of embryos transferred was comparable between treatment groups for each study. Among women with GnRH antagonist IVF cycles, ongoing pregnancy rates were 44.0% and 46.9% in the PVI and PIO treatment groups, respectively. Similar findings were observed in the PCOS study, with ongoing pregnancy rates of 47.2% (PVI) and 49.1% (PIO). Women who were treated with PVI reported greater administration convenience, ease of use, and overall satisfaction than did womenwho received PIO. Studymedications were generally well tolerated; the majority of adverse events that occurred during the luteal support phase were mild to moderate in intensity. CONCLUSION(S): Luteal support via PVI is as effective as PIO yet provides greater convenience and ease of use. Progesterone vaginal inserts are a patient-friendly alternative to PIO for women undergoing IVF cycles. FINANCIAL SUPPORT: This study was supported by Ferring Pharmaceuticals, Inc.