Timing luteal support in assisted reproductive technology: a systematic review

Abstract

Objective To summarize the available published randomized controlled trial data regarding timing of progesterone supplementation during the luteal phase of patients undergoing ART. Design A systematic review. Setting Not applicable. Patient(s) Undergoing in vitro fertilization. Intervention(s) Different starting times of progesterone for luteal support. Main Outcome Measure(s) Clinical pregnancy and live birth. Results Five randomized controlled trials were identified that met inclusion criteria with a total of 872 patients. A planned meta-analysis was not performed due to a high degree of clinical heterogeneity in regards to the timing, dose, and route of progesterone. Two studies compared progesterone initiated before oocyte retrieval versus the day of oocyte retrieval and pregnancy rates were 5–12% higher when starting progesterone on the day of oocyte retrieval. One study compared starting progesterone on post retrieval day 6 versus day 3, reporting a 16% decrease in pregnancy in the day 6 group. Trials comparing progesterone start times on the day of oocyte retrieval versus two or three days post retrieval showed no significant differences in pregnancy. Conclusions There appears to be a window for progesterone start time between the evening of oocyte retrieval and day 3 after oocyte retrieval. While some studies have suggested a potential benefit in delaying vaginal progesterone start time to 2 days after oocyte retrieval, this review could not find randomized controlled trials to adequately assess this. Further randomized clinical trials are needed to better define progesterone start time for luteal support after ART.

Clinical use of progesterone in infertility and assisted reproduction

“…More recently, a meta‐analysis was published to summarize the results of all available randomized controlled trials focused on the timing of the luteal phase support in ART. Only five studies were eligible for the analysis, for a total of 872 patients and 1010 cycles.…”

Clinical roles and applications of progesterone in reproductive medicine: an overview

“…Progesterone administration can be initiated at the time of oocyte retrieval, or 1–2 days before embryo transfer, and continued until pregnancy tests become positive in successful cycles, or menstruation ensues in non‐conception cycles . A recent development is the availability of novel parenteral progesterone preparations that are water‐soluble, and that can thus be administered subcutaneously to reduce patient discomfort, while maintaining the clinical efficacy of oil‐based preparations that must be administered intramuscularly and are often painful and associated with rare but potentially serious complications such as inflammation and abscesses .…”

Recent advances in the development of transdermal delivery systems for treatment of infertility

“…The long half-life of hCG compared with that of luteinizing hormone results in continued stimulation of the corpus luteum after oocyte retrieval, leading to sustained release of endogenous estrogen and progesterone. 28 Recently, GnRH agonists have been used to trigger release of endogenous luteinizing hormone, resulting in oocyte maturation followed by rapid involution of the corpus luteum and a decreased risk of ovarian hyperstimulation syndrome. However, this results in a dysfunctional luteal hormonal milieu with low levels of estrogen and progesterone.…”