Estrogen addition to progesterone for luteal phase support in cycles stimulated with GnRH analogues and gonadotrophins for IVF: A systematic review and meta-analysis

BACKGROUND: The purpose of the present systematic review and meta-analysis was to examine whether the probability of pregnancy is increased by adding estrogen to progesterone for luteal phase support in patients treated by in vitro fertilization (IVF). METHODS: A literature search covering MEDLINE, EMBASE, CENTRAL, meeting proceedings and reference lists of published articles was performed to identify relevant RCTs. Data were extracted for meta-analysis yielding pooled relative risks (RR) and 95% confidence intervals (CI). Sensitivity analyses by including studies with pseudo-randomization or unclear method of randomization were also performed (n=1141 patients in total). RESULTS: Four RCTs (n=587 patients) were eligible for inclusion. No statistically significant differences were present between patients who received a combination of progesterone and estrogen for luteal support when compared with those who received only progesterone, in terms of positive hCG rate (RR: 1.02, 95% CI: 0.87-1.19), clinical pregnancy rate (RR: 0.94, 95% CI: 0.78-1.13) and live birth rate (RR: 0.96, 95% CI: 0.77-1.21) per woman randomized. These results did not materially differ in the sensitivity analyses performed. CONCLUSIONS: The currently available evidence suggests that the addition of estrogen to progesterone for luteal phase support does not increase the probability of pregnancy in IVF. However, there is an obvious need for further RCTs that will assess, with more confidence, the effect of estrogen addition to progesterone during the luteal phase on the probability of pregnancy.