Evaluation of progestogen supplementation for luteal phase support in fresh in vitro fertilization cycles

Luteal phase deficiency commonly occurs after ovarian stimulation in women undergoing assisted reproduction. Progestogen supplementation is a routine and critical component for luteal phase support; how- ever, the optimal regimen remains unresolved.

Volume 112, Issue 3, Pages 491–502.e3


Amal Mohammed, M.Sc., Kathryn J. Woad, Ph.D., George E. Mann, Ph.D., Jim Craigon, B.Sc., Nick Raine-Fenning, M.B.Ch.B., M.R.C.O.G., Ph.D., Robert S. Robinson, Ph.D.



To evaluate the effectiveness of progestogen supplementation in improving clinical pregnancy rates in women undergoing fresh IVF cycles and to compare different routes, start times, durations, and estrogen coadministration regimen.


Comprehensive systematic review and meta-analysis.




Women undergoing fresh IVF cycles who did and did not receive progestogen supplementation.


Summary odds ratios (ORs) were calculated by binomial logistic regression.

Main Outcome Measure(s)

Clinical pregnancy rates.


Eighty-two articles (26,726 women) were included. Clinical pregnancy rates were increased by IM (OR = 4.57), vaginal (OR = 3.34), SC (OR = 3.36), or oral (OR = 2.57) progestogen supplementation versus no treatment. The greatest benefit was observed when progestogens were supplemented IM versus vaginally (OR = 1.37). The optimal time to commence administration was between oocyte retrieval and ET (OR = 1.31), with oocyte retrieval +1 day being most beneficial. Coadministration of estrogen had no benefit (OR = 1.33), whether progestogens were coadministered vaginally or IM. Clinical pregnancy rates were equivalent when progestogen supplementation was ceased after ≤3 weeks or continued for up to 12 weeks (OR = 1.06).


This broad-ranging meta-analysis highlights the need to reevaluate current clinical practice. The use of progestogens in fresh IVF cycles is substantially beneficial to clinical pregnancy. Critically, the use of IM progestogens should not be dismissed, as it yielded the greatest clinical pregnancy rates. Pregnancy success was impacted by initiation of therapy, with 1 day after oocyte retrieval being optimal. There is little evidence to support coadministration of estrogen or prolonging progestogen treatment beyond 3 weeks.

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