GnRHa (alone or combined with hCG) vs. hCG alone for ovulation triggering during controlled ovarian stimulation for in vitro fertilization/intracytoplasmic sperm injection: a systematic review and meta-analysis

Systematic Review

VOLUME 2, ISSUE 4, P353-370, OCTOBER 01, 2021


Mathilde Bourdon, M.D., Ph.D., Maëliss Peigné, M.D., Céline Solignac, Pharm.D., Bernadette Darné, M.D., Solène Languille, Ph.D., Khaled Pocate-Cheriet, M.D., Ph.D., Pietro Santulli, M.D., Ph.D. 



To evaluate whether gonadotropin-releasing hormone agonist (GnRHa) triggering improves oocyte maturation, pregnancy outcomes, and safety compared with human chorionic gonadotropin (hCG) triggering during controlled ovarian stimulation.

Evidence Review

A systematic review was performed using the following keywords: “GnRH agonist”; “hCG”; and “triggering.” Searches were conducted on MEDLINE, Embase, the Cochrane Library,, and EudraCT for randomized controlled clinical trials between January 1, 1990, and April 15, 2020. The primary outcomes were the total number of retrieved oocytes and the number of mature oocytes. The main secondary outcomes were the number of embryos obtained, clinical pregnancy rate (CPR), early pregnancy loss rate, live birth rate, and incidence of ovarian hyperstimulation syndrome (OHSS). Two independent reviewers performed the study selection, bias assessment using the RoB2 tool, and data extraction according to the Cochrane methods. Random-effects meta-analysis was performed followed by prespecified sensitivity and subgroup analyses.


Our search yielded 1,369 published studies and 216 unpublished studies. After screening the titles and abstracts, 65 published studies and 25 unpublished abstracts were assessed for eligibility. Of these, we excluded 61 studies. A total of 29 randomized controlled trials were included. The 26 studies with the number of oocytes retrieved enrolled a total of 2,755 women, of whom 1,419 had GnRHa triggering and 1,336 had hCG alone for triggering. A total of 12 studies reported the number of mature oocytes with a total of 1,619 women (806 had GnRHa triggering and 813 had hCG alone for triggering). The mean numbers of retrieved oocytes (difference in the means [95% confidence interval], 0.99 [0.21, 1.78]; n = 26) and mature oocytes (0.68 [0.04, 1.33]; n = 12) were statistically significantly higher after GnRHa than after hCG triggering. A similar difference was observed for the number of embryos (0.94 [0.19, 1.68]; n = 10). No differences in the CPR (risk ratio, 1.01 [0.90, 1.14]; n = 23), early pregnancy loss (1.27 [0.94, 1.71]; n = 16), and live birth rate (1.00 [0.77, 1.29]; n = 6) were noted. Gonadotropin-releasing hormone agonist was associated with a lower incidence of OHSS (odds ratio, 0.25 [0.08, 0.74]; n = 20). Moreover, after dual triggering (GnRHa associated with hCG) compared with hCG alone, the meta-analysis showed a statistically significantly higher number of retrieved and mature oocytes and CPR.


The final triggering using GnRHa allows a higher number of retrieved and mature oocytes to be obtained with comparable clinical outcomes and, after GnRHa alone, a lower OHSS risk compared with hCG triggering.


Go to the profile of Bruce Pier
4 months ago

To the authors- I am very grateful for your manuscript.  I am curious if instead of using just number of oocytes and number of mature oocytes, if the authors considered a ratio of mature oocytes per cohort?  Also, do you have any concern of increased risk of pregnancy loss in the lupron cohort?  In your study, there was an insignificant increase of pregnancy loss in the lupron cohort, but the numbers were low.  Thanks for any insight you all further have on these questions.

Bruce Pier MD

Madigan Army Medical Center

Tacoma, WA