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Review
. 2024 Mar 29;12(4):760.
doi: 10.3390/biomedicines12040760.

Pituitary Suppression with Gonadotropin-Releasing Hormone Agonist Prior to Artificial Endometrial Preparation in Frozen-Thawed Embryo Transfer Cycles: A Systematic Review and Meta-Analysis of Different Protocols and Infertile Populations

Nguyen-Tuong Ho  1   2   3 , Dang Khanh Ngan Ho  4 , Xuan Hong Tomai  5 , Nam Nhat Nguyen  2 , Hung Song Nguyen  6 , Yu-Ming Hu  1 , Shu-Huei Kao  7   8 , Chii-Ruey Tzeng  1   2
Affiliations
Review

Pituitary Suppression with Gonadotropin-Releasing Hormone Agonist Prior to Artificial Endometrial Preparation in Frozen-Thawed Embryo Transfer Cycles: A Systematic Review and Meta-Analysis of Different Protocols and Infertile Populations

Nguyen-Tuong Ho et al. Biomedicines. .

Abstract

This study investigates the effect of GnRHa pretreatment on pregnancy outcomes in artificial endometrial preparation for frozen-thawed embryo transfer (AC-FET) cycles. A systematic review of English language studies published before 1 September 2022, was conducted, excluding conference papers and preprints. Forty-one studies involving 43,021 participants were analyzed using meta-analysis, with a sensitivity analysis ensuring result robustness. The study found that GnRHa pretreatment generally improved the clinical pregnancy rate (CPR), implantation rate (IR), and live birth rate (LBR). However, discrepancies existed between randomized controlled trials (RCTs) and observational studies; RCTs showed no significant differences in outcomes for GnRHa-treated cycles. Depot GnRHa protocols outperformed daily regimens in LBR. Extended GnRHa pretreatment (two to five cycles) significantly improved CPR and IR compared to shorter treatment. Women with polycystic ovary syndrome (PCOS) saw substantial benefits from GnRHa pretreatment, including improved CPR and LBR and reduced miscarriage rates. In contrast, no significant benefits were observed in women with regular menstruation. More rigorous research is needed to solidify these findings.

Keywords: frozen–thawed embryo transfer; gonadotropin-releasing hormone agonist; pituitary suppression; pregnancy outcomes.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
PRISMA flowchart. **: Records that were irrelevant to the research question.
Figure 2
Figure 2
Summary of study quality assessment using the Effective Public Health Practice Project (EPHPP) quality assessment tool (n = 41 studies)—Data shown as percentage of number of studies.
Figure 3
Figure 3
Forest plots of meta-analysis for pregnancy outcomes following AC-FET cycles with and without GnRHa pretreatment [9,10,11,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53]. (A) Clinical Pregnancy Rate. (B) Implantation Rate. (C) Live Birth Rate. (D) Miscarriage Rate. *, **, and ***: three populations of infertile women were reported in the same study with matched or non-matched designs. a and aa: two different protocols were applied in the same study. RCTs: randomized controlled trials.
Figure 3
Figure 3
Forest plots of meta-analysis for pregnancy outcomes following AC-FET cycles with and without GnRHa pretreatment [9,10,11,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53]. (A) Clinical Pregnancy Rate. (B) Implantation Rate. (C) Live Birth Rate. (D) Miscarriage Rate. *, **, and ***: three populations of infertile women were reported in the same study with matched or non-matched designs. a and aa: two different protocols were applied in the same study. RCTs: randomized controlled trials.
Figure 3
Figure 3
Forest plots of meta-analysis for pregnancy outcomes following AC-FET cycles with and without GnRHa pretreatment [9,10,11,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53]. (A) Clinical Pregnancy Rate. (B) Implantation Rate. (C) Live Birth Rate. (D) Miscarriage Rate. *, **, and ***: three populations of infertile women were reported in the same study with matched or non-matched designs. a and aa: two different protocols were applied in the same study. RCTs: randomized controlled trials.
Figure 4
Figure 4
Subset meta-analyses on specific populations: women with PCOS and women with regular menstruation and no ovulation disorders. CPR: clinical pregnancy rate, IR: implantation rate, LBR: live birth rate, MR: miscarriage rate. *: statistically significant.
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