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Meta-Analysis
. 2025 Oct 8;25(1):1046.
doi: 10.1186/s12884-025-08127-5.

Effects of co administration of gonadotropins and letrozole during the ovarian stimulation on IVF outcome for poor responders: a systematic review and meta-analysis of randomized controlled trials

Faezeh Zakerinasab #  1 , Mersad Khalili #  2 , Fatemeh AbdollahyBiroon #  3 , Qumars Behfar  4 , Reza Parsaee  5 , Mahdis Sadat Miri  6 , Arina Ansari  7 , Fariba Arbab Mojeni  8 , Niloofar Deravi  9 , Ramina Fazeli  10   11 , Mobina Fathi  12
Affiliations
Meta-Analysis

Effects of co administration of gonadotropins and letrozole during the ovarian stimulation on IVF outcome for poor responders: a systematic review and meta-analysis of randomized controlled trials

Faezeh Zakerinasab et al. BMC Pregnancy Childbirth. .

Abstract

Background: Letrozole utilizing, an aromatase inhibitor, has been examined to improve pregnancy rate in poor ovarian response women. Increasing the dose of gonadotropins and enhancement of follicles' sensitivity to androgens, are the possible mechanism of letrozole. This meta-analysis aimed to evaluate the effect of co-administration of letrozole and gonadotropin on IVF/ICSI outcomes in poor ovarian response women.

Method: Relevant randomized controlled trials were obtained through search in several databases including PubMed, Scopus, Clinicaltrials.gov, Google scholar, and Cochrane Library. The RCTs investigating the effect of letrozole + gonadotropin versus gonadotropin reporting pregnancy outcome were selected.

Results: After analyzing 13 RCTs comprising 1692 patients, letrozole was associated with a reduction in the dose (SMD: -147.96 (-180.49, -115.42), P < 0.01) and duration (SMD: -2.82 (-4.21, -1.42), P < 0.01 of gonadotropin administration. There was no evidence of a difference between groups in the number of retrieved oocytes, clinical pregnancy rate, or live birth rate. A small reduction in the number of transferred embryos was observed (SMD: -0.26 (-0.49, -0.02), P = 0.03), though this finding should be interpreted with caution given heterogeneity across studies. Overall, no significant improvement in reproductive outcomes was demonstrated.

Conclusions: Despite the lack of significant improvement in pregnancy and live birth rate in the letrozole group, the dose and duration of gonadotropins decreased. This has the potential to reduce the side effects of gonadotropins. However, further studies are necessary to confirm its safety and whether its use translates into clinically meaningful benefits.

Keywords: Gonadotropin; IVF; Letrozole; Meta-analysis; Systematic review.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
PRISMA flow diagram of the systematic review
Fig. 2
Fig. 2
Forest plot for demographics; (A) Age, (B) BMI, (C) Duration of infertility
Fig. 3
Fig. 3
Forest plot for Secondary outcomes; (A) No. retrieved oocytes, (B) No. transferred embryos, (C) Total gonadotropin, (D) Duration of gonadotropin therapy
Fig. 4
Fig. 4
Forest plot of the (A) Pregnancy, (B) Live birth in total population, and (C) Live birth in pregnant population
Fig. 5
Fig. 5
Leave-one-out sensitivity analysis plot
See this image and copyright information in PMC

References

    1. Keay S, Liversedge N, Mathur R, Jenkins J. Assisted conception following poor ovarian response to gonadotrophin stimulation. BJOG: Int J Obstet Gynecol. 1997;104(5):521–7. - PubMed
    1. Loutradis D, Vomvolaki E, Drakakis P. Poor responder protocols for in-vitro fertilization: options and results. Curr Opin Obstet Gynecol. 2008;20(4):374–8. - PubMed
    1. Giannelou P, Simopoulou M, Grigoriadis S, Makrakis E, Kontogeorgi A, Pantou A et al. The conundrum of poor ovarian response: from diagnosis to treatment. Diagnostics (Basel). 2020;10(9). - PMC - PubMed
    1. Ferraretti A, La Marca A, Fauser B, Tarlatzis B, Nargund G, Gianaroli L, et al. ESHRE consensus on the definition of ‘poor response’to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011;26(7):1616–24. - PubMed
    1. Bozdag G, Polat M, Yarali I, Yarali H. Live birth rates in various subgroups of poor ovarian responders fulfilling the Bologna criteria. Reprod Biomed Online. 2017;34(6):639–44. - PubMed

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