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Endometrial preparation for frozen–thawed embryo transfer cycles: a systematic review and network meta-analysis

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Abstract

Purpose

To compare the effects of different endometrial preparation protocols for frozen–thawed embryo transfer (FET) cycles and present treatment hierarchy.

Methods

Systematic review with meta-analysis was performed by electronic searching of MEDLINE, the Cochrane Library, Embase, ClinicalTrials.gov and Google Scholar up to Dec 26, 2020. Randomised controlled trials (RCTs) or observational studies comparing 7 treatment options (natural cycle with or without human chorionic gonadotrophin trigger (mNC or tNC), artificial cycle with or without gonadotropin-releasing hormone agonist suppression (AC+GnRH or AC), aromatase inhibitor, clomiphene citrate, gonadotropin or follicle stimulating hormone) in FET cycles were included. Meta-analyses were performed within random effects models. Primary outcome was live birth presented as odds ratio (OR) with 95% confidence intervals (CIs).

Results

Twenty-six RCTs and 113 cohort studies were included in the meta-analyses. In a network meta-analysis, AC ranked last in effectiveness, with lower live birth rates when compared with other endometrial preparation protocols. In pairwise meta-analyses of observational studies, AC was associated with significant lower live birth rates compared with tNC (OR 0.81, 0.70 to 0.93) and mNC (OR 0.85, 0.77 to 0.93). Women who achieved pregnancy after AC were at an increased risk of pregnancy-induced hypertension (OR 1.82, 1.37 to 2.38), postpartum haemorrhage (OR 2.08, 1.61 to 2.78) and very preterm birth (OR 2.08, 1.45 to 2.94) compared with those after tNC.

Conclusion

Natural cycle treatment has a higher chance of live birth and lower risks of PIH, PPH and VPTB than AC for endometrial preparation in women receiving FET cycles.

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Funding

This work was supported by the National Natural Science Foundation of China grant (81671435 to S. Z).

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Authors and Affiliations

  1. Department of Obstetrics and Gynaecology, Hangzhou Women’s Hospital, No. 369 Kun Peng Road, Zhejiang, 310008, Hangzhou, China

    Hanglin Wu

  2. Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Road, Zhejiang, 310016, Hangzhou, China

    Ping Zhou, Xiaona Lin, Shasha Wang & Songying Zhang

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Contributions

S.Y.Z. conceived and designed the study. H.L.W. selected articles for inclusion, extracted data, performed the statistical analyses and drafted the first version of the manuscript. P. Z. conducted literature searches, and selected articles for inclusion. S.S.W. and X.N.L. extracted data and assessed study quality. All the authors contributed to the revision of the first draft of the manuscript, critically checked its content and approved its final version.

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Correspondence to Songying Zhang.

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Ping Zhou and Hanglin Wu should be considered similar in author order.

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Wu, H., Zhou, P., Lin, X. et al. Endometrial preparation for frozen–thawed embryo transfer cycles: a systematic review and network meta-analysis. J Assist Reprod Genet 38, 1913–1926 (2021). https://doi.org/10.1007/s10815-021-02125-0

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