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. 2023 Oct;40(10):2343-2356.
doi: 10.1007/s10815-023-02923-8. Epub 2023 Sep 4.

Comparative effectiveness and safety of 36 therapies or interventions for pregnancy outcomes with recurrent implantation failure: a systematic review and network meta-analysis

Yunan He #  1   2 , Ruonan Tang #  1   2   3 , Haikun Yu  1   2 , Hui Mu  1   2 , Hongbin Jin  4 , Jie Dong  1   2 , Wenwen Wang  5 , Lu Wang  1   2 , Shuqiang Chen  1   2 , Xiaohong Wang  6   7
Affiliations

Comparative effectiveness and safety of 36 therapies or interventions for pregnancy outcomes with recurrent implantation failure: a systematic review and network meta-analysis

Yunan He et al. J Assist Reprod Genet. 2023 Oct.

Abstract

Purpose: To investigate the effectiveness and safety of 36 different therapies for recurrent implantation failure (RIF) patients.

Methods: We searched PubMed, Embase, the Cochrane Library (CENTRAL), Web of Science, and China National Knowledge Internet (CNKI) from inception to August 24, 2022, with language in both English and Chinese. Randomized controlled trials (RCTs) and observational studies that provided data with one of pregnancy outcomes on RIF patients were included in the network meta-analysis (NMA). The odds ratios (OR) and 95% credible interval (CrI) on pregnancy outcomes were summarized by NMA with a random-effects model. We also analyzed data from only RCTs and compared whether the optimal treatment is the same for different failed embryo transfer attempts.

Results: The total of 29,906 RIF patients from 154 clinical studies (74 RCTs and 80 non-RCTs) were included in the NMA. In terms of implantation rate (IR), growth hormone (GH) (OR: 3.32, 95% CrI: 1.95-5.67) is the best treatment in all included studies; IVIG+PBMC (5.84, 2.44-14.1) is the best for clinical pregnancy rate (CPR); hyaluronic acid (HA) (12.9, 2.37-112.0) for live birth rate (LBR); and aspirin combined with glucocorticoids (0.208, 0.0494-0.777) for miscarriage rate (MR). The two-dimensional graphs showed that GH could maximize IR and CPR simultaneously; HA and GH could simultaneously increase IR and LBR to a large extent; HA could maximize IR and minimize MR.

Conclusion: IVIG+PBMC, GH, and embryo medium enriched with HA could significantly improve pregnancy outcomes in patients with RIF. It appears that combination therapy is a potential administration strategy.

Trial registration: This study has been registered on PROSPERO (CRD42022353423).

Keywords: Administration; Clinical pregnancy rate; Hyaluronic acid; Meta-analysis; Repeated implantation failure; Treatment.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
PRISMA flow chart (articles screening process)
Fig. 2
Fig. 2
The network meta-analysis of all included studies of eligible comparisons for IR (A), CPR (B), LBR (C), and MR (D). The width of brown lines represents the number of studies
Fig. 3
Fig. 3
The forest plots of network meta-analysis of all included studies compared with control group. A IR, B CPR, C LBR, and D MR. The list of the forest plots is consistent with the ranking results of the network meta-analysis
Fig. 4
Fig. 4
Two-dimensional graphs about IR and CPR in all included studies (A), IR and LBR in all included studies (B), IR and MR in all included studies (C). Data are reported as ORs in comparison with control and error bars are 95% CrIs
See this image and copyright information in PMC

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