Does preimplantation genetic testing for aneuploidy improve live birth rate in women diagnosed with recurrent implantation failure: A systematic review and meta‐analysis?

Introduction: The prevalence of unexplained recurrent implantation failure (RIF) is reported as 2%–15% in the literature. The variation in prevalence reflects the heterogeneity in definition. Recent work has suggested unexplained RIF is unlikely to be endometrial or cycle synchronicity related but is, in fact, an embryological phenomenon. The most likely embryological phenomenon is aneuploidy. Preimplantation genetic testing for aneuploidy (PGT‐A) has proven to reduce miscarriage rates in almost all infertility patients, including those with recurrent pregnancy loss, suggesting aneuploidy plays an important role in unsuccessful in vitro fertilization. No guidance for PGT‐A use in RIF exists. This review aimed to address this evidence gap.

Material and Methods: A systematic search of Medline, Embase, Web of Science, CINAHL, and Cochrane Database from inception until November 2024 was undertaken. Selection criteria included experimental and observational studies comparing euploid blastocyst transfer using PGT‐A to standard care. The population included those with RIF or undergoing a minimum of three transfers. The primary outcome was cumulative live birth rate (CLBR). The primary aim of this review is to evaluate the impact of PGT‐A on live birth rate (LBR) following a diagnosis of RIF. The secondary aim was to estimate the true prevalence of RIF, using a definition of three failed cycles. A random effects meta‐analysis was conducted reporting pooled odds ratios between groups using IBM SPSS v29.0.2.0 (20). The review was prospectively registered on PROSPERO:CRD42024580037.

Results: A total of 13 studies were included with low‐to‐moderate risk of bias. Eleven studies addressed PGT‐A after an RIF diagnosis while two studies addressed RIF prevalence after successive PGT‐A cycles. Four studies reported a statistically significant increase in CLBR with OR 4.23 [95% CI: 2.14, 8.38]. Similar results were seen in studies reporting a single embryo transfer using PGT‐A following an RIF diagnosis, OR 2.79 [95% CI: 1.90, 4.10].

Conclusions: PGT‐A results in a statistically significant increase in both LBR per embryo transfer and CLBR per cycle. This finding supports the hypothesis that RIF may be an embryological phenomenon. Further research is required before routine recommendation of PGT‐A for the management of RIF can be inferred.