Causes of embryo implantation failure: A systematic review and metaanalysis of procedures to increase embryo implantation potential

Abstract

Introduction: Infertility is characterized by the failure to conceive after 12 months of unprotected sexual intercourse. In assisted reproduction technologies (ARTs), in-vitro fertilization and embryo transfer (IVF-ET) are pivotal, with the quality of embryo quality essential for successful implantation.

Objective: This systematic review with meta-analysis aimed to explore the prevalence of embryonic factors involved in the implantation process, concentrating on the following research inquiries: 1) the implantation rates of euploid versus untested embryo transfers; 2) the efficiency of transferring good embryos in different age groups; 3) the impact of age on good embryo transfers to gestational carriers; and 4) the transfer of donated gametes/embryos. The goal is to identify critical points in implantation to improve therapies.

Methods: A comprehensive literature search identified 1474 relevant papers, 11 of which met the inclusion criteria. The information was gathered using a standardized form, and the risk of bias was evaluated. A meta-analysis of subgroups to determine euploid embryo transfer efficiency was conducted to synthesize and explore the results. Furthermore, data extracted from registries document the persistent secondary role of extraembryonic determinants in successful implantation.

Results: The meta-analysis demonstrated that preimplantation genetic testing for aneuploidy (PGT-A) significantly increased the odds of implantation. Age was found to influence extraembryonic factors, with older women experiencing reduced embryo implantation as gestational carriers. However, the overall incidence of extraembryonic factors was low. This review highlights the need to focus on PGT-A, diagnostic hysteroscopy, and endometrial receptivity for improving implantation rates.

Conclusion: Implantation success in ARTs largely depends on embryo euploidy. While achieving three euploid embryos greatly increases success rates, it is challenging in older women. Extraembryonic factors, although present, have a marginal impact. Subsequent studies ought to concentrate on modulating endometrial responses immunologically and developing algorithms to improve the precision of predicting implantation success; as well as the timing of endometrial receptivity and the occurrence of dormant embryo phenomena also warrants further investigation.

Keywords: assisted reproductive technologies; clinical pregnancy outcomes; euploid embryo transfer; gestational carriers; implantation failure; infertility.

Figure 1

Picture depicts the estimation and prediction results for IVF cycles according to age and age. Modified with permission from (5).

Figure 2

Pregnancy and delivery rates per transfer in Europe, 1997–2019. (A) Pregnancy rates for IVF versus ICSI and ED cycles. (B) Delivery rates for fresh versus frozen cycles. ED, egg donation. Modified from (1).

Figure 3

Data obtained from the databases were selected for quantitative assessment, as shown in the flow chart. The qualitative assessments reported here were obtained from registry data and were not included in the meta-analysis. * From (12).

Figure 4

PGT-A and live birth rate. There was a significant positive effect on the odds of implantation: according to the random effects model (to be preferred, given the presence of heterogeneity), the odds of implantation were significantly greater in the PGT-A group.

Figure 5

Estimated implantation rates across different age groups, comparing outcomes for women using their own uterus and eggs versus those using a gestational carrier. Data trends are derived from annual reports by the Society for Assisted Reproductive Technology (SART) and the Centers for Disease Control and Prevention (CDC) in the United States. These reports provide detailed statistics on ART (Assisted Reproductive Technology) outcomes, including implantation rates, use of gestational carriers, and related metrics. The data is sourced from SART’s Clinic Outcome Reporting System, which collects ART cycle information from U.S. clinics to offer insights into IVF cycles, pregnancy and implantation rates, live birth rates, and more, categorized by patient age and cycle type. (Source: SART registry, https://www.sart.org/).