Clinical outcomes following preimplantation genetic testing for monogenic conditions: a systematic review of observational studies

Abstract

Objective

We aimed to report a summary of clinical outcomes following preimplantation genetic testing for monogenic conditions, by performing a systematic review of published literature on clinical pregnancy and live birth rates following preimplantation genetic testing due to a monogenic indication. Additionally, we aimed to undertake a subgroup analysis of clinical outcomes of concurrent monogenic and aneuploidy screening.

Data sources

Three electronic databases (MEDLINE, EMBASE, and PubMed) were searched from inception to May 2024.

Study eligibility criteria

Quantitative data audits, observational studies, and case series reporting clinical outcomes for individuals undergoing preimplantation genetic testing for a monogenic indication were included. Only studies using blastocyst biopsies with polymerase chain reaction-based or genome-wide haplotyping methods for molecular analysis were eligible to reflect current laboratory practice.

Methods

Quality assessment was performed following data extraction using an adaptation of the Joanna Briggs critical appraisal tool for case series. Results were extracted, and pooled mean clinical pregnancy rates and birth rates were calculated with 95% confidence intervals (95% CI). We compared outcomes between those with and without concurrent preimplantation genetic testing for aneuploidy.

Results

Our search identified 1372 publications; 51 were eligible for inclusion. Pooled data on 5305 cycles and 5229 embryo transfers yielded 1806 clinical pregnancies and 1577 births. This translated to clinical pregnancy and birth rates of 34.0% [95% CI: 32.8%–35.3%] and 29.7% [95% CI: 28.5%–31.0%] per cycle and 24.8% [95% CI: 23.6%–26.0%] and 21.7% [95% CI: 20.8%–23.1%] per embryo transfer. In studies with concurrent aneuploidy screening, clinical pregnancy and birth rates were 43.3% [95% CI: 40.2%–46.5%] and 37.6% [95% CI: 34.6%–40.8%] per cycle and 37.0% [95% CI: 33.9%–40.3%] and 31.8% [95% CI: 28.8%–35.0%] per embryo transfer. Studies without aneuploidy screening reported clinical pregnancy and birth rates of 32.5% [95% CI: 31.0%–34.1%] and 28.1% [95% CI: 26.6%–29.7%] per cycle and 21.2% [95% CI: 19.8%–22.6%] and 18.6% [95% CI: 17.3%–20.0%] per embryo transfer.

Conclusion

This systematic review reveals promising clinical outcome figures for this indication group. Additionally, synthesizing the published scientific literature on clinical outcomes from preimplantation genetic testing for monogenic conditions provides a rigorous, noncommercial evidence base for counseling.