Clinical outcomes following preimplantation genetic testing for monogenic conditions: a systematic review of observational studies - 30/10/24

Doi : 10.1016/j.ajog.2024.09.114

Alice Poulton, MGenCouns ^a,^b,^d,^⁎ , Melody Menezes, PhD ^a,^c,^e, Tristan Hardy, PhD ^a,^c, Sharon Lewis, PhD ^c,^d, Lisa Hui, PhD ^b,^d,^f,^g
^a Genetics, Monash IVF Group Ltd, Clayton, VIC, Australia
^b Department of Obstetrics, Gynaecology and Newborn health, University of Melbourne, Parkville, VIC, Australia
^c Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia
^d Reproductive Epidemiology, Murdoch Children's Research Institute, Parkville, VIC, Australia
^e Victorian Clinical Genetics Service, Parkville, VIC, Australia
^f Mercy Perinatal, Mercy Hospital for Women, Heidelberg, VIC, Australia
^g The Northern Hospital, Epping, VIC, Australia

^∗Corresponding author: Alice Poulton.

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Wednesday 30 October 2024

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.

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Key words : 24-chromosome aneuploidy screening, karyomapping, monogenic disorder, PGT-M, preimplantation genetic testing, single gene disorder

Plan

	A.P. and T.H. are paid employees of Monash IVF Group Ltd, providing clinical services to patients. At the time the study was performed, M.M. was also a paid employee of Monash IVF Group Ltd. A.P. receives a Monash IVF Group Ltd PhD support stipend. S.L. and L.H. report no conflict of interest.
	A.P. was supported by an Australian Government Research Training Program Scholarship from the University of Melbourne, a Monash IVF Group Ltd PhD support stipend, and a Murdoch Children's Research Institute PhD top up scholarship. L.H. receives research salary support from the Medical Research Future Fund (#1196010) and the University of Melbourne. S.L. is supported by a Murdoch Children's Research Institute Award. Infrastructure support was provided by the Murdoch Children's Research Institute.
	Registration and conduct guidance: This review was registered with PROSPERO (ID: CRD42022354760 on 20 August 2022) and conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The Cochrane database of systematic reviews, the Joanna Briggs Institute of systematic reviews, MEDLINE and PROSPERO were searched, and we found no similar systematic reviews undertaken or underway. The MOOSE reporting guidelines for meta-analyses of observational studies was used to guide conduct and reporting.^{1Brooke B.S., Schwartz T.A., Pawlik T.M. MOOSE reporting guidelines for meta-analyses of observational studies JAMA Surg 2021 ; 156 : 787-788 Cliquez ici pour aller à la section Références}
	This paper was presented at the Fertility Society of Australia and New Zealand 2023 Conference, 3 to 6 June 2023 in the Gold Coast, Queensland, Australia, the Australasian Association of Clinical Geneticist Special Interest Group Meeting, 17 to 18 November, 2023 in Melbourne, Victoria, Australia and the International Conference on Prenatal Diagnosis and Therapy 8 to 10 July 2024 in Boston, the United States of America.
	Cite this article as: Poulton A, Menezes M, Hardy T, et al. Clinical outcomes following preimplantation genetic testing for monogenic conditions: a systematic review of observational studies. Am J Obstet Gynecol 2024;XXX:XX–XX.