Genetic Factors in Recurrent Pregnancy Loss

Pregnancy loss is common, occurring in up to 25% of pregnancies, and often caused by chromosomal aneuploidy. Recurrent pregnancy loss (RPL) is more specifically defined as two or more pregnancy losses, and studies have assessed various factors that may be related or causative, including genetic-related factors. In studies on products of conception (POC), up to 60% of first trimester pregnancy losses are associated with sporadic chromosomal aneuploidy, the risk of which increases with advancing maternal age. In approximately 2-5% of couples experiencing RPL, chromosomal abnormalities are instead due to parental chromosomal rearrangements (e.g. balanced translocations). In both scenarios, couples have the option of in vitro fertilization (IVF) with preimplantation genetic screening (PGS) and/or diagnosis (PGD) to help substantially reduce the risk of chromosomal abnormality in transferred embryos. Furthermore, as follow-up for IVF couples and for those couples not pursuing IVF, prenatal genetic testing options (such as non-invasive prenatal screening [NIPS] and invasive diagnostic procedures) are also available to help assess risk for an affected fetus and possible post-first trimester loss. Aside from chromosomal abnormalities, while not routinely recommended for assessment in RPL couples due to limited data, inherited thrombophilia factors may also be associated with an increased risk for RPL. Screening for common thrombophilia factors may be warranted in individuals with personal or family history of thrombotic events and may inform medical management. Lastly, several single gene disorders, including recessive conditions, have been shown to have an association with prenatal lethality, and thus carrier couples may experience RPL. To assess this risk, carrier screening for these conditions may be especially useful in RPL couples and present them with additional reproductive options, including PGD and prenatal diagnostic testing.