Identifying risks of and modifiable factors to improve placental outcomes in assisted conception in Ontario

Abstract

The use of assisted reproductive technologies (ART) in Canada has increased rapidly over the past decade, with a 235% increase in reported ART cycle starts and a 190% increase in resultant clinical pregnancies from 2008-2018, outpacing our understanding of potential adverse perinatal outcomes. This dissertation project recognizes that the use of ART will continue to increase in both scale and scope, and that it will continue to be a valued means of overcoming infertility and involuntary childlessness. The balance of risks and benefits of these rapid technological innovations for human health is uncertain. Therefore, this project seeks to produce evidence about both the risks associated with ART as well as component treatment factors amenable to modification to make its use safer. While available evidence indicates that medically assisted pregnancies are at greater risk of placental complications, data are scarce, and estimates of specific effects are varied and not reported in the context of service provision for Canada. Linking data from the Canadian Assisted Reproductive Technologies Register to the Better Outcomes Registry & Network Ontario data, this project commenced with a foundational retrospective cohort study to assess the relationship between ART (in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI)) and placental and placentally-mediated complications by comparing assisted conceptions from four years of ART cycle starts to non-assisted conceptions. Building on the findings from the foundational study, two additional studies were performed to investigate the contributions of two treatment factors, day or stage of embryo at transfer and cryopreservation, to the observed patterns of risk. Compared to non-assisted pregnancies, we find that assisted pregnancies are associated with an increased risk of placental and placentally-mediated complications. Within assisted pregnancies, risk profiles are best achieved by stratifying the analysis by both treatment type (IVF or ICSI) and embryo transfer type (fresh or frozen), in keeping with clinical practice. Although we did not find the day or stage of embryo at transfer to be a primary independent contributor to the observed increase in risk of these complication, patterns observed in the relationship between method of cryopreservation and these outcomes warrant further investigation. This thesis concludes by arguing for the pursuit of a hierarchy of risk approach to the use of ART, which is supported by the findings of this project, as it may be the most effective method to guide technological innovation and policy implementation to mitigate the risks associated with ART while not being overly restrictive of the options available to those seeking to build a family.