Introduction
Treatments of infertility are the different methods used to achieve pregnancy in case of female and/or male infertility, including induction of ovulation (IO) and assisted reproductive techniques (ART) stricto sensu such as in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI). These methods are increasingly used worldwide, and IVF alone accounted for nearly 1.6% of the total births in 2014 in the USA.1
Adverse perinatal outcomes (eg, low birth weight, preterm birth PTB) are more frequent in pregnancies conceived following infertility treatments as compared with spontaneously conceived pregnancies.1–4 Infertility treatments are also associated with a higher risk of congenital anomalies,5–7 in particular a higher risk of congenital heart defects (CHDs).5 7–11
CHD is the most common group of congenital anomalies at birth with an overall total prevalence of 8.0 per 1000 births.12 Despite progress in their medical and surgical management, CHD remains an important cause of morbidity and the first cause of infant death by malformation.12 13 Newborns with CHD are also at higher risk of adverse perinatal outcomes such as small for gestational age14 and PTB,15 16 which in turn are associated with higher morbidity and mortality.17 18
Newborns with CHD conceived following treatments of infertility may be exposed to both the adverse effects of CHD and treatments of infertility, including in particular PTB and multiple pregnancies. The degree of a higher risk of PTB for newborns with CHD conceived following treatments of infertility is not known. Moreover, the role of multiple pregnancies in the association between treatments of infertility and PTB in newborns with CHD has not been assessed.1 2
Using data from a large, prospective, population-based cohort of children with CHD (the EPIdémiologie des CARDiopathies congénitales (EPICARD) study),13 we (1) assessed the risk of PTB for newborns with CHD conceived following treatments of infertility (IO, IVF, ICSI) and compared it with the risk of PTB for newborns with CHD conceived without treatments of infertility; and (2) used a path-analysis approach to assess the role of multiple pregnancies in the association between treatments of infertility and PTB for newborns with CHD.