Perinatal and pediatric outcomes associated with the use of fertility treatment: a population-based retrospective cohort study in Ontario, Canada

Abstract

Background Around 2% of births in Ontario, Canada involve the use of assisted reproductive technology (ART), and it is rising due to the implementation of a publicly funded ART program in 2016. To better understand the impact of fertility treatments, we assessed perinatal and pediatric health outcomes associated with ART, hormonal treatments, and artificial insemination compared with spontaneously conceived births. Methods This population-based retrospective cohort study was conducted using provincial birth registry data linked with fertility registry and health administrative databases in Ontario, Canada. Live births and stillbirths from January 2013 to July 2016 were included and followed to age one. The risks of adverse pregnancy, birth and infant health outcomes were assessed by conception method (spontaneous conception, ART – in vitro fertilization and non-ART – ovulation induction, intra-uterine or vaginal insemination) using risk ratios and incidence rate ratios with 95% confidence intervals (CI). Propensity score weighting using a generalized boosted model was applied to adjust for confounding. Result(s) Of 177,901 births with a median gestation age of 39 weeks (IQR 38.0–40.0), 3,457 (1.9%) were conceived via ART, and 3,511 (2.0%) via non-ART treatments. There were increased risks (adjusted risk ratio [95% CI]) of cesarean delivery (ART: 1.44 [1.42–1.47]; non-ART: 1.09 [1.07–1.11]), preterm birth (ART: 2.06 [1.98–2.14]; non-ART: 1.85 [1.79–1.91]), very preterm birth (ART: 2.99 [2.75–3.25]; non-ART: 1.89 [1.67–2.13]), 5-min Apgar < 7 (ART: 1.28 [1.16–1.42]; non-ART: 1.62 [1.45–1.81]), and composite neonatal adverse outcome indicator (ART: 1.61 [1.55–1.68]; non-ART: 1.29 [1.25–1.34]). Infants born after fertility treatments had increased risk of admission to neonatal intensive care unit (ART: 1.98 [1.84–2.13]; non-ART: 1.59 [1.51–1.67]) and prolonged birth admission (≥ 3 days) (ART: 1.60 [1.54–1.65]; non-ART: 1.42 [1.39–1.45]). The rate of emergency and in-hospital health services use within the first year was significantly increased for both exposure groups and remained elevated when limiting analyses to term singletons. Conclusion(s) Fertility treatments were associated with increased risks of adverse outcomes; however, the overall magnitude of risks was lower for infants conceived via non-ART treatments.

Ovulation induction and subfertile untreated conception groups offer improved options for interpreting risks associated with ART

“…[ 9 ] report almost identical increasing prevalence of preterm birth from unassisted conception (5.9%) to subfertility without treatment (7.7%), OI/IUI treatment (8.1%) and ART (10.8%). Other studies without a subfertile untreated comparison group have reported increased risks of preterm birth and low birth weight for OI births intermediate between natural conceptions and ART births [ 12 , 13 , 30 , 31 ]. We were able to account for a greater range of chronic medical conditions and adverse obstetric history in adjusted analyses than previous studies; however, we were unable to adjust for BMI.…”

A decennial cross-sectional review of assisted reproductive technology in a Tertiary Hospital in Southwest Nigeria

“…We observed a miscarriage rate of 37.8%, multiple pregnancy rate of 0.7%, preterm live baby rate of 11.9% and term live baby rate of 49.7%. Dimanlig-Cruz et al in a Canadian population-based study found that crude cumulative incidences of adverse pregnancy and birth outcomes, except for small gestational age, were highest in ART pregnancies [ 26 ]. They observed, like some other European population-based studies [ 27 , 28 ], that “compared with spontaneously conceived pregnancies, ART pregnancies had significantly increased risks of stillbirth (aRR 2.26) multiple birth (aRR 8.95), cesarean delivery (aRR 1.44), preterm birth (aRR 2.06), very preterm birth (aRR 2.99), and low Apgar score (aRR 1.28)” [ 26 ].…”

“…Dimanlig-Cruz et al in a Canadian population-based study found that crude cumulative incidences of adverse pregnancy and birth outcomes, except for small gestational age, were highest in ART pregnancies [ 26 ]. They observed, like some other European population-based studies [ 27 , 28 ], that “compared with spontaneously conceived pregnancies, ART pregnancies had significantly increased risks of stillbirth (aRR 2.26) multiple birth (aRR 8.95), cesarean delivery (aRR 1.44), preterm birth (aRR 2.06), very preterm birth (aRR 2.99), and low Apgar score (aRR 1.28)” [ 26 ]. However, a limitation of our study is that we did not compare pregnancy outcomes in ART and non-ART pregnancies during the study period, to possibly corroborate findings by Dimanlig-Cruz et al This was because many data of non-ART pregnancy outcomes during the same period were incomplete and/or missing due to their non-electronic paper documentation.…”