Interpretation
The overall rate of PTB in our study is consistent with that reported in Canada (6.3 per 100 singleton livebirths).24 Our estimates of PTB are also in agreement with the Massachusetts Outcomes Study of Assisted Reproductive Technologies (MOSART),8which reported an OR of PTB of 1.24 (95% CI 1.21, 1.38) in patients with subfertility, and 1.53 (95% CI 1.40-1.67) following Invasive infertility treatment. The MOSART study did not provide information on non-invasive infertility treatment, or detail PTB subtypes. Moreover, in a recent meta-analysis of 15 studies, comprising 61,677 singleton births, and which reported a pooled OR of 1.63 (95% CI 1.30-2.05) for spontaneous PTB after IVF/ICSI, the risk provider-initiated PTB was not assessed therein.12 In a population-based study of 1813 sibling pairs in the Netherlands Perinatal Registry, no association was found between IVF and either spontaneous or provider-initiated PTB, compared to unassisted-conceived siblings.25
The overall contribution of provider-initiated PTB to all PTB in our study (27%), is similar to that reported in Canada (25%).9 However, this contribution varied in our study by mode of conception: 26% after unassisted conception and 40% after invasive infertility treatment. One-third of provider-initiated PTB are associated with preeclampsia and/or intrauterine growth restriction, and this proportion increases with earlier gestational age at birth.9 Assisted Reproductive technology (ART), including IVF, ICSI, oocyte donation and frozen embryo transfer, is associated with an increased risk of the hypertensive disorders of pregnancy,5 and fetal growth restriction4 – both established reasons for provider-initiated PTB. Subfertility and infertility treatment too are associated with an increased risk of prelabour cesarean delivery, both at term and preterm.26
Among women with subfertility, or those undergoing infertility treatment, strategies are needed to lessen their risk of provider-initiated PTB, while minimizing maternal and neonatal morbidity. Care plans for women pregnant after ART are few.27 In early pregnancy, a simple approach is to use available clinical risk factors, including ART, that readily identify women at risk for preeclampsia.28 Level 1 evidence shows that low-dose aspirin modestly reduces the risk of spontaneous PTB, small for gestational age, birthweight, and maternal preeclampsia.29 Future studies should consider the benefit of low-dose aspirin starting at 12 weeks’ gestation in women with subfertility, or those undergoing IT, who are at higher risk for preeclampsia and PTB.