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.