Risk of stillbirth similar after fresh/ frozen-ET compared with singletons conceived naturally
From its experimental beginning, assisted reproductive technology (ART) has grown into a successful treatment. Although most children born after ART so far were conceived by fresh embryo transfer (fresh-ET), the number of children conceived by frozen embryo transfer (frozen-ET) surged over the last decade, now comprising >50% of all children born after ART in many high-income countries.
Perinatal loss, whether stillbirth or neonatal death, is a traumatic outcome for expecting couples and often associated with preterm birth, congenital malformations, and placental complications. Studies show an overall high risk of perinatal death and of stillbirth after any ART compared with singletons conceived without medical assistance.
Singletons conceived after both fresh-ET and frozen-ET are at an increased risk of adverse perinatal outcomes, including preterm birth, which is a major contributor to neonatal death. It is not known whether pregnancies after fresh-ET and pregnancies after frozen-ET are at high risk of stillbirth or neonatal death during specific gestational ages or to what extent their increased risk of preterm birth contributes to neonatal mortality.
In this study Kjersti Westvik-Johari et al compared the risk of stillbirth and neonatal death in singletons born after fresh-ET and frozen ET to singletons born without medical assistance, in a large Nordic population of births between 1988 and 2015. Authors also estimated the associated risk according to gestational age.
It was a population-based cohort study. Data linkage was done between the nationwide Medical Birth Registries in Denmark (1994–2014), Norway and Sweden (1988–2015), and national quality registries and databases on assisted reproductive technology identified a total of 4,590,853 singletons, including 78,642 conceived by fresh-ET and 18,084 by frozen-ET.
Overall, 17,123 (0.37%) singletons were stillborn and 7,685 (0.17%) died neonatally. Compared with singletons conceived without medical assistance, the odds of stillbirth were similar after fresh-ET and frozen-ET, whereas the odds of neonatal death were high after fresh-ET (odds ratio [OR], 1.69; 95% confidence interval [CI], 1.46–1.95) and frozen-ET (OR, 1.51; 95% CI, 1.08–2.10).
Preterm birth (<37 gestational weeks) was more common after fresh-ET (8.0%) and frozen-ET (6.6%) compared with singletons conceived without medical assistance (5.0%), and strongly associated with neonatal mortality across all conception methods. Within gestational age categories, risk of stillbirth and neonatal death was similar for all conception methods, except that singletons from fresh-ET had a higher risk of stillbirth during gestational week 22–27 (OR, 1.85; 95% CI, 1.51–2.26).><37 gestational weeks) was more common after fresh-ET (8.0%) and frozen-ET (6.6%) compared with singletons conceived without medical assistance (5.0%), and strongly associated with neonatal mortality across all conception methods.
Within gestational age categories, risk of stillbirth and neonatal death was similar for all conception methods, except that singletons from fresh-ET had a higher risk of stillbirth during gestational week 22–27 (OR, 1.85; 95% CI, 1.51–2.26).
Compared with singletons born without medical assistance, singletons conceived after fresh-ET and frozen-ET had an overall similar risk of stillbirth, but a higher risk of neonatal death. Apart from a higher risk of stillbirth in pregnancies after fresh-ET at weeks 22–27, authors found no clear differences in associations for fresh-ET and frozen-ET. The higher risk of neonatal death after both fresh and frozen-ET might be attributed to a high risk of preterm birth in ART pregnancies.
“Our results suggest that singletons conceived by fresh-ETs and frozen-ETs are not at an overall higher risk of stillbirth compared with pregnancies conceived without medical conceptions, although singletons after fresh-ET may be at higher risk in gestational week 22–27. Both types of ART-conception have a higher risk of neonatal death, possibly mediated by preterm birth. The similarity of results between fresh-ET and frozen-ET treatment, indicate that for couples in need of ART, reassurance can be provided to ensure that a frozen ET is unlikely to increase the risk of stillbirth and neonatal mortality compared with fresh-ET (and vice versa).”
Source: Kjersti Westvik-Johari, Deborah A. Lawlor, Liv Bente Romundstad; Fertility and Sterility® Vol. 119, No. 2, February 2023 0015-0282
https://doi.org/10.1016/j.fertnstert.2022.10.020
