Reply: Extended culture and the risk of preterm delivery in singletons: confounding by indication?

Confounding by Indication and Related Concepts

“…The differentially higher rate of single-embryo transfers in the day 5/6 group (20.2 %) compared with the day 3 group (5.8 %) suggests that a significant fraction of the women in the day 5/6 group had a contraindication to multiple-embryo transfer and were at higher risk of preterm birth even before the embryo transfer. In their response [18], the authors of the original study conceded that the criticism was valid and reanalyzed their data after excluding women who had a prior preterm delivery or cervical incompetence.…”

“…Such confounding by contraindication can be addressed by restricting the study to a domain free of the contraindicationnamely, to nulliparous women, those without cervical incompetence, those without a previous history of preterm birth, etc. Although the discussion between the authors and their critics showed clarity with regard to issues of bias and the means for rectification, there was semantic confusion with regard to the terms and concepts related to confounding by indication and confounding by contraindication [17,18].…”

Effects of fifth day (D5) or sixth day (D6) frozen–thawed blastocysts on neonatal outcomes

“…Much more effective selection criteria should also include birth outcomes after the corresponding embryos are transplanted. Some studies have shown that the chance of premature delivery and of low birth weight after blastocysts transplantation was increased (Kalra et al, 2012;Dar et al, 2013aDar et al, , 2013b. Other studies also showed that the proportion of pregnancies involving fetal macrosomia after transplantation of frozen-thawed blastocysts increased (Mäkinen et al, 2013), while others showed that if culture was extended to the blastocyst stage, there was no effect on neonatal outcomes (Fernando et al, 2012;Oron et al, 2014).…”