Effects of in vitro fertilization and maternal characteristics on perinatal outcomes: a population-based study using siblings

Objective: To study birthweight in consecutively born sibling singletons conceived with and without in vitro fertilization (IVF) to disentangle the effects of maternal characteristics from those of the IVF treatment itself. Design: Population-based study. Setting: Not applicable. Patient(s): Firstborn and secondborn children from a 9-year birth cohort (1999-2007) comprising of 272,551 women who conceived two siblings. Intervention(s): No intervention; children were conceived naturally or through IVF. Main Outcome Measure(s): Birthweight. Result(s): The study included 545,102 children born by natural conception (NC) or IVF with the data set obtained from the population-based Netherlands Perinatal Registry (PRN) containing information on pregnancies, deliveries, and neonatal outcomes. We used two approaches: [1] the intersibling approach and [2] the sibling-ship approach. In the first approach we included children born to four groups of mothers who conceived in the following order (numbers indicate birth order): NC1-NC2 (reference, n = 254,721), IVF1-NC2 (n = 1342), NC1-IVF2 (n = 471), and IVF1-IVF2 (n = 687). Several comparisons were made to interpret the effects of IVF and maternal characteristics separately. In the second approach, perinatal outcomes of IVF children (n = 1,813) were compared with those of their NC siblings (n = 1,813). The intersibling analyses suggested an association between maternal characteristics and a lower birthweight, with estimates of the maternal effect ranging from -7 g (95% CI, -40; 26) to -101 g (95% CI, -170; -32). Neither the intersibling analyses nor the sibling-ship analyses indicated an additional adverse effect of IVF treatment itself. Conclusion(s): Maternal characteristics of subfertile women are associated with a lower birthweight. In vitro fertilization treatment itself does not additionally contribute to a lower birthweight in the offspring. (C) 2016 by American Society for Reproductive Medicin