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

Fertil Steril. 2016 Mar;105(3):590-598.e2. doi: 10.1016/j.fertnstert.2015.11.015. Epub 2015 Dec 1.


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.

Keywords: Assisted reproductive technology; in vitro fertilization; perinatal outcomes; siblings; subfertility.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Birth Weight* / genetics
  • Female
  • Fertility
  • Fertilization in Vitro* / adverse effects
  • Humans
  • Infant, Low Birth Weight
  • Infant, Newborn
  • Infertility / diagnosis
  • Infertility / epidemiology
  • Infertility / physiopathology
  • Infertility / therapy*
  • Live Birth
  • Netherlands / epidemiology
  • Pregnancy
  • Pregnancy Complications / diagnosis
  • Pregnancy Complications / epidemiology*
  • Pregnancy Complications / genetics
  • Registries
  • Risk Factors
  • Siblings*
  • Sperm Injections, Intracytoplasmic
  • Time Factors
  • Treatment Outcome