Childhood growth of singletons conceived following in vitro fertilization (IVF) – does gonadotropin-stimulation matter?

Introduction Several meta-analysis confirm a lower birthweight in singletons conceived by IVF compared to spontaneously conceived singletons. The etiology of the impaired intrauterine growth is unclear, but placental insufficiency or possible epigenetic effects are discussed. Data regarding normalization or continuation of reduced birth weight are scarce and controversial. To our knowledge, growth of children born after unstimulated natural cycle (NC-) IVF has never been studied before. The aim of our study was to evaluate if growth or weight gain of singletons conceived after NC-IVF and conventional gonadotropin-stimulated IVF (cIVF) differ from standard growth references.

Materials/Methods We conducted a single-center, university based cohort study. We included 139 singletons born after NC- or cIVF in 2010–2017. CIVF treatment was done by standard agonist or antagonist protocols, using≥150 international units (IU) of human menopausal gonadotropin (HMG) for hormonal stimulation. We collected weight, length and head circumference at birth and at one, two, four, six, 12, 18 and 24 months. We calculated standard deviation scores based on national growth references. Growth parameters (weight, length and head circumference) were compared between NC-IVF and cIVF singletons using Mann-Whitney-U tests.

Results In general, growth of children conceived after IVF did not differ from national references. Of the 139 singletons, 98 singletons were conceived after NC-IVF and 41 after cIVF. The parents did not differ in ethnicity, age, BMI or health status between groups, and there was no significant difference in gestational age, pregnancy complications and smoking or breastfeeding habits either. The median birth weight in NC-IVF children was 3.4 kg (0.1 standard deviation score, SDS) and in cIVF 3.3 kg (−0.3 SDS) (p=0.53). Median length at birth in NC-IVF was 50cm (−0.5 SDS) and did not differ from cIVF children 50cm (−0.8 SDS) (p=0.52). At age 12 months, the median weight was 9.3 kg (0.0 SDS) for NC-IVF children compared to 9.0 kg (−1.7 SDS) for cIVF children (p=0.44). Median lengths was 75cm (0.1 SDS) in NC-IVF versus 71cm (−1.6 SDS) in cIVF children (p=0.89). At age 24 months, median weight in NC-IVF children was 12.3 kg (0.3 SDS) versus 10.5 kg (−1.2 SDS) in cIVF (p=0.72) and median lengths 87.5cm (0.1 SDS) in NC-IVF versus 87.6 cm (0.1 SDS) in cIVF children.

Discussion To our knowledge, this is the first study investigating weight and length gain in children after unstimulated IVF. Growth is an important proxy for the health of children. These reassuring results are of imminent importance for parents and their children conceived after IVF treatment with and without gonadotropin stimulation.

Publication History

Article published online:
26 November 2021