Perinatal outcomes after in vitro fertilization – a comparison of the national live birth registry with a tertiary cohort and an IVF cohort.

Mitter, V R; Fasel, Pascale Denise; Berlin, C; Amylidi-Mohr, S; Mosimann, B; Zwahlen, M; von Wolff, M; Kohl Schwartz, A (2021). Perinatal outcomes after in vitro fertilization – a comparison of the national live birth registry with a tertiary cohort and an IVF cohort. Zeitschrift für Geburtshilfe und Neonatologie, 225(Suppl 1), e44-e44. Thieme

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Introduction: In vitro fertilization (IVF) treatment is performed increasingly in Switzerland. Conception by IVF negatively affects obstetric and perinatal outcomes. Possible risk factors are parental health and subfertility, gonadotropin stimulation, gamete manipulation or culture of the embryo. Our primary aim was to assess the impact of IVF on perinatal outcomes in comparison to i) children born in tertiary care (university hospital), ii) all children born in Switzerland in the same time; and secondary, to address the effect of gonadotropin stimulation.

Methods: We performed IVF using 75IU-300IU gonadotropin per day to stimulate ovarian growth, or in the unstimulated natural cycle, where we collected the single oocyte. Fresh cleavage embryos were transferred on day 2 or 3. We recruited tertiary care births during first trimester check-up. We assessed differences in continuous perinatal outcomes, birthweight and gestational age, using linear regression; and the relative risk (RR) for preterm delivery (<37 GW), small for gestational age (<10th percentile) and low birthweight (<2500 g) using Poisson regression with robust error variance. We clustered for siblings and adjusted for maternal age, parity and foetal sex.

Results: Of the 636'639 live births from 2010–2018, 311 were in the Bern IVF Cohort (167 unstimulated, 144 stimulated), 2332 in tertiary care and 633'996 from the Swiss Live Birth Registry (SLBR). IVF mothers were on average 3.6 years (95%CI 3.2, 4.1) older and more often primiparous (76 vs. 49%; p<0,001). Perinatal outcomes (RR or adjusted RR (aRR); 95% CI) after IVF did not differ compared to SLBR, beside the crude risk for being born small for gestational age (1.31; 1.01, 1.70; aRR 1.12; 0.87, 1.45). Children born following stimulated IVF had lower crude mean birthweight (−115 g; −212 g, −17 g) and higher risk for low birthweight (RR 2.17; 1.27, 3.69; aRR 1.72; 1.01, 2.93) and small for gestational age (RR 1.50; 1.05, 2.14; aRR 1.31; 0.92, 1.87) whereas the children born after natural IVF cycles had no increased risks compared to the LBR. Gestational age and birthweight were lower in tertiary care born children and their risk was increased for preterm birth (RR 1.19; 1.02, 1.40), low birthweight (RR 1.29; 1.09, 1.52), and small for gestational age (RR 1.11; 1.00, 1.24) compared to LBR. Cesarean delivery rate was 42% in IVF deliveries whereas it was 36% (p=0,03) in tertiary care and the Swiss average is 32%. Higher maternal age is mainly associated with higher section rate in IVF mothers (aRR for CS: 1.04; 0.89, 1.22).

Discussion: IVF seems not to be a risk factor for adverse perinatal outcome in IVF births. Gonadotropin stimulation seems to affect birthweight and increased the risk for low birthweight and small for gestational age compared to the LBR. A strength of our study are the data quality and completeness. Selection bias for the tertiary care singletons with higher risk pregnancies explains worse outcome compared to SLBR.

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