In vitro fertilization. Obstetric outcome and health in children. Predictors of preterm birth in twin pregnancies

Abstract

Background In Sweden, infants born after assisted reproductive technology (ART) now account for 1-2% of all newborns. There has been much concern about the health of children born after ART and the high rate of multiple births, as well as the potential increased risks associated with the introduction of new technologies, such as cryopreservation and intracytoplasmic sperm injection (ICSI).Aims The aims of these studies were to evaluate the obstetric and neonatal outcome and early infant development (up to 18 months of age) after different in vitro fertilization (IVF) techniques and to analyse different screening markers for preterm birth in twin gestations.Methods Observational retrospective studies were undertaken of the first birth cohorts (100 deliveries) after conventional IVF (Paper I), after ICSI (175 deliveries) (Paper II) and cryopreservation (215 deliveries) (Papers III and IV) occurring between 1982 and 1989, 1993 and 1995 and 1990 and 1995, respectively. Children born after cryopreservation as embryos were compared with two control groups, consisting of children born after conventional IVF and spontaneous conceptions. Delivery records and records from Child Health Centres were studied. The effect of two different ways of calculating gestational age in ART pregnancies, either from the day of oocyte retrieval or from ultrasound measurements of fetal biparietal diameter and femur length in the second trimester of pregnancy was evaluated (Paper V). In a prospective longitudinal study, women with twin pregnancies (n=121) were examined every second week from 24 to 34 weeks of gestation (Papers VI and VII). Cervico/vaginal fluid was analysed for fetal fibronectin (FFN), endotoxin, bacterial vaginosis (BV), interleukin (IL)-1a, IL-6 and IL-8. Cervical length was measured by transvaginal sonography.Results In the conventional IVF study, multiple births occurred in 27%. Obstetric pathology was dominated by preterm birth and low birth weight, with 30% of all deliveries being preterm (<37 weeks) and 34% of all infants having a low birth weight (<2500g). The perinatal mortality rate was 4.6%. No problems during follow-up were apparent in children who had had an uneventful neonatal period. The incidence of multiple births was 20% (only twins) in the ICSI study, and 24% in the study of children born after cryopreservation. For singletons and twins, born after ICSI, the incidence of preterm birth, low birth weight and perinatal mortality was comparable with population-based data from the Swedish Medical Birth Registry. In the cryopreserved group, the incidence of preterm birth was 5.6%, 44.9% and 100% for singletons, twins and triplets, respectively, and low birth weight occurred in 5.0%, 40.8% and 100% of the singletons, twins and triplets, respectively, equivalent to the control groups. At follow-up, children born after cryopreservation as embryos had a normal growth and no increased morbidity. None of the studies showed any increased incidence of malformation. The mean gestational age estimated from ultrasound was 1.4-2.1 days shorter than gestational age calculated from the day of oocyte retrieval for both singletons and twins. With ultrasound dating, women with singleton pregnancies were more likely to deliver within 7 days of term, and the number of pregnancies classified as post-term was reduced.Of all screening markers evaluated for preterm birth in twin pregnancies, FFN was the best predictor of preterm birth and neonatal morbidity. A positive FFN test at 28 weeks of gestation was associated with an increased risk of preterm birth <35 weeks (Relative Risk 6.3, 95% CI 2.6-15.1). An independent association between a positive FFN test at 28 weeks and preterm birth (<35 weeks) was verified with logistic regression (p=0.03). A positive FFN test predicted neonatal morbidity and a longer stay in neonatal intensive care units. Cervical length and IL-8 were of limited value in predicting preterm birth, whereas IL-1a, IL-6, endotoxin and BV had no predictive value in these studies.