Research suggests that singleton births following assisted fertilisation are associated with adverse outcomes; however, these results might be confounded by factors that affect both fertility and pregnancy outcome. We therefore compared pregnancy outcomes in women who had singleton pregnancies conceived both spontaneously and after assisted fertilisation. In a population-based cohort study, we assessed differences in birthweight, gestational age, and odds ratios (OR) of small for gestational age babies, premature births, and perinatal deaths in singletons (gestation >/=22 weeks or birthweight >/=500 g) born to 2546 Norwegian women (>20 years) who had conceived at least one child spontaneously and another after assisted fertilisation among 1 200 922 births after spontaneous conception and 8229 after assisted fertilisation. In the whole study population, assisted-fertilisation conceptions were associated with lower mean birthweight (difference 25 g, 95% CI 14 to 35), shorter duration of gestation (2.0 days, 1.6 to 2.3) and increased risks of small for gestational age (OR 1.26, 1.10 to 1.44), and perinatal death (1.31, 1.05 to 1.65) than were spontaneous conceptions. In the sibling-relationship comparisons, the spontaneous versus the assisted-fertilisation conceptions showed a difference of only 9 g (-18 to 36) in birthweight and 0.6 days (-0.5 to 1.7) in gestational age. For assisted fertilisation versus spontaneous conception in the sibling-relationship comparisons, the OR for small for gestational age was 0.99 (0.62 to 1.57) and that for perinatal mortality was 0.36 (0.20 to 0.67). Birthweight, gestational age, and risks of small for gestational age babies, and preterm delivery did not differ among infants of women who had conceived both spontaneously and after assisted fertilisation. The adverse outcomes of assisted fertilisation that we noted compared with those in the general population could therefore be attributable to the factors leading to infertility, rather than to factors related to the reproductive technology.
Abstract What are the obstetric and neonatal clinical implications of large-for-gestational age (LGA) babies conceived after a frozen-thawed embryo transfer (FET)? Besides a lower risk of neonatal hypoglycaemia, obstetric and neonatal risks for FET LGA babies were comparable to those conceived spontaneously or after fresh ET. It has been shown that conception after a FET is an independent risk factor for LGA babies. The underlying physiologic mechanism is still unclear but is likely different to the mechanisms that lead to LGA after fresh embryo transfers or spontaneous conception. As the freeze-all strategy and FETs are becoming increasingly popular, an important clinical question revolves around the significance of this complication both for the mother and the baby and whether the obstetric and neonatal risks differ between LGA babies conceived following FET compared to those conceived after fresh embryo transfer (Fresh) and spontaneously conceived babies (SC). Study design, size, duration
This population-based cohort study is based on the Medically Assisted Reproduction data linkage which is a bespoke data linkage of the Australian ART registry to nine population health datasets including births, hospital admissions, medical services, medications, and deaths. All singleton LGA babies in New South Wales (2009-2017) and the Australian Capital Territory (2009-2016) (N = 81,075) conceived either spontaneously or after fresh or frozen-thawed embryo ART were included. Participants/materials, setting, The LGA births were divided into those conceived a) spontaneously without history of subfertility (SC) (n = 73,321), b) spontaneously with history of subfertility (SC-SubFert) (n = 4,516), c) after fresh ET (Fresh) (n = 1,461) d) after FET (n = 1,777). Relevant obstetric and neonatal outcome data were compared between LGA deliveries following FET and those following Fresh, SC and SC-SubFert while adjusting for important confounders including preexisting comorbidities (diabetes mellitus) and stratified by mode of delivery (vaginal birth-VB vs. cesarean section-CS). Main The caesarean section rate was similar between FET (58.2%) and Fresh LGA babies (57.9%) but significantly higher compared to the SC (39.1%) and SC-SubFert (49.9%) cohorts (p < 0.001). The use of forceps was also significantly (p < 0.001) higher in FET (4.6%) and Fresh (4.7%) LGA babies compared to the SC (3.5%) and SC-SubFert (2.1%) cohorts. Mean APGAR Scores at 1min (range: 8.3-8.4) and 5min (8.9 for all groups) after birth were similar between the four groups (p > 0.05).
In VB, the adjusted risk ratios (aRR) for perineal tear, shoulder dystocia and postpartum haemorrhage, neonatal resuscitation, respiratory distress, transient tachypnea, admission to the NICU, perinatal death and hospitalization in the first 2 years of life were not significantly different between the four groups. The risk of neonatal hypoglycaemia was significantly elevated in the Fresh (aRR: 1.87, 95% CI: 1.16-3.01), SC-SubFert (aRR: 1.55, 95% CI: 1.03-2.34) and SC (aRR: 1.63, 95% CI: 1.11-2.40) compared to the FET LGA babies.
In CS births, no significant differences were detected between the groups compared regarding all outcomes evaluated, apart from neonatal hypoglycaemia where SC LGA babies had significantly elevated risk compared to FET LGA babies (aRR: 1.22, 95% CI: 1.02-1.45). Limitations, As data were sourced from population health registries, some risk of misclassification might be present, although this is unlikely to be systematically different between groups compared. Despite controlling for important confounders, including maternal age at delivery, nulliparity, history of diabetes mellitus and socioeconomic variables, residual bias may still be present. This is the first study evaluating the clinical implications of FET LGA babies, suggesting largely similar risks to other LGA babies. However, the difference in risk of hypoglycemia supports a different pathophysiological mechanism for LGA after FET compared to the one of LGA babies conceived spontaneously and following fresh ET. No
Barnhart KT, 2013·Fertility and Sterility·
Open Access
Interrogating the association between assisted reproductive technologies (ART) and perinatal outcome is complicated but very important. This is an introduction to a series of articles that review this potential association with an eye toward etiology of risk, and what aspects of in vitro fertilization (IVF) can be modified to reduce this risk. When an association is not due to chance (i.e., statistically significant), one must also consider how the association may be affected due to bias or confounding. Despite lack of the perfect study, perinatal consequences of ART are apparent, even though the vast majority of children conceived with ART are healthy. Pregnancy after IVF is altered as evidenced by risk of preterm delivery, low birth weight among infants, and an alerted prevalence of preeclampsia. The long-term clinical implications of ART, such as childhood development and metabolism, have not been established and ongoing study is proceeding. The risk attributed to multiple births is iatrogenic and needs to be minimized. Optimizing the environment at the time a woman conceives will likely have an effect on gestation as well as the health of children. Reproduction effects health and health effects reproduction.
To quantify the contribution of in vitro fertilization (IVF) on changes in the rates of low birth weight (LBW), preterm delivery, very low birth weight, and multiple births during the past 3 years. Data on IVF pregnancies from 1994 to 1996 within Alberta were reviewed. Population data were obtained from the Provincial notice of a live or stillbirth. The IVF component of increased LBW rate in the province was 17.8% for infants <2500 g and 43.5% for those born <1500 g. IVF accounted for 10.5% of the provincial rate increase in deliveries <37 weeks' gestation and 66.2% of those <30 weeks' gestation. IVF accounted for 21.4% of the twins and all of the sets of triplets in the province. During a 3-year period IVF has affected the incidence of LBW, preterm delivery, and multiple birth. IVF is a substantial contributor to changes in very low birth weight and delivery before 30 weeks, which is partly related to multiple births.
The Medical Research Council In-Vitro Fertilization (IVF) Register report on births resulting from assisted conception in Great Britain demonstrated a high incidence of preterm and low birthweight babies. This incidence remained high even when the analysis was restricted to singleton babies. The present paper investigates possible risk factors for prematurity, low birthweight and small-for-gestational-age (SGA) in singleton IVF births. Thirteen per cent of singleton IVF babies were preterm, 11% low birthweight and 17% small-for-gestational-age. Analysis by multiple regression indicated that hypertension during pregnancy was an independent risk for preterm delivery, low birthweight and SGA, bleeding during pregnancy for preterm delivery, and the number of embryos transferred and the type of infertility for low birthweight.