In Vitro fertilization and adverse obstetric and perinatal outcomes

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Abstract

<p class="first" id="P1">Most IVF-conceived children are healthy, but IVF has also been associated with adverse obstetric and perinatal outcomes as well as congenital anomalies. There is also literature suggesting an association between IVF and neurodevelopmental disorders as well as potentially long-term metabolic outcomes. The main driver for adverse outcomes is the higher risk of multiple gestations in IVF, but as the field moves toward single embryo transfer, the rate of multiple gestations is decreasing. Studies have shown that singleton IVF pregnancies still have a higher incidence of adverse outcomes compared to unassisted singleton pregnancies. Infertility itself may be an independent risk factor. Animal models suggest that epigenetic changes in genes involved in growth and development are altered in IVF during the hormonal stimulation and embryo culture. Further animal research and prospective human data is needed to elucidate the mechanisms by which IVF may contribute to adverse outcomes and to decrease risks. </p>

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Obesity in young men after famine exposure in utero and early infancy.

G Ravelli, Z Stein, M. Susser (1976)

In a historical cohort study of 300,000 19-year-old men exposed to the Dutch famine of 1944-45 and examined at military induction, we tested the hypothesis that prenatal and early postnatal nutrition determines subsequent obesity. Outcomes were opposite depending on the time of exposure. During the last trimester of pregnancy and the first months of life, exposure produced significantly lower obesity rates (P less than 0.005). This result is consistent with the inference that nutritional deprivation affected a critical period of development for adipose-tissue cellularity. During the first half of pregnancy, however, exposure resulted in significantly higher obesity rates (P less than 0.0005). This observation is consistent with the inference that nutritional deprivation affected the differentiation of hypothalamic centers regulating food intake and growth, and that subsequent increased food availability produced an accumulation of excess fat in an organism growing to its predetermined maximum size.

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Obesity at the age of 50 y in men and women exposed to famine prenatally.

A C J Ravelli, J van der Meulen, C Osmond … (1999)

It was shown that men who were conceived during the Dutch famine of 1944-1945 had higher rates of obesity at age 19 y than those conceived before or after it. Our objective was to study the effects of prenatal exposure to the Dutch famine on obesity in women and men at age 50 y. We measured the body size of 741 people born at term between November 1943 and February 1947 in Amsterdam. We compared people exposed to famine in late, mid, or early gestation (exposed participants) with those born before or conceived after the famine period (nonexposed participants). The body mass index (BMI; in kg/m(2)) of 50-y-old women exposed to famine in early gestation was significantly higher by 7. 4% (95% CI: 0.7%, 14.5%) than that of nonexposed women. BMI did not differ significantly in women exposed in mid gestation (-2.1%; -7.0%, 3.1%) or in late gestation (-1.3%; -6.3%, 3.9%). In 50-y-old men, BMI was not significantly affected by exposure to famine during any stage of gestation: BMI differed by 0.4% (-3.5%, 4.5%) in men exposed to famine in late gestation, by -1.2% (-5.5%, 3.3%) in those exposed in mid gestation, and by 0.5% (-4.6%, 6.0%) in those exposed in early gestation compared with nonexposed men. Maternal malnutrition during early gestation was associated with higher BMI and waist circumference in 50-y-old women but not in men. These findings suggest that pertubations of central endocrine regulatory systems established in early gestation may contribute to the development of abdominal obesity in later life.

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Obstetric and perinatal outcomes in singleton pregnancies resulting from IVF/ICSI: a systematic review and meta-analysis.

Shilpi Pandey, Ashalatha Shetty, Mark Hamilton … (2015)

Earlier reviews have suggested that IVF/ICSI pregnancies are associated with higher risks. However, there have been recent advances in the way IVF/ICSI is done, leading to some controversy as to whether IVF/ICSI singletons are associated with higher perinatal risks. The objective of this systematic review was to provide an up-to-date comparison of obstetric and perinatal outcomes of the singletons born after IVF/ICSI and compare them with those of spontaneous conceptions. Extensive searches were done by two authors. The protocol was agreed a priori. PRISMA guidance was followed. The data were extracted in 2 × 2 tables. Risk ratio and risk difference were calculated on pooled data using Rev Man 5.1. Quality assessment of studies was performed using Critical Appraisal Skills programme. Sensitivity analysis was performed when the heterogeneity was high (I(2) > 50%). There were 20 matched cohort studies and 10 unmatched cohort studies included in this review. IVF/ICSI singleton pregnancies were associated with a higher risk (95% confidence interval) of ante-partum haemorrhage (2.49, 2.30-2.69), congenital anomalies (1.67, 1.33-2.09), hypertensive disorders of pregnancy (1.49, 1.39-1.59), preterm rupture of membranes (1.16, 1.07-1.26), Caesarean section (1.56, 1.51-1.60), low birthweight (1.65, 1.56-1.75), perinatal mortality (1.87, 1.48-2.37), preterm delivery (1.54, 1.47-1.62), gestational diabetes (1.48, 1.33-1.66), induction of labour (1.18, 1.10-1.28) and small for gestational age (1.39, 1.27-1.53). Singletons pregnancies after IVF/ICSI are associated with higher risks of obstetric and perinatal complications when compared with spontaneous conception. Further research is needed to determine which aspect of assisted reproduction technology poses most risk and how this risk can be minimized.