This study assessed the risk for maternal complications in women and neonatal outcomes in children conceived following assisted reproductive treatment as compared with spontaneously conception and also separately evaluated conventional IVF and intracytoplasmic sperm injection (ICSI). The prospective cohort included 1161 women with singleton pregnancies: 561 who conceived following assisted reproduction (223 following IVF and 338 following ICSI) and 600 who conceived spontaneously. No differences were observed in pregnancy complications (including spontaneous abortion, pregnancy-induced hypertension, gestational diabetes and Caesarean delivery) except for significantly increased risk for excess vaginal bleeding in assisted reproduction pregnancies (21.4% versus 12.9%; OR 1.67, 95% CI 1.18–2.37), which was prominent in women who reported polycystic ovary syndrome. Neonates born following assisted reproduction had increased risk for prematurity (10.6% versus 5.3%; OR 1.72, 95% CI 1.04–2.87), and IVF, but not ICSI, was associated with significantly increased risk for prematurity (OR 2.36, 95% CI 1.28–4.37) and low birthweight (OR 1.89, 95% CI 1.03–3.46). In conclusion, this study observed only an increased risk for excess vaginal bleeding as a pregnancy-associated complication in singleton pregnancies following assisted compared with spontaneous conception. However, singleton neonates born following IVF, but not ICSI, were at increased risk for prematurity.
The current study evaluated the risk for maternal complications in women and outcomes of children conceived following assisted reproduction treatment as compared with spontaneously conceived pregnancies. In addition, conventional IVF and intracytoplasmic sperm injection (ICSI) were separately evaluated against spontaneously conceived pregnancies. The study cohort included 1161 women with singleton pregnancies: 561 who conceived following assisted reproduction (223 following IVF and 338 following ICSI) and 600 women who conceived spontaneously. No differences were observed in the risk for complications during pregnancy including spontaneous abortion, pregnancy-induced hypertension, gestational diabetes and Caesarean delivery, except for a significantly increased 1.6-fold risk for vaginal bleeding in assisted reproduction treatment. A 1.7-fold excess risk for prematurity was present in the assisted reproduction group. When the two assisted reproduction methods were compared separately with spontaneous conception, IVF cycles were associated with significantly increased risk for prematurity and low birthweight. However, no significantly increased risk was found in preterm birth or low birthweight following ICSI as compare to spontaneous conception. In conclusion, this study did not show increased risk of pregnancy-associated complications in singleton pregnancies following assisted reproduction compared with spontaneous pregnancies except for excess vaginal bleeding. However, singleton neonatals born following IVF, but not ICSI, were at increased risk for prematurity.
Introduction
Despite the widespread use of assisted reproduction treatment, there is still concern regarding the safety of these treatments to both mothers and their neonates. Although the rate of multiple births following assisted reproduction is increased as compared with spontaneously conceived pregnancies and complications following multiple births are well known (McDonald et al., 2005), singleton assisted reproduction pregnancies are also at increased risk for adverse pregnancy outcome compared with spontaneously conceived singleton pregnancies, as reported in two systematic reviews (Helmerhorst et al., 2004, Jackson et al., 2004). These include an increased risk for preterm birth (<37 weeks), low birthweight (<2500 g) and very low birthweight (<1500 g), small-for-gestational-age and Caesarean delivery. In addition, Jackson et al. (2004) reported increased risk for maternal complications including placenta praevia, vaginal bleeding, pre-eclampsia and gestational diabetes mellitus.
Although maternal age and parity were usually adjusted in these analyses, data regarding other potential confounders such as past obstetric outcome, medical history, infertility (type and treatment), smoking, educational level and body mass index (BMI) are limited.
In Israel, assisted reproduction treatment is funded in the framework of the national health insurance for the first two children, with no limitation on the number of treatment cycles for women up to the age of 45. Currently, 4.2% of all live births in Israel are conceived following assisted reproduction and the percentage is rising (Department of Health Information, Ministry of Health, Israel, 2010). Considering recent concerns (Helmerhorst et al., 2004, Jackson et al., 2004, McDonald et al., 2009) and the increasing number of children born following assisted reproduction, this study was designed to evaluate the risks for maternal and neonatal complications following assisted reproduction treatment as compared with spontaneously conceived pregnancies, as well as conventional IVF and intracytoplasmic sperm injection (ICSI) compared with spontaneously conceived pregnancies.
Section snippets
Materials and methods
The prospective cohort was composed of singleton pregnancies following assisted reproduction and spontaneously conceived singleton pregnancies. Women were identified at 6–12 weeks of gestation, during ultrasound examination at the two participating IVF units (Sheba Medical Centre and Assaf Harofeh Medical Centre). Spontaneously conceived pregnancies were recruited at five community women’s healthcare centres and at the two participating medical centres. Of these, 133 women were identified during
Results
The prospective cohort was composed of 1161 women: 561 women pregnant following assisted reproduction, of whom 52 terminated with abortions (45 spontaneous and seven induced) and 509 births, including one stillbirth. The spontaneous conception group included 600 women: 467 recruited during their post-delivery hospitalization and 133 recruited at the beginning of pregnancy, of whom 11 had spontaneous abortions and two had induced abortions, resulting in a total of 587 live births.
The maternal
Discussion
This prospective study conducted in Israel followed women who conceived by assisted reproduction treatment in comparison to women conceiving spontaneously. This study reports three main findings. Firstly, no increased risk for spontaneous abortions was observed with assisted reproduction treatment compared with spontaneous conception. Secondly, after adjustment for maternal characteristics, pregnancy complications were similar except for an increased risk for vaginal bleeding. Thirdly, assisted
Acknowledgement
The study was partially funded by the Israel National Institute for Health Policy and Health Services Research (Grant no. 05/79).
Comparison of cryopreservation of supernumerary pronuclear human oocytes obtained after intracytoplasmic sperm injection (ICSI) and after conventional in-vitro fertilization
Hum. Reprod.
(1996)
Department of Health Information, Ministry of Health, Israel, 2010. In vitro fertilization (IVF) treatments....
P. De Sutter et al.
First-trimester bleeding and pregnancy outcome in singletons after assisted reproduction
What are the risk factors for prematurity other than intrauterine growth restriction in singletons after IVF?
Data were collected from a national registry, based on an observational prospective cohort of 30,737 live births after assisted reproductive technology (fresh embryo transfers: n = 20,932 and frozen embryo transfer [FET] n = 9805) between 2014 and 2015. A population of not-small for gestational age singletons conceived after fresh embryo transfers and FET, and their parents, was selected. Data on a number of variables were collected, including type of infertility, number of oocytes retrieved and vanishing twins.
Preterm birth occurred in 7.7% (n = 1607) of fresh embryo transfers and 6.2% (n = 611) of frozen–thawed embryo transfers (P < 0.0001; adjusted odds ratio [aOR] = 1.34 [1.21–1.49]). Endometriosis and vanishing twin increased the risk of preterm birth after fresh embryo transfer (P < 0.001; aOR 1.32 and 1.78, respectively). Polycystic ovaries or more than 20 oocytes retrieved also increased preterm birth risk (aOR 1.31 and 1.30; P = 0.003 and P = 0.02, respectively); large oocyte cohort (>20) was no longer associated with the risk of prematurity in FET.
Endometriosis remains a risk for prematurity even in the absence of intrauterine growth retardation, which suggests a dysimmune effect. Large oocyte cohorts obtained by stimulation, without clinical polycystic ovary syndrome diagnosed before attempts, do not affect FET outcomes, reinforcing the idea of a phenotypic difference in the clinical presentation of polycystic ovary syndrome.
The elevated number of multiple pregnancies is the most serious and frequent complication of ART. Twin pregnancies are associated with higher rates of obstetrical complications, preterm delivery, and perinatal morbidity and mortality than singleton pregnancies.3–7 Moreover, it is well documented in different studies that ART singleton pregnancies are at a higher risk for adverse obstetrical and perinatal outcomes than those conceived spontaneously.8–11
The rate of twin pregnancies conceived via assisted reproductive technology has increased markedly in recent years. The elevated number of multiple pregnancies is the most serious and frequent complication of assisted reproductive technology. Twin pregnancies are associated with higher rates of obstetrical complications, preterm delivery, and perinatal morbidity and mortality than singleton pregnancies.
This study aimed to investigate the association between the mode of conception and obstetrical and perinatal outcomes in twin pregnancies, adjusting for parity, age, and chorionicity.
This was a retrospective cohort study of 1135 twin pregnancies between May 2006 and April 2021. All spontaneous (n=369) and assisted reproductive technology–conceived (n=766) twin pregnancies with antenatal care and delivery in the Universitari Quiron-Dexeus Hospital, Barcelona, Spain, a tertiary obstetrical care center, were studied according to chorionicity.
The mean maternal age was higher among assisted reproductive technology twin pregnancies than among naturally conceived ones, and there were also less parous women in the assisted reproductive technology twin group. The global survival rates in both groups of twins were practically identical, namely 744 of 766 (97.1%) assisted reproductive technology twins and 357 of 369 (96.8%) spontaneously conceived twins. Patients with dichorionic assisted reproductive technology twins had a higher incidence of gestational diabetes (relative risk, 1.69; 95% confidence interval, 1.10–2.59) and gestational hypertension or preeclampsia (relative risk, 2.75; 95% confidence interval, 1.60–4.729). Monochorionic diamniotic assisted reproductive technology twins had a higher risk for gestational diabetes (relative risk, 4.12; 95% confidence interval, 1.35–12.56). We analyzed the gestational age at delivery, onset of labor, type of delivery, rate of preterm births, weight discordance, rate of small for gestational age neonates and intrauterine growth restriction, and admission to the neonatal intensive care unit. We could not find any statistical differences between monochorionic diamniotic assisted reproductive technology twins and spontaneously conceived twins. Among dichorionic twins, those conceived by assisted reproductive technology had an earlier gestational age at delivery (36.3±2.29 vs 36.6±2; P<.05) and we found statistical differences in the onset of labor with more cesarean deliveries (relative risk, 1.27; 95% confidence interval, 1.06–1.51). When adjusting for cofounding factors (maternal age, parity, chorionicity), the type of conception remained an independent risk factor for gestational hypertension and preeclampsia but not for gestational diabetes or cesarean delivery.
Pregnancy outcomes are comparable between assisted reproductive technology and spontaneously conceived twins, and when adjusted for confounding factors, only the risk for gestational hypertension and preeclampsia remained increased in the assisted reproductive technology group.
The aim of the current research was to evaluate cognitive development, visual-motor ability, attention, and verbal and performance skills required for successful scholastic achievement, all of which become more obvious and significant during early school years. This is a follow-up study of a cohort recruited in the perinatal period [9], thus together with the maternal reproductive health data available, it could serve to elucidate possible associations between reproductive health, ART and cognitive outcomes, in order to improve the quality of information given to couples considering ART. This prospective follow-up study of an Israeli cohort originally included 561 ART and 600 spontaneously-conceived (SC) singleton pregnancies, who were recruited from June 2006 to December 2008 [9].
While assisted reproductive technology is increasingly prevalent, there is concern amid conflicting findings reported regarding the long-term outcomes of children born following these treatments. The aim of this research was to investigate aspects of cognitive development in early school-age Israeli children born following assisted reproductive technology (ART) treatments, compared to those spontaneously conceived (SC).
This prospective follow-up study was based on an Israeli cohort recruited from June 2006 to December 2008, that included 561 women whose pregnancies were achieved by ART treatments and 600 women whose pregnancies were SC. When the children were 7–8 years old, 759 of their mothers were interviewed by telephone, and 294 were came for developmental assessment. The examination included: Kaufman Brief Intelligence Test; Kaufman Assessment Battery for Children (arithmetic only); Test of Everyday Attention for Children; Beery-Buktenica Developmental Test of Visual-Motor Integration and Supplemental Test for Visual Perception; Rey-Osterrieth Complex Figure Test; Aleph-ad-Tav Hebrew reading and writing; Tavor Picture Naming Expressive Vocabulary Test. Multivariable analyses were adjusted for maternal years of education (≤12, 13+) at child's birth and child's sex.
Cognitive function, visual-motor ability, attention, and verbal skills of children born after ART treatments were similar to those of SC children, upon both univariate and multivariable analysis.
No significant differences were found between the ART and SC groups on any of the measures examined. This finding offers couples seeking ART treatments improved information regarding child development during the important and formative school years.
Increasing rates of ART treatments arouse concern about long-term outcomes for offspring, and conflicting findings have been reported with respect to the skills necessary to their academic success. This prospective follow-up study compared school-age children born following ART with spontaneously-conceived children. Children were examined by developmental psychologists, and cognitive function, visual-motor, attention, verbal, and performance skills were similar in both groups.
When comparing the differences in the risks of hypospadias and cryptorchidism between IVF and ICSI, we concluded that these 2 main ART methods had no significantly different effects on the risk of hypospadias or cryptorchidism in offspring. In contrast to our findings, several studies have shown that ICSI may be more likely to cause urogenital tract defects in offspring than IVF [20,22,49,50]. In general, those studies had relatively small sample sizes for IVF and ICSI; therefore, these results need to be confirmed by more clinical studies.
A systematic review was conducted to evaluate the relationship between ART and the risk of urogenital tract malformations, especially hypospadias and cryptorchidism. Thirty-three papers were selected. Meta-analysis showed that ART was correlated with an increased risk of urogenital tract malformation in offspring (odds ratio (OR) = 1.61, 95% confidence interval (CI): 1.41–1.85), hypospadias (OR = 1.87, 95% CI: 1.47–2.40) and cryptorchidism (OR = 1.83, 95% CI: 1.54–2.18). Among offspring conceived by ART, multiple pregnancies appeared to result in a higher risk of urogenital tract malformation than singleton pregnancies (OR = 1.42, 95% CI: 0.99–2.04; P = 0.058). No significant difference in the risk of urogenital tract malformation was found between in vitro fertilization and intracytoplasmic sperm injection technologies. A sensitivity analysis showed that the above conclusions were relatively consistent. Conclusion: ART is correlated with an increased risk of urogenital tract malformations in offspring, especially hypospadias and cryptorchidism. Among ART offspring, multiple pregnancies may lead to a higher risk of urogenital tract malformations than singleton pregnancies, but more studies are needed for confirmation.
Considering the high prevalence of both ART and obesity, the objective of this study was to analyse data from an Israeli prospective cohort in order to assess the effect of pre-pregnancy BMI and inappropriate GWG on the risk for adverse obstetrical outcomes among women undergoing ART treatments as compared to spontaneously-conceived (SC) pregnancies. The study population consisted of participants from a prospective cohort described in detail elsewhere [10]. Briefly, the cohort comprised 509 women with singleton pregnancies following ART treatments and 587 women with SC singleton pregnancies from two medical centres (Sheba Medical Centre and Assaf Harofeh Medical Centre).
To compare the effect of pre-pregnancy body mass index (BMI) and inappropriate gestational weight gain (GWG) on adverse obstetrical outcomes among women undergoing assisted reproductive technology (ART) treatments as compared to spontaneously-conceived (SC) pregnancies.
This prospective cohort study included 1058 pregnant women from two medical centres; 504 women who conceived following ART treatments and 554 who conceived spontaneously. The women were recruited at 8 weeks of gestation and follow-up telephone interviews were conducted 6 weeks after delivery. Obstetrical outcomes included pregnancy hypertension, gestational diabetes (GD), low birth weight (LBW) (<2500 g) and small for gestational age (SGA). Multivariate analyses were used to assess the effect of pre-pregnancy BMI and inappropriate GWG on these obstetrical outcomes adjusted for risk factors.
The effect of pre-pregnancy BMI and inappropriate GWG on adverse obstetrical outcomes did not differ between ART and SC pregnancies. Pre-pregnancy obesity was found to be associated with increased risk for pregnancy hypertension (OR = 2.16; 95%CI 1.16–4.03), GD (OR = 2.89; 95%CI 1.61–5.17), caesarian section (OR = 1.77; 95%CI 1.10–2.85) and SGA (OR = 1.91; 95%CI 1.05–3.46). GWG below recommendations was associated with increased risk for GD (OR = 1.73; 95%CI 1.06–2.82) and SGA (OR = 1.69; 95%CI 1.17–2.40) while GWG above recommendations was associated with increased risk for pregnancy hypertension (OR = 1.77; 95%CI 1.02–3.06).
Pre-pregnancy obesity and inappropriate GWG were associated with adverse obstetrical outcomes in both ART and SC pregnancies. Emphasis should be given on the importance of an optimal pre-pregnancy BMI and appropriate GWG during pregnancy.
Adel Farhi, PhD, MHA is a senior researcher in epidemiology and public health with special emphasis on reproductive epidemiology at the Women and Children’s Health Research Unit at the Gertner Institute for Epidemiology and Health Policy Research. Dr. Farhi received her PhD in epidemiology and preventive medicine from School of Public Health, Sackler Faculty of Medicine in 2010 and her Master degree in health administration from the Faculty of Management, Leon Recanati Graduate School of Business Administration at Tel-Aviv University.
