Does subfertility explain the risk of poor perinatal outcome after IVF and ovarian hyperstimulation?

Leiden University, Leyden, South Holland, Netherlands
Human Reproduction (Impact Factor: 4.57). 12/2006; 21(12):3228-34. DOI: 10.1093/humrep/del311
Source: PubMed


The primary objective of this study was to investigate whether subfertility explains poor perinatal outcome after assisted conception. A secondary objective was to test the hypothesis that ovarian hyperstimulation rather than the IVF procedure may influence the perinatal outcome.
Using data from a Dutch population-based historical cohort of women treated for subfertility, we compared perinatal outcome of singletons conceived after controlled ovarian hyperstimulation (COHS) and IVF (IVF + COHS; n = 2239) with perinatal outcome in subfertile women who conceived spontaneously (subfertile controls; n = 6343) and in women who only received COHS (COHS only; n = 84). Furthermore, we compared perinatal outcome of singletons conceived after the transfer of thawed embryos with (Stim + Cryo; n = 66) and without COHS (Stim - Cryo; n = 73).
The odds ratios (ORs) for very low birthweight (<1500 g) and low birthweight (1500-2500 g) were 2.8 [95% confidence interval (95% CI) 1.9-3.9] and 1.6 (95% CI 1.2-1.8) in the IVF + COHS group compared with the subfertile control group. The ORs for very preterm birth (<32 weeks) and for preterm birth (32-37 weeks) were 2.0 (95% CI 1.4-2.9) and 1.5 (95% CI 1.3-1.8), respectively. Adjustment for confounders did not materially change these risk estimates. The difference in risk between the COHS-only group and the subfertile group was significant only for very low birthweight (OR 3.5; 95% CI 1.1-11.4), but the association became weaker after adjustment for maternal age and primiparity (OR 3.1; 95% CI 1.0-10.4). No significant difference in birthweight and preterm delivery was found between the group of children conceived after ovarian stimulation/ovulation induction and (Stim + Cryo) and the group of children conceived after embryo transfer of thawed embryos in a spontaneous cycle without ovarian stimulation/ovulation induction (Stim - Cryo).
The poor perinatal outcome in this database could not be explained by subfertility and suggests that other factors may be important in the known association between assisted conception and poor perinatal outcome.

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    • "Furthermore , a 1.1-fold risk of congenital malformations has been published (Zhu et al., 2006). In the study of Kapitejn et al., the rates of low and very low birthweights, and preterm and very preterm infants born after natural pregnancies to subfertile women, were compared with the corresponding rates among women conceived after ovarian hyperstimulation, IVF and hyperstimulation or frozen embryo transfer in a natural cycle, concluded that both the method and subfertility partly explained the observed impaired pregnancy outcomes , not solely subfertility (Kapiteijn et al., 2006). During childhood, also, psychomotor development and behavioural problems of these children has been compared, being very similar for both groups regardless of treatment (Zhu et al., 2009; Middelburg et al., 2010; Zhu et al., 2011). "
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    ABSTRACT: Adverse obstetric outcomes in pregnancies achieved through assisted reproductive technology (ART) could either be due to the technology or to the underlying subfertility or to both. To address this issue, we compared the pregnancy outcomes of singletons conceived naturally after a long time to pregnancy (TTP) with those of ART pregnancies. We analysed an existing birth database. Altogether 428 ART pregnancies were compared with 928 spontaneously conceived pregnancies with TTP of 2 years or more, during the period 1989-2007 at Kuopio University Hospital, Finland. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for pregnancy outcomes. Between treated and untreated subfertile women no significant differences were found in the rates of Caesarean sections (OR 1.21, 95% CI 0.89-1.64), preterm births (OR 1.28, 95% CI 0.81-2.03), small for gestational age (SGA) birthweight (OR 0.95, 95% CI 0.65-1.39), need of neonatal intensive care (OR 1.28, 95% CI 0.88-1.88) or low Apgar scores (OR 1.19, 95% CI 0.47-3.04). However, compared with pregnancies of women with TTP 0-6 months, ART pregnancies had significantly increased risks of preterm or very preterm birth, low birthweight and need of neonatal intensive care. The risks of preterm birth, SGA, need for neonatal intensive care and low Apgar scores were not significantly different between subfertile women who conceived spontaneously and those who conceived through ART indicating that maternal factors relating to subfertility and not only infertility treatment are associated with adverse pregnancy outcomes.
    Preview · Article · Feb 2012 · Human Reproduction
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    • "The etiology of these complications is likely diverse: the infertile population could be predisposed to diseases (Draper et al., 1999; Bahceci et al., 2005; Kapiteijn et al., 2006); epigenetic dysregulation, or altered placentation following in vitro culture are additional possibilities . Given the key role of the placenta throughout pregnancy, and the evidence of placental abnormalities in ART pregnancies, we hypothesized that ART may lead to suboptimal placentation that may cause impaired embryo development. "
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    ABSTRACT: Abnormal placentation is a potential mechanism to explain the increased incidence of low birthweight observed after IVF. This study evaluates, in a mouse model, whether the method of conception and embryo transfer affect placentation and fetal development. IVF blastocysts (CF1 x B6D2F1/J) were cultured in Whitten's medium (IVF(WM), n = 55) or K modified simplex optimized medium with amino acids (IVF(KAA), n = 56). Embryos were transferred to the uteri of pseudo-pregnant recipients. Two control groups were created: unmanipulated embryos produced by natural mating (in vivo group, n = 64) and embryos produced by natural mating that were flushed from uterus and immediately transferred to pseudo-pregnant recipients (flushed blastocysts, FB group, n = 57). At gestation age 12.5 days, implantation sites were collected and fixed; fetuses and placentas were weighed and their developmental stage (DS) evaluated. Placental areas and vascular volume fractions were calculated; parametric statistics were applied as appropriate. IVF fetuses showed a modest but significant delay in development compared with FB mice (P < 0.05). In addition, IVF conceptuses were consistently smaller than FB (P < 0.05). Importantly, these differences persisted when analyzing fetuses of similar DS. The placenta/fetus ratio was larger in the IVF group (IVF(WM) 0.95; IVF(KAA) = 0.90) than the FB group (0.72) (P < 0.05 for all comparisons). Gross morphology of the placenta and ratio labyrinth/fetal area were equivalent in the IVF and FB groups, as were percentage of fetal blood vessels, maternal blood spaces and trophoblastic components. In vitro embryo culture affects fetal and placental development; this could explain the lower birthweight in IVF offspring.
    Full-text · Article · Aug 2010 · Human Reproduction
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    • "Potential IVF/ICSI associated adverse pregnancy outcomes that have been reported in previous studies include multiple births, birth defects, low birth weight, preterm birth, fetal growth restriction, maternal complications, and neonatal morbidity [5– 18]. However, except for multiple births, studies on the associations of IVF/ICSI with other adverse pregnancy outcomes have so far yielded inconsistent results [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18]. Differences in study population and methodology are the main reasons for the inconsistent findings. "
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    ABSTRACT: To assess the association between in vitro fertilization (IVF) with or without intracytoplasmic sperm injection (ICSI) and adverse birth outcomes. Retrospective cohort study involved IVF/ICSI patients who were treated in the Ottawa Fertility Centre from 1996 to 2005 with a viable pregnancy (>20 weeks of gestation) and mothers who conceived naturally. Eleven of the 1044 infants conceived with IVF/ICSI (1.1%) and 7 of the 1910 naturally conceived infants (0.4%) had congenital heart defects (P<0.01). Five of the 138 infants (3.6%) born to mothers with a body mass index>30 and conceived by IVF/ICSI had congenital heart defects, compared with none in the 240 infants born to mothers with a body mass index>30 and conceived naturally (P<0.01). Infants conceived with use of IVF/ICSI have three times as high a risk of a congenital heart defect as naturally conceived infants.
    Full-text · Article · Mar 2010 · European journal of obstetrics, gynecology, and reproductive biology
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