Preterm birth, low birth weight among in vitro fertilization singletons: A systematic review, meta-analyses

Division of Maternal-Fetal Medicine, Department of Obstetrics & Gynecology, McMaster University, Hamilton, Canada.
European journal of obstetrics, gynecology, and reproductive biology (Impact Factor: 1.7). 08/2009; 146(2):138-48. DOI: 10.1016/j.ejogrb.2009.05.035
Source: PubMed


Our objective was to determine the risks of preterm birth (PTB) and low birth weight (LBW) in singletons conceived through in vitro fertilization (IVF)+/-intracytoplasmic sperm injection (ICSI) compared to spontaneously conceived singletons after matching or controlling for at least maternal age. The MOOSE guidelines for meta-analysis of observational studies were followed. Medline and Embase were searched using comprehensive search strategies. Bibliographies of identified articles were reviewed. English language studies examining LBW or PTB in singletons conceived by IVF or IVF/intracytoplasmic sperm injection, compared with spontaneously conceived singletons, that matched or controlled for at least maternal age. Two reviewers independently assessed titles, abstracts, full articles and study quality and extracted data. Dichotomous data were meta-analyzed using relative risks (RR) as measures of effect size with a random effects model and for continuous data weighted mean difference was calculated. Seventeen studies were included with 31,032 singletons conceived through IVF (+/-ICSI) and 81,119 spontaneously conceived singletons. After matching or controlling for maternal age and often other factors, compared to spontaneously conceived singletons, IVF singletons had increased risks of our two primary outcomes, PTB (RR 1.84, 95% CI 1.54, 2.21) and LBW (<2500 g, RR 1.60, 95% CI 1.29, 1.98). Singletons conceived through IVF or IVF/ICSI were at increased risk for late PTB (32-36 weeks, RR 1.52, 95% CI 1.01, 2.30), moderate PTB <32-33 weeks (RR 2.27, 95% CI 1.73, 2.97), very LBW (<1500 g, RR 2.65, 95% CI 1.83, 3.84), and intrauterine growth restriction (RR 1.45, 95% CI 1.04, 2.00), lower birth weights (-97 g, 95% CI -161 g, -33 g) and shorter mean gestations (-0.6 weeks, 95% CI -0.9 weeks, -0.4 weeks). In conclusion, IVF singletons have significantly increased risks of PTB, LBW and other adverse perinatal outcomes compared to spontaneously conceived singletons after matching or controlling for maternal age at least.

16 Reads
  • Source
    • "Pregnancies following assisted reproductive treatments (ART) are associated with a significantly higher risk of adverse obstetric outcomes such as preterm birth (PTB) and low birthweight (LBW) compared with spontaneous pregnancies (Schieve et al., 2007; McDonald et al., 2009, 2010). The possible reason for adverse obstetric outcomes following ART has been attributed to the underlying infertility itself and embryo specific epigenetic modifications due to the IVF techniques (Pinborg et al., 2013). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Is there a relation between the number of oocytes retrieved following ovarian stimulation and obstetric outcomes of preterm birth (PTB) and low birthweight (LBW) following IVF treatment? There is an increased risk of PTB (<37 weeks gestation) and LBW (<2500 g) following IVF in women with a high number (>20) of oocytes retrieved. Pregnancies resulting from assisted reproductive treatments (ART) are associated with a higher risk of pregnancy complications compared with spontaneously conceived pregnancies. Whether ovarian ageing in women with poor ovarian response is associated with an increased risk of adverse obstetric outcomes is debated. It is also unclear if an excessive response and high egg numbers following ovarian stimulation have an association with adverse obstetric outcomes. Observational study using anonymized data on all IVF cycles performed in the UK from August 1991 to June 2008. Data from 402 185 IVF cycles and 65 868 singleton live birth outcomes were analysed. Data on all women undergoing a stimulated fresh IVF cycle with at least one oocyte retrieved between 1991 and June 2008 were analysed for birth outcomes. Logistic regression analysis of the association between ovarian response (quantified as number of oocytes retrieved) and outcomes of PTB and LBW was performed. There was a significantly higher risk of adverse obstetric outcomes of PTB and LBW among women with an excessive response (>20 oocytes) compared with women with a normal response (10-15 oocytes): adjusted odds ratio (OR) 1.15, 95% confidence interval (CI) 1.03-1.28 for PTB, adjusted OR 1.17, 95% CI 1.05-1.30 for LBW, respectively. There was no increased risk of the adverse outcomes among women with a poor ovarian response (≤3 oocytes) compared with women with a normal response: adjusted OR 0.88, 95% CI 0.76-1.01 for PTB, adjusted OR 0.92, 95% CI 0.79-1.06 for LBW, respectively. Although the analysis was adjusted for a number of potential confounders, the dataset had no information on other important confounders such as smoking, BMI and the medical history of women during pregnancy. Furthermore, the dataset did not allow specific identification of women with PCOS and its anonymized nature did not make it permissible to analyse one cycle per woman. Analysis of this large dataset suggests that a high oocyte number (>20) following IVF is associated with a higher risk of PTB and LBW. These findings lead to speculation whether ovarian dysfunction and/or an altered endometrial milieu resulting from supraphysiological steroid levels underlie the unfavourable outcomes and warrant further research. Ovarian stimulation regimens should optimize the number of oocytes retrieved to avoid the risk of adverse outcomes associated with very high numbers of oocytes. No funding was obtained. There are no competing interests to declare. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email:
    Human Reproduction 04/2015; 30(6). DOI:10.1093/humrep/dev076 · 4.57 Impact Factor
  • Source
    • " ) and an overall level of bias for each paper was determined from a combination of these subgroups ( Appendix S2 ) . Each type of bias was classified as ' minimal , ' ' low , ' ' moderate ' or ' high , ' and combined to form the overall level of bias for the paper . This method of bias and quality appraisal is described in more detail elsewhere ( McDonald et al . , 2009 ) ."
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Given the growing prevalence of birth by Caesarean section (CS) worldwide, it is important to understand any long-term effects CS delivery may have on a child's development. We assessed the impact of mode of delivery on autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD).Methods We conducted a systematic review of the literature in PubMed, Embase, CINAHL, PsycINFO and Web of Science up to 28 February 2014. No publication date, language, location or age restrictions were employed.ResultsThirteen studies reported an adjusted estimate for CS-ASD, producing a pooled odds ratio (OR) of 1.23 (95% CI: 1.07, 1.40). Two studies reported an adjusted estimate for CS-ADHD, producing a pooled OR of 1.07 (95% CI: 0.86, 1.33).Conclusions Delivery by CS is associated with a modest increased odds of ASD, and possibly ADHD, when compared to vaginal delivery. Although the effect may be due to residual confounding, the current and accelerating rate of CS implies that even a small increase in the odds of disorders, such as ASD or ADHD, may have a large impact on the society as a whole. This warrants further investigation.
    Journal of Child Psychology and Psychiatry 10/2014; 56(5). DOI:10.1111/jcpp.12351 · 6.46 Impact Factor
  • Source
    • "The findings reported herein, therefore, indicate that singleton pregnancies complicated by severe OHSS, necessitating ascitic or pleural fluid drainage, are not at risk for obstetric complications, except probably for preterm labor. While, studies relating to hypertensive diseases of pregnancy, gestational diabetes and IUGR show contradictory results [14-17], the observed increased prevalence of preterm labor (12.5%) in our study, is in accordance with previous studies [14,16,17], and is also a well-known complication of IVF pregnancies in general [20]. Moreover, the observed single case of unexplained antepartum fetal death requires attention and raises the question whether it is accidental or is associated to severe OHSS. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Various inflammatory cytokines have been implicated in the pathophysiology of severe ovarian hyperstimulation syndrome, as well as, various pregnancy complications, including preterm labor, pregnancy induced hypertension/preeclampsia and intra-uterine growth restriction. We aim to determine whether severe OHSS, complicated by third space fluid accumulation necessitating drainage, is associated with increased risk of late obstetrics complications. Methods We assessed the obstetrics and neonatal outcome measures of 16 patients admitted to our gynecology ward during a 6-year period, with severe OHSS complicated by third space fluid accumulation necessitating drainage. Results Patients delivered at 37.3 ± 5.9weeks, with a mean birth weight of 3062 ± 757 gr. There was no single case of gestational diabetes, hypertensive diseases of pregnancy, nor placental abruption. Two (12.5%) patients had preterm delivery: one at 23 weeks’ gestation and one at 28 weeks’ gestation following preterm premature rupture of membrane. Another patient experienced an unexplained antepartum fetal death at 27 weeks’ gestation. Conclusions Severe OHSS, complicated by third space fluid sequestration necessitating drainage, is not associated with adverse late pregnancy outcome, except probably for preterm labor. Following resolution of the OHSS, pregnancies should be regarded as any pregnancy resulting from IVF treatment, with special attention to prevent preterm labor.
    Journal of Ovarian Research 05/2014; 7(1):56. DOI:10.1186/1757-2215-7-56 · 2.43 Impact Factor
Show more