Infertility and preterm delivery, birthweight, and Caesarean section: a study within the Danish National Birth Cohort

Objective To estimate the effect of assisted reproductive technology (ART) on major malformation (MM) rate in ART offspring independent of the effect of subfertility on MM. Design Meta-analysis. Methods This meta-analysis is based on our previously published meta-analysis of observational studies evaluating the relationship between ART treatment and MM rates, as well as recent research by Zhu et al. to estimate the impact of subfertility alone on MM in subfertile couples conceiving spontaneously. Results The overall odds ratio for MM in our original metaanalysis, in which all studies used apparently inappropriate control groups of "normal" populations, was 1.29 (95% CI 1.01-1.67). Here we attempted to estimate the risk of subfertility and used this estimate to perform an adjusted meta-analysis. Zhu et al. found that about 40% of the odds of MM was due to subfertility. When we took Zhu's finding into account, the adjusted odds ratio in the meta-analysis was 1.01 (95% CI 0.82-1.23). Conclusions Our study suggests ART does not increase the risk of MM as much as previously reported. More research is needed to quantify the underlying risk of subfertility and separate it from the risk associated with ART. Physicians who counsel subfertile couples should recognize that previous studies of MM rates in ART patients probably overestimated the risk.

Section: Introductionsupporting

confidence: 87%

Section: Protective Effectmentioning

confidence: 99%

A meta-analysis of the impact of IVF and ICSI on major malformations after adjusting for the effect of subfertility

Rimm

Katayama

Katayama³

2011

“…Recurrent pregnancy loss is an indicator for increased risk for birth defects, again without regard to the use of ART (31). In two large registry studies (32,33) infertility itself, independent of treatment, appears to be associated with preterm birth and other adverse birth outcomes. The female partners of couples undergoing ART have been found to exhibit an increased frequency of chromosomal abnormalities (34).…”

Section: Discussionmentioning

confidence: 99%

A Meta-Analysis of Controlled Studies Comparing Major Malformation Rates in IVF and ICSI Infants with Naturally Conceived Children

Rimm

Katayama²,

Diaz

et al. 2004

250

120

Purpose : To estimate the risk of major malformations in IVF and ICSI infants. Methods : Forty-four studies published in English since 1990 where the major malformation rate for IVF or ICSI cases was compared to an appropriate control group were reviewed. Nineteen studies met all selection criteria. In addition, a quality score was developed to assess each study based on sample size, timing of diagnosis, appropriateness of control group and other factors. Results : In 19 studies, the major malformation rates ranged from 0-9.5% for IVF; 1.1-9.7 for ICSI; and 0-6.9% in the control groups. When ICSI was compared to IVF, and multiple births compared to singleton, there were no statistically significant differences. When data from 16 studies involving 28,524 IVF infants and 2,520,988 spontaneously conceived controls and 7 studies involving 7234 ICSI infants and 978,078 controls were pooled, we found an overall odds ratio for the 19 studies of 1.29 (95% CI 1.01-1.67). Conclusions : The overall odds ratio of 1.29 was statistically significant at the 5% level. These results may be useful for counseling ART patients and properly designing the consent forms used for ART procedures. It is not clear whether this risk is due to the procedures used in ART. We found that some of these studies have design flaws. All of them lacked an appropriate control group, i.e. infertile patients conceiving spontaneously. These flaws may create biases that would in almost all instances increase the risk of major malformations in the study group. Further research with better designed studies will likely result in a better estimate of the risk of major malformations associated with IVF and ICSI.KEY WORDS: ART major malformation rate; IVF/ICSI major malformation rate; meta-analysis.

“…Unadjusted analyses suggest a 2-fold increased risk of preeclampsia, placental abruption, Caesarean section, and vacuum extraction, and a 5-fold increased risk of placenta previa in spontaneous singleton pregnancies in women with a history of infertility compared with the general population [7]. Analyses adjusted for age and parity suggest a 1.4-1.8-fold increase in risk for preterm delivery in women requiring greater than 1 year to spontaneously conceive singleton pregnancies, compared with women conceiving without delay [8,9]. A 3-fold increased risk of perinatal mortality has been observed in women with untreated infertility compared to women without infertility after adjusting for potential confounders [10].…”

Section: Introductionmentioning

confidence: 92%

Congenital anomalies and other perinatal outcomes in ICSI vs. naturally conceived pregnancies: a comparative study

Al-Fifi

Al-Binali

Al-Shahrani

et al. 2009