Assisted Reproductive Technology is associated with higher risk of Birth Defects!

Since 1981, ART has been used in the United States. Today approximately 1.6% of all infants born in the United States every year are conceived using ART.  According to 2014 data by CDC, 208,786 ART cycles were performed, resulting in 57,332 live births (deliveries of one or more living infants) and 70,352 live born infants.

As the number of infants conceived by ART continues to increase, it was observed that those conceived after Assisted Reproductive Technology (ART) was born with several Birth defects, especially nonchromosomal birth defects as compared to those conceived the natural way! In fact according to CDC, the risk of certain birth defects was 2 to 4 fold as compared to those conceived naturally.

The largest study of its kind was published in April issue of JAMA pediatrics. The researchers linked ART surveillance, birth certificates, and birth defects registry data for 3 states (Florida, Massachusetts, and Michigan) during a period of 10 years from 2000-2010. The exposure studied was ART and certain techniques among ART births. The main outcome measures were prevalence of selected chromosomal and nonchromosomal birth defects that are usually diagnosed at or immediately after birth.

Of the total 4,618,076 live births, 64,861 or (1.4%) were conceived using ART. According to the lead investigator Sheree L. Boulet, DrPH, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia higher prevalence of  nonchromosomal birth defects (59.57 per 10,000) in ART infants compared with non-ART infants (48.40 per 10,000, P<0.001) was reported. Even after adjustment of all the confounders (maternal age), there was 28% higher risk of non chromosomal anomolies with ART.

Infants born after ART were also more likely to be born prematurely, have lower birth weights and mothers who underwent ART were higher educated, nulliparous, career oriented, elderly (>30 Years) and non-Hispanic white. They were also more likely to have Diabetes and Hypertension.

The birth defects most commonly observed were reduction deformity of the lower limbs (P=0.007), rectal and large intestinal atresia/stenosis (P<0.001), and tracheoesophageal fistula/esophageal atresia (P=0.001) compared with those conceived spontaneously. No statistically significant difference in birth defects was seen among fresh vs frozen embryos.

Other systemic reviews, metaanalysis and registry based studies have also concluded that birth defects are more common in infants conceived after ART, and stress upon need of further research according to various sub-groups of ART.

It was also seen that maternal age is inversely related to risk for chromosomal defects in ART, including trisomy 13, trisomy 21 (Down syndrome), and trisomy 18, probably because older mother undergo Preimplantation Genetic Diagnosis (PGD) as compared to younger woman, primarily for aneuploidy.

"It is possible that younger women with an ART-conceived pregnancy were less willing to undergo chorionic villue sampling or amniocentesis because of heightened concerns about risks to the fetus," wrote Boulet and colleagues. "Another potential explanation is that young women undergoing ART have more serious underlying health issues than older women and thus have poorer-quality embryos."

Other studies have found increased incidence of cancer, heart defects, genitourinary malformations and malformations of the eye later in life.

The current study has several limitations; it lacked data on pregnancies that did not end up in live births, so the prevalence of birth defects may be underestimated. Also infants born with ART are closely followed than those born naturally, so the detection of birth defects may be higher!

The study implies that patients should have a good discussion with their physicians about the ART procedure, including detail information on all the birth defects resulting due to the ART. They should also understand that the actual risk for individual family is very small, but the odds are increased. A careful evaluation of long term effects and defects later in life is also necessary by designing studies for long term follow up of such infants.

References:

http://www.cdc.gov/media/pressrel/2008/r081117.htm

http://www.medpagetoday.com/OBGYN/Pregnancy/57161

http://www.ncbi.nlm.nih.gov/pubmed/23449641

http://archpedi.jamanetwork.com/article.aspx?articleid=2506140

http://www.newsmax.com/Health/Health-News/IVF-reproductive-technology-birth/2016/02/04/id/712683/

http://www.reuters.com/article/us-health-ivf-birth-defects-idUSKCN0X122D

http://www.medscape.com/viewarticle/861447

Kelley-Quon L, et al "Congenital malformations associated with assisted reproductive technology: a California statewide analysis" AAP 2012.