Blastogenesis denotes the development that occurs in the first 28 days after conception, wherein the basic body plan, gene expression domains, and the embryo’s developmental fate are established. The defects or malformations arising at this stage are generally severe and lethal, owing to several reasons such as the embryo’s small size, interdependent nature of its development, and proximity of the organ rudiments. Now, a recent study published in the journal, Human Reproduction highlights the link between IVF/ICSI procedures and blastogenesis birth defects, with the probability of the specific risk being lower with frozen-thawed embryo transfer.
Several previous studies have suggested the increased prevalence of birth defects in infants conceived with ART, but the cause for this association has been unclear. The current study investigated the effect of classifying birth defects based on pathology as opposed to organ system, and the influence of using frozen-thawed embryos on the risk of developing the defects, as the scientists speculated that these two parameters may aid in understanding the underlying mechanism.
Jane L Halliday from the Murdoch Childrens Research Institute, Royal Children’s Hospital, Australia, and coworkers, analyzed the Australian population-based data (from 1991 to 2004) on births and birth defects, and related this to the data of 6,946 IVF or ICSI singleton pregnancies. The researchers compared these results with perinatal outcomes of 20,838 non-IVF/ICSI-conceived singletons in the same population. Classification of the birth defects was done based on pathogenesis.
The study results demonstrated an increased occurrence of birth defects following IVF/ICSI compared to controls (AOR=1.36). The scientists did not find any strong evidence with respect to risk variation between the two ART procedures, and also between the transfer of fresh and frozen embryos. However, a marked elevation in the risk of developing blastogenesis birth defects (specific group) was found in the ART-conceived children (OR=2.80) compared to the controls. The increase in the risk was noted to be substantial after fresh, but not thawed embryo transfer (OR=3.65 vs. 1.60). Based on the findings, it was suggested that there exists a specific risk of developing blastogenesis birth defects during the first 4 weeks of gestation after IVF/ICSI procedures, with the increase in risk being probably higher following fresh embryo transfer.
Similarly, Reefhuis et al (Human Reproduction, 2009) examined the link between ART and birth defects by using data from the National Birth Defects Prevention Study, a population-based, multi-center, case–control study (1997 to 2003) conducted in the US. The scientists noted the association of IVF/ICSI with many birth defects such as esophageal atresia (AOR=4.5), cleft lip with or without cleft palate (AOR=2.4), anorectal atresia (AOR=3.7), septal heart defects (AOR=2.1) in singletons. However, no substantial correlation was found between assisted conception techniques and birth defects in multiple births.
Contradictorily, Shevell et al (Obstetrics and Gynecology, 2005) did not find any higher incidence of structural or fetal chromosomal abnormalities with ART procedures (ovulation induction, with or without IUI and IVF) compared to natural conception, after analyzing 36,062 pregnancies.
Although many studies have suggested the potentially higher risk of developing birth defects with assisted conception methods, the underlying mechanism by which ART could result in phenotypes that affect various developmental pathways is not completely elucidated. Hence, larger studies are warranted to analyze if the association is due to some factors concerned with the procedures or due to inherent problems related to infertility.
A 2007 report of the Center for Genetics and Society indicated that nearly 1 million Americans had undergone some type of fertility treatment in 2004, and also estimated the costs associated with the ART industry to be around $3-5 billion every year in the US. Considering the social, economic, and psychological burden associated with ART, it is imperative to counsel couples opting for assisted conception on its potential risks and benefits.
References
1. Halliday JL, Ukoumunne OC, Baker HW, et al. Increased risk of blastogenesis birth defects, arising in the first 4 weeks of pregnancy, after assisted reproductive technologies. Hum Reprod. 2009 Oct 22. [Epub ahead of print]
2. Reefhuis J, Honein MA, Schieve LA, et al. Assisted reproductive technology and major structural birth defects in the United States. Hum Reprod. 2009 Feb;24(2):360-6.
3. Shevell T, Malone FD, Vidaver J, et al. Assisted reproductive technology and pregnancy outcome. Obstet Gynecol. 2005 Nov;106(5 Pt 1):1039-45.
4. Olson CK, Keppler-Noreuil KM, Romitti PA, et al. In vitro fertilization is associated with an increase in major birth defects. Fertil Steril. 2005 Nov;84(5):1308-15.
5. Assisted Reproductive Technologies: Overview and Perspective Using a Reproductive Justice Framework. Center for Genetics and Society. Last accessed November 25, 2009.
