On one hand, it is almost established that there is a strong, noncausal association between ART and congenital malformations. On the other hand, there is also vast evidence which demonstrates that, in general, there is no difference in the rates and types of congenital malformation when comparing ICSI and standard IVF pregnancies.[7
There are various confounding factors which give an impression that ART is associated with congenital malformations, when actually it is not.
- ART-conceived pregnancies are treated as high-risk pregnancies and have an increased surveillance. Hence, as compared to a spontaneous conception, there are higher chances that malformations are diagnosed in ART pregnancies.
- Women who have conceived with ART have a higher threshold for termination of pregnancy inspite of a malformation being diagnosed. Given that these pregnancies are characterized by intense desire and high levels of investment, it may be difficult for formerly infertile couples to consider termination of pregnancy.
- Although there has been a rising trend of younger women undergoing ART, these women are of a higher median age that those conceiving spontaneously. This itself increases chances of malformations.
- The cause of infertility in a woman, for e.g., diabetes mellitus type I and II, immunological causes, women on medications like antiepileptics, etc., are already inherently predisposed to congenital malformations. ART cannot be held completely responsible for the structural abnormalities in such cases.
- Multiple pregnancy is a well-documented adverse outcome of ART techniques. Twins have a higher chance of congenital malformation (monochorionic more than dichorionic) than a singleton.
- Procedures like preimplantation genetic diagnosis (PGD) and selective embryo reduction are proposed to increased malformations in ART pregnancies, though the evidence is not yet strong enough.
These are the plausible explanations as to why the association between ART and congenital malformations is not statistically significant. But the studies which prove this hypothesis continue to remain a minority, and most large studies have shown the association to exist strongly.
Does the incidence of congenital malformations vary according to the type of assisted reproductive techniques?
Evolution of intracytoplasmic sperm injection – is the embryo being handled too much?
Offsprings born by ICSI run a risk of gene abnormalities related to fertility issue inheritance, as the spermatozoa used for ICSI are more likely to be abnormal and predispose to genetic and chromosomal abnormalities. Even if the injection of spermatozoon with chromosomal abnormalities is the most probable cause of higher incidence of chromosomal abnormalities in fetus, risk may be linked to the process of ICSI itself. The breaking of the zona pellucida and cytoplasmic membrane could lead to injuries of internal structures of the oocyte and have deleterious consequences such as aneuploidy and chromosomal abnormalities.[28
Decreased birth defects in children conceived after IMSI as compared to ICSI has been reported.[29
Major malformations and increased chromosomal abnormalities were observed in ICSI children born after cryopreserved embryo transfer.[30
The data is limited and larger trials are needed to incorporate risk counseling prior to ART.
Why this association between assisted reproductive techniques and malformations?
Factors that may increase the risk of birth defects include the relatively advanced age of infertile couples; the underlying cause of their infertility; the medications used to induce ovulation or to maintain the pregnancy in the early stages; and factors associated with the procedures themselves, such as the freezing and thawing of embryos, the potential for polyspermic fertilization, and the delayed fertilization of the oocyte.
Although older maternal age and low parity did not appear to explain our results, it is not possible to separate the excess risk that may be associated with infertility treatment from the excess risk related to the underlying causes of infertility.
Implications of this review
In order to counsel prospective patients effectively, IVF clinicians must assess all the available data on birth defect risk in infants born following ART treatment.
Larger, population-based studies are now needed to address questions of etiology so that we can provide better information for counseling prospective patients.
Role of fetal medicine – prenatal diagnosis
Fetal medicine has evolved vastly as an adjunct to ART services and its importance in reproductive medicine cannot be overlooked. In ART conceptions, there needs to be an extra-cautious and vigilant surveillance for malformations. For e.g., an isolated omphalocele in an ART conception warranties that underlying Beckwith Wiedmann syndrome be rule out.[31
Also, as mentioned earlier, it should be noted that the parental decision-making process for couples who have undergone ART may differ from that associated with pregnancies following spontaneous conception.
Finally, it should be remembered that whilst the risk of congenital malformations is slightly, but significantly, increased following ART, the risks of other pregnancy complications, in particular multiple pregnancy and its consequences and preterm delivery, remain far more common obstetric complications in this patient group. This fact remains the core to guide a pre-ART counseling.[32