Birth defects in infants conceived by ICSI

The current prevailing view is that IVF and IVF/ICSI, in general, are associated with multiple gestation and an increased risk of congenital abnormalities (including hypospadias). IVF/ICSI in particular, appears to carry an increased risk of endocrine abnormalities, as well as epigenetic imprinting effects. ICSI conceived children are at a higher absolute risk of the following conditions:

• multiple gestation and its associated sequelae
• congenital defects (in particular genitourinary defects)
• epigenetic syndromes (such as Beckwith Wiedemann).

Nevertheless, the absolute incidence of these events remains rare.(1)

A 2019 study was conducted to evaluate and compare the incidence of birth defects in In-Vitro Fertilization-Intra Cytoplasmic Sperm Injection (IVF-ICSI) pregnancies with autologous and donor oocytes. As a secondary outcome, the prevalence of birth defects in IVF-ICSI pregnancies was compared with those from spontaneous conceptions. (2)

Overall, there was no significant difference in birth defects resulting from IVF-ICSI with autologous or donor oocytes. The births resulting from IVF-ICSI pregnancies did not tend to have a higher rate of birth defects compared with natural conceptions.

The differences in the prevalence of certain birth defects (cardiovascular or central nervous system) reported in IVF-ICSI pregnancies may be due to improved surveillance modalities and early detection in pregnancies following IVF-ICSI.

Another 2019 study that investigated the associations between male subfertility and the risk of major birth defects in children born after IVF and ICSI found that underlying male subfertility may play a role in the risk of major birth defects related to ICSI and IVF. (3)

Further research, including systematic reviews adjusting for confounders, is therefore required to confirm any association between male subfertility and major cardiac and urogenital birth defects.

References

1. Lamb D. Intracytoplasmic Sperm Injection (ICSI) – What are the risks? Urol Clin North Am. 2008 May;35(2):277–288.
2. Banker M et al. Prevalence of structural birth defects in IVF-ICSI pregnancies resulting from autologous and donor oocytes in Indian sub-continent: Results from 2444 births. Acta Obstet Gynecol Scand. 2019 Jun;98(6):715-721.
3. Jwa S et al. Male subfertility and the risk of major birth defects in children born after in vitro fertilization and intracytoplasmic sperm injection: a retrospective cohort study. BMC Pregnancy Childbirth. 2019 Jun 3;19(1):192.