A large study on fetal anomalies in children conceived with reproductive assistance suggests that the slight increase in birth defects associated with assisted conception may be caused by parental factors rather than the fertility treatments.

An analysis of data on all births in South Australia over a 17-year period was carried out. Overall, 6,136, of the 308,974 total births resulted from assisted conception.

Crude fetal anomaly rates were raised in the pregnancies following assisted conception compared with unassisted conception (8.3% vs 5.8%), unadjusted odds ratio (OR) 1.47 (95% CI: 1.33-1.62). However, the OR fell when adjusted for significant parental demographic differences (race, age, parity, smoking, affluence etc.). The overall adjusted OR was 1.28 (95% CI: 1.16-1.41).

The adjusted ORs for births after IVF and ICS were 1.07 (95% CI: 0.90-1.26) and 1.57 (95% CI: 1.30-1.90) respectively. For clomiphene ovulation induction ‘at home’, the adjusted OR was 3.39 (95% CI: 1.61-7.13), but this was based on seven fetal anomalies among just 36 births.

A fascinating sub-analysis looked at births following spontaneous pregnancy in women with previous fertility treatments, and in women with prior untreated sub-fertility. In both groups adjusted OR for fetal anomaly was raised compared with the general population; 1.25 (95% CI: 1.01-1.56) and 1.29 (95% CI: 0.99-1.68) respectively. This implies that the slight increase in fetal anomaly associated with assisted conception treatments may be caused by parental factors rather than the fertility treatments.

The authors conclude that the increased risk of birth defects associated with IVF was no longer significant following adjustment for parental factors.

This study is largely reassuring, but reported that clomiphene may be associated with a higher risk of fetal anomaly.

The suspicion, never proved, that clomiphene may increase the risk of neural tube defects and hypospadias has been around for several decades. The data in this paper cannot substantiate this hypothesis. The numbers involved were very small, and the authors themselves caution that the finding may be the result of chance or confounding. Their quoted references to the literature were to similarly weak or negative reports.

Personally, I am happy to continue using clomiphene, though discussion with patients of its potential side effects is, as ever, mandatory.

Dr Chris Barclay

• Davies M, Moore VM, Willson KJ et al. Reproductive technologies and the risk of birth defects. N Engl J Med 2012;366:1803-13