Assisted reproductive technology may increase clinical mutation detection in male offspring

To investigate the risks of chromosome mutation after ART for couples with comparable genetic backgrounds.

Prospective clinical observational study.

In vitro fertilization center at a tertiary-care, university-affiliated teaching hospital.

Ninety-seven male children whose fathers have normal spermatogenesis were recruited, including 19 babies conceived through IVF, 18 babies conceived through intracytoplasmic sperm injection (ICSI), and 60 naturally conceived babies, as well as the babies' fathers.

Collection of peripheral and umbilical cord blood samples.

The Yq genetic status of the babies and fathers according to 13 Y-specific markers covering four azoospermia factor (AZF) subregions, the karyotype, and the neonatal examination.

We found that all children had a normal 46, XY karyotype, but de novo Y-chromosome microdeletions were identified in 1 (5.3%) of 19 IVF offspring and in 3 (16.7%) of 18 ICSI offspring. The incidence of de novo Y-chromosome microdeletion in male children conceived through ICSI or IVF was statistically significantly higher than that in those conceived naturally (10.8% vs. 0). In four babies with microdeletion, one was complicated, with hypospadias.

Our results, for the first time, indicate that risks of gene mutation may increase in the ART offspring, even though their fathers have normal spermatogenesis and genetic background. Hence, intense attention should be placed on genetic safety in the ART children, and the benefits and risks of adopting ART should be balanced gingerly.