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Infertility affects 13-18% of couples and growing evidence from clinical and epidemiological studies suggests an increasing incidence of male reproductive problems. The pathogenesis of male infertility can be reflected by defective spermatogenesis due to pituitary disorders, testicular cancer, germ cell aplasia, varicocele and environmental factors or to defective sperm transport due to congenital abnormalities or immunological and neurogenic factors. Recent studies suggest an increased incidence of genetic disorders related to male infertility which may affect different levels, interfering with germ cell generation and maturation or leading to the production of non-functional spermatozoa. The identification of genetic causes of male infertility raises the issue of the transmission of defects to the offspring, a situation that is becoming more important given the increasing use of intracytoplasmic sperm injection (ICSI), a procedure in which the natural selection of the spermatozoa is by-passed. Fertilization can occur in vitro using ejaculated, epididymal or testicular spermatozoa, either fresh or frozen-thawed, providing opportunities hitherto not possible for men to be genetic fathers.

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Consistent evidence from meta-analysis has linked assisted conception by IVF, and particularly intracytoplasmic sperm injection (ICSI), with an increased risk of major birth defects. To compare the risk of major malformations of children born after standard ICSI and after intracytoplasmic injection of morphologically selected spermatozoa (IMSI), a prospective population-based study was conducted from 2005 to 2010. ICSI and IMSI were performed in only one assisted reproduction unit according to its classification of spermatozoa and using fresh semen. Medical data and follow up during 2 years of 1028 infants were collected. Major malformations were identified and classified by an external independent physician. The two groups were similar concerning the parents' age, treatment, number of oocytes recovered, days of transfer, gestational age and birthweight. However, major malformations were significantly lower with IMSI (6/450, 1.33%) versus ICSI (22/578, 3.80%; adjusted odds ratio 0.35, 95% confidence interval 0.14-0.87, P=0.014), mainly affecting boys (adjusted odds ratio 2.84, 95% confidence interval 1.24-6.53, P=0.009). In conclusion, the significantly decreased risk of major birth defects associated with IMSI remained decreased after multivariate adjustment and highlights the beneficial effect of sperm selection before ICSI.