Chromosomal abnormalities in 1663 infertile men with azoospermia: the clinical consequences

Area of Science:

• Reproductive Medicine
• Clinical Genetics
• Human Reproduction

Background:

• Worldwide infertility guidelines recommend chromosomal abnormality screening for non-iatrogenic azoospermic men.
• Limited data exist on the clinical consequences of this screening strategy.

Purpose of the Study:

• To determine the prevalence of chromosomal abnormalities in azoospermic men.
• To assess the clinical consequences, including risks for absent spermatogenesis, miscarriages, and offspring congenital malformations.

Main Methods:

• Retrospective multicenter cross-sectional study of 1663 non-iatrogenic azoospermic men (January 2000 - July 2016).
• Analysis of karyotyping and FSH serum levels.
• Estimation of the number needed to screen (NNS) for identified risks and calculation of surgical sperm retrieval rates.

Main Results:

• Overall prevalence of chromosomal abnormalities was 14.4%, higher in hypergonadotropic (20.2%) than normogonadotropic (4.9%) azoospermia.
• Klinefelter syndrome comprised 83% of abnormalities in hypergonadotropic azoospermia.
• NNS: 72 for absent spermatogenesis, 370-739 for miscarriage, 4751-23757 for congenital malformations. Surgical sperm retrieval rates were lower in men with chromosomal abnormalities (32%) compared to normal karyotype (60%).

Conclusions:

• The absolute number of chromosomal abnormalities with significant clinical consequences was limited.
• The NNS data can inform cost-effectiveness studies and guideline evaluations for azoospermia screening.
• Further research is needed on pregnancy outcomes in men with chromosomal abnormalities.