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Non-obstructive azoospermia accounts for 10-15% of male infertility, resulting in 60% of all cases of azoospermia and affecting about 1% of the male population. About 30% of these cases are due to Y chromosome microdeletions, chromosome abnormalities, or hormonal disorders. Pathogenic variants in genes on the sex chromosomes have key roles in spermatogenic failure. The co-occurrence of azoospermia and congenital cataracts ranges between 1 in 165,000 and 1 in 500,000. Our 28-year-old patient with normal intelligence and abnormally shaped teeth presented with both disorders. A microarray revealed a microdeletion at Xp23.13 with a whole NHS gene deletion as well as a contiguous deletion of two other genes [SCML1 and RAI2]. This observation represents the first report of non-obstructive azoospermia with congenital cataracts and a contiguous deletion of the SCML1 gene, a transcript of which is exclusively expressed in the testis. SCML1 is the putative culprit gene, which requires functional study or animal experiments. Our analysis of 60 known spermatogenesis failure-related genes by whole-exome sequencing revealed no other candidate. The Nance-Horan syndrome due to pathogenic variants in the NHS gene at Xp23.13 including whole gene deletion does not have azoospermia as a feature. Our report adds to the completeness of genetic counseling for an individual with azoospermia and congenital cataracts.

Cystic fibrosis is a life-threatening disease. Only recently has the prognosis improved. In the male patient there is an almost invariable absence or maldevelopment of the vas deferens, creating a situation of obstructive azoospermia. Consequently, their fertility potential has been considered nonexistent. Having gained experience in microscopic epididymal sperm aspiration coupled with the advanced reproductive technologies for the treatment of congenital absence of the vasa, we sought to extend this treatment option to the male cystic fibrosis population. An Indian male with clinically evident and genetically confirmed cystic fibrosis underwent microscopic retrieval of epididymal sperm. The anatomy of the epididymis and the quality of sperm obtained were similar to those patients with congenital absence of the vas deferens. After appropriate spousal genetic testing, superovulation, and transvaginal oocyte retrieval, in vitro insemination of sperm was performed. Fifty percent of the oocytes were subjected to partial zona dissection and a single embryo resulted. Subsequent to transfer, no conception was realized but the effort expanded the clinical usefulness of microscopic epididymal sperm aspiration. This should open up an avenue of treatment for couples in whom only the most dire predictions for fertility have been made to date.