What is the role of whole exome sequencing in infertility?

No guideline I have verified recommends whole exome sequencing in the routine evaluation of infertility, and that absence should be stated rather than filled in. What the guidelines do specify is targeted testing on indication — karyotype, Y-chromosome microdeletion, CFTR — as set out in the genetic testing question. WES is not among them. Where WES has a recognised role is in defined clinical scenarios rather than as an infertility investigation: suspected monogenic causes of disorders of sexual development, syndromic presentations, or research settings investigating unexplained non-obstructive azoospermia. The AUA/ASRM guideline is candid about the underlying knowledge gap: it states that the causes of male infertility, including their genetic basis, have only been superficially explained, and that most cases of apparently idiopathic severe male infertility including NOA likely have a genetic basis not yet characterised. That is an argument for research, not for offering broad sequencing clinically and interpreting whatever appears. The practical concern with WES outside a defined indication is variants of uncertain significance. A result that cannot be interpreted generates anxiety, may prompt further testing of relatives, and does not change management. Reviewer: if your unit offers WES for infertility, this answer should describe your specific indications and your variant interpretation pathway. As written it reflects the absence of guideline support, which is accurate but may not reflect what you do.