Shared genetics between nonobstructive azoospermia and primary ovarian insufficiency

Objective

Primary ovarian insufficiency (POI) and nonobstructive azoospermia (NOA) both represent disease states of early, and often complete, failure of gametogenesis. Because oogenesis and spermatogenesis share the same conserved steps in meiosis I, it is possible that inherited defects in meiosis I could lead to shared causes of both POI and NOA. Currently, known genes that contribute to both POI and NOA are limited. In this review article, we provide a systematic review of genetic mutations in which both POI and NOA phenotypes exist.

Evidence Review

A PubMed literature review was conducted from January 1, 2000, through October 2020. We included all studies that demonstrated human cases of POI or NOA due to a specific genetic mutation either within the same family or in separate families.

Results

We identified 33 papers that encompassed 10 genes of interest with mutations implicated in both NOA and POI. The genes were all involved in processes of meiosis I.

Conclusion

Mutations in genes involved in processes of meiosis I may cause both NOA and POI. Identifying these unique phenotypes among shared genotypes leads to biologic plausibility that the key error occurs early in gametogenesis with an etiology shared among both male and female offspring. From a clinical standpoint, this shared relationship may help us better understand and identify individuals at a high risk of gonadal failure within families and suggests that clinicians obtain the history of opposite-sex family members when approaching a new diagnosis of POI or NOA.