In December of 2016, Margus Punab and colleagues published “Causes of Male Infertility: A 9-year Prospective Monocentre Study on 1737 Patients with Reduced Total Sperm Counts,” hereafter “Male Infertility,” in the journal Human Reproduction. The study examines the main causes of severe male factor infertility, or SMF infertility, which occurs when a male’s semen has a very low number of healthy sperm cells or contains atypically low levels of sperm cells. In “Male Infertility,” the authors determine the primary cause of SMF infertility in forty percent of their participants, and among those participants, they found that the primary causes of SMF infertility were varicoceles, or enlarged veins within the loose bag of skin holding the testicles. The authors did not determine the cause of SMF infertility in the remaining sixty percent of the cases, noting a gap in the current understanding of the causes of SMF infertility. “Male Infertility” was one of the first large-scale studies to reveal certain underlying causes of SMF infertility, and its conclusions have allowed researchers to investigate fertility solutions for male patients who would otherwise not be able to reproduce.

A genome-wide association study, or GWAS, is a method for identifying variations in DNA that may contribute to the development of a particular trait, such as a disease. A GWAS relies on identifying statistical correlations between many, often thousands of, DNA markers and a particular trait. Scientists employ GWASs to try to identify the genetic contributions to complex traits, such as common human diseases. Complex traits are ones that scientists suspect are the result of multiple genes and environmental inputs acting together, in contrast to simple, Mendelian disorders that result primarily from the disturbance of a single gene. The genetic variants identified through a GWAS typically account for only a small proportion of the expected genetic contribution to a complex trait, which scientists refer to as the missing heritability problem. Since 2006, scientists have conducted thousands of GWASs aimed at identifying the genetic contributions to complex traits and have identified many thousands of genetic variations that correlate with those traits, although as of 2025, because of the missing heritability problem and other limitations, the concrete contributions of GWASs to medicine have so far been modest.