How Far Should We Investigate the Male Causes in Unexplained Infertility?

Abstract

According to a recent report by the Guideline Development Group of the ESHRE, the definition of Unexplained Infertility (UI) is ‘infertility in couples with apparently normal ovarian function, fallopian tubes, uterus, cervix and pelvis, age [Formula: see text]40 years and with adequate coital frequency; and apparently normal testicular function, genito-urinary anatomy and a normal ejaculate.’ This is anchored with the ICMART definition of infertility, where couples should have at least 12 months of regular, unprotected sexual intercourse before investigations are initiated. Since Unexplained Infertility is a diagnosis by exclusion, apart from evaluating female causes, it seems important that in evaluating male contributions to the UI, all necessary tests need to be carried out. Unfortunately, there are no robust standardized methods for establishing etiologic diagnosis in the male partner and that in some patients, underlying sperm dysfunction may not be detected during a routine assessment of the ejaculate, which may appear to be normal using the 2021 WHO standards. It is possible that some adverse reproductive outcomes that have been identified during medical and reproductive history examination may require the use of further tests procedures specified in the latest WHO manual to assess sperm function. However, these tests have a research status only or are not regarded for routine use in clinical practice until sound evidence is developed. These tests include testicular imaging, anti-sperm antibodies, sperm DNA fragmentation, sperm chromatin condensation, sperm aneuploidy screening, serum hormone testing, semen HPV testing, and semen microbiology testing all of which were found not routinely indicated based on current evidence when semen was found to be normal using the WHO 2021 semen standards. In summary, in evaluating male causes in unexplained infertility, there are no robust data to support the recommendation that additional tests about the male reproductive function may routinely be carried out when semen analysis based on the 2021 WHO standard is normal. However, additional tests may be carried out when adverse reproductive outcomes and findings in the medical and reproductive history may require the use of these further tests especially when there are no findings on the female side.