Review of Guidelines for the Evaluation and Treatment of Leukocytospermia in Male Infertility

Abstract

Leukocytospermia is an ill-defined and poorly understood condition affecting up to 30% of male factor infertility. Current guidelines on leukocytospermia vary significantly, although it has been linked to increased rates of infertility, uncertainty about its clinical significance, diagnosis, and treatment remains. The guidelines are conflicting with sparse data scattered across different specialties and continents. This study aims to compare and contrast available international guidelines and recommendations. In addition to these guidelines, we sought to consolidate the findings of trials over the last several decades. English language articles on human observational studies, retrospective, prospective, clinical trials and randomized control trials were searched for using the following terms: “leukocytospermia, pyospermia, and male infertility.” Articles about treatment and management of leukocytospermia that were published between January 2010 and April 2018 were included, as well as four articles referenced in best practice and guideline statements from urological and andrological associations. Disagreements on this topic are highlighted as some guidelines describe no correlation between leukocytospermia and infertility while others show that treatment leads to improvement of sperm quality by many measures including improved pregnancy rate. Various treatments have been suggested including antibiotics, anti-inflammatory medications, and frequent ejaculation. There is a need for definitive characterization of Leukocytospermia as an infectious or inflammatory marker and a re-evaluation of the leukocyte concentration threshold. Additional studies investigating rates of conception as a measure of outcome are needed, to provide greater level of evidence and generalizability of leukocytopsermia management.

Laboratory and clinical management of leukocytospermia and hematospermia: a review

“…In contrast, the European Association of Urology (EAU) recommends wet mount microscopy confirmed with peroxidase positive staining. 4 The WHO also recommends the peroxidase test, although this test distinguishes only granulocytes and no other WBC types. 3 The gold standard for assessment of WBCs in semen is immunohistochemical staining using monoclonal antibodies against specific WBC subpopulations, but this method is expensive, time-consuming, and not standardized.…”

“…1,2 Leukocytospermia is a condition in which there is abnormally high concentration of WBCs within the semen. 3 Leukocytospermia has been shown to be a negative prognostic factor for fertility, 4 and etiology can be from a wide variety of sources. Current methods for detecting leukocytospermia include identification of round cells, immunohistochemical staining using monoclonal antibodies, the Endtz test, the peroxidase test, and flow cytometry.…”

Reasons that should prompt a referral to a reproductive urologist: guidelines for the gynecologist and reproductive endocrinologist

“…Leukocytospermia (i.e., >1 million leukocytes/1 mL of semen) is a condition that may be associated with inflammation or infection in the genital tract. Interestingly, the link between leukocytospermia and infection/inflammation has been questioned, but even in the definitive absence of infection, this condition is adversely correlated with fertility outcomes (8). Specifically, the presence of leukocytes may generate reactive oxygen species, which negatively affects sperm parameters (8).…”

“…Interestingly, the link between leukocytospermia and infection/inflammation has been questioned, but even in the definitive absence of infection, this condition is adversely correlated with fertility outcomes (8). Specifically, the presence of leukocytes may generate reactive oxygen species, which negatively affects sperm parameters (8). With respect to therapies, antibiotics, anti-oxidants, and frequent ejaculation are all potential options recommended by various guidelines and the results of a systematic-review (8,9).…”

“…Specifically, the presence of leukocytes may generate reactive oxygen species, which negatively affects sperm parameters (8). With respect to therapies, antibiotics, anti-oxidants, and frequent ejaculation are all potential options recommended by various guidelines and the results of a systematic-review (8,9). In short, given that this condition is ill-defined yet affects up to 30% of men with infertility, a diagnosis of leukocytospermia should prompt referral to a reproductive urologist for a discussion of its significance and the various treatment options.…”