COVID-19 May Affect Male Fertility but is Not Sexually Transmitted: A Systematic Review

Tur-Kaspa, Ilan; Tur-Kaspa, Tomer; Hildebrand, Grace; Cohen, David

Objective SARS-CoV-2 has led to a rapidly spreading COVID-19 global pandemic. Since the putative receptor for the virus is identified in reproductive organs, it is important to examine if SARS-CoV-2 targets the human reproductive tract. And, if so, is COVID-19 a sexually transmitted disease (STD)? Evidence Review A systematic review of English publications to December 11, 2020, was conducted in PubMed, NIH iCite COVID-19 portfolio, Cochrane Library, and Google Scholar databases, searching for SARS-CoV-2 in testes, seminal, prostatic and vaginal fluids, and in cervical smears. 1,997 records were identified, duplicates were removed, and 1,490 records were reviewed for eligibility by examining titles and abstracts. 202 full-text relevant articles were reviewed by two independent reviewers. 47studies (literature reviews, editorials, and guidelines) were assessed qualitatively and 23 studies that tested the male and female reproductive tracts of COVID-19 patients for SARS-CoV-2 were quantitatively analyzed. Findings No epidemiological investigations to date have described evidence suggesting that COVID-19 is an STD. While ACE2 receptor is found in reproductive organs, the lack of co-expression of the TMPRSS2 modulatory protein, required for SARS-CoV-2 cell entry, in testicular cells, sperm, or oocytes, argues against the hypothesis that gametes transmit SARS-CoV-2. Molecular detection studies of SARS-CoV-2 RNA in the male and female reproductive tracts were summarized: 98.0% (293/299) of the seminal fluids, 16/17 testicular biopsies, all 89 prostatic fluids, 98.3% (57/58) of the vaginal fluids, all 35 cervical smears, and all 16 oocyte samples tested negative for SARS-CoV-2. None of the studies confirmed sexual transmission of SARS-CoV-2. Nonetheless, COVID-19 may have detrimental effects on male reproduction by inducing orchitis and/or decreasing testosterone levels, sperm counts, and motility. Conclusions Based on the current worldwide published information, COVID-19 is not an STD. This information is important for clinicians, proposed guidelines for public health, FDA guidelines for gamete and tissue donor eligibility, and for fertility treatments. Universal precautions, currently practiced worldwide, are adequate and sufficient at this time to prevent the transmission of known or unknown viral infections. We suggest that recovered patients of COVID-19, especially those with infertility, should be evaluated for their ovarian and testicular function.