Fertility considerations in individuals affected by human immunodeficiency virus: a scoping review

Abstract

Objective

Human immunodeficiency virus (HIV) has transformed from an almost universally terminal diagnosis to that of a chronic manageable condition over the last 4 decades. Patients of reproductive age make up the largest proportion of those with HIV. Our aim in this scoping review was to investigate how HIV sequelae, comorbidities, and antiretroviral treatment affect both male fertility and female fertility.

Evidence Review

A scoping review identified relevant articles on HIV, fertility, assisted reproductive technology, and HIV treatment. Included articles had one of the following study designs: prospective; retrospective; controlled; randomized controlled; or observational. Articles were excluded if they were of inappropriate study design or published in a non-English language. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines were used to assess eligibility of studies identified through PubMed, and manuscripts were reviewed independently by 2 reviewers.

Results

Fifty-nine manuscripts were included in the final qualitative synthesis, including 9 prospective studies, 14 retrospective studies, 35 observational studies, and 1 clinical trial. Articles on male fertility (n = 10) mainly focused on effects of HIV and/or antiretrovirals on semen quality, finding some level of abnormality in semen parameters compared with controls. Small observational studies (n = 4) found statistically significant effects of antiretroviral therapy on semen parameters. Large observational studies (n = 2) examining outcomes for serodiscordant couples pursuing intrauterine insemination with HIV+ male partner showed pregnancy outcomes comparable to those of controls. In studies examining outcomes of in vitro fertilization for serodiscordant couples with HIV+ male partner (n = 5), pregnancy outcomes were comparable to those of controls. In female patients with HIV (n = 7), HIV infection was associated with ovarian dysfunction and/or oligomenorrhea or prolonged amenorrhea. Markers of severe disease, such as a low CD4 count or viremia, were shown to be correlated with lower antimüllerian hormone levels. Three studies illustrated how the effects of comorbidities such as history of smoking, drug use, or pelvic infections can also compound infertility in these patients. Several cohort studies (n = 13) showed increased time to pregnancy, decreased pregnancy rates with and without in vitro fertilization, and an increased risk of spontaneous abortion. Given that the current backbone of preconception and antepartum management of HIV includes dual therapy with nucleoside reverse transcriptase inhibitors (NRTIs), most of the studies (n = 7) focused on NRTI’s potential toxicities such as mitochondrial depletion in gametes. In vitro and animal studies (n = 3) have shown negative implications on oocyte fertilizability and genomic disturbances in offspring.

Conclusion

Both HIV infection and treatment can impact male and female fertility. Human immunodeficiency virus–positive men have a higher risk of abnormal semen parameters, which is exacerbated by more severe disease states. Human immunodeficiency virus–positive women have a higher risk of oligomenorrhea or prolonged amenorrhea, and more advanced disease may negatively impact ovarian reserve. These women may experience decreased pregnancy and live birth rates and higher spontaneous abortion rates. Antiretroviral therapy has vastly decreased the risk of perinatal transmission; however, NRTIs have been associated with mitochondrial depletion, with potential effects on both male and female gametes.