Introduction

In December 2022, combined infection and vaccine-induced seroprevalence of COVID reached 98% of all US reproductive-aged adults. Additionally, the CDC estimates that 77.5% of the population has been infected at least once.¹ Given the ubiquitous nature of both exposure to and previous infection by the virus, its potential impact on fertility has been meticulously studied. Patients presenting for a reproductive health evaluation will commonly ask what the potential impact of COVID is on both their reproductive potential and chances of conception. Importantly, patients should be counseled that vaccination has no detrimental effects on fertility potential, while infection by the virus is known to have negative effects on both hormones and sperm production.^2,3 The virus has been found in both semen and the testis tissue, and its impact on testicular function and spermatogenesis are well described.⁴ Patients should be counseled that COVID is not transmitted sexually, but standard precautions should be followed in the infected state.⁵ COVID has been shown to induce orchitis, alter hormone levels, and affect sperm health acutely (Figure).

Hormone Levels

In the acute setting, COVID infection has been shown to cause changes in the hypothalamic-pituitary-gonadal axis. Studies report that up to half of patients will have below normal serum testosterone levels during acute infection, with the lowest levels seen in patients with severe symptoms.^4,6 The etiology for this finding is likely secondary to decreased testicular function brought on by inflammation.⁴ Additionally, these patients with acute infection concurrently had statistically significant increased luteinizing hormone and follicle stimulating hormone levels when compared with healthy controls.⁴

Of patients with decreased testosterone levels as a result of acute infection, most but not all return to normal testosterone levels at 3 months after infection.^4,6 Confounding this is the fact that men with persistent hypogonadism 12 months after infection may have been hypogonadal prior to infection.^4,6 Thus, patients exhibiting symptoms of hypogonadism even years out from infection should be evaluated and treated accordingly for this condition.

Spermatogenesis

Spermatogenesis is negatively affected by acute COVID infection. This is thought to be a result of fever, the inflammatory state brought about by infection, and dysregulation of the proteome in semen leading to spermatic dysfunction with regards to development, motility, and fertilization.⁴ Donders et al report that up to 60% of patients will have decreased motility within 1 month after infection and 37% of patients will have decreased sperm counts.² Studies have shown a decrease in normal sperm morphology during the acute phase as well.² Patients should be counseled that initial negative impacts of COVID on spermatogenesis are temporary. Literature supports that decreases in semen parameters resolve at around 3 months after infection, or 1 spermatogenic cycle.^2,4

The short-term nature of the effects of COVID on spermatogenesis is further supported in that patients who had a semen analysis prior to infection and after resolution of infection did not exhibit significantly different semen parameters.^4,7 Additionally, clinics have not seen an increase in the number of patients presenting with fertility issues nor the number of abnormal semen analysis results prepandemic vs present day.⁷

Conception and Pregnancy Outcomes

Females infected with COVID may have short-term hormonal, ovulatory, and menstrual irregularities as well.⁴ However, in a large cohort study using the Pregnancy Study Online database, infection was not associated with significant decreases in female fecundability, while male fecundability was significantly decreased transiently.⁸ Reassuringly, these authors did not find any persistence of decreased fecundability that extended beyond 60 days.⁸

For couples undergoing assisted reproductive techniques, history of COVID infection has not been shown to impact outcomes, including oocyte yield, fertilization and maturation rate, number of good quality embryos, and clinical pregnancy rates in fresh cycles.⁹ Furthermore, the majority of studies report no change in outcomes for patients with previous infection undergoing frozen embryo transfers.⁴ However, because of the known impact on spermatogenesis, reproductive endocrinologists may elect to delay assisted reproductive technique cycles in the event of male partner infection to allow spermatogenesis to recover.⁴ The COVID vaccine has not been shown to negatively impact ovarian reserve or ovarian function.⁴ Importantly, for couples who are already pregnant, exposure to the COVID vaccine in utero does not lead to an increased risk of spontaneous abortion.¹⁰

Infection with COVID does have acute effects on male fertility with both decreases in testosterone as well as decreased quality of sperm. Fortunately, these acute effects are reversed after resolution of acute infection for almost all patients. For those patients with persistent abnormalities postinfection, further workup into other potential etiologies should be performed.