New Answers to the Long-Term Effects of COVID-19 on Male Fertility

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New answers to the long-term effects of COVID-19 on male fertility

Effects of moderate COVID-19 infection on semen oxidative status and parameters 14 and 120 days after diagnosis

doi.org/10.1071/rd21153

Background

The results of previous studies indicate some effect of COVID-19 infection on semen parameters.

Also known as SARS-CoV-2, COVID-19 enters host cells via ACE2 (angiotensin-converting enzyme II) receptors, which is commonly found in the various cells within the testicles.

However, the exact mechanism of action and potential long-term fertility effects, remains contested among researchers, due to a lack of data.

Aim

To investigate the effects of COVID-19 on semen parameters and markers of oxidative stress, 14 and 120 days after diagnosis of COVID-19.

Methodology

A total of 63 males diagnosed with moderate COVID-19 infection was recruited for initial assessment. COVID-19 was confirmed using real-time polymerase chain reaction (PCR) analysis and chest computed tomography (CT).

Moderate infection was defined as respiratory symptoms, with or without fever, SpOlevels at 90.1-92.9%, with less than 50% lung involvement.

Male fertility status was confirmed via a questionnaire from which 20 males with proven fertility (healthy newborn in the last 2 years) was selected for the study.

Any males with a history of varicocele, cryptorchidism, congenital disorders, immunological and inflammatory diseases, malignant disease, hormone dysfunction, scrotal or inguinal surgery, diabetes, alcohol abuse, cigarette smoking, drugs or medication which affect the male reproductive tract and high-risk job environments were excluded from the study to minimise potential bias.

Semen samples were collected after 2-5 days of abstinence, at 14 and 120 days post COVID-19 diagnosis, and then analysed according to WHO guidelines.

At the same time, measurements of reactive oxygen species (ROS) concentrations, lipid peroxidation, total antioxidant capacity and sperm DNA fragmentation was carried out to better understand any changes.

Results

Following COVID-19, diagnosis, the 20 males were treated with a variety of medications, specifically dexamethasone, enoxaparin, bromhexine, famotidine, vitamin C and vitamin D for a maximum of 4 weeks.

Initial analysis of semen parameters revealed that both sperm progressive motility and total motility, along with normal sperm morphology was below the normal range on day 14, however all 3 parameters significantly improved by day 120 with sperm progressive motility and total motility returning back to normal levels.

Peroxidase-positive leucocytes, indicating genital infection, was similarly outside normal range on day 14, but returned to normal levels by day 120.

Day 14Day 120
Volume (mL)3.84.1
pH7.47.5
Concentration (x 106/mL)47.652.1
Progressive motility (%)30.644.1
Total motility (%)32.847.5
Normal morphology (%)1.33.2
Viability (%)73.180.3
Leucocytes (x 106/mL) 1.50.8
Mean semen parameters of male participants, 14 and 120 days, after diagnosis of COVID-19

Next measurement of ROS concentrations revealed a 55% decrease by day 120 post COVID-19 diagnosis, compared to day 14 (1.1 vs. 2.5 RLU/min/20).

A similar result was seen for lipid peroxidation, with a 35% decrease in malondialdehyde concentration by day 120 compared to day 14 (1.4 vs. 2.2 nmol/mL).

This improvement correlates positively with the 32% increase in total antioxidant capacity (TAC) observed on day 120, compared to day 14 post COVID-19 diagnosis.

Finally, measurement of sperm DNA fragmentation also revealed elevated DFI levels on day 14 (33.1%) which then decreased significantly back down within normal range by day 120 (21.8%).

SUMMARY: COVID-19 LONG-TERM EFFECTS ON MALE FERTILITY

In this study, males diagnosed with COVID-19 showed abnormal sperm progressive motility, total motility, morphology, DNA fragmentation and leucocytes initially, 14 days post-diagnosis, however by day 120 all but normal morphology levels had returned back to normal range, as defined by WHO.

Limitations

  1. Small study size
  2. No analysis of sperm function

Funding

No external funding was declared for this study.

Glossary

Cryptorchidism
Undescended Testicles.

DFI
DNA Fragmentation Index, which represents the integrity of and damage to the DNA.

Leucocytes
White blood cells, central to the immune system.

Peroxidase-positive leucocytes
Peroxidase test of leucocytes (white blood cells).

Varicocele
An enlargement of the veins within the scrotum.

Similar studies

Ma L, et al. (2021). Evaluation of sex-related hormones and semen characteristics in reproductive-aged male COVID-19 patients. https://doi.org/10.1002/jmv.26259

Guo L, et al. (2020). Absence of SARS-CoV-2 in semen of a COVID-19 patient cohort. https://doi.org/10.1111/andr.12848

Holtmann N, et al. (2020). Assessment of SARS-CoV-2 in human semen-a cohort study. https://dx.doi.org/10.1016/j.fertnstert.2020.05.028

Temiz M Z, et al. (2020). Investigation of SARS-CoV-2 in semen samples and the effects of COVID-19 on male sexual health by using semen analysis and serum male hormone profile: A cross-sectional, pilot study. https://doi.org/10.1111/and.13912


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