Determining the Reproductive Health of Men Post-COVID-19 Infection

Study Overview
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Brief Summary
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Study rationale An increasing proportion of the worldwide population is being infected with COVID-19. There are ongoing and currently unanswered safety concerns about the effects of COVID-19 on reproductive health. It will be immensely reassuring to rapidly report that COVID-19 has no detectable effects on male endocrine or sperm function. Conversely, if COVID-19 does impair male reproductive health, appropriate screening can be performed in couples trying to conceive, and further research can be undertaken. The proposed study will be simple, rapid, and authoritative for the UK and worldwide.

Detailed Description
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Male infertility results from impaired sperm function, and account for half of all infertility. Fertility services have been reported to cost £325M annually in the UK(4) (REF). Testosterone deficiency is one of the most common hormonal problems affecting men, leading to osteoporosis, type 2 diabetes, obesity and depression(5). Concerns have been raised about the potential effects of COVID-19 on male reproductive dysfunction (male infertility and testosterone deficiency). A recent study has suggested that COVID-19 may enter human cells by binding to receptors (special gates on cells that recognise a specific molecule) for angiotensin converting enzyme 2 (ACE2)(6) . ACE2 receptors are found at very high levels in the testes. Within the testes, ACE2 is found on developing sperm, the 'nurse cells' that help the sperm grow (Sertoli cells), and also on Leydig cells which are needed to make the male sex hormone testosterone. In summary, this evidence suggests that there is a plausible link why COVID-19 would cause male infertility and testosterone deficiency. All fertility treatment in the UK is regulated by the Human Fertility and Embryology Authority (HFEA). The HFEA has prohibited on all non-cancer fertility treatment in the UK between April 15th and May 12th 2020 due to the COVID-19 epidemic. It is important to rapidly screen and report whether COVID-19 has any obvious effects in causing male infertility and testosterone deficiency. It must be noted that a recent study(1) reported that COVID-19 is not spread by human semen and therefore, semen processing should not risk staff to COVID-19 infection.

Official Title
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Determining the Reproductive Health of Men Post-COVID-19 Infection

Conditions
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Infertility, Male, Testosterone Deficiency

Intervention / Treatment
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* Other: Exposure: Covid-19 infection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men 18-50 years of age Already attending hospital for another reason Low risk of prior COVID-19 infection(EITHER Negative positive COVID-19 PCR test result within last 4 weeks OR no history suggestive of COVID-19 illness) High risk of prior COVID-19 infection(EITHER Prior positive COVID-19 PCR test result OR history suggestive of COVID-19 illness) Exclusion Criteria: Men with current symptoms of COVID-19 infection Men currently self-isolating as per UK government advice for COVID-19 infection Needle-phobia Impaired ability to provide full consent to take part in the study History of co-morbidity likely to affect male reproductive function e.g. undescended testes, removal of testes, testicular cancer, drugs such as corticosteroids or testosterone therapy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Case group<br>Men 18-50 years of age Already attending hospital for another reason High risk of prior COVID-19 infection: EITHER Prior positive COVID-19 PCR test result OR history suggestive of COVID-19 illness | Other: Exposure: Covid-19 infection<br>* Previous history of COVID-19 infection.<br>|
| Control Group<br>Men 18-50 years of age Already attending hospital for another reason Low risk of prior COVID-19 infection: EITHER Negative positive COVID-19 PCR test result within last 4 weeks OR no history suggestive of COVID-19 illness | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Semen parameters | Sperm concentration (x10^6/ml) between case and control group. | 3 visits (up to 75 days apart) | 
| Sperm Parameters | Sperm Motility (%) between case and control group. | 3 visits (up to 75 days apart) | 
| Sperm Parameters | Sperm normal morphology (%) between case and control group. | 3 visits (up to 75 days apart) | 
| Hormones measurement | Testosterone (nmol/L) between case and control group. | 3 visits (up to 75 days apart) | 
| Hormones measurement | Follicle Stimulating Hormone(IU/L) between case and control group. | 3 visits (up to 75 days apart) | 
| Hormones measurement | Luteinising hormone(IU/L) between case and control group. | 3 visits (up to 75 days apart) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seminal Reactive oxygen species | Compare seminal reactive oxidative species (RLU/second/10^6sperm) between case and control group. | 3 visits (up to 75 days apart) | 
| Sperm DNA fragmentation rate | Compare Sperm DNA fragmentation rate (%) between case and control group. | 3 visits (up to 75 days apart) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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infertility, hypogonadism