Prospective Two-arm Study of Fertility in Men With COVID-19

COVID-19 infection is hypothesized to have a potentially negative effect on male fertility through direct damage to the testes. The current trial is aimed at investigating the effect of SARS-CoV-2 on fertility and determining if viral bodies are capable of directly damaging testicular cells

Study Overview

• Status: Recruiting
• Conditions: Covid19; Fertility Issues
• Intervention / Treatment: Diagnostic test: Sperm test; Diagnostic test: hormone levels (testosterone, FSH, LH, prolactin); Diagnostic test: SARS-CoV-2 Ig G levels; Other: Testis pathology samples

Detailed Description

In late December 2019, the Chinese city of Wuhan witnessed the emergence of a form of pneumonia of unknown etiology. By the middle of January 2020, the disease had managed to spread beyond the country of origin and is now classified by the WHO as the largest pandemic in modern history.

Rapidly spreading and highly contagious, the infection prompted medical professionals all over the world to begin research into the virus with the goal of developing early diagnostic techniques and treatment strategies.

The new pathogen named SARS-Cov-2 belongs to the Coronaviridae family. These viruses cause severe acute respiratory syndrome (SARS-CoV-1, 2002-2003) and Middle East respiratory syndrome (MERS, 2012-2013).

The effects of SARS-CoV-2 on the human body stem from its structure. The spike proteins on the surface of the virus, which are responsible for the name "Coronaviridae," means that it is able to bind to the host receptor protein, angiotensin-converting enzyme 2 (ACE2). This makes cells with high quantities of these receptors on the surface susceptible to the virus.

The genome of SARS-Cov-2 responsible for the COVID-19 pandemic contains both human coronavirus fragments and bat coronavirus fragments (HKU9-1). It is the genetic material of HKU9-1 that makes SARS-CoV-2 unknown to the immune system of the human body.

As of today, three transmission pathways are recognized: close contact, airborne and fomite. Moreover, the virus is known to retain its contagious properties on surfaces for up to 72 hours, and the incubation period ranges between 2 and 14 days. Recent reports indicate that up to 80% of those infected by COVID-19 showed mild or moderate symptoms whereas 20-30% develop severe forms of the disease characterized by shock as well as respiratory and multiple organ failure. According to Chinese and Italian healthcare providers, the mortality rate is between 3.8 and 7.2%.

Zou et al. (2020) reported that non-respiratory symptoms may be explained by the binding of the virus to ACE-2 in other organs. Shen and Wang (2020) proved that ACE-2 is also expressed by testicular cells (namely spermatogonia, Leydig cells and Sertoli cells) which makes them potential targets for the virus. In fact, there are reports of orchitis and epididymitis in patients diagnosed with COVID-19. This means that SARS-CoV-2 may directly damage testicular tissue potentially compromising male fertility.

In a number of studies, PCR did not detect the virus in semen samples obtained during both the acute phase and recovery phase. In another study, postmortem needle and open biopsies of the testicles performed within an hour after death from COVID-19 revealed that testicular tissues were free of SARS-CoV-2 in 10 of 11 cases (91%). At the same time, spermograms in COVID-19 patients showed low ejaculate volume, sperm motility and sperm count. Previously, it was shown that COVID-19 has a severe effect on vasculature and therefore a microthrombi could be a possible contributor to fertility impairment. An assessment of testes with a Doppler enhanced ultrasound was therefore necessary.

Data dedicated to testosterone levels in the blood and inflammatory markers in the semen and testicular tissues is lacking. Available literature indicates changes in the above-mentioned parameters in males with verified COVID-19.

There is ultimately too little information to draw reliable conclusions regarding the effects of the virus on male reproduction. Published reports are limited by small study groups, lack of the control group and absence of follow-up examinations during recovery warranting further research and in-depth exploration of the topic.

• Study Type: Interventional
• Enrollment (Anticipated): 88
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dmitry Enikeev, M.D.; Phone Number: +79670897154; Email: dvenikeev@gmail.com
• Study Contact Backup: Name: Mark Taratkin, M.D.; Phone Number: +79670897154; Email: marktaratkin@gmail.com

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 119991
    • Recruiting
    • Sechenov University.
    • Contact: Dmitry Enikeev, MD; Phone Number: +7 925 517 79 26; Email: enikeev-dv@1msmu.ru

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Clinical or imaging signs of COVID-19 infection
• Nasopharyngeal swab positive for SARS-CoV2 mRNA

Exclusion Criteria:

• Inability to collect semen for analysis
• Congenital anomalies of the testes
• Varicocele
• A history of fertility disorders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with COVID-19; Patients with confirmed COVID-19 infection	Diagnostic test: Sperm test; The semen sample will be collected and analyzed within an hour after collection.; Diagnostic test: hormone levels (testosterone, FSH, LH, prolactin); Hormone levels (testosterone, FSH, LH, prolactin) will be assessed on 5-7 days after symptom onset until the end of hospital stay.; Diagnostic test: SARS-CoV-2 Ig G levels; SARS-CoV-2 Ig G levels will be assessed on 3 months after discharge; Other: Testis pathology samples; Postmortem examination of the testes of patients deceased as a result of COVID-19 infection will be carried out using immunohistochemistry analysis.
Other: Healthy participants; The controlled group with healthy participants without COVID-19 infection.	Diagnostic test: Sperm test; The semen sample will be collected and analyzed within an hour after collection.; Diagnostic test: hormone levels (testosterone, FSH, LH, prolactin); Hormone levels (testosterone, FSH, LH, prolactin) will be assessed on 5-7 days after symptom onset until the end of hospital stay.; Diagnostic test: SARS-CoV-2 Ig G levels; SARS-CoV-2 Ig G levels will be assessed on 3 months after discharge

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Semen quality analysis - motility	motility of spermatozoa	3 months
Semen quantity analysis	count of spermatozoa	3 months
Semen quality analysis - shape	shape of spermatozoa	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Testosterone	testosteron (ng/dL) level in the blood test	3 months
FSH	Follicle-Stimulating Hormone (IU/L) level in the blood test	3 months
LH	Luteinizing hormone (IU/L) level in the blood test	3 months
Prolactin	prolactin (ng/ml) level in the blood test	3 months
Damage of the testes on pathology	Damage of the testes assessment using imminohistochemistry at autopsy specimen	3 months

Collaborators and Investigators

• Sponsor: I.M. Sechenov First Moscow State Medical University
• Investigators: Principal Investigator: Dmitry Enikeev, M.D., Sechenov University

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2021
• Primary Completion (Actual): May 18, 2021
• Study Completion (Anticipated): August 31, 2021

Study Registration Dates

• First Submitted: January 17, 2021
• First Submitted That Met QC Criteria: January 19, 2021
• First Posted (Actual): January 20, 2021

Study Record Updates

• Last Update Posted (Actual): July 22, 2021
• Last Update Submitted That Met QC Criteria: July 21, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Infertility; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Androgens; Hormones; Testosterone
• Other Study ID Numbers: COVID-MFert-20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No