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

NCT ID: NCT04716179

Last Updated: 2021-07-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

88 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-01-18

Study Completion Date

2021-08-31

Brief Summary

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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

Detailed Description

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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.

Conditions

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Covid19 Fertility Issues

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Parallel groups, non-randomized:

1. \- patients with COVID-19;
2. \- healthy participants without COVID-19.
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Patients with COVID-19

Patients with confirmed COVID-19 infection

Group Type EXPERIMENTAL

Sperm test

Intervention Type DIAGNOSTIC_TEST

The semen sample will be collected and analyzed within an hour after collection.

hormone levels (testosterone, FSH, LH, prolactin)

Intervention Type DIAGNOSTIC_TEST

Hormone levels (testosterone, FSH, LH, prolactin) will be assessed on 5-7 days after symptom onset until the end of hospital stay.

SARS-CoV-2 Ig G levels

Intervention Type DIAGNOSTIC_TEST

SARS-CoV-2 Ig G levels will be assessed on 3 months after discharge

Testis pathology samples

Intervention Type OTHER

Postmortem examination of the testes of patients deceased as a result of COVID-19 infection will be carried out using immunohistochemistry analysis.

Healthy participants

The controlled group with healthy participants without COVID-19 infection.

Group Type OTHER

Sperm test

Intervention Type DIAGNOSTIC_TEST

The semen sample will be collected and analyzed within an hour after collection.

hormone levels (testosterone, FSH, LH, prolactin)

Intervention Type DIAGNOSTIC_TEST

Hormone levels (testosterone, FSH, LH, prolactin) will be assessed on 5-7 days after symptom onset until the end of hospital stay.

SARS-CoV-2 Ig G levels

Intervention Type DIAGNOSTIC_TEST

SARS-CoV-2 Ig G levels will be assessed on 3 months after discharge

Interventions

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Sperm test

The semen sample will be collected and analyzed within an hour after collection.

Intervention Type 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.

Intervention Type DIAGNOSTIC_TEST

SARS-CoV-2 Ig G levels

SARS-CoV-2 Ig G levels will be assessed on 3 months after discharge

Intervention Type DIAGNOSTIC_TEST

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.

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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I.M. Sechenov First Moscow State Medical University

OTHER

Sponsor Role lead

Responsible Party

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Dmitry Enikeev, MD, PhD

Deputy Director for Research

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Dmitry Enikeev, M.D.

Role: PRINCIPAL_INVESTIGATOR

Sechenov University

Locations

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Sechenov University.

Moscow, , Russia

Site Status RECRUITING

Countries

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Russia

Central Contacts

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Dmitry Enikeev, M.D.

Role: CONTACT

+79670897154

Mark Taratkin, M.D.

Role: CONTACT

+79670897154

Facility Contacts

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Dmitry Enikeev, MD

Role: primary

+7 925 517 79 26

Other Identifiers

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COVID-MFert-20

Identifier Type: -

Identifier Source: org_study_id

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