Male InfertilityNCT00012480
Effect of Environmental Exposures on the Egg Fertilizing Ability of Human Sperm
An observational study of Male Infertility and Testicular Diseases, run by National Institute of Environmental Health Sciences (NIEHS) at 3 sites in United States.
Trial summary
Our data indicate that environmental exposure to the heavy metal lead are more widespread than currently appreciated and that such exposures are associated with the production of human male subfertility. Read more about this study
- Who is it for?
- Ages 21 to 55 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Male Infertility, Testicular Diseases, Urologic and Male Genital Diseases
- How many people
- 400 participants
- Where
- 3 sitesUnited States
- Study dates
- Aug 2002to Jul 2007
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 55 years
- Men only
- Healthy volunteers accepted
- Adult
- Otherwise healthy men seeking fertility evaluation, without history of urologic infections or varicocele.
- Non-smokers.
- Occupationally exposed to lead or not exposed to lead.
- Otherwise healthy men undergoing testis biopsy for clinical assessment of spermatogenesis or for sperm retrieval prior to an attempt at assisted reproduction.
- Otherwise healthy men providing semen specimens for clinical analysis prior to an attempt at assisted reproduction.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Southern California Women's and Children's Hospital
Los Angeles, California, 90033
North Shore University Hospital
Manhasset, New York, 11030
Copper Hospital and Fertility Testing Laboratory and Sperm Bank
Philadelphia, Pennsylvania, 19107
About this study
Official title: Human Sperm Zona Acceptor: Environmental Effects
Our data indicate that environmental exposure to the heavy metal lead are more widespread than currently appreciated and that such exposures are associated with the production of human male subfertility. Lead's effects are observed in male partners of infertile couples attending an IVF clinical, in men acting as semen donors in an artificial insemination program and in men representative of the general public. Our goal is to identify the mechanism(s) underlying lead's anti-fertility action.
Read the detailed description
Our goal is to understand how environmental and occupational exposures to heavy and transition metal ions injure the human male reproductive tract.
The American Urological Association and the American Society for Reproductive Medicine report that ~15% of couples (i.e., more than 6.1 million people in the U.S.) experience infertility at some time. The male is responsible for infertility of 20% of these couples and contributes to the infertility of another 30-40%. However, the cause(s) of male infertility in many cases is unknown. Our data suggest that lead exposures (in the air, in food and in drinking water) underlie a significant fraction of "unexplained" male infertility. We found that blood and seminal plasma lead levels were elevated in 22% of normospermic males from couples seeking infertility treatment, in 29% of semen donors participating in an artificial insemination program and in 23% of unselected semen donors answering an advertisement for research participation. These elevated lead levels were associated with decreased sperm fertility potential in IVF, in artificial insemination and in pregnancy by coitus. The negative effects of lead on sperm function was correlated with expression of specific forms of sperm ion channels (metal binding proteins that allow lead to enter cells), suggesting that such proteins serve as markers for susceptibility or resistance to the reproductive toxic effects of lead. Further, in cases in which human male lead levels changed markedly over time, there were corresponding changes in sperm ion channel, sperm function and sperm fertility potential. These changes were linked to changes in calcium modulated processes in human testis biopsies obtained from infertility patients and could be mimicked in testes of rats experimentally fed lead.
In the current study, we plan to identify changes in gene expression important to the production of the infertile state by comparing the genes expressed in the testis of control and lead exposed rats which are resistant or susceptible to lead. These findings will help to explain how lead exposure kill cells within the testis. We will then determine whether the same changes occur in human testis biopsies and ejaculated sperm from infertile males with high body burdens of lead. The expected outcome of this study is the identification of a possible mechanism explaining male infertility associated with low sperm counts or idiopathic male infertility, tools for diagnosis of male infertility and the hope for rationale treatment.
- Keywords
- Lead, Male infertility, Gene expression, Economics, Medical
- Medical subject headings
- Infertility, Male, Testicular Diseases, Genital Diseases, Male, Lead Poisoning
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2001 (estimated)
- Study startAug 2002
- Primary completionJul 2007
- Study completionJul 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Male InfertilityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Institute of Environmental Health Sciences (NIEHS)
- Sponsor type
- US National Institutes of Health
- Investigators
- Susan H Benoff, PhD, Principal investigator, North Shore University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00012480
- Sponsor's protocol ID
- 6100-CP-001
- Status last verified
- Apr 2015
- First submitted
- 9 Mar 2001
- Last updated
- 15 Apr 2015
- Results posted
- No
Publications
Benoff S, Cooper GW, Centola GM, Jacob A, Hershlag A, Hurley IR. Metal ions and human sperm mannose receptors. Andrologia. 2000 Sep;32(4-5):317-29. doi: 10.1046/j.1439-0272.2000.00401.x.
PubMed 11021525Benoff S, Jacob A, Hurley IR. Male infertility and environmental exposure to lead and cadmium. Hum Reprod Update. 2000 Mar-Apr;6(2):107-21. doi: 10.1093/humupd/6.2.107.
PubMed 10782569Millan C, Sokol RZ, Shi Q, Hurley IR, Centola GM, Ilasi J, Rooney E, Benoff S. Lead induces epigenetic modification of rat testicular gene expression: a DNA microarray study. In: Robaire B, Chemes H, Morales CR, eds. Andrology in the 21st Century. Proceedings of the VII International Congress on Andrology. Short Communications. Englewood, New Jersey: Medimond Publishing Co. Inc. 2001:335-339.
Benoff S, Centola GM, Millan C, Napolitano B, Marmar JL, Hurley IR. Increased seminal plasma lead levels adversely affect the fertility potential of sperm in IVF. Hum Reprod. 2003 Feb;18(2):374-83. doi: 10.1093/humrep/deg020.
PubMed 12571177Benoff S, Cooper GW, Paine T, Hurley IR, Napolitano B, Jacob A, Scholl GM, Hershlag A. Numerical dose-compensated in vitro fertilization inseminations yield high fertilization and pregnancy rates. Fertil Steril. 1999 Jun;71(6):1019-28. doi: 10.1016/s0015-0282(99)00136-3.
PubMed 10360904
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Human Sperm Zona Acceptor: Environmental Effects
- ClinicalTrials.gov ID
- NCT00012480
- Acronym / sponsor ID
- 6100-CP-001
- Keywords
- Lead, Male infertility, Gene expression, Economics, Medical
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- National Institute of Environmental Health Sciences (NIEHS)US National Institutes of Health
- Study start
- Aug 2002
- Primary completion
- Jul 2007 (actual)
- Study completion
- Jul 2007 (actual)
- First posted
- 12 Mar 2001 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Our data indicate that environmental exposure to the heavy metal lead are more widespread than currently appreciated and that such exposures are associated with the production of human male subfertility. Lead's effects are observed in male partners of infertile couples attending an IVF clinical, in men acting as semen donors in an artificial insemination program and in men representative of the general public. Our goal is to identify the mechanism(s) underlying lead's anti-fertility action.
Detailed description
Our goal is to understand how environmental and occupational exposures to heavy and transition metal ions injure the human male reproductive tract.
The American Urological Association and the American Society for Reproductive Medicine report that ~15% of couples (i.e., more than 6.1 million people in the U.S.) experience infertility at some time. The male is responsible for infertility of 20% of these couples and contributes to the infertility of another 30-40%. However, the cause(s) of male infertility in many cases is unknown. Our data suggest that lead exposures (in the air, in food and in drinking water) underlie a significant fraction of "unexplained" male infertility. We found that blood and seminal plasma lead levels were elevated in 22% of normospermic males from couples seeking infertility treatment, in 29% of semen donors participating in an artificial insemination program and in 23% of unselected semen donors answering an advertisement for research participation. These elevated lead levels were associated with decreased sperm fertility potential in IVF, in artificial insemination and in pregnancy by coitus. The negative effects of lead on sperm function was correlated with expression of specific forms of sperm ion channels (metal binding proteins that allow lead to enter cells), suggesting that such proteins serve as markers for susceptibility or resistance to the reproductive toxic effects of lead. Further, in cases in which human male lead levels changed markedly over time, there were corresponding changes in sperm ion channel, sperm function and sperm fertility potential. These changes were linked to changes in calcium modulated processes in human testis biopsies obtained from infertility patients and could be mimicked in testes of rats experimentally fed lead.
In the current study, we plan to identify changes in gene expression important to the production of the infertile state by comparing the genes expressed in the testis of control and lead exposed rats which are resistant or susceptible to lead. These findings will help to explain how lead exposure kill cells within the testis. We will then determine whether the same changes occur in human testis biopsies and ejaculated sperm from infertile males with high body burdens of lead. The expected outcome of this study is the identification of a possible mechanism explaining male infertility associated with low sperm counts or idiopathic male infertility, tools for diagnosis of male infertility and the hope for rationale treatment.
Study design
Who may qualify
- Ages
- 21 to 55 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2015.
- Background: PubMed 11021525Benoff S, Cooper GW, Centola GM, Jacob A, Hershlag A, Hurley IR. Metal ions and human sperm mannose receptors. Andrologia. 2000 Sep;32(4-5):317-29. doi: 10.1046/j.1439-0272.2000.00401.x.
- Background: PubMed 10782569Benoff S, Jacob A, Hurley IR. Male infertility and environmental exposure to lead and cadmium. Hum Reprod Update. 2000 Mar-Apr;6(2):107-21. doi: 10.1093/humupd/6.2.107.
- BackgroundMillan C, Sokol RZ, Shi Q, Hurley IR, Centola GM, Ilasi J, Rooney E, Benoff S. Lead induces epigenetic modification of rat testicular gene expression: a DNA microarray study. In: Robaire B, Chemes H, Morales CR, eds. Andrology in the 21st Century. Proceedings of the VII International Congress on Andrology. Short Communications. Englewood, New Jersey: Medimond Publishing Co. Inc. 2001:335-339.
- Background: PubMed 12571177Benoff S, Centola GM, Millan C, Napolitano B, Marmar JL, Hurley IR. Increased seminal plasma lead levels adversely affect the fertility potential of sperm in IVF. Hum Reprod. 2003 Feb;18(2):374-83. doi: 10.1093/humrep/deg020.
- Background: PubMed 10360904Benoff S, Cooper GW, Paine T, Hurley IR, Napolitano B, Jacob A, Scholl GM, Hershlag A. Numerical dose-compensated in vitro fertilization inseminations yield high fertilization and pregnancy rates. Fertil Steril. 1999 Jun;71(6):1019-28. doi: 10.1016/s0015-0282(99)00136-3.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Susan H Benoff, PhD principal investigator
North Shore University Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Male Infertility and Testicular Diseases, run by National Institute of Environmental Health Sciences (NIEHS) at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00012480, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Apr 2015.