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Endocrine Disrupting Chemicals: Potential Effects on Male and Female Reproductive Health in Saskatchewan

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02272439
Recruitment Status : Completed
First Posted : October 23, 2014
Last Update Posted : December 21, 2015
Sponsor:
Collaborator:
Royal University Hospital Foundation
Information provided by (Responsible Party):
Angela Baerwald, University of Saskatchewan

Tracking Information
First Submitted Date April 11, 2013
First Posted Date October 23, 2014
Last Update Posted Date December 21, 2015
Study Start Date March 2012
Actual Primary Completion Date September 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: October 22, 2014)
Exposure to BPA [ Time Frame: March 2012 to September 2013 (up to 2 years) ]
Concentrations of Bisphenol A (BPA), di-2-ethylhexyl phthalate (DEHP), di-n-octyl phthalate (DNOP), di-n-butyl phthalate (DNBP), n-butyl benzyl phthalate (BBP), diethyl phthalate (DEP), diisononyl phthalate (DINP) and diisodecyl phthalate (DIDP) will be quantified in the blood cells, blood plasma, and follicular fluid (individual and pooled samples) by use of liquid chromatography and tandem mass spectrometry methods and will be compared between study groups using multivariate Analyses of Variance (ANOVA).
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: October 22, 2014)
Exposure to Phthalates [ Time Frame: March 2012 to Sep. 2013 (up to 2 years) ]
Exposure to phthalates will be determined by quantifying concentrations of 5 different pthalates. Concentrations of BPA and phthalates in blood cells, blood plasma, seminal plasma and pooled follicular fluid will be compared between study groups using multivariate Analyses of Variance (ANOVA).
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Endocrine Disrupting Chemicals: Potential Effects on Male and Female Reproductive Health in Saskatchewan
Official Title Endocrine Disrupting Chemicals: Potential Effects on Male and Female Reproductive Health in Saskatchewan.
Brief Summary

The overall objective of this study is to determine whether serum BPA and/or phthalate concentrations differ in fertile versus infertile men and women in Saskatchewan. The investigators will test the following hypothesis:

  1. Serum BPA and/or phthalate concentrations will be greater in women with unexplained infertility or PCOS compared to a control group
  2. Serum BPA and/or phthalate concentrations will be greater in men with male factor infertility compared to a control group
Detailed Description

Study Sample:

Couples undergoing in vitro fertilization (IVF) and/or Intracytoplasmic Sperm Injection (ICSI) for assisted reproduction at ARTUS as well as healthy male and female volunteers 18-43 years of age will be asked to participate. In order for infertility patients to be eligible, both the male and female partners must agree to participate. Couples with a combination of both male and female factor infertility will not be eligible to participate. Couples undergoing infertility treatment for the following reasons will be evaluated:

  • unexplained infertility (n=15 men, n=15 women)
  • PCOS (n=15 men, n=15 women)
  • Male factor infertility (n=15 men, n=15 women)

Couples with male factor infertility will serve as controls for the female comparisons (i.e., follicular fluid analyses), and couples with PCOS will serve as controls for the male comparisons (i.e., seminal plasma analyses).

Additional participants will be assigned to the following control groups (for blood sample analyses):

-Healthy volunteers with no history or current diagnosis of reproductive dysfunction (n=15 men, n=15 women)

Participant Recruitment:

Infertile couples will be recruited from the clinical practices of Drs. Allison Case and Adrian Gamelin at the Assisted Reproductive Technologies Centre at the University of Saskatchewan (ARTUS). Posters for recruiting ARTUS patients will also be placed in the waiting room and examining rooms in the Dept of OB/GYN, Division of REI. Healthy male and female volunteers will be recruited from advertisements on the PAWS website at the University of Saskatchewan and Health E-News newsletters in the Saskatoon Health Region.

Pre-Study Visit:

Eligible participants will be asked to visit the ARTUS Centre for a pre-study appointment. At this appointment, study procedures will be discussed with participants and consent will be obtained.

Study Visits:

Blood and follicular fluid samples will be obtained from female partners of infertile couples. Blood and seminal plasma samples will be obtained from male partners of infertile couples. Only blood samples will be collected from healthy men and women. All samples will be collected in both fertile and infertile couples over a 2 week time interval.

A. Infertile couples:

Infertile couples participating in this study will undergo fertility treatment as per the normal standard of care. In other words, the fertility medications, ultrasound assessments, blood work during treatment, oocyte retrieval, semen collection, laboratory procedures and embryo transfer procedures will not be affected by participating in this study.

Both the male and female partner will be asked to provide 1 extra blood sample (approximately 7 mL or 1 teaspoon of blood) on each of the following regularly-scheduled appointments:

  1. First ultrasound visit (approximately day 1 of FSH therapy)
  2. Day of egg retrieval
  3. Day of embryo transfer

Women normally undergo regular blood draws during their IVF treatment; therefore, one additional tube will be drawn for research purposes at the regularly-scheduled blood draw appointments. Men do not normally provide a blood sample during IVF treatment, but will be asked to do so in this study. Blood draws will be performed by phlebotomists (staff that specialize in drawing blood) at Royal University Hospital, physicians, nurses and/or researchers with training in phlebotomy. The blood samples will be processed to remove the cells, and the serum will be frozen for 12-24 months until the completion of the study.

The follicles in the woman's ovaries will be drained and the eggs will be retrieved from the follicular fluid, as per the standard of care. After the eggs are collected, the follicular fluid is normally thrown away. In this study, we will collect the fluid from the follicles on each ovary after the eggs are retrieved. The follicular fluid will be frozen for 12-24 months until study completion.

A semen sample will be provided by the man on the day of the oocyte retrieval procedure, as per standard of care. The semen sample is processed by allowing the semen to pass through a column to separate the most motile sperm (moving very quickly) from the less motile and non-motile sperm. The seminal plasma is the fluid portion of the semen that remains after the most motile sperm have been obtained. The seminal plasma is normally thrown away after the motile sperm are obtained. In this study, we will collect the seminal plasma and freeze it for 12-24 months until the study is completed.

B. Healthy Volunteers:

Healthy volunteers will be asked to provide 1 blood sample (approximately 7 mL or 1 teaspoon of blood) on 3 separate days. Blood draws will be performed by physicians, nurses and/or researchers with training in phlebotomy (i.e., drawing blood). Appointments for blood draws will be made approximately 4-7 days apart.

At the completion of the study all of the frozen blood, follicular fluid, and seminal plasma samples will be transported to the Toxicology Center at the University of Saskatchewan. The levels of exposure to BPA and phthalates will be evaluated. The samples will be destroyed upon completion of the study. The expected duration of study participation is approximately 13-20 days (in accordance with standard fertility therapy) for fertility patients and 3 days for healthy volunteers. All samples will be obtained over a 2 week time period.

Statistical Analysis

Include a summary of the primary and secondary end-points/outcomes, the planned sample size (with justification) and planned statistical and interim analyses.

Study Endpoints:

Exposure to phthalates will be determined by quantifying concentrations of 5 different pthalates. Concentrations of Bisphenol A (BPA), di-2-ethylhexyl phthalate (DEHP), di-n-octyl phthalate (DNOP), di-n-butyl phthalate (DNBP), n-butyl benzyl phthalate (BBP), diethyl phthalate (DEP), diisononyl phthalate (DINP) and diisodecyl phthalate (DIDP) will be quantified in the blood cells, blood plasma, and follicular fluid (individual and pooled samples) by use of liquid chromatography and tandem mass spectrometry methods already developed in our laboratory. Analyses will be conducted by use of an Agilent 1200 series High Performance Liquid Chromatography (HPLC) system interfaced to an ABI SCIEX 3200 triple quadrapole mass spectrometer system or to a QToF II quadrapole time of flight mass spectrometer (Micromass, Beverly MD). Toxicant concentrations will be the dependent variables. Reproductive status (i.e, unexplained infertility, PCOS, male factor infertility, controls) will be the independent variable. Concentrations of BPA and phthalates in blood cells, blood plasma, seminal plasma and pooled follicular fluid will be compared between study groups using multivariate Analyses of Variance (ANOVA).

n=15 per group is appropriate for conducting this pilot study.

Potential Significance/Justification:

Greater knowledge about the possible effects of BPA and phthalates on reproductive function may increase our understanding of the causes of infertility, assist in preventing reproductive disease, and optimize reproductive health, which will thereby improve patient care. We believe that the results of our study, whether positive or negative, will be of interest to the general public, health professionals and scientific community.

Study Type Observational [Patient Registry]
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration 3 Weeks
Biospecimen Retention:   Samples With DNA
Description:
Blood, Follicular Fluid and Seminal Plasma Samples
Sampling Method Probability Sample
Study Population Infertile couples with unexplained infertility, male factor infertility and PCOS Healthy volunteers with history of fertility
Condition
  • Unexplained Infertility
  • Polycystic Ovarian Syndrome
  • Male Infertility
Intervention Not Provided
Study Groups/Cohorts
  • Unexplained (male)
    Men of couples with a diagnosis of Unexplained infertility (n=15)
  • Unexplained (female)
    Women of couples with a diagnosis of Unexplained infertility (n=15)
  • male factor (male)
    Men of couples with a diagnosis of male factor infertility (n=15)
  • male factor (female/control)
    Women of couples with a diagnosis of male factor infertility (n=15)
  • PCOS (female)
    Women of couples with a diagnosis of Polycystic Ovarian Syndrome-related infertility (n=15)
  • PCOS (male/control)
    Men of couples with a diagnosis of Polycystic Ovarian Syndrome-related infertility (n=15)
  • healthy volunteer (male/control)
    Men with a history of no reproductive dysfunction and proven fertility (n=15)
  • healthy volunteer (female/control)
    Women with a history of no reproductive dysfunction and proven fertility (n=15)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: October 22, 2014)
118
Original Actual Enrollment Same as current
Actual Study Completion Date January 2015
Actual Primary Completion Date September 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Age: 18-43 years
  • Couples undergoing IVF for:

Unexplained infertility Male factor infertility Polycystic Ovary(PCOS)

-Both male and female partners must agree to participate

Exclusion Criteria:

  • Age: <18 and >43 years
  • Couples with both male and female factor infertility
  • Only female or male partner agrees to participate
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 43 Years   (Adult)
Accepts Healthy Volunteers Yes
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Canada
Removed Location Countries  
 
Administrative Information
NCT Number NCT02272439
Other Study ID Numbers EDC-ARB-002
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Angela Baerwald, University of Saskatchewan
Study Sponsor University of Saskatchewan
Collaborators Royal University Hospital Foundation
Investigators
Principal Investigator: Angela Baerwald, PhD Assistant Professor
PRS Account University of Saskatchewan
Verification Date December 2015