Endocrine Disrupting Chemicals: Potential Effects on Male and Female Reproductive Health in Saskatchewan
|ClinicalTrials.gov Identifier: NCT02272439|
Recruitment Status : Completed
First Posted : October 23, 2014
Last Update Posted : December 21, 2015
|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
||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|
|Current Secondary Outcome Measures
||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|
|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.|
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:
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:
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)
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.
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.
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:
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.
Include a summary of the primary and secondary end-points/outcomes, the planned sample size (with justification) and planned statistical and interim analyses.
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.
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
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|
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|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)|
Unexplained infertility Male factor infertility Polycystic Ovary(PCOS)
-Both male and female partners must agree to participate
|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|
|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|
|PRS Account||University of Saskatchewan|
|Verification Date||December 2015|