The Effect of Periconceptional Phthalates Exposure on Couples' Reproductive Health

Study Overview
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Brief Summary
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The study is a prospective cohort study, which is aiming to explore periconceptional phthalates exposure and its potential epigenetic effect on fertility, embryo development, and neonatal outcomes.

Detailed Description
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The study is a prospective cohort study, and its subjects are childbearing couples who are seeking assisted reproductive technologies for having a baby in the reproductive center in Tongji Hospital. All enrolled couples will be needed to sign an informed consent and complete a questionnaire for collecting information about demographics, life-style, and medical and reproductive histories. Biological samples will be collected from the participants to measure phthalates metabolites in order to evaluate the exposure of single person or the couple in different time phase.The samples include urine, blood that will be left after the hormones measurement for both spouses. The follicular fluid will be obtained from females on the day of oocyte retrieval. The left sperm samples after sperm analysis will be obtained from men. In the reproductive center of Tongji Hospital, hormone measurement for women and sperm analysis for men are required for the In vitro fertilization and embryo transfer in order to evaluate the fertility of couples.And the blastocyst culture medium will be obtained from couples after blastocyst transfer. All samples will be stored at -80℃ until further analysis. Measurements of phthalates metabolites in the biological samples. Collecting data from electronic medical records and follow-up.The basic information, clinical data and reproductive outcomes of the subjects will be collected by reviewing the electronic medical charts, including the height, weight, basic hormone levels, stimulation protocol and time, insemination protocol, fertilization rate, cleavage rate, excellent embryo rate, blastocyst formation rate, clinical pregnancy rate, as well as live birth rate，the newborns' height, weight, and gestational age, etc. Analyze the miRNA expression profiles of blastocyst culture medium. Statistical analysis. The investigators will analyze the association between the couples' phthalates exposure levels and the reproductive outcomes, and explore the association among periconceptional phthalates exposure, epigenetic changes and reproductive outcomes.

Official Title
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Periconceptional Phthalates Exposure and Its Epigenetic Effect on Fertility, Embryo Development, and Neonatal Outcomes: a Prospective Study

Conditions
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Environmental Exposure, Infertility

Participation Criteria
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Eligibility Criteria
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一. Inclusion and exclusion criteria for primary study: The exclusion of men: Occupational exposures Couples living in separate places Congenital diseases Congenital azoospermia Ejaculation dysfunction Family history of genetic diseases Acquired diseases Genitourinary infections Mumps Endocrine diseases Sexually transmitted diseases Hyperthyroidism Liver failure Renal failure Neurological diseases Paraplegia Acquired testicular injury Patient who have received surgeries： Inguinal hernia surgery Vasectomy Bladder neck surgery Pelvic surgery Patients who have used antitumor drugs and hormone The exclusion of women: Occupational exposures Couples living in separate places Congenital gonadal dysplasia Genital malformation Chromosomal abnormalities Family history of genetic diseases Endocrine and metabolic diseases Diabetes Hyperprolactinemia Thyroid and adrenal diseases Cardiovascular diseases Dyslipidemia Systemic lupus erythematosus Other rheumatic immune diseases Patients who have received the following treatment: Ovarian surgery Thyroid surgery Pituitary surgery Anti-tumor radiotherapy Chemotherapy Patients with previous history as followed: Endometrial injury Endometrial polyps Endometritis Uterine fibroids Endometriosis Tubal effusion 二. Inclusive and exclusive criteria for blastocyst culture medium collection at the later stage. Inclusion criteria: Subjects in the primary part of the study ·Normal gender of men and women No genetic diseases or congenital diseases No family genetic history Normal sperm analysis for men Female age <35 years ·Normal Ovarian function for women Normal endocrine function for women No uterine disease or abnormality The causes of infertility : Tubal factors Unexplained The protocol of controlled ovary hyperstimulation : A routine long-term protocol Exclusion criteria: Subjects with smoking or alcohol abuse in the past 3 months Patients with overweight or obesity (BMI ≥ 25) Embryos with chromosomal abnormalities confirmed by PGS

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| The reproductive health of couples<br>The study is a prospective cohort study, and its participants are childbearing couples who are seeking assisted reproductive technologies for having a baby in the reproductive center in Tongji Hospital.The study is a observational study. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phthalates exposure levels | Concentrations of phthalates in ng/ml | 12/2021 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exposure characteristics of phthalates | The exposure of different personal care products in weeks | 12/2021 | 
| Reproductive outcomes | The different reproductive outcomes in percent | 12/2021 | 
| The expression profiles of miRNA | The expression profiles of miRNA in different quantity | 12/2021 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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environmental exposure, epigenetic process, embryo development, infertility, cohort study