Epigenetic Safety of Assisted Reproductive Technology

Study Overview
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Brief Summary
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The primary purpose of the study is to investigate the relationship between different protocols of assisted reproductive technology and the epigenetic safety of the offspring. Different interventions of assisted reproductive technology include controlled ovarian hyperstimulation (COH), in vitro embryo culture, in vitro fertilization(IVF), intracytoplasmic sperm injection(ICSI), frozen-thawed embryo transfer(FET), preimplantation genetic testing(PGT). The investigators are also interested in the relationship between pregnancy outcomes in ART or natural conception and environmental, nutritional and lifestyle factors.

Official Title
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Epigenetic Safety of Various Protocols in Assisted Reproductive Technology

Conditions
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Infertility

Intervention / Treatment
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* Other: Completion questionnaires/providing biological samples


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Couples undergoing treatment for infertility or getting pregnant naturally and wanting to deliver their babies in Women's Hospital School of Medicine Zhejiang University, The International Peace Maternity & Child Health Hospital, and Changhai Hospital of Shanghai. Men 22-55 years old Women 20 - 45 years old Exclusion Criteria: Any individual or couple who is outside of age range . Any couple who don't plan to complete their pregnancy check-up or deliver their babies in Women's Hospital School of Medicine Zhejiang University, The International Peace Maternity & Child Health Hospital, or Changhai Hospital of Shanghai.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Couples undergoing ART treatment<br>Couples in reproductive age undergoing ART treatment in Women's Hospital School of Medicine Zhejiang University, The International Peace Maternity & Child Health Hospital, and Changhai Hospital of Shanghai. | Other: Completion questionnaires/providing biological samples<br>* Participant completes baseline interview at enrollment, then completes questionnaires and provides biological samples at each scheduled study visit.<br>|
| Couples getting pregnant naturally<br>Couples who get pregnant naturally and want to deliver the babies in Women's Hospital School of Medicine Zhejiang University, The International Peace Maternity & Child Health Hospital, and Changhai Hospital of Shanghai. | Other: Completion questionnaires/providing biological samples<br>* Participant completes baseline interview at enrollment, then completes questionnaires and provides biological samples at each scheduled study visit.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| live birth rate | Number of women with live births / number of women randomized to the specific group.Live birth is defined as the delivery of any viable infant at 28 weeks or more of gestation after our interventions. | 1 day after delivery | 
| birth weight | Weight of newborns at delivery. | 1 day after delivery | 
| implantation rate | Implantation rate was defined as the percentage of fetal heart beat among total transferred embryos at 12 weeks' gestational age. | 11-12 weeks after embryo transfer | 
| clinical pregnancy rate | Clinical pregnancy was defined as an observation of gestational sac via ultrasonography. | 6 weeks after embryo transfer | 
| congenital anomalies rate | Congenital anomaly included deformity and development abnormality of any organs or systems. | 1 day after delivery | 
| weight | the weight of offspring | Change from the date of delivery up to 4 years after delivery | 
| height | the height of offspring | Change from the date of delivery up to 4 years after delivery | 
| Incidence of mental diseases and metabolic dysfunction |  | 4 years after delivery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| biochemical pregnancy rate | Biochemical pregnancy is defined as numbers of women with an elevated serum β-hCG level of more than 10 mIU/ml. | 2 weeks after embryo transfer | 
| pregnancy loss rate | Pregnancy loss is defined as any reason that resulted in failure of an embryo to develop, embryonic or fetal death, or spontaneous expulsion of a pregnancy. | 28 gestational weeks in maximum | 
| ectopic pregnancy rate | Ectopic pregnancy is defined as an embryo implanted outside the uterine. | 12 gestational weeks in maximum | 
| preterm birth rate | preterm birth is defined as gestational weeks between 28 to 37. | 28 gestational weeks to 37 gestational weeks | 
| Incidence of moderate to severe ovarian hyperstimulation syndrome(OHSS) | Number of cycles of moderate to severe OHSS/total number of fresh stimulation cycle. | 3 months after controlled ovarian hyperstimulation | 
| neonatal complication rate | Neonatal complication includes neonatal respiratory disorders, neonatal cerebral palsy, neonatal encephalopathy and other disease that should been sent into neonatal ICU. | 1 day after delivery |