Embryo Selection by Noninvasive Preimplantation Genetic Test

Study Overview
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Brief Summary
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The objective of this study is to explore whether non-invasive chromosome screening (NICS) can be used as an effective indicator for embryos selection besides morphology through a multicenter randomized controlled trial, by comparing the differences of live birth rate, pregnancy rate and miscarriage rate between the two groups of embryo selection by NICS+ morphology and embryo selection only by morphology in IVF cycle.

Detailed Description
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Chromosomal abnormalities commonly exist in early human embryos, and often cause embryo implantation failure and pregnancy loss in in-vitro fertilization (IVF) treatments. Preimplantation genetic testing for aneuploidies (PGT-A) by comprehensive chromosome screening (CCS) has been widely applied in IVF practices to select embryos with normal ploidy. Although multiple clinical trials have demonstrated improved clinical outcomes with PGT-A, it's in controversial for whether PGT-A is truly worthwhile to be offered to all IVF patients. One of the main concerns is that it involves an embryo biopsy procedure, which is invasive and the long-term safety issue of the embryo biopsy remains to be fully investigated. In recent years, researchers have found that the spent medium of embryo culture contains trace amount of cell-free DNA, which may reflect the ploidy of the embryo. The non-invasive chromosome screening (NICS) approach utilizing spent culture medium samples has been evaluated in studies. However, the clinical value of NICS as a new effective indicator to evaluate embryo competence so far has not been justified by randomized clinical trials. The main purpose of this project is to verify whether NICS can be used as a new effective indicator for evaluating embryo developmental potential through multi-center, randomized clinical trials

Official Title
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A Multicenter Clinical Study on Embryo Selection by Using the Ploidy of Cell Free DNA in Embryo Culture Medium

Conditions
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Infertility, Chromosome Abnormality

Intervention / Treatment
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* Diagnostic Test: Non-invasive chromosome screening（NICS）


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infertile couples receiving IVF- ICSI procedure for assisted reproduction cycle Female age: 35 - 42 years old Women receiving controlled ovarian hyperstimulation treatment (including ultra-long protocol、long-protocol 、short protocol treatment with GnRH agonist and GnRH antagonist treatment protocol); and the number of oocytes ≥6; The female BMI is from 18 to 30kg/m2. Culture embryos to blastocyst stage and all the blastocysts will be single cryopreserved. Single frozen-thawed blastocyst Transferred for the first time The number of blastocysts ≥2, morphology grade (above 4BC/4CB) Written informed consent Exclusion Criteria: One of couples with IVF or ICSI contraindications(such as poorly controlled type I or type II diabetes; liver disease or dysfunction; kidney disease or renal function abnormality; significant anemia; history of deep venous thrombosis, pulmonary embolus; history of cerebrovascular accident; uncontrolled hypertension or diagnosed heart disease; history of cervical, endometrial or breast cancer; undiagnosed vaginal bleeding.) PGT cycles Women who have pathologies or malformations that affect the pregnancy outcome: genital malformations, untreated hydrosalpinx, untreated uterine infections, intramural myomas > 4cm , benign tumor of pelvic and abdominal cavity> 4cm, intimal thickness<8mm, pituitary tumors and malignant tumors of various tissues and organs during the patient's participation in the study Untreated hyperprolactinemia, thyroid disease, adrenal disease Women with endometrial polyps that were not treated before embryo transfer

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 42 Years

Sexes Eligible for Study
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Female

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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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Single thawed blastocyst transfer with blastocyst selection according to the analysis of NICS and morphologic score. | Diagnostic Test: Non-invasive chromosome screening（NICS）<br>* NICS is noninvasive chromosome screening approach to analysis the euploidy by free DNA in embryo culture medium<br>|
| No Intervention: Group B<br>Single thawed blastocyst transfer with blastocyst selection according to morphologic score. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ongoing pregnancy rate | Number of women with ongoing pregnancies after the first transfer/ number of women randomized to the specific group | 12 weeks after the first embryo transfer | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical pregnancy rate | Number of women with clinical pregnancies after the first transfer / number of women randomized to the specific group | 7 weeks after the first embryo transfer | 
| Miscarriage rate | Number of pregnancy losses / number of clinical pregnancies after the first transfer. | 28 weeks of after the first embryo transfer | 
| Live birth rate | Number of women with live births after the first transfer / number of women randomized to the specific group. | within 2 weeks after live birth | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Culture media, Embryonic cell-free DNA, Euploidy