Chromosome Abnormality, Infertility
Conditions
Keywords
Culture media, Embryonic cell-free DNA, Euploidy
Brief summary
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
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
Interventions
DIAGNOSTIC_TESTNon-invasive chromosome screening（NICS）
NICS is noninvasive chromosome screening approach to analysis the euploidy by free DNA in embryo culture medium
Sponsors
Jinling Hospital, China
Reproductive Medical Center of Hebei Maternity Hospital
Northwest Women's and Children's Hospital, Xi'an, Shaanxi
The First Medical Center of Chinese People's Liberation Army General Hospital
Shengjing Hospital
First Affiliated Hospital, Sun Yat-Sen University
Reproductive & Genetic Hospital of CITIC-Xiangya
Yikon Genomics Company, Ltd
Peking University Shenzhen Hospital
The Second Hospital of Hebei Medical University
West China Second University Hospital
Second Affiliated Hospital of Wenzhou Medical University
Third Affiliated Hospital of Zhengzhou University
Peking University Third Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SCREENING
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
35 Years to 42 Years
Healthy volunteers
Yes
Inclusion criteria
1. Infertile couples receiving IVF- ICSI procedure for assisted reproduction cycle 2. Female age: 35 - 42 years old 3. 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. 4. Culture embryos to blastocyst stage and all the blastocysts will be single cryopreserved. 5. Single frozen-thawed blastocyst Transferred for the first time 6. The number of blastocysts ≥2, morphology grade (above 4BC/4CB) 7. Written informed consent
Exclusion criteria
1. 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.) 2. PGT cycles 3. 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 4. Untreated hyperprolactinemia, thyroid disease, adrenal disease 5. Women with endometrial polyps that were not treated before embryo transfer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ongoing pregnancy rate | 12 weeks after the first embryo transfer | Number of women with ongoing pregnancies after the first transfer/ number of women randomized to the specific group |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical pregnancy rate | 7 weeks after the first embryo transfer | Number of women with clinical pregnancies after the first transfer / number of women randomized to the specific group |
| Miscarriage rate | Miscarriage：28 weeks of after the first embryo transfer； First trimester miscarriage(early miscarriage)：12 weeks of after the first embryo transfer； | Number of pregnancy losses / number of clinical pregnancies after the first transfer. |
| Live birth rate | within 2 weeks after live birth | Number of women with live births after the first transfer / number of women randomized to the specific group. |
Countries
China
Outcome results
None listed