Embryo Selection by Noninvasive Preimplantation Genetic Test

Not Applicable

Completed

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

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Group A	Non-invasive chromosome screening（NICS）	Single thawed blastocyst transfer with blastocyst selection according to the analysis of NICS and morphologic score.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Miscarriage rate	28 weeks of after the first embryo transfer	Number of pregnancy losses / number of clinical pregnancies after the first transfer.
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
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.

Locations (13): The First Affiliated Hospital,Sun Yat-sen University
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Guanzhou, Guangdong, China
Peking University Shenzhen Hospital
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Shenzhen, Guangdong, China
The Second Hospital of Hebei Medical University
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Shijia Zhuang, Hebei, China
Hebei Maternity and Reproductive hospital
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Shijiazhuang, Hebei, China
The Third Affiliated Hospital of Zhengzhou University
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Zhengzhou, Henan, China
Reproductive & Genetic Hospital of Citic-Xiangya
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Changsha, Hunan, China
Jinling Hospital,Nanjing University,School Medicine
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Nanjing, Jiangsu, China
Shengjing Hospital of China Medical University
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Shenyang, Liaoning, China
West China Second Hospital of Sichuan University
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Chengdu, Sichuan, China
The Second Affiliated Hospital of Wenzhou Medical University
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Wenzhou, Zhejiang, China
Peking University Third Hospital
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Beijing, China
The First Medical Center of Chinese People's Liberation Army General Hospital
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Beijing, China
Northwest women's and children's hospital
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Xi'an, China