Clinical trial NCT04339166: Embryo Selection by Noninvasive Preimplantation Genetic Test
Official title: A Multicenter Clinical Study on Embryo Selection by Using the Ploidy of Cell Free DNA in Embryo Culture Medium
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Infertility
Chromosome Abnormality
Keywords: Culture media
Embryonic cell-free DNA
Euploidy
Lead sponsor: Peking University Third Hospital
Sponsor class: OTHER
Collaborators: name: Jinling Hospital, China
name: Reproductive Medical Center of Hebei Maternity Hospital
name: Northwest Women's and Children's Hospital, Xi'an, Shaanxi
name: The First Medical Center of Chinese People's Liberation Army General Hospital
name: Shengjing Hospital
name: First Affiliated Hospital, Sun Yat-Sen University
name: Reproductive & Genetic Hospital of CITIC-Xiangya
name: Yikon Genomics Company, Ltd
name: Peking University Shenzhen Hospital
name: The Second Hospital of Hebei Medical University
name: West China Second University Hospital
name: Second Affiliated Hospital of Wenzhou Medical University
name: Third Affiliated Hospital of Zhengzhou University
First posted: 2020-04-09
Enrollment: 1152
Sex: FEMALE
Minimum age (years): 35
Maximum age (years): 42
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

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

Eligibility criteria: 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

Primary outcomes:
measure: Ongoing pregnancy rate
timeFrame: 12 weeks after the first embryo transfer
Secondary outcomes:
measure: Clinical pregnancy rate
timeFrame: 7 weeks after the first embryo transfer
measure: Miscarriage rate
timeFrame: 28 weeks of after the first embryo transfer
measure: Live birth rate
timeFrame: within 2 weeks after live birth
Other outcomes:
Locations:
city: Guanzhou
country: China
facility: The First Affiliated Hospital,Sun Yat-sen University
state: Guangdong
city: Shenzhen
country: China
facility: Peking University Shenzhen Hospital
state: Guangdong
city: Shijia Zhuang
country: China
facility: The Second Hospital of Hebei Medical University
state: Hebei
city: Shijiazhuang
country: China
facility: Hebei Maternity and Reproductive hospital
state: Hebei
city: Zhengzhou
country: China
facility: The Third Affiliated Hospital of Zhengzhou University
state: Henan
city: Changsha
country: China
facility: Reproductive & Genetic Hospital of Citic-Xiangya
state: Hunan
city: Nanjing
country: China
facility: Jinling Hospital,Nanjing University,School Medicine
state: Jiangsu
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
city: Chengdu
country: China
facility: West China Second Hospital of Sichuan University
state: Sichuan
city: Wenzhou
country: China
facility: The Second Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
city: Beijing
country: China
facility: Peking University Third Hospital
city: Beijing
country: China
facility: The First Medical Center of Chinese People's Liberation Army General Hospital
city: Xi'an
country: China
facility: Northwest women's and children's hospital
Study officials:
affiliation: Peking University Third Hospital
name: Jie Qiao
role: PRINCIPAL_INVESTIGATOR
References:
citation: Huang J, Rong L, Zeng L, Hu L, Shi J, Cai L, Yao B, Wang XX, Xu Y, Yao Y, Wang Y, Zhao J, Guan Y, Qian W, Hao G, Lu S, Liu P, Qiao J. Embryo selection through non-invasive preimplantation genetic testing with cell-free DNA in spent culture media: a protocol for a multicentre, double-blind, randomised controlled trial. BMJ Open. 2022 Jul 27;12(7):e057254. doi: 10.1136/bmjopen-2021-057254.