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The study is designed to evaluate the effectiveness of pre-implantation genetic screening (PGS) for infertility patients of advanced maternal age undergoing assisted reproductive treatment. Half of the patients will have their embryos tested by PGS and 1 or 2 chromosomally normal embryos with the highest morphological grading transplanted back to the uterus. The other half of the participants will not have their embryos tested and 1 or 2 untested embryos with the highest morphological grading transplanted back to the uterus.
PGS is an assisted reproductive technology that screens patients embryos, discriminating between embryos with a normal set of chromosomes (euploid) and those with an abnormal set of chromosomes (aneuploid). In this study, we will apply a novel validated next generation sequencing technology called copy number variation sequencing (CNV-Seq) to comprehensively screen a trophectoderm biopsy sample from patient's embryos for chromosomal abnormalities that commonly arise in human embryos. The hypothesis is that PGS performed using CNV-Seq on embryos produced by patients with a poor prognosis for pregnancy (maternal age > 35), followed by transfer of chromosomally normal euploid embryos, will result in significantly higher implantation, pregnancy and live birth rates and lower miscarriage rates compared to patients having no PGS.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group A | Experimental | Transfer of 1 or 2 biopsied euploid embryo of high morphological grade based on NGS testing using CNV-Seq (PGS) |
|
| Group B | No Intervention | Transfer of 1 or 2 non-biopsied embryo of high morphological grade (no PGS) |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PGS | Other | Embryos screened by the validated NGS technology CNV-Seq |
|
| Measure | Description | Time Frame |
|---|---|---|
| Ongoing pregnancy | Gestational week 20 |
| Measure | Description | Time Frame |
|---|---|---|
| Genetic health of the fetus | The patient will be offered a noninvasive prenatal test for fetal aneuploidies between 12-18 weeks gestation | Gestational week 18 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Li Wang, PhD | Contact | pkulwang@126.com | ||
| Yao Yuanqing, MD | Contact | yqyao@126.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Obstetrics and Gynecology | Recruiting | Beijing | 100853 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24193117 | Background | Wang Y, Chen Y, Tian F, Zhang J, Song Z, Wu Y, Han X, Hu W, Ma D, Cram D, Cheng W. Maternal mosaicism is a significant contributor to discordant sex chromosomal aneuploidies associated with noninvasive prenatal testing. Clin Chem. 2014 Jan;60(1):251-9. doi: 10.1373/clinchem.2013.215145. Epub 2013 Nov 5. | |
| 24998187 | Background |
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| ID | Term |
|---|---|
| D007246 | Infertility |
| D000782 | Aneuploidy |
| ID | Term |
|---|---|
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D002869 | Chromosome Aberrations |
| D010335 | Pathologic Processes |
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| Liang D, Peng Y, Lv W, Deng L, Zhang Y, Li H, Yang P, Zhang J, Song Z, Xu G, Cram DS, Wu L. Copy number variation sequencing for comprehensive diagnosis of chromosome disease syndromes. J Mol Diagn. 2014 Sep;16(5):519-526. doi: 10.1016/j.jmoldx.2014.05.002. Epub 2014 Jul 3. |
| 24648399 | Background | Wang L, Wang X, Zhang J, Song Z, Wang S, Gao Y, Wang J, Luo Y, Niu Z, Yue X, Xu G, Cram DS, Yao Y. Detection of chromosomal aneuploidy in human preimplantation embryos by next-generation sequencing. Biol Reprod. 2014 May 8;90(5):95. doi: 10.1095/biolreprod.113.116459. Print 2014 May. |
| 24966395 | Background | Wang L, Cram DS, Shen J, Wang X, Zhang J, Song Z, Xu G, Li N, Fan J, Wang S, Luo Y, Wang J, Yu L, Liu J, Yao Y. Validation of copy number variation sequencing for detecting chromosome imbalances in human preimplantation embryos. Biol Reprod. 2014 Aug;91(2):37. doi: 10.1095/biolreprod.114.120576. Epub 2014 Jun 25. |
| 25160978 | Background | Wang H, Wang L, Ma M, Song Z, Zhang J, Xu G, Fan J, Li N, Cram DS, Yao Y. A PGD pregnancy achieved by embryo copy number variation sequencing with confirmation by non-invasive prenatal diagnosis. J Genet Genomics. 2014 Aug 20;41(8):453-6. doi: 10.1016/j.jgg.2014.06.007. Epub 2014 Jul 17. No abstract available. |
| 32898291 | Derived | Cornelisse S, Zagers M, Kostova E, Fleischer K, van Wely M, Mastenbroek S. Preimplantation genetic testing for aneuploidies (abnormal number of chromosomes) in in vitro fertilisation. Cochrane Database Syst Rev. 2020 Sep 8;9(9):CD005291. doi: 10.1002/14651858.CD005291.pub3. |
| D013568 |
| Pathological Conditions, Signs and Symptoms |