Clinical trial NCT02353364: Blastocyst Euploidy Assessment and Conditioned embryO traNsfer
Official title: Prospective Randomised Control Trial of Blastocyst Euploidy Assessment and Conditioned Embryo Transfer for Infertility Patients of Advanced Maternal Age
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Infertility
Keywords: Advanced maternal age
Aneuploidy
Lead sponsor: Chinese PLA General Hospital
Sponsor class: OTHER
First posted: 2015-02-02
Enrollment: 1000
Sex: FEMALE
Minimum age (years): 35
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Patient undergoing in vitro fertilization (IVF)
* Normal uterine function by ultrasound and absence of hysteromyoma
* Regular menstrual cycle of 25-35 days
* Normal hormone levels (WHO standard) for LH, PRL, E2, PROG, TEST and TSH
* FSH 1-12 IU/L and follicle number \> 5 on day 2-3 of menstrual cycle
* Minimum of 3 blastocysts on day 5 of embryo development
* Signed consent form

Exclusion Criteria:

* Known endometriosis
* Abnormal vaginal bleeding with no known cause
* Known genital organ system malformation, unsuitable to conceive
* Known currently active pelvic inflammation
* Abnormal liver, kidney lab results, with clinical implications.
* Known endocrine or metabolic disorders (pituitary gland, adrenal glands, pancreas, liver or kidney）
* Known ovarian, breast, uterine, adrenal glands, pituitary gland or hypothalamus tumor
* Known abnormal cervical cancer lesions, with clinical implications, within one year before PGS
* History of chemo- or radio-therapy
* Seropositive for HIV, Hep B, Hep C or TPPA/RPR (Syphilis)
* Known ovarian poor response in previous cycles, i.e. after administration of GnRH for \> 20 days
* More than 2 implantation failures
* More than 2 miscarriages
* Known altered parental karyotype such as Robertsonian or reciprocal translocation
* Use of sperm or oocyte donors
* Severe male factor (surgical retrieval of sperm)
* Preimplantation genetic diagnosis cycles for single gene diseases or sex selection
* Participation in other IVF research studies
* Patient refusal or inability to follow the protocol for any good reason, including clinical visit or lab test

Primary outcomes:
measure: Ongoing pregnancy
timeFrame: Gestational week 20
Secondary outcomes:
measure: Genetic health of the fetus
timeFrame: Gestational week 18
Other outcomes:
Locations:
city: Beijing
country: China
facility: Department of Obstetrics and Gynecology
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.