Blastocyst Euploidy Assessment and Conditioned embryO traNsfer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Prospective Randomised Control Trial of Blastocyst Euploidy Assessment and Conditioned Embryo Transfer for Infertility Patients of Advanced Maternal Age

Conditions
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Infertility

Intervention / Treatment
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* Other: PGS


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Transfer of 1 or 2 biopsied euploid embryo of high morphological grade based on NGS testing using CNV-Seq (PGS) | Other: PGS<br>* Embryos screened by the validated NGS technology CNV-Seq<br>|
| No Intervention: Group B<br>Transfer of 1 or 2 non-biopsied embryo of high morphological grade (no PGS) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ongoing pregnancy |  | Gestational week 20 | 

Secondary Outcome Measures

| Outcome Measure | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced maternal age, Aneuploidy