RCT of niPGT for Aneuploidy and Morphology Compared With Morphology Alone in IVF

Study Overview
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Brief Summary
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This study is to compare the efficacy in embryo selection based on morphology alone compared to morphology and non-invasive preimplantation genetic testing for aneuploidy (NIPGT-A) in infertile women undergoing in vitro fertilization (IVF). We supposed the embryo selection based on morphology and NIPGT-A results in a higher live birth rate and a lower miscarriage rate in IVF as compared with that based on morphology alone. Therefore we would like to conduct a double-blind randomized controlled trial. Infertile women undergoing IVF will be enrolled. The spent culture medium (SCM) of each blastocyst will be frozen individually. They will be randomized into two groups: (1) the intervention group based on morphology and NIPGT-A and (2) the control group based on morphology alone. In the control group, blastocysts with the best quality morphology will be replaced first. In the intervention group, blastocysts with the best morphology and euploid result of SCM will be replaced first.The primary outcome is a live birth per the first embryo transfer. We would like to compare live birth rates and miscarriage rates between the two groups.

Official Title
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A Randomized Double Blind Controlled Trial of Non-invasive Preimplantation Genetic Testing for Aneuploidy and Morphology Compared With Morphology Alone in in Vitro Fertilisation

Conditions
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Preimplantation Diagnosis

Intervention / Treatment
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* Genetic: Non-invasive Preimplantation genetic testing for aneuploidy status


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women aged less than 43 years at the time of ovarian stimulation At least two blastocysts suitable for freezing on day 5 or 6 after oocyte retrieval Exclusion Criteria: Less than two blastocysts suitable for freezing on day 5 or 6 after oocyte retrieval; Women undergoing PGT for monogenic diseases or structural rearrangement of chromosomes; Use of donor oocytes; Hydrosalpinx shown on pelvic scanning and not surgically treated

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 43 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: intervention group using morphology and NIPGT-A<br>Both morphology and NIPGT-A result will be used to prioritize the sequence of embryo transfer in the intervention group. | Genetic: Non-invasive Preimplantation genetic testing for aneuploidy status<br>* In the intervention group, comprehensive chromosome screening using NGS will be performed according to the recommendations of the company in all SCM samples. Sequence of replacement shall be altered by the NiPGT result after morpholgy.<br>|
| No Intervention: control group based on morphology alone<br>Morphology only will be used to prioritize the sequence of embryo transfer in the intervention arm. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Live birth | Birth beyond 22 weeks of gestation per the first FET | Number of live births beyond 22 weeks of gestation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative live birth rate | Number of pregnancies leading to live birth within 6 months of randomization | Number of pregnancies leading to live birth within 6 months of randomization | 
| Time to pregnancy | between time of IVF and pregnancy | 1 year | 
| Positive urine pregnancy test | Urine pregnancy test positive | Positive urine pregnancy test 14 days after embryo transfer | 
| Clinical pregnancy | Presence of intrauterine gestational sac on scanning at gestational week 6 | 6 weeks | 
| Ongoing pregnancy | Presence of a fetal pole with pulsation at 8-10 weeks of gestation | 10 weeks | 
| Miscarriage defined | Clinically recognized pregnancy loss before the 22 weeks of pregnancy and whose denominator is the clinical pregnancy. | Pregnancy loss up to 22 weeks | 
| Multiple pregnancy | presence of more than one intrauterine sac at 6 weeks of gestation | more than one intrauterine sac at 6 weeks | 
| Ectopic pregnancy | Pregnancy not in the uterus | 12 weeks | 
| Birth weight | Pregnancy outcome | 1 year | 
| Apgar score | Pregnancy outcome | 1 year |