Effects of PGS2.0 in Patients With Unexplained RPL

Study Overview
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Brief Summary
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50%-60% of the known causes of recurrent pregnancy loss(RPL) are associated with embryonic aneuploidy, such that preimplantation genetic screening (PGS) on embryos acquired by assisted reproductive treatment should improve the rate of pregnancy and live birth in those patients. In dispute though the clinical application of PGS has been, a series of studies show that the new generation of PGS(PGS 2.0), based on blastocyst biopsy followed by whole genome analysis, has significantly improved the clinical outcome of IVF treatment. At present, there is still a need for the evidence of the use of PGS 2.0 in RPL patients, who may benefit from this emerging technology considering the prevalence of genetic abnormalities and the number of transferable embryos in this population. An earlier single center RCT conducted by our IVF center displayed higher implantation rate, clinical pregnancy rate and ongoing pregnancy rate calculated by per embryo transfer(ET) cycle in IVF/ICSI+PGS group compared with IVF/ICSI group. This multi-center prospective randomized clinical trial is to provide more data to determine whether the clinical outcomes are significantly improved per treatment cycle such that provide evidence for the application of PGS in RPL patients. Besides, risk factors of PGS outcome are to be analyzed from multi-center data to build a model for prediction of the possible outcomes of PGS and direction of the clinical choice.

Official Title
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Effects of Preimplantation Genetic Screening 2.0 on the Clinical Outcomes of Assisted Reproductive Treatment in Patients With Recurrent Pregnancy Loss : A Multi-center-based Prospective Randomized Clinical Trial

Conditions
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Recurrent Pregnancy Loss, Infertility, Female

Intervention / Treatment
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* Procedure: IVF/ICSI
* Genetic: PGS 2.0
* Other: Conventional embryo morphology evaluation


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: The couple has experienced two or more failed pregnancies (according to ASRM definition). The karyotypes of both husband and wife are normal (polymorphic chromosomes are considered normal either). 3. Women ages ≥20 and <38 years old. Exclusion criteria: the wife has history of the following diseases: a, the history of thyroid disease; b, the history of adrenal diseases; c, the history of sexually transmitted diseases; d, the history of hereditary diseases; e, the history of mental and psychological disorders. the wife has the following uterine abnormalities: a, uterine malformations (uterus unicorns and duplex uterus), untreated septate uterus, adenomyoma, submucous uterine fibroids, endometrial polyps, or intrauterine adhesions (including the history of intrauterine adhesions). the wife has a medical condition that contraindicate ART or pregnancy, including poorly controlled type I or type II diabetes; undiagnosed liver and renal disease or liver and renal insufficiency (based on blood test); deep vein thrombosis; pulmonary embolism; history of cerebrovascular accident; uncontrolled hypertension; cardiac disease; carcinoma; severe anemia; suspicious or undiagnosed vaginal bleeding.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 37 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: With PGS 2.0<br>Patients will undergo IVF/ICSI procedure, and experience oocyte aspiration, fertilization,blastocyst formation,conventional embryo morphology evaluation and trophectoderm biopsy before blastocyst cryopreservation. Preimplantation genetic screening (PGS) will be performed to select euploid embryo. The patients will go through up to three times of frozen-thawed transfers of euploid blastocysts until ongoing pregnancy or live birth is acquired. Only one euploid blastocyst will be transferred at a time. | Procedure: IVF/ICSI<br>* in vitro fertilization or intracytoplasmatic sperm injection<br>Genetic: PGS 2.0<br>* Blastocysts are selected by PGS 2.0(NGS based) and only euploid embryos will be transferred.<br>|
| Active Comparator: Without PGS 2.0<br>Patients will undergo IVF/ICSI procedure, and experience oocyte aspiration, fertilization,blastocyst formation,and conventional embryo morphology evaluation before blastocyst cryopreservation. The patients will go through up to three times of frozen-thawed transfers of good quality blastocysts until ongoing pregnancy or live birth is acquired. Only one good quality blastocyst will be transferred at a time. | Procedure: IVF/ICSI<br>* in vitro fertilization or intracytoplasmatic sperm injection<br>Other: Conventional embryo morphology evaluation<br>* Blastocysts are selected by morphology criteria and only good-scored embryo will be transferred.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Live birth rate per initiated cycle | live birth rate of a baby per oocyte retrieval cycle initiated | up to 42 days of a live birth | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Embryo implantation | positive serum hCG after 2 weeks of embryo transfer | 2 weeks after embryo transfer | 
| Clinical pregnancy | the presence of a gestational sac confirmed by transvaginal ultrasound examination | 4 weeks after embryo transfer | 
| Ongoing pregnancy | the fetal heat beat continued at 10 weeks after embryo transfer | 10 weeks after embryo transfer | 
| Time to pregnancy | From the day of entering oocyte retrieval cycle to the embryo transfer day of a later assured ongoing pregnancy,which is up to 24 months within the study period.If the patient fails to obtain ongoing pregnancy during the study period, this outcome measure will not be recorded. | From the day of entering oocyte retrieval cycle to the embryo transfer day of a later assured ongoing pregnancy,which is up to 24 months within the study period. | 
| Pregnancy outcome | abortion, multiple birth, birth defects, preterm delivery, small for gestational age, still birth | up to 42 days of a live birth | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unexplained recurrent pregnancy loss, infertility, female, preimplantation genetic screening, in vitro fertilization, intracytoplasmic sperm injection