Effects of PGS2.0 in Patients With Unexplained RPL

ShangHai Ji Ai Genetics & IVF Institute710 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

710

Conditions

Recurrent Pregnancy Loss

Interventions

IVF/ICSIPROCEDURE

in vitro fertilization or intracytoplasmatic sperm injection

PGS 2.0GENETIC

Blastocysts are selected by PGS 2.0(NGS based) and only euploid embryos will be transferred.

Conventional embryo morphology evaluationOTHER

Blastocysts are selected by morphology criteria and only good-scored embryo will be transferred.

Eligibility

Sex: FEMALEMin age: 20 YearsMax age: 37 Years

Medical Language ↔ Plain English

Inclusion criteria: 1. The couple has experienced two or more failed pregnancies (according to ASRM definition). 2. 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: 1. 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. 2. 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). 3. 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.

Outcomes

Primary Outcomes

Live birth rate per initiated cycle

live birth rate of a baby per oocyte retrieval cycle initiated

Time frame: up to 42 days of a live birth

Secondary Outcomes

Embryo implantation

positive serum hCG after 2 weeks of embryo transfer

Time frame: 2 weeks after embryo transfer

Clinical pregnancy

the presence of a gestational sac confirmed by transvaginal ultrasound examination

Time frame: 4 weeks after embryo transfer

Ongoing pregnancy

the fetal heat beat continued at 10 weeks after embryo transfer

Time frame: 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.

Time frame: 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