Effects of PGS in Infertile Female Patients With RPL

Sponsor

ShangHai Ji Ai Genetics & IVF Institute (Other)

Overall Status

Completed

CT.gov ID

NCT02223221

Collaborator

(none)

189

Enrollment

Location

Arms

Duration (Months)

5.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Recurrent pregnancy loss (RPL) is a multifactorial disorder which affects about 1% of all couples and challenges both patients and clinicians technically and emotionally. IVF clinics see higher prevalence of RPL, since many RPL patients are seeking for assist reproduction treatment with or without other infertile factors. Guidelines for evaluation and treatment of RPL patients include screening for uterine abnormalities, parental chromosomes, autoimmune antibodies and cure gynecological infections, but there are still half of RPL patients remain unexplained.

The documented high incidence of chromosomal errors in first-trimester miscarriages and an increased rate of aneuploidy in patients with RPL has led to the theory that screening embryos before implantation for aneuploidy may decrease the risk of a subsequent loss and serve as a possible treatment. The technology, indications of use, and even terminology for genetic testing of embryos have greatly changed since the first PGD(pre-implantation genetic diagnosis) baby was born in 1990. The current best evidence shows blastocyst biopsy followed by new rapid comprehensive chromosome screening(termed pre-implantation chromosomal screening or comprehensive chromosome screening, PCS or CCS, or the investigators generally termed PGS) based on array-comprehensive genome hybridization(aCGH), single nucleotide polymorphism array(SNP-array) or next generation sequencing(NGS), to be the most powerful technology. However, for whom this PGS technique is most suitable to achieve improved clinical outcome have not yet been identified by well defined, ITT based research with carefully selected control and adequate sample size.

The investigators research is to determine whether in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI) combined with SNP-array based pre-implantation comprehensive chromosome screening (CCS) will improve the clinical outcome of infertile female patients with recurrent spontaneous abortion history.

Condition or Disease	Intervention/Treatment	Phase
Infertility, Female Abortion, Habitual	Procedure: IVF/ICSI Genetic: PGS Other: Without PGS	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

189 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Care Provider)

Primary Purpose:

Treatment

Official Title:

Effects of Preimplantation Genetic Screening for Aneuploidies in Infertile Female Patients With Recurrent Spontaneous Abortion History

Study Start Date :

Aug 1, 2014

Actual Primary Completion Date :

Jul 31, 2016

Actual Study Completion Date :

Apr 30, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: With PGS IVF/ICSI cycles with PGS. Select embryos by SNP-array based PGS for the number of all chromosomes on day 5, only euploid embryos will be transferred. A maximum of 2 embryos will be transferred for each treatment cycle. Up to 3 treatment cycles will be offered.	Procedure: IVF/ICSI In vitro fertilization or intracytoplasmic sperm injection. Genetic: PGS Selection of embryos are based on SNP-array-based preimplantation genetic screening for the number of all chromosomes on the 5th day of IVF/ICSI.
Active Comparator: Without PGS IVF/ICSI cycles without PGS. Selection of embryos are based on blastocyst morphology criteria on day 5. A maximum of 2 embryos will be transferred for each treatment cycle. Up to 3 treatment cycles will be offered.	Procedure: IVF/ICSI In vitro fertilization or intracytoplasmic sperm injection. Other: Without PGS Selection of embryos are based on morphology criteria on the 5th day of IVF/ICSI.

Arm

Intervention/Treatment

Experimental: With PGS

IVF/ICSI cycles with PGS. Select embryos by SNP-array based PGS for the number of all chromosomes on day 5, only euploid embryos will be transferred. A maximum of 2 embryos will be transferred for each treatment cycle. Up to 3 treatment cycles will be offered.

Procedure: IVF/ICSI

In vitro fertilization or intracytoplasmic sperm injection.

Genetic: PGS

Selection of embryos are based on SNP-array-based preimplantation genetic screening for the number of all chromosomes on the 5th day of IVF/ICSI.

Active Comparator: Without PGS

IVF/ICSI cycles without PGS. Selection of embryos are based on blastocyst morphology criteria on day 5. A maximum of 2 embryos will be transferred for each treatment cycle. Up to 3 treatment cycles will be offered.

Procedure: IVF/ICSI

In vitro fertilization or intracytoplasmic sperm injection.

Other: Without PGS

Selection of embryos are based on morphology criteria on the 5th day of IVF/ICSI.

Outcome Measures

Primary Outcome Measures

Ongoing pregnancy [12 weeks after embryo transfer for the patient]
Ongoing pregnancy is defined as a viable intrauterine pregnancy after 12 weeks of embryo transfer. Ongoing pregnancy rate per treatment cycle will also be calculated on intend-to-treat(ITT) basis.

Secondary Outcome Measures

Implantation of transferred embryo [2 weeks after embryo transfer for the patient]
Implantation rate per embryo transferred will also be calculated.
Clinical pregnancy [4 weeks after embryo transfer for the patient]
Clinical pregnancy is defined as the presence of a gestational sac confirmed by transvaginal ultrasound examination. Clinical pregnancy rate per treatment cycle will also be calculated based on ITT.
Time to pregnancy [from the date of the first time entering oocyte retrieval cycle until the embryo transfer day of a later assured ongoing pregnancy, accessed up to 24 months during the whole research period]
Time to pregnancy is defined as from the first time 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 obtain ongoing pregnancy during the study period, the "time to pregnancy" will not be recorded for the specific patient or be calculated for the "average time to pregnancy" for the arm.
Pregnancy outcome [up to 42 days of a live birth]
abortion, live birth, multiple births, birth defect, preterm delivery, small-for-gestational age, still birth, maternal complications will be recorded.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 48 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Women 18-48 years of age who are scheduled for IVF or ICSI with a history of recurrent spontaneous abortion (continous miscarriage occurred earlier than 20 weeks of gestation for equal or greater than 2 times) in our IVF institute while meeting the following criteria:

regular menstrual cycles and normal level of E2, P, FSH, LH, T, RPL in the early follicular phase;
no history of hormone medicine application in the last 3 months;
no history of poison contact;
normal uterine and adnexal ultrasonography;
TORCH(-), chlamydia(-), mycoplasma(-), normal leucorrhoea routine, anti-phospholipid antibody (-), antinuclear antibody(-);
for the couple, no blood type incompatibility or ABO antibody IgG≤1：64 and normal blood chromosome analysis.

Exclusion Criteria:

hydrosalpinx without operation; endometriosis; polycystic ovary syndrome; adenomyosis; uterine leiomyomata(submucous myoma or non-submucous myoma which size was exceed 4cm and/or with the compressed endometrium);uterine cavity lesions(such as uterine malformation, intrauterine adhesions, the septate uterus, endometritis etc);
the former abortion is because of luteal phase defect without treatment;
thyroid dysfunction or increased CA125 level;
acute inflammation of genitourinary system or STD carriers;
unable to comply with the study procedures.