Effects of PGS in Infertile Female Patients With RPL

ShangHai Ji Ai Genetics & IVF Institute

Status: Completed

Conditions: Abortion, Habitual; Infertility, Female

Treatments: Genetic: PGS; Procedure: IVF/ICSI; Other: Without PGS

Study type: Interventional

Funder types: Other

Identifiers

NCT02223221

JIAI E2014-02

Details and patient eligibility

About

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.

Enrollment: 189 patients

Sex: Female

Ages: 18 to 48 years old

Volunteers: No 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:

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

Exclusion criteria

1. 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);
2. the former abortion is because of luteal phase defect without treatment;
3. thyroid dysfunction or increased CA125 level;
4. acute inflammation of genitourinary system or STD carriers;
5. unable to comply with the study procedures.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

---

189 participants in 2 patient groups

With PGS

Experimental group

Description:

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.

Treatment:

Procedure: IVF/ICSI

Genetic: PGS

Without PGS

Active Comparator group

Description:

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.

Treatment:

Procedure: IVF/ICSI

Other: Without PGS