Clinical trial NCT02223221: Effects of PGS in Infertile Female Patients With RPL
Official title: Effects of Preimplantation Genetic Screening for Aneuploidies in Infertile Female Patients With Recurrent Spontaneous Abortion History
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Infertility, Female
Abortion, Habitual
Keywords: In Vitro Fertilization
Intracytoplasmic Sperm Injections
Infertility, Female
Abortion, Habitual
recurrent pregnancy loss
comprehensive chromosome screening
preimplantation genetic screening
SNP array
Lead sponsor: ShangHai Ji Ai Genetics & IVF Institute
Sponsor class: OTHER
First posted: 2014-08-22
Enrollment: 189
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 48
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Ongoing pregnancy
timeFrame: 12 weeks after embryo transfer for the patient
Secondary outcomes:
measure: Implantation of transferred embryo
timeFrame: 2 weeks after embryo transfer for the patient
measure: Clinical pregnancy
timeFrame: 4 weeks after embryo transfer for the patient
measure: Time to pregnancy
timeFrame: 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
measure: Pregnancy outcome
timeFrame: up to 42 days of a live birth
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Jiai Genetics & IVF Institute
Study officials:
affiliation: Shanghai Jiai Genetics & IVF Institute
name: XIAOXI SUN, MD
role: STUDY_DIRECTOR
affiliation: Shanghai Jiai Genetics & IVF Institute
name: YILUN SUI, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cornelisse S, Zagers M, Kostova E, Fleischer K, van Wely M, Mastenbroek S. Preimplantation genetic testing for aneuploidies (abnormal number of chromosomes) in in vitro fertilisation. Cochrane Database Syst Rev. 2020 Sep 8;9(9):CD005291. doi: 10.1002/14651858.CD005291.pub3.