Study on the Association Between SXCI and RM and the Possible Genetic Mechanism

Study on the Association Between Skewed X Chromosome Inactivation(SXCI) and Recurrent Miscarriage(RM) and the Possible Genetic Mechanism

To determine whether there is higher incidence of skewed X chromosome inactivation(SXCI) in the recurrent miscarriage(RM) population compared with normal population, and verify the existing hypothesis of the possible genetic mechanisms underlying the association between SXCI and RM.

Study Overview

• Status: Completed
• Conditions: Recurrent Miscarriage; Infertility Female

Detailed Description

Recurrent spontaneous abortion (RSA), defined as 2 or more consecutive pregnancy losses before 20-22 weeks of gestation, is a multifactorial disorder that affects about 5% of all couples.In up to 50% of women who have experienced RSA, the cause still remains unexplained, with genetic problem proposed as a main cause. X chromosome inactivation (XCI) is a physiological phenomenon in female mammals for 'dosage compensation' of X-linked genes with males. A normal female is mosaic, with about one-half of her somatic cells expressing the paternal derived X and the remainder of her cells using maternal X. In some situations, however, the inactivation is not random, resulting in a female having most or even all her somatic cells inactivating the same X chromosome from either paternal or maternal resource, which is known as skewed X-chromosome inactivation (SXCI).Evidence of an association between skewed X chromosome inactivation (SXCI) and idiopathic recurrent spontaneous abortion (RSA) is conflicting. This is a single-center observational case-control trial to determine whether there is higher incidence of skewed X chromosome inactivation(SXCI) in the recurrent miscarriage(RM) population compared with normal population, and verify the existing hypothesis of the possible genetic mechanisms underlying the association between SXCI and RM.

• Study Type: Observational
• Enrollment (Actual): 257

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 200011
    • ShangHai JIAI Genetics&IVF Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 43 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Women visiting our centre for IVF/ICSI during 2015.01.01-2016.01.01 will enter RM group or control group according to their pregnant history or infertility factor.

RM group: Women with a history of recurrent spontaneous abortion (miscarriage occurred earlier than 22 weeks of gestation for equal or greater than 2 times).

Control group:Infertility women because of only male factor. Both groups meet the same elgibility criteria

Description

Inclusion Criteria:

• 1) regular menstrual cycles and normal level of E2, P, FSH, LH, T, RPL in the early follicular phase; 2) no history of gynecologic or other pelvic operations; 3) no history of hormone medicine application in the last 3 months; 4) no history of poison contact; 5) normal uterine and adnexal ultrasonography; 6) TORCH(-), chlamydia(-), mycoplasma(-), normal leucorrhoea routine, anti-phospholipid antibody (-), antinuclear antibody(-); 7) for the couple, no blood type incompatibility or ABO antibody IgG≤1：64 and normal blood chromosome analysis; 8) condoms are used for contraception.

Exclusion Criteria:

• 1) BMI<18.5 or >24.9; 2) 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); 3) the former abortion is because of luteal phase defect without treatment; 4) FSH≥12IU/L or AMH<1.2ng/ml 5) thyroid dysfunction or increased CA125 level; 6) acute inflammation of genitourinary system or STD carriers; 7) unable to comply with the study procedures.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
RM; Women 18-43 years of age who are scheduled for IVF or ICSI with a history of recurrent spontaneous abortion (miscarriage occurred earlier than 22 weeks of gestation for equal or greater than 3 times) in our IVF institute.
Control; Normal females who are visiting Shanghai JIAI genetics and IVF institute for IVF/ICSI because of only male factor.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
degree of X chromosome inactivation skewing	Within 3 months after blood collection
percentage of extremely skewed X chromosome inactivation(SXCI>90%) in each group	Within 3 months after blood collection

Collaborators and Investigators

• Sponsor: ShangHai Ji Ai Genetics & IVF Institute
• Investigators: Study Director: XIAOXI SUN, MD, ShangHai Ji Ai Genetics & IVF Institute

Publications and helpful links

General Publications

• Sui Y, Fu J, Zhang S, Li L, Sun X. Investigation of the role of X chromosome inactivation and androgen receptor CAG repeat polymorphisms in patients with recurrent pregnancy loss: a prospective case-control study. BMC Pregnancy Childbirth. 2022 Nov 2;22(1):805. doi: 10.1186/s12884-022-05113-z.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2015
• Primary Completion (ACTUAL): July 1, 2021
• Study Completion (ACTUAL): December 1, 2021

Study Registration Dates

• First Submitted: July 19, 2015
• First Submitted That Met QC Criteria: July 19, 2015
• First Posted (ESTIMATE): July 21, 2015

Study Record Updates

• Last Update Posted (ACTUAL): April 11, 2022
• Last Update Submitted That Met QC Criteria: April 2, 2022
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pregnancy Complications; Infertility; Abortion, Spontaneous; Abortion, Habitual; Infertility, Female
• Other Study ID Numbers: JIAI E2015-02