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.

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.

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.

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