What are the causes of recurrent miscarriage?

  The occurrence of spontaneous miscarriage for 2 or more times in a row is called recurrent miscarriage, and the incidence is about 1%. If spontaneous miscarriage occurs for 3 or more times in a row, it is also called habitual miscarriage. Therefore, recurrent miscarriage is commonly used internationally instead of habitual miscarriage.  1 Human cytomeganovims (HCMV) is a common human pathogenic virus, which can infect the fetus through the placenta during pregnancy, leading to miscarriage and stillbirth. 2 Toxoplasmosis is a widely spread disease caused by Toxoplasma gondii, and Toxoplasma gondii infection causes habitual miscarriage through the placenta from mother’s blood to fetus. Chlamydia trachomatisl is associated with miscarriage, mainly due to CT. It causes miscarriage during pregnancy through episodic or hematogenous infection of the fetal membranes, amniotic fluid, or fetus.4 Mycoplasma urealytieum (UU) is a prokaryotic microorganism between bacteria and viruses. UU infects the fetal membranes, amniotic fluid, and fetus episodically through the cervix and vagina, and can be transmitted from maternal blood to the fetus via the placenta.5 Listeria monocyto.genes is an anaerobic bacterium that infects the fetal membranes or chorion episodically or hemorrhagically, causing abortion.6 Parvovirus B 19 is a microvirus. B19 is the smallest single-stranded DNA virus, which can cause infectious erythema in pregnant women, and the virus infects the placenta and spreads to the fetus through bloodstream, causing fetal edema.7 Treponema pallidum, commonly known as syphilis spirochetes, is a sexually transmitted disease. Syphilis is transmitted hematologically and infects the fetus through the placenta.8 Herpes simplex virus (HSV), while HSV I II often infects the genitalia during pregnancy, cervical and vaginal HSV I infection can lead to both upstream and hematogenous transmission.9 Rubella virus (rubella) Rubella virus is an RNA virus. It is transmitted to the fetus via blood-borne transmission.10 Human immunodeficiency virus (HIV) HIV is transmitted mainly through sexual contact and illicit drug use, and is transmitted vertically to the fetus via blood-borne transmission after infection in pregnant women.  Second, autoimmune type and homoimmune type antibodies Autoimmune type body immune system recognizes and reacts to its own components to produce autoantibodies or autoantibody abnormalities is one of the causes of high miscarriage rate, women with unexplained HA may have underlying early autoimmune disorder.1 Anti-cardiolipin antibody (ACAb) causes recurrent miscarriage mainly by interfering with the formation and development of placenta, amniotic membrane,2 Anti-uterine Once produced, EMAb can bind to target antigens in the endometrium, resulting in an antigenic endometrial reaction, activation of the antibody system, and activation of complement can cause immunopathological damage to the endometrium, interfering with and preventing implantation of the fertilized egg and embryo development, leading to infertility and miscarriage.3 Anti-HCG antibodies can block the action of HCG and lead to HA.4 Anti-sperm antibodies (ASAb) can reduce sperm viability and the ability of sperm to penetrate the mucus and zona pellucida of the official neck, interfering with sperm capacitation, fertilization and embryo sac implantation causing miscarriage.5. Tumor necrosis factor a, soluble interleukin a receptor. Soluble interleukin a levels in the patient’s serum respond to the level of antigenic stimulation, and elevation is a sign of stronger antigenic stimulation. Tumor necrosis factor a is mainly produced by activated macrophages and is an important inflammatory mediator and immunomodulatory factor, which is involved in the regulation of various biological functions during normal pregnancy. 6 Lupus anticoagulation factor (LA) Anti-thyroid antibodies. Thyroid is a hidden antigen. Patients with recurrent miscarriage have autoimmune dysfunction and elevated anti-thyroid antibodies. Anti-thyroid antibodies are more reactive to the placenta during pregnancy, leading to decreased placental function and increased risk of miscarriage, while patients with unimpaired thyroid function or only in the sub-I clinical stage may develop autoimmune thyroid disease postpartum. Anti-ovarian antibodies (AovAb), antinuclear antibodies (ANA) have all been reported to be associated with recurrent miscarriage.  Alloimmune antibodies: closed antibody negative refers to abnormal maternal recognition of the paternal antigen of the embryo and resulting in immune hyporesponsiveness, leading to maternal closed and/or protective antibody deficiency and other cellular and humoral immune abnormalities, resulting in miscarriage due to abnormal immune system attack on the embryo.  Endocrine abnormalities during pregnancy 1. low serum progesterone level is the main endocrine factor of habitual miscarriage. 2. insufficient serum estradiol follicular secretion of estradiol, resulting in delayed endometrial development. After ovulation, the follicular development of the corpus luteum, which secretes estradiol, is still not improved, so that progesterone cannot fully act on the endometrium, which further aggravates the endometrial dysplasia, resulting in obstruction of embryo implantation and miscarriage. 3. follicle-maturation hormone follicle-maturation hormone is an indispensable hormone for follicular maturation, and patients with habitual miscarriage often show low levels of follicle-maturation hormone in the early and middle follicular stages or luteinizing hormone/follicle-maturation hormone. This follicle-maturation hormone deficiency may be related to abnormal secretion of luteinizing hormone-releasing hormone.4. Luteinizing hormone Domestic and foreign studies have confirmed that only low concentrations of luteinizing hormone are required during the follicular phase. Prolactin is a necessary substance for follicular development and maturation, a necessary hormone for corpus luteum development, and a major regulator of sex hormones. Progesterone can promote the release of prolactin, which is a prerequisite for the production of progesterone and the maintenance of luteal function. High prolactin levels may also be associated with unexplained habitual miscarriage. Therefore, patients with habitual abortion should be routinely tested for prolactin.7. Abnormal thyroid function, including hypo- and hyperthyroidism.  Abnormal anatomy of the reproductive tract Abnormal anatomy of the female reproductive tract can cause habitual abortion, especially abnormal uterine development.1 Inadequate blood supply Some abnormal uteruses have inadequate blood supply after pregnancy, such as double uterus, unicornuate uterus, with blood supply from only one side of the blood vessels, and poor metaphase formation after pregnancy, which affects fetal development and growth and miscarriage. In some abnormal developmental uterus, such as longitudinal uterus, if the fertilized egg is implanted in the longitudinal septum, the vascular formation of the longitudinal mucosa is poor and the blood supply to the embryo is insufficient, resulting in miscarriage.2 The uterine cavity is narrow and the pressure in the uterine cavity is high after pregnancy, making it prone to miscarriage and preterm delivery during midtrimester, such as unicornuate uterus.3 The uterus with cervical insufficiency is abnormally developed and the cervix is also poorly developed. If the ratio of cervical muscle tissue to connective tissue is imbalanced, recurrent midtrimester miscarriages are likely to occur.  In spontaneous abortions before 8 weeks of pregnancy, about 50% of the embryos have chromosomal abnormalities, very few of which develop into fetuses, and most of those who survive after birth have congenital developmental abnormalities including neural tube defects, such as anencephaly and spina bifida. Chromosomal abnormalities that result in miscarriage often result in empty gestational sacs or structurally abnormal embryos. In addition to chromosomal abnormalities in miscarried embryos, which are caused by chromosomal abnormalities in both parents, the normal process of cell division can be affected by the interference of internal and external teratogenic factors in male and female germ cells or fertilized eggs, resulting in chromosomal abnormalities in the embryo, which cannot develop normally and cause early death of the embryo and miscarriage.  Sixth, the relationship between hyperhomocysteinemia (HHey) and the development of diseases such as atherosclerosis and coronary heart disease has received increasing attention. It has been found that mutations in homocysteine metabolism-related enzyme genes are hereditary contributors to impaired folate metabolism and HHcy, and women with impaired folate metabolism and HHcy have a higher incidence of habitual abortion.  VII. Endometritis. Endometrial polyps. Submucosal fibroids of the uterus.  VIII. Abnormal semen of the male partner.