Explanation of the etiology of recurrent spontaneous abortion

       Recurrent miscarriage was once defined as 3 or more consecutive spontaneous abortions. However, studies have shown that the risk of recurrent miscarriage after 2 spontaneous abortions is similar to that after 3 or more spontaneous abortions, 30% and 33% respectively, so the possible causes should be looked for in those with 2 or more spontaneous abortions. Currently, recurrent spontaneous abortion is defined as 2 or more consecutive spontaneous abortions.  The most common of these is chromosomal ectopic balance, which leads to duplication or deletion of chromosomal fragments during meiotic chromosome separation, thus causing miscarriage; in addition, inversion is also the cause of a few recurrent miscarriages. In recent years, DNA analysis techniques have been applied to find highly distorted x chromosome inactivation associated with unexplained recurrent miscarriages, but this test has not been widely performed. Recurrent miscarriage is also caused by chromosomally normal couples and abnormal karyotype of the aborted embryo itself. Recent studies have shown that 48% or more of the embryos of women with a history of recurrent miscarriage have chromosomal abnormalities in their recurrently miscarried embryos. The repeated aneuploidy of the embryo may be an important reason for recurrent miscarriage.  Hormonal or metabolic abnormalities have long been thought to be associated with recurrent miscarriage, accounting for 25%-40% of recurrent miscarriages. It is believed that when the corpus luteum is underactive, it does not produce enough progesterone and thus does not provide a mature endometrial layer for placental formation. However, in a controlled study conducted at the same time, the probability of LPD changes in the endometrium of normal women in a single menstrual cycle was about 50%; in consecutive menstrual cycles, the rate was also 25%. In an international multicenter study, 75 women were randomized into groups, one with placebo and the other with 10,000 IU of intramuscular hCG as soon as pregnancy was diagnosed and 5,000 IU weekly thereafter, with no significant difference in pregnancy success between the two groups (83% versus 79%). Therefore, the relationship between LPD and recurrent miscarriage remains unclear. Polycystic ovary syndrome (PCOS) is considered to be an endocrine disorder associated with recurrent miscarriage. Polycystic ovaries (PCO) are found in 36% to 56% of women with recurrent miscarriage by ultrasonography. However, women with a history of recurrent miscarriage diagnosed by ultrasound only with PCO have no difference in pregnancy outcome from those without PCO. Elevated androgen levels have been shown to be associated with miscarriage. The rate of miscarriage is increased in women with type 1 diabetes who have poorly controlled disease. However, there is no evidence that asymptomatic endocrine or metabolic disorders such as mild thyroid disease or impaired glucose tolerance cause recurrent miscarriage.  Congenital uterine anatomical abnormalities are most closely associated with mid-pregnancy miscarriage, and 10% to 15% of women with recurrent miscarriage in early pregnancy also have congenital uterine abnormalities. The anomalies most closely associated with miscarriage include bicornuate uterus and septated uterus, especially septated uterus, which some believe may be due to poor vascular supply in the septum. Severe uterine adhesions and exposure of the uterus to hexestrol may also be associated with miscarriage. The understanding of the relationship between saddle uterus and submucosal fibroids and recurrent miscarriage is still divided.  IV. Infectious factors Certain pathogens such as Listeria monocytogenes, Toxoplasma gondii and some viruses (e.g. rubella, herpes simplex, measles virus, cytomegalovirus, coxsackievirus) are thought to be associated with disseminated spontaneous abortion, but they have not been found to be associated with recurrent miscarriage. The association of cervical chlamydia and mycoplasma infections with recurrent miscarriage remains controversial. A higher than normal rate of positive endometrial cultures for Mycoplasma solium has been found in women with a history of recurrent miscarriage, and it has been hypothesized that endometrial mycoplasma infection may be the cause of recurrent miscarriage, however, the effect of treatment or not on pregnancy outcome in cervical canal mycoplasma-positive individuals is inconclusive. Bacterial vaginosis may be associated with midtrimester miscarriage.  Environmental factors, occupational factors and personal habits are not significantly related to miscarriage, and occupational exposure to certain substances such as organic solvents rarely causes miscarriage; exercise does not increase the rate of miscarriage; the relationship between smoking, alcohol and coffee consumption and miscarriage is still controversial, and their effects may be dose-related or synergistic to increase the rate of miscarriage; however, none of these factors has been found to be related to recurrent miscarriage. However, the above factors were not found to be related to recurrent miscarriage.  The most common hereditary thrombotic disorders are mutations in factor VLeiden, active protein C resistance and prothrombin G20210A, while others include anticoagulant protein C, protein S and anticoagulant factor III deficiency. Yoshiro et al. reported that reduced coagulation factor XII activity was associated with recurrent miscarriage in early pregnancy, whereas the common polymorphism 46C/T in the coagulation factor XII gene was not. They recommended that coagulation factor XII activity should be investigated in women with recurrent miscarriage in early pregnancy because of the simplicity of coagulation factor XII measurement and the availability of alternative methods to treat women with deficiency of this factor. The relationship between these disorders and recurrent miscarriage is controversial. Some studies have suggested that these disorders are associated with fetal death in mid- to late-term pregnancies, but not with early pregnancy miscarriage. It is unknown which treatments may improve the success of pregnancy in such women, as no experimental treatment has ever been performed.  APS is an autoimmune disease characterized by increased antiphospholipid antibodies and recurrent miscarriages, stillbirths, and thrombosis, etc. The diagnostic criteria for APS are positive for lupus anticoagulant antibodies and/or B2.globulin I-dependent anticardiolipin antibodies in two consecutive tests at least 6 weeks apart. If only anticardiolipin antibodies are positive, the diagnosis is made when the antibody level is 20 U or more on two occasions. Autoantibodies to thyroid antigens (thyroglobulin and thyroid peroxidase) are associated with an increased rate of miscarriage if detected in early pregnancy or just before, but the relationship between this and recurrent miscarriage has not been established so far. There is no effective way to improve the outcome of the next pregnancy. ANA is detected in about 15% of women with a history of recurrent miscarriage, and if left untreated, pregnancy outcomes in the ANA-positive group are similar to those in the negative group. There was also no difference in pregnancy outcomes between the prednisone and low-dose aspirin treatment groups and the placebo treatment group. Immunological differences between couples have been suggested as a cause of unexplained recurrent miscarriages, including couples with different leukocyte antigens, lack of serum confinement factors in women and production of antileukotoxin antibodies against male leukocytes. However, these studies lacked appropriate controls and failed to provide effective treatments. Recent studies on maternal. Recent studies of the maternal-fetal immune relationship have revealed that miscarriage may be caused by dysregulation of normal immune mechanisms at the maternal-fetal interface. It has been suggested that the predominant expression of Th.2 lymphocytes is essential for a successful pregnancy, whereas Th.1 lymphocytes such as interferon “y” (IFN.) and tumor necrosis factor et (TNF. a) x. have a negative effect on embryonic and trophoblastic development. Natural killer (NK) cells, which secrete transforming growth factors at the maternal-fetal interface, are necessary for a successful pregnancy. Pregnancy outcomes are poor when NK-like cells are increased, but further studies are needed to draw definitive conclusions. It has also been reported that women with recurrent miscarriage who have excess circulating NK cells have a poorer outcome in their next pregnancy. However, there is no effective method to treat recurrent miscarriage in women with excess NK cells.