Spontaneous abortion causes
Etiology:
Lead to a lot of reasons for spontaneous abortion can be divided into factors of embryonic factors and mother.
Common causes of early abortions are embryonic chromosomal abnormalities, maternal endocrine abnormalities, genital malformations, reproductive tract infections, local or systemic reproductive tract abnormalities, such as immunization; and late abortion cervical dysfunction by many maternal and fetal blood group incompatibility and other factors.
1. Fetal chromosomal abnormalities. spontaneous chromosomal abnormalities are the most common reasons.reported in the literature at home and abroad, in the spontaneous abortion, 46% ~ 54% with the embryonic chromosomal abnormalities, ch as under Warburton summation happen sooner abortion, embryo chromosomal abnormalities of higher the frequency. mosomal abnormalities, including the number of abnormalities and structural abnormalities in the quantity anomaly in three-body staining ranked one, accounting for 52 percent, with the exception of staining on the 1st three body not been reported, the various three-body were found in one of 13,16, 18,21 and 22, the most common chromosome, trisomy 16 accounting for about 1 / 3; the first two are 45, X monomer about 19%, after the three bodies are more common chromosomal abnormalities such as to survive , full-term delivery after the formation of Turner syndrome. Triploid placenta blisters are often associated with degeneration of coexistence not completely block the fetal-like blisters can develop into triploid fetus or No. 16 chromosome trisomy, miscarriage earlier a handful survive, continue to develop after many hair malformation with no live births, live births Autotetraploid rarely, the vast majority of very early abortion. Chromosomal abnormalities are the major structural abnormalities of chromosome translocation (3.8%), mosaicism (1.5%) and so on, chromosome inversion, deletion and duplication has been reported also see From the epidemiological point of view, the abortion rate as the increase in women's age increased, therefore, someone think of embryonic chromosomal abnormalities may be related to maternal age-related, but studies have shown that apart from trisomy 21 and maternal age-related, the other three-body has nothing to do with the age of the mother.
2. Mothers factors
(1) couples chromosome abnormalities: early in 1960, Schmiel been found, such as recurrent spontaneous abortion with chromosomal abnormalities related to the couple. Reported in the literature at home and abroad, habitual abortion couples frequency of chromosomal abnormalities of 3.2% is mostly one of mutual translocation chromosome, accounting for 2%, Robertsonian translocation accounted for 0.6 percent of domestic data proved that the recurrent spontaneous abortion couples the frequency of chromosomal abnormalities 2.7%.
(2) endocrine factors:
① luteal dysfunction: the mid-luteal progesterone peak below 9ng/ml, or endometrial biopsy and menstrual bad time synchronization more than two days can be diagnosed with luteal dysfunction. High concentrations of progesterone to prevent uterine contraction of the uterus so that pregnancy status remained relatively static; insufficient ogesterone secretion, can cause adverse pregnancy decidual reaction, affecting implantation and development, resulting in abortion of the source of progesterone during pregnancy in two ways: one are generated by the corpus luteum, are two placental trophoblast cells. 6 ~ 8 weeks pregnant after the corpus luteum produce progesterone gradually reduced after the substitution of progesterone produced by the placenta if the convergence between the two disorders are prone to miscarriage and abortion insufficient progesterone secretion is closely related to habitual abortion at 23% ~ 60% of the cases exist luteal phase defect.
② polycystic ovary: someone found in habitual abortion in the incidence of polycystic ovary can be up to 58%, but there is one of 56% of patients with high LH secretion in polycystic ovary status is considered high concentrations of LH may lead to the second egg the completion of meiosis prematurely thereby affecting the process of fertilization and implantation .
③ hyperprolactinemia: a high level of prolactin can directly inhibit luteinizing granulosa cell proliferation and functions. Hyperprolactinemia Clinical mainly manifested amenorrhea and lactation, when prolactin in the upper limit of normal may be manifested as luteal phase defect.
④ diabetes: Milis such forward-looking studies have shown that patients with diabetes during early pregnancy (21 days) of good blood sugar control, and the incidence of abortion and non-diabetic group but no difference in poor blood sugar control the incidence of abortion can be as high as 15% ~ 30%. In addition, high blood sugar during early pregnancy are probably caused by the risk factors of fetal malformation.
⑤ thyroid function: the past, or consider hypothyroidism and hyperthyroidism abortion-related, but this view has been controversial.
3. Genital anatomical factors
(1) uterine malformation: uterus malformation such as a single horn of uterus, double uterus, double uterus, uterine mediastinal and so on, can affect the uterine blood supply and the intrauterine environment Abortion
(2) Asherman syndrome: from intrauterine trauma (such as curettage too deep), infection or placental residue caused intrauterine adhesions and fibrosis. Does hysteroscopic endometrial resection or submucosal fibroid surgery can also result in intrauterine adhesions. Inadequate endometrial embryo can affect the plant, resulting in recurrent spontaneous abortion. Hysteroscopy help eigen diagnosis. Romer hysteroscopy, etc. to a group of cases to check and found that incomplete abortion and missed abortion in cases of intrauterine adhesions after the occurrence rate is about 20% of cases of recurrent spontaneous abortion up to 50%.
(3) of cervical dysfunction: Cervical dysfunction are a result, the main reasons for late abortion. Cervical sfunction at autopsy on the performance of too short for the cervical canal or cervical relaxation within the mouth. Up because of the existence of anatomical defects in the process of uterine pregnancy with increased intrauterine pressure increased, the majority of patients appeared in late pregnancy the cervical canal painless receded, Miyaguchi expansion, rupture of amniotic sac membranes prominent, finally happened abortion. Cervical dysfunction, mainly because of partial cervical trauma (childbirth, midwifery surgery, post-cervical cone excision Palace, Manchester operation, etc.) caused by, congenital cervical dysplasia is less common; another period of embryonic exposure to diethylstilbestrol also can cause cervical dysplasia.
(4) Others: uterine tumor can affect the uterine environment leading to abortion.
4. Reproductive tract infections have a number of chronic genital tract infection is considered one of the reasons for early abortion. Can lead to recurrent abortion are persistent pathogens often exist in the maternal reproductive tract and rarely produce symptoms, and that pathogens can directly or indirectly lead to embryonic death. Retrograde reproductive tract infection generally occurs during pregnancy 12 weeks ago, over this period, the placenta and decidua integration, constitutes a mechanical barrier but also with the process of pregnancy, amniotic fluid anti-infectious also gradually increased, and reduce the chances of infection.
(1) bacterial infection: genus Brucella (Brucella) and Vibrio (campylobacter) can lead to infection of animals cattle, pigs, sheep, etc.) abortion, but certainly not in humans. Some people think that listeria bacteria (Listeria monocytogens) and the relevance of the relationship between abortion must have, but the lack of conclusive evidence
(2) Chlamydia trachomatis (chlamydia trachomatis): reported in the literature, pregnancy Chlamydia trachomatis fection rate was 3% ~ 30%, but whether or not a direct result of abortion can not be determined.
(3), Mycoplasma: abortion in patients with cervical and streaming products mycoplasma positive rate were higher, serum also supported the study on Human Mycoplasma (mycoplasma hominis) and Ureaplasma urealyticum (ureaplasma urealyticlum) and abortion-related.
(4) of Toxoplasma gondii (toxoplasma): Toxoplasma gondii infection caused by abortion are distributed, and the ionship between habitual abortion have not yet been fully proved.
(5) virus infection: CMV (cytomegalovirus) may affect the fetus through the placenta, cardiovascular system and nervous system malformation, death or abortion of pregnancy the first half of herpes simplex (herpes simplex) infection in the incidence of abortion can be as high as 70%, if not abortion happened, but also easy to affect the fetus, newborn. Early pregnancy rubella virus (rubella virus) infected with a higher incidence of abortion. Human immunodeficiency virus (human immunodeficiency virus, HIV) infection and is closely related to abortion, Temmerman such reports, HIV-1 antibody positive independent abortion are relevant factors.
5. Immunological factors in the immune factors in particular recurrent miscarriage abortion habitual abortion can be divided into two kinds, namely, auto-immune type and the same types of immune-type auto-immune type usually can be detected in vivo in patients with a variety of autoantibodies, mainly anti - antibody. The same etiology in patients with immune-based screening, to exclude it, also known as common cause of unexplained habitual abortion; mainly related to pregnancy such physiological protective immune response undesirable, the immune inhibitory factor or lack of closure factor eventually embryos subjected to the immune injury, leading to abortion.
(1) auto-immune type: auto-immune type of habitual abortion patients mainly related to antiphospholipid antibodies (antiphospholipide antibody), and some patients may be simultaneously accompanied by thrombocytopenia and romboembolic phenomenon, these patients can be described as an early anti-phospholipid antibody syndrome (antiphospholipide ntibody syndrome). In addition, auto-immune type of habitual abortion with other relevant autoantibodies.
The composition of antiphospholipid antibodies: anti-phospholipid antibody is an autoimmune antibodies,including lupus anticoagulant (LAC), anticardiolipin antibodies (ACL), anti-phosphatidylserine antibodies (APSA), anti-hatidylinositol antibody (APIA) Triethanolamine antiphospholipid antibody (APEA) and antiphospholipid antibody acid (APAA), such as in a variety of autoimmune diseases can be detected simultaneously in several antibody; to one of anticardiolipin ibodies and lupus anticoagulant factor, the most representative and clinical significance. Anticardiolipin antibodies have three kinds of types: IgG, IgA, IgM; to one of the most clinical significance of IgG
(2) the same kinds of immune-type: modern reproductive immunology consider pregnancy to be successful the process of semi-allograft, pregnant women because of their own immune system to produce a series of adaptive changes in which intrauterine embryo showing graft immune tolerance rather than happen rejection, so that pregnancy can continue bility gene or monomer: In recent years, scholars believe that there is habitual abortion patients with possible sceptibility genes exist or monomer. According to the theory of genetics infer the existence of the human genome in clinical susceptibility gene or monomer; Moreover, this susceptibility gene or monomer HLA complex may exist in vivo or in connection with other genes closely linked abortion to contain susceptibility genes or monomer The mother of the embryonic antigen reaction was low status, should not stimulate the maternal immune system to produce closed factor. Scholars reported the existence of susceptibility genes or monomer site or site differences, which may be associated with ethnic-specific HLA-related .
(3) uterine local immune: the current study showed that normal pregnancy uterine decidua partial apparent adaptive response, NK cell subsets happened phenotype conversion, that is, from the CD56 + CD16-type (anti-type) mainly into CD56 + CD16 + type (secreted), and secreted a number of NK cells can secrete cytokines, such as TGF-β and other cytokines on uterine partial immunomodulator, playing an immune nutrition or immunosuppressive effects. Our study found that patients with habitual abortion uterine partial lack of physiological immune response, NK cells are still mainly of this type of anti-probably directly related to the pathogenesis of the disease.
6. Other
(1) Chronic wasting disease: tuberculosis and malignant tumors often leads to early abortion, and threatened the lives of pregnant women. High fever can lead to uterine contraction; anemia and heart disease can cause fetal placental unit hypoxia; chronic nephritis hypertension can happen placental infarction.
(2) malnutrition: acute malnutrition can lead to abortion directly. Now emphasize the balance of various nutrients, such as vitamin E can also be caused by the lack of abortion.
(3) psychological factors: nervous anxiety, intimidation and other severe mental stimulation may also lead to abortion has also found that noise and vibration on human reproduction must also have impact.
(4) smoking alcohol: In recent years, women of childbearing age, smoking, drinking, or even an increased number of drug addicts; these factors are risk factors for miscarriage during pregnancy drinking too much coffee also increased the risk of miscarriage. There is no proof of the exact basis for the use of contraceptive drugs and abortion-related, however, have reported that intrauterine contraceptive devices losers, the incidence of infectious abortion has been elevated
(5) environmental toxic substances:
① Mercury: Mercury can be metal mercury, inorganic mercury and organic mercury compounds in the form of existence. Teratogenic effect of mercury in animal experiments has been confirmed that the deformity showed dysplasia and eye defects in addition it can also provide cleft lip and palate and maxillofacial deformities rib fusion of occupational exposure to mercury in the crowd found that their spontaneous abortion, stillbirth and The incidence of birth defects than the control group 1 times. Teratogenicity of mercury and lead to abortion may be related to injury-related genetic material, mercury can cause chromosome changes in protein binding would also allow an increase in ntracellular free radicals leading to damage DNA molecules can cause cell damage and the effects of spindle cells normal split.
② cadmium: cadmium on the development of offspring have obvious adverse effects of animal exposure to cadmium during pregnancy, can lead to embryo resorption, death and a variety of deformities, deformed parts of the highest incidence rate for the brain, limbs and bones. Cadmium toxicity on embryonic mechanism and cadmium inhibit cell growth and division, mainly inhibit DNA and protein synthesis, it can block thymidine incorporation. DNA, the reduction of DNA synthesis, are probably inhibited the activity of thymidine activation results.
③ Lead: Lead can affect the fetus through the placenta. A large number of animal experiments showed that experimental animals can lead fetal deformities happen, mainly for nervous system defects. Teratogenic effect of lead on the role of human beings is also very clear that pregnant women exposure to excessive levels of lead, can cause abortion and fetal death, birth defects can also lead to offspring increases the incidence of lead teratogenicity mechanism may be related to the following role: on the germ cells DNA and chromosomal damage; injury spindle cells affect cell mitosis; into the mitochondrial TCA cycle impact; lead the excitement caused by uterine muscle lead to abortion
④ arsenic: Animal studies show that the lack of arsenic can affect growth and reproduction of animals to high trations of arsenic have teratogenic teratogenic role of the central nervous system has the type of defects, eye defects such as cleft lip and palate fusion. Arsenides inorganic arsenic can increase breast-feeding can also cause the fetus through the placenta and abortion deformity. Its teratogenic and caused abortion mechanisms are interfered with the development of visceral yolk sac.
⑤: induced embryonic death.
⑥ vinyl chloride: lead to abortion and to increase the incidence of malformations.
⑦ DDT (dichloro-diphenyl-trichloro-ethaneDDT): can be so spontaneous abortion and low birth weight infants increase the incidence.
Pathogenesis:
Under normal circumstances a variety of negatively charged phospholipids located in the inner membrane lipid bilayer, are not immune system recognition; Once exposed to the immune system can produce a variety of anti-phospholipid ibody. Antiphospholipid antibodies are not only a strong procoagulant activity substances, platelet activation and the promotion of coagulation, leading to platelet aggregation, thrombosis; at the same time, a direct result of vascular endothelial cell injury, increased thrombosis, so that cycle happen partial placenta placenta thromboembolic infarction, fetal lead to abortion of intrauterine death of the recent study also found that antiphospholipid antibodies may be directly combined with the trophoblast cells and thus inhibit trophoblast cell function, affecting the process of placental implantation.
Currently known in the immunomodulatory process, trophoblast HLA-G antigen expression probably plays a very important role. In addition, in normal pregnancy maternal serum, the existence of one or more can inhibit immune recognition and immune response to the closure factor (blocking factors), also known as blocking antibody (blocking antibody), as well as the immunosuppressive factor, while in patients with habitual abortion in vivo is the lack of these factors, therefore, makes the mother's immune embryos subjected to the exclusion of combat.
1. Closed factor blocking factor is a group of anti-IgG antibody lymphocytotoxicity spouse. Is generally believed that the closure factor can act directly on the mother cell, but also with the trophoblast cell surface antigen-binding specificity thus blocking between maternal and fetal immune recognition and immune response, closure of maternal lymphocytes to trophoblast cytotoxicity. Have closed to consider is a possible factor, anti-idiotypic antibodies, directed against the T lymphocyte or B lymphocyte surface antigen receptor (BCR / TCR), in order to prevent maternal and fetal lymphocyte responses from target cells in vitro, closed factor can inhibit the mixed lymphocyte reaction (MLR).
Antigen 2.HLA the past several decades, with the kinds of immune-type of habitual abortion and HLA antigen mpatibility relationship has been controversial. In recent years, observed that the HLA-G antigen in the pathogenesis of habitual abortion may play an important role. Habitual abortion in another susceptibility gene or on the study on monomer also made some progress.
HLA-G: At the 20th century, early 70's, some scholars put forward habitual abortion may be associated with couples compatibility antigen HLA-related. Consider, in the course of normal pregnancy couples or HLA antigens between mother and fetus are incompatible, the embryo brought HLA antigen derived parent can stimulate the maternal immune system, resulting in the closure factor. Of HLA antigen compatibility study involving HLA-Ⅰ antigen molecules AB loci and HLA-Ⅱ MHC molecules DR, DQ loci. However, after more than 20 years of research,the current difficult conclusion compatible HLA antigens and habitual abortion precise relationship. In recent years, with the level of molecular biology raise more found in patients with recurrent spontaneous abortion couples or mothers and infants do not necessarily exist between the HLA compatibility of the situation increased. However, found that HLA-G antigen expression may be involved in the pathogenesis of habitual abortion.
Is generally believed that trophoblast does not in itself a classic expression of HLA-Ⅰ antigen molecules in recent years, most scholars have proved trophoblasts can express a class of non-classical HLA-Ⅰ antigen, the antigen and β2m with W6/32 antibody combination low molecular weight. This HLA-Ⅰ antigen has now been named as HLA-G antigen. Experimental observation to trophoblast cells expressed HLA-G levels are in the process of pregnancy with a gradual decline in that HLA-G gene expression is subject to regulation and control embryos outside the organization is currently believed that trophoblast HLA-G antigen expression in the main role is to regulation of uteroplacental partial immune response. HLA-G can inhibit immune response caused by this reaction of the fetus can have a protective role in suppression of maternal immune system attacks fetal placenta. Although scholars have suggested that habitual abortion may be associated with trophoblastic HLA-G expression abnormalities; but its exact mechanism is unclear, pending further study.