Spontaneous abortion definition.
A termination of pregnancy at less than 28 weeks, or a fetus weighing less than 1000g, is called a miscarriage. If the pregnancy is terminated by artificial factors such as surgery or medication, it is considered an induced abortion; while a miscarriage caused by natural factors is called a spontaneous abortion.
What to do if you have had one spontaneous abortion in the past.
Normal couples also have about 20% probability of spontaneous abortion. Couples with only one history of spontaneous abortion do not need to be nervous, it is recommended to take a break for 3 months and prepare for pregnancy again after doing pre-conception health check-ups. If you are pregnant, it is better to have an early check-up and if necessary, to keep the pregnancy.
What to do if you have had 2 or 3 spontaneous miscarriages in the past.
Those who have had 2 or more consecutive spontaneous miscarriages are called habitual miscarriages or recurrent miscarriages. In this case, both spouses should be examined for the cause of spontaneous abortion and treated for the cause to avoid another miscarriage.
Causes of recurrent miscarriage.
There are many factors that cause recurrent miscarriage, mainly including anatomical factors, endocrine factors, genetic factors, infectious factors and immunological factors. Other factors include male factor, maternal combined internal diseases, bad living habits and environmental factors. However, with the current medical methods, only about 50% of recurrent miscarriages can be identified, and those who cannot be identified are called recurrent miscarriages of unknown origin.
Etiology and screening
The etiology of RSA is very complex, mainly including genetic factors, anatomical factors, endocrine factors, infectious factors, abnormal immune function, pre-thrombotic state, systemic diseases of the pregnant woman and environmental factors. The etiology of RSA varies in different periods of pregnancy. Early miscarriage before 12 weeks of gestation is mostly caused by genetic factors, endocrine abnormalities, reproductive immune dysfunction and pre-thrombotic state; late miscarriage between 12 and 28 weeks of gestation with embryonic arrest is mostly due to pre-thrombotic state, infection, abnormal gestational appendages (including amniotic fluid, placental abnormalities, etc.), severe congenital anomalies ( In late miscarriages but with fresh embryonic tissues, even if the fetus is still alive after delivery, most of them are due to anomalies of uterine anatomy, which can be divided into two types according to the specific situation: one is the absence of obvious contractions before the opening of the uterus or the rupture of the fetal membranes, the cause of which is mainly cervical insufficiency; the other is the presence of contractions first, followed by the opening of the uterus or the rupture of the fetal membranes, the cause of which is mostly The causes are mostly reproductive tract infection, post-placental hematoma or placental abruption.
(i) Epidemiological factors
The clinical incidence of spontaneous abortion is 15%-25%, and more than 80% of them are early abortions that occur before 12 weeks of gestation. The risk of recurrent RSA increases with the number of miscarriages, and studies have shown that a history of previous spontaneous abortion is an independent risk factor for subsequent pregnancy failure, with embryo loss rates approaching 40% in patients with a history of 3 or more consecutive spontaneous abortions. In addition, maternal age and obesity are also high-risk factors for spontaneous abortion.
Expert opinion or recommendation] The medical history of both partners should be asked in detail, including age, menstrual and marital history, previous history, and family history. The chronological description of previous miscarriages, including the week of gestation when the miscarriage occurred, the presence or absence of causative factors and special accompanying symptoms, the presence or absence of aborted embryos and whether karyotype analysis has been performed, and the calculation of their body mass index (BMI).
(ii) Anatomical factors
Uterine anatomical abnormalities include congenital malformations of the uterus, cervical insufficiency, uterine adhesions, uterine fibroids, and adenomyosis. Data from some studies show that the incidence of uterine anomalies in patients with RSA can range from 1.8% to 37.6%. In addition, RSA due to anatomical factors is mostly associated with late miscarriage or preterm delivery. Retrospective studies have shown that women with untreated uterine anomalies will have a significantly higher rate of miscarriage or preterm delivery when they have another pregnancy. Cervical insufficiency is an important cause of late spontaneous abortion.
Expert opinion or recommendation] It is recommended that pelvic ultrasonography be performed in all patients with early RSA and those with a history of one or more late spontaneous abortions to clarify the presence of abnormal uterine development, the presence of uterine fibroids or adenomyosis, and the presence of pelvic lesions. For those who are suspected of having abnormal uterine anatomy, further examination by hysteroscopy, laparoscopy or 3D ultrasound is required to clarify the diagnosis.
(iii) Pre-thrombotic state of the patient
The clinical pre-thrombotic state includes both congenital and acquired types.
(1) Congenital prothrombotic state is caused by mutations in genes related to coagulation and fibrinolysis, such as mutations in factor V and factor II (thrombin) genes and protein S deficiency. The meta-analysis showed that late spontaneous abortion was closely associated with congenital thrombosis due to mutations in factor V and factor II (coagulins) genes and protein S deficiency. However, factor V and factor II (coagulins) gene mutations are rare in the Han Chinese population.
(2) Acquired prothrombotic states mainly include anti-phospholipid syndrome (APS), acquired homocysteinemia, and various other diseases that cause hypercoagulable state of blood. At present, the specific mechanism of spontaneous abortion caused by pre-thrombotic state is not completely clear. It is generally believed that the hypercoagulable state during pregnancy changes the state of blood flow in the uteroplacental area, which is prone to the formation of local microthrombosis and even placental infarction, resulting in the decrease of blood supply to the placental tissues, embryonic or fetal ischemia and hypoxia, and eventually leading to the miscarriage of embryo or fetus with poor development. Unfortunately, women with pre-thrombotic state do not have obvious clinical manifestations, and their hematological examination has no clear diagnostic criteria.
Expert opinion or recommendation] Currently, commonly used indicators for detecting prothrombotic state include coagulation-related tests [prothrombin time (TT), activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen and D-dimer, related autoantibodies [anti-cardiolipin antibody (ACA), anti-β2 glycoprotein 1 (β2GP1) antibody and lupus anticoagulant (LA) and homocysteine (Hcy). In addition, pre-thrombotic status markers such as protein C, protein S, Ⅻ factor, and antithrombin III (AT-III) can also be tested in medical institutions that are in a position to do so.
(iv) Genetic factors
1. Chromosomal abnormalities in couples: 2% to 5% of RSA couples have chromosomal structural abnormalities, including chromosomal translocation, chimerism, deletion or inversion, etc., among which chromosomal balanced translocation and Roche translocation are the most common. People with clinically normal phenotypes of balanced chromosomal translocations have been found to be at significantly increased risk of miscarriage after pregnancy and more likely to have abnormal offspring. Homozygous Roche translocations theoretically cannot produce normal gametes, whereas germ cells of non-homozygous Roche translocations can produce six gametes after meiosis, and after fertilization, 1/6 are normal karyotypes and 1/6 are balanced translocation carriers.
2. Embryonic chromosomal abnormalities: Embryonic chromosomal abnormalities are the most common cause of RSA. According to domestic and foreign literature, about more than half of the embryos in episodic early spontaneous abortions have chromosomal abnormalities, but the possibility of embryonic chromosomal abnormalities decreases with the increase of the number of abortions. In addition, it has been reported that the earlier the miscarriage occurs, the higher the incidence of chromosomal abnormalities in the embryos.
Expert opinion or recommendation] It is recommended that couples with a history of RSA should undergo karyotype analysis of peripheral blood to observe whether there are numerical and structural aberrations of chromosomes and the type of aberrations in order to infer their RSA probability; genetic counseling is also recommended. If conditions allow, karyotype analysis of their abortion products is recommended.
(V) Endocrine factors
The RCOG guidelines suggest that polycystic ovary syndrome (PCOS) can increase the incidence of spontaneous abortion. Although the mechanism by which PCOS causes RSA is not fully understood, some studies suggest that the presence of RSA in such patients may be related to insulin resistance, hyperinsulinemia and hyperandrogenemia; however, the American Society for Reproductive Medicine believes that it is still controversial whether PCOS causes RSA to occur. The American Society for Reproductive Medicine believes that hyperprolactinemia is associated with RSA by affecting oocyte development and causing luteal insufficiency leading to the development of RSA. In addition, endocrine disorders in pregnant women such as uncontrolled diabetes mellitus and thyroid disorders are associated with the development of RSA.
Expert opinion or recommendation] Commonly used tests include reproductive hormone levels, including prolactin (PRL), FSH, LH, estrogen, and androgen on the 3rd day of menstruation, and progesterone levels on the 7th to 12th day after ovulation. In addition, thyroid function and fasting glucose should be tested, and if necessary, glucose tolerance test should be performed.
(vi) Infectious factors
Any serious infection that can cause bacteremia or viremia can lead to incidental miscarriage, however, there is a correlation between various pathogens of the reproductive tract and TORCH infection and the occurrence of RSA, but not necessarily a causal relationship. Bacterial vaginosis is a high-risk factor for late miscarriage and preterm delivery, but the relationship with early miscarriage remains unclear.
[Expert opinion or recommendation] Routine TORCH screening is not recommended for patients with RSA. For pregnant women with a previous history of late RSA, regular testing for indicators of reproductive tract infection during pregnancy is recommended.
(vii) Immunological factors
In recent years, reproductive immunology studies have shown that about half of the etiology of RSA is related to immune dysfunction. The immunopathological changes of miscarriage due to different factors are different, and immune miscarriage can be divided into two types: autoimmune RSA and alloimmune RSA.
1, Autoimmune RSA includes.
(1) Tissue non-specific autoantibody production: such as antiphospholipid antibodies, anti-nuclear antibodies, anti-DNA antibodies, etc.
(2) Tissue-specific autoantibodies: such as anti-sperm antibodies, anti-thyroid antibodies, etc.
2. Alloimmune RSA includes.
(1) Intrinsic immune disorders: including elevated number and activity of natural killer (NK) cells, abnormal macrophage function, abnormal dendritic cell function, abnormal complement system, etc.
(2) Acquired immune disorders: including closed antibody deficiency, abnormal T and B lymphocytes, and abnormal helper T lymphocyte (Th)1/Th2 cytokines, etc. APS is a non-inflammatory autoimmune disease characterized by the production of large amounts of antiphospholipid antibodies (APL), including ACA, LA, and anti-β2GP1 antibodies in the body, with clinical manifestations including arteriovenous thrombosis, The clinical manifestations include arterial and venous thrombosis, pathological pregnancy, reduced platelet count, etc. It is one of the most important and treatable causes of RSA. Antiphospholipid antibodies are detected in 5% to 20% of RSA patients, and the live birth rate of untreated pregnancies is reduced to 10%.
In addition, there is also a clinical autoimmune disease secondary to systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA), called secondary APS. Other studies have also found an increased incidence of RSA in women with positive autoantibodies to the thyroid gland. At present, homozygous RSA is still under investigation and is therefore often referred to as “recurrent miscarriage of unknown origin”. It is believed that the lack of closed antibody and abnormal number and activity of NK cells are closely related to URSA.
Expert opinion or recommendation
(1) It is recommended that all patients with early RSA and those who have had one or more unexplained fetal losses after 10 weeks of gestation should be screened for antiphospholipid antibodies, including ACA, LA and anti-β2GP1 antibodies, and the positive diagnostic criteria are two or more positive LAs or ACA and anti-β2GP1 antibody titers >99th percentile at 12 weeks or more intervals. For the diagnosis of APS patients should also be checked for anti-nuclear antibodies, anti-double-stranded DNA antibodies, anti-dry syndrome (SS) A antibodies and anti-SSB antibodies to exclude autoimmune diseases such as SLE and RA.
(2) It is recommended that medical institutions in a position to do so should screen patients with RSA whose cause is unclear for autoantibodies, such as anti-thyroid antibodies, including anti-thyroid peroxidase antibodies (TPOAb) and anti-thyroglobulin antibodies (TGAb). However, the relationship between anti-sperm antibodies, anti-endometrial antibodies, and anti-ovarian antibodies and RSA still lacks evidence-based medical evidence, and routine screening is not recommended.
(3) After excluding the above-mentioned non-immune factors and autoimmune disorders, unexplained RSA should be considered whether it is related to an alloimmune disorder. If available, closed antibody tests and examination of the number and/or activity of NK cells in peripheral blood are feasible.
(viii) Other adverse factors
RSA is also associated with many other adverse factors, including adverse environmental factors, such as excessive exposure to harmful chemicals, excessive exposure to radiation, etc.; adverse psychological factors, such as women’s mental tension, negative emotional depression, as well as fear and sadness, etc. All kinds of adverse psychological stimuli can affect the neuroendocrine system, making the internal environment of the body change, thus affecting the normal development of the embryo; excessive The problem is that the body’s internal environment is altered, thus affecting the normal development of the embryo; excessive physical labor, smoking, alcoholism, excessive coffee consumption, drug abuse and drug addiction, etc.
The clinician should not ignore the influence of the above-mentioned adverse factors on pregnancy, and should pay attention to asking patients whether they have been exposed to the above-mentioned adverse factors during screening for the etiology of miscarriage, and instruct them to avoid them as much as possible in their next pregnancy. It is worth noting that some patients may have multiple causative factors at the same time and should be screened for all factors as comprehensively as possible.