What do you know about recurrent miscarriage?

  The occurrence of 2 or more consecutive spontaneous abortions is called recurrent miscarriage (RSA). Miscarriage is defined as termination before 28 weeks of gestation and a fetus weighing less than 1000 g. In 1977, the World Health Organization (WHO) defined miscarriage as termination before 20 weeks of gestation and a fetus weighing less than 500 g. The classical theory defines spontaneous abortion as habitual abortion when it occurs three or more times in a row.
  Only 50% of patients with recurrent miscarriage can identify its etiology, which mainly includes chromosomal abnormalities, maternal reproductive tract abnormalities, maternal endocrine abnormalities, immune function abnormalities, reproductive tract infections, cervical insufficiency and thrombotic tendency.
  1、Chromosomal abnormalities
  These include chromosomal abnormalities in couples and chromosomal abnormalities in embryos. Common chromosomal abnormalities in couples are balanced translocation, Robertson translocation, etc.
  2、Maternal endocrine disorders
  (1) Luteal insufficiency accounts for 23% to 60%, basal body temperature biphasic type, but the high temperature phase is less than 11 days, or the difference between high and low temperature is less than 0,3, endometrial biopsy shows that the secretory response is at least 2 days behind, progesterone in the luteal phase is less than 15ng/ml causing poor metaphase response of pregnancy, 2 to 3 cycles of luteal function test shows deficiency before inclusion in the diagnosis, luteal insufficiency affects the implantation of pregnant eggs.
  (2) The incidence of polycystic ovary syndrome is 58% in patients with recurrent spontaneous abortion. High levels of luteinizing hormone, hyperandrogenism and hyperinsulinemia reduce egg quality and endometrial tolerance.
  (3) Hyperprolactinemia has luteinizing receptors in the luteal cells, and hyperprolactin inhibits granulosa cell luteinization and steroid hormones, leading to luteal insufficiency and decreased egg quality. It has been found that prolactin reduces the secretion of early human placental chorionic gonadotropin.
  (4) Thyroid disorders hypothyroidism is associated with recurrent spontaneous abortion. It is also believed that recurrent spontaneous abortions are associated with the presence of thyroid antibodies (thyroid function is mostly normal in such patients).
  (5) Diabetes mellitus with subclinical or satisfactorily controlled diabetes mellitus does not cause recurrent spontaneous abortion, and uncontrolled insulin-dependent diabetes mellitus has an increased rate of spontaneous abortion.
  3. Abnormalities of the maternal reproductive tract
  (1) Uterine anomalies 15% to 20% of recurrent spontaneous abortions are associated with uterine anomalies. These include unicornuate uterus, bicornuate uterus, double uterus and uterine longitudinal septum. Among them, incomplete longitudinal uterus is most likely to lead to recurrent miscarriage. The endometrium of the mediastinum is dysplastic, insensitive to steroid hormones and has poor blood supply.
  (2) Asherman’s syndrome has a reduced volume of the uterine cavity and a decreased response to steroid hormones.
  (3) Cervical insufficiency causes late miscarriage and preterm delivery, accounting for 8% of recurrent miscarriages. Cervical insufficiency is defined as: painless loss of the cervical canal and dilatation of the uterine orifice during pregnancy. Non-pregnancy 8 Hagar dilation rod passes through the inner cervical opening without resistance.
  (4) Submucosal fibroids and intermuscular fibroids larger than 5 cm are associated with recurrent miscarriage.
  4. Reproductive tract infection
  0, 5% to 5% of recurrent miscarriages are associated with infection. The incidence of late pregnancy miscarriage and preterm delivery is increased in patients with bacterial vaginosis; endometritis or cervicitis caused by Chlamydia trachomatis and Mycoplasma solium can cause miscarriage.
  5. Abnormal immune function
  (1) Autoimmune antiphospholipid antibody syndrome (APS): a group of clinical signs of antiphospholipid antibody positivity with thrombosis or pathological pregnancy. APS is characterized by the presence of at least one clinical and laboratory criterion. Clinical criteria are: (i) one or more confirmed thromboses, including venous, arterial, and small vessel thromboses; (ii) pregnancy complications including three or more pregnancy losses less than 10 weeks; and (iii) one or more fetal deaths greater than 10 gestational weeks or at least one preterm delivery due to preeclampsia or placental insufficiency. Laboratory criteria: moderate or higher levels of anticardiolipin antibodies (IgG or IgM) or positive antibodies to lupus anticoagulation factor and β2 glycoprotein 1. The above 3 tests should be repeated at least 2 times at 6-week intervals.
  (2) Alloimmune pregnancy is a successful semi-allogeneic transfer process in which the pregnant woman exhibits immune tolerance to intrauterine embryonic grafts without rejection due to a series of adaptive changes in her autoimmune system. If there is an imbalance of immune regulatory and suppressor cells, such as abnormal expression of HLA-G in trophoblast membranes, imbalance of NK cell subpopulation balance, imbalance of Thl/Th2 balance, abnormal protective and/or confining antibodies, abnormal cytokines secreted by macrophages, maternal immune hyporesponsiveness due to abnormal recognition of embryonic paternal antigens, resulting in maternal confining antibodies or protective Antibody deficiency, immune rejection, and miscarriage occur.
  6、Hereditary thrombotic tendency
  Hereditary thrombotic tendency: such as factorVLeiden gene mutation and abnormal expression of methylenetetrahydrofolate reductase (MTHFR) gene, protein S and protein C deficiency lead to thrombotic tendency affecting the development and function of the placenta.
  Unhealthy lifestyles are associated with miscarriage. It has been reported that women who smoke more than 14 cigarettes per day have a 2-fold increased risk of miscarriage compared to the control group. Alcohol abuse, excessive caffeine consumption and environmental factors such as organic solvents and toxins. Obesity is associated with early miscarriage and recurrent miscarriage.
  Clinical presentation
  With 2 or more consecutive spontaneous abortions, miscarriage may present with postmenopausal vaginal bleeding and abdominal pain, and some patients have no clinical symptoms.
  Recurrent miscarriage should be diagnosed by taking a detailed medical history, improving physical examination, and performing auxiliary examinations related to the cause.
  (1) History of miscarriage: month, characteristics and form of miscarriage, etc.
  (2) History of menstruation.
  (3) History of infection.
  (4) History of endocrine abnormalities related to thyroid function, prolactin, glucose metabolism, hyperandrogenemia, etc.
  (5) Personal and family history of blood clots.
  (6) Features associated with antiphospholipid antibody syndrome.
  (7) History of other autoimmune diseases.
  (8) Lifestyle: primarily smoking, alcohol abuse, excessive caffeine, and history of medication use during pregnancy
  (9) family history, history of obstetric complications, history of syndromes associated with fetal loss
  (10) History of past diagnosis and treatment.
  2、Physical examination
  (1) Routine general examination: obesity, hirsutism, thyroid gland examination, breast discharge, etc.
  (2) Pelvic examination, especially for the presence of genital tract abnormalities and infections, etc.
  3、Auxiliary examinations
  (1) Fallopian tube imaging, hysteroscopy, ultrasonography.
  (2) Chromosome screening for both partners.
  (3) Female sex hormone six, thyroid hormone and its autoantibodies, blood sugar and insulin resistance test.
  (4) Anti-cardiolipin antibodies or lupus anticoagulation factor, anti-beta2 glycoprotein-1 antibody test.
  (5) homocysteine.
  (6) FactorVLeidenmutation, protein S, protein C tests.
  (7) routine blood tests and their coagulation factors
  (8) platelet aggregation test.
  (9) blood group check of both parties
  (10) Ovarian reserve function examination
  (11) Semen examination of the male partner.
  Differential diagnosis
  The first step is to differentiate the type of miscarriage. It also needs to be differentiated from ectopic pregnancy, gravida, dysfunctional uterine bleeding, pelvic inflammatory disease and acute appendicitis.
  In patients with recurrent miscarriage, different treatments are chosen for different etiologies.
  1. Treatment of luteal insufficiency
  Application of clomiphene and HMG to promote follicular development; human chorionic gonadotropin 1000-2000 U after the rise of basal body temperature, intramuscular injection every other day to stimulate luteal function; progesterone replacement therapy for luteal function.
  2. Treatment of polycystic ovary syndrome
  Weight control, oral metformin, luteal support during pregnancy.
  3、Treatment of hyperprolactinemia
  Bromocriptine, initial dose 1, 25mg, taken every night at bedtime, gradually increase the dose can be increased to 2, 5mg, once or twice a day, if the dose is not reached can be further increased. Medication is maintained at an effective low dose. Application during pregnancy is controversial.
  4、Maintain normal thyroid function
  Thyroid tablets are applied to those with low thyroid function. The application of thyroid hormone during pregnancy is controversial for those with normal thyroid hormone but positive thyroid antibodies.
  5、Correction of anatomical abnormalities of the uterus
  Longitudinal hysterectomy, uterine adhesion release, submucosal myoma removal. It is controversial whether single interstitial fibroids larger than 5 cm need to be removed. Cervical cerclage is an option for cervical insufficiency.
  6. Treatment of antiphospholipid antibody syndrome
  The literature reports that oral aspirin and/or combined with low-dose prednisone therapy has some effect, and combined with low-dose heparin therapy has also been reported.
  7. Treatment of patients with hereditary thrombotic tendency
  Supplementation with folic acid, vitamin B6 and B12 in patients with homocysteinemia due to abnormal expression of methylenetetrahydrofolate reductase (MTHFR) gene. heparin anticoagulation can be considered during pregnancy in patients with factorVLeiden gene mutation, protein S or protein C deficiency.
  8. Treatment of patients with unexplained recurrent miscarriage
  Patients who are excluded from the above-mentioned causes and who also meet the diagnosis of recurrent miscarriage become recurrent miscarriage of unknown cause. The treatment mainly includes active immunotherapy and passive immunotherapy.

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