I. Classification and typing
1.Non-immune type RSA
Chromosomal abnormal type, anatomical abnormal type, infection type and endocrine disorder type.
2.Immune RSA
1.Autoimmune RSA
Laboratory criteria are specifically: positive blood anti-cardiolipin antibody or anti-β2-glycoprotein-1 antibody or anti-β2-GP-1 antibody, or positive lupus anticoagulation factor LAC, found at six weeks or more between two times.
2. Isoimmune RSA
Patients have a history of 3 or more spontaneous abortions, no history of live births, stillbirths, or stillbirths; factors such as chromosomal, anatomical and endocrine abnormalities and infections are excluded by etiological screening, negative autoantibody tests, and discharge of autoimmune diseases; negative microlymphocytotoxic antibodies.
II. Systematic outpatient screening programs for etiology
1.General examination.
Including history taking gynecological examination, ultrasound and other physical diagnostic techniques.
2.Special examinations.
1.Chromosome examination: karyotype analysis of couple’s karyotype, nuclear analysis of chorionic villus culture cells;
2, anatomical factor examination: ultrasound examination, if necessary, add hysterosalpingography or hysteroscopy;
3.Endocrine examination: including sex hormone, thyroid and pancreatic function measurement, etc;
4, cytomegalovirus, toxoplasma infection, herpes simplex virus and other aspects of testing;
5, blood coagulation state detection: platelet aggregation test PagT, D-dimer, platelet membrane granule protein GMP-140, and partial blood clotting time APTT;
6, autoantibody detection: including IFANA fluorescent anti-nuclear antibody, ACL anti-cardiolipin antibody, anti-β2 glycoprotein-1 antibody anti-β2-GP-1 antibody, LAC lupus anticoagulation factor, etc.;
3. Notes on etiological screening for recurrent miscarriage
Etiological screening is the key to clinical classification and typing as well as guiding clinical treatment, for which attention should be paid to the following aspects.
1, karyotype analysis: not only the couple should be included, but also pay attention to the karyotype analysis of each pregnancy discharge specimen.
2. Uterine anatomical abnormalities: first of all, non-invasive examination methods should be used, mainly B-ultrasound. In case the B-ultrasound cannot be determined, hysteroscopy and hysterosalpingography HSG can be considered.
3.Cervical function examination: Ultrasound examination is performed at 12 and 20 weeks of pregnancy, and 200ml of water bladder is placed in the vagina to observe morphological changes of the cervical canal. If the length of the cervix is less than 2,6cm and the inner diameter of the cervical canal is ≥0,5cm, cervical insufficiency can be diagnosed and cervical cerclage can be performed.
4. Endocrine abnormalities examination: attention should be paid to exclude luteal insufficiency, PCOS, hyperlactatemia, thyroid dysfunction and diabetes mellitus.
II. Treatment of autoimmune RSA
Individualized – small dose – short course of immunosuppressive or anticoagulant therapy, as follows.
1.Establishment of observation indexes
1. Blood coagulation indexes APTT, D-dimer.
2, platelet agglutination indicators: PagT, GMP-140.
3, antiphospholipid antibodies: anti-cardiolipin antibody ACA,, β2-GP-1.
2.Observation time
1.A for patients with elevated PagT/GMP-140 alone.
2.P for patients with elevated antibody titers alone.
3.L is used for patients with elevated D-dimer alone.
4.A+L is used for patients with elevated PagT/GMP-140 and D-dimer at the same time.
5.A+P for patients with simultaneous elevation of PagT/GMP-140 and autoantibody titers.
6. L+P is used for patients with concurrently elevated D-dimer and autoantibody titers.
7. A+L+P is used in patients with elevated Pag7/GMP-140, D-dimer and autoantibody titers.
Note: A: aspirin; L: low molecular heparin; P: adrenocorticotropic hormone.
III. Treatment of isoimmune RSA
1.The husband or unrelated third individual of the immunogenic patient, and both patients should check blood routine, urine routine, blood type, HIV, syphilis, hepatitis C, hepatitis B five, liver and kidney function.
2, using a small dose of lymphocyte active immunotherapy: immunogen can be the husband of the patient or unrelated third individual lymphocyte male or female can use, the course of treatment from the pre-conception, active immunization before pregnancy three times for a course of treatment, after pregnancy and then active immunization for three courses. The total number of immunized lymphocytes is 20-30×106 per session, injected subcutaneously, at 3-week intervals. After the first course, the patient is encouraged to become pregnant within three months, and if pregnancy is obtained, another course of treatment is performed. If pregnancy is not obtained, a new 1-month course of immunization will be administered if sterility is expelled.
3. Individualization: Homozygous immune patients should be tested for platelet activation status and hypercoagulability during pregnancy, and if so, a combination anticoagulation regimen, aspirin and or, low molecular heparin, based on active immunization, should be administered as above.
Specific regimens:
① Homozygous immune type without increased platelet aggregation and hypercoagulable state: apply active immunization.
(2) Homozygous type with increased platelet aggregation: active immunization and aspirin.
(3) Homozygous immune type with increased platelet aggregation and hypercoagulability: active immunization, aspirin and low molecular heparin.
IV. Follow-up contents.
Follow up the pregnancy, and the condition of the newborn after birth, and count the success rate.