The occurrence of 3 or more consecutive spontaneous abortions is called recurrent or habitual miscarriage. Incidence:15%-20% Miscarriage: usually refers to the failure of the pregnancy process, resulting in embryonic death and expulsion of the embryo and appendages, with expulsion or embryo and appendages ≤ 1000g and gestational week ≤ 28 weeks.
Recurrent miscarriage: refers to 3 or more consecutive spontaneous miscarriages (at the same time of pregnancy).
Chromosomal abnormalities.
Numerical abnormalities: aneuploidy is the most common, among which chromosome trisomies are the most common in spontaneous abortions, and all autosomes can be present, with trisomies 16,22,21,15,13,2 and 14 being the most common, accounting for a total of 70% of the aborted trisomies.
Structural aberrations: These refer to chromosome breaks, rearrangements, and chromosome rejoining after breaks. Balanced translocations are the most common type of human chromosomal aberrations and include reciprocal translocations, Robertson translocations and inversions, which are associated with low pregnancy rates and high miscarriage rates.
Anomalies of reproductive tract anatomy?
refers to congenital anatomical abnormalities of the uterus or uterine anatomy due to acquired uterine diseases, accounting for 12%-15%; uterine malformations: longitudinal uterus, unicornuate uterus, saddle-shaped uterus, bicornuate uterus & Oslash; uterine adhesions: hysteroscopic decomposition of adhesions & Oslash; uterine fibroids: submucosal fibroids are the most harmful and are removed before pregnancy; intermuscular fibroids, less than 4 cm in diameter and not deforming the uterine cavity, have no significant impact on pregnancy outcome, while those larger than 4 cm in diameter should be treated before pregnancy.
Adenomyosis: diffuse adenomyosis is treated directly with GnRha, with the duration of the drug depending on the uterine morphology, until the uterine morphology returns to normal and immediate IVF is performed.
Endometriosis.
a) luteal insufficiency; b) reduced endometrial tolerance (mainly referring to mid-secretory D20-24 of menstruation).
Treatment: laparoscopic surgery is the best treatment; assisted conception techniques are the best treatment; multifactorial considerations; individualization of the protocol.
Cervical insufficiency: causes late miscarriage and preterm delivery, accounting for 8% of RSA. Diagnostic criteria: no resistance to the passage of the No. 8 dilation rod through the cervix during non-pregnancy; loss of the cervical canal through painlessness during pregnancy and dilatation of the uterine orifice (ultrasound suggests an opening of more than 2.5 cm and a cervical length of less than 2 cm).
Treatment: Cervical cerclage endocrine abnormality type mainly refers to abortion due to endocrine dysfunction, accounting for 10%-20%;
Treatment of luteal insufficiency.
a) Promote follicular development: CC, HMG. b) Promote mid-luteal LH peak formation: monitor follicular maturation with HCG 5000-10000 IU intramuscular injection. c) Luteal stimulation therapy: after basal body temperature rises, HCG 1000-2000 IU every other day for 5 times. d) Luteal replacement therapy: after ovulation, daily intramuscular injection of progesterone 20mg for 10-14 days. 14 days.
Causes of polycystic ovary syndrome (PCOS): reduced egg quality and endometrial tolerance; hyperandrogenemia, hyperinsulinemia Treatment: androgen reduction, weight control, metformin, luteal support during pregnancy Ø hyperprolactinemia: high PRL inhibits granulosa cell luteinization and steroid hormones, decreased egg quality and immune factors.
Treatment: Bromocriptan treatmentØ Thyroid diseaseØ Diabetes mellitus: subclinical or satisfactorily controlled diabetes mellitus does not cause RSA, uncontrolled insulin-dependent diabetes mellitus has an increased rate of spontaneous abortion.
Reproductive tract infection type reproductive tract infection type: infection mainly refers to the prognosis of miscarriage due to toxoplasma and cytomegalovirus; chromosomal abnormalities, for which there is no effective treatment. Early pregnancy chorionic villus or amniotic fluid chromosome examination, selective abortion, so the prognosis is the worst, the probability of success of another pregnancy is 20%.
Those with abnormal endocrine factors have the best prognosis because they have a 90% or higher probability of successful pregnancy with effective treatment methods.
The prognosis of RSA with other factors is intermediate between the above two. The diagnosis of this type of miscarriage is an exclusionary diagnosis, which means that chromosomal, anatomical, infectious, endocrine and autoimmune etiologies are excluded and the cause of the miscarriage is not found, which can also be called recurrent miscarriage of unknown origin. The diagnosis of APS is based on at least one clinical symptom (miscarriage or thromboembolism) and one laboratory indicator, i.e. two or more positive antiphospholipid antibodies at an interval of 6 weeks or more, and the commonly used tests for antiphospholipid antibodies (APA) are
a) anti-cardiolipin antibody (ACL); b) anti-β2-GP1 antibody; c) lupus anticoagulation factor APA on pregnancy.
APA exerts pathotoxic effects from the stage of embryonic implantation and early placental formation: the
a) ACL infiltrates phospholipid-like molecules on the surface of trophoblast cells and inhibits trophoblast cell proliferation through antibody-mediated immunotoxic effects; b) interferes with trophoblast cell secretion and synthesis functions; c) inhibits trophoblast cell differentiation into syncytial trophoblast cells; and d) inhibits embryo implantation and growth.
After embryonic implantation and during the gradual formation of the placenta, APA causes microthrombosis of the intraplacental vascular network and inadequate blood perfusion through accelerated thrombogenic mechanisms, leaving the patient in a thrombus-prone state.
Pathogenic mechanisms
a) ACL inhibits the metabolism of arachidonic acid and prostaglandins by binding phospholipids on the surface of endothelial cells of uterine spiral arteries, accelerating vasoconstriction and promoting platelet aggregation; b) ACL binds phospholipids on the surface of platelets, inducing full platelet activation and causing intravascular thrombosis; c) inhibits protein C activation through the physiological effects of infected thrombomodulators, further inhibiting fibrinogen and protein S activation; d) inhibits the antithrombotic physiological effects of anti-B2-GP1 upon binding to anti-B2-GP1.
Ultimately, it causes imbalance of coagulation, anticoagulation and fibrinolytic system, and although it has not reached the level of thrombosis generation, it may lead to microthrombosis of uterine spiral arteries or chorionic vessels due to imbalance of coagulation-anticoagulation mechanism or fibrinolytic activity, causing poor placental perfusion or even infarction, resulting in recurrent miscarriage and other adverse pregnancy immunoassay indications; age > 35 years, 2 natural or 2 failed IVF or GIFT; & Oslash; age <35 years, 3 spontaneous or failed IVF or GIFT.
Stimulated ovulation cycle with follicular dysplasia (less than 6 follicles); unexplained infertility; history of immune disorders (rheumatoid arthritis, SLE, etc.); history of IUGR pregnancy; one live birth with subsequent recurrent miscarriages.
Treatment; low-dose active immunotherapy.
The course of treatment starts before pregnancy, with 2 immunizations per course, 2 course method (1 course of immunization each before and after pregnancy). The total number of immunized lymphocytes was 20-30×106 per session, with an interval of 3 weeks.
After the first course, patients are encouraged to become pregnant within 3 months, and if pregnancy is obtained, 1 more course is performed. If pregnancy is not achieved, a new course of immunization is administered with exclusion of infertility.
There are 4 types of treatment based on laboratory monitoring.
Active immunization alone: in the absence of increased platelet aggregation and hypercoagulable state.
Active immunization + aspirin: those with increased platelet aggregation
active immunization + low molecular heparin: those with hypercoagulable state
Active immunity + aspirin + low-molecular heparin: those with increased platelet aggregation and hypercoagulable state.
Autoimmune low-dose, short-course, individualized treatment regimen
High titration of anti-cardiolipin antibodies and/or anti-β2-GP-1 antibodies: prednisone PAGT > 78%, GMP-140³20ng/ml: aspirin D-dimer³0.8mg, elevated APTT: heparin
7 therapeutic regimens.
Aspirin: anticardiolipin antibodies with low titers and/or elevated platelet aggregation
Prednisone: high titration of anticardiolipin antibodies
Low-molecular heparin: low titration of anticardiolipin antibodies and pure hypercoagulability
Aspirin + low molecular heparin: low titration of anticardiolipin antibodies and/or increased platelet aggregation and hypercoagulability
Aspirin + prednisone: high titers of anticardiolipin antibodies and increased platelet aggregation
Prednisone + low-molecular heparin: high titration of anticardiolipin antibodies and hypercoagulability
Aspirin + low molecular heparin + prednisone: patients with high titers of anti-cardiolipin antibodies, increased platelet aggregation and hypercoagulability.
Prednisone prophylaxis: If the anticardiolipin antibody is high or persistently positive, start with the adrenocorticosteroid prednisone 5 mg and continue until menstruation on the day after ovulation. In case of pregnancy, continue the medication.
Treatment regimen: In principle, prednisone 5mg should be started daily once pregnancy occurs and continued until the anti-cardiolipin antibody is negative and stopped for one month. For patients with SLE combined with positive anti-cardiolipin antibodies: start prednisone as soon as pregnancy occurs, and adjust the dose and duration of treatment according to the condition of SLE.
Aspirin prophylaxis regimen: aspirin 25 mg orally daily from day 5 of the menstrual cycle until the onset of menstruation, which can be repeated each menstrual cycle.
Treatment regimen: Start once pregnancy has occurred, at a dose of 25 mg orally daily and continue until PAGT is maintained at 35% or higher, most patients can stop at 28 weeks of gestation. Most patients require only 25 mg/d of aspirin.
Low molecular heparin prophylaxis regimen: 5000u daily, subcutaneously administered in the absence of pregnancy, starting on day 21 of the menstrual cycle and maintaining D-dimer levels below 0.4mg/l.
Treatment regimen: Once pregnant, maintain the drug to keep the D-dimer level between 0.3 and 0.5 mg/l, and discontinue when the D-dimer is below 0.3 mg/l.
Precautions for etiological screening
Karyotype analysis should not only include both husband and wife, but also pay attention to each embryo discharge specimen and send it for karyotype analysis; uterine anatomical abnormalities should firstly be examined by non-invasive methods, mainly B-ultrasound method, and in case of uncertainty by B-ultrasound, hysteroscopy and HSG can be considered;
Endocrine abnormalities screening should pay attention to: exclude luteal insufficiency, PCOS, hyperprolactinemia, thyroid dysfunction, diabetes mellitus; infectious diseases mainly screening cytomegalovirus, toxoplasmosis and herpes simplex virus; for immune RSA to exclude non-immune etiology premise, pay attention to the detection of autoantibodies, mainly cardiolipin antibodies and anti-β2-GP1 antibodies, at least 5 times with an interval of 3-4 weeks. The test should be performed at least 5 times at an interval of 3-4 weeks.