I. Definition of recurrent spontaneous abortion
Recurrent spontaneous abortion is defined as having 2 or more consecutive spontaneous abortions.
Etiology of recurrent spontaneous abortion
There is a certain percentage of spontaneous healing in recurrent miscarriage (ERSA). Epidemiological studies have shown that even if there are 4 consecutive spontaneous abortions, there is a 55% chance of success for another pregnancy. The worst prognosis is for chromosomal abnormalities, which have a 20% probability of success in repeat pregnancies, regardless of the type of chromosomal abnormality. In the case of ERSA due to endocrine factors, the probability of successful pregnancy is more than 90% due to targeted treatment, and the prognosis is the best.
1. Chromosomal factors.
(1) Parental chromosomal abnormalities.
Chromosomal ectopic: male partner is a carrier, the probability of recurrence is 1-5%.
The probability of recurrence is 10-15% if the female partner is the carrier.
Chromosomal inversions: the recurrence rate is related to the type of inversion, the size of the inverted chromosomal fragment involved in the inversion, and who is the carrier.
Sex chromosome abnormalities: mainly various types of chimeric sex chromosome abnormalities.
Such as 45,XO/46,XX; 45,X/46,XX/47,XXX, etc.
Chromosomal polymorphisms: the large Y chromosome variant is closely related to ERSA.
(2) Embryonic chromosomal abnormalities.
Chromosomal number abnormalities: including trisomic, haploid, and polyploid.
Chromosome structure abnormalities: chromosome translocations, chimerism, etc.
2. Recurrent miscarriage caused by genes
Common monogenic diseases causing miscarriage.
Ankylosing muscle camp dysplasia ;
Autosomal inherited diseases: such as lethal bone dysplasia;
X-linked diseases: such as pigment incontinence, etc;
Polygenic diseases cause miscarriages mostly affecting neural tube development.
3, anatomical factors.
(1) uterine malformation: bicornuate uterus, unicornuate uterus, double uterus, longitudinal uterus, etc., accounting for 12% to 15% of the causes of miscarriage. Among them, longitudinal uterus is the most common. Uterine malformation can affect the blood supply to the uterus and the environment of the uterine cavity, affecting the implantation of the pregnant egg and the development of the embryo, resulting in miscarriage.
(2) Cervical insufficiency: The incidence of cervical insufficiency in women with recurrent miscarriage is 3% to 5%, which may be related to the increase in early pregnancy abortions and mid-pregnancy inductions, resulting in traumatic cervical insufficiency.
(3) Uterine adhesions: lesions leading to deformation of the uterine cavity, abnormal endometrium, obstruction of placenta formation, and insufficient endometrium may affect embryo implantation and lead to recurrent miscarriage.
(4) Uterine fibroids: the influence of fibroids in recurrent miscarriage is still controversial, and it is generally believed that submucosal fibroids have a high chance of recurrent miscarriage.
(5) Endometriosis: it is related to the abnormal immune microenvironmental changes of endometriosis and its often associated luteal insufficiency.
4.Endocrine factors
(1) Luteinizing insufficiency
High concentration of progesterone can prevent uterine contraction and keep the pregnant uterus in a relatively static state. Insufficient secretion of progesterone can cause poor reaction of the pregnant meconium and affect the implantation and development of the pregnant egg, leading to miscarriage. Insufficient progesterone secretion is closely related to miscarriage.
(2) Polycystic ovary syndrome
It is now clear that elevated androgen levels that inhibit luteal function are associated with miscarriage. And high levels of LH may lead to premature completion of the second meiosis of the oocyte, thus affecting the fertilization and implantation process.
(3) Diabetes mellitus
Diabetes can lead to vascular lesions, poor blood flow to the uterus, and impaired embryonic development. In addition, hyperglycemia in early pregnancy may be a risk factor for embryonic malformations.
(4) Hyperprolactinemia
Hyperprolactinemia may manifest as luteal insufficiency and is associated with miscarriage.
(5) Thyroid disease
The incidence of miscarriage is significantly higher in those with positive thyroid autoantibodies.
5. Infectious factors
(1) Chlamydia trachomatis: The rate of Chlamydia trachomatis infection during pregnancy is 3-30%, causing cervical canal mucositis and endometritis, affecting fertilized egg implantation or causing chorioamnionitis leading to miscarriage, preterm delivery or stillbirth.
(2) Mycoplasma cervicis: Mycoplasma cervicis has a high detection rate in the lower genital tract of married women, and can invade the fetal membranes and placenta in the middle of pregnancy, which is associated with miscarriage in the middle and late stages of pregnancy, but its effect on recurrent miscarriage is unclear.
(3) Toxoplasma gondii infection: miscarriage caused by Toxoplasma gondii infection is disseminated, and its relationship with recurrent miscarriage has not been fully demonstrated.
(4) Viral infections: rubella virus, cytomegalovirus, herpes simplex virus, hepatitis B virus, and human immunodeficiency virus can pass through the placenta and affect embryonic development, leading to miscarriage.
(5) Other infections: other pathogenic microorganisms such as gram-negative diplococci can infect the endometrium through the reproductive tract and cause endometritis or cause chorioamnionitis, as well as the toxic effect of bacterial metabolites on the embryo and cause miscarriage.
6, immune factors
(1) Anti-sperm antibodies: The rate of positive anti-sperm antibodies in recurrent miscarriage is more than 50%. The mechanism of occurrence is that anti-sperm antibodies can activate macrophages to produce toxic effects on gametes and embryos; the trophoblast may have common antigenicity with sperm, and antibodies can directly destroy trophoblast.
(2) Anti-cardiolipin antibodies: are autoimmune antibodies, the incidence of miscarriage in those positive for anti-cardiolipin antibodies is as high as 66-89%, the mechanism of occurrence is not fully understood, probably because anti-cardiolipin antibodies inhibit the production of endothelial prostacyclin leading to vasoconstriction or damage platelets and easy to bind with the endothelium of blood vessels to clot and lead to thrombosis.
(3) Blood group antigen system: ABO blood group incompatibility is the main cause of fetal hemolysis in China, and another is Rh blood group incompatibility.
(4) Human histocompatibility antigen HLA: HLA is an antigen widely present on the surface of various tissue cells that can cause rejection, embryos are maternal homozygous immune grafts, the chance of having a common HLA antigen in couples with miscarriage is quite high, and recent studies have found that the frequency of miscarrying couples with the same HLA-DR is significantly higher.
7.Maternal systemic diseases
It has been found clinically that the incidence of ERSA is significantly higher in patients with systemic lupus erythematosus, scleroderma, ichthyosis, progressive systemic sclerosis than in the general population, and other possibly related cardiovascular diseases, renal diseases and hematological diseases. In addition, 66% of women with recurrent abortions were clinically found to have a tendency to thrombosis.
8. Environmental factors
The environmental factors that cause ERSA are difficult to determine, but fertile women should try to avoid potential risk factors in the environment, such as alcohol abuse, smoking, long-term exposure to certain chemicals (such as organic solvents, pesticides) and heavy metals (lead, mercury) and radiation, etc.
9.Semen abnormalities
Semen abnormalities can directly or indirectly cause ERSA, the incidence of oligospermia or polyspermia ERSA is 37.6% and 20.0%, respectively. Increased malformed sperm can also cause ERSA.
Third, the diagnosis of recurrent miscarriage
1. Medical history: mainly includes marital history, reproductive history, family history and history of exposure to radiation or chemical toxins during the peri-pregnancy period.
2. Physical examination: including routine physical examination and gynecological related examination.
3. Immunological examination
Autoantibodies: anti-cardiolipin antibody and lupus anticoagulation factor determination, anti-nuclear antibody and anti-thyroid antibody determination, immune complex and complement C3 determination. Blocking antibody examination.
4. Chromosomal factors
Genetic examination methods: chromosome examination for both husband and wife, and analysis by family line survey if the disease is hereditary.
5.Anatomical factors
Examination of anatomical factors: ultrasonography, hysterosalpingography, hysteroscopy, MRI, endocervical examination.
6.Endocrine factors
Endocrinological examination: luteal function examination, thyroid function examination, serum prolactin determination
7.Cervical function examination
Medical history: Miscarriage mostly occurs in the middle of pregnancy.
Diagnosis in case of non-pregnancy.
1.Cervical dilatation type test: no resistance to pass the No. 8 cervical dilator suggests cervical insufficiency.
2, cervical balloon traction test: the catheter is inserted into the uterine cavity and 1ml of saline is injected into the balloon, if less than 600g weight is traction out, it suggests cervical insufficiency.
3.Iodine oil imaging of the uterine tube: shortening of the cervical canal and a canal diameter greater than 6 mm at the level of the endocervix suggest cervical insufficiency.
Diagnosis during pregnancy.
1.Cervical finger examination: the vaginal part of the cervix is shorter or even receding, and the internal and external openings are relaxed to allow 1 finger to pass.
2.B ultrasound examination: to understand the length of the cervix, the width of the inner opening and the protrusion of the amniotic sac, etc. Any condition of cervical length <25mm, width >32mm and inner diameter >5mm at 12 weeks of gestation indicates cervical insufficiency.
IV. Western medical treatment
1.Chromosomal abnormalities
There is no effective treatment for miscarriage caused by carriers of chromosomal abnormalities, and the main measures are genetic counseling and estimation of the probability of recurrence of fetal chromosomal abnormalities. If both spouses have normal chromosomes and the embryo has chromosomal abnormalities, the influence of adverse environmental factors should be avoided to prevent the aging of eggs or sperm.
2.Renatal tract abnormalities
Plastic surgery for uterine malformation, separation of uterine adhesions, excision of uterine fibroids and intrauterine foreign bodies, etc. Cervical insufficiency: endocervical ring ligation at 16 to 22 weeks of pregnancy.
3.Luteal insufficiency
Luteinizing insufficiency: progesterone injection 10-20mg intramuscularly once a day, start after pregnancy is found, continue until 8 weeks of pregnancy and then start to reduce the dosage and stop until 16 weeks of pregnancy; or HCG 2000U 1 injection daily or 1 injection every other day until 8 weeks of pregnancy, or the combination of the two is better.
4.Hyperprolactinemia
Hyperprolactinemia: Bromocriptine 2.5~5mg/day, divided into 2~3 times orally, regularly measure the blood PRL level, adjust the dose, and stop taking it after pregnancy.
5.Immune factor abnormalities
Autoimmune abnormalities: such as antiphospholipid antibody, lupus anticoagulant positive can be treated with low-dose aspirin or steroid hormone. Steroid hormone therapy: low-dose maintenance method: prednisone 5mg, 1 time/day, applied for 3 to 12 months; high-dose impact method: 7 days in a row. Low-dose aspirin + prednisone therapy: aspirin 75mg/day + prednisone 60mg/day, taken until the antiphospholipid antibody turns negative. Immunotherapy is available for those lacking in blocking antibodies, i.e. using the husband’s or third party’s lymphocytes as the immunogen, the patient is induced to produce individual-specific factors or blocking factors that inhibit T-cell recognition of fetal antigens through allogeneic sensitization reactions. Immunizations can be administered before and during pregnancy, with two to four sessions per course and a general interval of two to four weeks between injections. The success rate of another pregnancy is higher when conception occurs after a positive blocking antibody. Cut off the transmission route for different pathogenic microorganisms to treat the cause.
6.Infection factors
(1) Mycoplasma, Chlamydia: Doxycycline 0.1 Bid PO, for 7 days. Or Azithromycin 1.0 Single dose. Erythromycin 0.5, q6h for 7 days during pregnancy is recommended.
(2) Neisseria gonorrhoeae: ceftriaxone sodium 1.0 intramuscular injection; clinical 25-30% of Neisseria gonorrhoeae infection combined with Chlamydia trachomatis infection, so at the same time need anti-chlamydial treatment.
(3) Toxoplasmosis: Acetylspiramycin, 1.0g q6h PO, for 2 weeks, can be repeated after an interval of 2 weeks, is mostly used for pregnant women.
(4) Rubella: so far there is no special treatment, acute symptomatic treatment of infection.
(5) cytomegalovirus infection: early pregnancy clear cytomegalovirus infection, there is no drug with high efficacy and few side effects.
(6) genital herpes: acyclovir ointment applied externally to the affected area, while acyclovir 0.5, taken orally five times a day, 7-10 days as a course of treatment.
(7) syphilis: syphilis treatment for pregnant women, at the same time, to prevent or reduce the occurrence of congenital syphilis.
(8) Early syphilis: procaine penicillin G, 800,000 U/d, qd,im, 10 days as a course of treatment. Use 1 course each for the first 3 months of pregnancy and the last 3 months of pregnancy. For penicillin allergy, erythromycin 0.5 q6h po for 15 days.
(9) Late mycotoxicity: procaine penicillin G, 800,000 U/d, qd,im, 20 days as a course, repeat a course after 2 weeks. Use 1 course each in the first 3 months of pregnancy and the last 3 months of pregnancy. In case of penicillin allergy, erythromycin 0.5 q6h po for 30 days.
V. Chinese medicine treatment
Recurrent miscarriage belongs to the category of “slippery fetus”, “fetal leakage”, “fetal movement” and “fetal atrophy” in Chinese medicine. Chinese medicine has unique advantages in preventing and treating this disease. We can treat recurrent miscarriage with standardized Chinese medicine before trying to conceive again, prevent and control before pregnancy, help pregnancy during the peri-pregnancy period, and treat the fetus after pregnancy, according to the patient’s symptoms and signs, and treat with evidence, such as tonifying the kidney, strengthening the spleen, nourishing the blood, or invigorating the blood, etc., which can significantly improve the success rate of fetus preservation compared with the treatment of Western medicine alone.