I. Introduction to the etiology associated with (recurrent) spontaneous abortion
Recurrent spontaneous abortion (RSA) refers to two or more consecutive, unwanted early to midterm pregnancy terminations. Its causes are complex and difficult to treat, and has been a concern of clinicians and researchers for many years. To date, the cause of more than 50% of recurrent miscarriages is unknown, and physicians can only analyze and speculate on the etiology of miscarriage in different patients based on clinical experience and limited examination results. The unknown cause of recurrent miscarriage brings great difficulties to clinical treatment, as it is difficult to provide targeted treatment; or a small amount of vaginal bleeding and abdominal distension continues after treatment, which is difficult for patients to understand; moreover, a considerable number of patients still end up having miscarriage after treatment; what’s more, some patients get deformed fetuses or die in the womb during late pregnancy after fetal preservation treatment. Guo Peifen, Department of Obstetrics and Gynecology, Guangdong General Hospital of the Armed Police
In spite of this, we have gained considerable knowledge about this disease, some of which are described below. Moreover, we have found that even after experiencing multiple miscarriages, some patients may still end up with a successful natural pregnancy; therefore, this confidence in success and peace of mind is especially needed for couples with recurrent spontaneous miscarriages.
1. Embryonic factors: mainly abnormalities in the genetic material DNA, related to genetic gene defects, drugs, infections, advanced age of the couple, etc., accounting for 50%-60%: including: (1) abnormalities in the number of chromosomes: trisomy, haploid X, triploidy, tetraploidy; (2) abnormalities in the structure of genes: translocation, breakage, deletion. It also includes abnormalities of embryonic anatomy. It is necessary to examine the chromosomes of both spouses, and if there are aborted tissues, an accurate examination for chromosomal abnormalities can determine the cause of miscarriage in this pregnancy and guide the focus of attention in the next pregnancy. For miscarried fetuses it is recommended that autopsy be performed to understand if there are clear abnormalities.
2, female genital anatomical abnormalities: uterine malformations (longitudinal or bicornuate m), uterine fibroids, endometrial polyps, foreign body stay after previous abortion, uterine m rao sink 4 dead hackles and serve the purpose of the U.S. µs to guide the frightened fetus with the bones to guide the fetus (3) also chafed paper wont room Fei T诩 palm frightened to be resistant to the stupid to allow the quality of excel plague beer W庸诳谒沙劭梢plant honestly 14-16 weeks to perform endocervical ring ligation.
3, infection: vaginitis (trichomoniasis, pseudofilamentous yeast, bacterial), m cervicitis, chronic pelvic inflammatory and systemic infections (syphilis, tuberculosis) may lead to spontaneous abortion. The pathogens include generalized bacteria, Mycobacterium tuberculosis, mycoplasma rest, chlamydia, viruses, etc. (TORCH). The inflammatory factors produced continuously irritate the uterus and are detrimental to the growth and development of the fetus in the middle. Inflammatory factors are one of the categories of causes that can be detected and can be cured at present. Its treatment includes conjugal treatment.
4. Endocrine factors: thyroid function, undetected diabetes mellitus, abnormal luteal function (measured P/HCG level), etc. The presence of gynecological endocrine abnormalities (e.g. PCOS, hyperandrogenism, manifested as irregular menstruation, etc.) before pregnancy predisposes to miscarriage in case of unplanned pregnancy. Dynamic testing of hormone levels and corresponding treatment are needed.
5. Systemic factors: medical and surgical diseases, severe anemia and malnutrition, hypertension, chronic nephritis; other surgical diseases. Endometrial anomalies have various manifestations, some of which simply lead to infertility or multiple miscarriages. Less invasive laparoscopy can clearly diagnose and remove the lesion and improve the reproductive environment in the pelvis. Antiphospholipid antibody syndrome, thrombogenic diseases, and positive antinuclear antibodies all lead to RSA.
6, traumatic stimulation and lifestyle: accidental injury after pregnancy, exposure to X-rays, electromagnetic waves, drugs and poisons, contact with dogs and cats, etc.; continuous tension, anxiety, social pressure; addiction to alcohol and tobacco, irregular work and rest, etc. may lead to miscarriage.
7, immune factors: some autoimmune diseases during pregnancy aggravate or remit, the recognition of the fetus is low or excessive recognition, will lead to miscarriage. Detection of closed antibodies, anti-endometrial antibodies, and anti-blood type antibodies are all tested. Immunotherapy with lymphocytes can regulate the immune status of the female organism and thus prevent the occurrence of miscarriage. New immunomodulators (CsA) can also be used with good results.
2. Common treatment options for (recurrent) spontaneous miscarriage
1. For patients in miscarriage, it is very important to collect the meconium and chorionic villi of the miscarriage. Such patients should be hospitalized as much as possible. The above will be communicated and signed by both spouses. If the uterus is cleared, it is recommended that the aborted tissue be examined for pathology and genetic material.
(1) Characterization: whether it is chorionic (to identify intrauterine pregnancy from suprauterine pregnancy) and send to the hospital pathology department.
(2) Culture of cells of fetal origin for chromosomal analysis, see article 8 of this paper for the specific protocol.
(3) To study whether the meconium is infected with UU, CT and other pathogens
It is required to take the material aseptically, and not to wait for it to flow out naturally through the vagina. Otherwise, contamination by vaginal bacteria will lead to experimental failure and error of results.
2.Anatomical abnormalities
Longitudinal uterus and bowed uterus: people often ask if they want to do surgery, this depends on the individual situation. If you have had more than 2 miscarriages and other causes are ruled out, it is still recommended to perform a longitudinal resection or uterine plastic surgery.
Uterine fibroids: submucosal fibroids can be resected hysteroscopically, and interstitial fibroids can be excavated transabdominally.
Uterine adhesions: hysteroscopic separation of adhesions, postoperative placement of intrauterine device for 3 months to prevent re-formation of adhesions + estrogen and progesterone repair of the endometrium.
In case of multiple spontaneous abortions and pelvic inflammatory disease (specific and non-specific infections) cannot be excluded, laparoscopy, extraction of peritoneal fluid for UU/CT, and scientific sampling. Intraoperative improvement of the microenvironment of the abdominopelvic cavity; postoperative conditioning with Chinese medicine.
For cervical insufficiency: admission at 14-16 weeks for cervical cerclage and antiretroviral treatment, and high-risk clinic. Preoperative ultrasonography should be routinely performed to exclude gravidity, fetal malformation or intrauterine death to ensure normal fetal development. In cases where the opening of the uterus has been opened (less than 2 cm), annuloplasty should be done as soon as possible, but its therapeutic effect is poor and the complications for mother and child are high, such as premature rupture of membranes, preterm delivery and intrauterine infection.
3. Outpatient medication (non-pregnant state)
(1) Infectious factors: Chlamydia infection can be treated with oral erythromycin, 0.25g each time, 4 times a day for 4 days. (2) Toxoplasma gondii infection: oral acetaminophen, 75mg on the first day and 25mg daily for 30 days thereafter: or spiramycin, 0.2g daily, 4 times a day for 14 days. The male partner is also often infected, so he should be medicated at the same time. The treatment of CMV carriers is not yet available, but it is possible to get pregnant without treatment in CMVIgG-positive cases, and it is advisable to get pregnant after the transfer of CMVIgM. The treatment of bacterial infection is described in the section on infectious abortion.
(2) Treatment of internal and external diseases and correction of anemia
(3) Endocrine abnormalities: polycystic ovary syndrome, hyperprolactinemia, abnormal thyroid function or diabetes mellitus, etc. should be treated with appropriate endocrine therapy before pregnancy, and progestin should be added in early pregnancy.
The endometrial lining is thin, 0.6 at 12 days and 0.8 at 16 days, while the optimal value of endometrial lining for pregnancy is 1.0-1.2, and the range of pregnancy is mostly considered to be 0.8-1.5, and the chance of pregnancy is very small if it is less than 0.8, and even if it is pregnant, it is easy to abort early or stop developing (no germ, empty sac).
(4) Psychological guidance: it is advisable to let nature take its course and not to force the matter of pregnancy.
4.Women who have had a spontaneous abortion and are now pregnant again and have symptoms of abortion such as uncontrolled vaginal bleeding and abdominal pain.
According to the actual situation of the patient (importance, mentality, age, economic conditions), it is recommended to be hospitalized for consultation and treatment as much as possible.
(1) Content of monitoring
Blood progesterone and HCG levels on alternate days
Ultrasound monitoring of gestational sac and germ size every 3-5 days
Observation of the amount of vaginal bleeding, abdominal pain and bloating
Culture of vaginal secretions + drug sensitivity (checked upon admission and rechecked when hospitalized >10 days)
Monitoring and treatment of early pregnancy reaction
(2) Settlement of pregnancy
Endocrine abnormalities
Luteinizing insufficiency Progesterone 20mg every other day or daily intramuscular injection until about 10 weeks of pregnancy, or hCG 1000-2000U, intramuscular injection once every other day can be used in pregnancy. Or use Darvon, taken orally.
Others If the patient has polycystic ovary syndrome, hyperprolactinemia, abnormal thyroid function or diabetes mellitus, it is advisable to have appropriate endocrine treatment before pregnancy and add progesterone in early pregnancy.
Infectious factors
Treatment of Immune Habitual Miscarriage
Treatment of autoimmune habitual miscarriage Antiphospholipid antibody-related miscarriage, there is no universally accepted treatment plan, and it is mostly treated with anticoagulants and immunosuppressive agents. Commonly used anticoagulants include aspirin and heparin, and immunosuppressive agents are mainly prednisone. Successful treatment with human propecia (2.5 g/strips, propecia immunoglobulin) has also been reported.
(1) Adrenocorticotropic hormone (prednisone): Larger doses of prednisone (10-40 mg/d) are used abroad for treatment, which is started upon confirmation of pregnancy and continues until the end of pregnancy. Clinical observation shows that this method can be associated with a variety of maternal and child complications, such as secondary infection, preterm delivery, hyperemesis, premature rupture of membranes, intrauterine growth retardation, and Cushing’s syndrome. The use of low-dose prednisone (5mg/d) not only does not cause these complications, but also most of the patients have their antibodies turned negative soon after taking the drug.
(2) Aspirin: foreign countries advocate the use of drugs once the pregnancy is started, a few days before delivery to stop the drug, aspirin dosage of 75-100mg / d, but this method is prone to bleeding tendency. Some people in China use a small dose of 25mg per day, starting after the pregnancy is determined until the end of the pregnancy: the blood coagulation parameters, such as bleeding and clotting time, platelet count and platelet aggregation test, should be closely monitored during treatment. A small number of patients with platelet hypoplasia, PT below 38% after taking the drug, and mild bleeding tendency, need to stop the drug in time, there are still a few patients need to increase the dose to 50mg per day, in order to bring the PT value down to the normal range.
(3) Combination medication: At present, prednisone plus aspirin combination therapy is advocated. In foreign countries (prednisone 15mg/d plus aspirin 75mg/d), the success rate is about 70%, and there are maternal and child complications, such as fetal growth restriction, preterm delivery, premature rupture of membranes, obstetric bleeding, etc. In China (prednisone 5mg/d plus aspirin 25mg/d), the success rate is 95%, and no obvious obstetric complications have been seen.
In view of the anticoagulation and microcirculation effect of heparin, some foreign scholars use small dose of aspirin plus heparin treatment, the dosage of aspirin is 80mg/d, the first dose of heparin is 10000U/d, divided into 2 subcutaneous injections, after which the dosage of heparin is adjusted according to the partial thrombospondin activation time, and the medication is used until the full term of pregnancy, the success rate of this method is 80%, but there are also certain obstetric complications.
(4) High-dose propecia injection (2.5g/stem, propecia immunoglobulin): High-dose immunoglobulin input has the effect of inhibiting the production of antibodies. Immediately after definite pregnancy, intravenous infusion of gammaglobulin 0.5g is given for 2 days and repeated every 4 weeks until 33 weeks of pregnancy. This method is expensive and carries the risk of potential blood-borne infection (equivalent to blood transfusion).
(5) Use of cyclosporine A (CsA): FDA has not approved its use for pregnancy. Informed patient consent is required. There are at least three domestic studies for basic and clinical applications, which have good prospects.
Active immunotherapy for alloimmune habitual abortion
Since the 1980s, some foreign scholars have started to use active immunotherapy to treat alloimmune type of habitual abortion. In other words, active immunosensitization of the wife with lymphocytes from the husband or an unrelated individual is used to induce the production of closed antibodies in the woman’s body to avoid maternal immune rejection of the embryo.
(1) Indications: ①3 consecutive early abortions, excluding other causative factors; ②negative autoantibodies; ③lack of closed antibodies in the patient’s serum or low proliferation inhibition rate in the MLC inhibition test results.
(2) Treatment: Immunogen can be selected from lymphocytes or leukocytes of the husband or unrelated individuals, as the blood donor should do strict pre-treatment testing to avoid the potential risk of blood-borne infection. The more commonly used route of immunization is subcutaneous injection.
Currently, immunotherapy is mostly administered by subcutaneous injection of lymphocytes from the husband or lymphocytes from unrelated individuals. In terms of immunization dose selection, foreign countries mostly use larger doses of lymphocytes (50-120×106 per lymphocyte dose), do immunosensitization tests before pregnancy, and inject intradermally in 3 points in the upper limbs, once every 2-3 weeks, for a total of 2-4 times, until the skin reaction area is reduced to allow their pregnancy, and those whose skin reaction does not reduce can be immunized additional times. In China, the dosage of lymphocytes is 20-30×106 at 3-week intervals for 2-4 times. After the course of treatment, patients are encouraged to get pregnant within 3 months, and those with successful pregnancies are reinforced 1-2 times during early pregnancy. If pregnancy is not achieved, a new course of treatment can be given if infertility factors are excluded. The pregnancy success rate is 86.4%, which is better than the 75%-80% reported abroad, and there are no significant complications. The results of a study on the offspring of active immunotherapy showed that there was no difference in birth weight, postnatal growth and intellectual development between the offspring and the zheng control group, proving that active immunotherapy is safe for the offspring.
5.Chinese medicine treatment
According to the microscopic identification of reproductive immunology, combined with the macroscopic identification of Chinese medicine, RSA can make three kinds of etiological typing.
(1) Low maternal-fetal immune recognition type
This is the main cause of RSA, which is mainly manifested by the lack of closed antibody.
TCM evidence: kidney qi is not fixed, fetal fire is inflamed. Insufficient kidney qi, the fetus is not fixed. At the same time, fetal fire is the extreme of heat, forcing the blood to move delicately and damaging the fetal element. For treatment, leukocyte immunization is given to such patients before conception. Immunization is given every 3-4 weeks, and 3 times is a course of immunization. After one course of immunization, recheck the closed antibody. If the closed antibody is elevated, arrange for conception; if the closed antibody is not elevated, recheck the closed antibody after 1-2 times of strengthening immunization until the closed antibody is elevated.
For this type of RSA, intravenous immunoglobulin infusion therapy can be used.
Chinese medicine treatment is to tonify the kidney and benefit the qi, clear heat and calm the fetus.
Chinese medicine prescription: Semen Cuscutae, Radix et Rhizoma, Radix et Rhizoma Eucommiae, 12g Radix Codonopsis, 6g Radix Scutellariae, 18g Radix Scutellariae, 6g Rhizoma Atractylodes, 6g Radix et Rhizoma, 6g Radix et Rhizoma, 9g Radix Paeoniae.
Red House Hospital found that the prognosis of pregnancy was poorer in leukocyte immunization plus the use of herbal fetal preservation formula.
(2) Maternal-fetal immune over-recognition type
This type is mainly manifested by abnormally high autoimmunity and/or alloimmunity in the mother and is an important etiological type of RSA, which can be caused by a variety of immune abnormal factors.
Chinese medical diagnosis: damp-heat stagnation, stagnation of Qi and blood stasis.
In RSA patients with elevated phospholipid antibodies, treatment with immunosuppressive adrenocorticotropic hormones and/or doses of aspirin is used abroad, aiming to inhibit the production and action of phospholipid antibodies.
TCM treatment: nourish kidney yin and clear deficiency fire: for patients with positive hyaline bands.
Clearing heat and dampness, nourishing blood and invigorating blood: for patients with positive phospholipid antibodies and blood type antibodies. Zhi Bai Di Huang Wan is used for nourishing kidney yin and clearing deficiency fire.
Yin Chen 15g, Prepared Rhubarb 12g, Mast 6g, Fried Scutellaria 12g, Radix Angelicae Sinensis 9g, Red Peony 12g, White Peony 12g, Motherwort 18g, Glycyrrhiza glabra 6g
(3) Maternal-fetal immune recognition disorder
The incidence is not high, but the management is very difficult. On the one hand, it manifests as a lack of closed antibodies, showing low maternal-fetal alloimmune recognition and weakened maternal immune protection of the embryo; on the other hand, it shows an abnormally high autoimmune or alloimmune damage effect.
Chinese medical evidence: dampness and heat accumulation, kidney deficiency and blood stasis.
Leukocyte immunotherapy not only does not increase the production of phospholipid antibodies, but on the contrary can convert some phospholipid-positive RSA patients to negative and obtain a good pregnancy prognosis. In this sense, leukocyte immunotherapy is still indicated for patients with this type of RSA and may have a better clinical outcome if low-dose aspirin is added. Recent studies have shown that intravenous immunoglobulin injections are also effective in improving the prognosis of pregnancies with immune overload; therefore, intravenous immunoglobulin therapy may be indicated for RSA with immune disorders.
6. For patients with chromosomal abnormalities
(1) Embryonic chromosomal abnormalities: If each miscarriage is due to embryonic chromosomal abnormalities, this suggests that the cause of miscarriage is related to the quality of the gametes. If the rate of sperm abnormality is too high, it is recommended to go to male department for treatment, and donor artificial insemination (AID) is feasible for those who cannot be cured for a long time. If the female partner is of advanced age, the embryo chromosomal abnormality is mostly san body, and repeated treatment failure can be considered for in vitro fertilization with egg donation and embryo transfer (IIVF).
(2) Chromosomal abnormalities in both partners AID can be done for male chromosomal abnormalities and IVF can be done for female chromosomal abnormalities, if one or both partners are chromosomally translocated, IVF and preimplantation diagnosis (PGD) can be done.
7. Preparation of recurrent or habitual miscarriage patients before conceiving again
(1) Habitual miscarriage often emphasizes that both spouses should be investigated and treated together.
(2) Women who have had recurrent miscarriages should receive the necessary tests before their next pregnancy or three months after the miscarriage.
(3) The general understanding of both men and women’s health: blood routine + blood type, liver and kidney function, hepatitis B and half, gynecological examination of the woman (gynecological examination, white belt routine + culture UU, CT, NGH, cervical scraping TCT.) and semen routine + pathogenic bacteria culture analysis of the man. To rule out their own disease, to see if there is anemia, hepatitis, kidney disease. Diabetes mellitus, inflammation of the reproductive system, sexually transmitted infections, cervical cancer, etc. These tests are not significant for recurrent habitual miscarriage, but some conditions are only a factor in inducing miscarriage.
(4) Habitual miscarriage should be examined by the following special items
6.4.1 Chromosomal examination should be done first to rule out genetic problems.
6.4.2 Basal body temperature measurement is the most economical and easy way to understand ovarian function and predict ovulation. Sex hormones and thyroid hormone tests are performed to exclude endocrine factors. The gonadal hormone test requires venous blood on the third to fifth day of menstruation, three months after the first miscarriage, on an empty stomach.
6.4.3 Ultrasound examination of the female for abnormalities in the development of the uterine adnexa and the thickness of the endometrium, as well as to monitor the size of the developing follicles and ovulation. Hysteroscopy can be performed in conjunction with hysteroscopy if hysterosalpingia or adhesions are suspected. These examinations are performed to exclude anatomical factors.
6.4.4 Eugenics testing (TORCT)
6.4.5 There are many types of immuno-antibody tests, which should be considered if the above tests are unexplained
Anti-sperm antibodies (AsAB)
Anti-endometrial antibodies
Anti-cardiolipin antibodies
Anti-Zona pellucida antibodies
Anti-embryonic antibodies
7. Lifestyle and menstrual regulation
Most of the patients have irregular menstruation before pregnancy, some of them have low volume, some have high volume, some have prolonged menstrual period, and the basal body temperature is not so normal. This should be well-treated before pregnancy.
After pregnancy, you must pay attention to the treatment of fetal preservation in order to avoid further
The following programs are available
Anti-emetic feeding program.
The monitoring program for labor and delivery.
Medical abortion scraping program.
Eight, miscarriage chorionic hair delivery process
1. Collect 2-3ml of anticoagulated blood from each patient couple (with routine blood tube). 2. Clear pipette with tube, aseptically collect the chorionic villi and place them in a sterile 20ml syringe.
3. The blood specimen and chorionic villus specimen will be delivered in 1 hour as far as possible. 4. Go to the 5th floor of the outpatient building of Southern Hospital, find Nurse Xiao Chaoqun, contact the registration number and find the physician for billing.
5. After paying the fee, send the bill together with the specimen to the 17th floor of the new laboratory building (prenatal diagnosis center) 6. Contact number of prenatal diagnosis center, Dr. Liu, 61641549