There is such a special group of patients who go to great lengths to visit famous doctors; Baidu search “habitual miscarriage, embryonic abortion, recurrent miscarriage ……”; during a simple consultation, they usually pour out their woes to the doctor while taking out a thick stack of examination reports, and even sobbing. The company’s main business is to provide a wide range of products and services to the public. Look at these painful histories.
1. repeated embryo transfer failures;
2. repeated unexplained biochemical pregnancy;
3. repeatedly empty gestational sac, no fetal heartbeat, fetal heartbeat disappeared;
4. intrauterine fetal death;
5. Repeated amniotic fluid reduction ……
What causes them to have such a bumpy road to motherhood, is it always natural elimination and poor quality embryos? Some doctors told them to give up, others suggested to try again! Without their own children, they don’t want to give up, and without finding out the cause of the disease, they don’t dare to get pregnant! In fact, the above-mentioned patients belong to the category of recurrent miscarriage, the causes of which are very complicated. Only through detailed medical history and a series of specialized examinations can doctors find the causes and make individualized medication plans.
I. Definition of recurrent miscarriage
Recurrent miscarriage is defined as two or more spontaneous abortions before 28 weeks of gestation with the same sexual partner. The classical theory defines 3 or more consecutive spontaneous abortions as habitual abortion.
II. About the etiology of recurrent miscarriage
The etiology of recurrent miscarriage is complex, including genetic, infectious, anatomical structure, endocrine, immune and blood coagulation abnormalities, environmental factors and maternal systemic diseases. The current medical technology and testing methods can only detect 50%-60% of the causes, and there are still 40%-50% of patients with unknown causes.
1. Genetic factors
These include chromosomal abnormalities in the couple and chromosomal abnormalities in the embryo. About 2%-5% of RSA couples have chromosomal structural abnormalities in at least one partner, including translocation, chimerism, deletion or inversion, etc. The most common ones are balanced translocation and Robertson translocation. Embryonic chromosomal abnormalities are the most common cause of spontaneous abortion, including quantitative and structural abnormalities.
2. Infection factors
Both female reproductive tract and systemic infections can cause spontaneous abortion. Common systemic infections causing miscarriage include acute pneumonia, acute appendicitis, acute pyelitis, acute pancreatitis, etc. Any serious infection leading to bacteremia or viremia can cause miscarriage. Reproductive tract infections that cause miscarriage include vaginitis, such as bacterial vaginosis, cervicitis (e.g., Chlamydia trachomatis or Neisseria gonorrhoeae infection), endometritis, and pelvic inflammatory disease. The pathogens causing infections include bacteria, viruses, fungi, mycoplasma, chlamydia, syphilis spirochetes, TORCH (toxoplasma, rubella virus, cytomegalovirus, herpes simplex virus), etc.
3. Anatomical factors
The occurrence of RSA is closely related to uterine development and anatomical abnormalities, including congenital uterine malformation, cervical insufficiency, uterine cavity adhesions, submucosal fibroids, etc.
4. Endocrine factors
(1) Luteal insufficiency
Insufficient secretion of progesterone during the luteal phase or premature decline of the corpus luteum, resulting in poor secretion of endometrial glands during the secretory phase. High concentration of progesterone can prevent the uterus from contracting, so that the pregnant uterus remains relatively stationary; insufficient secretion of progesterone can cause poor response of the pregnant meconium, affecting the implantation and development of the pregnant egg, resulting in miscarriage. There are two sources of progesterone during pregnancy: one is produced by the ovarian corpus luteum and the other is secreted by the placental trophoblast. The progesterone produced by the ovarian corpus luteum gradually decreases after 6 to 8 weeks of pregnancy and is then replaced by progesterone produced by the placenta.
(2) Polycystic ovary syndrome
The incidence of polycystic ovary syndrome in patients with recurrent spontaneous abortion is 58%. High levels of luteinizing hormone, hyperandrogenism and hyperinsulinemia reduce egg quality and endometrial tolerance.
(3) Thyroid disorders
Hypothyroidism is associated with recurrent spontaneous abortions. Also, recurrent spontaneous abortion is thought to be associated with the presence of thyroid antibodies (thyroid function is mostly normal in such patients).
(4) Hyperprolactinemia
High levels of prolactin directly inhibit the proliferation of luteal granulosa cells and their secretory function. The main clinical manifestations of hyperprolactinemia are amenorrhea and lactation, and when the level of prolactin is higher than normal, it can manifest as suppression of ovulation and luteal insufficiency.
(5) Diabetes mellitus
The incidence of miscarriage in women with well-controlled metabolic syndrome is reduced and approximates the incidence of miscarriage in non-diabetic women. Women with early pregnancy who have elevated blood glucose and glycosylated hemoglobin have a significantly increased risk of spontaneous abortion. In women with poorly controlled blood glucose, the risk of miscarriage increases with elevated glycosylated hemoglobin levels. The incidence of miscarriage in poorly controlled blood glucose can be as high as 15% to 30%, and hyperglycemia in early pregnancy may also cause risk factors for embryonic malformation.
5. Immune factors
(1) Autoimmune type
The autoantibodies known to be related to recurrent miscarriage are mainly non-organ-specific antibodies, such as antiphospholipid antibodies, anti-nuclear antibodies, anti-thyroid antibodies, tissue-specific antibodies and so on. The autoantibodies that are more closely related to recurrent miscarriage are antiphospholipid antibodies.
(2) Homozygous immune type
Pregnancy is a successful semi-allogeneic transfer process in which the pregnant woman shows immune tolerance to intrauterine embryo grafts without rejection due to a series of adaptive changes in her own immune system. If there is an imbalance in immune regulation and suppressor cells, maternal immune hyporesponsiveness due to abnormal recognition of embryonic paternal antigens results in maternal closed antibody or protective antibody deficiency and immune rejection, which leads to the occurrence of miscarriage.
6. Embolism
In short, if the coagulation, anticoagulation and fibrinolytic system of the body are abnormal during pregnancy, pathological blood hypercoagulation may occur, forming a pre-thrombotic state, which may then develop into a thrombus. Thrombophilia does not necessarily occur in thrombophilia, but may result in a variety of adverse pregnancy outcomes: recurrent miscarriage, severe early-onset pre-eclampsia major, neonatal coagulation abnormalities, and stillbirth due to imbalance in coagulation-anticoagulation mechanisms or fibrinolytic activity, and microthrombosis of the uterine spiral arteries or chorionic vessels, leading to poor placental perfusion or even infarction. It was found that 67% of patients with recurrent spontaneous abortion had defects in the fibrinolytic pathway, and 66% of those with pregnancy loss had a tendency to thrombosis.
Third, about recurrent miscarriage should do the test
1. Chromosomal abnormalities
(1) Embryonic chromosomal abnormalities (in case of unavoidable miscarriage, embryonic villi are taken for chromosomal examination during uterine clearance, and fresh villi tissue is required)
(2) Chromosomal abnormalities in couples (venous blood is taken from couples, not affected by dietary menstrual cycle)
2. Endocrine abnormalities
(1) Polycystic ovary syndrome (blood will be drawn from the third to the fifth day of menstruation for sex hormone measurement, monthly self-test of basal body temperature and gynecologic ultrasound after menstruation)
(2) Hyperthyroidism or hypothyroidism (thyroid hormone test, not affected by menstrual cycle)
(3) Hyperprolactinemia (around 9:00 a.m., you can sit for 15 minutes without fasting and have your blood drawn for measurement, not affected by menstrual cycle)
(4) Diabetes mellitus/insulin resistance (fasting blood glucose and insulin, oral glucose followed by blood glucose and insulin)
(5) Luteal insufficiency (self-measurement of basal body temperature each month)
(6) Ovulation disorder (ultrasound monitoring of follicular development to follicular discharge after the 12th day of menstruation)
3. Reproductive system anatomical abnormalities
(1) Uterine adhesions (ultrasound, hysterosalpingography, hysteroscopy, can be performed after menstruation)
(2) Uterine malformation (ultrasound, hysteroscopy, hysteroscopy, etc.)
(3) Cervical insufficiency (cervical dilatation test, ultrasound, imaging, etc.)
4. Infection factors
(1) Mycoplasma, Chlamydia, etc. (take cervical mucus, non-menstrual period)
(2) TORCH, HIV, RPR, etc. (blood sampling is always available)
5. Thrombotic factors
(1) Congenital pre-thrombotic state (coagulation factor V mutation, prothrombin gene mutation, protein C defect, protein S defect, homocysteine, prothrombin III activity)
(2) Acquired pre-thrombotic state (anti-cardiolipin syndrome: requires more than 2 repeated blood draws, each at an interval of about one month, without fasting; platelet aggregation requires fasting)
6. Immune factors
Autoimmune type (anti-cardiolipin syndrome: 2 or more repeated blood draws, one month interval each, not related to menstrual cycle)
7. Uterine blood supply factors
Uterine artery at 6-7 weeks of early pregnancy / 12 weeks of middle pregnancy; ultrasound examination of umbilical artery at 20 and 30 weeks of pregnancy.
8. Male side examination: complete set of semen (semen check for 3-5 days of abstinence)