Causes and examination of recurrent spontaneous abortion

Many patients have experienced embryo arrest, spontaneous abortion, and recurrent miscarriage. Since there are many factors that affect pregnancy, the diagnosis of the cause of miscarriage is also more complicated. It is necessary to go to a hospital with a relatively high level of medical care for a comprehensive examination. Many patients are very worried about whether it will affect their health in the future. Let's take a look at the causes and examinations of recurrent miscarriage.

1 Causes

1.1 Chromosomal abnormalities

1.1.1 Embryonic chromosomal abnormalities 46% to 54% of spontaneous abortions are related to embryonic chromosomal abnormalities. The earlier the abortion occurs, the higher the frequency of embryonic chromosomal abnormalities, which is 53% in early abortions and 36% in late abortions. Chromosome abnormalities include numerical abnormalities and structural abnormalities. Numerical abnormalities include chromosome trisomy, X monomer and autosomal monomer. Structural abnormalities are mainly chromosome translocation, mosaicism, etc., and chromosome inversion, deletion and duplication have also been reported. In recent years, animal studies have found that some single gene mutations can directly lead to embryonic death. These genes are also called lethal genes.

1.1.2 Chromosomal abnormalities in couples Domestic and foreign literature shows that the frequency of chromosomal abnormalities in couples with habitual miscarriage is 3.2%, of which the most common is reciprocal chromosome translocation, accounting for 2%, and Robertsonian translocation, accounting for 0.6%. If the gametes stay in the female reproductive tract for too long before implantation, gamete aging will occur, and the chance of miscarriage will also increase.

1.2 Abnormalities in the anatomical structure of the maternal reproductive tract

1.2.1 Uterine malformations Unicornuate uterus, bicornuate uterus, didelphic uterus, uterine septum, etc. can affect the uterine blood supply and intrauterine environment, causing miscarriage.

1.2.2 Asherman syndrome: Uterine adhesions and fibrosis caused by uterine trauma (such as excessively deep curettage), infection or placental retention can affect embryo implantation and lead to habitual abortion.

1.2.3 Cervical insufficiency Cervical insufficiency is manifested anatomically as a short cervical canal or a loose internal cervical os, which is the main cause of late habitual abortion.

1.2.4 Other uterine tumors can affect the intrauterine environment and lead to habitual abortion.

1.3 Maternal endocrine disorders

1.3.1 Luteal insufficiency If the peak progesterone level in the mid-luteal phase is lower than 28.62 nmol/L, or the endometrial biopsy is not synchronized with the menstrual period by more than 2 days, it can be diagnosed as luteal insufficiency. The incidence of luteal insufficiency in habitual abortion is 23% to 60%. Insufficient progesterone secretion can cause adverse reactions to the decidua during pregnancy, affect the implantation and development of the fertilized egg, and lead to abortion.

1.3.2 Polycystic ovary syndrome The incidence of polycystic ovary syndrome in recurrent miscarriage is as high as 58%, and 56% of these patients have a high secretion of LH. It is now believed that the high concentration of LH in polycystic ovary syndrome may lead to the premature completion of the second meiotic division of the oocyte and premature maturation of the blastocyst, resulting in an "old egg" at ovulation, thus affecting the fertilization and implantation process [2].

1.3.3 Hyperprolactinemia High levels of prolactin can directly inhibit the proliferation and function of corpus luteum granulosa cells. The main clinical manifestations of hyperprolactinemia are amenorrhea and galactorrhea. When prolactin is at the upper limit of normal values, it can manifest as corpus luteum insufficiency.

1.3.4 Diabetes In early pregnancy (within 21 days), the incidence of miscarriage in diabetic patients with good blood sugar control is no different from that in the non-diabetic group, but the incidence of miscarriage in patients with poor blood sugar control can be as high as 15% to 30%. In addition, high blood sugar in early pregnancy may be a risk factor for fetal malformation.

1.3.5 Abnormal thyroid function It was previously believed that hypothyroidism or hyperthyroidism was related to miscarriage, but this view has always been controversial. Some studies have shown that people with positive thyroid autoantibodies may have abnormal thyroid function and a significantly increased incidence of miscarriage, but other studies have shown that there is no significant correlation between thyroid autoantibodies and miscarriage rates in people with habitual miscarriage.

1.4 Genital tract infection Pathogens that can cause habitual abortion often persist in the reproductive tract, but rarely produce symptoms, and these pathogens can directly or indirectly cause embryonic death. Retrograde infection of the reproductive tract generally occurs before 12 weeks of pregnancy. Infections such as bacteria, Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum, Toxoplasma gondii, cytomegalovirus, herpes simplex virus, rubella virus and human immunodeficiency virus can all lead to abortion.

1.5 Autoimmunity Autoimmune habitual abortion is mainly related to three diseases (antiphospholipid antibody syndrome, systemic lupus erythematosus, Sjögren's syndrome) and their related three autoantibodies (antiphospholipid antibodies, antinuclear antibodies, anti-extractable nuclear antigen antibodies). Antiphospholipid antibodies (mainly lupus anticoagulant factor and anticardiolipin antibodies) account for 13.5%, and this type of patients can be called early antiphospholipid antibody syndrome. Antiphospholipid antibody syndrome mainly causes thromboembolism through multiple pathways such as activating vascular endothelium and platelets, and can also directly damage trophoblast cells to damage the embryo, thereby causing abortion.

1.6 Unexplained causes (alloimmune factors) After screening the above causes, habitual abortions caused by chromosomal abnormalities, anatomical abnormalities, endocrine disorders, reproductive tract infections, autoimmune diseases, etc. are strictly excluded. Clinically, they are called unexplained habitual abortions. According to modern reproductive immunology, this type of habitual abortion can be considered to be related to alloimmunity, also known as alloimmune habitual abortion. Modern reproductive immunology believes that pregnancy is a successful semi-homologous transplantation process. Pregnant women have a series of adaptive changes in their own immune system, thereby showing immune tolerance to intrauterine embryo transplants without rejection, allowing the pregnancy to continue. It is currently known that this immune regulation process, including the expression of HLA-G, HLA-C and HLA-E antigens in trophoblasts at the fetal-maternal interface, decidual immune regulatory cells and their related immunosuppressive factors, plays a very important role. In addition, there are one or more substances in maternal serum that can inhibit

Blocking factors that inhibit immune recognition and immune response are also called blocking antibodies. If the immune tolerance state is unbalanced, the embryo may be attacked by the mother's immune system and rejected.

2. Etiology screening methods

At present, clinical requirements require systematic screening of the causes of habitual abortion from at least the above six aspects, namely chromosomal abnormalities, maternal reproductive tract anatomical abnormalities, endocrine disorders, reproductive tract infections, autoimmune diseases and unknown causes (isoimmune factors). Screening should be comprehensive to avoid omissions in order to achieve the level of etiological diagnosis. The first five causes have clear laboratory diagnostic indicators, while there is no clear laboratory test indicator for unexplained habitual abortion. In fact, it is an exclusionary diagnosis, that is, only when the first five causes mentioned above are definitely excluded can a diagnosis of "unexplained cause" be made. Therefore, it is required that the screening of various causes be comprehensive and careful. In the etiology screening, in addition to detailed medical history and routine gynecological examination, the following laboratory tests should also be performed.

2.1 Chromosome karyotype analysis includes chromosome karyotype analysis of the couple's peripheral blood and embryos (what is difficult to do clinically is the chromosome karyotype analysis of aborted embryos).

2.2 Examination of the maternal reproductive tract anatomy for abnormalities

2.2.1 Congenital developmental abnormalities and uterine cavity structural abnormalities caused by acquired factors such as uterine fibroids are currently mainly examined by ultrasound. In some cases, laparoscopy or hysterosalpingography is also required.

2.2.2 Examination of cervical incompetence Before pregnancy: ① Cervical dilation test. No resistance when passing through the No. 8 cervical dilator indicates cervical incompetence. ② Cervical balloon traction test. Insert the Foley catheter into the uterine cavity and inject 1ml of 0.9% sodium chloride into the balloon. If the weight is less than 600g, it can be pulled out, indicating cervical incompetence. ③ Hysterosalpingography. The cervical canal is shortened and the diameter is greater than 6mm, indicating cervical incompetence. During pregnancy: ① Cervical digital examination. The vaginal part of the cervix is ​​shorter or even disappears, and the internal and external openings are loose, allowing one finger to pass through. Sometimes the amniotic sac can be touched or the amniotic sac can be seen protruding from the external opening of the cervix. ② B-ultrasound examination. At 12 weeks of pregnancy, the length, width and inner diameter of the cervical canal are measured. If one of the three diameters is abnormal, it indicates cervical incompetence, which includes: cervical length 32mm and inner diameter ≥5mm.

2.3 Endocrine examination A full set of sex hormone tests are performed in the early and mid-luteal phases of endometrial hyperplasia. In addition, thyroid function tests and blood sugar tests are also included.

2.4 Screening for infectious factors mainly includes examinations for Toxoplasma gondii and cytomegalovirus.

2.5 Autoantibody tests mainly include antiphospholipid antibodies, anti-extractable nuclear antigen antibodies, and antinuclear antibodies. Antiphospholipid antibodies should be tested at least 3 times, with an interval of 6 weeks between each test. A diagnosis can only be made if the results are positive 2 or more times.

2.6 Special immunological examinations related to alloimmunization For cases where no abnormalities are found in the first five etiology screenings mentioned above, that is, patients with "unknown causes" clinically determined, further examinations should be conducted to determine whether there are blocking antibodies in the woman's body in order to guide treatment. At present, the more commonly used method for detecting blocking antibodies is the micro-anti-husband lymphocyte toxicity test. A negative result indicates that the woman's serum lacks this blocking antibody and is prone to habitual abortion.

Here I hope women will take care of their bodies and discover and seek treatment in a timely manner.