For couples who are preparing for pregnancy, once the woman stops menstruating, it is a great joy, and the joy is overflowing at once. They often cannot wait to go for blood tests and even ultrasound examinations, but after the blood is drawn and then go for ultrasound, the ultrasonographer tells them that no heart tube pulsation is seen at the moment, and suggests to review the ultrasound in a week. Three days later, they went back for a blood test, but the obstetrician said that the beta-hCG doubling was not ideal at the moment, and the progesterone P level was not high. When the ultrasound was scheduled, the doctor said that the embryo had stopped developing. The couple fell into an ice cell and couldn’t accept the fact that there was no vaginal bleeding or abdominal pain, so why was the baby gone? In fact, embryonic abortion is very common in clinical practice and is a type of spontaneous abortion.
Definition of embryonic abortion
Embryo damage refers to the death of an embryo during early pregnancy due to a defective fertilized egg or adverse factors such as external influences. Embryonic abortion can be divided into 2 categories: first, the fertilized egg does not develop a fetal bud after implantation, the color ultrasound shows no fetal bud after 7 weeks of gestation but only an empty (fetal) sac, and second, there was a fetal bud but soon died of abortion, the ultrasound result shows a fetal bud in the sac but the development is obviously behind the gestational week, at the same time there is no fetal heart tube pulsation, the size of the sac is in accordance with the gestational week or atrophy and deformation, which is called blighted sac.
Etiology of embryonic abortion
(1) Anatomical abnormalities
The causes of embryonic abortion in early pregnancy include uterine malformation, such as uterine dysplasia, unicornuate uterus, double uterus and uterine longitudinal septum; uterine anomalies, such as uterine adhesions (Asherman syndrome), uterine fibroids, endometrial diseases, cervical insufficiency, etc. These can affect the intrauterine environment and uterine blood supply, thus affecting embryo implantation and development.
(2) Genetic abnormalities
Abnormalities in chromosome number or structure, gene polymorphism, gene mutation, hereditary pre-thrombotic state, endocrine or reproductive tract structural abnormalities, etc. in both spouses and embryos are all genetic abnormalities. Chromosomal abnormalities are one of the most common causes of embryonic abortion in early pregnancy. It accounts for 50% to 60% of embryonic abortions resulting from gestational age <8 gestational weeks. The common chromosome number abnormality is triploidy; chromosome structure abnormality includes chromosome deletion, overlap, inversion and balanced translocation, etc., with inversion and balanced translocation being the most common, the proportion of factors leading to early pregnancy embryonic abortion is higher due to inter-arm inversion of chromosome 9 (p11;q13). inter-arm inversion of chromosome 16 can also cause spontaneous abortion or embryonic arrest in early pregnancy. Studies have shown that large Y chromosome karyotypes have a genetic effect and are associated with spermatogenesis and embryonic arrest in early pregnancy. The large Y chromosome refers to the heterochromatin region extension so that the Y chromosome length ≥ chromosome 18, the patient's spermatozoa occur various abnormalities (azoospermia, oligospermia, dead sperm, sperm malformation), infertility, growth retardation, etc. The patient's wife may have different types of reproductive abnormalities (miscarriage, birth of genetically defective fetus, embryonic arrest, stillbirth, abnormal fetus, premature birth.
(3) Infectious factors
Infectious factors leading to embryonic abortion in early pregnancy include systemic infections and infections of the female genital tract. Chlamydia and mycoplasma are the two most important pathogens causing infection in the female reproductive tract. They can cause damage to the epithelium of the cervical mucosa, resulting in intrauterine infection, which can damage the integrity of the fetal membranes and cause embryonic abortion. Recent studies have found that bacterial or viral infections can cause embryonic abortion, as well as rubella, cytomegalovirus and Toxoplasma gondii, which can also cause fetal chromosomal abnormalities through the placenta and lead to embryonic abortion. Other microorganisms such as syphilis spirochetes, Neisseria gonorrhoeae, Listeria monocytogenes and B19 microvirus, as well as rare infections such as Q fever, dengue fever, Lyme disease and malaria may cause embryonic abortion.
(4) Immunological abnormalities
Alloimmune abnormalities refer to abnormalities in the immune tolerance mechanism between mother and fetus, where the embryo is attacked by the maternal immune response to the embryo, resulting in a rejection reaction. Implantation of the fertilized egg in the mother can be considered as a semi-allogeneic transfer in which the embryo and the mother develop immune tolerance through a complex and specific immune relationship so that the embryo is not rejected. Studies have shown that the number of embryonic developmental disorders is positively correlated with abnormal immune function. The main immune factors that lead to embryonic abortion are the following: confined antibodies pregnancy-related plasma protein A, etc., insufficient production of alloimmune disorders, formation of anti-cardiolipin antibodies, enhanced expression of tissue-specific antibodies: anti-sperm antibodies (AsAb), anti-endometrial antibodies (EmAb), anti-hCG antibodies, etc. AsAb is a potent immunosuppressive substance within the seminal plasma that, by digesting macrophages AsAb is a potent immunosuppressive agent in seminal plasma, which has toxic effects on gametes and embryos, and can also directly damage trophoblast cells causing embryonic developmental disorders. Tissue non-specific antibodies: anti-nuclear antibodies, anti-DNA antibodies; enhanced cellular immunity mediated by CD4+ T cells, cellular secretion of interleukin 2, interferon γ and tumor necrosis factor β, etc. In addition, there is a correlation between blood group incompatibility and embryonic arrest. In China, the ABO blood group disorder is mainly caused by the mother’s type O and the fetus’s type A or B. The ABO antigen is attached to the surface of the fetal red blood cells, and when the red blood cells enter the maternal circulation through the placenta, it can stimulate the mother to produce antibodies, resulting in an alloimmune reaction due to maternal-fetal blood group incompatibility, which directly affects the development of the embryo and leads to miscarriage.
(5) Endocrine abnormalities
Luteal insufficiency (LPD), elevated prolactin (PRL), polycystic ovary syndrome (PCOS) and thyroid disease are important endocrine factors causing embryonic abortion, which can affect the function of hypothalamic-pituitary-ovarian axis and mainly manifest as abnormal secretion of progesterone and its metabolites, thus causing early miscarriage. Luteal insufficiency is caused by insufficient progesterone production or short maintenance time of the corpus luteum, endometrial dysplasia or delayed maturation of endometrium for more than 2 d, which prevents the implantation of pregnant egg and embryo development and leads to miscarriage, and is usually treated clinically by oral progesterone capsules or intramuscular injection of HCG
and progesterone injection to increase the progesterone level in the body to achieve the effect of fetal preservation. In patients with polycystic ovary syndrome, the miscarriage rate is significantly reduced when treated with metformin during pregnancy. ③In case of abnormal pituitary function or occupational lesion, it can cause hyperprolactinemia, which inhibits hypothalamic gonadotropin synthesis and release, causing impaired follicular development and ovulation, and interferes with fertilization and embryonic development, resulting in embryonic arrest. It is still controversial whether bromocriptine should be discontinued after pregnancy in patients with hyperprolactinemia. For patients with prolactin microadenoma, bromocriptine should be reviewed every 2 months if it is discontinued after pregnancy, and bromocriptine treatment should be restarted if headache or visual impairment occurs. (4) In patients with abnormal thyroid function, such as hypothyroidism, use thyroxine or levothyroxine sodium, while in patients with hyperthyroidism, pregnancy should be followed by control of hyperthyroidism and close observation of changes in the condition during pregnancy.
(6) Pre-thrombotic state
It refers to the state of easy clotting of blood caused by the increase of concentration of coagulation factors or decrease of concentration of coagulation inhibitors, which has not yet reached the level of thrombosis, or the small amount of thrombus formed is in the state of dissolution. Antiphospholipid antibody syndrome is currently well studied and has been definitely associated with early and mid-term fetal loss. It is widely believed that hypercoagulable state changes the blood flow in the placental area of the uterus, making it easy to form local microthrombosis or even placental infarction, which decreases the blood supply to the placenta and causes embryonic or fetal ischemia and hypoxia, resulting in miscarriage due to poor embryonic or fetal development. Low molecular heparin (LMWH) alone or in combination with aspirin is the main treatment method at present. The general dosage of LMWH is 5000 U subcutaneously twice a day.
twice a day. The timing of dosing begins in early pregnancy. In patients with more severe cases or those who have not used aspirin before pregnancy, dosing should be started before ovulation. It has been reported that aspirin alone is less effective than low molecular heparin alone or in combination with both.
(7) Environmental factors
With the progress of society and technology, the influence of environmental factors on embryonic abortion during early pregnancy is receiving more and more attention. Environmental influences can impair or interfere with reproductive function and lead to embryonic abortion. It was previously believed that
(1) physical factors: X-ray, microwave, noise, ultrasound and high temperature; (2) chemical factors: chemical drugs and ionizing radiation; (3) bad habits: alcohol, smoking, drugs and coffee, etc.
(8) Psychological factors
Emotional tension puts the body in a state of stress, destroying the original stable state, causing neuroimmune and endocrine disorders in the body, especially the change of progesterone. The level of progesterone in the body decreases and the embryo develops poorly, resulting in fetal abortion. Therefore, pregnant women should pay attention to the regulation of emotions and avoid excessive mental tension.
(9) Trauma stimulation
Uterus trauma such as surgery, direct impact, excessive sexual intercourse can also lead to fetal arrest.
(10) Unexplained embryonic arrest
It is found that vascular insufficiency and apoptosis during placental formation is one of the important factors leading to embryonic arrest. The abnormal expression of meconium angiogenesis and angiogenic factors such as VEGF, placental growth factor, angiopoietin, matrix metalloproteinases, Notch receptor protein, etc., through a series of cascade reactions, participate in angiogenesis and affect the nutrition of the placenta to the embryo, resulting in the occurrence of embryonic arrest.
Knowing the causes of fetal arrest, one can go to a hospital where there are conditions for examination, and after appropriate treatment, most couples are eventually blessed with a baby or a thousand children.