Post Date April, 15 2023
In women of childbearing age, recurrent miscarriages or embryonic arrest occur around us for a long time, with an increasing trend. While these patients are actively looking for female factors, gynecologists or reproductive center doctors will also recommend that the patient's husband come to the andrology department to seek out the male's pathogenic factors. This is because the formation of an embryo is caused by the formation of a fertilized egg together with the sperm of the male and the egg of the female. Factors from either side can lead to recurrent miscarriage and the cessation of embryo development. Wu Zongchuan, Department of Andrology, Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine
What are recurrent miscarriages and embryonic arrest?
Recurrent Spontaneous Abortion (RSA) refers to two or more consecutive spontaneous abortions. The incidence of RSA is approximately 2% to 5%.
Embryo arrest refers to the cessation of development of an embryo in the early stages of pregnancy due to some reason. Traditionally, it is referred to as embryo arrest. B-ultrasound examination showed abnormal fetal buds or fetal morphology within the gestational sac, no fetal heartbeat, or the appearance of withered eggs. Clinically, it belongs to the category of abortion or stillbirth, and was formerly known as overdue abortion or missed abortion.
What factors can lead to it?
1 Genetic factors
This includes abnormalities in the color of autosomes and Y-chromosomes. This is a clear reason for miscarriage and embryo arrest in women, and it is also why we need to examine chromosomes. Human beings contain 23 pairs of chromosomes, with chromosomes 1 to 22 called autosomes. The differences between chromosomes 23 determine the gender of men and women. It has been reported that 22% to 61% of aborted embryos have chromosome abnormalities.
(1) Abnormality in the number of autosomes: One is an abnormality in chromosome aneuploidy, in which the embryo often undergoes spontaneous abortion and few surviving fetuses. The other is aneuploidy abnormalities of chromosomes, including haplotypes, trisomies, and polymorphisms. Surviving offspring often have significantly abnormal clinical manifestations, including trisomy 21 syndrome, Klinefelmann syndrome, and others. These men are often associated with low fertility or infertility.
(2) Abnormal autosomal structure: This is caused by chromosome breakage, loss, and improper recombination during the genetic process. The most common is translocation, followed by inversion. The unbalanced gametes produced by the germ cells of carriers of balanced chromosomal translocation during meiosis can lead to adverse outcomes such as miscarriage and malformations. High abortion rates are associated with abnormal karyotypes in men. The probability of miscarriage in men with reciprocal translocation is 61.1%, and the probability of miscarriage in men with inversion is about 28% to 42.9%; For embryopause, the rate of chromosomal karyotype abnormalities was 5.22%, with autosomal abnormalities accounting for 14.6%.
(3) Y chromosome: Y chromosome length variation has genetic effects and is associated with abortion and embryo arrest. Y chromosome integrity plays an important role in embryonic development and maintenance of pregnancy. There are two situations: a large Y chromosome, which refers to a Y chromosome with a length greater than chromosome 18 in the same karyotype. The detection rate of large Y staining in patients with continuous abortion can reach 40.05%; The other is the small Y chromosome, which refers to the length of Y chromosome The long arm of the Y chromosome contains genes that regulate spermatogenesis, known as AZF genes. Its deletion, known as a microdeletion of the Y chromosome, not only affects spermatogenesis, but also may affect the continued pregnancy of the spouse. Handling principles: Generally speaking, for genetic factors, most patients have no specific treatment. For some translocations, the unbalanced embryos formed end in miscarriage - recurrent miscarriage and the birth of abnormal chromosomal offspring can be avoided through third generation in vitro fertilization (PGD). Sperm donation may be a helpless choice for patients. Sperm DNA Damaged sperm quality is related to the development of fertilized eggs to the blastocyst stage and their implantation ability. Genes expressed in the paternal line can regulate the proliferation and invasiveness of trophoblastic cells and subsequent placental proliferation. Sperm DNA integrity is extremely important for sperm egg interaction, fertilization, and early fertilization and cleavage. Studies have shown that RSA and Embryonic arrest significantly increase sperm DNA damage. Handling principles: Currently, there is no specific treatment, and it is necessary to search for all possible causes of sperm DNA damage, as well as causal treatment. Such as genital tract inflammation, testicular hyperthermia, varicocele, smoking, environmental factors, drugs and radiation, chemotherapy, etc. Symptomatic treatment of the cause and auxiliary antioxidant drugs. Some studies have shown that antioxidant therapy: vitamin C, vitamin E, etc. have the effect of improving sperm DNA. Traditional Chinese medicine may have effects on this group of patients, and it is clinically effective for some patients, but there is a lack of scientific research. Antisperm antibody Normal men do not produce antisperm antibodies due to the protective effect of the blood testosterone barrier. Some studies have shown that the positive rate of anti sperm antibodies in men with RAS is higher than that in normal men. The possible mechanisms are as follows: ⑴ Antibodies adhere to the sperm surface, leading to sperm aggregation and affecting sperm movement; ⑵ When the complement activity in seminal plasma is high, it can also cause a complement mediated attack response that damages sperm; ⑶ Affecting the activity of sperm enzymes and inhibiting the dispersion of radiation crowns; ⑷ Sealing the antigen points of the acrosome membrane, inhibiting sperm adhesion and penetration to the zona pellucida; ⑸ Affecting the binding of sperm and eggs It can affect the development of embryos. Handling principles: Due to the side effects of hormones and the development of assisted reproductive technology, the use of hormones in the treatment of antisperm antibodies is not very common. Traditional Chinese medicine has a certain effect on the negative conversion of anti sperm antibodies and improving the pregnancy rate. If drug treatment is not effective, assisted reproductive techniques such as sperm washing, IUI, IVF-ET, ICIS, and other methods can be used to assist pregnancy. Sperm morphology The World Health Organization (Fifth Edition) describes sperm with normal morphology as normal if it is greater than 4%. Although this standard is currently highly controversial, the relationship between poor semen quality and embryonic dysplasia has been widely confirmed. Abnormal sperm morphology is related to abnormal karyotype transformation of sperm nucleoproteins, abnormal chromatin structure, defects in sperm nucleoproteins, and DNA breakage. Chromosome abnormalities in sperm often manifest as abnormal head morphology (such as large headed sperm), with a significantly increased likelihood of miscarriage; Abnormalities in the acrosome of the sperm head can lead to sperm loss of fertilization ability, infertility, and even abortion; The mitochondria in the sperm tail provide energy and the microtubule structure in normal morphology is the basis for sperm movement. Abnormality of sperm tail can cause sperm movement disorders, leading to decreased fertility. Handling principles: Actively search for the cause of pregnancy. Antioxidant therapy is the most common treatment method for cause treatment (such as infection, sperm motility, external physical and chemical factors, etc.), and traditional Chinese medicine has room to play. Although there are few research reports on whether traditional Chinese medicine can improve sperm deformity rate, it can improve the pregnancy rate, possibly due to the role of multiple targets, improving sperm vitality and improving semen quality through multiple links. For those who do not respond to medication, sperm can be processed (such as upstream methods) to assist reproduction. 5 Infectious factors Currently, it is believed that Chlamydia trachomatis (CT) and Ureaplasma urealyticum (UU) infections are important pathogens that cause RSA. UU attached to the sperm surface can secrete neurotransmitters, and when sperm enters the oocyte, the embryo will die and miscarry; They can cause endometritis, affect the regulatory mechanism of the maternal autoimmune system to protect embryos, interfere with embryo implantation or damage growing embryos and induce abortion; Infection destroys the blood testis barrier, leading to an immune response that produces ASAB, which affects the development of early embryos and leads to miscarriage. In addition, the sperm DNA damage rate of patients infected with UU or CT is 3.2 times higher than that of the control group, and after antibiotic treatment, the DNA damage rate can decrease. Of course, infection with TORCH can also lead to miscarriage and embryo arrest. Handling principles: For the most common UU and CT infections, anti infective therapy involves macrocyclic intralipid antibiotics first, followed by quinolones. Attention should be paid to the simultaneous infection and drug resistance of two or more microorganisms. Therefore, for male patients with RAS and Embryo Stop, it is necessary to routinely conduct microbial culture and drug sensitivity. In the case of infection, sensitive antibiotics should be given according to the drug sensitivity, and treatment should be given for a full course of treatment. Couples should be examined and treated together. After the course of treatment, both parties should review. 6. Unknown reasons (1) As men age, atypical spermatogonia, abnormal sperm cells, interstitial fibrosis of the seminiferous tubules, and shedding of immature germ cells all increase, leading to decreased sperm quality, reduced pregnancy rates, increased abortion rates, autosomal regional dominant genetic diseases in offspring, and increased fetal mortality. The study found that there was a significant increase in the structural abnormality rate of sperm chromatin in men aged 59 to 74 compared to men aged 23 to 29. (2) Environmental factors: Male spermatozoa continue to be produced after puberty, and the testicular position is superficial. Therefore, during spermatogenesis, they are susceptible to external exposure factors, leading to mutations or aneuploidy. High temperature, air pollution, ionizing radiation, radiation and chemotherapy, mercury, and dibromochloropropane can all increase the mutation rate of sperm DNA. Handling principles Age is an irresistible factor, and from the perspective of eugenics, it is recommended that couples with high expectations for "starting a career" conceive babies at the appropriate time. Environmental factors can only be avoided under certain conditions. In summary, a large number of studies have shown that male factors can affect embryogenesis, implantation, birth defects, and abortion. Gene mutations, advanced age, infection, and any paternal genetic abnormalities that affect the placenta all indicate a risk of miscarriage or embryo arrest. Therefore, actively dealing with male factors is of great significance for preventing RSA and embryo abortion, as well as eugenics and fertility.
