In the clinic, we often encounter a couple with a sperm test report and ask, “How can I use medicine to reduce the sperm malformation rate?” Upon closer questioning, they realize that they are patients with recurrent spontaneous abortions, either 2 or even up to 6 times, and most of them are still in the early stages of pregnancy (within 3 months) when the embryo stops developing. The male partner’s sperm report showed a sperm malformation rate of over 95% or even higher. Therefore, it is natural for many patients to associate the two together.
Sperm malformation, also called malformed sperm, refers to the morphological variation of the head, neck and tail. Head malformations include round, giant head, amorphous, double head and missing acrosome; neck and mid-section malformations include body bending, asymmetric insertion, thick and thin; tail malformations include coiled tail, double tail, missing tail, etc. Sperm with tail deformity and neck deformity have reduced motility or even loss, and basically cannot pass through the vagina, cervical opening and other various obstacles before fertilization normally and smoothly. In contrast, sperm with head malformations either lose the ability to fertilize or fail to form a normally developing fertilized egg after fertilization due to abnormal genetic information in the head.
It is a basic argument of Darwin’s theory of evolution that the more adaptable organisms are preserved and the less adaptable are eliminated in the competition for survival. This law of nature also applies to the process of embryo formation.
Therefore, a high rate of deformed sperm will only cause a lower chance of pregnancy and lead to male infertility, and has nothing to do with miscarriage after pregnancy.
What factors are associated with spontaneous abortion? The following is a detailed description of spontaneous abortion.
I. Concept
Miscarriage that occurs in a natural state (not caused by human purpose) is called spontaneous abortion. The incidence of spontaneous abortion is about 15% of all clinically confirmed pregnancies. Miscarriages that occur before 12 weeks of gestation are defined as early miscarriages, and miscarriages between 12 and less than 28 weeks of gestation are defined as late miscarriages. Spontaneous abortion that occurs three or more times in a row and occurs within three months of pregnancy is called recurrent early spontaneous abortion, or habitual abortion (RSA).
II. Causes of morbidity
1.Genetic factors
Chromosomal abnormalities cause about 5% of the total number of habitual abortions. 80% of spontaneous abortions occur before 12 weeks of gestation, and 70% of these embryos have chromosomal abnormalities. Numerous reports in the literature suggest that chromosomal abnormalities are closely associated with habitual abortion.
There are two types of chromosomal abnormalities: structural and quantitative. The structural abnormalities include deletions, translocations, inversions and duplications, with translocations and inversions being the most common in reports of RSA. Translocations mainly include equilibrium translocations and Robertson translocations. According to the law of inheritance, the germ cells of balanced translocation carriers can form 18 kinds of gametes during meiosis and form 18 kinds of congeners after combining with normal gametes, of which only one is normal and one is a balanced translocation carrier, and the rest are abnormal and lead to miscarriage, stillbirth or birth of malformed children.
2. Uterine factors
Anatomical abnormalities
The anatomical abnormalities of female uterus include: uterine malformation, cervical adhesion, cervical insufficiency, uterine fibroids, etc. The mechanisms leading to habitual abortion are
①Insufficient blood supply: such as double uterus, unicornuate uterus, only one side of the blood vessel supply, poor metaphase formation after pregnancy, affecting fetal development and growth and miscarriage. In some abnormal development of the uterus, such as longitudinal uterus, if the fertilized egg is implanted in the longitudinal septum, the vascular formation of the longitudinal mucosa is poor and the blood supply to the embryo is insufficient, resulting in miscarriage.
②Small cavity: The uterine cavity of dysplastic uterus is small and the pressure in the uterine cavity is high after pregnancy, which makes it easy for miscarriage and preterm delivery to occur in mid-trimester, such as unicornuate uterus.
(③) Cervical insufficiency: an abnormally developed uterus with an underdeveloped cervix. If the ratio of cervical muscle tissue to connective tissue is imbalanced, recurrent midtrimester miscarriages are likely to occur, such as bicornuate uterus.
Thin endometrium
The endometrium is the site of embryo implantation. During in vitro fertilization and embryo transfer (IVF-ET) treatment, a large number of clinical studies have concluded that the endometrial thickness of 8-12 mm on the day of hCG has a high pregnancy rate; while in the endometrium <8 mm< span="">, it can affect the embryonic blastocysts’ implantation and development in the endometrium, and clinical pregnancy is rarely seen.
3. Endocrine factors
The normal endocrine system of human body is related to the embryo’s implantation, development and delivery. Any malfunction of one of the links may interrupt the development of the fetus. Luteinizing insufficiency, hyper- or hypothyroidism, elevated lactogen, polycystic ovary syndrome, etc. often affect the function of the hypothalamic-pituitary-ovarian axis, resulting in abnormal function of the corpus luteum in pregnancy and causing miscarriage.
4. Pathogenic infection
TORCH is a generic term for a group of pathogenic infections, including Toxoplasma (TOX), rubella virus (RUV), cytomegalovirus (CMV), herpes simplex virus (HSV-II), and others (syphilis spirochetes, hepatitis B virus, microviruses, etc.). If TORCH infection is present in pregnant women, adults may have no obvious symptoms, but it can cause intrauterine infection through the placenta or birth canal, resulting in miscarriage, stillbirth, fetal growth retardation malformation, and even neonatal infection or (and) puberty disorders.
5. Immunological factors
Infertility caused by immunological factors is collectively called “immunological infertility”. With the progress of research in reproductive immunology, it is believed that most of the unexplained infertility is caused by immunological factors. The relationship between immunological factors and habitual abortion is gaining attention.
Immunological factors include autoimmune and alloimmune types. The autoimmune types are currently well studied and include antiphospholipid antibodies (AcAb), serum anti-sperm antibodies (AsAb), anti-endometrial antibodies (EmAb), anti-ovarian antibodies (AovAb), anti-nuclear antibodies (ANA), anti-thyroid antibodies (ATA) and anti-chorionic gonadotropin antibodies (AhcGAb). The diagnosis of miscarriage caused by the homozygous type is an exclusionary diagnosis, which means that chromosomal, anatomical, endocrine, infectious and autoimmune etiologies are excluded and no other cause of miscarriage is found, which is called the homozygous type and can also be called recurrent miscarriage of unknown cause. Among them, women with closed antibody deficiency account for a significant proportion. Since the mother is a humoral immune-dominated physiological phenomenon, and closed antibody, as a humoral immune factor, is considered to be an important factor in the success of pregnancy. Therefore, clinically closed antibody negative women are often the subject of medical focus and active treatment.
6. Other factors
Although many of the above factors are constantly being researched and discovered, there are still a considerable number of habitual abortions with unknown causes. With the continuous progress of medical technology, more and more unknown mechanisms leading to RSA will be discovered by human beings.
III. Diagnosis and treatment of RSA
1. Genetic factors
Chromosome examination of peripheral blood cells to clarify the diagnosis.
Estimate the incidence of chromosomal abnormal fetus through genetic counseling. If the incidence is high, pre-implantation genetic diagnosis, donor sperm or donor egg IVF can be used to eliminate or avoid abnormal embryos; if the incidence is low, pregnancy can be initiated followed by chorionic villus biopsy or amniocentesis to check fetal chromosomes and terminate the pregnancy in case of fatal or teratogenic abnormalities.
2. Uterine factors
Ultrasound, hysterosalpingography, hysteroscopy, MRI, etc. are performed to clarify the diagnosis.
Those with abnormal uterine anatomy can be treated by hysteroscopic surgical plastic surgery.
Those with too thin endometrium can be treated with small doses of aspirin, vancomycin, vincristine E, hexoketone cocaine combined with large doses of vitamin E, and short-acting GnRH-a. However, there is no unanimously accepted ideal drug and method.
3. Endocrine factors
Endocrine examination and ovulation under ultrasound should be performed to clarify the diagnosis.
Appropriate treatment plan should be selected before or after pregnancy according to different etiologies.
4. Immunological factors
Autoimmune recurrent spontaneous abortion can be checked by blood sampling for female infertility set; homoimmune recurrent spontaneous abortion can be diagnosed by blood sampling for closed antibody test.
The autoimmune person can be treated by immunosuppression such as sodium heparin, prednisone and aspirin.
Homozygous immune patients are mainly treated by active immunotherapy (intradermal injection of husband or third party lymphocytes), and also need to check both husband (or third party) wife’s pre-transfusion eight, liver function, the course of treatment is once every 3 weeks, 3 to 4 times as a course of treatment, and then adjust the program according to the results of the review.
Attachment: RSA diagnosis and treatment process
①Chromosomal factors: blood sampling for chromosomal examination for both spouses → genetic counseling, prenatal genetic diagnosis, chorionic villus biopsy or amniocentesis
②Uterine factors: ultrasound, hysterosalpingography, hysteroscopy, MRI, etc. → hysteroscopic surgery and plastic surgery
③Endocrine factors: ovulation monitoring under ultrasound, blood sampling to determine endocrine → endocrine therapy such as ovulation promotion and luteal support and Chinese medicine treatment
④Autoimmune antibody and TORCH factor: blood sampling for female infertility set → immunosuppression or antibacterial and antiviral drug treatment and Chinese medicine treatment
⑤Closing antibody factor: blood sampling for closing antibody set → active immunotherapy and Chinese medicine treatment
⑥Unspecified causes: luteal support therapy plus TCM identification therapy