Diagnosis and treatment of infertility

  I. What is infertility?
  Infertility is defined as a couple with a desire to have children who have regular sex and have not been pregnant for one year without contraception. Infertility is divided into two cases: primary infertility and secondary infertility. Primary infertility refers to those who have never had a pregnancy without contraception after marriage. Secondary infertility refers to those who have had a pregnancy and have not conceived for one year without contraception.
  The worldwide prevalence of infertility is 5%-15%, and in some areas of developing countries it is as high as 30%, and it is estimated that there are about 100 million infertility patients worldwide.
  What are the causes of infertility?
  Infertility can be caused by both male and female factors, with female factors accounting for about 50%, male factors accounting for 30%, male and female factors accounting for 10%, and unknown causes accounting for 10%. The diagnosis of the cause of infertility is important to guide its treatment.
  Causes of female infertility.
  1. tubal infertility:
  It accounts for about 30% of female infertility. Tubal obstruction caused by various inflammatory diseases is the most common cause, which can be manifested as occlusion of different parts of the fallopian tubes and fluid accumulation at the umbilical end of the fallopian tubes. In addition, tubal adhesions, tortuosity, scar stenosis and congenital tubal defects caused by various reasons can also be seen.
  2. Anovulatory infertility.    
  It accounts for about 25% of female infertility. Ovulation disorders can occur due to abnormalities and dysfunctions of various parts of the sexual axis, among which polycystic ovary syndrome is the most common.
  3. Uterine infertility.  
  Congenital uterine agenesis and dysplasia, uterine malformation, submucosal fibroids, endometrial polyps, endometrial tuberculosis and severe inflammation, uterine adhesions, etc. can affect the fertilization of eggs and lead to infertility.
  4. Endometriosis. 
  20%-30% of patients with endometriosis are accompanied by infertility, which may be related to tubal dysfunction and abnormal immune function.
  5. Vaginal and cervical factors.  
  Abnormal vaginal development and scar atresia, abnormal cervical mucus and inflammation can also cause infertility, which is relatively rare clinically.
  Male infertility causes.
  1. Semen abnormalities.  
  It is manifested as oligospermia, weak sperm, azoospermia, high rate of deformed sperm and poor semen liquefaction, etc. It can be related to abnormal spermatogenesis, high local temperature, varicocele and bad living habits.
  2. Sexual dysfunction.  
  Genital development abnormalities, impotence, premature ejaculation, non-ejaculation, retrograde ejaculation, etc. can cause male infertility.
  3, immune factors.  
  Self-anti-seminal antibodies can make the semen produce self-coagulation that cannot cross the cervical mucus causing infertility.
  Unexplained infertility.
  About 10% of infertile couples cannot find a clear cause of infertility, part of which may be related to mild endometriosis, mild tubal mucosal inflammation and immune factors.
  How to examine and diagnose infertility?
  (i) Medical history and physical examination.  
  Detailed questioning of both women’s medical history, living habits, sexual life and women’s menstruation and fertility, as well as a comprehensive physical examination are important for analyzing and finding the causes of infertility.
  (ii) Male related examination.
  Semen analysis can understand the number, vitality, malformation rate and liquefaction of sperm, which should not be neglected in the diagnosis of infertility couples. It should be performed first because it is non-invasive and painless, so that the female partner is not found to have no abnormality after all the examinations before the final examination reveals that the semen abnormality is causing infertility.
  (iii) Female related examinations.
  1. Tubal patency examination.
  (1) tubal lavage: this method is simple and easy to use as a screening method for tubal obstruction, but it is impossible to make an accurate judgment on the site of obstruction, and the wrong diagnosis is often given for tubal umbilical obstruction (i.e. hydrosalpinx).
  (ii) Hysterosalpingography: it is one of the common diagnostic methods for infertility, which can clearly determine the obstruction site, alignment and uterine cavity morphology of the fallopian tubes, and can also play a role in unblocking treatment for patients with early obstruction.
  (③Ultrasound-monitored hysteroscopic tubal intubation and lavage: this method has accurate positioning and relatively high pushing fluid pressure, which can not only better diagnose tubal patency but also have a certain therapeutic effect on tubal obstruction, as well as observe and diagnose intrauterine cavity lesions. However, it is difficult to carry out in basic primary hospitals because of the expensive equipment.
  Laparoscopic Melanoplasty: This method can accurately diagnose tubal patency and obstruction site under direct vision, and can treat pelvic adhesions and hydrocele. However, there is also the problem of expensive equipment.
  2.Ovulation test.
  ①Basal body temperature (BBT) measurement: measure the body temperature every morning before waking up and mark it on the temperature sheet, and link the body temperature of a month with a line segment to form a basal body temperature curve. The monophasic shape indicates no ovulation, while the biphasic shape indicates ovulation. This method is economical and can help determine the function of the corpus luteum.
  Ultrasound monitoring of ovulation: Starting from the 10th to 12th day of menstruation, ultrasound monitoring of follicle development and ovulation can determine the presence or absence of ovulation more accurately, and it can also determine the thickness of the endometrium and diagnose follicular luteinization non-rupture syndrome. This method is non-invasive, accurate and has more clinical applications.
  (3) Serum hormone level measurement: Blood test on the 2nd-5th day of menstruation can be used to determine the basal hormone level in women’s body, and blood test on the 7th-8th day after ovulation can determine the presence or absence of ovulation and luteal function, which is of diagnostic value for women with infertility and miscarriage.
  Urinary LH test paper: The peak of urinary LH occurs 5-12 hours after the peak of serum LH, and ovulation occurs 24-36 hours after the peak of LH. However, since the LH peak lasts for a short time, the peak may be missed, so ovulation may occur even if the LH peak is not measured.
  ⑤ Endometrial biopsy: endometrial scraping within 6 hours before or at the onset of menstruation indicates ovulation in the secretory phase. This method used to be the gold standard for ovulation assessment, but because it is invasive and causes discomfort to the patient, its clinical use is decreasing and is now mainly used in infertile women with suspected endometrial lesions.
  3. Imaging examinations.
  ①Vaginal ultrasonography: It can find out the size of the uterus, thickness of the endometrium, size of the ovaries and follicle development, as well as some occupying lesions of the uterus and ovaries, such as uterine fibroids, ovarian tumors, endometrial polyps, etc.
  ②Hysteroscopy: It is a standard diagnostic tool for uterine malformations, uterine adhesions, endometrial polyps and other lesions.
  (③) Hysterosalpingography: it can not only understand the morphology of the uterine cavity and fallopian tubes, but also has a certain diagnostic effect on uterine adhesions, occupying lesions in the uterine cavity and tuberculosis of the fallopian tubes.
  4.Immune infertility examination.
  ①Post-coital test: choose to perform 2-8h after intercourse during ovulation. 20 motile sperm per high magnification field in cervical mucus is normal. If sperm motility is poor or inactive, immune abnormalities should be suspected.
  ②Sperm immunological examination: anti-sperm antibodies can exist in serum, seminal plasma, cervical mucus and sperm surface, anti-sperm antibodies are mainly IgG and IgM. The presence of anti-sperm antibodies can inhibit the function of sperm and fertilization, causing infertility.
  (3) Anti-ovarian antibody and anti-hyaline antibody tests: positive anti-ovarian antibody can affect the function of ovaries and positive anti-hyaline antibody can affect the fertilization of eggs, causing infertility.
  5. Genetic testing.
  Genetics such as chromosomal examination should be performed for patients with suspected history of hereditary diseases, recurrent miscarriage and male infertility. Some patients with oligospermia and azoospermia have microdeletions of Y chromosome or karyotype abnormalities.
  IV. Treatment methods of infertility.
  The treatment of infertility varies according to the cause of infertility, and individualized treatment should be developed according to the specific conditions of the patient.
  (i) Uterine infertility.
  Infertility caused by longitudinal diaphragm, uterine adhesions, endometrial polyps and submucosal fibroids can be treated by hysteroscopic surgery, and if necessary, surgery under ultrasound or laparoscopic surveillance can effectively prevent the occurrence of uterine perforation.
  (ii) Tubal infertility.
  Tubal obstruction is the most common cause of infertility, and the treatment for obstruction varies in different areas.
  The following treatment options are available.
  1. tubal lavage.
  Tubal lavage is only useful for patients with early obstruction (loose adhesions in the lumen).
  2. Hysterosalpingography.
  It is one of the common diagnostic methods for infertility, which can clearly determine the obstruction site, shape and morphology of the uterine cavity, and can also play a role in unblocking treatment for patients with early obstruction. Clinical examples of infertile women who became pregnant and gave birth immediately after the imaging can often be seen.
  3. Blind tubal guide cannula.
  A specially designed guide tube is placed through the uterine cavity to insert a catheter into the fallopian tube and inject drugs for the purpose of unblocking the proximal segment of the fallopian tube. This method is an innovative method designed by experts from the Department of Obstetrics and Gynecology of the First Affiliated Hospital of Zhengzhou University for the treatment of tubal obstruction and is suitable for patients with proximal tubal obstruction. The method is simple and easy to perform with relatively good results. The accuracy of the operation is slightly poor because the opening of the fallopian tube cannot be seen directly.
  4. Hysteroscopic tubal cannulation.  
  With the development of hysteroscopy and continuous improvement of technology, tubal cannulation has become a commonly used method for unblocking the fallopian tubes and is suitable for patients with proximal tubal obstruction. This method is operated under direct vision, and the positioning is accurate with little damage to the endometrium. However, due to the poor smoothness, toughness and histocompatibility of the common catheter, it is not easy for the catheter to enter the interstitial part of the fallopian tube and the isthmus, so the effect of unblocking is not satisfactory, and in most cases, it only plays the role of tubal cannulation and fluid flow, which cannot achieve the effect of real unblocking of the fallopian tube.
  5.Hysteroscopic COOK guidewire tubal evacuation.
  It is an effective method for the treatment of tubal obstruction that has emerged in recent years. It is suitable for patients with proximal and middle tubal obstruction, and is considered to be the best treatment method that is worth promoting.
  The COOK guidewire system consists of two delicate catheters and one platinum guidewire. The outer catheter is about 30 cm long with an outer diameter of 3 mm and its front end is about 3 cm with the catheter forming an obtuse angle to fit the shape of the uterine horn to facilitate reaching and holding against the opening of the uterine tube. The inner catheter has an outer diameter of 2mm and can be inserted into the interstitial part of the fallopian tube and the isthmus for lavage. The platinum guidewire has a diameter of about 1mm and is inserted into the fallopian tube through the inner catheter to act as a lavage. The guidewire is smooth and soft after dipping in water and can be inserted to separate the obstructed tubal lumen without easily damaging the tubal wall, resulting in a high success rate of unblocking.
  6. Separation of peri-fallopian tube adhesions and tubal ostomy.
  It can be done via laparoscopy or open surgery and is suitable for patients with tortuous tubes, uplift and hydrocele.
  7. IVF.
  It is suitable for patients with tubal obstruction and lesions in various areas who still do not get pregnant after failure of the above treatment methods. In vitro fertilization technique has a success rate of 30% to 50% in one conception.
  (iii) Ovulation promotion therapy.
  1. Clomiphene citrate.
  It is the most commonly used ovulation-promoting drug for patients with intact sexual axis feedback mechanism and a certain amount of estrogen in the body. It is started on 3-5 days of menstruation, 50mg/day for 5 days. The maximum dosage should not exceed 150mg/day. The literature reports that the ovulation rate of CC can reach 70%-80%, the pregnancy rate is about 30%, of which the rate of multiple pregnancy is 8% (86% for twins).
  2.Gonadotropins.
  For patients with hypothalamic and pituitary anovulation. Intramuscular injection of 1-2 injections/day is started on 2-5 days of menstruation, and the dosage is adjusted according to the follicle development condition monitored by ultrasound. When the follicle grows to an appropriate size, HCG is injected intramuscularly to induce ovulation. The ovulation rate is 60%-80% and the pregnancy rate is 40%-60%. Multiple pregnancy and ovarian hyperstimulation syndrome (OHSS) are likely to occur, so attention must be paid to monitoring and prevention.
  3.Gonadotropin-releasing hormone.
  Applicable to hypothalamic amenorrhea. It can be administered in pulses by micropump at a frequency of 60-120 minutes, 10-25 μg per pump, with dosage adjusted according to follicular development. When the appropriate dose is reached 80%-100% ovulation occurs, with a cycle pregnancy rate of about 25%, mostly singleton pregnancies.
  4. Bromocriptine.
  For patients with anovulation in hyperprolactinemia (PRL). Generally, it starts from 2.5mg/day and can be increased to 7.5mg/day if necessary. After 3-4 weeks of continuous use, PRL will be reduced to normal and ovulation and conception can be achieved by maintaining the appropriate dose after menstruation resumes.
  (iv) Treatment of immune infertility.
  1. Male tetrasexual autoanti-seminal antibody positivity. 
  The first step is to find the cause and treat it symptomatically. Steroid hormones can be applied to reduce the anti-sperm antibody titer and intrauterine insemination can be used to help conception when it is not effective.
  2.Women with positive anti-sperm antibodies.
  Use local isolation method, i.e. condom contraception for 3-6 months to make the sperm antibodies gradually decline or disappear, while corticosteroid hormone treatment can be applied, and intrauterine insemination fertility treatment can be carried out if it is not effective.
  3.Female humoral immune abnormalities. 
  Patients with anti-cardiolipin antibody positive syndrome can be treated with small doses of aspirin or heparin.
  (v) Treatment of male infertility.
  Male patients can be seen in the male sexually transmitted disease department or urology department of the hospital and treated medically or surgically for different etiologies. Severe oligospermia or obstructive azoospermia can be treated with assisted reproduction techniques.
  V. Prevention of infertility.
  With the gradual increase in the incidence of infertility, the prevention of infertility becomes very important. Active prevention, early detection and treatment of diseases that can cause infertility are of great importance for the prevention and treatment of infertility.
  1. Popularize the knowledge of sex and the principle of conception.
  Widely disseminating sexual knowledge to the public and advocating a healthy sexual lifestyle can reduce the occurrence of diseases, especially reducing the occurrence of inflammatory diseases of sexual organs and creating favorable conditions for pregnancy.
  2. Active prevention and treatment of inflammatory diseases of reproductive organs.  
  Inflammation of the vagina and cervix can affect the activity of sperm causing infertility, and can also cause endometritis, tubitis and pelvic inflammatory disease by retrograde infection. If treated thoroughly during the acute phase, it will not become chronic pelvic inflammatory disease and tubal obstruction.
  3, keep a happy mood, reduce mental tension.  
  The actual fact is that you will be able to get a lot more than just a couple of days to get a lot more than just a couple of days. Therefore, do not be impatient, low self-esteem and mental tension.
  4, good contraception, avoid abortion.  
  Surgery can cause damage and infection of reproductive organs, leading to tubal inflammation, endometritis, uterine adhesions and other causes of infertility.
  5. Pay attention to self-protection.  
  Certain people engaged in special jobs such as exposure to radiation and certain toxic substances should take serious measures to protect themselves so that the factors of infertility can be reduced to a minimum. In addition, they should develop good living habits, avoid wearing tight pants for a long time, and actively participate in physical exercise to enhance their physical fitness.