Essential reading for azoospermia patients: What is azoospermia? How is azoospermia treated? Can azoospermia be cured?
What is azoospermia?
Azoospermia refers to the failure to find sperm after more than three consecutive centrifugal smear microscopies of semen. These patients can ejaculate during sexual intercourse and the semen volume can be normal, and they have no obvious clinical symptoms. Azoospermia is a complex and difficult to treat syndrome in male infertility, accounting for about 7-14% of male infertility. In the past, there was no good treatment for azoospermia, but now the application of IVF technology and microscopic male surgery has made it possible for many azoospermia patients to have their own offspring.
How should azoospermia patients be tested and choose their treatment?
The actual azoospermia patients can go to the reproduction center of public tertiary hospitals through doctor’s referral or internet inquiry to find professional male doctors with good reputation, good medical ethics and good medical skills for consultation and treatment in order to get regular treatment in time to avoid being duped and delaying treatment time. Given that there are relatively few male doctors skilled in the treatment of azoospermia in China, many azoospermia patients waste a lot of time and money in the process of blind treatment, and even miss the best time for treatment, so it is most important for azoospermia patients to choose the right hospital and doctor. The following are some suggestions and advice.
1. Almost all azoospermia patients have to obtain fertility through IVF technology, so it is important for azoospermia patients to visit a fertility center that can do IVF.
2. Because many patients with azoospermia are accompanied by dysplasia or absence of the testes, epididymis and vas deferens, scrotal palpation (examination of the patient’s scrotum by the doctor’s hand) is very important for the diagnostic classification and treatment selection of azoospermia. Therefore, patients with azoospermia should keep in mind that if your primary care physician prescribes medication or surgery without performing scrotal palpation, it is advisable to see a different doctor.
3. Because varicocele is not the main cause of azoospermia, and given that many normal fertile men also have varicocele, most azoospermia patients with varicocele do not need to have varicocele surgery. Because prostatitis is not the main cause of azoospermia, azoospermia patients should not waste too much time and money on treating prostatitis.
4. Don’t blindly perform epididymal puncture before you are sure you want to do IVF, because epididymal puncture for sperm retrieval can damage the epididymis and destroy the integrity of the vas deferens tract, depriving azoospermia patients of the opportunity to be treated with medication or microscopic male surgery. Testicular biopsy is the preferred method of diagnosis for azoospermia, and epididymal puncture is not the first choice. This is because testicular puncture biopsy is less damaging to the testes and most testicular spermatogenic functions can be restored after the biopsy. Epididymal puncture for sperm retrieval is generally used as a surgical method to obtain sperm when doing IVF and is not recommended as a diagnostic method.
5, azoospermia patients, do not blindly believe in the false propaganda of private male hospitals or private infertility hospitals, and do not blindly believe in the so-called expert professors of large hospitals, to find a male doctor who can really see azoospermia to avoid being duped and delaying treatment time.
The treatment process for azoospermia is generally as follows, and experienced doctors can make slight changes according to the patient’s condition.
①doctor’s consultation (mandatory), including fertility history, history of previous diseases, etc.; ②conduct physical examination: mainly scrotal palpation (mandatory), feel the testicles, epididymis, vas deferens and spermatic veins; spermatogenic function of the testicles can be inferred by the size and texture of the testicles, and understand whether there is obstruction or dysplasia of the epididymis and vas deferens, and whether there is varicocele.
③ Perform relevant non-invasive examinations, mainly including
Examination of semen to confirm the diagnosis of azoospermia by semen centrifugal sediment smear microscopy (mandatory), analysis of possible sites and causes of obstruction of the vas deferens by seminal plasma biochemical analysis (including fructose and neutral glycosidase, optional) and seminal fluid internal infection indicators (leukocytes and elastase); blood sampling for sex hormones (to estimate the spermatogenic capacity of the testes and to check for endocrine disorders, mandatory), peripheral blood chromosomes and Y chromosome microdeletion (to check for hereditary diseases); scrotal ultrasonography (to observe the testes, epididymis and spermatic veins, optional), transrectal ultrasonography (to observe the ejaculatory ducts, seminal vesicles and prostate, optional); pelvic magnetic resonance imaging (MRI, optional) to observe the ejaculatory ducts, seminal vesicles and prostate.
④The need for an invasive test – testicular aspiration biopsy – will be decided by a specialist male surgeon to clarify whether sperm can be produced in the testes and to assess the spermatogenic function of the testes.
⑤ A professional male surgeon will make a categorical diagnosis and decide on the treatment.
Classification and diagnosis of azoospermia and treatment.
Azoospermia is mainly classified into the following types.
(i) Obstructive azoospermia: semen examination has no sperm, but testicular biopsy suggests normal testicular spermatogenesis (more mature sperm are found). Obstructive azoospermia accounts for only a minority of azoospermia, and almost all patients with obstructive azoospermia can have offspring through IVF technology, so obstructive azoospermia is also known as “curable azoospermia”.
Common types and causes include: epididymal obstruction caused by bilateral epididymitis, epididymal tuberculosis or epididymal cyst; ejaculatory duct obstruction caused by seminal vesicle inflammation or prostate cyst; congenital bilateral vas deferens or dysplasia; congenital bilateral seminal vesicle deficiency or dysplasia; congenital bilateral epididymal deficiency or dysplasia; vas deferens blockage caused by vasectomy or inflammation.
2. Examination and diagnosis of obstructive azoospermia: scrotal palpation and biochemical analysis of seminal plasma (to determine whether there is obstruction and analyze the site of obstruction, mandatory), centrifugal sediment smear microscopy of semen (to confirm the diagnosis of azoospermia, mandatory), scrotal and transrectal ultrasound and pelvic magnetic resonance (to understand the situation of seminal vesicles and ejaculatory ducts, optional), vasovasography (traumatic and radiological injury, not recommended) and other examinations are needed to The site of obstruction in the vas deferens canal can be clearly identified; and the spermatogenic function of the testes can be understood through chromosomal (mandatory), serum sex hormone (mandatory) and testicular biopsy (mandatory to determine whether sperm can be produced in the testes and to assess the spermatogenic function of the testes).
3, obstructive azoospermia treatment: almost all patients with obstructive azoospermia can use IVF (surgical sperm retrieval + ICSI) technology and other methods to have their own offspring. A very small number of patients with obstructive azoospermia can be treated with medication or microsurgery to reopen the vas deferens, so that sperm reappear in the semen, and then choose natural intercourse, artificial insemination or IVF technology to have offspring according to the quantity and quality of sperm and the physical condition of the female partner. The specific treatment methods are as follows.
(1) Drug treatment. Very few patients with obstructive azoospermia can be treated with medication to make sperm appear in the semen. In some patients with epididymitis or vesiculitis, if the inflammatory obstruction is not severe or has just appeared, sperm can be found in the semen after a period of treatment with anti-infective and spermopoietic drugs. If the quantity and quality of sperm are good enough, pregnancy can be attempted through natural intercourse; however, if the quantity and quality of sperm are not good enough, or if the woman is still not pregnant after trying for more than 1 year, assisted reproductive techniques such as artificial insemination or IVF can be used to produce their own offspring.
The advantages of drug therapy are: no surgery and no trauma; lower cost than surgery or assisted reproduction techniques; and the chance of getting pregnant with natural intercourse. The disadvantages of this method are: only a very small number of patients with obstructive azoospermia (inflammatory obstruction is not serious or obstruction has just appeared) are suitable for this method and need to be seen and decided by an experienced professional male surgeon; anti-infection treatment with antibiotics takes longer, usually more than 3 weeks; the success rate of sperm appearing in semen after treatment is relatively low.
(2) Microscopic male surgical treatment. In a very small number of patients with obstructive azoospermia, after the site and cause of obstruction are clearly identified, the vas deferens can be unblocked through microscopic epididymal vasectomy (for patients with caudal epididymal obstruction), microscopic vasectomy (for patients with vasectomy), transurethral ejaculatory ductotomy (for patients with ejaculatory duct obstruction) and other microscopic male surgeries to unblock the vas deferens, so that sperm can appear in the semen again and then conceive through natural intercourse, artificial insemination In this way, they can have their own offspring through natural intercourse, artificial insemination, in vitro fertilization, and other methods.
The advantages of microscopic male surgical treatment are: it can make sperm appear in the semen of azoospermia patients, which is a method to cure the root of the problem and can give the patient a sense of psychological recovery; there is a chance of pregnancy through natural intercourse. The disadvantages of this method are: the indications are relatively few, only a few patients with a clear and single obstruction site are suitable for surgery; the technical requirements of the surgeon are very high, only a few urologists or male surgeons in China can master this kind of surgery (the First Hospital of Sun Yat-sen University carries out this kind of surgery); the surgery is somewhat traumatic; the recovery period after surgery is long, many patients can only find sperm in their semen after six months or even one year after surgery. Many patients can find sperm in the semen only after six months or even one year after the surgery, and it may take several years to succeed in trying to conceive through natural intercourse; the cost is expensive, and the cost of surgical treatment plus post-operative medication is tens of thousands of yuan, almost the same as the cost of IVF; the success rate of vasectomy is relatively low, with a recanalization rate of about 20-60%, and many patients still have no sperm in the semen after the surgery; the natural pregnancy rate after the surgery is low, with a natural pregnancy rate of about 10% after the surgery. The natural pregnancy rate after surgery is low, about 10%, because the sperm in the semen after vasectomy is often insufficient in quantity or poor in quality, and these sperm must be used for artificial insemination or IVF and other assisted reproduction techniques to produce their own offspring.
In conclusion, very few patients with obstructive azoospermia are suitable for surgical revascularization. Patients with obstructive azoospermia whose vas deferens is not clear or has multiple obstructions and whose testes have low spermatogenic function are not suitable for surgical treatment. Urologists or male surgeons who have mastered this type of surgery should not abuse it and should only use it when they encounter patients who strictly meet the indications for the procedure and when the patient’s desire for treatment is still relatively strong after being informed of the risks of the procedure.
(3) Almost all patients with obstructive azoospermia can have their own offspring through in vitro fertilization (ICSI), which is currently the main method of obtaining offspring for patients with obstructive azoospermia. The method starts with obtaining sperm from the testes or epididymis through a sperm retrieval procedure, then using these sperm for intra-oval single sperm injection (ICSI, a second generation IVF technique), forming a fertilized egg and embryo, and then selecting a good quality embryo and placing it in the woman’s uterus to conceive her own offspring. The advantages of this method are: it has a wide scope of application, almost all patients with obstructive azoospermia can have their own offspring through IVF technology, which is the ultimate treatment for obstructive azoospermia; the treatment cycle is short, as long as the female partner can be tested for fertility, IVF can be done immediately after obtaining sperm from the testes or epididymis through sperm retrieval surgery, and often the female partner can become pregnant within a few months to six months. It is particularly suitable for older infertile couples (the woman is over 30 years old); the success rate is high, with an average pregnancy success rate of about 50-80% for testicular or epididymal surgical sperm retrieval + intra-oval single sperm injection (ICSI). The disadvantages of this method are: it only solves the fertility problem and does not achieve the effect of curing the root cause, and the patient still has no sperm in the semen; if the woman fails to conceive, she has to try again to have a baby through surgical sperm retrieval and IVF technology; it is expensive, and it costs 40,000 yuan or more for one IVF (ICSI), and repeated IVF (ICSI) may bring serious financial pressure to the patient.
(2) Non-obstructive azoospermia: semen examination does not reveal sperm (semen centrifugal sediment smear microscopy, used to confirm the diagnosis of azoospermia, must be done), and scrotal palpation and seminal plasma biochemical analysis (the main test to determine whether there is obstruction, must be done), ultrasound, magnetic resonance imaging, vasectomy and other tests find that there is no obstruction or dysplasia of the vas deferens, serum sex hormones (must be done) may indicate testicular spermatogenic function The testicular biopsy (to determine whether sperm can be produced in the testes and to assess testicular spermatogenesis, optional) also reveals no sperm or very few mature sperm. The majority of patients with non-obstructive azoospermia have no testicular sperm production, and only a small percentage of patients have focal testicular spermatogenesis. Since testicular puncture biopsies do not always penetrate local spermatogenic foci, pathologic findings often suggest significantly fewer, rare, or no mature spermatozoa. Non-obstructive azoospermia accounts for the majority of azoospermia and is the most common type of azoospermia.
1. Common types and causes of non-obstructive azoospermia include
Congenital microspermia (Creutzfeldt-Jakob syndrome, chromosome 47, XXY); hypogonadotropic hypogonadism (low FSH, LH and T, e.g. Kaman syndrome); hypergonadotropic hypogonadism (high FSH and LH, low T); hyperprolactinemia (high PRL); testicular spermatogenic dysfunction (testicular biopsy pathology suggesting low numbers of spermatogenic cells in the varicocele or (very low number of mature spermatozoa); supportive cell only syndrome (testicular biopsy pathology indicates no spermatogenic cells in the cystic ducts, only supportive cells); bilateral cryptorchidism or late bilateral cryptorchidism descent (irreversible damage to testicular spermatogenic function is often present when surgery is performed after 2 years of age); history of mumps (commonly known as swollen mumps, often associated with viral orchitis leading to irreversible damage to testicular spermatogenic function). traumatic bilateral testicular atrophy; testicular atrophy due to aging; testicular atrophy due to severe or long-term varicocele; history of toxic chemical or radiation exposure (e.g., consumption of crude cottonseed oil, exposure to toxic chemicals such as benzene at work, or long-term exposure to radioactivity); history of genetically modified food consumption (some genetically modified foods contain sterility genes that may lead to testicular spermatogenic dysfunction); history of high-temperature environment Work history or history of hyperthermia (temperature higher than body temperature will kill sperm, long-term high temperature will lead to testicular spermatogenic dysfunction); idiopathic (unknown cause).
2. Treatment of non-obstructive azoospermia.
(1) When testicular biopsy pathology reveals a small amount of mature sperm, you can try to obtain sperm through testicular sperm retrieval surgery for in vitro fertilization (ICSI) technology to have your own offspring, although the risk of not getting sperm is high. These patients often undergo a period of spermatogenic treatment before surgical sperm retrieval so that there are enough mature sperm in the testes. Multi-point testicular puncture or microscopic testicular dissection for sperm retrieval can help improve the success rate of sperm retrieval. In these patients undergoing in vitro fertilization (ICSI), it is best to find and freeze the sperm through testicular sperm retrieval before allowing the woman to undergo ovulation treatment and egg retrieval to minimize the risk and cost.
It is important to emphasize that a testicular biopsy with pathological section staining results suggesting rare or reduced mature sperm implies that mature sperm for IVF may not be found in the testicular tissue because the stained pathological section often does not see the sperm as a whole, and when a sperm head is seen, it is assumed that there is mature sperm, whereas in fact mature sperm can only be done if a tadpole-like sperm with the head, body and tail intact is found under the microscope. In vitro fertilization. Therefore, the decision of whether IVF can be done when testicular biopsy pathology staining results suggest that mature sperm are rare or reduced requires a comprehensive analysis by an experienced professional male physician.
(2) When testicular biopsy pathology reveals no mature sperm, artificial insemination or IVF can only be done by purchasing sperm from a sperm bank.
(3) Some patients with non-obstructive azoospermia can be treated with medication to make sperm appear in the semen. For example, in patients with hypogonadotropic hypogonadism (low FSH, LH and T, such as Kaman syndrome), sperm can be found in the semen of some patients after more than six months of treatment with HCG/HMG and other medications.
(iii) Mixed azoospermia: there is both obstruction of the vas deferens and low spermatogenic function of the testes.
1. Diagnosis of mixed azoospermia: The presence of obstruction or dysplasia of the vas deferens such as epididymis, vas deferens, seminal vesicles or ejaculatory ducts is detected by scrotal palpation, seminal plasma biochemistry, ultrasound, magnetic resonance imaging, vasectomy and other examinations, as well as the presence of small testicular volume assessed by scrotal palpation, elevated serum FSH or testicular biopsy pathology suggesting low testicular spermatogenic function.
2. Treatment of mixed azoospermia: If vasectomy is not suitable, we can only try to obtain sperm through testicular sperm retrieval for in vitro fertilization (ICSI); if sperm cannot be obtained, we can consider purchasing sperm from a sperm bank for artificial insemination or IVF treatment.
(iv) Cryptospermia: In some infertile patients, no sperm can be found by routine semen tests, but a very small amount of sperm can be found by centrifugal sediment smear microscopy, and these patients are called cryptospermia. These patients are called cryptospermia. Because of the low spermatogenic function of the testes, sometimes the testes can produce a small amount of sperm to be excreted through the semen, which manifests as very severe oligospermia; sometimes the testes cannot produce enough sperm to cause no sperm to be found in the semen, which manifests as azoospermia. These patients, often misdiagnosed as azoospermia by doctors in primary hospitals. However, strictly speaking, cryptospermia belongs to very severe oligospermia and does not belong to azoospermia, but its diagnosis and treatment can be referred to azoospermia.
1. Diagnosis of patients with occult spermatozoa: several centrifugal sediment smear microscopic examinations of semen are required. Patients often have small testicular volume, elevated serum FSH and other manifestations of low testicular spermatogenic function. Since testicular spermatogenesis in these patients may be focal, the pathological results of testicular puncture biopsy often suggest a significant decrease in mature sperm or the absence of mature sperm.
2. Treatment for patients with cryptospermia: Through a period of spermopoietic medication and life care conditioning, when active sperm can be found for more than two consecutive times during semen examination, in vitro fertilization (ICSI) treatment can be attempted using a small amount of active sperm in the semen. If no sperm can be found in the semen on the day of egg retrieval during IVF treatment, testicular sperm retrieval can be attempted to obtain sperm.
How is azoospermia caused?
Azoospermia can be caused by a variety of etiologies, and there are two main causes of azoospermia.
(a) Testicular spermatogenic dysfunction: caused by azoospermia.
The testis has two main functions, the production of sperm by the testicular varicocele and the secretion of androgens (testosterone) by the testicular interstitial cells, which play a decisive role in the occurrence and growth of sperm. When pathogenic factors act on the testes through direct pathways or indirectly through the body, they affect the spermatogenic function of the testes and make the testes unable to produce sperm.
Common causes of testicular spermatogenic dysfunction: ① congenital abnormalities of the testes, including abnormal testicular development and abnormal testicular position, such as: congenital orchidrosis, cryptorchidism, Creutzfeldt-Jakob syndrome, etc.; ② testicular inflammation, such as: testicular inflammation caused by mumps, testicular tuberculosis, syphilis, non-specific orchitis, etc.; ③ testicular injury caused by testicular trauma or surgery; ④ vascular diseases, such as: varicocele, testicular torsion, etc. ⑤ compression and temperature increase caused by scrotal diseases, such as: large testicular syringomyelia, inguinal hernia, etc.; ⑥ impaired thermal regulation function of the scrotum, such as: history of hyperthermia, varicocele, wearing tight pants, frequent hot baths, high temperature working environment, etc.; ⑦ neuroendocrine disorders, so that the pituitary gland cannot release gonadotropins and secrete androgens, causing testicular hypoplasia and impaired spermatogenesis; ⑧ nutritional disorders and Industrial hazards, such as: consumption of crude cottonseed oil, vitamin A, E, C deficiency, heavy metals such as lead, arsenic, cadmium and environmental factors; ⑨ drug effects, such as: furans, hormones, anserine, 5-hydroxytryptamine, monoamine oxidase inhibitors, cyclophosphamide, methotrexate, large amounts of aspirin, etc.
(B) Vas deferens obstruction: due to azoospermia.
Vas deferens obstruction can be divided into two categories: congenital abnormal development and acquired obstruction. (1) Congenital vas deferens obstruction: congenital dysplasia in any part of the vas deferens can cause vas deferens obstruction, with congenital abnormalities in the head of the epididymis being the most common. Common clinical types of vas deferens obstruction include: vas deferens dysplasia; obstruction of epididymal collaterals and epididymal vas deferens collaterals; prostate, seminal vesicle and ejaculatory duct dysplasia, as well as Mullerian duct cysts; obstruction due to pressure on the vas deferens caused by extra-vas deferens factors such as sphincter bundles and cysts. ②Acquired vas deferens obstruction: the most common factor is infection. The most common cause of obstruction due to epididymal infection is gonorrhea. Gonococci can destroy the tail of the epididymis, but rarely invade the head of the epididymis, and the vas deferens is also often invaded by streptococci and causes obstruction of the vas deferens. Surgical injuries include syringomyelia, varicocele, cryptorchidism surgery and misligation of the vas deferens during hernia surgery. The ejaculatory ducts are also often obstructed due to inflammation or prostate heat therapy.