What Is Testicular Failure?
Primary spermatogenic failure refers to the changes in spermatogenic function caused by various hypothalamic pituitary diseases. The degree of primary spermatogenic failure caused by different causes is different. It is clinically collectively referred to as non-obstructive azoospermia.
Primary spermatogenic failure
- Chinese name
- Primary spermatogenic failure
- Object
- male
- Population ratio
- About 2%
- Clinical collective
- Non-obstructive azoospermia
- Primary spermatogenic failure refers to the changes in spermatogenic function caused by various hypothalamic pituitary diseases. The degree of primary spermatogenic failure caused by different causes is different. It is clinically collectively referred to as non-obstructive azoospermia.
- The incidence of azoospermia accounts for about 2% in the general population and as high as 10-20% in male infertility. Histology of the testis shows various changes in spermatogenic function from tubule damage to hypospermia. Even in the cases of Sertoli-only Syndrome (SCOS), different degrees of spermatogenic function may be found in the seminiferous tubules.
- In strict procedures, an increase in blood FSH levels is consistent with a decrease in testicular volume and / or texture. Prior to the era of single sperm intracytoplasmic injection (ICSI), elevated blood FSH was a sign of severe spermatogenic failure and did not require further evaluation of other diagnostic methods. ICSI is now thought to be used to treat some cases of non-obstructive azoospermia, but 20% of these cases may be associated with chromosomal abnormalities or genetic transformation of the Yq chromosome.
- The causes of primary testicular failure are shown in Table 3:
- Table 3 : Causes of Primary Testicular Failure
- No testis
- Congenital factors (dysplastic testis)
- Acquired factors (trauma, tumor, testicular torsion, surgery)
- Poor testicular decline
- Creutzfeldt-Jakob sign
- Other chromosomal abnormalities
- Germ cell dysplasia
- Complete or local germ cell dysplasia (support cell syndrome only), congenital or acquired: testicular decline, poor radiation cytotoxic drugs
- Spermatogenic block
- After inflammation (orchitis)
- Exogenous factors (drugs, toxins, radiation and heat)
- Systemic diseases (cirrhosis, kidney failure)
- Testicular tumor
- Varicocele
- Surgery that causes testicular blood supply damage
- Idiopathic
- The most serious pathological change of spermatogenic function is severe vitrification, that is, no cells exist in seminiferous tubules; more serious is the complete atrophy of seminiferous cells, SCOS or del castillo syndrome, and the diameter of these seminiferous tubules usually becomes smaller.
- Another more serious is the complete spermatogenic arrest at the spermatocyte level, which is characterized by normal Rai cells and support cells, spermatogonia and spermatocytes, but lacking spermatids and sperm. Maturation arrest is rare at the level of spermatogonia and round-headed spermatids, the latter of which is characterized by a lack of mature and growing spermatids. Mild changes in spermatogenic function include low spermatogenic function (part of spermatogenic cells are reduced), partial block of spermatogenic maturity, focal SCOS, and mixed types.
- Based on histology, the incidence of non-obstructive azoospermia accounts for about 40-60% of azoospermia. Testicular biopsy recommends using the JOHNSEN score, see Figure 4.
- Figure 4 : Testicular biopsy recommended JOHNSEN score sheet
- Histological criteria
- 10 Fine functioning
- 9 Spermatogenic function is slightly changed.Sperm cells are more late and disorderly arranged.
- 8 Less than 5 spermatozoa per tubule, fewer sperm cells in the late stage
- 7 Azoospermia and late spermatids, more early spermatids
- 6 Azoospermia and late spermatids, fewer early spermatids
- 5 Azoospermia and sperm cells, more spermatocytes
- 4 Azoospermia and sperm cells, fewer spermatocytes
- 3 spermatogonia only
- 2 No spermatogenic cells, only supporting cells
- 1 Spermatogenic epithelium
- Medical history and signs related to spermatogenic failure:
- Cryptorchidism
- Testicular torsion
- Genitourinary tract infection
- Testicular trauma
- Exposure to a toxic environment
- Drugs that damage gonadal function
- Exposure to radiation and chemical toxicity
- Testicular cancer
- Missing testicles
- Secondary sexual characteristics
- Gynecomastia
- Abnormal testicular volume and / or texture
- Varicocele
- Routine examinations mainly include semen examinations and sex hormone determinations, and special examinations depend on specific circumstances:
- 1) Semen check
- The amount of semen in non-obstructive azoospermia patients is generally normal, and no conclusion can be drawn after sperm are not found after several centrifugations. After centrifugation (600g, 10M), all semen droplets were carefully searched under a high-power microscope (600x), and the supernatant was centrifuged (8000g, 10M) and examined under the microscope. All specimens were stained and examined microscopically.
- 2) Determination of sex hormones
- In general, blood FSH levels are closely related to the number of spermatogonia, and when these cells are deficient or significantly reduced, blood FSH often increases. When the number of spermatogonia is normal, but complete spermatogenic arrest of spermatocytes or spermatids occurs, the blood FSH is generally in the normal range. Individually, blood FSH cannot accurately predict the state of spermatogenic function. Preliminary data show that there is a clear correlation between low inhibin B and spermatogenic damage, but it is currently not recommended to use inhibin B as a routine detection item.
- 3) obstructive non-obstructive azoospermia
- Some patients with obstructive azoospermia may have spermatogenic disorders or elevated blood FSH. Testicular biopsy is performed in patients with elevated blood FSH, reduced testicular volume on one side, and / or soft texture but suspected of having obstructive factors. Wise choice.
- 4) Sertoli cell syndrome only (SCOS)
- SCOS patients have normal or elevated blood FSH. These patients generally have no spermatozoa, normal semen volume, elevated blood FSH, normal T and LH, normal PRL, and normal secondary sexual characteristics, but bilateral testicular volume is reduced. Blood T and LH are generally only detected in patients with clinical signs of hypogonadism.
- 5) Testicular biopsy
- Testis biopsy should be performed when there is no clear basis to distinguish between obstructive and non-obstructive azoospermia (normal FSH and testicular volume).
- For those patients who are clinically suspected of non-obstructive azoospermia and require ICSI, testicular biopsy can also be used for therapeutic sperm retrieval. The spermatogenic function may be focal, with spermatogenic function in one or more seminiferous tubules, but not in other tubules, about 50-60% of non-obstructive azoospermia spermatozoa. The presence of sperm in the tube can be used for ICSI treatment.
- Most scholars believe that multiple specimens at different locations during biopsy can reflect the spermatogenic status of different parts, and some authors support the view that specimens from one site can explain the type of spermatogenesis in the entire testis. Many authors find diagnostic testicular biopsy pathology and TESE The relevance of obtaining sperm for ICSI is high.
- This information comes from: European Society of Urology, male infertility diagnosis and treatment guidelines and China Hematology Network
- Testicular biopsy is a small outpatient surgery that only requires local anesthesia. Here are a few surgical methods:
- 1) Open biopsy
- The incision was chosen at the midline of the testis on either side. The skin and capsule were cut open to expose the white membrane. The white membrane was cut with a knife blade. The tissue was cut with a small straight cut after gently squeezing the testicle. The specimen was placed in Bouin's solution and could not be used. Use Formamarin. In this procedure, epididymis activity can be carefully evaluated for morphological characteristics to rule out mechanical causes. Based on the current data, it is not yet possible to judge whether the minimally invasive surgery has better results. Standard testicular biopsy methods should be performed at the same time as smear cell blood tests.
- 2) Percutaneous testicular biopsy
- Some authors prefer to use percutaneous testicular biopsy as a diagnostic method because it is simpler and more convenient than open testicular biopsy. However, the number of specimens obtained by this method may be too small for histological examination. At the same time, unintended damage to specimens, hematomas, and epididymis may occur.
- 3) Fine needle aspiration
- Some authors advocate the use of fine needle aspiration in diagnostic biopsies, while others do not believe that the technique is as effective in pathological diagnosis as open biopsy.
- Either surgical method should provide sufficient sperm cryopreservation for ICSI use. If these sperm are still active, the fertility rate or implantation rate after ICSI will be higher.
- TESE and ICSI began to be used in patients with obstructive azoospermia in 1993. It was soon discovered that the technique can also be used in patients with non-obstructive azoospermia. If sperm are found on a biopsy, these frozen or fresh sperm can be treated with ICSI These infertile couples.
- These patients should be tested for karyotype and Y microdeletion, and if abnormal, they should be consulted appropriately. (Consult: China Blood Sperm Network of Andrology Center, Daping Hospital, Third Military Medical University.)
- 616 TESE cycles, 373 for ICSI cycles (60.5%), the average fertilization rate was 52.5% (38.6-69%), and the average pregnancy rate was 29.2% (11.3-31%).
- It is impossible for TESE to predict the etiology, age, blood FSH, testicular volume, and pathological tissue types to predict the presence of sperm.
- 8 , TESE technology
- Open biopsy and fine needle aspiration are two main surgical methods for obtaining sperm from the testis. Fine needle aspiration can obtain a larger range of tissues in different parts, while open biopsy can obtain more tissue and sperm.
- 1 Overview
- TESE is always performed on both sides of the testis at the same time. Make 2-3 small white membrane incisions at different positions on each side of the testis. After gently squeezing, the tissue is cut off and placed in a 2 ml culture fluid dish to the IVF laboratory. .
- The device for fine needle aspiration is a 21G butterfly needle attached to a 20 ml syringe (negative pressure suction). Fix the testis with the index finger and thumb, pierce the butterfly-shaped puncture needle directly into different positions of the testis, and clamp the microtube of the butterfly-shaped puncture needle with Venturi forceps before removing the needle from the testicle. In the hole. Use a new butterfly needle for each puncture.
- 2) Physiological outcomes after TESE
- In non-obstructive azoospermia, multiple testicular punctures can cause local inflammation, hematoma, and damage to the testicular blood supply. In small testicles, it is controversial whether there is a decrease in interstitial blood testosterone levels. The long-term outcome is unclear.
- 9 , frozen testicular sperm line ICSI
- Frozen testicular sperm can successfully perform ICSI. Most studies have shown that the results of frozen spermatozoa for ICSI are not significantly different from fresh sperm. After freezing, sperm survival seems to be independent of etiology, age, and blood FSH concentration.
- 10. TESE and ICSI in patients with Creutzfeldt-Jakob syndrome
- Palermo underwent 7 TESEs in 6 patients with non-chimeric Creutzfeldt-Jakob's sign, 4 of which found sperm, with a fertilization rate of 68%. Five children with normal karyotypes were born. There are other similar reports.
- 11.ICSI with testicular sperm cells
- Previous studies have shown that injecting round spermatid nuclei into rabbits or mice's eggs using microscopy have normal fertilization and healthy offspring are born. Edwards first proposed the use of sperm cells for intracellular injection of non-obstructive azoospermia. Reports indicate that fertilization and pregnancy rates are acceptable after injection of cytoplasm with round-headed sperm cells. The complete absence of sperm in a semen or testicular biopsy has poor clinical results.
- This information comes from: European Society of Urology, male infertility diagnosis and treatment guidelines and China Hematology Network
- 12.Conclusion
- 1) Impaired spermatogenic function is generally accompanied by an increase in blood FSH levels, but patients with elevated blood FSH levels may have normal spermatogenic functions.
- 2) Testicular biopsy is the best method for testicular histopathology and obtaining sperm. When spermatozoa are obtained, they should be stored frozen for ICSI cycles.
- 3) Taking 2-3 tissue specimens in different positions of the testis can better reflect the focal spermatogenic function. Open testicular biopsy can obtain more testicular tissue, and fine needle aspiration is easier to obtain tissue in different parts of the testis. .
- 4) Non-obstructive azoospermia has a sperm acquisition rate of 60%, but it is important to give these patients appropriate genetic counseling. Pre-implantation genetic diagnosis (PGD) should be performed in patients with chimeric or non-chimeric Creutzfeldt-Jakob syndrome.
- 5) In those patients with non-obstructive azoospermia whose sperm are found on testicular biopsy, fresh or frozen testicular sperm for ICSI is the only treatment option.
- 6) Fertility rate and pregnancy rate can reach 30-50%. The outcome of ICSI with sperm cells is disappointing, and the technique is still experimental.
- 13.Recommended plan
- (1) Diagnostic testicular biopsy is performed only in azoospermia patients with normal testicular volume and normal blood FSH.
- (2) In patients with non-obstructive azoospermia, sperm obtained from TESE can be frozen for ICSI treatment.