- •Series Editor Foreword
- •Preface
- •Contents
- •Contributors
- •Differential Diagnosis
- •Evaluation
- •Treatment
- •Discussion
- •References
- •Background
- •Normal Pubertal Stages
- •Differential Diagnosis of Precocious Puberty
- •Evaluation [1, 3, 4]
- •Treatment [1, 2]
- •Discussion
- •References
- •Background
- •Differential Diagnosis of Delayed Puberty
- •Evaluation
- •History and Physical Examination
- •Laboratory Investigation and Imaging
- •Treatment
- •Discussion
- •Suggested Readings
- •Discussion
- •Differential Diagnosis
- •References
- •Discussion
- •References
- •Differential Diagnosis
- •Evaluation
- •Treatment
- •Discussion
- •References
- •Discussion
- •References
- •Discussion
- •References
- •Discussion
- •References
- •Discussion
- •References
- •Discussion
- •References
- •Discussion
- •Interpretation of Thyroid Function Tests (TFTs)
- •Iodine Supplementation for Pregnancy and Lactation
- •Screening for Maternal Hypothyroidism
- •Maternal Subclinical Hypothyroidism
- •Thyroid Autoimmunity
- •Maternal Hyperthyroidism: Diagnosis
- •Maternal Hyperthyroidism: Treatment
- •Postpartum Thyroiditis
- •Summary
- •References
- •Discussion
- •References
- •Discussion
- •References
- •Discussion
- •References
- •Discussion
- •References
- •Discussion
- •References
- •Discussion
- •References
- •Discussion
- •References
- •Discussion
- •References
- •Discussion
- •Intrauterine Pathology
- •Thin Lining
- •Endometrial Receptivity Analysis (ERA)
- •Chronic Endometritis
- •Conclusion
- •References
- •Discussion
- •References
- •Discussion
- •History
- •Physical Exam
- •Semen Analysis
- •Laboratory Testing
- •Genetic Testing
- •Adjunctive Tests
- •Imaging
- •References
- •Discussion
- •Pathophysiology
- •Evaluation
- •Treatment
- •Lifestyle Changes
- •Medications
- •Phosphodiesterase 5 Inhibitors
- •Vacuum Erection Device
- •Intraurethral Alprostadil
- •Intracavernosal Injections
- •Surgery
- •References
- •Discussion
- •History
- •Semen Analysis
- •Physical Examination
- •Proper Varicocele Examination
- •Laboratory Investigations
- •Additional Investigations for the Pain Include
- •Other Investigations for Infertility in the Context of Varicoceles
- •Treatment
- •Indications for Varicocele Treatment Include the Following
- •Numerous Treatments for Varicocele Exist
- •References
- •Discussion
- •Semen Analysis
- •History and Physical Examination
- •Laboratory Investigations
- •Testicular Biopsy
- •Treatment
- •Surgical Techniques for Sperm Retrieval [13]
- •Fresh Vs. Frozen Sperm
- •Counseling
- •References
- •Discussion
- •References
- •Discussion
- •References
- •Discussion
- •References
- •Background
- •Epidemiology
- •Evaluation
- •Treatment
- •Non-ART Treatment
- •Accelerated Utilization of ART
- •ART Success Rates
- •Recent Trends in ART
- •Discussion
- •Conclusion
- •Suggested Readings
- •Evaluation
- •Differential Diagnosis
- •Discussion
- •References
- •Discussion
- •References
- •Discussion
- •References
- •Discussion
- •Suggested Readings
- •Diagnosis
- •Management
- •Discussion
- •References
- •Index
180 |
N. Punjani and P. Schlegel |
•\ Post-ejaculatory urinalysis [1]: utilized for the assessment of men with low semen volume, including aspermia, for retrograde ejaculation. Patients are asked to void after ejaculation and urine is subsequently centrifuged and assessed for the presence of sperm. A tablet of sodium bicarbonate is taken beforehand to help alkalinize the urine as the acidic urine environment may be harmful to sperm. Some have historically suggested placement of appropriate media in the bladder before ejaculation in an effort to protect sperm [6].
•\ Ultrasound (transrectal and/or scrotal) [1]: for assessment of varicocele, ejaculatory duct dilation or any other suspected genitourinary abnormality.
•\ Cystic brosis transmembrane conductance regulator (CFTR) Testing [4]: serum measurement for patients with CAVD either unilaterally or bilaterally to assess for the presence of cystic brosis gene mutations. Partners should also be tested and genetic counseling referral should be initiated where appropriate. Testing for the 5T allele is also indicated for men with BCAVD.
•\ Abdominal ultrasound [4]: performed in patients with BCAVD and negative CFTR testing as patients may have associated renal anomalies (i.e., renal agenesis).
Genetic Work-Up andImplications
Karyotype and Y-microdeletion testing should be offered to all patients with non- obstructive azoospermia or severe oligospermia (< ve million sperm/mL), based on AUA guidelines [4].
The most common chromosomal abnormality in men with infertility is Kleinfelter syndrome (47XXY or 46XY with mosaicism). The phenotype is variable from complete azoospermia to compromised sperm production [4].
Microdeletions may occur in the long arm of the Y chromosome, which are often due to ampliconic and palindromic sequences in this region. Three commonly detected regions of deletions may occur including AZFa, AZFb, and AZFc [7]. Complete microdeletions of AZFa or AZFb regions will reliably predict azoospermia with no reasonable chance of surgical sperm retrieval. AZFa speci cally tends to result in uniform Sertoli cell only syndrome. However, patients with AZFc microdeletion have been reported to have sperm in the ejaculate in a majority of cases with surgical sperm retrieval rates of up to 50–70% [8].
Testicular Biopsy
Biopsy provides for a limited evaluation of testicular function and is only utilized to distinguish between obstructive and non-obstructive azoospermia, for example, in patients with normal testicular volume and normal or borderline elevated FSH [3]. This could be done as a therapeutic intervention as well, with sperm from removed
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26 Azoospermia |
181 |
tissue utilized for assisted reproduction or cryopreserved. Various histologies may be found at the time of biopsy with subsequent sperm retrieval rates with TESE:
•\ Obstructive Azoospermia.
––Normal spermatogenesis—very high sperm retrieval rates. •\ Non-obstructive Azoospermia [4].
––Hypospermatogenesis—sperm retrieval rates reached up to 79%
––Maturation Arrest—sperm retrieval rates reached up to 47%.
––Sertoli Cell Only—sperm retrieval rates reached up to 24%.
Treatment
Treatment options for patients with azoospermia are dictated by its etiology. Obstructive azoospermia or retrograde ejaculation [1, 2]:
•\ Medical—utilization of medication to promote antegrade ejaculation in cases of retrograde ejaculation.
•\ Sperm retrieval for assisted reproductive technology—includes percutaneous or open sperm aspiration/retrieval.
•\ Minimally invasive procedure—for individuals who have failure to ejaculate due to neurological injury or spinal cord injury, techniques such as vibratory stimulation or electro-ejaculation may be utilized.
•\ Endoscopic surgery—transurethral resection of the ejaculatory ducts if there is evidence of ejaculatory duct obstruction.
•\ Surgical reconstruction—for obstructed patients, may require vasal or epididymal reconstruction to bypass the area of concern.
•\ Donor sperm, surrogacy, and/or adoption.
Non-obstructive azoospermia [1, 2]:
•\ Medical—for those with hypothalamic-pituitary disorders.
•\ Sperm retrieval for assisted reproductive technology—includes percutaneous or open sperm aspiration/retrieval.
•\ Donor sperm, surrogacy and/or adoption.
Medical options may include hormonal treatment in an attempt to increase spermatogenesis by enhancing endogenous testosterone production. Although controversial, there is some evidence suggesting the potential bene t of these treatments in non-obstructive azoospermic men [9]. Hormone values should be closely followed after initiation of these medications. Various medications have been implicated [10, 11] (Table 26.2).
•\ Pseudoephedrine: an alpha-agonist which attempts to convert retrograde ejaculation to antegrade ejaculation.
182 |
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N. Punjani and P. Schlegel |
|
Table 26.2 Medications and |
|
|
|
Medication |
Dose |
||
dosages [11] |
|
|
|
Pseudoephedrine |
60 mg po qid |
||
|
|||
|
FSH |
100–450 IU 2–3×/week |
|
|
hCG |
1500–5000 IU 2×/week |
|
|
Anastrozole |
1 mg/day |
|
|
|
|
|
|
Letrozole |
2.5 mg/day |
|
|
Clomiphene citrate |
12.5–50 mg/day |
|
|
Tamoxifen |
10–20 mg/day |
•\ Recombinant FSH: works by stimulating FSH receptors in Sertoli cells to stimulate spermatogenesis in men with hypogonadotropic hypogonadism.
•\ Gonadotropins (i.e., human chorionic gonadotropin (hCG)): these medications directly stimulate LH receptors in Leydig cells and can therefore potentially improve. Spermatogenesis. This is commonly used in patients with low testosterone, especially those with hypogonadotropic hypogonadism, in whom there is a desire to raise intratesticular testosterone levels without compromising fertility.
•\ Aromatase Inhibitors (i.e., anastrozole, letrozole): these medications not only work through inhibition of the conversion of androgens to estrogens which increases testosterone levels, but also decrease estrogen feedback that increases GnRH and LH release. This is commonly used in patients with low serum testosterone-to-estradiol levels, with a threshold ratio of 10 as the lower limit of normal [12].
•\ Selective estrogen receptor modulator (i.e., clomiphene citrate, tamoxifen): these medications block the negative feedback of estrogen on the hypothalamic- pituitary axis thereby increasing FSH and LH production to stimulate testosterone and spermatogenesis. These are commonly used in patients with low testosterone levels.
Surgical Techniques for Sperm Retrieval [13]
•\ MESA (Microsurgical epididymal sperm aspiration): utilizes a scrotal incision where the testis is delivered and both testis and epididymis are observed under an operative microscope. The epididymis is examined for dilated tubules whereby sperm is aspirated. Multiple different segments of the epididymis are sampled, including the efferent ducts, where different sperm quality is typically found in each of the various segments of the epididymis. This is the gold standard for patients with obstruction.
•\ PESA (Percutaneous epididymal sperm aspiration): requires a needle to be placed transcutaneously into the caput of the epididymis whereby sperm is aspirated.
•\ TESA (Testicular sperm aspiration): utilization of a needle for transcutaneous aspiration of sperm from the testicle.
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26 Azoospermia |
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183 |
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Table 26.3 Selected sperm |
|
|
|
Technique |
Success rate |
||
retrieval technique |
|
|
|
MESA |
99–100% for OA [14, 15] |
||
success rates |
|||
PESA |
61–96% for OA [16, 17] |
||
|
|||
|
micro-TESE |
45–63% for NOA [18] |
•\ MicroTESE (Microsurgical testicular sperm extraction): this utilizes a midline scrotal incision to deliver the testicle which is then bivalved under the microscope and seminiferous tubules are examined for the presence of dilated tubules which may contain sperm. This will likely yield a greater chance of nding sperm compared to a random biopsy given the ability to directly identify dilated tubules. Processing of the specimen in the IVF laboratory is a critical component and may impact on the actual yields of sperm. This technique is often used for patients with non-obstructive azoospermia. (Note: up to 15% of men may have sperm on pre-operative semen analysis and therefore repeat semen analysis should be routinely performed before surgical retrieval) [4] (Table 26.3).
Sperm retrieved from these methods will be used in conjunction with assisted reproductive technology, either fresh at certain centers or may be cryopreserved for utilization at a later date.
Fresh Vs. Frozen Sperm
For patients undergoing sperm retrieval with obstructive azoospermia no differences have been observed in IVF success rates after use of fresh or cryopreserved sperm. However, some data highlights that in patients with non-obstructive azoospermia, overall results for fertilization and pregnancy rates are improved using fresh specimen synchronized with oocyte retrieval [4]. Using cryopreserved sperm in men with non-obstructive azoospermia has yielded poorer pregnancy outcomes often due to the limited number of sperm obtained or failure of sperm to survive freeze-thaw. Repeat sperm retrieval procedures in non-obstructive men are always not as successful.
Counseling
In the event when chromosomal abnormality, or genetic condition, is noted in azoospermic men, counseling should be provided. Patients with cystic brosis must also have genetic screening of the female partner due to the potential risk of disease in the offspring. For any Y-chromosome-related genetic aberrations, any male offspring would inherit the abnormality but they pose no risk of transmission to a female offspring. For Y-microdeletions, this would not apply to patients with AZFa and AZFb deletions s as these men would not be able to conceive.