Role of varicocelectomy in men with nonobstructive azoospermia

OBJECTIVE: To evaluate the benefits of varicocelectomy in men with nonobstructive azoospermia. DESIGN: Retrospective review of effect of prior varicocelectomy on sperm retrieval rates in men with nonobstructive azoospermia. Chart review of men with nonobstructive azoospermia who underwent microsurgical varicocelectomy to determine the effect of the procedure on the need for testicular sperm extraction (TESE). SETTING: Tertiary, university-based referral center. PATIENT(S): Men with clinical varicoceles and nonobstructive azoospermia. INTERVENTION(S): Microsurgical varicocelectomy, TESE. MAIN OUTCOME MEASURE(S): Return of sperm to the ejaculate and need for TESE after varicocele repair, ability to find sperm using microdissection TESE. RESULT(S): Of 31 men who underwent varicocele repair at one institution for documented nonobstructive azoospermia, 7/31 (22%) had sperm reported on at least one semen analysis postoperatively. However, only 3/31 (9.6%) men after varicocele repair had adequate motile sperm in the ejaculate for ICSI, without TESE. Sperm retrieval rates for men with varicoceles were not affected by a history of prior varicocelectomy. CONCLUSION(S): Men with clinical varicoceles that are associated with nonobstructive azoospermia will rarely have adequate sperm in the ejaculate after varicocele repair to avoid TESE. A history of prior varicocele repair does not appear to affect the chance of sperm retrieval by TESE for men with clinical varicoceles and nonobstructive azoospermia. The benefits of varicocelectomy in men with nonobstructive azoospermia may be less than previously reported.     

Percutaneous epididymal sperm aspiration and short time insemination in the treatment of men with obstructive azoospermia

Objective

To study the efficacy of percutaneous epididymal sperm aspiration (PESA) in combination with short time insemination to treat infertile men with obstructive azoospermia (OA).

Design

Paired randomized controlled trial in which each couple’s cohort of oocytes was divided into two equal groups.

Setting

Center for reproductive care.

Patients

Twenty men with OA.

Interventions

Motile spermatozoa were collected using PESA. Half of the oocytes were used for intracytoplasmic sperm injection (ICSI). The rest were inseminated briefly with PESA sperm in vitro fertilization (IVF). After 4–5 h, the remaining cumulus cells were removed mechanically for second polar body observation to decide whether to apply “rescue” ICSI (RE-ICSI).

Main outcome measures

Rates of oocyte maturation, fertilization, cleavage, and good quality embryos. Numbers of available embryos and good quality embryos were compared between PESA-IVF (using a short incubation protocol + rescue ICSI) group and PESA-ICSI group.

Results

In the short time insemination group, cumulus cells were dispersed by PESA spermatozoa. No second polar bodies were found, so RE-ICSI was done. PESA-IVF + RE-ICSI and PESA-ICSI outcomes were comparable in terms of fertilization rates, 2PN cleavage rate and good quality embryo rates with no statistically significant differences.

Conclusions

PESA sperm without centrifugation could disperse the cumulus cells but were infertile and therefore could substitute for synthetic hyaluronidase. The outcomes of PESA-IVF with rescue ICSI were equivalent to PESA-ICSI. Using spermatozoa obtained by PESA and IVF before RE-ICIS is a viable treatment for men with OA.     

A comparison of the morphology of testicular, epididymal, and ejaculated sperm from fertile men and men with obstructive azoospermia

Objective: To assess the morphology of testicular, epididymal, and ejaculated sperm.

Design: Morphology of the three types of sperm was assessed by using Tygerberg strict criteria.

Setting: The Regional Fertility Center, Royal Maternity Hospital, Belfast, Northern Ireland, United Kingdom.

Patient(s): Thirty-two men with obstructive azoospermia and 10 fertile men.

Intervention(s): Trucut needle testicular biopsy and percutaneous epididymal sperm aspiration under local anesthetic.

Main Outcome Measure(s): Percentages of normal sperm and sperm with head, midpiece, and tail defects for testicular, epididymal, and ejaculated sperm. Testicular sperm morphology in men with obstructive azoospermia was compared with that of fertile men.

Result(s): The percentage of normal testicular sperm (4.3%) differed significantly from the percentages of normal epididymal (10.8%) and ejaculated sperm (9.6%). Testicular sperm morphology in men with obstructive azoospermia did not differ from that in fertile men.

Conclusion(s): Tygerberg strict criteria are not suitable for the assessment of testicular sperm morphology.     

Y chromosome and new concept of azoospermia factor

The completion of a draft sequence of the entire human genome in 2001 was followed by a complete sequencing of the Y chromosome in 2003. It is now possible to refer to a physical map of the Y chromosome. The Y chromosome can be classified into X-transposed, X-degenerate and ampliconic sequences depending on the origins of its sequences. In particular, the ampliconic sequences are complexes of massive palindrome structures in which sequences having higher than 99.9% homology are present symmetrically. Interestingly, palindromic repeats may undergo frequent gene conversion associated with intrachromosomal recombination and play an important role in the maintenance of the genetic materials of the Y chromosome. The azoospermia factor (AZF) region of the ampliconic region is the most probable candidate for spermatogenesis, and forms a palindrome structure. Thus, there is a limit in the detection of microdeletion using conventional sequence-tagged sites based on polymerase chain reaction because of their structure. It is now necessary to update the AZF concept.     

A rational approach to the management of varicocele-associated nonobstructive azoospermia

A consensus needs to be reached on a rational approach to infertile men with varicocele-associated nonobstructive azoospermia. Future studies are warranted to understand the mechanism behind the variable influence of varicocele on testicular function, which causes partial or complete damage of spermatogenesis in some cases and leaves it unaltered in others.     

The role of varicocele repair in nonobstructive azoospermia must be evaluated with controlled trials rather than observational studies

Certainly, varicoceles can have a substantive effect on sperm production in infertile males. In addition, varicocele repair may optimize sperm production. However, additional studies and evaluation of the role of varicocele repair in men with this condition (nonobstructive azoospermia) are warranted.     

Diagnostic testicular biopsy before varicocele repair plays a realistic and important role

We believe that diagnostic testicular biopsy before varicocele repair is important, despite the risks.     

Prediction of candidates for seminal tract reconstructive surgery among patients with clinically suspected idiopathic or inflammatory obstructive azoospermia

Background and Aim:  We reviewed the findings of scrotal exploration, histological examination and clinical parameters in patients with clinically suspected idiopathic or inflammatory obstructive azoospermia without confirmation by isolated testis biopsy in advance.
Methods:  The present study included 27 patients who underwent scrotal exploration for the purpose of vasoepididymostomy, with simultaneous testicular sperm extraction.
Results:  Sperm in the epididymis was proven in 11 patients (40.7%). In two of these patients, the vas deferens was obstructed on the seminal vesicle side. Histologically, normal spermatogenesis was seen in all patients. The 16 (59.2%) patients with no sperm in the epididymis included two with normal spermatogenesis. Serum follicle stimulating hormone (FSH) levels were significantly higher in men with no sperm in the epididymis in contrast to those in men with sperm proven in the epididymis ( P  = 0.0057). By using a cut-off point of 6.02 mIU/mL, serum FSH can predict the existence of sperm in the epididymis, with a sensitivity of 81.8%, a specificity of 81.2% and a positive predictive value of 75.0%.
Conclusion:  No more than a third of the patients in the present study who had clinically suspected obstructive azoospermia were actual candidates for vasoepidydimostomy. A serum FSH level cut-off point of 6.02 mIU/mL might be useful to determine its indication. (Reprod Med Biol 2006; 5 : 211–214)     

Genetic analysis of three polymorphic sites of the luteinizing hormone beta-subunit gene in infertile Korean men with nonobstructive azoospermia

OBJECTIVE: To investigate the genetic background of nonobstructive male factor infertility. DESIGN: Clinical and controlled study. PATIENT(S): Ninety-five nonobstructive male infertile patients (75 with azoospermia, 18 with oligoasthenoteratozoospermia, and two with oligozoospermia) and 200 healthy fertile control men. INTERVENTION(S): Patients were investigated for genetic background including karyotype, Yq chromosome deletion, and three polymorphisms of the LH beta-subunit gene (Trp8Arg, Ile15Thr, and Gly102Ser). MAIN OUTCOME MEASURE(S): To determine three polymorphisms of the LH beta-subunit gene. RESULT(S): An abnormal karyotype was found in 11 of the 75 patients with azoospermia and one of the 18 patients with oligoasthenoteratozoospermia. Eleven (12%) had one or more deleted sites at 13 loci on Yq. The Gly102Ser variant of the LH beta-subunit gene was not detected at all. The frequency of double Trp8Arg and Ile15Thr heterozygotes was similar between the fertile (14.5%, n = 200) and infertile (12.6%, n = 95) groups, with the exception of one homozygous mutation (Arg8 and Thr15) from patient with azoospermia. CONCLUSION(S): Three variants of the LH beta-subunit gene (Trp8Arg, Ile15Thr, and Gly102Ser) may not be associated with male factor infertility. We found one homozygous Arg8 and Thr15 mutation in a patient with azoospermia with normal hormone levels (FSH, LH, PRL, T), a normal karyotype, and no Yq microdeletions.     

Intracytoplasmic sperm injection with testicular spermatozoa is less successful in men with nonobstructive azoospermia than in men with obstructive azoospermia

OBJECTIVE: To assess the efficiency of intracytoplasmic sperm injection (ICSI) using testicular spermatozoa in cases of nonobstructive azoospermia. DESIGN: Retrospective case series. SETTING: Tertiary university-based infertility center. PATIENT(S): Overall, 595 couples were included. In 360 couples, the man had normal spermatogenesis. In 118, 85, and 32 couples the man had germ-cell aplasia, maturation arrest, and tubular sclerosis/atrophy, all with focal spermatogenesis present. INTERVENTION(S): We performed 911 ICSI cycles using fresh sperm obtained after testicular biopsies: 306 ICSI cycles used testicular sperm from men with nonobstructive azoospermia, and 605 ICSI cycles used testicular sperm from men with obstructive azoospermia. MAIN OUTCOME MEASURE(S): Fertilization, cleavage, implantation, and pregnancy rates. RESULT(S): Overall, the 2PN fertilization rate was lower in the nonobstructive group: 48.5% vs. 59.7%. There were no differences in in vitro development or in the morphological quality of the embryos. In the nonobstructive group, a total of 718 embryos were transferred (262 transfers) vs. 1,525 embryos in the obstructive group (544 transfers). Both the clinical implantation rate and clinical pregnancy rate per cycle were significantly lower in the nonobstructive group compared with the obstructive group: 8.6% vs. 12.5% and 15.4% vs. 24.0%, respectively. CONCLUSION(S): A statistically significant lower rate of fertilization and pregnancy results from ICSI with testicular sperm from men with nonobstructive azoospermia, compared with men with obstructive azoospermia.     

Chromosome abnormalities in embryos derived from microsurgical epididymal sperm aspiration and testicular sperm extraction

ObjectiveTo evaluate the patterns of chromosome abnormalities in embryos derived from intracytoplasmic sperm injection (ICSI) in microsurgical epididymal sperm aspiration (MESA) or testicular sperm extraction (TESE) in comparison to embryos that are derived from naturally ejaculated (EJAC) patients.Materials and methodsMale partners with azoospermia who required MESA or TESE for ICSI were studied for chromosomal abnormalities. The ICSI patients with EJAC sperm served as the control group. Preimplantation genetic diagnosis (PGD) was performed by fluorescence in situ hybridization (FISH). Chromosome abnormalities were categorized as polyploidy, haploidy, aneuploidy, and complex abnormality (which involves more than two chromosomes). Fertilization, embryo development, and patterns of chromosome abnormalities were accessed and evaluated.ResultsThere was no difference between the MESA, TESE, and EJAC patient groups in the rates of fertilization and pregnancy and the percentages of euploid embryos. In all three groups, less than one-half of the embryos for each group were normal (41 ± 31%, 48 ± 38%, and 48 ± 31% in MESA, TESA, and EJAC, respectively). Complex chromosomal abnormality was significantly more frequent in the MESA group than in the EJAC group (48.3% vs. 26.5%, respectively; p < 0.001). Furthermore, the overall pattern of chromosomal aneuploidy was similar among all three studied groups.ConclusionWe suggest that MESA and TESE, followed by ICSI and PGD, appear to be acceptable approaches for treating men with severe spermatogenesis impairment.