Outcome of first and repeated testicular sperm extraction and ICSI in patients with non-obstructive azoospermia

BACKGROUND: It is unclear whether or not testicular sperm extraction (TESE) should be repeated for patients in whom no sperm were found during their first TESE attempt. METHODS AND RESULTS: The outcome of repeated TESE was evaluated in patients with non-obstructive azoospermia (NOA) after failing to obtain sperm in their first extraction attempt, or having used all available cryopreserved testicular tissue. Out of 83 patients with NOA, patients repeated TESE two (n = 22), three (n = 8), four (n = 6) and five (n = 3) times. Distribution of main testicular histology included germ cell aplasia (55%), maturation arrest (29%) and germ cell hypoplasia (16%). The first TESE yielded mature sperm for ICSI in 39% of patients (sp+), and failed in the remaining 61% (sp-). A second TESE yielded mature sperm in 1/4 from the sp- group and in 16/18 from the sp+ group. At the third, fourth and fifth trials, 8/8, 5/6 and 3/3 of the original sp+ patients were sp+ again respectively. Compared with the outcome of the first trial, all further trials did not differ statistically in the rate of fertilization (54 versus 49%), implantation (9.5 versus 5.4%), or clinical pregnancy/cycle (19 versus 15%). No pregnancies were achieved among the three patients after their fifth TESE. Pregnancies occurred in all histological groups, except maturation arrest. CONCLUSIONS: The outcome of repeated TESE cycles, up to the fourth trial, justifies the procedure.     

Outcome of testicular sperm recovery and ICSI in patients with non-obstructive azoospermia with a history of orchidopexy

BACKGROUND: Little is known about sperm recovery and ICSI using testicular sperm from men with non-obstructive azoospermia who had a previous orchidopexy. We therefore studied the sperm recovery in this subgroup and evaluated clinical parameters predicting successful sperm retrieval and the outcome of ICSI. METHODS: A total of 79 non-obstructive azoospermic men with a history of orchidopexy underwent a sperm recovery procedure. The predictive value of clinical parameters such as age at sperm retrieval, age at orchidopexy, testicular volume, FSH, FSH/LH ratio, testosterone and androgen sensitivity index (LH x testosterone) for successful testicular sperm retrieval was evaluated using receiver operating characteristics (ROC) curve analysis. A comparison between 64 ICSI cycles performed in these couples and 92 cycles performed in couples in which the men had an unexplained non-obstructive azoospermia was carried out. RESULTS: Testicular spermatozoa were recovered in 41 patients (52%). The mean age at orchidopexy of the patients with a positive sperm recovery was 10.6 years [95% confidence interval (CI) 7.3-13.8] versus 15.5 years (95% CI 11.3-19.8) for those where no spermatozoa were found. The mean testicular volume of the largest testis of patients with spermatozoa found was 10 ml (95% CI 8.3-11.9) versus 8.5 ml (95% CI 5.8-11.1) in patients with no spermatozoa found. The mean FSH and testosterone value for patients with successful and unsuccessful sperm recovery, respectively, was 24.1 IU/l (95% CI 17.9-30.3) and 4.4 ng/ml (95% CI 3.7-5.1) versus 28.8 IU/l (95% CI 19.4-38.2) and 3.4 ng/ml (95% CI 2.2-4.5). All clinical and biological parameters examined failed to predict the outcome of the testicular sperm extraction. No differences were observed between the orchidopexy and unexplained group for the number of oocytes retrieved, fertilization rate, embryo quality, pregnancy rate and implantation rate. CONCLUSIONS: As in the population of men with non-obstructive azoospermia, the sperm recovery rate for patients with a history of orchidopexy is approximately 50% and there are currently no clinical parameters predicting successful sperm retrieval in this subpopulation of patients. The outcome of the ICSI cycles is comparable with that in the population of men with non-obstructive azoospermia.     

Serum inhibin B cannot predict testicular sperm retrieval in patients with non-obstructive azoospermia

BACKGROUND: Serum inhibin B, a direct product of the Sertoli cells, may serve as a marker of spermatogenesis. The present retrospective study aimed at evaluating the predictive value of inhibin B for retrieving testicular sperm in non-obstructive azoospermic men. METHODS: The serum inhibin B concentration before sperm retrieval was reviewed in 185 non-obstructive azoospermic patients. RESULTS: Testicular sperm were successfully recovered in 92 of 185 patients (49.7%). The mean inhibin B concentration in these patients was 37.3 pg/ml. No sperm were found in 93 patients (50.3%), and the mean serum inhibin B concentration was 44.9 pg/ml. The discrimination between successful and unsuccessful sperm retrieval was analysed using the receiver operating characteristics (ROC) curve analysis. The best discriminating inhibin B concentration was 13.7 pg/ml (sensitivity 44.6%, specificity 63.4%) with an area under the ROC curve (AUC) of 0.51. Combining both serum FSH and inhibin B did not improve the predictive value: the AUC of inhibin B in men with a serum FSH concentration <25 and > or = 25 IU/l (being the best threshold value in the population studied) was respectively 0.53 and 0.50. The AUC of the inhibin B:FSH ratios was 0.55. CONCLUSIONS: This analysis shows that inhibin B, either alone or in combination with serum FSH, fails to predict the presence of sperm in men with non-obstructive azoospermia undergoing testicular sperm extraction.     

Serum inhibin B determination is predictive of successful testicular sperm extraction in men with non-obstructive azoospermia

Recent work indicates that serum inhibin B is a useful marker of spermatogenesis and inhibin B production sufficient to maintain detectable serum concentrations in adults depends on spermatogenic activity. The purpose of the present study was to investigate the usefulness of serum inhibin B measurement to predict the success of testicular sperm extraction (TESE) in 17 men with nonobstructive azoospermia to be treated by intracytoplasmic sperm injection (ICSI) (group 1). Two additional groups were used as positive controls; group 2 comprised 22 infertile men having obstructive azoospermia, and group 3, which included 29 semen donors having normal seminal parameters. Follicle stimulating hormone (FSH) was significantly higher (P < 0.01) and inhibin B significantly lower (P < 0.001), in group 1 as compared with groups 2 and 3. Serum inhibin B concentrations were significantly higher (P < 0.001) among successful TESE men as compared with those having failed TESE. In contrast, no differences were detected between these two groups with respect to serum FSH or testicular size. In addition, serum inhibin B but not FSH discriminated between successful and failed TESE in group 1 subjects as compared with control groups. According to the receiver operating characteristics curve analysis, the best inhibin B value for discriminating between successful and failed TESE was >40 pg/ml (sensitivity 90%, specificity 100%). It is concluded that inhibin B measurement is a useful non-invasive predictor of spermatogenesis and thus, all azoospermic males should have serum inhibin B concentrations determined in addition to FSH measurement and karyotyping prior to undergoing TESE.     

Testicular sperm extraction (TESE) and ICSI in patients with permanent azoospermia after chemotherapy

BACKGROUND: Patients persistently azoospermic after chemotherapy have been considered traditionally as sterile unless sperm was frozen before therapy. Recent advances during the last decade combining testicular sperm extraction (TESE) and ICSI in patients with non-obstructive azoospermia allow these males to father their own genetic offspring. METHODS: A retrospective study was conducted of 12 patients with non-obstructive azoospermia after chemotherapy undergoing TESE between 1995 and 2002. Cancer type and anti-neoplastic treatments were recorded, together with maximum testicular volume, serum FSH levels and testicular histopathology. When TESE was successful, spermatozoa were cryopreserved for performing ICSI later. RESULTS: In five patients (41.6%) motile spermatozoa for cryopreservation and ICSI were retrieved. Four of them had received chemotherapy for testicular cancer, and one had been treated by chemotherapy/radiotherapy for Hodgkin's disease. Clinical and histological parameters were unable to predict with certainty TESE outcome in an individual patient. Eight ICSI cycles were performed on five couples and one pregnancy was obtained which resulted in the delivery of a healthy girl. CONCLUSION: Some patients with permanent azoospermia after chemotherapy can be successfully treated by TESE-ICSI. This procedure, however, may have potential genetic risks. Therefore, freezing semen before starting gonadotoxic therapy is the strategy of choice, and patients should be counselled accordingly.     

Testicular fine needle aspiration: the alternative method for sperm retrieval in non-obstructive azoospermia.

The objective of this prospective open study was to determine the feasibility of obtaining mature spermatozoa for intracytoplasmic sperm injection (ICSI) by testicular fine needle aspiration (TEFNA) in men diagnosed with non-obstructive azoospermia. TEFNA consisted of a mean of 15 punctures and aspirations in each testis, using 23 gauge butterfly needles, connected to a 20 ml syringe with an aspiration handle. Patients (n = 85) underwent 111 TEFNA cycles. Mature testicular spermatozoa were recovered in 65 (58.5%) cycles from 50 (58.8%) patients. The sperm recovery rate by testicular histology was 14 out of 29 (48.3%) in patients with Sertoli cell-only, 13 out of 28 (46.4%) in patients with maturation arrest, 19 out of 20 (95%) in patients with hypospermatogenesis, four out of six (66.6%) in patients with tubular hyalinization due to non-mosaic Klinefelter's syndrome. No spermatozoa were found in two cases with post-irradiation fibrosis. ICSI was performed in all 65 cycles. In 58 cycles in which only the husbands' spermatozoa were used, 406 mature oocytes were injected, and 154 (37.9%) were normally fertilized. Of the 143 embryos that developed (92.8%), 119 were transferred in 42 cycles resulting in 18 clinical pregnancies (42. 8%), with 31 gestational sacs, providing an implantation rate of 26%. One abortion of a singleton pregnancy occurred (5.6%). No major side-effects, such as haematoma or infection were recorded. In conclusion, we have found TEFNA to be efficient, easy to learn, safe and well tolerated by all patients. In our opinion, TEFNA should be considered the first choice whenever sperm recovery is attempted in patients with non-obstructive azoospermia.     

Fertilization, pregnancy and embryo implantation rates after ICSI in cases of obstructive and non-obstructive azoospermia

The aetiology of azoospermia can be grossly divided into obstructive and non-obstructive causes. Although in both cases testicular spermatozoa can be used to treat male fertility, it is not well established whether success rates following intracytoplasmic sperm injection (ICSI) are comparable. Therefore, a retrospective analysis of fertilization, pregnancy and embryo implantation rates was performed following ICSI with testicular spermatozoa in obstructive or non-obstructive azoospermia. In total, 193 ICSI cycles were carried out with freshly retrieved testicular spermatozoa; in 139 cases of obstructive and 54 cases of non-obstructive azoospermia. The fertilization rate after ICSI with testicular spermatozoa in non-obstructive azoospermia was significantly lower than in obstructive azoospermia (67.8% versus 74.5%; P = 0.0167). Within the non-obstructive group, the fertilization rate in the group of maturation arrest (47.0%) was significantly lower than in case of Sertoli cell-only (SCO) syndrome (71.2%) or germ cell hypoplasia (79. 5%). Embryo quality on day 2 after ICSI was similar for all groups. Pregnancy rates per transfer between obstructive (36.8%) and non-obstructive groups (36.7%) were similar. In cases of maturation arrest the pregnancy rate per transfer was lowest (20.0%) although not significantly different from SCO syndrome or hypoplasia groups. Embryo implantation rates were not different between the obstructive (19.6%) and non-obstructive groups (25.8%), and were lowest in cases of germ cell hypoplasia (15.8%). This retrospective analysis shows that although fertilization rate after ICSI with testicular spermatozoa in non-obstructive azoospermia is significantly lower than in obstructive azoospermia, pregnancy and embryo implantation rates are similar.     

Factors influencing the outcome of ICSI in patients with obstructive and non-obstructive azoospermia: a comparative study

BACKGROUND: Factors influencing success of sperm retrieval in azoospermic patients and outcome of ICSI were evaluated. METHODS AND RESULTS: Uni- and multifactorial analysis were performed using logistic and stepwise analysis, following surgical sperm retrieval by percutaneous epididymal sperm aspiration (55 cycles) or testicular sperm extraction (142 cycles) in 52 and 123 patients with obstructive azoospermia (OA) and non-obstructive azoospermia (NOA) respectively. ICSI cycles using fresh or cryopreserved-thawed sperm were included. Sperm were retrieved to allow ICSI in 100 and 41% of OA and NOA patients, with no significant correlation with patients' age or FSH level. Occurrence of pregnancy was significantly correlated with female age (90th quantile: 38 years), number of oocytes retrieved (10th quantile: five oocytes) and number of oocytes injected (10th quantile: four oocytes). Sperm origin (epididymal versus testicular), status (fresh or thawed), male partner's age, and serum FSH had no significant effect upon implantation rate, pregnancy rate per embryo transfer or spontaneous miscarriage rate. CONCLUSIONS: In OA patients ICSI should be planned in conjunction with surgical sperm retrieval. In contrast, the lack of efficient non-invasive parameters to predict sperm retrieval in NOA suggests that elective surgical sperm retrieval may be offered to these patients prior to ovarian stimulation of their partners, especially when donor back-up is not an alternative. Female factors such as age and ovarian reserve have significant impact upon clinical success rates.     

A homozygous loss-of-function mutation in FBXO43 causes human non-obstructive azoospermia

Non-obstructive azoospermia (NOA) represents one of the most serious forms of male infertility caused by spermatogenic failure. Despite multiple genes found to be associated with human NOA, the genetic basis of this idiopathic disease remains largely unknown. FBXO43 is a direct inhibitor of the anaphase-promoting complex/cyclosome (APC/C) E3 ligase and crucially important in mouse spermatogenesis. In this study, for the first time, we identified a homozygous nonsense mutation in FBXO43 c.1747C > T:p.Gln583X in two NOA brothers from a Chinese consanguineous family via whole-exome sequencing. FBXO43 was absent from testicular tissue of the proband, and FBXO43-immunostaining signals were invisible in the affected seminiferous tubules. Furthermore, in humans, FBXO43 defects cause meiotic arrest within early diplotene of prophase I. The results here demonstrate the pathogenicity of this loss-of-function mutation and confirmed that spermatocytes were unable to complete meiotic divisions without FBXO43 in humans. In mouse testicular protein extracts, three subunits of the APC/C, including ANAPC2, ANAPC8 and ANAPC10, were validated to interact directly with FBXO43, whereas no interactions were detected for FBXO43 and SKP1. This study furthers our understanding of the genetic basis of human NOA and provides insights into FBXO43 and male infertility.     

Synaptic defects at meiosis I and non-obstructive azoospermia

BACKGROUND: Recent advances in immunofluorescence methodology have made it possible to directly monitor protein localization patterns in germ cells undergoing meiosis. We used this technology to examine the early stages of meiosis in testicular material obtained from men presenting for evaluation at infertility clinics. METHODS: Specifically, we compared meiotic progression, synapsis and recombination in 34 individuals with obstructive azoospermia ('controls') to 26 individuals with non-obstructive azoospermia (NOA) ('cases'). RESULTS: In 9 of the 26 cases, no germ cells were identified, but in the remaining 17, there was at least some progression through meiosis. Most of these individuals appeared to have normal levels of spermatogenic activity, with little evidence of meiotic impairment. However, in three individuals, we observed either complete or partial meiotic arrest associated with abnormalities in synapsis. CONCLUSIONS: This suggests that >10% of cases of unexplained NOA may be attributable to severe meiotic defects. The characterization of these meiotic arrest phenotypes may guide further research into the molecular basis of unexplained infertility.     

Birth after treatment of a male with seminoma and azoospermia with cryopreserved-thawed testicular tissue

The case of an infertile couple in which a testicular seminoma and azoospermia were discovered in the husband during infertility treatment is described. A small piece of testicular tissue, obtained by biopsy from the healthy testis [testicular sperm extraction (TESE)], was deep-frozen before oncology therapy was initiated. The patient's lymphocyte karyotype was normal and no Y microdeletions were found. After conclusion of oncology treatment, the tissue was thawed and successfully used in the intracytoplasmic sperm injection (ICSI) procedure. A healthy girl was born. Testicular tumours are known to impair fertility in the majority of patients, and fertility deteriorates further after cytotoxic and surgical oncology treatment. Until recently in Slovenia, for young oncology patients cryopreservation was applied only to high quality ejaculate fulfilling the criteria for intrauterine insemination or in-vitro fertilization after thawing. Failing that, the only remaining options were fertilization by donor spermatozoa or child adoption. New assisted reproductive technologies, of which the ICSI procedure is the most successful, are suitable for the treatment of only the most severe cases of male infertility. It is reasonable to cryopreserve even poor quality ejaculate prior to the oncology therapy, as well as testicular tissue in cases of azoospermia.     

Impact of repeated testicular fine needle aspirations (TEFNA) and testicular sperm extraction (TESE) on the microscopic morphology of the testis: an animal model

BACKGROUND: The aim of this work was to compare testicular histological changes occurring following testicular fine needle aspiration (TEFNA) and testicular sperm extraction (TESE). METHODS: TESE or TEFNA were performed on normal male rats, in a similar manner to azoospermic men. The animals were killed after 7, 14 and 31 days and their testes were examined. RESULTS: TESE caused chronic inflammation, occasional necrosis and degenerative changes in testicular germ cells in only approximately 10% of the remaining testicular tissue. TEFNA caused widespread architectural distortion of seminiferous tubules into irregular and deformed lumens lined by Sertoli cells only, as well as focal chronic inflammation, necrosis and degenerative changes accompanied by decreased spermatogenesis. Similar but less extensive changes were noted when fewer punctures were performed. When negative suction pressure was not applied during TEFNA, similar histological changes occurred, indicating that testicular damage was related to the puncture itself. Following either procedure, the contralateral non-operated testes were unaffected. CONCLUSION: In this animal model, TEFNA inflicts severe, progressive and irreversible damage on the architecture of the tubules in the needle's path. The multi-focal nature of this technique eventually leads to widespread tubular atrophy that is proportional to its extent. In contrast, TESE causes localized scarring and fibrosis, rendering most of the remaining testicle intact. The clinical relevance of such findings, produced in normal animal testes, to testes of azoospermic men, is yet to be determined.     

High implantation and pregnancy rates with testicular sperm extraction and intracytoplasmic sperm injection in obstructive and non-obstructive azoospermia

Thirty-two infertile couples with obstructive and non-obstructiveazoospermia were included in this study. Testicular sperm extraction(TESE) was performed in 16 obstructive azoospermic cases wheremicrosurgical sperm aspiration (MESA) or percutaneous spermaspiration (PESA) were impossible because of totally destroyedepididymis and 16 non-obstructive azoospermia cases with severespermatogenetic defect where the testicles were the only sourceof sperm cells. A total of 288 oocytes was obtained from 32females and 84% were injected. The fertilization rates (FR)with 2 pronuclei (PN) and cleavage rate were 50.8 and 68.2%respectively. A total of 15 pregnancies was achieved (53% perembryo transfer), nine from the obstructive and six from thenon-obstructive group. Four pregnancies resulted in clinicalabortion (26.6%). The ongoing pregnancy rate was 39.2% per embryotransfer (ET) and 343% per started cycle. A high implantationrate was also achieved (26.6% in non-obstructive and 30% inobstructive azoospermia group). Using testicular spermatozoain combination with ICSI in both obstructive and non-obstructiveazoospermic groups, high implantation and pregnancy rates canbe achieved.     

Meiotic defects in a man with non-obstructive azoospermia: case report

Infertile men have an increased frequency of aneuploid sperm. We have determined that decreased recombination is associated with the production of aneuploid sperm in humans. The aim of this study was to determine whether some cases of infertility are associated with decreased meiotic recombination. Analysis of the early stages of meiosis was performed in a 33-year-old man with non-obstructive azoospermia. Newly developed immunocytogenetic techniques were used to identify the synaptonemal complex (SC) in various stages of prophase. Antibodies to meiotic proteins identified the SC (SYN1/SCP3), the centromere (CREST) and recombination sites (MLH1). Only 36 meiotic spreads were recovered from the infertile man, compared with hundreds available from controls. One-third of the cells were in zygotene compared with 4% in controls, demonstrating an inability of bivalents to synapse and progress to pachytene. The infertile man had a greatly reduced frequency of recombination, with a mean of only 32.7 MLH1 foci/cell (range 1-60) compared with 46.0 (range 21-62) in control donors. A high proportion of cells (73%) contained at least one autosomal bivalent with zero MLH1 foci, compared with only 4.5% in control donors. Discontinuities in the SC were also more prevalent (68% of cells versus 26% in controls). This is the first demonstration of dramatic pachytene-stage abnormalities in an infertile man using these powerful new immunocytogenetic techniques.     

Outcome of intracytoplasmic sperm injection with testicular spermatozoa in obstructive and non-obstructive azoospermia

From 1 August 1993 until 30 September 1994, 69 couples sufferingfrom azoospermia underwent testicular sperm extraction and intracytoplasmicsperm injection. In 50 couples with obstructive azoospermiaa total of 631 meta-phase-II oocytes were injected after testicularsperm extraction yielding a 2-PN fertilization rate of 57%.In female patients <40 years of age an ongoing pregnancyrate per transfer of 42% (14/33) was obtained. So far, eighthealthy babies have been born, including two singletons andthree twin gestations. In 19 couples with non-obstructive azoospermiaa total of 264 metaphase-II oocytes were injected after testicularsperm extraction, yielding a 2-PN fertilization rate of 58%.An ongoing pregnancy rate per transfer of 31% (5/16) was established.So far, six healthy babies have been born including one singleton,one twin and one triplet gestation.     

Enzymatic digestion of testicular tissue may rescue the intracytoplasmic sperm injection cycle in some patients with non-obstructive azoospermia

Recovery of testicular spermatozoa from azoospermic patientswith testicular failure, followed by intracytoplasmic sperminjection (ICSI) is a recent advance in the treatment of maleinfertility. In most cases, free spermatozoa are recovered fromtesticular tissue after mechanical mincing of multiple biopsies.Testicular sperm retrieval, however, remains unsuccessful in30–50% of male patients suffering from Sertoli cell-onlysyndrome and maturation arrest. In this study, a strategy wasdeveloped in order to maximize the chance of sperm retrievalin difficult cases of testicular failure. The ultimate stepwas the use of enzymatic procedures (collagenase type IV) todissociate the testicular tissue completely. Testicular tissueof 41 patients for whom no spermatozoa were found after mechanicalmincing of the testicular tissue was investigated. In 14 outof the 41 cases (34%), enough spermatozoa for ICSI were foundafter fine mincing of multiple biopsies and several hours' searchin the cell suspension treated with the erythrocyte-lysing buffer(ELB). In 27 out of the 41 patients, no spermatozoa were foundeven after the use of ELB. In seven out of these 27 failures(26%), spermatozoa for ICSI were retrieved after enzymatic dissociationof the residual minced tissue pieces, thus making ICSI possibledespite failure to find spermatozoa with conventional mincing.From this study, we may conclude that enzymatic digestion oftesticular tissue is easy to perform, is not time-consumingand constitutes a successful method in reducing the sperm recoveryfailures in patients with non-obstructive azoospermia.     

Pregnancies achieved after frozen-thawed pronuclear oocytes obtained by intracytoplasmic sperm injection with spermatozoa extracted from frozen-thawed testicular tissues from non-obstructive azoospermic men.

The use of frozen-thawed testicular tissue as a source of spermatozoa for intracytoplasmic sperm injection (ICSI) in non-obstructive azoospermia yields favourable fertilization and pregnancy rates while avoiding both repetitive biopsies and unexpected cycle cancellations. Spermatozoa were obtained from frozen-thawed testicular biopsy specimens from 67 non-obstructive azoospermic men. Following fertilization, supernumerary two pronuclear (2PN) oocytes were frozen. After thawing, 17 cycles of embryo transfer were carried out with a mean number of 2.7 embryos and a mean cumulative embryo score (CES) of 18.3 per transfer. The clinical pregnancy and implantation rates per transfer in these cycles (23.5 and 8.3% respectively) were comparable to those of fresh embryo transfers (35.7 and 12.7% respectively) with a mean number of 2.7 embryos and a mean CES of 28.7 per transfer. Abortion rates, although higher with cryopreserved 2PN oocytes were not significantly different. With this approach, cryopreservation of supernumerary 2PN oocytes can be used to improve the cumulative pregnancy rates in a severely defective spermatogenetic population. To our knowledge, these are the first pregnancies reported which have been obtained by the transfer of cryopreserved pronuclear oocytes obtained from ICSI using cryopreserved testicular spermatozoa.     

Pregnancy outcome and neonatal data of children born after ICSI using testicular sperm in obstructive and non-obstructive azoospermia

BACKGROUND: Registries on outcome of ICSI pregnancies obtained with testicular sperm do not differentiate between obstructive (OA) and non-obstructive azoospermia (NOA). We evaluated the pregnancy outcome and neonatal data on children born after ICSI using testicular sperm of men with histologically proven OA or NOA. METHODS: Pregnancies obtained after ICSI using testicular sperm of men with defined NOA (n = 70) were compared with those of men with OA (n = 204). RESULTS: Multiple birth rates in NOA and OA couples, respectively, were 21 versus 27% (P = NS), overall preterm delivery rates were 38 versus 26% (NS), and prematurity rates were 24 versus 13% for singletons (NS) and 86 versus 54% for twins (relative risk 1.59, 95% confidence interval 1.04-2.42). Median gestational age for singletons was 38.3 versus 39.3 weeks, respectively (P < 0.05). The low birth weight rates were 34 versus 31%, respectively (NS). The early perinatal mortality rate was 66 versus 15 per 1000 births, respectively, (NS). Major congenital malformations were observed in 4 versus 3%, respectively, of the live born babies (NS). Prenatal karyotypes showed 7% de-novo abnormalities in the NOA group versus 1% in the OA group (NS). CONCLUSIONS: Our data do not show differences between NOA and OA pregnancies except for a strong tendency towards a lower gestational age in singletons and a higher percentage of premature twins in the NOA group. Although our data are based on a limited sample, the differences observed call for further analysis. Given the low pregnancy rates after ICSI with NOA, a multicentre study, differentiating NOA and OA patients, would be recommended.     

Testicular sperm retrieval and cryopreservation prior to initiating ovarian stimulation as the first line approach in patients with non-obstructive azoospermia.

The potency for fertilization and successful implantation was compared between fresh and cryopreserved testicular spermatozoa obtained from the same patient with non-obstructive azoospermia. Spermatozoa cryopreserved at the outset were also evaluated. Non-obstructive azoospermic men (n = 55) underwent testicular sperm extraction (TESE); mature spermatozoa were found in 33 (60%) of them. Of 57 intracytoplasmic sperm injection (ICSI) cycles in 25 patients, 15 used fresh spermatozoa (14 patients, group 1), 24 used the excess spermatozoa cryopreserved after 'fresh' ICSI (11 couples who did not conceive in the 'fresh' cycle, group 2) and 18 cycles used cryopreserved spermatozoa at the outset (11 other patients, group 3). Fertilization, cleavage, embryo quality, implantation and take home baby rates were not significantly different in groups 1 and 2, and 6/14 couples ultimately had healthy babies (42.8% cumulative take home baby rate per TESE). In group 3, neither the fertilization rate, embryo development, pregnancy nor implantation rates per embryo transfer were significantly different from groups 1 and 2. The cumulative delivery and ongoing pregnancy rate in this group was 36. 4%. Cryopreservation did not impair the availability of motile spermatozoa for ICSI. When immotile spermatozoa were injected, however, fertilization rate decreased dramatically. Since criteria for predicting the presence of spermatozoa in the testicular tissue of patients with non-obstructive azoospermia are inadequate, it is suggested that TESE be performed prior to initiating ovarian stimulation.     

A high predictive value of the first testicular fine needle aspiration in patients with non-obstructive azoospermia for sperm recovery at the subsequent attempt.

BACKGROUND: The objective of this retrospective study, which included 51 men with non-obstructive azoospermia, was to evaluate the predictive value of the results of the first sperm recovery attempt on the probability for sperm recovery in a second attempt. METHODS AND RESULTS: A positive testicular fine needle aspiration (TEFNA) was defined as the recovery of any number of mature sperm. At the first and second TEFNA attempts, mature sperm were recovered in 33 (64.7%) and 25 (49%) of 51 patients respectively. In 23 of the 33 (69.7%) patients with a positive first TEFNA, sperm were recovered at both attempts, whereas in only two of 18 (11.1%) with a negative first TEFNA, sperm were recovered at the second attempt. Our analysis revealed a high predictive value of the first TEFNA for sperm recovery at the subsequent attempt, with a mean positive predictive value of 69.7%, with the highest probability being 90.9% in hypospermatogenesis, 72.7% in Sertoli cell-only pattern, 75% in tubular hyalinization, and the lowest being 28.6% in maturation arrest. The mean negative predictive value was 88.9%, which was high in all categories (80% in Sertoli cell-only pattern and 100% in maturation arrest and tubular hyalinization). CONCLUSION: A second TEFNA attempt should be offered to all non-obstructive azoospermic patients with a positive first TEFNA. Patients with a negative first TEFNA may undergo a repeated attempt, but a donor sperm back-up is strongly advised.