Pregnancy after intracytoplasmic sperm injection following extended sperm preparation and hormone therapy in an azoospermic man with maturation arrest and microlithiasis: a case report and literature review

In the management of azoospermia, a combination of testicular sperm extraction and intracytoplasmic sperm injection (ICSI) is usually the most successful option for fatherhood. However, an outstanding question remains: How can at least a few spermatozoa be obtained from the ejaculate, thus avoiding the need for a surgical procedure? A 36‐year‐old man presented to Assisted Reproduction Unit with his 26‐year‐old wife. The ultrasound assessment revealed bilateral microlithiasis. Two spermograms revealed absolute azoospermia. Levels of follicle‐stimulating hormone (FSH) and luteinising hormone were normal–low. The patient underwent 10 months of treatment with clomiphene citrate. A bilateral testicular sperm extraction failed to retrieve spermatozoa and revealed a maturation arrest at spermatocyte/spermatid stages depending on the tubules. Clomiphene citrate was replaced with recombinant FSH (rFSH). After 9‐month treatment with rFSH, motile spermatozoa from droplets of ejaculate pellet were cryopreserved as a single straw. Ovarian stimulation was provided using classic antagonist protocol, and five mature oocytes were collected. Two consecutive fresh semen samples on the day of ICSI yielded seven motile spermatozoa, and fertilisation was achieved in all five oocytes. On day 3, two embryos were transferred, yielding positive beta‐human chorionic gonadotropin and a healthy delivery of a boy and a girl.     

Testicular Sperm Retrieval in Azoospermic Men

ContextSperm retrieval in combination with IVF/ICSI is the only medical procedure for an azoospermic man to father a child. Different techniques, especially testicular sperm extraction (TESE), have evolved over time and have dramatically improved the outlook for men with testicular azoospermia. However sperm retrieval rates are associated not only with the operation proposed but especially with a distinct pattern of prognostic factors that must be effectively managed for all these infertile patients for their best benefit.ObjectivesTo review the etiology, clinical work-up including operative techniques, and prognostic factors for testicular sperm retrieval in azoospermic men to maximin clinical benefit by these procedures.Evidence AcquisitionData from basic and clinical studies with a defined, standardized approach pre- and postoperatively were analyzed.Evidence SynthesisDifferent standardized surgical techniques can be offered to extract spermatozoa of azoospermic men from either the epididymis and/or the testis for ICSI. Sperm retrieval offers a treatment for both patients with testicular azoospermia and men with obstructive azoospermia in cases where microsurgical refertilization is not an option or has already failed. Among surgical techniques testicular sperm extraction (TESE) and microsurgical epididymial sperm aspiration (MESA) have become the most popular techniques. However, also percutaneous techniques are employed due their easy feasibility and low costs. By utilizing these techniques together with kryopreservation of extracted spermatozoa a single surgical intervention is able to provide spermatozoa for several ICSI attempts. Extensive surgical interventions in the testis of azoospermic patients have raised concerns about the potential influence on the endocrine compartment of the testis, particularly in patients with small testes and low levels of testosterone.ConclusionsTesticular sperm retrieval is a feasible and successful procedure. Testicular spermatozoa can be retrieved from the testis in up to 70% of patients, even in cases with testicular azoospermia and severe disorders of spermatogenesis. However, surgical damage of the testis might also compromise the interstitial compartment of the testis with testosterone deficiency as a consequence. Conclusively, endocrine follow-up can be considered mandatory.     

High prevalence of urogenital infection/inflammation in patients with azoospermia does not impede surgical sperm retrieval

Considering infection/inflammation to be an important risk factor in male infertility, the aim of this study was to make a comprehensive evaluation of the prevalence of urogenital tract infection/inflammation and its potential impact on sperm retrieval in azoospermic patients. In this prospective study, 71 patients with azoospermia were subjected to an extensive andrological workup including comprehensive microbiological diagnostics (2‐glass test, semen, testicular swab and testicular tissue analysis) and testicular biopsy/testicular sperm extraction (TESE). Medical history suggested urogenital tract infection/inflammation in 7% of patients, 11% harboured STIs, 14% showed significant bacteriospermia, 15% had seminal inflammation, 17% fulfilled the MAGI definition, and 27% had relevant pathogens. At the testicular level, 1 patient had a swab positive for bacteria, no viruses were detected, tissue specimens never indicated pathogens, whereas histopathology revealed focal immune cell infiltrates in 23% of samples. Testicular sperm retrieval rate was 100% in obstructive and 46% in nonobstructive azoospermia. None of the infection/inflammation‐related variables was associated with the success of sperm retrieval or inflammatory lesions in the testis. The high prevalence of urogenital infection/inflammation among azoospermic men underpins their role as significant aetiologic factors in male infertility. However, this observation does not refer to the chances of sperm retrieval at the time of surgery/TESE.     

Sperm retrieval by microdissection testicular sperm extraction and intracytoplasmic sperm injection outcomes in nonobstructive azoospermic patients with Klinefelter syndrome

Klinefelter syndrome is the most frequent chromosomal abnormality in patients with nonobstructive azoospermia. The development of advanced assisted reproductive techniques, such as testicular sperm extraction and intracytoplasmic sperm injection, has provided the possibility of biological fathering in nonobstructive azoospermic patients with Klinefelter syndrome. We aimed to evaluate our sperm retrieval rate by microdissection testicular sperm extraction and to analyse the intracytoplasmic sperm injection outcomes in these patients. Medical records of 110 nonobstructive azoospermic patients with Klinefelter syndrome were retrospectively reviewed. We found that the sperm retrieval rate by microdissection testicular sperm extraction is lower than published reports on other types of secretory azoospermia. The statistical analyses yielded that age, FSH and testosterone levels as predictive factors for successful sperm retrieval.     

Beneficial effect of tamoxifen on sperm recovery in infertile men with nonobstructive azoospermia

About 10% of infertile men have azoospermia. After the introduction of microinjection [intracytoplasmic sperm injection (ICSI)], many of these men obtain the chance to be a father. But still in many cases of nonobstructive azoospermia, we are not able to find spermatozoa for ICSI. Medications may be able to increase the chance of finding spermatozoa in testis samples. So in this study, we evaluated the effect of tamoxifen citrate on the results of sperm recovery from testis tissue in infertile men with nonobstructive azoospermia. Thirty-two azoospermic infertile men with proved nonobstructive azoospermia were selected. Tamoxifen was administered for 3 months. Semen samples and in the cases of azoospermia second testis biopsy were taken, and the results were compared with the first samples. According to first testis samples, 13 patients had hypospermatogenesis, 9 had maturation arrest and 10 patients sertoli cell syndrome. After tamoxifen treatment, six patients showed spermatozoa in their ejaculates. From other patients all in hypospermatogenesis group, 75% in maturation arrest group and 20% in sertoli cell group showed spermatozoa in their second testis samples. Our study showed that treatment of patients with nonobstructive azoospermia with anti-oestrogenic drugs like tamoxifen can improve the results of sperm recovery in testis samples and also increase the chance of pregnancy by microinjection.     

Efficiency of percutaneous testicular sperm aspiration as a mode of sperm collection for intracytoplasmic sperm injection in nonobstructive azoospermia

PURPOSE: We determined the feasibility of obtaining mature spermatozoa for intracytoplasmic sperm injection (ICSI) by percutaneous testicular sperm aspiration in men with nonobstructive azoospermia. We also compared the results of ICSI using spermatozoa recovered by open excisional biopsy versus percutaneous testicular sperm aspiration. MATERIALS AND METHODS: A total of 84 men with nonobstructive azoospermia underwent percutaneous testicular sperm aspiration to recover testicular spermatozoa for ICSI on the day of ova retrieval from the wife. Percutaneous testicular sperm aspiration was performed with the patient under general anesthesia in the upper and lower poles of each testis. It was followed by immediate microscopic search of the aspirate to confirm the presence of spermatozoa. In the absence of spermatozoa open excisional biopsy was performed in the same setting. RESULTS: Percutaneous testicular sperm aspiration resulted in the recovery of mature spermatozoa in 45 men (53.6%). Of the remaining 39 men (46.4%) requiring open biopsy adequate spermatozoa were recovered in 28 (71.8%). Although the fertilization rate was significantly higher in the sperm aspiration group, the cleavage and pregnancy rates were similar in the 2 groups. CONCLUSIONS: Percutaneous testicular sperm aspiration was a successful initial approach to collect mature spermatozoa in a high proportion of men with nonobstructive azoospermia. It is safe, minimally invasive and well tolerated by all patients.     

Diagnostic findings from testis fine needle aspiration mapping in obstructed and nonobstructed azoospermic men

PURPOSE: Although helpful for defining extratesticular obstruction, the testis biopsy offers limited information on nonobstructive azoospermic testes. Guided by diagnostic biopsies, testis sperm extraction procedures fail in 25% to 50% of patients with nonobstructive azoospermia, largely because it is clinically difficult to know where sperm are located. To provide a more complete assessment of spermatogenesis in nonobstructive azoospermic patients and to simplify the confirmation of sperm production in men with obstruction, we use a systematic, fine needle aspiration "mapping" procedure. We summarize the diagnostic findings in a series of azoospermic men. MATERIALS AND METHODS: From 118 azoospermic infertile men (22 with obstructed and 96 with nonobstructed azoospermia) fine needle aspiration data were used to generate location specific, sperm frequency maps for obstructed and nonobstructive azoospermic testes to determine if "sperm rich" locations existed. RESULTS: Fine needle aspiration map analysis revealed that all aspiration locations from obstructed cases showed sperm. In men with nonobstructive azoospermia, sperm was identified in the right testis in 134 of 652 (20.5%) and in the left testis in 151 of 716 (21.1%) separate aspirations. Rates of sperm detection among various intratesticular sites were not statistically different. In 27.1% of cases the fine needle aspiration map found sperm in men with sperm negative biopsies. The likelihood of heterogeneity in fine needle aspiration sperm findings was 25% within individual nonobstructive azoospermic testes and 19.2% between testis sides. At post-procedure followup of 88 patients (74%), no clinical or surgical complications were observed. CONCLUSIONS: Testis fine needle aspiration mapping is a simple, reliable and informative diagnostic tool in the evaluation of azoospermic infertile men.     

Does varicocelectomy improve semen in men with azoospermia and clinically palpable varicocele?

The effectiveness of varicocelectomy in nonobstructive azoospermia is controversial. The current study assessed the efficacy of microsurgical subinguinal varicocelectomy in nonobstructive azoospermic men with palpable varicocele and to evaluate predictive parameters of outcome. We reviewed the records of 723 patients who had microsurgical varicocelectomy and diagnostic testicular biopsy between 2012 and 2016 at a tertiary medical centre. Data pertaining to the physical, laboratory (semen analysis and hormonal profile) and histopathology features were examined, exploring the predictors of improvement in semen analysis post-varicocelectomy. In total, 42 patients with mean age 35.71 ± 6.35 years were included. After a mean varicocelectomy follow-up of 6.7 months, motile spermatozoa in the ejaculate could be observed in 11 patients (26.2). Out of all the factors examined, only testicular histopathology significantly predicted post-varicocelectomy outcome, where 8/11 patients exhibited hypospermatogenesis, and 3/11 Sertoli cell-only regained spermatozoa in semen. Microsurgical varicocelectomy in nonobstructive azoospermic men with clinically palpable varicocele can result in sperm appearance in the ejaculate with the highest success expected in hypospermatogenesis.     

Probability of sperm detection in nonobstructive azoospermic men undergoing testicular sperm extraction procedures unrelated to clinical parameters

The study was conducted to evaluate the significance of preoperative clinical parameters for detection of mature testicular sperm cells in nonobstructive azoospermic men. Sixty-five consecutive men with nonobstructive azoospermia underwent testicular sperm extraction procedures. Testicular samples were analyzed histologically with patterns classified as mature spermatogenesis (normal or partial), arrest of spermatogenesis, and Sertoli cell only. Testicular sperm cells were isolated for use in an IVF/ICSI program. Histologic patterns and detection rate of sperm cells were correlated to clinical characteristics. Mature sperm cells were found in all levels of serum FSH. The men were divided into 3 groups based on their clinical characteristics (serum FSH level and testicular size). The distribution of the different testicular histologic patterns, as well as detection rate of sperm cells, was similar in all groups. No correlation was found between serum levels of FSH, LH, prolactin, or testosterone and sperm presence. None of these parameters, nor the testicular size and consistency, can serve as predictive variables of the histological pattern or the presence of mature sperm cells in the testicular biopsies in cases of nonobstructive azoospermia. Until an effective predictive tool is available, a trial of sperm retrieval is recommended for all azoospermic men independent of their clinical characteristics.     

The role of testicular biopsy in the modern management of male infertility.

PURPOSE: We evaluate the traditional role of isolated testicular biopsy as a diagnostic tool, as opposed to the value as a therapeutic procedure for azoospermic men. MATERIALS AND METHODS: The medical records of azoospermic patients who were evaluated, and treated between 1995 and 2000 were retrospectively analyzed for history, physical examination findings, endocrine profiles, testicular histology and sperm retrieval rates. Based on these parameters, cases were placed into diagnostic categories that included obstructive or nonobstructive azoospermia. Diagnostic parameters used to distinguish obstructive from nonobstructive azoospermia were subjected to statistical analysis with the t-test, analysis of variance and receiver operating characteristics curve. RESULTS: A total of 153 azoospermic men were included in our analysis. Of men with obstructive azoospermia 96% had follicle-stimulating hormone (FSH) 7.6 mIU/ml. or less, or testicular long axis greater than 4.6 cm. Conversely, 89% of men with nonobstructive azoospermia had FSH greater than 7.6 mIU/ml., or testicular long axis 4.6 cm. or less. Receiver operating characteristics analysis revealed that FSH, testicular long axis, and luteinizing hormone were the best individual diagnostic predictors, with areas 0.87, 0.83 and 0.79, respectively. CONCLUSIONS: In the vast majority of patients obstructive azoospermia may be distinguished clinically from nonobstructive azoospermia with a thorough analysis of diagnostic parameters. Based on this result, we believe that the isolated diagnostic testicular biopsy is rarely if ever indicated. Men with FSH 7.6 mIU/ml. or greater, or testicular long axis 4.6 cm. or less may be considered to have nonobstructive azoospermia and counseled accordingly. These men are best treated with therapeutic testicular biopsy and sperm extraction, with processing and cryopreservation for usage in in vitro fertilization and intracytoplasmic sperm injection if they accept advanced reproductive treatment. Diagnostic biopsy is of no other value in this group. Men with FSH 7.6 mIU/ml. or less, or testicular long axis greater than 4.6 cm. may elect to undergo reconstructive surgery with or without testicular biopsy and sperm extraction, or testicular biopsy and sperm extraction alone depending on their reproductive goals.     

Power Doppler ultrasound mapping in nonobstructive azoospermic patients prior to testicular sperm extraction

This study was conducted to localize the testicular regions, which have better blood circulation by power Doppler ultrasonography in patients with nonobstructive azoospermia before testicular sperm extraction (TESE), and to investigate whether these vascularized areas have a high sperm retrieval rate or not. We evaluated 110 testes of 55 cases that were diagnosed as nonobstructive azoospermia. The mean age of the study group was 33 years (range 26 to 42). Patients with Y chromosome microdeletions, karyotype and hormonal abnormalities (except elevated FSH levels) were excluded from the study. In all cases, testes were evaluated by power Doppler ultrasonography before testicular sperm extraction. Testis was divided vertically into five equal parts and the area with maximum vascularity was determined subjectively. During testicular sperm extraction, starting from best-perfused areas, biopsies were done. If no motile or sufficient amount of sperm was found, TESE procedure was tried on the contralateral testis. TESE were performed from 82 testes and for the regions that show good and poor vascularity. The sperm finding rate was 38% and 14%, respectively (OR = 3.55)(p = 0.001). Power Doppler ultrasound mapping of the testis in nonobstructive azoospermic cases is a reliable and informative method to assess spermatogenic foci. It is a noninvasive technique that minimizes the unnecessary removal of hormone producing tissue and gives chance to end the TESE earlier than currently practiced procedures.     

Uniform testicular maturation arrest: a unique subset of men with nonobstructive azoospermia

PURPOSE: We evaluated the clinical characteristics of men with uniform testicular maturation arrest and nonobstructive azoospermia or severe oligospermia, including the frequency of genetic defects and outcome of intracytoplasmic sperm injection with or without testicular sperm extraction. MATERIALS AND METHODS: We identified a group of 32 men with nonobstructive azoospermia or severe oligospermia, uniform maturation arrest (single spermatogenic pattern on biopsy), and normal follicle-stimulating hormone (7.6 IU/l or less). These patients were identified from 150 intracytoplasmic sperm injection candidates with severe oligospermia (less than 10,000/cc) and 600 men with nonobstructive azoospermia undergoing attempted testicular sperm extraction-intracytoplasmic sperm injection between November 1995 and September 2006. These patients were characterized based on the frequency of genetic anomalies (karyotype or Y chromosome microdeletions). Rates of sperm retrieval by testicular sperm extraction, fertilization and pregnancy after ICSI were measured. RESULTS: Genetic anomalies were more common (45%) in men with uniform maturation arrest and normal follicle-stimulating hormone than other men with nonobstructive azoospermia (17%) undergoing testicular sperm extraction at our center (p <0.001). They had a lower sperm retrieval rate with testicular sperm extraction compared to other nonobstructive azoospermia patients (41% vs 60%, p = 0.05). Fertilization rate (37%) and clinical pregnancy (13%) were significantly less common than in other men with nonobstructive azoospermia (54% and 49%, respectively, p <0.01). CONCLUSIONS: Patients with uniform maturation arrest and normal follicle-stimulating hormone are a clinically definable subgroup of men with nonobstructive azoospermia that have different treatment outcomes. They have a higher incidence of chromosomal abnormalities and Y chromosome microdeletions compared to other men with nonobstructive azoospermia. Despite having normal follicle-stimulating hormone and typically normal testicular volume, sperm retrieval may be difficult and the chance of successful pregnancy is limited.     

睾丸精子获取和单精子卵胞浆内注射术治疗非梗阻性无精子症不育

目的　探讨非梗阻性无精子症患者外科获取睾丸精子的方法和意义。　方法　 4 9例非梗阻性无精子症患者行开放睾丸活检和诊断性睾丸精子获取术 (TESE) ,诊断性TESE有精子者至少 3个月后行单精子卵胞浆内注射 (ICSI)治疗。　结果　 12例 (2 4 .9% )诊断性TESE中发现精子 ,其中 3例为生精减少 ,2例为生精阻滞 ,7例为Sertoli细胞综合征。睾丸体积、血FSH水平和睾丸病理类型不能准确预测是否有精子。 8例行ICSI治疗 ,7例 (87.5 % )再次TESE获得睾丸精子行显微注射 ,3例获得临床妊娠。　结论　非梗阻性无精子症患者有必要行诊断性TESE确定睾丸内是否存在精子 ,获取睾丸精子结合ICSI可以有效治疗非梗阻性无精子症不育。     

Clomiphene test and clomiphene therapy in idiopathic male infertility.

Clomiphene citrate, 50 mg/day, was administered to 105 patients with idiopathic azoospermia or oligoasthenospermia. Plasma FSH, LH, testosterone, and in a few cases estradiol were evaluated on day 0 and day 15 of therapy. Twelve other patients with no treatment were assayed in the same way. Statistical analysis demonstrated that, as a group, the infertile male population responds normally to clomiphene administration. On the other hand, three types of individual responses were recorded: complete positive response, dissociated positive response, and negative response. Sixty-nine patients were randomly selected for clomiphene therapy, 50 mg/day for 100 days; however, of 54 who completed the treatment schedule, only 11 showed elevated sperm counts. A study of correlations between hormonal and semen responses to clomiphene indicates that a complete or dissociated endocrine response is not an accurate predictor of possible semen amelioration on long-term therapy; on the other hand, sperm characteristics did not improve in those patients who did not demonstrate a positive hormonal response, mainly testosterone, on the 15th day of therapy.     

Morphology of testicular spermatozoa obtained by testicular sperm extraction in obstructive and nonobstructive azoospermic men and its relation to fertilization success in the in vitro fertilization-intracytoplasmic sperm injection system

The aim of the present study was to evaluate the morphology of testicular spermatozoa by 3 different determinants. Sperm cells were obtained and their morphology was evaluated from 27 testicular sperm extraction (TESE) operations, of which 20 men had nonobstructive azoospermia and 7 had obstructive azoospermia. In 17 cases, 2 biopsies were obtained from 2 different locations of the testis. Only mature spermatozoa presenting full-grown tail (tail dimension about 10-fold greater than the head dimension) were counted. Three characteristics of sperm morphology were evaluated: head dimensions, and acrosome and midpiece irregularities. The percentage of sperm cells with normal morphology (considering the 3 characteristics) in specimens from patients with obstructive and nonobstructive azoospermia were 47% +/- 4.6% and 29 +/- 1.8%, respectively (P < .01). The percentage of spermatozoa with normal head dimensions were 76% +/- 3.2% and 63% +/- 2.6% (P > .05), those with normal acrosome were 58% +/- 4.6% and 41% +/- 3.4% (P < .05), and those with normal midpiece were 74% +/- 4.1% and 67% +/- 1.6% (P > .05), in obstructive and nonobstructive azoospermia, respectively. No significant differences were observed in sperm morphology between different locations of the testis. Sperm morphological characteristics were not associated with fertilization rate in intracytoplasmic sperm injection (ICSI). Follicle-stimulation hormone and luteinizing hormone were inversely correlated with normal morphology of testicular spermatozoa (r = -0.49 and r = -0.47, respectively; P < .05). It can be concluded that a relatively high portion of testicular sperm are morphologically normal. The higher rate of normal spermatozoa in obstructive azoospermia compared with nonobstructive spermatozoa suggests that the factors leading to azoospermia may affect testicular sperm morphology. The morphological characteristics of testicular sperm do not affect fertilization rate in ICSI.     

显微切割睾丸活检在非梗阻性无精子症中的应用

一直以来,学者们认为非梗阻性无精子症因睾丸生精功能受损,导致精液中无精子,而无法生育自己的后代。但随着卵胞质内单精子注射技术的问世,近十几年来涌现出多种睾丸取精术(包括开放性睾丸活检、细针穿刺抽吸、显微切割睾丸活检等)。之后,大量研究表明非梗阻性无精子症患者睾丸中仍存有局部的生精灶,即使是Klinefelter综合征,也可成功取出精子。2010年欧洲泌尿外科学会(EAU)指南明确推荐非梗阻性无精子症采用开放性睾丸活检或显微切割睾丸活检取精。与开放性睾丸活检相比,显微切割睾丸活检的取精成功率高且并发症少,本文就其取精前预测指标、手术操作方法、取精成功率及术后并发症进行综述。     

Virtual azoospermia and cryptozoospermia--fresh/frozen testicular or ejaculate sperm for better IVF outcome?

Men diagnosed as having azoospermia occasionally have a few mature sperm cells in other ejaculates. Other men may have constant, yet very low quality and quantity of sperm cells in their ejaculates, resulting in poor intracytoplasmic sperm injection (ICSI) outcome. It has not been conclusively established which source of sperm cells is preferable for ICSI when both ejaculate and testicular (fresh or frozen) sperm cells are available. It is also unclear whether there is any advantage of fresh over frozen sperm if testicular sperm is to be used. We used ejaculate, testicular (fresh or frozen) sperm cells, or both for ICSI in 13 couples. Five of these couples initially underwent ICSI by testicular sperm extraction, because the males had total azoospermia, and in later cycles with ejaculate sperm cells. Ejaculate sperm cells were initially used for ICSI in the other 8 patients, and later with testicular sperm cells. The fertilization rate was significantly higher when fresh or frozen-thawed testicular sperm cells were used than when ejaculated sperm cells were used. Likewise, the quality of the embryos from testicular (fresh and frozen) sperm was higher than from ejaculated sperm (65.3% vs 53.2%, respectively, P < .05). The use of fresh testicular sperm yielded better implantation rates than both frozen testicular sperm and ejaculate. Therefore, fresh testicular sperm should be considered first for ICSI in patients with virtual azoospermia or cryptozoospermia because of their superior fertility.     

Microdissection testicular sperm extraction: an update

Patients with non-obstructive azoospermia (NOA) were once considered to be infertile with few treatment options due to the absence of sperm in the ejaculate. In the last two decades, the advent of intracytoplasmic sperm injection (ICSI), and the application of various testicular sperm retrieval techniques, including fine needle aspiration (FNA), conventional testicular sperm extraction (TESE) and microdissection testicular sperm extraction (micro-TESE) have revolutionized treatment in this group of men. Because most men with NOA will have isolated regions of spermatogenesis within the testis, studies have illustrated that sperm can be retrieved in most men with NOA, including Klinefelter''s syndrome (KS), prior history of chemotherapy and cryptorchidism. Micro-TESE, when compared with conventional TESE has a higher sperm retrieval rate (SRR) with fewer postoperative complications and negative effects on testicular function. In this article, we will compare the efficacy of the different procedures of sperm extraction, discuss the medical treatment and the role of testosterone optimization in men with NOA and describe the micro-TESE surgical technique. Furthermore, we will update our overall experience to allow counseling on the prognosis of sperm retrieval for the specific subsets of NOA.     

Quality of cryopreserved testicular sperm in patients with obstructive and nonobstructive azoospermia

PURPOSE: Sperm retrieved by testicular sperm extraction is routinely used to attempt pregnancy by in vitro fertilization-intracytoplasmic sperm injection. We evaluated the efficacy of cryopreserving testicular sperm collected by testicular sperm extraction at diagnostic biopsy. MATERIALS AND METHODS: A total of 73 men with obstructive and 42 with nonobstructive azoospermia underwent testicular sperm extraction at diagnostic biopsy. Sperm was retrieved and cryopreserved in all cases of obstruction and in 15 of nonobstructive azoospermia cases. Before freezing we determined sperm count, motility, morphology and viability, and after thawing we assessed sperm motility and viability. In 17 couples a total of 20 cycles of in vitro fertilization-intracytoplasmic sperm injection were performed and fertilization, cleavage and pregnancy rates were determined in cases of obstruction and nonobstruction. RESULTS: Sperm count and morphology were lower in the testicular biopsies of men with nonobstructive versus obstructive azoospermia. Motility was low or absent in all testicular sperm extraction specimens. Importantly, pre-freeze (63%) and post-thaw (31%) viability was the same in both patient groups. After in vitro fertilization-intracytoplasmic sperm injection using frozen and thawed testicular sperm the fertilization, cleavage, implantation and clinical pregnancy rates were 60, 86, 16 and 50%, respectively. Using cryopreserved sperm we observed no differences in outcome of any in vitro fertilization-intracytoplasmic sperm injection procedure in patients with obstructive versus nonobstructive azoospermia. CONCLUSIONS: Cryopreservation of testicular sperm provides enough good quality sperm after thawing to result in excellent in vitro fertilization-intracytoplasmic sperm injection outcomes. Cryopreservation does not adversely affect intracytoplasmic sperm injection outcomes, including pregnancy rate. Therefore, we recommend routine testicular sperm extraction and cryopreservation of sperm at testicular biopsy.     

Testicular sperm extraction with intracytoplasmic sperm injection for nonobstructive azoospermia: testicular histology can predict success of sperm retrieval

PURPOSE: We present treatment results of testicular sperm extraction with intracytoplasmic sperm injection for men with nonobstructive azoospermia and reevaluate the role of testicular histology on open diagnostic testicular biopsy as a predictor of sperm retrieval success. MATERIALS AND METHODS: We evaluated 75 men diagnosed with nonobstructive azoospermia. Cases were categorized into 3 groups of hypospermatogenesis, maturation arrest or Sertoli-cell-only based on the most advanced pattern of spermatogenesis seen on histology. A total of 81 testicular sperm extractions with intracytoplasmic sperm injection were performed for these 75 men. The main outcome measures reviewed included sperm retrieval, fertilization and pregnancy rates with intracytoplasmic sperm injection. Sperm retrieval success rates for men in the 3 histological categories were compared. RESULTS: Spermatozoa were successfully retrieved during 47 of 81 (58%) testicular sperm extraction attempts, with subsequent fertilization of 268 of 439 (61%) injected metaphase II oocytes using intracytoplasmic sperm injection. Clinical pregnancies were obtained in 26 of 47 (55%) cycles when sperm were retrieved, with ongoing pregnancies or live deliveries for 20 of 47 (43%). Of 39 men with hypospermatogenesis on diagnostic biopsy 31 (79%) had successful sperm retrieval, compared to 9 of 19 (47%) with maturation arrest and 5 of 21 (24%) with a pure Sertolicell-only pattern. CONCLUSIONS: Critical examination of the most advanced pattern of spermatogenesis from open diagnostic testis biopsy allows prediction of sperm retrieval success with testicular sperm extraction. In this study population spermatozoa were retrieved in 58% of attempts. When this testicular sperm was used with intracytoplasmic sperm injection, clinical pregnancy rate was 55% for men with nonobstructive azoospermia.