Microdissection testicular sperm extraction: Prediction, outcome, and complications

Testicular spermatozoa can be retrieved successfully by the testicular sperm extraction (TESE) procedure and used for intracytoplasmic sperm injection in cases of non-obstructive azoospermia (NOA). The successful application of TESE depends on the identification of seminiferous tubules containing spermatozoa; testicular tubules of patients with NOA are usually heterogeneous, and TESE may not always be successful in these patients. Microdissection TESE with an operative microscope is advantageous because larger, more opaque, and whitish tubules, presumably containing germ cells with active spermatogenesis, can be identified directly. This procedure is currently the best method for the certain identification of sperm, resulting in a high spermatozoa retrieval rate and minimal postoperative complications. The present review considers the surgical procedure, outcome, prediction for spermatozoa retrieval, and postoperative complications of microdissection TESE.     

Achieved pregnancy with the delivery of a healthy child by TESE‐ICSI 7 years after bilateral adult orchidopexy: a case report

We report pregnancy with the delivery of a healthy child by TESE‐ICSI 7 years after bilateral adult orchidopexy. A 29‐year‐old patient presented with infertility and previous bilateral cryptorchidism, but no surgical treatment had ever been performed. His partner had been assessed by a gynaecologist, and no contributing female factors were detected. Orchidopexy and conventional testicular sperm extraction (TESE) were performed and microdissection TESE 10 months after orchidopexy. The second microdissection TESE with intracytoplasmic sperm injection (ICSI) was performed 7 years after orchidopexy. The couple achieved pregnancy with the delivery of a healthy child by TESE‐ICSI. It is concluded that bilateral orchidopexy in adulthood progresses spermatogenesis gradually, and microdissection TESE may succeed after a certain period of time following treatment.     

The diagnosis and treatment of the azoospermic patient in the age of intracytoplasmic sperm injection

Microsurgical reconstruction remains the treatment of choice for men with reconstructable obstructive azoospermia. Sperm retrieval techniques performed with ICSI are highly effective for men in whom reconstruction is not feasible. In men with nonobstructive azoospermia, the optimization of spermatogenesis with hormonal therapy and, when appropriate, microsurgical varicocelectomy can result in the appearance of adequate sperm in the ejaculate for ICSI. In men with persistent nonobstructive azoospermia, TESE with ICSI has provided encouraging results. Caution must be used when this ART is applied in couples in whom genetic aberrations are detected given certain inheritance of these anomalies, as the genetic consequences of this procedure have not been thoroughly elucidated. Just as the possibility of ICSI was thought to be inconceivable several decades ago, the advent of future sentinel discoveries will present the possibility for realization of achievements that now seem incredulous.     

Sperm Cells for Artificial Reproduction and Germ Cell Transplantation

Sperm retrieval for in vitro fertilization/intracytoplasmic sperm injection is the only medical procedure that enables a man with testicular azoospermia to father a child. In obstructive azoospermia after failed refertilization, microsurgical epididymal sperm aspiration is the gold standard, with retrieval rates up to 100%. In nonobstructive azoospermia (NOA), testicular spermatozoa (spermatids) can be recovered by testicular sperm extraction (TESE) in approximately half of the men. No parameters are available to definitively predict a successful recovery individually, but genetic factors, reduced testicular volume, and high serum follicle-stimulating hormone levels are associated with an unfavorable outcome. Retrieval surgery is well standardized, chiefly performed with microsurgical assistance and without severe local complications. Microsurgically assisted TESE (M-TESE) and TESE that is not microscopically supported in low-chance NOA patients may result in hypogonadism in the long term. In patients with Klinefelter syndrome, the outcome is worse with increasing age. For children before chemotherapy, M-TESE for stem cell preservation must be performed with minimal damage to the testicles.     

TESE und M-TESE

Modern techniques of testicular sperm extraction (TESE) make it possible for an infertile man to father a child. The operations are standardized to a large extent and the underlying morphological alterations of spermatogenesis also appear to be sufficiently known. Current research is focused on prognostic factors for the testicular material that determine the sperm retrieval rate and success rates after in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI).TESE and microTESE are accepted standard operations for testicular sperm retrieval for IVF/ICSI. Predictions for effective sperm recovery are addressed.     

Varicocelectomy: semen parameters and protamine deficiency

Different methods have been used to evaluate the beneficial effect of varicocelectomy; these include semen parameters and pregnancy rate. Because of high biological variability of semen parameters, sperm functional tests have been considered as an efficient end point in assessment of fertility. Therefore, the aim of this study was to evaluate the effect of varicocelectomy on semen parameters and sperm protamine deficiency in 192 patients. The results of the present study show that all the three semen parameters and percentage of sperms with normal protamine content have improved post-surgery. The cumulative pregnancy rate was 34.6%. Comparing the results of the semen parameters and protamine content between patients whose partner became pregnant to those who did not benefit from varicocelectomy before and 6 months after surgery, show that patients may benefit from varicocelectomy that had higher initial semen density and better sperm morphology prior to surgery. Detailed analyses of sperm morphology, along with aforementioned results reveal that the factors which account for pregnancy difference are: (i) improvement in early events of spermatogenesis, possibly during spermatocytogensis and reduction division; and (ii) late spermiogenesis events. Thus, it can be suggested that patients with low initial sperm count may benefit more from assisted reproductive techniques or varicocelectomy followed by assisted reproduction.     

Ultrastructural analysis of TESE and semen sperm tails from patients exhibiting absolute immotility on the day of ICSI

Sperm flagellar pathology was found to be the underlying cause of motility disorders that lead to male infertility. Conventional in vitro fertilization (IVF) procedures will fail when sperm show a total absence of motility. In such difficult cases intracytoplasmic sperm injection (ICSI) is the only available technique to fertilize an oocyte. Fertilization rates are low and may also be reduced when immotile sperm are used for ICSI from ejaculate of other than epididiymal or testicular origin. Presence of totally immotile sperm in the ejaculate on the day of ICSI if spermatogenesis is normal testicular sperm recovery can improve ICSI outcomes. But for patients having severe morphological or functional sperm defects embryos of lower quality tend to be produced when totally immotile sperm are used. In this study the 2 patients exhibiting totally immotile sperm in their ejaculates and TESE samples on the day of ICSI showed the same ultrastructural abnormalities. Peri-axonemal and axonemal abnormalities that were seen in association with sperm nucleus structural defects suggested that the source of sperm has no effect on morphologic characteristics and also reflects abnormality in both spermatogenesis and spermiogenesis. In this study the two patients who presented with oligoteratozoospermia with total immotility, using either ejaculate or TESE sperm fertilization and embryo development, can be obtained with ICSI, but no pregnancies were established after embryo transfers.     

Operative Spermiengewinnung

The introduction of intracytoplasmic sperm injection (ICSI) into the catalogue of assisted reproductive technologies in the mid-nineties has, for the first time, offered men who suffer from severe disorders of spermatogenesis and azoospermia the possibility of fathering a child. Different surgical techniques can be used to extract spermatozoa from these men from either the epididymis and/or the testis for ICSI. Surgical sperm retrieval offers a treatment for both patients with testicular or obstructive azoospermia in cases where microsurgical refertilization is not an option or has already failed. Among surgical techniques that have been developed over the years, microsurgical epididymial sperm aspiration (MESA) and testicular sperm extraction (TESE) have become the most popular. By utilizing these techniques together with the cryopreservation of extracted spermatozoa, a single surgical intervention is able to provide spermatozoa for several ICSI attempts.     

Surgical sperm retrieval

The introduction of intracytoplasmic sperm injection (ICSI) into the catalogue of assisted reproductive technologies in the mid-nineties has, for the first time, offered men who suffer from severe disorders of spermatogenesis and azoospermia the possibility of fathering a child. Different surgical techniques can be used to extract spermatozoa from these men from either the epididymis and/or the testis for ICSI. Surgical sperm retrieval offers a treatment for both patients with testicular or obstructive azoospermia in cases where microsurgical refertilization is not an option or has already failed. Among surgical techniques that have been developed over the years, microsurgical epididymial sperm aspiration (MESA) and testicular sperm extraction (TESE) have become the most popular. By utilizing these techniques together with the cryopreservation of extracted spermatozoa, a single surgical intervention is able to provide spermatozoa for several ICSI attempts.     

In the era of micro‐dissection sperm retrieval (m‐TESE) is an isolated testicular biopsy necessary in the management of men with non‐obstructive azoospermia?

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? There are a number of ways to retrieve sperm from the testis however there is no universal consensus as to which is the best approach. Furthermore, there is controversy as to whether a diagnostic biopsy has a role in management of non‐obstructive azoospermia (NOA). This study gives support to the growing consensus that micro‐dissection TESE (m‐TESE) is the optimum approach to retrieve sperm in patients with NOA even when previous attempts have failed. Moreover, it strongly suggests that histology is unreliable in determining success rates with m‐TESE and therefore isolated diagnostic biopsies should not be performed.

OBJECTIVES

• ? To assess the outcome of sperm retrieval using micro‐dissection‐TESE (m‐TESE) and simultaneous diagnostic biopsy in NOA to determine if the final definitive histology correlated with the outcome of sperm retrieval by m‐TESE in men with NOA.
• ? To determine if there was a correlation between FSH levels and positive sperm retrieval rates and assessed the success rate of m‐TESE as either a primary or a salvage procedure after previous negative sperm retrieval.
• ? The EAU guidelines (2010) recommend that in men with non obstructive azoospermia ‘a testicular biopsy is the best procedure to define the histological diagnosis and the possibility of finding sperm’. However, these guidelines do not identify which patients should have a diagnostic biopsy and if this biopsy should be performed as an isolated procedure or synchronously with sperm retrieval. It is also suggested that there is a correlation between the histological diagnosis and possibility of finding sperm on testis biopsy.

PATIENTS AND METHODS

• ? 100 men with NOA underwent a m‐TESE sperm retrieval between 2005 and 2010 at a single centre.
• ? All patients underwent hormonal analysis (serum FSH, Testosterone and LH levels) and genetic analyses after full counselling including; Y‐deletion, CF‐gene analysis and karyotype.
• ? Thirty five men had previously undergone unsuccessful TESA/TESE or diagnostic biopsy at other centres. All patients underwent synchronous sperm retrieval and biopsy of the testis, which was sent for histopathological examination on the day of an ICSI cycle or as an isolated procedure.

RESULTS

• ? Mean age of patients was 37.25 (range 29–56 years). The mean serum FSH levels in the Sertoli cell only, maturation arrest and hypospermatogenesis groups were 21.3 IU/L (2.8–75), 16.18 (1.6–67) and 14.17 IU/L (0.8–42.3) respectively. SR rates in the respective groups were 42.85%, 26.6% and 75.86% (P= 0.023). There were no post‐operative complications.
• ? In the 35 men who had previously undergone unsuccessful procedures elsewhere, the SR rates were 57.1%. The overall sperm retrieval rate was 50%. There was no correlation between SR and FSH levels (P= 0.28).

CONCLUSION

• ? M‐TESE should be considered the gold standard for retrieval of testicular sperm in NOA, even in cases where there has been previously unsuccessful attempts. FSH levels and histology cannot be used to predict the success of sperm retrieval. An isolated diagnostic testicular biopsy is not recommended in men with NOA, as a significant proportion of men undergoing m‐TESE will have successful a sperm retrieval irrespective of previous histology or previous unsuccessful surgery.

     

Treatment of azoospermia: surgical sperm retrieval (MESA, TESE, micro-TESE)

The introduction of intracytoplasmic sperm injection (ICSI) into the spectrum of assisted reproductive technologies has offered men who suffer from severe disorders of spermatogenesis and azoospermia the possibility of fathering a child. Different surgical techniques can be used to extract spermatozoa from these men from either the epididymis and/or the testis. Surgical sperm retrieval offers a treatment for patients with testicular and/or obstructive azoospermia in cases where microsurgical refertilization is not an option or has already failed. Among surgical techniques that have been explored over the years, microsurgical epididymal sperm aspiration (MESA) and testicular sperm extraction (TESE) have become the most popular. Percutaneous techniques (such as TEFNA) are available but have disadvantages versus open surgical procedures. Together with cryopreservation of extracted spermatozoa, these techniques facilitate retrieval of spermatozoa for several ICSI attempts by a single surgical intervention.     

Comparison of efficacy of two techniques for testicular sperm retrieval in nonobstructive azoospermia: multifocal testicular sperm extraction versus multifocal testicular sperm aspiration

To compare the efficacy of 2 sperm-retrieval procedures, testicular sperm extraction (TESE) and testicular sperm aspiration (TESA), during the same procedure using the same subjects as their own controls. The presence of mature testicular sperm cells and motility were evaluated in 87 men with nonobstructive azoospermia (NOA) by means of multifocal TESE and multifocal TESA, which were performed during the same procedure using the same subjects as their own controls. Sperm cells were recovered by TESE in 54 cases, but by TESA in only 36 cases. There were significantly more cases (n = 20) in which sperm cells were recovered by TESE only, compared with 2 cases in whom cells were recovered by TESA only (McNemar's test, P < .001). The mean number of locations in each testis in which sperm cells were detected was significantly higher in the TESE group. In significantly more cases (n = 27), motility was observed in TESE material only, compared with 3 cases in which motility was present in material extracted by TESA only (McNemar's test, P < .001). Mean number of locations in each testis with motile sperm cells was significantly higher in the TESE group. The TESE procedure yielded significantly more sperm cells, as was also reflected by the difference in number of straws with cryopreserved sperm. This comparative prospective clinical study revealed that multifocal TESE is more efficient than multifocal TESA for sperm detection and recovery in men with NOA and should be the procedure of choice for sperm retrieval for them.     

Can serum Inhibin B and FSH levels, testicular histology and volume predict the outcome of testicular sperm extraction in patients with non-obstructive azoospermia?

Introduction In our study, we evaluated the diagnostic accuracy of serum follicle stimulating hormone (FSH), Inhibin B, testicular volumes and distribution of testicular sperm extraction (TESE) outcome according to the histological diagnosis in men with non-obstructive azoospermia. Materials and methods Between February 2001 and April 2002, 66 men presenting with infertility of at least 1 year were found to have non-obstructive azoospermia. Serum FSH and Inhibin B levels, testicular volumes and pathological analysis were reviewed retrospectively using medical records of these patients. Results Of 66 patients, 52 were enrolled into the study and sperm extraction was successful in 31 of 52 patients (59.6%). There was no statistically significant difference between the patients who had successful and unsuccessful TESE in terms of mean serum Inhibin B, FSH levels and testicular volumes (P > 0.05). The area under ROC analysis for serum Inhibin, serum FSH and testicular volume was 0.557, 0.523 and 0.479, respectively. For Inhibin B, the best cut-off value for discriminating between successful and failed TESE at 90% sensitivity was 6.25 with a very low level of specificity (14%) and diagnostic accuracy that was 53.8. Conclusion Besides the controversies about the direct marker role of serum Inhibin B in determination of spermatogenesis, it does not seem to give a clue about the prediction of sperm presence before TESE. Because of the conflicting results in the literature, the potential role of serum Inhibin B as a marker for prediction of sperm presence in testis is yet to be determined.     

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.     

Testicular sperm extraction for non-obstructive azoospermia: results with conventional and microsurgical techniques

Testicular sperm extraction (TESE) was performed on patients with non-obstructive azoospermia using the conventional or microdissection technique. First, conventional TESE was attempted on all patients. If the sperm was retrieved successfully, the TESE procedure was terminated. Microdissection TESE was indicated only for patients for whom the conventional sperm retrieval was unsuccessful. Sperm was successfully retrieved with conventional TESE from four (24%) of 17 patients with non-obstructive azoospermia. The remaining 13 patients underwent microdissection TESE and sperm was successfully retrieved from four of them. Application of the microdissection technique resulted in an improvement in sperm retrieval rates from 24% with conventional TESE to 48% when combined with the microdissection technique. None of the patients showed any acute or chronic complications after TESE. Intracytoplasmic sperm injection (ICSI) was performed on five of the eight patients with successful sperm retrieval and the partner of four of these patients became pregnant and progressed to delivery. These results indicate the usefulness of microdissection for improving the sperm retrieval rate in men with non-obstructive azoospermia.     

Parameters predicting sperm retrieval rates during microscopic testicular sperm extraction in nonobstructive azoospermia

The aim of this study was to investigate the predictive value of the parameters that might have an effect on the success of microscopic testicular sperm extraction (micro‐TESE) in infertile patients with nonobstructive azoospermia (NOA). Between 2003 and 2014, 860 patients with NOA were retrospectively analysed. The effect of age, infertility duration, history of varicocelectomy, herniorrhaphy or orchiopexy, presence of solitary testis, tobacco use, previous testicular biopsy results, history of orchitis, usage of human chorionic gonadotropin in the past three months, presence of undescended or retractile testis, presence of varicocele, testicular volume, levels of serum follicle‐stimulating hormone, luteinising hormone, and testosterone, presence of Klinefelter syndrome and micro‐deletion of Y chromosome on sperm retrieval rates were evaluated. In 45.8% (n = 394) of the patients who underwent micro‐TESE, spermatozoon was adequately obtained. Multiple logistic regression analysis demonstrated that previous successful testicular biopsy (OR = 15.346; GA = 5.45–43.16; p < .001) and higher testicular volumes significantly increase sperm retrieval rate in micro‐TESE. The testicular volume cut‐off as 11 ml was found to be the most significant factor. Although currently testicular biopsy result is not being used as a diagnostic method, it is significantly associated with micro‐TESE result.     

Klinefelter syndrome and fertility—Impact of X‐chromosomal inheritance on spermatogenesis

With the use of testicular sperm extraction (TESE), spermatozoa can be retrieved in about 30%‐50% of men with Klinefelter syndrome (KS). The reason for the absence or presence of spermatozoa in half of the men with KS remains unknown. Therefore, the search for an objective marker for a positive prediction in finding spermatozoa is of significant clinical value to avoid unnecessary testicular biopsies in males with (mostly) low testicular volume and impaired testosterone. The objective of this study was to determine whether paternal or maternal inheritance of the additional X‐chromosome can predict the absence or presence of spermatogenesis in men with KS. Men with KS who have had a testicular biopsy for diagnostic fertility workup TESE were eligible for inclusion. Buccal swabs from nine KS patients and parents (trios) were taken to compare X‐chromosomal inheritance to determine the parental origin of both X‐chromosomes in the males with KS. Spermatozoa were found in TESE biopsies 8 of 35 (23%) patients after performing a unilateral or bilateral TESE. Different levels of spermatogenesis (from the only presence of spermatogonia, up to maturation arrest or hypospermatogenesis) appeared to be present in 19 of 35 (54%) men, meaning that the presence of spermatogenesis not always yields mature spermatozoa. From the nine KS‐trios that were genetically analysed for X‐chromosomal inheritance origin, no evidence of a correlation between the maternal or paternal origin of the additional X‐chromosome and the presence of spermatogenesis was found. In conclusion, the maternal or paternal origin of the additional X‐chromosome in men with KS does not predict the presence or absence of spermatogenesis.     

Salvage microdissection testicular sperm extraction after failed conventional testicular sperm extraction in patients with nonobstructive azoospermia

PURPOSE: TESE is considered the best procedure for identifying a tubule for spermatozoa retrieval. This technique improves the SRR to around 50%. However, it has been unclear whether it is useful in patients in whom conventional TESE has failed. We compared the outcome of microdissection TESE in patients in whom conventional TESE failed to that in patients who did not undergo conventional TESE. We also evaluated relations between the outcome of salvage microdissection TESE and the characteristics of previous conventional TESE. MATERIALS AND METHODS: A total of 46 patients with nonobstructive azoospermia in whom salvage microdissection TESE was performed after failed conventional TESE were included. Patient characteristics and the SRR were compared between these patients and 134 in whom conventional TESE had not been performed previously. The previous TESE procedure, testicular histology and interval between TESEs were also evaluated. RESULTS: Patient characteristics did not differ significantly between the groups. The microdissection TESE SRR also did not differ significantly between the groups (45.7% vs 44.0%). The possibility of successful spermatozoa retrieval by salvage microdissection TESE remained regardless of the previous failure of any other TESE procedure and regardless of testicular histology. The salvage microdissection TESE SRR was not related to the interval between TESEs. CONCLUSIONS: Because salvage microdissection TESE is effective in patients in whom conventional TESE has failed, this option should be made available to them with the understanding that extended followup after salvage microdissection TESE is necessary due to the risk of hypogonadism.     

无精子症病人100例取精方法及妊娠结局

目的 :回顾性分析 2 0 0 1年 1月～ 2 0 0 2年 1月在生殖中心行卵胞质内单精子注射 (ICSI)治疗的 10 0例无精子症男性的治疗结果。　方法 :经皮附睾精子抽吸术 (PESA)或睾丸精子抽提术 (TESE)获得精子 ,女方进行常规超排卵。分析激素水平 ,行睾丸组织学检查 ,评估取精的成功率、受精率、种植率和临床妊娠率。　结果 :76例(76 % )经PESA获得精子 ,2 3例 (2 3% )通过TESE获得精子。PESA和TESE组的受精率、种植率和临床妊娠率分别为 71.3%和 75 .18% ,2 0 .35 %和 2 2 .0 5 % ,4 2 .11%和 4 1.6 0 %。PESA组有 32例临床妊娠 ,其中 15例继续妊娠 ,15例已分娩 ,2例流产。TESE组有 10例临床妊娠 ,其中 6例继续妊娠 ,2例已分娩 ,2例流产。两组的受精率、种植率和临床妊娠率差异无显著性。在TESE组有 1例取精失败而放弃治疗。　结论 :激素水平和睾丸组织学检查不能预测附睾或睾丸取精的成功 ,PESA和TESE获得精子进行单精子注射是治疗男性无精子症的有效方法 ,两组的受精率 ,种植率和临床妊娠率差异无显著性 (P >0 .0 5 )。