Conventional Testicular Sperm Extraction Research Articles

Future prospects for the advancement of treatment of men with NOA: focus on gene editing, artificial sperm, stem cells, and use of imaging.

Nonobstructive azoospermia (NOA) affects about 60% of men with azoospermia, representing a severe form of male infertility. The current approach to manage NOA primarily involves testicular sperm retrieval methods such as conventional testicular sperm extraction (c-TESE) and microdissection testicular sperm extraction (micro-TESE). While combining testicular sperm retrieval with intracytoplasmic sperm injection (ICSI) offers hope for patients, the overall sperm retrieval rate (SRR) stands at around 50%. In cases where micro-TESE fails to retrieve sperm, limited options, like donor sperm or adoption, can be problematic in certain cultural contexts. This paper delves into prospective treatments for NOA management. Gene editing technologies, particularly clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) protein 9 (CRISPR/Cas9), hold potential for correcting genetic mutations underlying testicular dysfunction. However, these technologies face challenges due to their complexity, potential off-target effects, ethical concerns, and affordability. This calls for research to address key challenges associated with NOA management within the clinical settings. This also necessitate ongoing research essential for developing more sensitive diagnostic tests, validating novel treatments, and customizing current treatment strategies for individual patients. This review concluded that the future of NOA management may entail a combination of these treatment options, tailored to each patient's unique circumstances, providing a comprehensive approach to address NOA challenges.

Prediction of testicular histology in azoospermia patients through deep learning-enabled two-dimensional grayscale ultrasound.

Testicular histology based on testicular biopsy is an important factor for determining appropriate testicular sperm extraction surgery and predicting sperm retrieval outcomes in patients with azoospermia. Therefore, we developed a deep learning (DL) model to establish the associations between testicular grayscale ultrasound images and testicular histology. We retrospectively included two-dimensional testicular grayscale ultrasound from patients with azoospermia (353 men with 4357 images between July 2017 and December 2021 in The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China) to develop a DL model. We obtained testicular histology during conventional testicular sperm extraction. Our DL model was trained based on ultrasound images or fusion data (ultrasound images fused with the corresponding testicular volume) to distinguish spermatozoa presence in pathology (SPP) and spermatozoa absence in pathology (SAP) and to classify maturation arrest (MA) and Sertoli cell-only syndrome (SCOS) in patients with SAP. Areas under the receiver operating characteristic curve (AUCs), accuracy, sensitivity, and specificity were used to analyze model performance. DL based on images achieved an AUC of 0.922 (95% confidence interval [CI]: 0.908-0.935), a sensitivity of 80.9%, a specificity of 84.6%, and an accuracy of 83.5% in predicting SPP (including normal spermatogenesis and hypospermatogenesis) and SAP (including MA and SCOS). In the identification of SCOS and MA, DL on fusion data yielded better diagnostic performance with an AUC of 0.979 (95% CI: 0.969-0.989), a sensitivity of 89.7%, a specificity of 97.1%, and an accuracy of 92.1%. Our study provides a noninvasive method to predict testicular histology for patients with azoospermia, which would avoid unnecessary testicular biopsy.

Predictors of successful salvage microdissection testicular sperm extraction (mTESE) after failed initial TESE in patients with non-obstructive azoospermia: A systematic review and meta-analysis.

There has been no systematic review and meta-analysis to analyze and summarize the predictive factors of successful sperm extraction in salvage microdissection testicular sperm extraction. We aimed to investigate the factors predicting the result of salvage microdissection testicular sperm extraction in patients with non-obstructive azoospermia who failed the initial microdissection testicular sperm extraction or conventional testicular sperm extraction. We conducted a systematic literature search in PubMed, Web of Science, EMBASE, and the Cochrane Library for literature that described the characteristics of patients with non-obstructive azoospermia who underwent salvage microdissection testicular sperm extraction after failing the initial microdissection testicular sperm extraction or conventional testicular sperm extraction published prior to June 2022. This meta-analysis included four retrospective studies with 332 patients with non-obstructive azoospermia who underwent a failed initial microdissection testicular sperm extraction and three retrospective studies with 177 non-obstructive azoospermia patients who underwent a failed conventional testicular sperm extraction. The results were as follows: among non-obstructive azoospermia patients whose first surgery was microdissection testicular sperm extraction, younger patients (standard mean difference: -0.28, 95% confidence interval [CI]: -0.55 to -0.01) and those with smaller bilateral testicular volume (standard mean difference: -0.55, 95% CI: -0.95 to -0.15), lower levels of follicle-stimulating hormone (standard mean difference: -0.86, 95% CI: -1.18 to -0.54) and luteinizing hormone (standard mean difference: -0.68, 95% CI: -1.16 to -0.19), and whose testicular histological type was hypospermatogenesis (odds ratio: 3.52, 95% CI: 1.30-9.53) were more likely to retrieve spermatozoa successfully, while patients with Sertoli-cell-only syndrome (odds ratio: 0.41, 95% CI: 0.24-0.73) were more likely to fail again in salvage microdissection testicular sperm extraction. Additionally, in patients who underwent salvage microdissection testicular sperm extraction after a failed initial conventional testicular sperm extraction, those with testicular histological type of hypospermatogenesis (odds ratio: 30.35, 95% CI: 8.27-111.34) were more likely to be successful, while those with maturation arrest (odds ratio: 0.39, 95% CI: 0.18-0.83) rarely benefited. We found that age, testicular volume, follicle-stimulating hormone, luteinizing hormone, hypospermatogenesis, Sertoli-cell-only syndrome, and maturation arrest were valuable predictors of salvage microdissection testicular sperm extraction, which will assist andrologists in clinical decision-making and minimize unnecessary injury to patients.

An examination of predictive markers for successful sperm extraction procedures: a linear model and systematic review.

The authors performed a comprehensive review of current literature to create a model comparing commonly evaluated variables in male factor infertility, for example, follicle-stimulating hormone (FSH), testicular volume (TV), and testosterone (T), to better predict sperm retrieval rate (SRR). Twenty-nine studies were included, 9 with data on conventional testicular sperm extraction (cTESE) for a total of 1227 patients and 20 studies including data on microdissection testicular sperm extraction (mTESE) for a total of 4760 patients. A weighted-means value of SRR, FSH, T, and TV was created, and a weighted linear regression was then used to describe associations among SRR, type of procedure, FSH, T, and TV. In this study, weighted-means values demonstrated mTESE to be superior to cTESE with an SRR of 51.9% vs 40.1%. Multiple weighted linear regressions were created to describe associations among SRR, procedure type, FSH, T, and TV. The models showed that for every 1.19 mIU ml-1 increase in FSH, there would be a significant decrease in SRR by 1.0%. Seeking to create a more clinically relevant model, FSH values were then divided into normal, moderate elevation, and significant elevation categories (FSH <10 mIU ml-1, 10-19 mIU ml-1, and >20 mIU ml-1, respectively). For an index patient undergoing cTESE, the retrieval rates would be 57.1%, 44.3%, and 31.2% for values normal, moderately elevated, and significantly elevated, respectively. In conclusion, in a large meta-analysis, mTESE was shown to be more successful than cTESE for sperm retrievals. FSH has an inverse relationship to SRR in retrieval techniques and can alone be predictive of cTESE SRR.

Azoospermia and Sperm Retrieval in Post-Pubertal Testicular Torsion; Benefits and limitations

To assess the risk of azoospermia development and the value of sperm retrieval in post-pubertal testicular torsion (TT). This prospective study included patients with post-pubertal TT. Surgical exploration was urgently performed with either orchiopexy or orchiedectomy and contralateral orchiopexy. With the intention of cryopreservation, all cases underwent conventional testicular sperm extraction. Patients were followed-up after 1, 3, and 6 months with semen analysis and hormonal assay (FSH, LH and testosterone). Sperm retrieval rate (SRR), azoospermia rate and changes in hormonal profile were evaluated. The study included 62 patients with a median (IQR) age of 19 (18-20.7) years and duration of testicular torsion of 32.5 (18.3-48) hours. Testicular salvage was successful in 20 (32.3%) while orchiedectomy was performed on 42 patients. The duration of torsion [OR, 95% CI=0.75 (0.61-0.93), P=.008] was the independent predictor of testicular salvage. Successful SR was achieved in 58 patients (93.5%); (40 from the affected testis and 18 from the contralateral side). After 6 months, 21 patients (33.8%) developed azoospermia [19 (45.2%) in orchidectomy group and 2 (10%) in orchiopexy group, P=.006]. Abnormal contralateral testis was the independent predictor of azoospermia [OR, 95% CI=92(8.4-101.5), P < .001]. Azoospermia patients showed a statistically significant increase in FSH and LH and decrease in testosterone level as compared to the non-azoospermia group (P < .001). Azoospermia is not rare in post-pubertal TT patients; therefore, SR at time of intervention seems to be a good option for them to preserve their fertility potentials.

Is testicular microdissection the only way to retrieve sperm for non-obstructive azoospermic men?

Men presenting with non-obstructive azoospermia are the most challenging clinical scenario for an infertile couple. Intracytoplasmic Sperm Injection (ICSI) with testicular sperm retrieval gave a chance for biological fatherhood once sperm can be found, but unfortunately sperm recovery rate (SSR) is something near 50%, leading to a discussion about what surgical retrieval technique is the best. Historically sperm have been retrieved using conventional Testicular Sperm Extraction (c-TESE), Testicular Sperm Aspiration (TESA), a combination of Testicular Fine Needle Aspiration (TfNA)/c-TESE, Testicular Microdissection (TM) and Open Testicular Mapping (OTEM). c-TESE published in 1995 by Devroey and cols. consists of testis delivery, a large unique albuginea incision and extraction of a portion from the majority of testicular tubules. TESA published in 1996 by Lewin and cols. is done percutaneously using a 21–23 gauge needle and a syringe to aspire testicular tubules. TfNA was published in 1965 by Obrant and Persson as an aspiration biopsy and cytological exam to verify sperm production. In 1999 Turek and cols. published the use of TfNA combined with c-TESE for sperm retrieval. In 1999, Peter Schlegel published a technique using a microsurgical approach to identify more probable sperm production areas inside the testicle that could be excised with better precision and less tissue. OTEM is a multiple biopsy approach, published in 2020 by Vieira and cols., based on TfNA principles but done at the same time without albuginea opening or surgical microscope need. Since Testicular Microdissection publication, the method became the gold standard for sperm retrieval, allowing superior SSR with minimal tissue removal, but the amount of testicular dissection to find more probable spermatogenesis areas, difficulties in comparative design studies, diversity TM results among doctors and other methods that can achieve very similar results we question TM superiority. The objective is review existing literature and discuss advantages and disadvantages of all the methods for sperm retrieval in non-obstructive azoospermia.

Determining the expression levels of CSF-1 and OCT4, CREM-1, and protamine in testicular biopsies of adult Klinefelter patients: Their possible correlation with spermatogenesis.

Klinefelter syndrome (KS) is the most prevalent genetic disorder of infertile males. This study aimed to determine in Klinefelter patients (KS) the expression levels of spermatogenic markers and testicular growth factors that might predict spermatogenesis based on conventional testicular sperm extraction (TESE). The expression levels of the pre-meiotic (OCT4, CD9, GFR-α1, α-6-INTEGRIN, SALL4, C-KIT), meiotic (CREM-1), and post-meiotic (protamine) markers, as well as the colony stimulating factor-1 (CSF-1) were examined in testicular biopsies with and without mature sperm of KS and normal karyotype of azoospermic patients (AZO) with complete spermatogenesis. In the biopsies of AZO, the expression levels (fold of expression compared to the PPI of the same sample) of OCT4 were 9.68± 7.93, CREM 42.78± 28.22, CSF-1 3.07 ± 3.19, and protamine 78498.12 ± 73214.40. Biopsies from KS included 7 with sperm and 17 without sperm. Among the biopsies with sperm, the expression levels of OCT4 were 7.27± 9.29, CREM 3.13± 7.89, CSF-1 35.5 ± 48.01, and protamine 902.97 ± 2365.92. In 14 biopsies without sperm, we found low expression levels of OCT4, CREM and CSF-1, and no expression of protamine. However, in three of the biopsies without sperm that highly expressed OCT4 and CSF-1, the expression levels of CREM-1 and protamine were high. These results may be used for further consulting with patients considering repeating conventional TESE or micro TESE and cryopreservation for possible future in-vitro spermatogenesis.

Sexual activity of patients undergoing testicular sperm extraction

ABSTRACT Introduction For couples who wish for a baby, sexual activity (though intercourse) is the only way to conceive naturally. However, the sexual activity of men undergoing testicular sperm extraction (TESE) and factors that influence it among affected couples are not clearly understood. Objective To examine sexual activity among infertile men undergoing TESE and identify factors that influenced Methods Married Japanese male patients undergoing TESE were included. Sexual activity during the previous month was surveyed using a questionnaire, and potential predictive factors influencing sexual activity were examined. Results 226 married men who answered a questionnaire regarding sexual frequency were reviewed retrospectively. Patients’ mean age was 35.8 ± 7.5 years (range 23–67) and that of their partners was 32.9 ± 4.5 years (range 23–44). Most couples (n = 193) were in their first marriage, and 33 were re-married. The mean marriage duration was 52.6 ± 42.2 months (range 1–192). Micro-dissection TESE and conventional TESE were performed for 152 and 74 patients, respectively. Overall, the mean sexual activity during the last month was 3.6 ± 2.6 times (range 0–15). Marriage duration was negatively correlated with the frequency of sexual activity (r = −0.23; P &amp;lt; .01). There were no correlations between sexual activity and patients’ age, partners’ age, marriage type (first marriage/re-married), testicular volume, or serum total testosterone concentration. Regression analysis showed marriage duration (odds ratio [OR] 1.01, 95% confidence interval [CI] 1.003–1.019, P = .009) and testicular volume (OR 0.94, 95% CI 0.88–0.99, P = .033) were significant predictors of low sexual activity (0–1 times/month). There were no significant differences in sexual activity per month between patients treated with micro-TESE and c-TESE; between those in a first marriage and those re-married; and between patients with Klinefelter syndrome and patients who underwent c-TESE. Conclusions The sexual activity of patients undergoing TESE was almost the same as reported previously. Patients’ age, partners’ age, testicular volume, and serum total testosterone concentration had no correlations with the reported frequency of sexual activity. Disclosure Work supported by industry: no.

P–038 Clinical outcomes of 77 testicular sperm extraction treatment cycles in non-mosaic Klinefelter syndrome patients

Abstract Study question What are the clinical results of patients with azoospermia and nonmosaic Klinefelter syndrome, using fresh and cryopreserved sperm? Summary answer The results showed a recovery rate of testicular sperm in the order of 40% and a life newborn rate of 52% when using fresh sperm What is known already In Klinefelter syndrome (KS), the rates of successful testicular sperm retrieval were shown to be similar either using conventional TESE or micro-TESE (Corona et al., 2017), which highlights that the variability observed between studies is due to differences in patient characteristics. There are a few works with a large number of KS patients elucidating the clinical outcomes using fresh and cryopreserved testicular sperm. However, these studies revealed contradictory outcomes, either revealing better (Greco et al., 2013; Vicdan et al., 2016) or worst (Madureira et al., 2014) results with cryopreserved testicular sperm, or finding no differences (Chen et al, 2019). Study design, size, duration This study includes all patients up to 2019 presenting azoospermia due to non-mosaic Klinefelter syndrome (n = 76) that went for infertility consultations in a private fertility clinic. Patients were evaluated by the same Urologist. The genetic analysis of the patients was performed at an academic institution. At examination patients did not refer other complaints besides infertility, and referred to have not received any hormone replacement therapy in the past. Participants/materials, setting, methods The 76 azoospermic patients with non-mosaic Klinefelter syndrome (KS) were treated by testicular sperm extraction (TESE) followed by intracytoplasmic sperm injection (ICSI), using fresh and cryopreserved testicular sperm. Most patients used fresh testicular sperm, where others preferred to postpone ICSI treatment cycles and used cryopreserved testicular sperm. Aneuploidy screening in children was performed by prenatal diagnosis and MLPA (Multiplex ligation-dependent probe amplification). Full embryological, clinical and newborn outcomes are provided. Main results and the role of chance Of the 76 patients with non-mosaic Klinefelter syndrome, one repeated the testicular sperm extraction (TESE) procedure. Testicular sperm were recovered in 31/77 (40.3%) of the cases. Comparisons between the 31 cases with successful sperm recover (group–1) and the 46 cases without a successful TESE (group–2) revealed no significant differences regarding age, time of infertility, testicular volume, serum levels of FSH, LH and testosterone, total number of testicular fragments analyzed, and time of search in samples. The mean male age was 34 years. In most of the cases, the testicular volume was reduced (96.1%), the levels of FSH (98.3%) and LH (94.1%) were increased, and the levels of testosterone were normal (77.6%). There were 25 intracytoplasmic sperm injection (ICSI) treatment cycles using fresh testicular sperm and 22 ICSI treatment cycles using frozen testicular sperm. The rates of fertilization (63.5% fresh sperm vs 41.6% frozen sperm), implantation (37% fresh sperm vs 13.2% frozen sperm), clinical pregnancy (60.9% fresh sperm vs 19% frozen sperm), live birth delivery (52.2% fresh sperm vs 19% frozen sperm) and newborn (65.2% fresh sperm vs 23.8% frozen sperm) were higher in the group using fresh testicular sperm. Chromosome analysis of the 21 newborn was normal. Limitations, reasons for caution Although presenting a high number of cases with azoospermic non-mosaic Klinefelter syndrome treated with testicular sperm extraction and intracytoplasmic sperm injection, future studies are needed with a higher number of cycles using frozen testicular sperm, in order to confirm or rebut that the freezing methodology affects negatively the clinical outcomes. Wider implications of the findings: Data adds further information regarding testicular sperm retrieval rates and use of fresh or frozen testicular sperm in Klinefelter syndrome (KS) patients. High newborn rates were obtained only with fresh testicular sperm. Results also reassure KS patients about the safety relative to any abnormal chromosomal transmission to the born children. Trial registration number Not applicable

P–002 Prediction model for salvage microdissection testicular sperm extraction in patients with failed conventional testicular sperm extraction

Abstract Study question Is there any intra-surgical parameter able to predict the outcome of salvage microdissection testicular sperm extraction (mTESE) in patients with previous failed TESE? Summary answer Among all the variables under consideration, only the seminiferous tubules (ST) caliber pattern found at high magnification was able to significantly predict the mTESE outcome... What is known already Several studies have demonstrated that no clinical or hormonal parameters are able to predict the outcome of a salvage mTESE performed in patients with previous sperm retrieval failure (SRF). It has been previously demonstrated that a prediction model with the combination of two intra-surgical parameters such as the STs caliber, defined as dilated tubule (DT), slightly dilated tubules (SDT) and not dilated tubules (NDT), and testis histology had an excellent discrimination ability (AUC 0.93) to distinguish between cases with and without the outcome, but such prediction model has not been tested in patients undergoing salvage mTESE. Study design, size, duration A prediction model was built on a dataset of 63 patients, 29–50 years old, undergoing unilateral (15 ) or bilateral (48) salvage mTESE after failed TESE from 2015 through 2019, with a resulting N = 111 testes under consideration. Two models were compared, one with STs and histology as covariates, the other with STs alone: the second model was chosen due to better discrimination... Participants/materials, setting, methods we assessed internal validity with a bootstrapping procedure for a realistic estimate of the performance of the prediction model in similar future patients with NOA undergoing salvage mTESE. We repeated the entire modeling process in 259 samples drawn with replacement from the original sample, and determined the performances (AUC, sensitivity, specificity) of the selected prediction model. Calibration (correspondence between the predicted and observed probabilities) was visually assessed by inspecting the calibration belt... Main results and the role of chance Sperm retrieval was successful in 24 out of 63 patients (38%): age, testis volume and hormonal parameters did not vary among patients with successful sperm retrieval (SSR) or SRF. The prevalent histological pattern was Sertoli cell only syndrome (69.6%), while hypospermatogenesis, maturation arrest and hyalinosis were found in 4.5%, 23% and 1.8% of cases. The STs pattern was heterogeneous, with DTs being found only in 23.4% of testes. Sperm were found in 69% of DTs, 29% of SDTs, and 5% of NDTs. The prediction model correctly classified 82.88% of patients and explained the 26.5% variability of the outcome. The STs pattern significantly predicted the mTESE outcome with a sensitivity of 62% and a specificity of 90.2%, PPV 69.2%, NPV 87%. Both SDT (OR 0.105, 95% CI 0.034–0.317, p &amp;lt; 0.0001) and NDT (OR 0.024, 95% CI 0.004–0.128, p &amp;lt; 0.0001) were negatively associated with the chance of retrieving sperm, the resulting prediction equation being Log (SSR)= 0.81 – 2.2 SDT – 3.7 NDT. The model had a clearly useful discrimination (AUC 0.813). The optimism corrected AUC was 0.7977, and the model was well calibrated (p = 1.00) with both the 80% and 95% calibration belts encompassing the bisector over the whole range of the predicted probabilities Limitations, reasons for caution The STs caliber pattern was subjectively evaluated at high magnification (24–36x) by comparing the individual ST appearance with the surrounding ones, however such evaluation was performed by the same experienced urologist with more than 1000 mTESE procedures performed to date. Wider implications of the findings: No clinical data but the STs appearance at high magnification could discriminate between patients with and without chances of SSR. These results reinforce the evidence supporting the superiority of mTESE compared to conventional TESE in retrieving sperm, particularly in lower prognosis patients with NOA such as those with previous SR. Trial registration number Not applicable

Intrasurgical parameters associated with successful sperm retrieval in patients with non‐obstructive azoospermia undergoing salvage microdissection testicular sperm extraction

Patients with non-obstructive azoospermia with a previously failed conventional testicular sperm extraction may undergo a salvage microdissection testicular sperm extraction with the probability of successful sperm retrieval being almost dependent upon the number of previous surgical attempts and to different histopathologic categories. To determine whether the seminiferous tubules pattern and the histological categories could affect the sperm retrieval rate in patients with non-obstructive azoospermia undergoing salvage microdissection testicular sperm extraction after failed conventional testicular sperm extraction. Seventy-nine patients undergoing unilateral or bilateral salvage microdissection testicular sperm extraction were evaluated. During microdissection testicular sperm extraction, if present, dilated tubules were retrieved, otherwise, tubules with slightly larger caliber than that of the surroundings were removed. When no dilated tubule or tubule with slightly larger caliber was found, not dilated tubules were excised. A prediction model was built with seminiferous tubules pattern and testis histology as covariates. Sperm retrieval was successful in 30 out of 79 patients. The prediction model correctly classified 88.3% of cases, explained the 29.7% variability of the outcome, and significantly predicted the microdissection testicular sperm extraction outcome with a sensitivity of 67.7% and a specificity of 90.2%, Both tubules with slightly larger caliber and not dilated tubules were negatively associated with the chance of retrieving spermatozoa. Among the histological categories, only early maturation arrest was significant to the model (log(SSR)=0.57 - 1.9SDT - 3.3NDT - 1.76EMA) (where SSR is sperm retrieval rate, SDT is tubule with slightly larger caliber, NDT is not dilated tubule, and EMA is early maturation arrest). The model had a clearly useful discrimination (area under the curve = 0.814), the estimated performance was 0.8105, and internal calibration was acceptable (p>0.05). Seminiferous tubules pattern and testis histology may reliably explain the salvage microdissection testicular sperm extraction outcome in all patients with non-obstructive azoospermia apart from those with early maturation arrest, where the homogeneous apparent seminiferous tubules pattern may be misleading. The outcome of salvage microdissection testicular sperm extraction can be predicted by the same intrasurgical parameters that have been demonstrated to predict the outcome of microdissection testicular sperm extraction in naïve patients with non-obstructive azoospermia.

Does mirabegron deteriorate spermatogenesis? A lesson from spinal cord injury cases.

To evaluate whether the long-term usage of mirabegron, which was reported to have potential side effects on male reproductive organs in animal studies, was harmful to spermatogenesis in human testis. Thirty consecutive patients with spinal cord injury (20-48 years old) who performed clean intermittent catheterization were involved in this study. Ten patients were treated with mirabegron (50 mg/d) for more than 2 years and refrained from using an antimuscarinic agent due to the side effects of constipation and dry mouth. Twenty patients were treated with neither anticholinergic agents nor mirabegron. All underwent conventional testicular sperm extraction. The sperm recovery rate and histopathologic findings of the retrieved testicular tissue were compared between both groups. We found no difference in the sperm recovery rate (P=.083) between both groups. Spinal cord injury patients treated with mirabegron had better spermatogenesis than those not treated with mirabegron (P < .05). From these data, we conclude that the therapeutic dose of mirabegron had no harmful effect on spermatogenesis in spinal cord injury patients of reproductive age.

Testicular sperm extraction in male infertility : Indications, success rates, practical implementation, and possible complications

Unwanted childlessness is aburden on acouple's relationship. The therapeutic spectrum of male infertility has increased significantly in recent years so that even azoospermia patients can be given biological paternity by testicular sperm extraction (TESE). The indications, success rates, practical implementation, and possible complications of conventional and microscopic TESE in male infertility are presented in this review. Anonsystematic search of the relevant literature was carried out. In obstructive azoospermia (OA), primarily desobstructive surgical procedures are used, while TESE is the surgical procedure of choice in nonobstructive azoospermia (NOA). In the latter, sperm extraction can be performed conventionally or microscopically (mTESE) assisted, whereby the latter offers an advantage in terms of sperm detection rate in the case of small testicular volumes (<12 ml), chemotherapy, Klinefelter's disease and AZFc microdeletions. The sperm detection rate of TESE is about 50%. Postoperative controls are useful because of the possible induction of symptomatic hypogonadism. Before performing TESE, determining the hormone status and human genetic clarification are necessary. Any costs incurred and the possibility of missing sperm proof must be discussed. Close cooperation between andrologists, gynecologists, reproductive physicians, and human geneticists is necessary. All in all, TESE is asafe surgical procedure with a low complication rate.

How Successful Is Surgical Sperm Retrieval in Klinefelter Syndrome?

Klinefelter Syndrome (KS) is characterized by the presence of an extra X chromosome. It was first diagnosed in 1942 in a group of azoospermic men. KS is the most common chromosomal abnormality encountered in infertile men and accounts for more than 10% of the causes of azoospermia. Men who are azoospermic may still father children via testicular sperm extraction followed by intracytoplasmic sperm injection (ICSI). This review article summarizes the success rates of the available techniques for surgical sperm retrieval (SSR) in KS including conventional testicular sperm extraction (cTESE) and micro testicular sperm extraction (mTESE), as well as the risks of these procedures for future fertility. The evidence indicates that the SSR rate is as successful in non-mosaic men with KS as those with normal karyotypes, with retrieval rates of up to 55% reported. The influence of different factors that affect the chances of a successful outcome are discussed. In particular, the impact of aneuploidy rate, physical characteristics, co-morbidities, reproductive endocrine balance and the use of different hormone management therapies are highlighted. Evidence is presented to suggest that the single most significant determinant for successful SSR is the age of the patient. The success of SSR is also influenced by surgical technique and operative time, as well as the skills of the surgeon and embryology team. Rescue mTESE may be used successfully following failed TESE in KS patients in combination with hormone stimulation.

Nfertilite Tedavisinde TESE Başarısını Etkileyen Faktörler: Tek Merkez Deneyimi Ön Sonuçları

Objective: Today, infertility is a health problem with increasing treatment seeking. Testicular sperm extraction (TESE) is the only possible procedure to offer genetic parenting to men with nonobstructive azoospermia (NOA). Our aim in this study is to present our clinical experiences that affect the success of sperm retrieval in men with NOA in the light of the literature. Materials and Methods: In our study, patients who underwent TESE with a diagnosis of NOA between 2017-2020 were retrospectively analyzed. According to the TESE procedure; the patients were divided into two groups as conventional TESE and TESE performed under microscopic magnification (micro-TESE). Medical histories, hormone values, and physical examination findings of all patients were recorded. Results: Our micro-TESE success rate was found to be 100%. A positive correlation (rho 0.714, p = 0.009) was found between the factors affecting sperm retrieval , and the application of micro-TESE, and a negative correlation was detected with FSH levels (rho -0.759, p = 0.004). Conclusion: The success of sperm retrieval increases with the micro-TESE procedure. As FSH levels increase, sperm retrieval success rates decrease.

Sperm retrieval rates in non-mosaic Klinefelter patients undergoing testicular sperm extraction: What expectations do we have in the real-life setting?

A recent meta-analysis (Human Reproduction Update 23, 2017 and 265) reported positive sperm retrieval rates (SRR) in 50% of patients with Klinefelter syndrome (KS) undergoing testicular sperm extraction (TESE). However, these results do not reflect the rates of SR that we observe in clinical practice. We assessed the rate and potential predictors of SR in Klinefelter patients in the real-life setting. We reviewed clinical data of 103 KS men who underwent TESE between 08/2008 and 03/2019 at five tertiary referral Andrology centers. Patients underwent testis ultrasound, hormonal evaluation, and genetic testing. All patients were azoospermic based on the 2010 WHO reference criteria. Conventional TESE (cTESE) or microsurgical TESE (mTESE) was performed based on the surgeon's preference. We used descriptive statistics and logistic regression models to describe the whole cohort. Median (IQR) patient's age was 32 (24-37) years. Baseline serum FSH and total testosterone levels were 29.5 (19.9-40.9) mUI/mL and 3.8 (2.5-11.0) ng/mL, respectively. Conventional TESE and mTESE were performed in 38 (36.5%) and 65 (63.5%) men, respectively. The sperm retrieval rate was 21.4% (22/103 men). Fifteen patients used spermatozoa for ICSI and five ended in live birth children. Patients with positive SR were similar to those with a negative TESE in terms of clinical, hormonal, and procedural parameters (all P>.05). Logistic regression analyses confirmed the lack of association between clinical, hormonal, and procedural parameters with SR outcome. Given the conflicting results in the literature regarding SRR in KS, patients should be carefully counseled regarding TESE outcomes based on data from published literature and local results. In the real-life setting, we observed a lower SRR (21.4%) than that reported in meta-analyses in our cohort of KS patients. No associations between clinical, hormonal, and procedural variables with TESE success were found.

Sexual Activity of Patients Undergoing Testicular Sperm Extraction.

IntroductionFor couples who wish for a baby, sexual activity (through intercourse) is the only way to conceive naturally. However, the sexual activity of men undergoing testicular sperm extraction (TESE) and factors that influence it among affected couples are not clearly understood.AimTo examine sexual activity among infertile men undergoing TESE and to identify factors that influenced it.MethodsMarried Japanese male patients undergoing TESE were included. Sexual activity during the previous month was surveyed using a questionnaire, and potential predictive factors influencing sexual activity were examined.Main Outcome MeasuresTwo hundred twenty-six married men who answered a questionnaire regarding sexual frequency were reviewed retrospectively.ResultsThe patient mean age was 35.8 ± 7.5 years (range 23–67) and the mean age of their partners was 32.9 ± 4.5 years (range 23–44). Most couples (n = 193) were in their first marriage, and 33 were remarried. The mean marriage duration was 52.6 ± 42.2 months (range 1–192). Microdissection TESE and conventional TESE were performed for 152 and 74 patients, respectively. Overall, the mean sexual activity during the last month was 3.6 ± 2.6 times (range 0–15). Marriage duration was negatively correlated with the frequency of sexual activity (r = −0.23; P < .01). There were no correlations between sexual activity and patient age, partner age, marriage type (first marriage or remarried), testicular volume, or serum total testosterone concentration. Regression analysis showed that marriage duration (odds ratio = 1.01; 95% CI, 1.003–1.019; P = .009) and testicular volume (odds ratio = 0.94; 95% CI, 0.88–0.99; P = .033) were significant predictors of low sexual activity (0–1 times/month).ConclusionThe sexual activity of patients undergoing TESE was almost the same as reported previously. Patient age, partner age, testicular volume, and serum total testosterone concentration had no correlation with the reported frequency of sexual activity.Taniguchi H, Matsuda T, Nakaoka Y, et al. Sexual Activity of Patients Undergoing Testicular Sperm Extraction. Sex Med 2019;8:30–35.

Sperm recovery and ICSI outcomes in men with non-obstructive azoospermia: a systematic review and meta-analysis.

Factor affecting sperm retrieval rate (SRR) or pregnancy rates (PR) after testicular sperm extraction (TESE) in patients with non-obstructive azoospermia (NOA) have not been systematically evaluated. In addition, although micro-TESE (mTESE) has been advocated as the gold standard for sperm retrieval in men with NOA, its superiority over conventional TESE (cTESE) remains conflicting. The objective was to perform a meta-analysis of the currently available studies comparing the techniques of sperm retrieval and to identify clinical and biochemical factors predicting SRR in men with NOA. In addition, PRs and live birth rates (LBRs), as derived from subjects with NOA post-ICSI, were also analysed as secondary outcomes. An extensive Medline, Embase and Cochrane search was performed. All trials reporting SRR derived from cTESE or mTESE in patients with NOA and their specific determinants were included. Data derived from genetic causes of NOA or testicular sperm aspiration were excluded. Out of 1236 studies, 117 studies met the inclusion criteria for this study, enrolling 21 404 patients with a mean age (± SD) of 35.0 ± 2.7years. cTESE and mTESE were used in 56 and 43 studies, respectively. In addition, 10 studies used a mixed approach and 8 studies compared cTESE with mTESE approach. Overall, a SRR per TESE procedure of 47[45;49]% (mean percentage [95% CI]) was found. No differences were observed when mTESE was compared to cTESE (46[43;49]% for cTESE versus 46[42;49]% for mTESE). Meta-regression analysis demonstrated that SRR per cycle was independent of age and hormonal parameters at enrolment. However, the SRR increased as a function of testis volume. In particular, by applying ROC curve analysis, a mean testis volume higher than 12.5ml predicted SRR >60% with an accuracy of 86.2% ± 0.01. In addition, SRR decreased as a function of the number of Klinefelter's syndrome cases included (S = -0.02[-0.04;-0.01]; P < 0.01. I = 0.12[-0.05;0.29]; P = 0.16). Information on fertility outcomes after ICSI was available in 42 studies. Overall, a total of 1096 biochemical pregnancies were reported (cumulative PR = 29[25;32]% per ICSI cycle). A similar rate was observed when LBR was analysed (569 live births with a cumulative LBR = 24[20;28]% per ICSI cycle). No influence of male and female age, mean testis volume or hormonal parameters on both PR and LBR per ICSI cycle was observed. Finally, a higher PR per ICSI cycle was observed when the use of fresh sperm was compared to cryopreserved sperm (PR = 35[30;40]%, versus 20[13;29]% respectively): however, this result was not confirmed when cumulative LBR per ICSI cycle was analysed (LBR = 30[20;41]% for fresh versus 20[12;31]% for cryopreserved sperm). This analysis shows that cTESE/mTESE in subjects with NOA results in SRRs of up to 50%, with no differences when cTESE was compared to mTESE. Retrieved sperms resulted in a LBR of up to 28% ICSI cycle. Although no difference between techniques was found, to conclusively clarify if one technique is superior to the other, there is a need for a sufficiently powered and well-designed randomized controlled trial to compare mTESE to cTESE in men with NOA.

Sperm retrieval rates and clinical outcomes with testicular sperm extraction in relation to the etiology of azoospermia

Sperm retrieval rates (SRR) and clinical outcomes after intracytoplasmic sperm injection (ICSI) in testicular sperm extraction (TESE) cases in relation to the etiology of azoospermia have not well been investigated yet. Here we report our latest five-year experience in TESE. Retrospective clinical analysis. This study investigated SRR of conventional TESE in obstructive azoospermia (OA) and microdissection TESE in cryptozoospermia and non-obstructive azoospermia (NOA) patients between September 2013 and December 2018 (1455 TESE attempts with 1222 patients). The etiologies of NOA were categorized as unexplained, Klinefelter’s syndrome (KS), post chemotherapy, post orchiopexy, and microdeletion of azoospermia factor (AZF) c on the Y chromosome. A total of 473 couples had 1128 TESE-ICSI cycles (136 couples and 332 cycles with OA and 337 couples and 796 cycles with NOA) were evaluated with respect to fertilization, embryonic development and clinical pregnancy rates (CPR). SRR of patients with first TESE attempts (49.9%) was significantly higher than that of patients who previously failed sperm retrieval (32.5%) (P<0.001). In the first TESE cases, SSRs were 100% (155/155) in OA, 21.2% (102/482) in unexplained NOA, 50.5% (54/107) in KS, 47.8% (22/46) in post chemotherapy, 75.0% (33/44) in post orchiopexy, and 87.1% (27/31) in AZFc microdeletion, respectively. SRR of OA was significantly higher, while that of unexplained NOA was lower than any other groups. Normal fertilization rates in OA (62.0%) and post chemotherapy (63.4%) were significantly higher, but that of AZFc microdelecion (39.7%) was significantly lower than any other groups. Blastocyst development rate and good-quality blastocyst rate in AZFc microdeletion (27.4% and 9.3%) were significantly lower than any other groups and the rates in KS (40.5% and 15.1%) were lower than in OA (51.3% and 22.1%), post chemotherapy (50.6% and 23.6%), and post orchiopexy (52.1% of blastulation). CPRs per embryo transfer were lower in unexplained NOA (29.7%), and AZFc microdeletion (27.5%) than in OA (39.9%). We have had a total of 243 newborns so far with comparable congenital anomaly rate comparing to those with ejaculated sperm-ICSI. The success of sperm recovery, fertilization and pre- and post-implantation development was significantly influenced by the etiology of azoospermia. However, the offspring with testicular sperm was as healthy as that with ejaculated sperm at least in our experience.

Step-by-step loupes-mTESE in non-obstructive azoospermic men, a retrospective study

BackgroundMen with non-obstructive azoospermia (NOA) may have sperm in their testes and a procedure of sperm retrieval and assisted reproduction is required in them to allow fertility. Standard procedures such as fine needle aspiration (FNA) and conventional testicular sperm extraction (cTESE) harvest random samples with a sperm retrieval rate (SRR) of 45%. Microdissection testicular sperm extraction (mTESE) is nowadays considered to be the most accurate technique to retrieve sperm in men with NOA. This procedure can identify dilated tubules that are more likely to contain viable sperm with a SRR of 60%.ResultsIn our center, testicular biopsy was conducted in a standard fashion in 321 patients with NOA until March 2003. From then to December 2017, due to the lack of an operating microscope, we used 6 fold magnifying loupes to perform a step-by-step macro- mTESE in 1050 patients. Sperm was found in the first testis in 61% of the cases, leading to stop the procedure with less testicular damage. We increased our SRR from 43 to 51.8% in an acceptable operating time of 75mn for both sides.ConclusionsIn institutions where surgeons cannot afford an operating microscope, this modified mTESE technique using × 6 magnifying loupes is reliable, especially in patients with low testicular volumes and high FSH, in whom dilated tubules can be easily identified from the surrounding tissue.