Seminal plasma anti-Müllerian hormone level correlates with semen parameters but does not predict success of testicular sperm extraction （TESE）

Aim： To assess seminal plasma anti-Müllerian hormone （AMH） level relationships in fertile and infertile males. Methods： Eighty-four male cases were studied and divided into four groups： fertile normozoospermia （n = 16）, oligoastheno- teratozoospermia （n = 15）, obstructive azoospermia （OA） （n = 13） and non-obstructive azoospermia （NOA） （n = 40）. Conventional semen analysis was done for all cases. Testicular biopsy was done with histopathology and fresh tissue examination for testicular sperm extraction （TESE） in NOA cases. NOA group was subdivided according to TESE results into unsuccessful TESE （n = 19） and successful TESE （n = 21）. Seminal plasma AMH was estimated by enzyme linked immunosorbent assay （ELISA） and serum follicular stimulating hormone （FSH） was estimated in NOA cases only by radioimmunoassay （RIA）. Results： Mean seminal AMH was significantly higher in fertile group than in oligoasthenoteratozoospermia with significance （41.5±10.9 pmol/L vs. 30.5±10.3 pmol/L, P 〈 0.05）. Seminal AMH was not detected in any OA patients. Seminal AMH wascorrelated positively with testicular volume （r = 0.329, P = 0.005）, sperm count （r = 0.483, P = 0.007）, sperm motility percent （r = 0.419, P = 0.021） and negatively with sperm abnormal forms percent （r = -0.413, p = 0.023）. Nonsignificant correlation was evident with age （r = -0.155, P = 0.414） and plasma FSH （ r = -0.014, P = 0.943）. In NOA cases, seminal AMH was detectable in 23/40 cases, 14 of them were successful TESE （57.5%） and was undetectable in 17/40 cases, 10 of them were unsuccessful TESE （58.2%）. Conclusion： Seminal plasma AMH is an absolute testicular marker being absent in all OA cases. However, seminal AMH has a poor predictability for successful testicular sperm retrieval in NOA cases.

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.

Outcome of repeated micro-surgical testicular sperm extraction in patients with non-obstructive azoospermia

Aim： To evaluate the outcome of repetitive micro-surgical testicular sperm extraction （mTESE） attempts in non-obstructive azoospermia （NOA） cases, in relation to patients＇ initial testicular histology results. Methods： A total of 68 patients with NOA in whom mTESE had been performed in previous intracytoplasmic sperm injection （ICSI） attempts were reviewed. Results： Among the 68 patients with NOA, the first mTESE yielded mature sperm for ICSI in 44 （64%） （Sp^＋）, and failed in the remaining 24 （36%） （Sp^-）. Following their first trial, 24 patients decided to undergo a second mTESE. Of these 24 patients, no spermatozoa were obtained in 5 patients, and Sp^＋ but no fertilization/pregnancy were achieved in 19. In these 24 cases, mTESE was successively repeated for two （n = 24）, three （n = 4） and four （n = 1） times. The second attempt yielded mature sperm in 3/5 patients from the Sp group and 16/19 patients from the Sp^＋ group. At the third and fourth trials, 4/4 and 1/1 of the original Sp^＋ patients were Sp^＋ again, respectively. Distribution of main testicular histology included Sertoli cell-only syndrome （16%）, maturation arrest （22%）, hypospermatogenesis （21%） and focal spermatogenesis （41%）. Overall, in repetitive mTESE, 24/29 （82%） of the attempts were finally Sp^＋. Conclusion： Repeated mTESE in patients with NOA is a feasible option, yielding considerably high sperm recovery rate. In patients with NOA, mTESE may safely be repeated one or more times to increase sperm retrieval rate, as well as to increase the chance of retrieving fresh spermatozoa to enable ICSI.

Testis sperm extraction

The last 20 years have produced developments in the treatment for patients with non-obstructive azoospermia(NOA)who were once considered to be infertile.The combination of intracytoplasmic sperm injection together with various testicular sperm retrieval techniques,including conventional testicular sperm extraction(TESE),microdissection TESE(micro-TESE)and fine needle aspiration(FNA),have revolutionized treatment for these men.In men with NOA,isolated regions of spermatogenesis within the testis are common.The goal for all types of sperm retrieval procedures is locating the focal region(s)of spermatogenesis,and harvesting the sperm for assisted reproduction.This review article explores the surgical management of men with NOA and describes all techniques that can be used for testicular sperm retrieval.A PubMed search was conducted using the key words:“sperm extraction”,“NOA”,“testicular FNA”,“testicular mapping”,“TESE”,and“testicular biopsy”.All articles were reviewed.Articles were included if they provided data on sperm retrieval rates.The methods for performing sperm retrieval rates and outcomes of the various techniques are outlined.Micro-TESE has a higher sperm retrieval rates with fewer postoperative complications and negative effects on testicular function compared with conventional TESE.

Laboratory and Clinical Outcomes of Single Sperm Cryopreservation in Patients Underwent Micro-TESE

For men with severe oligozoospermia, sperm cryopreservation can preserve surgically obtained sperm. How to cryopreserve single sperm in men is still a hot topic in assisted reproduction technology. Aim to analyze the laboratory and pregnancy outcomes of single sperm cryopreservation group, we retrospectively selected 38 cycles underwent single sperm cryopreservation and thawing as the study group and 618 cycles underwent conventional sperm cryopreservation and thawing as the control group, which were performed in the reproductive medicine center of the Sixth Affiliated Hospital, Sun Yatsen University, from April 2014 to October 2023. All the sperm came from microdissection testicular sperm extraction (micro-TESE), and performed intracytoplasmic sperm injection (ICSI) for fertilization. Zygotes were cultured to Day 3 embryo, which were freshly transferred to female uterus. Surplus embryos were cultured to blastosphere and cryopreserved. There was no statistical difference in female/male age, female BMI, infertility duration and female basal sex hormone (FSH, LH E2, AMH), No. of oocytes retrieved per cycle, No. of ICSI oocytes per cycle and No. of embryos transferred per cycle between the two groups (P > 0.05). No significant difference was found in two-pronuclear oocyte fertilization rate (59.23% VS 58.84%), Day 3 available embryo rate (61.81% VS 63.55%), Day 3 good-quality embryo rate (45.73% VS 50.27%), blastocyst formation rate (47.83% VS 49.46%), the implantation rate (47.37% VS 52.16%), clinical pregnancy rate (36.84% VS 47.18%), miscarriage rate (14.29% VS 12.68%) and live birth rate (85.71% VS 81.70%) between two groups (P > 0.05). In conclusion, single-sperm cryopreservation was the optimal method to preserve sperm after micro-TESE. It can increase the utilization of each sperm and lead to clinical pregnancy.

Aberrant methylation of the TDMR of the GTF2AIL promoter does not affect fertilisation rates via TESE in patients with hypospermatogenesis

Increasing evidence shows a relationship between epigenetic regulation and male infertility. The GTF2A1L gene promoter contains the DNA methylation site of a tissue-specific differentially methylated region （TDMR）. Eighty-six patients with non-obstructive azoospermia were assessed for the DNA methylation state of CpG islands in the GTF2AIL promoter using testicular genomic DNA. Based on histological criteria, 26 of the 86 patients had normal spermatogenesis （controls）, 17 had hypospermatogenesis and 26 had a Sertoli cell-only phenotype or tubular sclerosis. GTF2AIL TDMR methylation was significantly lower in testes DNA from control samples than from hypospermatogenic samples （P=0.029）. Patients with hypospermatogenesis were divided into two subgroups： high DNA methylation （HM, n=5） and low DNA methylation （LM, n= 12）. The GTF2AIL TDMR methylation rate differed significantly between the HM and LM groups （P=0.0019）, and GTF2A 1L expression was significantly higher among the LM than in the HM patients （P=0.023）. High TDMR methylation was correlated with low GTF2AIL gene expression levels. Both groups demonstrated relatively good outcomes with respect to sperm retrieval, fertilisation, pregnancy and childbirth rates. We observed that aberrant GTF2AIL gene expression was not correlated with fertilisation rates. The testicular sperm extraction （TESE） technique may be used to overcome male infertility due to aberrant TDMR methvlation.

No relationship between biopsy sites near the main testicular vessels or rete testis and successful sperm retrieval using conventional or microdissection biopsies in 220 non-obstructive azoospermic men

In 220 consecutive patients with non-obstructive azoospermia, sperm retrieval was attempted by a combination of conventional and microdissection testicular sperm extraction （TESE）. For sperm retrieval, 2-3 conventional biopsies were performed followed by a microdissection TESE in cases of negative conventional biopsies. During the surgery, the vasculature of the testis was assessed using the operative microscope, and the location of positive biopsies was registered in relation to the blood supply. The overall sperm retrieval rate was 58.2%. From the initial conventional biopsies, sperm could be retrieved in 46.8% of the patients. With microdissection TESE, sperm could be retrieved from an additional 11.4% of the patients. The further use of microdissection TESE improved the sperm retrieval rate significantly （P=0.017）. No significant accumulation of positive biopsies was found towards the rete testis or the main testicular vessels.

Probability to retrieve testicular spermatozoa in azoospermic patients

Aim: The degree of probability to retrieve spermatozoa from testicular tissue for intracytoplasmic sperm injection intooocytes is of interest for counselling of infertility patients. We investigated the relation of sperm retrieval to clinical dataand histological pattern in testicular biopsies from azoospermic patients. Methods: In 264 testicular biopsies from142 azoospermic patients, the testicular tissue was shredded to separate the spermatozoa, histological semi-thin sec-tions of which were then evaluated using Johnsen score. Results: The retrieval of spermatozoa correlated signifi-cantly (P < 0.001) with the testicular volume (r = 0.49), the FSH concentration ( r = -0.66), the maximum score(r = 0.85) and the mean Johnsen score (r = 0.81). In the multivariate regression analysis the successful testicularsperm extraction showed the closest relationship to the maximum score. The testicular volume correlated significantlywith the mean Johnsen score ( r = 0.64, P < 0. 001), and the basal serum FSH concentration mainly with the maxi-mum score ( r = -0.77; P < 0. 001 ). Patients with a history cryptorchidism showed a significantly lower Johnsenscore compared to the patients who did not have any testicular disease in the past (3.7 ± 2.4 vs. 5.9 ± 2. 5; P < O.01). Conclusion: In a limited range, the testicular volume and the FSH concentration in serum were related to theJohnsen score which correlated significantly with the sperm retrieval. The successful sperm retrieval can be expected inall azoospermic patients irrespective of the results of clinical examination. However, the probability of retrieval of sper-matozoa decreased significantly in patients with a FSH level > 18 U/L, tesficular volume < 5mL, mean Johnsen score< 5, and maximum Johnsen score < 7.

A laboratory modification to testicular sperm preparation technique improves spermatogenic cell yield

Testicular sperm extraction is a common procedure used to find spermatogenic cells in men with nonobstructive azoospermia. The laboratory processing of biopsied testicular tissues needs to be performed meticulously to acquire a high yield of cells. In this study, the effectiveness of mincing the tissues after testicular biopsy was assessed using histological evaluation, as was the possible adverse effect of residual tissue on the migration of spermatogenic cells during density gradient centrifugation. Our results indicate that testicular residual tissue, when laid on the density gradient medium along with the sperm wash, hinders the spermatogenic cells＇ forming a pellet during centrifugation, and therefore impairs the intracytoplasmic sperm injection procedure. Whereas the mean number of recovered cells from the sperm wash medium （SWM） with residual tissue is 39.435 ~ 24.849, it was notably higher （60.189 ~ 28.214 cells） in the SWM without minced tissues. The remaining tissue contained no functional seminiferous tubules or spermatogenic cells in histological sections. In conclusion, the remaining residual tissue after mincing biopsied testicular tissue does not add any functional or cellular contribution to spermatogenic cell retrieval; in fact, it may block the cellular elements in the accompanying cell suspension from migrating through the gradient layers to form a pellet during centrifugation and cause loss of spermatogenic cells.

Development of a predictive model for increasing sperm retrieval sucpess by microdissection testicular sperm extraction in patients with nonobstructive azoospermia

Microdissection testicular sperm extraction(micro-TESE)is widely used to treat nonobstructive azoospermia.However,a good prediction model is required to anticipate a successful sperm retrieval rate before performing micro-TESE.This retrospective study analyzed the clinical records of 200 nonobstructive azoospermia patients between January 2021 and December 2021.The backward method was used to perform binary logistic regression analysis and identify factors that predicted a successful micro-TESE sperm retrieval.The prediction model was constructed using acquired regression coefficients,and its predictive performance was assessed using the receiver operating characteristic curve.In all,67 patients(sperm retrieval rate:33.5%)underwent successful micro-TESE.Follicle-stimulating hormone,anti-Miillerian hormone,and inhibin B levels varied significantly between patients who underwent successful and unsuccessful micro-TESE.Binary logistic regression analysis yielded the following six predictors:anti-Mullerian hormone(odds ratio[OR]=0.902,95%confidence interval[Cl]:0.821-0.990),inhibin B(OR=1.012,95%Cl:1.001-1.024),Klinefelter’s syndrome(OR=0.022,95%Cl:0.002-0.243),Y chromosome microdeletion(OR=0.050,95%Cl:0.005-0.504),cryptorchidism with orchiopexy(OR=0.085,95%Cl:0.008-0.929),and idiopathic nonobstructive azoospermia(OR=0.031,95%Cl:0.003-0.277).The prediction model had an area under the curve of 0.720(95%Cl:0.645-0.794),sensitivity of 65.7%,specificity of 72.2%,Youden index of 0.379,and cut-off value of 0.305 overall,indicating good predictive value and accuracy.This model can assist clinicians and nonobstructive azoospermia patients in decision-making and avoiding negative micro-TESE results.

Testicular sperm extraction(TESE)outcomes in the context of malignant disease:a systematic review

Advances in the oncology field have led to improved survival rates.Consequently,quality of life after remission is anticipated,which includes the possibility to conceive children.Since cancer treatments are potentially gonadotoxic,fertility preservation must be proposed.Male fertility preservation is mainly based on ejaculated sperm cryopreservation.When this is not possible,testicular sperm extraction(TESE)may be planned.To identify situations in which TESE has been beneficial,a systematic review was conducted.The search was carried out on the PubMed,Scopus,Google Scholar,and CISMeF databases from 1 January 2000 to 19 March 2020.Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)recommendations were followed in selecting items of interest.Thirty-four articles were included in the systematic review,including 15 articles on oncological testicular sperm extraction(oncoTESE),18 articles on postgonadotoxic treatment TESE and 1 article on both oncoTESE and postgonadotoxic treatment TESE.Testicular sperm freezing was possible for 42.9%to 57.7%of patients before gonadotoxic treatment and for 32.4%to 75.5%of patients after gonadotoxic treatment,depending on the type of malignant disease.Although no formal conclusion could be drawn about the chances to obtain sperm in specific situations,our results suggest that TESE can be proposed before and after gonadotoxic treatment.Before treatment,TESE is more often proposed for men with testicular cancer presenting with azoospermia since TESE can be performed simultaneously with tumor removal or orchiectomy.After chemotherapy,TESE may be planned if the patient presents with persistent azoospermia.

Testicular volume is a noninvasive predictor of sperm retrieval failure in idiopathic nonobstructive azoospermia

We investigated the prognostic importance of noninvasive factors in predicting sperm retrieval failure in idiopathic nonobstructive azoospermia(iNOA).We studied 193 patients with nonobstructive azoospermia who underwent microsurgical testicular sperm extraction.The Chi-square test and Mann–Whitney U tests for clinical parameters and seminiferous tubule distribution were used for between-group comparisons.A logistic regression analysis was conducted to identify predictors of retrieval failure.Area under the receiver operating characteristic curve for each variable was evaluated,and the net clinical benefit was calculated using a clinical decision curve.Patients with iNOA had a lower sperm retrieval rate than those with known causes.Moreover,testicular volume was an independent factor affecting sperm extraction outcomes(odds ratio=0.79,P<0.05).The testicular volume cut-off value was 6.5 ml(area under the curve:0.694).The patients with iNOA were categorized into two groups on the basis of the distribution of seminiferous tubules observed.The sperm retrieval rate and testicular volume were significantly different between the groups with a uniform or heterogeneous tubule distribution.There was also a significant association between a uniform tubule distribution and testicular volume.In conclusion,a testicular volume of more than 6.5 ml effectively predicts microsurgical testicular sperm extraction failure due to a uniform tubule distribution in patients with iNOA.

原发性纵隔精原细胞瘤放化疗后无精子症1例并文献复习

目的探讨原发性纵隔精原细胞瘤放化疗后无精子症患者的诊疗思路。方法通过分析2024年1月北京大学第一医院太原医院诊治的1例原发性纵隔精原细胞瘤放化疗后无精子症患者的诊疗过程,结合相关文献报道,探讨此类患者的临床诊疗策略。结果该例患者通过显微镜下睾丸切开取精术获得精子。结论对于放化疗后无精子症患者,应综合评估患者情况后选择合适的治疗方法,帮助患者合理解决生育问题。

睾丸显微取精术结局预测指标的研究进展

非梗阻性无精子症(NOA)是指由于睾丸精子发生障碍而导致精液中无精子,但睾丸中可能仍存在多处或孤立的生精灶。由于通过取精手术仍能在睾丸内获取到精子,NOA男性也可以借助ICSI生育自己的生物学后代。不同于传统睾丸取精手术,睾丸显微取精术(M-TESE)借助手术显微镜对睾丸组织进行显微解剖以寻找精子发生灶,大大提高了精子的获取率。虽然M-TESE是NOA患者获取精子的最佳方法,但阳性率不高。目前缺乏更准确的预测指标,因此生精灶的定性和定位诊断具有重要意义。本文旨在对M-TESE结局的预测因素以及未来可能具有应用价值的预测技术进行总结,为NOA的临床诊疗和研究提供参考。

非嵌合型克氏综合征患者行睾丸显微取精术的临床结局分析

目的分析非嵌合型克氏综合征(KS)患者行睾丸切开显微取精术(M-TESE)的临床结局。方法回顾性分析2018年1月至2023年12月于南昌市生殖医院行M-TESE的38例KS患者(染色体核型为47,XXY)的临床资料。所有患者均行M-TESE,根据是否成功获取精子分为获取组(n=17)与未获取组(n=21)。比较两组临床资料,分析新鲜精子和冷冻精子行卵泡浆内单精子注射术(ICSI)的临床结局。结果两组年龄、身高、体质量、体重指数(BMI)、睾丸体积及卵泡刺激素(FSH)、黄体生成素(LH)、睾酮(T)水平比较差异无统计学意义。新鲜精子和冷冻精子的受精率、卵裂率、优质胚胎率、囊胚率、妊娠率比较差异无统计学意义。结论KS患者相关参数无法预测睾丸显微取精获取率,新鲜精子和冷冻精子有同样的临床结局,可根据实际情况和需求选择同周期或非同周期行ICSI。

Machine learning-based prediction of pregnancy outcomes in couples with non-obstructive azoospermia using micro-TESE for ICSI: a retrospective cohort study

Objective:To develop a clinically applicable tool for predicting clinical pregnancy,providing individualized patient counseling,and helping couples with non-obstructive azoospermia(NOA)decide whether to use fresh or cryopreserved spermatozoa for oocyte insemination before microdissection testicular sperm extraction(mTESE).Methods:A total of 240 couples with NOA who underwent mTESE-ICSI were divided into two groups based on the type of spermatozoa used for intracytoplasmic sperm injection(ICSI):the fresh and cryopreserved groups.After evaluating several machine learning algorithms,logistic regression was selected.Using LASSO regression and 10-fold cross-validation,the factors associated with clinical pregnancy were analyzed.Results:The area under the curves(AUCs)for the fresh and cryopreserved groups in the Logistic Regression-based prediction model were 0.977 and 0.759,respectively.Compared with various modeling algorithms,Logistic Regression outperformed machine learning in both groups,with an AUC of 0.945 for the fresh group and 0.788 for the cryopreserved group.Conclusion:The model accurately predicted clinical pregnancies in NOA couples.

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.

微小RNA在非梗阻性无精症中的研究进展

微小RNA(miRNA)在细胞增殖、分化和凋亡等多种生物过程中发挥着关键作用。精子发生是一个非常复杂的细胞分裂分化过程,miRNA同样在其中扮演着极其重要的角色。miRNA表达失调极大影响着精子的发生,精子发生严重障碍可表现为非梗阻性无精子症(NOA)。目前,显微睾丸取精(micro-TESE)是NOA患者获精率最高的手术,但仍有一半的患者无法获取精子。最新研究发现,精浆miRNAs模型预测micro-TESE获精显示出了一定潜力。本文综述了miRNA在NOA中的作用以及精浆miRNA预测micro-TESE精子获取的相关模型,讨论了miRNA作为NOA潜在治疗靶点的可能性。

生精细胞形态学检查联合血清FSH水平检测在NOA患者M-TESE中的应用价值

目的探讨精液生精细胞形态学检查联合血清卵泡刺激素(FSH)水平检测在非梗阻性无精子症(NOA)患者睾丸显微取精术(M-TESE)中的应用价值。方法以2019年10月至2021年10月在该院生殖医学中心接受M-TESE的41例NOA患者为研究对象,采集精液标本进行生精细胞形态学检查和血清FSH水平检测。将精液生精细胞形态学检查检出生精细胞的患者作为阳性组,未检出生精细胞的患者作为阴性组;显微镜下找到成熟精子为M-TESE成功,未找到成熟精子为M-TESE未成功。分析两组患者的血清FSH水平和M-TESE的成功率。结果41例NOA患者中,阳性组18例,占43.9%;阴性组23例,占56.1%。M-TESE成功15例,未成功26例,总成功率为36.6%,其中阳性组M-TESE成功率为66.7%(12/18),阴性组M-TESE成功率为13.0%(3/23),两组的M-TESE成功率比较,差异有统计学意义(P<0.001)。阳性组血清FSH水平为(27.2±14.2)mIU/mL,阴性组为(39.3±15.0)mIU/mL,差异有统计学意义(P=0.012)。结论NOA患者精液生精细胞形态学检查联合血清FSH水平检测对M-TESE成功率有一定的预测作用。

Testicular biopsy： clinical practice and interpretation

Testicular biopsy was considered the cornerstone of male infertility diagnosis for many years in men with unexplained infertility and azoospermia. Recent guidelines for male infertility have limited the indications for a diagnostic testicular biopsy to the confirmation of obstructive azoospermia in men with normal size testes and normal reproductive hormones. Nowadays, testicular biopsies are mainly performed for sperm harvesting in men with non-obstructive azoospermia, to be used for intracytoplasmic sperm injection. Testicular biopsy is also performed in men with risk factors for testicular malignancy. In a subgroup of infertile men, there is an increased risk for carcinoma in situ of the testis, especially in men with a history of cryptorchidism and testicular malignancy and in men with testicular atrophy. Ultrasonographic abnormalities, such as testicular microlithiasis, inhomogeneous parenchyma and lesions of the testes, further increase the risk of carcinoma in situ （CIS） in these men. For an accurate histological classification, proper tissue handling, fixation, preparation of the specimen and evaluation are needed. A standardized approach to testicular biopsy is recommended. In addition, approaches to the detection of CIS of the testis testicular immunohistochemistry are mandatory. In this mini-review, we describe the current indications for testicular biopsies in the diagnosis and management of male infertility.