Project description:BackgroundFor male infertility patients with suspected non-obstructive azoospermia, fine needle aspiration mapping (FNAM) of the testis identifies and locates sperm and guides surgical sperm retrieval (SSR), offering an alternative approach to microsurgical testicular sperm extraction (mTESE). Our objectives were to (I) identify success rates with less invasive methods of SSR guided by FNAM, (II) understand how hormone levels influence sperm presence on FNAM, and (III) describe surgical complications in a contemporary cohort of individuals undergoing FNAM of the testis.MethodsWe completed an institutional review board (IRB) approved retrospective medical records review of men with azoospermia or cryptozoospermia who underwent a 12-point systematic sampling of each testicle between May 2009 and May 2023 including results of subsequent SSR. Possible cytopathologic diagnoses included germ cell aplasia (GCA), maturation arrest (MA), hypospermatogenesis (HS) and normal spermatogenesis (NS). Hormone levels and detection of sperm on FNAM were compared utilizing analysis of variance (ANOVA) and subsequent unpaired t-tests.ResultsOf the 220 men who underwent FNAM, 84 (38%) were found to have sperm. Of those 84, 52 subsequently underwent SSR based on their FNAM. Of these, 4 (8%) underwent testicular sperm extraction (TESE), 30 (59%) underwent testicular sperm aspiration (TESA), and 18 (33%) underwent mTESE. SSR successfully obtained sperm in all 52 (100%) patients. Average follicle stimulating hormone (FSH) levels were 13.9±11.3 and 19.6±10.7 mU/mL in those with and without sperm on FNAM, respectively (P<0.001). When patients were stratified by detailed cytopathologic FNAM diagnosis, no difference was noted between FSH levels in those with HS from those with GCA or MA, however a difference was noted between HS and NS (P<0.001). In men with FSH levels between 7.7 and 14.9 mU/mL, 36% were found to have sperm and in men with FSH exceeding 15 mU/mL, 28% were found to have sperm on FNAM. Of those patients with FSH levels exceeding 7.6 mU/mL, 47% had successful office-based sperm extraction based on their FNAM.ConclusionsFNAM allows for de-escalation of sperm extraction technique, even in patients with poor clinical predictors of sperm presence, such as those with significantly elevated FSH levels.
Project description:PurposeTo determine whether there was a significant impact on using cryopreservation of testicular or epididymal sperm upon the outcomes of intracytoplasmic sperm injection (ICSI) in patients with obstructive azoospermia (OA).MethodSystematic review and meta-analysis of 20 retrospective studies in databases from January 1, 1995, to June 1, 2020.ResultTwenty articles were included in this study. A total of 3602 (64.1%) of 5616 oocytes injected with fresh epididymal sperm were fertilized, compared with 2366 (61.2%) of 3862 oocytes injected with cryopreserved sperm (relative risk ratio (RR) 0.96, 95% confidence interval (CI) (0.90, 1.02), P > 0.05). A total of 303 (44.1%) of 687 ICSI cycles using fresh epididymal sperm resulted in a clinical pregnancy, compared with 150 (36.6%) of 410 ICSI cycles using cryopreserved epididymal sperm (RR 0.84, 95% CI (0.72, 0.97), P < 0.05). In the testis, a total of 2147 (68.7%) of 3125 oocytes injected with fresh sperm were fertilized, compared with 1623 (63.5%) of 2557 oocytes injected with cryopreserved sperm (RR 0.97, 95% CI (0.90, 1.06), P > 0.05). A total of 151 (47.8%) of 316 ICSI cycles using fresh testicular sperm resulted in a clinical pregnancy, compared with 113 (38.2%) of 296 ICSI cycles using cryopreserved sperm (RR 0.87, 95% CI (0.72, 1.05), P > 0.05).ConclusionsIn men with OA, there was a statistical lower clinical pregnancy rate (CPR) by using frozen epididymal sperm compared with fresh epididymal sperm, but showing no difference on fertilization rate (FR). Additionally, FR and CPR were not affected by whether the retrieved testicular sperm was frozen or fresh.
Project description:BackgroundBeclin-1 is an autophagy gene and higher levels suggest mammalian testicular damage. Our study aims at exploring the role of Beclin-1 in non-obstructive azoospermia (NOA) patients and clarifying the predictive value of Beclin-1for sperm retrieval in microdissection testicular sperm extraction (micro-TESE).MethodsIn the present study, 62 NOA patients were finally recruited. Serum hormone including luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol II (E2), testosterone (T) and prolactin (PRL), as well as testicular volume were measured. Testicular histopathology was diagnosed by two independent pathologists. The expression of Beclin-1 was detected by real-time PCR in testicular tissue.ResultsOur study illustrated that Beclin-1 was differently expressed in three pathological types of NOA. Compared with hypospermatogenesis (HS, P=0.002) or maturation arrest (MA, P=0.049), Beclin-1 showed significantly up-regulated in Sertoli cell-only syndrome (SCOS) group. Moreover, Beclin-1 expression was obviously positive related with serum LH (rho =0.269, P=0.036), meanwhile significantly negative correlation with testicular volume (rho =-0.370, P=0.003), serum T (rho =-0.326, P=0.010), Johnsen score (rho =-0.318, P=0.012), and pathologic type (rho =-0.452, P<0.001). Furthermore, a logistic regression model demonstrated that Beclin-1 is an important predictor of failed sperm retrieval (OR =0.001, P=0.007), which exhibited a pretty AUC =78.6 (P=0.001).ConclusionsBeclin-1 may play a critical role in spermatogenesis. Elevated Beclin-1 may be obviously associated with lower chances of positive sperm retrieval.
Project description:PurposeThe present study sought to determine the diagnostic accuracy of FSH level, testicular volume, and testicular histology in predicting the successful sperm retrieval (SSR) in a large cohort of patients with non-obstructive azoospermia undergoing conventional testicular sperm extraction (TESE).MethodsWe retrospectively evaluated 356 patients with non-obstructive azoospermia between June 2004 and July 2009. Binary logistic regression was used to evaluate the diagnostic accuracy of our predicting model, identifying sperm retrieval rate as binary dependent variable. The predictive accuracy of all variables individually evaluated was quantified with area under curve (AUC) estimates derived from receiver operating characteristic (ROC) curve.ResultsThe mean patients' age was 36.8 years. Testicular sperm were retrieved in 158 out of 356 patients (44.3 %). Histological diagnosis of Sertoli cell only syndrome (SCO) was obtained in 216 patients (60.6 %), while 55 patients (15.4 %) had maturation arrest (MA) and 85 (23.8 %) had hypospermatogenesis (HYPO). The binary logistic regression model was statistically significant (χ 2 = 96.792, p < 0.0001) and correctly classified 72.8 % of cases with 46.8 % sensitivity and 93.4 % specificity, positive predictive value (PPV) 85.06 %, negative predictive value (NPV) 68.7 %, +likelihood ratio (LR) 7.13, and -LR 0.57. Only testicular histology was significant to the model, while FSH and testicular volume were not. Sperm retrieval rate (SRR) was significantly higher in patients with HYPO compared to patients with SCO or MA (88.2 vs 30.5 and 30.9 %, respectively, p < 0.0001) CONCLUSIONS: This study demonstrates that including testicular histology in a model for predicting sperm retrieval increases its diagnostic accuracy. As histology is not available prior to TESE, this model applies only to patients with previous testicular surgery.
Project description:The project aimed to compare testicular proteomes from patients with obstructive and non-obstructive azoospermia in order to identify molecular signatures involved in spermatogenesis as well to identify candidate biomarkers for discriminating between different types of azoospermia. The samples used in this study were formalin fixed paraffin embedded (FFPE) testicular tissues obtained by biopsy from men with clinical diagnosis of azoospermia. Samples were grouped according to the histopathological report in 3 groups: 1) Spermatogenesis (obstructive azoospermia), 2) Hypospermatogenesis and 3) Sertoli cell only syndrome (SCO). Patients were aged 31–46 years with no differences among groups regarding age (Median age (Hypospermatogenesis) =35; Median age (SCO) =34 and Median age (Spermatogenesis) =39). Each group had 9 samples or 27 samples in total were used for the comparative proteomics analysis by label-free data-independent LC-MS/MS.
Project description:BackgroundA very small number of studies have indicated that azoospermia or negative testicular sperm extraction (TESE) outcomes are linked to depression or erectile dysfunction. However, the data are often weak, conflicting and gathered with non-validated questionnaires. Hence, we performed a cross-sectional study of 44 men with non-obstructive azoospermia. Levels of self-esteem and the quality of the couple's sex life and overall relationship were assessed with validated questionnaires before and after the TESE procedure as a function of the TESE outcome.ResultsA positive TESE outcome (n = 24) was associated with a statistically significant increase in self-esteem (particularly with regard to family aspects), sexual health and couples' adjustment quality. In contrast, a negative TESE outcome (n = 20) was associated with statistically significant decreases in self-esteem, erectile function, intercourse satisfaction, orgasmic function, couples' adjustment quality and all aspects of the couple's relationship (consensus, cohesion, satisfaction and affection).ConclusionFor men with non-obstructive azoospermia (NOA), negative TESE outcomes may have a negative impact on self-esteem and the quality of the couple's sex life and overall relationship. This should be borne in mind when counselling men with NOA and their partners to (ideally) help them to cope with and decrease the harmful impacts of azoospermia and negative TESE.
Project description:BackgroundMicrodissection testicular sperm extraction (mTESE) is the gold standard treatment for men with non-obstructive azoospermia (NOA). However, many men do not elect to pursue this surgical intervention. We aimed to identify factors associated with NOA patients undergoing mTESE after initial evaluation by a reproductive urologist (RU) through a retrospective cohort study.MethodsWe retrospectively reviewed NOA patient who underwent evaluation by a RU between 2002-2018. Demographic and clinical data were collected. Our primary outcome was electing to undergo mTESE.Results44.4% (75/169) of NOA men underwent mTESE. These patients earned significantly higher median neighborhood income ($133,000 vs. $97,000, P<0.001), spent fewer years trying to conceive before seeking care {1.3 [interquartile range (IQR): 1-3] vs. 2.3 (IQR: 1-5), P=0.012}, and were more likely to be married (79.7% vs. 53.9%, P=0.001). On univariate analysis, married men [odds ratio (OR) 3.37, 95% confidence interval (CI): 1.67-6.79, P=0.001] and men with higher neighborhood income (OR 1.14, 95% CI: 1.06-1.21, P<0.001) were more likely to undergo mTESE, while couples attempting to conceive for a longer period of time prior to initial evaluation were less likely to undergo mTESE (OR 0.79, 95% CI: 0.68-0.92, P=0.003). On multivariable regression analysis, marital status and years attempting to conceive remained significantly associated with NOA patients undergoing mTESE (OR 4.61, 95% CI: 1.16-18.25, P=0.03; OR 0.67, 95% CI: 0.52-0.88, P=0.003, respectively).ConclusionsHigher neighborhood income and marital status were positively associated with patients undergoing mTESE, while couples who attempted to conceive for a longer period of time before seeking infertility care were less likely to undergo mTESE.
Project description:BackgroundMany circular RNAs (circRNAs) are specifically expressed in the testes and seminal plasma of patients with non-obstructive azoospermia (NOA), highlighting them as potential predictors of microdissection testicular sperm extraction (micro-TESE) outcomes. Although research has indicated that circular RNA monoglyceride lipase (circ_MGLL) is highly expressed in the testicular tissues of patients with NOA, the association between circ_MGLL expression and sperm retrieval outcomes (SROs) in patients with idiopathic non-obstructive azoospermia (iNOA) receiving micro-TESE remains unclear.MethodsThis single-center, retrospective cohort study enrolled 114 patients with iNOA who underwent micro-TESE at Northwest Women's and Children's Hospital from January 2017 to November 2021. A logistic regression model was used to examine associations between SRO and circ_MGLL expression in testicular tissues, the results of which were used in conjunction with previous findings to establish a nomogram. The predictive performance of the circ_MGLL-based nomogram was evaluated via calibration curves, receiver operating characteristic curves, and decision curve analysis (DCA) using an internal validation method.ResultsThe generalized additive model indicated that the probability of successful SRO for micro-TESE decreased as circ_MGLL expression increased in testicular tissues. Across the entire cohort, univariate logistic regression analysis revealed that circ_MGLL expression was inversely associated with SRO in patients with NOA. This trend did not change after stratification according to age, body mass index, testicular volume, follicle-stimulating hormone (FSH) level, luteinizing hormone (LH) level, testosterone (T) level, or pathological type (or after adjusting for these confounders) (odds ratio <1, P < 0.001). A nomogram was then generated by integrating circ_MGLL, pathological types, and FSH, LH, and T levels. The circ_MGLL-based predictive model achieved satisfactory discrimination, with an area under the curve of 0.857, and the calibration curves demonstrated impressive agreement. The DCA indicated that the net clinical benefit of the circ_MGLL-based predictive model was greater than that of circ_MGLL alone.Conclusioncirc_MGLL is significantly associated with the SRO of micro-TESE in patients with iNOA. The circ_MGLL-based nomogram developed in the current study can predict successful SRO with high accuracy.
Project description:BackgroundTesticular sperm extraction (TESE) is the method of choice for recovering spermatozoa in patients with azoospermia. However, the lack of reliable biomarkers makes it impossible to predict sperm retrieval outcomes at TESE. To date, little attention has been given to anti-Müllerian hormone (AMH) serum levels in adult men with altered spermatogenesis. In this study we aimed to investigate whether serum concentrations of AMH and the AMH to total testosterone ratio (AMH/T) might be predictive factors for sperm retrieval outcomes during TESE in a cohort of 155 adult Caucasian men with azoospermia.ResultsAMH serum levels were significantly lower in nonobstructive azoospermia (NOA) that was unexplained, cryptorchidism-related, cytotoxic and genetic (medians [pmol/l] = 30.1; 21.8; 26.7; 7.3; and p = 0.02; 0.001; 0.04; <0.0001, respectively]) compared with obstructive azoospermia (OA) (median = 44.8 pmol/l). Lowest values were observed in cases of genetic NOA (p < 0.0001, compared with unexplained NOA) and especially in individuals with non-mosaic Klinefelter syndrome (median = 2.3 pmol/l, p <0.0001). Medians of AMH/T values were significantly lower in genetic NOA compared to unexplained, cryptorchidism-related NOA as well as OA. Only serum concentrations of AMH differed significantly between positive and negative groups in men with non-mosaic Klinefelter syndrome. The optimal cut-off of serum AMH was set at 2.5 pmol/l. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of this cut-off to predict negative outcomes of SR were 100 %, 76.9 %, 66.6 %, 100 and 84.2 %, respectively.ConclusionsSerum AMH levels, but not AMH/T values, are a good marker for Sertoli and germ cell population dysfunction in adult Caucasian men with non-mosaic Klinefelter syndrome and could help us to predict negative outcomes of SR at TESE with 100 % sensitivity when serum levels of AMH are below 2.5 pmol/l.
Project description:BackgroundMicrodissection testicular sperm extraction (micro-TESE) in combination with ICSI can make paternity possible for non-obstructive azoospermia (NOA) patients. Testicular sperm can be successfully retrieved in nearly half of NOA patients. Nevertheless, not many convincing protocols are established to improve sperm retrieval rate (SRR). The goal of this study was to evaluate whether gonadotropins therapy before micro-TESE could improve sperm retrieval rate and affect the ICSI outcomes in non-obstructive azoospermia patients with hypergonadotropic hypogonadism.MethodsThis retrospective cohort study included a total of 569 non-obstructive azoospermia men who underwent micro-TESE with or without 3-month of preoperative hCG / hCG plus highly purified urinary FSH (uFSH) between January 2016 and December 2019. The primary outcome was the sperm retrieval rate of micro-TESE.ResultsSperm was found in 27 patients among 395 NOA men who accepted preoperative gonadotropins treatment (6.8%, 27/395) in post-treatment semen analysis for ICSI. One hundred forty nine out of 542 patients could successfully obtain enough sperm for ICSI through the micro-TESE (overall SRR = 27.5%). There was a statistically significant difference in the SRR between the preoperative gonadotropins treatment and non-gonadotropins treatment groups (31.2%, 115/368 vs. 19.5%, 34/174, P = 0.006). In the multivariable analysis with IPTW according to the propensity score, there was a significant association between preoperative gonadotropins treatment and the SRR (OR, 1.59; 95% CI: 1.02-2.52; P = 0.042). No differences in the clinical pregnancy rate, live birth delivery rate, or miscarriage rate were observed between the two groups.ConclusionPreoperative gonadotropins therapy seems to have a role in improving SRR in NOA patients with hypergonadotropic hypogonadism. We found that gonadotropins therapy had no effect on ICSI clinical outcomes and live birth.