Successful Sperm Retrieval Research Articles

Nomogram based on a circular RNA biomarker for predicting the likelihood of successful sperm retrieval via microdissection testicular sperm extraction in patients with idiopathic non-obstructive azoospermia.

Many 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. This 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. The 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. circ_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.

Inhibin B-to-Anti-Mullerian Hormone Ratio as Noninvasive Predictors of Positive Sperm Retrieval in Idiopathic Non-Obstructive Azoospermia.

The lack of clinically useful biomarkers for predicting micro-TESE outcomes in males with idiopathic NOA. To find clinically reliable serum reproductive hormone markers to predict the outcome of sperm retrieval in men with idiopathic NOA undergoing micro-TESE. We analyzed the clinical data of 168 men with idiopathic NOA treated with micro-TESE. The clinical predictors of a successful sperm retrieval were put to the test using logistic regression analysis. The clinical net benefit was calculated using a decision-curve analysis, and the predictive power of each variable was assessed using the ROC-derived area under the curve. Between positive group and negative group for sperm retrieval, there was a statistically significant difference in INHB, AMH, and INHB/AMH. AMH, INHB, and INHB/AMH were each independent predictors of successful sperm retrieval, with INHB (OR1.02, p = 0.03), AMH (OR0.85, p = 0.01), INHB/AMH (OR1.08, p &lt; 0.01). The ROC curve determined the optimal cut-off values for serum INHB and INHB/AMH in positive sperm retrieval patients undergoing micro-TESE. 21.51 pg/mL was the cut-off value for INHB. The cut-off value for INHB/AMH was 3.19, which had a 86.3% sensitivity and a 53.8% specificity. Using INHB and INHB/AMH prior to micro-TESE sperm retrieval in idiopathic NOA patients improved the net benefit of positive sperm retrieval, and the net benefit score of INHB/AMH was better than that of INHB, according to decision analysis curves. Serum INHB have predictive value for sperm retrieval outcomes in idiopathic NOA patients undergoing micro-TESE. Combining INHB and AMH, INHB/AMH seems to be a better predictor.

Histological and immunohistochemical outcomes after microdissection TESE in contrast with hormonal profile, testis volume and genetics in patients with azoospermia.

A limited number of individuals with non-obstructive azoospermia (NOA) may recover spermatozoa through traditional testicular sperm extraction (TESE) techniques. There is an ongoing debate over the effectiveness of microdissection TESE compared to standard TESE methods. Microdissection TESE (micro-TESE) techniques enable the identification of spermatogenesis foci in non-obstructive forms of azoospermia. Only histological examination can provide an objective and definitive assessment of the testicular phenotype. This study aimed to evaluate the correlation between histopathological findings after microdissection TESE (micro-TESE) and the predictive role of various factors in determining the success of sperm retrieval. We evaluated 24 patients with azoospermia who underwent micro-TESE and considered the patient's hormonal profile, testis ultrasound, genetic evaluation, histology, and immunohistology (PLAP antibody) of collected testis biopsies. The preoperative blood FSH level, in conjunction with other parameters, may aid in the prediction of micro-TESE success. Sensitivity increases, and specificity decreases with higher FSH levels. Furthermore, testicular volume and FSH levels are typically normal in patients with maturation arrest. In conclusion, hormones, ultrasound evaluation of the testicles, testis volume, and available genetic tests have a predictive value in differentiating obstructive azoospermia (OA) from NOA with various sensitivity and specificity rates. Histological and immunohistochemical evaluation establishes the testicular phenotype accurately and guides patient management.

Correlation of Serum FSH and Rate of Testicular Sperm Retrieval in Non-Obstructive Azoospermia.

Sperm retrieval from men with azoospermia has evolved in recent times, providing patient hope for fulfilling their dream of having their own genetic child through testicular sperm extraction followed by intracytoplasmic sperm injection (TESE-ICSI). In the present study, we are correlating the serum follicle stimulating hormone (FSH) levels and the rate of testicular sperm retrieval. To correlate the serum FSH levels with surgically retrieved sperms from testes in non-obstructive azoospermia. Sixty-six men presenting with male infertility, diagnosed with non-obstructive azoospermia based on standard guidelines were included in the study. The surgically retrieved tissue was washed in 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) gamete buffer media and scanned under an inverted microscope at ×400. Outcome analysis was assessed through sperm retrieval rate. Testicular sperms were successfully retrieved in 62% (41/66) of men. Sperm retrieval rate (SRR) with FSH values (Group A <10, Group B 10-20 and Group C >20) mIU/mL were 84% (26/31), 75% (12/16) and 15% (3/19), respectively. Chances of sperm retrieval in non-obstructive azoospermia using surgically retrieved sperm are as common for men with FSH levels <10 mIU/mL with 84% (26/31) retrieval as for the borderline 10-20 mIU/mL FSH levels with 75% (12/16) retrieval. We do have retrieved sperms with >20 IU/mL serum FSH also which is not a contradiction for TESE for such patients; however, such patient's need to be counselled about the chances of successful sperm retrieval and the consequent pregnancy outcomes.

Mate-pair genome sequencing reveals structural variants for idiopathic male infertility.

Currently, routine genetic investigation for male infertility includes karyotyping analysis and PCR for Y chromosomal microdeletions to provide prognostic information such as sperm retrieval success rate. However, over 85% of male infertility remain idiopathic. We assessed 101 malepatients with primary infertility in a retrospective cohort analysis who have previously received negative results from standard-of-care tests. Mate-pair genome sequencing (large-insert size library), an alternative long-DNA sequencing method, was performed to detect clinically significant structural variants (SVs) and copy-number neutral absence of heterozygosity (AOH). Candidate SVs were filtered against our in-house cohort of 1077 fertile men. Genes disrupted bypotentially clinically significant variants were correlated with single-cellgene expression profiles ofhuman fetal and postnatal testicular developmental lineages and adult germ cells. Follow-up studies were conducted for each patient with clinically relevant finding(s). Molecular diagnoses were madein 11.1% (7/63) of patients with non-obstructive azoospermia and 13.2% (5/38) of patients with severe oligozoospermia. Among them, 12 clinically significant SVs were identified in 12 cases, including five known syndromes, one inversion, and six SVs with direct disruption of genes by intragenic rearrangements or complex insertions. Importantly, a genetic defect related to intracytoplasmic sperm injection (ICSI) failure was identified in a patient withnon-obstructive azoospermia, illustrating the additional value of an etiologic diagnosis in addition to determining sperm retrieval rate. Our study reveals a landscape of various genomic variants in 101 males with idiopathic infertility, not only advancing understanding of the underlying mechanisms of male infertility, but also impacting clinical management.

The effect of hormonal stimulation in hypogonadal men with non obstructive azoospermia (noa) undergoing microsurgical testicular sperm retrieval (mtese) - a single centre retrospective analysis.

NOA is often associated with hypogonadism and testicular failure. This study aims to evaluate the role of endocrine stimulation therapy prior to mTESE in men with hypogonadism and NOA. This is a retrospective study on infertile men who underwent mTESE with or without prior endocrine stimulation therapy (clomiphene or hCG). Hypogonadism was defined as serum testosterone(T) level <12 nm/L. We recorded duration-type of stimulation, pre/post-stimulation hormone levels(T,FSH,LH) and successful sperm retrieval(SSR) rate. 168 men underwent mTESE out of which 59men received stimulation therapy. Among them, we selected men with hypogonadism (43% of the cohort). The hypogonadal group included 71 men; 28/71 had Klinefelter syndrome and 40/71 received endocrine stimulation for 13.9 ± 9.2 months. T levels significantly increased after endocrine stimulation (6.3±3.3 nm/L vs 11.7±7.4 nm/L) with mean change in serum T(∆T) of 5.7 nm/L (-5.5-23.3, N35). In the stimulated group, pre-operative serum T levels were significantly higher (11.7±7.4 vs 7.8±3.0 p:0.007) as compared to unstimulated men but the SSR did not differ significantly (16/40 vs 13/31 – 40% vs 42%). Men with Klinefelter syndrome demonstrated significant differences with regards to age, lower T levels, higher FSH and LH levels, lower SSR compared to other causes of NOA. Comparing men who had successful mTESE vs unsuccessful mTESE - higher level of T and lower levels of FSH and LH seemed to correlate with SSR. Among men who received stimulation therapy the ∆T before and after stimulation seemed to correlate with successful mTESE (AUC:0.701,SE:0.089,p:0.043). In the stimulated group a ΔT>3.5nm/L showed a significant association with successful mTESE(p:0.041). Our study shows that there is a significant improvement of serum T concentration following endocrine stimulation therapy in hypogonadal men with serum T<12nm/L. Overall, in hypogonadal men, the hormonal stimulation seems not to be related to a higher success rate of mTESE but our data do suggest a positive correlation between ∆T before and after stimulation, and a successful mTESE. None

Outcomes and affecting factors for ICSI and microTESE treatments in nonobstructive azoospermia patients with different etiologies: A retrospective analysis.

Nonobstructive azoospermia (NOA) is a common and severe form of male infertility. Microdissection testicular sperm extraction (microTESE) combined with intracytoplasmic sperm injection (ICSI) is an optimal treatment for men with NOA. However, the outcomes and affecting factors of ICSI for NOA patients with different etiologies receiving microTESE treatment are still unclear. A total of 335 NOA patients undergoing microTESE from January 2017 to December 2021 were included in this retrospective analysis. The patients were divided into five groups (idiopathic, Klinefelter syndrome (KS), Y chromosome microdeletions (YCMDs), cryptorchidism and mumps orchitis) according to the etiologies. The clinical characteristics and outcomes of microTESE and ICSI were collected and comparisons were performed between clinical characteristics of patients who had successful sperm retrieval (SSR) and sperm retrieval failure (SRF). In addition, relationships between clinical characteristics and rates of SSR were explored by Kendall correlation analysis. The overall SSR rate was 40.90%. SSR rate of the idiopathic group (31.22%) was the lowest and was much lower than that of other groups (KS: 48.65%, 28/58; YCMDs: 60.87%; cryptorchidism: 80.95%; mumps orchitis: 75.00%). The overall fertilization rate was 72.26%. No group differences were found among five groups (idiopathic: 73.91%; KS: 71.43%; YCMDs: 64.29%; cryptorchidism: 70.59%; mumps orchitis: 77.78%). The overall clinical pregnancy rate was 66.67%. No group differences were found among five groups (idiopathic: 68.63%; KS: 65.00%; YCMDs: 44.44%; cryptorchidism: 66.67%; mumps orchitis: 85.71%). The overall live birth rate was 66.67%. No group differences were found among five groups (idiopathic: 71.43%; KS: 53.85%; YCMDs: 50.00%; cryptorchidism: 75.00%; mumps orchitis: 66.67%). For SSR patients, the average age was significantly lower in the idiopathic group, while the average testicular volume was significantly greater in the cryptorchidism and mumps orchitis groups. However, no significant differences were found in the level of follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T) between patients who had SSR and SRF. In addition, negative relationships were found between age and rates of SSR in idiopathic NOA patients while positive relationships were found between testis volume and rates of SSR in patients with cryptorchidism and mumps orchitis. Patients with idiopathic NOA had lowest SSR. In addition, the age in idiopathic NOA patients was a predictor for SSR while testicular volume in NOA patients with cryptorchidism and mumps orchitis was a predictor for SSR. However, the relationships between clinical characteristics and clinical outcomes in NOA patients were preliminary, and further validation needed to be carried out in a larger sample to increase statistical capacity before a definitive conclusion could be drawn.

Proteomics of azoospermia: Towards the discovery of reliable markers for non-invasive diagnosis.

Azoospermia, as the most severe form of male infertility, no longer indicates sterility due to modern medical advancements. The current diagnostic procedure based on testicular biopsy has several drawbacks which urges the development of novel, non-invasive diagnostic procedures based on biomarkers. In the last two decades, there have been many proteomics studies investigating potential azoospermia biomarkers. In this review, we aimed to provide a critical evaluation of these studies. Published articles were gathered by systematic literature search using Pubmed, Science Direct, and Google Scholar databases until March 2022 and were further preselected to include only studies on human samples. A detailed review of these studies encompassed the proteomics platforms, sources of material, proposed candidate biomarkers, and their potential diagnostic specificity and sensitivity. In addition, emphasis was put on the top, most identified and validated biomarker candidates and their potential for discriminating azoospermia types and subtypes as well as predicting sperm retrieval success rate. Proteomics research of azoospermia has laid the groundwork for the development of a more streamlined biomarker testing. The future research should be focused on well-designed studies including samples from all types/subtypes as well as further testing of the most promising biomarkers identified so far.

Micro-TESE strategy in patients with NOA caused by AZFc deletion: synchronous or asynchronous?

In the treatment of infertile patients with non-obstructive azoospermia (NOA) caused by the deletion of the azoospermia factor c region (AZFc) on the Y chromosome, synchronous and asynchronous surgical strategies are discussed. Clinical data from NOA patients with the AZFc deletion who underwent micro-TESE were analyzed retrospectively. The sperm retrieval rate (SRR) and sperm utilization rate of synchronous and asynchronous operation groups were followed up and compared. The fertilization rate, high-quality embryo rate, clinical pregnancy rate, abortion rate, and cumulative live birth rate of ICSI in patients with successful sperm retrieval were compared between the two groups. The two groups had sperm utilization rates of 98.9% (93/94) and 50.0% (14/28), respectively. The asynchronous group's sperm consumption rates were much lower than those of the synchronous operation group. Fertilization rate, high-quality embryo rate, clinical pregnancy rate of fresh transfer cycle, abortion rate, and cumulative live birth rate of patients in the synchronous operation group with fresh sperm, and the asynchronous operation group with thawed sperm, respectively, were 30.6% vs 33.8%, 33.8% vs 40.7%, 40.0% vs 12.5%, 30.4% vs 7.1%. Between the two groups, there was no significant difference. This suggests that individuals with NOA caused by the AZFc deletion have a high possibility of successfully acquiring sperm using micro-TESE and ICSI to conceive their own offspring. Synchronous micro-TESE is recommended to improve sperm utilization rate and the cumulative live birth rate.

DEVELOPMENT OF A MACHINE LEARNING APPLICATION FOR INTRAOPERATIVE OBJECT DETECTION OF POSITIVE SEMINIFEROUS TUBULES IN MICRODISSECTION TESTICULAR SPERM EXTRACTION FOR NONOBSTRUCTIVE AZOOSPERMIA

Approximately 1 in 100 men in the general population have azoospermia, and 80% of them have nonobstructive azoospermia (NOA). For couples with NOA who wish for a baby, the only effective treatment options are sperm retrieval by microdissection TESE (micro-TESE) and subsequent ICSI. However, the current sperm recovery rate is generally only 30-40%. Favorable seminiferous tubules that contain sperm are generally white and thicker in diameter than other tubules, and the success of sperm retrieval is largely dependent on the surgeon's attentiveness and observational ability.

The piRNA-pathway factor FKBP6 is essential for spermatogenesis but dispensable for control of meiotic LINE-1 expression in humans

Infertility affects around 7% of the male population and can be due to severe spermatogenic failure (SPGF), resulting in no or very few sperm in the ejaculate. We initially identified a homozygous frameshift variant in FKBP6 in a man with extreme oligozoospermia. Subsequently, we screened a total of 2,699 men with SPGF and detected rare bi-allelic loss-of-function variants in FKBP6 in five additional persons. All six individuals had no or extremely few sperm in the ejaculate, which were not suitable for medically assisted reproduction. Evaluation of testicular tissue revealed an arrest at the stage of round spermatids. Lack of FKBP6 expression in the testis was confirmed by RT-qPCR and immunofluorescence staining. In mice, Fkbp6 is essential for spermatogenesis and has been described as being involved in piRNA biogenesis and formation of the synaptonemal complex (SC). We did not detect FKBP6 as part of the SC in normal human spermatocytes, but small RNA sequencing revealed that loss of FKBP6 severely impacted piRNA levels, supporting a role for FKBP6 in piRNA biogenesis in humans. In contrast to findings in piRNA-pathway mouse models, we did not detect an increase in LINE-1 expression in men with pathogenic FKBP6 variants. Based on our findings, FKBP6 reaches a "strong" level of evidence for being associated with male infertility according to the ClinGen criteria, making it directly applicable for clinical diagnostics. This will improve patient care by providing a causal diagnosis and will help to predict chances for successful surgical sperm retrieval.

Experimental validation of seminal miR-31-5p as biomarker for azoospermia and evaluation of the effect of preanalytical variables.

Predicting the origin of azoospermia with non-invasive biomarkers is clinically relevant for determining the chance of successful sperm retrieval from the testes before attempting assisted reproduction treatment. Here, the semen small extracellular vesicle microRNA miR-31-5p-based biomarker test to distinguish obstructive azoospermia from secretory azoospermia (previously described by our group) is validated for clinical use, and additionally, the sample source (seminal small extracellular vesicles vs. total seminal plasma) as a preanalytical variable is considered to optimize the procedure. Our results provide evidence that altered miR-31-5p expression can be determined both from extracellular vesicles and from the whole seminal plasma to discriminate obstructive from secretory azoospermic samples. Not only have we validated this microRNA-based molecular model as a clinically useful test for predicting the origin of azoospermia in a sample from azoospermic individuals, but additionally, and more interestingly for the clinicians, we have evidenced its usefulness for predicting the presence of spermatogenic failure in azoospermic patients with follicle-stimulating hormone values <10 IU/L as a sensitive and specific biomarker (area under the receiver operating characteristic curve >0.88; p-value < 0.006). The use of total seminal plasma as an analytical sample would facilitate the use of a simplified technical procedure for miR-31-5p quantification and would represent a great improvement in reproductive treatment decision protocols for azoospermia in clinical practice.

The predictive factors of successful sperm retrieval for men with Y chromosome AZFc microdeletion.

To identify key predictors for successful sperm retrieval in men with AZFc microdeletion. Totally, 71 infertile men with confirmed AZFc microdeletion were studied. For each patient, the endocrine profile including serum follicle stimulating hormone (FSH), luteinizing hormone, total testosterone, prolactin, and estradiol was recorded, along with intratesticular testosterone levels (ITT), age, and testicular size. The factors were further analyzed to determine the key predictors for successful sperm retrieval. Of the 71 men with AZFc microdeletion, 52 (73.2%) were classified as having non-obstructive azoospermia (NOA), 7 (9.9%) as having cryptozoospermia, and 12 (15.8%) as having severe oligoasthenoteratozoospermia. Of the 52 men with azoospermia, 47 received microdissection testicular sperm retrieval, and sperm retrieval was successful in 35 of those cases (74.5%). A significantly lower serum FSH (p = 0.03) was found in those patients from whom sperm could be successfully retrieved. The area under the receiving operating characteristic curve for FSH was determined to be 0.721. Using an FSH cutoff point of 12.95 mIU/mL, the model for predicting successful sperm retrieval was found to have 51.4% sensitivity, 83.3% specificity, 90.0% positive predictive value, and 37.0% negative predictive value. ITT levels were obtained from 7 NOA patients, the mean ITT and the mean ITT/serum testosterone ratio was 1932.8ng/ml and 567.2 in 6 men with successful sperm retrieval, whereas, in a patient with fail sperm retrieval, the levels were 2370ng/ml and 393.0. Men exhibiting AZFc microdeletion with discernible spermatogenesis from whom sperm was successfully retrieved by mTESE generally presented with relatively lower FSH levels.

Micro-TESE Outcomes for Non-Obstructive Azoospermia — The First Australian Series

Background: Micro-dissection testicular sperm extraction (micro-TESE) for non-obstructive azoospermia (NOA) was shown to achieve the best sperm retrieval rate (SRR) compared to other techniques. However, to date there is no large series of published Australian data. Aim: To study the incidence and predicting factors of successful sperm extraction in men with NOA undergoing micro-TESE in Victoria. Method: We retrospectively analyzed the clinical data of all consecutive patients with confirmed NOA who were treated between August 2014 and April 2020 in a single medical centre in Melbourne, Victoria. None were excluded. Patients underwent micro-TESE and upon a successful sperm retrieval, sperm was either frozen for fertility preservation or used fresh for ICSI. Results: During the study period, 85 men with NOA underwent micro-TESE in our centre. The overall sperm retrieval rate (SRR) was 61.2% (52/85). All patients with a history of surgically treated cryptorchidism or childhood diseases had a successful sperm retrieval. Patients with Kleinfelter syndrome had a 75% SRR. Patients with Idiopathic NOA and patients with a history of chemotherapy had a 50% and 40% SRR, respectively. Among the different types of testicular pathology, the highest SRR was found in men with complete hyalinization (100%). Hypospermatogenesis was associated with a high SRR of 93.3%, while Sertoli-cell-only histology was associated with only 46.3% SRR. The SRR has significantly increased from 33.3% in 2015-2016 to 73.6% in 2019-2020 (p=0.003). On Multivariate logistic regression analysis, baseline FSH levels &lt;20 IU and history of childhood disease or Klinefelter syndrome were significantly associated with successful sperm retrieval. The cumulative pregnancy rate was 23.7%. Conclusion: This first report from Australia indicates that micro-TESE is an effective method for the treatment of NOA with high SRR and pregnancy rate. Our results can help patient management and counseling.

Are Clinical Outcomes of Microdissection Testicular Sperm Extraction in Non-Obstructive Azoospermic Men Affected by the Use of Fresh or Frozen Gametes?

Background: Non-obstructive azoospermia (NOA) is a severe form of male factor infertility, evident in approximately 5% of infertile couples seeking fertility treatment. The combination of microsurgical testicular sperm extraction (mTESE) and ICSI has become one of the treatment options, with sperm motility positively associated with outcome success rates. Few studies have investigated whether use of fresh or thawed gamete combinations affect clinical outcomes. Aim: To determine the clinical outcomes of ICSI cycles using mTESE recovered testicular sperm of NOA patients and whether these are affected by the use of fresh or thawed gametes. Method: A retrospective study of NOA patients who underwent mTESE between March 2017 and September 2020. Clinical outcomes investigated included successful surgical sperm retrieval (SSR), sperm motility, fertilisation, embryo utilisation and live-birth/ongoing pregnancy rates. Results: A total of 105 NOA patients underwent mTESE, with a 65.7% successful SSR. In total 58 patients contributed to 72 ICSI cycles, with a 37.5% 2PN fertilisation rate and 29.4% live-birth/ongoing pregnancy rate. Cycles using only motile sperm had a greater fertilisation rate than those using a motile/non-motile sperm combination (51.7% vs 31.1%, p[Formula: see text]0.05). Compared with fresh, thawed testicular spermatozoa didn’t affect clinical outcomes, including live-birth/ongoing pregnancy rates (Fresh 18.2%; Thawed 17.9%; Odds ratio (OR) 1.02 (0.34-2.86) p=0.98). In contrast, use of thawed oocytes decreased fertilisation rate [Fresh-oocytes: 45.0%; Vitrified-oocytes: 35.5%; OR 1.47(1.03-2.10), p=0.03] but had no differences for other clinical outcomes, including live-birth/ongoing pregnancy rate (p=0.74). Importantly, injection of exclusively non-motile-spermatozoa (n=26 cycles) resulted in a very low fertilisation rate (2.7%) and no live-birth/ongoing pregnancies were recorded. Conclusion: Microdissection TESE is an effective treatment for NOA patients, with no clear negative effects of using thawed spermatozoa, however, the use of vitrified oocytes requires further investigation. The use of non-motile spermatozoa in mTESE ICSI cycles is discouraged.

The Value of Serum Follicle-Stimulating Hormone in Predicting Successful Surgical Sperm Retrieval in Cases of Male Infertility: A Literature Review

Azoospermia is a common cause of male infertility; however, surgical sperm retrieval (SSR) and subsequent intracytoplasmic sperm injection offers couples the chance to have a biological child. SSR success is highly variable and dependent on a number of factors. One such factor is male follicle-stimulating hormone (FSH), which has been researched extensively. The aim of this literature review is to ascertain if there is a ‘cut off’ FSH value that correlates with successful SSR, whether this value differs depending on method of SSR, and if there is a correlation between male FSH level and obstetric outcomes. Thirty-five articles were identified and reviewed, with 10 papers suggesting FSH cut off values. These ranged from &lt;8.5 to &lt;25.0 IU/L, with a mean value of 14.0 IU/L. Generally the results suggested that lower FSH values were associated with increased SSR success. Few papers considered pregnancy and birth outcomes following intracytoplasmic sperm injection with surgically retrieved sperm, and there was no clear correlation with male FSH levels. Clinical implications include considering FSH results when counselling patients about both SSR and intracytoplasmic sperm injection. Suggested future research implications are to further investigate the predictive role of FSH in combination with other clinical and endocrinological markers.

Evaluation of PGK2 and ACR proteins in seminal plasma: suggestion of potential new biomarkers for prediction of sperm retrieval in non-obstructive azoospermia patients

This study aimed to assess the role of testis-specific proteins, PGK2 and ACR, in the prediction of sperm retrieval results by microdissection testicular sperm extraction (micro-TESE) in men with non-obstructive azoospermia (NOA). This was a case-control study including 48 semen samples of NOA patients undergoing the micro-TESE procedure, 15 semen samples from normozoospermic men as the positive control, and 12 semen samples from obstructive azoospermia/post-vasectomy (OA/PV) as negative controls. We investigated the levels of PGK2 and ACR proteins by ELISA tests in seminal plasma samples. The ELISA results revealed a significantly higher concentration of PGK2 and ACR in the NOA patients with successful sperm retrieval (NOA+) in comparison to NOA patients with failed sperm retrieval (NOA−) group (p = 0.0001 in both cases). For the first time, the data from this study suggests that a seminal PGK2 concentration of 136.3 pg/ml and ACR concentration of 21.75 mIU/ml can be used as cut-off values for the prediction of micro-TESE outcomes in NOA patients. These findings may be useful to avoid unnecessary micro-TESE operations. Overall, the seminal levels of the PGK2 and ACR proteins may be useful in predicting sperm retrieval success by micro-TESE in NOA patients.

Development and validation predictive models of sperm retrieval for azoospermic men undergoing testicular sperm aspiration: a multicentre, retrospective, cohort study.

Testicular sperm aspiration (TESA) is widely used to retrieve sperm from testis. Diagnostic testicular biopsy should not be routinely performed for azoospermia. Therefore, a good predictive model is needed before TESA. A total of 1972 azoospermia patients constituted the modelling set, and 260 azoospermia patients from two other centres constituted the validation set. An integrated predictive model was built using logistic regression. Receiver operating characteristic (ROC), calibration and decision curve analyses were performed to evaluate the performance of follicle-stimulating hormone (FSH), semen volume, testicular volume and the integrated model. The FSH level was the best univariate predictor for successful sperm retrieval (SSR) and was better than semen volume and testicular volume alone (p<0.001, threshold 6.17 IU/L, modelling set area under receiver operating characteristic curve (AUC) 0.80, accuracy 0.79; validation set AUC 0.87, accuracy 0.78). The integrated predictive model had excellent accuracy for predicting SSR (modelling set: AUC 0.93, accuracy 0.89; validation set: AUC 0.96, accuracy: 0.89). Calibration curve analysis indicated that the integrated model calibration was good and better than that of FSH, semen volume and testicular volume alone. Decision curve analysis indicated with a threshold probability between 0.05 and 0.98, the integrated model added more benefit than treating either all or no patients. The integrated model has excellent discrimination and good calibration. It can help azoospermic men make better decisions before TESA. It should be noted that TESA is not the first-line treatment for non-obstructive azoospermia because of a low sperm retrieval rate.

Seminal plasma extracellular vesicles tRF-Val-AAC-010 can serve as a predictive factor of successful microdissection testicular sperm extraction in patients with non-obstructive azoospermia

BackgroundThere is a lack of biomarkers for distinguishing non-obstructive azoospermia (NOA) patients with successful sperm retrieval (Sp+) from those with failed sperm retrieval (Sp-). This study aimed to determine the potential of extracellular vesicles tRNA-derived small RNA (tsRNA) as a novel non-invasive biomarker for successful sperm retrieval by microdissection testicular sperm extraction (mTESE).MethodsThe study included 18 patients with NOA with successful sperm retrieval (Sp+) and 23 patients with NOA with failed sperm retrieval (Sp-), 15 obstructive azoospermia (OA) patients, 5 idiopathic oligospermia (IO) patients, and 12 healthy people. Seminal plasma extracellular vesicles tsRNA levels were used in a two-stage case-control study (screened by tsRNA sequencing on Illumina NextSeq instrument and validated by qRT-PCR). The bioinformatic analysis was performed to determine the role of tsRNA in the pathogenesis of non-obstructive azoospermia.ResultsTwo tsRNAs (tRF-Val-AAC-010: AUC = 0.96, specificity = 80%, sensitivity = 95%; tRF-Pro-AGG-003: AUC = 0.96, specificity = 87%, sensitivity = 95%) were found to have high predictive accuracy for distinguishing the origin of azoospermia. In addition, the extracellular vesicles tRF-Val-AAC-010 resulted in high predictive ability (AUC = 0.89, sensitivity = 72%, specificity = 91%, P < 0.0001) in predicting the presence of sperm in non-obstructive azoospermia undergoing mTESE. Finally, bioinformatic analysis revealed that tRF-Val-AAC-010 were involved in spermatogenesis.ConclusionsThis study identified that the extracellular vesicles tRF-Val-AAC-010 and tRF-Pro-AGG-003 are biomarkers for the diagnosis of non-obstructive azoospermia, and that tRF-Val-AAC-010 as a potential non-invasive biomarker for predicting the presence of sperm in non-obstructive azoospermia testicular tissue.

Factors predicting successful sperm retrieval in men with nonobstructive Azoospermia: A single center perspective.

Predicting successful sperm retrieval is essential in counseling infertile men with Azoospermia.ObjectivesTo assess the predictors of successful sperm extraction in men with nonobstructive Azoospermia.Patients and MethodsA retrospective study included all patients with nonobstructive Azoospermia from January 2018 to May 2019. Subdivided into two groups, group I (negative sperm retrieval) and group II (positive sperm retrieval).ResultsA total of 108 patients with a mean age of 36.8 ± 10 years were included. The rate of successful sperm retrieval was 47.2%. Group I included 57 patients (52.8%) with a mean age of 33.98 ± 6.18, and group II included 51 patients (47.2%) with a mean age of 40.04 ± 12.22 (p = 0.008). Follicular stimulating hormone (FSH) levels were significantly higher in group I (18.55 ± 13 vs. 7.97 ± 7.11; p < 0.004). Similarly, in group I, luteinizing hormone was significantly higher (11.4 ± 7.45 vs. 5.9 ± 4.4; p < 0.001). Age and FSH were the independent predictors of successful micro‐TESE. Additionally, successful pregnancies were 13.7% of patients, 28.6% of which gave rise to living birth.ConclusionPatients' age and serum FSH are independent predictors of successful sperm retrieval for infertile men with nonobstructive Azoospermia; young patients with high FSH levels could have little chance of sperm retrieval.