Successful Sperm Retrieval Research Articles

MP31-05 PREDICTION OF MICRODISSECTION TESTICULAR SPERM EXTRACTION OUTCOME IN POST-CHEMOTHERAPY AZOOSPERMIC MEN USING CYCLOPHOSPHAMIDE EQUIVALENT DOSE

You have accessJournal of UrologyInfertility: Therapy (MP31)1 Sep 2021MP31-05 PREDICTION OF MICRODISSECTION TESTICULAR SPERM EXTRACTION OUTCOME IN POST-CHEMOTHERAPY AZOOSPERMIC MEN USING CYCLOPHOSPHAMIDE EQUIVALENT DOSE Shi-Jie Tsai, I-shen Huang, and William J. Huang Shi-Jie Tsai Shi-Jie Tsai More articles by this author , I-shen HuangI-shen Huang More articles by this author , and William J. HuangWilliam J. Huang More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002035.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Cancer per se or therapies, particularly treatment involved with chemotherapy, appears to potentiate gonadal toxicity. For men with persistent postchemotherapy azoospermia, fatherhood can be possibly achieved via microdissection testicular sperm extraction (mTESE) combine with intracytoplasmic sperm injection (ICSI). Yet, the recovery of viable testicular sperm with mTESE is unpredictable in this population. Using cyclophosphamide equivalent dose (CED) as a means of quantifying exposure to alkylating agent, a cytotoxic agent that has been demonstrated to disrupt spermatogenesis, we sought to discover the sperm retrieval rate in men with persistent azoospermia postchemotherapy in relation to CED. METHODS: We retrospectively reviewed records of 910 patients with the diagnosis of non-obstructive azoospermia who had undergone mTESE between 2010 to 2018 in our institution and enrolled 14 patients with a prior history of chemotherapy. The oncological data and chemotherapy regimen of each individual were reviewed. For each patient’s regimen received, a CED was calculated using the equation proposed by Daniel Green et al. in 2014. The pretreatment hormone profile, CED, and outcomes of mTESE were analyzed. RESULTS: Testicular spermatozoa were successfully retrieved in 6 (43%) of the patients. The mean patient age was 36 years (range, 27-42 years) and the mean time interval from chemotherapy to mTESE was 10.4 years (range, 1-26 years). Although CED and alkylating agent exposure were not predictive factors for successful sperm retrieval (p=0.14), however, no men with CED >4000 mg/m2 (n=4) had viable sperm detected in testis during mTESE. As for the other 10 patients without alkylating agent exposure (i.e. CED=0 mg/m2), sperm can be recovered in 6 (60%) of them. Regarding cancer subtypes, patients diagnosed with testicular non-seminomatous germ cell tumor had favorable sperm retrieval rate (3/5, 60%), compared to patients with non-Hodgkin’s lymphoma (0/3, 0%) or leukemia (1/2, 50%), respectively. CONCLUSIONS: The chance of successful sperm retrieval using mTESE for men with persistent postchemotherapy azoospermia and a calculated CED >4000 mg/m2 is zero. These patients should be properly counseled with the CED model before pursuing surgical sperm retrieval . Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e556-e557 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Shi-Jie Tsai More articles by this author I-shen Huang More articles by this author William J. Huang More articles by this author Expand All Advertisement Loading ...

MP31-07 THE EFFECT OF HORMONAL STIMULATION IN HYPOGONADAL MEN UNDERGOING MICROSURGICAL TESTICULAR SPERM RETRIEVAL (MTESE)

You have accessJournal of UrologyInfertility: Therapy (MP31)1 Sep 2021MP31-07 THE EFFECT OF HORMONAL STIMULATION IN HYPOGONADAL MEN UNDERGOING MICROSURGICAL TESTICULAR SPERM RETRIEVAL (MTESE) Giovanni Chiriaco, Katy Naylor, Vikram Talaulikar, Elizabeth Williamson, Gerard Conway, David Ralph, and Philippa Sangster Giovanni ChiriacoGiovanni Chiriaco More articles by this author , Katy NaylorKaty Naylor More articles by this author , Vikram TalaulikarVikram Talaulikar More articles by this author , Elizabeth WilliamsonElizabeth Williamson More articles by this author , Gerard ConwayGerard Conway More articles by this author , David RalphDavid Ralph More articles by this author , and Philippa SangsterPhilippa Sangster More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002035.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Non obstructive azoospermia (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. METHODS: This is a retrospective study on infertile men who underwent mTESE with or without prior endocrine stimulation therapy (clomiphene or human chorionic gonadotropin). Hypogonadism was defined as serum testosterone (T) level <12 nm/L. We recorded cause of testicular failure, duration and type of hormonal stimulation, pre- and post-stimulation hormone levels (T, FSH, LH), pre-operative hormone levels, successful sperm retrieval rate, average Johnsen score and total number of vials of sperm retrieved. The success criteria for mTESE was defined as at least 1 vial of viable sperm retrieved. RESULTS: 168 men underwent mTESE out of which 59 men received stimulation therapy for NOA. Among them, we selected men with hypogonadism defined as serum T <12 nm/L (43% of the cohort). The hypogonadal group included 71 men - 28/71 had Klinefelter syndrome and 40/71 received endocrine stimulation prior to the procedure for a mean duration of 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 (ΔT) 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 success rate of mTESE 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 Johnsen score and success rates 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 successful sperm retrieval. Among men who received endocrine stimulation therapy the ΔT 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>3.5 nm/L showed a significant association with successful mTESE (p:0.041). CONCLUSIONS: Our study shows that there is a significant improvement of serum T concentration following endocrine stimulation therapy in hypogonadal men with serum T<12 nm/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 ΔT before and after stimulation, and a successful mTESE. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e557-e557 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Giovanni Chiriaco More articles by this author Katy Naylor More articles by this author Vikram Talaulikar More articles by this author Elizabeth Williamson More articles by this author Gerard Conway More articles by this author David Ralph More articles by this author Philippa Sangster More articles by this author Expand All Advertisement Loading ...

MP31-03 MICRODISSECTION TESTICULAR SPERM EXTRACTION VS MULTIPLE NEEDLE-PASS PERCUTANEOUS TESTICULAR SPERM ASPIRATION IN MEN WITH NON-OBSTRUCTIVE AZOOSPERMIA: A RANDOMIZED CLINICAL TRIAL

You have accessJournal of UrologyInfertility: Therapy (MP31)1 Sep 2021MP31-03 MICRODISSECTION TESTICULAR SPERM EXTRACTION VS MULTIPLE NEEDLE-PASS PERCUTANEOUS TESTICULAR SPERM ASPIRATION IN MEN WITH NON-OBSTRUCTIVE AZOOSPERMIA: A RANDOMIZED CLINICAL TRIAL Christian Fuglesang S. Jensen, Dana A. Ohl, Mikkel Fode, Niels Jørgensen, Aleksander Giwercman, Angel Elenkov, Anna Klajnbard, Claus Y. Andersen, Lise Aksglaede, Marie Louise Grøndahl, Mette C. Bekker, and Jens Sønksen Christian Fuglesang S. JensenChristian Fuglesang S. Jensen More articles by this author , Dana A. OhlDana A. Ohl More articles by this author , Mikkel FodeMikkel Fode More articles by this author , Niels JørgensenNiels Jørgensen More articles by this author , Aleksander GiwercmanAleksander Giwercman More articles by this author , Angel ElenkovAngel Elenkov More articles by this author , Anna KlajnbardAnna Klajnbard More articles by this author , Claus Y. AndersenClaus Y. Andersen More articles by this author , Lise AksglaedeLise Aksglaede More articles by this author , Marie Louise GrøndahlMarie Louise Grøndahl More articles by this author , Mette C. BekkerMette C. Bekker More articles by this author , and Jens SønksenJens Sønksen More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002035.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Non-obstructive azoospermia (NOA) is a severe infertility diagnosis. No level-1 evidence supports a specific surgical sperm retrieval procedure. Microdissection testicular sperm extraction (mTESE) has gained popularity due to reports on relatively high sperm retrieval rates (SRR) ranging 30–70%. However, mTESE is an invasive, demanding and costly procedure. We previously reported SRR for a modified needle aspiration (TESA) applied in NOA men (Jensen et al. 2016). Modified TESA is done with an 18-gauge needle performing multiple passes (50-100) while applying a vacuum. The SRR from this procedure was 30%. When performing salvage mTESE after an unsuccessful modified TESA, the SRR was only 11%. Therefore, we hypothesized that modified TESA is an effective alternative to mTESE. Accordingly, we conducted the first randomized clinical trial on surgical sperm retrieval in NOA men comparing modified TESA with mTESE. METHODS: Ethical approval was obtained, and a prospective randomized clinical trial was conducted between 04/2017–10/2020. Inclusion criteria were azoospermia according to WHO, testis volume ≤15ml and no indication of obstructive causes of azoospermia. Exclusion criteria were previous surgical sperm retrieval or testicular biopsy, anejaculation, retrograde ejaculation, Klinefelter’s Syndrome, XX male, AZFa/b microdeletion and CFTR mutation. The calculated population size was 100 (using 25% SRR for TESA and 52% for mTESE, power 80% and alpha 0.05) and with an expected drop-out rate of 10%, 110 men with NOA needed to be included. Men were randomized to mTESE or modified TESA. Patients with a failed TESA proceeded directly to mTESE while in the operating room. The primary outcome was successful sperm retrieval. SRRs were compared using Chi-square test. Statistical significance was set at p<0.05. RESULTS: 110 men were included, 10 withdrew before randomization and 100 underwent surgery. Median age was 33 years (range 22–54). Spermatozoa were retrieved in 11/51 (22%) men randomized for TESA and 21/49 (43%) men undergoing mTESE (p=0.02). SSR from salvage mTESE was 4/38 (11%). Thus, the combined SRR for men randomized to TESA was 15/51 (29%) which did not reach statistical significance compared to mTESE (p=0.16). CONCLUSIONS: In direct comparison SRR was higher in mTESE compared to modified TESA. Although not powered for such comparison, the study may indicate that combining salvage mTESE with the modified TESA is a viable alternative reducing invasiveness and cost for a proportion of patients. Source of Funding: European Reasearch Council, ReproUnion © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e555-e556 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Christian Fuglesang S. Jensen More articles by this author Dana A. Ohl More articles by this author Mikkel Fode More articles by this author Niels Jørgensen More articles by this author Aleksander Giwercman More articles by this author Angel Elenkov More articles by this author Anna Klajnbard More articles by this author Claus Y. Andersen More articles by this author Lise Aksglaede More articles by this author Marie Louise Grøndahl More articles by this author Mette C. Bekker More articles by this author Jens Sønksen More articles by this author Expand All Advertisement Loading ...

Predicting successful sperm retrieval in transfeminine adolescents after testicular biopsy.

Increasing numbers of transgender adolescents are receiving gender-affirming treatments (GAT). Given GAT can impair reproductive function, clinical guidelines advise prior counselling regarding fertility preservation (FP). For transgender adults assigned male at birth, FP is usually achieved via a masturbatory sample and sperm cryopreservation. This is less straightforward in transgender adolescents, since they may not be developmentally ready to masturbate and/or masturbation may cause unacceptable gender dysphoria. Testicular biopsy represents an alternative method for sperm retrieval in these adolescents, but for those in early/mid puberty, it is difficult to predict whether sperm will be found. The purpose of this study was therefore to identify factors that predict successful sperm retrieval for cryopreservation via testicular biopsy. A retrospective cohort study was undertaken at a tertiary-referral pediatric gender service. Subjects were included if they'd received a testicular biopsy in association with the commencement of GAT between 2010 and 2019. The primary outcome measure was successful sperm retrieval, and potential predictors included age, testicular volume and serum testosterone, LH and FSH levels. Of 25 subjects who received a biopsy prior to starting any GAT, 17 had successful sperm retrieval. While age, testosterone, LH and FSH levels showed minimal differences, testicular volume was significantly higher in those with successful sperm retrieval, and a threshold of ≥ 10mL showed 92% sensitivity and 71% specificity in predicting successful retrieval. An additional 6 patients received a biopsy after starting puberty suppression and before commencement of oestrogen, and one of these individuals had sperm successfully retrieved despite > 2years of regular puberty suppression. These findings suggest that testicular volume is most useful in predicting successful sperm retrieval following testicular biopsy in transgender adolescents and are likely to be of relevance to other young people undertaking FP, including those with cancer.

Anti-Müllerian hormone level as a predictor of sperm retrieval with microdissection testicular sperm extraction in nonobstructive azoospermia.

Limited factors effectively predict sperm retrieval with microdissection testicular sperm extraction in men with nonobstructive azoospermia. We therefore sought to evaluate the role of serum anti-Müllerian hormone as a predictive biomarker for successful sperm retrieval. We included patients with pre-operative anti-Müllerian hormone levels and stratified them based on prior history of prior sperm retrieval procedure. We compared hormone levels between those who did and did not have a successful sperm retrieval and used receiver operating curves to determine an optimal cut-off value. A total of 46 men were included, of whom 18 (39.1%) had no prior sperm retrieval and 11 (61.1%) had sperm successfully retrieved. Pre-operative serum anti-Müllerian hormone levels were predictive of sperm retrieval in patients with no prior attempts at retrieval (p=.03). Receiver operating curve for those without prior retrieval was 0.6753. The optimal anti-Müllerian hormone cut-off for those without prior sperm retrieval was 0.133ng/ml with a sensitivity of 0.91 and specificity of 0.29. Therefore, serum anti-Müllerian hormone levels have modest predictive value for sperm retrieval in this cohort. The combination of clinical history, examination and laboratory investigations should continue to be used to guide surgeons in counselling patients regarding the chance of sperm retrieval.

Microdissection testicular sperm extraction (micro-TESE) in men with infertility due to nonobstructive azoospermia: summary of current literature.

Nonobstructive azoospermia (NOA) is associated with intrinsic testicular defects that severely impair sperm production. Although NOA invariably leads to infertility, focal sperm production may exist in the testicles of affected patients, which canbe retrieved and usedforintracytoplasmic sperm injection (ICSI) to generate healthy offspring. However, geographic locations of testicular sperm producing-areas are uncertain, making microsurgical-guided sperm retrieval (microdissection testicular sperm extraction; micro-TESE) an attractive method to identify and retrieve sperm in patients with NOA due to spermatogenic failure. Given the widespread use of micro-TESE, its effectiveness in harvesting sperm and related potential complications need to be clarified. We queried PubMed/MEDLINE for studies published in English, from inception to May 2021, concerning the effect of micro-TESE on sperm retrieval rate (SRR), complication rate and ICSI pregnancy rate-using retrieved testicular sperm in subfertile couples where the male had NOA. We found 116 articles, including 70 original papers, 32 review articles, and 14 systematic reviews. The evidence accounted for 4895 patients. Micro-TESE retrieved sperm in 46.6% of men with NOA,but SRRs varied considerably (18.4-70.8%) and were mainly related to the treated population characteristics. Concerning the general population of NOA patients who have not undergone previous sperm retrieval (naïve population), the SRR by micro-TESEwas 46.8% (1833 of 3914 patients; range 20-70.8%; 28 studies). In studies reporting SR by micro-TESE for men who had failed percutaneous testicular sperm aspiration or non-microsurgical testicular sperm extraction, the SRR was 39.1% (127 of 325 patients; range 18.4-57.1%; 4 studies). Dataon adverse events indicated that micro-TESE was associated with low (~ 3%) short-term postoperative complication rates. The fertilizing ability of testicular sperm retrieved by micro-TESE and usedfor ICSI was adequate (~ 57%), whereas clinical pregnancy and live birth were obtained in 39% and 24% of couples who had an embryo transfer, respectively. The health of the resulting children seems reassuring, but the evidence is limited. The procedure increases sperm retrieval success compared to non-microsurgical retrieval methods, particularly in men with Sertoli cell-only testicular histopathology. We concluded that micro-TESE is an effective and safe method to retrieve sperm from men with NOA-relatedinfertility, with potential advantages over non-microsurgical methods. Nevertheless, high-quality, head-to-head comparative randomized controlled trials by sperm retrievalmethod,focusing on SRR, live birth rate and assessing long-term adverse events and health of children conceived using testicular sperm from NOA patients are lacking. Therefore, further research is required to determine the full clinical implications of micro-TESE in male infertility treatment.

The fertility preservation decision-making and testicular sperm retrieval outcome in older adolescents with nonmosaic Klinefelter syndrome and azoospermia.

This study aims to analyze the fertility preservation decision-making and the sperm retrieval rate (SRR) in older adolescents (age 15-19 years) with nonmosaic Klinefelter syndrome (KS) and azoospermia in a male reproductive clinic, and to determine the accumulated SRR in older adolescents by literature review. Older adolescents with nonmosaic KS and azoospermia referred for hypogonadism and fertility concerns were enrolled. Reproductive counseling and fertility preservation options were offered to patients/parents. The acceptability and the reasons affecting the reproductive decision-making were analyzed. Patients/parents who agreed on fertility preservation received microdissection testicular sperm extraction (mTESE) and cryopreservation. A comprehensive literature review regarding the SRRs in older adolescents with KS was conducted. A total of eight older adolescents were enrolled. After fertility preservation counseling, three patients/parents (37.5%) agreed to receive mTESE, and spermatozoa were successfully retrieved in two. "Lack of interest" and "inconsistent sperm retrieval result" were the main reasons for refusal. A total of 89 older adolescents from nine articles, and ours were collected for SRR analysis. Most of the reports had a limited number of cases, and none of them described the acceptance rate of sperm retrieval in adolescents. Forty-three out of 89 older adolescents (48.3%) had successful sperm retrieval, and there was no significant difference in the SRR between the mTESE and conventional TESE. Successful testicular sperm retrieval in older adolescents with KS is not superior to those reported in adults. Adolescents and their parents should undergo a detailed reproductive consultation process and shared decision-making discussion before considering testicular sperm retrieval.

P–076 Probability of sperm retrieval in azoospermic patients and mRNA expression profile of JMJD1A, TNP2 and PRM2 : in a subset of karachi population

Abstract Study question To access successfulness of sperm retrieval by evaluating the mRNA expression profile of JMJD1A, TNP1, TNP2, PRM1 and PRM2 in patients undergoing surgical sperm retrieval procedure. Summary answer Probability of sperm retrieval in azoospermia is decreased when mRNA expression profile of JMJD1A TNP2 and PRM2 in testicular tissue is decreased. What is known already Studies have been done on expression of JMJD1A in non-obstructive azoospermic patients in other part of the world with smaller sample size but this is the first study in Pakistan with larger number of patients. Study design, size, duration: Crossectional study, 100 azoospermic patients coming for purpose of sperm retrieval by TESE or micro-TESE in Australian Concept Infertility Medical Center, Karachi,from March, 2018 to December, 2019 Participants/materials, setting, methods All recruited azoospermic patients were evaluated by history, physical examination, and hormonal assessment. RNA was extracted by pureLink RNA Micro kit and mRNA expression of the JMJD1A, TNP1, TNP2, PRM1 and PRM2 genes was determined using innu-SCRIPT One Step RT_qPCR SyGreen kit. For quantitative variables independent t test and for categorical variables chi-square/ Fisher Exact test was used. Unadjusted and adjusted prevalence ratio were reported by using cox regression algorithm. Main results and the role of chance: The patients were categorized into (i) Group-I: Patients with successful sperm retrieval n = 42, (ii) Group-II: Patients with unsuccessful sperm retrieval n = 58. The patients were categorized into (i) Group-I: Patients with successful sperm retrieval n = 42, (ii) Group-II: Patients with unsuccessful sperm retrieval n = 58. Azoospermic men in the successful sperm retrieval group had significantly decreased expression of JMJD1A (P &amp;lt; 0.001), TNP2(P &amp;lt; 0.001), and PRM2 (P 0.008). In addition to this regarding hormonal parameters: FSH (P 0.004), LH(P &amp;lt; 0.001), TSH(P&amp;lt;.011) were significantly different in azoospermic men with successful and unsuccessful sperm retrieval. In multivariate analysis, after adjusting for the other covariates, a significant association was found between JMJD1A, TNP2, PRM2 and successful sperm retrieval (p-value &amp;lt;0.05). Limitations, reasons for caution It is unicentric and outcomes for fertilization were not assessed. Azoospermic patients from multi-centeres were difficult because of lack of facility of sperm retrieval procedures at these centers and it was difficult to follow the fertrilization outcome. Wider implications of the findings: This will be useful for making the decision in azoospermic men to proceed for ICSI or not. In addition to this, the repetition of unnecessary surgical procedures can be avoided, as the azoospermic men often undergo number of rounds of ICSI, with the hope of becoming biological father. Trial registration number non-clinical trials

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

P–028 Single centre retrospective analysis of endocrine stimulation therapy prior to microsurgical testicular sperm retrieval (mTESE) in men with hypogonadism and non-obstructive azoospermia (NOA)

Abstract Study question What is the role of endocrine stimulation therapy prior to mTESE in men with hypogonadism and non obstructive azoospermia (NOA)? Summary answer In hypogonadal men there is a positive correlation between change of serum Testosterone (ΔT) before and after stimulation, and a successful mTESE. What is known already NOA is the most common cause of azoospermia and it is often associated with hypogonadism and testicular failure. It is common practice for endocrine stimulation therapies such as gonadotropines or selective estrogens receptor modulators to be used prior mTESE; however there is currently paucity of data regarding their efficacy. Study design, size, duration Retrospective analysis on infertile men with hypogonadism (defined as T &amp;lt; 12nmol/L) and NOA who underwent mTESE with or without prior endocrine stimulation therapy (clomiphene or human chorionic gonadotropin). Retrospective data from 2015–2020, total number of patient: 71; stimulated group (N:40) vs unstimulated group (N:31). Participants/materials, setting, methods Retrospective study on infertile men who underwent mTESE with or without prior endocrine stimulation therapy. Hypogonadism was defined as serum testosterone (T) level &amp;lt;12nm/L. We recorded demographic data, cause of testicular failure, previous testosterone therapy, duration and type of endocrine stimulation, pre-and post-stimulation hormone levels(T, FSH, LH), pre-operative hormone levels, successful sperm retrieval rate (at least 1 vial of viable sperm), average Johnsen score and total number of vials of sperm retrieved. Main results and the role of chance One-hundred-sixty-eight men underwent mTESE out of which 59 men received endocrine stimulation therapy for NOA between 2015–2020. Among them, we selected men with hypogonadism defined as serum T &amp;lt; 12nmol/L which comprised 43% of the entire patient cohort. The hypogonadal group included 71 men, 28/71 had Klinefelter syndrome and 40/71 received endocrine stimulation for 13.9±9.2 months. Testosterone levels significantly increased after endocrine stimulation (6.3±3.3nm/L vs 11.7±7.4nm/L) with mean change in serum testosterone (ΔT) 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 success rate of mTESE did not differ significantly (16/40–40%) vs 13/31–42%). Men with Klinefelter syndrome demonstrated significant differences with regards to age, lower T levels, higher FSH and LH levels, lower Johnsen score and success rates compared to other causes of NOA. Comparing men who had successful mTESE vs unsuccessful mTESE - higher T and lower FSH and LH seemed to correlate with successful sperm retrieval. Among men who received endocrine stimulation therapy the ΔT before and after stimulation seemed to correlate with successful sperm retrieval (AUC:0.701, SE:0.089, p:0.043). In the stimulated group a ΔT&amp;gt;3.5nm/L showed a significant association with successful mTESE(p:0.041). Limitations, reasons for caution Retrospective study limitations. Wider implications of the findings: Our study shows a significant improvement of serum T following endocrine stimulation therapy. 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 ΔT before and after stimulation, and a successful mTESE. Trial registration number Not applicable

P–085 Sperm retrieval after microdissection testicular sperm extraction (micro-TESE) and pregnancy outcomes of intracytoplasmic sperm injection (ICSI) in men with Klinefelter syndrome

Abstract Study question What are the sperm retrieval rate and ICSI outcomes in azoospermic men with Klinefelter syndrome (KS)? Summary answer In men with KS, a sperm retrieval rate of 51.3% after the first attempt micro-TESE, and 4 live births after ICSI were observed. What is known already: Klinefelter syndrome (KS) is encountered in 10% of men with azoospermia. Micro-TESE is presently used to treat infertility for KS patients with nonobstructive azoospermia. The retrieved sperms can be used for ICSI. Study design, size, duration: From June 2019 to July 2020, 39 azoospermic patients with KS were examined for the presence of testicular spermatozoa. Participants/materials, setting, methods: Participants were recruited from couples attending the Andrology and Fertility Hospital of Hanoi Vietnam, for infertility treatment. Micro-TESE was performed to extract testicular tissue. After retrieval, ICSI was used with fresh sperm. Main results and the role of chance: The sperm retrieval rate of first attempt micro-TESE in KS men was 51.3% (20/39). Logistic regression analysis showed patient age did not affect the sperm retrieval rate of micro-TESE (OR 0.99, 95% CI 0.88 - 1.11). Similarly, no association was observed between serum FSH, LH, testosterone level, and testicular volume with the success of sperm retrieval. The fertilization rate after ISCI in patients with retrieved sperm was 60% (12/20). Clinical pregnancy and ongoing pregnancy rates were 50% (10/20) and 40% (8/20). There were 4 live births. No sufficient data were available to test the effect of clinical or biological parameters on ICSI outcomes. Limitations, reasons for caution Our data rely on a cohort of KS patients attending a single fertility clinic. The sample size did not allow regression analysis for any ICSI outcome. Wider implications of the findings: Micro-TESE is helpful in retrieving sperm in azoospermia KS patients with sperm retrieval rate reaching 50%. ICSI following micro-TESE can lead to an ongoing pregnancy rate of 40% with some result in live births. The outcome of micro-TESE is independent of any clinical or biochemical parameters tested. Trial registration number Not applicable

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

Is a contralateral testicular exploration required at microdissection testicular sperm extraction for men with nonobstructive azoospermia, cryptozoospermia or severe oligozoospermia?

Men with nonobstructive azoospermia (NOA), cryptozoospermia and severe oligozoospermia are candidates for microdissection testicular sperm extraction (micro-TESE) and intracytoplasmic sperm injection (ICSI). We sought to evaluate micro-TESE outcomes and the need for bilateral testicular exploration in the three groups of men. We conducted a retrospective study of 233 consecutive micro-TESEs in men with nonobstructive azoospermia (n=173), cryptozoospermia (n=43) and severe oligozoospermia (n=17). The decision to terminate the micro-TESE after a unilateral or bilateral testicular exploration was determined at the time of surgery and was based on the presence or absence of mature spermatozoa in the harvested micro-biopsies. Final assessment of sperm recovery, on the day of ICSI, was reported as successful (available spermatozoon for ICSI) or unsuccessful (no spermatozoon for ICSI). Unilateral testicular exploration resulted in successful sperm retrieval in 43% (75/173), 79% (34/43) and 100% (17/17) of men with NOA, cryptozoospermia and severe oligozoospermia respectively. Therefore, 57%, 21% and none of the men with NOA, cryptozoospermia and severe oligozoospermia, respectively, required a bilateral micro-TESE. Overall, micro-TESE resulted in successful sperm retrieval in 52% (90/173), 91% (39/43) and 100% (17/17) of men with NOA, cryptozoospermia and severe oligozoospermia respectively. Our data indicate that men with severe oligozoospermia are unlikely to require a bilateral testicular exploration at micro-TESE. Moreover, most cryptozoospermic men will have a successful sperm retrieval by micro-TESE with the majority of these patients requiring a unilateral exploration. In contrast, over 50% of the men with nonobstructive azoospermia will require a bilateral micro-TESE.

Longitudinal vs horizontal capsular incision! Does it alter micro-TESE outcome?

Micro-TESE (Testicular Sperm Extraction), a procedure performed for treatment of Non-Obstructive Azoospermia, a leading infertility issue among males globally accounting for about 7% of the male population. Azoospermia is the absence of sperms in ejaculate upon semen analysis, 2% of the global population has encountered. A lot is discussed upon sperm retrieval success in both variants of Micro-TESE, which are Transverse or horizontal and longitudinal or vertical approaches, established studies have identified about 45% to 65% of success retrieving spermatozoa. The objective is the identification of the success of both the variants of procedure separately and also of postop complications to both approaches for micro-TESE. A cohort study, for which data, secondary (retrospective), was obtained from King Abdulaziz Medical City (KAMC), Riyadh. The time frame for data covered January 2016 to November 2018; 87 patients underwent micro-TESE, as in the logbook available in “Best Care System at KAMC. Data obtained was analyzed using SPSS Software, 87 of these patients who underwent micro-TESE procedure, 45 were done with the transverse approach and 42 with longitudinal approach, accounting for 51.7% and 48.3%, respectively. Upon postop evaluation, in the transverse approach, sperm were retrieved in 25.29% and for the longitudinal approach, retrieval was about 19.54%. The success rate was 48.9% out of 45 procedures in the transverse approach and 40.5% out of 42 procedures in the vertical/Longitudinal approach. The most common reported post-operative complication in transverse type was atrophy 20% and pain 13.3% on other hand common complications recorded for vertical type, atrophy was about 17.2% and pain in12.6% of patients. Not much statistical significance was observed between the transverse and longitudinal approach in either of the outcomes whether it is success rate or post-op complications. Both approaches are influenced by the factors of surgeon expertise and certain other factors that include pre and postop hormonal therapy, baseline hormonal status, and ICSI.

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.

Semen biomarker TEX101 predicts sperm retrieval success for men with testicular failure

Background: Azoospermia could be due to either obstruction (obstructive azoospermia: OA) or spermatogenic failure (non-obstructive azoospermia: NOA). Close to 50% of men with NOA have small pockets of sperm in the testis which could be retrieved surgically and then injected into oocytes in a program of intra-cytoplasmic sperm insertion. Presently, there are no accepted non-invasive tests allowing clinicians to predict the success rates of sperm retrieval. Previously, we have identified a germ cell-specific protein TEX101 in semen found in the primary spermatocytes and more mature sperm forms, but not in spermatogonia, Sertoli or Leydig cells. We hypothesized that the semen concentration of TEX101 could be used to predict sperm production in men with NOA. Methods: This was a prospective cohort study on men with NOA being treated at a male infertility centre. Men with NOA planning sperm retrieval provided 1–3 semen samples prior to surgery. Semen TEX101 concentrations were measured by an in-house-developed ELISA assay and compared with the results of the surgery to retrieve sperm. Results: 20/60 karyotypically normal men with NOA had semen TEX101 &lt; LOD (&lt;0.2ng/mL). Of these, 0% had successful sperm retrieval(0-17%: 95% CI) . In contrast, of the 40 men with TEX101&gt; LOD, sperm was found in 50% (34-66%: 95% CI, sig diff. Fisher’s exact test, p&lt;0.05). Conclusions: Undetectable (&lt;0.2 ng/mL) semen TEX101 is highly predictive of sperm retrieval failure for karyotypically normal men with NOA and is the single strongest non-invasive predictor of sperm retrieval failure reported so far. Semen TEX101 concentration will help couples decide their individual chances of successful sperm retrieval.

The timing of micro-TESE: what is the ideal age for male and female partner to bring a child to home?

The aim of this study was to analyze the results of microsurgical testicular sperm extraction (micro-TESE) and investigate the potential factors that may affect the successful sperm retrieval and timing of micro-TESE. A total of 56 patients with nonobstructive azoospermia (NOA) who underwent micro-TESE procedure between January 2017 and December 2019 were retrospectively analyzed. The patient age, marriage duration, infertility duration, smoking, chronic illness, varicocele status, previous scrotal surgeries, and the presence of genetic disease were noted by an urologist for all patients. The mean age of patients was 33.28±4.4 (22-44) years. Our total sperm-retrieval rate was 55.4% (n:31). Sixteen (28.6%) pregnancies were achieved and 15 (26.8%) healthy live births could be managed. Only the marriage duration (p=0.016) and infertility duration (p=0.015) were detected to be the significant factors to manage successful sperm retrieval. Men with NOA younger than 35.2 years and having a female partner younger than 36.9 years seemed to have the best chance to have a living healthy baby. The fertility decreased by both male and female age and for men with NOA. The early visit to doctor seemed to have positive effect.

Testicular Sperm Aspiration (TESA) or Microdissection Testicular Sperm Extraction (Micro–tese): Which Approach is better in Men with Cryptozoospermia and Severe Oligozoospermia?

ObjectivesTo evaluate and compare sperm retrieval outcomes by testicular sperm aspiration (TESA) and micro–dissection testicular sperm extraction (micro-TESE) in non-azoospermic men. MethodsWe conducted a retrospective study of 145 consecutive testicular sperm retrievals in men with cryptozoospermia (n = 56) or severe oligozoospermia (n = 84). The decision to perform a TESA or a micro-TESE was made after thorough discussion of the pros and cons of these procedures with the couple. Final assessment of sperm recovery, on the day of ICSI, was reported either as successful (available sperm for ICSI) or unsuccessful (no sperm for ICSI). ResultsMean sperm concentration, sperm motility, testicular volume and serum FSH level of men undergoing TESA were not significantly different from those of men undergoing micro-TESE. In men with severe oligozoospermia (<5 million/ml), sperm recovery was successful in 95% (18/19) of those who underwent micro-TESE and in 92% (60/65) of those who underwent TESA (P > 0.05). In men with cryptozoospermia, sperm recovery was successful in 88% (42/48) of men who underwent micro-TESE and 25% (2/8) of men who underwent TESA (P < .001). ConclusionsThese data indicate that in men with severe oligozoospermia, TESA and micro-TESE are equally successful sperm retrieval techniques. However, in men with cryptozoospermia, sperm retrieval rates are significantly higher with micro-TESE than TESA.

Omics in Seminal Plasma: An Effective Strategy for Predicting Sperm Retrieval Outcome in Non-obstructive Azoospermia.

Non-obstructive azoospermia (NOA) is a severe form of male factor infertility resulting from the impairment of sperm production. Surgical sperm retrieval followed by intracytoplasmic sperm injection (ICSI) is the only alternative for NOA patients to have their own genetic children. Nevertheless, due to an approximately 50% chance of success, harvesting sperm from these patients remains challenging. Thus, discovering noninvasive biomarkers, which are able to reliably predict the probability of sperm acquisition, not only can eliminate the risk of surgery but also can lower the costs of NOA diagnosis and treatment. Seminal plasma is the non-cellular and liquid portion of the ejaculate that consists of the secretions originating from testes and male accessory glands. In past years, a wide range of biomolecules including DNAs, RNAs, proteins, and metabolic intermediates have been identified by omics techniques in human seminal plasma. The current review aimed to briefly describe genomic, transcriptomic, proteomic, and metabolomic profiles of human seminal plasma in an attempt to introduce potential candidate noninvasive biomarkers for sperm-retrieval success in men with NOA.

Testicular function in males with infantile nephropathic cystinosis.

STUDY QUESTIONDo males with the rare lysosomal storage disease infantile nephropathic cystinosis (INC) have a chance of biological fatherhood?SUMMARY ANSWERCryostorage of semen could be an option for approximately 20% of young males with INC, with surgical sperm retrieval from the centre of the testes providing additional opportunities for fatherhood.WHAT IS KNOWN ALREADYBiallelic mutations in the cystinosin (CTNS) gene in INC cause dysfunction in cystine transport across lysosomal membranes and cystine accumulation throughout the body. Spontaneous paternity in cystinosis has not been described, despite the availability of cysteamine treatment. Azoospermia has been diagnosed in small case series of males with INC. ART using ICSI requires few spermatozoa, either from semen or extracted surgically from the testes of azoospermic men. However, there is limited evidence to suggest this could be successful in INC.STUDY DESIGN, SIZE, DURATIONIn this prospective cohort study performed between 2018 and 2019, we performed a cross-sectional investigation of 18 male patients with INC to delineate endocrine and spermatogenic testicular function.PARTICIPANTS/MATERIALS, SETTING, METHODSSerum hormone levels, semen samples (according to World Health Organization 2010 standards), and testicular ultrasound images were analysed in 18 male patients aged 15.4–40.5 years. Surgical sperm extraction was performed in two, and their testicular biopsies were investigated by light and electron microscopy. Past adherence to cysteamine treatment was assessed from medical record information, using a composite scoring system.MAIN RESULTS AND THE ROLE OF CHANCEAdherence to cysteamine treatment was high in most patients. Testicular volumes and testosterone levels were in the normal ranges, with the exception of two and three older patients, respectively. Serum LH levels were above the normal range in all subjects aged ≥20 years. FSH levels were elevated in all but four males: three with spermatozoa in semen and one adolescent. Inhibin B levels were shown to be lower in older men. Testicular ultrasound revealed signs of obstruction in 67% of patients. Reduced fructose and zinc seminal markers were found in 33%, including two patients with azoospermia who underwent successful surgical sperm retrieval. Histology identified fully preserved spermatogenesis in the centre of their testes, but also tubular atrophy and lysosomal overload in Sertoli and Leydig cells of the testicular periphery.LIMITATIONS, REASONS FOR CAUTIONLimitations of this study are the small number of assessed patients and the heterogeneity of their dysfunction in cystine transport across lysosomal membranes.WIDER IMPLICATIONS OF THE FINDINGSThis study suggests that testicular degeneration in cystinosis results from the lysosomal overload of Sertoli and Leydig cells of the testicular periphery, and that this can possibly be delayed, but not prevented, by good adherence to cysteamine treatment. Endocrine testicular function in INC may remain compensated until the fourth decade of life; however, azoospermia may occur during adolescence. Cryostorage of semen could be an option for approximately 20% of young males with INC, with surgical sperm retrieval providing additional opportunities for biological fatherhood.STUDY FUNDING/COMPETING INTEREST(S)This work was supported by the Cystinosis Foundation Germany. The authors have no competing interests to declare.TRIAL REGISTRATION NUMBERn/a.