No approved-drug candidate for spermatogenic failure 23 is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Medical therapy for primary spermatogenic failure remains largely ineffective. A 2011 review states that no treatments have consistently demonstrated efficacy and that it has not been possible to reliably identify patients likely to benefit. The review notes that idiopathic spermatogenic failure likely results from multiple discrete defects in sperm production that are as yet unidentified. A 2010 review similarly states that despite years of research, only few genetic factors have clearly been shown to cause spermatogenic failure, and that identification of additional genetic causes or risk factors has proven extremely difficult.
A 2022 study of 63 patients with recurrent implantation failure compared 80 cycles using testicular sperm aspiration (TESA) with 47 cycles using ejaculated sperm from the same patients. The testicular sperm group showed significantly higher rates of fertilisation (73% vs 64%), blastocyst development (62% vs 47%), implantation (27% vs 6%), clinical pregnancy (39% vs 10%), and live birth delivery (28% vs 5%). No significant differences were seen in embryo cleavage rates, high quality embryo rates, or abortion rate. The study reports 32 live newborns from the testicular sperm group with no pregnancy or delivery complications or congenital anomalies. The authors caution that the number of cycles needs to be increased for more definitive conclusions, as the women present a diversity of conditions rendering subgrouping difficult.
A 2022 prospective study of 18 non-oligozoospermic men with elevated sperm DNA fragmentation (median 26%) and recurrent pregnancy loss or IVF failure found histological evidence of spermatogenic failure. Median percentage of seminiferous tubules containing elongated spermatids was 74% in these men versus 92% in controls (p=0.0251). Hypospermatogenesis was the dominant pattern in 55.5% of specimens, while all control specimens had normal spermatogenesis (p=0.0457). The authors note this was an unexpected finding and that the testicular origin of DNA fragmentation is yet to be correlated with outcomes of testicular sperm injection.
What is still missing is a reliable way to identify which patients might benefit from any given approach, larger studies with better stratification of the diverse conditions underlying spermatogenic failure, and a clearer understanding of where sperm DNA damage originates in individual patients.
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Asian Journal of Andrology · 2011 · 57 citations · open access
Medical therapy for spermatogenic failure
AbstractMedical treatment of men with primary spermatogenic failure remains largely ineffective in contrast to those with secondary testicular failure. Treatment has been attempted with a multitude of agents ranging from hormones to nutritional supplements (antioxidants). While some studies have demonstrated benefit to some treatments, no treatments have consistently demonstrated efficacy nor has it been possible to reliably identify patients likely to benefit. Idiopathic spermatogenic failure likely results from multiple discrete defects in sperm production that are as yet unidentified. A better understanding of these defects will yield more effective treatment options and appropriate triage of patients to specific therapeutic regimens. This review focuses on the rationale and current evidence for hormonal and antioxidant therapy in medical treatment of male infertility, spermatogenic failure in particular. Although empiric medical therapy for spermatogenic failure has been largely replaced by assisted reproductive techniques, both treatment modalities could play a role, perhaps as combination therapy.
https://doi.org/10.1038/aja.2011.63Human Reproduction · 2022 · 2 citations · open access
P-064 Clinical outcomes of 127 patients with recurrent implantation failure treated with testicular sperm aspiration (TESA)
AbstractAbstract Study question Are the embryological, clinical and newborn outcomes using aspirated testicular sperm improved in cases with recurrent implantation failure previously treated with ejaculated sperm? Summary answer Aspirated testicular sperm enabled to obtain significant higher embryological, clinical and newborn outcomes in cases with recurrent implantation failure previously treated with ejaculated sperm. What is known already High levels of sperm DNA fragmentation (SDF) were associated to poor clinical outcomes (1-Simon et al., 2017). Testicular sperm display lower SDF than ejaculated sperm (2-Sakas and Alvarez, 2010), improving clinical outcomes in cases with abnormal semen parameters (3-Awaga et al., 2018; 4-Kang et al., 2018), recurrent implantation failure (RIF) and pregnancy loss (RPL) (5-Esteves et al., 2017), and elevated SDF (6-Ambar et al., 2021). As only a few studies are specifically dedicated to RIF, we expanded the number of cases and first provided full demographic, stimulation, embryological, clinical and newborn outcomes. References 1-(https://doi.org/10.4103/1008-682X.182822); 2-(https://doi.org/10.1016/j.fertnstert.2009.10.046); 3-(https://doi.org/10.1016/j.rbmo.2018.08.017); 4-(https://doi.org/10.1038/s41598-018-26280-0); 5-(https://doi.org/10.1016/j.fertnstert.2017.06.018); 6-(https://doi.org/10.5534/wjmh.200084 Study design, size, duration We retrospectively evaluated during consecutive years (2010-2020) 63 patients with recurrent implantation failure, which accepted to perform testicular sperm aspiration (TESA) as an alternative treatment. These patients presented a long history of failed treatments (153 cycles) using ejaculated sperm. From these cycles, no pregnancy ensued. The present study compares 127 treatment cycles, 80 with testicular sperm (17 cases repeated TESA) and 47 with ejaculated sperm from the same patients performed at the present IVF clinic. Participants/materials, setting, methods Patients were screened for karyotype abnormalities, for Y-chromosome microdeletions (7-Gonçalves et al., 2016), and for SDF with the TUNEL assay (8-Sá et al., 2015). Conventional semen analysis was performed according to World Health Organization guidelines (9-WHO, 2010). Male evaluation and TESA was performed by the same experienced urologist (LF) according to established protocols (10-Madureira et al 2014). The procedure was performed entirely on an outpatient basis, with no complications reported. References 7-(https://doi.org/10.4103/1008-682X.172827); 8-(https://doi.org/10.1016/j.rbmo.2015.06.019); 9-(https://apps.who.int/iris/handle/10665/44261); 10-(https://doi.org/10.1111/j.2047-2927.2014.00231.x). Main results and the role of chance The mean ages were 35.5±3.4 (26-42)-female and 38.1±5.7 (29-59)-male. There were 4 abnormal karyotypes (3-female, 1-male), all without known relevance. Most cases had asthenozoospermia and teratozoospermia (65.1%), or oligoasthenoteratozoospermia (41.8%). Of the 19 cases with <5M/ml, none presented Y-chromosome microdeletions. Although we do not routinely perform SDF testing, 15 patients had previous SDF values (12, >20%; 8, >36%). Female basal characteristics and testicular evaluation were under normal values. The TESA procedure took about 15-20 min, and the time of laboratorial search around 30-60 min. Cases using testicular sperm showed significant higher rates of fertilization (64% vs 73%-p=0.005), blastocyst development (47% vs 62%-p=0.010), implantation (6% vs 27%-p=0.000), clinical pregnancy (10% vs 39%-p=0.001), live birth delivery (5% vs 28%-p=0.005) and newborn (5% vs 32%-p=0.000) than ejaculated sperm. No significant differences were observed regarding the rates of embryo cleavage (95% vs 94.8%) and high quality embryos (89.4% vs 94%), in the mean number of transferred embryos (1.8±0.4 vs 1.9±0.4), or in the abortion rate (2 cases-50% vs 7 cases-25.9%). Cases using testicular sperm had 22 frozen-thawed embryo transfer cycles, enabling per initiated cycle a cumulative pregnancy rate of 45%, live birth delivery rate of 31.3% and newborn rate of 37.5% (32 newborn). Limitations, reasons for caution Although presenting the higher number of cycles using TESA in the treatment of RIF, this number needs to be increased for drawing more definitive conclusions, as these women present a diversity of conditions, rendering subgrouping difficult. In the future, it would also be important to evaluate SDF in all cases. Wider implications of the findings In conclusion, the present results gave further evidence for the superiority of using testicular sperm instead of ejaculated sperm in cases with recurrent implantation failure. Data also evidences the security of using testicular sperm aspiration, as there were no pregnancy or delivery complications, or congenital anomalies among the 32 newborn. Trial registration number Not Applicable
https://doi.org/10.1093/humrep/deac107.060Human Reproduction · 2013 · 0 citations · open access
Session 69: Clinical endocrinology
AbstractLimitations, reason for caution: This study was mainly performed to optimize an aCGH protocol on human single sperm, not to have percentage of alterations in normal and pathological conditions. Wider implications of the findings: Future application of this method might give important information on the biology and pathophysiology of spermatogenesis and sperm chromosome aberrations in normal subjects and in patients at higher risk of producing unbalanced sperm, such as infertile men, carriers of karyotype anomalies, men with advanced age, subjects treated with chemotherapy, and partners of couples with repeated miscarriage and repeated failure during assisted reproduction techniques. Study funding/competing interest(s): University of Padova/no competing interests
https://doi.org/10.1093/humrep/det203The Japanese Journal of Urology · 2004 · 0 citations · open access
IL-12 Carcinoma in situ testis and testicular dysgenesis syndrome
AbstractMale infertility has become a rnajor health problem in many Western countries. In Denmark more than 6%of all children are new born after assisted reproduction. and many of these treatrnents are due to male factor infertility. Unfortunately. the causes of spermatogenic failure are not known in the majority of the cases, although recent ad-
https://doi.org/10.5980/jpnjurol.95.277Pure Amsterdam UMC · 2010 · 0 citations
Unravelling the genetics of spermatogenic failure
AbstractSubfertility, defined as the inability to conceive within I year of unprotected intercourse, affects 10-15% of couples. in up to 55%, of couples, the male partner is diagnosed with spermatogenic failure, i.e. one or more semen parameters fall below the WHO criteria for normozoospermia. In these cases, assisted reproductive technology is usually used to achieve pregnancy. Both genetic and environmental factors are thought to underlie spermatogenic failure. Despite years of research, only few genetic factors have clearly been shown to cause spermatogenic failure, and the identification of additional genetic causes or risk factors has proven to be extremely difficult. in this review, we will present an overview of established genetic causes of spermatogenic failure, describe pitfalls in searching for novel genetic factors and discuss research opportunities for the future. Reproduction (2010) 139 303-307
https://doi.org/10.1530/rfp-09-0229The Journal of Urology · 2022 · 0 citations
PD36-02 HISTOLOGICAL EVIDENCE OF SPERMATOGENIC FAILURE IN MEN WITH HIGH SPERM DNA FRAGMENTATION INDEX
AbstractYou have accessJournal of UrologyCME1 May 2022PD36-02 HISTOLOGICAL EVIDENCE OF SPERMATOGENIC FAILURE IN MEN WITH HIGH SPERM DNA FRAGMENTATION INDEX Taras Shatylko, Inessa Telezhnikova, Safar Gamidov, Alikhan Tambiev, Alina Popova, and Vlada Kometova Taras ShatylkoTaras Shatylko More articles by this author , Inessa TelezhnikovaInessa Telezhnikova More articles by this author , Safar GamidovSafar Gamidov More articles by this author , Alikhan TambievAlikhan Tambiev More articles by this author , Alina PopovaAlina Popova More articles by this author , and Vlada KometovaVlada Kometova More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002594.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Recurrent pregnancy loss and IVF failures may be attributed, among other factors, to sperm DNA fragmentation (SDF). Many conditions and lifestyle factors potentially cause sperm DNA damage, but it is currently unknown where exactly this damage occurs – in testis, epididymis or other portion of seminal tract. Various studies have demonstrated lower SDF index in testicular sperm when compared to ejaculated sperm. Intracytoplasmic testicular sperm injection (Testi-ICSI) is a controversial technique using surgically retrieved sperm from non-azoospermic men to improve IVF outcomes. We sought to evaluate histopathology of seminiferous tubules obtained during sperm retrieval for Testi-ICSI. METHODS: This is an ongoing prospective study. The inclusion criteria are: recurrent pregnancy loss or at least 2 IVF failures, elevated DNA fragmentation index (TUNEL >15%). The exclusion criteria are: known female factor causing pregnancy loss or IVF failures, abnormal karyotype, oligozoospermia (concentration <15 × 106; total sperm count <39 × 106), treatable causes of increased SDF index, history of hormone therapy. Eighteen patients underwent testicular sperm extraction (TESE) for Testi-ICSI. A portion of extracted tissue was sent to pathology. Specimens taken from 5 patients undergoing TESE for obstructive azoospermia (duration of obstruction less than 5 years) were used as controls. Bergmann-Kliesch score (BKS) was used to assess seminiferous tubules histology. Fisher’s exact test and Mann-Whitney test were used as a part of statistical analysis. RESULTS: Median DNA fragmentation index for ejaculated sperm was 26% (interquartile range [IQR]: 23-30). Median percentage of seminiferous tubules containing elongated spermatids was 74% (IQR: 61-89), while in control specimens it was 92% (IQR: 90-95), which was a statistically significant difference (p=0.0251). Median BKS in Testi-ICSI specimens was 7 (IQR: 6-9), which was significantly lower than in control specimens (median: 9; IQR: 9-10; p=0.0271). Hypospermatogenesis was a dominant histological pattern in 10 of 18 Testi-ICSI specimens (55.5%), while all control specimens had features of normal spermatogenesis (p=0.0457). CONCLUSIONS: High prevalence of hypospermatogenesis in non-oligozoospermic patients was an unexpected finding. In theory, Testi-ICSI should work better in cases of post-testicular sperm DNA damage. However, we have found histological evidence of spermatogenic failure in some patients, which hints at probable testicular origin of SDF, which is yet to be correlated with Testi-ICSI outcomes. Source of Funding: N/A © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e633 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Taras Shatylko More articles by this author Inessa Telezhnikova More articles by this author Safar Gamidov More articles by this author Alikhan Tambiev More articles by this author Alina Popova More articles by this author Vlada Kometova More articles by this author Expand All Advertisement PDF downloadLoading ...
https://doi.org/10.1097/ju.0000000000002594.02Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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