DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for spermatogenic failure 41 — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleSpermatogenic failure 41 maps to a 1-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for spermatogenic failure 41 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.
What the evidence adds up to
Two 1988 papers review 8879 vasectomies performed by one physician over 24 years. In a subgroup of 5331 men who returned for at least two postoperative semen tests, there were 97 failures of all types. Early overt failures numbered 32 (0.60%). Technical failures involving persistence of small numbers of spermatozoa, possibly of no significance, numbered 61 (1.14%). Four late overt failures (0.08%) were discovered because of a pregnancy, each occurring at least four years after two azoospermic test results. Four failures were due to missed vasa deferentia; the remainder were attributed to recanalisation. The paper notes that whether improved and reproducible failure rates can be consistently obtained by other techniques is not yet clear.
A 2005 study examined BOULE messenger RNA transcript levels in testicular tissue from 41 azoospermic patients. A significant decrease in BOULE transcript levels was detected in patients with spermatogenic failure, and levels progressively decreased with increasing severity of testicular failure. BOULE transcript levels did not correlate with serum hormone parameters. Significantly higher BOULE transcript levels were found in 19 patients with successful sperm retrieval than in 12 patients with failed sperm retrieval. Using a cut-off value of 0.5 for BOULE transcript ratio to predict success of sperm retrieval, both sensitivity and specificity were 100%. The authors suggest BOULE transcript levels may predict the presence of testicular sperm in patients with spermatogenic failure.
A 2022 study retrospectively evaluated 63 patients with recurrent implantation failure who underwent testicular sperm aspiration (TESA). These patients had a history of 153 failed treatment cycles using ejaculated sperm, from which no pregnancy ensued. The study compared 127 treatment cycles: 80 with testicular sperm and 47 with ejaculated sperm from the same patients. Cases using testicular sperm showed significantly higher rates of fertilisation (73% vs 64%), blastocyst development (62% vs 47%), implantation (27% vs 6%), clinical pregnancy (39% vs 10%), live birth delivery (28% vs 5%), and newborn rate (32% vs 5%). No significant differences were seen in embryo cleavage rates, high quality embryo rates, mean number of transferred embryos, or abortion rate. Cases using testicular sperm had 22 frozen-thawed embryo transfer cycles, yielding a cumulative pregnancy rate of 45%, live birth delivery rate of 31.3%, and newborn rate of 37.5% (32 newborns). The authors note the number of cycles needs to be increased for more definitive conclusions, and that it would be important to evaluate sperm DNA fragmentation in all cases.
What is still missing for spermatogenic failure 41 is a specific molecular diagnosis or genetic target that could be addressed by a drug. The existing literature describes surgical sperm retrieval and prediction of its success via BOULE transcript levels, but no pharmacological intervention is tested or proposed. No trial design, patient stratification strategy, or funding for a drug-repurposing study exists for this condition.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
JAMA · 1988 · 46 citations
The lurking sperm. A review of failures in 8879 vasectomies performed by one physician
AbstractVasectomy techniques and failure rates vary among surgeons, and the criteria for failure are not often clearly defined. To help establish a yardstick for comparative purposes, a series of 8879 consecutive vasectomies performed with uniform technique over 24 years was reviewed. A subgroup of 5331 men who had returned for at least two postoperative semen tests--the study group--was used for follow-up analysis. Failures were defined as early or late and also were categorized as overt or technical according to the numbers, motility, or persistence of the remaining spermatozoa. There were 97 failures of all types, including 32 (0.60%) early and overt failures and 61 (1.14%) technical failures that involved the persistence of small numbers of spermatozoa, possibly of no significance. Four (0.08%) late overt failures were also seen; each of these was discovered as a result of a pregnancy, and each occurred at least four years after two azoospermic test results. Of the 97 failures, four were recognized as due to missed vasa deferentia, and the remainder were attributed to recanalization. Whether improved and reproducible failure rates can be consistently obtained by other techniques is not yet clear.
AbstractVasectomy techniques and failure rates vary among surgeons, and the criteria for failure are not often clearly defined. To help establish a yardstick for comparative purposes, a series of 8879 consecutive vasectomies performed with uniform technique over 24 years was reviewed. A subgroup of 5331 men who had returned for at least two postoperative semen tests—the<i>study</i>group—was used for follow-up analysis. Failures were defined as<i>early</i>or<i>late</i>and also were categorized as overt or<i>technical</i>according to the numbers, motility, or persistence of the remaining spermatozoa. There were 97 failures of all types, including 32 (0.60%) early and overt failures and 61 (1.14%) technical failures that involved the persistence of small numbers of spermatozoa, possibly of no significance. Four (0.08%) late overt failures were also seen; each of these was discovered as a result of a pregnancy, and each occurred at least four years after two azoospermic test results. Of the 97 failures, four were recognized as due to missed vasa deferentia, and the remainder were attributed to recanalization. Whether improved and reproducible failure rates can be consistently obtained by other techniques is not yet clear. (<i>JAMA</i>1988;259:3142-3144)
Messenger RNA transcripts of the meiotic regulator BOULE in the testis of azoospermic men and their application in predicting the success of sperm retrieval
AbstractBACKGROUND: Testicular sperm retrieval can lead to paternity for azoospermic patients with spermatogenic failure. The human BOULE gene, a meiotic regulator of germ cells, is a gene whose altered expression may be associated with sterility. We determined the levels of BOULE transcripts in the testes of azoospermic patients, and evaluated the relationship between BOULE transcript levels and patients' testicular phenotypes, clinical parameters and sperm retrieval results. METHODS AND RESULTS: BOULE transcript levels in the testes of 41 azoospermic patients were examined by quantitative competitive-reverse transcription-polymerase chain reaction. A significant decrease in BOULE transcript levels was detected in patients with spermatogenic failure, and BOULE transcript levels progressively decreased with increasing severity of testicular failure. BOULE transcript levels did not correlate with the serum hormone parameters measured. Significantly higher BOULE transcript levels were detected in 19 patients with successful sperm retrieval than in 12 patients with failed sperm retrieval. When using a cut-off value of 0.5 for BOULE transcript ratio to predict the success of sperm retrieval, both the sensitivity and specificity value were 100%. CONCLUSIONS: We suggest the BOULE transcript plays an important role in human spermatogenesis and that the levels may predict the presence of testicular sperm in patients with spermatogenic failure.
Human 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 &lt;5M/ml, none presented Y-chromosome microdeletions. Although we do not routinely perform SDF testing, 15 patients had previous SDF values (12, &gt;20%; 8, &gt;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
Disease 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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