DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for azoospermia — screening already-approved drugs against its 20-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAzoospermia maps to a 20-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 azoospermia 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.
Molecular view
CLIC family member 1 (CLIC1) — CLIC1 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet mlidrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4K0N · 1.25 Å · ligand MALONATE ION (MLI). Experimental structure, not a prediction.
What the evidence adds up to
A 2001 trial in six healthy volunteers found that combined administration of the GnRH antagonist cetrorelix and the androgen 19-nortestosterone (19NT-HPP) suppressed spermatogenesis to azoospermia within 12 weeks in all six men. After cetrorelix was stopped at week 12, gonadotrophins and testosterone rose despite continued 19NT-HPP injections, and spermatogenesis returned in five of the six volunteers. The authors concluded that complete azoospermia could not be maintained by the non-aromatizable androgen alone.
A retrospective study of 139 men with azoospermia seen between 2004 and 2012 reported that 71% had non-obstructive azoospermia and 29% had obstructive azoospermia. Among the non-obstructive cases, the most common finding was Sertoli-cell only syndrome (34%), followed by idiopathic causes (26%), Klinefelter syndrome (9%), and maturation arrest (9%). Among obstructive cases, congenital bilateral absence of the vas deferens accounted for 40%. A separate retrospective study of 218 non-obstructive azoospermic men found that 41.3% had hypospermatogenesis. In that group, removal of a testicular insult led to sperm appearing in the ejaculate in 4 of 17 men (23.6%). Sperm retrieval was successful in all men with mild or moderate hypospermatogenesis, but in only 87.8% of those with severe hypospermatogenesis. No pre-operative parameters predicted retrieval success.
A 2017 review of non-obstructive azoospermia states that empirical drug treatment can yield small numbers of sperm in the semen for a few patients, but that most patients eventually require surgery to obtain sperm. The highest reported sperm retrieval rate with microdissection testicular sperm extraction is 20–60%. The same review notes that even when a cause is identified, there is no exact etiological treatment, and that there is no reliable way to predict whether sperm retrieval will succeed.
What is still missing are prospective trials large enough to stratify patients by aetiology and severity, reliable biomarkers to predict sperm retrieval success, and a proven pharmacological regimen that can restore or induce spermatogenesis in men with non-obstructive azoospermia. The 2001 trial of cetrorelix plus 19NT-HPP was designed as a contraceptive study, not a treatment for infertility, and it involved only six men. No drug has been shown to durably reverse azoospermia in a controlled clinical setting.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Human Reproduction · 2001 · 82 citations
Suppression of spermatogenesis to azoospermia by combined administration of GnRH antagonist and 19-nortestosterone cannot be maintained by this non-aromatizable androgen alone
AbstractBACKGROUND: For male hormonal contraception, combined administration of gonadotrophin-releasing hormone (GnRH) antagonists and androgens effectively suppresses spermatogenesis to azoospermia. In non-human primates this suppression can be maintained more easily by androgens alone. METHODS: A clinical trial with six healthy volunteers was performed to test this approach in man. Loading doses of 10 mg/day of the GnRH antagonist cetrorelix were given subcutaneously for 5 days, followed by maintenance doses of 2 mg/day up to week 12. At 2 weeks after the first GnRH antagonist injection, androgen substitution was initiated with a loading dose of 400 mg 19-nortestosterone hexyloxyphenylpropionate (19NT-HPP) intramuscularly, followed by injections of 200 mg 19NT-HPP every 3 weeks up to week 26. RESULTS: Serum concentrations of LH, FSH and testosterone were effectively suppressed by cetrorelix administration. Within 12 weeks, azoospermia was achieved in all six volunteers. After cessation of cetrorelix injections in week 12, gonadotrophins and testosterone increased significantly despite continued 19NT-HPP injections. In parallel, spermatogenesis was restimulated in five of six volunteers. CONCLUSIONS: Combined administration of cetrorelix and 19NT-HPP leads to azoospermia within 3 months. However, complete azoospermia cannot be maintained by continued injections of the non-aromatizable 19NT-HPP alone.
AbstractPURPOSE: Male infertility is commonly seen at urology clinics and 10% to 20% of infertile males are found to be azoospermic. Azoospermia is classically categorized as nonobstructive or obstructive. This classification tailors the evaluation, diagnosis and proper treatment. We performed a retrospective study to provide an updated etiology of azoospermia in patients in the United States in a universal health care model. MATERIALS AND METHODS: We retrospectively reviewed the records of men with azoospermia who presented to our institution between 2004 and 2012. Laboratory data were analyzed, included semen analysis, follicle-stimulating hormone, luteinizing hormone, testosterone, semen fructose and genetic studies. Patients underwent scrotal exploration as indicated for testis biopsy and sperm extraction. RESULTS: We reviewed 139 outpatient records. Nonobstructive azoospermia was diagnosed in 99 men (71%), including 33 (34%) identified with Sertoli-cell only syndrome. Other etiologies included an idiopathic cause in 25 cases (26%), Klinefelter syndrome in 9 (9%), maturation arrest in 9 (9%), Y chromosome microdeletion in 5 (5%), cryptorchidism in 4 (4%), trauma in 4 (4%), exogenous testosterone supplementation in 4 (4%) and other genetic disorders in 6 (6%). Obstructive azoospermia was identified in 40 men (29%), of whom 16 (40%) had congenital bilateral absence of the vas deferens. Other etiologies included an idiopathic cause in 11 cases (28%), an iatrogenic condition due to a surgical cause in 5 (13%), ejaculatory duct obstruction in 3 (8%), trauma in 1 (3%), retrograde ejaculation in 1 (3%), vas deferens occlusion in 2 (5%) and unilateral absence of the vas deferens in 1 (3%). CONCLUSIONS: This study delineates the etiology of azoospermia in men with universal access to care.
American Journal of Clinical Pathology · 1948 · 2 citations
Azoospermia and Aspermia
AbstractAzoospermia and Aspermia Get access O. J. Pollak, M.D. O. J. Pollak, M.D. From the Wilmington General Hospital, Wilmington, Delaware Search for other works by this author on: Oxford Academic Google Scholar American Journal of Clinical Pathology, Volume 18, Issue 7, 1 July 1948, Pages 542–547, https://doi.org/10.1093/ajcp/18.7.542 Published: 01 July 1948 Article history Received: 28 October 1947 Published: 01 July 1948
AB126. Clinical characteristics and sperm retrieval outcomes in non-obstructive azoospermic men with hypospermatogenesis
AbstractOBJECTIVE: To analyze the causes, clinical features and treatment outcomes in patients with non-obstructive azoospermia (NOA) and different severity of hypospermatogenesis (HS). METHODS: This is a retrospective study from our reproductive clinic. Data of history, physical findings, serum hormone profiles and genetic studies were collected. The severity of HS was subdivided into three groups (mild, moderate, and severe) based on spermatogenic score. Our goals are to evaluate the causes of HS, clinical features, treatment outcome, sperm retrieval rate (SRR) and factors affecting the SRR among these three groups. RESULTS: The prevalence of HS in our NOA patients is 41.3% (90/218). Twenty-eight (31.1%) patients had at least one prior/current testicular insult, and 12 (13.2%) patients had genetic anomalies. Patients with mild HS tended to have higher frequency of testicular insults, whereas patients with severe HS had a significantly higher frequency of genetic anomalies. Removal of testicular insults leads to sperm in ejaculates in four of 17 (23.6%) patients. All patients with mild and moderate HS had successful sperm retrieval; however, 36 of 41 (87.8%) patients with severe HS met with success. No pre-operative parameters were significant predictors of sperm retrieval in our patients. CONCLUSIONS: The causes of HS are complex and genetic anomaly is associated with severe HS. Not all patients with severe HS had successful sperm retrieval. Spermatogenesis might be induced in mild HS patients following removal of testicular insults.
Translational Andrology and Urology · 2017 · 0 citations · open access
AB026. Experience on diagnosis and treatment of non-obstructive azoospermia
AbstractBackground: To analyze the status of diagnosis and treatment of non-obstructive azoospermia, and to introduce the experience on diagnosis and treatment of non-obstructive azoospermia. Methods: Read the literature. The clinical characteristics such as sex hormones, testicular volume, chromosome karyotype and microdeletion of AZF gene of non-obstructive azoospermia patients were analyzed in this paper, and the gains and losses were analyzed in the course of diagnosis and treatment. Results: Drug preparation before sperm retrieval can help improve the success rate. Different causes of non-obstructive azoospermia have different success rate. Treatment of non-obstructive azoospermia should respect the individual wishes. Conclusions: Non-obstructive azoospermia is a difficult problem in the field of male infertility. The reason is that we know little about its cause. Even if some patients can get etiological diagnosis, there is no exact etiological treatment. A small amount of sperm can be found in the semen for a small number of patients through the empirical drug treatment, they have access to offspring through scarce sperm cryopreservation techniques. Most patients eventually need surgery to obtain sperm. There are many ways of surgery, in which highest probability of obtaining sperm is microdissection testicular sperm extraction. Success rate for sperm retrieval is 20–60%. Unfortunately, there is still no reliable means to predict whether a sperm retrieval will be successful. With the development of molecular biology, I believe that in the near future more non-obstructive azoospermia patients can be effectively treated.
AbstractZusammenfassung: Bericht über das kombinierte operative Vorehen mit Hodenbiopsie und Epididymovasostomie bei Azoospermie. Es wird herausgestellt, daß der diagnostische Eingriff stets der erste Schritt sein muß, bevor ihm aufgrund der exakten histologischen Auswertung der therapeutische Schritt, z.B. im Sinne einer Epididymovasostomie folgen kann. Summary: Case history concerning the combined diagnostically and therapeutically performed management in azoospermia. It is to pointed out that the diagnosis must be the first step; the treatment – especially in case of azoospermia with an expected epididymovasostomy – depends from the results of the diagnosis. Very often this management will not be noticed.
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.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
