Increasing evidence implicates disruptions in testicular fatty acid metabolism as a contributing factor in nonobstructive azoospermia(NOA),a severe form of male infertility.However,the precise mechanisms linking fatty...Increasing evidence implicates disruptions in testicular fatty acid metabolism as a contributing factor in nonobstructive azoospermia(NOA),a severe form of male infertility.However,the precise mechanisms linking fatty acid metabolism to NOA pathogenesis have not yet been fully elucidated.Multi-omics analyses,including microarray analysis,single-cell RNA sequencing(scRNA-seq),and metabolomics,were utilized to investigate disruptions in fatty acid metabolism associated with NOA using data from public databases.Results identified ACSL6,ACSBG2,and OLAH as key genes linked to fatty acid metabolism dysregulation,suggesting their potential causative roles in NOA.A marked reduction in omega-3 polyunsaturated fatty acids,especially docosahexaenoic acid(DHA),was observed,potentially contributing to the pathological process of NOA.Sertoli cells in NOA patients exhibited apparent fatty acid metabolic dysfunction,with PPARG identified as a key transcription factor(TF)regulating this process.Functional analyses demonstrated that PPARG is crucial for maintaining blood-testis barrier(BTB)integrity and promoting spermatogenesis via regulation of fatty acid metabolism.These findings reveal the pivotal role of fatty acid metabolism in NOA and identify PPARG as a potential therapeutic target.展开更多
Non-obstructive azoospermia is a common condition associated with significant health risks,including increased mortality,cancer,and chronic diseases such as metabolic and cardiovascular disorders.This review aims to h...Non-obstructive azoospermia is a common condition associated with significant health risks,including increased mortality,cancer,and chronic diseases such as metabolic and cardiovascular disorders.This review aims to highlight the potential health challenges faced by men with this condition compared to fertile counterparts.Through a comprehensive bibliographic search on PubMed,using the following algorithm:(“infertility,male”[MeSH Terms]OR“azoospermia”[MeSH Terms])AND(“mortality”[MeSH Terms]OR“neoplasms”[MeSH Terms]OR“chronic disease”[MeSH Terms]OR“diabetes mellitus”[MeSH Terms]OR“heart diseases”[MeSH Terms]),we analyzed existing literature to explore the associations between infertility,specifically azoospermia,and adverse health outcomes.Findings indicate that infertile men are at a higher risk of death,various cancers(particularly testicular cancer),metabolic syndrome,diabetes,hypogonadism,and cardiovascular disease.Although research specifically addressing azoospermia is limited,available studies support the notion that men with this condition may experience heightened health vulnerabilities.Given these risks,it is imperative for healthcare professionals,especially urologists,to conduct thorough health assessments for men diagnosed with azoospermia.Informing patients of these potential health issues and integrating comprehensive evaluations into their care can facilitate early detection and intervention for life-threatening conditions.Ultimately,men with azoospermia should receive ongoing monitoring to address their specific health concerns,thus improving their long-term health outcomes.展开更多
This special issue of the Asian Journal of Andrology is fully dedicated to the thematic area of non-obstructive azoospermia(NOA),one of the most complex and challenging conditions in the realm of andrology,urology,and...This special issue of the Asian Journal of Andrology is fully dedicated to the thematic area of non-obstructive azoospermia(NOA),one of the most complex and challenging conditions in the realm of andrology,urology,and reproductive medicine.展开更多
We investigated whether letrozole （2.5 mg day-1） improves sperm count in non-obstructive azoospermia （NOA） patients. Four men were included in this study, and they had folliculo-stimulating hormone and other hormo...We investigated whether letrozole （2.5 mg day-1） improves sperm count in non-obstructive azoospermia （NOA） patients. Four men were included in this study, and they had folliculo-stimulating hormone and other hormone levels within the normal range and no varicoceles or chromosomal aberrations. These four patients were administered letrozole for 3 months. Sperm count, testicular volume, gonadotropin, testosterone （T） and estradiol （E2） blood levels were assessed before, during and 1 week after the suspension of treatment. All patients showed spermatozoa in their ejaculate, increased gonadotropin and T levels and lower E2 levels （P〈0.05 in all cases）, when letrozole was administered. This suggests that letrozole treatment might improve sperm count in an NOA sub-population; however, more studies, including the proper controls, are needed to confirm its efficacy.展开更多
Aim： To evaluate the outcome of repetitive micro-surgical testicular sperm extraction （mTESE） attempts in non-obstructive azoospermia （NOA） cases, in relation to patients＇ initial testicular histology results. M...Aim： To evaluate the outcome of repetitive micro-surgical testicular sperm extraction （mTESE） attempts in non-obstructive azoospermia （NOA） cases, in relation to patients＇ initial testicular histology results. Methods： A total of 68 patients with NOA in whom mTESE had been performed in previous intracytoplasmic sperm injection （ICSI） attempts were reviewed. Results： Among the 68 patients with NOA, the first mTESE yielded mature sperm for ICSI in 44 （64%） （Sp^＋）, and failed in the remaining 24 （36%） （Sp^-）. Following their first trial, 24 patients decided to undergo a second mTESE. Of these 24 patients, no spermatozoa were obtained in 5 patients, and Sp^＋ but no fertilization/pregnancy were achieved in 19. In these 24 cases, mTESE was successively repeated for two （n = 24）, three （n = 4） and four （n = 1） times. The second attempt yielded mature sperm in 3/5 patients from the Sp group and 16/19 patients from the Sp^＋ group. At the third and fourth trials, 4/4 and 1/1 of the original Sp^＋ patients were Sp^＋ again, respectively. Distribution of main testicular histology included Sertoli cell-only syndrome （16%）, maturation arrest （22%）, hypospermatogenesis （21%） and focal spermatogenesis （41%）. Overall, in repetitive mTESE, 24/29 （82%） of the attempts were finally Sp^＋. Conclusion： Repeated mTESE in patients with NOA is a feasible option, yielding considerably high sperm recovery rate. In patients with NOA, mTESE may safely be repeated one or more times to increase sperm retrieval rate, as well as to increase the chance of retrieving fresh spermatozoa to enable ICSI.展开更多
Non-obstructive azoospermia （NOA） is a severe defect in male reproductive health that occurs in 1% of adult men. In a previous study, we identified that rs7099208 is located within the last intron of FAM160B1 at 10q...Non-obstructive azoospermia （NOA） is a severe defect in male reproductive health that occurs in 1% of adult men. In a previous study, we identified that rs7099208 is located within the last intron of FAM160B1 at 10q25.3. In this study, we analysed expression Quantitative Trait Loci （eQTL） of FAM16OB1, ABLIM1 and TRUB1, the three genes surrounding rs7099208. Only the expression level of FAM16OB1 was reduced for the homozygous alternate genotype （GG） of rs7099208, but not for the homozygous reference or heterozygous geno- types. FAM160B1 is predominantly expressed in human testes, where it is found in spermatocytes and round sper- matids. From 17 patients with NOA and five with obstructive azoospermia （OA）, immunohistochemistry revealed that expression of FAM160B1 is reduced, or undetectable in NOA patients, but not in OA cases or normal men. We conclude that rs7099208 is associated with NOA via a reduction in the expression of FAM160B1.展开更多
Circular RNAs(circRNAs)are highly conserved and ubiquitously expressed noncoding RNAs that participate in multiple reproductionrelated diseases.However,the expression pattern and potential functions of circRNAs in the...Circular RNAs(circRNAs)are highly conserved and ubiquitously expressed noncoding RNAs that participate in multiple reproductionrelated diseases.However,the expression pattern and potential functions of circRNAs in the testes of patients with non-obstructive azoospermia(NOA)remain elusive.In this study,according to a circRNA array,a total of 37881 circRNAs were identified that were differentially expressed in the testes of NOA patients compared with normal controls,including 19874 upregulated circRNAs and 18007 downregulated circRNAs.Using quantitative real-time polymerase chain reaction(qRT-PCR)analysis,we confirmed that the change tendency of some specific circRNAs,including hsa_circ_0137890,hsa_circ_0136298,and hsa_circ_0007273,was consistent with the microarray data in another larger sample.The structures and characteristics of these circRNAs were confirmed by Sanger sequencing,and fluorescence in situ hybridization revealed that these circRNAs were primarily expressed in the cytoplasm.Bioinformatics analysis was used to construct the competing endogenous RNA(ceRNA)network,and numerous miRNAs that could be paired with circRNAs validated in this study were reported to be vital for spermatogenesis regulation.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses indicated that genes involved in axoneme assembly,microtubule-based processes,and cell proliferation were significantly enriched.Our data suggest that there are aberrantly expressed circRNA profiles in patients with NOA and that these circRNAs may help identify key diagnostic and therapeutic molecular biomarkers forNoA patients.展开更多
Objective: To investigate the feasibility of obtaining mature spermatozoa for intracytoplasmic sperm injection (ICSI) by testicular fine needle aspiration (TEFNA) in men diagnosed non-obstructive azoospermia. Methods:...Objective: To investigate the feasibility of obtaining mature spermatozoa for intracytoplasmic sperm injection (ICSI) by testicular fine needle aspiration (TEFNA) in men diagnosed non-obstructive azoospermia. Methods: TEFNA was performed in 121 patients with a mean of 15 punctures and aspirations from each testis with a #23 butterfly needle connected to a 20 mL syringe with an aspiration handle. Results: One hundred and twenty-one patients underwent 176 TEFNA cycles. Testicular sperm were recovered in 56.3 % (99/176) cycles from 57 % (69/121) of patients. The sperm recovery rate was 46.7 % (21/45) in patients with Sertoli cell-only syndrome, 45.7 % (16/35) in patients with maturation arrest, 96.1 % (25/26) in patients with hypospermatogenesis and 63.6 % (7/11) in patients of non-mosaic Klinefelter's syndrome as judged by testicular histology. No sperm were found in 3 cases with post-irradiation fibrosis and one, after resection and chemotherapy of unilateral testicular cancer. In 87 cycles of ICSI using the husbands' sperm, 591 mature oocytes were injected, 218 (36.9 %) were normally fertilized and 202 embryos developed; 178 were transferred in 62 cycles resulting in 26 pregnancies (41.9 %) with 44 gestational sacs (implantation rate: 24.7 %). Conclusion: TEFNA was an efficient, easy to learn, safe and well tolerated treatment in patients with non-obstructive azoospermia.展开更多
The development of intracytoplasmic sperm injection （ICSI） opened a new era in the field of assisted reproduction and revolutionized the assisted reproductive technology protocols for couples with male factor infert...The development of intracytoplasmic sperm injection （ICSI） opened a new era in the field of assisted reproduction and revolutionized the assisted reproductive technology protocols for couples with male factor infertility. Fertilisation and pregnancies can be achieved with spermatozoa recovered not only from the ejaculate but also from the seminiferous tubules. The most common methods for retrieving testicular sperm in non-obstructive azoospermia （NOA） are testicular sperm aspiration （TESA： needle/fine needle aspiration） and open testicular biopsy （testicular sperm extraction： TESE）. The optimal technique for sperm extraction should be minimally invasive and avoid destruction of testicular function, without compromising the chance to retrieve adequate numbers of spermatozoa to perform ICSh Microdissection TESE （micro-TESE）, performed with an operative microscope, is widely considered to be the best method for sperm retrieval in NOA, as larger and opaque tubules, presumably with active spermatogenesis, can be directly identified, resulting in higher spermatozoa retrieval rates with minimal tissue loss and low postoperative complications. Micro-TESE, in combination with ICSI, is applicable in all cases of NOA, including Klinefelter syndrome （KS）. The outcomes of surgical sperm retrieval, primarily in NOA patients with elevated serum follicle-stimulating hormone （FSH） （NOA including KS patients）, are reviewed along with the phenotypic features. The predictive factors for surgical sperm retrieval and outcomes of treatment were analysed. Finally, the short- and long-term complications in micro-TESE in both 46XY males with NOA and KS patients are considered.展开更多
As the field of assisted reproduction has advanced, many previously untreatable men are now biological fathers. Although finding sperm in men with obstructive azoospermia is not difficult, locating and retrieving sper...As the field of assisted reproduction has advanced, many previously untreatable men are now biological fathers. Although finding sperm in men with obstructive azoospermia is not difficult, locating and retrieving spermatozoa in men with non-obstructive azoospermia remains a clinical challenge, largely because sperm production in these men can be patchy or focal in nature. In response to this challenge, strategies such as fine-needle aspiration （FNA） mapping have been developed to find spermatozoa. This review discusses the history, evolution and current clinical utility and findings with FNA mapping for male infertility）. Review of the current literature in the English language on FNA （diagnostic or therapeutic） with a keyword focuses on sperm detection, retrieval, safety and complications. FNA was described in human medicine over 100 years ago. Testis FNA was described 45 years ago and FNA ＇mapping＇ of spermatozoa was described in 1997. This comparative review of the literature on sperm detection and complication rates with FNA and open testis biopsy or microdissection procedures suggests that FNA is highly informative, minimally invasive and is associated with fewer complications than other commonly used approaches to sperm detection in non-obstructive azoospermic patients. FNA mapping has gained considerable traction as an informative, ＇testis sparing＇ technique for sperm detection in non-obstructive azoospermia. With knowledge of sperm presence and location prior to sperm retrieval, FNA maps can help clinicians tailor sperm retrieval to optimize time, effort and extent of procedures needed to procure spermatozoa in these difficult cases.展开更多
Objective: To evaluate the effects of intracytoplasmic sperm injection (ICSI) ontreatment of infertility due to obstructive and non-obstructive azoospermia..Methods: A retrospective analysis of fertilization, cleavage...Objective: To evaluate the effects of intracytoplasmic sperm injection (ICSI) ontreatment of infertility due to obstructive and non-obstructive azoospermia..Methods: A retrospective analysis of fertilization, cleavage, embryo implantationand pregnancy rates was done in 158 ICSI cycles including 112 obstructive azoospermiaand 46 non-obstructive azoospermia. Ovarian hyperstimulation and ICSI procedureswere performed by conventional protocol. The sperm was collected by percutaneous epi-didymal sperm aspiration (PESA) or testicular sperm extraction (TESE).Results:The fertilization rate (73.1% vs. 67.0%), cleavage rate (88.6% vs. 86.3%), embryo implantation rate (20.7% vs. 11.4%), clinical pregnancy rate per trans-fer cycle (35.7% vs. 19.6%) were obtained for obstructive and non-obstructiveazoospermia, respectively.Conclusion: The results revealed that in the cases of obstructive azoospermia, ferti-lization rate, embryo implantation rate and clinical pregnancy rate were significantlyhigher than those of non-obstructive azoospermia. But there was no significant differ-ence of the cleavage rate between two groups.展开更多
Introduction: Non-invasive methods that can predict sperm recovery in patients with non-obstructive azoospermia (NOA) arouse interest of clinicians. The aim of this study was to evaluate the predictive value of sperm ...Introduction: Non-invasive methods that can predict sperm recovery in patients with non-obstructive azoospermia (NOA) arouse interest of clinicians. The aim of this study was to evaluate the predictive value of sperm retrieval in NOA. Materials and Methods: In the retrospective study, fine needle aspiration (FNA) was performed on 306 patients with NOA at the department of andrology, Wuhan Tongji Reproductive Medical Hospital. Inhibin B, FSH and LH plasma levels were analyzed and sperms were retrieved in 67 of 306 cases (21.89%). Results: There were statistically significant differences between successful and unsuccessful sperm recoverygroups in terms of mean serum inhibin B, FSH and LH levels. The areas under the curve (AUC) of inhibin B, FSH and LH were 0.696, 0.729 and 0.747 respectively, and the AUC for the combined value of the three hormones is 0.832. The cut-off points were 27.31 pg/ml, 11.68 IU/L and 4.04 IU/L for inhibin B, FSH and LH respectively. Conclusions: This study suggests that the combined evaluation of inhibin B, FSH and LH is a more effective predictor for successful sperm retrieval in patients with NOA before decision making of an invasive procedure than any single factor.展开更多
Objective: The azoospermia is increasingly becoming prevalent year by year,which has been plaguing a great number of infertile couples. Testes biopsy is a gold index to evaluate the testicular spermatogenesis in patie...Objective: The azoospermia is increasingly becoming prevalent year by year,which has been plaguing a great number of infertile couples. Testes biopsy is a gold index to evaluate the testicular spermatogenesis in patients with anspermia. However, it is more invasive and may not accurately reflect the whole spermatogenic function of the testes. In recent years, with the continuous development of ultrasound and assisted reproductive technology, real-time sonoelastography has been widely applied in the evaluation of spermatogenic function in patients with azoospermia. It is still at the initial stage, but shows good application prospects. In this paper, we will summarize and review the present status of male infertility and the clinical application and research progress of real-time sonoelastography in the evaluation of the testicular spermatogenic function of non-obstructive azoospermia patients.展开更多
Ten percent of infertile males have azoospermia,classified into obstructive and nonobstructive types,which require specific medical or surgical treatments.In nonobstructive azoospermia,advancements in microsurgery all...Ten percent of infertile males have azoospermia,classified into obstructive and nonobstructive types,which require specific medical or surgical treatments.In nonobstructive azoospermia,advancements in microsurgery allow for effective sperm retrieval in about half of cases.This review aimed to highlight the most recent studies utilizing whole exome sequencing(WES)and seminal/serum biomarkers aim to predict micro-dissection testicular sperm extraction(micro-TESE)outcomes and reduce failure rates.WES identifies rare genetic mutations affecting spermatogenesis that could explain micro-TESE failures,improving preoperative assessments.Despite its potential,WES is limited by high costs.Biomarkers such as Anti-Müllerian Hormone and testis-expressed sequence 101 protein can indicate spermatogenic activity,though standardization of these measurements is needed for accuracy.Additionally,microRNAs as non-invasive markers offer potential in assessing spermatogenic reserve and classifying azoospermia types,but their efficacy in identifying specific spermatogenic disorders remains under researched,necessitating further studies on multivariate miRNA models.展开更多
Germ cell arrest is one kind of important disease in nonobstructive azoospermia(NOA)including spermatogonia arrest,spermatocyte arrest,and round spermatid arrest.1 There is an urgent need to explore the molecular mech...Germ cell arrest is one kind of important disease in nonobstructive azoospermia(NOA)including spermatogonia arrest,spermatocyte arrest,and round spermatid arrest.1 There is an urgent need to explore the molecular mechanisms underlying germ cell arrest,which are essentially unknown and could provide not only a promising approach for therapy but also novel possibilities for developing male contraceptives.展开更多
Saad et al.'s review~([1]),“Emerging trends in the management of non-obstructive azoospermia,”offers a compelling synthesis of cutting-edge diagnostic and therapeutic strategies for non-obstructive azoospermia(N...Saad et al.'s review~([1]),“Emerging trends in the management of non-obstructive azoospermia,”offers a compelling synthesis of cutting-edge diagnostic and therapeutic strategies for non-obstructive azoospermia(NOA),a challenging condition affecting 10%–15%o infertile men.By highlighting advances in whole exome sequencing(WES),biomarkers like Anti-Müllerian hormone(AMH)and microRNAs(miRNAs),and microdissection testicular sperm extraction(micro-TESE),the authors chart a path toward precision medicine in male infertility.Their exploration of AI and gene-editing technologies like CRISPR/Cas9 underscores the transformative potential of these innovations.展开更多
Background:Some cases of non-obstructive azoospermia(NOA)are characterized by normal clinical parameters,including testicular volume and levels of reproductive hormones,mimicking obstructive azoospermia(OA).Methods:We...Background:Some cases of non-obstructive azoospermia(NOA)are characterized by normal clinical parameters,including testicular volume and levels of reproductive hormones,mimicking obstructive azoospermia(OA).Methods:We performed a retrospective review of a consecutive series of 1417 patients undergoing primary surgical sperm retrieval between 2014 and 2023.Follicle-stimulating hormone(FSH)level below 7.6 IU/l and normal testicular size with a long axis measurement>4.6 cm were used as criteria to suspect OA.Results:Four hundred and eighteen patients with normal testicular volume and FSH levels had an initial diagnosis of OA.Among them,243(58.1%)had histological signs of spermatogenic dysfunction,and 175(41.9%)had true OA.One hundred eleven patients had long-standing obstruction(median:16.5 years)with a median Bergmann-Kliesch score(BKS)of 5(interquartile range[IQR]:4-6)and 100%sperm retrieval rate(SRR),though some required microdissection testicular sperm extraction(microTESE).Fifty-eight patients with a history of epididymo-orchitis had a median BKS of 4(IQR:2-6)and 100%SRR.Twenty patients with a history of unjustified medical treatment for male infertility had a median BKS of 3(IQR:1-4)and 80%SRR.Fifty-four patients had uniform maturation arrest with a 5.5%SRR on microTESE.Conclusion:Men with normal testicular volume and FSH level may have evidence of spermatogenic failure on pathology.Patients with complicated seminal tract obstruction commonly have hypospermatogenesis,but true NOA caused by uniform maturation arrest may also be observed.Patient counseling for suspected OA should not be overly optimistic,and couples should be warned about possibility of conversion to microTESE and risks of negative sperm retrieval.展开更多
We tested the hypothesis that letrozole increases sperm count in non-obstructive azoospermic or cryptozoospermic patients with a testosterone （T）/17-beta-2-oestradiol （E2） ratio 〈 10. Forty-six patients with no c...We tested the hypothesis that letrozole increases sperm count in non-obstructive azoospermic or cryptozoospermic patients with a testosterone （T）/17-beta-2-oestradiol （E2） ratio 〈 10. Forty-six patients with no chromosomal aberrations were randomized into two groups： 22 received letrozole 2.5 mg per day for 6 months （Group 1：6 azoospermic＋ 16 cryptozoospermic patients）, while 24 received a placebo （Group 2：5 azoospermic＋19 cryptozoospermic patients）. The following data were collected： two semen analyses, clinical history, scrotal Duplex scans, body mass index （BMI）, Y microdeletion, karyotype and cystic fibrosis screens and follicle-stimulating hormone （FSH）, luteinizing hormone （LH）, E2, T and prolactin levels. Both before and after letrozole or placebo administration, the patients underwent two semen analyses and hormonal assessments. The differences were evaluated using the Mann-Whitney Utest. The relationships between sperm concentration after letrozole administration with respect to FSH, TIE2 ratio, bilateral testicle volume and BMI before letrozole administration were assessed using multivariate analysis. The side effects were assessed using the chi-square test. Group 1 had sperm concentration （medians： 400-1.290× 10^6 ml^-1; P〈0.01） and motility （medians： class A from 2% to 15%; P〈0.01）, FSH, LH and T significantly increased, while Group 2 did not. E2 levels diminished significantly in Group 1, but not in Group 2. Eight patients in Group 1 demonstrated side effects, whereas no patient side effects were observed in Group 2. The sperm concentration after letrozole administration is inversely related to TIE2, FSH and BMI; a direct relationship emerged between sperm concentration and testicular volume.展开更多
The purpose of this study was to determine the relationships between monitors of spermatogenesis and predictors of the intracytoplasmic sperm injection （ICSI） outcome in patients with non-obstructive azoospermia （...The purpose of this study was to determine the relationships between monitors of spermatogenesis and predictors of the intracytoplasmic sperm injection （ICSI） outcome in patients with non-obstructive azoospermia （NOA） undergoing testicular sperm extraction （TESE）. Seventy-nine patients with NOA （mean age： 43.6±5.2 years）, each of whom yielded （97 000±3040） spermatozoa with conventional TESE, were considered in our analysis. Their partners （mean age： 35.8±5.1 years） underwent a total of 184 ICSI cycles; 632 oocytes were collected, 221 oocytes were injected, 141 oocytes were fertilized, 121 embryos were obtained, 110 embryos were transferred, 14 clinical pregnancies were achieved and only one miscarriage occurred. Multivariate regression analysis indicated relationships between the percentage of fertilized oocytes, transferred embryos and clinical pregnancies with the following variable values： female partner＇s age, number of spermatozoa collected, testicular volume, male partner＇s levels of follicle stimulating hormone （FSH）, number of oocytes collected, number of oocytes injected and number of ICSI cycles. A significant inverse relationship was found between female partner＇s age or male partner＇s FSH levels and biochemical pregnancies. A significant direct relationship emerged between the number of ICS! cycles and the percentage of oocytes fertilized, embryos transferred and biochemical pregnancies, and between the number of spermatozoa collected per testicular biopsy and biochemical pregnancies. The number of spermatozoa was positively linked to the number of clinical pregnancies, independent of the number of ICSI cycles and the number of oocytes collected/injected. The number of spermatozoa collected, FSH level and testicular volume are monitors of spermatogenesis linked to ICSI success.展开更多
Acute coronary syndromes constitute a variety of myocardial injury presentations that include a subset of patients presenting with myocardial infarction with non-obstructive coronary arteries(MINOCA).This acute corona...Acute coronary syndromes constitute a variety of myocardial injury presentations that include a subset of patients presenting with myocardial infarction with non-obstructive coronary arteries(MINOCA).This acute coronary syndrome differs from type 1 myocardial infarction(MI)regarding patient characteristics,presentation,physiopathology,management,treatment,and prognosis.Two-thirds of MINOCA subjects present ST-segment elevation;MINOCA patients are younger,are more often female and tend to have fewer cardiovascular risk factors.Moreover,MINOCA is a working diagnosis,and defining the aetiologic mechanism is relevant because it affects patient care and prognosis.In the absence of relevant coronary artery disease,myocardial ischaemia might be triggered by an acute event in epicardial coronary arteries,coronary microcirculation,or both.Epicardial causes of MINOCA include coronary plaque disruption,coronary dissection,and coronary spasm.Microvascular MINOCA mechanisms involve microvascular coronary spasm,takotsubo syndrome(TTS),myocarditis,and coronary thromboembolism.Coronary angiography with non-significant coronary stenosis and left ventriculography are first-line tests in the differential study of MINOCA patients.The diagnostic arsenal includes invasive and non-invasive techniques.Medical history and echocardiography can help indicate vasospasm or thrombosis,if one finite coronary territory is affected,or specify TTS if apical ballooning is present.Intravascular ultrasound,optical coherence tomography,and provocative testing are encouraged.Cardiac magnetic resonance is a cornerstone in myocarditis diagnosis.MINOCA is not a benign diagnosis,and its polymorphic forms differ in prognosis.MINOCA care varies across centres,and future multi-centre clinical trials with standardized criteria may have a positive impact on defining optimal cardiovascular care for MINOCA patients.展开更多
基金supported by the National Natural Science Foundation of China (U22A20277,81971373)Jiangsu Provincial Medical Key Discipline Cultivation Unit (JSDW202215)+1 种基金333 High-level Personnel Training Project of Jiangsu Province (BRA2019109)Postgraduate Research&Practice Innovation Program of Jiangsu Province (KYCX22_1826)。
文摘Increasing evidence implicates disruptions in testicular fatty acid metabolism as a contributing factor in nonobstructive azoospermia(NOA),a severe form of male infertility.However,the precise mechanisms linking fatty acid metabolism to NOA pathogenesis have not yet been fully elucidated.Multi-omics analyses,including microarray analysis,single-cell RNA sequencing(scRNA-seq),and metabolomics,were utilized to investigate disruptions in fatty acid metabolism associated with NOA using data from public databases.Results identified ACSL6,ACSBG2,and OLAH as key genes linked to fatty acid metabolism dysregulation,suggesting their potential causative roles in NOA.A marked reduction in omega-3 polyunsaturated fatty acids,especially docosahexaenoic acid(DHA),was observed,potentially contributing to the pathological process of NOA.Sertoli cells in NOA patients exhibited apparent fatty acid metabolic dysfunction,with PPARG identified as a key transcription factor(TF)regulating this process.Functional analyses demonstrated that PPARG is crucial for maintaining blood-testis barrier(BTB)integrity and promoting spermatogenesis via regulation of fatty acid metabolism.These findings reveal the pivotal role of fatty acid metabolism in NOA and identify PPARG as a potential therapeutic target.
文摘Non-obstructive azoospermia is a common condition associated with significant health risks,including increased mortality,cancer,and chronic diseases such as metabolic and cardiovascular disorders.This review aims to highlight the potential health challenges faced by men with this condition compared to fertile counterparts.Through a comprehensive bibliographic search on PubMed,using the following algorithm:(“infertility,male”[MeSH Terms]OR“azoospermia”[MeSH Terms])AND(“mortality”[MeSH Terms]OR“neoplasms”[MeSH Terms]OR“chronic disease”[MeSH Terms]OR“diabetes mellitus”[MeSH Terms]OR“heart diseases”[MeSH Terms]),we analyzed existing literature to explore the associations between infertility,specifically azoospermia,and adverse health outcomes.Findings indicate that infertile men are at a higher risk of death,various cancers(particularly testicular cancer),metabolic syndrome,diabetes,hypogonadism,and cardiovascular disease.Although research specifically addressing azoospermia is limited,available studies support the notion that men with this condition may experience heightened health vulnerabilities.Given these risks,it is imperative for healthcare professionals,especially urologists,to conduct thorough health assessments for men diagnosed with azoospermia.Informing patients of these potential health issues and integrating comprehensive evaluations into their care can facilitate early detection and intervention for life-threatening conditions.Ultimately,men with azoospermia should receive ongoing monitoring to address their specific health concerns,thus improving their long-term health outcomes.
文摘This special issue of the Asian Journal of Andrology is fully dedicated to the thematic area of non-obstructive azoospermia(NOA),one of the most complex and challenging conditions in the realm of andrology,urology,and reproductive medicine.
文摘We investigated whether letrozole （2.5 mg day-1） improves sperm count in non-obstructive azoospermia （NOA） patients. Four men were included in this study, and they had folliculo-stimulating hormone and other hormone levels within the normal range and no varicoceles or chromosomal aberrations. These four patients were administered letrozole for 3 months. Sperm count, testicular volume, gonadotropin, testosterone （T） and estradiol （E2） blood levels were assessed before, during and 1 week after the suspension of treatment. All patients showed spermatozoa in their ejaculate, increased gonadotropin and T levels and lower E2 levels （P〈0.05 in all cases）, when letrozole was administered. This suggests that letrozole treatment might improve sperm count in an NOA sub-population; however, more studies, including the proper controls, are needed to confirm its efficacy.
文摘Aim： To evaluate the outcome of repetitive micro-surgical testicular sperm extraction （mTESE） attempts in non-obstructive azoospermia （NOA） cases, in relation to patients＇ initial testicular histology results. Methods： A total of 68 patients with NOA in whom mTESE had been performed in previous intracytoplasmic sperm injection （ICSI） attempts were reviewed. Results： Among the 68 patients with NOA, the first mTESE yielded mature sperm for ICSI in 44 （64%） （Sp^＋）, and failed in the remaining 24 （36%） （Sp^-）. Following their first trial, 24 patients decided to undergo a second mTESE. Of these 24 patients, no spermatozoa were obtained in 5 patients, and Sp^＋ but no fertilization/pregnancy were achieved in 19. In these 24 cases, mTESE was successively repeated for two （n = 24）, three （n = 4） and four （n = 1） times. The second attempt yielded mature sperm in 3/5 patients from the Sp group and 16/19 patients from the Sp^＋ group. At the third and fourth trials, 4/4 and 1/1 of the original Sp^＋ patients were Sp^＋ again, respectively. Distribution of main testicular histology included Sertoli cell-only syndrome （16%）, maturation arrest （22%）, hypospermatogenesis （21%） and focal spermatogenesis （41%）. Overall, in repetitive mTESE, 24/29 （82%） of the attempts were finally Sp^＋. Conclusion： Repeated mTESE in patients with NOA is a feasible option, yielding considerably high sperm recovery rate. In patients with NOA, mTESE may safely be repeated one or more times to increase sperm retrieval rate, as well as to increase the chance of retrieving fresh spermatozoa to enable ICSI.
基金supported by the grants from the 973 program(2011CB944304 and 2015CB943003)
文摘Non-obstructive azoospermia （NOA） is a severe defect in male reproductive health that occurs in 1% of adult men. In a previous study, we identified that rs7099208 is located within the last intron of FAM160B1 at 10q25.3. In this study, we analysed expression Quantitative Trait Loci （eQTL） of FAM16OB1, ABLIM1 and TRUB1, the three genes surrounding rs7099208. Only the expression level of FAM16OB1 was reduced for the homozygous alternate genotype （GG） of rs7099208, but not for the homozygous reference or heterozygous geno- types. FAM160B1 is predominantly expressed in human testes, where it is found in spermatocytes and round sper- matids. From 17 patients with NOA and five with obstructive azoospermia （OA）, immunohistochemistry revealed that expression of FAM160B1 is reduced, or undetectable in NOA patients, but not in OA cases or normal men. We conclude that rs7099208 is associated with NOA via a reduction in the expression of FAM160B1.
基金supported by the National Natural Science Foundation of China(No.81901535,No.82071698)the National Key Research and Developmental Program of China(No.2021YFC2700203)the Natural Science Foundation of Beijing Municipality(No.722208).
文摘Circular RNAs(circRNAs)are highly conserved and ubiquitously expressed noncoding RNAs that participate in multiple reproductionrelated diseases.However,the expression pattern and potential functions of circRNAs in the testes of patients with non-obstructive azoospermia(NOA)remain elusive.In this study,according to a circRNA array,a total of 37881 circRNAs were identified that were differentially expressed in the testes of NOA patients compared with normal controls,including 19874 upregulated circRNAs and 18007 downregulated circRNAs.Using quantitative real-time polymerase chain reaction(qRT-PCR)analysis,we confirmed that the change tendency of some specific circRNAs,including hsa_circ_0137890,hsa_circ_0136298,and hsa_circ_0007273,was consistent with the microarray data in another larger sample.The structures and characteristics of these circRNAs were confirmed by Sanger sequencing,and fluorescence in situ hybridization revealed that these circRNAs were primarily expressed in the cytoplasm.Bioinformatics analysis was used to construct the competing endogenous RNA(ceRNA)network,and numerous miRNAs that could be paired with circRNAs validated in this study were reported to be vital for spermatogenesis regulation.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses indicated that genes involved in axoneme assembly,microtubule-based processes,and cell proliferation were significantly enriched.Our data suggest that there are aberrantly expressed circRNA profiles in patients with NOA and that these circRNAs may help identify key diagnostic and therapeutic molecular biomarkers forNoA patients.
文摘Objective: To investigate the feasibility of obtaining mature spermatozoa for intracytoplasmic sperm injection (ICSI) by testicular fine needle aspiration (TEFNA) in men diagnosed non-obstructive azoospermia. Methods: TEFNA was performed in 121 patients with a mean of 15 punctures and aspirations from each testis with a #23 butterfly needle connected to a 20 mL syringe with an aspiration handle. Results: One hundred and twenty-one patients underwent 176 TEFNA cycles. Testicular sperm were recovered in 56.3 % (99/176) cycles from 57 % (69/121) of patients. The sperm recovery rate was 46.7 % (21/45) in patients with Sertoli cell-only syndrome, 45.7 % (16/35) in patients with maturation arrest, 96.1 % (25/26) in patients with hypospermatogenesis and 63.6 % (7/11) in patients of non-mosaic Klinefelter's syndrome as judged by testicular histology. No sperm were found in 3 cases with post-irradiation fibrosis and one, after resection and chemotherapy of unilateral testicular cancer. In 87 cycles of ICSI using the husbands' sperm, 591 mature oocytes were injected, 218 (36.9 %) were normally fertilized and 202 embryos developed; 178 were transferred in 62 cycles resulting in 26 pregnancies (41.9 %) with 44 gestational sacs (implantation rate: 24.7 %). Conclusion: TEFNA was an efficient, easy to learn, safe and well tolerated treatment in patients with non-obstructive azoospermia.
文摘The development of intracytoplasmic sperm injection （ICSI） opened a new era in the field of assisted reproduction and revolutionized the assisted reproductive technology protocols for couples with male factor infertility. Fertilisation and pregnancies can be achieved with spermatozoa recovered not only from the ejaculate but also from the seminiferous tubules. The most common methods for retrieving testicular sperm in non-obstructive azoospermia （NOA） are testicular sperm aspiration （TESA： needle/fine needle aspiration） and open testicular biopsy （testicular sperm extraction： TESE）. The optimal technique for sperm extraction should be minimally invasive and avoid destruction of testicular function, without compromising the chance to retrieve adequate numbers of spermatozoa to perform ICSh Microdissection TESE （micro-TESE）, performed with an operative microscope, is widely considered to be the best method for sperm retrieval in NOA, as larger and opaque tubules, presumably with active spermatogenesis, can be directly identified, resulting in higher spermatozoa retrieval rates with minimal tissue loss and low postoperative complications. Micro-TESE, in combination with ICSI, is applicable in all cases of NOA, including Klinefelter syndrome （KS）. The outcomes of surgical sperm retrieval, primarily in NOA patients with elevated serum follicle-stimulating hormone （FSH） （NOA including KS patients）, are reviewed along with the phenotypic features. The predictive factors for surgical sperm retrieval and outcomes of treatment were analysed. Finally, the short- and long-term complications in micro-TESE in both 46XY males with NOA and KS patients are considered.
文摘As the field of assisted reproduction has advanced, many previously untreatable men are now biological fathers. Although finding sperm in men with obstructive azoospermia is not difficult, locating and retrieving spermatozoa in men with non-obstructive azoospermia remains a clinical challenge, largely because sperm production in these men can be patchy or focal in nature. In response to this challenge, strategies such as fine-needle aspiration （FNA） mapping have been developed to find spermatozoa. This review discusses the history, evolution and current clinical utility and findings with FNA mapping for male infertility）. Review of the current literature in the English language on FNA （diagnostic or therapeutic） with a keyword focuses on sperm detection, retrieval, safety and complications. FNA was described in human medicine over 100 years ago. Testis FNA was described 45 years ago and FNA ＇mapping＇ of spermatozoa was described in 1997. This comparative review of the literature on sperm detection and complication rates with FNA and open testis biopsy or microdissection procedures suggests that FNA is highly informative, minimally invasive and is associated with fewer complications than other commonly used approaches to sperm detection in non-obstructive azoospermic patients. FNA mapping has gained considerable traction as an informative, ＇testis sparing＇ technique for sperm detection in non-obstructive azoospermia. With knowledge of sperm presence and location prior to sperm retrieval, FNA maps can help clinicians tailor sperm retrieval to optimize time, effort and extent of procedures needed to procure spermatozoa in these difficult cases.
文摘Objective: To evaluate the effects of intracytoplasmic sperm injection (ICSI) ontreatment of infertility due to obstructive and non-obstructive azoospermia..Methods: A retrospective analysis of fertilization, cleavage, embryo implantationand pregnancy rates was done in 158 ICSI cycles including 112 obstructive azoospermiaand 46 non-obstructive azoospermia. Ovarian hyperstimulation and ICSI procedureswere performed by conventional protocol. The sperm was collected by percutaneous epi-didymal sperm aspiration (PESA) or testicular sperm extraction (TESE).Results:The fertilization rate (73.1% vs. 67.0%), cleavage rate (88.6% vs. 86.3%), embryo implantation rate (20.7% vs. 11.4%), clinical pregnancy rate per trans-fer cycle (35.7% vs. 19.6%) were obtained for obstructive and non-obstructiveazoospermia, respectively.Conclusion: The results revealed that in the cases of obstructive azoospermia, ferti-lization rate, embryo implantation rate and clinical pregnancy rate were significantlyhigher than those of non-obstructive azoospermia. But there was no significant differ-ence of the cleavage rate between two groups.
文摘Introduction: Non-invasive methods that can predict sperm recovery in patients with non-obstructive azoospermia (NOA) arouse interest of clinicians. The aim of this study was to evaluate the predictive value of sperm retrieval in NOA. Materials and Methods: In the retrospective study, fine needle aspiration (FNA) was performed on 306 patients with NOA at the department of andrology, Wuhan Tongji Reproductive Medical Hospital. Inhibin B, FSH and LH plasma levels were analyzed and sperms were retrieved in 67 of 306 cases (21.89%). Results: There were statistically significant differences between successful and unsuccessful sperm recoverygroups in terms of mean serum inhibin B, FSH and LH levels. The areas under the curve (AUC) of inhibin B, FSH and LH were 0.696, 0.729 and 0.747 respectively, and the AUC for the combined value of the three hormones is 0.832. The cut-off points were 27.31 pg/ml, 11.68 IU/L and 4.04 IU/L for inhibin B, FSH and LH respectively. Conclusions: This study suggests that the combined evaluation of inhibin B, FSH and LH is a more effective predictor for successful sperm retrieval in patients with NOA before decision making of an invasive procedure than any single factor.
基金Natural Science Foundation of Hubei Province(2016CFC749).
文摘Objective: The azoospermia is increasingly becoming prevalent year by year,which has been plaguing a great number of infertile couples. Testes biopsy is a gold index to evaluate the testicular spermatogenesis in patients with anspermia. However, it is more invasive and may not accurately reflect the whole spermatogenic function of the testes. In recent years, with the continuous development of ultrasound and assisted reproductive technology, real-time sonoelastography has been widely applied in the evaluation of spermatogenic function in patients with azoospermia. It is still at the initial stage, but shows good application prospects. In this paper, we will summarize and review the present status of male infertility and the clinical application and research progress of real-time sonoelastography in the evaluation of the testicular spermatogenic function of non-obstructive azoospermia patients.
文摘Ten percent of infertile males have azoospermia,classified into obstructive and nonobstructive types,which require specific medical or surgical treatments.In nonobstructive azoospermia,advancements in microsurgery allow for effective sperm retrieval in about half of cases.This review aimed to highlight the most recent studies utilizing whole exome sequencing(WES)and seminal/serum biomarkers aim to predict micro-dissection testicular sperm extraction(micro-TESE)outcomes and reduce failure rates.WES identifies rare genetic mutations affecting spermatogenesis that could explain micro-TESE failures,improving preoperative assessments.Despite its potential,WES is limited by high costs.Biomarkers such as Anti-Müllerian Hormone and testis-expressed sequence 101 protein can indicate spermatogenic activity,though standardization of these measurements is needed for accuracy.Additionally,microRNAs as non-invasive markers offer potential in assessing spermatogenic reserve and classifying azoospermia types,but their efficacy in identifying specific spermatogenic disorders remains under researched,necessitating further studies on multivariate miRNA models.
基金supported by the National Natural Science Foundation of China(No.81972909,31971151)the National Key Research and Development Program of China(No.2021YFC2700200)the Bio-ID Center at SJTU,and the K.C.Wong Education Foundation(H.K.).
文摘Germ cell arrest is one kind of important disease in nonobstructive azoospermia(NOA)including spermatogonia arrest,spermatocyte arrest,and round spermatid arrest.1 There is an urgent need to explore the molecular mechanisms underlying germ cell arrest,which are essentially unknown and could provide not only a promising approach for therapy but also novel possibilities for developing male contraceptives.
文摘Saad et al.'s review~([1]),“Emerging trends in the management of non-obstructive azoospermia,”offers a compelling synthesis of cutting-edge diagnostic and therapeutic strategies for non-obstructive azoospermia(NOA),a challenging condition affecting 10%–15%o infertile men.By highlighting advances in whole exome sequencing(WES),biomarkers like Anti-Müllerian hormone(AMH)and microRNAs(miRNAs),and microdissection testicular sperm extraction(micro-TESE),the authors chart a path toward precision medicine in male infertility.Their exploration of AI and gene-editing technologies like CRISPR/Cas9 underscores the transformative potential of these innovations.
文摘Background:Some cases of non-obstructive azoospermia(NOA)are characterized by normal clinical parameters,including testicular volume and levels of reproductive hormones,mimicking obstructive azoospermia(OA).Methods:We performed a retrospective review of a consecutive series of 1417 patients undergoing primary surgical sperm retrieval between 2014 and 2023.Follicle-stimulating hormone(FSH)level below 7.6 IU/l and normal testicular size with a long axis measurement>4.6 cm were used as criteria to suspect OA.Results:Four hundred and eighteen patients with normal testicular volume and FSH levels had an initial diagnosis of OA.Among them,243(58.1%)had histological signs of spermatogenic dysfunction,and 175(41.9%)had true OA.One hundred eleven patients had long-standing obstruction(median:16.5 years)with a median Bergmann-Kliesch score(BKS)of 5(interquartile range[IQR]:4-6)and 100%sperm retrieval rate(SRR),though some required microdissection testicular sperm extraction(microTESE).Fifty-eight patients with a history of epididymo-orchitis had a median BKS of 4(IQR:2-6)and 100%SRR.Twenty patients with a history of unjustified medical treatment for male infertility had a median BKS of 3(IQR:1-4)and 80%SRR.Fifty-four patients had uniform maturation arrest with a 5.5%SRR on microTESE.Conclusion:Men with normal testicular volume and FSH level may have evidence of spermatogenic failure on pathology.Patients with complicated seminal tract obstruction commonly have hypospermatogenesis,but true NOA caused by uniform maturation arrest may also be observed.Patient counseling for suspected OA should not be overly optimistic,and couples should be warned about possibility of conversion to microTESE and risks of negative sperm retrieval.
文摘We tested the hypothesis that letrozole increases sperm count in non-obstructive azoospermic or cryptozoospermic patients with a testosterone （T）/17-beta-2-oestradiol （E2） ratio 〈 10. Forty-six patients with no chromosomal aberrations were randomized into two groups： 22 received letrozole 2.5 mg per day for 6 months （Group 1：6 azoospermic＋ 16 cryptozoospermic patients）, while 24 received a placebo （Group 2：5 azoospermic＋19 cryptozoospermic patients）. The following data were collected： two semen analyses, clinical history, scrotal Duplex scans, body mass index （BMI）, Y microdeletion, karyotype and cystic fibrosis screens and follicle-stimulating hormone （FSH）, luteinizing hormone （LH）, E2, T and prolactin levels. Both before and after letrozole or placebo administration, the patients underwent two semen analyses and hormonal assessments. The differences were evaluated using the Mann-Whitney Utest. The relationships between sperm concentration after letrozole administration with respect to FSH, TIE2 ratio, bilateral testicle volume and BMI before letrozole administration were assessed using multivariate analysis. The side effects were assessed using the chi-square test. Group 1 had sperm concentration （medians： 400-1.290× 10^6 ml^-1; P〈0.01） and motility （medians： class A from 2% to 15%; P〈0.01）, FSH, LH and T significantly increased, while Group 2 did not. E2 levels diminished significantly in Group 1, but not in Group 2. Eight patients in Group 1 demonstrated side effects, whereas no patient side effects were observed in Group 2. The sperm concentration after letrozole administration is inversely related to TIE2, FSH and BMI; a direct relationship emerged between sperm concentration and testicular volume.
文摘The purpose of this study was to determine the relationships between monitors of spermatogenesis and predictors of the intracytoplasmic sperm injection （ICSI） outcome in patients with non-obstructive azoospermia （NOA） undergoing testicular sperm extraction （TESE）. Seventy-nine patients with NOA （mean age： 43.6±5.2 years）, each of whom yielded （97 000±3040） spermatozoa with conventional TESE, were considered in our analysis. Their partners （mean age： 35.8±5.1 years） underwent a total of 184 ICSI cycles; 632 oocytes were collected, 221 oocytes were injected, 141 oocytes were fertilized, 121 embryos were obtained, 110 embryos were transferred, 14 clinical pregnancies were achieved and only one miscarriage occurred. Multivariate regression analysis indicated relationships between the percentage of fertilized oocytes, transferred embryos and clinical pregnancies with the following variable values： female partner＇s age, number of spermatozoa collected, testicular volume, male partner＇s levels of follicle stimulating hormone （FSH）, number of oocytes collected, number of oocytes injected and number of ICSI cycles. A significant inverse relationship was found between female partner＇s age or male partner＇s FSH levels and biochemical pregnancies. A significant direct relationship emerged between the number of ICS! cycles and the percentage of oocytes fertilized, embryos transferred and biochemical pregnancies, and between the number of spermatozoa collected per testicular biopsy and biochemical pregnancies. The number of spermatozoa was positively linked to the number of clinical pregnancies, independent of the number of ICSI cycles and the number of oocytes collected/injected. The number of spermatozoa collected, FSH level and testicular volume are monitors of spermatogenesis linked to ICSI success.
文摘Acute coronary syndromes constitute a variety of myocardial injury presentations that include a subset of patients presenting with myocardial infarction with non-obstructive coronary arteries(MINOCA).This acute coronary syndrome differs from type 1 myocardial infarction(MI)regarding patient characteristics,presentation,physiopathology,management,treatment,and prognosis.Two-thirds of MINOCA subjects present ST-segment elevation;MINOCA patients are younger,are more often female and tend to have fewer cardiovascular risk factors.Moreover,MINOCA is a working diagnosis,and defining the aetiologic mechanism is relevant because it affects patient care and prognosis.In the absence of relevant coronary artery disease,myocardial ischaemia might be triggered by an acute event in epicardial coronary arteries,coronary microcirculation,or both.Epicardial causes of MINOCA include coronary plaque disruption,coronary dissection,and coronary spasm.Microvascular MINOCA mechanisms involve microvascular coronary spasm,takotsubo syndrome(TTS),myocarditis,and coronary thromboembolism.Coronary angiography with non-significant coronary stenosis and left ventriculography are first-line tests in the differential study of MINOCA patients.The diagnostic arsenal includes invasive and non-invasive techniques.Medical history and echocardiography can help indicate vasospasm or thrombosis,if one finite coronary territory is affected,or specify TTS if apical ballooning is present.Intravascular ultrasound,optical coherence tomography,and provocative testing are encouraged.Cardiac magnetic resonance is a cornerstone in myocarditis diagnosis.MINOCA is not a benign diagnosis,and its polymorphic forms differ in prognosis.MINOCA care varies across centres,and future multi-centre clinical trials with standardized criteria may have a positive impact on defining optimal cardiovascular care for MINOCA patients.
