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European Journal of Obstetrics,... Aug 2021To synthesize the evidence on Sertoli-Leydig cell tumour (SLCT) relapses, and identify the clinicopathological characteristics and prognosis of patients with recurrent... (Review)
Review
OBJECTIVE
To synthesize the evidence on Sertoli-Leydig cell tumour (SLCT) relapses, and identify the clinicopathological characteristics and prognosis of patients with recurrent SLCT.
METHODS
A literature search was undertaken of all published cases of SLCT relapse found in PubMed, Embase and Web of Science databases between January 1998 and January 2021. All articles in English reporting at least one case of SLCT relapse and mentioning the relapse location or the follow-up data were included. All reported data on relapsed cases were extracted. Student's t-test and Chi-squared test were used for the descriptive analysis, and the Kaplan-Meier statistical method was applied for survival analysis.
RESULTS
Eighty-five patients from 33 articles were included in this review. The median age was 20 years (range 3-76 years) with a median time to relapse of 14 months (range 1-168 months). Forty-eight percent (36/75) of relapses were local and 52% (39/75) were distant. In the subgroup of conservative primary surgery, contralateral ovarian SLCT events (metachronous or recurrent) were more frequent in the paediatric population than in the adult population (58.3 vs 18.2%; p = 0.005). Eleven cases had multiple relapses. Twenty-one percent (12/57) of cases were treated with conservative surgery after recurrence, and 64.9% (37/57) of cases were treated with radical surgery which tends to have a better 2-year survival rate (78.5% vs 61.0%; p = 0.177). Overall median survival was 48 months after recurrence (95% confidence interval ±21.0 months) with overall 5-year survival of 38.9%. The mean survival time was significantly higher for patients diagnosed at an early stage (I and II) compared with patients diagnosed at an advanced stage (p = 0.003).
DISCUSSION
The results showed that SLCT relapses have a poor prognosis and occur mainly in young patients, soon after the initial diagnosis. The majority of SLCT relapses are located in the abdominopelvic region. Contralateral ovarian SLCT events (metachronous or recurrent) occurred more frequently in paediatric cases. Multi-modal treatment with surgery and chemotherapy appears to be the best approach. The best chemotherapeutic regimen has yet to be defined.
Topics: Adult; Child; Child, Preschool; Female; Humans; Infant; Neoplasm Recurrence, Local; Ovarian Neoplasms; Prognosis; Sertoli-Leydig Cell Tumor
PubMed: 34245994
DOI: 10.1016/j.ejogrb.2021.06.036 -
The Journal of Clinical Endocrinology... Jan 2022Anti-Mullerian hormone (AMH) was originally described in the context of sexual differentiation in the male fetus but has gained prominence now as a marker of ovarian...
CONTEXT
Anti-Mullerian hormone (AMH) was originally described in the context of sexual differentiation in the male fetus but has gained prominence now as a marker of ovarian reserve and fertility in females. In this mini-review, we offer an updated synopsis on AMH and its clinical utility in pediatric patients.
DESIGN AND RESULTS
A systematic search was undertaken for studies related to the physiology of AMH, normative data, and clinical role in pediatrics. In males, AMH, secreted by Sertoli cells, is found at high levels prenatally and throughout childhood and declines with progression through puberty to overlap with levels in females. Thus, serum AMH has clinical utility as a marker of testicular tissue in males with differences in sexual development and cryptorchidism and in the evaluation of persistent Mullerian duct syndrome. In females, serum AMH has been used as a predictive marker of ovarian reserve and fertility, but prepubertal and adolescent AMH assessments need to be interpreted cautiously. AMH is also a marker of tumor burden, progression, and recurrence in germ cell tumors of the ovary.
CONCLUSIONS
AMH has widespread clinical diagnostic utility in pediatrics but interpretation is often challenging and should be undertaken in the context of not only age and sex but also developmental and pubertal stage of the child. Nonstandardized assays necessitate the need for assay-specific normative data. The recognition of the role of AMH beyond gonadal development and maturation may usher in novel diagnostic and therapeutic applications that would further expand its utility in pediatric care.
Topics: Anti-Mullerian Hormone; Child; Child Development; Cryptorchidism; Disorder of Sex Development, 46,XY; Female; Gonads; Humans; Male; Ovarian Reserve; Sexual Maturation
PubMed: 34537849
DOI: 10.1210/clinem/dgab687 -
Andrologia Oct 2020We performed this systematic review to evaluate the possibility of an impact of SARS-CoV-2 infection on male fertility. SARS-CoV-2 enters the cells with the help of...
We performed this systematic review to evaluate the possibility of an impact of SARS-CoV-2 infection on male fertility. SARS-CoV-2 enters the cells with the help of ACE2; therefore, testicular expression of ACE2 was analysed from transcriptome sequencing studies and our unpublished data. Literature suggested that SARS-CoV-1 (2002-2004 SARS) had a significant adverse impact on testicular architecture, suggesting a high possibility of the impact of SARS-CoV-2 as well. Out of two studies on semen samples from COVID-19 affected patients, one reported the presence of SARS-CoV-2 in the semen samples while the other denied it, raising conflict about its presence in the semen samples and the possibility of sexual transmission. Our transcriptome sequencing studies on rat testicular germ cells showed ACE expression in rat testicular germ cells. We also found ACE2 expression in transcriptome sequencing data for human spermatozoa, corroborating its presence in the testicular germ cells. Transcriptome sequencing data from literature search revealed ACE2 expression in the germ, Sertoli and Leydig cells. The presence of ACE2 on almost all testicular cells and the report of a significant impact of previous SARS coronavirus on testes suggest that SARS-CoV-2 is highly likely to affect testicular tissue, semen parameters and male fertility.
Topics: Angiotensin-Converting Enzyme 2; Animals; Betacoronavirus; COVID-19; Coronavirus Infections; Gene Expression Profiling; Humans; Infertility, Male; Male; Models, Animal; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; Rats; SARS-CoV-2; Semen; Spermatozoa; Spike Glycoprotein, Coronavirus; Testis
PubMed: 32578263
DOI: 10.1111/and.13712 -
The Oncologist Jul 2020Sertoli cell tumors (SCTs) of the testes are rare, and the literature provides only weak evidence concerning their clinical course and management. The objective of this... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sertoli cell tumors (SCTs) of the testes are rare, and the literature provides only weak evidence concerning their clinical course and management. The objective of this study was to summarize evidence on SCTs' clinical presentation, clinicopathological risk factors for malignancy, treatment options, and oncological outcomes.
MATERIALS AND METHODS
Data sources included Medline, Embase, Scopus, the Cochrane Database of Systematic Reviews, and Web of Science. Published case reports, case series, and cohorts were included. Data on clinicopathological variables, treatment of local or metastatic disease, site of metastasis, or survival were extracted from each study considered in this paper, and associations between clinicopathological variables and metastatic disease were analyzed. Whenever feasible, data on individual patients were collected.
RESULTS
Of the 435 patients included, only one (<1%) showed local recurrence after testis-sparing surgery (TSS). Three patients underwent adjuvant retroperitoneal lymphadenectomy. Fifty patients presented with metastases, located in the retroperitoneal lymph nodes (76%), lungs (36%), and bones (16%); median time to recurrence was 12 months. Risk factors for metastatic disease included age, tumor size, necrosis, tumor extension to the spermatic cord, angiolymphatic invasion, and mitotic index. Patients with metastases had a median life expectancy of 20 months. In six patients, metastasectomy resulted in complete remission.
CONCLUSION
Our findings suggest that few local recurrences result after TSS, and no adjuvant therapy can be regarded as a standard of care. Several risk factors are predictive of metastatic disease. Surgery leads to remission in metastatic disease, whereas systemic treatment alone does not result in long-term remission.
IMPLICATIONS FOR PRACTICE
Testicular Sertoli cell tumors usually present without metastatic disease and show low local recurrence rates after testis-sparing surgery; no adjuvant therapy option can be regarded as a standard of care. Patients with risk factors should undergo staging investigations. Those with metastatic disease have poor prognoses, and metastasectomy may be offered in selected cases.
Topics: Humans; Lymph Node Excision; Male; Neoplasm Recurrence, Local; Neoplasm Staging; Sertoli Cell Tumor; Systematic Reviews as Topic; Testicular Neoplasms
PubMed: 32043680
DOI: 10.1634/theoncologist.2019-0692 -
Cancers Jul 2023The objective of this review was to summarize the applications of sonoelastography in testicular tumor identification and inquire about their test performances. Two... (Review)
Review
The objective of this review was to summarize the applications of sonoelastography in testicular tumor identification and inquire about their test performances. Two authors independently searched English journal articles and full conference papers from CINAHL, Embase, IEEE Xplore, PubMed, Scopus, and Web of Science from inception and organized them into a PIRO (patient, index test, reference test, outcome) framework. Eleven studies ( = 11) were eligible for data synthesis, nine of which ( = 9) utilized strain elastography and two ( = 2) employed shear-wave elastography. Meta-analyses were performed on the distinction between neoplasm (tumor) and non-neoplasm (non-tumor) from four study arms and between malignancy and benignity from seven study arms. The pooled sensitivity of classifying malignancy and benignity was 86.0% (95%CI, 79.7% to 90.6%). There was substantial heterogeneity in the classification of neoplasm and non-neoplasm and in the specificity of classifying malignancy and benignity, which could not be addressed by the subgroup analysis of sonoelastography techniques. Heterogeneity might be associated with the high risk of bias and applicability concern, including a wide spectrum of testicular pathologies and verification bias in the reference tests. Key technical obstacles in the index test were manual compression in strain elastography, qualitative observation of non-standardized color codes, and locating the Regions of Interest (ROI), in addition to decisions in feature extractions. Future research may focus on multiparametric sonoelastography using deep learning models and ensemble learning. A decision model on the benefits-risks of surgical exploration (reference test) could also be developed to direct the test-and-treat strategy for testicular tumors.
PubMed: 37568585
DOI: 10.3390/cancers15153770 -
Arab Journal of Urology 2021: To explore the use of novel technologies in sperm retrieval in men with azoospermia due to a production defect. : We performed a Preferred Reporting Items for Systemic... (Review)
Review
: To explore the use of novel technologies in sperm retrieval in men with azoospermia due to a production defect. : We performed a Preferred Reporting Items for Systemic Reviews and Meta-Analysis (PRISMA)-compliant systemic literature review for manuscripts focussed on novel sperm-retrieval methods. We identified 30 studies suitable for qualitative analysis. : We identified multiple new promising technologies, each with its own distinct set of benefits and limitations, to enhance chances of sperm retrieval; these include the use of multiphoton microscopy, Raman spectroscopy, and full-field optical coherence tomography during a microdissection-testicular sperm extraction procedure. ORBEYE and ultrasonography technologies can also serve to better visualise areas of sperm production. Finally, artificial intelligence technology can play a role in the identification of sperm and, perhaps, better-quality sperm for use with assisted reproduction. AI: artificial intelligence; ANN: artificial neural network; ART: assisted reproductive technology; 3D: three-dimensional; DNN: deep neural networks; FFOCT: full-field optical coherence tomography; H&E: haematoxylin and eosin; ICSI: intracytoplasmic sperm injection; IVF: fertilisation; MESA: micro-epididymal sperm aspiration; MeSH: Medical Subject Heading; MPM: multiphoton microscopy; (N)OA: (non-)obstructive azoospermia; SCO: Sertoli cell-only syndrome; SRR: sperm retrieval rates; TESA: testicular sperm aspiration; (micro-)TESE: (microdissection-) testicular sperm extraction; (CE)US: (contrast-enhanced) ultrasonography.
PubMed: 34552774
DOI: 10.1080/2090598X.2021.1926752 -
Life Sciences Apr 2022Plastic particles (PP) pollution is a global environmental concern. Although the reproductive toxicity of PP is primarily understood for invertebrates, the evidence for... (Review)
Review
AIMS
Plastic particles (PP) pollution is a global environmental concern. Although the reproductive toxicity of PP is primarily understood for invertebrates, the evidence for mammals is still fragmented. We used a systematic review framework to investigate the reproductive impact of microplastics and nanoplastics (MNP) on mammals.
MATERIALS AND METHODS
Research records were screened from Embase, Medline, Scopus and Web of Science. Twelve original papers were identified and reviewed. Immunological, oxidative and morphofunctional outcomes, and the risk of bias in all studies reviewed were analyzed.
KEY FINDINGS
These studies indicated that PP can accumulate in the gonads, triggering seminiferous degeneration, Sertoli cells death, blood-testis barrier disruption, sperm degeneration, malformation, reduced number and mobility, ovarian cysts, reduced follicular growth and granulosa cells death. Gonadal damage was associated with upregulation of prooxidant mediators (oxygen reactive species, lipid and DNA oxidation), cell death, proinflammatory molecular pathways and cytokines, as well as inhibition of enzymatic and non-enzymatic antioxidant defense mechanisms. Spermatogenesis, folliculogenesis, testosterone, progesterone and estrogen levels were also impaired in PP-treated animals, which were potentially associated with down-regulation of molecules involved in germ cells microstructural organization (occludin, N-cadherin, β-catenin and connexin 43) and steroidogenesis, such as hydroxysteroid dehydrogenases, steroidogenic acute regulatory proteins, follicle stimulating and luteinizing hormones. Selection, performance and detection bias were the main limitations identified.
SIGNIFICANCE
Current evidence indicates that PP can induce dose-dependent microstructural and functional gonadal damage, which is orchestrated by pro-oxidant and pro-inflammatory mechanisms that disrupt genes, molecular effectors, and hormones that control spermatogenesis and folliculogenesis.
Topics: Animals; Estrogens; Female; Genitalia; Germ Cells; Granulosa Cells; Inflammation; Intestinal Mucosa; Luteinizing Hormone; Male; Mammals; Microplastics; Ovarian Follicle; Ovary; Oxidative Stress; Plastics; Progesterone; Reproduction; Sertoli Cells; Spermatogenesis; Testis; Testosterone
PubMed: 35176278
DOI: 10.1016/j.lfs.2022.120404 -
Arab Journal of Urology 2021While most men with non-obstructive azoospermia (NOA) are not amenable to medical treatment, some men can be treated effectively with hormonal therapy, prior to... (Review)
Review
While most men with non-obstructive azoospermia (NOA) are not amenable to medical treatment, some men can be treated effectively with hormonal therapy, prior to considering surgery. In some cases, hormonal therapy alone can treat NOA, without the need for surgery. In other cases, correction of a potential hormonal imbalance can enhance the chances of success of surgical sperm retrieval (SSR), with either conventional or microdissection testicular sperm extraction. Abnormal testicular function and low androgen levels can result from a primary dysfunction, a medical or surgical condition, or from an exogenous factor, and should be managed prior to more invasive interventions. Even men with normal androgen levels may benefit from hormonal therapy before sperm retrieval. Moreover, SSR may cause testicular injury and aggravate the pre-existing situation. If surgical extraction of sperm fails, it leaves the patients with less satisfactory options, like donor sperm or adoption. Therefore, it is the role of the infertility specialist to be vigilant and identify reversible causes of NOA, such as hormonal imbalance, prior to considering surgery. In the present paper we will systematically review the literature and highlight the available conventional medical regimens, as well as experimental ones. : ART: assisted reproductive technology; CAH: congenital adrenal hyperplasia; EAU: European Association of Urology; hCG: human chorionic gonadotrophin; HH: hypogonadotrophic hypogonadism; hMG: human menopausal gonadotrophin; IUI: intrauterine insemination; micro-TESE: microdissection testicular sperm extraction; NOA: non-obstructive azoospermia; OR: odds ratio; SCO: Sertoli-cell only; SERM: selective oestrogen receptor modulator; SRR: sperm retrieval rate; SSC: spermatogonia stem cell; TART: testicular adrenal rest tumour; WMD: weighted mean difference.
PubMed: 34552772
DOI: 10.1080/2090598X.2021.1956233 -
Andrology Mar 2023Men with Klinefelter Syndrome develop some degree of seminiferous tubule degeneration, hyalinization, and fibrosis by adulthood. However, the pathophysiology surrounding... (Review)
Review
BACKGROUND
Men with Klinefelter Syndrome develop some degree of seminiferous tubule degeneration, hyalinization, and fibrosis by adulthood. However, the pathophysiology surrounding testicular fibrosis in Klinefelter Syndrome patients remains incompletely understood.
OBJECTIVES
To perform a systematic review of literature studying the mechanisms of fibrosis initiation or propagation in Klinefelter Syndrome testes.
MATERIALS/METHODS
PubMed was searched systematically for articles specific to Klinefelter Syndrome and the process of fibrosis. Articles that did not contain original data or specifically addressed the target material were excluded. Additional references were extracted when pertinent from the reference lists of included studies.
RESULTS
Primary search yielded 139 articles for abstract review, which was narrowed to 16 for full-text review. Following full-text review, eight contained original data and met topic criteria, with one paper added from reference review for a total of nine papers.
DISCUSSION
The date range for included papers was 1992-2022. The proposed mechanisms of fibrosis mainly were centered around the impact of altered Sertoli cells on germ cells, the hormonal impact on Leydig cells, the inflammation mediated by mast cells, or the fibrous extracellular matrix deposition by peritubular myoid cells. Additionally, discussions of the role of the altered microvasculature and the specific proteins involved in the blood-testis barrier or the seminiferous tubule architecture are reviewed. Recent papers have incorporated advanced sequencing and offer future directions for targeted gene expression analysis. Still, much of the published data consists solely of immunohistological assessment by age range, creating difficulties in extrapolating causality.
CONCLUSION
The specific initiating factors of fibrosis of the seminiferous tubules and the propagation mechanisms unique to Klinefelter Syndrome remain incompletely understood with a relative paucity of data. Nonetheless, academic interest is increasing in this field as it may further elucidate the pathophysiology behind Klinefelter syndrome.
Topics: Male; Humans; Adult; Klinefelter Syndrome; Testis; Seminiferous Tubules; Sertoli Cells; Fibrosis
PubMed: 36252136
DOI: 10.1111/andr.13327 -
Chemico-biological Interactions Aug 2022The use of nanoscale materials for different biomedical applications has grown a lot in the last years and raised several concerns about toxic effects on human health.... (Review)
Review
The use of nanoscale materials for different biomedical applications has grown a lot in the last years and raised several concerns about toxic effects on human health. Several studies have shown that different types of NPs may exert toxic effects on organs such as the brain, the liver and the kidney. However, The toxicological effects of inorganic NPs on reproductive organs only recently has attracted attention. This systematic review selected data published in the last twelve years assessing rodent-male in vitro and in vivo reproductive toxicity caused by different types of inorganic nanoparticles (AgNPs, AuNPs, IONPs, ZnONPs, TiO2NPs and NiNPs). Structural and functional alterations were commonly observed in Sertoli, Leydig, germ and sperm cells in vitro and in vivo. Oxidative stress, apoptosis, and/or necrosis were the most common findings after inorganic nanoparticle exposure. The toxicity of different NPs depends strongly on their physicochemical characteristics and intrinsic properties. Although a broad overview of the toxicity of different inorganic NPs was found in the papers evaluated, the results are highly variable due to the lack of standardization of protocols, regarding NPs sizes, concentration/doses, and routes of administration. Despite focusing on the effect of different nanoparticles on male reproduction, the mechanisms and pathways related to cellular and/or organ toxicity were poorly discussed. Understanding the specific molecular interactions between NPs and male testicular cells is crucial for developing nanobiotechnologies related to reproductive medicine.
Topics: Animals; Gold; Humans; Male; Metal Nanoparticles; Nanoparticles; Oxidative Stress; Reproduction; Rodentia; Semen
PubMed: 35764125
DOI: 10.1016/j.cbi.2022.110023