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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 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 -
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 -
International Journal of Impotence... Sep 2022Subfertility is a risk factor for testicular cancers (TT), and conversely, TT may induce subfertility due to local and regional toxic effects. We aimed to identify the... (Review)
Review
Subfertility is a risk factor for testicular cancers (TT), and conversely, TT may induce subfertility due to local and regional toxic effects. We aimed to identify the association between TT characteristics and pre-orchidectomy azoospermia. A systematic review of the literature was performed according to the PRISMA checklist. Overall, eight non-randomised studies involving 469 men with TT (azoospermia, n = 57; no azoospermia n = 412) were included in the qualitative analysis. Bilateral TT (12.3% vs 2.9% in non-azoospermia), non-seminoma germ cell tumours (6.4% vs 1.9%), germ cell neoplasia in-situ (GCNIS) (11.1% vs 1.2%), stage 2-3 disease (22.2% vs 0%), Sertoli Cell only (SCO) on biopsy (60% vs 37.5%) and a history of undescended testis (UDT) (66.7% vs 50%) were more common in azoospermic men. FSH levels are higher (18.7-23.2 mIU/L vs <0.1-8 mIU/L in non-azoospermia), testosterone is lower, and testis size are smaller (lower range 1 mL vs 10 mL) in men with azoospermia. Leydig cell tumours and hyperplasia were only detected in men with azoospermia. In summary, bilateral TT, GCNIS, higher tumour stage, smaller testes, SCO and history of UDT may have direct effects on spermatogenesis. Small testis, raised FSH and low testosterone may reflect reduced testicular function in azoospermic men. Performing a pre-orchidectomy semen analysis is important to identify those with azoospermia or severe oligospermia in order to plan for cryopreservation or onco-TESE in young men who wish to conceive.
Topics: Azoospermia; Follicle Stimulating Hormone; Humans; Male; Testicular Neoplasms; Testosterone
PubMed: 34743192
DOI: 10.1038/s41443-021-00492-x -
Journal of Clinical Medicine Feb 2024Androgen insensitivity syndrome (AIS) is a rare Mendelian disorder caused by mutations of the androgen receptor () gene on the long arm of the X chromosome. As a result...
Androgen Insensitivity Syndrome with Bilateral Gonadal Sertoli Cell Lesions, Sertoli-Leydig Cell Tumor, and Paratesticular Leiomyoma: A Case Report and First Systematic Literature Review.
Androgen insensitivity syndrome (AIS) is a rare Mendelian disorder caused by mutations of the androgen receptor () gene on the long arm of the X chromosome. As a result of the mutation, the receptor becomes resistant to androgens, and hence, karyotypically male patients (46,XY) carry a female phenotype. Their cryptorchid gonads are prone to the development of several types of tumors (germ cell, sex cord stromal, and others). Here, we report a 15-year-old female-looking patient with primary amenorrhea who underwent laparoscopic gonadectomy. Histologically, the patient's gonads showed Sertoli cell hamartomas (SCHs) and adenomas (SCAs) with areas of Sertoli-Leydig cell tumors (SLCTs) and a left-sided paratesticular leiomyoma. Rudimentary Fallopian tubes were also present. The patient's karyotype was 46,XY without any evidence of aberrations. Molecular genetic analysis of the left gonad revealed two likely germline mutations-a pathogenic frameshift deletion in the gene (c.77delT) and a likely pathogenic missense variant in the gene (p.A94V). Strikingly, no somatic mutations, fusions, or copy number variations were found. We also performed the first systematic literature review (PRISMA guidelines; screened databases: PubMed, Scopus, Web of Science; ended on 7 December 2023) of the reported cases of patients with AIS showing benign or malignant Sertoli cell lesions/tumors in their gonads ( = 225; age: 4-84, mean 32 years), including Sertoli cell hyperplasia (1%), Sertoli cell nodules (6%), SCHs (31%), SCAs (36%), Sertoli cell tumors (SCTs) (16%), and SLCTs (4%). The few cases ( = 14, 6%; six SCAs, four SCTs, two SLCTs, and two SCHs) with available follow-up (2-49, mean 17 months) showed no evidence of disease (13/14, 93%) or died of other causes (1/14, 7%) despite the histological diagnosis. Smooth muscle lesions/proliferations were identified in 19 (8%) cases (including clearly reported rudimentary uterine remnants, 3 cases; leiomyomas, 4 cases). Rudimentary Fallopian tube(s) were described in nine (4%) cases. Conclusion: AIS may be associated with sex cord/stromal tumors and, rarely, mesenchymal tumors such as leiomyomas. True malignant sex cord tumors can arise in these patients. Larger series with longer follow-ups are needed to estimate the exact prognostic relevance of tumor histology in AIS.
PubMed: 38398243
DOI: 10.3390/jcm13040929 -
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 -
Journal of Pediatric Hematology/oncology Jul 2017It has been reported that germline DICER1 mutations correlate with a distinctive human disease syndrome. Many published studies within this field have been conducted... (Meta-Analysis)
Meta-Analysis Review
It has been reported that germline DICER1 mutations correlate with a distinctive human disease syndrome. Many published studies within this field have been conducted based on rare cases. We systematically searched bibliographic databases, including PubMed, Embase, and COSMIC for articles which are related to diseases covered by DICER1 syndrome. The weighted summary of mutation frequencies among patients with pleuropulmonary blastoma (PPB), cystic nephroma (CN), and Sertoli-Leydig cell tumor (SLCT) were calculated. Forty-nine eligible articles were included. In total, 72 cases with multimorbidity of DICER1 syndrome were identified. More females (n=46, 64%) presented with multimorbidity than males (n=18, 25%) and the remaining 8 patients' sex were unknown. Nineteen of 72 patients with multimorbidity suffered from another disease that was not yet included in DICER1 syndrome, which would provide potential phenotypes of DICER1 syndrome. The germline DICER1 mutation frequencies in PPB, CN, and SLCT were 66.9%, 73.2%, and 57.1%, respectively. The somatic DICER1 mutation frequencies of PPB, CN, and SLCT were 92.4%, 87.9%, and 43.3%, respectively. Majority of patients with multimorbidity of DICER1 syndrome were mutation positive individuals so that multimorbidity may suggest the possible germline mutation of these patients and their relatives.
Topics: DEAD-box RNA Helicases; Female; Germ-Line Mutation; Humans; Male; Mutation Rate; Nephroma, Mesoblastic; Pulmonary Blastoma; Ribonuclease III; Sertoli-Leydig Cell Tumor
PubMed: 27906793
DOI: 10.1097/MPH.0000000000000715 -
Fertility and Sterility Jan 2024To investigate whether Azoospermia Factor c (AZFc) microdeletions affect Assisted Reproductive Technology (ART) outcomes. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To investigate whether Azoospermia Factor c (AZFc) microdeletions affect Assisted Reproductive Technology (ART) outcomes.
DESIGN
Systematic review and meta-analysis.
SETTING
Not applicable.
PATIENTS
Infertile men with and without AZFc microdeletions.
INTERVENTION(S)
Electronic databases were searched for case-control studies reporting sperm retrieval rates and outcomes of ART in infertile men with and without AZFc microdeletions from inception to April 2023. Study quality was assessed using the Newcastle-Ottawa Scale. Summary effect sizes (odds ratio [OR] with 95% confidence interval [CI]) were calculated for both categories of infertile men.
MAIN OUTCOME MEASURES
The primary outcome was successful sperm retrieval and the secondary outcomes were outcomes of ART.
RESULTS
Case-control studies reporting sperm retrieval rates and ART outcomes in men with AZFa and AZFb deletions were unavailable. On the basis of the data from 3,807 men, sperm retrieval rates were found to be higher in men with AZFc microdeletions compared to their non-deleted counterparts [OR = 1.82, 95% CI 0.97, 3.41], but the difference was not statistically significant. A significantly lower fertilization rate (OR = 0.61, 95% CI [0.50, 0.74]), clinical pregnancy rate (OR = 0.61, 95% CI [0.42, 0.89]), and live birth rate (OR = 0.54, 95% CI [0.40, 0.72]) were observed in men with AZFc deletions compared with men without deletions. There was no statistically significant difference in rates of embryo cleavage, blastocyst formation, good-quality embryos, implantation, and miscarriage between the two groups. On correcting for female factors, the fertilization rate (OR = 0.76, 95% CI [0.71, 0.82]), cleavage rate (OR = 0.54, 95% CI [0.41, 0.72]), clinical pregnancy rate (OR = 0.39, 95% CI [0.30, 0.52]), and live birth rate (OR = 0.48, 95% CI [0.35, 0.65]) were significantly lower in men with AZFc deletions compared with controls.
CONCLUSIONS
Presence of AZFc microdeletions adversely affects outcomes of ART in infertile men. Further in-depth studies delineating the role of the AZF genes in embryonic development are necessary to understand the full-impact of this finding.
CLINICAL TRIAL REGISTRATION NUMBER
CRD42022311738.
Topics: Pregnancy; Humans; Male; Female; Azoospermia; Oligospermia; Retrospective Studies; Chromosome Deletion; Chromosomes, Human, Y; Semen; Infertility, Male; Sertoli Cell-Only Syndrome
PubMed: 37923163
DOI: 10.1016/j.fertnstert.2023.10.029 -
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 -
Proteomics. Clinical Applications Jan 2023Azoospermia, as the most severe form of male infertility, no longer indicates sterility due to modern medical advancements. The current diagnostic procedure based on... (Review)
Review
PURPOSE
Azoospermia, as the most severe form of male infertility, no longer indicates sterility due to modern medical advancements. The current diagnostic procedure based on testicular biopsy has several drawbacks which urges the development of novel, non-invasive diagnostic procedures based on biomarkers. In the last two decades, there have been many proteomics studies investigating potential azoospermia biomarkers. In this review, we aimed to provide a critical evaluation of these studies.
EXPERIMENTAL DESIGN
Published articles were gathered by systematic literature search using Pubmed, Science Direct, and Google Scholar databases until March 2022 and were further preselected to include only studies on human samples.
RESULTS
A detailed review of these studies encompassed the proteomics platforms, sources of material, proposed candidate biomarkers, and their potential diagnostic specificity and sensitivity. In addition, emphasis was put on the top, most identified and validated biomarker candidates and their potential for discriminating azoospermia types and subtypes as well as predicting sperm retrieval success rate.
CONCLUSIONS
Proteomics research of azoospermia has laid the groundwork for the development of a more streamlined biomarker testing. The future research should be focused on well-designed studies including samples from all types/subtypes as well as further testing of the most promising biomarkers identified so far.
Topics: Humans; Male; Azoospermia; Biomarkers; Proteomics; Semen; Testis
PubMed: 36177695
DOI: 10.1002/prca.202200060