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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 -
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 -
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 -
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 -
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 -
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 -
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 -
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