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European Urology Open Science Jul 2024No clear-cut markers for predicting positive sperm retrieval (+SR) at microdissection testicular sperm extraction (mTESE) have been identified thus far. Our aim was to... (Review)
Review
Role of Follicle-stimulating Hormone, Inhibin B, and Anti-Müllerian Hormone in Predicting Sperm Retrieval from Men with Nonobstructive Azoospermia Undergoing Microdissection Testicular Sperm Extraction: A Systematic Review and Meta-analysis.
BACKGROUND AND OBJECTIVE
No clear-cut markers for predicting positive sperm retrieval (+SR) at microdissection testicular sperm extraction (mTESE) have been identified thus far. Our aim was to conduct a systematic review and meta-analysis to evaluate the ability of follicle-stimulating hormone (FSH), inhibin B (InhB), and anti-Müllerian hormone (AMH) to predict +SR in men with nonobstructive azoospermia (NOA) undergoing mTESE.
METHODS
We performed a search in the PubMed, EMBASE, Web of Science, and Scopus databases according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Thirty-four publications were selected for inclusion in the analysis.
KEY FINDINGS AND LIMITATIONS
Overall, the mean +SR rate was 45%. Pooled standardized mean difference (SMD) values revealed significant hormonal differences between the +SR and -SR groups, with lower FSH (SMD -0.30), higher InhB (SMD 0.54), and lower AMH (SMD -0.56) levels in the +SR group. Pooled odds ratios (Ors) revealed no significant prediction of +SR by either FSH (OR 1.03, 95% confidence interval [CI] 1.00-1.06) or InhB (OR 1.01, 95% CI 1.00-1.02), despite variations in baseline levels and study heterogeneity. Conversely, AMH had significant predictive value (OR 0.82, 95% CI 0.73-0.92), with lower baseline levels in the +SR group. InhB and FSH levels were higher in the +SR group, while InhB exhibited the opposite trend.
CONCLUSIONS AND CLINICAL IMPLICATIONS
Despite study heterogeneity, our meta-analysis findings support the ability of AMH to predict +SR for men with NOA undergoing mTESE.
PATIENT SUMMARY
We conducted a review and analysis of results from previous studies. Our findings show that for men with an infertility condition called nonobstructive azoospermia, blood levels of anti-Müllerian hormone can predict successful extraction of sperm using a microsurgical technique. Levels of two other hormones did not predict successful sperm extraction.
PubMed: 38854995
DOI: 10.1016/j.euros.2024.05.001 -
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 -
Critical Reviews in Oncology/hematology May 2023Pancreato-biliary and gynecological adenocarcinomas need better tools to predict clinical outcome. Potential prognostic mesenchymal(-like) transcriptome-based subtypes... (Review)
Review
Pancreato-biliary and gynecological adenocarcinomas need better tools to predict clinical outcome. Potential prognostic mesenchymal(-like) transcriptome-based subtypes have been identified in these cancers. In this systematic review, we include studies into molecular subtyping and summarize biological and clinical features of the subtypes within and across sites of origin, searching for suggestions to improve classification and prognostication. PubMed and Embase were searched for original research articles describing potential mesenchymal(-like) mRNA-based subtypes in pancreato-biliary or gynecological adenocarcinomas. Studies limited to supervised clustering were excluded. Fourty-four studies discussing cholangiocarcinomas, gallbladder, ampullary, pancreatic, ovarian, and endometrial adenocarcinomas were included. There was overlap in molecular and clinical features in mesenchymal(-like) subtypes across all adenocarcinomas. Approaches including microdissection were more likely to identify prognosis-associated subtypes. To conclude, molecular subtypes in pancreato-biliary and gynecological adenocarcinomas share biological and clinical characteristics. Furthermore, separation of stromal and epithelial signals should be applied in future studies of biliary and gynecological adenocarcinomas.
Topics: Humans; Pancreatic Neoplasms; Adenocarcinoma; Prognosis; Bile Duct Neoplasms; Bile Ducts, Intrahepatic
PubMed: 37004743
DOI: 10.1016/j.critrevonc.2023.103982 -
Human Reproduction Update Aug 2022The beneficial effects of hormonal therapy in stimulating spermatogenesis in patients with non-obstructive azoospermia (NOA) and either normal gonadotrophins or... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The beneficial effects of hormonal therapy in stimulating spermatogenesis in patients with non-obstructive azoospermia (NOA) and either normal gonadotrophins or hypergonadotropic hypogonadism prior to surgical sperm retrieval (SSR) is controversial. Although the European Association of Urology guidelines state that hormone stimulation is not recommended in routine clinical practice, a significant number of patients undergo empiric therapy prior to SSR. The success rate for SSR from microdissection testicular sperm extraction is only 40-60%, thus hormonal therapy could prove to be an effective adjunctive therapy to increase SSR rates.
OBJECTIVE AND RATIONALE
The primary aim of this systematic review and meta-analysis was to compare the SSR rates in men with NOA (excluding those with hypogonadotropic hypogonadism) receiving hormone therapy compared to placebo or no treatment. The secondary objective was to compare the effects of hormonal therapy in normogonadotropic and hypergonadotropic NOA men.
SEARCH METHODS
A literature search was performed using the Medline, Embase, Web of Science and Clinicaltrials.gov databases from 01 January 1946 to 17 September 2020. We included all studies where hormone status was confirmed. We excluded non-English language and animal studies. Heterogeneity was calculated using I2 statistics and risk of bias was assessed using Cochrane tools. We performed a meta-analysis on all the eligible controlled trials to determine whether hormone stimulation (irrespective of class) improved SSR rates and also whether this was affected by baseline hormone status (hypergonadotropic versus normogonadotropic NOA men). Sensitivity analyses were performed when indicated.
OUTCOMES
A total of 3846 studies were screened and 22 studies were included with 1706 participants. A higher SSR rate in subjects pre-treated with hormonal therapy was observed (odds ratio (OR) 1.96, 95% CI: 1.08-3.56, P = 0.03) and this trend persisted when excluding a study containing only men with Klinefelter syndrome (OR 1.90, 95% CI: 1.03-3.51, P = 0.04). However, the subgroup analysis of baseline hormone status demonstrated a significant improvement only in normogonadotropic men (OR 2.13, 95% CI: 1.10-4.14, P = 0.02) and not in hypergonadotropic patients (OR 1.73, 95% CI: 0.44-6.77, P = 0.43). The literature was at moderate or severe risk of bias.
WIDER IMPLICATIONS
This meta-analysis demonstrates that hormone therapy is not associated with improved SSR rates in hypergonadotropic hypogonadism. While hormone therapy improved SSR rates in eugonadal men with NOA, the quality of evidence was low with a moderate to high risk of bias. Therefore, hormone therapy should not be routinely used in men with NOA prior to SSR and large scale, prospective randomized controlled trials are needed to validate the meta-analysis findings.
Topics: Azoospermia; Hormones; Humans; Klinefelter Syndrome; Male; Prospective Studies; Retrospective Studies; Semen; Sperm Retrieval; Spermatozoa; Testis
PubMed: 35526153
DOI: 10.1093/humupd/dmac016 -
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 -
Andrology Jul 2021Publications of microsurgical testicular sperm extraction (mTESE) techniques and outcomes are heterogeneous, which may limit creation of best surgical practices.
BACKGROUND
Publications of microsurgical testicular sperm extraction (mTESE) techniques and outcomes are heterogeneous, which may limit creation of best surgical practices.
OBJECTIVE
To study the quality and heterogeneity of published mTESE outcomes via a methodological analysis.
MATERIALS/METHODS
A systematic methodological analysis of all published literature on the use of mTESE in men with non-obstructive azoospermia from 1999 to the July 2020 was performed. PubMed and MEDLINE searches were performed using the search terms "microdissection TESE OR microsurgical TESE." Publications were evaluated on their reporting of pre-operative factors, intraoperative techniques, surgical and clinical outcomes, and adverse events.
RESULTS
Fifty-five studies met inclusion criteria. Surgical technique and sperm retrieval rates were the most reported criteria. Reporting on the presence of an embryologist intraoperatively was observed in approximately 30% of articles, while other procedural details including method of sperm quantification, quantity retrieved, and number of cryopreserved vials were observed in fewer than 10% of articles. Clinical outcomes, including pregnancy rates and live birth rates, were reported in fewer than 40% of the articles. Fetal outcomes including fetal and neonatal anomalies were rarely reported. Fetal growth restriction, preterm delivery, small or large for gestational age, and NICU admissions were never reported.
CONCLUSION
There are inconsistencies in reporting quality of mTESE outcomes, specifically a lack of information on the quantity and quality of sperm retrieved, the role of embryology intraoperatively, and clinical outcomes, such as live birth rate and fetal anomalies. These gaps may guide development of standardized reporting guidelines to better assess and compare clinical outcomes across institutions and maintain focus on couples-centric fertility outcomes in future mTESE studies.
Topics: Azoospermia; Humans; Male; Microsurgery; Research Design; Sperm Retrieval; Treatment Outcome
PubMed: 33675583
DOI: 10.1111/andr.12997 -
Asian Journal of Andrology 2023The authors performed a comprehensive review of current literature to create a model comparing commonly evaluated variables in male factor infertility, for example,... (Meta-Analysis)
Meta-Analysis
The authors performed a comprehensive review of current literature to create a model comparing commonly evaluated variables in male factor infertility, for example, follicle-stimulating hormone (FSH), testicular volume (TV), and testosterone (T), to better predict sperm retrieval rate (SRR). Twenty-nine studies were included, 9 with data on conventional testicular sperm extraction (cTESE) for a total of 1227 patients and 20 studies including data on microdissection testicular sperm extraction (mTESE) for a total of 4760 patients. A weighted-means value of SRR, FSH, T, and TV was created, and a weighted linear regression was then used to describe associations among SRR, type of procedure, FSH, T, and TV. In this study, weighted-means values demonstrated mTESE to be superior to cTESE with an SRR of 51.9% vs 40.1%. Multiple weighted linear regressions were created to describe associations among SRR, procedure type, FSH, T, and TV. The models showed that for every 1.19 mIU ml increase in FSH, there would be a significant decrease in SRR by 1.0%. Seeking to create a more clinically relevant model, FSH values were then divided into normal, moderate elevation, and significant elevation categories (FSH <10 mIU ml, 10-19 mIU ml, and >20 mIU ml, respectively). For an index patient undergoing cTESE, the retrieval rates would be 57.1%, 44.3%, and 31.2% for values normal, moderately elevated, and significantly elevated, respectively. In conclusion, in a large meta-analysis, mTESE was shown to be more successful than cTESE for sperm retrievals. FSH has an inverse relationship to SRR in retrieval techniques and can alone be predictive of cTESE SRR.
Topics: Humans; Male; Follicle Stimulating Hormone; Follicle Stimulating Hormone, Human; Infertility, Male; Linear Models; Semen; Sperm Retrieval; Spermatozoa; Testis
PubMed: 35645045
DOI: 10.4103/aja202221 -
Asian Journal of Andrology May 2024Microdissection testicular sperm extraction (mTESE) is commonly performed to retrieve sperm in the testes for assisted reproductive techniques in patients with...
Association between anti-Müllerian hormone concentrations and sperm retrieval outcomes in patients with idiopathic nonobstructive azoospermia: a systematic review and meta-analysis.
Microdissection testicular sperm extraction (mTESE) is commonly performed to retrieve sperm in the testes for assisted reproductive techniques in patients with idiopathic nonobstructive azoospermia (iNOA). However, the success rate of sperm retrieval varies among individuals. We aim to investigate the association between clinical parameters and sperm retrieval outcomes in patients with iNOA. We searched PubMed, EMBASE, and Web of Science from database inception to August 2, 2023. The main measure was whether sperm retrieval was successful in patients with iNOA who underwent mTESE. Pooled estimates of the sperm retrieval rate and weighted mean differences were calculated using random-effects models. The overall sperm retrieval rate was 36.8% (95% confidence interval [CI]: 27.5%-46.0%, I2 = 95.0%) in nine studies comprising 1892 patients with iNOA. No significant differences were found in age, testicular volume, serum total testosterone concentrations, or inhibin B concentrations between positive and negative sperm retrieval outcomes. Lower anti-Müllerian hormone concentrations in patients with iNOA were associated with a positive outcome of mTESE (weighted mean differences: -2.70; 95% CI: -3.94--1.46, I2 = 79.0%). In conclusion, this study shows a significant relationship between anti-Müllerian hormone and sperm retrieval outcomes in patients with iNOA, while age, testicular volume, total testosterone, and inhibin B show no significant association. These findings have important implications for assessing the potential success of sperm retrieval and selecting appropriate treatment strategies in patients with iNOA.
PubMed: 38748861
DOI: 10.4103/aja202419