To investigate whether Azoospermia Factor c (AZFc) microdeletions affect Assisted Reproductive Technology (ART) outcomes.
Systematic review and meta-analysis.
Not applicable.
Infertile men with and without AZFc microdeletions.
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.
The primary outcome was successful sperm retrieval and the secondary outcomes were outcomes of ART.
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.
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.
CRD42022311738.

BACKGROUND: There has been no systematic review and meta-analysis to analyze and summarize the predictive factors of successful sperm extraction in salvage microdissection testicular sperm extraction.
OBJECTIVE: We aimed to investigate the factors predicting the result of salvage microdissection testicular sperm extraction in patients with non-obstructive azoospermia who failed the initial microdissection testicular sperm extraction or conventional testicular sperm extraction.
METHODS: We conducted a systematic literature search in PubMed, Web of Science, EMBASE, and the Cochrane Library for literature that described the characteristics of patients with non-obstructive azoospermia who underwent salvage microdissection testicular sperm extraction after failing the initial microdissection testicular sperm extraction or conventional testicular sperm extraction published prior to June 2022.
RESULTS: This meta-analysis included four retrospective studies with 332 patients with non-obstructive azoospermia who underwent a failed initial microdissection testicular sperm extraction and three retrospective studies with 177 non-obstructive azoospermia patients who underwent a failed conventional testicular sperm extraction. The results were as follows: among non-obstructive azoospermia patients whose first surgery was microdissection testicular sperm extraction, younger patients (standard mean difference: -0.28, 95% confidence interval [CI]: -0.55 to -0.01) and those with smaller bilateral testicular volume (standard mean difference: -0.55, 95% CI: -0.95 to -0.15), lower levels of follicle-stimulating hormone (standard mean difference: -0.86, 95% CI: -1.18 to -0.54) and luteinizing hormone (standard mean difference: -0.68, 95% CI: -1.16 to -0.19), and whose testicular histological type was hypospermatogenesis (odds ratio: 3.52, 95% CI: 1.30-9.53) were more likely to retrieve spermatozoa successfully, while patients with Sertoli-cell-only syndrome (odds ratio: 0.41, 95% CI: 0.24-0.73) were more likely to fail again in salvage microdissection testicular sperm extraction. Additionally, in patients who underwent salvage microdissection testicular sperm extraction after a failed initial conventional testicular sperm extraction, those with testicular histological type of hypospermatogenesis (odds ratio: 30.35, 95% CI: 8.27-111.34) were more likely to be successful, while those with maturation arrest (odds ratio: 0.39, 95% CI: 0.18-0.83) rarely benefited.
CONCLUSIONS: We found that age, testicular volume, follicle-stimulating hormone, luteinizing hormone, hypospermatogenesis, Sertoli-cell-only syndrome, and maturation arrest were valuable predictors of salvage microdissection testicular sperm extraction, which will assist andrologists in clinical decision-making and minimize unnecessary injury to patients.

Retrieval of spermatozoa is unfortunately still only successful in a subset of patients suffering from non-obstructive azoospermia (NOA) by conventional testicular sperm extraction (TESE). Microdissection TESE may have some theoretical benefits over conventional TESE, but uncertainty exists about its superiority. The objective of this systematic review was therefore to compare the efficacy and safety of microTESE with conventional TESE in men with NOA. The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. Literature was searched for studies comparing outcome of conventional TESE with microdissection TESE. Primary outcome was sperm retrieval rate (SRR). Secondary outcomes were clinical predictors of sperm retrieval as well as complication rate. Of 62 articles, a total of seven studies were included in the final analysis. Overall SRR was significantly higher in the microTESE group in comparison with conventional TESE in five of these studies. Overall sperm retrieval ranged from 16.7 to 45% in the conventional TESE vs. 42.9 to 63% in the microTESE group. A sub-analysis of the SRR according to testicular histology was available in four of the selected articles. MicroTESE in men with Sertoli cell only syndrome and hypospermatogenesis carried a small but significant more favourable outcome according to, respectively, two and one of the studies. Correlation of serum follicle stimulating hormone and testicular volume with positive outcome was variable. Fewer complications were observed on ultrasound examination after microTESE procedure. Clinical randomized studies comparing microTESE with conventional TESE in NOA are still lacking to date. Pseudo-randomized prospective data, however, show more favourable sperm retrieval in NOA for microTESE, especially in histological patterns of patchy spermatogenesis such as Sertoli cell only syndrome. However, in patients with uniform histological patterns such as maturation arrest outcome of microTESE seems less favourable.

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