ICSI outcomes for infertile men with severe or complete asthenozoospermia.

BACKGROUND: Severe or complete asthenozoospermia is a rare entity that can lead to male infertility. In this study, we explored whether different extents of severe or complete asthenozoospermia could affect intracytoplasmic sperm injection (ICSI) outcomes and compared the ICSI outcomes using testicular spermatozoa with those using ejaculated spermatozoa in couples with complete asthenozoospermia. RESULTS: Ninety-seven couples with severe or complete asthenozoospermia who underwent ICSI between January 2014 and December 2018 were included. According to the sperm category used in ICSI, patients were categorized into four groups: ejaculated progressive motile sperm group (Ep-group), ejaculated non-progressive motile sperm group (En-group), ejaculated immotile sperm group (Ei-group), and testicular sperm group (TESE-group). We compared the baseline characteristics, hormone profile, semen parameters, normal fertilization, good-quality embryos on day 3, transferred embryos, and ICSI outcomes in the four groups. The clinical pregnancy rate was significantly increased in the Ep-group (65.4%, P = 0.019) and TESE-group (63.6%, P = 0.035) compared with that in the Ei-group (23.1%). The ongoing pregnancy rate in the Ei-group was significantly lower than that in the Ep-group (23.1% vs. 61.5%, P = 0.041). Moreover, the biochemical pregnancy rate, ongoing pregnancy rate, and live birth rate were much lower in the Ei-group than in the TESE-group (30.8% vs. 63.6%, 23.1% vs. 40.4% and 23.1% vs. 40.4%, respectively). CONCLUSIONS: In couples with complete asthenozoospermia, testicular spermatozoa should be preferred to ejaculated spermatozoa for obtaining a better ICSI outcome. With the appropriate selection of testicular spermatozoa, the extent of severe or complete asthenozoospermia may not affect the ICSI outcomes. Future studies with a larger sample size are warranted to validate these findings.

RéSUMé: CONTEXTE: L'asthénozoospermiesévère ou complète est une entité rare qui peut conduire à l'infertilité masculine. Dans cette étude, nous avons exploré si les différentes étendues de l'asthénozoospermie sévère ou complète pouvaient affecter les résultats de l'injection intracytoplasmique de spermatozoïdes (ICSI), et nous avons comparé les résultats de l'ICSI obtenus avec des spermatozoïdes testiculaires à ceux obtenus avec des spermatozoïdes éjaculés chez les couples atteints d'asthénozoospermie complète. RéSULTATS: Quatre-vingt-dix-sept couples atteints d'asthénozoospermie sévère ou complète qui ont eu une ICSI entre janvier 2014 et décembre 2018 ont été inclus. Selon la catégorie de spermatozoïdes utilisée dans l'ICSI, les patients ont été classés en quatre groupes : groupe de spermatozoïdes mobiles progressifs éjaculés (groupe Ep), groupe de spermatozoïdes mobiles non progressifs éjaculés (groupe En), groupe de spermatozoïdes immobiles éjaculés (groupe Ei) et groupe de spermatozoïdestesticulaires (groupe TESE). Nous avons comparé les caractéristiques de base, le profil hormonal, les paramètres du sperme, la fécondation normale, les embryons de bonne qualité au jour 3, les embryons transférés, et les résultats de l'ICSI dans les quatre groupes. Le taux de grossesse clinique était significativement augmenté dans le groupe Ep (65,4%, P = 0,019) et le groupe TESE (63,6%, P = 0,035) par rapport à celui du groupe Ei (23,1%). Le taux de grossesse en cours dans le groupe Ei était significativement inférieur à celui du groupe Ep (23,1% contre 61,5%, P = 0,041). De plus, le taux de grossesse biochimique, le taux de grossesse en cours et le taux de naissances vivantes étaient beaucoup plus faibles dans le groupe Ei que dans le groupe TESE (30,8 % vs 63,6%,23,1 % vs 40,4 % et 23,1 % vs 40,4 %, respectivement). CONCLUSIONS: Chez les couples atteints d'asthénozoospermie complète, les spermatozoïdes testiculaires devraient être préférés aux spermatozoïdes éjaculés pour obtenir un meilleur résultat en ICSI. Avec une sélection appropriée des spermatozoïdes testiculaires, l'étendue de l'asthénozoospermie sévère ou complète pourrait ne pas affecter les résultats de l'ICSI. De futures études avec des échantillons de plus grande taille sont donc justifiées pour valider ces résultats. MOTS-CLéS: Asthénozoospermie; spermatozoïdes éjaculés ; injection intracytoplasmique de spermatozoïdes (ICSI) ; infertilité masculine ; spermatozoïdes testiculaires.

Single-cell RNA-sequencing analysis reveals MYH9 promotes renal cell carcinoma development and sunitinib resistance via AKT signaling pathway.

Clear cell renal cell carcinoma (ccRCC) is a serious threat to human health worldwide, while its heterogeneity limits therapeutic success and leads to poor survival outcomes. Single-cell RNA-sequencing (scRNA-seq) is an important technology, which provides deep insights into the genetic characteristics of carcinoma. In this study, we profiled the gene expression of single cells from human ccRCC tissues and adjacent normal tissues using the scRNA-seq. We found that MYH9 was commonly upregulated in the ccRCC cell subgroup. Additionally, MYH9 was of highly expression in ccRCC tissues and predicted poor prognosis of ccRCC patients. MYH9 knockdown in ccRCC cells dampened their proliferative and metastatic potentials, whereas MYH9 overexpression enhanced these properties. In vivo, MYH9 also promoted ccRCC growth. Mechanistic studies showed that MYH9 played these vital roles through AKT signaling pathway. Furthermore, MYH9/AKT axis determined the responses of ccRCC cells to sunitinib treatment and might serve as a biomarker for sunitinib benefits in ccRCC patients. Thus, MYH9 might be a novel therapeutic target and prognostic predictor for ccRCC.

Possible misdiagnosis of 46,XX testicular disorders of sex development in infertile males.

Objectives: The 46,XX disorders of sex development (DSD) is a rare genetic cause of male infertility and possible misdiagnosis of this condition has never been reported. We aim to investigate clinical characteristics and laboratory results of infertile males with possibly misdiagnosed 46,XX DSD. Methods: Between January 2008 and December 2017, a retrospective case series study was performed involving sixteen 46,XX DSD males without azoospermia factor (AZF) deletion. Demographics, clinical features, laboratory results and assisted reproductive technology (ART) outcomes of these patients were depicted, and the underlying accurate diagnosis was also discussed. Results: The mean age was 30.06 ± 5.40 years old. Thirteen patients (81.25%) merely obtained secondary school education. Gynaecomastia occurred in one case, and cryptorchidism appeared in two cases. Testicular volumes were equal to 15 mL on two sides in one patient who had severe asthenozoospermia. Thirteen patients (81.25%) had bilateral atrophic testes which were below 5 mL. The majority of patients were observed with elevated levels of gonadotropic hormones and decreased testosterone values. Neither AZF region nor sex-determining region Y gene was absent among all patients. Twelve patients had normal ejaculatory function, whereas four were diagnosed with ejaculatory dysfunction. Eleven patients (68.75%) were diagnosed with azoospermia. Testicular sperm aspiration was performed in six subjects (37.50%). The pathological results showed that Leydig cell hyperplasia with spermatic failure was found in each case, and no sperm was found in testicular tissue. ART with donor sperm was conducted in 15 patients. Live birth was achieved in three cases through artificial insemination by donor and in one case using in-vitro fertilization by donor. Conclusions: Chromosomal analysis rarely yields 46,XX karyotype combined with no deletion of AZF in infertile males. Under this condition, molecular analysis should be conducted to avoid potential misdiagnosis and false interpretation of other findings.

Prognostic significance of PI3K/AKT/ mTOR signaling pathway members in clear cell renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) is a fatal disease, in which the PI3K/AKT/mTOR signaling pathway serves an important role in the tumorigenesis. Previous studies have reported the prognostic significance of PI3K/AKT/mTOR signaling pathway members in RCC; however, there is insufficient evidence to date to confirm this. Thus, the present study aimed to systematically investigate the prognostic roles of multiple PI3K/AKT/mTOR signaling proteins in clear cell RCC (ccRCC) using online large-scale databases. METHODS: The mRNA expression profiles of PI3K/AKT/mTOR signaling pathway proteins PTEN, PIK3CA, PIK3CB, PIK3CD, PIK3CG, AKT1, AKT2, AKT3 and mTOR were investigated using the Gene Expression Profiling Interactive Analysis (GEPIA) and Oncomine databases, and the protein expression levels of PI3K, AKT and mTOR were detected using western blotting (WB) analysis. In addition, the correlation between mRNA or protein expression levels and the prognostic significance was analyzed using the Kaplan-Meier (K-M) plotter (n = 530), the Human Protein Atlas (HPA; n = 528) and The Cancer Protein Atlas (TCPA; n = 445) databases. RESULTS: The GEPIA revealed that the mRNA expression of major PI3K/AKT/mTOR pathway members, including PTEN, PIK3CA, PIK3CB, AKT1, AKT2 and AKT3, were negatively correlated with ccRCC stages (P < 0.05), though most of their mRNA and protein expression levels were notsignificantly different between ccRCC and normal tissues using GEPIA, Oncomine and WB analyses (P < 0.05). Meanwhile, using the K-M plotter and HPA prognostic analysis, it was found that the mRNA expression levels of the majority of the PI3K/AKT/mTOR signaling pathway members, including PTEN, PIK3CA, PIK3CB, PIK3CG, AKT3 and mTOR were positively correlated with overall survival (OS), whereas PIK3CD mRNA expression was negatively correlated with OS (P < 0.05). Furthermore, TCPA prognostic analysis observed that several of the key molecules of the PI3K/AKT/mTOR signaling pathway [PTEN, p-AKT (S473) and p-mTOR (S2448)] were also positively correlated with OS in patients with ccRCC (P < 0.05). In conclusion, the present study suggested that several members of the PI3K/AKT/mTOR signaling pathway, especially PTEN, may be favorable prognostic factors in ccRCC, which indicated that the PI3K/AKT/mTOR signaling pathway may be implicated in ccRCC initiation and progression.