The aim of the present study is to evaluate the presence of ghrelin and orexin in the testicular tissue of patients who have undergone microscopic testicular sperm extraction (micro‐TESE) due to idiopathic non‐obstructive azoospermia. Seventy azoospermic cases were included in this study; serum hormone levels were measured and genetic investigations were performed. The patients were divided into two groups: micro‐TESE (+) and micro‐TESE (−). The number of Leydig cells and stained cells in the seminiferous tubules were counted under a light microscope, and we analyzed ghrelin and orexin activity. The relationship between serum hormone levels and ghrelin and orexin distributions in testicular tissue was evaluated according to micro‐TESE results. While sperm was found in 33 cases (47.1%), micro‐TESE was negative in 37 cases (52.9%). Peptide hormone activity in testicular tissue was higher in micro‐TESE (+) cases. However, interstitial orexin (p = 0.038) and ghrelin (p = 0.002) activity showed statistically meaningful differences. Many different peptides, genes, and other unknown mechanisms play important roles in testicular function. In particular, the peptides orexin and ghrelin may play regulatory roles in testicular function in humans.
Study question What is CHLOE’s (Fairtility) efficacy of prediction of blastulation (at 30hpi), pregnancy and ongoing clinical pregnancy following single embryo transfer (SET)? Summary answer CHLOE(Fairtility) algorithms are effective predictors of blastulation, ploidy, pregnancy, implantation and ongoing clinical pregnancy What is known already Time-lapse incubators have increased the amount of information available to the embryologist to help determine the fate of embryos. This has led to differences in clinical practice between clinics in how this information is prioritised. Moreover, inter-operator inconsistencies and the time-consuming nature of manually annotating time-lapse videos are challenges currently experienced by time-lapse users that can be relieved with Artificial Intelligence(AI) tools, such as CHLOE(Fairtility). CHLOE levergaes AI-based predictors to predict blastulation and implantation, whilst providing transparency to which biological characteristics have led to that determination. There is a need to validate AI tools before their incorporation into clinical practice. Study design, size, duration This was a single centre study that took place between 2017-2020, at Istanbul Memorial Sisli Hospital in Turkey, ART and Center. This was a retrospective cohort analysis that reviewed 6748 time-lapse videos containing 5392 cleaved embryos, 3763 blastocysts, 877 single embryo transfers(SET) with known ongoing pregnancy outcome (KOPO), 306 euploid SETs and 25 mosaic embryo SETs with KOPO. CHLOE blastocyst and implantation score efficacy of prediction of clinical outcomes was quantified using the metric AUC. Participants/materials, setting, methods Time-lapse videos were assessed using CHLOE(Fairtility), an AI based tool, to quantify quantitative and qualitative morphokinetics (including automated annotations of tPNa,tPNf,t2,t3,t4,t5,t6,t7,t8,t9,tM,tSB,tB,tEB), CHLOE implantation score and CHLOE blastocyst score (calculated at 30hpi) relative to laboratory (ploidy results, blastulation) and clinical outcomes (biochemical, clinical and ongoing pregnancy) following overall SET. Binary logistic regression was used to calculate area under the curve (AUC) as a measure of prediction efficacy. Main results and the role of chance Blastulation score assessment of cleaved embryos was predictive of blastulation (AUC=0.96, baseline=70% n = 5392, p < 0.001). Following PGT-A, implantation score was predictive of euploids (AUC=0.61, baseline=34%, n = 1456, p < 0.001), but not of embryos classified as mosaics (AUC=0.5, baseline=19%, n = 1456, p > 0.05). Following SET, implantation score was predictive of biochemical (AUC=0.71, baseline=49%, n = 866, p < 0.001), clinical and ongoing pregnancy rate (AUC=0.69, baseline=37%, n = 866, p < 0.001). Following SET of non-PGT-A embryos, implantation score decreased with increasing patient age (p < 0.001). The type of aneuploidy (such as monosomy, trisomy, segmental) did not affect implantation score or blastulation score (p > 0.05). Implantation score prediction of outcome was higher for non-PGT-A transfers than overall transfers for biochemical (Non-PGTA: AUC=0.73, baseline=33%, n = 535, p < 0.001; OVERALL: AUC=0.71, baseline=49%, n = 866, p < 0.001), clinical and ongoing pregnancy (Non-PGTA: AUC=0.76, baseline=24%, n = 535, p < 0.001; OVERALL: AUC=0.69, baseline=37%, n = 866, p < 0.001), despite lower baselines. Limitations, reasons for caution This is a single centre study, using retrospective data where embryos were selected for transfer by human embryologists. Despite the data has heterogeneity in terms of clinical features, the study is part of a larger framework for responsible incorporation of AI into clinical practice through robust validation. Wider implications of the findings AI-based tools have the potential of increasing consistency, efficiency and efficacy of embryo selection. The additional information on quantitative and qualitative morphokinetics that AI tools such as CHLOE provide, bring transparency to the prediction, allowing for improvement in personalisation of care down to each individual embryo. Trial registration number None
With an overall successful repeat SSR rate (45%) close to reported success rates of primary SSR in NOA, men with NOA should not be considered infertile until they have had a micro-TESE and been found to be infertile. In the redo setting, further retrieval with micro-TESE is safe and effective (79-100% success). In those with previous failed micro-TESE, salvage micro-TESE may be a therapeutic option, particularly in those with hypospermatogenesis on initial pathology.
Study question Are hypo-osmotic swelling test (HOST) and intracytoplasmic morphologically selected sperm injection (IMSI) both effective alternative methods for sperm selection? Summary answer Similar results were obtained in embryo morphokinetics between HOST and IMSI. What is known already HOST is a simple, low-cost and rapid test based on the swelling of the tail of the sperm in a hypoosmotic environment. Less DNA fragmentation, membrane integrity and aneuploidy rates have been found in sperm selected by the HOST method. It also allows identification of viable sperm in a totally immotile sperm sample. IMSI, on the other hand, is a method for identifying the morphologically best sperm using high-magnification microscope. In studies, IMSI has been associated with high fertilization rates. However, it is a time-consuming method that requires expensive equipment. Study design, size, duration Time-Lapse Monitoring (TLM)-incubated sibling embryos of 25 male factor patients who applied for ART treatment to Istanbul, Sisli Memorial ART and Genetics Center in 2021 were included into the study. Sibling embryos were grouped according to their sperm selection method. In the IMSI group 170 embryos, in the HOST group 173 embryos were evaluated retrospectively in terms of the morphokinetic parameters, the rates of blastulation, Top- Quality (TQ) and Good Quality (GQ) embryos and euploidy. Participants/materials, setting, methods Blastocyst grading was performed according to Gardner’s classification. Blastocysts 3AA,4AA,4AB,4BA,4BB,5AA,5AB,5BA,5BB were accepted as TQ+GQ. Blastulation rates was determined including the embryos at least 2 expansion. PGT-A results were obtained by Next Generation Sequencing(NGS) method. The comparison of the TLM parameters and clinical features of the patients were performed using Student’s t-test. Chi-square test was used for comparing the rates of fertilization, blastulation, TQ+GQ embryo and euploidy in each group. Main results and the role of chance No statistical difference was observed between IMSI and HOST groups in terms of morphokinetic parameters (tPN, tPNf, t2, t3, t4, t5, t6, t7, t8, t9, tSC, tM, tSB, tB, tEB) (p > 0.05). There were higher rates of normal fertilization in the HOST group (90.8%) than in the IMSI group (82.4%) and of TQ+GQ embryo (HOST: 50%, IMSI: 47.3%). However, these diffrences were not statistically significant (p > 0.05). There was statistically lower abnormal fertilization rate was found in HOST group (2.3% vs 7.1%, p = 0.038). When PGT-A results were compared (HOST:19 embryos, IMSI: 19), slightly higher results were observed in IMSI group than HOST group ( 63%, 58% respectively) (p > 0.05). Limitations, reasons for caution This was a retrospective of a small number of cases. Wider implications of the findings The similarity of the outcome in these initial findings studying a small number of cases, suggest that this study should be extended. Trial registration number None
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