Reproductive and obstetric outcomes in TESE-ICSI cycles: A comparison between obstructive and non-obstructive azoospermia.

PURPOSE: Comparison of intracytoplasmic sperm injection cycles with testicular sperm extraction in obstructive azoospermia and non-obstructive azoospermia are limited, and few studies have addressed obstetric and neonatal outcomes. DESIGN: This study analyzed couples who underwent testicular sperm extraction-intracytoplasmic sperm injection cycles for obstructive azoospermia and non-obstructive azoospermia to determine whether impaired spermatogenesis in non-obstructive azoospermia patients would lead to worse reproductive outcomes and higher rates of pregnancy complications and fetal anomalies. This study is a retrospective, single-center analysis of all testicular sperm cycles performed between January 1, 2001 and December 31, 2020. RESULTS: A total of 392 couples were considered in the study, leading to 1066 induction cycles, 620 (58.2%) from patients with obstructive azoospermia and 446 (41.8%) from non-obstructive azoospermia. The cumulative delivery rate did not significantly differ between the two groups (34% vs. 31%; p = 0.326). The miscarriage rate was similar between obstructive azoospermia and non-obstructive azoospermia patients. Fertilization rate instead showed a statistically significant difference (obstructive azoospermia: 66.1 ± 25.7 vs. non-obstructive azoospermia: 56.1 ± 27.0; p < 0.001). The overall maternal complication rate in the non-obstructive azoospermia group was higher (10.7% vs. 18.4%; p = 0.035), but there was no statistical significance for each pathology. There was no statistical difference in gestational age between the two groups for both single and twin pregnancies. Seven cases of congenital defects occurred in the obstructive azoospermia group, while two cases occurred in the non-obstructive azoospermia group. CONCLUSIONS: Despite impaired spermatogenesis in non-obstructive azoospermia patients, there were no substantial differences in reproductive outcomes compared to patients with obstructive azoospermia, even in terms of obstetric safety and neonatal well-being.

Molecular biomarkers predicting early development of endometrial carcinoma: A pilot study.

OBJECTIVE: Endometrial carcinoma represents the most common gynaecological cancer and the sixth most frequent cancer among women worldwide. The 5-year survival of patients with stage I endometrial carcinoma is 75%-88% versus 50% for stage III or 15% for stage IV disease. Therefore, early detection could improve survival rates. Specifically, in the most prevalent, type 1 endometrial cancer develops from hyperplastic endometrium. The aim of the study was to evaluate the utility of cancer gene mutations from endometrial biopsies towards predicting synchronous or metachronous development of malignant lesions. The aim of the study was to evaluate whether endometrial biopsies could already carry mutations in cancer genes useful for predicting or anticipating subsequent cancer development. METHODS: Patients with a previous endometrial biopsy negative for cancer, followed by a subsequent biopsy positive for cancer, were included in the study. A fifty cancer genes targeted next-generation sequencing panel were used to investigate mutations in matched non-cancerous and malignant samples. RESULTS: All biopsies from cancer tissues harboured mutations in one or more of the following genes: APC, CTNNB1, FBXW7, HNF1A, KRAS, MTOR, NRAS, PIK3CA, PTEN, RB1 and TP53. Additionally, 50% of the biopsies from matched non-cancerous tissues exhibited mutations in PTEN, KRAS or PIK3CA genes. CONCLUSIONS: These results suggest that detecting pathogenic mutations in oncogenes or tumour suppressor genes in an otherwise benign condition is associated with a risk of developing a malignant disease. Given the identification of mutations several months or years before the appearance of a malignancy, our finding suggests that a closer monitoring of patients who present such molecular alterations in non-cancerous uterine mass is warranted.

SLUG/HIF1-α/miR-221 regulatory circuit in endometrial cancer.

BACKGROUND AND PURPOSE: The pathogenesis of endometrial cancer (EC) involves many regulatory pathways including transcriptional regulatory networks supported by transcription factors and microRNAs only in part known. The aim of this retrospective study was to explore the possible correlation in the EC microenvironment between master regulators of complex phenomena such as steroid responsiveness through estrogen receptor alpha (ERα) and progesterone receptor (PR), epithelial-to-mesenchymal transition (supported by SLUG transcription factor), hypoxia (with hypoxia inducible factor-1 alpha, HIF-1α), and obesity that has been recognized as a EC risk factor. METHODS: Formalin-Fixed Paraffin-Embedded (FFPE) blocks from University of Ferrara Pathology Archive were used and allocated into 2 groups according to their immunohistochemical positivity to ERα and PR, distinguishing the samples with a more benign prognosis (ERα+/PR+) from those with a poorer prognosis (ERα-/PR-). Immunohistochemistry for HIF1-α and SLUG was also performed. Body mass index (BMI) was registered at the time of diagnosis: patients with BMI ≥ 30 kg/m2 were defined obese (OB). Total RNA was isolated for miR-221 analysis. RESULTS: We showed a comparable percentage of HIF1-α and SLUG positive samples in the ERα+/PR+ and ERα-/PR- groups. However, the obesity factor impacted more in the ERα+/PR+ group since the ratio between OB and non-obese (NOB) patients with high expression of HIF1-α and SLUG was higher in ERα+/PR+ than in the ERα-/PR- group. miR-221 levels were significantly higher in the OB than NOB patients, and, also in this case, obesity impacted more in the ERα+/PR+ group. CONCLUSIONS: A molecular circuit of mutual regulation between ERα, PR, HIF1-α, SLUG and miR-221 is feasible in the EC and was firstly suggested by our research. In this interplay miR-221 seems to be in a nodal point of the regulatory system that is particularly strengthened by the metabolic changes in obesity.

Ductal Breast Carcinoma Metastatic to the Stomach Resembling Primary Linitis Plastica in a Male Patient.

Breast cancer metastases to the gastrointestinal tract are very rare occurrences. Among the histological subtypes of breast cancer, invasive lobular carcinomas have a high capacity of metastasis to uncommon sites including the stomach. Conversely, there has not been sufficient evidence supporting the gastric metastasis of invasive ductal carcinoma. Herein, we report a unique case of metastatic ductal breast carcinoma mimicking primary linitis plastica in a male patient, particularly focusing on the clinical and pathological features of presentation. Moreover, we propose a immunohistochemical panel of selected antibodies including those for cytokeratin 20, cytokeratin 7, estrogen receptor, progesterone receptor, E-cadherin, gross cystic disease fluid protein 15, and GATA binding protein 3 for an accurate differential diagnosis.