Evidence suggests that the pericentric inversion of chromosome 9 (inv(9)) does not affect the aneuploidy rate (38.5%) after IVF. Herein, we report a successful live female twin birth through IVF/ICSI with a high aneuploidy rate from a couple within which the infertile father has inv(9)(p12q13). A couple (a 34-year-old male and a 35-year-old female) was referred to our clinic due to infertility. The wife has a child with her previous husband. Results from the infertility workup of both parents were normal. Karyotyping revealed that the inv(9)(p12q13) of the father was the only cytogenetic abnormality. Preimplantation genetic testing for aneuploidies (PGT-A) after IVF/ICSI revealed a high aneuploidy rate (77%; 10/13). Two euploid blastocysts were transferred, resulting in a successful live female twin birth. The presented case highlights the possibility that inv(9)(p12q13) in males may impact the fertility and euploidy rate. PGT-A facilitates the selection of qualified blastocysts for the optimization of live-birth outcomes.
Background/Objectives: Dysbiosis of the vaginal microbiota, particularly the loss of Lactobacillus spp. dominance, is linked to female infertility. While community state types (CSTs) I–III and V have been studied extensively, CST IV remains underexplored. The aim of this prospective study was to compare vaginal microbiota composition—specifically CST IVA and IVB—between fertile and infertile women. Methods: Vaginal samples were collected from 22 women (15 infertile, 7 fertile) using cervical brushes and analyzed via 16S rRNA gene sequencing. DNA was extracted, and V3–V4 regions were sequenced using the Illumina MiSeq platform. Taxonomic classification was performed with QIIME 2 and the Greengenes database. Differences in microbial composition were assessed using the Wilcoxon rank-sum test (p < 0.05) in SPSS v21.0. Results: Infertile women showed lower relative abundances of Lactobacillus spp. (31.54% vs. 42.32%) and Oscillospira spp. relative to fertile women. CST IV was more frequent in the infertile group (29.75% vs. 21.61%). Within CST IV, CST IVA accounted for a higher proportion in infertile women (7.0% vs. 0.94%), with Prevotella spp. representing 95.18% of CST IVA in infertile subjects, as opposed to the figure of 69.77% in fertile counterparts. No clear differences in CST IVB were observed between groups. Conclusions: Increased prevalence of Prevotella spp. in CST IVA may contribute to an unfavorable vaginal environment in infertile women, potentially affecting sperm viability. The presence of Oscillospira spp. in fertile women suggests it is associated with a healthy vaginal microbiota profile.
Background/Objectives: The detection of ovarian cancer remains challenging due to the lack of reliable serum biomarkers that reflect malignant transformation rather than mere tumor presence. We developed a novel biotest using an immortalized human fallopian tube epithelial cell line (TY), which exhibits anchorage-independent growth (AIG) in response to cancer-associated serum factors. Methods: Sera from ovarian and breast cancer patients, non-cancer controls, and ID8 ovarian cancer-bearing mice were tested for AIG-promoting activity in TY cells. Results: TY cells (passage 96) effectively distinguished cancer sera from controls (68.50 ± 2.12 vs. 17.50 ± 3.54 colonies, p < 0.01) and correlated with serum CA125 levels (r = 0.73, p = 0.03) in ovarian cancer patients. Receiver operating characteristic (ROC) analysis showed high diagnostic accuracy (AUC = 0.85, cutoff: 23.75 colonies). The AIG-promoting activity was mediated by HGF/c-MET and IGF/IGF-1R signaling, as inhibition of these pathways reduced phosphorylation and AIG. In an ID8 mouse ovarian cancer model, TY-AIG colonies strongly correlated with tumor burden (r = 0.95, p < 0.01). Conclusions: Our findings demonstrate that the TY cell-based AIG assay is a sensitive and specific biotest for detecting ovarian cancer and potentially other malignancies, leveraging the fundamental hallmark of malignant transformation.
A BSTRACT: Objectives: Endometriosis is a chronic, estrogen-dependent disorder characterized by the ectopic growth of endometrial-like tissue. Despite its significant impact on fertility and quality of life, the pathogenesis of endometriosis remains poorly understood. This study investigates the potential role of ovulatory follicular fluid (FF) in driving disease progression. Based on the “double engines theory,” which posits that retrograde menstruation provides the “seeds” for ectopic lesions while ovulation fuels their growth, we hypothesize that FF enhances endometrial cell proliferation, clonogenicity, migration, and invasion. Materials and Methods: Primary eutopic and ectopic endometrial cells were isolated from infertile women and treated with 10% diluted FF collected from in vitro fertilization patients. Cellular morphology, proliferation, clonogenicity, migration, and invasion were evaluated using colony formation, transwell, and Matrigel assays. Statistical analyses were performed to compare cellular responses between eutopic and ectopic cells. Results: Morphological analysis revealed distinct adaptive changes, with ectopic cells predominantly adopting a more fibroblast-like phenotype. Ectopic cells exhibited higher clonogenicity (29.8-fold) capacities, lower proliferation (0.49-fold) and migration (0.11-fold) capacities, and similar invasion capabilities compared to eutopic cells. FF significantly enhanced proliferation (1.7-fold in eutopic and 1.3-fold in ectopic cells) and clonogenic capacity, with eutopic cells forming 31.3 times more colonies and ectopic cells showing a 1.3-fold increase. The clonogenic area expanded dramatically, increasing 261-fold in eutopic and 4.9-fold in ectopic cells. In addition, FF promoted migration (1.8-fold in eutopic and 2.9-fold in ectopic cells) and invasion (9.1-fold in eutopic and 4.8-fold in ectopic cells). These findings suggest that FF may play a pivotal role in the early establishment and progression of ectopic lesions. Conclusion: The results highlight the critical role of FF in enhancing endometrial cell survival, proliferation, and dissemination. This supports the “double engines theory” of endometriosis, emphasizing the significant contribution of ovulation to the pathogenesis of the disease.
High-grade serous ovarian carcinoma (HGSC) is predominantly diagnosed at advanced stages with extensive peritoneal metastasis. A pivotal early event in HGSC development is the peritoneal seeding of tumor cells originating from the fallopian tube epithelial (FTE) precursor lesions. Ovulation releases follicular fluid (FF), which is known to contain oncogenic factors that promote FTE cell transformation. However, the specific mechanisms and factors within FF that drive the early metastatic seeding of precancerous FTE cells remain poorly defined. We investigated the role of FF in the peritoneal dissemination of FTE-derived cells, and the abundance of fibronectin (FN) as a potential key mediator. Functional assays were performed using FN-depleted FF to assess its impact on migration, invasion, anchorage-independent growth, and peritoneal attachment. The role of the fibronectin receptor, integrin β1 (ITGB1), and the signaling pathways were evaluated via knockdown studies. In vivo xenograft models were used to quantify peritoneal seeding, and mechanistic studies elucidated the involved signaling pathways. We identified FN as a critical component of FF, present at high concentrations (~210 µg/mL), that potently drives FTE cell migration, invasion, and peritoneal seeding. Depletion of FN from FF abrogated the majority of these pro-metastatic activities in vitro and led to a dramatic 82% reduction in peritoneal tumor seeding in vivo. Knockdown of ITGB1 similarly impaired seeding. Mechanistically, FF-derived FN activates the ITGB1/FAK-SRC signaling pathway to promote tumor cell motility and colonization. Our study establishes FF-fibronectin as an important regulator of the early peritoneal seeding of HGSC precursor cells. These findings reveal a direct link between ovulation and HGSC development, suggesting that targeting the FN-ITGB1 signaling axis may offer a novel preventive strategy for high-risk individuals.