Search Results (47)

Background/Objectives: Dual stimulation starting in the follicular phase allows retrieval of more oocytes than single follicular-phase controlled ovarian stimulation (COS). However, dual stimulation excludes fresh embryo transfer (ET), forcing us to postpone the first ET. If dual stimulation is performed in a reverse way (“reverse”-dual stimulation, R-DS), fresh ET can be performed, potentially reducing the time to pregnancy. The aim of the present study is to investigate reproductive outcomes of R-DS compared to two consecutive COS starting in the follicular phase (2FP-COS). Methods: A retrospective study was performed on 146 poor responders matching Bologna criteria, among which 45 underwent R-DS and 101 received 2FP-COS. In the R-DS group, the first COS began 5 days after ovulation and the second 5 days after oocyte retrieval. The primary outcome was the time to pregnancy. Results: In R-DS, stimulation length, retrieved oocytes, and blastocyst formation rate were comparable in the luteal and follicular COS rounds. Circulating progesterone was always <1.0 ng/mL at ovulation trigger, and fresh ET was performed with a mean endometrial thickness of 9.27 ± 2.28 mm. Comparing R-DS and 2FP-COS, no differences were found in terms of retrieved oocytes and cumulative live birth rate; however, the R-DS group showed significantly shorter time to pregnancy (52.9 ± 11.6 vs. 103.2 ± 23.2 days, p < 0.05). Conclusions: This study suggests that R-DS is not inferior to two consecutive COS starting in the follicular phase in terms of oocytes retrieved and cumulative live birth rate. R-DS allows immediate fresh ET and can significantly shorten the time to pregnancy, a relevant issue for poor responders’ patients. Full article

Objective: To systematically analyze and synthesize the evidence from the literature, we compared outcomes of the PPOS + LE protocol versus standard PPOS in patients undergoing IVF. Materials and Methods: We systematically searched the MEDLINE, Scopus, EMBASE, and Science Citation Index databases to identify relevant studies. The clinical questions were developed according to the PICO framework. Quality assessment of the included studies was performed using the Newcastle–Ottawa Scale. Primary outcomes were ovarian stimulation outcomes (oocyte retrieved and mature oocytes). Secondary outcomes were hormonal levels during COS and pregnancy outcome. Results: Five retrospective studies compared oocyte yields between the PPOS and PPOS + LE protocols across diverse populations. While some authors reported significantly higher numbers of retrieved and mature oocytes with letrozole co-administration in a normal infertile population and in POSEIDON group 4, others found no benefit in the PCOS or POSEIDON 3 groups, indicating variable efficacy depending on patient characteristics. Conclusions: Incorporating letrozole counteracts the intense pituitary suppression typically associated with standard PPOS, increasing LH levels and the number of retrieved and mature oocytes in normal and poor responders, but not in PCOS women. Retrospective data do not allow for definitive conclusions to be drawn. Further studies are needed to confirm these results. Full article

The final trigger of oocyte maturation is a pivotal step in assisted reproductive technology (ART). Different molecules and protocols—including human chorionic gonadotropin (hCG), gonadotropin-releasing hormone agonists (GnRHa), the dual trigger, the double trigger, and emerging agents such as kisspeptin—have been investigated to optimize oocyte competence, embryo development, and pregnancy outcomes while minimizing the risk of ovarian hyperstimulation syndrome (OHSS). HCG remains the most widely used trigger, but its pharmacological profile is associated with a significant risk of OHSS. GnRHa has emerged as an alternative in antagonist cycles, abolishing the risk of severe OHSS but often requiring tailored luteal phase support. Several strategies, including hCG, GnRHa, and combined approaches, have shown improvements in specific outcomes such as the oocyte maturity (MII) rate, fertilization rate, embryo development parameters, and, in selected contexts, a reduction in OHSS risk. Kisspeptin represents a promising option; however, its use remains predominantly within the research setting, with clinical application still limited to early-phase or highly selected studies. Beyond the choice of molecule, the timing of trigger administration—adjusted to follicle size, estradiol concentrations, and progesterone levels—also influences oocyte competence and subsequent clinical outcomes. Triggering final oocyte maturation remains a multifaceted decision that should be individualized according to patient characteristics, ovarian response, and risk of OHSS. Although hCG remains the historical reference standard, accumulating but heterogeneous evidence suggests that GnRHa-based strategies, including dual-trigger protocols, may improve specific outcomes in selected patient subgroups. However, results across trials are inconsistent, particularly in poor responders, and any exposure to hCG maintains a residual risk of OHSS. Kisspeptin represents a promising but still experimental option, with current data largely limited to early-phase clinical studies in highly selected high-risk populations. Well-designed randomized trials are required to clarify the true impact of these strategies on live birth, to refine timing and dosing, and to better define which patients are most likely to benefit. Full article

Background/Objectives: Therapeutic resistance remains a major obstacle in breast cancer management, particularly among estrogen receptor-positive (ERα⁺) tumors that initially respond to endocrine therapy such as tamoxifen. Type XI collagen (COL11A1), a minor fibrillar collagen secreted by cancer-associated fibroblasts, has recently emerged as a stromal biomarker linked to tumor progression, immune modulation, and poor prognosis in several solid malignancies. Methods: We conducted a narrative review of the literature indexed in PubMed, Scopus, and Web of Science between 2011 and 2025, including original research, reviews, and clinical studies addressing COL11A1 expression and function in breast cancer. Mechanistic studies in other cancer types (ovarian, pancreatic, lung) were also evaluated when relevant to breast cancer biology. Results: Across multiple cancer types, COL11A1 overexpression correlates with stromal remodeling, epithelial–mesenchymal transition, and resistance to both hormone therapy and chemotherapy. In breast cancer, emerging data suggest a potential prognostic role and possible involvement in shaping the immune microenvironment. Nevertheless, most evidence derives from retrospective or preclinical studies, and clinical validation remains limited. Conclusions: COL11A1 represents a promising, though still exploratory, biomarker of therapeutic resistance and immune modulation in breast cancer. Future prospective and subtype-specific studies are needed to clarify its diagnostic and therapeutic value and to determine whether its inclusion in immunohistochemical panels could enhance patient stratification and guide personalized treatment. Full article

Endometriosis (ENDO) and poor ovarian response (POR) represent challenging conditions in assisted reproduction. Both, associated with altered follicular fluid (FF) composition, specifically impact on granulosa cell (GC) function in an incompletely understood way. GCs from male factor (MF, n = 30), ENDO (n = 38), and POR (n = 27) patients were cultured in media supplemented with FF from each group (FF-MF, FF-ENDO, FF-POR). Proliferation, morphology, and secretory activity (cortisol, estradiol, progesterone, IL-6) were assessed. GC proliferation depended primarily on FF origin, being highest with FF-ENDO, intermediate with FF-POR, and lowest with FF-MF. Morphological analysis revealed enrichment of muscle-like and fibroblast-like morphologies under FF-ENDO and FF-POR, suggestive of dysregulated luteinization and extracellular matrix remodeling. Secretory activity reflected a complex interplay between GC origin and FF type: IL-6 was strongly induced by FF-MF and FF-POR but consistently suppressed by FF-ENDO; cortisol and estradiol were generally consumed, while progesterone synthesis was largely confined to MF-GCs, with only variable induction in ENDO-GCs exposed to FF-POR. These findings indicate that pathological FF milieus reprogram GC behavior in distinct ways, with potential consequences for luteal function and oocyte competence. Identifying the molecular mediators of these alterations may guide tailored strategies to improve ART outcomes in ENDO and POR patients. Full article

Background/Objectives: Fertility preservation is a key component of oncological care. This study evaluated the effectiveness of different controlled ovarian stimulation (COS) protocols, including dual stimulation (DuoStim), for oocyte preservation, with a specific focus on breast cancer patients, and aimed to identify predictors of mature oocyte yield. Methods: A retrospective single-center study was conducted on 203 women under 40 years undergoing fertility preservation before cancer treatment between August 2013 and May 2024 at the Fertility Unit of the University Hospital of Pisa. COS protocols were stratified by menstrual cycle phase: early follicular (EFP), late follicular (LFP), luteal (LP), and DuoStim. The primary outcome was fertility preservation, assessed by the number of mature oocytes retrieved (MII). Independent predictors of oocyte yield were assessed using multivariable Poisson regression. Results: A total of 244 COS cycles were analyzed. The DuoStim group showed a lower median number of MII oocytes collected during the second stimulation compared to EFP, LFP, and LP (all adjusted p-value < 0.05, FDR); however, cumulative MII counts across both stimulations were comparable to other protocols. Oocyte maturity rates were similar across groups. Multivariable analysis identified AMH and AFC, but not age, basal FSH, hormonal parameters, and year of cryopreservation, as independent predictors of MII oocyte yield. Conclusions: COS is effective for fertility preservation across different cycle phases without delaying cancer treatment. DuoStim is not inferior but rather a valuable strategy for poor responders with insufficient oocyte yield after an initial cycle, thereby broadening opportunities for cryopreservation in time-sensitive oncological settings. Full article

Recent progress in assisted reproductive medicine has introduced novel therapeutic possibilities for couples experiencing various reproductive challenges or subfertility. A critical concern in this field is the diminished ovarian response to hormonal treatments preceding ovum pickup, necessitating personalised and optimised protocols to enhance ovarian response across different age groups. Furthermore, a common male factor in IVF couples, oligozoospermia, characterised by a low sperm count, significantly impacts the success rates of assisted reproductive technologies, posing an increasing challenge for in vitro fertilisation clinics. Lifestyle choices, dietary habits, and overall health behaviours have also demonstrably affected fertility outcomes in the 21st century. This original article aims to highlight the synergistic importance of both partners’ health, specifically addressing poor ovarian response and oligozoospermia, in achieving successful conception. Our study analysed intracytoplasmic sperm injection outcomes in couples affected by both aforementioned conditions and proposed an optimal management strategy. This study shows that oligozoospermia significantly reduced ICSI fertilisation and cleavage rates. Poor ovarian responders experienced more cancelled cycles due to fewer embryos. While blastocyst rates relative to zygotes were comparable, overall success was lower in groups with male factor infertility and poor ovarian response, necessitating personalised treatment approaches. Full article

Background and Objectives: Ovarian carcinosarcoma (OCS) is a rare gynecologic malignancy defined by both epithelial and mesenchymal components, generally associated with advanced clinical stage and poor outcomes. We present a 66-year-old patient initially presenting with right iliac vein thrombosis, ultimately diagnosed with OCS, and place these findings in context with a focused literature review from 2000 through to 2024. Methods: A comprehensive account of the patient’s clinical course—spanning diagnostic imaging, surgical pathology, neoadjuvant chemotherapy, and interval debulking—was combined with a review of the current data on OCS pathogenesis, treatment protocols, and outcomes. Results: The patient’s tumor showed predominantly sarcomatous histology (approximately 90%) with high-grade serous features, responded to platinum/taxane chemotherapy, and was resected to no visible residual disease. The updated literature indicates that the majority of OCS cases present at advanced stages (often exceeding 60%), with suboptimal cytoreduction closely tied to worse prognosis. Up to 64% of tumors may harbor homologous recombination deficiency, offering a rationale for PARP inhibitor therapy; nonetheless, five-year survival rarely surpasses 45% in most series. Conclusions: Despite its aggressive course, optimal debulking surgery plus platinum-based chemotherapy remain central in treating OCS. Emerging molecular insights highlight homologous recombination deficiency and BRCA mutations as potential therapeutic targets. Multidisciplinary care and future prospective studies are key to improving long-term outcomes in this challenging malignancy. Full article

Ovarian cancer is a lethal malignancy, with most patients initially responding to chemotherapy but frequently experiencing recurrence. Previous studies primarily examined tumor characteristics using limited genetic markers or bulk RNA sequencing. Here, we used spatial transcriptomics via the GeoMx^® platform, alongside multispectral immune cell immunofluorescence (IF), to identify biomarkers associated with disease progression following first-line treatment of high-grade serous carcinoma (HGSC). We identified several spatial biomarkers linked to non-recurrence, including elevated NKG7 expression in CD45+ immune cell regions (p = 0.0011) and higher TFPI2 and PIGR expression in tumor areas (p = 2.09 × 10⁻⁶), both associated with improved progression-free survival. Multispectral IF revealed significantly higher regulatory T cell (Treg) to CD8+ T cell ratios in the tumor nests and stroma of recurrent patients (p = 0.016, 0.048). Tregs were also found closer to cancer cells or macrophages than CD8+ T cells in recurrent tumors (p = 0.048), correlating with poor survival. Integrated analysis showed that immune cell density and immune pathway scores in the recurrent group positively correlated with cancer pathway scores, except for NF-κB. This comprehensive analysis revealed clues to interactions between different immune cells and identified biomarkers that may be useful for predicting recurrence of HGSC. Full article

Background/Objectives: Poor responder patients represent the greatest challenge in ART. An inadequate response to COS strongly correlates with a reduced chance of conception. A novel classification of poor responders overcame a deficiency in the Bologna criteria and distinguished an expected and unexpected low ovarian response, allowing for an individual treatment approach to be created. In this study, we compared the clinical outcomes in poor responders, according to two different ovarian stimulation protocols, GnRH agonists and antagonists, classified according to the Poseidon criteria, to determine the most effective protocol for each group. Methods: This retrospective study involved 1323 low-prognosis women ranked according to the Poseidon classification and a control group of normal responders. Results: The GnRH-antagonist protocol showed some advantage in the Poseidon 1b group whereas the GnRH-agonist protocol was more effective in the Poseidon 4 group. There were no differences in live births or miscarriage rates in poor responders among these two protocols. Conclusions: Using both the agonist/antagonist approaches, live birth rates are two or even three times less in Poseidon patients in comparison to normal responders. The number of obtained oocytes, their maturity and quality, and women’s ages were found to be the most influential determinants for a successful outcome. Further investigations into ovarian stimulation strategies are required to enhance oocyte number and live birth occurrence. Full article

Background and Objectives: POSEIDON 4 (P4) patients face the most adverse outcomes among poor responders. Oocyte donation has overcome unsatisfactory live birth rates (LBRs) in P4 patients and has become an indispensable approach. However, many patients refuse oocyte donation despite poor live birth likelihood using autologous oocytes. This study aimed to determine clinical outcomes and live birth chances in P4 patients using autologous and donated oocytes. We also identified influencing factors of fertility outcome in P4 patients who underwent donor cycles. Materials and Methods: Retrospective data of 345 P4 patients who explored the first ovarian stimulation cycle (control group) were compared to 105 patients who failed to conceive and underwent repeated autologous ovarian stimulations with an increased starting gonadotropin dose and 100 unpregnant patients who received donated oocytes. Univariate analysis was used to identify prognostic factors of oocyte donation outcomes in P4 patients. Results: LBRs were significantly higher in the donor oocyte group. A higher number of retrieved and good-quality oocytes without differences in the blastocyst number and LBRs were found in the autologous patient group with adjusted gonadotropin dose compared to the control group. Univariate analysis showed that oocyte and embryo quality as well as blastocyst development had a positive impact on live birth in the donor patient group. Conclusions: Autologous in vitro fertilization (IVF) retreating and oocyte donation should be strongly advised for poor-prognosis P4 patients. Still, efforts in tailoring ovarian stimulation to obtain higher oocyte and embryo numbers in autologous cycles should be continued. Full article

Background/Objectives: Ovarian cancer is a complex disease with poor outcomes that affects women worldwide. The lack of successful therapeutic options for this malignancy has led to the need to identify novel biomarkers for patient stratification. Here, we aim to develop the outcome predictors based on the gene expression data as they may serve to identify categories of patients who are more likely to respond to certain therapies. Methods: We used The Cancer Genome Atlas (TCGA) ovarian cancer transcriptomic data from 372 patients and approximately 16,600 genes to train and evaluate the deep learning survival models. In addition, we collected an in-house validation dataset of 12 patients to assess the performance of the trained survival models for their direct use in clinical practice. Despite deceptive generalization capabilities, we demonstrated how our model can be interpreted to uncover biological processes associated with survival. We calculated the contributions of the input genes to the output of the best trained model and derived the corresponding molecular pathways. Results: These pathways allowed us to stratify the TCGA patients into high-risk and low-risk groups (p-value 0.025). We validated the stratification ability of the identified pathways on the in-house dataset consisting of 12 patients (p-value 0.229) and on the external clinical and molecular dataset consisting of 274 patients (p-value 0.006). Conclusions: The deep learning-based models for survival prediction with RNA-seq data could be used to detect and interpret the gene-sets associated with survival in ovarian cancer patients and open a new avenue for future research. Full article

Objective: The objective was to examine the association between poor ovarian response to gonadotropin stimulation for in vitro fertilization (IVF) and adverse perinatal outcomes in singleton gestations in young patients. Methods: This was a retrospective cohort study including women aged 17–39 who underwent fresh embryo transfer and delivered a singleton neonate at a single center (pre-implantation genetic testing excluded) (2007–2022). Patients were classified as one of the following categories: poor responders—daily follicle-stimulating hormone (FSH) ≥ 150 IU yielding ≤ 3 retrieved oocytes; normal responders—4–15 oocytes; and high responders with ≥16 oocytes. The primary outcome was a composite of pre-eclampsia (mild or severe), small-for-gestational-age, gestational diabetes mellitus, and preterm birth (<37 weeks). We compared maternal and neonatal outcomes between the three groups. Multivariable logistic regression was used to control for confounders. Results: Overall, 507 women met the inclusion criteria. Of them, there were 44 (8.68%) poor responders, 342 (67.46%) normal responders, and 121 (23.87%) high responders. Poor responders, compared to normal and high responders, were characterized by a higher maternal age (34.64 ± 4.01 vs. 31.4 ± 5.04 vs. 30.01 ± 4.93, p < 0.001, respectively) and total FSH dosage (3028.41 ± 1792.05 IU vs. 2375.11 ± 1394.05 IU vs. 1869.31 ± 1089.63 IU, p < 0.001). The perinatal outcomes examined, including cesarean delivery (CD) rate and the composite outcome, were comparable between groups. Using multivariable logistic regression and adjusting for ovarian response group, maternal age, nulliparity, and estradiol level and endometrial thickness before ovulation triggering, poor response was not associated with CD rate or the composite outcome, with maternal age associated with CD (p = 0.005), and nulliparity with the composite outcome (p = 0.007). Similar results were obtained when comparing poor responders to each other group separately or to all other responders. Conclusions: Poor ovarian response is not associated with increased adverse maternal or neonatal outcomes. Full article

Prostate cancer remains a significant public health concern in sub-Saharan Africa, particularly impacting South Africa with high mortality rates. Despite many years of extensive research and significant financial expenditure, there has yet to be a definitive solution to prostate cancer. It is not just individuals who vary in their response to treatment, but even different nodules within the same tumor exhibit unique transcriptome patterns. These distinctions extend beyond mere differences in gene expression levels to encompass the control and networking of individual genes. Escalating chemotherapy resistance in prostate cancer patients has prompted increased research into its underlying mechanisms. The heterogeneous nature of transcriptomic organization among men makes the pursuit of universal biomarkers and one-size-fits-all treatments impractical. This study delves into the expression of drug resistance-associated genes, ABCB1 and CYP1B1, in cancer cells. Employing bioinformatics, we explored the molecular pathways and cascades linked to drug resistance following upregulation of these genes. Samples were obtained from archived prostate cancer patient specimens through pre-treatment biopsies of two categories: good vs. poor responders, with cDNAs synthesized from isolated RNAs subjected to qPCR analysis. The results revealed increased ABCB1 and CYP1B1 expression in tumor samples of the poor responders. Gene enrichment and network analysis associated ABCB1 with ABC transporters and LncRNA-mediated therapeutic resistance (WP3672), while CYP1B1 was linked to ovarian steroidogenesis, tryptophan metabolism, steroid hormone biosynthesis, benzo(a)pyrene metabolism, the sulindac metabolic pathway, and the estrogen receptor pathway, which are associated with drug resistance. Both ABCB1 and CYP1B1 correlated with microRNAs in cancer and the Nuclear Receptors Meta-Pathway. STRING analysis predicted protein–protein interactions of ABCB1 and CYP1B1 with Glutathione S-transferase Pi, Catechol O-methyltransferase, UDP-glucuronosyltransferase 1-6, Leucine-rich Transmembrane and O-methyltransferase (LRTOMT), and Epoxide hydrolase 1, with scores of 0.973, 0.971, 0.966, 0.966, and 0.966, respectively. Furthermore, molecular docking analysis of the chemotherapy drug, docetaxel, with CYP1B1 and ABCB1 revealed robust molecular interactions, with binding energies of −20.37 and −15.25 Kcal/mol, respectively. These findings underscore the susceptibility of cancer patients to drug resistance due to increased ABCB1 and CYP1B1 expression in tumor samples from patients in the poor-responders category that affects associated molecular pathways. The potent molecular interactions of ABCB1 and CYP1B1 with docetaxel further emphasize the potential basis for chemotherapy resistance. Full article

Platelet-rich plasma is an autologous plasma containing platelets prepared from fresh whole blood drawn from a peripheral vein. Through processing, it can be prepared to contain supraphysiologic levels of platelets at three to five times greater than the level of normal plasma. PRP has been explored both in vivo and ex vivo in the human endometrium model in its ability to harness the intrinsic regenerative capacity of the endometrium. Intrauterine autologous PRP infusions have been shown to increase endometrial thickness and reduce the rate of intrauterine adhesions. In the setting of recurrent implantation failure, intrauterine infusion of PRP has been shown to increase clinical pregnancy rate. PRP also appears to hold a potential role in select patients with premature ovarian insufficiency, poor ovarian responders and in improving outcomes following frozen–thawed transplantation of autologous ovarian tissue. Further studies are required to explore the potential role of PRP in reproductive medicine further, to help standardise PRP protocols and evaluate which routes of administration are most effective. Full article