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Publication Metadata only A comparison of the survival and implantation rates of blastocysts that were vitrified on postfertilization day five, six and seven(Taylor & Francis Ltd, 2019) Berrin, Avci; Isil, Kasapoglu; Goktan, Kuspinar; Seda, Saribal; Gurkan, Uncu; N/A; Ata, Mustafa Barış; Faculty Member; School of Medicine; 182910The goal of this retrospective cohort study was to compare survival, implantation, clinical and ongoing pregnancy rates between blastocysts that were vitrified on post-fertilization days 5, 6 and 7. Before vitrification, blastocysts were evaluated in terms of morphology and blastocyst expansion, inner cell mass and trophectoderm quality. They were thawed and transfered in a subsequent artificial cycle. Embryo implantation rates were 39%, 25% and 25% for blastocysts that were vitrified on days 5, 6, and 7, respectively (p = 0.006). Clinical and ongoing pregnancy rates were 19%, 12%, 13% (p = 0.100) and 9%, 7%, 12% (p = 0.99) for days 5, 6 and 7 blastocysts, respectively. Day 5 blastocysts had significantly higher full-collapsing score after assisted-hatching compared to days 6 and 7 blastocysts (p = 0.014). As blastocyst quality increased, implantation and clinical pregnancy rates increased in all groups and both parameters were statistically significantly higher on day 5 blastocysts than on days 6 or 7 (p = 0.001). It was clearly found that good quality blastocysts obtained on day 5 have higher implantation and clinical pregnancy rates than 6th and 7th day cryopreserved embryos. There were no statistically significant differences between the cryopreserved embryos on days 6 and 7 regarding the implantation, clinic and ongoing pregnancy rates.Publication Open Access A new definition of recurrent implantation failure on the basis of anticipated blastocyst aneuploidy rates across female age(Elsevier, 2021) Somigliana, Edgardo; Ata, Mustafa Barış; Kalafat, Erkan; Faculty Member; Faculty Member; School of Medicine; Koç University Hospital; 182910; 197389Objective: to present a definition of recurrent implantation failure that accounts for the effects of female age and anticipated blastocyst euploidy rates on cumulative implantation rates. Design: mathematical modeling. Setting: not applicable. Patient(s): not applicable. Intervention(s): mathematical modeling of cumulative implantation probability on the basis of published blastocyst euploidy rates across categories of female age. Main Outcome Measure(s): the number of blastocysts required to achieve 95% cumulative implantation probability under the assumption of the absence of any other factor affecting implantation. Result(s): when the euploidy status of the transferred embryo is unknown (i.e., not subjected to preimplantation genetic testing for aneuploidies), our simulation shows that no age category reaches 95% cumulative probability of implantation of at least one embryo until after transfer of seven blastocysts. The number of blastocysts required to reach the same threshold is higher for older patients. For example, women older than 38 years require transfer of more than 10 untested blastocysts for the upper range of predictive probability to meet the threshold of 95%. On the other hand, if the implantation rate for a euploid blastocyst is assumed to be 55%, then 4 blastocysts are enough to reach a cumulative probability rate greater than 95%, regardless of age. Conclusion(s): the term ""recurrent implantation failure""should be a functional term guiding further management. We suggest that recurrent implantation failure should not be called until implantation failure becomes reasonably likely to be caused by factors other than embryo aneuploidy, the leading cause of implantation failure. We propose a new definition that factors in anticipated blastocyst euploidy rates across categories of female age, euploid blastocyst implantation rate, and a specified threshold of cumulative probability of implantation. / Objetivo: Presentar una definicion de fallo recurrente de implantacion que tenga en cuenta los efectos de la edad de la mujer y las tasasanticipadas de euploidia de blastocisto sobre las tasas acumulativas de implantacion. Dise no: modelo matematico. Lugar: no aplicable. Pacientes(s): no aplicable. Intervencion(es): modelo matematico de probabilidad acumulativa de implantacion basado en las tasas de euploidia de blastocistopublicadas segun categorias de edad de la mujer. Principal(es) medida(s) de resultado(s): el numero de blastocistos requerido para obtener una probabilidad acumulativa de im-plantacion del 95% asumiendo la ausencia de cualquier otro factor que afecte la implantacion. Resultado(s): cuando es estado de euploidia del embrion transferido es desconocido (i.e., no sujeto a diagnostico genetico preimplan-tacional para aneuploidias), nuestra simulacion demuestra que ninguna categoria de edad llega al 95% de probabilidad acumulativa deimplantacion de al menos un embrion hasta despues de transferir siete blastocistos. El numero de blastocistos requeridos para alcanzarel mismo nivel es mayor en pacientes mayores. Por ejemplo, las mujeres mayores de 38 anos requieren transferencia de mas de 10 blas-tocistos sin evaluar para que el rango superior de probabilidad predictiva alcance el nivel de 95%. Por otra parte, si la tasa de im-plantacion de un blastocisto euploide se estima en 55%, entonces 4 blastocistos son suficientes para alcanzar una tasa deprobabilidad acumulativa mayor del 95%, sin importar la edad. Conclusion(es): el termino ‘‘fallo recurrente de implantacion’’debería ser un termino funcional para guiar el manejo posterior. Suger-imos que no deberia llamarse fallo recurrente de implantacion hasta que sea razonablemente probable que el fallo de implantacion seacausado por otros factores ademas de la aneuploidía embrionaria, la principal causa de fallo de implantacion. Proponemos una nuevadefinicion que tenga en cuenta las tasas anticipadas de euploidia de blastocistos segun categorias de edad de la mujer, tasa de im-plantacion de blastocisto euploide y un nivel especifico de probabilidad acumulativa de implantacion.Publication Metadata only A systematic review of uterine cervical elongation and meta-analysis of Manchester repair(ELSEVIER, 2024) Aktoz, Fatih; Çekiç, Sebile Güler; Urman, Cumhur Bülent; Aydın, Serdar; School of Medicine; Koç University HospitalObjective: This review aims to consolidate current research on cervical elongation, a common but often overlooked complication in pelvic organ prolapse and hysteropexy procedures. It seeks to define, diagnose, and manage cervical elongation, aiming to establish standardized criteria and strategies to enhance clinical outcomes for this condition. Data Sources: A comprehensive search of the PubMed/MEDLINE, Cochrane Library, and Web of Science databases was executed utilizing the keywords: "cervical elongation," "long cervix uteri," "Manchester," and "cervical amputation". Data were gathered and organized in an Excel spreadsheet, with the analysis conducted according to each category, methodology, or reference range. Study Eligibility Criteria: All types of study designs with full-text availability, including randomized controlled trials, cohort studies, case-control studies, case reports, and systematic reviews, were considered for inclusion. Included studies were fully accessible in English and focused on the topic of interest. Exclusions were made for studies addressing cervical elongation not pertinent to pelvic organ prolapse, and publications such as secondary analyses, case reports, literature reviews, and opinion papers. Results: Out of 108 relevant studies, only 63 defined their inclusion criteria; of these, 57 were utilized for the narrative review and 8 were used in a meta-analysis comparing the Manchester operation with vaginal hysterectomy. Magnetic Resonance Imaging offers the highest sensitivity in measuring cervical elongation, its practical limitations and high cost necessitate the use of the more feasible Pelvic Organ Prolapse Quantification System (POP-Q), particularly effective for stage 2 and 3 prolapse cases. The POP-Q point C emerges as a pivotal marker for identifying cervical elongation, with specific measurements indicating the condition's presence. The Manchester-Fothergill procedure presents a viable management option for isolated cervical elongation, showing fewer complications and comparable recurrence rates to vaginal hysterectomy. Conclusion: This review highlights the diagnostic and definitional diversity of cervical elongation within populations experiencing pelvic organ prolapse. It emphasizes the critical role of preoperative cervical evaluation, particularly in patients with uterine descensus for selecting the most appropriate surgical intervention.Publication Metadata only Adenomyosis: single-cell transcriptomic analysis reveals a paracrine mesenchymal-epithelial interaction involving the WNT/SFRP pathway(Elsevier Science Inc, 2023) Kinali, Meric; Wei, Jian Jun; Milad, Magdy; Yin, Ping; Adli, Mazhar; Bulun, Serdar E.; Yıldız, Şule; School of MedicineObjective: To assess the cellular and molecular landscape of adenomyosis.Design: Single-cell analysis of genome-wide messenger RNA (mRNA) expression (single-cell RNA sequencing) of matched tissues of endometrium, adenomyosis, and myometrium using relatively large numbers of viable cells.Setting: Not applicable. Patient(s): Patients (n 1/4 3, age range 40-44 years) undergoing hysterectomy for diffuse adenomyosis. Main Outcome Measure(s): Definition of the molecular landscape of matched adenomyotic, endometrial and myometrial tissues from the same uterus using single-cell RNA sequencing and comparison of distinct cell types in these tissues to identify disease-specific cell populations, abnormal gene expression and pathway activation, and mesenchymal-epithelial interactions.Result(s): The largest cell population in the endometrium was composed of closely clustered fibroblast groups, which comprise 36% of all cells and seem to originate from pericyte progenitors differentiating to estrogen/progesterone receptor-expressing endometrial stromal-cells. In contrast, the entire fibroblast population in adenomyosis comprised a larger (50%) portion of all cells and was not linked to any pericyte progenitors. Adenomyotic fibroblasts eventually differentiate into extracellular matrix protein-expressing fibroblasts and smooth muscle cells. Hierarchical clustering of mRNA expression revealed a unique adenomyotic fibroblast population that clustered transcriptomically with endometrial fibroblasts, suggestive of an endometrial stromal cell population serving as progenitors of adenomyosis. Four other adenomyotic fibroblast clusters with disease-specific transcriptomes were distinct from those of endometrial or myometrial fibroblasts. The mRNA levels of the natural WNT inhibitors, named, secreted frizzled-related proteins 1, 2, and 4, were higher in these 4 adenomyotic fibroblast clusters than in endometrial fibroblast clusters. Moreover, we found that multiple WNTs, which originate from fibroblasts and target ciliated and unciliated epithelial cells and endothelial cells, constitute a critical paracrine signaling network in adenomyotic tissue. Compared with endometrial tissue, unciliated and ciliated epithelial cells in adenomyosis comprised a significantly smaller portion of this tissue and exhibited molecular evidence of progesterone resistance and diminished regulation of estrogen signaling.Conclusion(s): We found a high degree of heterogeneity in fibroblast-like cells in the adenomyotic uterus. The WNT signaling involving differential expression of secreted frizzled-related proteins, which act as decoy receptors for WNTs, in adenomyotic fibroblasts may have a key role in the pathophysiology of this disease.Publication Metadata only Advancements in three-dimensional bioprinting for reproductive medicine: a systematic review(Elsevier Sci Ltd, 2024) Aydın, Serdar; Yaşlı, Mert; Yıldız, Şule; Urman, Cumhur Bülent; School of Medicine; Koç University HospitalReproductive failure due to age, genetics and disease necessitates innovative solutions. While reproductive tissue transplantation has advanced, ongoing research seeks superior approaches. Biomaterials, bioengineering and additive manufacturing, such as three-dimensional (3D) bioprinting, are harnessed to restore reproductive function. 3D bioprinting uses materials, cells and growth factors to mimic natural tissues, proving popular for tissue engineering, notably in complex scaffold creation with cell distribution. The versatility which is brought to reproductive medicine by 3D bioprinting allows more accurate and on-site applicability to various problems that are encountered in the field. However, in the literature, there is a lack of studies encompassing the valuable applications of 3D bioprinting in reproductive medicine. This systematic review aims to improve understanding, and focuses on applications in several branches of reproductive medicine. Advancements span the restoration of untapped potential in reproductive medicine.Publication Metadata only Altered expression of Notch signaling, Tlr receptors, and surfactant protein expression after prostaglandin inhibition may be associated with the delayed labor in LPS-induced mice(Springer/Plenum Publishers, 2022) Avcı, Sema; Kuşçu, Nilay; Durkut, Begüm; Kılınç, Leyla; Üstünel, İsmail; N/A; Özenci, Çiler Çelik; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; 127168Purpose This study aims to investigate whether indomethacin (IND) delays preterm birth by regulating the Notch pathway, Tlr receptors, and Sp-A in the placenta in lipopolysaccharide (LPS)-induced preterm labor (PTL) model. Methods CD-1 mice were distributed to the pregnant control (PC), Sham, PBS, IND (2 mg/kg; i.p.), LPS (25 mu g/100 mu l; intrauterine), and LPS + IND groups. The injections were performed on day 14.5 of pregnancy. Placentae were collected on day 15.5 of pregnancy, and immunohistochemical analyzes were performed. Differences in staining intensities between the Cox-1, Notch-1 (N1), Dll-1, Jagged-2 (Jag-2), Tlr-2, and Tlr-4 proteins were compared. Results Preterm labor rates were 100% and 66% (preterm delivery delayed 5 h) in the LPS and LPS + IND groups, respectively. In LPS-treated mice, a general morphological deterioration was observed in the placenta. Total placental mid-sagittal measurement was significantly reduced in the LPS-treated group, while it was similar to the PC group in the LPS + IND group. Cox-1 expression in the LZ increased, and Sp-A expression decreased after LPS injection, and IND administration diminished this increase. N1 expression increased in the labyrinth zone (LZ) and the junctional zone (JZ). Dll-1 and Jag-2 expression increased in the JZ after LPS injection (p < 0.0001). IND administration diminished Tlr-2 expression in the LZ and Tlr-4 expression in the JZ after LPS injection. Conclusion In conclusion, PG (prostaglandin) inhibition may alter Notch signaling, Tlr, and Sp-A protein expression and may be associated with delayed labor in LPS-induced mice.Publication Open Access An example from the rural areas of Turkey: women breast cancer risk levels and application and knowledge regarding early diagnosis-scan of breast cancer(Aves, 2017) Türk, Rukiye; Terzioglu, Füsun; Taşkın, Lale; N/A; Eroğlu, Kafiye; Faculty Member; School of Nursing; 6061Objective: This research has been conducted for the purpose of determining the cancer risk levels of women living in a small village of in Saraycık village of Ankara and their knowledge and application of breast cancer early diagnose-scan methods. Materials and Methods: 317 women were taken as examples for the study. Data were collected by giving survey forms to women and conducting face-to-face interviews. In determining breast cancer risk, ''the form to determine the breast cancer risk'' has been used. For breast cancer informational questions, one point has been given for each correct answer. In evaluating the data, number, percentage calculations, average and standard deviation, Mann-Whitney U (MU), Kruskal-Wallis (KW), One-way analysis of variance (F) independent sample T (t) tests have been used. Results: It has been found that breast cancer risk is low, the knowledge level about cancer early recognition methods are medium among the women. It has been determined that 74.4% women didn't perform breast self-examination. 89.6% of women don't have mammography taken and 88.6% don't have their breast examined by health personnel. Conclusion: In our study, it has been found that the risk levels of women are low, their knowledge about early diagnosis and cure are at a medium level and their use of these methods are inadequate. For this reason, we suggest that responsibility of healthcare professionals have to be increased in determining breast cancer risk among women and education and advisory services for this subject to be offered.Publication Metadata only Anogenital distance in newborn infants conceived by assisted reproduction and natural conception(Oxford Univ Press, 2020) Ercin, S.; Ertas, S.; Dundar, O.; N/A; Öktem, Özgür; Yakın, Kayhan; Faculty Member; Faculty Member; School of Medicine; School of Medicine; 102627; 106822N/APublication Metadata only Application of seminal plasma to female genital tract prior to embryo transfer in assisted reproductive technology cycles (IVF, ICSI and frozen embryo transfer)(Oxford Univ Press, 2018) Abou Setta, A.; Seyhan, A.; Buckett, W.; N/A; Ata, Mustafa Barış; Faculty Member; School of Medicine; 232576N/APublication Metadata only Can endometrial compaction predict live birth rates in assisted reproductive technology cycles? a systematic review and meta-analysis(Springer/Plenum Publishers, 2023) Türkgeldi, Engin; Yıldız, Şule; Kalafat, Erkan; Keleş, İpek; Ata, Mustafa Barış; Bozdağ, Gürkan; School of Medicine; Koç University HospitalPurpose: Endometrial compaction (EC) is defined as the difference in endometrial thickness from the end of the follicular phase to the day of embryo transfer (ET). We aimed to determine the role of EC in predicting assisted reproductive technology (ART) success by conducting a meta-analysis of studies reporting the association between EC and clinical outcomes of ART. Methods: MEDLINE via PubMed, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched from the date of inception to May 19, 2023. The primary outcome was live birth rate (LBR) per ET. Secondary outcomes were live birth or ongoing pregnancy per ET, ongoing pregnancy per ET, clinical pregnancy per ET, and miscarriage per clinical pregnancy. Results:Fifteen studies were included. When data from all studies reporting live birth were pooled, overall LBR rates were comparable in cycles showing EC or not [RR = 0.97, 95%CI = 0.92 to 1.02;10 studies, 11,710 transfer cycles]. In a subgroup of studies that included euploid ET cycles, a similar LBR for patients with and without EC was noted [RR = 0.99, 95%CI = 0.86 to 1.13, 4 studies, 1172 cycles]. The miscarriage rate did not seem to be affected by the presence or absence of EC [RR = 1.06, 95%CI = 0.90 to 1.24;12 studies]. Conclusion: The predictive value of EC in determining LBR is limited, and assessment of EC may no longer be necessary, given these findings. Trial registration: PROSPERO CRD42023410389