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    Publication
    A drop in serum progesterone(p4) levels between 5th and 7th days of triggering ovulation is associated with lower ongoing pregnancy rate(opr) in intrauterine insemination cycles
    (Oxford Univ Press, 2022) Orhan, N.; Gunalp, G. S.; Yarali, H.; Mumusoglu, S.; N/A; Bozdağ, Gürkan; Faculty Member; School of Medicine; 55090
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    PublicationOpen 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; 197389
    Objective: 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.
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    A novel flexible progestin primed ovarian stimulation protocol: comparison of pregnancy outcomes with the flexible GnRH antagonist protocol in an oocyte donation program
    (Elsevier, 2019) Eraslan, Alper; Angun, Berk; N/A; Yıldız, Şule; Türkgeldi, Engin; Ata, Mustafa Barış; Faculty Member; Faculty Member; Faculty Member; School of Medicine; School of Medicine; School of Medicine; Koç University Hospital; Koç University Hospital; N/A; 134205; 329649; 232576
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    Activin-a promotes luteal regression by down-regulating the expression of steroidogenic enzymes and up-regulating BMP-6 and activin-A subunit in human luteal granulosa cells
    (Elsevier, 2015) Güzel, Yılmaz; Seyhan Ata, Ayşe; Balaban, Başak; N/A; Akın, Nazlı; Bildik, Gamze; Urman, Cumhur Bülent; Öktem, Özgür; Master Student; Master Student Faculty Member; Faculty Member; Graduate School of Health Sciences; Graduate School of Health Sciences; School of Medicine; School of Medicine; N/A; N/A; 12147; 102627
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    Add-ons in the art clinic
    (Oxford University Press, 2023) Pinborg, A.; Bentzen, J.; Ebner, T.; Harper, J.; Le Clef, N.; Moffett, A.; Norcross, S.; Polyzos, N. P.; Rautakallio-Hokkanen, S.; Sfontouris, I.; Sermon, K.; Vermeulen, N.; Lundin, K.; Bozdağ, Gürkan;  ; School of Medicine;  
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    Add-ons in the art lab
    (Oxford University Press, 2023) Lundin, K.; Bentzen, J.; Ebner, T.; Harper, J.; Le Clef, N.; Moffett, A.; Norcross, S.; Polyzos, N. P.; Rautakallio-Hokkanen, S.; Sfontouris, I.; Sermon, K.; Vermeulen, N.; Pinborg, A.; Bozdağ, Gürkan;  ; School of Medicine;  
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    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 Medicine
    Objective: 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.
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    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 Hospital
    Reproductive 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.
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    Agonist trigger is associated with defective progesterone production and decreased LH receptor and VEGF expression in luteal granulosa cells that are partially reversed by hCG
    (Oxford University Press (OUP), 2017) Seyhan, A.; Balaban, B.; N/A; N/A; N/A; N/A; Akın, Nazlı; Bildik, Gamze; Urman, Cumhur Bülent; Öktem, Özgür; Master Student; Teaching Faculty; Faculty Member; Faculty Member; Graduate School of Health Sciences; School of Medicine; School of Medicine; School of Medicine; N/A; N/A; 12147; 102627
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    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; 232576
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