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Publication Metadata only 3D ultrasound assessment of effect of controlled ovarian stimulation on endometrioma volume(Oxford University Press (OUP), 2016) Seyhan, A.; Balaban, B.; Urman, Cumhur Bülent; Ata, Mustafa Barış; Faculty Member; Faculty Member; School of Medicine; School of Medicine; 12147; 232576N/APublication Metadata only A Bayesian generalized linear model for Crimean–Congo hemorrhagic fever incidents(Springer, 2018) Ryu, Duchwan; Bilgili, Devrim; Liang, Faming; Ebrahimi, Nader; Ergönül, Önder; Faculty Member; School of Medicine; 110398Global spread of the Crimean-Congo hemorrhagic fever (CCHF) is a fatal viral infection disease found in parts of Africa, Asia, Eastern Europe and Middle East, with a fatality rate of up to 30%. A timely prediction of the prevalence of CCHF incidents is highly desirable, while CCHF incidents often exhibit nonlinearity in both temporal and spatial features. However, the modeling of discrete incidents is not trivial. Moreover, the CCHF incidents are monthly observed in a long period and take a nonlinear pattern over a region at each time point. Hence, the estimation and the data assimilation for incidents require extensive computations. In this paper, using the data augmentation with latent variables, we propose to utilize a dynamically weighted particle filter to take advantage of its population controlling feature in data assimilation. We apply our approach in an analysis of monthly CCHF incidents data collected in Turkey between 2004 and 2012. The results indicate that CCHF incidents are higher at Northern Central Turkey during summer and that some beforehand interventions to stop the propagation are recommendable. Supplementary materials accompanying this paper appear on-line.Publication Metadata only A comprehensive comparative transcriptional and translational analyses of the impact of ovarian response type, stimulation protocol and mode of trigger on the luteal function(Elsevier Science Inc, 2018) Seyhan, A; Yakın, Kayhan; Ata, Mustafa Barış; Öktem, Özgür; Bildik, Gamze; Urman, Cumhur Bülent; Faculty Member; Faculty Member; Faculty Member; Teaching Faculty; Faculty Member; School of Medicine; School of Medicine; School of Medicine; School of Medicine; School of Medicine; Koç University Hospital; 106822; 182910; 102627; N/A; 12147Objective: We aimed to compare molecular characteristics of the luteal granulosa cells between natural vs. stimulated IVF cycles in good and poor-responders. Design: Translational research study. Materials and Methods: Luteinized granulosa cells were obtained from good (n=154) and poor responder (n=64) IVF patients comparable for age, type and dose of gonadotropin and IVF etiology. Good-responders (4-15 oocytes) underwent natural (n=22), GnRH agonist (long protocol n=44) and antagonist IVF cycles triggered with rec-hCG (n=46) or GnRH agonist leuprolide acetate (n=42). Poor-responders fulfilling the Bologna criteria consisted of 64 patients undergoing GnRH antagonist protocol triggered with hCG (n=36) or hCG+GnRH agonist (n=28). Results: In the good-responders, natural cycle (NC) granulosa cells were significantly more viable (88%) compared to the stimulated IVF cycles (66%, 64% and 37% for agonist and antagonist cycles triggered with hCG and agonist respectively, p<0.05). The mRNA expression of steroidogenic enzymes (SCC, stAR, 3B-HSD, 17B-HSD and aromatase), LH receptor and VEGF and in vitro E2 and P productions were comparable between hCG-triggered agonist and antagonist cycles, but significantly higher than NC in the first days of culture. However, on the following days their hormone productions and viability began to decline very rapidly with the most drastic decrease being observed in the agonist triggered cycles. By contrast, NC granulosa cells maintained their viability and produced E 2 and P in increasing amounts in culture up to six days. The expression of anti-apoptotic genes (AKT-1, BCL2-L2) were significantly lower, and pro-apoptotic genes (BAD, BID, BAX, Cas3) were significantly higher in the stimulated cycles particularly in the agonist triggered ones compared to NC granulosa cells. Pulse exposure to cisplatin induced apoptosis only in a small fraction of the cells from the NCs whereas the same exposure caused massive apoptosis in the cells of the stimulated cycles (27% vs. 78% respectively, p<0.01). In the poor-responders both viability and steroidogenic activity of the cells were more severely reduced compared to the antagonist cycles of the good-responders. There were no significant differences between hCG and hCG+agonist triggered cycles in terms of viability, hormone production, VEGF and LH receptor expressions in the luteal granulosa cells. Conclusions Reduced survival and increased apoptosis of luteal granulosa cells leading to defective steroid production in stimulated cycles in comparison to natural ones may at least in part explain why luteal phase is defective and requires exogenous P supplementation for support in these cycles. Also dual trigger does not appear to improve luteal function in the poor-responders.Publication Metadata only A novel and simple method to schedule GNRH antagonist cycles with a short course of oral estradiol in the early follicular phase(Oxford Univ Press, 2019) Angun, B.; Türkgeldi, Engin; Yıldız, Şule; Ata, Mustafa Barış; Faculty Member; Faculty Member; Faculty Member; School of Medicine; School of Medicine; School of Medicine; Koç University Hospital; 329649; 134205; 182910N/APublication Metadata only A novel flexible progestin primed ovarian stimulatıon protocol: Comparıson of pregnancy outcomes with the flexible GnRH antagonist protocol in an oocyte donation program(Oxford Univ Press, 2019) Angun, B.; N/A; Yıldız, Şule; Türkgeldi, Engin; Ata, Mustafa Barış; Faculty Member; Faculty Member; Faculty Member; School of Medicine; Koç University Hospital; 134205; 329649; 182910N/APublication Metadata only A survey of women who cryopreserved oocytes for non-medical indications(Elsevier Science Inc, 2017) N/A; N/A; N/A; N/A; Ata, Ayşe Seyhan; Akın, Öznur Dündar; Urman, Cumhur Bülent; Yakın, Kayhan; Doctor; Doctor; Faculty Member; Faculty Member; N/A; N/A; School of Medicine; School of Medicine; American Hospital; N/A; N/A; 12147; 106822Objective: What are the expectations, experiences, and fertility awareness status of women who underwent social oocyte cryopreservation? Design: All women who underwent social oocyte cryopreservation between January 2015 and June 2016 were recruited. One hundred thirty three women were invited to participate in a survey at least 6 months after completion of the treatment cycle. Materials and Methods: Eigthy-one patients completed the survey.All women were given personalized counselling before starting the treatment cycle. Counselling included, chances of natural conception at a given age and the concept of ovarian reserve. The questionnaire investigated initial motivation towards freezing, intentions to use cryopreserved oocytes, treatment experience, awareness of fertility and knowledge about chances of having a live birth with their frozen oocytes. Results: The mean (± standard deviation) age at the time of oocyte freezing was 38.5 ± 2.68 years. The average number (min - max) of mature oocytes cryopreserved was 5.48 ± 6.6 (1-16). Two major motivations were absence of a male partner at the time of decision (40%) and an anticipated age-related fertility decline (42%). Majority of women (42%) opted to limit the use of cryopreserved oocytes up to the age of 45, and 51% of bankers wished that they had completed their family by the age of 35. 41% of the women told that they would donate their oocytes for research, 35% discard, and 24% donate to other infertile couples, if they did not use for own reproduction. 54% of patients thought that they did not have an adequate number of stored oocytes, 43 % wanted to do another cycle. 59% of the latter, were not able to undergo another cycle since they couldn’t afford another cycle. 42% and 35% of the women reported anxiety and injections, respectively, as the most challenging factor during treatment. Almost 60% overestimated the chances of natural conception, as well as the success of IVF at the age of 40 years. Half of the oocyte bankers reported that fertility declined between ages 35-39 but only 28% of patients estimated the live birth rate per cryopreserved oocyte correctly. Overall 98.8% stated that they would recommend oocyte cryopresevation to a friend and 72% felt more secure in terms of reproductive potential. Conclusions: Despite comprehensive personalized counselling prior to the start of ovarian stimulation, many women, as well as some health care policy makers do not seem to have a realistic understanding of reproductive ageing. Overestimaing effectiveness of assisted reproductive technology and arbitrarily delaying childbearing can lead to future childlessnes. Even though gamete cryopreservation provides some insurance, overestimating the effectiveness of oocyte cryopreservation can also lead to a false sense of security. Increasing awareness and knowledge about reproductive ageing is needed.Publication Metadata only A survey of women who cryopreserved oocytes for non-medical indications (social fertility preservation)(Springer, 2021) Akin, Öznur Dündar; Ertaş, Sinem; N/A; N/A; N/A; N/A; Ata, Ayşe Seyhan; Ata, Mustafa Barış; Yakın, Kayhan; Urman, Cumhur Bülent; Doctor; Faculty Member; Faculty Member; Faculty Member; N/A; School of Medicine; School of Medicine; School of Medicine; American Hospital; School of Medicine; N/A; N/A; N/A; 182910; 106822; 12147To evaluate the expectations, experiences, and fertility awareness status of women who underwent social oocyte cryopreservation. Cohort survey study was conducted at an academic medical center. All women who underwent social oocyte cryopreservation between January 2015 and June 2016 were recruited. One hundred thirty-three women were contacted by phone to participate in a survey. The questionnaire investigated the initial motivation towards freezing, intentions to use cryopreserved oocytes, treatment experience, awareness of fertility and knowledge about chances of having a live birth with their frozen oocytes. The mean age at the time of oocyte freezing was 38.5 +/- 2.68 years. The average number of mature oocytes cryopreserved was 5.48 +/- 6.6 (1-16). Two major motivations were absence of a male partner (40%) and an anticipated age-related fertility decline (42%). Almost 60% overestimated the chances of natural conception, as well as the success of IVF at the age of 40 years. Half of the oocyte bankers reported that fertility declined between ages 35 and 39, but only 28% of patients estimated the live birth rate per cryopreserved oocyte correctly. Overall 98.8% stated that they would recommend oocyte cryopresevation to a friend, and 72% felt more secure in terms of reproductive potential. Despite comprehensive personalized counseling prior to the start of ovarian stimulation, many women do not seem to have a realistic understanding of reproductive aging. Even though gamete cryopreservation provides some insurance, overestimating the effectiveness of oocyte cryopreservation can also lead to a false sense of security.Publication Metadata only Adaptive tracking algorithm for trajectory analysis of cells and layer-by-layer assessment of motility dynamics(Pergamon-Elsevier Science Ltd, 2022) Bayraktar, Halil; N/A; Department of Molecular Biology and Genetics; Qureshi, Mohammad Haroon; PhD Student; Faculty Member; Department of Molecular Biology and Genetics; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); N/A; Graduate School of Sciences and Engineering; College of Sciences; N/A; 105301Tracking biological objects such as cells or subcellular components imaged with time-lapse microscopy enables us to understand the molecular principles about the dynamics of cell behaviors. However, automatic object detection, segmentation and extracting trajectories remain as a rate-limiting step due to intrinsic challenges of video processing. This paper presents an adaptive tracking algorithm (Adtari) that automatically finds the op-timum search radius and cell linkages to determine trajectories in consecutive frames. A critical assumption in most tracking studies is that displacement remains unchanged throughout the movie and cells in a few frames are usually analyzed to determine its magnitude. Tracking errors and inaccurate association of cells may occur if the user does not correctly evaluate the value or prior knowledge is not present on cell movement. The key novelty of our method is that minimum intercellular distance and maximum displacement of cells between frames are dynamically computed and used to determine the threshold distance. Since the space between cells is highly variable in a given frame, our software recursively alters the magnitude to determine all plausible matches in the trajectory analysis. Our method therefore eliminates a major preprocessing step where a constant distance was used to determine the neighbor cells in tracking methods. Cells having multiple overlaps and splitting events were further evaluated by using the shape attributes including perimeter, area, ellipticity and distance. The features were applied to determine the closest matches by minimizing the difference in their magnitudes. Finally, reporting section of our software were used to generate instant maps by overlaying cell features and trajectories. Adtari was validated by using videos with variable signal-to-noise, contrast ratio and cell density. We compared the adaptive tracking with constant distance and other methods to evaluate performance and its efficiency. Our algorithm yields reduced mismatch ratio, increased ratio of whole cell track, higher frame tracking efficiency and allows layer-by-layer assessment of motility to characterize single-cells. Adaptive tracking provides a reliable, accurate, time efficient and user-friendly open source software that is well suited for analysis of 2D fluorescence microscopy video datasets.Publication Metadata only Anomalies in the transcriptional regulatory network of the Yeast Saccharomyces cerevisiae(Elsevier, 2010) N/A; Department of Physics; Tuğrul, Murat; Kabakçıoğlu, Alkan; N/A; Faculty Member; Department of Physics; Graduate School of Sciences and Engineering; College of Sciences; N/A; 49854We investigate the structural and dynamical properties of the transcriptional regulatory network of the Yeast Saccharomyces cerevisiae and compare it with two "unbiased" ensembles: one obtained by reshuffling the edges and the other generated by mimicking the transcriptional regulation mechanism within the cell. Both ensembles reproduce the degree distributions (the first-by construction-exactly and the second approximately), degree-degree correlations and the k-core structure observed in Yeast. An exceptionally large dynamically relevant core network found in Yeast in comparison with the second ensemble points to a strong bias towards a collective organization which is achieved by subtle modifications in the network's degree distributions. We use a Boolean model of regulatory dynamics with various classes of update functions to represent in vivo regulatory interactions. We find that the Yeast's core network has a qualitatively different behavior, accommodating on average multiple attractors unlike typical members of both reference ensembles which converge to a single dominant attractor. Finally, we investigate the robustness of the networks and find that the stability depends strongly on the used function class. The robustness measure is squeezed into a narrower band around the order-chaos boundary when Boolean inputs are required to be nonredundant on each node. However, the difference between the reference models and the Yeast's core is marginal, suggesting that the dynamically stable network elements are located mostly on the peripherals of the regulatory network. Consistently, the statistically significant three-node motifs in the dynamical core of Yeast turn out to be different from and less stable than those found in the full transcriptional regulatory network.Publication Metadata only Are live birth rate and obstetric outcomes different between immediate and delayed embryo transfers following a freeze-all cycle? a retrospective study combined with a meta-analysis(Oxford Univ Press, 2021) N/A; N/A; N/A; N/A; N/A; N/A; Yıldız, Şule; Türkgeldi, Engin; Kalafat, Erkan; Gökyer, Dilan; Keleş, İpek; Ata, Mustafa Barış; Faculty Member; Faculty Member; Faculty Member; Undergraduate Student; Doctor; Faculty Member; School of Medicine; School of Medicine; School of Medicine; School of Medicine; N/A; School of Medicine; Koç University Hospital; 134205; 329649; 197389; N/A; N/A; 182910Study Question: Do livebirth rate (LBR), obstetric and perinatal outcomes vary between frozen embryo transfers (FET) in the first or subsequent menstrual cycles following a freeze-all approach? Summary Answer: Immediate FET has a higher LBR and similar perinatal outcomes than delayed FET. Quantitative synthesis of available literature shows an increased LBR with immediate transfer. What is Known Already: Whether FET should be done in the first menstrual cycle following oocyte collection (OC) is controversial and the duration of a possible detrimental effect of supraphysiological sex steroid levels on pregnancy outcome is unknown. A multinational survey centers showed that, 61% of clinicians prefer to wait for a washout period before proceeding to FET, even after a failed fresh embryo transfer. Limited number of studies compared FET in the first menstrual cycle with delayed FET in a subsequent cycle with varying results. There is limited data on obstetric outcomes of pregnancies resulting from FET in the first menstrual cycle. Study Design, Size, Duration: 198 women who underwent a freeze-all cycle followed by FET between July 2017 and June 2020 were included. 119 FET in the first menstrual cycle (<30 days from oocyte collection) and 79 FET in subsequent cycles (>30 days from oocyte collection) were retrospectively compared. MEDLINE was searched on 01 January 2021 using relevant keywords. Cohort studies comparing immediate versus delayed transfer following freeze all cycles were included and quantitative summary for LBR was obtained. Participants/Materials, Setting, Methods: Freeze-all was undertaken when (i) the woman is deemed to be at high risk for OHSS, (ii)serum progesterone level is > 1.5 ng/ml on the day of trigger, (iii)preimplantation genetic testing is planned, (iv)the woman will undergo surgery prior to ET, (v)couple preference. Main Results and the Role of Chance: Baseline characteristics were similar between the groups except for antral follicle count (22 vs 18, MD = 5, 95% CI = 0 to 8), and number of metaphase-two oocytes (13 vs 10, MD = 3, 95% CI = 1 to 6) all of which were significantly higher in the immediate transfer group. Clinical pregnancy rate (CPR) per ET was similar in two groups (50.4% vs 44.3%, RR = 1.14, 95% CI = 0.84 to 1.54). Miscarriage rate per pregnancy was significantly lower (12.3 vs 31.1, RR = 0.40, 95% CI = 0.19 to 0.84) and LBR per ET was significantly higher (42.9 vs 26.6, RR = 1.61, 95% CI = 1.06 to 2.46) in the immediate transfer group. Median gestational age at delivery was similar (267.5 (262.5–273) vs 268 (260–271.5) days, MD = 1.00, 95% CI= –4.00 to 5.00). Median birthweight was significantly higher in the delayed transfer group (3520 vs 3195 grams, MD= –300, 95% CI= –660 to –20 grams). Birthweight percentile, height at birth and head circumference were similar between groups. Literature search revealed 1712 studies from which nine were eligible for quantitative summary. Cumulative risk ratio showed a 10% increase in LBR with immediate transfer ompared to delayed transfer (RR = 1.10, 95% CI = 1.01 – 1.20, I2=67%, 17369 embryo transfers). Limitations, Reasons for Caution: Our study is limited by its retrospective design and relatively limited sample size for multivariate analyses. Yet, it is reassuring that the majority of our findings are consistent with previous publications. Wider Implications of the Findings: The hypotheses generated by our retrospective findings, i.e., FET in the immediate menstrual cycle resembling fresh ETs with strong trends towards lower birthweight and lower incidence of preeclampsia is noteworthy for the design of future studies, and these outcomes should be followed and reported.