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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 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 Open Access Outcomes of SARS-CoV-2 infected pregancies after medically assisted reproduction(Oxford University Press (OUP), 2022) Gianaroli, Luca; Lundin, Kersti; Mcheik, Saria; Mocanu, Edgar; Rautakallio-Hokkanen, Satu; Tapanainen, Juha S.; Vermeulen, Nathalie; Veiga, Anna; Eshre COVID-19 Working Group; Ata, Mustafa Barış; Faculty Member; School of Medicine; 182910Study question: what is the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the outcome of a pregnancy after medically assisted reproduction (MAR)?. Summary answer: our results suggest that MAR pregnancies are not differentially affected by SARS-CoV-2 infection compared to spontaneous pregnancies. What is known already: information on the effects of coronavirus disease 2019 (COVID-19) on pregnancy after MAR is scarce when women get infected during MAR or early pregnancy, even though such information is vital for informing women seeking pregnancy. Study design, size, duration: data from SARS-CoV-2 affected MAR pregnancies were collected between May 2020 and June 2021 through a voluntary data collection, organised by the European Society of Human Reproduction and Embryology (ESHRE). Participants/materials, setting, methods: all ESHRE members were invited to participate to an online data collection for SARS-CoV-2-infected MAR pregnancies. Main results and the role of chance: the dataset includes 80 cases from 32 countries, including 67 live births, 10 miscarriages, 2 stillbirths and 1 maternal death. An additional 25pregnancies were ongoing at the time of writing. Limitations, reasons for caution: an international data registry based on voluntary contribution can be subject to selective reporting with possible risks of over- or under-estimation. Wider implications of the findings: the current data can be used to guide clinical decisions in the care of women pregnant after MAR, in the context of the COVID-19 pandemic.Publication Open Access Placental deficiency during maternal SARS-CoV-2 infection(Elsevier, 2021) Duru, Banu; Ergönül, Önder; Can, Füsun; Çelik, Ebru; Vatansever, Cansel; Özcan, Gülin; Kapucuoğlu, Fatma Nilgün; Manici, Mete; Çekiç, Sebile Güler; Ata, Mustafa Barış; Gürsoy, Tuğba; Turğal, Mert; Doğan, Özlem; Faculty Member; Faculty Member; Faculty Member; Undergraduate Student; Faculty Member; Faculty Member; Doctor; Faculty Member; Faculty Member; Faculty Member; Faculty Member; Koç Üniversitesi İş Bankası Enfeksiyon Hastalıkları Uygulama ve Araştırma Merkezi (EHAM) / Koç University İşbank Center for Infectious Diseases (KU-IS CID); School of Medicine; Graduate School of Health Sciences; Koç University Hospital; 110398; 103165; 116631; N/A; N/A; 7421; N/A; N/A; 182910; 214691; 199792; 170418; N/A; N/A; N/AIntroduction: maternal anti-SARS-CoV-2 Spike antibodies can cross the placenta during pregnancy, and neonates born to infected mothers have acquired antibodies at birth. Few studies reported data on the histopathological changes of the placenta during infection and placental infection. SARS-CoV-2 infection may cause impaired development of the placenta, thus predisposing maternal and fetal unfavorable outcomes. The prospective study aims to evaluate the risk of vertical transmission of SARS-CoV-2 and placental passage of anti-Spike antibodies as well as the impact of clinical severity on placental structures. Methods: this is a prospective cohort study on 30 pregnant women infected by SARS-CoV-2 with their neonates. The demographic features and pregnancy outcomes were collected. Gross and microscopic examinations of the placentas were done. Maternal and umbilical cord sera were obtained at the time of delivery. Nasopharyngeal swabs were collected from neonates immediately after birth. Results: the concentrations of total anti-SARS-CoV-2 Spike antibodies were higher in pregnant women with moderate to severe/critical disease. The maternal total anti-SARS-CoV-2 Spike levels were correlated with those of neonatal levels. The rate of placental abnormalities is high in the mothers with severe disease, and those with positive anti-SARS-CoV-2 IgM. All neonates had negative nasopharyngeal swabs for SARS- CoV-2 infections and all placentas were negative in immunohistochemical staining for Spike protein. Discussion: the maternally derived anti-SARS-CoV-2 Spike antibody can transmit to neonates born to infected mothers regardless of gestational age. Our results indicated that the disease severity is associated with ischemic placental pathology which may result in adverse pregnancy outcomes.Publication Open Access SARS-CoV-2, fertility and assisted reproduction(Oxford University Press (OUP), 2022) Vermeulen, Nathalie; Mocanu, Edgar; Gianaroli, Luca; Lundin, Kersti; Rautakallio-Hokkanen, Satu; Tapanainen, Juha S.; Veiga, Anna; Ata, Mustafa Barış; Faculty Member; School of Medicine; 182910Background: in 2020, SARS-CoV-2 and the COVID-19 pandemic had a huge impact on the access to and provision of ART treatments. Gradually, knowledge of the virus and its transmission has become available, allowing ART activities to resume. Still, questions on the impact of the virus on human gametes and fertility remain. Onjective and rationale: This article summarizes published data, aiming to clarify the impact of SARS-CoV-2 and the COVID-19 disease on human fertility and assisted reproduction, as well as the impact of vaccination, and from this, provide answers to questions that are relevant for people contemplating pregnancy and for health care professionals. Search/methods: PUBMED/MEDLINE and the WHO COVID-19 database were searched from inception to 5 October 2022 with search terms focusing on 'SARS-CoV-2' and gametes, embryos, reproductive function, fertility and ART. Non-English studies and papers published prior to 2020 were excluded, as well as reviews and non-peer reviewed publications. Full papers were assessed for relevance and quality, where feasible. Outcomes: from the 148 papers included, the following observations were made. The SARS-CoV-2-binding proteins, angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2), are expressed in the testis, but co-expression remains to be proven. There is some evidence of SARS-CoV-2 RNA in the ejaculate of COVID-19 patients with severe disease, but not in those with mild/moderate disease. SARS-CoV-2 infection can impair spermatogenesis, but this seems to resolve after one spermatogenic cycle. Testosterone levels seem to be lower during and after COVID-19, but long-term data are lacking; disease severity may be associated with testosterone levels. COVID-19 cannot be considered a sexually transmitted disease. There is no co-expression of ACE2 and TMPRSS2 in the myometrium, uterus, ovaries or fallopian tubes. Oocytes seem to have the receptors and protease machinery to be susceptible to SARS-CoV-2 infection; however, viral RNA in oocytes has not been detected so far. Women contemplating pregnancy following COVID-19 may benefit from screening for thyroid dysfunction. There is a possible (transient) impact of COVID-19 on menstrual patterns. Embryos, and particularly late blastocysts, seem to have the machinery to be susceptible to SARS-CoV-2 infection. Most studies have not reported a significant impact of COVID-19 on ovarian reserve, ovarian function or follicular fluid parameters. Previous asymptomatic or mild SARS-CoV-2 infection in females does not seem to negatively affect laboratory and clinical outcomes of ART. There are no data on the minimum required interval, if any, between COVID-19 recovery and ART. There is no evidence of a negative effect of SARS-CoV-2 vaccination on semen parameters or spermatogenesis, ovarian function, ovarian reserve or folliculogenesis. A transient effect on the menstrual cycle has been documented. Despite concerns, cross reactivity between anti-SARS-CoV-2 spike protein antibodies and Syncytin-1, an essential protein in human implantation, is absent. There is no influence of mRNA SARS-CoV-2 vaccine on patients' performance during their immediate subsequent ART cycle. Pregnancy rates post-vaccination are similar to those in unvaccinated patients. Wider implication: this review highlights existing knowledge on the impact of SARS-CoV-2 infection or COVID-19 on fertility and assisted reproduction, but also identifies gaps and offers suggestions for future research. The knowledge presented should help to provide evidence-based advice for practitioners and couples contemplating pregnancy alike, facilitating informed decision-making in an environment of significant emotional turmoil.Publication Open Access The bladder is an unreliable witness: the case for urodynamic investigations in female stress urinary incontinence(Elsevier, 2020) Serati, Maurizio; Finazzi-Agro, Enrico; Soligo, Marco; Braga, Andrea; Athanasiou, Stavros; Balzarro, Matteo; Tarcan, Tufan; Other; School of Medicine; 173289For some years, the role of urodynamics (UDS) in female stress urinary incontinence (SUI) has been a topic of intense debate. The findings of the VaLUE and VUSIS-11 randomised clinical trials (RCTs) published in 2012 appeared to suggest that UDS is not useful in women with uncomplicated SUI, with the result that several authoritative guidelines were amended and the routine use of UDS in this setting fell sharply. However, many experts have raised concerns about the design of these two RCTs and their subsequent interpretation - including the inappropriate generalisation of the findings beyond uncomplicated cases, which represent only a small minority of the overall patient population. In this paper, we consider a range of issues and confounding factors which raise doubts about how influential these RCTs should have been and reflect on the potential value of UDS both for objective diagnosis and patient counselling in female SUI.