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Yayın The Effects of Glutathione on Clinically Essential Fertility Parameters in a Bleomycin Etoposide Cisplatin Chemotherapy Model(Mdpi, 2023) Bayram, Hale; Dönmez Çakıl, Yaprak; Sitar, Mustafa Erinc; Demirel, Gamze; Selam, Belgin; Cincik, MehmetChemotherapeutic agents used in the treatment of testicular cancer cause damage to healthy tissues, including the testis. We investigated the effects of glutathione on sperm DNA integrity and testicular histomorphology in bleomycin etoposide cisplatin (BEP) treated rats. Twelve-week-old male rats of reproductive age (n = 24) were randomly divided into three groups, the (i) control group, (ii) BEP group, and (iii) BEP+ glutathione group. Weight gain increase and testes indices of the control group were found to be higher than that of the BEP group and BEP+ glutathione group. While the BEP treatment increased sperm DNA fragmentation and morphological abnormalities when compared to the control group, GSH treatment resulted in a marked decrease for both parameters. Moreover, BEP treatment significantly decreased serum testosterone levels and sperm counts in comparison to the control group, yet this reduction was recovered in the BEP+ glutathione treated group. Similarly, seminiferous tubule epithelial thicknesses and Johnsen scores in testicles were higher in the control and BEP+ glutathione groups than in the BEP-treated group. In conclusion, exogenous glutathione might prevent the deterioration of male reproductive functions by alleviating the detrimental effects of BEP treatment on sperm quality and testicular histomorphology.Yayın ICSI sonrası erken dönem ß-hCG artış oranın 35 yaş altı ve üzeri kadınlarda gebelik prognozunu öngörmedeki rolü(T.C. Sağlık Bakanlığı Ankara Şehir Hastanesi, 2022) Uzunhasanoğlu, Özge; Dönmez Çakıl, Yaprak; Selam, Belgin; Cincik, MehmetAmaç: İlk trimester maternal serum belirteçlerinden olan ?-human koryonik gonadotropin (?-hCG), gebeliğin erken döneminde hızla artar. Birçok çalışma, ?-hCG değerinin artma seyrinin gebelik sonucunu öngörmede yararlı olduğunu bildirmiştir. Çalışmamızda intrasitoplazmik sperm enjeksiyonu (ICSI) işlemlerini takiben erken dönem ?-hCG artış oranının, maternal yaşa bağlı olarak gebelik prognozunu öngörmedeki yerinin değerlendirilmesi ve bu sayede, bu yaş gruplarında gelişebilecek kimyasal gebelik, abortus gibi olguların daha erken ve hassas yönetimi ve takibi için faydalı olup olamayacağının araştırılması amaçlanmıştır. Gereç ve Yöntemler: ICSI tedavisi sonrası gebelik oluşan ve ß-hCG değerleri embriyo transferinden 10 ve 12 gün sonra ölçülmüş 1977 hastanın verileri retrospektif olarak incelenmiştir. Hastalar 35 yaş altı ve üzeri olarak iki gruba ayrılarak, ß-hCG artış oranları, kimyasal gebelik, klinik gebelik, abortus, ektopik gebelik, devam eden gebelik ve canlı doğum olgularında karşılaştırılmıştır. Anlamlılık p<0,05 düzeyinde değerlendirilmiştir. Bulgular: Her iki gün elde edilen ölçümler ve ß-hCG artış oranı 35 yaş altı hastalarda daha yüksek bulunmuştur (sırasıyla: p=0,001; p=0,001; p=0,006). Her iki yaş grubunda da kimyasal gebelik olgularında ß-hCG artış oranı daha düşük izlenmiştir (<35 yaş: p=0,001; ?35 yaş: p=0,001). Klinik gebelik, abortus, ektopik gebelik, devam eden gebelik ve canlı doğum olgularında, ß-hCG artış oranı karşılaştırıldığında, istatistiksel olarak anlamlı farklılık saptanmamıştır. Sonuç: Artan maternal yaş ile birlikte ?-hCG artış oranı azalmıştır. Hem 35 yaş altı hem de üzerindeki hastalarda, ß-hCG artış oranı, kimyasal gebelik olgularında diğer gebelik gruplarına göre daha düşük izlenmektedir. Erken dönem ?-hCG artış oranı, özellikle kimyasal gebelik olgularının daha erken yönetimi ve hassas takibi için faydalı olabilir.Yayın The impact of oocyte denudation without a pre-incubation on intracytoplasmic sperm injection outcomes(Gülhane Faculty of Medicine, 2022) Kanaat, Şenay; Selam, Belgin; Düzgün, Zehra Beyza; Cincik, Mehmet; Dönmez Çakıl, YaprakAims: Debate over the optimal timing of oocyte denudation following oocyte retrieval continues. Multinucleation has been associated with lower embryo quality and implantation rate. Defining oocyte characteristics might increase the chances of better embryo selection. This study aimed to investigate the laboratory and clinical outcomes of intracytoplasmic sperm injection when the oocytes were denuded immediately after oocyte retrieval. Methods: A prospective randomized sibling-oocyte study was performed. The participants were under 40 years of age with more than 5 oocytes. Patients with male factors were excluded. The study and control groups were formed by simple randomization. The study group underwent oocyte denudation immediately. In the control group, oocytes were routinely incubated in an equilibration solution for 2 h until the removal of the cumulus cells. Outcome measures were normal fertilization (two pronuclei, 2PN), multinucleation rate, the proportion of good quality embryos, blastocyst formation, and pregnancy rate. Results: A total of 792 oocytes were collected from 54 participants (mean age: 30.6±3.7 years). The fertilization rate was higher in the study group (n=209 in 376) compared with the controls (n=201 in 416) (55.6% vs. 48.3%, p=0.041). The multinucleation rate (6.6% vs. 4.3%, p=0.150), proportion of grade 1 embryos on day 3 (48.7% vs. 43%, p=0.112) and day 5 (27.7% vs. 23.8%, p=0.214), the proportion of embryos reaching blastocyst stage (34.0% vs. 28.1%, p=0.072), and the pregnancy rates (78.6% vs. 71.4%, p=1.000) were similar. Conclusions: Our results demonstrated that immediate removal of cumulus cells does not have any negative impact on intracytoplasmic sperm injection outcomes.Yayın Mikro akışkan çip, yüzdürme (swim up) ve gradient yöntemleri kullanılarak hazırlanan sperm örneklerinde DNA fragmantasyon oranlarının karşılaştırılması(Maltepe Üniversitesi Tıp Fakültesi, 2018) Murtaz, Tuğçe; Öztürk, Güler; Cincik, Mehmet; Selam, BelginAmaç: Sperm hazırlama yöntemleri, yardımlı üreme tekniklerinin sonuçlarını önemli ölçüde etkiler. Sperm yıkama işlemi, fertilizasyon için zararlı olabilecek hücrelerin ayrıştırır ve daha hareketli ve morfolojik olarak iyi spermlerin elde edilmesini sağlar. Geleneksel sperm yıkama teknikleri, santrifüjlü ve santrifüjsüz swim-up ve santrifüjlü gradient yöntemleridir. Sperm DNA fragmantasyonu, erkek infertilitesi için önerilen faktörlerden biridir. Sperm yıkama yöntemleri DNA fragmantasyonu oranlarını etkileyebilir. Bu çalışmanın amacı, geleneksel sperm yıkama yöntemleri ile yeni bir yöntem olan mikro akışkan çip yöntemi arasında DNA hasarı oranlarını kıyaslamaktır. Gereç ve Yöntem: Çalışma grubu 14 gönüllü erkekten oluşmaktadır. Alınan her semen örneği 3’e ayrılarak gradient, santrifüjsüz swim up ve mikro akışkan çip yöntemleriyle ayrı ayrı yıkandı. Her gruptaki sperm DNA fragmantasyon oranları TUNEL (terminal deoksinükleotidil transferaz-aracılı dUTP işaretleme) testi ile karşılaştırıldı. Bulgular: DNA fragmantasyonlu TUNEL pozitif sperm oranları, gradient, santrifüjsüz swim up ve mikro akışkan çip yöntemleri için sırasıyla %12, %4 ve %4,5 izlendi. Gradient yöntemi ile sperm DNA fragmantasyon oranları, diğer iki yöntemle karşılaştırıldığında istatistiksel olarak anlamlı yüksek bulundu (p<0.002). Swimup ile mikro akışkan çip yöntemleri karşılaştırıldığında DNA fragmantasyonu açısında istatistiksel olarak anlamlı bir fark izlenmedi. (p=0.583). Sonuç: Mevcut çalışmada santrifüj olmayan swim-up ve microfluidic chip yöntemlerine kıyasla gradient yöntemiyle sperm DNA fragmantasyon oranlarında artış tespit edilmiştir. Santrifüj oksidatif stresi arttırabilir ve böylece serbest radikal üretimine yol açabilir.Yayın Rescue IVM of denuded GV- and MI-stage oocytes of premenopausal rats with oncostatin M, insulin-like growth factor I, and growth hormone(MDPI, 2022) Akdemir, Yeşim; Selam, Belgin; Dönmez Çakıl, Yaprak; Sitar, Mustafa Erinç; Cincik, MehmetImmature oocytes are retrieved and matured through in vitro maturation (IVM). Maturation, fertilization rates, and embryo development via IVM are all lower than those found in vitro fertilization (IVF) cycles. We investigated the effects of oncostatin M (OSM), insulin-like growth factor-1 (IGF-I), and growth hormone (GH) in rescue IVM. A total of 111 germinal vesicle (GV) and 17 metaphase I (MI) oocytes were obtained after conventional IVF from 28 female Wistar albino rats. Denuded immature oocytes were cultured in maturation medium supplemented with OSM, IGF-1, or GH. The quantities of metaphase II (MII) oocytes matured from the GV stage were 17 of 30 (56.6%), 15 of 28 (53.5%), 10 of 30 (33.3%), and 7 of 23 (30.3%), in control, OSM, IGF-I, and GH groups, respectively. Maturation rates in control and OSM groups were higher than those in IGF-I and GH groups (p = 0.001). The quantities of MII oocytes matured from MI stage were 7 of 7 (100%), 4 of 4 (100%), 1 of 1 (100%), and 1 of 5 (20%) in control, OSM, IGF-I, and GH groups, respectively. Maturation rates from MI to MII stages in control, OSM, and IGF-I groups were higher than those in the GH group (p = 0.004). Acceptable maturation rates are observed with OSM in rat oocytes in rescue IVM.Yayın Short term follow up results of the first human uterus transplantation from cadaver(Elsevier, 2012) Akar, M. Erman; Özkan, O.; Erdoğan, O.; Cincik, Mehmet; Mutlu, D.; Gunseren, F.; Pestereli, E.; Kocak, H.; Dinckan, A.; Hadimioglu, N.; Suleymanlar, G.Study Objective: To present the short term follow up results of the first human uterus transplantation from cadaver. Design: Case report. Setting: University hospital. Patients: A 19 year old female patient with complete mullerian agenesis presented with primary amenorrhea and inability to achieve intercourse. Intervention: Vaginal reconstruction with jejunum graft, in vitro fertilization and embryo vitrification procedures were performed. Following immunocompatibility tests for the transplantation, the patient was elected as the most suitable recipient for the uterus. The cadaver uterus was screened for the presence of any structural abnormalities and infections preoperatively. Uterus transplantation procedure consisted of revascularisation, reanastomoses of the right and left uterine arteries and veins(ishemia time for five hours), fixation of the uterovesical flap to the preexisting urinary bladder, suspension of the uterosacral ligament to sacrum. Measurements and Main Results: Early postoperative course was uneventful. Intraoperative and postoperative induction immunosuppressive therapy with thymoglobulin, tacrolimus, mycophenolate mofetil and prednisone was well tolerated. Maintanance immunosuppressive therapy with tacrolimus, mycophenolate mofetil and prednisone and prophylactic antiviral, antibacterial therapy was initiated. Bilateral uterine artery doppler ultrasonography showed good perfusion. We observed no signs of rejection and infection confirmed with laboratory and cytological findings. She has had six menstrual cycles since the operation. Conclusion: We have described restoration of menstrual cycles following uterus transplantation which might be a promising option to restore fertility in this selected group of patients.Yayın Sperm selection and embryo development: a comparison of the density gradient centrifugation and microfluidic chip sperm preparation methods in patients with astheno-teratozoospermia(MDPI, 2021) Selam, Belgin; Çağla, Güler; Melil, Süreyya; Özekici, Ümit; Dönmez Çakıl, Yaprak; Cincik, MehmetIn recent years, microfluidic chip-based sperm sorting has emerged as an alternative tool to centrifugation-based conventional techniques for in vitro fertilization. This prospective study aims to compare the effects of density gradient centrifugation and microfluidic chip sperm preparation methods on embryo development in patient populations with astheno-teratozoospermia. In the study, the semen samples of the patients were divided into two groups for preparation with either the microfluidic or density gradient methods. Selected spermatozoa were then used to fertilize mature sibling oocytes and the semen parameters and embryo development on days 3 and 5 were assessed. While the density gradient group was associated with a higher sperm concentration, motility (progressive and total) was significantly higher in the microfluidic chip group. No significant differences were observed in the fertilization rates or grade 1 (G1) and grade 2 (G2) proportions of the third-day embryos. Furthermore, while the proportions of the poor, fair and good blastocysts on day 5 did not differ significantly, excellent blastocysts (indicating high-quality embryos) were observed in a significantly higher proportion of the microfluidic chip group. When compared to the classical density gradient method, the microfluidic chip sperm preparation yielded sperm with higher motility and higher quality blastocysts at day 5; in patients with astheno-teratozoospermia.
