Tıp Fakültesi / Faculty of Medicine
Permanent URI for this collectionhttps://hdl.handle.net/11727/1403
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Item Remedies for Recurrent Implantation Failure(2014) Zeyneloglu, Hulusi Bulent; Onalan, Gogsen; https://orcid.org/0000-0002-0289-2642; 24919029; B-6487-2009; GZG-9810-2022In vitro fertilization (IVF) is expensive, time consuming, and the most successful treatment of fertility; however, in general the cumulative chance of having a live birth with the treatment is still around 40%. Many couples still remain unsuccessful after several IVF attempts, causing deep impact on quality of life, and each failed cycle causing a financial burden. Several adjuvant therapies have been used along with IVF to increase the pregnancy rates for women with repeated implantation failure. Testing of adjuvant therapies in properly conducted randomized controlled trials is rarely done so that potential benefits and risks are unlikely to be clearly presented to patients and clinicians. In this review, we assessed the effects of adjuvants, such as growth hormone, androgens, and glucocorticoids to enhance oocyte number and quality; sildenafil, low-dose aspirin, heparin, corticosteroids, granulocyte colony-stimulating factor, endometrial injury, intrauterine injection of human chorionic gonadotropin, and intrauterine administration of autologous peripheral blood mononuclear cells to improve poor endometrial response; antioxidants, complementary and alternative medicine modalities, such as Chinese herbal medicine and acupuncture; and assisted hatching and preimplantation genetic screening to correct embryonic factors.Item Possible Impact of Immunosuppressive Therapy Regimens on Histopathologic Outcomes of Abnormal Uterine Bleeding in Solid-Organ Transplant Recipients(2018) Tohma, Yusuf Aytac; Akilli, Huseyin; Kirnap, Mahir; Haberal, Asuman Nihan; Akyel, Dilan; Zengin, Hatice Yagmur; Zeyneloglu, Hulusi Bulent; Kuscu, Esra; Ayhan, Ali; Haberal, Mehmet; https://orcid.org/0000-0001-9418-4733; https://orcid.org/0000-0002-5240-8441; https://orcid.org/0000-0001-9852-9911; https://orcid.org/0000-0002-9855-2449; https://orcid.org/0000-0002-0289-2642; https://orcid.org/0000-0002-3462-7632; 29851156; AAE-6482-2021; AAX-3230-2020; AAH-9198-2019; AAK-4587-2021; ABA-3224-2021; B-6487-2009; AAJ-8097-2021Background: In this study, we aimed to determine the frequency of histopathologic outcomes of solid-organ transplantation in women with abnormal uterine bleeding (AUB) receiving immunosuppressive therapies. Methods: This is a retrospective study including a single-center experience. Data were extracted from hospital records, and solid-organ transplant recipients who were diagnosed with AUB were included. Results: Fifty-five of these patients were renal transplant recipients (79.7%), and 14 were liver transplant recipients (20.3%). Histopathologic examination showed various histopathologic patterns of endometrium in patients with AUB consisting of normal histopathologic findings of endometrium in 31 patients (48.4%); 29 hormonal imbalance during proliferative and secretory phases of menstrual cycle and two atrophic endometrium. Endometrial hyperplasia without atypia was observed in 11 patients (17.2%). Polyp was seen in 22 patients (34.4%); 21 endometrial polyp and one endocervical polyp. There were significant differences in terms of histopathologic findings among the three groups of patients according to different immunosuppressive regimens (P = .029). There was no endometrial hyperplasia in women receiving sirolimus-based immunosuppressive regimens. Moreover, there was no endometrial hyperplasia in the liver transplant recipient group. Conclusions: Sirolimus-based immunosuppressive regimens may be administered to patients who have risk factors for endometrial precancerous lesions, such as endometrial hyperplasia. However, additional well-designed, large-scale studies are warranted to confirm our findings.Item Effect of Etanercept on the Success of Assisted Reproductive Technology in Patients with Endometrioma(2018) Onalan, Gogsen; Tohma, Yusuf Aytac; Zeyneloglu, Hulusi Bulent; https://orcid.org/0000-0001-9418-4733; https://orcid.org/0000-0002-0289-2642; 29208847; GZG-9810-2022; AAE-6482-2021; B-6487-2009Aims: To determine the effects of a tumor necrosis factor inhibitor (etanercept) on pregnancy outcomes in patients with endometrioma who were treated with assisted reproductive technology. Methods: Sixty-eight infertile patients who had endometrioma were included in our retrospective case-control study. We administered etanercept (Enbrel, 50 mg in 1 mL intramuscularly) to 19 patients on the second day of their previous menstrual cycle. All patients were treated with assisted reproductive technology. Pregnancy and live birth rates (LBR) were documented. Results: When all other parameters (age, body mass index, infertility) are supposed to be constant, the clinical pregnancy rate was significantly higher in patients who used etanercept in an antagonist protocol than in patients who did not use etanercept (chi(2) = 5.547; p = 0.019) but LBR did not reach a statistical significance (chi(2) = 3.179; p = 0.075). The use of etanercept had an OR of 4.17 (95% CI 1.23-14.14) compared with not using etanercept for clinical pregnancy rate. The use of etanercept increased the rate of pregnancy (chi(2) = 6.55; p = 0.01). The pregnancy rate with the use of etanercept had an OR of 4.23 (95% CI 1.35-13.25) compared with patients who did not use etanercept. In the same way, the use of etanercept increased LBR twofold, but it is not significant in the border line (chi(2) = 3.771; p = 0.052). Conclusions: Etanercept may be a new non-hormonal therapy that may be an adjunct to treatment of infertile women with endometrioma. However, the safety of etanercept on embryos and fetuses has not been fully clarified. (C) 2017 S. Karger AG, BaselItem Serum endocan levels in fresh IVF/ICSI cycles in women with endometriosis: a comparative prospective study(2022) Ceran, Mehmet Ufuk; Yilmaz, Nafiye; Colak, Eser; Bayraktar, Nilufer; Tohma, Yusuf Aytac; Zeyneloglu, Hulusi BulentBackground: The current study tested the level of endocan, which is thought to have an effective role in both endothelial dysfunction and inflammation, in infertile women with endometriosis treated with in vitro fertilizationlintracytoplasmic sperm injection (IVF/ICSI). It is based on the hypothesis of chronic inflammation in the pathophysiology of endometriosis. Methods: This prospective case control study included a total of 64 women who were in the IVF/ICSI program. The women were divided into two groups: endometriosis (n = 32) and non-endometriosis (n = 32). Their baseline characteristics, stimulation parameters, and IVF/ICSI outcomes (clinical pregnancy and live birth rates) were recorded. Blood samples collected at the beginning of the IVE cycle for endocan levels were analyzed with a sandwich enzyme immunoassay and the results were documented. Results: The endocan levels in the endometriosis group were significantly higher than those in the non-endometriosis group, i.e., 5010 pg/mL and 2738 pg/mL, respectively (p < 0.05). A significant weakly positive correlation was found between endocan levels and the presence of endometriosis (p < 0.05, r: 0.284). The cut-off value for endometriosis was determined as 4693 pg/mL with a sensitivity of 53.13% and a specificity of 78.12%. Clinical pregnancy was insignificantly higher in the non-endometriosis group (p = 0.079). However, live birth rates were significantly higher in the non-endometriosis group (p < 0.05). No correlation was found between clinical pregnancy and live birth rate and endocan levels (p > 0.05). Conclusion: High endocan levels were detected in women who underwent IVF/ICSI treatment for endometriosis and infertility and there was a positive correlation between them. However, there was no relationship between endocan levels and IVF/ICSI outcomes.Item Diet and pravastatin administration prior to in vitro fertilization treatment may improve pregnancy outcome in women with dyslipidemia(2022) Zeyneloglu, Hulusi Bulent; Tohma, Yusuf Aytac; Gunakan, Emre; Abasiyanik, Mehmet Ali; Sozen, Ceren; Onalan, Gogsen; 0000-0002-0289-2642; 0000-0001-9418-4733; 0000-0001-8854-8190; 0000-0002-5741-8489; 35257641; B-6487-2009; ABI-1707-2020In this study, we aimed to identify whether using statins may increase the chance of pregnancy in In Vitro Fertilisation / Intra-Cytoplasmic Sperm Injection (IVF/ICSI) patients with hyperlipidaemia. Therefore, in this retrospective cohort study, 70 patients constituted the study population and all patients were managed by lipid lowering diet. Ten mg pravastatin (pravachol DEVA, Istanbul, Turkey) was added to therapy in case of resistant hypercholesterolaemia after 15 days of the diet. Fifty-one patients were treated with diet only and the remaining nineteen patients were offered both diet and pravastatin. Clinical pregnancy rate was significantly better with the patients who used pravastatin (68.4% vs. 39.2%, p = .029). Ongoing pregnancy rates were 63.2% and 33.3% with pravastatin and diet only, respectively, which were statistically significant (p:.024). According to multivariate analysis, pravastatin use was found independently and statistically significant for clinical pregnancy and ongoing pregnancy rate after IVF/ICSI in patients with dyslipidemia (HR 3.79; 95% CI 1.31-10.97; p:.014 and HR 3.18; 95% CI 1.22-8.27; p:.018). When we analysed stratified data according to the AMH levels, we noticed that as AMH levels increased, the pregnancy rates increased; the most benefit from pravastatin was in the group with AMH levels >2 ng/mL.IMPACT STATEMENT What is already known on this subject? Dyslipidemia in In IVF/ICSI patients with polycystic ovary syndrome had negative impact on pregnancy rates What the results of this study add? The findings of the study support that pravastatin may help to improve pregnancy outcome, especially in normal and high responders, regardless of whether decreased serum LDL or total cholesterol level. What the implications are of these findings for clinical practice and/or further research? As a result of our data, we speculated that it should be routine to investigate the lipid profile in every IVF/ICSI patient and should be treated accordingly, if necessary.Item Dydrogesterone primed luteal phase stimulation may be better than follicular phase stimulation in patients with diminished ovarian reserve(2021) Zeyneloglu, Hulusi Bulent; Tohma, Yusuf Aytac; Gunakan, Emre; 0000-0002-0289-2642; 0000-0001-9418-4733; 0000-0001-8854-8190; 33944650; B-6487-2009; AAE-6482-2021; ABI-1707-2020Objective In this study, we aimed to compare the efficacy of luteal phase stimulation (LPS) and follicular phase stimulation (FPS) in two separate menstrual cycles (2-5 months intervals) of the same patient, utilizing LPS with dydrogesteron only. Methods This retrospective case control study was conducted with patients with diminished ovarian reserve (DOR) (Group 1) and infertile patients with Anti-Mullerian hormone >1.2 ng/mL (Group 2) undergoing two ovarian stimulations (FPS and LPS with dydrogesteron only) and two oocyte retrievals in two separate menstrual cycles (2-5 months intervals) in the Division of Reproductive Endocrinology and Infertility of Baskent University, Ankara, between April 2019 and December 2019. Results In group 1, the number of frozen embryos was significantly higher in LPS when compared to FPS; 1.71 vs. 0.54, (p < .001), respectively. In group 2, the number of frozen embryos was higher in LPS when compared to FPS (0.8 vs. 0.4) however the difference did not reach a statistical significance (p: 0.157). Conclusion LPS may be beneficial especially in the patients with diminished ovarian reserve with follicular asynchronization in the menstrual onset. In addition, it should be kept in mind that dydrogesterone only may be used instead of gonadotropin-releasing hormone antagonist to prevent possible luteinizing hormone rise in LPS.Item Gut dysbiosis may be associated with hyperemesis gravidarum(2020) Balci, Serdar; Tohma, Yusuf Aytac; Esin, Sertac; Onalan, Gogsen; Tekindal, Mustafa Agah; Zeyneloglu, Hulusi Bulent; 0000-0001-9418-4733; 0000-0002-0289-2642; 0000-0002-1782-7325; 0000-0001-9577-4946; 32519907; AAE-6482-2021; B-6487-2009; AAJ-1097-2021; AAI-8810-2021Purpose:In this study, we aimed to determine the frequency of different intestinal microorganisms of patients with normal pregnancies and HG and to compare these frequencies between the two groups. Materials and methods:This case-control study was carried out in Baskent University Department of Obstetrics and Gynecology and included 20 patients; 10 of whom had normal pregnancies and 10 of whom had HG. A stool flora scan was routinely planned for all patients. Transient and continuous fecal bacteria and fungal flora were analyzed. All data were evaluated statistically and their relationships with clinical condition were discussed. Results:The study group consisted of 20 pregnant women with a mean age of 31.5 years. All patients were nonsmokers and free of chronic diseases and of any medications. Aerobic and anaerobic bacteria groups, fungal colonies, and parasites were examined and bowel pH values were measured separately for each patient. Bacterial and fungal species outside the reference ranges were recorded for each patient. There was a statistically significant increase inClostridiumspp. (p:.01) andCandidaspp. (p:.033) and a statistically significant decrease inBifidobacteriumspp.(p:.008) in patients with HG compared to women with normal pregnancies. There was a significant difference between the group with HG and the group with normal pregnancies in terms of flora dysbiosis (p:.001). Conclusion:Our results suggest that gut dysbiosis may be a factor in HG. The effect of the severity of gut dysbiosis on the disease may be the subject of future studies.Item The Role of Analysis of NK Cell Subsets in Peripheral Blood and Uterine Lavage Samples in Evaluation of Patients with Recurrent Implantation Failure(2020) Tohma, Yusuf Aytac; Musabak, Ugur; Gunakan, Emre; Akilli, Huseyin; Onalan, Gogsen; Zeyneloglu, Hulusi Bulent; 0000-0003-1511-7634; 0000-0002-0289-2642; 0000-0001-8854-8190; 32413518; AAU-1810-2020; B-6487-2009; ABI-1707-2020; AAX-3230-2020Objective: In this study, we aimed to determine the role of analyses of NK cell subsets in peripheral blood and uterine lavage samples in evaluation of patients with unexplained RIF. Methods: This retrospective single-institution case-control study included two different cohorts between 2017-2019. First cohort included patients examined with peripheral blood samples for evaluation of possible immunologic problems in patients with unexplained recurrent implantation failure; in the study period, a total of 75 consecutive patients with RIF (study group; n: 42) or infertile patients without RIF (control group; n: 33) were included. Second cohort included those patients whose uterine samples were assessed for immunologic problems; RIF (study group ; n: 16) or infertile patients without RIF (control group; n: 25). Results: In the first cohort, the percentage of NK cells (CD3-CD16(+)56(+)) is statistically significantly lower (9.8 vs. 12.6, respectively, p: 0.038) in the study group than those of the controls whereas there was no statistical significance in the absolute number of NK cells (CD3-CD16(+)56(+)). In the second cohort, the only remarkable finding in uterine lavage samples was significantly increased uNKs cells (CD3-CD16(di)(m)56(bright)) percentages in controls (9.95 vs 12.7, respectively, p: 0.026) compared to those of study group. Conclusion: Our data shows that the analysis of NK cell subtypes in peripheral blood does not seem appropriate to investigate the patients with RIF and we suggest that uterine lavage samples instead of peripheral blood samples be implemented and evaluated. (C) 2020 Elsevier Masson SAS. All rights reserved.Item Phosphodiesterase 4 inhibitor plus metformin is superior to metformin alone for the treatment of polycystic ovary syndrome: A rat model study(2019) Tohma, Yusuf Aytac; Onalan, Gogsen; Tepeoglu, Merih; Bayraktar, Nilufer; Colak, Eser; Ozcimen, Emel Ebru; Zeyneloglu, Hulusi Bulent; 30988783The role of metformin in the management of polycystic ovary syndrome (PCOS) and PCOS-related obesity remains controversial. Recent research on the treatment of PCOS-related obesity investigated novel therapeutic agents with the potential to work synergistically with metformin. The aim of the present study was to determine the synergistic effect of a phosphodiesterase 4 inhibitor (PDE4i) and metformin on weight and hormonal changes in a rat model of PCOS. A total of 40 female Sprague-Dawley rats were randomly divided into 4 groups (n=10/group): Sham; PCOS control (no medication after PCOS induction with dehydroepiandrosterone); metformin (300 mg/kg/day p.o. after PCOS induction); and metformin + PDE4i (300 mg/kg/day p.o. metformin + 0.5 mg/kg/day p.o. PDE4i after PCOS induction). The body weight was measured every 7 days, from day 1 to day 49. Vaginal smears were performed and examined daily via light microscopy for determination of the stage of each rat's estrous cycle. At the end of 21st day and at the end of the study, blood samples were collected from rats and the testosterone and insulin levels were measured. Immunohistochemical staining was performed to quantify phosphorylated cyclic AMP response element-binding protein expression in all groups. At the end of the study, the median body weight differed significantly among the groups ((2)=30.581, P<0.001), being the highest in the PCOS control group and the lowest in the metformin + PDE4i group. At the end of the study, the median testosterone level differed significantly among the groups ((2)=27.057, P<0.001), being the highest in the PCOS control group and the lowest in the metformin + PDE4i group. The cycle was restored to normal at the end of the study in all the rats in the metformin and metformin + PDE4i groups, whereas an irregular cycle persisted in all the rats in the PCOS control group. In conclusion, PDE4i + metformin was superior to metformin alone in reducing weight gain and decreasing the testosterone levels in a rat model of PCOS.Item Granulocyte colony-stimulating factor for intracytoplasmic sperm injection patients with repeated implantation failure: which route is best?dagger(2019) Zeyneloglu, Hulusi Bulent; Tohma, Yusuf Aytac; Onalan, Gogsen; Moran, Utkun; 0000-0002-0289-2642; 0000-0001-9418-4733; 31496328; B-6487-2009The aim of this study was to assess whether the dual administration of granulocyte colony-stimulating factor (G-CSF) increases the effect of only systemic administration in patients with RIF. This retrospective study included 111 infertile normoresponder cases with two or more unsuccessful in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) treatments, despite the transfer of good quality embryos. Patients were divided into three groups according to using G-CSF and administration route; Group 1 included patients who received subcutaneous (SC) G-CSF only (n = 38), Group 2 comprised patients who received both intrauterine (IU) and SC G-CSF (n = 39), the control group included patients who did not receive G-CSF who were matched by age (n = 34). The IU route of G-CSF was employed on ovulation triggering day. G-CSF was administered via an IU insemination catheter. SC injection was started on the day of oocyte retrieval and administered for 15 days at 100,000 IU/kg. Foetal cardiac activity (clinical pregnancy) was present in 50 patients (46.2%) after embryo transfer, with 20 patients included in SC group (Group 1) (52.6%), 25 in SC + IU group (Group 2) (64.1%) and 8 (23.5%) in control group and significant difference was observed between groups (p: .001). Pregnancy resulted in live birth in 43 patients (39.8%), with 13 patients belonging in Group 1 (34.2%), 25 in Group 2 (61.5%) and 8 (23.5%) in control group; significant differences were observed between groups (p: .001). In conclusion, our results showed that dual administration of G-CSF was significantly more effective that the SC only method.Impact statement What is already known on this subject? A number of studies reported the possible benefits of granulocyte colony-stimulating factor (G-CSF) administration in recurrent implantation failure (RIF) and recurrent pregnancy loss patients; however, it is unclear which administration route is better. What do the results of this study add? Our results showed that G-CSF is a promising and safe agent for increasing live birth rates in patients with RIF. Additionally, dual administration is considered the better method than SC only administration.