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Yayın Assessment of carotid artery intima-media thickness and lipid profile in term neonates born to smoking mothers(Tehran University of Medical Sciences, 2021) Turan, Hande; Meşe, Timur; Doksöz, Önder; Turan, VolkanBackground: It is well-known that cigarette smoke contains chemical substances, including nicotine and carbon monoxide, which can have harmful effects on cardiovascular function. Objectives: This study aimed to investigate and compare lipid levels and carotid artery intima-media thickness (CAIMT) among neonates born to smoking and nonsmoking mothers. Methods: This study was conducted on 40 term neonates (over 37 weeks of gestation) within the age range of 0 - 30 days born to smoking mothers (study group) and 34 term neonates born to nonsmoking mothers (control group). Both groups were assessed prospectively for triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and CAIMT. Results: There was no difference in the mean age of mothers between control and study groups (29.0 4.5 vs. 29.3 5.7 years; P = 0.31). The CAIMT was observed as similar between the groups (0.35 0.05 vs. 0.36 0.05 mm in control and study groups, respectively; P = 0.665). Although HDL-C levels were significantly lower in the study group (48.5 16.2 vs. 39.1 17.8 mg/dL; P = 0.021), no difference was observed in LDL-C, TC, and TG levels between the two groups. Conclusions: Based on the results, there were no differences in CAIMT and lipid profile other than low HDL levels between term neonates born to smoking mothers and neonates born to nonsmoking mothers. Atherosclerosis is a disease in which numerous factors play a role in the formation beginning in the fetal period and emerging with clinical findings in advanced age; therefore, it is required to perform further studies with longer follow-up and larger sample size to confirm the present study findings.Yayın Assessment of the ovarian reserve in patients with Beta-thalassemia major; A prospective longitudinal study(Galenos Publishing House, 2023) Özcan, Aykut; Gülseren, Varol; Özcan, Esin; Toz, Emrah; Turan, VolkanObjective: Repeated blood transfusions in women with Beta-thalassemia major (BTM) may lead to iron overload and increase oxidative stress and consequently resulting in ovarian damage. We aimed to evaluate the alterations in the ovarian reserve of transfusion-dependent BTM patients over a time period of one year and compared the anti-mullerian hormone (AMH) levels between women with BTM and healthy population. Material and methods: This longitudinal prospective study was conducted in 41 women with transfusion-dependent BTM at the tertiary hospital. The hospital database between 1996 to 2021 was screened for women diagnosed with BTM. Anti-mullerian hormone levels were assessed at baseline and one year later. Results: Twenty-five (60.9%) of the patients had amenorrhea while 16 (39.1%) were observed to have normal cycles. The mean AMH values of all women were 2.7±1.8 ng/mL at the initial measurement which was significantly lower compared to age related AMH (mean 4.0±0.4 ng/mL) nomogram of healthy population (P= 0.001). The baseline AMH values of the patients with amenorrhea were found to be lower than the patients with normal menstrual cycles (2.1±1.8 vs 3.6±1.5 ng/mL, P= 0.009). After a one-year follow-up, there was a trend towards to a decrease in AMH levels of the patients with normal menstrual cycles. Conclusion: Serum AMH values is decreased in patients with transfusion-dependent BTM. It would be beneficial to inform all patients about possible effects of repeated blood transfusions on fertility.Yayın Association of germline BRCA pathogenic variants with diminished ovarian reserve: A meta-analysis of individual patient-level data(American Society of Clinical Oncology, 2021) Turan, Volkan; Lambertini, Matteo; Lee, Dong-Yun; Wang, Erica; Clatot, Florian; Karlan, Beth Y.; Demeestere, Isabelle; Bang, Heejung; Oktay, KutlukPURPOSE: To determine whether germline BRCA (gBRCA) pathogenic variants are associated with decreased ovarian reserve. MATERIALS AND METHODS: An individual patient-level data meta-analysis was performed using five data sets on 828 evaluable women who were tested for gBRCA. Of those, 250 carried gBRCA, whereas 578 had tested negative and served as controls. Of the women with gBRCA, four centers studied those affected with breast cancer (n = 161) and one studied unaffected individuals (n = 89). The data were adjusted for the center, age, body mass index, smoking, and oral contraceptive pill use before the final analysis. Anti-Müllerian hormone (AMH) levels in affected women were drawn before presystemic therapy. RESULTS: The mean age of women with versus without gBRCA1/2 (34.1 ± 4.9 v 34.3 ± 4.8 years; P = .48) and with gBRCA1 versus gBRCA2 (33.7 ± 4.9 v 34.6 ± 4.8 years; P = .16) was similar. After the adjustments, women with gBRCA1/2 had significantly lower AMH levels compared with controls (23% lower; 95% CI, 4 to 38; P = .02). When the adjusted analysis was limited to affected women (157 with gBRCA v 524 without, after exclusions), the difference persisted (25% lower; 95% CI, 9 to 38; P = .003). The serum AMH levels were lower in women with gBRCA1 (33% lower; 95% CI, 12 to 49; P = .004) but not gBRCA2 compared with controls (7% lower; 95% CI, 31% lower to 26% higher; P = .64). CONCLUSION: Young women with gBRCA pathogenic variants, particularly those affected and with gBRCA1, have lower serum AMH levels compared with controls. They may need to be preferentially counseled about the possibility of shortened reproductive lifespan because of diminished ovarian reserve.Yayın Autologous bone marrow-derived nucleated cell (aBMNC) transplantation improves endometrial function in patients with refractory Asherman's syndrome or with thin and dysfunctional endometrium(Springer Nature, 2023) Arıkan, Gürkan; Turan, Volkan; Kürek Eken, Meryem; Göksoy, Hasan Sami; Doğusan, ZeynepPurpose: The purpose was to evaluate the effect of intrauterine injection of aBMNC on the endometrial function in patients with refractory Asherman's syndrome (AS) and/or thin and dysfunctional endometrium (TE). Study design: This is a prospective, experimental, non-controlled study MATERIAL AND METHODS: The study was carried out between December 2018 and December 2020 on 20 patients, who were of age < 45 years and had oligo/amenorrhea and primary infertility due to refractory AS and/or TE. One hundred ml BM was extracted. aBMNC cells were separated according to generic volume reduction protocol by using the Cell Separation System SEPAX S-100 table top centrifuge system. We have evaluated CD34+, mononuclear cell (MNC), and total nucleated cell (TNC) counts. The transplantation aBMNC was performed by two intrauterine injections at an interval of one week, transvaginally into the endometrial-myometrial junction by an ovum aspiration needle. Midcyclic endometrial thickness (ET) and gestations after transplantation were evaluated. Results: The mean TNC, MNC, and CD34+ cells were 11.55 ± 4.7 × 108, 3.85 ± 2.01 × 108, and 7.00 ± 2.88 × 106 at first injection, respectively, and 6.85 ± 2.67 × 108, 2.04 ± 1.11 × 108, and 3.44 ± 1.31 × 106 at second injection, respectively. The maximum posttransplantation ET was significantly higher than the maximum pretransplantation ET: 2.97 ± 0.48 vs. 5.76 ± 1.19 (mean ± standard deviation, p < 0.01). Twelve patients had frozen-thaw embryo transfers after the study. In 42% (n = 5 of 12) of the patients, pregnancy was achieved. One of the five patients delivered a healthy baby at term. Conclusions: Autologous BMNC transplantation may contribute to endometrial function in patients with AS and/or TE.Yayın Autologous ovarian tissue transplantation: Preoperative assessment and preparation of the patient(Wolters Kluwer Health, 2024) Turan, Volkan; Öktem, ÖzgürImportance: Ovarian tissue cryopreservation (OTC) is an innovative and established fertility preservation method. More than 150 live births have been reported worldwide to date with the use of this strategy. OTC is one of the options to preserve fertility in prepubertal girls and for women who have time constraints and/or contraindications for ovarian stimulation for oocyte/embryo freezing before cancer treatment. The success rate of the ovarian tissue transplantation (OTT) depends on many interrelated factors. Therefore, preoperative evaluation and preparation of the candidate patients for the procedure are of paramount importance. Objective: In this review, our aim was to provide a guide for the clinicians, which demonstrates step-by-step assessment and preparation of the patients and ovarian tissue samples for transplantation. Evidence Acquisition: We searched for published articles in the PubMed database containing key words, such as OTT, OTC, preoperative assessment, primordial follicle density, and cancer, in the English-language literature until May 2024. We did not include abstracts or conference proceedings. Results: OTT is still a developing method as an effective fertility preservation approach. It is essential to perform a thorough preoperative evaluation of the patient to improve the success rates of transplantation. Conclusions and Relevance: Preoperative evaluation and preparation of women for ovarian transplantation surgery should include safety management to prevent reimplantation of malignant cells, transplanting ovarian tissue with minimum follicle loss and the decision of the best transfer site.Yayın Comparison of random start controlled ovarian stimulation with kiandard start in letrozole gonadotropin cycles for fertility preservation in women with breast cancer(Elsevier, 2023) Turan, Volkan; Lafuente, Sonia Gayete; Arkfeld, Christopher Ke; Oktay, Kutluk H.Random start controlled ovarian stimulation (RSCOH) was introduced as an option for women with cancer who do not have sufficient time for early follicular start ovarian stimulation protocols for fertility preservation. Our aim was to determine if the outcomes of RSCOH were similar to standard start (early follicular) controlled ovarian hyperstimulation (SSCOH) cycles in women with breast cancer.Yayın Evaluation of intrafollicular syndecan 1, glypican 3, and spermidine levels in women with diminished ovarian reserve(Springer, 2023) Gökçe, Şefik; Herkiloğlu, Dilşad; Çevik, Özge; Turan, VolkanWe aimed to evaluate the levels of Spermidine, Syndecan 1, and Glypican 3 (GPC3) in the follicle fluid of women with diminished ovarian reserve (DOR) and to examine the relationship of these markers with the number of embryos and clinical pregnancy. A total of 27 women with DOR and 34 women with normal ovarian reserve who underwent in vitro fertilization procedure were included in this prospectively designed study. Spermidine, Syndecan 1, and GPC3 levels were studied in the follicle fluid samples taken from the women at the time of oocyte retrieval by ELISA method, and their relations with the cycle outcomes were examined. The mean age was found as 38.1 ± 7.4 years in the DOR group and 35.1 ± 5.2 years in the control group (p = 0.027). When adjusted for age and body mass index, while the median Spermidine level was significantly higher (p < 0.001), both Syndecan 1 (p < 0.001) and GPC3 (p = 0.006) were significantly lower in the DOR group compared with control group. The cut-off value of Spermidine for clinical pregnancy prediction was found as 74.08 ng/mL with 78.9% sensitivity and 57.1% specificity [OR: 5 (95% CI: 1.4-17.6); AUC: 0.621; p = 0.138], while it was 0.96 ng/mL with 84.2% sensitivity and 59.5% specificity [OR: 7.8 (95% CI: 2-31.1); AUC: 0.701; p = 0.004] for GP3 and 1.15 ng/mL with 78.9 sensitivity and 57.1% specificity [OR: 5 (95% CI: 1.4-17.6); AUC: 0.680; p = 0.009] for Syndecan 1. Intrafollicular spermidine, Syndecan 1, and GPC3 levels may have a role in ovarian aging. Further randomized controlled studies in a larger population are needed for the relationship of these markers with cycle and pregnancy outcomes.Yayın Fertility preservation in breast cancer patients(Springer, 2022) Marin, Loris; Turan, Volkan; Oktay, KutlukBreast cancer is the most common malignancy in women as it currently represents 15.2% of all new cancer cases in the United States with 268,600 estimated new cases in 2019 [1]. Under 45 years of age, the percentage of new cases is 10.3% as it is the most common of all in women of childbearing age. Due to the increasingly advanced diagnostic and therapeutic techniques, the mortality rate remains low in recent years. For stages I and II, the 5-year survival is estimated to be respectively 95% and 85–70% (depending on whether they are IIA and IIB), while in advanced stages, survival rates are between 18 and 52% (for stages IIIA and B) [1]. Because the number of young cancer survivors is increasing and as women tend to have children in later reproductive ages, increasing attention has been paid to chemotherapy-related ovarian toxicity [2]. Most women with breast cancer are likely to undergo neoadjuvant or adjuvant chemotherapy that may result in premature ovarian failure and infertility [3–5].Yayın Impact of adjuvant chemotherapy or tamoxifen-alone on the ovarian reserve of young women with breast cancer(Springer, 2021) Goldfarb, Shari B.; Turan, Volkan; Bedoschi, Giuliano; Taylan, Enes; Abdo, Nadia; Cigler, Tessa; Bang, Heejung; Patil, Sujita; Dickler, Maura N.; Oktay, Kutluk H.Purpose To determine the longitudinal impact of adjuvant chemotherapy and tamoxifen-only treatments on the reproductive potential of women with breast cancer by using a sensitive ovarian reserve marker anti-Mullerian hormone (AMH) as a surrogate. Methods One-hundred-and-forty-two women with a primary diagnosis of breast cancer were prospectively followed with serum AMH assessments before the initiation, and 12, 18 and 24 months after the completion of adjuvant chemotherapy or the start of tamoxifen-only treatment. The chemotherapy regimens were classified into Anthracycline-Cyclophosphamide-based (AC-based) and Cyclophosphamide-Methotrexate + 5-Fluorouracil (CMF). Longitudinal data were analyzed by mixed effects model for treatment effects over time, adjusting for baseline age and BMI. Results Both chemotherapy regimens resulted in significant decline in ovarian reserve compared to the tamoxifen-only treatment (p < 0.0001 either regimen vs. tamoxifen for overall trend). AMH levels sharply declined at 12 months but did not show a significant recovery from 12 to 18 and 18 to 24 months after the completion of AC-based or CMF regimens. The degree of decline did not differ between the two chemotherapy groups (p = 0.53). In contrast, tamoxifen-only treatment did not significantly alter the age-adjusted serum AMH levels over the 24-month follow up. Likewise, the use of adjuvant tamoxifen following AC-based regimens did not affect AMH recovery. Conclusions Both AC-based regimens and CMF significantly compromise ovarian reserve, without a recovery beyond 12 months post-chemotherapy. In contrast, tamoxifen-only treatment does not seem to alter ovarian reserve. These data indicate that the commonly used chemotherapy regimens but not the hormonal therapy compromise future reproductive potential.Yayın Ongoing pregnancy and healthy live births following very short ovarian stimulation of incidentally observed big antral follicles in oligoamenorrheic patients with extremely decreased ovarian reserve(Sociedade Brasileira de Reproducao Assistida, 2021) Turan, Volkan; Sönmezer, Meltem; Sönmezer, MuratIn the present case series our aim is to present seven patients with extremely decreased ovarian reserve and oligomenorrhea, conceived with in vitro fertilization following a very short ovarian stimulation of incidentally detected big antral follicles. The study included women pursuing in vitro fertilization due to premature ovarian failure risk. When an incidental growing antral follicle was detected under ultrasound, immediate ovarian stimulation was initiated if the blood estradiol, luteinizing hormone and progesterone levels were correlated. Serum anti-Mullerian hormone measurements of all patients were consistent with extremely diminished ovarian reserve (ranged between 0.01 and 0.09ng/ml) and FSH levels varied between 13-104IU/l. The mean stimulation length ranged between 2-4 days. A total of 8 oocytes were retrieved; 6 MII, 1 GV and 1 degenerated. All 6 MII oocytes were fertilized with intracytoplasmic sperm injection. Two patients conceived after fresh embryo transfer, whereas the one conceived following frozen thawed embryo transfer. The ongoing pregnancy rate was 50% per transfer, and two of them resulted in a healthy live birth. In conclusion, close monitoring of oligoamenorrheic infertile patients who are at high risk of imminent ovarian failure using ultrasound and blood hormone levels is very important. Albeit low, the possibility of having a healthy pregnancy following "a very short ovarian stimulation" in such a specific patient group is emphasized.Yayın Oocyte cryopreservation with in vitro maturation for fertility preservation in girls at risk for ovarian insufficiency(Springer/Plenum Publishers, 2023) Gayete-Lafuente, Sonia; Turan, Volkan; Oktay, Kutluk H.Purpose To assess the feasibility and outcomes of oocyte cryopreservation with in vitro maturation (IVM) in post-pubertal girls undergoing fertility preservation (FP) for primary ovarian insufciency (POI) risk. Methods Ovarian stimulation was performed with an antagonist protocol or progesterone priming. Ultrasound monitoring was performed transabdominally. Oocytes were retrieved transvaginally under IV sedation. Immature oocytes were subjected to IVM for up to 36 h. All MII oocytes were vitrifed. The main outcome measure was the total number of mature oocytes cryopreserved. The secondary outcome was the increase in the mature oocyte yield after IVM. Results Indications for FP included mosaic Turner syndrome (mTS; n=10), malignancy (n=3), and POI risk (n=2). The mean±SD age, antral follicle count (AFC), and AMH levels were 14.2±1.4 years, 8±5.2 and 1.3±1.3 ng/mL. In girls with mTS, the ovarian reserve was low for age (AFC 7.4±4.7 and AMH 1.4±1.6 ng/mL). Oocyte cryopreservation was possible in all girls with a range of 1–27 mature oocytes obtained, even in those who were previously exposed to chemotherapy or with low ovarian reserve, and no surgical complications were encountered. After IVM, the median mature oocyte yield increased signifcantly from 7.5 to 10.5 (p=0.001). Conclusions Oocyte cryopreservation appears to be feasible and safe in girls as young as 12 years of age at risk for POI The utility of IVM increases the yield of cryopreserved mature oocytes. Prior exposure to chemotherapy or low ovarian reserve should not be an automatic reason to exclude these girls from FP consideration.Yayın Outcomes of random-start letrozole protocol with PGT-A in women with breast cancer undergoing fertility preservation(Springer/Plenum Press, 2023) Turan, Volkan; Gayete-Lafuente, Sonia; Bang, Heejung; Oktay, Kutluk H.PURPOSE : To compare the cycle characteristics and outcomes of random-start-controlled ovarian stimulation (RSCOS) protocols to the outcomes of standard-start-controlled ovarian stimulation (SSCOS) cycles and to report the utility of PGT-A in these cycles. Methods: One hundred and seventeen who underwent SSCOS and 39 who underwent RSCOS for oocyte and/or embryo cryopreservation before breast cancer chemotherapy were retrospectively evaluated. Mean number of embryos and blastocyst euploidy rates were the main outcome measures. Results: A majority of RSCOS cycles were initiated in the luteal phase (66.6% luteal vs. 33.3% follicular). While the total dose of gonadotropins was significantly higher in the RSCOS (3720.8 ± 1230.0 vs. 2345.1 ± 803.6 IU; P < 0.001), the mean number of mature oocytes and embryos was similar to SSCOS. However, there was a trend for a higher number of mean embryos with luteal start RSCOS (6.9 ± 2.7 in late follicular start vs. 9.4 ± 4.2 in luteal start, P = 0.08). PGT-A was performed in 48% of the cases that underwent embryo cryopreservation in RSCOS (12 women, mean age = 35.3 ± 4.1; 87 blastocysts), revealing a euploidy rate of 36.2 ± 22.3% per patient. This rate was comparable to a 45% aneuploidy rate from similarly aged published data. Of the 7 RSCOS patients who returned for frozen embryo transfer, 5 delivered and one has an ongoing pregnancy, while in SSCOS, 18 out of 40 cycles resulted in live birth. Conclusion: Our data suggests that RSCOS fertility preservation cycle outcomes are similar to those with SSCOS and result in age-appropriate euploidy rates.Yayın Ovarian stimulation and oocyte cryopreservation in females with cancer(Lippincott Williams & Wilkins, 2023) Oktay, Kutluk H.; Turan, VolkanPurpose of review: We reviewed the most recent developments including the safety and effectiveness data and success rates in individualized ovarian stimulation protocols for adult and postpubertal females with cancer. Recent findings: In women with breast cancer, aromatase inhibitor- and tamoxifen-supplemented stimulation protocols increase the margin of safety by limiting estrogen exposure. The outcomes of ovarian stimulation appear similar between cancer and noncancer populations, even with the recently developed random-start protocols, which allow initiation of ovarian stimulation anytime during the menstrual cycle. Based on lower anti-Mullerian hormone levels and primordial follicle density, carriers of BRCA pathogenic variants (BRCApv) have decreased ovarian reserve in comparison to women without those variants and may lose larger portion of their ovarian reserve post chemotherapy. Oocyte cryopreservation is also emerging as a suitable fertility preservation approach for selected postpubertal girls as young as 12 years of age. Summary: Individualized ovarian stimulation approaches combined with improvements in cryopreservation techniques increased the success and safety margin to preserve fertility with oocyte freezing. Women with BRCApv, on the other hand, may be at disadvantage as they have lower ovarian reserve and may lose larger portion of their ovarian reserve post chemotherapy compared to women who do not carry these variants.Yayın Ovarian stimulation and PGT-A outcomes with random start letrozole protocol for fertility preservation in breast cancer patients(Oxford University Press, 2022) Arkfeld, Christopher; Gayete-Lafuente, Sonia; Turan, Volkan; Oktay, KutlukStudy question Data on random start letrozole ovarian stimulation (RSL) in breast cancer patients is scant. We studied RSL outcomes from a single-center with fertility preservation expertise. Summary answer RSL appears to result in high oocyte and embryo/blastocyst yield, with an age-appropriate aneuploidy rate.Yayın Overall approach to fertility preservation and ındications for ovarian tissue harvesting and cryopreservation(Elsevier, 2022) Turan, Volkan; Türkgeldi, Engin; Öktem, Özgür; Oktay, KutlukThe field of fertility preservation has significantly evolved in the last two decades. Embryo, oocyte, and ovarian tissue cryopreservation are the well-established options for women pursuing fertility preservation. Ovarian tissue cryopreservation is the preferred method in prepubertal females and in postpubertal females who are not able to undergo controlled ovarian stimulation due to time constraints and by now, more than 158 live births have been recorded following reimplantation of cryopreserved ovarian tissues (Oktay et al., 2022). In this chapter, we will review overall approach to fertility preservation and indications for ovarian tissue harvesting and cryopreservation (Anderson et al., 2017).Yayın Patients with gynecological malignancies are similar to other IVF patients without cancer for clinical and molecular reproductive parameters and DNA damage response pattern(Nature Portfolio, 2024) Esmaeilian, Yashar; Yusufoğlu, Sevgi; İltumur, Ece; Uğurlu Çimen, Deniz; Vatansever, Doğan; Taşkıran, Çağatay; Turan, Volkan; Yakın, Kayhan; İncir, Said; Urman, Bülent; Öktem, ÖzgürThis study intended to investigate if gynecological cancers compromise ovarian function and reduce the success of assisted reproduction techniques (ART). No clinical and molecular data together is available on this issue for gynecological or other organ cancers. Steroidogenic pathways and DNA damage response characteristics of the granulosa cells retrieved from the 39 gynecological cancer patients were analyzed together with their clinical ART characteristics in comparison to 31 control ART patients. Patients with gynecological malignancies were similar to the control IVF patients for the number of mature oocytes retrieved, fertilization rates and embryo development competency. Molecular analyses of the granulosa cells retrieved from these cancer patients did not detect any perturbations in gonadotropin receptor expression and response, sex steroid production, cholesterol utilization/storage and, DNA damage response pattern in comparison to control IVF patients without cancer. This study provides the first reassuring clinical and molecular combined data set that the presence of gynecological malignancy does not appear to have any detrimental effect on clinical IVF cycle characteristics and ovarian functioning at molecular level.Yayın Preoperative evaluation and preparation for ovarian tissue transplant surgery(Elsevier, 2022) Oktay, Kutluk; Turan, VolkanOvarian tissue cryopreservation is a fertility preservation method which is no longer experimental. The number of healthy babies born with this technique is approaching 200 worldwide. It is the only option for preserving fertility in prepubertal girls and when women have time constraints to undergo ovarian stimulation before chemotherapy. The success of ovarian tissue transplantation surgery is contingent on many interactive factors. A sound, evidence-based preoperative evaluation and preparation of women for ovarian transplantation surgery represents one of the key determinants of success with this procedure. In this chapter, we discuss steps of preoperative evaluation and preparation for a safe and successful ovarian autotransplantation.Yayın Presence of BRCA mutations and a pre-chemotherapy AMH level of < 2NG/ML strongly predict risk of amenorrhea in women with breast cancer(Elsevier, 2023) Oktay, Kutluk H.; Turan, Volkan; Bedoschi, Giuliano; Goldfarb, Shari; Bang, HeejungThe likelihood of post-chemotherapy (ChT) amenorrhea is still empirically determined. Breast cancer is the most prevalent malignancy among the women of reproductive age. Our aim was to determine the predictors of amenorrhea risk post-ChT in women with breast cancer (ca). As acute amenorrhea (<12mo post-ChT) can be temporary, we used amenorrhea status 12- and 18-months post-ChT as the primary endpoint.Yayın A prospective longitudinal analysis of the predictors of amenorrhea after breast cancer chemotherapy: Impact of BRCA pathogenic variants(Wiley, 2023) Oktay, Kutluk H.; Turan, Volkan; Bedoschi, Giuliano; Abdo, Nadia; Bang, Heejung; Goldfarb, ShariBackground: Better tools for post-chemotherapy amenorrhea risk assessment are needed for fertility preservation decision-making. Our aim was to determine the predictors of amenorrhea risk at 12 and 18 months post-chemotherapy in women with breast cancer. Methods: 142 women with breast cancer were longitudinally followed for their menstrual changes at 6, 12, and 18 months after the completion of adjuvant chemotherapy with an Anthracycline-Cyclophosphamide-based (AC-based) or Cyclophosphamide-Methotrexate +5-Fluorouracil regimen. Pre- and/or post-chemo AMH levels, age, BMI, tamoxifen use, regimen type, and germline BRCA pathogenic variant (gBRCApv) status were evaluated for the prediction of amenorrhea at 6-18 months. Results: In multivariable-adjusted logistic regression, age (p = 0.03) and AMH (p = 0.03) at 12 months, and gBRCApv status (p = 0.03) at 18 months were significant predictors of amenorrhea (areas under the ROC curve of 0.77 and 0.76, for 12 and 18 months, respectively) among 102 evaluable subjects. An undetectable AMH immediately post-chemotherapy was predictive of amenorrhea with <18 month follow-up. In longitudinal analysis estimating time trends, baseline AMH and gBRCApv status was associated with the risk of amenorrhea over 6-18 months; the AMH >2.0 ng/mL group showed attenuated time-trend risk of amenorrhea versus AMH ≤2.0 group (ratio of ORs = 0.91, 95% CI = 0.86-0.97, p = 0.002), while the gBRCApv + showed a steeper time trend, versus the controls (ratio of ORs = 1.12, 95% CI = 1.04-1.20, p = 0.003). Conclusions: In addition to the pre- and post-treatment AMH levels, gBRCApv status is a novel potential predictor of amenorrhea at 12 and 18 months after chemotherapy. The higher likelihood of amenorrhea in women gBRCApv suggests that they are more prone to losing their fertility post-chemotherapy.Yayın Role of chemokines in early pregnancy loss(Spandidos Publications, 2022) Gökçe, Şefik; Herkiloğlu, Dilşad; Çevik, Özge; Turan, VolkanThe present study aimed to compare decidual protein levels and gene expression levels of chemokines between patients with early pregnancy loss and those with voluntary abortion. A total of 15 patients between 6 and 10 gestational weeks, who presented with negative fetal heartbeat to the obstetrics and gynecology outpatient clinics of Gaziosmanpasa Hospital (Yeni Yuzyil University, Istanbul, Turkey) and who had no additional systemic disease and 13 patients between 6 and 10 gestational weeks, who presented with positive fetal heartbeat for voluntary abortion were included in the present study. CX3CL1, CCL17, CXCR4, chemokine ligand 12 (CXCL12) and intercellular adhesion molecule (ICAM)5 protein expression levels were determined by ELISA and gene expression levels by reverse transcription-quantitative PCR in fresh materials recovered after therapeutic curettage. CX3CL1, CCL17, CXCR4, CXCL12 protein levels were significantly higher and ICAM protein level was significantly lower in pregrant women with missed abortion compared with those with voluntary abortion. While the amount of increase in mean CX3CL1, CCL17, CXCR4 and CXCL12 gene expression levels in the tissues of pregnant women with missed abortion was statistically higher than the pregnant women who underwent voluntary abortion, the amount of increase in ICAM5 gene expression was found to be lower (P<0.001) in those with missed abortion. In conclusion, the findings of the present study suggested that CCL17, CX3CL1, CXCL12, CXCR4 and ICAM5 may be associated with missed abortion and may play an important role in placental invasion and the continuation of pregnancy.
