Safety of ovarian cryopreservation and transplantation in patients with acute leukemia: a case series.

BACKGROUND: With increased success, ovarian tissue cryopreservation has recently become a standard technique for fertility preservation. However, malignant cell introduction through ovarian tissue transplantation remains a major concern for patients with acute leukemias. OBJECTIVE: This study aimed to investigate the safety of performing autologous ovarian tissue transplantation in survivors of acute leukemia. STUDY DESIGN: Clinical, histopathological, and molecular data of 4 women with acute myeloid leukemia and 2 women with acute lymphoblastic leukemia who underwent ovarian tissue cryopreservation and transplantation were analyzed in this case series. Following cryopreservation of 66% to 100% of an ovarian cortex with a slow freezing method, all women received high-dose multiagent alkylating preconditioning chemotherapy for allogeneic hematopoietic stem cell transplantation. Before the ovarian tissue transplantation, (1) antral follicle counts, serum antimüllerian hormone and follicle-stimulating hormone levels were assessed to confirm primary ovarian insufficiency; (2) all recipients were cleared by their hematologist-oncologists; (3) representative cortical strips were screened for leukemia infiltration by histologic (hematoxylin and eosin staining), immunohistochemical (CD3, CD20, CD34, CD68, CD117, CD163, PAX-5, Tdt, lysozyme, and MPO), and molecular marker evaluation (BCR/ABL p190 and AML1/ETO) where appropriate. RESULTS: The median age was 20 years (interquartile range, 15-32) at ovarian tissue cryopreservation. Before undergoing hematopoietic stem cell transplantation, all patients received induction or consolidation chemotherapy that included cytarabine + daunorubicin or Berlin-Frankfurt-Munich-95 protocol and were in remission. The mean serum antimüllerian hormone was 1.9±1.7 ng/mL before ovarian tissue cryopreservation. In all cases, ovarian tissue screening for leukemic cells was negative. Ovarian transplantation was performed laparoscopically with or without robotic assistance, after a median of 74.5 months (interquartile range, 41-120) after ovarian tissue cryopreservation. Ovarian function resumed in all patients after a median of 3.0 months (range, 2.5-4.0), and 2 women had 1 live birth each. The median graft longevity was 35.5 months (interquartile range, 18-57) after ovarian tissue transplantation. After a median follow-up of 51 months (interquartile range, 20-74), all patients remained relapse-free. In 1 patient, the graft was removed during cesarean delivery and was negative for immunochemical leukemia markers. CONCLUSION: Our long-term follow-up demonstrated no evidence of disease relapse after ovarian tissue transplantation in patients with acute leukemia who received allogeneic hematopoietic stem cell transplantation. This safety profile may be explained by the fact that these patients are induced into remission by nongonadotoxic induction chemotherapy before undergoing ovarian tissue cryopreservation. We propose that ovarian tissue cryopreservation should not be excluded as a fertility preservation option for young women with leukemia who are due to receive preconditioning chemotherapy before allogeneic hematopoietic stem cell transplantation.

Proposal for Diagnostic Criteria of Y-Shaped Dysmorphic Uterus Based on 3-Dimensional Transvaginal Ultrasound Measurements.

STUDY OBJECTIVE: To define objective and readily applied diagnostic criteria for Y-shaped uteri using 3-dimensional transvaginal ultrasound (3D-TVUS) volume recordings. DESIGN: A retrospective case-control diagnostic measurements study. SETTING: A tertiary university hospital's reproductive health and research center. PATIENTS: Two hundred thirteen patients who presented with infertility between January 2020 and December 2022. INTERVENTIONS: Two blinded physicians re-evaluated the 3D-TVUS images of all patients for the presence of a uterine abnormality. The images of patients with a Y-shaped uterus were re-evaluated, and descriptive measurements were done. MEASUREMENTS AND MAIN RESULTS: The most common uterine abnormality in this cohort was the Y-shaped uterus with a prevalence of 12.2%, followed by the arcuate, T-shaped, and septate uteri, respectively. Reviewers identified 26 and 28 Y-shaped uteri, respectively, and came to a consensus on 25 images. Diagnostic criteria for the Y-shaped uterus based on 3D-TVUS findings have been specified as: lateral indentation depths between 4 and 7 mm, fundal indentation depth between 5 and 9 mm, lateral indentation angles between 121° and 149°, fundal indentation angle between 121° and 145°, and Y-angles 25° to 46°. CONCLUSION: Some subtypes of dysmorphic uteri, such as the Y-shaped uterus, whose clinical significance is unknown and may be variants of the normal, may actually be more common than thought. Determining objective diagnostic criteria with 3D-TVUS will allow standard research on these anomalies and their clinical significance.

Evaluation of the Impact of Letrozole in Combination with the GnRH Antagonist Ovarian Stimulation Protocol in Patients Expected to Have a Poor Ovarian Response (POSEIDON Groups 3 and 4).

Background and Objectives: The objective of this study was to evaluate the impact of adjuvant letrozole administration during ovarian stimulation using the gonadotropin-releasing hormone (GnRH) antagonist protocol on treatment outcomes in women categorized into POSEIDON groups 3 and 4. Materials and Methods: This retrospective cohort study analyzed data from patients classified into POSEIDON groups 3 and 4 who underwent fresh embryo transfer subsequent to intracytoplasmic sperm injection following a GnRH antagonist stimulation protocol between January 2017 and December 2021. Patients were divided into two groups: the GnRH-LZ group, who received letrozole at a dosage of 5 mg/day for five consecutive days, and the GnRH-ant group, who did not receive adjuvant letrozole. The primary outcome measure of the study was a comparative analysis of live birth rates between the two groups. Results: A total of 449 patients were deemed suitable for final analysis and were allocated into two groups: 281 patients in the GnRH-ant group and 168 patients in the GnRH-LZ group. Live birth rates were found to be comparable in both groups (11% vs. 9%, p = 0.497). Letrozole administration significantly reduced the total amount of gonadotropins required (2606.2 ± 1284.5 vs. 3097.8 ± 1073.3, p < 0.001), the duration of ovarian stimulation (11.2 ± 3.9 vs. 10.2 ± 3, p = 0.005), and the serum peak estradiol concentration (901.4 ± 599.6 vs. 463.8 ± 312.3, p < 0.001). Conclusions: Adjuvant letrozole administration did not demonstrate a significant impact on live birth rates among women categorized into POSEIDON groups 3 and 4. However, this approach may offer potential cost reductions by diminishing the necessity for exogenous gonadotropins and shortening the duration of ovarian stimulation.

Random start ovarian stimulation before gonadotoxic therapies in women with cancer: a systematic review and meta-analysis.

The aim of this systematic review and meta-analysis was to quantify the effect of random start ovarian stimulation (RSOS) compared with conventional start ovarian stimulation (CSOS) in cancer patients before gonadotoxic treatment. The final analytical cohort encompassed 688 RSOS and 1076 CSOS cycles of cancer patients before gonadotoxic treatment. Eleven studies were identified by database searches of MEDLINE, Cochrane Library and cited references. The primary outcomes of interest were the number of oocytes and mature oocytes collected, the number of embryos cryopreserved and the metaphase II (MII)-antral follicle count (AFC) ratio. The studies were rated from medium to high quality (from 6 to 9) according to the Newcastle-Ottawa Quality Assessment Scale. The two protocols resulted in similar numbers of oocytes collected, MII oocytes, embryos available for cryopreservation and comparable MII-AFC and fertilization rates. The duration of ovarian stimulation was longer (standardized mean difference [SMD] 0.35, 95% CI 0.09 to 0.61; P = 0.009) and gonadotrophin consumption was higher (SMD 0.23, 95% CI 0.06 to 0.40; P = 0.009) in RSOS compared with CSOS. This systematic review and meta-analysis show that the duration of stimulation is longer, and the total gonadotrophin consumption is higher in cancer patients undergoing RSOS compared with those undergoing CSOS, with no significant effect on mature oocyte yield.

Transabdominal ultrasound-guided oocyte retrieval for oocyte cryopreservation using a vaginal probe: a comparison of applicability, effectiveness, and safety with conventional transvaginal approach.

PURPOSE: We aimed to compare the feasibility, effectiveness, and safety of transabdominal ultrasound-guided oocyte retrieval (TUGOR) using a vaginal probe and traditional vaginal approach in virgin patients undergoing oocyte cryopreservation. METHODS: A total of 116 virgin patients who underwent transabdominal ultrasound-guided oocyte retrieval using a vaginal ultrasound probe and 33 patients matched for BMI, antral follicle count, age, day 3 FSH, estradiol, and AMH who underwent vaginal approach were enrolled. Mean number of total oocytes collected, mean number of cryopreserved MII oocytes, duration of the procedure, duration of stimulation, mean gonadotropin consumption, mature oocyte ratio, and a modified follicle-oocyte index were compared between the groups. RESULTS: No statistical difference was found between the groups in mean number of follicles > 12 mm (4.62 ± 4.54 vs. 5.44 ± 4.52), mean number of oocytes collected (4.44 ± 4.14 vs. 5.33 ± 4.52), mean number of cryopreserved MII oocytes (4.01 ± 3.67 vs. 4.53 ± 4.13), mean duration of the procedure (12.4 ± 1.2 vs. 13.4 ± 1.6 min), mean days of stimulation (8.05 ± 1.91 vs. 8.35 ± 1.72 days), mean gonadotropin consumption (1507.9 ± 475.3 vs. 1571.74 ± 404.6 units), mature oocyte ratio (0.78 ± 0.24 vs. 0.82 ± 0.26), and modified follicle oocyte index (0.86 ± 0.63 vs. 0.84 ± 0.19). In the TUGOR group, superficial epigastric artery injury occurred in two patients and resolved spontaneously. CONCLUSION: Transabdominal oocyte retrieval using a vaginal ultrasound is a safe, effective, and feasible method of oocyte retrieval in some selected patient groups.

Intrauterine insemination with ovarian stimulation is a successful step prior to assisted reproductive technology for couples with unexplained infertility.

The present retrospective cohort study analysed data of couples with unexplained infertility who underwent two to three intrauterine insemination (IUI) cycles. The inclusion criteria were age 20-40 years, failure to conceive for at least two years of unprotected intercourse, ovulation, normal semen analysis, and tubal patency. Total of 578 IUI cycles of 286 couples with unexplained infertility were included in the final analyses. The mean age and duration of infertility of the study population were 28.8 ± 5.1 and 5.2 ± 3.4 years, respectively. The clinical pregnancy rate (CPR) and live birth rate (LBR) per cycle were 16.6 and 13.1%, respectively. The cumulative CPR following two to three IUI cycles was 33.5% and the cumulative LBR was 26.5% for the entire cohort. The duration of infertility was significantly shorter in women whose IUI attempt were successful (p = .036). Up to three cycles of IUI with ovarian stimulation seems as an effective first-line treatment modality in unexplained infertility.IMPACT STATEMENTWhat is already known on this subject? Cont rolled ovarian stimulation combined with intrauterine insemination (IUI) is a common infertility treatment as a low-cost, less-invasive alternative to in vitro fertilisation (IVF) and was approved as a first line treatment option for unexplained infertility However, the UK National Institute for Health and Care Excellence (NICE) guideline states that IUI is not recommended to couples with unexplained infertility, male factor and mild endometriosis, unless the couples have religious, cultural or social objections to proceed with IVF.What do the results of this study add? Up to three IUI cycles with ovarian stimulation can be considered as an effective treatment modality in unexplained infertility even in couples who could not achieve pregnancy by expectant management for two years.What are the implications of these findings for clinical practice and/or further research? The clinicians should reconsider the NICE recommendation of IVF in the light of recent studies including ours which recommend IUI together when dealing couples with unexplained infertility.

Longitudinal change in serum inflammatory markers in women with tubo-ovarian abscess after successful surgical treatment: a retrospective study.

High levels of serum inflammatory markers are related to extended hospitalisation and more severe disease in the case of tubo-ovarian abscess (TOA). There is scarce information on the serial measurement of inflammatory markers during the postoperative follow-up period of surgically treated TOA. The present study aimed to assess the postoperative longitudinal changes in serum inflammatory markers following surgery for TOA. In this retrospective cohort study, patients who underwent surgery for TOA between January 2010 and March 2020 were reviewed. All inflammatory markers peaked within 48 hours after surgical intervention and then declined with time. The predicted mean of white blood cell count (WBC) to return to normal was 2.5 days (95% CI: 1.0-4.3), which was followed by neutrophil to lymphocyte ratio (NLR) (7.1 days, 95% CI: 4.7-10.8) and C-reactive protein (CRP) (+14 days). In conclusion, serum inflammatory markers increase in the very early post-operative period. While the normalisation period is very slow, it may not be appropriate to use CRP for evaluating the treatment success of TOA surgery. However, WBC and NLR measurements might be useful for follow-up and predicting the need for medical or surgical intervention.Impact statementWhat is already known on this subject? Serum inflammatory markers such as C-reactive protein, white blood cell count, and neutrophil to lymphocyte ratio are usually elevated in women with tubo-ovairan abscess, and high levels of these markers are associated with extended hospitalisation and more severe disease.What do the results of this study add? Our results indicate that the serum inflammatory markers increase and peak within the first 48 hours after surgery for tubo-ovarian abscess. Normalisation of white blood cell count is the fastest in successfully treated patients. However, normalisation of C-reactive protein is slowest, reaching 14 days and might not be as feasible as white blood cell count and neutrophil to lymphocyte ratio in postoperative patient follow-up.What are the implications of these findings for clinical practice and further research? The serum inflammatory markers should be interpreted with caution within 48 hours after surgical treatment for tubo-ovarian abscess. Instead of C-reactive protein white blood cell count, and neutrophil to lymphocyte ratio measurements can be preferred in post-operative follow-up to predict the need for further medical or surgical intervention.

Transabdominal ultrasound guided oocyte retrieval using vaginal ultrasound probe: Definition of the technique.

PURPOSE: To define whether transabdominal ultrasound guided oocyte retrieval (TUGOR) is a feasible, effective and safe method. METHODS: A total of 64 patients who underwent TUGOR in a tertiary referral university hospital in vitro fertilization (IVF) clinic were enrolled. Indications, total number of oocytes collected, total number and percentage of mature oocytes, duration of procedure, complication rates and total number of fertilized oocytes were assessed. RESULTS: The indications for TUGOR were as follows; virgin women with decreased ovarian reserve who opted fertility preservation (n = 52, 81.1%), Ewing Sarcoma (n = 1, 1.56%), breast cancer (n = 4, 6.2%), lymphoma (n = 1, 1.56%) endometrioma (n = 1, 1.56%), immature teratoma of the ovary (n = 1, 1.56%), multiple large uterine fibroids (n = 2, 3.1%), adnexal transposition due to bowel surgery (n = 1, 1.56%) and Mayer Rokitansky Küster Hauser Syndrome (n = 1, 1.56%). Total number of oocytes retrieved and mean number of oocytes collected were 315 and 4.92 ± 1.7 (range 1-21), respectively. The mean duration of the procedure was 12.4 ± 1.2 min. The number and percentage of mature oocytes were 272 and 86.3%, respectively. A total of 14 embryos were frozen in four patients and one blastocyst transfer was performed ending up with live birth. Superficial epigastric artery injury occurred in two patients and resolved spontaneously. No oocyte was retrieved in five patients with single growing follicle in the first attempt. CONCLUSION: TUGOR is a feasible, effective and safe method of oocyte retrieval for the purpose of fertility preservation or in patients with inaccessible ovaries via transvaginal route undergoing IVF.

The association between operative hysteroscopy prior to assisted reproductive technology and cervical insufficiency in second trimester.

PURPOSE: To assess the association between operative hysteroscopy prior to assisted reproductive technology (ART) cycle and cervical insufficiency (CI) in the second trimester of pregnancy. METHODS: A retrospective cohort study was conducted. The charts of all women who got pregnant following an ART cycle between January 2015 and June 2018 were reviewed. The study group consisted of pregnant women who underwent operative hysteroscopy within 6 months before conception. The control group consisted of pregnant women who did not undergo hysteroscopy or any type of cervical surgical procedure before conception. The primary outcome measure was CI during the second trimester (13-27 weeks of gestation). RESULTS: A total of 363 pregnancies achieved by ART cycles were assessed. After the exclusion of multiple pregnancies (n = 19), previous surgical procedures (n = 4) and first-trimester pregnancy losses (n = 80), there were 29 women in the study group and 231 women in the control group. The mean ages of the study and control groups were 31.2 ± 4.06 and 29.82 ± 4.71 years, respectively (P = 0.13). The indications for operative hysteroscopy were uterine septum (n = 19), T-shaped uterus (n = 4), endometrial polyp (n = 4), and submucosal fibroids (n = 2). The rates of CI in the study and control groups were 13.7% (4/29) and 3.4% (8/231), respectively (P = 0.012). The term delivery rates in the study and control groups were 79.3 and 91.8%, respectively (P = 0.044). CONCLUSIONS: Operative hysteroscopy prior to ART cycles is significantly associated with CI between 13 and 27 weeks of gestation. Further investigation with larger cohorts is urgently needed to clarify this issue.

Endometrioma surgery is associated with increased risk of subsequent assisted reproductive technology cycle cancellation; a retrospective cohort study.

The aim of this study was to assess the effect of laparoscopic removal of endometrioma on assisted reproductive technology (ART) outcome. A retrospective cohort study was conducted at a university hospital between January 2014 and December 2017. The ART group consisted of 26 women who underwent 44 ART cycles in the presence of ovarian endometrioma and the surgery group consisted of 53 women who underwent 58 ART cycles after laparoscopic removal of ovarian endometrioma/s. There were no statistically significant differences between the groups regarding demographic parameters and background features including cycle parameters. The live birth rates in the ART and Surgery groups per embryo transfer were 23.7 and 26.1%, respectively (p = .800). The rate of cycle cancellation due to poor response and/or failed oocyte retrieval was significantly higher in the Surgery group than ART group (13.7 vs. 0%, respectively; p = .018). In conclusion, cystectomy significantly increases the risk of cycle cancellation due to poor ovarian response, which might be catastrophic individually. However, it does not seem to affect the live birth rates.IMPACT STATEMENTWhat is already known on this subject? Both the presence of an endometrioma or surgical removal may have deleterious effects on fertility potential.What do the results of this study add? Our results confirm that although cystectomy has no benefit on the number of oocytes collected and live birth rate, it increases the risk of cycle cancellation significantly in assisted reproductive technology cycles following endometrioma surgery.What are the implications of these findings for clinical practice and/or further research? Postponing cystectomy until a freeze-all cycle may be the best option to maximise the number of oocytes retrieved and to maximise the ovarian response.

First pregnancy and live birth in Turkey following frozen-thawed ovarian tissue transplantation in a patient with acute lymphoblastic leukemia who underwent cord blood transplantation.

PURPOSE: To report the first live birth after frozen-thawed ovarian transplantation in Turkey and the second case for an acute lymphoblastic leukemia (ALL) survivor in the world. METHODS: A 19-year-old patient underwent ovarian tissue cryopreservation (OTC) before cord blood transplantation in 2010. She was diagnosed as ALL with a bone marrow biopsy revealing 90% blast ALL-L2 type, and karyotype analyses indicated reciprocal translocation at t(9;22)(q34;q11). The patient received the Berlin-Frankfurt-Munster (BFM) protocol, and complete remission was achieved before fertility preservation. Serum AMH level was measured as 1.5 ng/ml, and 12 antral follicles were counted on ultrasound. She was informed about fertility preservation options and decided to proceed with OTC, with her signed consent before cord blood transplantation in April 2011. Ovarian tissue transplantation (OTT) was performed in 2017 when the patient was menopausal with serum FSH levels > 100 IU/ml and estradiol < 20 pg/ml and hematologically in molecular remission. Detailed molecular analysis, standard histology, and immunohistochemistry demonstrated that the thawed tissue is free of malignant cells. RESULTS: Six months following OTT, she had spontaneous menstruation with serum FSH 11 IU/ml and estradiol 53 pg/ml. Two consecutive IVF cycles yielded three top-quality embryos. Following three embryo transfer cycles, one fresh and two frozen, a healthy term live birth was achieved. Frozen-thawed-transplanted tissues were extracted during caesarean delivery upon the patient's request after a total period of 25 months in vivo, and histopathological evaluation revealed that the tissue was free of leukemic infiltration. CONCLUSION: The authors report the first pregnancy and live birth in Turkey and the second live birth in the world following transplantation of frozen-thawed ovarian tissue in a leukemia survivor. As the transplanted tissues were removed during caesarean delivery, histological findings prove the functionality and the malignant-free status of the transplanted tissue during the grafted period.

Random start controlled ovarian hyperstimulation for fertility preservation during incidental pregnancy: a case report of blastocyst vitrification from in vitro matured oocytes.

Here, we present a diffuse large B cell lymphoma patient admitted for fertility preservation before cancer therapy and whose pregnancy was recognized incidentally just after the start of random start controlled ovarian stimulation (RSCOH) during the stimulation cycle. Despite an optimal homogenous growth of follicle cohort, majority of the retrieved oocytes were immature after GnRHa trigger. Possible effects of extremely high serum progesterone and/or ß-hCG levels on oocyte in vivo maturation are discussed with the surprising high rate of in vitro maturation and subsequent good embryo development. It seems that in case of need for pregnancy termination as a result of an urgent cancer therapy, RSCOH can be started and patients may benefit from overnight in vitro maturation of oocytes.

Does different subfertility etiology affect pregnancy rates in intrauterineinsemination cycles?

Background/aim: To investigate the relationship between subfertility etiologies and success rates in controlled ovarian stimulation and intrauterine insemination (COS­IUI) cycles. Materials and methods: The medical records of 218 couples who applied to a university-based fertility center were analyzed retrospectively. Detailed infertility examination data and pregnancy outcomes were compared according to different subfertility etiologies. The study groups with regard to subfertility etiologies were minimal­mild endometriosis, unexplained infertility, and mild male infertility. The primary outcome measure was live birth rate. Results: There were no statistically significant differences between the groups regarding demographics except for total motile sperm count. Live birth rates in the male infertility group were comparable to the endometriosis and unexpected infertility groups (6.6%, 11.9%, and 10.3%, respectively; P = 0.63). Conclusion: The success rate of the mild male subfertility group following COS­IUI cycles for live birth rates was similar to those of the endometriosis and unexplained subfertility groups.

Extrapelvic Sentinel Lymph Nodes in Endometrial Cancer Patients With Unmapped Pelvic Side: A Brief Report.

OBJECTIVE: The aim of the study was to evaluate extrapelvic sentinel lymph nodes (SLNs) in clinical early-stage endometrial cancer patients with unmapped pelvic side(s) during fluorescent imaging-based sentinel mapping. MATERIALS AND METHODS: Eligible patients underwent sentinel mapping using cervical injection of indocyanine green and near-infrared florescent imaging compatible endoscopic systems. Pelvic SLNs were identified and resected. If bilateral mapping was not achieved, upper lymph nodes areas including presacral, upper common iliac, and para-aortic caval regions were explored for any SLN. Systematic lymphadenectomy was performed after applying SLN algorithm steps. RESULTS: In 24 of 101 patients, bilateral pelvic mapping was not achieved. Bilateral unmapping was seen in 4 of 24 and unilateral pelvic side mapping in 20 of 24 patients. There was no extrapelvic SLN among 4 cases with bilateral pelvic unmapping, whereas 8 (40%) of 20 patients with unilateral pelvic mapping had extrapelvic SLNs. Five of extrapelvic SLNs were in presacral, 2 in upper common iliac, and 1 in paracaval regions. CONCLUSIONS: Observing for extrapelvic SLNs in cases with unmapped pelvic side(s) could increase detection rate of SLN mapping in clinical early-stage endometrial cancer.

Prognostic factors for disease-free and overall survival of patients with uterine carcinosarcoma.

BACKGROUND: Uterine carcinosarcoma (UCS) is a relatively rare and very aggressive tumor. The predictors of survival for patients with UCS have not been determined clearly yet. The aim of the present study was to investigate the possible predictors of disease-free survival (DFS) and overall survival (OS) for patients with UCS. METHODS AND MATERIALS: All patients with UCS who were treated surgically at a university-based Gynecology Oncology Clinic between January 2008 and December 2014 were recruited into this retrospective cohort study. Data regarding clinical, pathologic and treatment information were obtained retrospectively from hospital records. The Kaplan-Meier method was used to calculate DFS and OS, and Cox regression analysis was performed to define the effects of risk factors on survival. RESULTS: A total of 88 UCS patients with a median age of 64.5 years were included in the study. Forty-seven (53.4%) patients were diagnosed with stage III disease and seven (7.9%) with stage IV disease. The median follow-up time was 16 months. Among all patients, 60 (68.1%) underwent lymphadenectomy. Optimal cytoreductive surgery was achieved in 67 (76.1%) patients. Stepwise variable selection Cox regression analysis showed that lymph node metastasis was associated with poor DFS (hazard ratio 6.524; 95% CI 2.625-16.211; P < 0.001) and OS (hazard ratio 6.993; 95% CI 2.631-18.587; P < 0.001). Subgroup analysis in both early and advanced-stage diseases revealed no significant impact of risk factors on survival. CONCLUSIONS: Lymph node metastasis is the most significant prognostic factor associated with poor DFS and OS in UCS patients.

Final oocyte maturation with two different GnRH agonists in antagonist co-treated cycles at risk of ovarian hyperstimulation syndrome.

Triptorelin 0.2 mg and leuprolide 1 mg subcutaneous injections for triggering final follicular maturation were compared in patients with a high risk for ovarian hyperstimulation syndrome (OHSS). Infertile patients treated with GnRH antagonist protocol between January 2014 and March 2016 were recruited. Patients with high serum oestradiol levels on HCG day (>3000 pg/ml) indicating a risk of OHSS consisted of the study groups (A and B). Patients with serum oestradiol levels less than 3000 pg/ml consisted of the control group (C). A single injection of 0.2 mg triptorelin, 1 mg leuprolide and 10000 IU HCG were administered for final oocyte triggering in groups A (n = 63), B (n = 74) and C (n = 131), respectively. Demographic parameters were comparable between the groups. No cases of severe or moderate OHSS occurred in any group. The clinical pregnancy rates were 31.7%, 37.8% and 32.8% in groups A, B and C, respectively. Both injections had comparable efficacy in clinical outcome and OHSS risk. Regardless of preferred drug, GnRH agonist trigger for final oocyte maturation seems to be safe for patients with high OHSS risk, and can be safely used in fresh embryo transfer cycles.

Preoperative 18F-Fluorodeoxyglucose Positron Emission Tomography/CT in Prediction of Uterine Risk Factors and Lymph Node Metastasis: An Analysis of 111 Endometrioid Endometrial Cancer Patients.

INTRODUCTION: This study evaluated the role of 18F-fluorodeoxyglucose (FDG) positron emission tomography/CT (PET/CT) in the detection of lymph node metastases and the association between uterine maximum standardized uptake values (SUVmax) and the histopathological features in endometrial cancer patients. MATERIALS AND METHODS: Patients with endometrioid endometrial cancer underwent preoperative 18F-FDG PET/CT imaging and were staged surgically. 18F-FDG PET/CT findings were compared with final pathology reports. Grade 3 histology or grade 2 histology with myometrial invasion ≥50% was established as a high risk feature. RESULTS: One hundred and eleven patients were analysed. Sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of 18F-FDG PET/CT in the detection of lymph node metastasis in all patients (n = 111) were 67, 96, 93, 60 and 97%, respectively. In the high-risk group, sensitivity, specificity, accuracy, PPV and NPV of 18F-FDG PET/CT were 75, 92, 91, 60 and 96%, respectively. Uterine SUVmax was found to be associated with myometrial invasion, grade and cervical stromal involvement. CONCLUSIONS: 18F-FDG PET/CT has limited sensitivity and accuracy in detecting lymph node metastasis. Therefore, as of now, it is not accepted as a modality that can replace lymphadenectomy. SUVmax values can predict high-risk factors.

Comparison of alternative ßhCG follow-up protocols after single-dose methotrexate therapy for tubal ectopic pregnancy.

PURPOSE: To evaluate the performances of five different ßhCG follow-up protocols after single-dose methotrexate therapy for tubal ectopic pregnancy (EP). METHODS: Data of patients who received single-dose methotrexate therapy for tubal EP at a university hospital between January 2011 and July 2016 were reviewed. A 'successful methotrexate treatment' was defined if the EP treated with no need for surgery. The performances of different protocols were tested by comparing with the currently used '15% ßhCG decrease between days 4 and 7' protocol. The tested follow-up protocols were '20, 25%, and any ßhCG decrease between days 0/1 and 7' and '20% and any ßhCG decrease between days 0/1 and 4'. RESULTS: Among the 96 patients evaluated, 12 (12.5%) required second dose. Totally, 91 (94.8%) patients treated successfully with no need for surgery. Four patients were operated within 4 days following the second dose. One patient who did not need second dose according to the standard follow-up protocol was operated on the 10th day due to rupture (specificity = 80%). Two protocols, namely '20% ßhCG decrease between days 0/1 and 7' and 'any ßhCG decrease between days 0/1 and 7' did not show statistically significant differences from the index protocol regarding the number of patients who should be assigned to 2nd dose. CONCLUSIONS: 'Any ßhCG decrease between days 0/1 and 7' protocol may substitute the currently used one to decide second dose methotrexate in tubal EP management. Omitting 4th day measurement seems to be more convenient and cost effective.

Nomogram with potential clinical use to predict lymph node metastasis in endometrial cancer patients diagnosed incidentally by postoperative pathological assessment.

PURPOSE: To determine the clinical and pathological risk factors for lymph node metastasis (LNM) in patients with endometrial cancer and to create a nomogram to predict LNM in patients without surgical staging. METHODS: All patients with endometrial adenocarcinoma who were treated surgically at a university based gynecologic oncology clinic between January 2011 and December 2014 were recruited. Women with endometrial adenocarcinoma who were surgically staged including lymphadenectomy were included in the study. Data regarding clinical and pathological risk factors were recorded. The histopathologic slides from the staging surgeries were re-evaluated microscopically by a gynecologic pathologist for all parameters along with lymphovascular space invasion (LVSI). RESULTS: A total of 279 patients with endometrial cancer were analyzed. Among those, 31 (11.1%) had lymph node metastasis. According to the univariate analyses, elevated CA 125 (>35 U/mL), LVSI, myometrial invasion ≥50%, grade 3 disease, non-endometrioid type, and cervical stromal involvement were significantly associated with LNM. The multivariate logistic regression analysis showed that LVSI, non-endometrioid type, elevated CA 125, and cervical stromal involvement increased the risk of LNM. However, myometrial invasion and grade did not significantly affect the risk of LNM. A nomogram to predict LNM was constructed using these factors (concordance index 0.92). CONCLUSIONS: LVSI is the most important predictor for LNM. The present nomogram can be useful to decide if adjuvant therapy is required for patients who undergo simple hysterectomy for a benign etiology and incidentally diagnosed with endometrial cancer by pathological evaluation.