Prevalence of occult leiomyosarcomas and atypical leiomyomas after laparoscopic morcellation of leiomyomas in reproductive-age women.

STUDY QUESTION: What is the prevalence of leiomyosarcomas and atypical leiomyomas after laparoscopic morcellation of fibroids in reproductive age women? SUMMARY ANSWER: No case of leiomyosarcomas but seven atypical leiomyomas were found in 1216 subjects. WHAT IS KNOWN ALREADY: Although uterine sarcoma is a rare entity affecting usually older peri- or post-menopausal women, the Food and Drug Administration discourages use of laparoscopic power morcellation of uterine fibroids. STUDY DESIGN, SIZE, DURATION: Retrospective review of data extracted from a single center database of 1216 consecutive women who underwent laparoscopic morcellation of 2582 unsuspicious leiomyomas between June 2003 and December 2015 and were followed-up until December 2016. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: A total of 1216 women, aged 18-45 years, underwent laparoscopic morcellation of 2582 apparently benign leiomyomas by the same surgeon and all specimen slides were examined by the same experienced pathologist. MAIN RESULTS AND THE ROLE OF CHANCE: The prevalence of leiomyosarcomas and atypical leiomyomas was 0% (95% CI: 0-0.3%) and 0.6% (95% CI: 0.23-1.18%) (six atypical-bizarre and one mitotically active leiomyoma) respectively. In addition, there were identified 34 cases of adenomyomas, 45 leiomyomas with infarcts, 81 cellular leiomyomas and 133 degenerated leiomyomas. No morcellator-associated complication was recorded and none of the patients included in this study required conversion to laparotomy. LIMITATIONS, REASONS FOR CAUTION: Retrospective and single referral center study design. WIDER IMPLICATIONS OF THE FINDINGS: Laparoscopic morcellation of unsuspicious leiomyomas after careful preoperative work up seems to be safe in women of reproductive age. STUDY FUNDING/COMPETING INTEREST(S): None.

Transdermal testosterone pretreatment in poor responders undergoing ICSI: a randomized clinical trial.

STUDY QUESTION: Does pretreatment with transdermal testosterone increase the number of cumulus-oocyte complexes (COCs) retrieved by more than 1.5 in poor responders undergoing intracytoplasmic sperm injection (ICSI), using recombinant follicle stimulating hormone (FSH) and gonadotrophin releasing hormone agonists (GnRHa)? SUMMARY ANSWER: Testosterone pretreatment failed to increase the number of COCs by more than 1.5 as compared with no pretreatment in poor responders undergoing ICSI (difference between medians: 0.0, 95% CI: -1.0 to +1.0). WHAT IS KNOWN ALREADY: Androgens are thought to play an important role in early follicular development by enhancing ovarian sensitivity to FSH. In a recent meta-analysis, testosterone pretreatment resulted in an increase of 1.5 COCs as compared with no pretreatment. However, this effect was based on the analysis of only two randomized controlled trials (RCTs) including 163 patients. Evidently, there is a need for additional RCTs that will allow firmer conclusions to be drawn. STUDY DESIGN, SIZE, DURATION: The present RCT was designed to detect a difference of 1.5 COCs (sample size required = 48 patients). From 02/2014 until 04/2015, 50 poor responders fulfilling the Bologna criteria have been randomized (using a randomization list) to either testosterone pretreatment for 21 days ( ITALIC! n = 26) or no pretreatment ( ITALIC! n = 24). PARTICIPANTS/MATERIALS, SETTING, METHODS: All patients underwent a long follicular GnRHa protocol. Recombinant FSH stimulation was started on Day 22 following GnRHa initiation. In the testosterone pretreatment group, a daily dose of 10 mg of testosterone gel was applied transdermally for 21 days starting from GnRHa initiation. Results are expressed as median (interquartile range). MAIN RESULTS AND THE ROLE OF CHANCE: No differences in baseline characteristics were observed between the two groups compared. Testosterone levels [median (interquartile range)] were significantly higher in the testosterone pretreatment on the day of initiation of FSH stimulation [114 (99.5) ng/dl versus 20 (20) ng/dl, respectively, ITALIC! P < 0.001]. Duration of FSH stimulation [median (interquartile range)] was similar between the groups compared [12.5 (3.0) days versus 12 (3.0) days, respectively, ITALIC! P = 0.52]. The number of COCs retrieved [median (interquartile range)] was not different between the testosterone pretreatment and the no pretreatment groups [3.5 (4.0) versus 3.0 (3.0), 95% CI for the median: 2.0-5.0 versus 2.7-4.3, respectively; difference between medians: 0.0, 95% CI: +1.0 to -1.0). Similarly no differences were observed regarding fertilization rates [median (interquartile range)] [66.7% (32.5) versus 66.7% (42.9), respectively, ITALIC! P = 0.97] and live birth rates per randomized patient (7.7% versus 8.3%, respectively, rate difference: -0.6%, 95% CI: -19.0 to +16.9). LIMITATIONS, REASONS FOR CAUTION: The study was not powered to detect differences less than 1.5 COCs, although it is doubtful whether these differences would be clinically relevant. Moreover, due to sample size restrictions, no conclusions can be drawn regarding the probability of live birth. WIDER IMPLICATIONS OF THE FINDINGS: The results of this randomized clinical trial, suggesting that pretreatment with 10 mg of transdermal testosterone for 21 days does not improve ovarian response by more than 1.5 oocytes, could be used to more accurately consult patients with poor ovarian response. However, an improvement in IVF outcome using a higher dose of testosterone or a longer pretreatment period cannot be excluded. STUDY FUNDING/COMPETING INTEREST: The study was partially funded by a Scholarship from the Academy of Athens. C.A.V. reports personal fees and non-financial support from Merck, Sharp and Dome, personal fees and non-financial support from Merck Serono, personal fees and non-financial support from IPSEN Hellas S.A., outside the submitted work. B.C.T. reports grants from Merck Serono, grants from Merck Sharp & Dohme, personal fees from Merck Serono, personal fees from Merck Sharp & Dohme, personal fees from IBSA & Ferring, outside the submitted work. TRIAL REGISTRATION NUMBER: NCT01961336. TRIAL REGISTRATION DATE: 10 October 2013. DATE OF FIRST PATIENT'S ENROLLMENT: 02/2014.

Corifollitropin alfa compared with follitropin beta in poor responders undergoing ICSI: a randomized controlled trial.

STUDY QUESTION: Does substituting 150 µg corifollitropin alfa for 450 IU follitropin beta during the first 7 days of ovarian stimulation in proven poor responders, result in retrieval of a non-inferior number (<1.5 fewer) of cumulus oocyte complexes (COCs)? SUMMARY ANSWER: A single s.c. dose of 150 µg corifollitropin alfa on the first day of ovarian stimulation, followed if necessary, from Day 8 onwards, with 450 IU of follitropin beta/day, is not inferior to daily doses of 450 IU follitropin beta. The 95% CI of the difference between medians in the number of oocytes retrieved was -1 to +1 within the safety margin of 1.5. WHAT IS KNOWN ALREADY: Recent data from retrospective studies suggest that the use of corifollitropin alfa in poor responders is promising since it could simplify ovarian stimulation without compromising its outcome. STUDY DESIGN, SIZE, DURATION: Seventy-nine women with previous poor ovarian response undergoing ICSI treatment were enrolled in this open label, non-inferiority, randomized clinical trial (RCT). PARTICIPANTS/MATERIALS, SETTING, METHODS: Inclusion criteria were: previous poor response to ovarian stimulation (≤4 COCs) after maximal stimulation, age <45 years, regular spontaneous menstrual cycle, body mass index: 18-32 kg/m(2) and basal follicle stimulating hormone ≤20 IU/l. On Day 2 of the menstrual cycle, patients were administered either a single s.c dose of 150 µg corifollitropin alfa (n = 40) or a fixed daily dose of 450 IU of follitropin beta (n = 39). In the corifollitropin alfa group, 450 IU of follitropin beta were administered from Day 8 of stimulation until the day of human chorionic gonadotrophin (hCG) administration, if necessary. To inhibit premature luteinizing hormone surge, the gonadotrophin releasing hormone antagonist ganirelix was used. Triggering of final oocyte maturation was performed using 250 µg of recombinant hCG, when at least two follicles reached 17 mm in mean diameter. MAIN RESULTS AND THE ROLE OF CHANCE: The number of COCs retrieved was not statistically different between the corifollitropin alfa and the follitropin beta groups [Median 3 versus 2, 95% CI 2-4, 2-3, respectively, P = 0.26]. The 95% CI of the difference between medians in the number of oocytes retrieved was -1 to +1. A multivariable analysis adjusting for all the potential baseline differences confirmed this finding. No significant difference was observed regarding the probability of live birth between the corifollitropin alfa and the follitropin beta group (live birth per patient reaching oocyte retrieval: 7.9 versus 2.6%, respectively, difference +5.3%, 95% CI: -6.8 to +18.3). LIMITATIONS, REASONS FOR CAUTION: The present study was not powered to test a smaller difference (e.g. 1 COC) in terms of COCs retrieved as well as to show potential differences in the probability of pregnancy. Moreover, it would be interesting to assess whether the continuation of stimulation in the long acting FSH arm, where necessary, with 200 IU instead of 450 IU of follitropin beta would have altered the direction or the magnitude of the effect of the type of FSH, observed on the number of COCs retrieved. WIDER IMPLICATIONS OF THE FINDINGS: Corifollitropin alfa simplifies IVF treatment because it is administered in a GnRH antagonist protocol and replaces seven daily FSH injections with a single one of a long acting FSH without compromising the outcome. It could greatly reduce the burden of treatment for poor responders and this deserves further investigation.

Effect of short-term tibolone treatment on risk markers for cardiovascular disease in healthy postmenopausal women: a randomized controlled study.

OBJECTIVE: The aim of this prospective randomized controlled cross sectional study was to evaluate the effect of a six month tibolone treatment in healthy postmenopausal women on biochemical CVD markers by calculating the changes of the blood serum levels of total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (Tg), high-sensitivity C-reactive protein (hsCRP), homocysteine (Hcy), and endothelin-1 (ET-1) at the beginning of the treatment and after six months. MATERIALS AND METHODS: Fifty-two healthy postmenopausal women were enrolled in a prospective, randomized, case-controlled outpatient trial. Group 1 (n = 26) received 2,5 mg/d tibolone for six months, while Group 2 (n = 26) received no treatment. Serum levels ofTC, LDL, HDL, Tg, hsCRP, Hcy, and ET-1 were evaluated at baseline and after six months. RESULTS: The two groups did not statistically differ at baseline characteristics. In Group 1 tibolone treatment decreased significantly TC (p = 0.01), HDL (p < 0.001), and Tg (p < 0.001) serum levels while a significant increase ofhsCRP (p < 0.001) was observed. Finally no changes were noticed on LDL, Hcy, and ET-1 serum levels. Regarding Group 2, no changes were observed. CONCLUSION: Short-term tibolone treatment in healthy postmenopausal women exerts a mixed action, acting beneficially in some markers (TC, LDL, Tg, Hcy, and ET-1) where as detrimentally in others (HDL, hsCRP).

Increased serum C-reactive protein levels in normal weight women with polycystic ovary syndrome.

BACKGROUND: The clinical spectrum of polycystic ovary syndrome (PCOS) includes components of the metabolic syndrome, such as central obesity, insulin resistance, dyslipidemia, arterial hypertension and, even, disturbances of the clotting mechanism. All these disorders are epidemiologically related to cardiovascular disease, most probably through low-grade intravascular chronic inflammation. The aim of this study was to evaluate the serum concentrations of high sensitivity C-reactive protein (hsCRP), a non-specific marker of low-grade inflammation and a predictive marker for cardiovascular disease, in normal weight women with (PCOS). PATIENTS AND METHODS: One hundred and eighty-eight (188) normal weight [body mass index (BMI) < 25 kg/m(2)] women with PCOS were included in the study. Forty-three (43) normal weight women without PCOS (normal ovulation without clinical or biochemical hyperandrogenemia) served as controls. Serum samples for luteinizing hormone, folliclestimulating hormone, prolactin, total testosterone, Δ4-androstenedione, 17α-hydroxy-progesterone, sex hormone-binding globulin (SHBG), insulin, glucose and hsCRP were collected in early follicular phase (third to sixth day) of a menstrual cycle in the control group or during a spontaneous bleeding episode in the PCOS group. RESULTS: Normal weight women with PCOS had higher concentrations of serum hsCRP as compared to normal weight women without PCOS (mean ± standard error of the mean 0.55 ± 0.08 versus 0.27 ± 0.08 mg/dL, p = 0.001). CONCLUSIONS: As normal weight women with PCOS are characterized by elevated serum concentrations of hsCRP, they have to be considered as carrying at least one marker of low-grade inflammation.

Operative vaginal delivery in singleton term pregnancies: short-term maternal and neonatal outcomes.

BACKGROUND: The rate of operative vaginal delivery has remained stable the last decade, however the rate of vacuum has increased against forceps application. Different maternal and neonatal outcomes have been proposed by many reports. The aim of the present study is to compare the short term maternal and neonatal outcomes between vacuum and forceps delivery. MATERIAL AND METHODS: We conducted a medical record review of live born singleton, vacuum and forceps-deliveries. Maternal and delivery characteristics were recorded. Maternal and neonatal outcomes were also assessed. Out of 7098 deliveries, 374 were instrument assisted, 324 were conducted by vacuum (86.7%) and 50 by forceps (13.3%). RESULTS: The incidence of 3rd degree lacerations and periurethral hematomas was similar between vacuum and forceps (3.4% vs. 2% and 0.3% vs 0% respectively), while perineal hematomas were more common in forceps compared with vacuum application (2% vs 0.3% respectively), albeit not significantly. The rate of neonates with Apgar scores

Clear cell ovarian carcinoma following polymyositis diagnosis: a case report and review of the literature.

BACKGROUND: The association of ovarian malignancy with dermatomyositis (DM) is well established from previous reports, while the relationship with polymyositis (PM) is rare. CASE REPORT: We report a case of a 50 years old nulliparous woman who developed clear cell ovarian cancer four years after the PM diagnosis. The patient presented with deep lower abdominal pain and distension. CA-125 was elevated and the preoperative MRI showed pelvic tumor occupying the Douglas pouch. Exploratory laparotomy revealed a gross mass of clear cell ovarian carcinoma. CONCLUSION: Physicians must be alert of the possibility of malignancy in patients with a previous diagnosis of polymyositis.

Immunohistochemical bcl-2 expression, p53 overexpression, PR and ER status in endometrial carcinoma and survival outcomes.

Immunohistochemical expression of bcl-2, p53, PR and ER in cases with endometrial carcinomas arrayed on a tissue microarray (TMA) was tested and correlated with clinicopathologic features, overall survival (OS), cancer-related survival (CRS) and disease-free survival (DFS). Seventy-seven patients with endometrial cancer were reviewed. Slides were evaluated by two pathologists blinded to patient clinical characteristics and survival data. Mean age of patients was 62.5 years (range 35-80), median follow up 60 months (range 9-120). Seventy-nine percent of patients were FIGO Stage I; 39% of the cases showed bcl-2 cytoplasmic staining and its expression was significantly correlated with low-grade tumor differentiation and age < or = 60 years. Nuclear p53 overexpression was detected in 23.4% of the cases and was significantly correlated with advanced stages (IIB-IV), non-endometrioid histology, nodal metastasis and advanced age (> 60 years). PR and ER were positive in 63.6% and 30% of the cases, respectively. Analysis of p53 overexpression and bcl-2 expression in relationship with PR and ER status showed a direct correlation between bcl-2 expression and PR positivity (p = 0.001). In a multivariate analysis FIGO staging was the only clinicopathologic parameter independently correlated with DFS. In conclusion p53 overexpression was directly associated with unfavorable clinicopathologic factors such as advanced stage, histologic subtype, advanced patient age and nodal metastasis. Bcl-2 expression was related with younger age, favorable grade and PR expression by tumor cells. Patient survival was not related to the tested biomarkers.

Pelvic lymphadenectomy as alternative to postoperative radiotherapy in high risk early stage endometrial cancer.

OBJECTIVE: The purpose of the study is to evaluate whether surgery followed by radiotherapy in high-risk patients of early stage endometrial cancer can be replaced by formal surgical staging. Cancer-related survival and recurrence-free survival (RFS) were the endpoints of the analysis. STUDY DESIGN: One hundred and eighteen patients with endometrioid endometrial adenocarcinoma between 1996-2003 were reviewed. Patients with incomplete follow-up and extrauterine spread excluded, leaving 78 women in the final analysis. Low-risk patients (n=37) (Grade 1, myometrial infiltration <1/2 or Grade 2, <1/3), treated by standard surgical procedure including total abdominal hysterectomy, bilateral salpingo-oophorectomy and peritoneal washing, while staging lymphadenectomy (n=24) or postoperative irradiation (n=17) was added in the high-risk group (Grade 1, >1/2 or Grade 2, >1/3 or Grade 3). RESULTS: The median age of patients was 65 years (range, 35-80 years) and the median follow-up 38 months (range, 9-98 months). The recurrence rate in low-risk patients was 2.7%, the cancer-related survival 97.5% and RFS 97%, while in the high-risk patients 12%, 93% and 88%, respectively. Comparing the therapeutic modalities (staging lymphadenectomy vs. postoperative irradiation) in the high-risk group the cancer-related survival and RFS was not differed (P=0.70, P=0.90, respectively). The high grade of the tumor was significantly correlated with RFS, while age, stage and myometrial infiltration were not. No moderate or severe complications developed after lymphadenectomy, while two moderate gastrointestinal complications occurred after adjuvant radiotherapy. CONCLUSION: According our results the low-risk patients of early stage endometrial adenocarcinoma had excellent survival with minimal intervention. The cancer-related survival and RFS in high-risk patients concerning the therapeutic modalities were comparable. Poor tumor differentiation was the most unfavorable prognostic factor related with RFS. Moderate complications developed only after postoperative radiotherapy.

Results on the treatment of uterine cervix cancer: ten years experience.

The aim of the study is to present our experience in the treatment of uterine cervix cancer over the last decade. This is a retrospective study of 90 patients with cervical cancer treated in a University Department of Obstetrics and Gynecology from 1993 to 2002. After the disease was histologically confirmed and staged the patients were treated according to stage with surgery (S) radiotherapy (RT), RT alone or Chemoradiaton (C-RT). The course of the disease and follow-up was traced from patient notes and after a structured telephone questionnaire. Mean age of patients was 48 +/- 14.3 years (29-84). Nine of 90 patients (10%) were lost to follow-up. FIGO (1994) staging was I in 50% of patients, II in 33.5%, III in 13.5% and IV in 3%. The size of tumor was < or = 4 cm in 75%. Of the tumors 87% were of squamous histology and 13% adenocarcinomas. Patients were treated with cone biopsy (5.5%), type I hysterectomy pelvic RT (10%), radical (type II-III) hysterectomy and pelvic lymphadenectomy +/- radiotherapy (41%), RT alone in 38% and C-RT in 5.5%. Incidence of complications after surgery was 19.5% and after RT 12.5%. Mean follow-up was 41 +/- 19 months (6-110). Five-year survival in Stage I was 84%, Stage II 64% and Stage III 40%. A single patient with Stage IV disease is alive with disease after two years. In conclusion uterine cervical cancer has improved survival because of early diagnosis. Treatment should be individualized according to the status of disease. Surgery and RT had similar rates of complications.