Reproductive and obstetric outcomes following operative hysteroscopy for treatment of retained products of conception.

BACKGROUND: Retained products of conception following delivery or early pregnancy failure are often treated by operative hysteroscopy. We aimed to evaluate reproductive and obstetric outcomes following operative hysteroscopy for treatment of retained products of conception. We also investigated the effect of time interval between operative hysteroscopy and pregnancy on these outcomes. METHODS: A retrospective cohort study conducted at the gynecology department of a tertiary teaching hospital between January 2012 and December 2016. Included were women who underwent operative hysteroscopy for treatment of retained products of conception and became pregnant following the procedure. Reproductive and obstetric data were retrieved from electronic medical records and by telephone questionnaire. The effect of time interval between operative hysteroscopy and pregnancy on reproductive outcomes was also evaluated by comparing women who conceived 6 months or less and women who conceived more than 6 months following surgery. RESULTS: Seventy-nine women who underwent operative hysteroscopy for treatment of retained products of conception and who conceived later were included. Mean time from women's attempt to conceive to conception was 4.6 (SD=6.4) months. Conception rate was 84.8% at 6 months and reached 92.4% at 12 months postsurgery. Miscarriage rate for the consecutive pregnancy following hysteroscopy was 15.2% and delivery rate was 84.8%. Two cases of obstetric complications including one case of retained placenta and one case of post-partum hemorrhage were noted. Time interval between operative hysteroscopy and pregnancy did not affect reproductive or obstetric outcomes. CONCLUSIONS: Women treated by operative hysteroscopy for retained products of conception have no negative reproductive and obstetric outcomes. Time interval between the procedure and pregnancy has no effect on these outcomes.

Risk factors for recurrent Pelvic Inflammatory Disease.

OBJECTIVE: Pelvic inflammatory disease (PID) is a common infection which can result in severe long term morbidity, such as chronic pelvic pain and infertility. The morbidity increases in correlation to the number of PID events. Our study aim to assess the risk factors for recurrence of pelvic inflammatory disease. METHODS: A retrospective case control study was conducted using data for all women who were admitted to a tertiary medical center for a recurrent PID over a duration of 15 years. Women who had a recurrent PID were compared to women admitted for PID treatment without further recurrence. Forward stepwise multivariate logistic regression analysis was subsequently carried out. RESULTS: The study included 133 women of whom 33 had recurrent PID. Women in the recurrent PID group had a higher rate of previous pelvic surgery (12 (36 %) vs. 20 (20 %), adjusted odds ratio [OR] 2.2 (95 % confidence interval CI 1.06-5.4, p = 0.05) and more had intrauterine devices (IUD) still in place if they had been previously present (5 (71.4 %) vs. 9(25.7 %), OR 7.2, (95 % CI 1.18-43.9), p = 0.02). The majority were treated with a combination of Ampicillin and Gentamycin, fewer received Augmentin or a cephalosporin base regimen (28 (84.8 %) vs 56 (56.0 %), OR 4.4, (95 % CI 1.5-12.3, p = 0.02), (1 (3.0 %) vs 27 (27.0 %), OR 0.08, (95 % CI 0.01-0.64), (4 (12.2 %) vs 17 (17.0 %)) respectively. In addition, invasive treatment had been required in more patients who later had a recurrent PID (6 (18.1 %) vs. 4(4.0 %), OR 5.3 (95 % CI 1.1.4-20.2), p = 0.007). Antibiotic regimens and invasive treatment were independently associated with recurrent PID (OR 2.69; 95 % CI 1.13-6.41, OR 2.10; 95 % CI 1.19-3.71, respectively). CONCLUSION: Among women with PID, special awareness should be given to women with previous pelvic surgery, who required an additional interventional treatment and have an IUD inserted. Efforts should be made to achieve treatment success and optimal prevention to prevent recurrent PID.

Success rate of methotrexate treatment for recurrent vs. primary ectopic pregnancy: a case-control study.

The aim of this study was to compare the success rate of methotrexate (MTX) treatment in patients with recurrent ectopic pregnancy (REP) and primary EP (PEP). A retrospective cohort study. The study cohort comprised all patients diagnosed with an EP and treated by intention with single-dose regimen of intramuscular MTX in a tertiary medical centre during 2010-2018. Cases (REP) and controls (PEP) were compared.262 patients had PEP and 32 had a REP. Women with REP had significantly higher gravidity order and higher incidence of previous abortions (5 vs. 3, median, p < .001, 59.3% vs. 32.8%, p < .001, respectively). Women with REP had a higher proportion of a history of previous surgery in general, and specifically pelvic surgery (46.8% vs. 20.6%, p < .001, 24.4% vs. 7.2%, p < .001, respectively). Treatment success was lower in the REP group (40.6% vs. 66.4%, p = .006, Odds ratio 0.34, 95% confidence interval 0.16, 0.73). In a logistic regression analysis, the only factor found to be independently associated with treatment failure was REP (adjusted odds ratio 0.30, 95% confidence interval 0.12, 0.77, p = .01). Our study suggests that medical treatment success with a single-dose regimen of MTX is lower than expected among REP cases, suggesting that different treatment approach should be considered in this setting.Impact statementWhat is already known on this subject ? There is paucity of data regarding success rate of methotrexate treatment for a recurrent ectopic pregnancy (REP).What do the results of this study add? Medical treatment success with a single-dose regimen of MTX in patients with a REP is lower than expectedWhat are the implications of these findings for future clinical practice and/or further research? As medical treatment success with a single-dose regimen of MTX for women with a REP is lower than expected, different treatment approach should be considered. Further and prospective studies with a larger sample size are needed to confirm our findings.

Reproductive health counseling, attitudes, and practices: a cross-sectional survey among bariatric surgeons.

BACKGROUND: Women of childbearing age constitute a substantial proportion of patients who undergo weight loss procedures. However, little is known regarding family planning knowledge, attitudes, and practices among bariatric surgeons. OBJECTIVES: We explored the reproductive health and contraceptive practices among bariatric surgeons. SETTING: A national society of bariatric surgeons. METHODS: A cross-sectional study. Anonymous surveys were sent to all members of the Israeli Society for Metabolic and Bariatric Surgery. RESULTS: The Israeli Society for Metabolic and Bariatric Surgery survey elicited a response rate of 96% (n = 48). Most (89.6%, n = 43) considered female reproductive health perioperative counseling very important, and the majority of respondents (66.7%, n = 32) felt comfortable discussing these issues. Nevertheless, only 54.2% (n = 25) reported routinely having family planning and pregnancy conversations with their patients. There was a general awareness that women should delay conception after surgery; however, only a minority of bariatric surgeons consistently either recommended the use of contraception after surgery (39.6%, n = 19) or referred patients for contraceptive advice (25.0%, n = 12). Most (81.3%, n = 39) practitioners reported not having accurate knowledge of contraception and felt that collaboration with other bariatric healthcare providers would provide patients with optimal reproductive-health counseling. CONCLUSIONS: Bariatric surgeons acknowledged the importance of reproductive healthcare and the need to delay conception among women undergoing bariatric surgery. However, they inconsistently addressed family planning and contraceptive issues and reported lack of accurate knowledge in this regard. This highlights the need for multidisciplinary collaboration between bariatric healthcare providers to improve reproductive and contraceptive care in these patients.

Growth pattern of uterine leiomyoma along pregnancy.

BACKGROUND: Uterine leiomyomas are often discovered during early pregnancy and in most cases will have no effect on pregnancy outcomes. However, in rare cases uterine leiomyomas may lead to obstetric complications. The aim of the study was to evaluate rate of uterine leiomyoma growth in the 3 trimesters of pregnancy. METHODS: We conducted a retrospective cohort study. Included were women who were diagnosed with uterine leiomyoma during pregnancy and had at least two sonographic measurements in different trimesters. Data regarding leiomyoma growth, recorded by ultrasound examination, during 1st 2nd and 3rd trimesters were collected from electronic patient records. RESULTS: Two-hundred forty-eight uterine leiomyomas were included in the study. Leiomyoma area increased substantially in size between the 1st and 2nd trimesters (54.5% ± 75.9%, p = .007) and to a lesser degree between the 2nd and 3rd trimesters (17.9% ± 59.7%, NS). Evaluation of the change in size throughout the pregnancy - between 1st and 3rd trimesters revealed a significant increase of 95.9% ± 191.3% (p < .001). There was no significant growth of the leiomyomas between the 2nd and 3rd trimesters. CONCLUSIONS: Uterine leiomyomas tend to grow substantially during the 1st trimester of pregnancy. This trend is attenuated later with minimal growth towards the end of gestation.

Risk factors for recurrent ectopic pregnancy following single-dose methotrexate treatment.

Objective: Our study aimed to investigate the predisposing factors for recurrence of an ectopic pregnancy (EP) following single-dose methotrexate (MTX) treatment for a primary EP. Methods: This was a retrospective cohort study performed in a tertiary care medical centre including all patients diagnosed with primary EP and treated with a single-dose regimen of intramuscular MTX. EPs with future recurrence were compared with first time only EPs, to identify risk factors for recurrent EP. Forward stepwise multivariate logistic regression analyses were subsequently carried out. Results: The study included 272 women. Of those, 22 (8.1%) had a recurrent EP. Women in the recurrent EP group had a higher rate of abortions (45.5% vs 32.7%; p = 0.02), previous pelvic surgery (45.5% vs 6.5%; p < 0.001) and both pelvic and uterine surgery (4.5% vs 1.6%; p < 0.001). Conception by assisted reproductive technology (ART) was more common among the non-recurrent EP group (23.0% vs 4.5%; p = 0.04). Success of single-dose MTX treatment was lower in the recurrent EP group compared with the non-recurrent EP group (36.4% vs 65.7%; p = 0.006). A history of pelvic surgery was independently associated with recurrent EP (adjusted odds ratio [OR] 17.6; 95% confidence interval [CI] 4.9, 63.2; p = 0.001). Treatment success of single-dose MTX was independently protective for recurrent EP (adjusted OR 0.25; 95% CI 0.08, 0.76; p = 0.02). Conclusions: Among women with an EP, attention should be paid to those with previous pelvic surgery. Efforts should be made to achieve medical treatment success to prevent recurrent EP.

The predictive role of CA-125 in the management of tubo-ovarian abscess. A retrospective study.

OBJECTIVE: Tubo-ovarian abscess (TOA) is a well-established sequel of acute pelvic inflammatory disease (PID). While as up to 25% of women will experience conservative treatment failure, the factors associated with treatment failure are not clearly-established, and the role of Cancer antigen 125 (CA-125) is under-studied. We aim to evaluate the role of CA-125 in the conservative management of TOA. STUDY DESIGN: A retrospective cohort study conducted at tertiary university-affiliated hospital during 2007-2018. Ninety one patients were diagnosed with a TOA and underwent a trial of conservative management with intravenous antibiotics. Patients who eventually underwent surgical intervention were compared with patients managed conservatively. RESULTS: Overall, 39/91 (42.8%) underwent an invasive intervention subsequent to failed antibiotic treatment. Patients who experienced conservative treatment failure had higher medians of inflammatory markers as CRP (15.7 vs. 10.8 mg/L, p = 0.02), WBC count (14.2 vs. 12.4 1,000/mm3, p = 0.04) and platelet count (374 vs. 295 109/L, p = 0.04) at admission. Higher levels of CA-125 at admission were found in those who required an invasive intervention (57 vs. 30 U\ml, p = 0.02) as well. The largest diameter of TOA at admission was higher in those who required an invasive intervention as compared to those who were successfully treated conservatively (75 mm vs. 57 mm, p = 0.01). CA-125 level was found to be the only independent factor associated with conservative treatment failure (OR; 95% confidence interval [CI], 1.27, 1.08-1.48, p = 0.03). CONCLUSION: Elevated CA-125 serum levels were found to be associated with failure of conservative parenteral antibiotic therapy for TOA. This finding should be better evaluated in a prospective manner.

Early prediction of the success of methotrexate treatment success by 24-hour pretreatment increment in HCG and day 1-4 change in HCG.

RESEARCH QUESTION: Several studies have tried to identify early markers of treatment outcome after methotrexate (MTX) treatment for ectopic pregnancy, including pretreatment and day 4 human chorionic gonadotrophin (HCG) concentrations and their corresponding changes, and the increment in HCG during the initial 24 h after treatment. There have, however, been conflicting results. This study aimed to re-evaluate the role of these markers in the earlier identification of treatment success in a large cohort of women. DESIGN: This was a retrospective cohort study including women diagnosed with an ectopic pregnancy and treated with a regimen of a single dose of MTX. A comparison of maternal and gestation characteristics was made between groups in whom treatment was successful or failed. RESULTS: A total of 292 women treated with single-dose intramuscular MTX for ectopic pregnancy were included in this study. In the overall cohort, the treatment success rate with a single dose of MTX was 62.7% (183/292). Only two independent determinants were significantly associated with treatment success: the initial 24-h percentage increase in HCG (adjusted odds ratio [OR] 1.82, 95% confidence interval [CI] 1.26-2.63; P < 0.001) and the percentage change in HCG from day 1 to day 4 (adjusted OR 1.12, 95% CI 1.04-1.21; P < 0.001). The optimal cut-off points for prediction of treatment success were an increment of less than 17% in the 24 h before treatment and a decrease of more than 22% between the day 1 and day 4 HCG concentrations. CONCLUSIONS: A small increase in HCG concentration 24 h before treatment with MTX, alongside a decline in HCG concentration from day 1 to day 4, may predict the success of medical treatment for an ectopic pregnancy.

Selective Progesterone Receptor Modulators for the Treatment of Uterine Leiomyomas.

Uterine leiomyomas have drawn much attention since being described more than 200 years ago. These common benign uterine tumors often present with prolonged menstrual bleeding, pelvic pressure, and reproductive disorders and pose a true financial burden on health care systems all over the world. Over the past few decades, surgical treatment of uterine leiomyomas has received most of the focus compared with other treatment options. Choosing the appropriate surgical technique depends on many factors such as uterine leiomyoma location, patient's age, interest in future fertility, concomitant comorbidities, and the patient's preference. Pharmacologic treatments such as gonadotropin-releasing hormone agonists and antagonists have been used for the treatment of symptomatic uterine leiomyomas with only partial success. Myriad side effects and limited clinical results have rendered them less popular and have exposed a true need for new effective medical treatments. Recently, treatment with selective progesterone receptor modulators has shown promising results with shrinkage of uterine leiomyomas and a prolonged clinical effect. Selective progesterone receptor modulators provide hope for women with this challenging condition and are a promising new option in the armamentarium of medical treatments for uterine leiomyomas.

Reducing Fluid-Related Complications During Operative Hysteroscopy: Use of a New Mandatory Fluid-Balance Form.

STUDY OBJECTIVE: To examine whether our new reporting system and mandatory fluid-balance form could improve the communication and awareness within the surgical team and therefore the safety of hysteroscopic operations. DESIGN: A case-control study (Canadian Task Force classification II-2). SETTING: An endoscopic gynecology unit at a tertiary-care university hospital. PATIENTS: Women aged 17 to 88 years (median, 43.9) who underwent operative hysteroscopy to treat uterine pathology. INTERVENTIONS: Operative hysteroscopy was performed using bipolar technology and normal saline as an irrigation media with the new fluid-balance form and a mandatory reporting system. The control group was composed of women who underwent the procedure using the same technology, with a previous protocol. MEASUREMENTS AND MAIN RESULTS: Data regarding intraoperative and postoperative short-term complications were prospectively collected during surgery and at the 2-week follow-up visit. About 2000 procedures were investigated (601 in the study group and 1396 in the control group). In the control group there were 20 incidents of fluid deficit over 2 L. In 4 of these cases the procedure was terminated, but in the other 16 cases the procedure was continued, with or without awareness of the surgeons to the deficit. Of these cases, 2 suffered from media-related complications, and in 3 others complications were avoided by diuretics. In contrast, in the study group there were 10 incidents of fluid deficit over 2 L, of which 5 cases were terminated on time and the other 5 continued under the informed decision of the surgeon. In this group, none of the women experienced a media-related complication. The difference between the number of procedures that were terminated on time between the control and study groups was not statistically significant (p = .115). There was a statistically significant reduction in the total complication rate between the study group (1.8%) and the control group (3.9%; p = .019). CONCLUSIONS: The fluid-balance form and mandatory reporting system have been shown to reduce the rate of total complications in hysteroscopic surgeries, in particular media-related complications. This result is achieved by an improvement of the awareness and communication among the operating team, leading to an improvement in procedure safety.

Targeting leiomyomas with all-trans-retinoic acid at phosphoinositide 3-kinase pathway suppression: Effective roles of ß-catenin and of signaling interactions.

AIM: Leiomyomas, monoclonal tumors developed by the transformation of myometrium somatic stem cells, are a major health concern that can severely impair quality of life. Pathological alterations of signaling pathways have been recognized as a key feature in a variety of human diseases. Our objective was to analyze treatment with all-trans-retinoic acid (ATRA) by suppression of the phosphoinositide 3-kinase (PI3K) pathway on growth, signaling pattern and interactions among PI3K/B-cell lymphoma 2 (Bcl2)/retinol leiomyoma proteins. METHODS: Cultures of paired myometrium and leiomyoma cells from premenopausal women undergoing hysterectomy were collected. Western blot and analysis of variance were used for analysis. RESULTS: Significant differences were detected between treatment with ATRA alone or with LY294002 (a PI3K growth suppressor) in response to treatment and among cell samples and cell numbers. Leiomyoma cells were less affected. Immunochemical analysis of signaling patterns demonstrated that treatments affected most of the examined protein levels differently. Significant differences between the cell type responses to treatment in pyruvate phosphate dikinase 1 (pPDK1), Bad and pß-catenin levels were identified. The pß-catenin level showed highly significant interaction between response to treatment and cell type. CONCLUSIONS: ATRA treatment on PI3K pathway suppression significantly affected growth, signaling pattern and interactions among PI3K/Bcl2/retinol proteins involved in the growth, survival and apoptosis of leiomyomas. Interpretation of our results suggests that increasing knowledge of the role of signaling interplay in the pathogenesis of leiomyomas may present an opportunity to use specific signal transduction inhibitors for treating and preventing this disorder.

Operative hysteroscopy for treatment of intrauterine pathologies does not interfere with later endometrial development in patients undergoing in vitro fertilization.

PURPOSE: Operative hysteroscopy procedure is extensively used for the treatment of intrauterine abnormalities that can potentially cause infertility. To date, there are little data addressing the effect of operative hysteroscopy that applies electrical current for excision and its subsequent effect on endometrial thickness. This study was aimed to assess the effect of thermal resection used in operative hysteroscopy on endometrial thickness and on fertility outcome in women undergoing in vitro fertilization (IVF). METHODS: A retrospective study conducted at Hadassah-Hebrew University Medical Center, a tertiary referral center. Included were IVF women who underwent an operative hysteroscopy throughout the years 2000-2010 for intrauterine pathologies. RESULTS: Throughout the years 2000-2010, 41 IVF women who underwent an operative hysteroscopy using electric current between their 82 IVF cycles were studied. The mean age of women at the time of the intervention was 37.1 years (36.7 and 37.5 at the IVF cycles before and after intervention, respectively). The maximal endometrial thickness before operative hysteroscopy was 10.7 mm compared to 9.5 mm after all procedures (P < 0.001). Excluding polypectomy cases (n = 24) the endometrial thickness was 9.9 mm before vs. 9.1 mm after operative hysteroscopy (P < 0.001). The clinical pregnancy rate was 19.5 % before as compared to 24.4 % after operative hysteroscopy (NS). The take home baby rate (THBR), however, was significantly increased following operative hysteroscopy for all indications from 2.4 to 12.2 % (P < 0.05). CONCLUSION: Despite the small change in endometrial thickness, our results indicate that using electric current is safe to treat intrauterine pathologies.

Case-control study of complications associated with bipolar and monopolar hysteroscopic operations.

STUDY OBJECTIVE: To examine whether all hysteroscopic operations can be performed using bipolar technology and to compare the complication rates of hysteroscopic surgery performed using monopolar and bipolar technology. DESIGN: Case-control study (Canadian Task Force classification II-2). SETTING: Endoscopic gynecology unit at a tertiary-care university hospital. PATIENTS: Women aged 17 to 88 years (median, 43.9 years) who underwent operative hysteroscopy to treat uterine disease. INTERVENTIONS: Operative hysteroscopy using bipolar technology and normal saline solution as irrigation medium. The control group was composed of women who underwent the procedure using monopolar technology, with glycine as irrigation medium, before adoption of bipolar technology. MEASUREMENTS AND MAIN RESULTS: Data regarding short-term complications were prospectively obtained during surgery and at 2-week follow-up. More than 1800 procedures were investigated (1318 in the study group and 524 in the control group). The complication rate was 4.1% in the study group and 2.8% in the control group (p = .08). CONCLUSION: Both monopolar and bipolar hysteroscopic techniques are safe and feasible. The bipolar hysteroscopic system has eliminated the need to use hypotonic solutions as irrigation medium, with its life-threatening complications. When limiting normal saline solution to 2 L, no serious complications associated with irrigation medium are expected. Therefore, we believe that when available, the bipolar system should be preferred.

Uterine sarcoma: prognostic factors and treatment evaluation.

BACKGROUND: Uterine sarcoma constitutes a highly malignant group of uterine tumors. It accounts for 2-6% of uterine malignancies and its incidence is 1.7 in 100,000 women. The three most common variants of uterine sarcoma are endometrial stromal sarcoma, leiomyosarcoma and carcinosarcoma. Based on relatively small case series, the literature provides little information on the risk factors, the natural course of the disease and the preferred treatment. OBJECTIVES: To evaluate uterine sarcoma patients treated in a tertiary referral center in Israel over a 20 year period (1980-2005). METHODS: We conducted a retrospective review of the charts of 40 uterine sarcoma patients, including their tumor characteristics, stage at diagnosis, treatment modalities, follow-up and survival. RESULTS: The patients' mean age was 53 years (range 32-76); 30% of the patients had carcinosarcoma, 55% had leiomyosarcoma and 15% had ESS. Half of the patients presented with stage I disease, 23% stage II, 10% stage III and 15% stage IV. Thirty-nine patients were treated with surgery. Adjuvant radiotherapy was administered to 39% of the patients, adjuvant chemotherapy to 21% and combined radiotherapy and chemotherapy to 9%. The mean follow-up period was 44 months, at which time disease had recurred in 44% of the patients. The disease stage was correlated with the 5-year survival rate, which was 73.1% for stages I-II and 22.2% for stages III- IV. CONCLUSIONS: In accordance with other larger studies our data show that the only prognostic factor that was significantly correlated with prognosis was the stage of the disease at diagnosis. Despite advances in diagnosis and treatment, survival has not improved over the last 25 years.

All-trans-retinoic acid mediates changes in PI3K and retinoic acid signaling proteins of leiomyomas.

OBJECTIVE: To detect changes induced by all-trans-retinoic acid (ATRA) on the expression and activation of target proteins of the retinoic acid (RA) and PI3K/Akt pathways involved in leiomyoma growth. DESIGN: A study on human tissue cultures. SETTING: Hadassah University Hospital. PATIENT(S): Premenopausal women with uterine leiomyomas. INTERVENTION(S): Paired cultures of normal myometrium and leiomyomas, from women undergoing hysterectomy, were obtained. MAIN OUTCOME MEASURE(S): The effect of ATRA was examined on the expression and phosphorylation of relevant RA, PI3K/Akt, and Bcl2 proteins (immunochemical analysis), cell proliferation, cell cycle distribution, and apoptosis. RESULT(S): Applying our cell culture model, we demonstrated that ATRA induced changes in the expression and activation of the RA and PI3K/Akt pathway proteins in leiomyoma cells, with significant increases of alcohol dehydrogenase 1 and cyclin D2 protein levels. In part of the leiomyoma cells, ATRA induced a relative increase of Bax (proapoptotic) as well as a relative decrease of phosphorylated glycogen synthase kinase 3ß (proapoptotic). CONCLUSION(S): Our results highlight the involvement of ATRA in the RA and PI3K/Akt pathways, whose specific signaling products may influence the outcome of leiomyoma growth by regulating cell proliferation, apoptosis, and survival. These results might be useful for the on-going research into alternative methods for treating and preventing this disorder.

Fertility in women after surgical treatment of nonepithelial ovarian tumors.

Conservative treatment is an acceptable option for women with nonepithelial ovarian tumors who wish to preserve fertility.

Endometrial thermal balloon ablation in women with previous cesarean delivery: pilot study.

STUDY OBJECTIVE: To evaluate the safety and efficacy of thermal balloon ablation in the management of menorrhagia in women with history of cesarean delivery. DESIGN: Descriptive study (Canadian Task Force classification II-2). SETTING: Tertiary care university hospital. PATIENTS: One hundred sixteen premenopausal women with dysfunctional uterine bleeding were offered endometrial thermal balloon ablation. This group included 26 women who had previously delivered via cesarean section (CS): 11 women with 1 CS, 8 women with 2 CS, 4 women with 3 CS, 2 women with 4 CS, and 1 woman with 5 CS. INTERVENTION: Endometrial thermal balloon ablation. MEASUREMENTS AND MAIN RESULTS: One hundred thirteen procedures were completed successfully; in 3 women, the procedure could not be completed. There were no major immediate operative complications. Sixteen patients (13.8%) required further gynecologic interventions after ablation: hysterectomy in 15, and dilation and curettage in 1. This included 13 women (14.4%) in the group with no previous CS and 3 women (11.5%) in the group with previous CS. CONCLUSION: Within the limitations of this preliminary study, endometrial thermal balloon ablation seems to be a possible therapeutic option for treatment of dysfunctional uterine bleeding in women with previous cesarean delivery.

Changes related to phosphatidylinositol 3-kinase/Akt signaling in leiomyomas: possible involvement of glycogen synthase kinase 3alpha and cyclin D2 in the pathophysiology.

OBJECTIVE: To identify changes in the expression and phosphorylation of phosphatidylinositol 3-kinase (PI3K)/Akt protein kinases controlling survival and/or apoptosis of in vitro cell cultures of uterine leiomyomas. DESIGN: Establishment of paired cell cultures of leiomyoma and myometrial specimens. SETTING: Hadassah gynecology research laboratory. PATIENT(S): Eleven white premenopausal women, 35 to 50 years of age, undergoing hysterectomy because of symptomatic uterine leiomyomas. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Immunochemical analysis of expression and phosphorylation of relevant PI3K/Akt and BCL2 proteins. RESULT(S): Analysis of total phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and of nonphosphorylated and phosphorylated (p) PDK1, Akt, glycogen synthase kinase 3 (GSK3), FKHR, tuberin (TSC2) and hamartin (TSC1) complex, and cyclin D2 proteins indicated that [1] the level of pGSK3alpha and cyclin D2 proteins was elevated significantly in the leiomyoma compared with the normal myometrium, [2] there was a significant interaction between PTEN- PDK1 and between pAkt-pGSK3beta in the leiomyoma compared with the myometrial cells, and [3] there was a significant interaction between pAkt-pGSK3alpha in the paired leiomyoma and myometrial cultures. CONCLUSION(S): Our study suggests that the downstream signaling components of the PI3K/Akt pathway, GSK3 (a regulator of apoptosis), and cyclin D2 (a promoter of G1/S progression), as well as the significant interaction between PTEN-PDK and between pAkt-pGSK3beta, are involved in the survival and proliferation of leiomyomas.