Diagnosis and management of endometrial hyperplasia: A UK national audit of adherence to national guidance 2012-2020.

BACKGROUND: Endometrial hyperplasia (EH) is a precusor lesion for endometrial cancer (EC), the commonest gynaecological malignancy in high-income countries. EH is a proliferation of glandular tissue, classified as either non-atypical endometrial hyperplasia (NEH) or, if the cytological features are abnormal, atypical endometrial hyperplasia (AEH). The clinical significance of AEH is that patients face both a high risk of having occult EC and a high risk of progression to EC if untreated. Recommendations on the care of women with EH were introduced by United Kingdom-wide guidance (Green-top Guide No. 67, 2016). National adherence to guidance is unknown. We aimed to describe the care of patients with EH; to compare the patterns of care for those with EH with national guidance to identify opportunities for quality improvement; and to compare patterns of care prior to and following the introduction of national guidance to understand its impact. METHODS AND FINDINGS: In this UK-wide patient-level clinical audit, we included 3,307 women who received a new histological diagnosis of EH through a gynaecology service between 1 January 2012 and 30 June 2020. We described first-line management, management at 2 years, and surgical characteristics prior to and following national guidance for EH using proportions and 95% confidence intervals (CIs) and compared process measures between time periods using multilevel Poisson regression. Of the 3,307 patients, 1,570 had NEH and 1,511 had AEH between 2012 and 2019. An additional 85 patients had NEH and 141 had AEH during 2020. Prior to national guidance, 9% (95% CI [6%, 15%]) received no initial treatment for NEH compared with 3% (95% CI [1%, 5%]) post-guidance; 31% (95% CI [26%, 36%]) and 48% (95% CI [43% 53%]) received an intrauterine progestogen, respectively, in the same periods. The predominant management of women with AEH did not differ, with 68% (95% CI [61%, 74%]) and 67% (95 CI [63%, 71%]) receiving first-line hysterectomy, respectively. By 2 years, follow-up to histological regression without hysterectomy increased from 38% (95% CI [33%, 43%]) to 52% (95% CI [47%, 58%]) for those with NEH (rate ratio (RR) 1.38, 95% CI [1.18, 1.63] p < 0.001). We observed an increase in the use of total laparoscopic hysterectomy among those with AEH (RR 1.26, 95% CI [1.04, 1.52]). In the later period, 37% (95% CI [29%, 44%]) of women initially diagnosed with AEH who underwent a first-line hysterectomy, received an upgraded diagnosis of EC. Study limitations included retrospective data collection from routine clinical documentation and the inability to comprehensively understand the shared decision-making process where care differed from guidance. CONCLUSIONS: The care of patients with EH has changed in accordance with national guidance. More women received first-line medical management of NEH and were followed up to histological regression. The follow-up of those with AEH who do not undergo hysterectomy must be improved, given their very high risk of coexistent cancer and high risk of developing cancer.

The feasibility, safety, and effectiveness of hysteroscopic sterilization compared with laparoscopic sterilization.

BACKGROUND: In contrast to conventional laparoscopic sterilization, newer hysteroscopic approaches avoid the need for hospital admission, general anesthesia, and prolonged recovery. However, there are concerns that the feasibility, safety, and efficacy of hysteroscopic sterilization may be lower than established laparoscopic sterilization. OBJECTIVE: We sought to evaluate the outcomes of hysteroscopic sterilization compared with laparoscopic sterilization in routine clinical practice in a comparative observational cohort study. STUDY DESIGN: This study was carried out at University of Birmingham, United Kingdom, National Health Service teaching hospital, office hysteroscopy clinics, and day-case hospital unit. In all, 1085 women underwent hysteroscopic sterilization and 2412 had laparoscopic sterilization. Hysteroscopic sterilization was carried out using the tubal implant permanent birth control system in the office setting and laparoscopic sterilization using the tubal ligation system as a day-case under general anesthesia. Outcome data were collected regarding feasibility (technical completion of the sterilization procedure, satisfactory radiological confirmation at 3 months-hysterosalpingogram or transvaginal pelvic ultrasound scan), safety events within 30 days of procedures, reoperations, and unintended pregnancies within 1 year of procedures. RESULTS: Hysteroscopic sterilization was successful in 992/1085 (91.4%; 95% confidence interval, 89.6-93.0%) at the first attempt. In comparison, bilateral tubal ligation was successfully performed in 2400/2412 (99.5%; 95% confidence interval, 99.2-99.8%) of patients who underwent laparoscopic sterilizations (odds ratio, 18.8; 95% confidence interval, 10.2-34.4). In all, 902/1085 (83.1%; 95% confidence interval, 80.8-85.2%) of successfully performed hysteroscopic procedures attended for radiological confirmation testing were considered satisfactory. The rate of adverse events within 30 days were similar: 2/1085 (0.2%) vs 3 (0.12%; 95% confidence interval, 0.04-0.36%). There were 3/1085 (0.3%; 95% confidence interval, 0.1-0.8%) unintended pregnancies after hysteroscopic sterilization compared with 5/2412 (0.2%; 95% confidence interval, 0.1-0.5%) laparoscopic sterilization (odds ratio, 1.3; 95% confidence interval, 0.3-5.6). Median length of follow-up for pregnancy outcome was 5 years. Hysteroscopic sterilization was associated with a higher risk of reoperation at 1 year compared to laparoscopic sterilization (odds ratio, 6.2; 95% confidence interval, 2.8-14.0) and the commonest reintervention was unilateral salpingectomy (12/22, 54.5%). CONCLUSION: Hysteroscopic sterilization has been introduced as a more convenient, office-based method of permanent fertility control. However, while the small risk of unintended pregnancy is comparable to conventional laparoscopic sterilization, women should also be counselled regarding its lower success rate in successfully completing the procedure and its higher rate of failed reoperation.

Position in the second stage of labour for women without epidural anaesthesia.

BACKGROUND: For centuries, there has been controversy around whether being upright (sitting, birthing stools, chairs, squatting, kneeling) or lying down (lateral (Sim's) position, semi-recumbent, lithotomy position, Trendelenburg's position) have advantages for women giving birth to their babies. This is an update of a review previously published in 2012, 2004 and 1999. OBJECTIVES: To determine the possible benefits and risks of the use of different birth positions during the second stage of labour without epidural anaesthesia, on maternal, fetal, neonatal and caregiver outcomes. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register (30 November 2016) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised, quasi-randomised or cluster-randomised controlled trials of any upright position assumed by pregnant women during the second stage of labour compared with supine or lithotomy positions. Secondary comparisons include comparison of different upright positions and the supine position. Trials in abstract form were included. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and assessed trial quality. At least two review authors extracted the data. Data were checked for accuracy. The quality of the evidence was assessed using the GRADE approach. MAIN RESULTS: Results should be interpreted with caution because risk of bias of the included trials was variable. We included eleven new trials for this update; there are now 32 included studies, and one trial is ongoing. Thirty trials involving 9015 women contributed to the analysis. Comparisons include any upright position, birth or squat stool, birth cushion, and birth chair versus supine positions.In all women studied (primigravid and multigravid), when compared with supine positions, the upright position was associated with a reduction in duration of second stage in the upright group (MD -6.16 minutes, 95% CI -9.74 to -2.59 minutes; 19 trials; 5811 women; P = 0.0007; random-effects; I² = 91%; very low-quality evidence); however, this result should be interpreted with caution due to large differences in size and direction of effect in individual studies. Upright positions were also associated with no clear difference in the rates of caesarean section (RR 1.22, 95% CI 0.81 to 1.81; 16 trials; 5439 women; low-quality evidence), a reduction in assisted deliveries (RR 0.75, 95% CI 0.66 to 0.86; 21 trials; 6481 women; moderate-quality evidence), a reduction in episiotomies (average RR 0.75, 95% CI 0.61 to 0.92; 17 trials; 6148 women; random-effects; I² = 88%), a possible increase in second degree perineal tears (RR 1.20, 95% CI 1.00 to 1.44; 18 trials; 6715 women; I² = 43%; low-quality evidence), no clear difference in the number of third or fourth degree perineal tears (RR 0.72, 95% CI 0.32 to 1.65; 6 trials; 1840 women; very low-quality evidence), increased estimated blood loss greater than 500 mL (RR 1.48, 95% CI 1.10 to 1.98; 15 trials; 5615 women; I² = 33%; moderate-quality evidence), fewer abnormal fetal heart rate patterns (RR 0.46, 95% CI 0.22 to 0.93; 2 trials; 617 women), no clear difference in the number of babies admitted to neonatal intensive care (RR 0.79, 95% CI 0.51 to 1.21; 4 trials; 2565 infants; low-quality evidence). On sensitivity analysis excluding trials with high risk of bias, these findings were unchanged except that there was no longer a clear difference in duration of second stage of labour (MD -4.34, 95% CI -9.00 to 0.32; 21 trials; 2499 women; I² = 85%).The main reasons for downgrading of GRADE assessment was that several studies had design limitations (inadequate randomisation and allocation concealment) with high heterogeneity and wide CIs. AUTHORS' CONCLUSIONS: The findings of this review suggest several possible benefits for upright posture in women without epidural anaesthesia, such as a very small reduction in the duration of second stage of labour (mainly from the primigravid group), reduction in episiotomy rates and assisted deliveries. However, there is an increased risk blood loss greater than 500 mL and there may be an increased risk of second degree tears, though we cannot be certain of this. In view of the variable risk of bias of the trials reviewed, further trials using well-designed protocols are needed to ascertain the true benefits and risks of various birth positions.

Effectiveness of Embolization or Sclerotherapy of Pelvic Veins for Reducing Chronic Pelvic Pain: A Systematic Review.

PURPOSE: Chronic pelvic pain (CPP) in the presence of dilated and refluxing pelvic veins is often described as pelvic congestion syndrome (PCS), although the causal relationship between pelvic vein incompetence and CPP has not been established. Percutaneous embolization is the principal treatment for PCS, with high success rates cited. This study was undertaken to systematically and critically review the effectiveness of embolization of incompetent pelvic veins. MATERIALS AND METHODS: A comprehensive search strategy encompassing various terms for pelvic congestion, pelvic pain, and embolization was deployed in 17 bibliographic databases, with no restriction on study design. Methodologic quality was assessed. The quality and heterogeneity generally precluded meta-analysis. Results were tabulated and described narratively. RESULTS: Twenty-one prospective case series and one poor-quality randomized trial of embolization (involving a total of 1,308 women) were identified. Early substantial relief from pain was observed in approximately 75% of women undergoing embolization, and generally increased over time and was sustained. Significant pain reductions following treatment were observed in all studies that measured pain on a visual analog scale. Repeat intervention rates were generally low. There were few data on the impact on menstruation, ovarian reserve, or fertility, but no concerns were noted. Transient pain was common following foam embolization, and there was a < 2% risk of coil migration. CONCLUSIONS: Embolization appears to provide symptomatic relief of CPP in the majority of women and is safe, although the quality of the evidence is low.

Uterine artery embolization for symptomatic uterine fibroids.

BACKGROUND: Uterine fibroids cause heavy prolonged bleeding, pain, pressure symptoms and subfertility. The traditional method of treatment has been surgery as medical therapies have not proven effective. Uterine artery embolization has been reported to be an effective and safe alternative to treat fibroids in women not desiring future fertility. There is a significant body of evidence that is based on case controlled studies and case reports. This is an update of the review previously published in 2012. OBJECTIVES: To review the benefits and risks of uterine artery embolization (UAE) versus other medical or surgical interventions for symptomatic uterine fibroids. SEARCH METHODS: We searched sources including the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and trial registries. The search was last conducted in April 2014. We contacted authors of eligible randomised controlled trials to request unpublished data. SELECTION CRITERIA: Randomised controlled trials (RCTs) of UAE versus any medical or surgical therapy for symptomatic uterine fibroids. The primary outcomes of the review were patient satisfaction and live birth rate (among women seeking live birth). DATA COLLECTION AND ANALYSIS: Two of the authors (AS and JKG) independently selected studies, assessed quality and extracted data. Evidence quality was assessed using GRADE methods. MAIN RESULTS: Seven RCTs with 793 women were included in this review. Three trials compared UAE with abdominal hysterectomy, two trials compared UAE with myomectomy, and two trials compared UAE with either type of surgery (53 hysterectomies and 62 myomectomies).With regard to patient satisfaction rates, our findings were consistent with satisfaction rates being up to 41% lower or up to 48% higher with UAE compared to surgery within 24 months of having the procedure (odds ratio (OR) 0.94; 95% confidence interval (CI) 0.59 to 1.48, 6 trials, 640 women, I(2) = 5%, moderate quality evidence). Findings were also inconclusive at five years of follow-up (OR 0.90; 95% CI 0.45 to 1.80, 2 trials, 295 women, I(2) = 0%, moderate quality evidence). There was some indication that UAE may be associated with less favourable fertility outcomes than myomectomy, but it was very low quality evidence from a subgroup of a single study and should be regarded with extreme caution (live birth: OR 0.26; 95% CI 0.08 to 0.84; pregnancy: OR 0.29; 95% CI 0.10 to 0.85, 1 study, 66 women).Similarly, for several safety outcomes our findings showed evidence of a substantially higher risk of adverse events in either arm or of no difference between the groups. This applied to intra-procedural complications (OR 0.91; 95% CI 0.42 to 1.97, 4 trials, 452 women, I(2) = 40%, low quality evidence), major complications within one year (OR 0.65; 95% CI 0.33 to 1.26, 5 trials, 611 women, I(2) = 4%, moderate quality evidence) and major complications within five years (OR 0.56; CI 0.27 to 1.18, 2 trials, 268 women). However, the rate of minor complications within one year was higher in the UAE group (OR 1.99; CI 1.41 to 2.81, 6 trials, 735 women, I(2) = 0%, moderate quality evidence) and two trials found a higher minor complication rate in the UAE group at up to five years (OR 2.93; CI 1.73 to 4.93, 2 trials, 268 women).UAE was associated with a higher rate of further surgical interventions (re-interventions within 2 years: OR 3.72; 95% CI 2.28 to 6.04, 6 trials, 732 women, I(2) = 45%, moderate quality evidence; within 5 years: OR 5.79; 95% CI 2.65 to 12.65, 2 trials, 289 women, I(2) = 65%). If we assumed that 7% of women will require further surgery within two years of hysterectomy or myomectomy, between 15% and 32% will require further surgery within two years of UAE.The evidence suggested that women in the UAE group were less likely to require a blood transfusion than women receiving surgery (OR 0.07; 95% CI 0.01 to 0.52, 2 trials, 277 women, I(2) = 0%). UAE was also associated with a shorter procedural time (two studies), shorter length of hospital stay (seven studies) and faster resumption of usual activities (six studies) in all studies that measured these outcomes; however, most of these data could not be pooled due to heterogeneity between the studies.The quality of the evidence varied, and was very low for live birth, moderate for satisfaction ratings, and moderate for most safety outcomes. The main limitations in the evidence were serious imprecision due to wide confidence intervals, failure to clearly report methods, and lack of blinding for subjective outcomes. AUTHORS' CONCLUSIONS: When we compared patient satisfaction rates at up to two years following UAE versus surgery (myomectomy or hysterectomy) our findings are that there is no evidence of a difference between the interventions. Findings at five year follow-up were similarly inconclusive. There was very low quality evidence to suggest that myomectomy may be associated with better fertility outcomes than UAE, but this information was only available from a selected subgroup in one small trial.We found no clear evidence of a difference between UAE and surgery in the risk of major complications, but UAE was associated with a higher rate of minor complications and an increased likelihood of requiring surgical intervention within two to five years of the initial procedure. If we assume that 7% of women will require further surgery within two years of hysterectomy or myomectomy, between 15% and 32% will require further surgery within two years of UAE. This increase in the surgical re-intervention rate may balance out any initial cost advantage of UAE. Thus although UAE is a safe, minimally invasive alternative to surgery, patient selection and counselling are paramount due to the much higher risk of requiring further surgical intervention.

Relapse of endometrial hyperplasia after conservative treatment: a cohort study with long-term follow-up.

STUDY QUESTION: What is the risk of relapse for women with endometrial hyperplasia treated with levonorgestrel-releasing intrauterine system (LNG-IUS) or oral progestogens? SUMMARY ANSWER: Relapse of complex endometrial hyperplasia after initial regression occurs often and it occurs less often in women treated with LNG-IUS than with oral progestogens. WHAT IS KNOWN ALREADY: The LNG-IUS and oral progestogens are used to treat women with endometrial hyperplasia and achieve regression. There is uncertainty over whether further surveillance for these women is necessary as the risk for relapse is unknown. STUDY DESIGN, SIZE, DURATION: A cohort study of 219 women with complex non-atypical or atypical endometrial hyperplasia who were treated and achieved initial regression with LNG-IUS (n = 153) or oral progestogens (n = 66) from August 1998 until December 2007 and followed up for >5 years. The mean length of follow-up was 74.7 ± SD 31.8 months for the LNG-IUS versus 87.6 ± SD 42.2 months for the oral progestogen group. PARTICIPANTS/MATERIALS, SETTING, METHODS: We evaluated the proportion of women who relapsed or had hysterectomy after initial regression with LNG-IUS compared with oral progestogens by logistic regression and adjusting for confounding. The time from regression to relapse was explored through a survival analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Relapse of hyperplasia occurred in 13.7% (21/153) of women treated with LNG-IUS compared with 30.3% (20/66) of women treated with oral progestogens [adjusted odds ratio (OR) = 0.34, 95% confidence interval (CI): 0.17-0.7, P = 0.005]. Relapse rates over long-term follow-up were lower for complex non-atypical hyperplasia compared with atypical hyperplasia for both LNG-IUS (12.7%, 18/142 versus 27.3%, 3/11, respectively; P ≤ 0.001) and oral progestogens (28.3%, 17/60 versus 50%, 3/6, respectively; P ≤ 0.001). The survival analysis indicates that relapse occurred less often with LNG-IUS at 12, 24, 36, 48, 60 and >60 months of follow-up (hazard ratio 0.37, 95% CI: 0.2-0.7, P = 0.0013). There were no events of relapse after 48 months from regression with oral progestogens, but 5 women treated with LNG-IUS relapsed after 60 months when treatment was discontinued. Hysterectomy rates were lower in the LNG-IUS than oral progestogen group during follow-up (19.6%, 30/153 versus 31.8%, 21/66, respectively, OR = 0.52, 95% CI: 0.27-1, P = 0.05). Endometrial cancer was diagnosed in 2 (11.8%) women who had hysterectomy (n = 17) because of relapse. LIMITATIONS, REASONS FOR CAUTION: We are unable to accurately estimate the cancer risk in women who relapse during follow-up as only 17 out of 41 who relapsed underwent hysterectomy. WIDER IMPLICATIONS OF THE FINDINGS: Relapse of endometrial hyperplasia after initial regression occurs often and long-term follow-up is advised. STUDY FUNDING/COMPETING INTEREST(S): Ioannis D. Gallos and this study were funded through a grant from Wellbeing of Women (ELS022). No competing interests.

LNG-IUS versus oral progestogen treatment for endometrial hyperplasia: a long-term comparative cohort study.

STUDY QUESTION: What are the regression and hysterectomy rates for women treated with the levonorgestrel-releasing intrauterine system (LNG-IUS) compared with oral progestogens for endometrial hyperplasia (EH)? SUMMARY ANSWER: The LNG-IUS achieves higher regression and lower hysterectomy rates than oral progestogens in the treatment of complex and atypical hyperplasia. WHAT IS KNOWN ALREADY: The LNG-IUS and oral progestogens are both equally used to treat women with EH. There is uncertainty about whether the LNG-IUS is a better therapy for EH. STUDY DESIGN, SIZE, DURATION: This comparative cohort study included 344 women recruited from August 1998 until December 2010. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with complex non-atypical or atypical EH were treated with the LNG-IUS (n = 250) or oral progestogens (n = 94) in a tertiary referral hospital. We evaluated the proportion of women who regressed or underwent hysterectomy after treatment with the LNG-IUS compared with oral progestogens by logistic regression adjusting for confounding. The time from diagnosis to regression was explored through a survival analysis. MAIN RESULTS AND THE ROLE OF CHANCE: The follow-up rate was 95.3%. The mean length of follow-up in the two groups was 66.9 ± SD 35.1 months for the LNG-IUS and 87.2 ± SD 45.5 months for the oral progestogen group. Regression of hyperplasia was achieved in 94.8% (237/250) of patients with the LNG-IUS compared with 84.0% (79/94) of patients treated with oral progestogens (adjusted odds ratio (OR) = 3.04, 95% CI 1.36-6.79, P = 0.001). Hysterectomy rates were lower in the LNG-IUS group during follow-up (22.1, 55/250 versus 37.2%, 35/94, adjusted OR = 0.48, 95% CI 0.28-0.81, P < 0.004). Endometrial cancer was diagnosed in 8 (33%) women who had hysterectomy because of a failure to regress to normal histology during follow-up (n = 24). LIMITATIONS, REASONS FOR CAUTION: The observational design cannot exclude residual confounding from unmeasured variables. WIDER IMPLICATIONS OF THE FINDINGS: In treating EH, LNG-IUS achieves higher regression rates and lower hysterectomy rates than oral progestogens and should be the first-line therapy. Failure to achieve regression carries a high risk of underlying endometrial cancer and hysterectomy is advised.

Predictive ability of estrogen receptor (ER), progesterone receptor (PR), COX-2, Mlh1, and Bcl-2 expressions for regression and relapse of endometrial hyperplasia treated with LNG-IUS: a prospective cohort study.

OBJECTIVE: To test the predictive ability of immunohistochemical estrogen receptor(ER), progesterone receptor (PR), COX-2, Mlh1, and Bcl-2 expressions for predicting the outcomes of regression and relapse in women with endometrial hyperplasia treated with the Levonorgestrel-releasing intrauterine system (LNG-IUS). METHODS: We recruited prospectively all women diagnosed with complex or atypical complex hyperplasia that underwent treatment with LNG-IUS from August 1998 until September 2008. Immunohistochemistry was performed with conventional methods and recorded using a semi-quantitative score (Q score) by two blinded assessors. Women were followed with endometrial biopsies to record regression and relapse. The biomarker predictive ability was analysed using the Cox proportional hazards model. RESULTS: The median follow-up was 72.1 months (IQR 59.1-89.8). The Q score agreement between assessors was 82.6% (K statistic=0.801 ± 0.036). The majority of study participants initially regressed to normal endometrium following LNG-IUS therapy (n = 164 regressed; n = 10 persisted). From the 164 women that regressed with LNG-IUS we were able to assess 152 women for relapse from which 18 relapsed. We found a weak association for persisted endometrial hyperplasia with ER and PR expressions with Q score on the 5th and 10th centiles. No associations were found for COX-2, Mlh1 and Bcl-2 protein expressions for regression and for any of the biomarkers for relapse. CONCLUSION: We found that poor expression of ER and PR is weakly associated with persisting endometrial hyperplasia and COX-2, Mlh1, and Bcl-2 expressions are not predictive. None of the biomarkers is predictive for relapse in women with endometrial hyperplasia treated with LNG-IUS.

Ezrin and Its Phosphorylated Thr567 Form Are Key Regulators of Human Extravillous Trophoblast Motility and Invasion.

The protein ezrin has been shown to enhance cancer cell motility and invasion leading to malignant behaviours in solid tumours, but a similar regulatory function in the early physiological reproduction state is, however, much less clear. We speculated that ezrin may play a key role in promoting first-trimester extravillous trophoblast (EVT) migration/invasion. Ezrin, as well as its Thr567 phosphorylation, were found in all trophoblasts studied, whether primary cells or lines. Interestingly, the proteins were seen in a distinct cellular localisation in long, extended protrusions in specific regions of cells. Loss-of-function experiments were carried out in EVT HTR8/SVneo and Swan71, as well as primary cells, using either ezrin siRNAs or the phosphorylation Thr567 inhibitor NSC668394, resulting in significant reductions in both cell motility and cellular invasion, albeit with differences between the cells used. Our analysis further demonstrated that an increase in focal adhesion was, in part, able to explain some of the molecular mechanisms involved. Data collected using human placental sections and protein lysates further showed that ezrin expression was significantly higher during the early stage of placentation and, importantly, clearly seen in the EVT anchoring columns, further supporting the potential role of ezrin in regulating migration and invasion in vivo.

Regression, relapse, and live birth rates with fertility-sparing therapy for endometrial cancer and atypical complex endometrial hyperplasia: a systematic review and metaanalysis.

OBJECTIVE: The objective of the study was to evaluate the regression, relapse, and live birth rates of early-stage endometrial cancer (EC) and atypical complex hyperplasia (ACH) with fertility-sparing treatment. STUDY DESIGN: This was a metaanalysis of the proportions from observational studies with a random-effects model and a meta-regression to explore for heterogeneity. RESULTS: Thirty-four observational studies, evaluating the regression, relapse, and live birth rates of early-stage EC (408 women) and ACH (151 women) with fertility-sparing treatment. Fertility-sparing treatment for EC achieved a pooled regression rate of 76.2%, a relapse rate of 40.6%, and a live birth rate of 28%. For ACH the pooled regression rate was 85.6%, a relapse rate of 26%, and a live birth rate of 26.3%. Twenty women were diagnosed with ovarian cancer (concurrent or metastatic) during follow-up (3.6%) and 10 progressed to higher than stage I EC (1.9%) from which 2 women died. CONCLUSION: Fertility-sparing treatment of EC and ACH is feasible and selected women can satisfy their reproductive wishes.

Position in the second stage of labour for women without epidural anaesthesia.

BACKGROUND: For centuries, there has been controversy around whether being upright (sitting, birthing stools, chairs, squatting, kneeling) or lying down have advantages for women delivering their babies. OBJECTIVES: To assess the benefits and risks of the use of different positions during the second stage of labour (i.e. from full dilatation of the uterine cervix). SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group Trials Register (28 February 2012). SELECTION CRITERIA: Randomised or quasi-randomised controlled trials of any upright or lateral position assumed by pregnant women during the second stage of labour compared with supine or lithotomy positions. Secondary comparisons include comparison of different upright positions and the lateral position. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and assessed trial quality. At least two review authors extracted the data. Data were checked for accuracy. MAIN RESULTS: Results should be interpreted with caution as the methodological quality of the 22 included trials (7280 women) was variable.In all women studied (primigravid and multigravid) there was a non-significant reduction in duration of second stage in the upright group (mean difference (MD) -3.71 minutes; 95% confidence interval (CI) -8.78 to 1.37 minutes; 10 trials, 3485 women; random-effects, I(2) = 94%), a significant reduction in assisted deliveries (risk ratio (RR) 0.78; 95% CI 0.68 to 0.90; 19 trials, 6024 women, I(2)= 27%), a reduction in episiotomies (average RR 0.79, 95% CI 0.70 to 0.90, 12 trials, 4541 women; random-effects, I(2) = 7%), an increase in second degree perineal tears (RR 1.35; 95% CI 1.20 to 1.51, 14 trials, 5367 women), increased estimated blood loss greater than 500 ml (RR 1.65; 95% CI 1.32 to 2.60; 13 trials, 5158 women, asymmetric funnel plot indicating publication bias), fewer abnormal fetal heart rate patterns (RR 0.46; 95% CI 0.22 to 0.93; two trials, 617 women). In primigravid women the use of any upright compared with supine positions was associated with: non-significant reduction in duration of second stage of labour (nine trials: mean 3.24 minutes, 95% CI 1.53 to 4.95 minutes) - this reduction was largely due to women allocated to the use of the birth cushion. AUTHORS' CONCLUSIONS: The findings of this review suggest several possible benefits for upright posture in women without epidural, but with the possibility of increased risk of blood loss greater than 500 mL. Until such time as the benefits and risks of various delivery positions are estimated with greater certainty, when methodologically stringent data from trials are available, women should be allowed to make choices about the birth positions in which they might wish to assume for birth of their babies.

Uterine artery embolization for symptomatic uterine fibroids.

BACKGROUND: Uterine fibroids cause heavy prolonged bleeding, pain, pressure symptoms and subfertility. The traditional method of treatment has been surgery as medical therapies have not proven effective. Uterine artery embolization (UAE) has been reported to be an effective and safe alternative to treat fibroids in women not desiring future fertility. There is a significant body of evidence based on case controlled studies and case reports. This is an update of the review previously published in 2006. OBJECTIVES: To review the benefits and risks of uterine artery embolization (UAE) versus other medical or surgical interventions for symptomatic uterine fibroids. SEARCH METHODS: We searched the Cochrane Menstrual Disorders & Subfertility Group Trials register (searched November 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, 4th Quarter 2011), MEDLINE (1950 to November 2011) and EMBASE (January 1980 to November 2011). We also contacted authors of eligible RCTs for unpublished data. SELECTION CRITERIA: Randomised controlled trials (RCTs) of UAE versus any medical or surgical therapy for symptomatic uterine fibroids. DATA COLLECTION AND ANALYSIS: Two of the authors (AS and JKG) assessed the trials and extracted the data independently. MAIN RESULTS: Five RCTs were included in this review. Three trials compared UAE with abdominal hysterectomy in 291 women. A fourth trial included 157 women and compared UAE with surgery (43 hysterectomies and 8 myomectomies). The fifth trial included 121 women and compared UAE with myomectomy in women wishing to preserve fertility.There was moderately good evidence that there is no significant difference between UAE and surgery in patient satisfaction rates at two years (OR 0.69, 0.40 to 1.21, 516 women, 5 trials) nor at five years (OR 0.90, 95% CI 0.45 to 1.80, 295 women, 2 trials). There was very low level evidence suggesting that myomectomy may be associated with better fertility outcomes than UAE, but this analysis was restricted to the limited cohort of women (n=66) who tried to conceive in the single study of UAE versus myomectomy (live birth: OR 0.33, 95% CI 0.11 to 1.00; pregnancy: OR 0.29, 95% CI 0.10 to 0.85). There was no significant difference between the two interventions in the rate of major complications. Compared to surgery, UAE significantly reduced the length of the procedure, length of hospital stay and time to resumption of routine activities and also decreased the likelihood of needing a blood transfusion. However, UAE was associated with higher rates of minor short term and long term complications, more unscheduled readmissions after discharge and an increased surgical reintervention rate. This increase in the surgical reintervention rate may balance out the initial cost advantage of UAE (reinterventions within 2 years: OR 5.64, 95% CI 2.92 to 10.90, 486 women, 4 trials; within 5 years: OR 5.79, 95% CI 2.65 to 12.65. 289 women, 2 trials). There was no significant difference in ovarian failure rates at long term follow-up. AUTHORS' CONCLUSIONS: UAE appears to have an overall patient satisfaction rate similar to hysterectomy and myomectomy and offers an advantage with regards to a shorter hospital stay and a quicker return to routine activities. However, UAE is associated with a higher rate of minor complications and an increased likelihood of requiring surgical intervention within two to five years of the initial procedure. There is very low level evidence suggesting that myomectomy may be associated with better fertility outcomes than UAE, but more research is needed.

A randomized trial of synthetic osmotic cervical dilator for induction of labor vs dinoprostone vaginal insert.

BACKGROUND: Induction of labor is a commonly performed obstetrical intervention. Vaginal prostaglandin E2 (dinoprostone) is a first-choice agent. Mechanical methods of induction are slower in achieving cervical ripening but have a lower risk of adverse effects. OBJECTIVE: This study aimed to compare the efficacy, maternal and neonatal safety, and maternal satisfaction of a synthetic osmotic cervical dilator (Dilapan-S) with those of dinoprostone. STUDY DESIGN: This was an open-label superiority randomized controlled trial in 4 English hospitals. Eligible participants were women ≥16 years of age undergoing induction of labor for a singleton pregnancy at ≥37 weeks' gestation with vertex presentation and intact membranes. The women were randomly assigned to receive either Dilapan-S or dinoprostone using a telephone randomization system minimized by hospital, parity, body mass index, and maternal age. The induction agent was replaced as required until the cervix was assessed as favorable for labor by the Bishop score. The primary outcome was failure to achieve vaginal delivery (ieor a cesarean delivery being performed). The secondary outcome measures included maternal and neonatal adverse events. Analysis was by intention-to-treat, adjusting for design variables where possible. RESULTS: Between December 19, 2017 and January 26, 2021, 674 women were randomized (337 to Dilapan-S, and 337 to dinoprostone). The trial did not reach its planned sample size of 860 participants because of restrictions on research during the COVID-19 pandemic. The primary outcome was missing for 2 women in the dinoprostone group. Failure to achieve vaginal delivery (or a cesarean delivery being performed) occurred in 126 women (37.4%) allocated to Dilapan-S and in 115 (34.3%) women allocated to dinoprostone (adjusted risk difference, 0.02; 95% confidence interval, -0.05 to 0.10). There were similar maternal and neonatal adverse events between the groups. CONCLUSION: Women undergoing induction of labor with Dilapan-S have similar rates of cesarean delivery and maternal and neonatal adverse events compared with dinoprostone.

Synthetic osmotic dilators (Dilapan-S) or dinoprostone vaginal inserts (Propess) for inpatient induction of labour: A UK cost-consequence model.

OBJECTIVE: To estimate the costs of synthetic osmotic dilators (Dilapan-S) compared to dinoprostone vaginal inserts (Propess) for inpatient induction of labour (IOL). STUDY DESIGN: A population-level, Markov model-based cost-consequence analysis was developed to compare the impact of using Dilapan-S versus Propess. The time horizon was modelled from admission to birth. The target population was women requiring inpatient IOL from 37 weeks with an unfavourable cervix in the UK. Mean population characteristics reflected those of the SOLVE (NCT03001661) trial. No patient data were included in this analysis. The care pathways and staff workload were modelled using data from the SOLVE trial and clinical experience. Cost and clinical inputs were sourced from the SOLVE trial and peer-reviewed literature. Costs were inflated to 2020 British pounds (GBP, £). Outcomes were reported as an average per woman for total costs and required staff time (minutes) from admission for IOL until birth. The model robustness was assessed using a probabilistic, multivariate sensitivity analysis of 2,000 simulations with results presented as the median (interquartile range, IQR). RESULTS: Dilapan-S was cost neutral compared to Propess. Midwife and obstetrician times were decreased by 146 min (-11%) and 11 min (-54%), respectively. Sensitivity analysis showed that in 78% of simulations, use of Dilapan-S reduced midwife time with a median of -160 min (IQR -277 to -24 min). Costs were reduced in 54% of simulations (median -£33, IQR -£319 to £282). CONCLUSIONS: The model indicates that adoption of Dilapan-S is likely to be cost-neutral and reduce staff workload in comparison to Propess. Results require support from real-world data and further exploration of Dilapan-S is to be encouraged.

Oral progestogens vs levonorgestrel-releasing intrauterine system for endometrial hyperplasia: a systematic review and metaanalysis.

OBJECTIVE: To conduct a systematic review and metaanalysis of studies evaluating the regression rate of endometrial hyperplasia with oral progestogens and levonorgestrel-releasing intrauterine system. STUDY DESIGN: Searches were conducted on Medline, Embase, Cochrane Library, and Web of Science, and reference lists of relevant articles were examined. The methodologic index for nonrandomized studies was used for quality assessment. Metaanalysis was performed with random effects model. RESULTS: There were 24 observational studies (1001 women), of low methodologic quality, evaluating the outcome of regression of endometrial hyperplasia with oral progestogens or levonorgestrel-releasing intrauterine system. Metaanalysis showed that oral progestogens achieved a lower pooled regression rate compared with levonorgestrel-releasing intrauterine system for complex (pooled rate, 66% vs 92%; P < .01) and atypical hyperplasia (pooled rate, 69% vs 90%; P = .03). There was no statistical difference in simple hyperplasia (pooled rate, 89% vs 96%; P = .41). CONCLUSION: Oral progestogens appear to induce a lower disease regression rate than Levonorgestrel-releasing intrauterine system in the treatment of endometrial hyperplasia.

Prognostic significance of estrogen and progesterone receptor expression in LNG-IUS (Mirena) treatment of endometrial hyperplasia: an immunohistochemical study.

We performed immunohistochemical analysis of estrogen (ERalpha) and progesterone receptors (PRA and PRB), phosphatase and tensin homolog (PTEN) and aromatase in endometrial hyperplasia treated with Mirena (levonorgestrel-releasing intrauterine system; LNG-IUS) and explored their prognostic significance. The baseline pre-treatment endometrial hyperplasia of a selected prospective cohort was analyzed [complex (n = 29) and atypical (n = 5)]. Study participants were categorized into those that showed endometrial regression (responders, n = 28) and those that showed non-regression or histological progression to atypia or malignancy (non-responders, n = 6). Immunohistochemical expression was expressed as a histological score (HS). Responders compared to non-responders showed significantly higher HSs for estrogen and progesterone receptors. Absence of estrogen and progesterone receptors predicted non-responder status with likelihood ratios of 9.33 (95% CI 2.19-39.81) and 2.92 (95% CI 1.47-5.79), respectively. Neither PTEN nor aromatase expression were associated with LNG-IUS therapy responsiveness. Responsiveness of endometrial hyperplasia to LNG-IUS therapy may be determined through analysis of baseline estrogen and progesterone receptors, but these exploratory findings require confirmation in a larger dataset.

Outpatient Thermachoice endometrial balloon ablation: long-term, prognostic and quality-of-life measures.

STUDY OBJECTIVE: To evaluate short- and long-term treatment outcomes of outpatient local anaesthetic thermal balloon endometrial ablation (LA-TBEA) and identify any prognostic factors. STUDY DESIGN: Prospective observational study in a UK teaching hospital involving 102 menorrhagic women undergoing LA-TBEA between 2001 and 2005. Women underwent either Gynecare® Thermachoice I (n = 51) or Thermachoice III (n = 51) TBEA performed in the outpatient setting under local anaesthesia without conscious sedation. The main outcome measures were: treatment completion, pain and analgesia, duration of stay (from admission to discharge), duration of follow-up, primary treatment success and nature of any secondary treatment, menstrual symptoms and amenorrhoea, patient satisfaction, and quality of life. RESULTS: TBEA was completed in 97% of women. Mean duration of stay was 8.0 h (95% CI 6.6-9.3). Mean follow-up was 30 months (95% CI 26-32). Secondary treatment with the levonorgestrel intrauterine system, repeat TBEA or hysterectomy occurred in 19/102 (19%). Overall, 50% of surgical re-interventions occurred by 19 months. There were high rates of amenorrhoea (29%) and treatment satisfaction (76%). Higher mean intrauterine ablation pressure was associated with increased treatment satisfaction. CONCLUSION: TBEA can be successfully performed in the outpatient setting. Higher endometrial ablation pressure may improve long-term treatment outcome.