Re-intervention and patient satisfaction rates following office radiofrequency endometrial ablation: a comparative retrospective study of 408 cases.

This retrospective study assessed the efficacy and long-term satisfaction of radiofrequency endometrial ablation outside the context of clinical trials in 408 women, and compared the outcome between office-setting (211, 52%) and day-case procedures under general anaesthetics (197, 48%). The Kaplan Meir time-to-event analysis showed that the cumulative number of women undergoing surgical re-intervention was 32 with a probability of 9.4% (95% CI: 6.3 - 12.5%) at 2-years, and 45 with a probability of 14.5% (95% CI: 10.3 - 18.2%) at 5-years. There was no statistically significant difference in the re-intervention rate between office and day-case groups (HR = 0.7, 95% CI: 0.68 - 3.1, p = .3). The satisfaction rate, measured by Visual Analogue Scale, was not statistically different (p = .5) between office (109; 80.7%) and day-case (96; 82.8%) groups. This study showed lower surgical re-intervention rate than previously reported in observational studies, and high rates of long-term women satisfaction. The outcomes were similar in office and day-case settings.Impact statementWhat is already known on this subject? Previous studies have shown the safety and effectiveness of radiofrequency endometrial ablation for treating heavy periods. However, studies investigating it, outside clinical trials, either included a small sample size, a short-term follow-up, poor reporting so that it is impossible to judge whether some women underwent re-intervention in another centre, failed to discriminate in analysis between second-generation techniques, or assessed only short-term satisfaction.What do the results of this study add? This is the largest series reported from a single centre and the first study reporting long-term satisfaction in women, outside clinical trials. Surgical re-intervention was used as the primary outcome measure which is an objective measure rather than the change in the monthly flow which is rather subjective. More importantly, the study records the similarity, in the outcome and women's satisfaction rate, between office and day-case procedures under general anaesthetics.What are the implications of these findings for clinical practice and/or further research? Endometrial ablation service is widely implemented in office-setting in the UK. We hope the result of this study encourages implementation on a larger scale in office across centres in the world with its multiple advantages both to women and service alike.

Caesarean section operation is not associated with myometrial hypertrophy-a prospective cohort study.

Maternity statistics of England in 2020 showed rise in Caesarean Section (CS) rate to 31%. Some studies correlated adverse gynaecological symptoms e.g. menstrual irregularities and pelvic pain to 'niche' formation at CS scar site. Niche formation was speculated to cause myometrial hypertrophy aggravating these symptoms. This was a prospective comparative histological study including 52 consecutive benign hysterectomy specimens which were categorised into 2 groups: (i) specimens with CS scar (n = 22), (ii) specimens with no CS scar (n = 30). Median (IQ range) uteri weight was 97.2grms (43.5-226) and 91.7grms (35.7-201.7) in study and control groups, respectively (p = .991). Mean (±SD) thickness of anterior myometrial wall was 18.7 mm (±3.6) and 19.4 mm (±4.5) in study and control groups, respectively (p = .58). Mean (±SD) thickness of posterior myometrial wall was 19.1 mm (±3.7) and 18.7 mm (±3.9) in study and control groups, respectively (p = .78). The assumption that CS scar causes myometrial hypertrophy was not demonstrated in this study.IMPACT STATEMENTWhat is already known on this subject? Maternity statistics world-wide show a continuous rise in the rate of Caesarean Section (CS) operation. The CS scar is assumed to be related to adverse clinical gynaecological symptoms such as intermenstrual bleeding, dysmenorrhoea, dyspareunia and chronic pelvic pain; however, the mechanism of this association is not clear. Further, little is known about the effects of CS scar on uterine wall morphology and function.What do the results of this study add? This study was the first prospective series in the literature to compare the uteri with scar with those without in respect of weight and myometrial wall thickness. It was not able to demonstrate the association between having CS scar and myometrial hypertrophy which was hypothesised to be the cause of adverse gynaecological symptoms. However, the microscopic examination of the CS scar revealed adenomyosis, haemorrhage and/or chronic inflammation in most cases.What are the implications of these findings for clinical practice and/or future research? The clinical implication of the histological changes shown in the CS scar requires large comparative clinical studies.

A Randomized Trial of Progesterone in Women with Recurrent Miscarriages.

BACKGROUND: Progesterone is essential for the maintenance of pregnancy. However, whether progesterone supplementation in the first trimester of pregnancy would increase the rate of live births among women with a history of unexplained recurrent miscarriages is uncertain. METHODS: We conducted a multicenter, double-blind, placebo-controlled, randomized trial to investigate whether treatment with progesterone would increase the rates of live births and newborn survival among women with unexplained recurrent miscarriage. We randomly assigned women with recurrent miscarriages to receive twice-daily vaginal suppositories containing either 400 mg of micronized progesterone or matched placebo from a time soon after a positive urinary pregnancy test (and no later than 6 weeks of gestation) through 12 weeks of gestation. The primary outcome was live birth after 24 weeks of gestation. RESULTS: A total of 1568 women were assessed for eligibility, and 836 of these women who conceived naturally within 1 year and remained willing to participate in the trial were randomly assigned to receive either progesterone (404 women) or placebo (432 women). The follow-up rate for the primary outcome was 98.8% (826 of 836 women). In an intention-to-treat analysis, the rate of live births was 65.8% (262 of 398 women) in the progesterone group and 63.3% (271 of 428 women) in the placebo group (relative rate, 1.04; 95% confidence interval [CI], 0.94 to 1.15; rate difference, 2.5 percentage points; 95% CI, -4.0 to 9.0). There were no significant between-group differences in the rate of adverse events. CONCLUSIONS: Progesterone therapy in the first trimester of pregnancy did not result in a significantly higher rate of live births among women with a history of unexplained recurrent miscarriages. (Funded by the United Kingdom National Institute of Health Research; PROMISE Current Controlled Trials number, ISRCTN92644181.).

Thickened endometrium in asymptomatic postmenopausal women - determining an optimum threshold for prediction of atypical hyperplasia and cancer.

There is a lack of consensus about the significance and the management of an incidental finding of endometrial thickness (ET) > 4 mm on transvaginal ultrasound scans in postmenopausal women without postmenopausal bleeding (PMB). The data of 1995 consecutive women attending PMB clinic were collected prospectively; of them 81 (4.1%) were referred because of ET >4 mm without PMB. The prevalence of endometrial atypical hyperplasia and cancer was 4/81 (4.9%), and polyp was 20/81 (24.7%). On using a receiver operator characteristic curve, the diagnosis of endometrial atypical hyperplasia and cancer using the ET threshold of ≥10 mm had a sensitivity of 100% (95% CI = 40-100%), a specificity of 60% (95% CI = 48-71%) with AUC = 0.8 (95% CI = 0.66-0.93), p = .04. For the 35 women with an ET ≥10 mm, the prevalence of endometrial atypical hyperplasia and cancer was 4/35 (11.4%) and benign endometrial polyps was 16/35 (45.7%). The use of ≥10 mm ET threshold to prompt investigations did not miss any case of endometrial atypical hyperplasia or cancer. Impact Statement What is already known on this subject? Unlike women with PMB in whom an endometrial thickness (ET) ≤ 4 mm is considered as low risk for endometrial hyperplasia and cancer, in postmenopausal women without PMB, the threshold that separates normal from a pathologically thickened endometrium has not been standardised. A decision-analysis study in a hypothetical cohort found that ET threshold of 11 mm yields a similar separation as ≤4 mm in those with PMB. What the results of this study add? The study uses prospectively collected data from consecutive patients using a standardised format, thus minimising bias from incomplete data. This study is the third prospective series in the literature to address the dilemma of the management of asymptomatic postmenopausal women with an incidental finding of a thickened endometrium. It showed that the prevalence of endometrial atypical hyperplasia and cancer is high enough to justify investigation and for the clinical problem not to be trivialised. All cases of endometrial atypical hyperplasia and cancer had ET of ≥10 mm. What are the implications of these findings for clinical practice and/or future research? Our data strengthen the current body of literature to help the development of clinical practice guidelines about the management work-up. However, a well-designed multi-centre large prospective study is required to confirm the findings since most studies in the literature are either retrospective or small.

Is routine adnexal scanning for postmenopausal bleeding of value? Observational study of 2101 women.

Our objective is to assess the merits of adnexal scanning during the investigation of women with postmenopausal bleeding (PMB) in terms of adnexal cancer diagnosis. This observational study was designed utilising an institutional PMB database in a teaching hospital, analysing a sample of 2101 consecutive women with PMB seen between 16th February 2012 and 12th August 2014 looking at the prevalence of cancer in adnexal masses identified on Trans-vaginal ultrasound scanning (TVS) in these PMB women. This study suggests that routine adnexal scanning in women with PMB may provide no benefit. It could be exposing women to unnecessary surgery or surveillance with the associated risks and cost implications. Most of the women who underwent surgery presented with palpable masses. Those with negative clinical examination had either benign masses which may have remained inconsequential or non-suspicious scan findings. A well-designed randomised controlled trial is needed to confirm the findings. Impact statement Trans-vaginal ultrasound scanning (TVS) is the standard first line investigation for women presenting with postmenopausal bleeding (PMB) primarily to assess the endometrial thickness. This has led to a widespread practice of opportunistic adnexal scanning, which generated a debate amongst gynaecologists about the value of such practice. This observational study, assessing the merits of routine adnexal scanning in these women in terms of adnexal cancer diagnosis, suggests that this practice may provide no benefit to women with isolated self-limiting PMB and unremarkable bimanual examination. It could be exposing women to unnecessary surgery or surveillance with the associated risks and cost implications when insignificant adnexal masses are identified on the scan. A well-designed randomised controlled trial is needed to elucidate if clinical examination in combination with endometrial scanning only is more effective and cost-effective than clinical examination followed by systematic pelvic scanning to detect cases of ovarian cancer in women with PMB.

The optimal endometrial thickness threshold for prediction of endometrial cancer in postmenopausal women without bleeding remains uncertain-Systematic review and meta-analysis.

The incidental finding of endometrial thickness (ET) >4 mm in the absence of postmenopausal bleeding (PMB) is a common cause of referring women to secondary care. However, there is lack of consensus amongst gynecologists as regards the management. It is estimated that up to 15 % of endometrial cancers occur in women without PMB. The aim this study was to determine the optimal ET threshold, on trans-vaginal ultrasound scan, that discriminates normal endometrium from endometrial hyperplasia and cancer in this cohort. On using a thorough search strategy, a total 16 studies including 4088 women were deemed eligible. However, the data were not amenable to meta-analysis. There were wide variations in the thresholds reported with potential bias given the retrospective nature of the majority of the studies. Despite contacting authors, we could not obtain the primary data to generate a Receiver Operating Characteristic (ROC) Curve. No linear or curvilinear association was found between ET thresholds and the percentage of women diagnosed with endometrial hyperplasia and cancer using either Pearson's correlation, linear or curvilinear regression, or a simple visual scan/scatter diagram. The result of this study reveals the lack of evidence to inform clinical practice in this area, and there is a need for a well-designed multi-center prospective study.

Office hysteroscopic morcellation service: Evaluation of women experience and factors affecting satisfaction.

OBJECTIVES: To evaluate the hysteroscopic morcellation service in office-setting in everyday practice outside the context of clinical trials. The primary objectives were to assess level of acceptability and factors affecting women satisfaction. The secondary objectives included assessment of complete resection rate, complications rate, pain score during the procedure and on discharge, and the correlation between the lesion size as subjectively estimated by the hysteroscopists versus the volume of morcellated tissues as semi-quantitively measured by the laboratory. METHOD: The clinical data was compiled for 287 consecutive women undergoing hysteroscopic morcellation in office-setting from 1 January 2017 to 31 March 2021 in a teaching hospital in the UK. A questionnaire, formulated on the Visual Analogue Scale (VAS), was completed immediately after the procedure by the last 110 women undergoing the procedure. RESULTS: The mean age of the cohort (n = 278) was 54.5 years (SD ± 12.5). Only 7 (2.4%) women required two-stage procedure because of size (fibroid ≥ 4 cm), vascularity or multiplicity of lesions. No complications were encountered. The majority of women completing the questionnaire (n = 110) found office procedure acceptable (105, 95.5%, VAS ≥ 7), were willing to have it again if indicated (102, 92.7%, VAS ≥ 7), would recommend it to family and friends (105, 95.5%, VAS ≥ 7) and confirmed receiving adequate preoperative information by doctors and nurses (107, 97.3%, VAS ≥ 7). The level of preoperative explanation and information-giving showed significant (p < 0.01) positive correlation with the level of acceptability and recommendation to others and significant (p = .007) negative correlation with the pain experienced on discharge. The median (IQR) estimated size at hysteroscopy was 2 cm (1-6 cm) for polyps and 2.5 cm (1-4 cm) for fibroid. The median (IQR) volume of the morcellated specimens as estimated by laboratory was 2000 mm3 (1100-3800 mm3). The estimated size at hysteroscopy was positively correlated with the specimen's volume (Spearman's rho (r) = 0.31, 95% = CI, 0.14-0.45, p < 0.01). CONCLUSION: Office hysteroscopic morcellation is associated with high satisfaction rate and low pain score on discharge. Good preoperative explanation and information-giving was the crucial factor that increased women satisfaction. Subjective estimation of lesion size by hysteroscopists may be an accurate and simple method of measurement.

Folic acid supplementation may cure hot flushes in postmenopausal women: a prospective cohort study.

BACKGROUND: Neurotransmitter norepinephrine seems to be involved in the pathophysiology of hot flushes in postmenopausal women, and folic acid was found to interact with its receptors. OBJECTIVES: To examine the effect of folic acid supplementation on the occurrence of hot flushes and the plasma level of 3-methoxy 4-hydroxy phenyl glycol (MHPG, the main metabolite of brain norepinephrine). METHOD: Forty-six postmenopausal women were allocated (by alternation) into 2 groups (n = 23 each); Group 1 received folic acid 5mg tablets daily for 4 weeks and group 2 received placebo tablets. Four women in group 2 discontinued the study. RESULTS: The number of women who reported improvement in hot flushes was significantly higher in the treatment group. On comparing the mean plasma levels of MHPG before and after treatment, a significant lowering was found in the treatment group (mean % change = -24.1 +/- 17.9, p < 0.001) when compared with the placebo-control group (mean % change = -5.59 +/- 16.4, p = 0.10). In the treatment group, there was a significant negative correlation between improvement in hot flushes and the plasma level of MHPG (r = -0.453, p = 0.03). CONCLUSION: Folic acid supplementation may cause subjective improvement of hot flushes by lowering the increased central noradrenergic activity.

The Prevalence of Thyroid Dysfunction and Autoimmunity in Women With History of Miscarriage or Subfertility.

OBJECTIVE: To describe the prevalence of and factors associated with different thyroid dysfunction phenotypes in women who are asymptomatic preconception. DESIGN: Observational cohort study. SETTING: A total of 49 hospitals across the United Kingdom between 2011 and 2016. PARTICIPANTS: Women aged 16 to 41years with history of miscarriage or subfertility trying for a pregnancy. METHODS: Prevalences and 95% confidence intervals (CIs) were estimated using the binomial exact method. Multivariate logistic regression analyses were conducted to identify risk factors for thyroid disease. INTERVENTION: None. MAIN OUTCOME MEASURE: Rates of thyroid dysfunction. RESULTS: Thyroid function and thyroid peroxidase antibody (TPOAb) data were available for 19213 and 19237 women, respectively. The prevalence of abnormal thyroid function was 4.8% (95% CI, 4.5-5.1); euthyroidism was defined as levels of thyroid-stimulating hormone (TSH) of 0.44 to 4.50 mIU/L and free thyroxine (fT4) of 10 to 21 pmol/L. Overt hypothyroidism (TSH > 4.50 mIU/L, fT4 < 10 pmol/L) was present in 0.2% of women (95% CI, 0.1-0.3) and overt hyperthyroidism (TSH < 0.44 mIU/L, fT4 > 21 pmol/L) was present in 0.3% (95% CI, 0.2-0.3). The prevalence of subclinical hypothyroidism (SCH) using an upper TSH concentration of 4.50 mIU/L was 2.4% (95% CI, 2.1-2.6). Lowering the upper TSH to 2.50 mIU/L resulted in higher rates of SCH, 19.9% (95% CI, 19.3-20.5). Multiple regression analyses showed increased odds of SCH (TSH > 4.50 mIU/L) with body mass index (BMI) ≥ 35.0 kg/m2 (adjusted odds ratio [aOR] 1.71; 95% CI, 1.13-2.57; P = 0.01) and Asian ethnicity (aOR 1.76; 95% CI, 1.31-2.37; P < 0.001), and increased odds of SCH (TSH ≥ 2.50 mIU/L) with subfertility (aOR 1.16; 95% CI, 1.04-1.29; P = 0.008). TPOAb positivity was prevalent in 9.5% of women (95% CI, 9.1-9.9). CONCLUSIONS: The prevalence of undiagnosed overt thyroid disease is low. SCH and TPOAb are common, particularly in women with higher BMI or of Asian ethnicity. A TSH cutoff of 2.50 mIU/L to define SCH results in a significant proportion of women potentially requiring levothyroxine treatment.

The first-line investigation of postmenopausal bleeding: transvaginal ultrasound scanning and endometrial biopsy may be enough.

Postmenopausal bleeding is a common problem in clinical practice with significant implications; however, the diagnostic strategies often vary among different centers. In the recent years, there was a trend to adopt less invasive procedures without compromising efficacy and safety. There is continuous debate about the different available modalities for investigation, and a large number of studies were conducted to define their roles. Some authors recommended that hysteroscopy should be the standard investigation procedure for women with postmenopausal bleeding. Nonetheless, there is a strong evidence to suggest that transvaginal ultrasound scanning, with or without endometrial biopsy, is a safe and more cost-effective initial tool in investigating these women. This commentary highlights this important issue and discusses the role of these different modalities.

Levonorgestrel-releasing intrauterine system--the discontinuing story.

Levonorgestrel-releasing Intrauterine System (LNG-IUS) is licensed for use as a contraceptive, for the treatment of heavy menstrual bleeding and during estrogen replacement therapy. It is publicized as a local source of progestogen with minimal systemic adverse effects. However, there is overwhelming evidence of elevated serum and tissue levels of levonorgestrel, and high discontinuation and dissatisfaction rates amongst users. The guidelines of The National Institute for Health and Clinical Excellence (NICE), United Kingdom recommended that the healthcare professionals should be aware that upto 60% of women discontinue using LNG-IUS within 5 years because of unscheduled bleeding, pain, and/or systemic progestogenic adverse effects. This article highlights these issues to healthcare professionals to ensure that the rates of adverse effects are not underestimated, and full information are made available to women to enable them making an informed choice.

Changes in transcription profile and cytoskeleton morphology in pelvic ligament fibroblasts in response to stretch: the effects of estradiol and levormeloxifene.

Failure of ligamentous support of the genital tract to resist intra-abdominal pressure is a plausible underlying mechanism for the development of pelvic organ prolapse, but the nature of the molecular response of pelvic tissue support remains unknown. We hypothesized that the expression of genes coding for proteins involved in maintaining the cellular and extracellular integrity would be altered as a result of mechanical stretch. Therefore, cDNA microarrays were used to examine the difference in transcriptional profile in RNA of primary culture fibroblasts subjected to mechanical stretch and those that remained static. Out of 34 mechano-responsive genes identified (P < 0.05), four were coding for regulation of actin cytoskeleton remodelling, and its interaction with the extracellular matrix proteins; these are phosphatidyl inositol-4-phosphate 5-kinase (PIP5K1C), the human signal-induced proliferation associated gene-1 (SIPA-1), TNFRSF1A-associated via death domain (TRADD) and deoxyribonuclease 1-like 1 (DNase 1-L1). The transcriptosomal changes led us to investigate the phenotypic consequences of stretch, levormeloxifene and estradiol (E(2)) on the cytoskeleton of cultured fibroblasts. The percentage of cells with abnormal F-actin configuration was significantly higher in fibroblasts subjected to stretch compared with the static model (P < 0.0001). Levormeloxifene caused similar significant alterations in actin morphology of the static fibroblasts. The use of E(2) did not reverse the process or protect the cells from the effect of stretch, but significantly increased the rate of fibroblast proliferation, suggestive of a role in healing process. Mechanical stretch and/or levormeloxifene disturb the fibroblasts ability to maintain the cytoskeleton architecture and we speculate that they may disrupt ligamentous integrity and result in clinical prolapse.