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OBJECTIVE: To compare the effectiveness of endometriosis excision alone to excision plus hysterectomy, with and without bilateral oophorectomy, for endometriosis-related symptoms. DESIGN: Multicentre prospective cohort. SETTING: Eighty-six specialist endometriosis centres. POPULATION: Women undergoing rectovaginal endometriosis surgery between 2009 and 2021. METHODS: We performed multivariable regression with random effects for patient and centre, controlling for age, BMI, smoking, laparoscopic versus open approach and type of bowel surgery performed, with sensitivity analysis for loss to follow-up. MAIN OUTCOME MEASURES: Pain scores, bowel symptoms and quality-of-life measures. RESULTS: Compared to endometriosis excision alone, women undergoing hysterectomy with conservation of ovaries had greater improvement in non-cyclical pain (MD: 1.41/10, 95% CI: 1.03-1.78, p < 0.001), dyspareunia (MD: 1.12/10, 95% CI: 0.71-1.53, p < 0.001), back pain (MD: 1.29/10, 95% CI: 0.92-1.67, p < 0.001) and quality-of-life scores (MD: 8.77/100, 95% CI: 5.79-11.75, p < 0.001) at 24 months post-operatively. Women undergoing hysterectomy with bilateral oophorectomy also had greater improvement in non-cyclical pelvic pain (MD: 2.22/10, 95% CI: 1.80-2.63, p < 0.001), dyspareunia (MD: 1.05/10, 95% CI: 0.59-1.52, p < 0.001), back pain (MD: 1.18/10, 95% CI: 0.77-1.59, p < 0.001) and quality of life (MD: 12.41/100, 95% CI: 9.07-15.74, p < 0.001) at 24 months compared to endometriosis excision alone. Compared to hysterectomy with ovarian conservation, hysterectomy with bilateral oophorectomy was associated with greater improvement in non-cyclical pelvic pain (MD: 0.81/10, 95% CI: 0.32-1.30, p = 0.001) at 24 months and quality of life (MD: 3.74/100, 95% CI: 0.56-6.92, p = 0.021) at 12 months, although this result was sensitive to loss to follow-up. CONCLUSIONS: Patients who undergo endometriosis excision plus hysterectomy experience greater improvement in pain and quality of life compared to those who have endometriosis excision alone. There are additional benefits of bilateral oophorectomy with hysterectomy, although its value is less clear due to loss of follow-up.
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The International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) and International Deep Endometriosis Analysis (IDEA) group, the European Endometriosis League (EEL), the European Society for Gynaecological Endoscopy (ESGE), the European Society of Human Reproduction and Embryology (ESHRE), the International Society for Gynecologic Endoscopy (ISGE), the American Association of Gynecologic Laparoscopists (AAGL) and the European Society of Urogenital Radiology (ESUR) elected an international, multidisciplinary panel of gynecological surgeons, sonographers and radiologists, including a steering committee, which searched the literature for relevant articles in order to review the literature and provide evidence-based and clinically relevant statements on the use of imaging techniques for non-invasive diagnosis and classification of pelvic deep endometriosis. Preliminary statements were drafted based on review of the relevant literature. Following two rounds of revisions and voting orchestrated by chairs of the participating societies, consensus statements were finalized. A final version of the document was then resubmitted to the society chairs for approval. Twenty statements were drafted, of which 14 reached strong and three moderate agreement after the first voting round. The remaining three statements were discussed by all members of the steering committee and society chairs and rephrased, followed by an additional round of voting. At the conclusion of the process, 14 statements had strong and five statements moderate agreement, with one statement left in equipoise. This consensus work aims to guide clinicians involved in treating women with suspected endometriosis during patient assessment, counseling and planning of surgical treatment strategies.
Subject(s)
Endometriosis , Endometriosis/diagnostic imaging , Endometriosis/classification , Humans , Female , Ultrasonography/methods , Magnetic Resonance Imaging/methods , Pelvis/diagnostic imaging , ConsensusABSTRACT
In vitro fertilization (IVF) is an established option for the management of infertility in patients with endometriosis, though there remains ongoing debate around the extent to which endometriosis may compromise IVF treatment success, in which fertilization and preimplantation embryo development occur outside the pelvis. Whether endometriosis impacts oocyte and embryo quality and/or endometrial receptivity remains central to this debate. Here, we review the current literature relating to the impact of endometriosis on IVF outcomes and management strategies to consider when performing IVF treatment.
Subject(s)
Endometriosis , Fertilization in Vitro , Infertility, Female , Humans , Endometriosis/complications , Endometriosis/therapy , Female , Fertilization in Vitro/methods , Infertility, Female/therapy , Infertility, Female/etiology , PregnancyABSTRACT
BACKGROUND: Acceptance of the role of the fallopian tube in 'ovarian' carcinogenesis and the detrimental sequelae of surgical menopause in premenopausal women following risk-reducing salpingo-oophorectomy (RRSO) has resulted in risk-reducing early-salpingectomy with delayed oophorectomy (RRESDO) being proposed as an attractive alternative risk-reducing strategy in women who decline/delay oophorectomy. We present the results of a qualitative study evaluating the decision-making process among BRCA carriers considering prophylactic surgeries (RRSO/RRESDO) as part of the multicentre PROTECTOR trial (ISRCTN:25173360). METHODS: In-depth semistructured 1:1 interviews conducted using a predeveloped topic-guide (development informed by literature review and expert consultation) until informational saturation reached. Wording and sequencing of questions were left open with probes used to elicit additional information. All interviews were audio-recorded, transcribed verbatim, transcripts analysed using an inductive theoretical framework and data managed using NVIVO-v12. RESULTS: Informational saturation was reached following 24 interviews. Seven interconnected themes integral to surgical decision making were identified: fertility/menopause/cancer risk reduction/surgical choices/surgical complications/sequence of ovarian-and-breast prophylactic surgeries/support/satisfaction. Women for whom maximising ovarian cancer risk reduction was relatively more important than early menopause/quality-of-life preferred RRSO, whereas those more concerned about detrimental impact of menopause chose RRESDO. Women managed in specialist familial cancer clinic settings compared with non-specialist settings felt they received better quality care, improved hormone replacement therapy access and were more satisfied. CONCLUSION: Multiple contextual factors (medical, physical, psychological, social) influence timing of risk-reducing surgeries. RRESDO offers women delaying/declining premenopausal oophorectomy, particularly those concerned about menopausal effects, a degree of ovarian cancer risk reduction while avoiding early menopause. Care of high-risk women should be centralised to centres with specialist familial gynaecological cancer risk management services to provide a better-quality, streamlined, holistic multidisciplinary approach.
Subject(s)
Clinical Decision-Making , Genes, BRCA1 , Genes, BRCA2 , Ovarian Neoplasms/prevention & control , Prophylactic Surgical Procedures , Salpingectomy , Salpingo-oophorectomy , Adult , Cohort Studies , Female , Heterozygote , Humans , Middle Aged , Ovarian Neoplasms/genetics , Ovariectomy , Premenopause , Prophylactic Mastectomy , Risk Reduction BehaviorABSTRACT
STUDY OBJECTIVE: To retrospectively evaluate the ability of routinely collected preoperative ultrasound data to predict bowel resection during surgery for rectovaginal endometriosis. DESIGN AND SETTING: Patients at the University College London Hospital who underwent surgery for rectovaginal endometriosis during a 6-year period were identified from the prospectively generated hospital (British Society for Gynaecological Endoscopy) database. Imaging data were collected and analyzed to determine associations with the requirement for bowel resection. PATIENTS: We evaluated 228 consecutive women undergoing bowel surgery (shave, disc resection, or segmental resection) for rectovaginal endometriosis. INTERVENTIONS: The patients in our study underwent surgical resection of rectovaginal endometriosis and interventions included shave, disc resection, and segmental resection of the bowel. All patients underwent a preoperative transvaginal ultrasound to assess the extent of endometriosis. MEASUREMENTS AND MAIN RESULTS: There were 206 rectal shaves (90.4%), 2 disc resections (0.9%), and 20 segmental bowel resections (8.8%). A multivariable analysis demonstrated an association between bowel resection and ≥2 nodules located in the rectovaginal space (odds ratio [OR] 6.85; 95% confidence interval [CI], 1.37-34.2), nodules in the vesicouterine pouch (OR 5.87; 95% CI, 1.03-33.3), and increasing nodule size (OR 2.39 per 1 cm increase per 1 cm diameter increase; 95% CI, 1.56-3.64). CONCLUSION: Ultrasound findings of endometriotic nodule location, number of nodules, and increasing size are independent predictors of segmental bowel resection at the time of surgery for rectovaginal endometriosis. This highlights the importance of accurate diagnostic evaluation to aid counseling and surgical planning in the preoperative setting for women with rectovaginal endometriosis.
Subject(s)
Endometriosis , Laparoscopy , Rectal Diseases , Endometriosis/complications , Endometriosis/diagnostic imaging , Endometriosis/surgery , Female , Humans , Laparoscopy/methods , Rectal Diseases/complications , Rectal Diseases/diagnostic imaging , Rectal Diseases/surgery , Retrospective Studies , Treatment OutcomeABSTRACT
OBJECTIVE: To develop a consensus statement of recommended terminology to use for describing different aspects of hysteroscopic procedures that can be uniformly used in clinical practice and research. DESIGN: Open forum discussion followed by online video meetings. SETTING: International community of hysteroscopy experts PATIENTS: Not applicable. INTERVENTIONS: Series of online video meetings to complete a previously established agenda until a final agreement for standardized nomenclature was obtained. MEASUREMENT AND MAIN RESULTS: The adoption and implementation of a common terminology to standardize reporting of hysteroscopic procedures was proposed to cover five domains: pain management, healthcare setting, model of care, type of hysteroscopic procedure and the hysteroscopic approach to the uterine cavity. A final agreement was obtained after 3 online video meetings. CONCLUSION: Hysteroscopy is the gold standard technique for the evaluation and management of uterine disorders. A clear definition and understanding of the terminology used to describe hysteroscopic procedures is lacking. The production of this international consensus statement for terminology to describe hysteroscopic procedures, covering pain management, setting, model of care, type of procedure and hysteroscopic approach, has the potential to enable more effective communication for both clinical and research purposes with the ultimate aim of improving patient care and clinical outcomes.
Subject(s)
Hysteroscopy , Uterine Diseases , Consensus , Female , Humans , Hysteroscopy/methods , Pregnancy , UterusABSTRACT
BACKGROUND: Risk-reducing salpingo-oophorectomy is the 'gold standard' for preventing tubo-ovarian cancer in women at increased risk. However, when performed in pre-menopausal women, it results in premature menopause and associated detrimental health consequences. This, together with acceptance of the central role of the fallopian tube in etiopathogenesis of high-grade serous carcinoma, by far the most common type of tubo-ovarian cancer, has led to risk-reducing early salpingectomy with delayed oophorectomy being proposed as a two-step surgical alternative for pre-menopausal women declining/delaying oophorectomy. PRIMARY OBJECTIVE: To evaluate the impact on sexual function of risk-reducing early salpingectomy, within a two-step, risk-reducing, early salpingectomy with delayed oophorectomy tubo-ovarian cancer prevention strategy in pre-menopausal women at increased risk of tubo-ovarian cancer. STUDY HYPOTHESIS: Risk-reducing early salpingectomy is non-inferior for sexual and endocrine function compared with controls; risk-reducing early salpingectomy is superior for sexual/endocrine function, non-inferior for quality-of-life, and equivalent in satisfaction to the standard risk-reducing salpingo-oophorectomy. TRIAL DESIGN: Multi-center, observational cohort trial with three arms: risk-reducing early salpingectomy with delayed oophorectomy; risk-reducing salpingo-oophorectomy; controls (no surgery). Consenting individuals undergo an ultrasound, serum CA125, and follicle-stimulating hormone measurements and provide information on medical history, family history, quality-of-life, sexual function, cancer worry, psychological well-being, and satisfaction/regret. Follow-up by questionnaire takes place annually for 3 years. Women receiving risk-reducing early salpingectomy can undergo delayed oophorectomy at a later date of their choosing, or definitely by the menopause. MAJOR INCLUSION/EXCLUSION CRITERIA: Inclusion criteria: pre-menopausal; aged >30 years; at increased risk of tubo-ovarian cancer (mutation carriers or on the basis of a strong family history); completed their family (for surgical arms). EXCLUSION CRITERIA: post-menopausal; previous bilateral salpingectomy or bilateral oophorectomy; pregnancy; previous tubal/ovarian/peritoneal malignancy; <12 months after cancer treatment; clinical suspicion of tubal/ovarian cancer at baseline. PRIMARY ENDPOINT: Sexual function measured by validated questionnaires. SAMPLE SIZE: 1000 (333 per arm). ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: It is estimated recruitment will be completed by 2023 and results published by 2027. TRIAL REGISTRATION NUMBER: ISRCTN registry: 25 173 360 (https://doi.org/10.1186/ISRCTN25173360).
Subject(s)
Neoplasms, Cystic, Mucinous, and Serous/prevention & control , Ovarian Neoplasms/prevention & control , Ovariectomy/methods , BRCA1 Protein , BRCA2 Protein , Female , Humans , Multicenter Studies as Topic , Neoplasms, Cystic, Mucinous, and Serous/genetics , Ovarian Neoplasms/genetics , Ovariectomy/adverse effects , Premenopause , Prospective StudiesABSTRACT
Advances in preoperative diagnostics as well as in surgical techniques for the treatment of endometriosis, especially for deep endometriosis, call for a classification system, that includes all aspects of the disease such as peritoneal endometriosis, ovarian endometriosis, deep endometriosis, and secondary adhesions. The widely accepted revised American Society for Reproductive Medicine classification (rASRM) has certain limitations because of its incomplete description of deep endometriosis. In contrast, the Enzian classification, which has been implemented in the last decade, has proved to be the most suitable tool for staging deep endometriosis, but does not include peritoneal or ovarian disease or adhesions. To overcome these limitations, a comprehensive classification system for complete mapping of endometriosis, including anatomical location, size of the lesions, adhesions and degree of involvement of the adjacent organs, that can be used with both diagnostic and surgical methods, has been created through a consensus process and will be described in detail-the #Enzian classification.
Subject(s)
Consensus , Endometriosis/classification , Severity of Illness Index , Symptom Assessment/standards , Databases, Factual , Endometriosis/diagnosis , Endometriosis/pathology , Female , Humans , Societies, MedicalABSTRACT
BACKGROUND: Endometriosis is a common gynaecological disorder affecting 5-10% of women of reproductive age who often experience chronic pelvic pain and infertility. Definitive diagnosis is through laparoscopy, exposing patients to potentially serious complications, and is often delayed. Non-invasive biomarkers are urgently required to accelerate diagnosis and for triaging potential patients for surgery. METHODS: This retrospective case control biomarker discovery and validation study used quantitative 2D-difference gel electrophoresis and tandem mass tagging-liquid chromatography-tandem mass spectrometry for protein expression profiling of eutopic and ectopic endometrial tissue samples collected from 28 cases of endometriosis and 18 control patients undergoing surgery for investigation of chronic pelvic pain without endometriosis or prophylactic surgery. Samples were further sub-grouped by menstrual cycle phase. Selected differentially expressed candidate markers (LUM, CPM, TNC, TPM2 and PAEP) were verified by ELISA in a set of 87 serum samples collected from the same and additional women. Previously reported biomarkers (CA125, sICAM1, FST, VEGF, MCP1, MIF and IL1R2) were also validated and diagnostic performance of markers and combinations established. RESULTS: Cycle phase and endometriosis-associated proteomic changes were identified in eutopic tissue from over 1400 identified gene products, yielding potential biomarker candidates. Bioinformatics analysis revealed enrichment of adhesion/extracellular matrix proteins and progesterone signalling. The best single marker for discriminating endometriosis from controls remained CA125 (AUC = 0.63), with the best cross-validated multimarker models improving the AUC to 0.71-0.81, depending upon menstrual cycle phase and control group. CONCLUSIONS: We have identified menstrual cycle- and endometriosis-associated protein changes linked to various cellular processes that are potential biomarkers and that provide insight into the biology of endometriosis. Our data indicate that the markers tested, whilst not useful alone, have improved diagnostic accuracy when used in combination and demonstrate menstrual cycle specificity. Tissue heterogeneity and blood contamination is likely to have hindered biomarker discovery, whilst a small sample size precludes accurate determination of performance by cycle phase. Independent validation of these biomarker panels in a larger cohort is however warranted, and if successful, they may have clinical utility in triaging patients for surgery.
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STUDY OBJECTIVE: To review surgical outcomes and histopathological findings after laparoscopic myomectomy by a team at a university teaching hospital. DESIGN: This was a retrospective review of consecutive cases of laparoscopic myomectomy performed by members of our minimal access surgery team between January 2004 and December 2015 (Canadian Task Force classification II-3). SETTING: A university teaching hospital. PATIENTS: Women undergoing laparoscopic myomectomy. INTERVENTIONS: Laparoscopic myomectomy. MEASUREMENTS AND MAIN RESULTS: We collected women's demographic data, clinical histories, and surgical outcomes, including complication rates and the incidence of undiagnosed uterine malignancy. Five hundred fourteen women were booked for laparoscopic myomectomy during the study period. Five hundred twelve of 514 (99.6%; 95% confidence interval [CI], 99.05-100.00) procedures were successfully completed. Two cases were converted to open surgery: one because of suspected uterine malignancy and another because of bowel injury at initial entry. The median number of myomas removed at laparoscopy was 1 (range, 1-12; mode = 1). The median size of the largest myoma removed at each procedure was 70 mm (range, 10-200 mm) as assessed subjectively by the operating surgeon. The median blood loss was 73 mL (range, 5-3000 mL). The median length of stay in the hospital was 2 nights (range, 0-24 nights). Breach of the uterine cavity occurred in 50 of 514 (9.7%; 95% CI, 7.17-12.29) cases. Electromechanical morcellation was used in 496 of 514 (96.5%; 95% CI, 94.9-98.1) patients. Eighteen of 514 (3.5%; 95% CI, 1.91-5.09) women suffered significant complications including blood loss >1000 mL (n = 15), bowel injury (n = 1), bladder injury (n = 1), and small bowel obstruction secondary to port site hernia (n = 1). There were no cases of undiagnosed uterine malignancies after myoma morcellation. CONCLUSION: Laparoscopic myomectomy can be conducted with a low rate of major complications, and, in our experience, the chance of discovering occult malignancy is very low.
Subject(s)
Laparoscopy/statistics & numerical data , Leiomyoma/surgery , Uterine Myomectomy/statistics & numerical data , Uterine Neoplasms/surgery , Adolescent , Adult , Aged , Female , Humans , Laparoscopy/adverse effects , Laparoscopy/methods , Middle Aged , Minimally Invasive Surgical Procedures , Retrospective Studies , Uterine Myomectomy/adverse effects , Uterine Myomectomy/methods , Young AdultSubject(s)
Cilia , Fallopian Tubes , Epithelium , Female , Gene Expression , Germ Cells , Humans , TestosteroneSubject(s)
Hysteroscopy , Uterus , Cohort Studies , Female , Humans , Pregnancy , Prospective StudiesABSTRACT
STUDY QUESTION: Is temporary ovarian suspension following laparoscopic surgery for severe pelvic endometriosis an effective method for reducing the prevalence of postoperative ovarian adhesions? SUMMARY ANSWER: Temporary ovarian suspension for 36-48 h following laparoscopic treatment of severe endometriosis does not result in a significant reduction of postoperative ovarian adhesions. WHAT IS KNOWN ALREADY: Pelvic adhesions often develop following laparoscopic surgery for severe pelvic endometriosis. Adhesions can cause chronic pelvic pain and fertility problems compromising the success of treatment. Small observational studies suggested that temporary postoperative ovarian suspension to the abdominal wall may significantly reduce the prevalence of postoperative ovarian adhesions. STUDY DESIGN, SIZE, DURATION: This was a prospective within group comparison double-blind RCT. We recruited premenopausal women with severe pelvic endometriosis who required extensive laparoscopic surgery with preservation of the uterus and ovaries. Severity of the disease and eligibility for inclusion were determined at surgery. A total of 55 women were randomized to unilateral ovarian suspension for 36-48 h, 52 of which were included in the final analysis. Both ovaries were routinely suspended to the anterior abdominal wall during surgery. At the end of the operation, each woman was randomized to having only one ovary suspended postoperatively. The suture suspending the contralateral ovary was cut and a new transabdominal suture was inserted to act as a placebo. Both sutures were removed 36-48 h after surgery prior to discharge. Three months after surgery, all women attended for a detailed transvaginal ultrasound scan to assess ovarian mobility. Both the women and the ultrasound operators were blinded as to the side of postoperative ovarian suspension. The primary outcome was the prevalence of ovarian adhesions as described on ultrasound examination. Secondary outcomes were the severity of adhesions and the presence and intensity of postoperative pain. PARTICIPANTS/MATERIALS, SETTING, METHODS: All 55 participants had severe pelvic endometriosis confirmed at laparoscopy. As each participant had only one of their ovaries suspended at the end of surgery, they acted as their own control. MAIN RESULTS AND THE ROLE OF CHANCE: The median interval between ovarian suspension and postoperative scan was 99 days (interquartile range 68-114). There was no significant difference (P = 0.23) in the prevalence of postoperative ovarian adhesions between the suspended (20/52) and unsuspended (27/52) side (38.5 versus 51.9%) [odds ratio 0.56 (95% confidence interval 0.22-1.35)]. LIMITATIONS, REASONS FOR CAUTION: Ovaries were suspended postoperatively for 36-48 h. Longer suspension could result in lower prevalence of postoperative adhesions. WIDER IMPLICATIONS OF THE FINDINGS: The value of temporary ovarian suspension in women having surgery for mild-to-moderate endometriosis should be investigated further. The potential benefits of other adhesion prevention strategies, such as surgical barrier agents, in women undergoing surgical treatment for severe pelvic endometriosis should also be explored. STUDY FUNDING/COMPETING INTERESTS: E.S. received honoraria from Ethicon for provision of training to healthcare professionals and consultancy fees from Bayer. W.H. was supported by the research fund provided by the Gynaecology Ultrasound Centre, London UK. A.C. is on the advisory board for surgical innovations for which he receives an annual honorarium. A.C. also received support for courses and education from Storz and Johnson and Johnson and support for clinical nursing from Covidien and Lotus. The other authors declared no competing interests. TRIAL REGISTRATION NUMBER: Current Controlled Trials ISRCTN24242218.
Subject(s)
Endometriosis/surgery , Gynecologic Surgical Procedures/methods , Ovary/surgery , Tissue Adhesions/prevention & control , Double-Blind Method , Female , Humans , Laparoscopy , Ovary/diagnostic imaging , Tissue Adhesions/epidemiology , UltrasonographyABSTRACT
This study designed a double-blind, randomized controlled trial to assess whether adequate visibility can be achieved with lower uterine filling pressures using normal saline for diagnostic outpatient hysteroscopy and whether patient discomfort can be reduced. A total of 234 patients were randomized to 40 mmHg (77 patients), 70 mmHg (78 patients) or 100 mmHg (79 patients) of uterine filling pressures. The primary outcome measure was the proportion of procedures where adequate visibility was achieved during diagnostic outpatient hysteroscopy. The secondary outcome was the level of pain experienced by the patient as assessed using a visual analogue scale. There was adequate visibility in 87.0% of cases in 40 mmHg group, 94.9% in 70 mmHg group and 97.5% in 100 mmHg group. Visibility was lower with 40 mmHg compared with 70 and 100 mmHg (P < 0.05). The mean pain score in each group was not significantly different. In conclusion, this study showed that there was a higher trend towards inadequate visibility with lower filling pressures. Pressures of 70 and 100 mmHg may be equivalent to each other but not to a pressure level of 40 mmHg. Pain scores do not differ significantly with the pressure options used.
Subject(s)
Hysteroscopy/methods , Insufflation/methods , Pressure , Uterus/anatomy & histology , Adult , Ambulatory Care/methods , Double-Blind Method , Female , Humans , Hysteroscopy/adverse effects , Insufflation/standards , Pain Measurement , Sodium ChlorideABSTRACT
Due to increasing life expectancy, women spend a significant part of their lives in menopause. Women with a history of endometriosis are more likely to become menopausal at an early age due to bilateral oophorectomy or repeated ovarian surgery. In addition, some medical therapies used for endometriosis, such as gonadotropin releasing hormone agonists or progestins reduce bone mineral density. Furthermore, women with endometriosis have a higher background risk of cardiovascular disorders and hypercholesterolemia. Hence, it is important to recommend the use of hormone replacement therapy (HRT) to these women when they become menopausal, at least until the age of natural menopause. Although based on limited data, there is a possibility of reactivation of symptoms of endometriosis or its lesions, and a theoretical possibility of malignant transformation, although this remains unproven. Therefore, women should be advised in the light of this information before starting HRT after the age of natural menopause and are asked to seek help if they experience symptoms that may indicate these changes. Estrogen only HRT should be avoided and combined HRT preparations should be recommended, even after a hysterectomy.
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IMPORTANCE: Adenomyosis can reduce the chance of clinical pregnancy in women undergoing assisted conception. Treatment with prolonged gonadotrophin-releasing hormone analogue (GnRHa) downregulation prior to IVF/ICSI has been postulated to improve pregnancy outcomes. OBJECTIVE: We aimed to evaluate the effectiveness and safety of prolonged GnRHa treatment (minimum one month) versus no pre-treatment in women with adenomyosis undergoing IVF/ICSI using a systematic review and meta-analysis. DATA SOURCES: We searched electronic databases: Embase (OVID), MEDLINE® (OVID), APA PsycInfo (OVID), Maternity & Infant Care Database (MIDIRS (OVID), HMIC Health Management Information Consortium (OVID) and ClinicalTrials.gov from inception until 27th of March 2023. STUDY SELECTION AND SYNTHESIS: We included studies that reported on women with adenomyosis receiving GnRHa to down-regulate the hypothalamic-pituitary-ovarian axis for one to six months before IVF/ICSI. We pooled data using the Haensel-Mantel method and reported using Odds Ratio (OR) with 95 % confidence intervals (CI). We assessed the quality of included studies using the Newcastle-Ottowa Scale and confidence in evidence using the GRADE criteria. Bias analysis was conducted via the Cochrane recommended tool (RevMan Web, Academic License). MAIN OUTCOMES AND RESULTS: We screened 365 citations and eight retrospective studies were included in the meta-analysis (n = 2422 women). The median age was 34 years [IQR 31.95-35.05], median BMI 21.30 kg/m2 [IQR 21.05-23.55] and median duration of GnRHa downregulation was 2.5 months [Range 1-4; IQR 1.37-3]. Women with adenomyosis receiving prolonged GnRHa treatment had a higher implantation rate 1/OR 1.69 [95 % CI 1.09, 2.56], I2 = 81 %, (P = 0.02) and clinical pregnancy rate 1/OR 1.42 [95 % CI 1.03, 2.0], I2 70 %, P = 0.03. There was no overall difference in live birth rate 1/OR 1.12 [95 % CI 0.70, 1.79], I2 = 78 %, p = 0.63), miscarriage rate 1/OR 0.92 [95 % CI 0.63, 1.28, P = 0.61, I2 0 % or mean number of oocytes retrieved (10 oocytes [IQR 8.95; 11.15] vs. 9.28 [IQR 8; 10.20], p = 0.22) between groups. CONCLUSIONS AND RELEVANCE: The benefit of prolonged GnRHa treatment in women with adenomyosis undergoing assisted conception treatment is uncertain based on existing retrospective studies. Implantation and clinical pregnancy rates were higher following prolonged downregulation in this population, though there was no statistically significant difference in live birth and miscarriage rates. Given the limited, low-quality existing data, there is a need for a well-designed, prospective randomised controlled trial to precisely evaluate the effectiveness of prolonged GnRHa treatment in this population.
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OBJECTIVES: To evaluate the clinical effectiveness of long acting progestogens compared with the combined oral contraceptive pill in preventing recurrence of endometriosis related pain. DESIGN: The PRE-EMPT (preventing recurrence of endometriosis) pragmatic, parallel group, open label, randomised controlled trial. SETTING: 34 UK hospitals. PARTICIPANTS: 405 women of reproductive age undergoing conservative surgery for endometriosis. INTERVENTIONS: Participants were randomised in a 1:1 ratio using a secure internet facility to a long acting progestogen (depot medroxyprogesterone acetate or levonorgestrel releasing intrauterine system) or the combined oral contraceptive pill. MAIN OUTCOME MEASURES: The primary outcome was pain measured three years after randomisation using the pain domain of the Endometriosis Health Profile 30 (EHP-30) questionnaire. Secondary outcomes (evaluated at six months, one, two, and three years) included the four core and six modular domains of the EHP-30, and treatment failure (further therapeutic surgery or second line medical treatment). RESULTS: 405 women were randomised to receive a long acting progestogen (n=205) or combined oral contraceptive pill (n=200). At three years, there was no difference in pain scores between the groups (adjusted mean difference -0.8, 95% confidence interval -5.7 to 4.2, P=0.76), which had improved by around 40% in both groups compared with preoperative values (an average of 24 and 23 points for long acting progestogen and combined oral contraceptive pill groups, respectively). Most of the other domains of the EHP-30 also showed improvement at all time points compared with preoperative scores, without evidence of any differences between groups. Women randomised to a long acting progestogen underwent fewer surgical procedures or second line treatments compared with those randomised to the combined oral contraceptive pill group (73 v 97; hazard ratio 0.67, 95% confidence interval 0.44 to 1.00). CONCLUSIONS: Postoperative prescription of a long acting progestogen or the combined oral contraceptive pill results in similar levels of improvement in endometriosis related pain at three years, with both groups showing around a 40% improvement compared with preoperative levels. While women can be reassured that both options are effective, the reduced risk of repeat surgery for endometriosis and hysterectomy might make long acting reversible progestogens preferable for some. TRIAL REGISTRATION: ISRCTN registry ISRCTN97865475.
Subject(s)
Contraceptives, Oral, Combined , Endometriosis , Levonorgestrel , Medroxyprogesterone Acetate , Adult , Female , Humans , Young Adult , Contraceptives, Oral, Combined/therapeutic use , Contraceptives, Oral, Combined/administration & dosage , Endometriosis/surgery , Endometriosis/drug therapy , Endometriosis/complications , Intrauterine Devices, Medicated , Levonorgestrel/administration & dosage , Levonorgestrel/therapeutic use , Medroxyprogesterone Acetate/administration & dosage , Medroxyprogesterone Acetate/therapeutic use , Pain Measurement , Pelvic Pain/drug therapy , Pelvic Pain/prevention & control , Pelvic Pain/etiology , Progestins/administration & dosage , Progestins/therapeutic use , Secondary Prevention/methods , Treatment OutcomeABSTRACT
BACKGROUND: Endometriosis is a common condition which causes pain and reduced fertility. Treatment can be difficult, especially for severe disease, and an accurate preoperative assessment would greatly help in the managment of these patients. The objective of this study is to assess the accuracy of pre-operative transvaginal ultrasound scanning (TVS) in identifying the specific features of pelvic endometriosis and pelvic adhesions in comparison with laparoscopy. METHODS: Consecutive women with clinically suspected or proven pelvic endometriosis, who were booked for laparoscopy, were invited to join the study. They all underwent a systematic transvaginal ultrasound examination in order to identify discrete endometriotic lesions and pelvic adhesions. The accuracy of ultrasound diagnosis was determined by comparing pre-operative ultrasound to laparoscopy findings. RESULTS: 198 women who underwent preoperative TVS and laparoscopy were included in the final analysis. At laparoscopy 126/198 (63.6%) women had evidence of pelvic endometriosis. 28/126 (22.8%) of them had endometriosis in a single location whilst the remaining 98/126 (77.2%) had endometriosis in two or more locations. Positive likelihood ratios (LR+) for the ultrasound diagnosis of ovarian endometriomas, moderate or severe ovarian adhesions, pouch of Douglas adhesions, and bladder deeply infiltrating endometriosis (DIE), recto-sigmoid colon DIE, rectovaginal DIE, uterovesical fold DIE and uterosacral ligament DIE were >10, whilst for pelvic side wall DIE and any ovarian adhesions the + LH was 8.421 and 9.81 respectively.The negative likelihood ratio (LR-) was: <0.1 for bladder DIE; 0.1-0.2 for ovarian endometriomas, moderate or severe ovarian adhesions, and pouch of Douglas adhesions; 0.5-1 for rectovaginal, uterovesical fold, pelvic side wall and uterosacral ligament DIE. The accuracy of TVS for the diagnosis of both total number of endometriotic lesions and DIE lesions significantly improved with increasing total number of lesions. CONCLUSIONS: Our study has shown that the TVS diagnosis of endometriotic lesion is very specific and false positive results are rare. Negative findings are less reliable and women with significant symptoms may still benefit from further investigation even if TVS findings are normal. The accuracy of ultrasound diagnosis is significantly affected by the location and number of endometriotic lesions.
Subject(s)
Endometriosis/diagnostic imaging , Pelvis/diagnostic imaging , Adnexa Uteri/diagnostic imaging , Adnexa Uteri/surgery , Adnexal Diseases/diagnostic imaging , Adnexal Diseases/surgery , Adult , Douglas' Pouch/diagnostic imaging , Douglas' Pouch/surgery , Endometriosis/surgery , Female , Humans , Laparoscopy , Likelihood Functions , Middle Aged , Pelvis/surgery , Peritoneal Diseases/diagnostic imaging , Peritoneal Diseases/surgery , Prospective Studies , Sensitivity and Specificity , Tissue Adhesions/diagnostic imaging , Tissue Adhesions/surgery , Ultrasonography , Young AdultABSTRACT
Management of advanced endometriosis frequently requires a multidisciplinary team approach and international guidelines suggest treatment in centres of expertise. Due to variability of published outcome data, prospective data collection and standardisation of reporting systems have been suggested to improve our understanding of surgical outcomes. The British Society for Gynaecological Endoscopy (BSGE) Endometriosis Centres were established to manage rectovaginal endometriosis, to collect treatment and outcome data, and to provide these data to patients, clinicians and healthcare commissioners. The BSGE Endometriosis Centres Project works on the principle of voluntary participation. Centres that would like to be recognised or accredited as a BSGE Endometriosis Centre need to fulfil a number of basic requirements including working in appropriate multidisciplinary clinical teams, auditing their outcome and having sufficient workload to maintain their surgical skills. The project has already had an impact on where the patients with advanced endometriosis are treated in the United Kingdom. Patients and healthcare professionals are becoming aware of their presence and more patients with the condition are being referred to these centres. It is also expected that the accredited centre status would be required for funding by healthcare commissioners for this type endometriosis.