Intraoperative transvaginal ultrasound to standardize bowel endometriosis shaving.

OBJECTIVE: To study the use of intraoperative transvaginal ultrasound after bowel endometriosis shaving. DESIGN: Stepwise demonstration with a narrated video footage of preoperative and intraoperative ultrasound to evaluate the extent of an endometriotic rectal nodule. SETTING: Lausanne University Hospital and Geneva University Hospital. PATIENT(S): Two women with symptomatic endometriosis rectal lesion. INTERVENTION(S): Preoperative transvaginal ultrasound was performed to measure the rectal nodule. After completing bowel shaving, the surgeon conducted both clinical and sonographic evaluations of the rectal wall. Clinically, this was performed using laparoscopic grasping forceps and sonographically with a transvaginal probe after filling the pelvis with saline solution. MAIN OUTCOME MEASURE(S): Assessment of the rectal wall for residual disease after bowel shaving and evaluation of the necessity for additional bowel resection. RESULT(S): After sonographic evaluation of the rectal wall, the surgeon decided in both patients to perform a discoid resection because of the presence of a residual rectal disease despite thorough bowel shaving. CONCLUSION(S): Intraoperative transvaginal ultrasound after bowel endometriosis shaving is a promising technique that is safe, reproducible, and efficient. It aids surgeons in accurately assessing the extent of excision of deep rectosigmoid infiltrating endometriosis and determining the necessity of additional bowel resection to reduce recurrence risk. Moreover, intraoperative ultrasound provides precise measurements of residual nodules, enabling differentiation between persistent, recurrent, or new lesions during follow-up.

Why do oestrogens matter: systematic review and meta-analysis assessing GnRH antagonists, considering add-back therapy, for endometriosis-associated pain.

Gonadotrophin-releasing hormone (GnRH) antagonists have been demonstrated to reduce endometriosis-associated pain. Because of the hypo-oestrogenic state they induce, however, higher dosages of GnRH antagonists are not recommended for used long term. This unwanted effect may be eliminated by so-called add-back therapy (ABT). This review was conducted to assess the safety and efficacy of GnRH antagonists, with or without add-back hormonal replacement therapy. Out of the 345 studies selected through the initial search, seven randomized controlled trials were included, comparing different oral GnRH antagonists at varying dosages, from a minimum of 50 mg to a maximum of 200 mg once or twice daily. Women treated with the lowest dose of GnRH antagonists had significantly greater mean pain score reductions from baseline throughout treatment compared with those treated with placebo (odds ratio [OR] -13.12, 95% CI -17.35 to -8.89 and OR -3.08, 95% CI -4.39 to -1.76 for dysmenorrhoea and non-menstrual pelvic pain, respectively). Compatible with the dose-response effect, a positive correlation was found between response rates and adverse event rates. While GnRH antagonists offer an advantage in terms of pain reduction for endometriosis, the more recent literature suggests using GnRH antagonists with ABT, which, while mitigating the hypo-oestrogenic effects of GnRH antagonists, maintain their efficacy, while allowing their long-term use.

Vitrification of human blastocysts for couples undergoing assisted reproduction: an updated review.

Over the past 40 years there has been a worldwide critical change in the field of assisted reproduction technology (ART), leading to the increased application of single blastocyst transfer, which is extremely important to avoid the risks of multiple pregnancy and associated complications for both mother and babies. Indeed, advancements in ART over the last few decades have been obtained thanks to several improvements, including ovarian stimulation, embryo culture conditions and, of course, progress in cryopreservation methods, especially with the application of vitrification. The ability to cryopreserve human embryos has improved significantly with vitrification compared to the initially adopted slow-freezing procedures. Since the introduction of vitrification, it has become the gold standard method to effectively cryopreserve human blastocysts. However, some new protocols are now being explored, such as the short warming procedure and even shorter exposure to the equilibration solution before vitrification, which seem to provide optimal results. Therefore, the main aim of the current narrative review, will be to illustrate the benefit of vitrification as an effective method to cryopreserve the human blastocyst and to illustrate new protocols and variations which in future may increase the performance of vitrification protocols.

Women's lived experience of endometriosis-related fertility issues.

OBJECTIVE: The aim of the present study is to conduct a qualitative investigation to provide a deeper understanding of women's views about endometriosis, fertility and their perception of reproductive options. METHODS: Semi-structured interviews were conducted by two female psychiatrists, specialized in gynecology and obstetrical consultation-liaison psychiatry, trained in qualitative procedures, with experience in qualitative studies and in psychological support of women attending infertility consultations. No prior relationship with respondents was established before data collection. Interviews were tape-recorded and transcribed. Interviews lasted 45-75 minutes. The transcripts were then analysed using thematic content analysis. RESULTS: Twenty-nine women were contacted. Twelve agreed to an interview at the hospital's infertility clinic. Eleven women with diverse sociodemographic characteristics were included. The key findings of thematic content analysis can be grouped into four topics: (1) Diagnostic announcement and initial delay; (2) Negative perceptions of initial care: pre-diagnosis phase; (3) Struggle with endometriosis and its treatment; (4) Issues related to health problems, fertility and reproductive options. CONCLUSION: Our analysis of the interviews corroborates the distressing impact of the trivialization of pain and the uncertainty of or the long quest for diagnosis. The findings also stress various associated issues, from the diagnostic delay to the low success rates of fertility treatments. This qualitative analysis contributes to better understand the accumulation of negative emotions within the illness trajectory and the poor dyadic adjustment within the couple.

Review of human oocyte cryopreservation in ART programs: Current challenges and opportunities.

Oocyte cryopreservation has notably increased in recent times, to become an essential part of clinical infertility treatment. Since the 1980s, many improvements in oocyte cryopreservation (OC) have been adopted, including the great advance with the application of vitrification. The commonly used vitrification protocol applies different cryoprotectants (Ethylene glycol and/or DMSO and/or PROH and sucrose and/or Trehalose) and two different steps: firstly, exposure in equilibration solution for 5-15 min, followed by a vitrification solution for 60-90 s at room temperature. The warming method includes a first step for 1 min at 37 °C and 3 subsequent steps at room temperature to remove the cryoprotectant for a total of 9-12 min. In addition, biosafety is a critical aspect to mention, and it is related to devices used during the vitrification, mainly in terms of whether the biological vitrified material comes in direct contact with liquid nitrogen (open vitrification) or not (closed vitrification), where LN2 may contain potentially contaminating viruses or pathogens. Furthermore, during early development major waves of epigenetic reprogramming take place. Recent literature suggests that epigenetic and transcriptomic profiles are sensitive to the stress induced by vitrification, including osmotic shock, temperature, rapid changes of pH and toxicity of cryoprotectants. It is, therefore, important to better understand the potential perturbations of epigenetic modifications that may be associated with the globally used vitrification methods. Therefore, we here discuss the benefits and efficiency of human oocyte vitrification; we also review the evidence surrounding oocyte cryopreservation-related epigenetic modifications and potential epigenetic dysregulations, together with long-term consequences for offspring health.

Human Male Genital Tract Microbiota.

The human body is vastly colonised by microorganisms, whose impact on health is increasingly recognised. The human genital tract hosts a diverse microbiota, and an increasing number of studies on the male genital tract microbiota suggest that bacteria have a role in male infertility and pathological conditions, such as prostate cancer. Nevertheless, this research field remains understudied. The study of bacterial colonisation of the male genital tract is highly impacted by the invasive nature of sampling and the low abundance of the microbiota. Therefore, most studies relied on the analysis of semen microbiota to describe the colonisation of the male genital tract (MGT), which was thought to be sterile. The aim of this narrative review is to present the results of studies that used next-generation sequencing (NGS) to profile the bacterial colonisation patterns of different male genital tract anatomical compartments and critically highlight their findings and their weaknesses. Moreover, we identified potential research axes that may be crucial for our understanding of the male genital tract microbiota and its impact on male infertility and pathophysiology.

Case report Iatrogenic parasitic leiomyoma: the surgeon's invisible hand.

Uterine leiomyoma is the most common benign tumour of the uterus in women of reproductive age. When removed surgically, a mini-invasive procedure is preferentially used (laparoscopic or robotic) and the extraction of the specimen can be managed by power morcellation. In this consecutive case-series, we present three cases of parasitic leiomyoma that appeared following previous surgical management of leiomyoma using the technique of laparoscopic myomectomy with uncontained power morcellation. The time frame in between the initial surgery and the diagnosis of the parasitic leiomyoma was 5.7 years. All three patients were diagnosed with endometriosis: 2 cases prior to the initial surgery and 1 case after the initial surgery. One hypothesis could be that, due to pelvic inflammation, endometriosis is a risk factor for iatrogenic parasitic leiomyoma development in case of uncontained morcellation of leiomyoma during myomectomy.

Combining Sclerotherapy with CO2 Laser Ablation for the Laparoscopic Management of Large Endometrioma: Advantages and Pitfalls.

STUDY OBJECTIVE: To demonstrate the feasibility of management of large endometrioma laparoscopically. DESIGN: Stepwise demonstration with narrated video footage of the laparoscopic 2-step procedure starting with alcohol sclerotherapy of the large endometrioma followed by CO2 laser ablation and 6-month follow-up. SETTING: The debate surrounding the best approach for the management of large endometriomas has been ongoing. Cystectomy especially when treating large endometriomas has been shown to decrease ovarian reserve proportionally to the endometrioma's size.2,4 This is why 2-step approaches have been considered to preserve the ovarian reserve.1,3 We present the case of a 22-year-old nulliparous woman who has primary severe dysmenorrhea resistant to medical treatment. Magnetic resonance imaging shows uterine adenomyosis and a 10 cm large endometrioma of the left ovary and no signs of deep infiltrative endometriosis. She has a desire for pregnancy in the distant future. INTERVENTION: The first step is the laparoscopic ethanol sclerotherapy. After emptying and rinsing the endometrioma's cavity through a 5 mm suction cannula, it is then filled with ethanol through a 14 French Foley catheter to avoid any overflow.5,6 After a time exposure of 10 minutes, the ethanol is withdrawn and the cavity rinsed (Figure 2). The second step of the surgery is performed 12 weeks later (Figure 3). Using CO2 laser, the untreated portion of the inner wall of the remaining endometrioma is vaporized along with remaining superficial endometriosis lesions (Figure 1). CONCLUSION: Laparoscopy sclerotherapy combined to CO2 laser ablation is a feasible technique for the management of a large endometrioma. Further research is still required to evaluate the benefit of a 2-step surgery approach over standard cystectomy and to understand the long-term effects of ethanol-induced ovarian fibrosis.

A systematic review and meta-analysis of digital application use in clinical research in pain medicine.

Importance: Pain is a silent global epidemic impacting approximately a third of the population. Pharmacological and surgical interventions are primary modes of treatment. Cognitive/behavioural management approaches and interventional pain management strategies are approaches that have been used to assist with the management of chronic pain. Accurate data collection and reporting treatment outcomes are vital to addressing the challenges faced. In light of this, we conducted a systematic evaluation of the current digital application landscape within chronic pain medicine. Objective: The primary objective was to consider the prevalence of digital application usage for chronic pain management. These digital applications included mobile apps, web apps, and chatbots. Data sources: We conducted searches on PubMed and ScienceDirect for studies that were published between 1st January 1990 and 1st January 2021. Study selection: Our review included studies that involved the use of digital applications for chronic pain conditions. There were no restrictions on the country in which the study was conducted. Only studies that were peer-reviewed and published in English were included. Four reviewers had assessed the eligibility of each study against the inclusion/exclusion criteria. Out of the 84 studies that were initially identified, 38 were included in the systematic review. Data extraction and synthesis: The AMSTAR guidelines were used to assess data quality. This assessment was carried out by 3 reviewers. The data were pooled using a random-effects model. Main outcomes and measures: Before data collection began, the primary outcome was to report on the standard mean difference of digital application usage for chronic pain conditions. We also recorded the type of digital application studied (e.g., mobile application, web application) and, where the data was available, the standard mean difference of pain intensity, pain inferences, depression, anxiety, and fatigue. Results: 38 studies were included in the systematic review and 22 studies were included in the meta-analysis. The digital interventions were categorised to web and mobile applications and chatbots, with pooled standard mean difference of 0.22 (95% CI: -0.16, 0.60), 0.30 (95% CI: 0.00, 0.60) and -0.02 (95% CI: -0.47, 0.42) respectively. Pooled standard mean differences for symptomatologies of pain intensity, depression, and anxiety symptoms were 0.25 (95% CI: 0.03, 0.46), 0.30 (95% CI: 0.17, 0.43) and 0.37 (95% CI: 0.05, 0.69), respectively. A sub-group analysis was conducted on pain intensity due to the heterogeneity of the results (I 2 = 82.86%; p = 0.02). After stratifying by country, we found that digital applications were more likely to be effective in some countries (e.g., United States, China) than others (e.g., Ireland, Norway). Conclusions and relevance: The use of digital applications in improving pain-related symptoms shows promise, but further clinical studies would be needed to develop more robust applications. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42021228343.

Is intracrinology of endometriosis relevant in clinical practice? A systematic review on estrogen metabolism.

Endometriosis is a chronic, multifactorial, estrogen-dependent disease. The abnormal endocrine microenvironment of endometriosis lesions is considered a main feature and multiple enzymatic pathways leading to local increased synthesis of estrogens have been identified. However, the relevance of intracrinology in clinical practice is still lacking. Medline, Embase, Scopus database were systematically searched for studies reporting on local estrogens metabolism of endometriotic lesions. The main enzymatic pathways involved in the intracrinology of endometriosis such as aromatase (CYP19A1), 17ß-hydroxysteroid dehydrogenase (HSD17B) type 1, type 2 and type 5, steroid sulfatase (STS), estrogen sulfotransferase (SULT1E1) were assessed with a critical perspective on their role in disease endocrine phenotyping, drug resistance and as therapeutic targets. Overall, studies heterogeneity and missing clinical data affect the interpretation of the clinical role of these enzymes. Although the use of some drugs such as aromatase inhibitors has been proposed in clinical practice for two decades, their potential clinical value is still under investigation as well as their modality of administration. A closer look at new, more realistic drug targets is provided and discussed. Altered expression of these key enzymes in the lesions have far reaching implication in the development of new drugs aimed at decreasing local estrogenic activity with a minimal effect on gonadal function; however, given the complexity of the evaluation of the expression of the enzymes, multiple aspects still remains to be clarified. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022311329, identifier CRD42022311329.

Surgical Training for Bowel Endometriosis: A New Wet-lab Model.

STUDY OBJECTIVE: To demonstrate a new wet-lab model for training in conservative bowel endometriosis surgery (shaving and discoid resection). DESIGN: Video demonstration. MATERIALS AND METHODS: (1) Modeling deep infiltrating endometriosis using cryopreserved porcine rectum. (2) Conservative resection (shaving and discoid resection) using cold scissor and carbon dioxide laser (free beam and fiber). (3) Discoid resection. RESULTS: In this video, we present a new training model for improving the surgical management of bowel endometriosis. After dissection of the serosa and muscular layers, a modified biological glue is injected into the porcine rectum to accurately simulate an infiltrating bowel endometriosis lesion. Once dried, the simulated lesion can be resected using conventional laparoscopic instruments (cold scissors) or using more advanced techniques such as carbon dioxide laser, free beam and fiber (Storz and Lumenis). In case of bowel perforation during resection, this model enables realistic suturing. CONCLUSION: This new and highly realistic model allows the next generation of endometriosis surgeons to acquire adequate training to make bowel surgery safer and more effective.

[Avenues of reflection for endometriosis research in France]. / Des pistes de réflexion pour la recherche sur l'endométriose en France.

Endometriosis is a chronic disease in which lesions resembling endometrial tissue are found outside the uterus, mainly in the pelvis or abdomen. It may affect 10% of women of childbearing age. It is the cause of a significant alteration in quality of life and a major cost to the health system. Few research teams are working on this subject, and its pathophysiology is still poorly understood. This article proposes avenues of reflection for research on endometriosis in France, notably based on the mobilization of related scientific communities (involved in cancer, development, epigenetics, and neurosciences research studies).

Title: Des pistes de réflexion pour la recherche sur l'endométriose en France. Abstract: L'endométriose est une maladie chronique dans laquelle des lésions ressemblant à du tissu endométrial se retrouvent hors de l'utérus, principalement dans la cavité abdomino-pelvienne. Cette maladie pourrait toucher 10 % des femmes en âge de procréer. Elle est à l'origine d'une importante altération de la qualité de vie et d'un coût majeur pour le système de santé. Peu d'équipes de recherche sont mobilisées sur ce sujet, et la physiopathologie de la maladie reste mal comprise. Nous proposons dans cet article des pistes de réflexion pour la recherche sur l'endométriose en France, fondées notamment sur la mobilisation de communautés scientifiques connexes (notamment celles impliquées dans la recherche sur le cancer, la biologie du développement, l'épigénétique, les neurosciences).

Fast-Track in Minimally Invasive Gynecology: A Randomized Trial Comparing Costs and Clinical Outcomes.

Study Objective: Evaluate the effects of a fast-track (FT) protocol on costs and post-operative recovery. Methods: One hundred and seventy women undergoing total laparoscopic hysterectomy for a benign indication were randomized in a FT protocol or a usual care protocol. A FT protocol included the combination of minimally invasive surgery, analgesia optimization, early oral refeeding and rapid mobilization of patients was compared to a usual care protocol. Primary outcome was costs. Secondary outcomes were length of stay, post-operative morbidity and patient satisfaction. Main Results: The mean total cost in the FT group was 13,070 ± 4,321 Euros (EUR) per patient, and that in the usual care group was 3.5% higher at 13,527 ± 3,925 EUR (p = 0.49). The FT group had lower inpatient surgical costs but higher total ambulatory costs during the first post-operative month. The mean hospital stay in the FT group was 52.7 ± 26.8 h, and that in the usual care group was 20% higher at 65.8 ± 33.7 h (p = 0.006). Morbidity during the first post-operative month was not significantly different between the two groups. On their day of discharge, the proportion of patients satisfied with pain management was similar in both groups [83% in FT and 78% in the usual care group (p = 0.57)]. Satisfaction with medical follow-up 1 month after surgery was also similar [91% in FT and 88% in the usual care group (p = 0.69)]. Conclusion: Implementation of a FT protocol in laparoscopic hysterectomy for benign indications has minimal non-significant effects on costs but significantly reduces hospital stay without increasing post-operative morbidity nor decreasing patient satisfaction. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04839263.

A systematic review and meta-analysis of the Endometriosis and Mental-Health Sequelae; The ELEMI Project.

BACKGROUND: It is important to evaluate sequalae for complex chronic health conditions such as endometriosis and mental health disorders. Endometriosis impacts 1 in 10 women. Mental health outcomes can be a primary determinant in many physical health conditions although this is an area not well researched particularly in women's health. This has been problematic for endometriosis patients in particular, who report mental health issues as well as other key comorbidities such as chronic pelvic pain and infertility. This could be partly due to the complexities associated with comprehensively exploring overlaps between physical and mental health disorders in the presence of multiple comorbidities and their potential mechanistic relationship. METHODS: In this evidence synthesis, a systematic methodology and mixed-methods approaches were used to synthesize both qualitative and quantitative data to examine the prevalence of the overlapping sequalae between endometriosis and psychiatric symptoms and disorders. As part of this, an evidence synthesis protocol was developed which included a systematic review protocol that was published on PROSPERO (CRD42020181495). The aim was to identify and evaluate mental health reported outcomes and prevalence of symptoms and psychiatric disorders associated with endometriosis. FINDINGS: A total of 34 papers were included in the systematic review and 15 were included in the meta-analysis. Anxiety and depression symptoms were the most commonly reported mental health outcomes while a pooled analysis also revealed high prevalence of chronic pelvic pain and dyspareunia. INTERPRETATION: It is evident that small-scale cross-sectional studies have been conducted in a variety of settings to determine mental health outcomes among endometriosis patients. Further research is required to comprehensively evaluate the mental health sequalae with endometriosis.

Pelvic MRI for Endometriosis: A Diagnostic Challenge for the Inexperienced Radiologist. How Much Experience Is Enough?

PURPOSE: The purpose of this study was to investigate the impact of radiologist experience on diagnostic performance of pelvic magnetic resonance imaging (MRI) for the evaluation of endometriomas and different localisations of deep pelvic endometriosis (DPE). MATERIALS AND METHODS: In this prospective study all pelvic MRI examinations performed for pelvic endometriosis from December 2016 to August 2017 were evaluated by readers with different experience levels; junior resident (0-6 weeks of experience in female imaging), senior resident (7-24 weeks), fellow (6-24 months), and expert (10 years) in female imaging for the presence of endometriomas and DPE. Their evaluations were compared with surgery confirmed with pathology. Diagnostic performances of readers with different levels of experience were studied by the means of receiving operating characteristic curves and areas under the curve (AUC) were compared with the ones of the expert reader. RESULTS: Of 174 patients evaluated, the standard of reference was available for 59, consisting the final population of the study. The AUC for endometriomas, DPE for the posterior and anterior pelvic compartment, for rectosigmoid DPE and for overall evaluation were 0.983, 0.921, 0.615, 0.862, and 0.914 for the expert reader, 0.966 (p = 0.178), 0.805 (p = 0.001), 0.605 (p = 0.91), 0.872 (p = 0.317), and 0.849 (p = 0.0009) for the fellow level, 0.877 (p = 0.002), 0.757 (p < 0.001), 0.585 (p = 0.761), 0.744 (p = 0.239), and 0.787 (p = < 0.001) for the senior resident level and 0.861 (p = 0.177), 0.649 (p < 0.001), 0.648 (p = 0.774), 0.862 (p = 1), and 0.721 (p < 0.001) for the junior resident level. CONCLUSIONS: According to our results, interpretation of pelvic MRI for DPE should be performed by specialists as; even the performance of radiologists with up to 2 years of experience in female imaging was statistically inferior to that of experts.

Oocyte vitrification offers more space for a tailored surgical management of endometriosis.

Oocyte vitrification is an attractive and efficient option in the long-term management of endometriosis patients. Which women would benefit from banked oocytes when pregnancy is attempted, and whether oocyte vitrification should be carried out before or after the surgical management of endometriosis, is still debated. On the basis of recent data, and in the absence of cost-effective modelling, a personalized strategy should assess crucial variables, such as type of surgery, effect on oocyte yield and the huge heterogeneity of the clinical scenarios possibly requiring surgery. Research into a more tailored approach to maximize the result of each available intervention, e.g. hormones, surgery, assisted reproductive technology or their combination to prevent infertility and reduce the actual burden of personal and societal cost of the disease, is recommended.

Estrogen receptor-α immunoreactivity predicts symptom severity and pain recurrence in deep endometriosis.

OBJECTIVE: To determine the relationship between steroid receptor expression and pain symptoms in endometriosis. DESIGN: Cross-sectional SETTING: University Hospital PATIENT(S): Women with endometriosis (N = 92). INTERVENTION(S): Tissue samples were obtained from patients with surgically diagnosed endometriosis. MAIN OUTCOME MEASURE(S): A tissue microarray (TMA) was generated from patients with endometriosis. Data were collected on the presence and severity of dysmenorrhea, deep dyspareunia, dyschezia, and nonmenstrual pain by use of a numerical rating scale (NRS) at the time of surgery and after 1 year. The intensity of receptor expression was evaluated through immunohistochemistry and measured according to an immunoreactive score (IRS). Clinical variables were correlated to IRS by multivariate logistic regression analysis. RESULTS: Estrogen receptor-α (ER-α), progesterone receptor (PR), androgen receptor (AR), and aromatase expression differed among study participants. ER-α expression was reduced by progestin therapy, whereas of expressions of PR, AR, and aromatase were unchanged. Higher ER-α expression increased the likelihood of moderate to severe dysmenorrhea and deep dyspareunia in women not receiving hormonal treatment. In women receiving progestin therapy, persistently higher ER-α expression was correlated with greater likelihood of deep dyspareunia, severe dyschezia, and endometriosis-associated pain persistence at 1 year. CONCLUSION(S): ER-α, PR, AR, and aromatase were all expressed in deep endometriosis. ER-α levels best correlated with severity of symptoms, which suggests that ER is a key driver of deep endometriosis. Progestin treatment was associated with a reduction of ER-α expression; however, failure of ER suppression by progestins was also a predictor of pain severity and recurrence at 1 year.