Minimal Endometriosis Research Articles

P-450 Prediction models for estimating treatment independent conception in unexplained infertility – a systematic review

Abstract Study question What are the best prediction models which can estimate the chance of natural conception in couples with unexplained infertility? Summary answer The best quality clinical prediction models were those generated by Hunault et al (2004), Van Eekelen et al (2017) and McLernon et al. (2019). What is known already Although couples with unexplained infertility have a chance of natural conception, a formal estimate of prognosis is not part of routine clinical decision making in most settings. In the UK, NICE recommends IVF after two years of unexplained infertility in all couples, regardless of their individual chances of conception without treatment. This approach risks overtreatment for some whilst delaying access to IVF for others. Since the last systematic review on this topic 10 years ago, several models which aim to predict natural conception in infertile couples have been published, but few are in routine clinical use Study design, size, duration We searched OVID MEDLINE, OVID EMBASE, and OVID PsycINFO systematically for primary articles published between 1978 and 2022, reporting on the development and/or validation of models in predicting spontaneous conception, pregnancy, or live birth. No language or any other restrictions were applied. Participants/materials, setting, methods We included couples with unexplained infertility / those with no major barriers to natural conception. Women who underwent any form of fertility treatment immediately after the initial diagnostic work up were excluded. The methodological quality of the included papers was assessed using criteria within the CHARMS checklist. Risk of bias was evaluated using the PROBAST tool while discrimination and calibration results, which rate the performance of the prediction model, were also reported. Main results and the role of chance Eighteen publications reported on 23 prediction models with natural conception, pregnancy, ongoing pregnancy and live birth as outcomes. Of 11 studies involving model development, internal and external validation were reported in 4 and 2 publications respectively . Two studies published extended versions of the same model (Hunault et al, 2004) while 3 studies focussed on independent validation of existing models. The methodological rigour of the models has improved over time, as demonstrated by accuracy measures including discrimination and calibration. Three models (Hunault et al, 2004, Van Eekelen et al, 2017, and McLernon et al, 2019) had low risk of bias. The static Hunault model can be used to determine the chance of conception at a single point in time – usually at the conclusion of the initial fertility work up, whereas the Van Eekelen and McLernon models are dynamic models that can estimate chances of conception at different time points. The discriminatory ability of models ranged between 0.59-0.64 in the internal validation and external validation studies. The calibration slope for the Hunault’s static model was 0.6 to 1.0 and for the dynamic models it ranged from 0.62 to 1.01 for Van Eekelen’s model and 0.65to 1.06 for McLernon’s model. Limitations, reasons for caution The quality of prediction models which predated the CHARMS checklist and PROBAST tool could not be adequately assessed. The population with most models went beyond unexplained infertility and included other couples with a chance of natural conception e.g. mild male infertility and minimal endometriosis. Wider implications of the findings Of the 3 models which are of high quality, the Hunault model can only be used once but the Van Eekelen and McLernon models have the potential to be used more flexibly, following further external validation in different settings and larger populations. Trial registration number not applicable

Diagnosis and treatment of early-stage endometriosis by Transvaginal Hydro laparoscopy.

Transvaginal Hydro Laparoscopy (THL) is known as a minimal invasive procedure allowing endoscopic exploration of the female pelvis. To evaluate the possibilities of the THL as a tool for early diagnosis and treatment of minimal endometriosis. A retrospective study of a consecutive series of 2288 patients referred for fertility problems to a tertiary centre for reproductive medicine was undertaken. Mean duration of infertility was 23.6 months (SD ±11-48), mean age of patients was 31.25 (SD± 3.8y). With normal findings at clinical and ultrasound examination patients underwent, as part of their fertility exploration, a THL. Evaluation of feasibility, identified pathology and pregnancy rate. Endometriosis was diagnosed in 365 patients (16%); the localisation was higher on the left side (n=237) than on the right side (n=169). Small endometriomas, with diameters between 0.5 and 2 cm, were present in 24.3% (right side in 31, left side 48 and bilateral 10). These early lesions were characterised by the presence of active endometrial like cells and a pronounced neo-angiogenesis. Destruction of the endometriotic lesions with bipolar energy resulted in an in vivo pregnancy rate (spontaneous/IUI) of 43.8% (CPR after 8 months: spontaneous 57.7%; IUI/AID 29.7%). THL allowed in a minimally invasive way an accurate diagnosis of the early stages of peritoneal and ovarian endometriosis with the possibility of offering treatment with minimal damage. This is the largest series reporting the usefulness of THL for the diagnosis and treatment of peritoneal and ovarian endometriosis in patients without obviously visible preoperative pelvic pathology.

Judicial medical management of mild and minimal endometriosis in selected patients of infertility is non-inferior to surgical treatment – a retrospective analysis

Background: Endometriosis is an enigmatic disease that affects approximately 10% of women of reproductive age and almost 50% of women with endometriosis experience infertility. These women experience symptoms of dysmenorrhea, premenstrual pain, dyspareunia, and infertility, but many affected women are asymptomatic. Objective: To analyse the clinical pregnancy rate after treating mild and minimal endometriosis causing infertility with dienogest (2 mg) or by surgical intervention. Materials and Methods: 146 subfertile women with mild and minimal endometriosis, enrolled over a period of 36 months (January 2017 to December 2019) at Calcutta Fertility Mission have been included in the present study. They were grouped in A and B and treated with dienogest (2mg) for 90days or by laparoscopic ablation, and ovulation induction. Clinical pregnancy rates were analysed. Results: In our study, 18.52% of patients with early stage asymptomatic endometriosis, had conceived spontaneously after treatment with dienogest for 3 months, and 37.04%, 44.44% had conceived after treating them with dienogest followed by letrozole and letrozole and GnRH, for subsequent 3-6months, respectively. 13.64% , 36.36% , 50% of women had conceived spontaneously after laparoscopic ablation, after treating them with ablative procedure and letrozole and with letrozole and GnRH in the next 3-6 cycles, respectively. Spontaneous pregnancy and pregnancy following letrozole only or letrozole and GnRH in Group A and B were also not statistically significant (p - 0.961, p - 0.698). Conclusion: Clinical pregnancy in infertile women with early endometriosis treated with dienogest is non-inferior to others treated with laparoscopic ablation and minimal adhesiolysis.

Transcriptomic analysis of cumulus cells shows altered pathways in patients with minimal and mild endometriosis

Endometriosis is a chronic inflammatory disorder that is highly associated with infertility. This association seems to be related to oocyte impairment, mainly in the initial stages of endometriosis (minimal and mild), where no distortions or adhesions are present. Nonetheless, invasive oocyte analyses are not routinely feasible; thus, indirect assessment of oocyte quality is highly desirable, and, in this context, cumulus cells (CCs) may be more suitable targets of analysis. CCs are crucial in oocyte development and could be used as an index of oocyte quality. Therefore, this prospective case–control study aimed to shed light on the infertility mechanisms of endometriosis I/II by analyzing the CCs’ mRNA transcription profile (women with endometriosis I/II, n = 9) compared to controls (women with tubal abnormalities or male factor, n = 9). The transcriptomic analyses of CCs from patients with minimal and mild endometriosis revealed 26 differentially expressed genes compared to the controls. The enrichment analysis evidenced some altered molecular processes: Cytokine-cytokine receptor interactions, Chemokine signaling, TNF signaling, NOD-like receptor signaling, NF-kappa B signaling, and inflammatory response. With the exception of CXCL12, all enriched genes were downregulated in CCs from patients with endometriosis. These findings provide a significant achievement in the field of reproductive biology, directing future studies to discover biomarkers of oocyte quality in endometriosis.

380 Unusual oocyte morphology: A rare case report

Introduction and aims: of the study: We present an unusual case of rare oocyte morphology during IVF cycle. Since there are no literature about these findings, it could become a great opportunity for the further investigations. Methods: A 31-year-old female has presented in the reproductive medicine center for 3-year primary infertility of the couple. She was diagnosed with minimal endometriosis and had only left tubal patent. The female hormonal status was normal, she had no history of any other surgeries and diseases.

Migraine Is More Prevalent in Advanced-Stage Endometriosis, Especially When Co-Occuring with Adenomoysis.

BackgroundEmerging data suggest a significant association between migraine and endometriosis, however the relationship between migraine and endometriosis severity or adenomyosis is unclear. Our objectives were to explore the relationship between migraine and endometriosis, according to the endometriosis severity and co-exist with adenomyosis or not.MethodsThis case-control study of 167 endometriosis patients verified by surgery and 190 patients for other benign gynecological conditions (control subjects) was performed from September 2017 and January 2021. There is 49 adenomyosis detected by transvaginal ultrasound or histologic diagnosis among the endometriosis patients. Besides, we also included 41 adenomyosis but without endometriosis patients as a subgroup. All women completed a self-administered headache questionnaire and diagnosed as migraine according to the International Headache Society classification. The severity and stage of endometriosis was evaluated with revised American Society of Reproductive Medicine (rASRM) score. We used logistic regression to estimate the association between the presence of migraine and endometriosis severity while accounting for important confounders, including age, body mass index (BMI) and family history of migraine. We also estimate the risk of adenomyosis alone and adenomyosis with co-occurring endometriosis in migrainous women.ResultsMigraine was significantly more prevalent in endometriosis patients compared with controls (29.9% vs. 12.1%, p<0.05), but the prevalence was similar between isolated adenomyosis patients and controls (9.8% vs.12.1%, p>0.05). For all endometriosis and control participants, migraineurs were 4.6-times (OR=4.6; 95% CI 2.7-8.1) more likely to have severe endometriosis. However, the strength of the association decreased when the analysis examined in moderate stage (OR=3.6, 95% CI 2.1-6.2). The risk of mild and minimal endometriosis was not significant (OR=1.9, 95%CI 0.9-4.0; OR=1.6, 95% CI 0.8-3.4; respectively). When we divided the endometriosis patients according to whether co-occurring with adenomyosis. We found in migrainous women, the risk of endometriosis co-exist with adenomyosis increased, with nearly fivefold greater odds compared with control (OR=5.4;95% CI 3.0-9.5), and nearly two times higher than the risk of endometriosis without co-exist adenomyosis patients (OR=2.2; 95% CI 1.2-3.8).ConclusionOur study supports the strong association between migraine and endometriosis. We found migrainous women suffer more frequently from sever endometriosis, especially endometriosis with co-occurring adenomyosis. It is advisable to heighten suspicion for patients who presenting with either these conditions in order to optimize therapy.

Symptoms based endometriosis prediction using machine learning

Endometriosis a painful disorder that stripes the uterus both inside and outside. Endometriosis can be diagnosed by the medical practitioners with the help of traditional scanning procedures. Laparoscopic surgery is the authentic method for identifying the advanced stages of endometriosis. The statistical approach is a state-of-art method for identifying the various stages of endometriosis using laparoscopic images. The paper focuses on a well-known statistical method known as chi-square and correlation coefficients are implemented for identifying the symptoms that are correlated with various stages of endometriosis. Chi-square analysis performs the association between symptoms and stages of endometriosis. With these analysis, an algorithm was proposed known as endometriosis prediction factor algorithm (EPF). The EPF algorithm predicts the presence of endometriosis if the derived value is greater than 1. From the chi-square analysis, it is identified that mild endometriosis is influenced 34% by menstrual flow, minimal endometriosis is influenced 40% by dysmenorrhea, where moderate endometriosis is influenced 31% by tenderness and deep infiltrating endometriosis is influenced 22% by adnexal mass.

O-024 Endoscopic management of the unexplained infertility, what does it add?

Abstract text Endoscopic management of the unexplained infertility, what does it add? Stephan Gordts stephan.gordts@lifeexpertcentre.be Unexplained infertility “strictu sensu” is not a diagnosis, but a description of a status where no causal factor is identified in a couple trying to conceive for at least one year. The more parameters are assessed, the more likely to identify an etiology, the less likely becomes “unexplained” infertility. Limiting the fertility exploration to indirect visualization techniques like ultrasound, HSG or HycoSy involves the risk of missing existing pathologies. Uterus Uterine volumetric abnormalities can be detected by indirect techniques, but information is lacking on the visualization of the endometrium in case of chronic endometritis and the presence of endometrial defects and hypervascularization areas as seen in patients with adenomyosis. Tubo-ovarian Even with the increased accuracy of indirect visualization techniques, lesions of minimal endometriosis and tubo-ovarian adhesions are not detected (Table). Tubal normality constitutes not only normal tubal patency but also normal tubal function. The importance of subtle tubal lesions is underestimated. Hydatid of Morgagni are detected in 38.1% in patients with infertility versus only in 16,7% in fertile women (Gupta et al. JMIG 2017).Removal of these lesions resulted in a spontaneous pregnancy rate of 58.7% versus 20.6 in the non-treated group (Rasheed et al. EJOG Repr. 2011). Endometriosis In a series of 107 patients with unexplained infertility and 3 failed IVF cycles (Agni Pantou et al. J. Clin. Med. 2019)laparoscopy revealed the presence of endometriosis in 57.97%, peri-adnexal adhesions in 23.3% and was normal in 18.69%. Also, in a group of patients with 3 failed IVF cycles and unexplained infertility (Xiaoming Yu et al.Medicine 2019) laparoscopy showed endometriosis in 57.7%, tubal abnormalities in 31.1% and adhesions in 33.3%. Laparoscopic correction of these pathologies did not only result in a spontaneous pregnancy rate of 35% but resulted also in a higher pregnancy rate after IVF compared to the non-treated control group. Unexplained infertility hides frequently undiagnosed endometriosis. Endometrial BCL6 levels, a proto-oncogene where overexpression is associated with increased cellular proliferation and progesterone resistance, are increased in patients with endometriosis. In case of elevated BCL6 in patients with unexplained infertility, laparoscopy confirmed the presence of endometriosis in 93.8% (Evans-Hoeker et al. 2016). Abnormal BCL6 expression in a population with unexplained infertility reduced the chance of having a successful IVF treatment in 74% of the population (Almquist et al. Fertil Steril 2017). Transvaginal Hydro Laparoscopy Direct endoscopic visualization remains important but due to the invasiveness, diagnostic standard laparoscopy is frequently postponed or omitted in the exploration of the infertile patient. The technique of transvaginal hydro-laparoscopy allows in a minimal invasive way the inspection of the pelvis. In a consecutive series of 2288 patients without obvious pelvic pathology, findings were normal in 49.3%, endometriosis was diagnosed in 15.9% and tubal pathology in 14.5% of the patients (Gordts et al. FVV 2021). The rate of failed access was 1% and the complication rate 0.74%. Causing a minimal ovarian trauma, treatment of these early endometriotic lesions resulted in a spontaneous pregnancy rate of 73.2%. Conclusion The inappropriate use of “unexplained infertility” by omitting the diagnostic endoscopy in the exploration of the infertile patient, can hide undiagnosed and treatable pathology, jeopardizing possibilities for patients for a spontaneous conception and can be responsible for reduced pregnancy rates after IVF.

Isolation of Uterosacral Ligament (USL): A Safe and Effective Way for Laparoscopic Usl Hysteropexy / Colpopexy

Study Objective Because of the potential complications from artificialmesh, native tissue repair has regained its popularity during pelvic floor reconstruction surgery. Uterosacral ligament (USL) is the most important structures for level I support. However, the attenuated or broken USL in pelvic organ prolapse (POP) patients makes it difficult to get enough strong tissue for durable pelvic support, which result in the high recurrence rate after USL suspension for uterus or vagina cuff. Besides, the close anatomical relationship between USL and other important retroperitoneal structures (ureter, vessels, nerves) and rectum may sometimes limit the accessibility and suture bite during USL colpopexy/hysteropexy. In this video, we will demonstrate the important anatomical structures near the USL, and the technique to isolate it, that will make USL suspension safe and effective. Design Video clips from different patients were collected and edited. Setting single hospital, single surgeon. Patients or Participants Video clips from young patient with minimal endometriosis as normal control (demonstrate transperitoneal view), video clips from patients undergoing nerve-sparing radical hysterectomy as teaching model for detailed retroperitoneal structures, and video clips from patients undergoing USL hysteropexy were collected and edited. Interventions Ureter was identified transperitoneally first. Peritoneal window was developed between ureter and USL, entering the Okabayashi pararectal space. All the retroperitoneal structures (including ureter, uterine artery and vein, hypogastric nerve and pelvic plexus) were lateralized. Perirectal space and rectovaginal space were opened, dissecting the rectum away from the USL. Measurements and Main Results After USL isolation, USL suspension can be performed with maximal durability (big bite) and safety (minimal risk of ureter kinking, nerve injury, or rectum injury). Conclusion Isolation of uterosacral ligament (USL) is a safe and effective way for laparoscopic USL hysteropexy / colpopexy. Because of the potential complications from artificialmesh, native tissue repair has regained its popularity during pelvic floor reconstruction surgery. Uterosacral ligament (USL) is the most important structures for level I support. However, the attenuated or broken USL in pelvic organ prolapse (POP) patients makes it difficult to get enough strong tissue for durable pelvic support, which result in the high recurrence rate after USL suspension for uterus or vagina cuff. Besides, the close anatomical relationship between USL and other important retroperitoneal structures (ureter, vessels, nerves) and rectum may sometimes limit the accessibility and suture bite during USL colpopexy/hysteropexy. In this video, we will demonstrate the important anatomical structures near the USL, and the technique to isolate it, that will make USL suspension safe and effective. Video clips from different patients were collected and edited. single hospital, single surgeon. Video clips from young patient with minimal endometriosis as normal control (demonstrate transperitoneal view), video clips from patients undergoing nerve-sparing radical hysterectomy as teaching model for detailed retroperitoneal structures, and video clips from patients undergoing USL hysteropexy were collected and edited. Ureter was identified transperitoneally first. Peritoneal window was developed between ureter and USL, entering the Okabayashi pararectal space. All the retroperitoneal structures (including ureter, uterine artery and vein, hypogastric nerve and pelvic plexus) were lateralized. Perirectal space and rectovaginal space were opened, dissecting the rectum away from the USL. After USL isolation, USL suspension can be performed with maximal durability (big bite) and safety (minimal risk of ureter kinking, nerve injury, or rectum injury). Isolation of uterosacral ligament (USL) is a safe and effective way for laparoscopic USL hysteropexy / colpopexy.

Endometriotic rectosigmoid stricture- a rare clinical entity

Endometriosis is defined as the presence of endometrial mucosa implanted in locations other than the uterine cavity. Endometriosis is usually a disease involving women of reproductive age. A probable estimate is that 5–10% of women in their reproductive age have endometriosis. When they do occur, women experience mostly dysmenorrhea, heavy or irregular periods, pelvic pain or dyspareunia. The most common sites for endometriosis are the ovaries (60%), uterosacral ligament (60%), posterior cul-de-sac (28%), broad ligament (15%), bladder (15%) and sigmoid colon (7%). Colonic endometriosis is a rare sequelae. It usually presents vaguely with nonspecific abdominal pain, dyspareunia, tenesmus, rectal bleeding or painful defecation. Laparoscopy is considered the best diagnostic modality for endometriosis with a sensitivity of 97% and specificity of 77%. Although there are some rare cases of large bowel obstruction due to endometriosis in pre-menopausal women, it is extremely rare in the postmenopausal group. Our report highlights such a case, mimicking a malignant rectosigmoid stricture leading to a large bowel obstruction with minimal extracolonic endometriosis involvement. Conclusion: This case report shows that colonic endometriosis, although rare, can be significantly infiltrative and lead to complications such as a large bowel obstruction. Very rarely, isolated colonic involvement without pelvic endometriosis can mimic malignant obstruction as in this patient. Diagnosing this condition can be challenging and usually requires histological confirmation.

Multicentre retrospective study to assess diagnostic accuracy of ultrasound for superficial endometriosis-Are we any closer?

To establish whether the ultrasound findings of minimal endometriosis are confirmed at laparoscopy and that a correlation can be established as to the anatomical sites in this mild form of the disease. Patients with pain and suspicion of endometriosis had an ultrasound scan by a sonologist with expertise in endometriosis as part of their pre-operative workup. The clinical histories of 53 patients who had laparoscopy to investigate pelvic pain were reviewed. Ultrasounds were performed between 2012 and 2015 by a single sonologist with expertise in endometriosis assessments. The ultrasound findings were divided into subgroups as follows - presence of uterosacral ligament thickness, thickened pericolic fat, ovarian mobility and focal tenderness. These were compared with operative findings of those patients with superficial endometriosis. Evidence Level 3 - observational studies with controls and health services research that includes adjustment for likely confounding factors. Seventy-nine percent (42/53) of the patients had laparoscopic findings consistent with their ultrasound findings (95% CI 68-90%, P<0.0001). Of the subgroups that we reviewed, uterosacral thickening (P<0.05) and thickened pericolic fat (P<0.05) were the most associated with superficial endometriosis at the time of laparoscopy. Markers on ultrasound that reliably demonstrated inflammation (thickened uterosacral ligaments and thickened pericolic fat) were shown to be significantly associated with the disease.

Endometrium metabolomic profiling reveals potential biomarkers for diagnosis of endometriosis at minimal-mild stages

Sensitivity and specificity of non-invasive diagnostic methods for endometriosis, especially at early stage, is not optimal. Clinical diagnostic indicator of cancer antigen 125 (CA125) performs poorly in diagnosing minimal endometriosis with a sensitivity of 24%. Therefore, it is urgent to explore novel diagnostic biomarkers. We evaluated metabolomic profile variation of eutopic endometrium between minimal-mild endometriosis patients and healthy women by ultra high performance liquid chromatography coupled with electrospray ionization high-resolution mass spectrometry (UHPLC-ESI-HRMS). Our study comprised 29 patients with laparoscopically confirmed endometriosis at stage I-II and 37 infertile women who underwent diagnostic laparoscopy combined with hysteroscopy from January 2014 to January 2015. Eutopic endometrium was collected by pipelle endometrial biopsy. The metabolites were quantified by UHPLC-ESI-HRMS. The best combination of biomarkers was then selected by performing step-wise logistic regression analysis with backward elimination. 12 metabolites were identified as endometriosis-associated biomarkers. The eutopic endometrium metabolomic profile of endometriosis patients was characterized by significant increase in concentration of hypoxanthine, L-arginine, L-tyrosine, leucine, lysine, inosine, omega-3 arachidonic acid, guanosine, xanthosine, lysophosphatidylethanolamine and asparagine. In contrast, concentration of uric acid was decreased. Metabolites were filtered by step-wise logistic regression with backward elimination and a model containing uric acid, hypoxanthine, and lysophosphatidylethanolamine were constructed. Receiver-operating characteristic (ROC) analysis confirmed the prognostic value of these parameters in diagnosing minimal/mild endometriosis with a sensitivity of 66.7%, a specificity of 90.0%. Metabolomics analysis of eutopic endometrium in endometriosis was effectively characterized by UHPLC-ESI-HRMS based metabolomics. Our study supports the importance of purine and amino acids metabolites in the pathophysiology of endometriosis and provides the potential biomarkers for semi-invasive diagnose of endometriosis at early stage.

MiR-194-3p Represses the Progesterone Receptor and Decidualization in Eutopic Endometrium From Women With Endometriosis.

Progesterone resistance in the eutopic endometrium (EuE) is suggested to be a critical factor for decreased endometrial receptivity and implantation failure in reproductive-aged women with endometriosis. Altered expression of miRNAs has been reported to play an important role in the pathophysiology of endometriosis-associated infertility. However, the underlying mechanisms of aberrant progesterone receptor (PR) and deficient decidualization regulated by miRNAs in endometriosis have not been thoroughly elucidated. The goal of this study was to explore the regulation and roles of miR-194-3p in aberrant PR expression and impaired decidualization in endometrial stromal cells (ESCs) from the EuE of women with mild or minimal endometriosis. Using a series of studies, we observed decreased PR mRNA expression and an increasing PR-A/PR-B mRNA ratio trend in the midsecretory phase of the EuE of women with minimal or mild endometriosis (n = 19) compared with controls (n = 14); the increased expression of miR-194-3p in the endometriosis group was consistent with previous microarray analysis. We also found that PR protein levels were inhibited by the transfection of ESCs with an miR-194-3p mimic and upregulated by miR-194-3p inhibition. As predicted by the bioinformatic analysis, the 3'-untranslated region luciferase assay indicated the direct regulation of PR expression by miR-194-3p. Furthermore, miR-194-3p overexpression inhibited the in vitro decidualization of ESCs via both cellular morphological changes and prolactin levels. Therefore, our study demonstrated that miR-194-3p contributes to progesterone resistance in endometriosis, which hinders fertility by repressing the levels of PR and decidualization in the EuE. Thus, miR-194-3p regulation is a future therapeutic strategy for endometriosis.

Endometrium metabolomic profiling reveals potential biomarkers for diagnosis of endometriosis at minimal-mild stages

BackgroundThe sensitivity and specificity of non-invasive diagnostic methods for endometriosis, especially at early stages, are not optimal. The clinical diagnostic indicator cancer antigen 125 (CA125) performs poorly in the diagnosis of minimal endometriosis, with a sensitivity of 24%. Therefore, it is urgent to explore novel diagnostic biomarkers. We evaluated the metabolomic profile variation of the eutopic endometrium between minimal-mild endometriosis patients and healthy women by ultra-high-performance liquid chromatography coupled with electrospray ionization high-resolution mass spectrometry (UHPLC-ESI-HRMS).MethodsOur study comprised 29 patients with laparoscopically confirmed endometriosis at stages I-II and 37 infertile women who underwent diagnostic laparoscopy combined with hysteroscopy from January 2014 to January 2015. Eutopic endometrium samples were collected by pipelle endometrial biopsy. The metabolites were quantified by UHPLC-ESI-HRMS. The best combination of biomarkers was then selected by performing step-wise logistic regression analysis with backward elimination.ResultsTwelve metabolites were identified as endometriosis-associated biomarkers. The eutopic endometrium metabolomic profile of the endometriosis patients was characterized by a significant increase in the concentration of hypoxanthine, L-arginine, L-tyrosine, leucine, lysine, inosine, omega-3 arachidonic acid, guanosine, xanthosine, lysophosphatidylethanolamine and asparagine. In contrast, the concentration of uric acid was decreased. Metabolites were filtered by step-wise logistic regression with backward elimination, and a model containing uric acid, hypoxanthine, and lysophosphatidylethanolamine was constructed. Receiver-operating characteristic (ROC) analysis confirmed the prognostic value of these parameters for the diagnosis of minimal/mild endometriosis with a sensitivity of 66.7% and a specificity of 90.0%.ConclusionsMetabolomics analysis of the eutopic endometrium in endometriosis was effectively characterized by UHPLC-ESI-HRMS-based metabolomics. Our study supports the importance of purine and amino acid metabolites in the pathophysiology of endometriosis and provides potential biomarkers for semi-invasive diagnosis of early-stage endometriosis.

Prognostic factors in intrauterine insemination cycles.

ObjectiveThis study aimed to evaluate the clinical pregnancy rate of intrauterine insemination cycles in relation to patient age, cause of infertility, ovulation induction method, number of mature follicles and sperm with progressive motility.MethodsThis retrospective observational study included 237 intrauterine insemination cycles performed from 2011 to 2015 at the Assisted Reproduction Service of the Hospital das Clínicas of the Ribeirão Preto Medical School, University of São Paulo. Student's t-test was used to compare quantitative variables and the chi-square test was used to compare qualitative variables.ResultsPatient age was inversely and significantly correlated with pregnancy rates (p=0.001) (Pregnant women = 32.56±5.64 years, non-pregnant women = 36.64±5.03 years). Cause of infertility, ovulation induction method, number of mature follicles and sperm with progressive motility were not associated with pregnancy rates. The overall clinical pregnancy rate was 7.59%. In the subgroup of patients (n=102 cycles) considered ideal for intrauterine insemination (age ≤35 years, unexplained infertility, ovarian factor infertility or minimal endometriosis, and a partner with sperm count ≥2.5×106 retrieved on the day of insemination) the pregnancy rate was 12.74%.ConclusionIn the studied group, female patient age was the only variable significantly correlated with intrauterine insemination success rates.

Comments on the ESHRE recommendations for the treatment of minimal endometriosis in infertile women

According to ESHRE recommendations for women with stage I/II endometriosis, if a decision is made to proceed to laparoscopy then operative laparoscopy (excision or ablation of the endometriotic lesions) should be performed rather than only diagnostic laparoscopy, to increase ongoing pregnancy rates. Also, for infertile women with stage I/II endometriosis doctors may consider complete surgical removal of endometriosis to improve live birth rate prior to assisted reproductive treatment. This last recommendation is not well established. Does laparoscopic treatment of minimal endometriosis increase the fertility of women with minimal endometriosis? Should we perform surgery in all cases of minimal endometriosis to improve reproductive outcomes prior to assisted reproductive treatment? The aim of this article is to present evidence on these two questions and comment on the ESHRE recommendations. Evidence is quite robust that laparoscopic destruction of minimal to mild endometriosis and associated adhesions enhances fecundity. On the other hand, to date no clear benefit has been demonstrated of performing laparoscopy for minimal endometriosis in women undergoing IVF/intracytoplasmic sperm injection, therefore it is not recommended in these cases. Further studies are needed to assess the mechanisms of endometriosis-associated infertility and how it may be overcome in cases of minimal and mild endometriosis.

Management of a high-risk pregnanacy with a severe form of bladder infiltrating endometriosis. Case report and literature review

Endometriosis is a gynecological estrogen-dependent disease, characterized by the presence of active endometrial tissue, represented by glandular epithelial and stromal cells, outside the uterine cavity. There have been described three types of endometriosis: peritoneal superficial endometriosis, ovarian endometriomas, and deep infiltrating endometriosis (DIE). DIE is deffined from a histologically perspective as a lesion that extends more than 5 mm into the peritoneal space or which affects the wall of the pelvic organs. Endometriosis of the bladder is considered to be a form of deeply infiltrating endometriosis. The relation with infertility involves multiple and complex mechanisms. It is estimated that over half of the patients affected by this condition are subfertile. Many women with either minimal, mild or severe endometriosis experience difficulties in conceiving or maintaining a pregnancy. We report the case of a women diagnosed with a severe form of infiltrating endometriosis, with endometrioma in the bladder, who obtained a pregnancy and delivered in the 39 week of gestation by caesarean section and had a good evolution.

The Impact of laparoscopic surgery of peritoneal endometriosis and endometrioma on the outcome of ICSI cycles

ABSTRACTOur objective was to assess the role of laparoscopic removal of ovarian endometriomas and ablation of peritoneal endometriosis on the outcome of intracytoplasmic sperm injection (ICSI) - Embryo Transfer cycles by comparing with the results of patients with untreated endometriomas and tubal factor without underlying endometriosis confirmed by laparoscopy. For this purpose, between 2002 and 2015, outcomes of 257 ICSI cycles of 150 patients, including 91 cycles of 48 patients in minimal endometriosis, 57 cycles of 25 patients in endometrioma removal, 65 cycles of 53 patients in non-operated endometrioma, and 44 cycles of 24 patients in tubal factor groups were retrospectively analyzed. Basal ovarian reserve was significantly lower, mean starting and total gonadotropin consumption was significantly higher, and mean serum E2 on the day of hCG injection, number of dominant follicles, number of retrieved total, and MII oocytes were all significantly lower in the endometrioma cystectomy group. Fertilization and embryo cleavage rates were also significantly the lowest in the endometrioma cystectomy group, whereas clinical pregnancy and live birth rates were comparable among all groups. The number of transferred embryos and duration of infertility were the most significant predictors of clinical pregnancy and live birth. Basal antral follicle count was also significant in predicting live birth.

Management of endometriosis‐related pelvic pain

Key content The variable signs and symptoms of endometriosis contribute to significant diagnostic delay. Empirical hormonal treatment of endometriosis‐related pain with cycle suppression may be considered without a definitive diagnosis of endometriosis. When considering laparoscopy to diagnose and treat endometriosis, a balance must be found between the need to avoid the very long diagnostic delays currently experienced and the likelihood of treatment benefits, set against the cost and risk of laparoscopy. Treatment for endometriosis‐related pain symptoms includes a range of medical and surgical options with varying levels of evidence. Minimally invasive surgery should be performed by a surgeon trained to undertake surgical treatment for mild to moderate disease, thereby avoiding the need for repeat laparoscopy in the absence of severe disease, i.e. a ‘see and treat’ policy. Women with deep infiltrating endometriosis should be referred to an accredited endometriosis centre, such as the British Society for Gynaecological Endoscopy (BSGE) in the UK. Learning objectives To understand the diagnostic difficulties surrounding endometriosis diagnosis and management. To identify the supporting evidence for treating endometriosis‐related pain. Ethical issues When should laparoscopy for women with minimal endometriosis symptoms be performed? Should radical surgery always be performed in women in whom deep infiltrating endometriosis is found?

SF-36 preoperative interest of predicting improvement of quality of life after laparoscopic management of minimal endometriosis

The purpose of the studyTo study preoperative thresholds of the SF-36 components above which we can predict a high risk of failure in order to improve the quality of life after surgery for patients with minimal endometriosis. Material and methodsDesign: prospective and multicenter observational study between February 2004 and 2011. Patients: 167 patients with operated minimal endometriosis. Setting: for the Physical Component Summary (PCS) or the Mental Component Summary (MCS) subscales of the SF-36 questionnaire, an improvement defined by an increase of 5 points. Intervention: evaluation by the SF-36 questionnaire the week before and one year after surgery. Measurement and main resultsSuccess of surgery measured by an improvement in both components. We found significantly different initial variables between patients with improvement and those without: initial MCS score (P=0.0003), initial PCS score (P<0.0001) and dyspareunia (P=0.004). Multivariate analysis revealed only two significant variables. Initial MCS higher than 40 (OR=4.6) and initial PCS higher than 50 (OR=10.6) are risk factors for failure of improvement after surgery. ConclusionSurgery is seldom a good treatment for improving QOL in minimal endometriosis. We set two thresholds for SF-36, 50 for PCS and 40 for MCS: above there is a very high risk of failure (86% of failure in our population). Under, the risk of failure remains high (54.3%). Canadian task force classification of study designEvidence obtained from well-designed cohort or case-control studies, preferably from more than one center or research group.