Outcomes of fertility preservation in women with endometriosis: comparison of progestin-primed ovarian stimulation versus antagonist protocols.

BACKGROUND: PPOS protocols, initially described for FP in women with cancer, have many advantages compared to antagonist protocols. PPOS protocols were not evaluated for women with endometriosis. The objective of the study was to describe fertility preservation outcomes in women with endometriosis and to compare an antagonist protocol with a Progestin-Primed Ovarian Stimulation (PPOS) protocol. METHOD: We conducted a prospective cohort study associated with a cost-effectiveness analysis in a tertiary-care university hospital. The measured outcomes included the numbers of retrieved and vitrified oocytes, and direct medical costs. In the whole population, unique and multiple linear regressions analysis were performed to search for a correlation between individual characteristics and the number of retrieved oocyte. RESULTS: We included 108 women with endometriosis who had a single stimulation cycle performed with either an antagonist or a PPOS protocol. Overall, 8.1 ± 6.6 oocytes were retrieved and 6.4 ± 5.6 oocytes vitrified per patient. In the multiple regression model, age (p = 0.001), prior ovarian surgery (p = 0.035), and anti-Mullerian hormone level (p = 0.001) were associated with the number of retrieved oocytes. Fifty-four women were stimulated with an antagonist protocol, and 54 with a PPOS protocol. A mean of 7.9 ± 7.4 oocytes were retrieved in the antagonist group and 8.2 ± 5.6 in the PPOS group (p = 0.78). A mean of 6.4 ± 6.4 oocytes were vitrified in the antagonist group and 6.4 ± 4.7 in the PPOS group (p = 1). In the cost-effectiveness analysis, the PPOS protocol was strongly dominant over the antagonist protocol. CONCLUSION: Fertility preservation procedures are feasible and effective for patients affected by endometriosis. Antagonist and PPOS protocols were associated with similar results but the medico-economic analysis was in favor of PPOS protocols.

Baseline severe constipation negatively impacts functional outcomes of surgery for deep endometriosis infiltrating the rectum: Results of the ENDORE randomized trial.

BACKGROUND: Predictive factors of functional outcomes after the surgery of rectal endometriosis are not well identified. Our recent randomized trial did not find significant differences between functional outcomes in patients managed by radical or conservative rectal surgery. OBJECTIVE: To identify preoperative factors which determine functional outcomes of surgery in patients with rectal endometriosis. STUDY DESIGN: We performed a cohort study on the population of a 2-arm randomised trial, from March 2011 to August 2013. Patients were enrolled in three French university hospitals and had either conservative surgery by shaving or disc excision, or radical rectal surgery by segmental resection. The primary endpoint was the proportion of patients experiencing one of the following symptoms: constipation, frequent bowel movements, anal incontinence, dysuria or bladder atony requiring self-catheterisation 24 months postoperatively. Secondary endpoints were the values of the Knowles-Eccersley-Scott-Symptom Questionnaire (KESS), the Gastrointestinal Quality of Life Index (GIQLI), the Wexner scale, the Urinary Symptom Profile (USP) and the Short Form 36 Health Survey (SF36). A logistic regression model based on backward selection was used to screen for baseline factors that could impact the primary endpoint. A generalized estimating equations model for repeated measures was used to assess whether a trend could be observed over the follow-up period as regards gastrointestinal and quality of life scores. RESULTS: 60 patients with deep endometriosis infiltrating the rectum were managed by conservative surgery (27 cases) and segmental colorectal resection (33 cases). The primary endpoint was recorded in 26 patients (48.1% for conservative surgery vs. 39.4% for radical surgery, OR = 0.70, 95% CI 0.22-2.21). There was a significant improvement in values of all gastrointestinal, quality of life and urinary scores after surgery. Comparing patients with KESS scores < 10 (reference) to those with scores between 10 and 17 (OR = 2.1, 95%CI 0.4-12.2), as well as those with scores >17 (OR = 11.1, 95%CI 2.2-20.5), revealed that the odds to record the primary endpoint are significantly higher in the latter group. Trend analyses suggest that the odds of an elevated KESS score are significantly higher at baseline than at 6 months, but significantly lower after 12 months. CONCLUSIONS: Patients with severe preoperative constipation are less likely to achieve normal bowel movements after surgery for rectal endometriosis, using either radical or conservative rectal procedures.

Conservative surgery versus colorectal resection in deep endometriosis infiltrating the rectum: a randomized trial.

STUDY QUESTION: Is there a difference in functional outcome between conservative versus radical rectal surgery in patients with large deep endometriosis infiltrating the rectum 2 years postoperatively? SUMMARY ANSWER: No evidence was found that functional outcomes differed when conservative surgery was compared to radical rectal surgery for deeply invasive endometriosis involving the bowel. WHAT IS KNOWN ALREADY: Adopting a conservative approach to the surgical management of deep endometriosis infiltrating the rectum, by employing shaving or disc excision, appears to yield improved digestive functional outcomes. However, previous comparative studies were not randomized, introducing a possible bias regarding the presumed superiority of conservative techniques due to the inclusion of patients with more severe deep endometriosis who underwent colorectal resection. STUDY DESIGN SIZE, DURATION: From March 2011 to August 2013, we performed a 2-arm randomized trial, enroling 60 patients with deep endometriosis infiltrating the rectum up to 15 cm from the anus, measuring more than 20 mm in length, involving at least the muscular layer in depth and up to 50% of rectal circumference. No women were lost to follow-up. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients were enroled in three French university hospitals and had either conservative surgery, by shaving or disc excision, or radical rectal surgery, by segmental resection. Randomization was performed preoperatively using sequentially numbered, opaque, sealed envelopes, and patients were informed of the results of randomization. The primary endpoint was the proportion of patients experiencing one of the following symptoms: constipation (1 stool/>5 consecutive days), frequent bowel movements (≥3 stools/day), defecation pain, anal incontinence, dysuria or bladder atony requiring self-catheterization 24 months postoperatively. Secondary endpoints were the values of the Visual Analog Scale (VAS), Knowles-Eccersley-Scott-Symptom Questionnaire (KESS), the Gastrointestinal Quality of Life Index (GIQLI), the Wexner scale, the Urinary Symptom Profile (USP) and the Short Form 36 Health Survey (SF36). MAIN RESULTS AND THE ROLE OF CHANCE: A total of 60 patients were enroled. Among the 27 patients in the conservative surgery arm, two were converted to segmental resection (7.4%). In each group, 13 presented with at least one functional problem at 24 months after surgery (48.1 versus 39.4%, OR = 0.70, 95% CI 0.22-2.21). The intention-to-treat comparison of the overall scores on KESS, GIQLI, Wexner, USP and SF36 did not reveal significant differences between the two arms. Segmental resection was associated with a significant risk of bowel stenosis. LIMITATIONS REASONS FOR CAUTION: The inclusion of only large infiltrations of the rectum does not allow the extrapolation of conclusions to small nodules of <20 mm in length. The presumption of a 40% difference favourable to conservative surgery in terms of postoperative functional outcomes resulted in a lack of power to demonstrate a difference for the primary endpoint. WIDER IMPLICATIONS OF THE FINDINGS: Conservative surgery is feasible in patients managed for large deep rectal endometriosis. The trial does not show a statistically significant superiority of conservative surgery for mid-term functional digestive and urinary outcomes in this specific population of women with large involvement of the rectum. There is a higher risk of rectal stenosis after segmental resection, requiring additional endoscopic or surgical procedures. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a grant from the clinical research programme for hospitals (PHRC) in France. The authors declare no competing interests related to this study. TRIAL REGISTRATION NUMBER: This study is registered with ClinicalTrials.gov, number NCT 01291576. TRIAL REGISTRATION DATE: 31 January 2011. DATE OF FIRST PATIENT'S ENROLMENT: 7 March 2011.

Impact of osteopathic manipulative therapy on quality of life of patients with deep infiltrating endometriosis with colorectal involvement: results of a pilot study.

OBJECTIVE: A prospective pilot study to evaluate the potential role of osteopathic manipulative therapy (OMT) on quality of life (QOL) of patients with Deep Infiltrating Endometriosis (DIE) and colorectal involvement. STUDY DESIGN: Twenty patients with DIE and colorectal infiltration completed the SF-36 QOL questionnaire before and after undergoing OMT. RESULTS: The median age (range) of the patients was 30.4 years (22-39). Thirty-five percent of the patients had undergone previous surgery for endometriosis and 70% were on medical treatment. Fifteen of the 20 patients (75%) completed the protocol. There was no difference in the epidemiological characteristics or in the pre-OMT Physical Component Summary (PCS) and Mental Component Summary (MCS) of the SF-36 questionnaire between patients who completed the protocol or not. After a mean period of 24 days (15-53), a significant improvement in PCS (p=0.03) and MCS (p=0.0009) compared to pre-OMT values was observed giving a success rate of 80% and 60% in intention-to-treat, respectively. CONCLUSION: Our results support that OMT can improve QOL of patients with DIE and colorectal involvement. Moreover, this pilot study can serve to determine power calculations for future randomized trials.

Contribution of Computed Tomography Enema and Magnetic Resonance Imaging to Diagnose Multifocal and Multicentric Bowel Lesions in Patients With Colorectal Endometriosis.

STUDY OBJECTIVE: To evaluate the diagnostic contribution of the computed tomography (CT) enema and magnetic resonance imaging (MRI) for multifocal (multiple lesions affecting the same segment) and multicentric (multiple lesions affecting several digestive segments) bowel endometriosis. DESIGN: Prospective cohort study (Canadian Task Force classification II-2). PATIENTS: Eighty-five patients. SETTING: Tenon University Hospital, Paris, France. INTERVENTION: All patients received a preoperative CT enema and underwent MRI interpreted by 2 radiologists. MEASUREMENTS AND MAIN RESULTS: Patients underwent colorectal resection for colorectal endometriosis from February 2009 to November 2012. Nineteen patients (22%) had multifocal lesions, and 11 patients (13%) had multicentric lesions. Six patients (7%) had both multifocal and multicentric lesions. The sensitivity, specificity, and positive and negative likelihood ratios (LRs) of MRI for the diagnosis of multifocal lesions were 0.58, 0.84, 3.55, and 0.5, respectively. The sensitivity, specificity, and positive and negative LRs of the CT enema for the diagnosis of multifocal lesions were 0.64, 0.86, 4.56, and 0.4, respectively. The sensitivity, specificity, and positive LR of MRI for the diagnosis of multicentric lesions were 1, 0.88, and 8.4, respectively. The sensitivity, specificity, and positive and negative LRs of MRI for the diagnosis of multicentric lesions were 0.46, 0.92, 5.6, and 0.59, respectively. No difference was observed between MRI and the CT enema for the diagnosis of multifocal and multicentric colorectal endometriosis. The interobserver agreement was good for MRI and the CT enema (κ = 0.45 and 0.45) for multifocality, and it was poor for both MRI and the CT enema (κ = 0.32 and 0.34) for multicentricity. CONCLUSIONS: Both MRI and the CT enema were able to diagnose multifocal and multicentric bowel endometriosis with similar accuracy.

External validation of the SF-36 quality-of-life questionnaire in Italian and Brazilian populations to select patients with colorectal endometriosis for surgery.

STUDY OBJECTIVE: To evaluate the external validity of the validated French model of the quality-of-life questionnaire (QOL) SF-36 in predicting improvement after colorectal resection for endometriosis. DESIGN: Italian and Brazilian cohort studies (Canadian Task Force classification II-3). SETTING: Tertiary referral university hospital in Brazil and expert center in endometriosis in Italy. PATIENTS: Patients with colorectal endometriosis from an Italian population (n = 63) and a Brazilian population (n = 151). INTERVENTION: Laparoscopic colorectal resection for treatment of endometriosis. MEASUREMENTS AND MAIN RESULTS: Preoperative and postoperative evaluations of the Physical Component Summary (PCS) and the Mental Component Summary (MCS) of the SF-36 were performed. Substantial improvement in PCS and MCS was observed after colorectal resection in both populations. In the Brazilian population, the receiver operating curve (ROC) (area under the curve [AUC]) was 0.83 (95% confidence interval [CI], 0.77-0.89) for MCS and 0.78 (95% CI, 0.71-0.83) for PCS, demonstrating good discrimination performance. The mean difference between the predicted and calibrated probabilities was 19.6% for MCS and 32.8% for PCS. In the Italian population, the ROC curve (AUC) was 0.65 (95% CI, 0.52-0.78) for PCS and 0.67 (95% CI, 0.55-0.78) for MCS. The model demonstrated poor discrimination and calibration performance for PCS (p < .001) and MCS (p = .003). The mean difference between the predicted and calibrated probabilities was 17.5% for MCS and 21.8% for PCS. CONCLUSION: Despite the use of validated translations of the SF-36, our results underline the limits of this tool in selection of patients for colorectal resection due to underestimation of predicted quality of life, possibly because of variations in epidemiologic characteristics of the populations.

Role of protective defunctioning stoma in colorectal resection for endometriosis.

STUDY OBJECTIVE: To evaluate the role of protective defunctioning stoma (PDS) on the occurrence of digestive tract complications after colorectal resection to treat endometriosis. DESIGN: Prospective cohort study (Canadian Task Force classification II-2). SETTING: University hospital. PATIENTS: All patients undergoing segmental colorectal resection to treat colorectal endometriosis with and without PDS between 2003 and 2011 at Tenon University Hospital, Paris, France. MEASUREMENTS AND MAIN RESULTS: Patients were assessed at 1, 6, and 12 months postoperatively and each year thereafter. Median follow-up was 60 months. Of 198 patients included for analysis, 53 (27%) had PDS. Overall, 15 (7.5%) digestive tract complications occurred: 9 (4.5%) rectovaginal fistulas and 6 (3%) anastomotic leakages. All rectovaginal fistulas occurred in patients with a low colorectal anastomosis (p < .001) and 88% (8 of 9) in patients with a partial colpectomy (p < .001). PDS was associated with a decrease in the number of rectovaginal fistulas in women undergoing partial colpectomy and low colorectal resection from 27% to 15%, without reaching significance (p = .4). No anastomotic leakage occurred in patients with PDS. CONCLUSION: Our results support that PDS can be omitted in patients with mid-colorectal anastomosis without partial colpectomy. In patients requiring partial colpectomy or partial colpectomy plus low colorectal anastomosis, PDS remains questionable.

[Sentinel node procedure and endometrial cancer: senti-endo results]. / Stratégie ganglionnaire et cancer de l'endomètre : résultats de senti-endo.

Based on two randomized trials and a meta-analysis, the recommendations of the National Cancer Institute (INCa) have validated the absence of systematic pelvic lymphadenectomy for patients with endometrial cancer at low risk (type 1 histology stage IA grade 1-2) and intermediate (type 1 histology stage IA grade 3 and IB grade 1-2) but without taking into account the contribution of the sentinel node (SN) procedure. The senti-endo trial assessing the role of the SN procedure in patients with early stages endometrial cancer showed that the detection rate by hemi-pelvis right and left were 77 and 76%, respectively. The detection rate per patient was 89%. Among patients with at least a SN detected, the detection was unilateral in 34 cases (31%) and bilateral in 77 cases (69%). Of the 111 patients with at least a SN detected, 19 had lymph node metastases (17%). Considering the hemi-pelvis right and left as a unit, no false negative case was observed, hence the sensitivity and NPV was 100%. Considering the NPV per patient, three false negative cases were observed. Among the 57 patients at low risk, six (11%) had lymph node metastases on SN with negative non sentinel nodes. Of the 33 patients at intermediate risk, five (15%) had lymph node metastases on SN with negative non sentinel nodes. Senti-endo results emphasize the contribution of the SN procedure to assess the nodal status in patients with low or intermediate risk group raising the issue on new definition of the recommendations of INCa.

Exploration of the retroperitoneum using the transvaginal natural orifice transluminal endoscopic surgery technique.

We sought to evaluate the feasibility of the retroperitoneum's exploration via natural orifice transluminal endoscopic surgery (NOTES) using transvaginal access in a porcine model, and its possible application in human beings. Six female pigs (25-30 kg) were used to establish anatomic landmarks and technical steps. Six additional pigs were used for the survival study. Under general anesthesia and with the pig supine, a 1-cm posterolateral colpotomy was performed with the double-channel gastroscope's needle knife. The incision was enlarged laterally using blunt dissection while keeping in contact with the psoas muscle. A retroperitoneal tunnel was created using carbon-dioxide dissection and the movements of the gastroscope up to the level of the kidney. The colpotomy site was closed using interrupted sutures (polyglactin 2/0). A follow-up laparoscopy and necropsy were performed 3 weeks postoperatively. Successful access to the retroperitoneum was achieved in all pigs with a mean operative time of 30 minutes. However, in the first 3 pigs used for the acute study, the peritoneum was perforated during the six-pig dissection and the procedure was abandoned because of the space's collapse. No perforation occurred during the survival study. An excellent view of the retroperitoneal space and structures, such as the vascular and lymphatic tissues, the kidney, the adrenal gland, and the ureter, was obtained. No intraoperative complications or bleeding or injury to any of the retroperitoneal structures occurred. The 3-week follow-up laparoscopy showed no adhesions or abscesses. These findings were confirmed at necropsy. The retroperitoneal space can be successfully accessed via NOTES. Transvaginal NOTES access to the retroperitoneum avoids any transparietal trocars, so it could decrease surgical trauma, be better tolerated, and offer better visualization, with the obvious gender limitation. Future clinical application in human beings may include procedures such as lymphadenectomy, nephrectomy, and adrenalectomy.

Transvaginal extraperitoneal lymphadenectomy by Natural Orifices Transluminal Endoscopic Surgery (NOTES) technique in porcine model: feasibility and survival study.

OBJECTIVE: Retroperitoneal pelvic and lomboartic lymphadenectomy is widely used as a staging and/or prognostic procedure in gynecologic malignancies. Associated morbidity ranges from 2 to 13% of cases. This study assesses the feasibility of extraperitoneal lymphadenectomy using Natural Orifices Transluminal Endoscopic Surgery (NOTES) in porcine survival model. METHODS: Six female pigs weighing 25 to 30 kg were used. Using a transvaginal access to the retroperitoneum, we performed three pelvic lymph node excision and three others in the laterocaval, interaorticocaval and lateroaortic regions. Colpotomy was closed with interrupted absorbable sutures. RESULTS: Retroperitoneal lymphadenectomies were performed successfully in all six pigs. We experienced one accidental peritoneal perforation, one diffuse anterior abdominal wall emphysema, one abdominal wall bleeding secondary to electrical muscle stimulation and two pneumoperitoneums evacuated by Veress needle insertion. All animals thrived until three weeks after the initial intervention. On laparoscopic second look there were no abscess, no infection and no adhesions even with the accidental peritoneal perforation. On laparotomy, no retroperitoneal abscess was found, but there was a small amount of fibrosis at the lymphadenectomy sites. All colpotomies were inspected and showed good healing. CONCLUSIONS: This study demonstrated the technical feasibility and safety of extraperitoneal lymphadenectomy by totally NOTES technique and provided the first report on survival porcine model. Cadaver experiments would test its feasibility in humans. Sentinel lymph node could be an application of NOTES lymphadenectomy in humans. NOTES endoscopic instruments are urgently needed for further advances in the technique. Further studies are mandatory to evaluate its future indications.

Effect of betamethasone in vivo on placental adrenomedullin in human pregnancy.

OBJECTIVE: The aim of the current study was to determine the effects of in vivo administration of prenatal betamethasone in patients at risk for preterm delivery on adrenomedullin (AM) concentrations in maternal and fetal plasma and on AM localization in placenta and fetal membranes. METHODS: A total of 62 pregnant women between 25 and 35 weeks' gestation were studied. Forty-seven pregnant women received betamethasone (2 x 12 mg intramuscularly given 24 hours apart) for stimulation of fetal lung maturity. Blood samples were collected before betamethasone administration and at different time points after the first and the second dose. Further samples were collected at delivery and, in women who did not deliver, after 1 week and 30 days from betamethasone administration. At delivery, placenta and membranes were collected. Fifteen patients who delivered at the same gestational age not receiving betamethasone represented the control group. AM concentration was determined by radioimmunoassay. Localization of AM in placental tissues was assessed by immunohistochemistry. RESULTS: Betamethasone caused approximately 50% increase in maternal plasma AM at 1 week after administration, whereas in fetal plasma AM levels increased by about 90% at 48 hours after betamethasone administration. There was increased immunohistochemical staining for AM in fetoplacental tissues collected after betamethasone administration. CONCLUSION: These results provide the first evidence for in vivo stimulation of AM, likely of placental origin, by glucocorticoids in the third trimester human pregnancy.