Robotic-assisted laparoscopy excision of a severe form of diaphragmatic endometriosis: a retrospective study of 60 patients.

STUDY OBJECTIVE: To assess the feasibility, effectiveness and safety of the robotic surgical approach in the treatment of severe diaphragmatic endometriosis (DE). DESIGN: Retrospective single-center study using data prospectively recorded in the Franco-European Multidisciplinary Institute of Endometriosis (IFEMendo) database and National observatory for endometriosis (NoEndo) database. SETTING: Tertiary referral center. Endometriosis care center. PATIENTS: Sixty consecutive patients undergoing robotic excision of severe DE from January 2020 to July 2023. INTERVENTIONS: Robotic excision of severe DE. MEASUREMENT: Categorical and continuous variables were evaluated and compared using descriptive statistics. A p-value of <0.05 was considered statistically significant. MAIN RESULTS: Full thickness diaphragmatic resection was performed in 76.7% of patients (46/60), partial diaphragmatic muscle resection in 10% (6/60) of cases. Peritoneal stripping technique was performed in 60% (36/60) of patients, divided as follows: as the only technique in case of extensive superficial diaphragmatic involvement in 13.3% of cases (8/60); in addition to full-thickness or partial diaphragmatic resection in case of concomitant multiple foci in 46.7% of patients (28/60). Median operative time was 79.6 minutes with no statistically significative difference related to the surgeon performing surgery (p>0.05). Intraoperative and postoperative complications occurred in 1.7% (1/60) and 6.6% (4/60) of cases, respectively. Diaphragmatic hernia (Clavien-Dindo 3b) was the most common postoperative complication and required surgical repair in all cases. Median hospital stay was 24 hours. The rate of patients with complete recovery from DE symptoms has gradually increased during follow-up, reaching 89% after 12 months from surgery. CONCLUSION: In this case series, robotic treatment of severe diaphragmatic endometriosis in expert hands was feasible, effective and safe. SUMMATION: A robotic stepwise approach allows safe and radical excision of a severe form of diaphragmatic endometriosis.

Intermittent Self-catheterization for Bladder Dysfunction After Deep Endometriosis Surgery: Duration and Factors that Might Affect the Recovery Process.

STUDY OBJECTIVE: To assess the duration needed for regaining normal bladder voiding function in patients with postoperative bladder dysfunction requiring intermittent self-catheterization after deep endometriosis surgery and identify risk factors that might affect the recovery process. DESIGN: Retrospective study based on data recorded in a large prospective database. SETTING: Endometriosis referral center. PATIENTS: From September 2018 to June 2022, 1900 patients underwent excision of deep endometriosis in our center; 61 patients were discharged with recommendation for intermittent self-catheterization and were thus included in the study. INTERVENTIONS: Intermittent self-catheterization after endometriosis surgery. MEASUREMENTS AND MAIN RESULTS: A total of 43 patients (70.5%) stopped self-catheterization during the follow-up period. Median follow-up was 25 weeks (range, 7-223 wk). Surgery was performed laparoscopically in 48 patients (78.7%) and robotically in 13 (21.3%); 47 patients (77%) had nodules involving the digestive tract, 11 (18%) had urinary tract involvement, 29 had parametrial nodules (47.5%), and 13 (21.3%) had sacral plexus involvement. The probability of bladder voiding function recovery and arrest of self-catheterization was 24.5%, 54%, 59%, 72%, and 77% at 4, 8, 12, 52, and 78 weeks, respectively. Cox's multivariate model identified preoperative bladder dysfunction as the only statistically significant independent predictor for arrest of self-catheterization (hazard ratio, 0.36; 95% confidence interval, 0.15-0.83). CONCLUSION: Patients requiring intermittent self-catheterization for bladder dysfunction after deep endometriosis excision may spontaneously recover bladder function in 77% of cases. Symptoms suggesting preoperative bladder voiding dysfunction should be reviewed before planning surgery, and patients should be informed of the higher postoperative risk of long-term bladder voiding dysfunction.

Surgical treatment of deep endometriosis: Impact on spontaneous conception.

Deep endometriosis (DE) is the most severe form of endometriosis and is commonly associated with infertility. Surgical treatment of DE appears to increase chances of spontaneous conception in appropriately selected patients wishing to conceive. Identifying, however, the exact impact of DE, and its surgical removal, on natural conception is highly challenging. The surgical approach should be favoured in symptomatic patients with pregnancy intention. Limited data from infertile patients suggest that outcomes may not differ from patients without known infertility. Complex DE surgery carries a risk of serious complications, therefore, it should be performed in centers of expertise. Such complications may, however, not have a significant negative impact on fertility outcomes, according to limited available data. Data on obstetric outcomes of spontaneous conceptions after DE surgery are too scarce. In asymptomatic, infertile patients the debate between primary surgery or Artifial Reproductive Technology is ongoing, until randomized studies report their results.

Robotic Surgery for Severe Endometriosis: A Preliminary Comparative Study of Cost Estimation.

STUDY OBJECTIVE: To compare the postoperative outcomes and the overall expenses between conventional laparoscopy and robotic surgery, in a series of consecutive patients managed for only severe endometriosis in our institute. DESIGN: A cohort comparative study. SETTING: Center of Excellence in Multidisciplinary Endometriosis Care. PATIENTS: A total of 175 symptomatic patients undergoing surgery for only severe endometriosis from March 2021 to August 2022. INTERVENTIONS: We treated patients with endometriosis involving the digestive tract such as rectum, sigmoid colon, and ileocecal junction by rectal shaving, discoid resection, or segmental resection (141 surgeries) with or without bladder (23 surgeries), sacral plexus (19 surgeries), and diaphragm involvements (14 surgeries). MEASUREMENTS AND MAIN RESULTS: Postoperative outcomes were evaluated in terms of total surgical time (total surgical room occupancy time and total operating time), hospitalization period, postoperative complications, rehospitalization, and second surgical procedures. A statistically higher total surgical room occupancy (203 minutes vs 151 minutes) and operating time (150 minutes vs 105 minutes) were observed in the robotic group (p = .001). No differences in terms of mean hospital stay (p = .06), postoperative complications (p = .91), rehospitalization (p = .48), and secondary surgical treatment (p = .78) were identified. Concerning the cost analysis only for disposable supply, the cost of colorectal resection was totaled at 2604 euros for the laparoscopic conventional approach vs 2957 euros for the robotic approach (+352.6 euros, +14%). The cost of rectal disc excision was 1527 euros for the laparoscopic conventional approach vs 1905.85 euros (+378 euros, +25%). CONCLUSIONS: Our study confirms the feasibility of the robotic approach for the treatment of severe endometriosis, with however a higher cost of robotic approach. Next studies should identify specific indications for robotic surgery, where technical advantages provided by the technology are followed by objective improvement of patients' outcomes.

Robotic-assisted versus conventional laparoscopic approach in patients with large rectal endometriotic nodule: the evaluation of safety and complications.

AIM: The aim was to compare postoperative complications in patients undergoing the excision of a rectal endometriotic nodule over 3 cm by a robotic-assisted versus a conventional laparoscopic approach. METHODS: We conducted a retrospective cohort study evaluating prospectively collected data. The main interventions included rectal shaving, disc excision or colorectal resection. All the surgeries were performed in one endometriosis reference institute. To evaluate factors significantly associated with the risk of anastomosis leakage or fistula and bladder atony, we conducted a multivariate logistic regression model. RESULTS: A total of 548 patients with rectal endometriotic nodule over 3 cm in diameter (#ENZIAN C3) were included in the final analysis. The demography and clinical characteristics of women managed by the robotic-assisted (n = 97) approach were similar to those of patients who underwent conventional laparoscopy (n = 451). The multivariate logistic regression demonstrated that the surgical approach (robotic-assisted vs. laparoscopic) was not associated with the rate of anastomosis leakage or fistula (adjusted odds ratio [aOR] 1.2, 95% confidence interval [CI] 0.3-4.0) and bladder dysfunction (aOR 0.5, 95% CI 0.1-1.8). A rectal nodule located lower than 6 cm from the anal verge was significantly associated with anastomosis leakage (aOR 4.1, 95% CI 1.4-10.8) and bladder atony (aOR 4.3, 95% CI 1.5-12.3). Anastomosis leakage was also associated with smoking (aOR 3.2, 95% CI 1.4-7.4), significant vaginal infiltration (aOR 2.7, 95% CI 1.2-6.7) and excision of nodules involving sacral roots (aOR 5.6, 95% CI 1.7-15.5). CONCLUSION: The robotic-assisted approach was not associated with increased risk of main postoperative complications compared to conventional laparoscopy for the treatment of large rectal endometriotic nodules.

Pain Reduction With an Immersive Digital Therapeutic in Women Living With Endometriosis-Related Pelvic Pain: At-Home Self-Administered Randomized Controlled Trial.

BACKGROUND: The management of chronic pelvic pain in women with endometriosis is complex and includes the long-term use of opioids. Patients not fully responsive to drugs or ineligible for surgical treatments need efficient alternatives to improve their quality of life and avoid long-term sequelae. OBJECTIVE: This randomized controlled trial aimed to assess the effects of repeated at-home administrations of a 20-minute virtual reality (VR) solution (Endocare) compared with a sham condition on pain in women experiencing pelvic pain due to endometriosis. METHODS: Patients were instructed to use the VR headsets twice daily for at least 2 days and for up to 5 days starting on their first day of painful periods. Pain perception was measured using a numerical scale (0-10) before and 60, 120, and 180 minutes after each treatment administration. General pain, stress, fatigue, medication intake, and quality of life were reported daily by patients. RESULTS: A total of 102 patients with endometriosis were included in the final analysis (Endocare group: n=51, 50%; sham group: n=51, 50%). The mean age was 32.88 years (SD 6.96) and the mean pain intensity before treatment was 6.53 (SD 1.74) and 6.22 (SD 1.69) for the Endocare group and the sham control group, respectively (P=.48). Pain intensity decreased in both groups from day 1 to day 5 along with a decrease in medication use. Maximum pain intensity reduction of 51.58% (SD 35.33) occurred at day 2, 120 minutes after treatment for the Endocare group and of 27.37% (SD 27.23) at day 3, 180 minutes after treatment for the control group. Endocare was significantly superior to the sham on day 1 (120 minutes, P=.04; 180 minutes, P=.001), day 2 (0 minutes, P=.02; 60, 120, and 180 minutes, all P<.001), and day 3 (60 minutes, P=.01; 120 minutes, P=.005; 180 minutes, P=.001). Similarly, the mean perceived pain relief was significantly higher with Endocare on day 1 (120 and 180 minutes P=.004 and P=.001, respectively) and day 2 (60, 120, and 180 minutes P=.003, P=.004, and P=.007, respectively) compared to the control. No adverse event was reported. CONCLUSIONS: This study confirmed the effectiveness and safety of self-repeated administrations of a VR immersive treatment used at home while reducing overall pain medication intake in women diagnosed with endometriosis experiencing moderate-to-severe pelvic pain. TRIAL REGISTRATION: ClinicalTrials.gov NCT05172492; https://clinicaltrials.gov/ct2/show/NCT05172492.

Long-term risk of repeated surgeries in women managed for endometriosis: a 1,092 patient-series.

OBJECTIVE: To assess the long-term risk of repeated surgery in women undergoing complete excision of endometriosis by an experienced surgeon and to identify circumstances leading up to repeat surgery. DESIGN: Retrospective study based on data recorded in a large prospective database. SETTING: University Hospital. PATIENT(S): A total of 1,092 patients managed for endometriosis, from June 2009 to June 2018, by one surgeon. INTERVENTION(S): Complete excision of endometriosis lesions. MAIN OUTCOME MEASURE(S): The recording of a repeated surgery linked to endometriosis performed during follow-up. RESULT(S): Endometriosis was exclusively superficial in 122 patients (11.2%) and 54 women (5%) had endometriomas without associated deep endometriosis nodules. Deep endometriosis was managed in 916 women (83.9%), leading to infiltration or not of the bowel in 688 (63%) and 228 (20.9%) patients, respectively. A majority of patients were managed for severe endometriosis infiltrating the rectum (58.4%). Mean and median follow-up was 60 months. A total of 155 patients underwent a repeated surgery relating to endometriosis; 108 procedures were required because of recurrences (9.9%), 39 surgeries were related to the management of infertility by assisted reproductive techniques (3.6%), and in 8 surgeries, a direct relationship between surgery and endometriosis was probable but not certain (0.8%). The majority of procedures involved hysterectomy for adenomyosis (n=45, 4.1%). The probability of requiring repeated surgery at 1, 3, 5, 7, and 10 years was 3%, 11%, 18%, 23%, and 28%, respectively. Cox's multivariate model identified postoperative pregnancy and hysterectomy as being statistically significant independent predictors for a reduction in the probability of having a repeated surgery, after adjustment on continuous postoperative amenorrhea, the main localization of the disease, and management for endometriosis infiltrating the rectum during the first surgery. CONCLUSION(S): Up to 28% of patients may require a repeated surgical procedure during the 10 years after complete excision of endometriosis. Conservation of the uterus is followed by an increased risk of repeated surgery. The study is based on outcomes resulting from a single surgeon, which limits the generalizability of results.

Excision of Deep Rectovaginal Endometriosis Nodules with Large Infiltration of Both Rectum and Vagina: What Is a Reasonable Rate of Preventive Stoma? A Comparative Study.

STUDY OBJECTIVE: To compare postoperative complications and rectovaginal fistula rate in women undergoing excision of large rectovaginal endometriosis requiring concomitant excision of rectum and vagina during 2 time periods with differing policies for preventive stoma confection. DESIGN: Retrospective before-and-after comparative cohort study on data prospectively recorded in a database. Patients managed from September 2018 to March 2020 (first period) were compared with those managed from April 2020 to June 2022 (second period). SETTING: Endometriosis Institute. PATIENTS: One hundred sixty-eight patients presenting with deep endometriosis infiltrating the rectum and vagina, with lesions more than 3 cm in diameter during 2 consecutive time periods with differing policies regarding use of preventive stoma. INTERVENTIONS: Rectal disc excision or colorectal resection, concomitantly with large vaginal excision. MEASUREMENTS AND MAIN RESULTS: A total of 87 and 81 women received surgery during the first and the second period, respectively, during which the rate of preventive stoma was, respectively, 32.2% and 8.6%. Deep rectovaginal nodule characteristics were comparable. The mean height (SD) of rectal sutures after disc excision and colorectal resection were, respectively, 6.5 cm (2.3 cm) and 7.2 cm (3.8 cm). Rectovaginal fistula was recorded in 17 patients, corresponding to an overall rate of 10.1%. The rates of rectovaginal fistula in the group of patients with and without preventive stoma, regardless of the period in which surgery was performed, were 11.4% and 9.8%, respectively (p = .76). The rates of fistula recorded during the first and the second period were, respectively, 9.2% and 11.1% (p = .80), and that of overall early main complications were 31% and 29.6% (p = .84). Regression logistic model identified an independent relationship between smoking and rectovaginal fistula (adjusted odds ratio [OR] 3.9, 95% confidence interval [CI] 1.1-14) after adjustment for the period (adjusted OR 1.4, 95% CI 0.4-4.9 related to the second period), stoma confection (adjusted OR 1.8, 95% CI 0.5-7.1 related to stoma confection), robotic surgery (adjusted OR 1.7, 95% CI 0.3-10.1 related to robotic assistance), and type of rectal surgery (adjusted OR 0.4, 95% CI 0.1-1.4 related to disc excision when compared with colorectal resection). CONCLUSION: No statistically significant differences were found concerning risk of rectovaginal fistula in women with rectovaginal endometriosis requiring large rectal and vaginal excision after a decision to no longer routinely perform preventive stoma.

Impact of Laparoscopic Sclerotherapy for Ovarian Endometriomas on Ovarian Reserve.

STUDY: Objective: To evaluate the impact of laparoscopic sclerotherapy on the management of endometrioma during surgery for deep infiltrative endometriosis (DIE). DESIGN: Observational study. SETTING: Tivoli-Ducos Clinic, Bordeaux. PATIENTS: Sixty-nine patients underwent laparoscopic sclerotherapy for endometrioma during surgery for DIE. INTERVENTIONS: Laparoscopic sclerotherapy with 95% ethanol solution and DIE surgery. MEASUREMENTS AND MAIN RESULTS: Antimüllerian hormone (AMH) levels before and at least 6 months after surgery, recurrences, and pregnancies. Mean AMH (ng/mL) levels were 3.4 (2.3) before surgery and 2 (1.7) after surgery (p <.001). Mean difference was 1.29 ng/mL. Preoperative AMH level was the only variable independently associated with an additive decrease in AMH. Mean (standard deviation) follow-up period was 17.5 months (4.6) (range 9-26 months); 18 of 44 patients (40.1%) with pregnancy intent conceived. Of 51 patients who underwent postoperative pelvic ultrasound, 6 (6 of 51, 11.8%) had a recurrence of endometrioma. CONCLUSION: Laparoscopic sclerotherapy for endometrioma >40 mm during surgery for DIE sclerotherapy has a low impact on AMH, preserves fertility, and prevents recurrence.

Pain Reduction With an Immersive Digital Therapeutic Tool in Women Living With Endometriosis-Related Pelvic Pain: Randomized Controlled Trial.

BACKGROUND: Chronic pelvic pain is a common and disabling condition in women living with endometriosis. Pharmacological and surgical treatments are not always effective at controlling pain and present important restrictions. Digital therapeutics (DTx) are emerging as major nonpharmacological alternatives that aim to extend the analgesic therapeutic arsenal of patients. OBJECTIVE: In this randomized controlled trial (RCT), we aimed to measure the immediate and 4-hour persisting effects of a single use 20-minute DTx (Endocare) on pain in women experiencing pelvic pain due to endometriosis. METHODS: A total of 45 women with endometriosis participated in a randomized controlled study comparing the analgesic effect of a single use of a virtual reality digital treatment named Endocare (n=23, 51%) to a 2D digital control (n=22, 49%). Perceived pain and pain relief were measured before the treatment and 15, 30, 45, 60, and 240 minutes after the end of the treatment. RESULTS: The clustered posttreatment pain was significantly reduced compared to the pretreatment for both Endocare and the control group (all P<.01). Endocare was significantly more effective than the control group (all P<.01). Endocare decreased the mean pain intensity from 6.0 (SD 1.31) before the treatment to 4.5 (SD 1.71) posttreatment, while the control only decreased it from 5.7 (SD 1.36) to 5.0 (SD 1.43). When comparing each posttreatment measures to the pretest, Endocare significantly reduced pain perception for all points in time up to 4 hours posttreatment. The differences did not reached significance for the control group. Moreover, Endocare was significantly superior to the control group 15, 30, and 45 minutes after the treatment (all P<.001). The mean perceived pain relief was significantly higher for Endocare at 28% (SD 2%) compared to the control, which was 15% (SD 1%) for all the posttreatment measurements (all P>.05). CONCLUSIONS: Our study aimed to test the effects of a single use of a DTx treatment on reported pain at different time points in women diagnosed with endometriosis experiencing moderate-to-severe pelvic pain. Importantly, our results support that Endocare, a virtual reality immersive treatment, significantly reduce pain perception compared to a digital control in women living with endometriosis. Interestingly, we are the first to notice that the effect persisted up to 4 hours posttreatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT04650516; https://tinyurl.com/2a2eu9wv.

Oocyte Vitrification for Fertility Preservation in Women with Benign Gynecologic Disease: French Clinical Practice Guidelines Developed by a Modified Delphi Consensus Process.

International guidelines are published to provide standardized information and fertility preservation (FP) care for adults and children. The purpose of the study was to conduct a modified Delphi process for generating FP guidelines for BGD. A steering committee identified 42 potential FP practices for BGD. Then 114 key stakeholders were asked to participate in a modified Delphi process via two online survey rounds and a final meeting. Consensus was reached for 28 items. Among them, stakeholders rated age-specific information concerning the risk of diminished ovarian reserve after surgery as important but rejected proposals setting various upper and lower age limits for FP. All women should be informed about the benefit/risk balance of oocyte vitrification-in particular about the likelihood of live birth according to age. FP should not be offered in rASRM stages I and II endometriosis without endometriomas. These guidelines could be useful for gynecologists to identify situations at risk of infertility and to better inform women with BGDs who might need personalized counseling for FP.

Large ovarian endometriomas are associated with high pre-operative anti-Müllerian hormone concentrations.

RESEARCH QUESTION: Are large ovarian endometriomas associated with high pre-operative anti-Müllerian hormone (AMH) concentrations? DESIGN: Data from 332 women who underwent AMH measurement before surgery for endometriosis were prospectively recorded in a large database. Univariate analysis compared AMH concentrations in terms of the patients' baseline characteristics. A multivariate model was used to identify variables having an independent relationship with AMH concentration. RESULTS: Among 332 women included in the study, 47.6% were aged 18-30 years, 67.8% were infertile and 85.5% were nulliparous. A total of 66.3% had ovarian endometriomas, and 10.8% had cysts measuring over 6 cm. Bilateral cysts over 3 cm were recorded in 24.7% of the women. Univariate analysis identified two variables that had a statistically significant relationship with AMH concentration: the woman's age (P = 0.01) and cyst size (P < 0.001). Multivariate analysis revealed that ages of 36-40 years and over 40 years showed a significant association with lower AMH concentrations (P = 0.02 and P = 0.009, respectively), while a cyst size of over 6 cm was statistically associated with high AMH concentrations (P < 0.001), after adjustment for smoking, parity, rectosigmoid endometriotic nodules and a bilateral location of endometriomas. CONCLUSIONS: Pre-operative AMH concentration was significantly increased in women with large endometriomas of over 6 cm, independent of their age or the presence of bilateral endometriomas. This is relevant for both surgeons and patients when planning surgery in women with an intention to conceive post-operatively.

Prevalence, intensity, impact on quality of life and insights of dysmenorrhea among French women: A cross-sectional web survey.

OBJECTIVE: Determine prevalence and intensity of primary dysmenorrhea in a sample of French women and assess impact on daily life and Quality of Life, care pathway and pain management METHODS: This cross-sectional web-based survey was conducted from December 19th2018 through January 10th2019 among a representative sample of 3001 French women aged 16 to 50. RESULTS: 2375 women (79%) reported having pain during menstruation, currently or in the past. 52% reported being currently affected, 27% had been affected in the past and 21% never suffered. Among younger women under 24, 66% reported current dysmenorrhea. Mean rating of pain intensity, evaluated on a visual analog scale from 0 to 10, was 6 + 1.9 in women presently having dysmenorrhea and 42% reported rating between 7 and 10. The impact on daily life was strong and there was a significant reduction of SF-36 scores in women experiencing dysmenorrhea. Among the 79% of women affected by dysmenorrhea, (current or past) 53% never used any medication and respectively 58% and 66% never sought medical advice. CONCLUSION: Dysmenorrhea is very frequent in France with a significant impact on daily life and Quality of Life. There is a real inadequacy in the recognition and the management of this pathology, too often considered as common by the patients. There is a strong need for better information of the women and to raise the awareness of first line health-care professionals that any dysmenorrhea and especially severe dysmenorrhea must be accurately assessed and managed with the available therapeutic means.

Pregnancy outcomes in women with history of surgery for endometriosis.

OBJECTIVE: To assess the relationship between history of surgery for endometriosis and adverse obstetrical outcomes. DESIGN: Retrospective study using prospectively recorded data. SETTING: Referral center. PATIENT(S): Total of 569 women with history of surgery for endometriosis, postoperative conception, and pregnancy evolution over 22 weeks of gestation. INTERVENTIONS(S): Surgery for endometriosis. MAIN OUTCOME MEASURE(S): Small for gestational age (SGA) status of the newborn, spontaneous preterm birth (PT, before 37 weeks' gestation), and placenta previa. RESULTS: Among 733 pregnancies included in the study, 566 deliveries were recorded (77.2%), of which 535 were singleton (72.9% of pregnancies) and 31 twins (4.2%). SGA was observed in 81 of 535 (15.1%) singleton pregnancies and in 9 of 31 (29%) twin pregnancies. PT occurred in 53 of 535 (9.9%) singleton pregnancies and in 19 of 31 (61.2%) twin pregnancies. The number of singleton and multiple pregnancies complicated by placenta previa were, respectively, 9 of 535 (1.7%) and 0 of 31. The independent factor found to relate to SGA was the absence of endometriomas; conception with the use of assisted reproductive technologies (ART) only tended toward statistical significance. Independent factors found to increase risk of PT were conception with the use of ART, body mass index >30 kg/m2, and surgery of deep endometriosis infiltrating the rectum and the bladder. Independent factors associated with placenta previa were conception with the use of ART and history of stage III or IV endometriosis. CONCLUSION(S): The risk of SGA and PT is increased in women with a history of surgery for endometriosis, and a high rate of conception with the use of ART may jeopardize outcomes.

Relationship between Patient Age and Disease Features in a Prospective Cohort of 1560 Women Affected by Endometriosis.

OBJECTIVE: To assess the relationship between age, location of the disease, and surgical procedures performed in patients undergoing surgical management of endometriosis. DESIGN: Retrospective study using data prospectively recorded in the North-West Inter Regional Female Cohort for Patients with Endometriosis database. SETTING: University tertiary referral center. PATIENTS: Women who underwent surgical management of symptomatic endometriosis between April 2009 and April 2014. INTERVENTIONS: Patients were allocated to 6 groups according to their age at the time of surgery: ≤20, 21 to 25, 26 to 30, 31 to 35, 36 to 40 and >40 years. Patient characteristics, prior history, location of endometriotic lesions, stage of disease, intraoperative findings, and surgical procedures were retrieved from a prospectively recorded database. MEASUREMENTS AND MAIN RESULTS: Patient characteristics, symptoms, location of endometriosis, and type of surgery performed were compared between groups. In total, 1560 procedures were performed. Of these, more than one-half were carried out in women between the age of 26 to 35 years and the majority were performed in women aged between 26 and 30 years. Only 2% of procedures were performed in women under the age of 20 years. The mean stage of the disease at the time of surgical diagnosis was stage II for women younger than 20 years, stage III for those in the age group of 21 to 25 years, and stage IV for those older than 26 years. The rate of diagnosis of deep colorectal nodules increased progressively from 20 to 26 years and remained stable thereafter. CONCLUSION: Our data confirm that endometriosis is a disease that probably progresses from adolescence until the adult period when symptoms (pain or infertility) become debilitating and require surgery. Our data suggest that policies relating to the prevention and early diagnosis of endometriosis should focus on women younger than 25 years.

Pregnancy Rates After Surgical Treatment of Deep Infiltrating Endometriosis in Infertile Patients With at Least 2 Previous In Vitro Fertilization or Intracytoplasmic Sperm Injection Failures.

STUDY OBJECTIVE: To assess the postoperative probabilities of pregnancy in patients with deep infiltrating endometriosis (DIE) and ≥2 previous in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) failures. DESIGN: Retrospective study using data prospectively recorded in the North-West Inter Regional Female Cohort for Patients with Endometriosis (CIRENDO) database. SETTING: University tertiary referral center. PATIENTS: Infertile patients under the age of 43 years, having undergone ≥2 previous IVF or ICSI failures, who were surgically managed for DIE. INTERVENTIONS: Complete excision of DIE. MEASUREMENTS AND MAIN RESULTS: The pregnancy rate after surgery was assessed. One hundred and four infertile patients had surgery in 7 different centers participating in the database. Seventy-seven women intended to get pregnant postoperatively. Four patients who got pregnant by oocyte donation were excluded, resulting in a sample of 73 women. The mean patient age was 31.9 years (standard deviation [SD], 4.1), and the mean length of history of infertility was 48.4 months (SD, 26.5). Stage III and IV endometriosis were recorded in 83.6% of patients. The mean postoperative follow-up was 46.6 months (SD, 20.5). The postoperative pregnancy rate was 43.8% with a mean time from surgery to pregnancy of 11.1 months. 21.8% of pregnancies were spontaneous, 31.2% were obtained by IVF, 21.8% by frozen embryo transfer, 18.7% by IVF-ICSI, and 3.1% by intrauterine insemination. Multivariate analysis revealed that ovarian surgery, age ≥35 years old, and stage II endometriosis was associated with the probability of conception. CONCLUSION: Infertile women with ≥2 IVF-ICSI failures may be referred for surgery as it appears related to reasonable postoperative pregnancy rates, particularly when endometriomas surgery is either not required or not performed. Surgery for DIE does not routinely delay conception, as it usually occurs during the year following surgery.

Progression of deep infiltrating rectosigmoid endometriotic nodules.

STUDY QUESTION: What is the risk of progression of deep endometriotic nodules infiltrating the rectosigmoid? SUMMARY ANSWER: There is a risk of progression of deep endometriotic nodules infiltrating the rectosigmoid, particularly in menstruating women. WHAT IS KNOWN ALREADY: Currently, there is a lack of acceptance in the literature on the probability that deeply infiltrating rectosigmoid endometriotic nodules progress in size. STUDY DESIGN, SIZE, DURATION: We conducted a monocentric case-control study between September 2016 and March 2018 at Rouen University Hospital. We enrolled 43 patients who were referred to our tertiary referral centre with deep endometriosis infiltrating the rectosigmoid, who had undergone two MRI examinations at least 12 months apart and had not undergone surgical treatment of rectosigmoid endometriosis during this interval. PARTICIPANTS/MATERIALS, SETTING, METHODS: MRI images were reinterpreted by a senior radiologist with experience and expertise in endometriosis, who measured the length and thickness of deep infiltrating colorectal lesions. Intra- and inter-observer reliability were tested on 30 randomly selected cases. We defined 'progression' of a nodule as an increase of ≥20% in length or in thickness and 'regression' of a lesion as a decrease of ≥20% in length or in thickness between two MRIs. Any nodule for which the variation in length and thickness was <20% was considered as 'stable'. Patients were divided into three groups based on evidence of progression, regression or stability of deep endometriotic nodules between their two MRI examinations. The total length of any period of amenorrhoea between the two MRI examinations, due to pregnancy, breastfeeding or hormonal treatment, was recorded. The total proportion of the time between MRIs where amenorrhoea occurred was compared between groups. MAIN RESULTS AND THE ROLE OF CHANCE: Eighty-six patients underwent at least two MRIs for deep endometriosis infiltrating the sigmoid or rectum between September 2016 and March 2018. Of these, we excluded 10 patients with an interval of <12 months between MRIs, 10 patients who underwent surgery between MRIs, 17 patients for whom at least 1 MRI was considered to be of poor quality and 6 patients for whom no deep colorectal lesion was found on repeat review of either MRI. This resulted in a total of 43 patients eligible for enrolment in the final analysis. Mean time (SD) between MRIs was 38.3 (22.1) months. About 60.5% of patients demonstrated stability of their colorectal lesions between the two MRIs, 27.9% of patients met the criteria for 'progression' of lesions and 11.6% met the criteria for 'regression' of lesions. There was no significant difference in time interval between MRIs for the three groups (P = 0.76). Median duration of amenorrhoea was significantly lower in women with progression of lesions (7.5 months) when compared to those with stability of lesions (8.5 months) or regression of lesions (21 months) (P < 0.001). Median duration of amenorrhoea (expressed as percentage of total time between two MRIs) was also found to be significantly lower in the group demonstrating progression (15.1%) when compared to the group demonstrating stability (19.2%) and the group demonstrating regression (94.1%; P = 0.006). Progression of rectosigmoid nodules was observed in 34% of patients without continuous amenorrhoea, in 39% who had never had amenorrhoea and in no patients with continuous amenorrhoea. LIMITATIONS, REASONS FOR CAUTION: Due to a lack of universally accepted criteria for defining the progression or regression of deep endometriotic nodules on MRI, the values used in our study may be disputed. Due to the retrospective design of the study, there may be heterogeneity of interval between MRIs, MRI techniques used, reason for amenorrhoea and duration of amenorrhoea. The mean inter-MRI interval was of short duration and varied between patients. Our findings are reported for only deep endometriosis infiltrating the rectosigmoid and cannot be extrapolated, without caution, to nodules of other locations. WIDER IMPLICATIONS OF THE FINDINGS: Patients with deeply infiltrating rectosigmoid endometriotic nodules, for which surgical management has not been performed, should undergo surveillance to allow detection of growth of nodules, particularly when continuous amenorrhoea has not been achieved. This recommendation is of importance to young patients with rectosigmoid nodules who wish to conceive, in whom first line ART is planned. There is a very low risk of progression of deep endometriotic nodules infiltrating the rectosigmoid in women with amenorrhoea induced by medical therapy, lactation or pregnancy. STUDY FUNDING/COMPETING INTEREST(S): No funding was received for this study. The authors declare no competing interests related to this study.

High postoperative fertility rate following surgical management of colorectal endometriosis.

STUDY QUESTION: What are fertility outcomes in patients surgically managed for large deep endometriosis infiltrating the rectum who intend to get pregnant postoperatively? SUMMARY ANSWER: Surgical management for rectal endometriosis is followed by high pregnancy rates, with a majority of natural conceptions. WHAT IS KNOWN ALREADY: Optimal management such as surgery versus first-line ART for patients with severe deep endometriosis who desire pregnancy is not defined. STUDY DESIGN, SIZE, DURATION: The study included the patients enrolled in ENDORE randomized trial who attempted pregnancy after the surgery. From March 2011 to August 2013, we performed a two-arm randomized trial, enrolling 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. Postoperative follow-up was prolonged in 55 patients recruited at Rouen University Hospital, and varied from 50 to 79 months. No women were lost to follow-up. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients had either conservative surgery by shaving or disc excision, or radical rectal surgery by segmental resection. One gynecologist experienced in deep endometriosis surgery performed all the procedures, assisted when required by three general surgeons experienced in colorectal surgery. Institutional review board approval was obtained to extend postoperative follow-up to 10 years after the surgery. Among patients enrolled at Rouen University Hospital, women who intended to get pregnant after surgery were selected and followed up postoperatively every 6 months for 2 years, then every year. Pregnancy intention, fertility outcomes, conception mode, endometriosis recurrences and digestive and urinary outcomes were rigorously recorded. The primary outcome was postoperative pregnancy rate. Secondary outcomes were conception mode, the delay to conception from the day of surgery and the day when hormonal treatment was stopped, and delivery rate. Kaplan Meier curves were used to estimate the probability of conception after surgery. MAIN RESULTS AND THE ROLE OF CHANCE: Among the 55 patients enrolled at Rouen University Hospital, 25 had conservative and 30 had radical surgery, and their postoperative follow-up varied from 50 to 79 months. No patient was lost to follow-up. Among the 55 patients, 36 intended to get pregnant after surgery, 23 of whom had unsuccessfully attempted to conceive for more than 12 months before surgery (63%). At the end of follow-up, 29 patients achieved pregnancy (81%), and natural conception was recorded in 17 of them (59% of conceptions). As several women had more than 1 pregnancy (range: 0-3), we recorded 37 pregnancies, 24 natural conceptions (65%) and 29 deliveries (78%). The probabilities of achieving pregnancy at 12, 24, 36 and 48 months postoperatively were 33.4% (95% CI: 20.6-51.3%), 60.6% (44.8-76.8%), 77% (61.5-89.6%) and 86.8% (72.8-95.8%), respectively. Women who had been advised to attempt natural conception achieved pregnancy significantly earlier than patients referred for ART (P = 0.008). In infertile patients, the postoperative pregnancy rate was 74%, and 53% of conceptions were natural. LIMITATIONS, REASONS FOR CAUTION: The main outcomes of the original trial were related to digestive function and not to fertility. Several factors impacting fertility could not be revealed due to small sample size. The study included a high percentage of young women with an overall satisfactory prognosis for fertility, as patients' median age was 28 years. The inclusion of only large infiltrations of the rectum does not allow the extrapolation of conclusions to small nodules of <2 cm in length. Only one skilled gynecologic surgeon performed all the procedures. WIDER IMPLICATIONS OF THE FINDINGS: First-line surgery can be considered in patients with deep endometriosis infiltrating the rectum and pregnancy intention. Patients receiving advice from experienced surgeons on conception modes were more likely to conceive faster after surgery. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a grant from the clinical research program for hospitals (PHRC) in France. The authors declare no competing interests related to this study. TRIAL REGISTRATION NUMBER: The original randomized trial is registered with ClinicalTrials.gov (number NCT 01291576).

Maintenance nifedipine therapy for preterm symptomatic placenta previa: A randomized, multicenter, double-blind, placebo-controlled trial.

OBJECTIVE: To assess the impact of maintenance nifedipine therapy on pregnancy duration in women with preterm placenta previa bleeding. METHODS: PPADAL was a randomized, double-blind, placebo-controlled trial conducted between 05/2008 and 05/2012 in five French hospitals. The trial included 109 women, aged ≥ 18 years, with at least one episode of placenta previa bleeding, intact membranes and no other pregnancy complication, at gestational age 24 to 34 weeks and after 48 hours of complete acute tocolysis. Women were randomly allocated to receive either 20 mg of slow-release nifedipine three times daily (n = 54) or placebo (n = 55) until 36 + 6 weeks of gestation. The primary outcome for the trial was length of pregnancy measured in days after enrolment. Main secondary outcomes were rates of recurrent bleeding, cesarean delivery due to hemorrhage, blood transfusion, maternal side effects, gestational age at delivery and adverse perinatal outcomes (perinatal death, chronic lung disease, neonatal sepsis, intraventricular hemorrhage > grade 2, perventricular leukomalacia > grade 1, or necrotizing enterocolitis). Analysis was by intention to treat. RESULTS: Mean (SD) prolongation of pregnancy was not different between the nifedipine (n = 54) and the placebo (n = 55) group; 42.5 days ± 23.8 versus 44.2 days ± 24.5, p = 0.70. Cesarean due to hemorrhage performed before 37 weeks occurred more frequently in the nifedipine group in comparison with the placebo group (RR, 1.66; 95% confidence interval, 1.05-2.72). Adverse perinatal outcomes were comparable between groups; 3.8% for nifedipine versus 5.5% for placebo (relative risk, 0.52; 95% confidence interval 0.10-2.61). No maternal mortality or perinatal death occurred. CONCLUSION: Maintenance oral nifedipine neither prolongs duration of pregnancy nor improves maternal or perinatal outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT00620724.