Endometriosis: seeking optimal management in women approaching menopause.

The incidence of endometriosis in middle-aged women is not minimal compared to that in the reproductive age group. The treatment of affected women after childbearing age to the natural transition toward menopause has received considerably poor attention. Disease management is problematic for these women due to increased contraindications regarding hormonal treatment and the possibility for malignant transformation, considering the increased cancer risk in patients with a long-standing history of the disease. This state-of-the-art review aims for the first time to assess the benefits of the available therapies to help guide treatment decisions for the care of endometriosis in women approaching menopause. Progestins are proven effective in reducing pain and should be preferred in these women. According to the international guidelines that lack precise recommendations, hysterectomy with bilateral salpingo-oophorectomy should be the definitive therapy in women who have completed their reproductive arc, if medical therapy has failed. Strict surveillance or surgery with removal of affected gonads should be considered in cases of long-standing or recurrent endometriomas, especially in the presence of modifications of ultrasonographic cyst patterns. Although rare, malignant transformation of various tissues in endometriosis patients has been described, and management is herein discussed.

Endometriotic ovarian cysts do not negatively affect the rate of spontaneous ovulation.

STUDY QUESTION: Do endometriotic ovarian cysts influence the rate of spontaneous ovulation? SUMMARY ANSWER: Endometriotic cysts, no matter what their volume, do not influence the rate of spontaneous ovulation in the affected ovary. WHAT IS KNOWN ALREADY: Endometriotic ovarian cysts may negatively affect spontaneous ovulation in the affected ovary. STUDY DESIGN, SIZE, DURATION: This was a prospective observational study performed between September 2009 and June 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study included women of reproductive age with regular menstrual cycles and unilateral ovarian endometriomas (diameter ≥20 mm) desiring to conceive. Exclusion criteria were: hormonal therapies in the 3 months prior to study entry and previous adnexal surgery. Patients underwent serial transvaginal ultrasound to assess the side of ovulation (for up to six cycles). MAIN RESULTS AND THE ROLE OF CHANCE: Ovulation was monitored in 1199 cycles in 244 women (age, mean ± SD, 34.3 ± 4.9 years). 55.3% of the patients had left endometriomas and 44.7% had right endometriomas (P = 0.024). The mean (±SD) diameter of the endometriomas was 5.3 cm (±1.7 cm). Ultrasonographically documented ovulation occurred in 596 cycles in the healthy ovary (49.7%; 95% CI, 46.8-52.6%) and in 603 cycles in the affected ovary (50.3%; 95% CI, 47.1-53.2%; P = 0.919). This observation was confirmed in patients with diameter of the cyst ≥4 cm (n = 166) and in those with diameter of the cyst ≥6 cm (n = 45). One hundred and five patients spontaneously conceived (43.0%; 95% CI, 36.7-49.5%). LIMITATIONS, REASON FOR CAUTION: The high pregnancy rate reported in this study was observed in a selected population of women with endometriomas and cannot be extrapolated to all patients with endometriosis. WIDER IMPLICATIONS OF THE FINDINGS: Since ovarian endometriomas do not impair spontaneous ovulation, the impact on fertility of surgical excision of ovarian endometriomas should be further investigated.

Obstetrics and Gynecology Emergency Department Activity during Lockdown in a Teaching Hospital, Hub Center, for COVID-19.

Background: The lockdown related to the SARS-CoV-2 pandemic has imposed profound changes in the interaction of the population with hospitals and emergency departments. The main aim of this research was to evaluate the impact of lockdown on the activity of obstetrics and gynecology emergency department (OGED) in a teaching hospital, hub center, for COVID-19. Methods: The study considers all visits to the OGED with their different triage color codes that represent the clinical severity of each case (from the most severe to the least one: red, yellow, green, white). Data were selected through the "PSNet" triage program and collected anonymously. We analyzed frequency distributions of the variables separately for each woman and calculated mean and standard deviations for continuous variables. We then analyzed the association between factors and outcomes for categorical variables (expressed as a number and percentage of the total) using the chi-square test (χ2). The level of significance was established with p < 0.05. Statistical analysis was performed using SPSS Statistics V20.0. Given the fact that the study has a retrospective observational nature and it is based on an anonymous routine database, approval by the Local Ethics Committee was not necessary. Results: The relative decrease of patients presenting to OGED in 2020 was -50.96%. The percentage of nonpregnant women was significantly lower in 2020 compared to 2019 (p ≤ 0.0001; Δ = -79.46%). Regarding the obstetric group, we saw an important decrease of visits in 2020 compared to 2019 (p < 0.0001; Δ = -40%). The prevalence of yellow codes was significantly higher in 2020 (Δ = +29.72%), while that of white (Δ = -61.58%) and green (Δ = -52.22%) codes was significantly lower (p ≤ 0.0001). Comparing the diagnoses at discharge, we could highlight significant reductions in 2020 for more than one diagnosis: bleeding (p ≤ 0.0001; Δ = -70.42%), pain (p ≤ 0.0001; Δ = -81.22%), urinary diseases (p = 0.004; Δ = -75.64%), and gastrointestinal diseases (p ≤ 0.0001; Δ = -87.50%). Conclusions: An evident change emerged in relation to the dynamics between the local obstetrical and gynecological population, and OGED resources. The COVID-19 lockdown greatly reduced the rate of admission to OGED without time-related obstetric and gynecological complications. The reduction of admissions suggests a more appropriate use of the ED by patients that may inspire future policies for the implementation of emergency services.

'Guess who'? An Italian multicentric study on pigmentation traits prevalence in endometriosis localizations.

OBJECTIVES: Previous evidence seems to support the more common presence of certain pigmentation types in women with endometriosis. The aim of this study was to assess the association of certain somatic phenotypes with specific localizations of the disease. The genetic makeup of those somatic traits may will help in better define the disease pathogenesis. STUDY DESIGN: Multicentric, retrospective study of women aged 18 to 45 with histologically confirmed endometriosis. 575 patients were recruited at eleven different Italian endometriosis clinics from March 2015 to January 2021. Data regarding clinical and surgical features were recorded following the self-administered endometriosis patient questionnaire and the surgical standard of reports approved by the World Endometriosis Research Foundation (WERF). Pigmentation types/somatic phenotypes frequencies among endometriosis localizations were reported. A logistic regression analysis was performed to determine somatic types independently associated with disease' localizations. RESULTS: Having green eyes increased by ∼4 folds (OR 3.7; 95% CI: 1.42-9.61; p = 0.007) the risk of having a ureteral nodule, whereas brown/black eyes decreased this risk (OR 0.34; 95% CI: 0.13-0.87; p = 0.025). Consistently, the combination of green eyes and blonde/light brown hairs increased the odds of ureteral endometriosis by more than 5 folds (OR 5.40; 95%CI: 2.02-14.49; p = 0.001), even after correction for anthropometric confounders (aOR 5.85; 95% CI: 2.13-16.09; p < 0.001). CONCLUSIONS: The association between endometriosis and pigmentary traits has been herein confirmed, with the novel finding of the possible predisposition of ureteral endometriosis in patients with green eyes and blonde/light brown hairs. Further investigation on the genetic makeup of somatic traits may provide new inroads also into the molecular aspects of endometriosis leading to a better understanding of this complex disease.

Multidetector computerized tomography enteroclysis vs. rectal water contrast transvaginal ultrasonography in determining the presence and extent of bowel endometriosis.

OBJECTIVES: To compare the accuracy of multidetector computerized tomography enteroclysis (MDCT-e) and rectal water contrast transvaginal ultrasonography (RWC-TVS) in determining the presence and extent of bowel endometriosis. METHODS: This prospective study included 96 patients of reproductive age with suspicion of bowel endometriosis. Patients underwent MDCT-e and RWC-TVS before operative laparoscopy. Findings of MDCT-e and RWC-TVS were compared with histological results. The severity of pain experienced during MDCT-e and RWC-TVS was measured by a 10-cm visual analog scale. RESULTS: Fifty-one patients had bowel endometriotic nodules at surgery. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy for the diagnosis of rectosigmoid endometriosis were 95.8% (46/48), 100.0% (48/48), 100.0% (46/46), 96.0% (48/50) and 97.9% (94/96) for MDCT-e and 93.8% (45/48), 97.9% (47/48), 97.8% (45/46), 94.0% (47/50) and 95.8% (92/96) for RWC-TVS. MDCT-e was associated with more intense pain than was RWC-TVS. CONCLUSIONS: MDCT-e and RWC-TVS have similar accuracy in the diagnosis of rectosigmoid endometriosis, but patients tolerate RWC-TVS better than they do MDCT-e.

Gestational Diabetes Mellitus: Clinical Characteristics and Perinatal Outcomes in a Multiethnic Population of North Italy.

AIM: To evaluate clinical characteristics and perinatal outcomes in a heterogeneous population of Caucasians born in Italy and High Migration Pressure Countries (HMPC) women with GDM living in Piedmont, North Italy. METHODS: We retrospectively analyzed data from 586 women referring to our unit (2015-2020). Epidemiological (age and country of origin) and clinical-metabolic features (height, weight, family history of DM, parity, previous history of GDM, OGTT results, and GDM treatment) were collected. The database of certificates of care at delivery was consulted in relation to neonatal/maternal complications (rates of caesarean sections, APGAR score, fetal malformations, and neonatal anthropometry). RESULTS: 43.2% of women came from HMPC; they were younger (p < 0.0001) and required insulin treatment more frequently than Caucasian women born in Italy (χ 2 = 17.8, p=0.007). Higher fasting and 120-minute OGTT levels and gestational BMI increased the risk of insulin treatment (OGTT T0: OR = 1.04, CI 95% 1.016-1.060, p=0.005; OGTT T120: OR = 1.01, CI 95% 1.002-1.020, p=0.02; BMI: OR = 1.089, CI 95% 1.051-1.129, p < 0.0001). Moreover, two or more diagnostic OGTT glucose levels doubled the risk of insulin therapy (OR = 2.03, IC 95% 1.145-3.612, p=0.016). We did not find any association between ethnicities and neonatal/maternal complications. CONCLUSIONS: In our multiethnic GDM population, the need for intensive care and insulin treatment is high in HPMC women although the frequency of adverse peripartum and newborn outcomes does not vary among ethnic groups. The need for insulin therapy should be related to different genetic backgrounds, dietary habits, and Nutrition Transition phenomena. Thus, nutritional intervention and insulin treatment need to be tailored.

Norethisterone acetate in the treatment of colorectal endometriosis: a pilot study.

BACKGROUND: This pilot study evaluates the efficacy of norethisterone acetate in treating pain and gastrointestinal symptoms of women with colorectal endometriosis. METHODS: This prospective study included 40 women with colorectal endometriosis, who had pain and gastrointestinal symptoms. Patients received norethisterone acetate (2.5 mg/day) for 12 months; in case of breakthrough bleeding, the dose of norethisterone acetate was increased by 2.5 mg/day. The degree of patient satisfaction with treatment (primary end-point) and the changes in symptoms (secondary end-point) were evaluated. Side effects of treatment were recorded. RESULTS: Norethisterone acetate determined a significant improvement in the intensity of chronic pelvic pain, deep dyspareunia, dyschezia. Treatment determined the disappearance of symptoms related to the menstrual cycle (dysmenorrhea, constipation during the menstrual cycle, diarrhoea during the menstrual cycle and cyclical rectal bleeding). The severity of diarrhoea, intestinal cramping and passage of mucus significantly improved during treatment. On the contrary, the administration of norethisterone acetate did not determine a significant effect on constipation, abdominal bloating and feeling of incomplete evacuation after bowel movements. At the completion of treatment, 57% of the patients with diarrhoea or diarrhoea during the menstrual cycle continued the treatment with norethisterone acetate compared with 17% of the patients with constipation or constipation during the menstrual cycle. CONCLUSIONS: In some patients with bowel endometriosis, the administration of norethisterone acetate may determine a relief of pain and gastrointestinal symptoms. This therapy has greater benefits in patients with gastrointestinal symptoms related to the menstrual cycle, diarrhoea and intestinal cramping.

Transvaginal ultrasonography with water-contrast in the rectum in the diagnosis of bowel endometriosis.

AIM: The rectosigmoid is the most frequent location of intestinal endometriosis. Although several techniques have been proposed for the diagnosis of intestinal endometriosis, no gold standard is currently available. In this review, we describe in details a new technique for the diagnosis of rectosigmoid endometriosis: rectal water-contrast transvaginal ultrasonography. METHODS: During transvaginal ultrasonography, an assistant inserts a 6-mm flexible catheter through the anal os into the rectal lumen; the insertion of this catheter is evaluated under ultrasonographic control. Water contrast is instilled slowly in the rectum to permit intestinal distension. The colonic wall evaluation is obtained by positioning the transvaginal probe against a length of the sigmoid colon to obtain either axial or longitudinal images. The injection of the saline solution facilitates the identification of recto-sigmoid endometriotic nodules which appear as rounded or triangular hypoechoic masses, located anterior or lateral to the bowel. RESULTS: This technique has high sensitivity and specificity in the diagnosis of rectal infiltration in women with rectovaginal endometriosis. The distance between the nodules and the mucosal layer permits to estimate the depth of infiltration of these endometriotic lesions within the intestinal wall. Rectal distensibility can be estimated. The procedure is well tolerated by the patients. CONCLUSION: Water distension of the rectum facilitates the identification of intestinal endometriosis during transvaginal ultrasonography.

Letrozole combined with norethisterone acetate compared with norethisterone acetate alone in the treatment of pain symptoms caused by endometriosis.

BACKGROUND: The available data on effectiveness of aromatase inhibitors in treating pain symptoms related to endometriosis is limited. We compared the efficacy and tolerability of the aromatase inhibitor letrozole combined with norethisterone acetate versus norethisterone acetate alone in treating pain symptoms. METHODS: This prospective, open-label, non-randomized trial included 82 women with pain symptoms caused by rectovaginal endometriosis. Patients received either a combination of letrozole and norethisterone acetate (group L) or norethisterone acetate alone (group N) for 6 months. Changes in pain symptoms during treatment and in the 12 months of follow-up were evaluated. Side effects of each treatment protocol were recorded. RESULTS: Intensity of chronic pelvic pain and deep dyspareunia significantly decreased during treatment (P < 0.001 versus baseline by 3 months) in both study groups. At both 3- and 6-month assessment, the intensity of chronic pelvic pain (P < 0.001, P = 0.002, respectively) and deep dyspareunia (P < 0.001, P = 0.005, respectively) was significantly lower in group L than group N. At completion of treatment, 63.4% of women in group N were satisfied with treatment compared with 56.1% in group L (P = 0.49). Pain symptoms recurred after the completion of treatment; at 6-month follow-up no difference was observed in the intensity of pain symptoms between the groups. Adverse effects were more frequent in group L than in group N (P = 0.02). CONCLUSIONS: The combination drug regimen was more effective in reducing pain and deep dyspareunia than norethisterone acetate; however, letrozole caused a higher incidence of adverse effects, cost more and did not improve patients' satisfaction or influence recurrence of pain.

Does transvaginal ultrasonography combined with water-contrast in the rectum aid in the diagnosis of rectovaginal endometriosis infiltrating the bowel?

BACKGROUND: The aim of this study was to determine whether adding water-contrast in the rectum during transvaginal ultrasonography (RWC-TVS) improves the diagnosis of rectal infiltration in women with rectovaginal endometriosis. METHODS: This prospective study included 90 women, with suspect rectovaginal endometriosis, who underwent operative laparoscopy. TVS and RWC-TVS were independently performed by different investigators. RWC-TVS was performed by injecting saline solution into the rectal lumen under ultrasonographic control through a 6-mm catheter. Presence of rectovaginal nodules, presence and degree of rectal infiltration, and the largest diameter of the bowel nodules were evaluated. Ultrasonographic results were compared to surgical and histological findings. RESULTS: Although RWC-TVS had higher accuracy than TVS in diagnosing rectovaginal endometriosis, the difference between the two techniques was not statistically significant. RWC-TVS was significantly more accurate than TVS in determining the presence of endometriotic infiltration reaching at least the muscular layer of the rectal wall. The sensitivity of RWC-TVS in identifying rectal lesions was 97%, the specificity 100%, the positive predictive value 100% and the negative predictive value 91.3%. RWC-TVS caused a higher intensity of pain than TVS. CONCLUSIONS: RWC-TVS determines the presence of rectovaginal nodules infiltrating the rectal muscularis propria more accurately than TVS; RWC-TVS could be used when TVS cannot exclude the presence of rectal infiltration.

Surgical outcome and long-term follow up after laparoscopic rectosigmoid resection in women with deep infiltrating endometriosis.

The aim of this study was to assess the long-term outcome of treating severely symptomatic women with deep infiltrating intestinal endometriosis by laparoscopic segmental rectosigmoid resection. Detailed intraoperative and postoperative records and questionnaires (preoperatively, 1 month postoperatively and every 6 months for 3 years) were collected from 22 women. The estimated blood loss during surgery was 290 +/- 162 ml (range 180-600), and average hospital stay was 8 days (range 6-19). One woman required blood transfusion after surgery. Two cases were converted to laparotomy. One woman had early dehiscence of the anastomosis. Six months after surgery, there was a significant reduction of symptom scores (greater than 50% for most types of pain) related to intestinal localisation of endometriosis (P < 0.05). Score improvements were maintained during the whole period of follow up. Noncyclic pelvic pain scores showed significant reductions (P < 0.05) after 6 and 12 months, but there was a high recurrence rate later. Dysmenorrhoea and dyspareunia improved in 18/21 and 14/18 women with preoperative symptoms, respectively. Constipation, diarrhoea and rectal bleeding improved in all affected women for the whole period of follow up. Laparoscopic segmental rectosigmoid resection seems safe and effective in women with deep infiltrating colorectal endometriosis resulting in significant reductions in painful and dysfunctional symptoms associated with deep bowel involvement.

Hydrothorax following ovarian hyperstimulation for assisted reproduction. Case report and review of the literature.

In case of ovarian hyperstimulation syndrome, the high incidence of dyspnea in relation with ascites and enlarged ovaries should not justify omission of thoracic evaluation. This manuscript reviews the pathogenesis and clinical presentation of hydrothorax following controlled ovarian hyperstimulation. In addition, we describe the case of a 33-year-old woman with a right massive hydrothorax resulting from controlled ovarian hyperstimulation for intracytoplasmic sperm injection.

Antiangiogenic therapies in endometriosis.

Oral contraceptives, androgenic agents, progestins and gonadotropin-releasing hormone analogues have all been successfully used in the treatment of endometriosis. However, none of these drugs can eradicate the disease. It is widely accepted that the growth of newly formed blood vessels is essential for the establishment and growth of endometriotic lesions; therefore, inhibition of angiogenesis may offer a new option for treatment of this disorder. In this paper, we reviewed anti-vascular endothelial growth factor agents and other angiostatic drugs (i.e., TNP470, endostatin, anginex, rapamycin) that have been studied in laboratory and animal models of endometriosis. Although preliminary results are interesting, further investigations are required before clinical trials can be planned in humans.

Naltrexone in functional hypothalamic amenorrhea and in the normal luteal phase.

Fifteen young women with a diagnosis of secondary hypothalamic amenorrhea of at least 2 years' duration were given either 50 mg naltrexone daily or placebo, following a randomized double-blind crossover scheme. Seven patients did not menstruate with either therapy. In the other eight, the following results were recorded (mean +/- SD and range): a cycle length of 28.7 +/- 7.6 (12-45) days for naltrexone compared with 30.8 +/- 5.9 (16-43) days for placebo, a follicular phase length of 20.8 +/- 5.4 (14-34) days for naltrexone and 23.2 +/- 4.3 (19-32) days for naltrexone and 8.3 +/- 1.6 (5-10) days for placebo. The number of ovulatory cycles was 18 of 24 (75%) with naltrexone and eight of 24 (33%) with placebo (P less than .05). Most luteal phases were short. In five normally menstruating women, we gave either naltrexone or placebo in the luteal phase using a crossover blinded scheme. Steroidogenesis in the normal luteal phase was not impaired by naltrexone therapy. In functional hypothalamic amenorrheic patients with normal weight, menstruation might be restored by either placebo or naltrexone, but naltrexone provides a clinical and therapeutic advantage by increasing the ovulation rate.

Unexpected pregnancies after tubal recanalization failure with selective catheterization.

OBJECTIVE: To evaluate selective salpingography sensitivity. DESIGN: Retrospective study. SETTING: Obstetrics and Gynecology Department, University of Genoa, Italy. PATIENTS: One hundred seventeen patients previously submitted to selective salpingography because of unilateral or bilateral proximal tubal injection failure. RESULTS: Seven pregnancies, one of which was ectopic, were obtained in 17 patients who had only recanalized tubes available for conception; 15 pregnancies were obtained in 39 patients who had one tube recanalized and one already patent; 3 tubal pregnancies were obtained in 12 patients who had only one tube already patent; 4 pregnancies, one of which was ectopic, were obtained in 19 patients who had neither patent nor recanalized tubes. CONCLUSIONS: Selective salpingography can give false-positive results; therefore, it is possible to obtain a pregnancy even after selective salpingography failure.

Use of combined exogenous gonadotropins and pulsatile gonadotropin-releasing hormone in patients with polycystic ovarian disease.

We previously tested a combined regimen based on the administration of gonadotropin in the early follicular phase followed by pulsatile gonadotropin-releasing hormone (GnRH) until complete follicular maturation in patients suffering from polycystic ovarian disease. Despite good clinical results, a high rate of premature luteinization was observed with this approach. We therefore evaluated in this study whether starting pulsatile GnRH therapy before gonadotropin administration might reduce premature luteinization. Eight women underwent induction of ovulation with both combined therapy and pure exogenous follicle-stimulating hormone alone using a crossover scheme. No premature luteinization and a single follicular growth were recorded with the modified combined regimen. Clinical results (8/8 versus 3/7 ovulatory cycles; 3/8 versus 1/7 pregnancies) favor the combined approach over gonadotropin alone.