Ethanol endometrioma sclerotherapy: safety through 8 years of experience.

STUDY QUESTION: What are the complications of transvaginal ethanol sclerotherapy for the treatment of endometriomas? SUMMARY ANSWER: Sclerotherapy is a reliable, minimally invasive method applicable in outpatient procedures but with specific and potential life-threatening complications that need to be identified and prevented. WHAT IS KNOWN ALREADY: There are currently few data on the use of transvaginal ethanol sclerotherapy, and we mainly note septic complications. STUDY DESIGN, SIZE, DURATION: A retrospective observational cohort study was carried out. The study was conducted at an academic hospital and included 126 women aged 31.9 ± 5.5 years (mean ± SD), between November 2013 and June 2021. We analyzed a total of 157 ethanol sclerotherapy treatment (EST), treated by 131 EST procedures, in 126 women. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study included women with an indication for transvaginal ethanol sclerotherapy. Indications were women with at least one endometrioma over 10 mm, isolated or associated with other endometriosis locations, requiring treatment for pain or infertility before assisted reproductive treatment. We followed a standardized transvaginal ethanol sclerotherapy procedure consisting of an ultrasound-guided transvaginal puncture of one or more endometriomas under general anesthesia. The cyst content was completely removed and flushed with saline solution. Ethanol (96%) was injected at 60% of the initial volume of the endometrioma, remained in the cyst for 10 min and was then completely removed. Ethanol loss was defined as a loss of 5 ml or more than 10% of the initial volume of the injected ethanol. Failure was defined by the contraindication of endometrioma puncture because of interposition of the digestive tract, ethanol loss in the previous endometrioma treated (in case of multiple ESTs), failure to aspirate the endometriotic fluid, contraindication to start ethanol injection owing to saline solution leakage, or contraindication to continue ethanol injection owing to suspicions of ethanol leakage at sonography. Intraoperative complications were defined by ethanol loss, positive blood alcohol level, and ethanol intoxication. Postoperative complications were defined by fever, biological inflammatory syndrome, and ovarian abscess. Complications were classified according to the Clavien and Dindo surgical classification, which is a system for classifying postoperative complications in five grades of increasing severity. MAIN RESULTS AND THE ROLE OF CHANCE: We reported a total of 17/157 (10.8%) transvaginal ethanol sclerotherapy failures during 14/131 (10.7%) transvaginal ethanol sclerotherapy procedures in 13/126 (10.3%) women. In the same sets of data, complication was reported for 15/157 (9.5%) transvaginal ethanol sclerotherapy in 13/131 (9.9%) transvaginal ethanol sclerotherapy procedures in 13/126 (10.3%) women. Nine of 126 women (7.1%) had a grade I complication, one (0.8%) had a grade II complication (medical treatment for suspicion of pelvic infection), two (1.6%) had a grade III complication (ovarian abscess) and one (0.8%) had a grade IV complication (ethanol intoxication). We did not observe any grade V complications. LIMITATIONS, REASONS FOR CAUTION: This was a retrospective study and pain assessment not considered. The benefit-risk balance of endometrioma transvaginal ethanol sclerotherapy was not evaluated. WIDER IMPLICATIONS OF THE FINDINGS: Our study is the first to evaluate the complications of transvaginal ethanol sclerotherapy with such a large cohort of women in a standardized protocol. Transvaginal ethanol sclerotherapy seems to be an effective alternative to laparoscopic surgery in the management of endometriomas and limits the alteration of ovarian reserve. Transvaginal ethanol sclerotherapy is a reliable, minimally invasive method applicable on an outpatient basis. The majority of complications are Clavien-Dindo ≤IV, for which preventative measures, or at least early diagnosis and treatment, can be easily performed. The risk of ethanol intoxication is rare, but it is a life-threatening risk that must be avoided by appropriate implementation and promotion of the sclerotherapy procedures. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: Aix Marseille University's ethics committee registration number 2021-06-03-01.

Tocilizumab is effective in preventing ovarian injury induced by ischemia- reperfusion in rats.

Ovarian torsion can be defined as the bending of the ovaries on the supporting ligament, disrupting both venous and arterial blood circulation. Insufficient blood flow causes ovarian tissue hypoxia and leads to ischemia. This study aimed to investigate whether tocilizumab has a protective effect on ischemia-reperfusion injury due to ovarian torsion in rats. Eighteen female Wistar albino rats were divided into three equal groups (Sham (SG), ischemia-reperfusion (OIR), and ischemia-reperfusion+tocilizumab (OIRT)). Degeneration, necrosis, vascular dilatation/congestion, interstitial edema, hemorrhage, and polymorphonuclear lymphocyte (PMNL) infiltration scores were significantly different between the groups (p=0.001 for all parameters). Moreover, the OIRT group had a significant improvement in these criteria compared to the OIR group (p<0.05). Additionally, there was a considerable difference between OIRT and OIR groups in the number of primordial, developing, and atretic follicles groups (p<0.05), while there was no difference in the number of corpus luteum (p=0.052). Stress markers or cytokines, such as MDA, tGSH, NF-κB, TNF-α, IL-1ß, and IL-6, were significantly different between groups (p<0.05). Furthermore, a significant improvement was found in the measured variables when the OIRT group was compared with the OIR group (p<0.05). Tocilizumab may be an alternative option for treating ischemia-reperfusion injury due to ovarian torsion.

Endometriosis is a risk factor for recurrent pelvic inflammatory disease after tubo-ovarian abscess surgery.

PURPOSE: To evaluate the clinical outcomes and prognosis of patients undergoing laparoscopic surgery for tubo-ovarian abscess (TOA) and identify risk factors for pelvic inflammatory disease (PID) recurrence. METHODS: We conducted a retrospective cohort analysis including 98 women who underwent laparoscopic surgery for TOA at the Department of Obstetrics and Gynecology at the Bern University Hospital from January 2011 to May 2021. The primary outcome studied was the recurrence of PID after TOA surgery. Clinical, laboratory, imaging, and surgical outcomes were examined as possible risk factors for PID recurrence. RESULTS: Out of the 98 patients included in the study, 21 (21.4%) presented at least one PID recurrence after surgery. In the univariate regression analysis, the presence of endometriosis, ovarian endometrioma, and the isolation of E. coli in the microbiology cultures correlated with PID recurrence. However, only endometriosis was identified as an independent risk factor in the multivariate analysis (OR (95% CI): 9.62 (1.931, 47.924), p < 0.01). With regard to the time of recurrence after surgery, two distinct recurrence clusters were observed. All patients with early recurrence (≤ 45 days after TOA surgery) were cured after 1 or 2 additional interventions, whereas 40% of the patients with late recurrence (> 45 days after TOA surgery) required 3 or more additional interventions until cured. CONCLUSION: Endometriosis is a significant risk factor for PID recurrence after TOA surgery. Optimized therapeutic strategies such as closer postsurgical follow-up as well as longer antibiotic and hormonal therapy should be assessed in further studies in this specific patient population.

APOE4 genotype exacerbates the impact of menopause on cognition and synaptic plasticity in APOE-TR mice.

The impact of sex and menopausal status in Alzheimer's disease remains understudied despite increasing evidence of greater female risk, particularly in APOE4 carriers. Utilizing female APOE-TR mice maintained on a high-fat diet background we induced ovarian failure through repeated VCD injections, to mimic human menopause. At 12 months of age, recognition memory and spatial memory were assessed using object recognition, Y-maze spontaneous alternation, and Barnes maze. A VCD*genotype interaction reduced the recognition memory (P < .05), with APOE4 VCD-treated animals unable to distinguish between novel and familiar objects. APOE4 mice displayed an additional 37% and 12% reduction in Barnes (P < .01) and Y-maze (P < .01) performance, indicative of genotype-specific spatial memory impairment. Molecular analysis indicated both VCD and genotype-related deficits in synaptic plasticity with BDNF, Akt, mTOR, and ERK signaling compromised. Subsequent reductions in the transcription factors Creb1 and Atf4 were also evident. Furthermore, the VCD*genotype interaction specifically diminished Ephb2 expression, while Fos, and Cnr1 expression reduced as a consequence of APOE4 genotype. Brain DHA levels were 13% lower in VCD-treated animals independent of genotype. Consistent with this, we detected alterations in the expression of the DHA transporters Acsl6 and Fatp4. Our results indicate that the combination of ovarian failure and APOE4 leads to an exacerbation of cognitive and neurological deficits.

Ovarian torsion: diagnosis, surgery, and fertility preservation in the pediatric population.

Ovarian torsion is rare in the pediatric population. Delayed diagnosis can significantly impact fertility. The aim of this review is to highlight current knowledge regarding clinical presentation, diagnosis, surgical management, and follow-up in the pediatric population. Whilst the presentation is often very unspecific, most children will present with sudden severe unilateral pelvic pain associated with vomiting. A key diagnostic test is pelvic ultrasonography, which may help demonstrate an asymmetric enlarged ovary with peripherally displaced follicles. In the pediatric population, ovarian torsion may occur in a normal ovary. However, underlying lesions can be found in half of cases. Benign neoplasms (teratomas or cystic lesions) represent the commonest etiology, with the risk of malignancy being less than 2%. Surgical management should be focused on fertility preservation. This is achievable through ovarian detorsion ± ovarian cystectomy ± oophoropexy to avoid recurrence. Follow-up studies demonstrate excellent recovery rates of detorsed ovaries including those with ischemic appearances. What is Known: • Ovarian torsion is a rare diagnosis in the pediatric population. • Aspecific symptoms and differential diagnoses lead to missed or delayed diagnosis increasing the risk of oophoprectomy and further infertility. What is New: • Reviewing the latest knowledge about clinical presentation, diagnostic, surgical management, and follow-up of ovarian torsion in the pediatric population. • Adiponectin was negatively associated with diastolic blood pressure and HOMA-IR, and chemerin was negatively associated with glucose.

Efficacy of intrauterine insemination in women with endometrioma-associated subfertility: analysis using propensity score matching.

BACKGROUND: Intrauterine insemination (IUI) treatment is recommended in subfertile women with AFS/ASRM stage I/II endometriosis. However, the efficacy of IUI in women with ovarian endometriomas with tubal patency is uncertain. We explored the efficacy of IUI for the treatment of endometrioma-associated subfertility. METHODS: We performed a retrospective matched cohort study using propensity matching (PSM) analysis. Subfertile couples undergoing IUI with and without ovarian stimulation between January 1, 2015, and May 30, 2020 were reviewed. RESULTS: After PSM, 56 women with endometrioma alone were matched to 173 patients with unexplained subfertility. The per-cycle pregnancy rate (PR) was comparable between women with endometrioma-associated subfertility (n = 56, 87 cycles) and women with unexplained subfertility (n = 173, 280 cycles) (9.2% vs. 17.9%, OR 0.47; 95% CI, 0.21-1.03). Subgroup analyses based on IUI with or without stimulation also resulted in comparable results. A trend toward a lower cumulative pregnancy rates (CPRs) was seen in women with endometrioma (14.3%, 8/56) compared with women with unexplained subfertility (28.9%, 50/173), but the differences were not significant (HR 0.49; 95% CI, 0.23-1.15). However, patients with endometrioma were nearly twice as likely to converse to IVF treatment compared with those without the disease (60.7% versus 43.9%; OR 1.97; 95% CI, 1.07-3.65). CONCLUSION: IUI may be a viable approach for subfertile women with endometrioma and no other identifiable infertility factor. More studies are needed to reassure the findings.

Factors associated with an unfavorable clinical course in hospitalized patients with pelvic inflammatory disease: a retrospective cohort study of 117 patients from a Japanese academic institution.

BACKGROUND: This study aimed to determine the factors associated with an unfavorable clinical course (emergency surgery and/or prolonged hospitalization) in patients requiring hospitalization owing to pelvic inflammatory disease (PID). METHODS: A retrospective study was performed on 117 patients diagnosed with PID who were admitted to our hospital between January 2014 and December 2018. Multivariate regression analysis was conducted to determine the factors associated with emergency surgical intervention, and prolonged hospitalization in a subgroup of successful expectant management (n = 93). RESULTS: The average age (mean ± standard deviation) of the patients was 41.2 ± 12.5 years; 16 (13.7%) were postmenopausal; 81 patients (69.2%) complicated with a tubo-ovarian abscess (TOA) of which 59 (72.9%) had an ovarian endometrioma; and 19 patients (16.2%) had a history of various intrauterine manipulations. Emergency surgery was performed in 24 patients (20.5%), and patients with TOA underwent emergency surgery more often than did patients without TOA (25.9% vs. 8.3%, p = 0.03), and TOA was associated with longer length of hospital stay (17.1 days vs. 8.0 days, p = 0.01). Smoking, postmenopausal status, past medical history of PID, and high C-reactive protein (CRP) level at admission were significantly associated with emergency surgery. In patients with successful expectant management, obesity (body mass index ≥ 30) and high WBC and CRP level at admission were significantly associated with prolonged hospitalization. CONCLUSIONS: Of the patients requiring hospitalization owing to PID, TOA was associated with both emergency surgery and prolonged hospital stay. Patients with increased inflammatory markers and obesity should be considered to be at a high risk for unfavorable clinical course in the management of PID.

Impact on ovarian reserve and fertility using carbon dioxide laser for endometriosis treatment: a systematic review.

BackgroundThe application of carbon dioxide (CO2) laser for laparoscopic gynecologic surgery was introduced in 1979 and spread after improving instrumentation, due to the versatility of the CO2 laser technology and the parallel increase of laparoscopic use. In a gynecologic setting, laser laparoscopy has been demonstrated to be effective in treating infertility and pain associated with mild to severe endometriosis.Aim and methods: This document aims at conducting a systematic review to provide a comprehensive literature overview regarding the rationale, indications, safety, and efficacy of CO2 laser treatment of endometriosis and related outcomes on ovarian reserve and fertility.ResultsCO2 laser seems to lead to lower heat damage in the ovarian tissue than bipolar energy during endometriomas treatment. Moreover, several reports have pointed out that laser vaporization allows to selectively destroy the endometrioma wall's internal surface, preserving the pericystic fibrotic capsule or the adjacent healthy ovarian cortex. Despite this, robust data we have so far indicates that the most effective laparoscopic approach for managing endometriomas is the traditional excisional technique providing better postoperative outcomes than drainage and electrocoagulation, and laser treatment. Data about fertility after treatment of deep infiltrating endometriosis (DIE) using dioxide laser are emerging but very poor.ConclusionsCurrent scientific evidence in this field is inconclusive, and the debate about the safety and efficacy of the CO2 laser on fertility outcomes is still ongoing. Further randomized case-control studies are mandatory to attain more consistent evidence.

The effect of protection of platelet-rich plasma against experimental ischemia/reperfusion injury in the rat ovary on in vitro fertilization outcomes.

OBJECTIVE: Ovarian torsion is a common cause of local ischemic damage, reduced follicular activity and infertility. This study aimed to investigate how well platelet-rich plasma (PRP) protects against experimental ischemic (I) and ischemia-reperfusion (I/R) injury in rat ovaries and its effect on in vitro fertilization (IVF) outcomes. METHOD: Fifty-six adult female Sprague-Dawley albino rats were randomly assigned to six groups of eight animals each: Sham, Ischemia, I/R, Sham + PRP, I + PRP, and I/R + PRP. The remaining eight animals were used to prepare the PRP. The ischemia groups were subjected to bilateral adnexal torsion for 3 h, while the I/R and I/R + PRP groups received subsequent detorsion for 3 h. Intraperitoneal (i.p.) PRP was administered 30 min prior to ischemia (I + PRP) or reperfusion (I/R + PRP). The ovaries were stimulated through an intraperitoneal injection of 150-300 internal units of IU/kg PMSG. After ovulation induction, oocytes were taken from the ovaries, and IVF was performed. RESULTS: The number of MII oocytes reached the highest number with 4.63 ± 0.74 in the S group and had the lowest number with 0.50 ± 0.53 in the I/R group. There were statistically significant differences for the number of embryos obtained on the second day between the I and I + PRP groups and the I/R and I/R + PRP groups (p = 0.000). In comparing anti-Müllerian hormone 1 (AMH1) and AMH2 values within the group, the highest decrease was observed in the I and I/R groups. CONCLUSION: PRP is effective in minimizing ovarian damage and preserving ovarian reserves following ovarian torsion.

An Insidious Cause of Abdominal Pain in a Preschooler Girl: The Asynchronous Bilateral Ovarian Torsion.

ABSTRACT: The ovarian torsion (OT) represents one of the most misleading and challenging diagnoses for the pediatrician. Symptoms are often nonspecific, including sudden, piercing localized lower abdominal pain and tenderness associated with a palpable mass and peritoneal signs. Although the adnexal torsion is most frequently unilateral, cases of bilateral synchronous or asynchronous have been recorded; in the latter, the OT involved both ovaries at different settings. We reported the case of a 6-year-old girl who presented an asynchronous bilateral OT.

Luteinised unruptured follicle syndrome: pathophysiological background and new target therapy in assisted reproductive treatments.

Luteinised unruptured follicle syndrome (LUFS) is a cause of infertility consisting in the unruptured of the dominant follicle after the LH-surge. In fact, during assisted reproductive treatments (ART) clomiphene citrate and letrozole are frequently administered in order to achieve ovulation. However, considering the pathophysiology of LUFS, new possible therapy can be proposed. On this scenario, we performed a review of the literature searching for LUFS recurrency and its impact in infertility and ART. An inflammation theory has been proposed that can be fuel for further therapeutic possibilities. In particular, considering the increase in granulocytes accumulation, the granulocyte colony-stimulating factor (G-CSF) administration has been proposed as target therapy in IUI cycles hampered by LUFS. Although data are encouraging, randomised controlled trials are needed in order to confirm the efficacy of G-CSF administration for LUFS patients.

UHPLC-MS-MS analysis of oxylipins metabolomics components of follicular fluid in infertile individuals with diminished ovarian reserve.

BACKGROUND: Diminished ovarian reserve (DOR) refers to a decrease in the number and quality of oocytes in the ovary, which results in a lack of sex hormones and a decline of fertility in women. DOR can potentially progress to premature ovarian failure (POF), which has a negative impact on women's quality of life and is a major cause of female infertility. Oxidative stress is a major contributor to fertility decrease in DOR patients, affecting the follicular microenvironment, oocyte maturation, fertilization, and embryo development. Understanding intracellular signal transduction can be achieved by defining specific oxidized lipid components in follicular fluid (FF) of DOR infertile patients. METHODS: The oxylipins metabolic signatures in the FF of DOR patients and females with normal ovarian reserve (NOR) enrolled for the in vitro fertilization (IVF) cycle were analyzed using UHPLC-MS-MS technology. Principal component analysis (PCA) and orthogonal projections to latent structure discriminant analysis (OPLS-DA) were used to analyze the derived metabolomic profiles. Pathway enrichment analysis was carried out using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and MetaboAnalyst databases. Furthermore, the Spearman rank correlation coefficient was used to determine the correlation between age, FSH, AMH, AFC, oocytes retrieved, MII oocytes, fertilization, high-quality embryos, and the concentration of differential oxidized lipid metabolites in FF. RESULTS: Fifteen oxylipins metabolites were found to be lower in the FF of DOR patients than those in the NOR group, including ±20-HDoHE, ±5-iso PGF2α-VI, 12S-HHTrE, 15-deoxy-Δ12,14-PGJ2, 1a,1b-dihomo PGE2, 1a,1b-dihomo PGF2α, 20-COOH-AA, 20-HETE, 8S,15S-DiHETE, PGA2, PGD2, PGE1, PGF1α, PGF2α, and PGJ2. The pathway enrichment analysis revealed that the 15 differentially oxidized lipid metabolites were closely related to the arachidonic acid metabolic pathway. Correlation analysis revealed that the concentration of 8 different oxidized lipid metabolites in FF was negatively correlated to FSH and positively correlated with AFC. AMH, the number of oocytes retrieved, MII oocytes and fertilization, were all positively correlated with 9 different oxidized lipid metabolites, but only one metabolite was positively correlated with the number of high-quality embryos. CONCLUSIONS: Metabolomic analysis of FF revealed that oxylipins metabolism disorders were closely related to ovarian reserve function. Among these oxylipins metabolites, arachidonic acid metabolism undergoes significant changes that may be related to oocyte development, resulting in decreased fertility in DOR patients. TRIAL REGISTRATION: ChiCTR, ChiCTR2000038182 , Registered 12 September 2020-Retrospectively registered.

Impact of endometriosis on oocyte morphology in IVF-ICSI: retrospective study of a cohort of more than 6000 mature oocytes.

BACKGROUND: Infertility associated with endometriosis can be explained by several non-exclusive mechanisms. The oocyte plays a crucial role in determining embryonic competence and this is particularly relevant for in vitro fertilization (IVF) outcomes. According to some authors, the morphology of oocytes could also be a non-invasive marker of oocyte quality. The aim of this study was to evaluate the relationship between endometriosis and oocyte morphology after controlled ovarian stimulation for intracytoplasmic sperm injection (ICSI) on a large oocyte cohort. METHODS: Single-center comparative retrospective study in the academic In Vitro Fertilization (IVF) unit of the Lille University Hospital. A total of 596 women treated for IVF-ICSI with ejaculated spermatozoa for sperm alterations were included. They were classified as endometriosis (n = 175) or control groups (n = 401). The morphological evaluation of 2,016 mature oocytes from 348 cycles of patients with endometriosis was compared with that of 4,073 mature oocytes from 576 control cycles. The main outcome measures were Average Oocyte Quality Index (AOQI) and metaphase II oocyte morphological scoring system (MOMS). Comparison of groups was carried out by a mixed linear model and by a generalized estimation equation model with a "patient" random effect to consider that a patient might have several attempts. RESULTS: No difference in AOQI and MOMS scores was found between endometriosis and control women (adjusted p = 0.084 and 0.053, respectively). In case of endometriosis, there were significantly fewer metaphase II oocytes retrieved, embryos obtained, grade 1 embryos and number of cumulative clinical pregnancies compared to controls. In the endometriosis group, endometriosis surgery was associated with a reduced number of mature oocytes retrieved, and the presence of endometrioma(s) was associated with some abnormal oocyte shapes. Nevertheless, no difference concerning the AOQI and MOMS scores was found in these subgroups. CONCLUSION: Endometriosis does not have a negative impact on oocytes' morphology in IVF-ICSI. TRIAL REGISTRATION: On December 16, 2019, the Institutional Review Board of the Lille University Hospital gave unrestricted approval for the anonymous use of all patients' clinical, hormonal and ultrasound records (reference DEC20150715-0002).

Improvements in PCOS characteristics and phenotype severity during a randomized controlled lifestyle intervention.

RESEARCH QUESTION: What is the effect of weight loss through different interventions (three-component lifestyle intervention with short message service [SMS+] versus three-component lifestyle intervention without SMS [SMS-] versus care as usual [CAU]) on polycystic ovary syndrome (PCOS) characteristics (ovulatory dysfunction, hyperandrogenism, polycystic ovarian morphology [PCOM]) and phenotype distribution? DESIGN: Analysis of secondary outcome measures of a randomized controlled trial. Women diagnosed with PCOS (n = 183), who wished to become pregnant, with a body mass index above 25 kg/m², were assigned to a 1-year three-component (cognitive behavioural therapy, diet, exercise) lifestyle intervention group, with or without SMS, or to CAU (advice to lose weight). RESULTS: The prevalence of biochemical hyperandrogenism was 30.9% less in the SMS- group compared with CAU after 1 year (P = 0.027). Within-group analyses revealed significant improvements in ovulatory dysfunction (SMS+: -39.8%, P = 0.001; SMS-: -30.5%, P = 0.001; CAU: -32.1%, P < 0.001), biochemical hyperandrogenism (SMS-: -27.8%, P = 0.007) and PCOM (SMS-: -14.0%, P = 0.034). Weight loss had a significantly favourable effect on the chance of having ovulatory dysfunction (estimate 0.157 SE 0.030, P < 0.001) and hyperandrogenism (estimate 0.097 SE 0.027, P < 0.001). CONCLUSIONS: All groups demonstrated improvements in PCOS characteristics, although these were more profound within the lifestyle intervention groups. Weight loss per se led to an amelioration of diagnostic characteristics and in the phenotype of PCOS. A three-component lifestyle intervention aimed at a 5-10% weight loss should be recommended for all women with PCOS before they become pregnant.

Ovarian cancer prognosis in women with endometriosis: a retrospective nationwide cohort study of 32,419 women.

BACKGROUND: Contradicting results regarding ovarian cancer prognosis in women with endometriosis have been reported in the literature. Owing to the small sample size of previous studies, larger studies are required to elucidate the role of endometriosis in ovarian cancer prognosis. OBJECTIVE: This study aimed to evaluate the survival rate in women with ovarian cancer with or without histologically proven endometriosis in a Dutch population-based cohort. STUDY DESIGN: All women with ovarian cancer diagnosed between 1990 and 2015 were identified from the Netherlands Cancer Registry. We linked these women with the Dutch nationwide registry of histopathology and cytopathology (Pathologisch-Anatomisch Landelijk Geautomatiseerd Archief) to identify all women with histologically proven endometriosis. We compared the prognosis of patients with ovarian cancer with and without histologically proven endometriosis. Primary outcome was the overall survival with subgroup analyses stratified by histologic ovarian cancer subtype and stage. Multivariable Cox proportional hazard analysis was used to estimate hazard ratios with 95% confidence intervals. RESULTS: We included 32,419 patients with ovarian cancer, of whom 1979 (6.1%) had histologically proven endometriosis. The median age of histologic endometriosis diagnosis was 53 years (interquartile range, 46-62). Of all women with ovarian cancer and endometriosis, 81.2% received a diagnosis of synchronous endometriosis and ovarian cancer. The endometriosis cohort was younger at ovarian cancer diagnosis, had more favorable tumor characteristics, and more often had surgical treatment for ovarian cancer than the women without endometriosis. These variables were included in the multivariable model as confounders. Women with histologically proven endometriosis had a significantly better prognosis in both crude and adjusted analyses (hazard ratio, 0.46; 95% confidence interval, 0.43-0.49; P<.0005, and adjusted hazard ratio, 0.89; 95% confidence interval, 0.83-0.95; P<.05, respectively). CONCLUSION: Women with ovarian cancer and histologically proven endometriosis had longer overall survival than women with ovarian cancer without endometriosis, even after adjustment for confounders. Future studies on ovarian cancer treatment and prognosis should consider stratifying by endometriosis status to elucidate its role. Furthermore, women diagnosed as having ovarian cancer and concurrent endometriosis should be explained the role of endometriosis in ovarian cancer survival.

Risk factors for the development of tubo-ovarian abscesses in women with ovarian endometriosis: a retrospective matched case-control study.

BACKGROUND: The purpose of this study was to assess the risk factors associated with the development of tubo-ovarian abscesses in women with ovarian endometriosis cysts. METHODS: This retrospective single-center study included 176 women: 44 with tubo-ovarian abscesses associated with ovarian endometriosis and 132 age-matched (1:3) patients with ovarian endometriosis but without tubo-ovarian abscesses. Diagnoses were made via surgical exploration and pathological examination. The potential risk factors of tubo-ovarian abscesses associated with ovarian endometriosis were evaluated using univariate analysis. The results (p ≤ 0.05) of these parameters were analyzed using a multivariate model. RESULTS: Five factors were included in the multivariate conditional logistic regression model, including in vitro fertilization, presence of an intrauterine device, lower genital tract infection, spontaneous rupture of ovarian endometriosis cysts, and diabetes mellitus. The presence of a lower genital tract infection (odds ratio 5.462, 95% CI 1.772-16.839) and spontaneous rupture of ovarian endometriosis cysts (odds ratio 2.572, 95% CI 1.071-6.174) were found to be statistically significant risk factors for tubo-ovarian abscesses associated with ovarian endometriosis. CONCLUSIONS: Among the factors investigated, genital tract infections and spontaneous rupture of ovarian endometriosis cysts were found to be involved in the occurrence of tubo-ovarian abscesses associated with ovarian endometriosis. Our findings indicate that tubo-ovarian abscesses associated with ovarian endometriosis may not be linked to in vitro fertilization as previously thought.

Clinical characteristics, treatment status and complications in women with tube ovarian abscess and endometriosis: a retrospective study.

BACKGROUND: The aim of our present study was to investigate the clinical characteristics, treatment status and complications in women with endometriosis (EM) and tube ovarian abscess (TOA) to determine the possible association between TOA and EM. METHODS: Medical records were used to analyze the clinical characteristics, treatment and complications. Twenty women who were diagnosed with TOA with EM were compared with 93 women diagnosed as having TOA without EM between January, 2008 and December, 2018. RESULTS: In this study, TOA patients with EM were significantly more likely to have a lower age range (20-39 years) than the non-EM group [11/20 (55.0%) vs 27/93 (29.0%)]. In addition, TOA patients with EM were associated with a significantly lower rate of parity [11/20 (55.0%) vs 75/93 (80.6%)], higher rates of infertility [8/20(40%) vs 0/93(0%)] and a significantly lower incidence of elevated blood platelet counts [5/20 (25%) vs 43/93 (46.2%)]. Furthermore, women with EM had greater blood loss (347 ± 445.77 vs 204.67 ± 289.46) and an increased complication rate [3/20(15%) vs 0/93(0%)]. Among the 3 patients who had complications in the EM group, 2 patients had septic shock and 1 patient had intestinal obstruction. And 1 case who had septic shock followed by IVF treatment. There was no significance difference on other factors. CONCLUSIONS: The present study indicated that EM did not increase the difficulty and time of treatment in patients with TOA, but increased bleeding during surgery and serious complications. It is suggested that doctors should pay more attention to postoperative treatment and nursing in women with TOA and EM, especially those who have a history of recent infertility treatment and related procedures.

Hyperthecosis: an underestimated nontumorous cause of hyperandrogenism.

Hyperthecosis is defined as the presence of nests of luteinized theca cells in the ovarian stroma. Persistent testosterone released by ovarian theca cells is unmasked postmenopausally through the loss of granulosa cell-mediated aromatization of testosterone to estradiol. Ovarian hyperthecosis (OH) usually presents with symptoms of hyperandrogenism and is often described as a severe or extreme form of Polycystic Ovary Syndrome (PCOS). Serum testosterone levels in excess of 150 ng/dl (>5.2 nmol/l) are seen in affected patients and this threshold is used to confirm a diagnosis. Treatment of hyperthecosis is multi-faceted. It addresses the attendant hyperandrogenism (hirsutism and virilization) as well as metabolic complications such as obesity and insulin resistance. Ultimately, laparoscopic bilateral salpingo-oophorectomy is definitive treatment. This remains the treatment of choice in postmenopausal women whereas treatment using GnRH agonists may be used in women of reproductive age, especially younger women. Nevertheless, if serum testosterone remains elevated despite several months of therapy with a GnRH agonist, surgery is often required for biopsy sample collection and further definitive therapy. In order to mitigate the common clinical manifestations of hyperandrogenism, anti-androgen therapy (either cyproterone acetate or spironolactone) may be used to suppress the actions of testosterone on tissues. In patients with impaired glucose metabolism and insulin resistance, Metformin should also be considered as part of treatment. Combined, such a treatment regimen will often lead to decreased ovarian androgen secretion.

What Have We Learned from Animal Models of Endometriosis and How Can We Use the Knowledge Gained to Improve Treatment of Patients?

Endometriosis is a complex disorder with a high socio-economic impact. Development of effective novel drug therapies which can be given to women to relieve chronic pain symptoms without side effects such as hormone suppression is urgently required, but progress has been slow. Several different rodent models of 'endometriosis' have been developed, the majority of which mimic aspects of peritoneal disease (e.g. 'lesions' in peritoneal cavity either surgically or spontaneously attached to wall, mesentery, fat). Results obtained using these models have informed our understanding of aetiology including evidence for differential expression of regulatory factors in lesions and impacts on pain perception and fertility. Refinement of these models to ensure reproducibility, extension of models to replicate ovarian and deep disease, complementary in vitro approaches and robust experimental design are all needed to ensure preclinical drug testing results in positive findings in clinical trials and translation for patient benefit.

Endometrial stromal cell inflammatory phenotype during severe ovarian endometriosis as a cause of endometriosis-associated infertility.

RESEARCH QUESTION: Do endometrial stromal cells from primary infertile patients with severe ovarian endometriosis display differential secretory profiles of inflammation-associated cytokines during the implantation window that may cause infertility? DESIGN: Forty-eight cytokines were measured in conditioned medium of isolated endometrial stromal cells obtained from primary infertile patients without endometriosis (control group, n = 12) or with stage IV ovarian endometriosis (ovarian endometriosis group, n = 14) using multiplex assays. Key cytokines showing differential secretory profiles were validated using Western immunoblotting. Cellular phenotypic validation was carried out in vitro by comparing proliferation and migration capacity between control (n = 6) and ovarian endometriosis (n = 7) groups. RESULTS: CCL3, CCL4, CCL5, CXCL10, FGF2, IFNG, IL1RN, IL5, TNFA, and VEGF could be detected only in the conditioned media of stromal cells obtained from the ovarian endometriosis group. Among other cytokines detected in the conditioned media of both groups, CCL2 (P = 0.0018), CSF3 (P = 0.0017), IL1B (P = 0.0066), IL4 (P = 0.036), IL6 (P = 0.0039) and IL13 (P = 0.036) were found to be higher, whereas the concentration of IL18 was lower (P = 0.023) in the ovarian endometriosis group. Concentrations of CCL2, IL1B, IL4 and IL13 in conditioned medium reflected significant diagnostic performance for predicting ovarian endometriosis. Cellular phenotypic validation in vitro revealed an enhanced proliferative phenotype (P = 0.046) with no change in cell migratory capacity of endometrial stromal cells from the ovarian endometriosis group. CONCLUSIONS: Endometrial stromal cells derived from severe ovarian endometriosis samples displayed a hyperinflammatory and hyperproliferative bias in the endometrial stroma during the 'window of implantation' putatively causing loss of fecundability.