Oocyte retrieval difficulties in women with ovarian endometriomas.

RESEARCH QUESTION: What are the frequency, characteristics and consequences of technical diffiiculties encountered by physicians when carrying out oocyte retrieval in women with ovarian endometriomas? DESIGN: We prospectively recruited women undergoing IVF and compared technical difficulties between women with (n = 56) and without (n = 227) endometriomas. RESULTS: In exposed women, the cyst had to be transfixed in eight cases (14%, 95% CI 7 to 25%) and accidental contamination of the follicular fluid with the endometrioma content was recorded in nine women (16%, 95% CI 8 to 27%). Moreover, follicular aspiration was more frequently incomplete (OR 3.6, 95% CI 1.4 to 9.6). In contrast, the retrievals were not deemed to be more technically difficult by the physicians and the rate of oocytes retrieved per developed follicle did not differ. No pelvic infections or cyst ruptures were recorded (0%, 95% CI 0 to 5%). CONCLUSIONS: Oocyte retrieval in women with ovarian endometriomas is more problematic but the magnitude of these increased difficulties is modest.

Predicting the success of IVF: external validation of the van Loendersloot's model.

STUDY QUESTION: Is the predictive model for IVF success proposed by van Loendersloot et al. valid in a different geographical and cultural context? SUMMARY ANSWER: The model discriminates well but was less accurate than in the original context where it was developed. WHAT IS ALREADY KNOWN: Several independent groups have developed models that combine different variables with the aim of estimating the chance of pregnancy with IVF but only four of them have been externally validated. One of these four, the van Loendersloot's model, deserves particular attention and further investigation for at least three reasons; (i) the reported area under the receiver operating characteristics curve (c-statistics) in the temporal validation setting was the highest reported to date (0.68), (ii) the perspective of the model is clinically wise since it includes variables obtained from previous failed cycles, if any, so it can be applied to any women entering an IVF cycle, (iii) the model lacks external validation in a geographically different center. STUDY DESIGN, SIZE, DURATION: Retrospective cohort study of women undergoing oocyte retrieval for IVF between January 2013 and December 2013 at the infertility unit of the Fondazione Ca' Granda, Ospedale Maggiore Policlinico of Milan, Italy. Only the first oocyte retrieval cycle performed during the study period was included in the study. Women with previous IVF cycles were excluded if the last one before the study cycle was in another center. The main outcome was the cumulative live birth rate per oocytes retrieval. PARTICIPANTS/MATERIALS, SETTING, METHODS: Seven hundred seventy-two women were selected. Variables included in the van Loendersloot's model and the relative weights (beta) were used. The variable resulting from this combination (Y) was transformed into a probability. The discriminatory capacity was assessed using the c-statistics. Calibration was made using a logistic regression that included Y as the unique variable and live birth as the outcome. Data are presented using both the original and the calibrated models. Performance was evaluated correlating the mean predicted chances of live births in the five quintiles and the observed rates. MAIN RESULTS AND THE ROLE OF CHANCE: Two-hundred-eleven live births (27%) were obtained. The c-statistic was 0.64 (95% CI: 0.61-0.67, P < 0.001). The slope of the linear predictor (calibration slope) expressed as an Odds Ratio was 1.81 (95% CI: 1.46-2.24, P < 0.001), corresponding to a beta of 0.630. The calibration intercept was +0.349 (P = 0.13). While a clear discrepancy exists using the original model, data appear properly distributed with the calibrated model. The Pearson coefficient of the correlation between the mean predicted chances of live births in the five quintiles and the observed rates was 0.99 (P = 0.002). LIMITATIONS, REASONS FOR CAUTION: Data were collected retrospectively, thus exposing them to potential inaccuracies. The selection criteria for access to IVF adopted in our center might be too stringent, leading to the exclusion of women with a poor, yet acceptable chance of live birth. Therefore, the validity of the model in women with a very low chance of live birth could not be tested. WIDER IMPLICATIONS OF THE FINDINGS: The van Loendersloot's model can be used in other contexts but it is important that it has local calibration. It may help in counseling couples about their chance of success but it cannot be used to exclude treatments. Further research is needed to improve the discriminatory performance of IVF predictive models. STUDY FUNDING/COMPETING INTERESTS: None. TRIAL REGISTRATION NUMBER: Not applicable.

Decidualization of endometriosis in a cohort of IVF-mediated pregnancies.

Decidualization is the process of endometrial change in pregnancy, a phenomenon that can involve also ovarian endometriomas. However, the frequency of this event remains unknown. In addition, there is no evidence on the decidualization of deep invasive endometriosis (DIE). To shed more light on this issue, we prospectively recruited women with ovarian endometriomas or DIE who underwent IVF. They were subsequently excluded if they did not become pregnant or if they had a miscarriage. The evaluation was repeated in five time points during pregnancy and post-partum. The primary outcome was the rate of decidualized endometriomas at 11-13 weeks' gestation. Data from 45 endometriomas and 15 nodules were available for data analyses. At the 11-13 weeks' ultrasound, endometriomas' decidualization was observed in seven cases, corresponding to 16% (95% CI 8-29%). Subsequent assessments in pregnancy failed to identify any additional case. DIE also underwent significant changes during pregnancy. At the 11-13 weeks' ultrasound, lesions were increased in size and more vascularized. In conclusion, decidualization of ovarian endometriomas in IVF pregnancies is not rare. DIE may also undergo decidualization, but further evidence is needed for a robust and shared definition of this process.

Natural Pregnancy Seeking in Subfertile Women with Endometriosis.

Several pathogenetic mechanisms have been postulated to explain the association between endometriosis and subfertility. However, to date, definitive conclusions cannot be drawn. In this study, we hypothesized that the reduced exploitation of the natural chances of conception could be an additional detrimental factor. Due to dyspareunia or the need for hormonal treatment to temper pelvic pain, one may expect affected women to exploit less the chances of natural pregnancy. In this cross-sectional study of 292 women undergoing IVF, we investigated the severity of pelvic pain symptoms, the sexual function (using the Female Sexual Function Index [FSFI]), and the reproductive strategies of women with (n = 62) and without (n = 230) endometriosis. Basal clinical and demographic characteristics did not differ between the two groups. Conversely, all pelvic pain symptom scores were increased in women with endometriosis. Endometriosis patients also showed greater pain at the FSFI, but no other significant differences were detected as regards sexual function. The use of hormonal contraceptive agents did not differ between the study groups. Moreover, questions aimed at disentangle whether affected women exploited less the natural chances of pregnancy did not reveal any significant difference. In conclusion, this study does not support the hypothesis that women with endometriosis exploit less the chances of natural pregnancy, despite the presence of pelvic pain.

Small non-coding RNA deregulation in endometrial carcinogenesis.

Small non-coding RNAs (sncRNAs) represent a heterogeneous group of <200nt-long transcripts comprising microRNAs, PIWI-interacting RNAs (piRNAs) and small-nucleolar-RNAs (snoRNAs) involved in physiological and pathological processes such as carcinogenesis and tumor progression. Aberrant sncRNA expression in cancer has been associated with specific clinical phenotypes, grading, staging, metastases development and resistance to therapy.Aim of the present work is to study the role of sncRNAs in endometrial carcinogenesis. Changes in sncRNA expression were identified by high-throughput genomic analysis of paired normal, hyperplastic and cancerous endometrial tissues obtained by endometrial biopsies (n = 10). Using smallRNA sequencing and microarrays we identified significant differences in sncRNA expression pattern between normal, hyperplastic and neoplastic endometrium. This led to the definition of a sncRNA signature (129 microRNAs, 2 of which not previously described, 10 piRNAs and 3 snoRNAs) of neoplastic transformation. Functional bioinformatics analysis identified as downstream targets multiple signaling pathways potentially involved in the hyperplastic and neoplastic tissue responses, including Wnt/ß-catenin, and ERK/MAPK and TGF-ß-Signaling.Considering the regulatory role of sncRNAs, this newly identified sncRNA signature is likely to reflect the events leading to endometrial cancer, which can be exploited to dissect the carcinogenic process including novel biomarkers for early and non-invasive diagnosis of these tumors.