Risk factors for the development of endometrial fluid in women undergoing IVF: A retrospective cohort study✰.

RESEARCH QUESTION: Presence of endometrial fluid (EF) is a poorly understood pathology and remains a challenge for clinicians, as very little data exists to explain its consequences and treatment. Our objective was to investigate risk factors for EF during IVF. DESIGN: This retrospective cohort study included all women with a freeze all embryos cycle (FAE) for EF between 2010 and 2016 at a university-affiliated private IVF center. Controls (2:1) were randomly selected out of the database of our fresh autologous IVF cycles during the same period. Main outcome measures were possible risk factors for EF, comprising polycystic ovarian syndrome (PCOS), ovarian hyperstimulation syndrome (OHSS), previous pelvic or endometrial surgery (polypectomy or synechia removal), cesarean section, myomas and severe endometriosis. A logistic regression model was used to assess independent risk factors for EF. RESULTS: Out of 9000 IVF cycles, 1204 were FAE cycles, among which we identified 86 EF cases. We then selected 171 controls. Independent risk factors for presence of EF were a history of previous myomectomy (adjusted odds ratio (aOR) 19.77, 95%CI [4.01-97.53]), severe endometriosis (aOR 5.97, 95%CI [2.09-17.05]), PCOS (aOR 5.72, 95%CI [2.66-12.33]) and previous cesarean section (aOR 5.17, 95%CI [1.84-14.49]). CONCLUSIONS: Our results are not only confirming the association between PCOS, severe endometriosis, previous cesarean procedure and EF, but also reporting for the first time an association between previous myomectomy and EF.

Transvaginal ethanol sclerotherapy for an endometrioma in 10 steps.

OBJECTIVE: To describe a minimally invasive 10-step technique of ethanol sclerotherapy for the treatment of an endometrioma. DESIGN: Step-by-step video demonstration of the technique. SETTING: University tertiary care hospital. PATIENT(S): Women with endometriomas defined as persistent endometriotic ovarian cysts between 25 and 100 mm of diameter, confirmed by magnetic resonance imaging. INTERVENTION(S): Endometriomas occur in 17%-44% of patients with endometriosis, who generally complain about pelvic pain or infertility. This technique may be offered to patients with endometriomas to preserve fertility. The local institutional review board stated that approval was not required because the video describes a technique and not a clinical case. In our center, all severe endometriosis cases are discussed during a multidisciplinary endometriosis meeting. MAIN OUTCOME MEASURE(S): This video presents the procedure divided into the following 10 steps: planning of the surgery; materials; ultrasound examination; transvaginal puncture of the endometrioma; aspiration of the cyst; cytology of the cyst; flushing the cyst with saline solution; injection of 96% ethanol; 10 minutes' exposure to ethanol; and aspiration of ethanol. RESULT(S): We presented 10 steps to make the procedure easier to adopt and to reduce the learning curve. This technique may be offered as an alternative to cystectomy. CONCLUSION(S): Ethanol sclerotherapy for endometriomas is a rapid outpatient procedure, requiring little equipment for a low cost.

In freeze-all embryo cycles due to endometrial fluid (EF), live birth rates are comparable to those of controls, despite high rates of EF recurrence and cycle cancellation.

RESEARCH QUESTION: Do cumulative live birth rates (CLBRs) differ between women who have had a freeze-all embryo cycle (FAE) for endometrial fluid (EF) and controls? DESIGN: This retrospective cohort study included 83 women who had a FAE cycle due to the presence of EF between 2010 and 2016 at a university-affiliated private IVF center. The controls were 219 women who had FAE for other indications during the same period and were randomly selected. The main outcome measures were CLBRs, EF recurrence, cancellation and pregnancy loss rates. RESULTS: Population characteristics were comparable between the two groups. The CLBR was not significantly different between the EF and the control group: 39.8 % vs. 47.0 %, respectively, p=0.26. Cancellation rates in the two first FETs were higher in the EF group than the control group: 18.1 % vs. 4.1 % (p<0.001) and 22.9 % vs. 8.5 % (p=0.02). After FAE for EF, we observed a significant risk of EF recurrence (32/177 cycles, 18.1 %), allowing us to identify a poor prognosis subgroup. When EF was detected, the LBR per transfer was 7.1 % (1/14) when the transfer was finally performed (after EF aspiration or EF disappearance), compared to 25 % (32/128) in cycles without EF recurrence (p<0.05). Conversely, in the absence of EF recurrence (145/177, 81.9 %), the LBR was comparable to that of the control group. The type of endometrial preparation does not seem to be associated with EF recurrence. CONCLUSION: Despite higher rates of EF recurrence and cycle cancellation, women with FAE for EF ultimately have comparable LBRs to those who have had a FAE for other indications. However, women presenting with at least one EF recurrence during FETs seem to have a lower LBR.

Risk factors for unsatisfactory colposcopy after large loop excision of the transformation zone: The results of a four-year multicenter prospective study.

OBJECTIVES: Not being able to completely examine the cervical squamocolummar junction (SCJ) in colposcopy after large loop excision of the transformation zone (LLETZ) is an important issue regarding surveillance, as high-grade cervical intra-epithelial neoplasia recurrence risk is high. This study was conducted in order to identify risk factors for post-LLETZ unsatisfactory colposcopy. METHODS: This prospective multicenter observational study was performed in nine French University hospitals, with inclusions running from December 2013 to December 2017. All patients scheduled for LLETZ were included and were divided into two groups after the two to four months post-procedure colposcopic examination: a satisfactory and an unsatisfactory post-LLETZ colposcopy group. RESULTS: In total, 601 cases were analyzed and 71 post-LLETZ colposcopies (12%) were described as unsatisfactory (including 19 cervical stenosis). In a univariate analysis, we only observed a statistically significant increase of the following parameters in the unsatisfactory post-LLETZ group in comparison with the satisfactory post-LLETZ group: parity (2.11 [±1.55] and 1.49 [±1.24] respectively, p < .01), depth of the LLETZ specimen (10.9 mm [±3.37] and 9.76 [±3.79] respectively, p < .01), age (45.9 years [±11.7] and 37.9 [±9.42] respectively, p < .001) and an unsatisfactory pre-LLETZ colposcopy (43 satisfactory pre-LLETZ colposcopies [61%] and 456 [86%] respectively, p < .001). In a stepwise binary logistic regression analysis, only the two latter parameters were found to be independently associated with unsatisfactory post-LLETZ colposcopies. CONCLUSIONS: Surgeons should consider other therapeutic strategies when contemplating iterative diagnosis-LLETZ in older women with initially invisible SCJ, as an appropriate post-LLETZ surveillance is at higher risk of being impossible to achieve.

Risk Factors of Post-Large Loop Excision of the Transformation Zone Recurrent High-Grade Cervical Intraepithelial Lesion: A Prospective Cohort Study.

OBJECTIVE: The aim of the study was to identify the risk factors of post-large loop excision of the transformation zone (LLETZ) recurrent disease and the impact of colposcopic guidance at the time of LLETZ on that risk. MATERIALS AND METHODS: From December 2013 to July 2014, 204 patients who had undergone LLETZ for the treatment of high-grade intraepithelial lesion with fully visible cervical squamocolumnar junction were included. The use of colposcopy during each procedure was systematically documented. The dimensions and volume of LLETZ specimens were measured at the time of the procedure before formaldehyde fixation. All participants were invited for a follow-up. The primary endpoint was the diagnosis of post-LLETZ recurrent disease defined as the histologic diagnosis of a high-grade cervical intraepithelial lesion. RESULTS: The median duration of post-LLETZ follow-up was 25.8 months. Recurrent disease was diagnosed in 8 (3.6%) patients. Older than 38 years (adjusted hazard ratio [aHR] = 11.9, 95% CI = 1.6-86.0), history of excisional therapy (aHR = 21.6, 95% CI = 3.5-135.3), and the absence of colposcopy for the guidance of LLETZ (aHR = 6.4, 95% CI = 1.1-37.7) were found to significantly increase the risk of post-LLETZ recurrent disease. The dimensions and volume of the specimen were not found to have any impact. Only positive endocervical margins were identified to significantly increase the risk of post-LLETZ recurrent disease (aHR = 14.4, 95% CI = 2.0-101.1). CONCLUSIONS: Risk factors of post-LLETZ recurrent disease are older than 38 years, history of excisional therapy, positive endocervical margins, and lack of colposcopic guidance at the time of LLETZ.

Risk Factors of Inadequate Colposcopy After Large Loop Excision of the Transformation Zone: A Prospective Cohort Study.

OBJECTIVE: The aim of the study was to identify the risk factors of post-large loop excision of the transformation zone (LLETZ) inadequate colposcopy. MATERIALS AND METHODS: From December 2013 to July 2014, a total of 157 patients who had a LLETZ performed for the treatment of high-grade intraepithelial lesion with fully visible cervical squamocolumnar junction were included. All procedures were performed using semicircular loops. The use of colposcopy made during each procedure was systematically documented. Dimensions and volume of LLETZ specimens were measured at the time of procedure, before formaldehyde fixation. All participants were invited for a follow-up colposcopy 3 to 6 months after LLETZ. Primary end point was the diagnosis of post-LLETZ inadequate colposcopy, defined by a not fully visible cervical squamocolumnar junction and/or cervical stenosis. RESULTS: Colposcopies were performed in a mean (SD) delay of 136 (88) days and were inadequate in 22 (14%) cases. Factors found to significantly increase the probability of post-LLETZ inadequate colposcopy were a history of previous excisional cervical therapy [adjusted odds ratio (aOR) = 4.29, 95% CI = 1.12-16.37, p = .033] and the thickness of the specimen (aOR = 3.12, 95% CI = 1.02-9.60, p = .047). The use of colposcopy for the guidance of LLETZ was statistically associated with a decrease in the risk of post-LLETZ inadequate colposcopy (aOR = 0.19, 95% CI = 0.04-0.80, p = .024) as the achievement of negative endocervical margins (aOR = 0.26, 95% CI = 0.08-0.86, p = .027). CONCLUSIONS: Although the risk of post-LLETZ inadequate colposcopy is increased in patients with history of excisional therapy and with the thickness of the excised specimen, it could be reduced with the use of colposcopic guidance and the achievement of negative endocervical margins.

The Accuracy of Large Loop Excision of the Transformation Zone Specimen Dimensions in Determining Volume: A Multicentric Prospective Observational Study.

OBJECTIVE: The aim of the study was to determine which mathematical formula of specimen dimensions is the most accurate method of determining volume of the excised specimen at loop excision of the transformation zone. MATERIALS AND METHODS: A multicenter prospective observational study was conducted. A total of 258 patients who had a loop excision of the transformation zone performed as treatment of cervical intraepithelial neoplasia 2-3 were included. The dimensions and the volume of the specimen were measured at the time of the procedure, before formaldehyde fixation. The volume was measured by immersing the specimen in a graduated cylinder using Archimedes fluid displacement technique. The measured volume was compared with the calculated volume using different volume formulas, that is, a cone, a cylinder, a parallelepiped, and a hemiellipsoid. The main outcome measure was the relationship between calculated volume (using the dimensions of thickness, length, and circumference) and the measured volume of the specimen. RESULTS: The mean (SD) thickness, length, and circumference of specimens were 8.8 mm (3.8), 12.7 mm (5.9), and 45.7 mm (16.8), respectively. The mean (SD) measured volume was 2.53 (1.49) mL. Using the formula for the volume of a cone, a cylinder, a parallelepiped and a hemiellipsoid, estimated volumes were 1.03 mL (1.22), 3.10 mL (3.65), 6.20 mL (7.31), and 2.07 mL (2.44), respectively. The highest intraclass correlation coefficient between measured and calculated volume was observed when using the formula for the volume of a hemiellipsoid specimen (0.47, 95% CI = 0.36-0.56). CONCLUSIONS: The hemiellipsoid formula is the most accurate determinant of the excised volume. Other formulas do not allow for an accurate estimation of the excised volume.

Benefits of Direct Colposcopic Vision for Optimal LLETZ Procedure: A Prospective Multicenter Study.

OBJECTIVE: The aim of the study was to assess whether direct colposcopic vision (DCV) of the cervix during large loop excision of the transformation zone (LLETZ) is associated with a decrease in the volume and dimensions of specimens or affects margin status at histology. MATERIALS AND METHODS: A prospective multicenter observational study of 216 women who underwent LLETZ for grades 2 and 3 cervical intraepithelial neoplasia was conducted. The volume and dimensions (circumference, length, and thickness) of the surgical specimens were measured before fixation. Data were compared according to the use of colposcopy during LLETZ. The following 3 groups were considered: LLETZ performed without colposcopy (n = 91), LLETZ performed immediately after colposcopy (n = 51), and LLETZ performed under DCV (n = 74). RESULTS: Patient characteristics were comparable with regard to age, parity, history of excision, indication of the procedure, and the size of the cervix. We found a significant decrease in all dimensions of the specimens obtained under DCV (p < .001). Margin status was not affected. After adjusting for confounders, the mean volumes were significantly lower in the DCV group (adjusted mean difference = -0.66 mL; 95% CI = -1.17 to -0.14). The probability that negative margins would be achieved together with the attainment of a volume less than 5 mL and a thickness less than 10 mm was the highest in the DCV group (adjusted OR = 2.80; 95% CI = 1.13 to 6.90). CONCLUSIONS: Direct colposcopic vision is associated with a significant decrease in the volume and in all dimensions of LLETZ specimens with no compromise in the margin status.

Cerium dioxide nanoparticles affect in vitro fertilization in mice.

Due to their catalytic and oxidative properties, cerium dioxide nanoparticles (CeO2NPs) are widely used as diesel additive or as promising therapy in cancerology; yet, scarce data are available on their toxicity, and none on their reproductive toxicity. We showed a significant decrease of fertilization rate, assessed on 1272 oocytes, during in vitro fertilization (IVF) carried out in culture medium containing CeO2NP at very low concentration (0.01 mg.l(-1)). We also showed significant DNA damage induced in vitro by CeO2NP on mouse spermatozoa and oocytes at 0.01 mg.l(-1) using Comet assay. Transmission Electron Microscopy did not detect any nanoparticles in the IVF samples at 0.01 mg.l(-1), but showed, at high concentration (100 mg.l(-1)), their endocytosis by the cumulus cells surrounding oocytes and their accumulation along spermatozoa plasma membranes and oocytes zona pellucida. We did not observe any nanoparticles in the cytoplasm of spermatozoa, oocytes or embryos. This study demonstrates for the first time the impact of CeO2NP on in vitro fertilization, as well as their genotoxicity on mouse spermatozoa and oocytes, at low nanoparticle concentration exposure. Decreased fertilization rates may result from: (1) CeO2NP's genotoxicity on gametes; (2) a mechanical effect, disrupting gamete interaction and (3) oxidative stress induced by CeO2NP. These results add new and important insights with regard to the reproductive toxicity of nanomaterials requesting urgent evaluation, and support several publications on metal nanoparticles reprotoxicity. Our data highlight the need for in vivo studies after low-dose exposure.