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

International audienceObjective: 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 colpos-copy 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 colpos-copy 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. L arge loop excision of the transformation zone (LLETZ) is a routine procedure worldwide, because it is the first-line treatment of high-grade intraepithelial lesion (HSIL) of the cervix. Quality criteria for optimal LLETZ include the completeness of excision with the achievement of negative margins, while producing the minimal excised volume and depth of excision to minimize subsequent obstetrical and neonatal morbidity. 1,2 Obtaining negative margins is important, because incomplete excision exposes women to a significant risk of posttreatment residual and/or recurrent disease, particularly when the lesion involves the endo-cervical canal. 3,4 However, this risk remains higher to the general female population, even when negative margins are achieved. Women who had had a LLETZ remain therefore exposed to a 3-to 4-fold increased risk of developing subsequent cervical cancer at least for 20 years. 5-8 Thus, prolonged and careful post-LLETZ follow-up is mandatory, whatsoever the margins status. For the last decade, the value of human papillomavirus testing has been demonstrated in this indication. Although a negative human papillomavirus test has now been admitted as the best test of cure for patients, colposcopy remains needed when this test is found to be positive. 9-12 Although being the key examination in this indication, the accuracy of colposcopy performed after previous excisional therapy of HSIL is however questionable because the healing process might result in changes in the appearance of the transformation zone (TZ). However, the main limitation of post-LLETZ colposcopic examination is the possibility of inadequate colposcopy due to the inability to visualize the entire TZ. Known risk factors for inadequate colposcopy include age, severity of lesion, and estrogen status of the patient. 13 However, inadequate colposcopy is also one of the main adverse effects of excisional therapies of the cervix, including LLETZ. 13 However, data on the precise risk factors for inadequate colposcopy after LLETZ are limited because most studies have focused on the sole risk of cervical stenosis without considering the position and visibility of the squamocolumnar junction. 14-17 This point is however crucial because it is clinically essential to identify how post-LLETZ inadequate colposcopy could be avoided, thus preserving the possibility for the follow-up of these women

Can we improve referrals for fertility preservation? Evolution of practices after the creation of a fertility network

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Transvaginal ethanol sclerotherapy for an endometrioma in 10 steps

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Endometrioma ethanol sclerotherapy could increase IVF live birth rate in women with moderate-severe endometriosis

International audienceObjectiveTo examine the impact of ethanol sclerotherapy (EST) for endometrioma on in vitro fertilization (IVF) cumulative live birth rates (CLBR) in women with moderate-severe endometriosis.MethodsThis retrospective cohort study included women with moderate-severe endometriosis (revised American Fertility Society stage III-IV) and endometrioma who underwent IVF with the ultra-long agonist protocol. We compared two groups: women undergoing EST for endometrioma before IVF (EST group), and women whose endometrioma was left in situ during IVF (No-EST group). The primary outcome was the CLBR per IVF cycle, including fresh and frozen embryo transfers. The secondary endpoints included the complication rate, number of mature oocytes retrieved, clinical pregnancy rate and pregnancy loss rate.ResultsSeventy-four women were included in the study, with 37 in the EST group and 37 in the No-EST group, representing 67 and 69 IVF cycles, respectively. The population and cycle characteristics were comparable between the two groups, especially the ovarian response to stimulation. The CLBR was significantly increased in the EST group compared to the No-EST group (31.3% vs. 14.5%, p = 0.03). The clinical and biochemical pregnancy rates were significantly increased in the EST group (37.3% vs. 15.9%, p = 0.01 and 43.3% vs. 23.2%, p = 0.01, respectively). Multivariate analysis revealed a significantly increased chance of live birth in women exposed to EST before IVF with an adjusted OR of 2.68 (95% confidence interval, CI: 1.13–6.36, p = 0.02). In the EST group, we reported one major complication Clavien and Dindo classification grade III, complication involving an ovarian abscess that required a laparoscopic drainage.ConclusionsEST is an interesting technique to improve IVF success rates in women with moderate-severe endometriosis. EST could be discussed before IVF in infertile women

Transvaginal ethanol sclerotherapy for an endometrioma in 10 steps

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

International audienceObjectivesNot 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.MethodsThis 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.ResultsIn 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.ConclusionsSurgeons 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

Cerium dioxide nanoparticles affect in vitro fertilization in mice

International audienceDue to their catalytic and oxidative properties, cerium dioxide nanoparticles (CeO(2)NPs) 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 (0.01mg.l(-1)). We also showed significant DNA damage induced in vitro by CeO2NP on mouse spermatozoa and oocytes at 0.01mg.l(-1) using Comet assay. Transmission Electron Microscopy did not detect any nanoparticles in the IVF samples at 0.01mg.l(-1), but showed, at high concentration (100mg.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

Risk Factors of Post-Large Loop Excision of the Transformation Zone Recurrent High-Grade Cervical Intraepithelial Lesion

International audienceOBJECTIVE: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

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

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