Philippe Descamps

Ovarian tumors are the most frequent adnexal mass, raising diagnostic and therapeutic issues linked to a large spectrum of tumors, with a continuum from benign to malignant. Thus far, none of the available diagnostic tools have proven efficient in deciding strategy, and no consensus exists on the best strategy between “single test”, “dual testing”, “sequential testing”, “multiple testing options” and “no testing”. In addition, there is a need for prognostic tools such as biological markers of recurrence and theragnostic tools to detect women not responding to chemotherapy in order to adapt therapies. Non-coding RNAs are classified as small or long based on their nucleotide count. Non-coding RNAs have multiple biological functions such as a role in tumorigenesis, gene regulation and genome protection. These ncRNAs emerge as new potential tools to differentiate benign from malignant tumors and to evaluate prognostic and theragnostic factors. In the specific setting of ovarian tumors, the goal of the present work is to offer an insight into the contribution of biofluid non-coding RNAs (ncRNA) expression.

Objective: Population screening programmes must make good use of resources for the health system and users. To evaluate impacts of the type of diagnostic test in the new French cervical screening programme, an messenger ribonucleic acid (mRNA) high-risk human papillomavirus assay was compared to a deoxyribonucleic acid (DNA) high-risk human papillomavirus assay for a hypothetical cohort of women aged 25 to 65 years. Perspective: This evaluation takes the perspective of the French healthcare system. Setting: France Methods: A decision tree model reflecting the French cervical screening algorithms was parametrised using French cost and population data and the Danish Horizon study. The outcomes were total costs, and number of colposcopies, HPV tests and cytology tests for the cohort. One-way and probabilistic sensitivity analyses and scenarios analyses were conducted to test the robustness of results to parameter and structural uncertainty. Results: Adopting an mRNA versus DNA assay as part of national cervical screening in France is estimated to save €6.5 million (95% credibility intervals €-1.3 - €13.5 million) and prevent 47,795 (95% credibility intervals 35,309 - 60,139) unnecessary colposcopies, 38,666 unnecessary HPV tests and 121,670 cytology tests over two years for a cohort of 2,168,806 million women aged 25 to 65 years. Sensitivity analyses indicated robust results across a range of inputs. Conclusion: The choice of high-risk human papillomavirus assay makes a significant difference to resource use and costs and is important to consider when implementing cervical screening in France. Using an mRNA versus DNA assay can result in cost savings and reductions in unnecessary testing and procedures, which in turn benefits women and the health care system.

The aim of our study was to describe the bioinformatics approach to analyze miRNome with Next Generation Sequencing (NGS) of 200 plasma samples from patients with and without endometriosis. Patients were prospectively included in the ENDO-miRNA study that selected patients with pelvic pain suggestive of endometriosis. miRNA sequencing was performed using an Novaseq6000 sequencer (Illumina, San Diego, CA, USA). Small RNA-seq of 200 plasma samples yielded ~4228 M raw sequencing reads. A total of 2633 miRNAs were found differentially expressed. Among them, 8.6% (n = 229) were up- or downregulated. For these 229 miRNAs, the F1-score, sensitivity, specificity, and AUC ranged from 0–88.2%, 0–99.4%, 4.3–100%, and 41.5–68%, respectively. Utilizing the combined bioinformatic and NGS approach, a specific and broad panel of miRNAs was detected as being potentially suitable for building a blood signature of endometriosis.

Background: Endometriosis diagnosis constitutes a considerable economic burden for the healthcare system with diagnostic tools often inconclusive with insufficient accuracy. We sought to analyze the human miRNAome to define a saliva-based diagnostic miRNA signature for endometriosis. Methods: We performed a prospective ENDO-miRNA study involving 200 saliva samples obtained from 200 women with chronic pelvic pain suggestive of endometriosis collected between January and June 2021. The study consisted of two parts: (i) identification of a biomarker based on genome-wide miRNA expression profiling by small RNA sequencing using next-generation sequencing (NGS) and (ii) development of a saliva-based miRNA diagnostic signature according to expression and accuracy profiling using a Random Forest algorithm. Results: Among the 200 patients, 76.5% (n = 153) were diagnosed with endometriosis and 23.5% (n = 47) without (controls). Small RNA-seq of 200 saliva samples yielded ~4642 M raw sequencing reads (from ~13.7 M to ~39.3 M reads/sample). Quantification of the filtered reads and identification of known miRNAs yielded ~190 M sequences that were mapped to 2561 known miRNAs. Of the 2561 known miRNAs, the feature selection with Random Forest algorithm generated after internally cross validation a saliva signature of endometriosis composed of 109 miRNAs. The respective sensitivity, specificity, and AUC for the diagnostic miRNA signature were 96.7%, 100%, and 98.3%. Conclusions: The ENDO-miRNA study is the first prospective study to report a saliva-based diagnostic miRNA signature for endometriosis. This could contribute to improving early diagnosis by means of a non-invasive tool easily available in any healthcare system.

Endometriosis and infertility are closely linked, but the underlying mechanisms are still poorly understood. This study aimed to evaluate the impact of endometriosis on in vitro fertilization (IVF) parameters, especially on embryo quality and IVF outcomes. A total of 1124 cycles with intracytoplasmic sperm injection were retrospectively evaluated, including 155 cycles with endometriosis and 969 cycles without endometriosis. Women with endometriosis had significantly lower ovarian reserve markers (AMH and AFC), regardless of previous ovarian surgery. Despite receiving significantly higher doses of exogenous gonadotropins, they had significantly fewer oocytes, mature oocytes, embryos, and top-quality embryos than women in the control group. Multivariate analysis did not reveal any association between endometriosis and the proportion of top-quality embryo (OR = 0.87; 95% CI [0.66–1.12]; p = 0.3). The implantation rate and the live birth rate per cycle were comparable between the two groups (p = 0.05), but the cumulative live births rate was significantly lower in in the endometriosis group (32.1% versus 50.7%, p = 0.001), as a consequence of the lower number of frozen embryos. In conclusion, endometriosis lowers the cumulative live birth rates by decreasing the number of embryos available to transfer, but not their quality.

To determine if a modification of the cytokine profile occurs in the follicular fluid (FF) of women with endometriosis undergoing in vitro fertilization (IVF), we performed a prospective observational study from January 2018 to February 2019. In total, 87 women undergoing IVF were included: 43 for severe endometriosis-related infertility and 40 controls with other causes of infertility. The cytokine profile of the FF was determined by multiplex fluorescent-bead-based technology allowing the measurement of 59 cytokines. Monocyte Chemoattractant Protein 1 (MCP-1) was the only variable retained in the multivariate analysis. We identified two subgroups of patients in the endometriosis group: MCP-1-low group (n = 23), which had FF MCP-1 levels comparable to the control group, and MCP-1-high (n = 20), which had significantly higher FF levels. Only patients in the MCP-1-high group had a significantly altered cytokine profile in the FF, and had a significantly higher serum estradiol level (p = 0.002) and a significantly lower number of oocytes recovered (p = 0.01) compared to the MCP-1-low and the control group. Our study has shown an alteration of the oocyte microenvironment in women with endometriosis associated with high follicular fluid levels of MCP-1, allowing the identification of a subgroup of endometriosis patients with a potentially worse prognosis.

The frequency of posterior presentations (occiput of the fetus towards the sacrum of the mother) in labor is approximately 20% and, of this, 5% remain posterior until the end of labor. These posterior presentations are associated with higher rates of cesarean section and instrumental delivery. Manual rotation of a posterior position in order to rotate the fetus to an anterior position has been proposed in order to reduce the rate of instrumental fetal delivery. No randomized study has compared the efficacy of this procedure to expectant management. We therefore propose a monocentric, interventional, randomized, prospective study to show the superiority of vaginal delivery rates using the manual rotation of the posterior position at full dilation over expectant management. Ultrasound imaging of the presentation will be performed at full dilation on all the singleton pregnancies for which a clinical suspicion of a posterior position was raised at more than 37 weeks’ gestation (WG). In the event of an ultrasound confirming a posterior position, the patient will be randomized into an experimental group (manual rotation) or a control group (expectative management with no rotation). For a power of 90% and the hypothesis that vaginal deliveries will increase by 20%, (10% of patients lost to follow-up) 238 patients will need to be included in the study. The primary endpoint will be the rate of spontaneous vaginal deliveries (expected rate without rotation: 60%). The secondary endpoints will be the rate of fetal extractions (cesarean or instrumental) and the maternal and fetal morbidity and mortality rates. The intent-to-treat study will be conducted over 24 months. Recruitment started in February 2017. To achieve the primary objective, we will perform a test comparing the number of spontaneous vaginal deliveries in the two groups using Pearson’s chi-squared test (provided that the conditions for using this test are satisfactory in terms of numbers). In the event that this test cannot be performed, we will use Fisher’s exact test. Given that the efficacy of manual rotation has not been proven with a high level of evidence, the practice of this technique is not systematically recommended by scholarly societies and is, therefore, rarely performed by obstetric gynecologists. If our hypothesis regarding the superiority of manual rotation is confirmed, our study will help change delivery practices in cases of posterior fetal position. An increase in the rates of vaginal delivery will help decrease the short- and long-term rates of morbidity and mortality following cesarean section. Manual rotation is a simple and effective method with a success rate of almost 90%. Several preliminary studies have shown that manual rotation is associated with reduced rates for fetal extraction and maternal complications: Shaffer has shown that the cesarean section rate is lower in patients for whom a manual rotation is performed successfully (2%) with a 9% rate of cesarean sections when manual rotation is performed versus 41% when it is not performed. Le Ray has shown that manual rotation significantly reduces vaginal delivery rates via fetal extraction (23.2% vs 38.7%, p < 0.01). However, manual rotation is not systematically performed due to the absence of proof of its efficacy in retrospective studies and quasi-experimental before/after studies. ClinicalTrials.gov, Identifier: NCT03009435 . Registered on 30 December 2016