Questionnaire-based screening of adolescents and young adult women can identify markers associated with endometriosis.

STUDY QUESTION: Do adolescents and young adult women (YAW) with histologically proven endometriosis present a specific clinical history? SUMMARY ANSWER: Questionnaire screening of adolescents and YAW can identify clinical markers associated with histologically proven endometriosis. WHAT IS KNOWN ALREADY: Some validated questionaries can contribute to an earlier endometriosis diagnosis in adults. None of these scores, however, have been validated for adolescents or YAW. STUDY DESIGN, SIZE, DURATION: This was an observational cross-sectional study using prospectively recorded data performed between January 2005 and January 2020 in a single university tertiary referral centre for endometriosis diagnosis and management. After a thorough surgical examination of the abdomino-pelvic cavity, women with histologically proven endometriosis were allocated to the endometriosis group, and symptomatic women without evidence of endometriosis were allocated to the endometriosis-free control group. The endometriotic patients were allocated into two sub-groups according to their age: adolescent (≤20 years) and YAW (21-24 years). PARTICIPANTS/MATERIALS, SETTING, METHODS: Adolescents and YAW ≤24 years of age were operated for a symptomatic benign gynaecological condition with signed informed consent. A standardized questionnaire was prospectively completed in the month before the surgery and included epidemiological data, pelvic pain scores, family history of endometriosis, and symptoms experienced during adolescence. The study searched for correlations by univariate analysis to determine clinical markers of endometriosis in adolescents and YAW compared with endometriosis-free control patients. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 262 study participants, 77 women were adolescents (≤20 years of age) and 185 patients (70.6%) were YAW. The endometriosis group included 118 patients (45.0%) and 144 (55.0%) were assigned to the control group. A family history of endometriosis, absenteeism from school during menstruation, history of fainting spells during menstruation, and prescription of oral contraceptive pills for intense dysmenorrhea were significantly more frequently observed in the endometriotic patients. The prevalence and mean pain scores for dysmenorrhea, deep dyspareunia, non-cyclic chronic pelvic pain and gastrointestinal and lower urinary tract symptoms were significantly greater in the endometriosis group, as was experienced rectal bleeding. LIMITATIONS, REASONS FOR CAUTION: The study was performed in a single referral centre that treats patients with potentially more severe disease. This questionnaire was evaluated on a population of patients with an indication for endometriosis surgery, which can also select patients with more severe disease. Women with asymptomatic endometriosis were not considered in this study. These factors can affect the external validity of this study. WIDER IMPLICATIONS OF THE FINDINGS: Patient interviews are relevant to the diagnosis of endometriosis in adolescents and YAW. Combined with imaging and clinical examination, this approach will enable earlier diagnosis and treatment, while remaining non-invasive and rapid. STUDY FUNDING/COMPETING INTEREST(S): The study received no funding from external sources. There are no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Fresh or frozen day 6 blastocyst transfer: is there still a question?

BACKGROUND: The Live Birth Rate (LBR) after day 5 (D5) blastocyst transfer is significantly higher than that with D6 embryos in both fresh and frozen-vitrified embryo transfer cycles, according to the most recently published meta-analyses. Therefore, for women obtaining only D6 blastocysts, the chances of pregnancy may be lower but nonetheless sufficient to warrant transferring such embryos. The best strategy for transfer (i.e., in fresh versus frozen cycles) remains unclear and there is a paucity of data on this subject. METHODS: A total of 896 couples with D6 single blastocyst transfers were retrospectively analyzed: patients receiving a fresh D6 embryo transfer (Fresh D6 transfer group, n = 109) versus those receiving a frozen-thawed D6 embryo transfer (Frozen D6 transfer group, n = 787). A subgroup comprising a freeze-all cycle without any previous fresh or frozen D5 embryo transfers (Elective frozen D6, n = 77) was considered and also compared with the Fresh D6 transfer group. We compared LBR between these two groups. Correlation between D6 blastocyst morphology according to Gardner's classification and live birth occurrence was also evaluated. Statistical analysis was carried out using univariate and multivariate logistic regression models. RESULTS: The LBR was significantly lower after a fresh D6 blastocyst transfer compared to the LBR with a frozen-thawed D6 blastocyst transfer [5.5% (6/109) vs. 12.5% (98/787), p = 0.034]. Comparison between LBR after Elective frozen D6 group to the Fresh D6 blastocyst transfers confirmed the superiority of frozen D6 blastocyst transfers. Statistical analysis of the blastocyst morphology parameters showed that both trophectoderm (TE) and inner cell mass (ICM) grades were significantly associated with the LBR after D6 embryo transfer (p < 0.001, p = 0.037). Multiple logistic regression revealed that frozen D6 thawed transfer was independently associated with a higher LBR compared with fresh D6 transfer (OR = 2.54; 95% CI: [1.05-6.17]; p = 0.038). Our results also show that transferring a good or top-quality D6 blastocyst increased the chances of a live birth by more than threefold. CONCLUSIONS: Our results indicate that transferring D6 blastocysts in frozen cycles improves the LBR, making it the best embryo transfer strategy for these slow-growing embryos. CLINICAL TRIAL NUMBER: Not applicable.

An integrated multi-tissue approach for endometriosis candidate biomarkers: a systematic review.

Biomarker identification could help in deciphering endometriosis pathophysiology in addition to their use in the development of non invasive diagnostic and prognostic approaches, that are essential to greatly improve patient care. Despite extensive efforts, no single potential biomarker or combination has been clinically validated for endometriosis.Many studies have investigated endometriosis-associated biological markers in specific tissues, but an integrative approach across tissues is lacking. The aim of this review is to propose a comprehensive overview of identified biomarkers based on tissue or biological compartment, while taking into account endometriosis phenotypes (superficial, ovarian or deep, or rASRM stages), menstrual cycle phases, treatments and symptoms.We searched PubMed and Embase databases for articles matching the following criteria: 'endometriosis' present in the title and the associated term 'biomarkers' found as Medical Subject Headings (MeSH) terms or in all fields. We restricted to publications in English and on human populations. Relevant articles published between 01 January 2005 (when endometriosis phenotypes start to be described in papers) and 01 September 2022 were critically analysed and discussed.Four hundred forty seven articles on endometriosis biomarkers that included a control group without endometriosis and provided specific information on endometriosis phenotypes are included in this review. Presence of information or adjustment controlling for menstrual cycle phase, symptoms and treatments is highlighted, and the results are further summarized by biological compartment. The 9 biological compartments studied for endometriosis biomarker research are in order of frequency: peripheral blood, eutopic endometrium, peritoneal fluid, ovaries, urine, menstrual blood, saliva, feces and cervical mucus. Adjustments of results on disease phenotypes, cycle phases, treatments and symptoms are present in 70%, 29%, 3% and 6% of selected articles, respectively. A total of 1107 biomarkers were identified in these biological compartments. Of these, 74 were found in several biological compartments by at least two independent research teams and only 4 (TNF-a, MMP-9, TIMP-1 and miR-451) are detected in at least 3 tissues with cohorts of 30 women or more.Integrative analysis is a crucial step to highlight potential pitfalls behind the lack of success in the search for clinically relevant endometriosis biomarkers, and to illuminate the physiopathology of this disease.

Assessment of the pelvic pain experienced by infertile women is of prime importance for diagnosing endometriosis.

OBJECTIVE: To provide evidence regarding the significance of painful symptoms among women suffering from infertility. DESIGN: An observational retrospective cross-sectional study SETTINGS: University hospital-based research center PATIENTS: Infertile patients aged between 18-42 years surgically explored for benign gynecological conditions between 01-2004 and 12-2020. INTERVENTION(S): For each patient, a standardized questionnaire was completed during a face-to-face interview conducted by the surgeon in the month preceding the surgery. Preoperative assessment the pain symptoms was recorded. Pain intensity was assessed with a 10cm visual analog scale (VAS). The pain was considered to be severe when the VAS score was ≥ 7. MEASUREMENTS AND MAIN RESULTS: Surgery was performed in 839 infertile women. 451 women had severe pelvic pain. Infertile patients with severe pain significantly more often had endometriosis (67.4% versus 30.7% respectively; p<0.001) than infertile women without severe pelvic pain, and especially deep infiltrating lesions (43.2% versus 8.5% respectively; p<0.001). Moreover, these women more often had intestinal endometriosis lesions (28.4% versus 1.8%; p<0.001). After multivariable regression analysis, the presence of endometriosis, irrespective of the phenotype (superficial lesions (OR1.84[1.19-2.86] and/or ovarian endometrioma OR 2.79[1.70-4.59] and/or deep infiltrating endometriosis OR 4.49[2.69-7.51]), and the presence of at least one intestine endometriosis lesion (OR6.49[2.69-7.51] were significantly associated with severe pelvic pain. CONCLUSION: Severe pelvic pain is significantly associated with endometriosis and especially deep infiltrating lesions in a population of infertile women. These results demonstrate the importance of thorough questioning regarding pelvic pain symptoms during the initial management of infertile patients.

Impact of Endometriosis Surgery on In Vitro Fertilization/Intracytoplasmic Sperm Injection Outcomes: a Systematic Review and Meta-analysis.

Endometriosis-related infertility remains a therapeutic challenge. A burning issue in this field of research is determining whether pre-assisted reproductive technology (ART) surgery may be of some benefit in terms of reproductive outcomes. This systematic review and meta-analysis aimed at comparing ongoing pregnancy rates (OPR) and/or live birth rates (LBR) in patients who underwent endometriosis surgery before ART (IVF/ICSI) in comparison with patients who underwent first-line ART (IVF/ICSI). Searches were conducted from January 1990 to June 2021 on PubMed, Embase, and Cochrane Library using the following search terms: endometriosis, surgery, reproductive outcomes, and IVF/ICSI. The primary outcomes were OPR or LBR. A total of 19 studies were included in the meta-analysis. No statistically significant differences in LBR [0.91[0.63, 1.30]; I2 = 66%; n = 11], OPR [1.28[0.66, 2.49]; I2 = 60%; n = 3], and early pregnancy loss rate [0.88[0.62, 1.25]; I2 = 0%; n = 7] per cycle were found when comparing patients who underwent endometriosis surgery before IVF/ICSI and those who did not. After the exclusion of the studies with high risks of bias, the LBR per cycle was significantly reduced in the case of surgical treatment before IVF/ICSI [0.53[0.33, 0.86]; I2 = 30%; n = 4]. These data urge the clinician to carefully weigh the pros and cons before referring infertile patients with endometriosis to surgery before IVF, highlighting the key role of multidisciplinary referral centers.

Investigating the medical journey of endometriosis-affected women: Results from a cross-sectional web-based survey (EndoVie) on 1,557 French women.

OBJECTIVE: To investigate the medical journey and the quality of life of French endometriosis-affected women, from the onset of the symptoms to the therapeutic management. STUDY DESIGN: Between January 15th 2020 and February 3rd 2020, a prospective cross-sectional web-based survey was conducted among women diagnosed with endometriosis. The questionnaire included 52 questions distributed in five sections (screening, sociodemographic characteristics, impacts on quality of life, SF36 questionnaire, management of endometriosis and proposals for care improvement). RESULTS: One thousand five hundred fifty-seven endometriosis-affected women aged of 42±12.8 years answered the questionnaire. On average, 7 years elapsed between the first symptoms (at 23.8 ± 10.2 years) and the diagnosis (31.0 ± 8.9 years). The mean number of symptoms was 4.6 ± 2.3, with 82 % of women experiencing pain scores between 7 and 10/10. Following diagnosis, 66 % women received a medical treatment, mostly hormonal treatments (45 %), with a significant decrease in pain intensity (VAS scores after treatment = 4.9 ± 2.7, p < 0.001). Most women (62 %) had already been operated, among whom 22 % by laparotomy. Finally, patients reported numerous impacts on their daily lives, particularly on the sexual, psychological, and physical fields. The overall mean score of quality of life was 4.3 ± 2.6 /10. CONCLUSION: This large prospective web-based survey underlines that the journey of women with endometriosis is long and difficult until diagnosis and efficient treatment. It emphasizes the urgent need to reduce the diagnostic delay and thereby the burden of endometriosis on women's lives. Moreover, the creation of referral multidisciplinary centers appears to be crucial to improve the management of the disease.

Menstrual Blood Donation for Endometriosis Research: A Cross-Sectional Survey on Women's Willingness and Potential Barriers.

An anonymous online survey in French was used to assess if endometriosis patients would be as ready as unaffected women to donate their menstrual blood for biological research on endometriosis and evaluate potential barriers to such donation. It was distributed in September 2022 by social media and two mailing lists, including a French patient organization. The questionnaire assessed participant age and brief medical history (hormonal contraception, endometriosis diagnosis, type of endometriosis), menstrual experience (menstrual blood abundance, dysmenorrhea), and whether participants would donate menstrual blood. Women who self-declared with an established endometriosis diagnosis versus no endometriosis were compared. Seven hundred seventy-eight women answered the survey. Among women with menstruation (n = 568), 78% are willing to donate menstrual blood for research. Importantly, this proportion was higher in women who declared having an established endometriosis diagnosis (83%, n = 299) compared to self-declared unaffected women (68%, n = 134, p < 0.001). The previous use of a menstrual cup and dysmenorrhea were significantly associated with the willingness to donate menstrual blood, while the use of hormonal contraception was significantly associated with an unwillingness to donate. Only the previous use of the menstrual cup had a predictive value for menstrual blood donation. No significant relationship was observed between menstrual blood donation and age, heavy menstrual bleeding and in endometriosis patients, endometriosis subtypes. In conclusion, women affected or not by endometriosis are largely willing to donate their menstrual blood for research on endometriosis, dysmenorrhea is not a barrier for donation, and women who use a menstrual cup are the more likely to donate.