Mid-Cycle Pain in Endometriosis: Clinical Correlations and Potential Etiological Factors
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Abstract
Objective
To characterize differences between individuals with and without mid-cycle pain in a registry cohort with endometriosis.
Design
Prospective analysis of data from the Endometriosis Pelvic Pain Interdisciplinary Cohort Data Registry (Clinicaltrials.gov #NCT02911090) at a tertiary referral center in Western Canada.
Subjects
Three hundred forty-five individuals aged 18-49 years who: (1) had at least one episode of menstrual bleeding in the last 3 months, (2) attended a baseline initial visit, and (3) subsequently had surgery with histological confirmation of endometriosis between January 2018 and December 2023. Exclusion criteria included (1) previous hysterectomy; (2) hormonal suppressive therapy use in the last 3 months; and (3) missing data on mid-cycle pain, history of hormonal therapy use, or menstrual cycle regularity.
Exposures
N/A.
Main Outcome Measures
Mid-cycle pain in the last month versus No mid-cycle pain in the last month.
Results
Of the 345 participants, 67% (n = 232) reported mid-cycle pain in the last month. Mid-cycle pain in the last month was significantly associated with higher mean Central Sensitization Inventory score (48 ± 17 versus 36 ± 16, p < 0.001) and more months of prior hormonal suppressive therapy use (58 [14-120] versus 26 [0-109], p = 0.012). Abnormal anatomy at the time of surgery (e.g., endometrioma, ovarian adhesions) was not associated with mid-cycle pain in the last month.
Conclusion
In this endometriosis cohort at a tertiary referral center, most participants reported mid-cycle pain in the last month, which was associated with central sensitization but was not clearly related to endometriosis anatomical distortion.
By this author
Effectiveness · Comparative Effectiveness
Validating ovulation prediction and confirmation with the Mira monitor: blinded ultrasound and serum hormone comparison
Bouchard TP et al., 2026 · Reproductive biomedicine online · Free to read
Do quantitative urinary hormone measurements on the Mira monitor predict and confirm ovulation accurately compared with ultrasound in women with regular menstrual cycles? Do Mira urine hormones correlate with serum hormones? This was a prospective, single-centre, blinded diagnostic accuracy study with 52 women aged 19-44 years with regular cycles (24-38 days) who tracked 153 cycles over 18 months. Daily first-morning urine was tested with the Mira monitor for follicle stimulating hormone (FSH), oestrone-3-glucuronide (E13G), luteinizing hormone (LH) and pregnanediol glucuronide (PDG). Serial transvaginal ultrasounds (890 scans) confirmed the day of ovulation. Serum hormones were measured twice per cycle. The 121 ovulatory cycles from 49 participants with sufficient index test and reference standard data were included in the final analysis. The Mira LH peak day strongly predicted ultrasound-confirmed ovulation (R² = 0.96, P < 0.001; intraclass correlation coefficient = 0.971), with 96% of ovulations occurring within ±1 day. The Mira PDG increase was also strongly associated with ultrasound-confirmed day of ovulation (R² = 0.87, P < 0.001). First-morning urine hormones were significantly associated with serum hormones when collected within 90 min (LH: R² = 0.92; E13G: R² = 0.73; R² = 0.61; R² = 0.75). Anovulatory cycles were identified in 11% of regularly cycling participants. Quantitative urinary hormone monitoring with the Mira monitor provides accurate prediction and confirmation of ovulation, with strong urine-serum associations supporting reduced reliance on serial serum draws in select patients. These findings support clinical adoption of quantitative urinary fertility monitoring.
Early Pregnancy · Miscarriage
Impact of the coronavirus disease-2019 (COVID-19) pandemic on reproductive outcomes in patients with recurrent pregnancy loss
Balachandran S et al., 2026 · Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC
To assess the impact of the COVID-19 pandemic on reproductive outcomes in patients with recurrent pregnancy loss (RPL) and the influence of material and social deprivation on these outcomes. This retrospective cohort study included RPL patients seen at a specialized clinic between March 1, 2018, and February 28, 2022. Patients were categorized into two groups based on care period: pre-pandemic (March 1, 2018-February 29, 2020) and pandemic (March 1, 2020-February 28, 2022). Cumulative probabilities of birth were estimated using the cumulative incidence function within a competing risk framework, treating pregnancy loss as a competing event. Fine and Gray regression models calculated sub-distribution hazard ratio (sHR) of birth. 544 patients were included in the study, with 255 in the pre-pandemic group and 289 in the pandemic group. Individuals in the pandemic group were less likely to achieve pregnancy than those in the pre-pandemic group (relative risk = 0.50, 95% confidence interval [CI] 0.39 - 0.66). Among those who conceived, the cumulative probability of live birth was 0.77 in both groups. Relative to individuals residing in high-social deprivation neighborhoods, those living in moderately deprived areas had higher sub-distribution hazards of live birth (adjusted sHR = 1.97, 95% CI 1.25 - 3.10; P = 0.003). Within specialized RPL care and a universal maternity care system, pregnancy rates were lower during the first two years of the COVID-19 pandemic. However, among those who conceived, the probability of achieving a live birth remained similar between the pre-pandemic and pandemic periods.
Ultrasound · Follicular Monitoring
Using corpus luteum formation with dominant follicle collapse to improve the criteria for identifying ovulation
Bouchard TP et al., 2026 · Reproductive biomedicine online · Free to read
Does formation of the corpus luteum help to identify the day of ovulation on ultrasound when follicular collapse is missed, and how reliable are sonographers versus a review panel in identifying the day of ovulation on ultrasound? Sonographers in a clinic in Canada performed serial endovaginal ultrasound scans (six to eight per cycle) to identify the day of ovulation in regularly cycling women (n = 40) who were followed for one to five cycles (n = 85). The day of ovulation was identified by: (i) identification of the dominant follicle; (ii) disappearance of the dominant follicle; and (iii) identification and dating of the corpus luteum. The main outcome measures were inter-rater reliability between two sonographers, and Bland-Altman agreement between the supervising sonographer and a panel that reviewed each scan to identify the day of ovulation. Of the 85 menstrual cycles reviewed, two cycles did not have sufficient data to date ovulation, one cycle showed an incidental dermoid cyst, and 11 cycles showed anovulatory patterns. This left a total of 71 cycles (84%) for which intra-rater reliability between two sonographers for identifying the day of ovulation was high (intraclass correlation coefficient = 0.99, P < 0.0001), and Bland-Altman agreement showed no significant difference in the estimated day of ovulation between the supervising sonographer and the panel (t = -0.28, P = 0.78). Corpus luteum criteria were necessary to help identify the day of ovulation in 14 of 71 cycles (20%). The estimated day of ovulation can be determined reliably on ultrasound by trained sonographers using collapse of the dominant follicle and formation of the corpus luteum based on six to eight scans per cycle.
Medical Management · Pain Management
Guideline No. 468: Clinical Management of Endometriosis
Yong PJ et al., 2026 · Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC
To provide health care professionals with an evidence-based approach to the management of endometriosis and its associated symptoms. Women and gender-diverse individuals affected by endometriosis. BENEFITS, HARMS, Timely and effective management of endometriosis has the potential to reduce pain, improve fertility and quality of life, and enhance long-term health outcomes. Early intervention may also help mitigate the financial and health system burdens associated with delayed diagnosis and treatment. Published literature was retrieved through searches of PubMed, Ovid, Medline, Embase, Scopus, and the Cochrane Library from August 2010 through December 2025, using relevant MeSH heading and keywords. Results were restricted to systematic reviews, meta-analyses, randomized controlled trials/controlled clinical trials, observational studies, and clinical practice guidelines. Results were limited to English or French language materials. Evidence was supplemented with references from the 2010 Society of Obstetricians and Gynaecologists of Canada guideline No. 244. The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and conditional recommendations). Health care providers involved in the care of individuals with endometriosis. Early identification and management of endometriosis can significantly improve patient outcomes, reduce long-term health care costs and improve their quality of life. RECOMMENDATIONS.
Related research
Pelvic Pain · Chronic Pelvic Pain
Association of Central Sensitization Inventory Scores With Pain Outcomes After Endometriosis Surgery
Orr NL et al., 2023 · JAMA network open · Free full text on PubMed Central
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Pelvic Pain · Chronic Pelvic Pain
Pain sensitivity questionnaire in endometriosis
Gentles AJ et al., 2025 · The journal of pain · Free to read
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Pelvic Pain · Chronic Pelvic Pain
What we know about primary dysmenorrhea today: a critical review
Iacovides S et al., 2015 · Human reproduction update
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Pelvic Pain · Chronic Pelvic Pain
Central sensitization inventory in endometriosis
Orr NL et al., 2022 · Pain
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Hannah E Rojas, Mohamed A Bedaiwy, Caroline E Lee, Catherine Allaire, Paul J Yong
H Rojas, M Bedaiwy, C Lee, Cathy Allaire, Kate Allaire, C Allaire, P Yong
PMID 42026880 42026880 DOI 10.1177/15409996261443813 10.1177/15409996261443813 Rojas et al. 2026, Rojas 2026
Keywords
central sensitization, endometriosis, hormonal contraception, menstrual cycles, mid-menstrual cycle pain