Dienogest-Based Progestin-Primed Ovarian Stimulation Versus GnRH Antagonist in IVF: A Preliminary Comparative Cohort Study

Authors: Ilaria Roncarati; M. Doglioli; L. Cipriani; L. De Meis; G. Borghese; R. Seracchioli

Progestin-primed ovarian stimulation has emerged as an alternative to gonadotropin-releasing hormone antagonist protocols for preventing premature luteinizing hormone surges during ovarian stimulation. Although different progestins have been evaluated, evidence on the effectiveness and safety of dienogest-based progestin-primed ovarian stimulation remains limited.

This monocentric observational cohort study evaluated whether dienogest-based progestin-primed ovarian stimulation (PPOS) provides ovarian response and embryological outcomes comparable to a gonadotropin-releasing hormone (GnRH) antagonist protocol in freeze-all in vitro fertilization (IVF) cycles. The study analyzed 409 consecutive IVF cycles conducted between January and October 2025. Women aged 18–45 years undergoing IVF with a freeze-all strategy were included. Participants underwent controlled ovarian stimulation using either dienogest-based PPOS (2 mg/day) or a flexible GnRH antagonist protocol. The primary outcome was the number of metaphase II (MII) oocytes retrieved. Secondary outcomes included estradiol levels, duration of stimulation, fertilization rate, blastulation rate, blastocyst availability, and cycle cancellation. Analyses were adjusted for age, body mass index (BMI), endometriosis, and anti-Müllerian hormone (AMH) levels.Baseline characteristics differed between the groups, with women in the dienogest group being younger, having higher AMH levels, a higher prevalence of endometriosis, and a higher BMI.

The mean number of MII oocytes retrieved was similar between the dienogest and GnRH antagonist groups (5.6 vs. 5.0; p = 0.18), and the difference remained non-significant after adjustment (β = +0.05; 95% bias-corrected and accelerated confidence interval [BCa CI] −0.30 to +0.36). Total oocyte yield, blastulation rate, frozen blastocyst availability, and cycle cancellation rates were also comparable in both unadjusted and adjusted analyses. The fertilization rate was significantly higher with dienogest-based PPOS than with the GnRH antagonist protocol (82.9% vs. 77.3%; p = 0.026). This difference remained significant after adjustment (β = +2.0%; 95% BCa CI 0.4–3.5). Estradiol levels on the trigger day were lower with dienogest (β = −112 pg/mL), while stimulation duration was slightly longer (β = +0.23 days). Multivariable analysis identified age greater than 40 years, obesity, and endometriosis as independent negative predictors of MII oocyte yield and blastocyst availability, whereas AMH was the strongest positive predictor. The stimulation protocol itself was not independently associated with ovarian or embryological outcomes. The study was limited by its observational design, baseline differences between groups, and the lack of pregnancy and live birth outcomes, which are still being collected.

Overall, dienogest-based PPOS produced ovarian and embryological outcomes comparable to those of the GnRH antagonist protocol while achieving a significantly higher fertilization rate in freeze-all IVF cycles.

C-Reactive Protein-Triglyceride-Glucose Index as a Potential Diagnostic Biomarker for Endometriosis, A Case-Control Study

Authors: Samaneh Rokhgireh; Z. Salehi; D. Roya; H. Neda; A. Mehdizadeh Kashi; M. Pourbarghi

The C‑reactive protein–triglyceride–glucose index (CTI) is a newly proposed biomarker that integrates systemic inflammation and metabolic status, with demonstrated predictive value for cardiovascular disease and insulin resistance. Since endometriosis is a chronic inflammatory condition, CTI may serve as a potential marker for endometriosis and help identify women at elevated cardiovascular risk.

This case–control study evaluated the association between the C-reactive protein–triglyceride–glucose index (CTI) and endometriosis and compared metabolic and inflammatory markers between women with and without the condition. The study included 153 women with confirmed endometriosis and 112 women without endometriosis. The two groups were matched for age and body mass index (BMI). Blood glucose, lipid profile, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were measured, and the CTI was calculated for all participants. Statistical analyses were performed using SPSS version 23, with a significance level of p < 0.05. Women with endometriosis had significantly higher triglyceride, low-density lipoprotein (LDL), and total cholesterol levels than controls (p < 0.001). Inflammatory markers, including ESR and CRP, were also significantly higher in the endometriosis group (p < 0.001). CTI values were significantly elevated in women with endometriosis compared with controls (p < 0.001).

Receiver operating characteristic (ROC) curve analysis showed that CTI had high diagnostic accuracy for identifying endometriosis, with an area under the curve (AUC) of 89.99% (95% confidence interval [CI] 85.86–94.13). At a cutoff value of 9.68, CTI demonstrated a sensitivity of 92.3% and a specificity of 83.9%. The study was limited by its single-center design and the inability to fully account for potential confounding factors such as lifestyle and diet. Larger multicenter studies with longitudinal follow-up are needed to validate these findings.

Overall, women with endometriosis had higher metabolic and inflammatory marker levels than controls, and the C-reactive protein–triglyceride–glucose index showed high diagnostic accuracy as a noninvasive biomarker for endometriosis.

Endometriosis and Risk of Autoimmune Diseases: Evidence from a Nationwide Korean Cohort

Authors: Eunhee Yu; J.K. Joo; H. Lee

Endometriosis is an estrogen-dependent inflammatory disorder marked by immune dysregulation. Prior studies have linked it to autoimmune diseases such as rheumatoid arthritis, lupus, inflammatory bowel disease, and thyroid disorders, but findings are inconsistent and often based on small Western cohorts or self-reported data. Large-scale longitudinal studies in East Asian populations are scarce, and few have examined multiple autoimmune disease categories together.

This nationwide population-based matched cohort study evaluated whether women with endometriosis have an increased risk of developing autoimmune diseases and whether this risk differs across autoimmune disease categories. The study used Korean national health insurance data and included 33,592 women with endometriosis who were propensity score matched to 33,592 women without endometriosis. Participants were followed longitudinally, and incident autoimmune diseases were identified using diagnostic codes. Time-varying Cox proportional hazards models were used to assess the association while reducing immortal time bias. After propensity score matching, baseline demographic, socioeconomic, and clinical characteristics were well balanced between the two groups. During follow-up, women with endometriosis had a higher incidence of autoimmune diseases than matched controls. Endometriosis was associated with a 25% higher risk of developing any autoimmune disease (adjusted hazard ratio [aHR] 1.25; 95% confidence interval [CI] 1.16–1.36). Disease-specific analyses showed significant associations with autoimmune rheumatic diseases, including rheumatoid arthritis, and with Behçet’s disease. Among endocrine autoimmune disorders, women with endometriosis had a significantly higher risk of Graves’ disease. However, no significant associations were observed for Hashimoto’s thyroiditis, type 1 diabetes mellitus, systemic lupus erythematosus, ulcerative colitis, or dermatologic and hematologic autoimmune diseases. The study was limited by the use of administrative claims data, which did not provide information on disease severity, stage, or clinical phenotype. Residual confounding is possible, and the observational design does not establish a causal relationship.

Overall, women with endometriosis had a significantly higher risk of developing autoimmune diseases, particularly autoimmune rheumatic disorders and Graves’ disease, compared with women without endometriosis.

Comparative Risks of Dienogest Versus Medroxyprogesterone Acetate in Women with Endometriosis and Adenomyosis: A Nationwide Population-Based Cohort Study

Authors: ChiaYi Hsu; T. Eing-Mei

Dienogest (DNG) is a fourth‑generation oral progestin with strong affinity for progesterone receptors, widely used in treating endometriosis and adenomyosis. Medroxyprogesterone acetate (MPA), though cheaper and more available, has been the traditional option. However, real‑world comparative safety data between DNG and MPA are limited, especially in patients with these conditions. In Taiwan, reimbursement policies also influence treatment choices, making robust evidence on their relative risk profiles particularly important.

This retrospective cohort study compared the safety profiles of dienogest (DNG) and medroxyprogesterone acetate (MPA) in women treated for endometriosis or adenomyosis using nationwide data from Taiwan. The analysis included 195,748 women aged 18–51 years diagnosed with endometriosis or adenomyosis between 2017 and 2020. Data were obtained from the Taiwan Cancer Registry, Taiwan Cancer Registry Long Form, National Health Insurance Research Database, and National Population Registry. Of the total cohort, 96,916 women (67.46%) were unexposed to either treatment, while 46,738 women (32.54%) received progestin therapy. Among treated women, 12,259 (26.23%) received MPA and 34,479 (73.77%) received DNG. Propensity score matching was performed in a 1:1 ratio using age variables to reduce baseline differences. Compared with MPA, DNG was associated with significantly lower incidence rates of several gynecologic and hormone-related conditions. The incidence rate ratio (IRR) for endometrial intraepithelial neoplasia was 0.44 (95% confidence interval [CI] 0.43–0.44), for endometrial hyperplasia 0.34 (95% CI 0.32–0.36), for endometrial cancer 0.37 (95% CI 0.37–0.38), for ovarian cancer 0.52 (95% CI 0.51–0.53), and for breast cancer approximately 0.88 (95% CI 0.87–0.89). DNG was also associated with lower risks of fracture (IRR 0.93; 95% CI 0.91–0.95) and venous thromboembolism (IRR 0.88; 95% CI 0.87–0.89). In contrast, the incidence of osteoporosis was higher in the DNG group than in the MPA group (IRR 1.22; 95% CI 1.21–1.23). Overall, DNG was associated with a lower risk of most endometrial-related diseases and cancers. The study was limited by its retrospective design, a relatively short follow-up period of about four years, and potential selection bias related to Taiwan’s reimbursement policies for DNG.

Overall, DNG showed a more favorable safety profile than MPA for women with endometriosis or adenomyosis, with lower risks of several gynecologic cancers, fracture, and venous thromboembolism, although the risk of osteoporosis was higher with DNG.

Should We Continue Screening for Chronic Endometritis? A Retrospective Analysis of More than 780 Infertile Patients Undergoing Hysteroscopy and Endometrial Biopsy

Authors: Dimitrios-Rafail Kalaitzopoulos; P. Petrone; C. Van Roy; A. Vaiarelli; C. Blockeel; W. Waelput; D. Cimadomo; S. Mackens

The presence of plasma cells in endometrial tissue is a recognized marker of chronic endometritis (CE), yet standardized diagnostic and severity criteria remain lacking. CE is often asymptomatic or minimally symptomatic, making detection difficult and prevalence among infertile patients hard to define. In addition, whether antibiotic treatment truly improves clinical outcomes in CE continues to be debated.

This retrospective observational study evaluated the prevalence of chronic endometritis (CE) and the impact of different treatment approaches on in vitro fertilization (IVF) outcomes. The study included 786 women who underwent hysteroscopy and endometrial biopsy at a university hospital between 2020 and 2021, with one year of follow-up. Chronic endometritis was diagnosed based on the number and distribution of plasma cells in endometrial tissue and classified into grades 0–3. Reproductive outcomes were assessed in 585 women who underwent at least one embryo transfer and were compared between women with and without CE. Additional analyses evaluated outcomes according to antibiotic treatment, number of treatment cycles, and whether a control biopsy was performed. Overall, 304 of 786 women (38.6%) were diagnosed with CE, including 29.0% with grade 1 disease and 9.6% with grades 2 or 3. CE was significantly associated with trophoblast retention identified during hysteroscopy (odds ratio [OR] 3.5; 95% confidence interval [CI] 1.4–8.7; p = 0.006), a greater number of previous miscarriages (OR 1.2; 95% CI 1.0–1.3; p = 0.015), and Arab ethnicity compared with Caucasian ethnicity (OR 2.6; 95% CI 1.2–5.4; p = 0.011). No other baseline characteristics were associated with CE.

Among the 585 women who underwent at least one embryo transfer, live birth rates after the first embryo transfer were similar in women with and without CE (35.8% vs. 34.6%; p = 0.310). There were also no significant differences in positive pregnancy test rates, biochemical pregnancy loss, miscarriage, ectopic pregnancy, or cumulative live birth rates within one year (55.5% vs. 56.2%; p = 0.865). Among women with CE, 92% (281/304) received antibiotic treatment, and 37% (104/281) underwent a control biopsy. Histological improvement was observed in 58% (60/104), while 42% (44/104) had persistent CE. Reproductive outcomes remained similar to those of women without CE regardless of treatment. Blastocyst-stage embryo transfer and euploid embryo transfer were the only factors independently associated with higher live birth rates. The study was limited by its retrospective design, non-standardized management of CE, limited subgroup sizes, indication-based hysteroscopy, and the lack of standardized diagnostic criteria for CE.

Overall, chronic endometritis was not associated with poorer IVF outcomes, and antibiotic treatment did not improve live birth rates, questioning the routine use of CE screening and empirical antibiotic therapy.

ESHRE 2026, July 5^th-8^th, London, UK.