Cumulative live birth rates under three consecutive IVF/ICSI treatment cycles are reduced in women with endometriosis and/or adenomyosis diagnosed by ultrasonography.

study questionDoes endometriosis and/or adenomyosis, diagnosed using the International Deep Endometriosis Analysis (IDEA) group and the Morphological Uterus Sonographic Assessment (MUSA) group revised definitions, impact cumulative live birth rates (CLBR) after three consecutive IVF or ICSI treatments? SUMMARY ANSWER: Women with endometriosis and/or adenomyosis, as diagnosed using transvaginal ultrasonography, had a 15% reduced chance of having a cumulative live birth after three consecutive IVF/ICSI treatments compared to women without these conditions. WHAT IS KNOWN ALREADY: Women with endometriosis or adenomyosis reportedly have lower live birth rates after their first IVF/ICSI treatment. However, most women undergo multiple cycles, and given their shared pathophysiology, the combined impact of both conditions over consecutive treatments remains unclear. STUDY DESIGN, SIZE, DURATION: This was a prospective cohort study of 1035 women undergoing up to three consecutive IVF/ICSI treatments at a university hospital between January 2019 and April 2024. Swedish regulations entitle women to up to three subsidized treatment cycles, including fresh and/or frozen embryo transfers, until the birth of a living child is achieved. PARTICIPANTS/MATERIALS, SETTING,

methodsAll 1035 included women underwent a transvaginal ultrasound examination prior to starting their first treatment. Using the IDEA and revised MUSA definitions, respectively, in total 293 (28.3%) women had endometriosis and/or direct features of adenomyosis on ultrasonography. All 1035 women underwent the first treatment cycle. In total, 818 (79.0%) women [595 (80.2%) of women without endometriosis and/or adenomyosis and 223 (76.1%) of women with either of the diseases] underwent all treatments they were eligible for. A total of 217 (21.0%) women dropped out after the first or second treatment even if they had not achieved a live birth. In total, 1725 fresh treatment cycles were initiated, leading to 1283 fresh and 622 frozen embryo transfers. Live births were recorded. The adjusted relative risk (aRR) for cumulative live birth after three consecutive IVF/ICSI treatment cycles was calculated on an intention-to-treat (ITT) as well as per-protocol (PP) basis, using a modified Poisson regression analysis, adjusting for age as a potential confounder. MAIN RESULTS AND THE ROLE OF CHANCE: The CLBR over three consecutive IVF/ICSI treatment cycles was 666/818 (81.4%) in the total cohort. In an ITT and PP analyses, respectively, women with endometriosis and/or adenomyosis had a lower CLBR of 156/293 (53.2%) or 156/223 (70.0%) compared to women without, CLBR of 510/742 (68.7%) or 510/595 (85.7%), P < 0.001. The aRR for cumulative live birth for women with endometriosis and/or adenomyosis was aRR (ITT) 0.80 (95% CI, 0.71-0.90), P < 0.001, and aRR (PP) 0.85 (95% CI, 0.77-0.93), P < 0.001 compared to women without the diseases. After stratifying the results per treatment cycle, the LBR after the first treatment for women with endometriosis and/or adenomyosis was 90/293 (30.7%), aRR 0.69 (95% CI 0.57-0.84), P < 0.001, after the second 44/154 (28.6%), aRR 0.72 (95% CI 0.54-0.96), P = 0.023, and after the third treatment 22/84 (26.2%), aRR 0.83 (95% CI 0.54-1.28), P = 0.183. For women without the diseases, the LBR was 335/742 (45.1%) in the first cycle, 132/319 (41.4%) in the second, and 43/133 (32.3%) in the third cycle. The largest differences were seen after fresh compared to frozen embryo transfers. LIMITATIONS, REASONS FOR CAUTION: The ultrasound examinations were performed at a tertiary care hospital by an examiner with expertise in endometriosis and adenomyosis. According to the revised MUSA definitions, direct features of adenomyosis are pathognomonic, whereas indirect features are only indicative of the disease. It is possible that some women with only indirect features, who were considered healthy in this study, in fact had the disease and therefore were wrongly classified. WIDER IMPLICATIONS OF THE

findingsDespite a lower CLBR over three IVF/ICSI cycles, women with endometriosis and/or adenomyosis still have a reasonable chance of achieving a live birth with consecutive treatments. Negative results after the first treatment should not be an argument to withhold further attempts. Future research should explore strategies to enhance treatment success in this population, including the role of long-term suppression protocols, exogenous progesterone dosing, and personalized embryo transfer approaches. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by regional research grants from Region Skåne, Sweden. TRIAL REGISTRATION NUMBER: N/A.