Objective: To determine whether there is an association between the type of natural cycle frozen embryo transfer (FET) (scheduled vs. traditional) and live birth outcomes.
Design: Retrospective cohort of all natural cycle FETs across a single network of fertility clinics in the United States.
Subjects: All natural cycle FETs performed in ovulatory patients between January 2019 and April 2022.
Exposure: Scheduled natural cycle FET cycles that received a short-duration of gonadotropin-releasing hormone antagonist (1 ampule/d) with low-dose gonadotropins (75 IU/d) to delay ovulation to enable more flexible scheduling of the FET were compared with cycles without delay.
Main outcome measures: Live birth.
Results: There were a total of 1,087 natural cycle FETs that met the inclusion criteria. The scheduled natural cycle FET protocol was used in 114 (10.5%) of these cycles. The mean age was 35 (interquartile range, 33-38) years. Preimplantation genetic testing for aneuploidy was used in 76.3% (n = 87) of scheduled natural cycle FET cycles and 68.9% (n = 670) of natural cycle FET cycles. The scheduled natural cycle FET group had a significantly higher estradiol level (318 vs. 249 pg/mL) and a lower luteinizing hormone level (5.7 vs. 13.4 mIU/mL) at ovulatory trigger but a comparable peak endometrial thickness (9.4 vs. 9.7 mm) compared with the natural cycle FET group. Overall, there was a significant increase in the rates of positive human chorionic gonadotropin (scheduled natural cycle, 81.6%, vs. natural cycle, 64.3%; relative risk [RR], 1.26 [95% confidence interval {CI}, 1.15-1.38]) and clinical pregnancy (scheduled natural cycle, 68.4%, vs. natural cycle, 57.1%; RR, 1.21 [95% CI, 1.06-1.38]) in the scheduled natural cycle group. There were a higher proportion of live births in the scheduled natural cycle group; however, this did not reach statistical significance (scheduled natural cycle, 57.0%, vs. natural cycle, 49.4%; RR, 1.15 [95% CI, 0.97-1.36]). A subanalysis of preimplantation genetic testing for aneuploidy cycles yielded similar results.
Conclusion: A scheduled natural cycle FET protocol using a short duration of gonadotropin-releasing hormone antagonist along with low-dose gonadotropin add-back did not reduce live birth compared with traditional natural cycle FET cycles. These results suggest that this is an alternative FET protocol that may serve as a viable strategy to provide flexibility in scheduling the day of FET while still allowing a patient to undergo a natural cycle protocol. This protocol modification may enable more clinics to offer natural cycle FET.
Clinical practice guidelines are critical tools to inform healthcare decision-making, yet development faces significant challenges in ensuring rigorous, reliable, and globally applicable recommendations. This review examines the essential standards and evolving approaches for creating high-quality, evidence-based guidelines that can effectively support clinical practice across diverse healthcare settings. Key standards for high-quality clinical practice guideline development emerge from leading global health organizations, emphasizing several critical components-establishing a multidisciplinary development group, defining a clear and relevant scope, conducting systematic evidence reviews and meta-analyses, and ensuring transparency throughout the development process. Innovative principles address emerging challenges such as research integrity assessment, incorporation of patient-centered methodologies, promotion of global collaborative approaches, and development of strategic implementation strategies. These evolving principles recognize the complex landscape of modern healthcare, where guidelines should adhere to rigorous standards to genuinely improve patient outcomes and encourage best practice care across diverse healthcare settings.
Objective: To evaluate the efficacy and safety of retaining a balloon stent in the uterus for 8 weeks to prevent adhesion reformation after hysteroscopic adhesiolysis.
Design: A single-center randomized controlled study.
Subjects: A total of 160 women with severe intrauterine adhesions (American Fertility Society intrauterine adhesion scores ≥9 and European Society for Gynaecological Endoscopy grade ≥IV).
Intervention: The participants were randomized 1:1 into two groups. In the study group, the balloon stent was left in place for 8 weeks after surgery and removed at the second-look hysteroscopy, with a third-look hysteroscopy performed 4 weeks later. In the control group, the balloon stent was maintained for 1 week, with participants undergoing second- and third-look hysteroscopies at 4 and 8 weeks postoperatively, respectively. Among 160 randomized patients, 136 (69 and 67 in the study and control groups, respectively) completed the study.
Main outcome measures: The primary outcome was the adhesion recurrence rate on third-look hysteroscopy.
Results: On third-look hysteroscopy, the adhesion reformation was significantly lower in the study group than in the control group (17.4% vs. 43.3%; relative risk, 0.40; 95% confidence interval, 0.22-0.72; rate difference, -25.89%; 95% confidence interval, -40.75% to -11.04%). Additionally, the reduction in American Fertility Society adhesion scores was significantly larger in the study group than in the control group (10 vs. 7). The outcomes of the second- and third-look hysteroscopies were consistent. No safety concerns were observed regarding extended stent placement.
Conclusion: In this randomized controlled study, extending the balloon stent application to 8 weeks proved an effective and safe method for preventing adhesion reformation after hysteroscopic adhesiolysis for severe intrauterine adhesions.