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The effect of changing endometrial preparation protocols on pregnancy outcomes after initial, unsuccessful euploid
Christine Whitehead1, Kristin Lefebvre2, Emre Seli3
1IVIRMA Global Research Alliance, IVIRMA New Jersey, Reproductive Medicine Associates of New Jersey, 140 Allen Road, Basking Ridge, NJ 07920, USA.; University of Jamestown, 6000 College Ln, Jamestown, ND 58405, USA..
Research Question:
Does changing frozen embryo transfer (FET) protocols after initial unsuccessful, autologous, single euploid FET improve pregnancy outcomes in the second cycle?
Design:
Retrospective cohort study (n = 2199) including patients without ongoing pregnancy (fetal cardiac activity at 8‒9 weeks' gestation) after first, single, euploid FET using programmed (exogenous hormones) or modified natural (MNC) with trigger protocols between January 2017 to December 2024 and changed protocols in the second FET. Primary outcome was ongoing pregnancy. Secondary outcomes were implantation (beta-HCG >5 mIU/ml), clinical pregnancy (intrauterine pregnancy with cardiac activity), pregnancy loss and live birth (liveborn infant >24 weeks).
Results:
Of the 2199 included patients, 1619 remained on same protocol and 580 changed protocols in the second FET. Changed patients had a higher oocyte age and maternal age at time of second FET and lower anti-Müllerian hormone. Parity, primary diagnosis, paternal age, endometrial thickness, blastulation day and SART embryo grade were comparable. Implantation was similar (adjusted RR [aRR] 1.03, 95% CI 0.98 to 1.08, P = 0.30), but patients who changed protocols had higher chances of clinical (aRR 1.09, 95% CI 1.02 to 1.16, P = 0.008) and ongoing pregnancy (aRR 1.14, 95% CI 1.06 to 1.22, P = 0.001), live birth (aRR 1.14, 95% CI 1.06 to 1.24, P = 0.001) and lower risk of loss (aRR 0.73, 95% CI 0.59 to 0.90, P = 0.003). Sensitivity analyses restricting nulliparous patients and patients with a negative beta-HCG after their first FET yielded similar results. No differences were found among parous patients. Subgroup analyses found improved probability of ongoing pregnancy changing from programmed to MNC (aRR 1.16, 95% CI 1.07 to 1.25) but not from MNC to programmed (aRR 1.01, 95% CI 0.84 to 1.21).
Conclusion:
Changing protocols in a second FET, particularly from programmed to MNC, may improve the probability of ongoing pregnancy and live birth.
