Changing stimulation protocol on repeat conventional ovarian stimulation cycles does not lead to improved laboratory outcomes

Changing stimulation protocols during conventional ovarian stimulation does not improve laboratory outcomes in subsequent in vitro fertilization cycles.

VOLUME 116, ISSUE 3, P757-765


Kaitlyn Wald, M.D., Eduardo Hariton, M.D., M.B.A., Jerrine R. Morris, M.D., M.P.H., Ethan A. Chi, Mr., Eleni G. Jaswa, M.D., M.Sc., Marcelle I. Cedars, M.D., Charles E. McCulloch, Ph.D., Mitchell Rosen, M.D.



To evaluate whether physicians’ choice of ovarian stimulation protocol is associated with laboratory outcomes.


Retrospective cohort study.


Single academic center.


The subjects were 4,458 patients who completed more than one in vitro fertilization ovarian stimulation cycle within 1 year. On second stimulation, 49% repeated the same protocol and 51% underwent a different one.


Estradiol priming antagonist, antagonist +/– oral contraceptive pill priming, long luteal protocol, Lupron (Lupron [AbbVie Inc, North Chicago, IL]) stop protocol, and flare were compared. Logistic or linear regression with cluster robust standard errors to account for covariates and paired data was used.

Main Outcome Measure(s)

Oocytes collected (OC), fertilization rate, blastocyst progression (BP), usable embryos (UE), and euploid rate (ER).


First stimulation outcomes were comparable across all protocols for FR, BP, UE, and ER but were different for OC, after adjustment for covariates. For OC, the effect of switching protocols differed according to the type of the second stimulation. There was improvement in OC if the same stimulation was repeated, except for flare. In addition, there were slight, significant improvements in fertilization rate (difference in values or coefficient of 0.02; 95% confidence interval [CI], 0.004, 0.4) and UE (coefficient 1.25; 95% CI, 0.79, 1.72) when the same stimulation was repeated. There were no changes in BP (coefficient 0.03; 95% CI, –0.01, 0.08) or ER (coefficient 0.01; 95% CI, –0.04, 0.06) when protocols were changed. In a low-BP subgroup, greater improvement was seen when the same protocol was repeated (coefficient 0.03; 95% CI 0.01, 0.04).


There was a slight but significant improvement in laboratory outcomes when the same stimulation protocol was repeated, so careful consideration should be made before switching stimulation protocols for the purpose of improving laboratory outcomes.