Assessing the adequacy of gonadotropin-releasing hormone agonist leuprolide to trigger oocyte maturation and management of inadequate response  Frank E. Chang, M.D., Stephanie A. Beall, M.D., Ph.D., Jeris M. Cox, M.D., Kevin S. Richter, Ph.D., Alan H. DeCherney, M.D., Michael J. Levy, M.D.  Fertility and Sterility  Volume 106, Issue 5, Pages 1093-1100.e3 (October 2016) DOI: 10.1016/j.fertnstert.2016.06.013 Copyright © 2016 American Society for Reproductive Medicine Terms and Conditions

Figure 1 Scatter plots illustrating (A) the significant decrease in post-trigger LH concentration with increasing time between GnRH agonist trigger administration and hormone assay; (B) the significant increase in post-trigger P concentration with increasing time between GnRH agonist trigger administration and hormone assay; and (C) post-trigger LH and P concentrations for successful GnRH agonist triggers (black data points), failed triggers that were retriggered with the use of hCG based on post-trigger hormone assays (red data points), and failed triggers in which retrieval was attempted but aborted after aspiration of several follicles without recovery of oocytes (yellow data points). Fertility and Sterility 2016 106, 1093-1100.e3DOI: (10.1016/j.fertnstert.2016.06.013) Copyright © 2016 American Society for Reproductive Medicine Terms and Conditions

Figure 2 Proportions of cycles in which the GnRH agonist trigger failed, requiring retrigger with hCG, according to body mass index (BMI), baseline LH, and total gonadotropin administration during stimulation. Fertility and Sterility 2016 106, 1093-1100.e3DOI: (10.1016/j.fertnstert.2016.06.013) Copyright © 2016 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 1 Scatter plot of post-trigger LH and P concentrations after GnRH agonist triggers, truncated at 7 ng/mL P and 60 mIU/mL LH to focus on the ranges within which all observed failed triggers occurred. Successful triggers are indicated by black data points, failures as determined by hormone assay by red data points, and failures as determined by lack of oocyte recovery from aspirated follicles by yellow data points. Our general guideline defining 3 ng/mL P or 15 mIU/mL LH as minimum thresholds to proceed with retrieval as scheduled is indicated by the area in the blue dashed line. Our empirically derived threshold below which laboratory results are considered to be “borderline” and indicative of a cycle in which oocyte retrieval should be undertaken with caution owing to an increased likelihood that oocytes will not be recovered, and retrigger may be required, is indicated by the diagonal blue dashed line. Fertility and Sterility 2016 106, 1093-1100.e3DOI: (10.1016/j.fertnstert.2016.06.013) Copyright © 2016 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 2 Flow diagram illustrating recommended treatment algorithm for management of potential failed GnRH agonist triggers. Preliminary assessments of trigger response are based on post-trigger assays of serum LH and P concentrations, measured ∼10–12 hours after trigger. Retrigger with the use of hCG without attempting oocyte retrieval as originally scheduled if both LH is <15 mIU/mL and P is <3 ng/mL. Within the “borderline” range (as illustrated in Supplemental Fig. 1), proceed with oocyte retrieval with caution, keeping in mind that a small but clinically significant minority of these cycles will require retrigger with the use of hCG if no oocytes are recovered from aspiration of the first six to seven follicles. Otherwise, proceed with oocyte retrieval as scheduled, with a very low probability that retrigger will be required. Fertility and Sterility 2016 106, 1093-1100.e3DOI: (10.1016/j.fertnstert.2016.06.013) Copyright © 2016 American Society for Reproductive Medicine Terms and Conditions