Risk factors for a suboptimal response to gonadotropin releasing hormone agonist trigger during in vitro fertilization cycles

Risk factors for suboptimal response to gonadotropin-releasing hormone agonist-agonist trigger include low luteinizing hormone (LH) and follicle stimulating hormone on in vitro fertilization cycle start day, low LH on trigger day, history of irregular menses, and long-term oral contraceptive use.

Laura Meyer, M.D., Lauren A. Murphy, M.D., Arielle Gumer, M.S., David E. Reichman, M.D., Zev Rosenwaks, M.D., Ina N. Cholst, M.D.

Volume 104, Issue 3, Pages 637-642


To identify risk factors for a suboptimal response to gonadotropin-releasing hormone (GnRH) agonist trigger in in vitro fertilization (IVF) cycles.

Retrospective cohort study.

Academic medical center.

All 424 patients undergoing fresh IVF cycles (n = 500) between August 2007 and June 2013 in whom a GnRH agonist was used as all or part of the ovulation trigger.

GnRH-antagonist-based IVF cycles triggered with leuprolide acetate alone or in combination with low-dose human chorionic gonadotropin.

Main Outcome Measure(s):
Suboptimal response to GnRH-agonist trigger, as defined by a serum luteinizing hormone (LH) level <15 mIU/mL on the morning after trigger. Result(s):
The rate of suboptimal response to the GnRH-agonist trigger was 5.2%. Patients with a suboptimal hormone response had lower follicle-stimulating hormone (<0.1 vs. 3.48) and LH (<0.1 vs. 2.51) levels on day 2 of the cycle start, lower LH (0.109 vs. 0.596) on the day of trigger, and required longer stimulation and more gonadotropins than those with an adequate response. Suboptimal responders were also more likely to have irregular menses and be on long-term oral contraception. Patients with an undetectable LH on the day of trigger had a 25% chance of a suboptimal LH surge. In our study cohort, limiting the use of the GnRH-agonist trigger alone to patients with a trigger day LH ≥0.5 would have reduced the rate of suboptimal response from 5.2% to 0.2%. Conclusion(s):
Long-term hormonal contraception use and a history of irregular menses are independent risk factors for suboptimal response to GnRH-agonist trigger. Patients with very low endogenous serum LH levels on the day of LH trigger are at increased risk for a suboptimal GnRH-agonist trigger response. Understanding the at-risk phenotype and using trigger day LH as a marker for increased risk of suboptimal GnRH-agonist trigger response can be helpful for individualizing treatment and selecting a safe and efficacious trigger medication for patients undergoing IVF.

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