Defining the "sweet spot" for administered luteinizing hormone-to-follicle-stimulating hormone gonadotropin ratios during ovarian stimulation to protect against a clinically significant late follicular increase in progesterone: an analysis of 10,280 first in vitro fertilization cycles

Fertil Steril. 2014 Nov;102(5):1312-7. doi: 10.1016/j.fertnstert.2014.07.766. Epub 2014 Aug 20.


Objective: To determine whether different ratios of administered LH-to-FSH influence the risk of clinically relevant late follicular P elevations and whether there is an optimal range of LH-to-FSH to mitigate this risk.

Design: Retrospective cohort.

Setting: Private academic center.

Patient(s): A total of 10,280 patients undergoing their first IVF cycle.

Intervention(s): None.

Main outcome measure(s): The ratio of exogenous LH-to-FSH throughout stimulation and association with absolute serum P level≥1.5 ng/mL on the day of hCG administration.

Result(s): Stimulations using no administered LH (N=718) had the highest risk of P elevation≥1.5 ng/mL (relative risk [RR]=2.0; 95% confidence interval [CI] 1.8-2.2). The lowest risk of P increase occurred with an LH-to-FSH ratio of 0.30:0.60 (20%; N=4,732). In contrast, ratios<0.30, reflecting proportionally less administered LH (N=4,847) were at increased risk for premature P elevation (32%, RR=1.6; 95% CI 1.5-1.7) as were ratios>0.60 (23%, RR 1.1; 95% CI 1.0-1.3). This pattern of lowest risk in the 0.30-0.60 range held true for cycles characterized by low, normal, and high response. When performing a logistic regression to control for multiple confounding variables this relationship persisted.

Conclusion(s): Absent or inadequate LH dosing is associated with a risk for a late follicular elevation in P sufficient to induce suboptimal outcomes. A total LH-to-FSH ratio of 0.30:0.60 was associated with the lowest risk of P elevation. Optimization of this parameter should be considered when making gonadotropin dosing decisions.

Keywords: Gonadotropins; exogenous FSH; exogenous LH; late follicular increase in progesterone; stimulation.

MeSH terms

  • Adult
  • Biomarkers / blood
  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Fertilization in Vitro
  • Follicle Stimulating Hormone / administration & dosage*
  • Follicular Phase / blood*
  • Humans
  • Infertility, Female / blood*
  • Infertility, Female / pathology
  • Infertility, Female / therapy
  • Luteinizing Hormone / administration & dosage*
  • Ovary / drug effects
  • Ovary / pathology*
  • Ovulation Induction / methods*
  • Pregnancy
  • Pregnancy Outcome
  • Progesterone / blood*
  • Reproducibility of Results
  • Retrospective Studies
  • Sensitivity and Specificity
  • Treatment Outcome


  • Biomarkers
  • Progesterone
  • Luteinizing Hormone
  • Follicle Stimulating Hormone