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 10280 first in vitro fertilization cycles

The ratio of exogenous LH-to-FSH during IVF stimulation impacts the risk for significant late follicular P elevation, with an LH-to-FSH ratio of 0.30-to-0.60 correlating with the lowest risk.

Marie D. Werner, M.D., Eric J. Forman, M.D., Kathleen H. Hong, M.D., Jason M. Franasiak, M.D., Thomas A. Molinaro, M.D., M.S.C.E., Richard T. Scott Jr., M.D., H.C.L.D.

Volume 102, Issue 5, Pages 1312–1317


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.

Retrospective cohort.

Private academic center.

A total of 10,280 patients undergoing their first IVF cycle.


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.

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.

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.

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