title: 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.
abstract: 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.
  
  
  METHODS
  Retrospective cohort.
  
  
  METHODS
  Private academic center.
  
  
  METHODS
  A total of 10,280 patients undergoing their first IVF cycle.
  
  
  METHODS
  None.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Reproductive Endocrinology, Department of Obstetrics, Gynecology and Reproductive Sciences, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey. Electronic address: mwerner@rmanj.com.
authors.forename: Marie D
authors.initials: MD
authors.lastname: Werner
authors.affiliation: Division of Reproductive Endocrinology, Department of Obstetrics, Gynecology and Reproductive Sciences, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey; Reproductive Medicine Associates of New Jersey, Basking Ridge, New Jersey.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Forman
authors.affiliation: Division of Reproductive Endocrinology, Department of Obstetrics, Gynecology and Reproductive Sciences, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey.
authors.forename: Kathleen H
authors.initials: KH
authors.lastname: Hong
authors.affiliation: Division of Reproductive Endocrinology, Department of Obstetrics, Gynecology and Reproductive Sciences, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Franasiak
authors.affiliation: Division of Reproductive Endocrinology, Department of Obstetrics, Gynecology and Reproductive Sciences, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey; Reproductive Medicine Associates of New Jersey, Basking Ridge, New Jersey.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Molinaro
authors.affiliation: Division of Reproductive Endocrinology, Department of Obstetrics, Gynecology and Reproductive Sciences, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey; Reproductive Medicine Associates of New Jersey, Basking Ridge, New Jersey.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Scott
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005307:Fertilization in Vitro; D005640:Follicle Stimulating Hormone / Q000008:administration & dosage*; D005498:Follicular Phase / Q000097:blood*; D006801:Humans; D007247:Infertility, Female / Q000097:blood* / Q000473:pathology / Q000628:therapy; D007986:Luteinizing Hormone / Q000008:administration & dosage*; D010053:Ovary / Q000187:drug effects / Q000473:pathology*; D010062:Ovulation Induction / Q000379:methods*; D011247:Pregnancy; D011256:Pregnancy Outcome; D011374:Progesterone / Q000097:blood*; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D011374:Progesterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone
keywords: Gonadotropins; exogenous FSH; exogenous LH; late follicular increase in progesterone; stimulation