Midluteal progesterone: A marker of treatment outcomes in couples with unexplained infertility

Karl R. Hansen, Esther Eisenberg, Valerie Baker, Micah J. Hill, Sixia Chen, Sara Talken, Michael P. Diamond, Richard S. Legro, Christos Coutifaris, Ruben Alvero, Randal D. Robinson, Peter Casson, Gregory M. Christman, Nanette Santoro, Heping Zhang, Robert A. Wild

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Context Adequate luteal phase progesterone exposure is necessary to induce endometrial changes required for a successful pregnancy outcome. The relationship between low midluteal progesterone concentration and the outcome of live birth in ovarian stimulation with intrauterine insemination (OS-IUI) treatments is not defined. Objective To determine the level of midluteal progesterone portending a low chance of live birth after OS-IUI in couples with unexplained infertility. Design and Setting Secondary analyses of data from a prospective, randomized, multicenter clinical trial that determined pregnancy outcomes following OS-IUI with clomiphene citrate, letrozole, or gonadotropins for couples with unexplained infertility. Participants Couples (n = 900) underwent 2376 OS-IUI cycles during the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation clinical trial. Main Outcome Measures Live birth as it relates to midluteal progesterone level and thresholds below which no live births occur by treatment group. Results Thresholds for non-live birth cycles were similar for clomiphene (14.4 ng/mL) and letrozole (13.1 ng/mL) yet were lower for gonadotropin (4.3 ng/mL) treatments. A midluteal progesterone level >10th percentile specific for each treatment group independently was associated with greater odds for a live birth in all OS-IUI cycles (adjusted OR: 2.17; 95% CI: 1.05, 4.48). Conclusions During OS-IUI, a low midluteal progesterone level was associated with a low probability of live birth. Thresholds differed by medication, with the lowest threshold for gonadotropin. Several pathophysiologic mechanisms may account for low progesterone levels. Refinement of the predictive range associated with particular ovarian stimulation medications during treatment of unexplained infertility may improve accuracy.

Original languageEnglish (US)
Pages (from-to)2743-2751
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Issue number7
StatePublished - Jul 1 2018

ASJC Scopus subject areas

  • Biochemistry, medical
  • Endocrinology
  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology, Diabetes and Metabolism


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