TY - JOUR
T1 - Midluteal progesterone
T2 - A marker of treatment outcomes in couples with unexplained infertility
AU - Hansen, Karl R.
AU - Eisenberg, Esther
AU - Baker, Valerie
AU - Hill, Micah J.
AU - Chen, Sixia
AU - Talken, Sara
AU - Diamond, Michael P.
AU - Legro, Richard S.
AU - Coutifaris, Christos
AU - Alvero, Ruben
AU - Robinson, Randal D.
AU - Casson, Peter
AU - Christman, Gregory M.
AU - Santoro, Nanette
AU - Zhang, Heping
AU - Wild, Robert A.
N1 - Funding Information:
Financial Support: This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Grants no. U10 HD077680 (to K.R.H.), U10 HD39005 (to M.P.D.), U10 HD38992 (to R. S. L.), U10 HD27049 (to C.C.), U10 HD38998 (to R.A.), U10 HD055942 (to R.D.R.), U10 HD055944 (to P.C.), U10 HD055936 (to G.M.C.), and U10 HD055925 (to H.Z.). This research was made possible by the funding of the American Recovery and Reinvestment Act. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NICHD, National Institutes of Health (NIH), or the United States Department of Defense.
Funding Information:
Disclosure Summary: G.M.C. reports grants from AbbVie PharmaceuticalsandBayerPharmaceuticalsoutsidethesubmitted work. C.C. reports grants from the NIH/NICHD during the conduct of the study and personal fees from ASRM outside the submitted work. M.P.D. reports grants from the NIH/NICHD during the conduct of the study. E.E. reports salary from the NICHD during the conduct of the study. K.R.H. reports grants from the NIH/NICHD during the conduct of the study and grants from Roche Diagnostics and Ferring International Pharmascience CenterUSoutsidethesubmittedwork.R.S.L.reportspersonalfees from Odega, Kindex, Fractyl, and Bayer, grants from Ferring Pharmaceuticals, and personal fees from AbbVie outside the submitted work. R.D.R. reports grants from the NIH during the conductofthestudyandgrantsfromAbbVieoutsidethesubmitted work. H.Z. reports grants from the NIH during the conduct of the study. The remaining authors have nothing to disclose.
PY - 2018/7/1
Y1 - 2018/7/1
N2 - 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.
AB - 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.
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U2 - 10.1210/jc.2018-00642
DO - 10.1210/jc.2018-00642
M3 - Article
C2 - 29767754
AN - SCOPUS:85050105176
VL - 103
SP - 2743
EP - 2751
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 7
ER -