Midluteal Progesterone: A Marker of Treatment Outcomes in Couples With Unexplained Infertility

Abstract

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.

Trial registration: ClinicalTrials.gov NCT01044862.

Figures

Figure 1.

Efficiency curves for live births by midluteal progesterone level. Efficiency curves were calculated (a) for all treatment groups combined and (b) for each treatment group individually (blue represents gonadotropin cycles, green represents letrozole cycles, and red represents clomiphene citrate cycles). The generated curves show the probability of a live birth on the y-axis at or below the integer progesterone value on the x-axis. This process results in the exclusion of cycles above the given value (both live birth and non‒live birth cycles). Thus, with each incremental decrease in progesterone, the total number of cycles decreases because of loss of both positive and negative outcomes. With this approach, it is possible for live birth rates to go up and down as progressively lower thresholds are evaluated.