A low midluteal progesterone level after undergoing ovarian stimulation with medications such as clomiphene citrate, letrozole, or gonadotropins, coupled with intrauterine insemination (OS-IUI) is associated with lower probability of obtaining a live birth, according to new findings published in the Journal of Clinical Endocrinology & Metabolism.
The relationship between luteal phase hormone dynamics and pregnancy outcomes in women who undergo OS-IUI cycles remains unclear, which may be at least partially because of the lack of consensus concerning the concept of luteal insufficiency, its frequency of occurrence, and its clinical significance. In the current study, the authors sought to determine the level and frequency of a low luteal phase serum progesterone level and its association with pregnancy outcomes in patients with unexplained infertility.
Midluteal progesterone levels and live birth outcomes were analyzed for 2376 cycles of 900 participants who underwent OS-IUI as part of the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation clinical trial.
In all treatment cycles, a normal midluteal progesterone level was associated with greater odds of having a live birth (odds ratio 2.47; 95% CI, 1.28-4.79), and this remained consistent even after adjustment for the number of follicles ≥16 mm on the day of human chorionic gonadotropin trigger alone or for peak estradiol. Greater odds of a live birth were also observed in normal vs low progesterone cycles after adjusting for variables that included age, body mass index, number of follicles ≥16 mm on the day of human chorionic gonadotropin trigger, follicular phase length, duration of infertility, treatment medication, and treatment cycle number (adjusted odds ratio 2.17; 95% CI, 1.05-4.48). With oral medications, cycles with normal midluteal progesterone levels had approximately a twofold to fourfold greater odds of achieving a live birth in the unadjusted and adjusted models.
Investigators concluded that, “a low midluteal progesterone level (≤15.8, 14.8, and 9.1 ng/mL for clomiphene, letrozole, and gonadotropin cycles, respectively) in OS-IUI treatment cycles was associated with lower probability of obtaining a live birth.” Additionally, there were no live births with a midluteal progesterone <14.4, <13.1, and <4.3 ng/mL in clomiphene citrate, letrozole, and gonadotropin cycles, respectively. They also note that, “Additional investigations are necessary to confirm this association and to help refine clinically useful cutoff values for what is a low midluteal progesterone by stimulation protocol associated with lack of success in OS-IUI treatment cycles.”
Hansen KR, Eisenberg E, Baker V, et all; NICHD Reproductive Medicine Network. Mid-luteal progesterone: a marker of treatment outcomes in couples with unexplained infertility [published online May 14, 2018]. J Clin Endocrinol Metab. doi: 10.1210/jc.2018-00642