Daytime Variation in Serum Progesterone During the Mid-Luteal Phase in Women Undergoing In Vitro Fertilization Treatment

OBJECTIVE: To investigate whether mid-luteal serum progesterone (P(4)) exhibits significant fluctuations during a 12-h daytime period in women undergoing in vitro fertilization (IVF) and to explore whether the extent of these fluctuations could impact the interpretation of luteal progesterone levels in a clinical setting. DESIGN: Explorative pilot study. SETTING: Public hospital-based fertility unit. PATIENTS: Ten women undergoing IVF treatment. INTERVENTION: Seven days after oocyte pick-up, patients underwent frequent repeated blood sampling (every 60 min for 12 h and during two of these hours, every 15 min). Serum samples were analyzed for progesterone, estradiol, and luteinizing hormone (LH). MAIN OUTCOME MEASURES: Daytime fluctuations in s-progesterone and s-estradiol. RESULTS: There was a significant positive correlation between median P(4) levels and the magnitude of P(4) variations—women with median P(4) < 60 nmol/l had clinically stable P(4) levels throughout the day, while patients with median P(4) > 250 nmol/l exhibited periodic P(4) peaks of several hundred nanomoles per liter. These endogenous P(4) fluctuations were observed irrespective of the type of stimulation protocol or mode of triggering of final oocyte maturation and despite the fact that LH was under the detection limit at the time of measurement. Simultaneously, large fluctuations were seen in s-estradiol. CONCLUSION: Monitoring of early to mid-luteal P(4) levels in IVF cycles may be valuable in the planning of individualized luteal phase support in the attempt to increase reproductive outcomes. The prerequisite for luteal phase monitoring is, however, that the validity of a single measured P(4) value is reliable. We show for the first time, that a single P(4) measurement in the low progesterone patient quite accurately reflects the corpus luteum function and that the measurement can be used to detect IVF patients with a need of additional exogenous luteal P(4) administration.