Detecting Ovulation by Progesterone Level


Question

Traditionally (often a euphemism for "We've always done it though we don't have the evidence") serum progesterone has been used in the UK to assess the likelihood of ovulation having occurred on day 21 of a day 28 day cycle (or 7 days before next period if cycle >28 days). A cut-off of >30 nmol/L ( = 943 ng/dL) is quoted as indicating a likely ovulatory cycle by some. My own response has been that this indicates "evidence of adequate luteal activity".

My understanding of the events leading to ovulation is that an ovarian follicle matures, and that if ovulation occurs, a corpus luteum develops which is responsible for progesterone production. If pregnancy ensues, the placenta takes over. If fertilisation does not occur, the CL regresses and progesterone falls.

I therefore have a question as follows:

If a serum progesterone is measured on day 21, and the result is <30 nmol/L, but, say, in double figures - 10-15 nmol/L - the UK perspcetive in many quarters would be that ovulation had not occurred. However, that being the case, where is the progesterone coming from ? Is it the case that ovulation has occurred but that the ovum is produced, is non-viable with rapid "failure" ensuing, and thus a brief burst of progesterone occurs but which peaks below 30 nmol/L ? Philip Hyde, Pilgrim Hospital, Lincolnshire, United Kingdom

Response

Progesterone is produced from both the adrenal gland and the corpus lutuem. Progesterone production from the adrenal gland is fairly stable and contributes approximately 1-1.5 ng/mL when measured in the serum of women during the follicular phase. Following ovulation, there is increasing production of progesterone from the corpus luteum and the progesterone levels gradually rises from a baseline of 1.5 to 3 ng/mL by the first day after ovulation. Levels then continue to rise until it reaches a peak 7 days after ovulation reaching levels of approximately 10-20 ng/mL. Levels of progesterone are secreted in a pulsatile pattern during the luteal phase and thus levels can vary depending on the timing of the blood draw. (See Filicori et al. J Clin Invest 1984;73(6):1638-47).

In this case, where progesterone is lower than the normal D21 peak probably suggests that the timing of the blood draw was either 3 or 4 days before the peak (i.e. the ovulation was occurring later) or 3 or 4 days after the peak ( i.e. the ovulation was occurring earlier). In the U.S. a level of 4 ng/mL is considered ovulatory. However, the most reliable clinical indicator for ovulation is regular menstrual cycles between 25-35 day intervals. Thus, reproductive endocrinologists seldom measure progesterone levels to confirm ovulation. James H. Liu, M.D. Case School of Medicine