Israel, R., Mishell DR Jr, Stone, S. C., Thorneycroft, I. H., & Moyer, D. L. (1972). Single luteal phase serum progesterone assay as an indicator of ovulation. American journal of obstetrics and gynecology, 112(8), 1043-1046. https://doi.org/10.1016/0002-9378(72)90178-0
Israel R, Mishell DR Jr, Stone SC, Thorneycroft IH, Moyer DL. Single luteal phase serum progesterone assay as an indicator of ovulation. Am J Obstet Gynecol. 1972;112(8):1043-1046. doi:10.1016/0002-9378(72)90178-0
Israel, R., et al. "Single luteal phase serum progesterone assay as an indicator of ovulation." American journal of obstetrics and gynecology, vol. 112, no. 8, 1972, pp. 1043-1046.
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A single midluteal progesterone blood test suggests ovulation
One blood test in the middle of the luteal phase suggested that ovulation had happened in that cycle. That was the finding in a 1972 study of 51 infertile women with regular periods and 35 women on clomiphene. Among women biopsied, samples above the authors' cutoff came with a secretory uterine lining.
Key Findings
Daily blood samples from 13 regularly cycling women showed progesterone rising 1 or 2 days after the LH peak. Each of the 13 cycles had a biphasic basal body temperature curve.
Among 72 single follicular-phase samples from 44 women, none reached the authors' cutoff, and most were undetectable.
Among 51 infertile women with regular menses, luteal samples taken 11 to 4 days before menstruation all exceeded the cutoff. All 42 biopsies showed secretory endometrium, except one taken 14 days before.
In 35 women on clomiphene citrate, 30 of 71 courses brought no withdrawal bleeding. Those 30 biopsies all showed proliferative endometrium, and every progesterone result fell below the cutoff.
For 41 courses followed by bleeding, samples taken more than 4 and fewer than 11 days beforehand all exceeded the cutoff. All 23 biopsies showed secretory endometrium.
Interpretation
The authors describe a series of women from one clinic, compared against endometrial biopsy and cycle timing. The report calls the result presumptive evidence. Egg recovery or pregnancy would confirm ovulation, and neither served as the standard. The sampling window was set by counting back from the period that followed. The authors call the fast assay not totally specific, since it picked up a small share of related hormones. They warn that congenital adrenal hyperplasia can produce falsely high values. The 51 infertile women had regular menses. The 35 others had irregular or absent ovulation and took clomiphene. The paper reports no data on other groups.
RRM Context
Restorative reproductive medicine treats ovulation as the central event of the cycle, and progesterone marks it. The 1972 study reports an early, simple blood measure that gave presumptive evidence of that event. A progesterone rise marks an ovulatory event. Only serial ultrasound or pregnancy confirms release of an egg. Cycle charting can supply the timing.
Our editorial summary of this paper, not the article's abstract.
Abstract
A study was undertaken to determine whether solitary progesterone as says performed on serum samples obtained in the midluteal phase would provide the clinician with a convenient indicator that ovulation had occurred in that cycle. After a normal luteal-phase range was establish ed, single luteal-phase serum progesterone sampling was performed in 51 infertile women with regular menses and 35 oligomenorrheic women undergoing clomiphene citrate therapy. In the follicular phase of the cycle, progesterone levels were consistently less than 2 ng/ml. Between 11 and 4 days prior to the onset of menses in presumptively ovulatory cycles, serum progesterone levels were always 3 ng/ml or greater. Progesterone values in this range were always accompanied by a secretory endometrium and can be considered presumptive evidence of ovulation. This rapid, easily performed technique enables 1 technician to assay 30 or more samples for progesterone in a single working day and the results are available within 24 hours. This assay technique is easier to perform and more reproducible than a urinary pregnanediol assay, and it is expected that clinical laboratories will soon perform serum progesterone assays as a routine procedure.
To compare the rates of ovulation and pregnancy after tamoxifen citrate (TMX) or clomiphene citrate (CC) among anovulatory women with infertility. Prospective randomized trial. Infertility clinic in a university teaching hospital. PATIENT(S): Eighty-six anovulatory women under 40 years of age undergoing ovulation induction. INTERVENTION(S): The women were assigned randomly to receive either TMX or CC on cycle days 5-9. MAIN OUTCOME MEASURE(S): Rates of ovulation and pregnancy for the two treatment modalities. RESULTS(S): The overall rate of ovulation in the TMX group was 50 of 113 (44.2%) and in the CC group, 41 of 91 (45.1%). There were 10 pregnancies in the TMX group and 6 pregnancies in the CC group. The cycle fecundity per ovulatory cycle was 20.0% in the TMX group and 14.6% in the CC group. CONCLUSION(S): The overall rate of ovulation and pregnancy were similar with TMX and CC. TMX is a suitable alternative agent to CC in the management of anovulatory infertility.
Dating of maturity of the endometrium by histologic examination was correlated with four methods of ovulation detection in 13 cycling parous women. Histologic dating was assessed independently by two pathologists and correlated with the postovulatory duration as determined by daily transvaginal ultrasound scanning, serum LH measurements, basal body temperature (BBT), and subtraction of 14 days from the onset of menses. In addition, progesterone and estradiol (E2) were measured in daily serum samples. Dating of the endometrial biopsy was highly correlated (P less than .002) with the day of ovulation as determined by ultrasound, and was found to be within 2 days of the correct postovulatory day on evaluation of 25 of 26 (96.1%) of the interpretations. The accuracy of dating using the LH surge was 84.6% (22 of 26 interpretations), and with the BBT thermogenic shift was 76.9% (20 of 26 interpretations). However, dating of the endometrium was within 2 days of the correct day in only 17 of the 26 interpretations as determined by subtracting 14 days from the onset of the subsequent menses. The accuracy of dating was significantly better correlated (P less than .025) with days from ovulation as determined by ultrasound than as calculated from the onset of menses. There was a significant correlation between endometrial dating and the amount of progesterone (P less than .01) and E2 (P less than .01) secreted from the day of ovulation, as determined by transvaginal ultrasound, to the day of biopsy. These data confirm a strong correlation between endometrial dating and ovarian hormone secretion during the postovulatory phase.(ABSTRACT TRUNCATED AT 250 WORDS)
To develop a practical yet statistically valid means of indicating ovulation and adequacy of corpus luteum function concentrations of plasma progesterone (P) were measured daily during the luteal phase of 30 normal and abnormal menstrual cycles. During a normal cycle any 3 P measurements taken from 11 days before the first day of the following menses (M) to Day M-4 gave a total equal to or greater than 15 ng/ml. An abnormal cycle was considered one in which the total P (for 3 measurements) was less than 15 ng. Individual levels were often at 3 ng/ml in normal cycle and above 3 ng/ml in abnormal cycles indicating that the single P measurement proposed by Israel et. al. would not always be valid.
The authors have further analyzed women diagnosed as having luteal phase insufficiency in hope of determining the value of specific screening tests as well as determining the degree of heterogeneity of pathophysiologic mechanisms involved in the disorder. Twelve women with the disorder were identified, 6 with two consecutive midluteal serum progesterone (P) levels less than 10 ng/ml (group 1) and 6 with two consecutive late luteal phase endometrial biopsies out of phase (group 2); 4 infertile women with normal serum P and late luteal biopsies also were studied (group 3). All underwent serum sampling for P and luteinizing hormone (LH) at 20-minute intervals for 24 hours, beginning at 9:00 A.M. of day 7 post-LH surge. No significant differences were noted among the three groups for LH area under the curve, pulse frequency, or pulse amplitude. Furthermore, no differences were ascertained for P area under the curve. However, individuals were identified who had one or more hormonal abnormalities but no abnormal biopsy, as well as patients with normal hormonal profiles but having abnormal endometrial development. Receiver Operating Characteristic curves demonstrated that pooled morning serum P levels provided optimal predictive ability of biopsy results. The authors conclude that luteal phase insufficiency is a heterogeneous disorder, and that neither endometrial biopsy nor serum hormonal analysis obviates the need for the other.
An integrated luteal progesterone (ILPL) was calculated on the basis of a luteal progesterone (P) level with the assumption that the daily plasma P level in the luteal phase closely approximates a sine curve. The midluteal P-amplitude (K) was also obtained mathematically. Daily luteal P levels from five normal ovulatory cycles were assessed for the biologic variation of ILPL and K, then compiled to construct a normogram of the ILP during the luteal phase. The coefficient of variation of K and total ILPL in each cycle ranged from 9.7% to 24.3% and 3.5% to 13.2%, respectively. Fifty-two infertility patients were evaluated for their luteal function by the luteal P and estradiol (E2) level, K, ILPL, endometrial biopsy (EBX)-lag-day, as well as the lengths of follicular phase, luteal phase (L#), and cycle. Thirty-nine patients had EBX-lag day less than or equal to 2 days and were designated as infertile-normal (INF-NL) luteal phase, while the remaining 13 patients who had EBX-lag day greater than 2 days were considered as luteal phase defect (LPD). Significant (P less than 0.05) differences were observed between INF-NL and LPD in: luteal length (13.2 +/- 0.31 versus 11.0 +/- 0.58 days, respectively), and total ILPL (170 +/- 8.3 versus 113 +/- 8.5 ng/ml-day, respectively). No differences were seen in luteal P, E2 and K levels, nor in follicular and cycle length. Significant (P less than 0.05) correlations were observed between total ILPL and luteal P, E2, L#, and K; while a negative correlation was noted between follicular and luteal length.(ABSTRACT TRUNCATED AT 250 WORDS)
In order to delineate factors contributing to variation in hormone levels, progesterone and prolactin (PRL) levels from 28 normal women, obtained daily during one menstrual cycle and every 20 minutes during a midluteal 24-hour admission in a subgroup of five subjects, provided a data base for analysis of these variables. Pulsatile analysis of the 24-hour data was conducted using an adaptive-threshold algorithm, and normal reference ranges were generated from randomly selected daily hormone values. Our data verify that inherent variation can significantly alter single random serum levels of reproductive hormones. These variations included menstrual cycle day, circadian influence, pulsatile secretion, assay error, and biologic heterogeneity. Besides the expected day-to-day change in progesterone levels during the luteal phase, seven of ten women exhibited a significant circadian variation in progesterone; however, the time of day of the peak level was not consistent among women. Prolactin levels did not demonstrate any clinically relevant change over the menstrual cycle, but did have a consistent circadian pattern (nocturnal rise) over the 24-hour study period. Pulsatile variation occurred in both progesterone and PRL levels during the 24-hour admission. Five different reference ranges were generated from randomly selected single daily values from the 28 normal menstrual cycles. Although the mean levels calculated for each reference range were similar, the reference ranges demonstrated considerable variation due to the random sampling. In the five progesterone reference ranges, the lower limit of the range varied from 2.7-6.1 ng/mL, whereas the upper limit varied from 24.2-42.1 ng/mL.(ABSTRACT TRUNCATED AT 250 WORDS)
Reproductive Endocrinology › Luteal Phase › Corpus Luteum Function · Menstrual Cycle › Cycle Biomarkers › Hormonal Markers · Diagnostics › Hormone Testing › Timing of Testing
PMID 5017634 5017634 DOI 10.1016/0002-9378(72)90178-0 10.1016/0002-9378(72)90178-0 Israel et al. 1972, Israel 1972
Cite this article
Israel, R., Mishell DR Jr, Stone, S. C., Thorneycroft, I. H., & Moyer, D. L. (1972). Single luteal phase serum progesterone assay as an indicator of ovulation. American journal of obstetrics and gynecology, 112(8), 1043-1046. https://doi.org/10.1016/0002-9378(72)90178-0
Israel R, Mishell DR Jr, Stone SC, Thorneycroft IH, Moyer DL. Single luteal phase serum progesterone assay as an indicator of ovulation. Am J Obstet Gynecol. 1972;112(8):1043-1046. doi:10.1016/0002-9378(72)90178-0
Israel, R., et al. "Single luteal phase serum progesterone assay as an indicator of ovulation." American journal of obstetrics and gynecology, vol. 112, no. 8, 1972, pp. 1043-1046.
Keywords
Adult, Chromatography, Clomiphene/therapeutic Use, Corpus Luteum/physiology, Cytodiagnosis, Endometrium/cytology, Female, Humans, Infertility, Female/diagnosis/drug Therapy, Menstruation, Methods, Ovulation, Progesterone/blood, Protein Binding, Clomiphene, Progesterone, Biology, Clomiphene--side Effects, Clomiphene--therapeutic Use, Endocrine System, Examinations And Diagnoses, Family Planning, Fertility Agents, Hematological Effects, Hemic System, Histology, Hormones, Infertility, Laboratory Examinations And Diagnoses, Laboratory Procedures, Ovulation, Ovulation Detection, Physiology, Progestational Hormones, Progesterone--analysis, Reproduction, Reproductive Control Agents
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