Mid-luteal Serum Progesterone Levels Research Articles

Does anovulation exist in eumenorrheic women?

To determine whether anovulation exists in normally menstruating women. In a database of 550 consecutive couples seeking pregnancy, results of the midluteal serum progesterone level analysis planned for 7 days before the onset of the next menses were examined in women with predictable cycles shorter than 35 days. Of the 550 couples seeking pregnancy, 410 of the female partners (74.5%) were eumenorrheic. Fifteen of these women (3.7%) had apparently anovulatory cycles with a progesterone lower than the normal ovulatory value of 15 nmol/L. Further examination showed that four of the 15 women (26.7%) had an isolated prolonged cycle, whereas an additional four (26.7%) failed to have their sample taken at an appropriate time. One (6.7%) had a low progesterone level that was normal in the subsequent cycle. Two patients (13.3%) were older than 40, both having elevated early follicular follicle-stimulating hormone levels. One patient (6.7%) conceived in the following menstrual cycle without further evaluation. The three remaining women (20%) showed consistently apparently anovulatory cycles. However, the levels were exclusively above the follicular range. Our findings cast doubt on the concept of anovulatory cycles in eumenorrheic women and suggest that further examination of the lower level of ovulatory progesterone may indeed be necessary.

Use of Crinone∗ vaginal progesterone gel for luteal support in in vitro fertilization cycles

Objective: To investigate the efficacy and safety of intravaginal Crinone 8% (Columbia Research Laboratories, Miami, FL) versus IM progesterone for luteal phase support after IVF-ET. Design: Prospective open trial with comparison to historical controls. Setting: University hospital. Patient(s): Two hundred six women undergoing IVF-ET. Intervention(s): One hundred patients received Crinone vaginal progesterone gel (90 mg once daily) and 106 patients received IM progesterone (50 mg once daily) beginning on the evening of oocyte retrieval. Main Outcome Measure(s): Pregnancy and miscarriage rates, and midluteal serum progesterone levels. Result(s): Positive β-hCG pregnancy rates, clinical pregnancy rates per transfer, and ongoing pregnancy rates were similar for the Crinone and IM progesterone groups. Women who received Crinone had higher rates of biochemical pregnancy loss but lower rates of clinical pregnancy loss (i.e., spontaneous abortion) than women who received IM progesterone. Midluteal serum progesterone concentrations were significantly higher in the IM progesterone group (94.3 ± 8.8 ng/mL versus 57.7 ± 7.4 ng/mL). Several women who received Crinone had vaginal bleeding 11–13 days after oocyte retrieval. Conclusion(s): For all age categories, positive β-hCG and ongoing pregnancy rates were similar when Crinone or IM progesterone was given for luteal phase support in IVF-ET cycles, despite lower serum progesterone concentrations and higher rates of biochemical pregnancy loss with Crinone. Although the results of this study support the use of Crinone as an acceptable alternative for luteal support after IVF-ET, differences in bleeding patterns and rates of biochemical pregnancy loss demonstrate the need for a prospective randomized study.

Three patterns of catamenial epilepsy.

On the basis of the neuroactive properties of estradiol and progesterone and the menstrually related cyclic variations of their serum concentrations, we propose the existence of three hormonally based patterns of seizure exacerbation. Because previous reports both support and refute the concept of catamenial epilepsy, we test the hypothesis by charting seizures and menses and measuring midluteal serum progesterone levels to estimate the frequency of epileptic women with catamenial seizure exacerbation. One hundred eighty-four women with intractable complex partial seizures (CPS) charted their seizure occurrence and onset of menstruation on a calendar for one cycle during which they had a midluteal blood sample taken for serum progesterone determination on day 22. Levels >5 ng/ml were considered ovulatory. The cycle was divided into four phases with onset of menstruation being day 1: menstrual (M) = -3 to +3, follicular (F) = 4 to 9, ovulatory (O) = 10 to -13, and luteal (L) = -12 to -4. Average daily seizure frequency for each phase was calculated and compared among phases by repeated-measures analysis of variance (ANOVA) and the Student-Newman-Keul's test, separately for ovulatory and anovulatory cycles. The 1,324 seizures recorded during 98 ovulatory cycles occurred with significantly greater (p < 0.001) average daily frequency during the M (0.59) and O (0.50) phases than during the F (0.41) and L (0.40) phases, offering support for perimenstrual (catamenial 1) and preovulatory (catamenial 2) patterns of seizure exacerbation. The 1,523 seizures recorded during 86 anovulatory cycles occurred with significantly lower (p < 0.001) average daily frequency during the F phase (0.49) than during all other phases (M = 0.78, O = 0.74, L = 0.74), offering support for seizure exacerbation throughout the second half of inadequate luteal phase cycles (catamenial pattern 3). Although 71.4% of the women with ovulatory cycles and 77.9% with inadequate luteal phase cycles had seizure exacerbation in relation to one of the three patterns of catamenial epilepsy, approximately one third of the women showed at least a twofold increase in average daily seizure frequency. We propose a twofold or greater increase as a reasonable definition of catamenial epilepsy. Charting of seizures and menses and determination of day 22 progesterone levels during each cycle may be sufficient to establish the existence of three distinct patterns of catamenial epilepsy. Approximately one third of women with intractable CPS may have catamenial epilepsy.

Blood flow changes in the intraovarian arteries during the periovulatory period: relationship to the time of day.

Intraovarian blood flow was assessed by transvaginal color and pulsed Doppler ultrasound prospectively in six women during the periovulatory period. All patients had regular ovulatory menstrual cycles and a mid-luteal serum progesterone level consistent with spontaneous ovulation in the preceding cycle. Each patient underwent serial transvaginal ultrasound examination and Doppler assessment of blood flow in the ovarian stroma and in the wall of the dominant follicle or corpus luteum. When the mean follicular diameter was > 16 mm or day -2 from the estimated day of ovulation was reached, patients were scanned at 6-h intervals at 06.00, 12.00, 18.00 and 24.00 until follicular rupture, to investigate the presence of circadian rhythms. The pulsatility index (PI) and the maximum peak systolic blood flow velocity (Vmax) were calculated as Doppler indices of impedance to blood flow and velocity, respectively. A venous blood sample was taken at each visit for subsequent hormonal analysis. There was no significant circadian fluctuation in either mean follicular Vmax or mean follicular PI before or after the luteinizing hormone (LH) surge. Similarly, mean Vmax and mean PI in the non-dominant ovarian stroma did not show any significant fluctuation over the same periods. The mean PI in the dominant ovarian stroma showed daily fluctuations with the highest values occurring most commonly at 06.00 and the nadir in the afternoon and late evening. This fluctuation was the reverse of the circadian variation previously demonstrated in the uterine artery. However, in contrast to the uterine artery, comparison between the mean PI values in the dominant ovarian stroma at 06.00 and 18.00 only approached significance after the LH surge. The dominant ovarian stroma Vmax tended to rise during the day, although the differences between 06.00 and 18.00 were also not significant. Although there are fluctuations in Doppler blood flow indices in the dominant ovarian stroma, further studies are necessary to demonstrate whether this represents a significant circadian rhythm.

Effects of follicular phase exercise on luteinizing hormone pulse characteristics in sedentary eumenorrhoeic women

Current studies reveal little regarding the inception of exercise-induced LH changes during physical training. This study aimed to assess the susceptibility of the hypothalamic-pituitary axis to the acute physical stress of exercise in untrained, physically inactive women. The acute effects of submaximal endurance exercise upon the pulsatile LH secretion in the follicular phase were compared with those accompanying leisurely strolling for a similar time period. All subjects were eumenorrhoeic, as determined by biphasic temperature patterns, detection of the urinary LH surge, and mid-luteal serum progesterone levels. Subjects were not physically active and had little history of strenuous exercise (VO2max = 38.0 +/- 1.8) (mean +/- SEM) ml/kg/min). All women completed a 13.5-hour pulsatility test which included three consecutive 20-minute runs on a treadmill at 50, 60 and 70% of the subjects' maximum oxygen uptake (n = 16). Six of these same subjects completed a separate test on another occasion in which one hour of leisurely strolling was substituted for exercise. Blood was sampled every 10 minutes via an indwelling cannula for 4.5 hours before and 8 hours after one hour of exercise and or strolling. A pulse algorithm (Pulsar) was used to quantify LH pulse characteristics. Exercise produced no significant effects upon LH pulse frequency or mean serum LH concentration. However, exercise of moderate intensity caused a significant increase in LH pulse amplitude (P < 0.05). Strolling produced no significant changes in LH secretion. Acute exercise of moderate intensity in the follicular phase of untrained women is an insufficient stimulus to inhibit the GnRH pulse generator in the post-exercise period, yet may produce a slight stimulatory effect on the amount of LH released per pulse.

A study with diagnostic standard of occult hyperprolactinemia (OHP) and the effect of bromocriptine administration

It is well known that the transient excessive increase of serum prolactin level is harmful for the mechanism of ovulation or the steroidogenesis of the ovaries. The pathogenesis of latent or occult hyperprolactinemia (OHP) has been investigated recently. The present study was conducted to determine the diagnostic standard of OHP, and to elucidate the efficacy of bromocriptine administration for the treatment of OHP and other ovulatory disturbances. 110 cases of hypothalamic anovulations were selected from 385 cases of infertile patients by the LH-RH and TRH loading tests. Bromocriptine (5mg/day) was administered to all of the subjects for more than three months, and the efficacy of the bromocriptine administration was investigated. Follicular development was observed by transvaginal ultrasonography (mature follicular diameters > or = 20mm), and also luteal function was estimated by the duration of the luteal phase in the BBT charts (high phase > or = 12 days), the mid-luteal serum estradiol (> or = 200pg/ml) and progesterone (> or = 10ng/ml) levels. The subjects were divided into two groups: group A, bromocriptine effective patients (63 cases) and group B, bromocriptine non effective patients (47 cases). The results of the LH-RH and TRH loading tests were compared between these two groups. Serum prolactin levels at 30 min. after TRH loading (PRL30) in group B (61.5 +/- 28.3 vs. 38.0 +/- 19.3ng/ml, p < 0.01). At the cut-off points of 50, 60 and 70ng/ml over in the values of the PRL, the efficacies of the bromocriptine administration were 77.4, 78.9 and 88.5%, respectively. From these facts, it was thought suitable that the diagnostic standard of OHP was PRL30 > or = 70ng/ml, and values of PRL30 from 50 to 70ng/ml were borderline cases of OHP. The efficacy of the bromocriptine administration in the cases without OHP (n = 57) was also investigated. Serum LH levels at 30 min. after LH-RH loading (LH30) were compared between the cases of the bromocriptine effective (n = 22) and non effective (n = 35). As a result, the LH30 of the former was significantly higher than that of the latter (96.5 +/- 64.2 vs. 45.1 +/- 31.5mIU/ml, p < 0.005). In conclusion, the diagnostic standard of OHP was determined as PRL30 > or = 70ng/ml (borderline: 50 > 70ng/ml), and bromocriptine administration was effective not only in cases of OHP, but also in cases of hyperreactivities of LH (so-called endocrinological PCOD).

Clomiphene treatment for women with unexplained infertility: placebo-controlled study of hormonal responses and conception rates

One hundred and eighteen patients with unexplained infertility were treated with clomiphene (Clomid, Merrell) in a randomized placebo-controlled cross-over study lasting up to 3 months with each preparation. Compared with placebo, clomiphene led overall to a 66% increase in mid-luteal serum progesterone levels (from mean 43 nmol/l to 71 nmol/l, p less than 0.001) and a 53% rise in the 3-month cumulative conception rate (from 14.6% to 22.33%, p less than 0.05). The greatest relative increase in conception rates with clomiphene was in women with infertility lasting more than 3 years (3-month rates from 2.9% to 14.4%, p less than 0.05). Differences in conception rates were not related to the rises in progesterone, and there was no carryover effect of clomiphene into the following placebo cycles in terms of progesterone levels or conceptions. The findings suggest that couples with unexplained infertility of less than 3 years duration are essentially normal, but with more than 3 years duration there is often a subtle disorder of ovulation that is corrected by clomiphene therapy.

The effect of therapy initiation day on clomiphene citrate therapy

Eighty-seven anovulatory patients were treated with clomiphene citrate (CC) to induce ovulation in 414 cycles. Clomiphene citrate was initiated randomly on the 2nd, 3rd, 4th, or 5th day of the menstrual cycle to evaluate the effectiveness of therapy. The results of therapy were assessed in terms of ovarian response and pregnancy outcome. Ovarian response was evaluated employing basal body temperature (BBT) to define follicular, luteal, and cycle lengths, and a midluteal serum progesterone (P) level and the integrated luteal P to define luteal adequacy. Pregnancy outcome was evaluated in the categories of total pregnancy, live birth, first trimester abortion, and fecundity rates. There were no significant differences noted between the groups who started CC on the 2nd, 3rd, 4th, or 5th day of cycle in terms of anovulation rates (12% to 21%), luteal dysfunction (28% to 39%), and normal ovulation rates (42% to 57%). Pregnancy was achieved in 31% (n = 27/87) of patients with a spontaneous abortion rate of 19% (n = 5/27). The fecundity rates ranged between 5.7% and 9.4%. Pregnancy outcomes also were not significantly different between the groups. Significantly shorter luteal phase length and longer follicular phase length were observed in the cycles with luteal dysfunction. The luteal progesterone parameters, including midluteal serum P concentration, the integrated luteal P, and the luteal P amplitude were significantly lower in the cycles with luteal dysfunction.

Twenty-four-hour progesterone and luteinizing hormone profiles in the midluteal phase of the infertile patient: correlation with other indicators of luteal phase insufficiency

AbstractThe 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 <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.

Effects of transient or occult hyperprolactinemia on luteal function

It is well known that the luteal function in the patients with hyperprolactinemia is much suppressed by high level of serum prolactin. Present study was performed to investigate whether the luteal function in the patients with transient or occulted hyperprolactinemia was affected by the transient increase of serum prolactin level. The circadian changes of serum FSH, LH, prolactin, estrone, estradiol and progesterone levels were examined in seven cases of the transient or occulted hyperprolactinemia whose BBT charts showed biphasic patterns. Serum prolactin levels of these patients were less than 25 ng/ml at daytime and more than 150 ng/ml at 30 minutes after the administration of 500 micrograms of TRH. Blood samplings were taken every two hours through an intravenous indwelling catheter without any disturbances. All of the patients had their breakfast at 7 to 8, lunch at 11 to 12 and dinner at 17 to 18 o'clock and slept from 22 until 6 in the next morning. Serum FSH, LH, prolactin, estrone, estradiol and progesterone levels were determined by RIA and the circadian changes of these hormones were analysed. Then, 5 mg of bromocriptine was administered every day to these patients for more than 30 days and the duration of the luteal phase and the mid-luteal serum estradiol and progesterone levels for the indicators of the luteal function were examined before and after the administration of bromocriptine. The circadian changes of serum prolactin levels in the patients showed significant increase during both daytime and night compared to those of the control (p less than 0.005, p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Both midluteal serum progesterone levels and late luteal endometrial histology should be assessed in all infertile women

Criteria for diagnosis of luteal phase deficiency vary among specialists. Adequacy of corpus luteum function usually is based on a midluteal serum progesterone (P) concentration or a late luteal biopsy. To compare these two methods of determining luteal phase adequacy, 42 midluteal P levels were compared with late luteal endometrial biopsies from the same cycles in 34 women undergoing evaluation for infertility. Eleven cycles contained both hormonal and histologic evidence of luteal phase inadequacy; 12 contained only hormonal evidence of inadequacy; 9 contained only histologic evidence of inadequacy; and 10 contained both hormonal and histologic evidence of adequate luteal function. These data suggest that both midluteal phase P levels and late luteal endometrial biopsies should be assessed in infertile women, because neither can be used to predict the other.

Shortened luteal phase after ovulation induction with human menopausal gonadotropin and human chorionic gonadotropin

Serum hormonal profiles were characterized in 126 treatment cycles from 24 anovulatory women who underwent ovulation induction therapy with sequential human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG). Of the 98 presumptively ovulatory treatment cycles, 18 had luteal phases lasting 11 days or less. Sixteen of these 18 cycles had one or more of the following features: serum hCG concentrations of less than 75 mIU/ml 24 hours after hCG administration or peak preovulatory estradiol (E2) levels either less than 200 pg/ml or greater than 2000 pg/ml. Midluteal serum progesterone levels were less than 10 ng/ml in seven of the shortened cycles. Only one of these features (E2 greater than 2000 pg/ml) was present in any cycle (n = 2) resulting in pregnancy. Our observations suggest that serum E2 and hCG levels will reflect the apparent adequacy of luteal function during hMG/hCG treatment cycles.