Follicular Phase Length Research Articles

Analysis of urinary immunoreactive steroid metabolites and gonadotropins for characterization of the estrous cycle, breeding period, and seasonal estrous activity of captive killer whales (Orcinus orca)

AbstractTo increase the basic understanding of killer whale (Orcinus orca) reproductive physiology necessary for the development of artificial breeding programs, we utilized radioimmunoassays (RIA) to detect urinary immunoreactive steroid metabolites (pregnanediol‐3α‐glucuronide [PdG] and estrone‐conjugates [EC]) and gonadotropins (luteinizing hormone [LH] and follicle‐stimulating hormone [FSH]) in urine samples from six female killer whales. Urine samples were collected from the whales by voluntary presentation behavior over a 2‐ to 4‐year period. All urinary hormone values were corrected for intersample urine concentration variations by indexing with creatinine. Daily urine samples from four whales were collected during two conceptions and 18 complete estrous cycles. LH, FSH, EC, and PdG immunoreactive levels were determined and combined with observed copulatory activity in five cycles, including two conceptive cycles from two whales. Mean luteal phase lengths ranged from 9.7 to 19.2 days. Mean follicular phase lengths ranged from 6.5 to 16.8 days. Mean estrous cycle lengths based on the first detectable PdG levels were 41.6 ± 6.72 S.E.M. days. After PdG nadir, immunoreactive FSH levels showed a bimodal pattern with the first peak being greater in size, and both preceding a follicular phase EC increase. LH levels > the 95% confidence interval of the mean were considered significant.Combined LH immunoreactive values from whales 2 and 6 during two and three estrous cycles, respectively, had significant LH peak concentrations on day minus 2. These significant LH peaks were assumed to represent the preovulatory LH surge. Eight copulations during two conceptive cycles were observed between whales 2 and 6 and a breeding male. Six of these copulations (3 with each female whale) occurred within 72 hours of the beginning or the end of the presumptive preovulatory LH surge. Estrous activity was seen throughout the year for the herd. However, individuals had varying periods of anestrus that could not be linked to environmental, social, or nutritional influences. The whales that were reproductively successful had anestrus intervals that were usually influenced by gestation, postparturient period, or lactation. The information obtained during this research enhances the foundation for future artificial reproductive management techniques. © 1993 Wiley‐Liss, Inc.

Effect of dietary fat on length of the follicular phase of the menstrual cycle in a controlled diet setting.

The length of the follicular phase of the menstrual cycle (defined as the time from the first day of menses until the day of urinary LH peak, inclusive) was examined in 30 healthy, premenopausal women. The women consumed defined, weight maintaining diets, with a ratio of polyunsaturated to saturated fatty acids (P/S ratio) of either 0.3 or 1.0. Both P/S groups consumed a high fat diet (40% energy from fat) for 4 menstrual cycles, followed by 4 menstrual cycles of a low fat diet (20% energy from fat). There was a significant increase (P less than 0.006) in the length of the follicular phase of the menstrual cycle during consumption of the low fat diet. Two thirds of the women showed increases in follicular phase length with an average increase of 1.9 days.

Effect of baseline ovarian cysts on in vitro fertilization and gamete intrafallopian transfer cycles

The presence of ovarian cysts may compromise the success of in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT). We prospectively studied 212 consecutive ovulation induction cycles in 120 patients for IVF and/or GIFT. A baseline cyst was defined as any intraovarian cystic structure≥12mm noted on ultrasonography before superovulation. Cycle outcomes were compared between patients with cysts (n=62) versus those with no cysts (n=150). There were no differences in follicular or luteal phase lengths or amount of human menopausal gonadotropins used. Peak estradiol (E 2 ) levels were significantly lower and cancellation rates significantly higher in the cyst group. For noncanceled cycles, there were no significant differences in peak E 2 levels, the mean number of follicles≥12mm, mature oocytes retrieved, or ova transferred for GIFT or embryos for IVF. The pregnancy rates overall and for noncanceled cycles were not significantly different.

Follicular Arrest during the Midfollicular Phase of the Menstrual Cycle: A Gonadotropin-Releasing Hormone Antagonist Imposed Follicular-Follicular Transition*

The functional dependency of the dominant follicle on pulsatile gonadotropin inputs was evaluated by using a GnRH antagonist as a probe. Hormonal dynamics, particularly the relationship of FSH, estradiol, and inhibin, during and after the withdrawal of GnRH receptor blockade achieved by treatment with Nal-Glu GnRH antagonist (50 micrograms/kg, im) for 3 days in the midfollicular phase of the cycle (days 7-9) were ascertained. Daily blood samples were obtained for LH, FSH, estradiol (E2), progesterone, and immunoreactive inhibin (i-INH) measurements by RIA during 2 consecutive (control and treatment) cycles in 12 women. In 5 women, LH pulsatility was assessed by 10-min blood sampling for 12 h before, during, and after Nal-Glu treatment. The administration of Nal-Glu prolonged both follicular phase (14.0 +/- 0.5 vs. 19.7 +/- 0.8 days; P less than 0.0001) and total cycle length (28.1 +/- 0.5 vs. 34.1 +/- 1.2 days; P less than 0.0001). Gonadotropin suppression (50-60%) was achieved, as reflected by a marked decrease in mean LH levels (14.3 +/- 1.9 to 5.4 +/- 0.5; P less than 0.01) and LH pulse amplitude (5.5 +/- 0.7 to 2.4 +/- 0.3 IU/L; P less than 0.01) in response to Nal-Glu antagonist. The number of LH pulses was reduced (36%), but pulses remained discernible. Concentrations of FSH (10.8 +/- 1.4 to 5.9 +/- 0.4 IU/L; P less than 0.05), E2 (322.7 +/- 71.9 to 84.8 +/- 7.7 pmol/L; P less than 0.01) and i-INH (284.0 +/- 25.9 to 164.4 +/- 7.5 U/L; P less than 0.01) decreased concomitantly. Within 24-48 h of the last injection of Nal-Glu, all hormones had returned to pretreatment levels. This was followed by normal functional expression of follicular growth and maturation, as reflected by an increase in E2 and i-INH levels, timely ovulation, and normal luteal function. These findings indicate that an approximately 50% decline in gonadotropin support to the dominant follicle leads to functional arrest, but not demise, of the developing follicle(s) without triggering new folliculogenesis. The follicular apparatus retained its ability to reinitiate its original functionality once appropriate gonadotropin inputs were reinstated.

Variable Tolerance of the Developing Follicle and Corpus Luteum to Gonadotropin-Releasing Hormone Antagonist-Induced Gonadotropin Withdrawal in the Human*

To examine the differential sensitivity of the ovary to temporary withdrawal of gonadotropin support at different stages of folliculogenesis and corpus luteum function, GnRH antagonist blockade of gonadotropin secretion was examined in 17 studies using the Nal-Glu GnRH antagonist. A vehicle control, antagonist treatment, and follow-up cycle format was used in each study. A previously determined ED100 dose of the Nal-Glu GnRH antagonist (150 micrograms/kg) or vehicle was administered sc every 24 h for 3 consecutive days in the midfollicular phase (MFP), late follicular phase (LFP), and midluteal phase (MLP). In studies in the MFP (n = 7), the largest follicle was 11 +/- 2 mm (mean +/- SEM), and the mean estradiol (E2) level was 220 +/- 44 pmol/L on the first day of antagonist administration. Administration of the antagonist resulted in a 75 +/- 6% suppression of LH (P less than 0.005), no significant change in FSH, and suppression of E2 to the assay detection limit (P less than 0.05). Total cycle length was increased compared to that of the vehicle control cycle (37.3 +/- 1.3 vs. 26.3 +/- 1.1 days; (P less than 0.005) due to prolongation of follicular phase length (P less than 0.005) and reinitiation of folliculogenesis. In the LFP (n = 5), the largest follicle was 16 +/- 1 mm (P less than 0.05 vs. MFP), and the E2 level was 394 +/- 95 pmol/L (P less than 0.05 vs. MFP) on the first day of antagonist administration. Antagonist administration resulted in a 65 +/- 6% suppression of LH (P less than 0.05), a 47 +/- 11% decrease in FSH (P less than 0.05), and no significant change in E2. Total cycle length was prolonged (32.4 +/- 2.2 vs. 25.6 +/- 0.4 days; P less than 0.05) due to an increase in follicular phase length (P less than 0.02); however, the prolongation of the follicular phase was significantly less than that of the MFP (8.0 +/- 1.5 vs. 15.1 +/- 0.1 days; P less than 0.001), suggesting ovulation from the initial dominant follicle. In studies in the MLP (n = 5), LH, E2, and progesterone decreased to the assay detection limit after antagonist administration, while FSH decreased by 36 +/- 4% (P less than 0.05). Menstrual bleeding occurred within 24-48 h of the final Nal-Glu antagonist injection.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of baseline ovarian cysts on in vitro fertilization and gamete intrafallopian transfer cycles

The presence of ovarian cysts may compromise the success of in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT). We prospectively studied 212 consecutive ovulation induction cycles in 120 patients for IVF and/or GIFT. A baseline cyst was defined as any intraovarian cystic structure greater than or equal to 12 mm noted on ultrasonography before superovulation. Cycle outcomes were compared between patients with cysts (n = 62) versus those with no cysts (n = 150). There were no differences in follicular or luteal phase lengths or amount of human menopausal gonadotropins used. Peak estradiol (E2) levels were significantly lower and cancellation rates significantly higher in the cyst group. For noncanceled cycles, there were no significant differences in peak E2 levels, the mean number of follicles greater than or equal to 12 mm, mature oocytes retrieved, or ova transferred for GIFT or embryos for IVF. The pregnancy rates overall and for noncanceled cycles were not significantly different.

A comparison of some clinical and endocrinological features between cycles with normal and defective luteal phases in women with unexplained infertility

The luteal phase in a group of women (n = 49) with unexplained infertility was evaluated by improved methods, including the use of the LH surge for precise timing of measurements, quantitative techniques for histological dating of endometrial biopsy and determination of the integrated progesterone concentration in the luteal phase. Overall, 10 out of 49 (20%) women were considered to have a retarded endometrium. The prevalence of retarded endometrium in women with primary infertility (10/37, 27%) was found to be significantly higher (P less than 0.05) than in women with secondary infertility (0/12, 0%). Women with retarded endometrial development had a significantly (P less than 0.01) lower integrated P concentration than those with normal endometrial development; however, of the 10 cases with retarded endometrium, only four were associated with an integrated P concentration below the normal range, whereas the remaining six were associated with an integrated P concentration within the normal reference range, suggesting that an abnormal response of the endometrium is a likely cause of abnormality in these latter cases. There was no difference in age, duration of infertility, follicular phase length, magnitude of the oestrogen surge, magnitude of the LH surge, maximum follicular diameter and luteal phase length between women with a normal or defective luteal phase, defined either by endometrial morphology or integrated progesterone concentration.

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.

Effects of Ovarian Tissue Reduction on the Menstrual Cycle: Persistent Normalcy after Near-Total Oophorectomy1

These experiments were designed to evaluate whether removal of approximately 95% visible ovarian tissue would interrupt the short- or long-term regulation of cyclic ovarian function. On cycle Days 2 4 (onset of menses = Day 1), the entire left ovary and approximately 90% of the right ovary were removed from three cycling cynomolgus monkeys. After approximately 95% ovariectomy, there was an acute elevation of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which lasted 11 +/- 2 days. A midcycle-like gonadotropin surge occurred 20 +/- 3 days following approximately 95% ovariectomy; the next menses occurred 19 +/- 1 days later. Follicular phase patterns of estradiol preceded the midcycle gonadotropin surge, and luteal phase progesterone levels indicated subsequent ovulation. Two of three monkeys resumed normal menstrual cyclicity in the following cycle with follicular phase, luteal phase, and menstrual cycle lengths similar to pretreatment levels. Histological examination of the ovarian remnant removed on Day 21 of the next cycle revealed a morphologically normal corpus luteum and many small follicles. A second group of 6 rhesus monkeys also underwent approximately 95% ovariectomy for long-term evaluation of menstrual cyclicity; typical 28-day menstrual cycle patterns were observed in 4 of the 6 monkeys for 5 mo, with 2 of these 3 animals maintaining regular menstrual cycles for 1 yr. In summary, our data suggest that normal ovarian function, i.e. recruitment, selection, and dominance of the ovulatory follicle, ovulation, and subsequent corpus luteum function, is maintained with only approximately 5% of functional ovarian tissue remaining.(ABSTRACT TRUNCATED AT 250 WORDS)

Predictive value of the FSH: LH ratio on follicular and luteal phase characteristics of the human menstrual cycle

A prospective study was designed to assess the predictive value of gonadotropin measurements obtained during the early follicular phase upon the hormonal characteristics of the subsequent cycle. The data obtained in 12 normal cycles were used to compute the mean and confidence interval (mean ± 2 SEM) of the FSH: LH ratio, FSH and LH plasma levels. The limits of the confidence intervals for these different parameters were used to classify the patients. Data of 204 patients were analysed. Low FSH: LH ratios (< 1.34) are associated with an increase in follicular phase length (+2.4 days), a lower ovulatory rate, but neither luteal phase length nor progesterone levels differ between these two groups. When patients are classified according to FSH levels, our results show that low FSH levels (< 2.94 mIU/ml) are associated with longer follicular (+2.6 days) and shorter (−1.1 days) luteal phase lengths, but ovulatory rate and progesterone levels in the luteal phase of the ovulatory cycles are similar to those obtained in patients of the normal or high FSH group. High LH levels (> 3.15 mIU/ml) are associated with a decreased ovulation rate but follicular and luteal phase characteristics are similar to those obtained in patients in the normal or low LH group. In conclusion, low FSH: LH ratios and low FSH plasma levels measured in the early follicular phase of the cycle are associated with longer follicular phase lengths; but basal gonadotropin measurements have limited predictive value on luteal phase characteristics.

Is the decrease in the hypophysiotropic signal frequency normally observed during the luteal phase important for menstrual cyclicity in the primate?

The two phases of the ovulatory menstrual cycle of the primate are characterized by divergent activities of the GnRH pulse generator. During the luteal phase, LH pulse frequency is significantly reduced below that observed during the follicular phase. In this report we investigate whether the decrease in pulse frequency during the luteal phase is of physiological relevance to normal menstrual cyclicity. We have tested the effect of a pulsatile GnRH infusion given iv at hourly intervals for a period of 8-10 days during the luteal phase on the subsequent three to five cycles in eight female rhesus monkeys. Three of the eight animals received two treatment courses. Amounts of GnRH infused were 1.5 micrograms/pulse (n = 2 trials); 3.0 micrograms/pulse (n = 7); and 4.0 micrograms/pulse (n = 2). LH response to GnRH pulses of 1.5 and 3.0 micrograms resembled spontaneous LH pulses observed during the luteal phase. During the GnRH infusion period, the monkeys were fitted with a primate vest and tethered. Eleven control experiments were performed in these monkeys under similar conditions. GnRH therapy during the luteal phase affected subsequent cycles significantly, while no differences were observed in the control experiments. Overall mean follicular phase length in the control cycle was 13.4 days; it was significantly increased (P less than 0.005) in all post-GnRH treatment cycles to reach 34.4 (+/- 10.9), 43.9 (+/- 12.7), 40.4 (+/- 13.0), and 23.1 (+/- 4.8) days (+/- SE) in the first to fourth post-GnRH cycles, respectively. Progesterone secretion was significantly lower (P less than 0.05) in the first two post-GnRH cycles than in the control cycles: progesterone, 46.4 (+/- 2.1) in all control cycles, decreased to 27.7 (+/- 3.7), 24.8 (+/- 4.3), 34.0 (+/- 5.4), and 32.0 (+/- 6.5) surface units (+/- SE) from the first to fourth post-GnRH cycles, respectively, while luteal phase length remained relatively unchanged. The data indicate that significant disturbances in the menstrual cycle of the rhesus monkey follow imposed changes in the normal frequency pattern of the GnRH hypophysiotropic signal during the luteal phase and suggest that the naturally occurring slowing of GnRH-LH pulse frequency during the luteal phase is a relevant phenomenon in the sequence of events which control menstrual cyclicity.

The Dependency of Folliculogenesis and Corpus Luteum Function on Pulsatile Gonadotropin Secretion in Cycling Women Using a Gonadotropin-Releasing Hormone Antagonist as a Probe

A potent GnRH antagonist, [Ac-delta 3-Pro1,p-F-D-Phe2,D-Trp3,6]GnRH (4F-Antag), was used as a probe to determine the relative dependency of ovarian cyclicity on pulsatile gonadotropin secretion. 4F-Antag was administered in a dose of 80 micrograms/kg sc twice a day for 3 consecutive days during different phases of the menstrual cycle. This treatment resulted in a prompt attenuation of pulsatile gonadotropin secretion in all women studied. Maximal suppression of gonadotropin levels, expressed as percent change from baseline, averaged 48% for LH and 22% for FSH. The reduced pulsatile gonadotropin release induced by 4F-Antag administration during the early follicular phase resulted in a significant decrease in serum estradiol levels during the period of treatment and was followed by a prolongation of follicular phase (2.4 days) and cycle length (3.5 days), but no alteration of subsequent cyclic ovarian steroid profiles compared to control cycles. Treatment initiated during the midfollicular phase 4-6 days before the expected LH surge resulted in a more dramatic decline in serum estradiol levels and prolongation of follicular phase length by 5-6 days compared to control cycles. Normal luteal function was preserved. These alterations were compatible with induction of the demise of the dominant follicle followed by the reinitiation of follicular recruitment. Administration of 4F-Antag during the midluteal phase resulted in rapid falls in serum estradiol and progesterone levels and the onset of menstrual bleeding in all women. The luteolytic effect of 4F-Antag was completely negated by the administration of hCG. These data indicate that 4F-Antag interferes with ongoing cyclic ovarian function by reducing pulsatile gonadotropin stimulation, which disrupts folliculogenic processes and induces the demise of the corpus luteum. From these findings we infer that the functional integrity of ovarian cyclicity is remarkably sensitive to brief (3 days) and partial reduction in pulsatile gonadotropin secretion.

The dependency of folliculogenesis and corpus luteum function on pulsatile gonadotropin secretion in cycling women using a gonadotropin-releasing hormone antagonist as a probe.

A potent GnRH antagonist, [Ac-delta 3-Pro1,p-F-D-Phe2,D-Trp3,6]GnRH (4F-Antag), was used as a probe to determine the relative dependency of ovarian cyclicity on pulsatile gonadotropin secretion. 4F-Antag was administered in a dose of 80 micrograms/kg sc twice a day for 3 consecutive days during different phases of the menstrual cycle. This treatment resulted in a prompt attenuation of pulsatile gonadotropin secretion in all women studied. Maximal suppression of gonadotropin levels, expressed as percent change from baseline, averaged 48% for LH and 22% for FSH. The reduced pulsatile gonadotropin release induced by 4F-Antag administration during the early follicular phase resulted in a significant decrease in serum estradiol levels during the period of treatment and was followed by a prolongation of follicular phase (2.4 days) and cycle length (3.5 days), but no alteration of subsequent cyclic ovarian steroid profiles compared to control cycles. Treatment initiated during the midfollicular phase 4-6 days before the expected LH surge resulted in a more dramatic decline in serum estradiol levels and prolongation of follicular phase length by 5-6 days compared to control cycles. Normal luteal function was preserved. These alterations were compatible with induction of the demise of the dominant follicle followed by the reinitiation of follicular recruitment. Administration of 4F-Antag during the midluteal phase resulted in rapid falls in serum estradiol and progesterone levels and the onset of menstrual bleeding in all women. The luteolytic effect of 4F-Antag was completely negated by the administration of hCG. These data indicate that 4F-Antag interferes with ongoing cyclic ovarian function by reducing pulsatile gonadotropin stimulation, which disrupts folliculogenic processes and induces the demise of the corpus luteum. From these findings we infer that the functional integrity of ovarian cyclicity is remarkably sensitive to brief (3 days) and partial reduction in pulsatile gonadotropin secretion.

Normal variation in the length of the follicular phase of the menstrual cycle: effect of chronological age.

Normal probability plots were used to analyse the distribution of follicular phase length in a population of 293 apparently ovulatory menstrual cycles from women aged between 18 and 39 years. The length of the follicular phase was defined as the interval (in days) from the onset of menstruation up to, but not including, the day of the LH peak. Follicular phase length appeared to be log-normally distributed and graphical inspection of the probability plot suggested that the geometric mean (and 95% confidence limits) of follicular phase length in this study group was 12.9 (10.3 to 16.3) days. There was a significant decrease (P less than 0.001) in follicular phase length with chronological age, from 14.2 days in women aged 18-24 years to 10.4 days in women aged 40-44 years.

The effects of superovulatory doses of clomiphene citrate on spontaneous luteinizing hormone peaks in regularly ovulating women

The effects of superovulatory doses of clomiphene citrate (150 mg orally every day for 5 days) on normal spontaneous menstrual cycles were studied in 16 women. Eight-eight percent of treatment cycles had clearly defined, timely luteinizing hormone (LH) peaks indistinguishable from those observed in normal cycles. Eight percent of treatment cycles did not have clearly defined LH peaks but were ovulatory. One cycle (4%) was anovulatory. Treated cycles were 2.1 days longer than previous control cycles (p < 0.005). The follicular phase was significantly longer than control cycles (p < 0.025) whereas the luteal phase was not (p > 0.05). There was a direct positive correlation between previous menstrual cycle length and follicular phase length in the treated cycle (r = 0.730, 0.01 < p < 0.05). The conclusion was that 96% of menstrual cycles of normally ovulating women remained ovulatory when the women were given superovulatory doses of clomiphene and that 88% of the cycles had clearly defined LH peaks.

Effect of bromocriptine on menstrual cycle length.

Forty-seven women with regular ovulatory menstrual cycles and normal plasma prolactin levels were treated with different doses of bromocriptine, and changes in follicular and luteal phase length determined by daily estimation of plasma gonadotrophin concentration. Follicular phase length was highly significantly reduced from a median duration of 12.7 days in the basal cycle to 11.7 days in the first treatment cycle, and to 10.7 days during the second treatment cycles. The length of the luteal phase was unaltered by treatment with bromocriptine. Reduction of follicular phase length was not influenced by the dose of bromocriptine used, and it is concluded that this effect is a consequence of the reduction of plasma prolactin concentration.

Hormonal Regulation of Ovarian Folliculogenesis in Rhesus Monkeys

This experiment was designed to determine the effect of exogenous steroids on the preovulatory follicle and to evaluate subsequent ovarian and pituitary function as related to development of a substitute follicle. The original preovulatory follicle was identified by laparoscopy on Day 6 of the menstrual cycle in 29 monkeys, and Silastic capsules containing cholesterol, estradiol-17j3 (E2), or progesterone (P) were implanted s.c. in the following groups of animals: A) one cholesterol capsule for 48 h, B) six E2 capsules for 48 h, C) four E2 capsules for 48 h, D) four E2 capsules for 24 h, E) four E2 plus one P capsule for 48 h, and F) one P capsule for 48 h. Serum concentrations of follicle stimulating hormone (FSH), luteinizing hormone (LH), E2, and P were determined by radioimmunoassay. As expected, treatment with E2, for48 h resultedinprematuresurgesofLH and FSH, butno surges were induced with E2 treatmentfor24 h or withP treatments. Rather, small increases in FSH (but not LH) were consistently noted following removal of the latter implants. Regardless of the E2 or P treatment used or the response observed in gonadotropmn secretion, serum concentrations of endogenous E2 declined within 36 h after the capsules were implanted, and the preovulatory follicle regressed. In animals receiving cholesterol, hormone profiles were typical of those in normal menstrual cycles and ovulation occurred at the usual time. Following the FSH increases described above and atresia of the original preovulatory follicle, a different follicle developed and ovulated with normal luteal function ensuing. These extended follicular phases averaged 23.1 days, but the intervals from the FSH increase to ovulation approximated the length of a normal follicular phase (13.5 days in our control animals). These results indicate that elevated serum concentrations of E2 or P during development of the follicle otherwise destined to ovulate disrupt the preovulatory development and result in atresia; based on declining amounts of estrogen in the peripheral circulation, this effect may be exerted within the first day of treatment. Furthermore, the consistent association between FSH increases and renewed follicular development suggests, but does not prove, a cause and effect relationship between these events.

Recruitment of an ovulatory follicle in the human following follicle-ectomy and luteectomy

The study was undertaken to explore the time required for the selection and ovulation of a dominant follicle after interference with the normal menstrual cycle of fertile women. At routine laparotomy (sterilization) a leading follicle or a fresh corpus luteum was excised, and the day of the next ovulation was estimated by monitoring of serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone, and 17 beta-estradiol and by registration of the growth of the follicles through ultrasonic scanning. The results are in accordance with earlier observations in the rhesus monkey demonstrating that the recruitment and selection of an ovulation-competent follicle takes 12 to 14 days in the primate. Since this time is close to the length of the normal follicular phase and approximately the same after follicle-ectomy and luteectomy, the results suggest an importance of local factors in regulating follicle recruitment.

Hormonal regulation of ovarian folliculogenesis in rhesus monkeys: III. Atresia of the preovulatory follicle induced by exogenous steroids and subsequent follicular development.

This experiment was designed to determine the effect of exogenous steroids on the preovulatory follicle and to evaluate subsequent ovarian and pituitary function as related to development of a substitute follicle. The original preovulatory follicle was identified by laparoscopy on Day 6 of the menstrual cycle in 29 monkeys, and Silastic capsules containing cholesterol, estradiol-17j3 (E2), or progesterone (P) were implanted s.c. in the following groups of animals: A) one cholesterol capsule for 48 h, B) six E2 capsules for 48 h, C) four E2 capsules for 48 h, D) four E2 capsules for 24 h, E) four E2 plus one P capsule for 48 h, and F) one P capsule for 48 h. Serum concentrations of follicle stimulating hormone (FSH), luteinizing hormone (LH), E2, and P were determined by radioimmunoassay. As expected, treatment with E2, for48 h resultedinprematuresurgesofLH and FSH, butno surges were induced with E2 treatmentfor24 h or withP treatments. Rather, small increases in FSH (but not LH) were consistently noted following removal of the latter implants. Regardless of the E2 or P treatment used or the response observed in gonadotropmn secretion, serum concentrations of endogenous E2 declined within 36 h after the capsules were implanted, and the preovulatory follicle regressed. In animals receiving cholesterol, hormone profiles were typical of those in normal menstrual cycles and ovulation occurred at the usual time. Following the FSH increases described above and atresia of the original preovulatory follicle, a different follicle developed and ovulated with normal luteal function ensuing. These extended follicular phases averaged 23.1 days, but the intervals from the FSH increase to ovulation approximated the length of a normal follicular phase (13.5 days in our control animals). These results indicate that elevated serum concentrations of E2 or P during development of the follicle otherwise destined to ovulate disrupt the preovulatory development and result in atresia; based on declining amounts of estrogen in the peripheral circulation, this effect may be exerted within the first day of treatment. Furthermore, the consistent association between FSH increases and renewed follicular development suggests, but does not prove, a cause and effect relationship between these events.

Endocrine profiles and fertility status of human menstrual cycles of varying follicular phase length

Assessment of the relationship between ovarian endocrine function and follicular phase length was made in 48 patients (51 cycles) with spontaneous ovular cycles of varying length. On the basis of follicular phase length when measured from the first day of menstruation to, and including, the day of the luteinizing hormone (LH) peak, cycles were grouped into short (less than 21 days), medium (12 to 16 days), and long (more than 6 days). Daily serum LH, androstenedione, 17 beta-estradiol, progesterone, and 17 alpha-hydroxyprogesterone concentrations were determined in the periovular period. The overall pattern of serum steroid concentrations in medium and long cycles was similar to that previously described for normal women. However, cycles with a short follicular phase had lower mean concentrations of androstenedione and estradiol. In order to assess the fertility potential of cycles with follicular phases of varying length, the prior 265 cycles of 92 consecutive patients who conceived with artificial insemination by donor (AID) were studied. In all cases, insemination occurred on day 0 and day + 1 with respect to the LH peak, and all cycles were assumed to have equal fertility potential. Statistical analysis revealed no significant difference in fertility potential among cycles with follicular phases of differing length.