Contraception with pure,synthetic progestogens of the norpregnane group,a new approach for the future?

The 19-norsteroid androstanes which are currently the most prescribed progestin-only oral contraceptive formulations are responsible for some undesirable metabolic effects. The lowering of high density lipoprotein cholesterol and increased peripheral resistance to insulin associated with their use make them unsuitable for prolonged treatment. The norpregnanes, a new family of progestins, do not appear to induce similar metabolic modifications because they lack the same androgenic properties. The norpregnane group is characterized by persistence of the terminal chain of progesterone in 17 and absence of the methyl radical in 19. 3 norpregnanes have been tested in contraception: promegestone, nomegestrol acetate, and ST-1435 which is not yet commercially available. Levels of folicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and progesterone were monitored daily to confirm that ovulation was inhibited in all cases. A minimum dosage was found to be necessary in all cases to avoid continuing secretion of estrogen, which otherwide reached levels higher than those occurring in normal menstrual cycles. 6 women receiving 500 mcg of promegestone/day from the 6th to the 25th cycle day had no preovulatory FSH or LH peak, progesterone was constantly unmeasurable, and the plasma estradiol level dropped very quickly after the 1st days of treatment and remained between about 10-80 pcg/day. At doses of 2.5-5 mg/day of nomegestrol acetate, the preovulatory peak of LH disappeared, progesterone was unmeasurable, and the plasma levels of estradiol diminished within a few days. In a separate study, ST-1435, in the form of long-acting subcutaneous capsules, was found to inhibit the preovulatory peak of the gonadostimulants as well as progesterone secretion. Differences were again observed according to the dose level utilized, and fewer than 3 capsules of 40 mg ST-1435 permitted follicular maturation with high levels of plasma estradiol. The small number of women studied does not permit conclusions about clinical tolerance of the norpregnanes, but some cases of breakthrough bleeding were observed in women treated with promegestone and nomegestrol acetate. Biological tolerance was studied in a fragmentary fashion for promegestone. No weight gain or diminution of high density lipoprotein cholesterol was observed. The plasma TeBG level did not decline, confirming the absence of androgenic properties. The fasting glucose level, total cholesterol level, and triglyceride levels were unchanged.     

LH surge induction by GnRH agonist at the time of ovulation

Eight women were treated for 1 cycle at the time of ovulation with GnRH agonist (3 injections of 0.2 mg buserelin s.c. at 12-hour intervals) to obtain follicular rupture. Clomiphene citrate was administered to 1 patient and pure FSH to 2 patients, whilst in the case of a woman with hypothalamic amenorrhea a pulsatile GnRH regimen was used. Four patients had an untreated follicular phase. When the maximal follicular diameter was 20-22 mm all treatments were withheld and GnRH-A was administered. Plasma LH, FSH, progesterone and estradiol were determined 24 hours before, at the time of and 12, 24 and 48 hours after the 1st injection of buserelin. Ovulation was detected in all cycles. LH levels increased dramatically from baseline levels of 14.4 +/- 4.1 to 155 +/- 48 IU/l 12 hours after the beginning of treatment, then returned to preovulatory values 48 hours later (13.0 +/- 3.9 IU/l). The duration of the luteal phase was 13.2 days and normal mid-luteal progesterone plasma levels were detected (39.8 +/- 9.3 nmol/l). These data suggest that the GnRH agonist can be successfully used at the time of ovulation to induce an endogenous ovulatory LH peak and that it can be used in conjunction with different medical treatments to induce follicular maturation.     

Oral contraceptives and plasma lipids

The effects of 2 types of oral contraceptives (OCs) on plasma lipids in 45 healthy women were studied. The women received 1 mg lynestrenol plus .1 mg mestranol (Days 5-27), 4 mg megesterol acetate plus .05 mg ethinyl estradiol (Days 5-26), or .05 mg megesterol acetate daily for 3 months. Blood samples were collected prior to medication and subsequently in each of 3 consecutive cycles during medication between Days 23 and 26. The only change observed was a significant rise (p .05) in beta lipoproteins with a corresponding decline in alpha lipoproteins in the group receiving lynestrenol plus mestranol. It is concluded that if the desired efficacy and minimum clinical side effects can be obtained, either progestogens alone or progestogens with a small dose of estrogen should be the choice of medication.     

Steroids and the prediction of ovulation

Prediction of ovulation is useful in artificial insemination but indispensable in gathering of ovocytes for in vitro fertilization (IVF). IVF programs represent quasi-experimental conditions for correlating hormone levels and sonographic findings with ovulation and ovocyte maturation during spontaneous and induced menstrual cycles. During the follicular phase, only 1 "dominant" follicle is usually selected for ovulation. Under the influence of follicle stimulating hormone (FSH) and luteinizing hormone (LH), the ovocyte develops and transforms androgens secreted by the follicle into estrogens. The plasma at this stage is a poor reflector of the hormonal status of the follicular liquid. The preovulatory LH peak occurs after the level of estradiol (E2) reaches 200 pg/ml for about 50 hours. Increased estrogen secretion is the first notable hormonal variation preceding ovulation, but until a stage near ovulation, hormonal changes in the follicular liquid are not reflected in the plasma. Levels of FSH and LH progressively increase at the beginning of the follicular phase. Beginning in the middle of the follicular phase, around the 6th or 7th cycle day, the plasma concentration of 17 beta estradiol begins to increase rapidly. Plasma levels of several other steroids also increase in the days before the LH peak. The androgens produced throughout the menstrual cycle are not all ovarian origin. Their pulsatile secretion and normal variation make them inappropriate for predicting ovulation. Until recently the urinary levels of estrogens were the only measures routinely available, but their reliability as a measure of the estrogen actually produced depended on several factors. They are still used because of their advantages in cost and practicality. Newer tests of plasma estrogen levels give quick results and are used in numerous clinical situations despite their cost and their technical complexity. Although the increased plasma concentration of estradiol is the first of a series of hormonal events leading to ovulation, great variations in E2 rates from 1 cycle to another mean that it is not a reliable or precise predictor of ovulation. For spontaneous cycles, only repeated measurement of plasma or urinary LH levels allow correct prediction of ovulation in clinical practice. Ovarian stimulation by clomiphene or other substances modifies follicular phenomena. In such cases, monitoring of the estradiol level in association with ultrasound provides useful information about follicular maturation and to some extent ovocyte maturation, both of which are essential for IVF and embryo transfer.     

Gonadotropin-releasing hormone-induced changes in testosterone secretion in normal women

This study investigated the pattern of testosterone (T) secretion in spontaneous (n = 14) and gonadotropin-releasing hormone (GnRH)-treated (n = 6) menstrual cycles in normal women. In spontaneous cycles, T was found to increase progressively over the follicular phase (P less than or equal to 0.001), with the peak T value occurring on cycle day 0 (luteinizing hormone [LH] surge). The mean (+/- standard error of the mean [SEM]) T values on cycle day -14 and cycle day 0 were 35 +/- 4 and 51 +/- 4 ng/dl, respectively. GnRH was administered intravenously to six women at 1.3 to 1.7 micrograms per dose every 30 minutes in a study that assessed the ovarian effects of a rapid gonadotropin pulse frequency. In three of the women, the T levels followed a normal follicular phase pattern, whereas in the remaining three GnRH-treated women, there were marked increases in T with peak levels of 97, 123, and 81 ng/dl on day 0. The GnRH-treated subgroup with increased T levels had significantly increased follicular levels of LH, follicle-stimulating hormone (FSH), LH-bio and number of preovulatory ovarian follicles. This study demonstrated that increased levels of LH, FSH, and LH/FSH are capable of acutely increasing the secretion of ovarian androgens.     

Comparative studies of the ethynyl estrogens used in oral contraceptives. III. Effect on plasma gonadotropins.

Twenty-one-day treatment cycles of ethynylestradiol or mestranol at dosages of 50 to 100 mug per day were administered to 191 normal volunteer women from six cycles, followed by six cycles of this estrogen treatment combined with 2.5 mg. of norethindrone acetate, 2 mg. of megestrol acetate, or 0.5 mg. of norgestrel. The drugs were prepared to insure uniform bioavailabiltiy. Plasma FSH and LH were determined by radioimmunoasay during the last week of medication intake in each cycle. In another study, a large number of blood samples were obtained at various times during the menstrual cycle from women using IUD's (as a control population) and from women who had been taking oral contraceptives regularly for 5 to 12 years. With the various estrogen treatments, the median FSH level showed no change at any estrogen dose at the end of the first cycle. From the second cycle on, a stable, dose-related fall was obtained with the 80 or 100 mug per day doses. The addition of any of the three progestins caused a prompt, stable, further fall in FSH level. By contrast, the median LH level rose in the first cycle with all estrogen regimens, and then fell progressively in a dose-related fashion in cycles 2 to 6. The addition of a progestational agent also caused a further prompt and stable fall in LH during cycles 7 to 12. Except for a minimal indication of greater LH suppression by ethynylestradiol as compared to mestranol at 50 mug per day, all other indices and dosages showed ethynylestradiol and mestranol to be essentially equipoten under these experimental conditions. Long-term administration of oral contraceptives produced a comparable degree of gonadotropin suppression. There was a suggestion of slightly less FSH suppression with agents using 50 to 75 mug per day of estrogen than from those with 100 mug per day. Both in normal controls (IUD cycles) and in cycles under chronic treatment with oral contraceptives, pulses of both FSH and LH were seen with some frequency, at times distant from the "periovulatory" period. The significance and origin of these random FSH and LH pulses is unknown.     

Serum gonadotropin and steroid patterns during the normal menstrual cycle

At the University of Southern California School of Medicine, the reproductive hormones follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone, and estradiol were measured in serum samples obtained daily from a group of women throughout a normal menstrual cycle. Competitive binding techniques were used for the analysis of aliquots from the 10 women, aged 20-28, whose hormonal levels were studied. The results were generally in agreement with those of previous investigators, whose separate researches were less extensive than the research described here. FSH showed an early follicular phase rise, a late follicular phase decline, and a midcycle peak occurring on the day of the LH peak or on the day before and followed by a luteal phase decline. LH showed a slight progressive rise in the follicular phase, a midcycle peak, and a slight fall in the luteal phase. Estradiol also reached a midcycle peak. After the midcycle peaks, a rise progesterone. Progesterone and estradiol fell a few days before menstruation.     

A comprehensive dose-response study of clomiphene citrate for enhancement of the primate ovarian/menstrual cycle

Despite the increasing use of clomiphene citrate (CC) in normally cycling women undergoing in vitro fertilization, comprehensive data on the dose-response effects of the drug are unavailable. Twenty-four adult, normally cycling monkeys were given CC on cycle days 5 through 9 in doses ranging from 1 mg/kg to 10 mg/kg. Serum estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and progesterone were measured daily. CC stimulated an early, attenuated rise in serum LH which correlated with subsequent follicle development. Concurrently, serum E2 rose to preovulatory levels. No significant increase in serum FSH concentration was seen as a result of CC therapy. No correlation was seen between CC dose and peak levels of E2, LH, or FSH. The ovulatory status of the treatment cycles was also independent of dose. The factors that modulate these hormonal changes may involve direct effects of CC, estrogen feedback, and/or ovarian factors as yet uncharacterized. The individual variation of ovarian response, however, appears to be independent of the dose of CC.     

Ovarian follicular maturation in women. II. Reversal of estrogen inhibited ovarian folliculogenesis by human gonadotropin

The current study was undertaken to investigate the role of follicle-stimulating hormone (FSH) in reversing estrogen-induced follicular atresia. Normal menstruating women received ethinyl estradiol (EE2) 50 micrograms/day orally from days 2 to 7 after the onset of menses. Concomitant intramuscular injections of 1.0 ml of saline were administered to group 1, 75 IU of FSH and luteinizing hormone (LH) to group 2, and 150 IU units of FSH and LH to group 3. Daily blood samples were obtained throughout the investigative cycle for FSH, LH, 17 beta-E2, and progesterone. The women in group 1 had evidence of follicular atresia and a significant reduction in serum FSH and LH when compared to group 3 (P less than 0.002 and less than 0.001 respectively). Ovarian follicular development was maintained in groups 2 and 3, based on ultrasound evidence and the interval from menses to midcycle LH surge. These data indicate that the exogenous administration of FSH and LH results in maintenance of ovarian follicular development in women treated with exogenous estrogen.     

Stimulation of luteinizing hormone (LH) and follicle-stimulating hormone by (D-Leu6, des-Gly10-NH2)-LH-releasing hormone ethylamide after subcutaneous, intravaginal, and intrarectal administration to women.

Women, most of whom had regular menstrual cycles, were administered D-Leu6,des-Gly10-NH2)-luteinizing hormone-releasing hormone (LH-RH) ethylamide (D-Leu6-LH-RH-EA)via different routes during the early or midfollicular phase of the cycle. Plasma LH, follicle-stimulating hormone (FSH), and estrogen levels were determined by radioimmunoassay before and after administration of D-Leu6-LH-RH-EA. plasma LH and FSH increased and reached peak levels 3 to 4 hours and 3 to 6 hours, respectively, after subcutaneous injection of 25 mug of the analog of LH-RH. Intravaginal or intrarectal application of 2 mg of D-Leu6-LH-RH-EA also increased plasma LH and FSH levels in most of the women, but the magnitude of the rise, the time of initiation of response, and the peak level varied among the women. The plasma estrogen level also rose after administration via either route.     

Urinary reproductive hormone level differences between African American and Caucasian women of reproductive age

OBJECTIVE: To compare urinary levels of reproductive hormones in African American and Caucasian women. DESIGN: Cross-sectional study. SETTING: Ten United States Air Force (USAF) bases. PATIENT(S): African American (n = 33) and Caucasian (n = 65) women of reproductive age from a larger study of USAF women (n = 170). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Urinary endocrine end points: follicular luteinizing hormone (LH), preovulatory LH, level of LH surge peak, early follicular follicle stimulating hormone (FSH), follicular LH:FSH ratio, midluteal FSH, FSH rise before menses, early follicular estrone 3-glucuronide (E(1)3G), midfollicular E(1)3G, periovulatory E(1)3G peak, midluteal E(1)3G, early follicular pregnanediol 3-glucuronide (Pd3G), follicular Pd3G, rate of periovulatory Pd3G increase, E(1)3G:Pd3G on the day of luteal transition, slope of E(1)3G:Pd3G, and midluteal Pd3G. RESULT(S): Relative to Caucasians, African American women had significantly lower follicular phase LH:FSH ratios (mean +/- SD: 0.7 +/- 0.4 vs. 1.0 +/- 0.6), lower follicular phase Pd3G levels (1.0 +/- 0.5 vs. 1.2 +/- 0.8 microg/mg creatinine), and lower rates of periovulatory Pd3G increase (0.5 +/- 0.7 vs. 1.0 +/- 1.2 microg/mg creatinine). CONCLUSION(S): Findings of this analysis should be considered preliminary evidence of racial differences in hormone levels. Future studies are needed to determine whether these differences have clinical significance.     

Plasma levels of FSH and LH in patients with gonadal dysgenesis during sequential estrogen and progestogen therapy

We describe the plasma levels of FSH and LH in ten patients with gonadal dysgenesis during treatment with a low dosage sequential estrogen-progestogen preparation. The daily dose of mestranol ranged from 12.5--50 microgram. Norethisterone was administered from day 16 onwards, the dose ranging between 0.75 and 1.5 mg. It was shown that 25 microgram mestranol was effective in lowering the elevated FSH levels significantly (alpha < 0.001). LH levels remained unaffected. The combination of 25 microgram mestranol and 1 mg norethisterone produced an increase of FSH and LH within 12 h, maximum levels being reached within 36 h after which there was a progressive decline. Low doses of estrogen and progestogen appeared capable of evoking physiological hypothalamic and pituitary responses in patients with gonadal dysgenesis. The doses employed were sufficient to induce breast development, growth of sexual hair, and withdrawal bleeding and were probably not high enough to induce rapid bone maturation and consequent stunting of growth.     

Serum estradiol in women ingesting combination oral contraceptive steroids

A study of the effect of combination oral contraceptives upon endogenous ovarian estrogen production was done by measuring serum estradiol levels in 3 groups of women. The first group of 3 women gave daily serum samples during 1 control and 2 treated cycles (2 mg. norethindrone and 100 mu-g mestranol received daily for 20 days), and levels of follicle-stimulating hormone, luteinizing hormone, estradiol and progesterone were measured. A second group (6) taking oral contraceptives for at least a year were measured daily during 1 cycle for estradiol only. Each of 97 women in the third group, taking the pill from 1 to 6 years, gave a single blood sample taken at random during the cycle, to be assayed for estradiol. Estradiol levels in women receiving oral contraceptives were low, usually in the range of 20-30 pg./ml., similar to those found in the early follicular phase in ovulatory cycles, and significantly higher than levels found in postmenopausal women. Exogenous estrogen in the pill, together with this level of endogenous estradiol, should be sufficient to prevent any harmful effects associated with estrogen deficiency. The finding that estradiol levels remain low in the first cycle of therapy is consistent with previous studies which indicate that one of the mechanisms of action of hormonal contraceptives is a direct effect upon the ovary.     

Influence of preovulatory estradiol concentration on diurnal and pulsatile prolactin secretion patterns

We evaluated the effect of preovulatory concentrations of estradiol on the 24-hour profile of prolactin secretion in women with regular menstrual cycles. An estradiol preparation was chosen to allow comparison with physiologic events. Estradiol benzoate, 1 mg intramuscularly, was administered for 7 days to achieve estradiol concentrations just above preovulatory levels (424 +/- 54 pg/ml); 24-hour mean prolactin concentrations increased threefold (14.0 +/- 2.1 to 40.6 +/- 7.1 ng/ml). Prolactin pulse frequency increased significantly (p less than 0.001) during waking hours after estradiol benzoate administration. The diurnal pattern of prolactin secretion was maintained with estradiol benzoate, although the sleep acrophase often reached high concentrations (86 +/- 11 ng/ml). These results suggest in women with regular menstrual cycles: (1) that estrogen administration that achieves slightly greater than preovulatory estradiol concentrations can stimulate prolactin release, (2) that estradiol may elevate prolactin by increasing its pulsatile secretion, (3) that estradiol does not alter the diurnal pattern of prolactin secretion, (4) that estradiol concentrations just above preovulatory levels can be associated with markedly elevated prolactin concentrations.     

Prediction of the time of ovulation

Prediction of ovulation was established by correlation of clinical parameters, follicular development by ultrasound, and estradiol, progesterone, and luteinizing hormone (LH) determination in 71 menstrual cycles. Laparoscopic follicular aspiration was accomplished in 41 of those cycles. A 28-hour interval from the ascending limb of the LH seems to be the "ideal time" for retrieval of a preovulatory oocyte. The variability in the amount of LH to which the follicle is exposed during the LH surge seems to indicate that there is a relatively low specific value necessary for ovulation. Ovulation occurs approximately 10 +/- 5 hours from the LH peak. Progesterone occurs in relation to the LH surge and is helpful for the retrospective analysis of the menstrual cycle.     

每周一次口服小剂量米非司酮用于常规避孕的临床研究

目的探讨每周一次口服小剂量米非司酮5mg或10mg用于避孕的可行性。方法将39例健康妇女随机分为两组，自月经第2～3天起，每周口服米非司酮5mg，共19例，为A组；每周口服米非司酮10mg，共20例，为B组。测定服药第1周期雌二醇（E2）、孕酮（P）、黄体生成素（LH）、卵泡刺激素（FSH）、血药浓度及子宫内膜孕酮受体（PR）、双花扁豆生物素（dolichusbiflorusagglutinin，DBA）、整合素αvβ3（CD51/61）的表达，并观察临床避孕效果。结果A组共服药64个周期，4例妊娠；B组共服药68个周期，3例妊娠。两组于月经第15～17天出现LH高峰。LH峰值A组为(42.14±16.38)IU/L，B组为(33.19±10.57)IU/L；FSH峰值A组为(12.90±3.84)IU/L，B组为(13.98±5.24)IU/L。P高峰期均值A组为(51.93±7.91)nmol/L,B组为(69.00±21.29)nmol/L；E2高峰期均值A组为(407.81±89.27)pmol/L，B组为(557.85±204.69)pmol/L。两组米非司酮血清浓度均可维持36h。内膜腺体为分泌早期改变，间质呈分泌中期改变；PR、DBA和整合素αvβ3表达减弱。结论每周一次口服小剂量米非司酮妇女的月经周期改变不大，血LH峰轻度延迟，E2均值低于正常；子宫内膜发育受到抑制，影响分泌期功能；临床避孕效果不理想，其常规用于避孕的可行性有待研究。     

Accuracy of basal body temperature for ovulation detection.

In 30 normally menstruating women, ages 19 to 41 (mean 24), gravida 0 to 5 (mean 0.7), basal body temperature (BBT) was correlated with serum luteinizing hormone (LH), progesterone, and estradiol or urinary estrogen levels assayed serially during one menstrual cycle. In 21 subjects (70%), a biphasic BBT correlated with an ovulatory hormonal pattern. Six women (20%) had a monophasic BBT but demonstrated a preovulatory estrogen peak, a midcycle LH surge, and a significant rise in serum progesterone levels during the luteal phase. The remaining three women (10%) showed anovulatory cycles (two women) or a deficient luteal phase (one woman) as determined by BBT and hormonal assays. The results indicate that in approximately 20% of ovulatory cycles the BBT failed to demonstrate ovulation.     

Relationship between midcycle luteinizing hormone surge quality and oocyte fertilization

OBJECTIVE: To determine whether alterations in preovulatory follicular fluid (FF) levels of LH, FSH, and steroids are associated with the probability of fertilization. DESIGN: Retrospective analysis of prospective study results. SETTING: Reproductive medicine clinic of a university teaching hospital. PATIENT(S): Infertile women, with unstimulated, apparently regular cycles in an IVF research program. INTERVENTION(S): Measurement of preovulatory FF levels of LH, FSH, E2, and P and serum LH levels by fluoroimmunometry. MAIN OUTCOME MEASURE: Oocyte fertilization. RESULT(S): There were 84 transferable embryos (rate of normal fertilization and cleavage, 67%), and 41 oocytes (33%) failed to fertilize. Analysis of the matched FF showed that the median concentration of FF LH was significantly higher for cleaving embryos than for unfertilized oocytes (14.6 vs. 10.4 IU/L). Serum LH concentrations were similarly higher in cycles with cleaving embryos. There were no statistically significant differences in FF concentrations of FSH, E2, or P in the two groups. CONCLUSION: Reduced preovulatory FF LH levels are associated with impaired fertilization of oocytes in vitro, despite normal FF FSH and steroid levels.     

Menstrual and Hormone Patterns in Women Treated with High-Dose Cisplatin and Bleomycin

Menstrual and hormone patterns were investigated in 10 fertile women (median age 37, range 25-43 years) with locally advanced cervical cancer treated with neoadjuvant chemotherapy (CT). CT consisted of two cycles of high-dose cisplatin (CDDP, 40 mg/m², Days 1 to 4) and bleomycin (B, 15 mg/m², Days 1 and 8) separated by an interval of 21 days. Menstrual patterns before and during CT were recorded. FSH, LH, estradiol, and progesterone were assayed on the day that treatment was begun, after 2 and 4 days of CDDP administration, and weekly between and after the two cycles. Hormone assays during the first week of CT showed no significant change in hormone levels. After the first course of CT, five patients showed hypergonadotrophic amenorrhea and five patients maintained menses, two showing ovulatory and three showing follicular phase hormone patterns. After the second course of CT, one more patient become amenorrheic, and endocrine follow-up showed that two patients maintained hypergonadotrophic amenorrhea, four with hypergonadotrophic amenorrhea had a return of hormone levels to the follicular range of 7-9 weeks after, three maintained follicular phase hormone patterns until operation, and one ovulated. Gonadal dysfunction should be included among the side effects of high-dose CDDP and B regimens.     

Human urinary follicle-stimulating hormone and human menopausal gonadotropin in induction of multiple follicle growth and ovulation

Five normally menstruating women were treated, in an attempt to induce development of multiple follicles, with pharmacologic doses of purified human urinary follicle-stimulating hormone (hU-FSH) and (in another instance) with human menopausal gonadotropin (hMG) administered on the second and third days after the onset of menses. All of the cycles were ovulatory: the follicular phase was short and the luteal phase length was normal in both hMG and hU-FSH treatment. No substantial differences were seen between the two types of treatment in regard to plasma values of FSH, luteinizing hormone (LH), estradiol (E2), testosterone, and progesterone (P). FSH, E2, and P increased to supraphysiologic levels, and LH fluctuated within the normal range. On ultrasound examination, a large number of growing and matured follicles were visualized during both treatments: at human chorionic gonadotropin administration, multiple preovulatory follicles (greater than or equal to 15 mm) and only a few small follicles (less than 10 mm) were imaged, without any difference between the two types of treatment. Multiple corpora lutea were often obtained. These data underline that pharmacologic doses of FSH alone are able to induce the growth of multiple preovulatory follicles when the initiation of stimulation is timed early. Besides this, exogenous LH does not seem to interfere with follicular recruitment, and it is not required for follicular maturation and ovarian steroidogenesis when endogenous normal LH mean values are present.