Ovulation induction increases serum levels of insulin-like growth factor binding protein 1.

The effect of ovulation induction on serum insulin-like growth factor binding protein 1 (IGFBP-1) level in relation to sex hormone binding globulin (SHBG) levels was evaluated. Serum samples were collected 8 to 12 days after ovulation from 26 women undergoing ovulation induction with clomiphene citrate (CC), and from 58 women treated with CC in combination with human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG). In addition, serum samples were obtained from 63 spontaneously ovulating women and from 12 women during an anovulatory cycle. Luteal phase serum IGFBP-1 levels were 4.22 +/- 2.95 micrograms/L (P less than .05) in the CC group and 7.31 +/- 6.13 micrograms/L (P less than .001) in the CC/hMG/hCG group as compared to unstimulated ovulatory cycles (2.64 +/- 2.52 micrograms/L). No significant difference in IGFBP-1 levels was seen between spontaneously ovulatory and anovulatory cycles. The serum IGFBP-1 levels correlated positively to SHBG levels (r = .52, P less than .001). The data show that ovulation induction increases serum IGFBP-1 levels in parallel to SHBG levels, indicating that ovarian stimulation, which results in increased steroid hormone production, also induces changes in other factors known to modulate steroid hormone actions.     

Mode of action of DL-norgestrel and ethinylestradiol combination in postcoital contraception.

Possible mechanisms of action of a combination of ethinylestradiol (EE) and dl-norgestrel as a postcoital contraceptive agent were studied in 12 healthy female volunteers. An oral dose of 0.1 mg of EE and 1.0 mg of dl-norgestrel was given at the predicted time of ovulation and again 12 hours later. Serum luteinizing hormone, prolactin, progesterone, 17 alpha-hydroxyprogesterone, and estradiol were measured by specific radioimmunoassays in blood samples obtained daily from the 8th day of the menstrual cycle to the 1st day of menses. Hormone profiles suggested that the medication elicited a range of individual variations in pituitary and/or ovarian responses. Histologic examination of the endometrium consistently showed significant alteration in endometrial development with a dissociation in maturation of glandular and stomal components. This postcoital contraceptive acts either by (1) suppressing ovulation or (2) disrupting luteal function by acting directly on the corpus luteum or by interfering with appropriate endometrial responses to ovarian steroids.     

Role of aromatase inhibitor in ovulation induction in patients with poor response to clomiphene citrate

AIM: To examine the efficacy of aromatase inhibitor in the induction of ovulation. METHODS: This prospective clinical trial in patients with infertility and poor response to clomiphene citrate (CC) was undertaken in a tertiary referral infertility clinic. Thirty-five infertile patients, who were treated by clomiphene citrate for several cycles and referred to the infertility clinic, were the target population. Initially, the response of CC was assessed by same dose of CC that the patient had in her last cycle. The patients who did not respond adequately were treated by aromatase inhibitor 2.5-5 mg/day from day 3-7 of the menstrual cycle. The main outcome measures were the number of mature follicles, ovulation rate, endometrial thickness and pregnancy rate. RESULTS: Twenty-seven (90%) patients developed mature follicles by day 12. The majority (77.77%) developed single follicle. Except for one cycle of one patient, the follicles of all patients were ruptured in all cycles and seven (25.94%) got pregnant. CONCLUSION: The aromatase inhibitor letrozole is effective for ovulation induction in anovulatory infertility in patients that failed to ovulate by CC.     

Clomiphene citrate does not adversely affect endometrial leukemia inhibitory factor levels

The aim of this study was to compare endometrial leukemia inhibitory factor (LIF) levels in spontaneous and clomiphene citrate (CC)-induced cycles of patients with unexplained infertility. The patients were followed in two consecutive cycles. Endometrial samples were obtained 7 days after ultrasonographic evidence that ovulation has occurred during the spontaneous cycle, then the patients were induced with CC from day 5 to day 9 during the subsequent cycle with 50 mg/day, and ovulation monitoring and endometrial biopsy were performed in the same manner. The samples were obtained using a Pipelle biopsy device without using local anesthesia, and kept in formaldehyde solution until the day of measurement. Then they were homogenized in phosphate buffered distilled water, and LIF levels were detected in the homogenized fluid by ELISA method. Endometrial LIF levels were 470 ± 52 and 501 ± 45 pg/1 gram wet tissue in spontaneous and CC-induced cycles respectively, revealing no significant difference. Ovulation induction with CC did not adversely affect endometrial LIF levels.     

Clomiphene citrate does not adversely affect endometrial leukemia inhibitory factor levels.

The aim of this study was to compare endometrial leukemia inhibitory factor (LIF) levels in spontaneous and clomiphene citrate (CC)-induced cycles of patients with unexplained infertility. The patients were followed in two consecutive cycles. Endometrial samples were obtained 7 days after ultrasonographic evidence that ovulation has occurred during the spontaneous cycle, then the patients were induced with CC from day 5 to day 9 during the subsequent cycle with 50 mg/day, and ovulation monitoring and endometrial biopsy were performed in the same manner. The samples were obtained using a Pipelle biopsy device without using local anesthesia, and kept in formaldehyde solution until the day of measurement. Then they were homogenized in phosphate buffered distilled water, and LIF levels were detected in the homogenized fluid by ELISA method. Endometrial LIF levels were 470 +/- 52 and 501 +/- 45 pg/1 gram wet tissue in spontaneous and CC-induced cycles respectively, revealing no significant difference. Ovulation induction with CC did not adversely affect endometrial LIF levels.     

Serum prolactin levels during sleep and in metoclopramide stimulation in normoprolactinemic anovulation and ovulation induction with bromocriptine

Diurnal and nocturnal serum prolactin (PRL) levels were determined in 37 normoprolactinemic anovulatory (nPRL-Anov) patients and 6 normal cycling women each in the early follicular phase (EFP) and the luteal phase (LP). PRL responsiveness to metoclopramide (MCP) was assessed. The nPRL-Anov patients received 5mg/day bromocriptine (CB-154) for 2 months and ovulation was investigated. To the CB-154 non-responders was added 150mg/day clomiphene (CL) for 5 days. The nPRL-Anov patients were classified into 3 groups; i.e. I: those who ovulated with CB-154 (n = 14), II: those who ovulated with CB-154 + CL (n = 6), and III: those who failed to ovulate (n = 10). Nocturnal serum PRL levels in I (42.0 +/- 26.2ng/ml; M +/- SD) were significantly higher than those in EFP, II and III (p less than 0.05). Eleven (78.6%) of I had nocturnal PRL levels higher than 25ng/ml. The peak PRL values at MCP provocation were significantly higher in I (213.3 +/- 89.1ng/ml) than in EFP, II and III (p less than 0.01). Thirteen (92.9%) of I had peak PRL values more than 150ng/ml. The peak PRL values and nocturnal PRL levels correlated. There were some exhibiting nocturnal or latent hyperprolactinemia, who responded effectively to CB-154, among nPRL-Anov patients. A MCP provocation test could be used in prediction of the efficacy of CB-154 treatment when applied to nPRL-Anov patients.     

Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate

OBJECTIVE: To use aromatase inhibition for induction of ovulation in women in whom clomiphene citrate (CC) treatment was unsuccessful. DESIGN: Prospective trial in infertility patients treated with CC. SETTING: Two tertiary-referral infertility clinics associated with the Division of Reproductive Sciences, University of Toronto. PATIENT(S): Twelve patients with anovulatory polycystic ovary syndrome (PCOS) and 10 patients with ovulatory infertility, all of whom had previously received CC with an inadequate outcome (no ovulation and/or endometrial thickness of < or =0.5 cm). INTERVENTION(S): The aromatase inhibitor letrozole was given orally in a dose of 2.5 mg on days 3-7 after menses. MAIN OUTCOME MEASURE(S): Occurrence of ovulation, endometrial thickness, and pregnancy rates. RESULT(S): With CC treatment in patients with PCOS, ovulation occurred in 8 of 18 cycles (44.4%), and all ovulatory cycles for the women included in this study had endometrial thickness of < or =0.5 cm. In 10 ovulatory patients, 15 CC cycles resulted in a mean number of 2.5 mature follicles, but all cycles had endometrial thickness of < or =0.5 cm on the day of hCG administration. With letrozole treatment in the same patients with PCOS, ovulation occurred in 9 of 12 cycles (75%) and pregnancy was achieved in 3 patients (25%). In the 10 patients with ovulatory infertility, letrozole treatment resulted in a mean number of 2.3 mature follicles and mean endometrial thickness of 0.8 cm. Pregnancy was achieved in 1 patient (10%). CONCLUSION(S): Oral administration of the aromatase inhibitor letrozole is effective for ovulation induction in anovulatory infertility and for increased follicle recruitment in ovulatory infertility. Letrozole appears to avoid the unfavorable effects on the endometrium frequently seen with antiestrogen use for ovulation induction.     

Endometrial biopsy during induction of ovulation with clomiphene citrate in polycystic ovary syndrome.

BACKGROUND: The dichotomy between ovulation rates and pregnancy rates for women with polycystic ovary syndrome (PCOS) treated with clomiphene citrate (CC) prompted the present study to determine the effect of CC on endometrial maturity. METHODS: Retrospective case-control study of anovulatory women with PCOS (n = 119) on their third ovulatory cycle of CC and controls, 238 healthy regularly ovulating women whose partners had abnormal sperm, all of whom had an endometrial biopsy in the late luteal phase. RESULTS: Endometrial histology classified according to the classical Noyes criteria revealed out-of-phase endometrium in 19/119 (16%) of the CC group compared with 7/238 (3%) in controls (p < 0.0001). Duration of the luteal phase was not influenced by histological age of the endometrium. Endometrial biopsy performed during 138 conception cycles extracted from the database did not increase the miscarriage rate significantly (23.9%). CONCLUSIONS: CC treatment significantly increases the prevalence of out-of-phase endometrium and this could explain, in part, the large difference between ovulation and pregnancy rates. There was no correlation between the results of the endometrial biopsy and the duration of the luteal phase. Performing an endometrial biopsy during a conception cycle does not seem to have a significant negative effect on the outcome of pregnancy.     

Management of anovulatory infertility associated with polycystic ovary syndrome: tamoxifen citrate an effective alternative compound to clomiphene citrate.

Clomiphene citrate (CC) is widely used as first-line treatment for ovulation induction in anovulatory women with polycystic ovary syndrome (PCOS). Tamoxifen citrate (TMX), another non-steroidal selective estrogen receptor modulator, may also be effective on the resumption of ovulation in these women. The aim of this controlled observational study was to compare the efficacy and safety of ovulation induction with TMX versus CC in anovulatory infertile women with PCOS. A total of 102 consecutive women (mean age+/-SD: 31+/-3.6 years; range: 26-38) with PCOS were studied. Following a spontaneous or progesterone-induced withdrawal bleed, women received either 50 mg daily of CC (days 2-6) or 20 mg daily of TMX (days 2-5). In case ovulation failed to occur, the dose was sequentially increased to 100 mg daily of CC and 40 mg daily of TMX, respectively. Serum progesterone levels were measured on cycle day 21 to monitor the ovulation pattern. The overall ovulation rate was significantly higher in women who received TMX compared with those who received CC (61/98, 62.2% vs. 60/127, 47.2%, p=0.03). Although not statistically significant, the pregnancy rate per ovulatory cycle was higher in the TMX group compared to the CC group (14/61, 22.9% vs. 11/60, 18.3%, respectively). All pregnancies were single and there were no side-effects in either group of treatment. Collectively, these data demonstrate that TMX is a safe and effective agent, and a suitable alternative to CC for anovulatory infertility in women with PCOS.     

Induction of ovulation with pulsatile subcutaneous administration of human menopausal gonadotropin in anovulatory infertile women

Pulsatile administration of human menopausal gonadotropin (hMG) via the subcutaneous route was evaluated in 15 patients with various ovulatory disorders. Administration of hMG was started at a dose of 4.6875 IU (75 IU/day) or 9.375 IU (150 IU/day) per pulse every 90 minutes. Ovulation was observed in 26 (92.9%) of 28 treatment cycles, and two singleton pregnancies were confirmed. Ovarian hyperstimulation was observed in 1 to 26 ovulatory cycles; however, no other side effects were observed during treatment. A regimen of 75 IU/day resulted in a significant increase (P less than 0.0001) of the total dose and prolongation of the treatment period for induction of ovulation, as compared with that of 150 IU/day. Shortened luteal phases occurred in ovulatory cycles induced by pulsatile subcutaneous treatment. Human chorionic gonadotropin administration given every other day until the midluteal phase significantly prolonged the duration of the luteal phase (P less than 0.05). This treatment in patients with the polycystic ovary syndrome was followed by a normalization of luteinizing hormone/follicle-stimulating hormone ratio and resulted in a successful induction of ovulation in 8 to 10 cycles. The present data demonstrated that pulsatile subcutaneous administration of hMG was effective in inducing follicular maturation and ovulation in patients with various types of anovulatory infertility.     

Pregnancies following use of metformin for ovulation induction in patients with polycystic ovary syndrome

OBJECTIVE: To assess pregnancy outcome in anovulatory infertility patients diagnosed with polycystic ovary syndrome (PCOS) who were treated with metformin. DESIGN: Case series. SETTING: Outpatient. PATIENT(S): Anovulatory patients (n = 48) with a diagnosis of PCOS based on clinical, diagnostic, and laboratory evaluations were enrolled in the study over a 15-month period. INTERVENTION(S): Metformin was started at 500 mg b.i.d. for 6 weeks and then increased to 500 mg t.i.d. if no ovulation occurred. Clomiphene citrate (CC; 50 mg) was added if no ovulatory response occurred after 6 weeks. MAIN OUTCOME MEASURE(S): Resumption of menses, presumptive ovulation, and pregnancy. RESULT(S): Nineteen of 48 (40%) patients resumed spontaneous menses following treatment and showed presumptive evidence of ovulation with metformin alone; 15/48 (31%) required CC (50 mg) in conjunction with metformin therapy, and 10 of these 15 (67%) had evidence of ovulation; 20/48 (42%) conceived with a median time to conception of 3 months, and 7 of these 20 (35%) had spontaneous abortions (SAB); 19/48 (40%) had gastrointestinal-related side effects, and 5 of 48 patients (10%) had to decrease the dosage of metformin. Only 1 patient discontinued therapy. CONCLUSION(S): Metformin alone in patients with PCOS results in a substantial number of pregnancies, with 69% (20/29) of those who ovulated conceiving in less than 6 months.     

Endometrial biopsy during induction of ovulation with clomiphene citrate in polycystic ovary syndrome

Background.?The dichotomy between ovulation rates and pregnancy rates for women with polycystic ovary syndrome (PCOS) treated with clomiphene citrate (CC) prompted the present study to determine the effect of CC on endometrial maturity.

Methods.?Retrospective case–control study of anovulatory women with PCOS (n = 119) on their third ovulatory cycle of CC and controls, 238 healthy regularly ovulating women whose partners had abnormal sperm, all of whom had an endometrial biopsy in the late luteal phase.

Results.?Endometrial histology classified according to the classical Noyes criteria revealed out-of-phase endometrium in 19/119 (16%) of the CC group compared with 7/238 (3%) in controls (p < 0.0001). Duration of the luteal phase was not influenced by histological age of the endometrium. Endometrial biopsy performed during 138 conception cycles extracted from the database did not increase the miscarriage rate significantly (23.9%).

Conclusions.?CC treatment significantly increases the prevalence of out-of-phase endometrium and this could explain, in part, the large difference between ovulation and pregnancy rates. There was no correlation between the results of the endometrial biopsy and the duration of the luteal phase. Performing an endometrial biopsy during a conception cycle does not seem to have a significant negative effect on the outcome of pregnancy.     

Detrimental effect of endometrial biopsies on pregnancy rate following human menopausal gonadotropin/human chorionic gonadotropin-induced ovulation

The effect of luteal phase endometrial biopsy was studied in 33 anovulatory women treated with human menopausal gonadotropins (hMG) to induce ovulation and pregnancy. Over-all, 33 of 85 ovulatory cycles resulted in pregnancy (39%). Of 50 nonbiopsied cycles, 26 resulted in pregnancy (52%) whereas only 7 of 35 biopsied cycles resulted in pregnancy (20() (P less than 0.01). Four pregnancies terminated in spontaneous first-trimester abortions, 12% in the nonbiopsied group and 14% in the biopsied group. Luteal phase endometrial biopsy significantly lowers pregnancy rates in hMG-induced ovulatory cycles, but does not change abortion rates.     

Advanced secretory changes in the proliferative human endometrial epithelium following clomiphene citrate treatment

In an effort to characterize the effect of clomiphene citrate (CC) on the human endometrium, we took biopsy specimens of the endometrium 24 to 48 hours after CC treatment (100 to 250 mg/day for 5 consecutive days). Nineteen biopsy specimens were taken from 19 patients. Fifteen of the patients suffered from anovulatory infertility associated with oligomenorrhea or normal cycle length. The other four patients were amenorrheic, two in association with hypogonadotropic hypogonadism and two with hypergonadotropic hypogonadism. The histopathology of all samples was evaluated with the use of light microscopy, including periodic acid-Schiff (PAS) and PAS-diastase staining for glycogen demonstration. All samples were also examined with the use of scanning electron microscopy (SEM). Serum levels of estradiol (E2), progesterone (P), luteinizing hormone, and follicle-stimulating hormone were determined on the day of biopsy. In 10 of the 19 biopsy specimens, local or diffuse signs of early secretory events were demonstrated by the presence of subnuclear vacuolization and glycogen in the glandular epithelial cells. SEM corroborated these findings of advanced secretory changes by demonstrating apical protrusions at luminal epithelial cells and secretory products within the glands' openings. The E2 levels ranged between 110 and 1500 pg/ml (mean, 371 pg/ml) and P levels were either undetectable or less than 1.1 ng/ml. The two patients with hypogonadotropic hypogonadism both exhibited the same phenomena; those with primary ovarian failure had atrophic endometrium even after high-dose CC treatment. This observation, together with the low P levels detected, indicating the lack of luteinization, suggests a possible direct effect of CC on the endometrium.(ABSTRACT TRUNCATED AT 250 WORDS)     

Monitoring techniques for improved pregnancy rates during clomiphene ovulation induction

Despite the introduction of new ovulation-inducing agents, CC remains the drug of choice for most anovulatory patients. Before initiating therapy, patients should be evaluated to determine the cause of anovulation. Patients with ovarian failure, hyperprolactinemia, hypothyroidism, or forms of CAH should be treated with the appropriate replacement therapy. Evaluation of male factor and tubal patency should be obtained. Once CC therapy is initiated, careful monitoring should be continued. Confirmation of ovulation by endometrial biopsy or serum P levels is essential. CC doses should be increased monthly until normal luteal function is demonstrated. If the patient does not conceive in three ovulatory cycles, her treatment should be further evaluated by postcoital testing, repeat serum P measurement, and review of her endocrine findings. Patients with poor cervical mucus may benefit from midcycle estrogen. Patients with elevated T may benefit from prednisone suppressive therapy. Patients with abnormal HSGs should have laparoscopy and surgical correction if feasible. After six ovulatory cycles without conception, all patients should undergo laparoscopy. If laparoscopy is normal, therapy can be continued for a total of 10 to 12 cycles. Patients with reduced fecundability (male factor, minimal endometriosis, or minimal tubal adhesions) may require a longer time to conceive.     

Yellow body function in bromocryptine induced early pregnancy in patients with hyperprolactinemia (author's transl)

In six patients estrogens and gonadotropins were low and the prolactin concentration was increased (36-128 micrograms/l). Amenorrhea in all patients lasted 8-60 months, while galactorrhea was observed in five patients. By the X-ray of the sella turcica and neurologic and ophthalmologic examinations no signs of an intrasellar expansive process were revealed. The progesterone test was negative in four patients and the clomiphene test in all six patients. The LH-RH test (100 micrograms i. m.) showed the increased LH and FSH concentrations in all six patients. They all became pregnant in the course of the bromocryptine treatment (5-7.5 mg daily). Pregnanediol and prolactin concentrations were recorded every 14 days in the first 16 weeks of pregnancy, both in six patients and in eleven controls with spontaneous pregnancy. The pregnanediol concentrations proved somewhat higher in the control group than in patients having become pregnant under the bromocryptine therapy, but the differences are not statistically significant. However, the prolactin concentrations were significantly lower in controls than in pregnant women with the hyperprolactinemic anovulatory syndrome (p less than 0.01) in the sixth to the twelfth week of pregnancy.     

Treatment of anovulatory sterility using clomiphen]

74 patients with anovulatory sterility were treated with clomiphene for 5 consecutive days starting on the 5th day of the cycle. The dosage was in the first course of treatment 50 mg daily. The patients, who did not conceive after this dosage, were treated with higher doses of clomiphene (100 and 150 mg daily). In 66% of the cases ovulation and in 32% (49% of induced ovulation) pregnancies were achieved. In the first treatment cycle with 50 mg/day for 5 days ovulation was obtained in 27 out of 74 patients. 14 patients, who failed to ovulate after this dosage, did ovulate after they were treated with 100 mg/day in the second treatment cycle. In 8 cases was a third treatment cycle with 150 mg/day needed to chieve a positive result. The conception rate per ovulatory cycle decreased with increasing dosage. The ovulation as judged on the basis of the temperature curve and pregnandiol excretion occured between the 4th and 25th day of treatment, whereas ovulation which were followed by pregnancy occured only between the 11th and 25th day.     

Ovulation Induction With Bromocriptine (CB154) in Patients With Hyperprolactinaemia

Summary: Bromocriptine was effective in inducing ovulation in 95% of 44 anovulatory subjects with hyperprolactinaemia and 73% conceived. Most subjects ovulated during treatment with bromocriptine in a dose of 5 mg/day, however 8 required 10 mg/day, 3 required 15 mg/day and 2 required 40 mg/day. Half of the subjects showed follicular maturation only or deficient corpus luteum function as their initial ovarian response. Increase in the dose of bromocriptine administered was not always necessary to improve this response to that of normal ovulation. At the time of conception the serum prolactin level had been suppressed to normal in all but one subject and in the majority was less than 10 ng/ml.
Three subjects who did not conceive during treatment with bromocriptine alone were also treated with thyroxine, although their thyroid function was normal. Two of these subjects conceived and the third had cycles of ovarian response of follicular maturation only or ovulation with deficient corpus luteum function having previously had no ovarian response when treated with bromocriptine alone.     

N-acetylcysteine as an adjuvant to clomiphene citrate for successful induction of ovulation in infertile patients with polycystic ovary syndrome

Aim: The aim of this study was to evaluate the effect of oral N-acetylcysteine (NAC) administration as an adjuvant to clomiphene citrate (CC) on induction of ovulation outcomes in patients with polycystic ovary syndrome (PCOS). Material and Methods: In this placebo-controlled double-blind randomized clinical trial, 180 PCOS infertile patients were randomly divided into two groups for induction of ovulation. Patients in group 1 received CC 100?mg/d plus NAC 1.2?g/d and patients in group 2 received CC plus placebo for 5?days starting at day 3 of the cycle. On the 12th day of the menstrual cycle in the presence of at least one follicle with an 18-20-mm diameter in ultrasound evaluation, 10?000?U hCG was injected intramuscularly and timed intercourse was advised 36?h after hCG injection. Serum β-hCG level was measured on the 16th day after hCG injection. Results: The number of follicles >18?mm and the mean endometrial thickness on the day of hCG administration were significantly higher among the CC+NAC group (P-value?=?0.001). The ovulation and pregnancy rates were also significantly higher in the CC+NAC group (P-value?=?0.02 and 0.04, respectively). No adverse side-effects and no cases of ovarian hyperstimulation syndrome were observed in the group receiving NAC. Conclusion: NAC as a safe and well-tolerated adjuvant to CC for induction of ovulation can improve the ovulation and pregnancy rates in PCOS patients. It may also have some beneficial impacts on endometrial thickness.     

A prospective,double-blind,randomized, placebo-controlled clinical trial of bromocriptine in clomiphene-resistant patients with polycystic ovary syndrome and normal prolactin level

OBJECTIVE: To evaluate the effects of administration of bromocriptine combined with clomiphene citrate (CC) in CC-resistant patients with polycystic ovary syndrome (PCOS) and normal prolactin (PRL) level. DESIGN: Prospective double-blind, placebo-controlled, randomized. SETTING: Referral university hospitals. PATIENTS: One hundred women with PCOS and normal PRL who failed to ovulate with a routine protocol of CC. INTERVENTIONS: Treatment group received 150 mg of CC from day 5 to 9 and 7.5 mg bromocriptine continuously, with hCG 10,000 units on day 16 or 17. Control group received the same protocol of CC combined with placebo. MAIN OUTCOME MEASURES: Follicular development, hormonal changes, ovulation rate, pregnancy rate. RESULTS: Follicular development (follicular size greater than 15 mm) was observed in 12 (25.5%) and 8 (15.1%) women in the treatment and placebo group, respectively (p = 0.29). The serum prolactin level was within normal limits in all patients before treatment. After 3 and 6 months of treatment with bromocriptine, there was a significant decrease in serum level of prolactin (p = 0.000001). No significant differences were seen in ovulation, pregnancy rate, or serum levels of FSH, LH, DHEAS, and progesterone between treatment and placebo groups after treatment. CONCLUSIONS: The only significant effect of long-term bromocriptine therapy in CC-resistant women with PCOS was to lower the serum PRL concentration. It is also concluded that 10%-15% of patients with PCOS experienced occasional ovulatory cycles and pregnancy whether or not they were on treatment.