Received Clomiphene Citrate Research Articles

The value of measuring anti-Mullerian hormone in women with anovulatory polycystic ovary syndrome undergoing laparoscopic ovarian diathermy

Anti-Müllerian hormone (AMH) has been implicated in the pathogenesis of polycystic ovary syndrome (PCOS). The aim of this study was to measure circulating AMH before laparoscopic ovarian diathermy (LOD) to evaluate its prognostic value for an ovulatory response and to investigate AMH changes after LOD to further explore the effects of LOD. This prospective study included anovulatory women with PCOS undergoing LOD (n = 29) or receiving clomiphene citrate (n = 18). Plasma AMH concentrations were measured before and 1 week after treatment. Further measurements of AMH were made at 3- and 6-month follow-up. The pretreatment median (range) plasma AMH concentrations were 6.1 (1.0-21.0) and 5.7 (1.3-9.5) ng/ml in women having LOD and clomiphene citrate treatment, respectively. Women who ovulated after LOD (n = 24) had a significantly (P = 0.032) lower pre-operative AMH [5.6 (1.0-21.0) ng/ml] compared with the non-responders [9.0 (6.1-17.1) ng/ml]. Using receiver-operating characteristic curve analysis, AMH was found to be a useful predictor of no ovulation after LOD with area under the curve of 0.804 (P = 0.025). Using a cut-off of 7.7 ng/ml, AMH had a sensitivity of 78% and a specificity of 76% in the prediction of no ovulation after LOD. For all patients (n = 47, clomiphene citrate or LOD), plasma AMH >or=7.7 ng/ml was associated with a reduced chance of ovulation after treatment (P = 0.004). Following LOD, the median AMH concentration significantly (P = 0.003) decreased to 4.7 (0.3-15.1) ng/ml and remained low at 3- and 6-month follow-up. Pretreatment circulating AMH level seems to be a good predictor of the ovarian response to LOD.

Adjuncts for ovarian stimulation: when do we adopt “orphan indications” for approved drugs?

Several drugs, shown to be safe for other uses, have proven to be highly effective adjuncts for ovarian stimulation. The authors evaluate these "orphan" indications and make recommendations so that more patients will benefit from their use.

Efficacy predictors for metformin and clomiphene citrate treatment in anovulatory infertile patients with polycystic ovary syndrome

To evaluate ovulation and pregnancy predictors in infertile polycystic ovary syndrome (PCOS) patients who received clomiphene citrate (CC) and metformin as first-line ovulation inductors. Prospective controlled study. Departments of Obstetrics and Gynecology, Universities Magna Graecia of Catanzaro and Federico II of Naples, Italy. Eighty infertile anovulatory PCOS patients allocated in two groups matched for body mass index (BMI) and age. Metformin (1700 mg/day for 6 months) or CC (50 mg/day, increasing doses up to 250 mg/day). Baseline clinical and biochemical parameters categorized according to interventions response. The BMI was statistically significantly lower in patients who ovulated under both treatments. Insulin sensitivity indexes were statistically significantly worse in patients who ovulated under metformin and statistically significantly better in patients who ovulated under CC. Androgen levels and free androgen index (FAI) were statistically significantly lower in ovulatory patients than in anovulatory ones who received CC. Age, BMI, infertility duration, and insulin sensitivity indexes were statistically significantly different between patients who achieved and those who did not achieve a pregnancy under both treatments. Androgens levels and FAI were statistically significantly lower in patients who achieved a pregnancy under CC. Insulin-resistant PCOS patients with low BMI are more likely to respond to metformin whereas CC treatment is more effective in less hyperandrogenic and insulin-resistant PCOS patients with low BMI.

Ovarian epithelial neoplasia after hormonal infertility treatment: long-term follow-up of a historical cohort in Sweden

To study the association between hormonal infertility treatment and ovarian neoplasia. Historical cohort study. Three university hospitals in Sweden. A total of 2,768 women assessed and treated for infertility and infertility-associated disorders between 1961 and 1975. Exposed women received clomiphene citrate and/or gonadotropins. Incidence of ovarian neoplasia. No overall excess risk of invasive ovarian cancer emerged compared with the general population. In women with gonadotropin treatment for non-ovulatory disorders, the risk was elevated (standardized incidence ratio [SIR] = 5.89; 95% confidence interval [CI] 1.91-13.75); four of the five cases reported hCG treatment only, rendering the biological plausibility uncertain. Multivariate analysis within the cohort indicated that treatment with gonadotropins only was associated with an increased risk of invasive cancer (relative risk = 5.28; 95% CI 1.70-16.47). For borderline tumors, a more than threefold overall increase of tumors (SIR = 3.61; 95% CI 1.45-7.44) was noted; women exposed to clomiphene because of ovulatory disorders showed the highest risk (SIR = 7.47; 95% CI 1.54-21.83). Our findings of increased risk of ovarian cancer after gonadotropins and of borderline tumors after clomiphene treatment need to be interpreted with caution. However, concern is raised, and further research on the long-term safety particularly of modern hormonal infertility treatment in IVF programs is warranted.

Comparison of clomiphene citrate, metformin, or the combination of both for first-line ovulation induction, achievement of pregnancy, and live birth in Asian women with polycystic ovary syndrome: a randomized controlled trial

To determine the first-line medication to be used in anovulatory patients with polycystic ovary syndrome (PCOS) for ovulation induction and pregnancy achievement. Randomized controlled trial. Infertility unit of a public hospital. One hundred fifteen newly diagnosed patients with PCOS based on ESHRE/ASRM criteria. These patients were assigned to three groups: group 1 (38 patients) received 500 mg of metformin three times a day; group 2 (39 patients) received clomiphene citrate (CC) at an incremental dose; group 3 (38 patients) received both medications. Rates of ovulation, pregnancy (PR), and live birth. The ovulation rate was 23.7% in the metformin group, 59% in the CC group, and 68.4% in the combination treatment group. This was translated into a similar PR and live birth rate, which were higher in the CC and combination groups compared to the metformin group (PR: 7.9%, 15.4%, and 21.1%; live birth rate: 7.9%, 15.4%, and 18.4% in metformin, CC, and combination treatment groups, respectively), although statistically the differences were not significant. There were no multiple pregnancies and the rate of spontaneous first trimester loss was similar to the general population. Clomiphene citrate should be the first-line treatment for ovulation induction in anovulatory patients with PCOS.

Adding phytoestrogens to clomiphene induction in unexplained infertility patients – a randomized trial

This study investigated the role of oral phytoestrogens in improving pregnancy rate and cycle outcomes with clomiphene citrate. Patients with unexplained infertility and recurrent clomiphene citrate induction failure, were randomly divided into two groups: group I ( n = 60) and group II ( n = 59). Both groups received clomiphene citrate 150 mg per day (days 3 to 7). Group I received additional oral phytoestrogen ( Cimicifuga racemosa) 120 mg/day from days 1 to 12. Human chorionic gonadotrophin (HCG) injection (10,000 IU i.m.) was given and timed intercourse was recommended when a leading follicle reached >17 mm and serum oestradiol exceeded 200 (pg/ml). There was a non-significant shortening of induction cycles in group I. Oestradiol and LH concentrations were higher in group I compared with group II. Endometrial thickness, serum progesterone and clinical pregnancy rate were significantly higher in group I (8.9 ± 1.4 mm versus 7.5 ± 1.3 mm, P < 0.001; 13.3 ± 3.1 ng/ml versus 9.3 ± 2.0 ng/ml, P < 0.01; 36.7% versus 13.6%, P < 0.01, respectively). It is concluded that adding C. racemosa rhizome dry extract to clomiphene citrate induction can improve the pregnancy rate and cycle outcomes in these couples.

Massive ovarian edema in pregnancy after ovulation induction using clomiphene citrate

Massive ovarian edema is a benign enlargement of the ovary caused by accumulation of fluid occurring mainly in young women. Most cases are thought to result from venous and lymphatic obstruction. We treated a 40-year-old multiparous pregnant woman with massive ovarian edema who had been received clomiphene citrate. She was admitted at 13th week of pregnancy for acute pelvic pain. Left oophorectomy was performed, and pathologic examination disclosed massive ovarian edema. Our report is the first case of massive ovarian edema with pregnancy after ovulation induction using clomiphene citrate.

THREE -DIMENSIONAL ULTRASOUND MONITORING THE UTERO-OVARIAN RESPONSES IN OF OVULATION INDUCTION IN POLYCYSTIC OVARY SYNDROME

Objective: 3D ultrasound will be used to monitor the response of controlled ovarian stimulation and determination ofuterine receptivity in patients of PCOS.Design : prospective study.Setting : Suez Canal University & Private clinicsMaterials and methods: This study was done for three successive menstrual cycles for each case, including 50 infertilepatients with PCOS. The patients had received clomiphene citrate (CC); Follicular growth was monitored by repeatedtrans-vaginal ultrasound. When lead follicle of >I8 mm in mean diameter was detected , at this stage 1) Bndomclrinlthickness was measured 2) Determine the presence or absence of three-line appearance of the endomeirium. 3) Presenceof myomeiiial contractions 4) Myomeiiial cchogeiiicity 5) Presence of cumulus oophorus 6) Presence of ccholiicenlspace in the endocervical canal. Then, 10000 u of hCG were given intramuscularly to induce ovulalion .Results : In three cycles respectively, pregnancy rate in patients showing triple appearance of the endomeirium ai ihctime of hCG administration was 70.6, 71.4, 91.7%, showing homogenous myomelrium 73.3. 91.7, 76.9%. showingmyomelrial contraciions 80.0, 84.6, 76.9%, showing Hie cumulus oophorus 76.5, 73.3, 90.9%, and showing ccholiicenlspace in the endocervical canal was 92.9. 73.3, 76.9%.Conclusion: Folliculomelry with 3D ultrasound offers good monitoring and helps in improving cycle fecundity. With3D folliculomelry. ii might be possible to lime the administration of hCG to coincide wilh optimal follicle maturity loithe release of the highest quality oocytes and optimal uterine receptivity.

Clinical significance of serum concentration of anti-Müllerian hormone in obese women with polycystic ovary syndrome

In the human ovary, expression of anti-Müllerian hormone (AMH) is detected primarily in granulosa cells of preantral and small antral follicles. The aim of this study was to compare serum AMH measurements in obese women with polycystic ovary syndrome (PCOS) with those in obese normo-ovulatory women and to evaluate the role of AMH as a predictor of ovulation induction by clomiphene citrate compared to FSH. Sixty-eight obese women with PCOS were compared to 17 normo-ovulatory obese women. All women had a body mass index greater than 30 kg/m 2. Women with PCOS received clomiphene citrate (150 mg/day) for 5 days starting from day 3 of cycle and were subdivided into responsive and non-responsive groups. There was a significant difference in AMH concentration between women with PCOS and the control group ( P < 0.05) and also between women with PCOS who responded to clomiphene citrate and those who did not ( P < 0.01). A value of 1.2 ng/ml AMH could be used to predict response to clomiphene citrate in obese women with PCOS (sensitivity 71%, specificity 65.7%). AMH production increases in women with PCOS compared to controls. AMH measurement could also be useful in the prediction of ovarian response to clomiphene citrate.

Comparison of clomiphene citrate, metformin, or the combination of both for first-line ovulation induction and achievement of pregnancy in 154 women with polycystic ovary syndrome

To determine which first-line medication is more effective in polycystic ovary syndrome (PCOS) patients for ovulation induction and pregnancy achievement and to verify whether any patient characteristic is associated with a better response to therapy. Observational comparative study. Fertility clinic. One hundred fifty-four infertile women with oligomenorrhea and hyperandrogenism. Group 1 (56 patients) received clomiphene citrate (CC) 50 mg from days 5-9 of the cycle. Group 2 (57 patients) received 500 mg of metformin 3 times a day. Group 3 (41 patients) received both medications. Ovulation and pregnancy. Patients receiving metformin alone had an increased ovulation rate compared with those receiving CC alone (75.4% vs. 50%). Patients on metformin had similar ovulation rates compared with those in the combination group (75.4% vs. 63.4%). Pregnancy rates were equivalent in the 3 groups. Response to metformin was independent of body weight and dose. Finally, nonsmoking predicted better ovulatory response overall as well as lower fasting glucose for CC and lower androgens for metformin. Metformin is better for ovulation induction than CC alone and equivalent for pregnancy achievement. We suggest that metformin can be used first for ovulation induction in patients with PCOS regardless of their weight and insulin levels because of its efficacy and known safety profile.

Neuroendocrine and reproductive aspects of adult male rats exposed neonatally to an antiestrogen

The present study was designed to investigate the effects of a single dose of an estrogen antagonist–clomiphene–during neonatal life, on later neuroendocrine system and reproductive performance. Immediately after birth, male pups received clomiphene citrate (s.c.). At adulthood, although testosterone levels and wet weights of reproductive organs were not altered, the treatment induced an increased number of spermatozoa and a delay in the transit time in the cauda epididymis. Additionally, there was impairment of sexual behavior evidenced by a delay in the latencies to the first mount and first intromission. Treated rats also showed decreased dopaminergic and serotonergic neurotransmissions in the hypothalamus and decreased dopaminergic neurotransmission in the striatum. The decreased dopaminergic activity could be related to the lower sexual motivation observed. These results indicate the necessity of preventing exposure to drugs that may impair sexual differentiation, which can compromise later mating success as well as the capacity to generate descendants.

Characteristics of baseline ovarian cysts in clomiphene citrate ovulation cycles

To evaluate the incidence and factors associated with ovarian cysts in infertile patients receiving clomiphene citrate (CC), we performed a retrospective cohort study involving 466 CC treatment cycles. Ovarian cysts are a common finding in patients presenting for CC, with approximately one in five patients having a baseline ovarian cyst >10 mm.

A novel protocol of ovulation induction with delayed gonadotropin-releasing hormone antagonist administration combined with high-dose recombinant follicle-stimulating hormone and clomiphene citrate for poor responders and women over 35 years

Objective To evaluate the efficacy of a novel protocol of ovulation induction for poor responders. Design Prospective, controlled, clinical study. Setting Research institute's reproductive unit. Patient(s) One hundred forty-five infertile women, aged 27–39 years, candidates for assisted reproductive techniques (ART). Intervention(s) Before undergoing ART, 85 patients received clomiphene citrate, high-dose recombinant human FSH, and a delayed, multidose GnRH antagonist, whereas 60 patients underwent a standard long protocol. Main outcome measure(s) Estradiol levels (pg/mL), cancellation rate, oocyte retrieval, embryo score, and fertilization and pregnancy rates. Result(s) Patients undergoing the study protocol obtained lower cancellation rates (4.7% vs. 34%) and higher E 2 levels (945.88 ± 173.2 pg/mL vs. 169.55 ± 45.07 pg/mL), oocyte retrieval (5.56 ± 1.13 vs. 3.36 ± 1.3), and pregnancy (22.2% vs. 15.3%) and implantation rates (13.5% vs. 7.6%) compared with those receiving the long protocol. Age negatively correlated with ovarian response in the latter, whereas the ovarian outcome results were comparable in younger (<35 yrs) and older (>35 yrs) women treated with the study protocol. Conclusion(s) The proposed protocol of ovulation induction can be usefully administered in poor responders as well as in aged woman, probably because the delayed administration of GnRH antagonist prevents its adverse effects on ovarian paracrine activity and on oocyte maturation.

Single dose nasal spray of gonadotropin releasing hormone (GnRH) agonist effectively matures oocytes for in vitro fertilization in an ovarian stimulation protocol using clomiphene citrate, gonadotropin, and GnRH antagonist

Objective: To investigate the efficacy of single dose nasal spray of gonadotropin releasing hormone (GnRH) agonist to mature oocytes for in vitro fertilization in a controlled ovarian stimulation protocol using clomiphene citrate, gonadotropin, and GnRH antagonist Design: Prospective, non-randomized clinical study at private clinics. Patients with repeated assisted reproduction technology failure were stimulated with clomiphene citrate, gonadotropin, and GnRH antagonist and allocated to either GnRH agonist nasal spray or intramuscular injection of human chorionic gonadotropin (HCG) for oocyte maturation. Outcome was measured by the number of oocytes retrieved and fertilized, and pregnancy rate. Materials and Methods: A total of 82 women who gave consent to receiving GnRH antagonist (Cetrorelix, Cetrotide, Serono, Switzerland) in their ovarian stimulation protocol were enrolled in the study. All patients received clomiphene citrate 100 mg/day from day 3 of menstrual period through day 7 and daily injection of 150–300 IU FSH/HMG commencing on day 4. Measurements of follicle diameter and serum E2 were initiated on menstrual day 8. When the leading follicle reached 14 mm in diameter, daily subcutaneous injection of 0.25 mg Cetrotide was initiated and continued until the day of GnRH agonist nasal spray or intramuscular HCG injection. When the leading follicle reached 20 mm in diameter, oocyte maturation was triggered by either 0.6 mg of single dose nasal spray of GnRH agonist (Buserelin, Sprecure, Aventis Pharma) (n = 40) or intramuscular injection of 10,000 IU HCG (n = 42). Oocyte retrieval was performed 36 hours after GnRH agonist/HCG administration. Only blastocysts were transferred on day 5 following oocyte retrieval. Pregnancy was defined as the visualization of gestational sac(s) at 6 weeks of gestation. Results: There was no difference in patient characteristics between the two groups. There was also no difference in the mean number of oocytes retrieved and those fertilized; 10.8 and 6.6, respectively, for the GnRH agonist group and 11.0 and 7.0 for the HCG group. Embryo transfer was possible in 38 and 39 cylces in the GnRH agonist group and HCG group, respectively, and an average of 2.2 and 2.3 blastocysts were transferred. A comparable pregnancy rate was achieved; 44.7% (17/38) for the GnRH agonist group and 53.8% (21/39) for the HCG group. Conclusion: Single dose nasal spray of GnRH agonist is as effective as intramuscular HCG injection to mature oocytes.

Clomiphene increases free testosterone levels in men with both secondary hypogonadism and erectile dysfunction: who does and does not benefit?

Secondary hypogonadism is more common than primary gonadal failure and is seen in chronic and acute illnesses. Although testosterone has a role in erections, its importance in erectile dysfunction (ED) has been controversial. Hypogonadism produced by functional suppression of pituitary gonadotropins has been shown to correct with clomiphene citrate, but with a modest effect on sexual function. We wondered if longer treatment would produce improved results. A total of 178 men with secondary hypogonadism and ED received clomiphene citrate for 4 months. Sexual function improved in 75%, with no change in 25%, while significant increases in luteinizing hormone (P<0.001) and free testosterone (P<0.001) occurred in all patients. Multivariable analysis showed that responses decreased significantly with aging (P<0.05). Decreased responses also occurred in men with diabetes, hypertension, coronary artery disease, and multiple medication use. Since these conditions are more prevalent with aging, chronic disease may be a more important determinant of sexual dysfunction. Men with anxiety-related disorders responded better to normalization of testosterone. Assessment of androgen status should be accomplished in all men with ED. For those with lower than normal age-matched levels of testosterone treatment directed at normalizing testosterone with clomiphene citrate is a viable alternative to giving androgen supplements.

Preeclampsia in Multiple Gestation

In Brief OBJECTIVE To estimate the relationship of assisted reproductive technologies and ovulation-inducing drugs with preeclampsia in multiple gestations. METHODS This historical cohort study was conducted on 528 multiple gestations from a Colorado health maintenance organization. Using univariate and logistic regression analysis, we determined if women who conceived a multiple gestation as a result of assisted conception were at a greater risk of preeclampsia than those who conceived spontaneously. RESULTS Between January 1994 and November 2000, there were 330 unassisted and 198 assisted multiple gestations. Sixty-nine multiple gestations followed assisted reproductive technologies (in vitro fertilization and gamete intrafallopian transfer). Human menopausal gonadotropins and clomiphene citrate were associated with 38 and 91 of the multiple gestations, respectively. Compared with unassisted multiple gestations, the relative risk of mild or severe preeclampsia among mothers who received assisted reproductive technologies was 2.7 (95% confidence interval [CI] 1.7, 4.7) and 4.8 (CI 1.9, 11.6), respectively. Adjusted for maternal age and parity, women who received assisted reproductive technologies were two times more likely to develop preeclampsia (odds ratio 2.1, CI 1.1, 4.1) compared with those who conceived spontaneously. The adjusted odds ratios of nulliparity and maternal age for preeclampsia were 2.1 (CI 1.3, 3.4) and 1.1 (CI 1, 1.1), respectively. Although the incidence of preeclampsia was greater in mothers who received clomiphene citrate and human menopausal gonadotropins, this association did not reach statistical significance at the P < .05 level. CONCLUSION Women who conceive multiple gestations through assisted reproductive technologies have a 2.1-fold higher risk of preeclampsia than those who conceive spontaneously. Adjusted for maternal age and parity, there is a 2.1-fold increased risk of preeclampsia among women conceiving multiple gestations through assisted reproductive technologies compared with spontaneously-conceived multiple gestations.

Preeclampsia in multiple gestation: the role of assisted reproductive technologies.

To estimate the relationship of assisted reproductive technologies and ovulation-inducing drugs with preeclampsia in multiple gestations. This historical cohort study was conducted on 528 multiple gestations from a Colorado health maintenance organization. Using univariate and logistic regression analysis, we determined if women who conceived a multiple gestation as a result of assisted conception were at a greater risk of preeclampsia than those who conceived spontaneously. Between January 1994 and November 2000, there were 330 unassisted and 198 assisted multiple gestations. Sixty-nine multiple gestations followed assisted reproductive technologies (in vitro fertilization and gamete intrafallopian transfer). Human menopausal gonadotropins and clomiphene citrate were associated with 38 and 91 of the multiple gestations, respectively. Compared with unassisted multiple gestations, the relative risk of mild or severe preeclampsia among mothers who received assisted reproductive technologies was 2.7 (95% confidence interval [CI] 1.7, 4.7) and 4.8 (CI 1.9, 11.6), respectively. Adjusted for maternal age and parity, women who received assisted reproductive technologies were two times more likely to develop preeclampsia (odds ratio 2.1, CI 1.1, 4.1) compared with those who conceived spontaneously. The adjusted odds ratios of nulliparity and maternal age for preeclampsia were 2.1 (CI 1.3, 3.4) and 1.1 (CI 1, 1.1), respectively. Although the incidence of preeclampsia was greater in mothers who received clomiphene citrate and human menopausal gonadotropins, this association did not reach statistical significance at the P <.05 level. Women who conceive multiple gestations through assisted reproductive technologies have a 2.1-fold higher risk of preeclampsia than those who conceive spontaneously.

Bilateral or Unilateral KTP Laser Ovarian Drilling in Polycystic Ovarian Disease

Bilateral or Unilateral KTP Laser Ovarian Drilling in Polycystic Ovarian Disease

Prospective, randomized, crossover study to evaluate the benefit of human chorionic gonadotropin–timed versus urinary luteinizing hormone–timed intrauterine inseminations in clomiphene citrate–stimulated treatment cycles

Objective: To compare two methods of timing IUI, urinary LH monitoring and transvaginal ultrasonography/hCG timing of ovulation, in patients receiving clomiphene citrate. Design: Prospective, randomized, crossover study. Setting: Yale University Reproductive Medicine Center. Patient(s): Infertile couples undergoing IUI because of unexplained infertility, anovulation, or male factor infertility. Intervention(s): Patients received clomiphene citrate on days 3–7 of the menstrual cycle and were randomized initially to one of two monitoring protocols. In protocol A, urinary LH monitoring was used to time IUI. Urinary LH levels were determined daily with the use of commercial kits, starting on day 10 of the cycle. When urinary LH was detected, IUIs were performed daily for the next 2 days. In protocol B, ultrasound monitoring of folliculogenesis was performed until a leading follicle of ≥18 mm was noted, at which time hCG (10,000 IU) was given intramuscularly and IUIs were performed daily for the next 2 days. If no pregnancy occurred, the couple crossed over to the alternate protocol for the next cycle and continued this alternating therapy for a total of four cycles. Main Outcome Measure(s): Pregnancy rate per cycle. Result(s): One hundred forty-one cycles were completed. In these cycles, six pregnancies occurred, for an overall pregnancy rate of 4.26% per cycle. The pregnancy rate with LH-timed IUI was 4.29% (3/70) and that with hCG-induced ovulation was 4.23% (3/71); the difference was not statistically significant. Conclusion(s): Timing IUI with the use of a relatively expensive and time-consuming method such as ultrasound monitoring of folliculogenesis and hCG induction of ovulation does not appear to produce an increased pregnancy rate over urinary LH monitoring of ovulation.

Octreotide is not useful for clomiphene citrate resistance in patients with polycystic ovary syndrome but may reduce the likelihood of ovarian hyperstimulation syndrome

Objective: To determine whether octreotide is effective for ovulation induction in patients with polycystic ovary syndrome (PCOS) and clomiphene citrate resistance or for reduction of the risk of ovarian hyperstimulation syndrome (OHSS) with gonadotropin therapy. Design: Prospective, double-blind, placebo-controlled, crossover trial. Setting: Private infertility practice. Patient(s): Twelve patients with PCOS undergoing therapy for infertility. Intervention(s): The patients were assigned randomly to receive either octreotide or placebo. Those with clomiphene citrate–resistant PCOS received clomiphene citrate, 150 mg. Patients at risk for the development of OHSS received urinary FSH for ovulation induction. Main Outcome Measure(s): Ovulation, pregnancy, the development of OHSS, and levels of fasting insulin, insulin-like growth factor 1, insulin-like growth factor binding proteins 1 and 3, testosterone, androstenedione, DHEAS, E 2, LH, and FSH. Result(s): Octreotide significantly reduced levels of fasting insulin, insulin-like growth factor 1, and LH in both clomiphene citrate– and urinary FSH–stimulated cycles. Levels of insulin-like growth factor binding protein 3 were increased. Two of six clomiphene citrate–stimulated cycles reached ovulation with the use of either octreotide or placebo. In urinary FSH–stimulated cycles, patients who received octreotide had significantly lower E 2 levels at the time of hCG administration and fewer mature follicles. No cases of OHSS occurred in either group. One pregnancy occurred in each group. Conclusion(s): Octreotide was no more effective than placebo for clomiphene citrate resistance in patients with PCOS, but it did reduce E 2 levels and follicle numbers when combined with urinary FSH. Thus, octreotide may reduce the incidence of OHSS in patients with PCOS.