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.     

Use of dexamethasone and clomiphene citrate in the treatment of clomiphene citrate-resistant patients with polycystic ovary syndrome and normal dehydroepiandrosterone sulfate levels: a prospective,double-blind,placebo-controlled trial

OBJECTIVE: To evaluate the effects of short-course administration of dexamethasone (DEX) combined with clomiphene citrate (CC) in CC-resistant patients with polycystic ovary syndrome (PCOS) and normal DHEAS levels. DESIGN: Prospective, double-blind, placebo-controlled, randomized study. SETTING: Referral university hospitals. PATIENT(S): Two hundred thirty women with PCOS and normal DHEAS who failed to ovulate after a routine protocol of CC. INTERVENTION(S): The treatment group received 200 mg of CC from day 5 to day 9 and 2 mg of DEX from day 5 to day 14 of the menstrual cycle. The control group received the same protocol of CC combined with placebo. MAIN OUTCOME MEASURE(S): Follicular development, hormonal status, ovulation rate, pregnancy rate. RESULT(S): Mean follicular diameters were 18.4124 +/- 2.4314 mm and 13.8585 +/- 2.0722 mm for the treatment and control groups, respectively. Eighty-eight percent of the treatment group and 20% of the control group had evidence of ovulation. The difference in the cumulative pregnancy rate in the treatment and control groups was statistically significant. CONCLUSION(S): Hormonal levels, follicular development, and cumulative pregnancy rates improved with the addition of DEX to CC in CC-resistant patients with PCOS and normal DHEAS. This regimen is recommended before any gonadotropin therapy or surgical intervention.     

Clomiphene citrate plus tamoxifen versus laparoscopic ovarian drilling in women with clomiphene-resistant polycystic ovary syndrome

Objective

To compare the efficacy of clomiphene citrate (CC) plus tamoxifen with that of laparoscopic ovarian drilling in clomiphene-resistant women with polycystic ovary syndrome (PCOS).

Method

We randomly allocated 150 women with CC-resistant PCOS to a combined medication group (group 1) or a laparoscopic surgery group (group 2). The primary outcome was the live birth rate in each group; secondary outcomes were the rates of ovulation, clinical pregnancy and miscarriage.

Results

There were no significant differences between the groups regarding rates of ovulation (81.3% vs 85.3%), pregnancy (53.3% vs 50.7%), or live births (49.3% vs 44.0%), but the mean endometrium thickness was significantly greater on the day of human chorionic gonadotropin administration in group 1 (P < 0.001).

Conclusion

Clomiphene citrate plus tamoxifen was as effective as laparoscopic ovarian drilling in promoting ovulation and pregnancy.     

Clomiphene citrate combined with metformin versus letrozole for induction of ovulation in clomiphene-resistant polycystic ovary syndrome: a randomized clinical trial

A total of 202 patients with clomiphene citrate (CC) -resistant polycystic ovary syndrome (PCOS) were randomly allocated into two arms of induction of ovulation; the first group (n?=?102) received CC 100?mg and metformin 500?mg while the second group (n?=?100) received letrozole 2.5?mg with ovulation rate, clinical pregnancy rate, adverse effects, and acceptability were assessed. Patients in the letrozole arm experienced higher rate of ovulation (82% versus 43.1%, p?p?p?p?p?p?p?相似文献   

Clomiphene citrate plus cabergoline versus clomiphene citrate for induction of ovulation in infertile euprolactinemic patients with polycystic ovary syndrome: A randomized clinical trial

Objective

To compare the effect of adjunctive use of cabergoline with clomiphene citrate (CC) in infertile polycystic ovarian syndrome (PCOS) patients with normal prolactin level.

增生期血清泌乳素水平与多囊卵巢综合征不孕的关系探讨

研究多囊卵巢综合征不孕与增生期血清泌素的关系。方法采用放射免疫测定法测定血清泌乳素质量浓度。结果ＰＣＯＳ不孕组和非ＰＣＯＳ不孕组的增生期血清泌乳素水平无明显差异,但两组与生育组比较,血清乳素水平明显增高。     

Metformin versus laparoscopic unilateral ovarian drilling in clomiphene resistant women with polycystic ovary syndrome

ObjectivesTo compare the hormonal-metabolic profiles and reproductive outcomes between women receiving metformin and women undergoing unilateral ovarian drilling in clomiphene citrate(CC) resistant patients with polycystic ovary syndrome (PCOS)DesignNon randomized controlled trial.SettingObstetrics and Gynecology department, Faculty of medicine, Zagazig University, Egypt.MethodsA total of 120 patients were divided into group 1(n=58) who received metformin therapy and group 2 (n=62) who underwent unilateral ovarian drilling. Hormonal-metabolic profiles changes after treatment were reported and reproductive outcomes were compared between both groups.Main outcomeFSH and LH were reduced significantly in unilateral drilling group (P=<0.001and 0.001), while there was significant improvement in testosterone level , fasting insulin, fasting glucose to insulin ratio and homeostasis model assessment index in metformin therapy group. Pregnancy and ovulation rates were higher after unilateral drilling with significant difference (P=0.048 and 0.004). No significant difference in early miscarriage rate between both groups (P=0.51).ConclusionUnilateral LOD was associated with greater ovulation and pregnancy rates than metformin in women with PCOS who did not conceive with CC.     

Comparison of clomiphene citrate and letrozole for ovulation induction in women with polycystic ovary syndrome: a prospective randomized trial

To compare the therapeutic efficacy of clomiphene citrate (CC) and letrozole (LE) on ovulation, pregnancy, and live birth in women with polycystic ovary syndrome (PCOS); and to ensure if LE can replace CC as the first-line therapy for ovulation induction in these women. This is a prospectively, randomized, controlled trial in the tertiary hospital. Two-hundred and sixty-eight anovulatory PCOS patients were treated by CC or CC plus metformin and LE or LE plus metformin for three continuous cycles or conception; their ovulation rates, pregnancy rates, and live birth rates were calculated and compared. No significant difference was noted among the four groups regarding to the baseline data of clinical manifestations, serum sex hormone levels, and serum insulin levels. A total of 240 patients completed the therapies. The ovulation rate was significantly higher in the group LE than the group CC; however, no significant difference was noted between the groups LE and CC, CC, and CC?+?MET, or LE and LE?+?MET in the pregnancy rate, abortion rate, and live birth rate. No birth defect was found in the total of 63 newborns. CC regimen was still recommended to be the first-line therapy of ovulation induction for PCOS.     

Systematic review and meta-analysis of letrozole and clomiphene citrate in polycystic ovary syndrome

This study aims to systematically evaluate the clinical efficacy and safety of both clomiphene citrate (CC) and letrozole, and to examine if the efficacy of letrozole is superior to CC in women with polycystic ovary syndrome (PCOS).Major databases were searched for eligible randomised controlled trials (RCTs). The methodological quality of the included studies was assessed by two independent reviewers. Meta-analysis was performed using random-effect model to account for the high levels of heterogeneity. Overall, ten eligible RCTs involving 1905 women were included. Letrozole was associated with significantly higher ovulation rate (relative risk (RR) 1.20; 95% CI 1.03–1.40; P?=?0.02); clinical pregnancy rate (RR 1.48; 95% Cl 1.12–1.94; P?=?0.005) and endometrial thickness (standardized mean difference (SMD) 2.31; 95% Cl 0.85–3.76; P?=?0.002). There was no evidence of a difference between the treatment groups in the rate of miscarriage, number of mature follicles and multiple pregnancy rates. The result suggests that letrozole is a superior ovulation induction agent for women with PCOS as it is associated with higher ovulation and clinical pregnancy rates with no obvious increased side effects. However, this conclusion should be considered with a slight caution in that the quality of the evidence could have improved if more recent studies on the subject were available to be included in the review.     

Short-term metformin treatment for clomiphene citrate-resistant women with polycystic ovary syndrome

Objective

To evaluate the effect of a short-course pretreatment with metformin on hyperandrogenism, insulin resistance, cervical scores, and pregnancy rates in women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS).

Methods

Thirty-seven women with CC-resistant PCOS were randomly assigned to be pretreated with 500 mg of metformin or placebo 3 times per day for 2 cycles, and 100 mg of CC was given on days 5 through 9 of the second cycle in both groups. Luteinizing hormone (LH), follicle stimulating hormone (FSH), dehydroepiandrostendione sulfate (DHEAS), total testosterone (T), glucose, and insulin levels were measured at baseline and after the first cycle, as well as body mass index (BMI), cervical score, and pregnancy rate.

Results

After 1 cycle, BMI, total T level, and percentage of participants with insulin resistance were significantly decreased in the metformin group, without any significant decrease in LH, FSH, and DHEAS levels; and in the second cycle, CC treatment resulted in a higher ovulation rate and a thicker endometrium in the metformin group. The pregnancy rate and cervical scores were also higher in that group.

Conclusion

The short-course pretreatment with metformin decreased hyperandrogenism and insulin resistance and improved cervical sores, ovulation rate, and pregnancy rate among women with CC-resistant PCOS.     

难治性多囊卵巢综合征的治疗策略及结局

目的 探讨对持续无排卵的多囊卵巢综合征（ＰＣＯＳ）患者使用诱发排卵的治疗方案及其治疗效果。方法 收集氯米芬抵抗的ＰＣＯＳ患者５９例,共８１个治疗周期,分为３组：（１）促卵泡激素（ＦＳＨ）组,４９个治疗周期;（２）ＦＳＨ＋促性腺激素释放激素（ＧｎＲＨ）泵组,１３个周期;（３）常规体外受精（ＩＶＦ）组,１９个周期。前两组给予前期降黄体生成素（ＬＨ）及睾酮（Ｔ）治疗。观察用促排或超排治疗后雌二醇（Ｅ２）     

A randomized controlled trial of laparoscopic ovarian diathermy versus gonadotropin therapy for women with clomiphene citrate-resistant polycystic ovary syndrome

OBJECTIVE: To compare the effectiveness of laparoscopic ovarian diathermy with gonadotropin ovulation induction for women with clomiphene citrate-resistant polycystic ovary syndrome. DESIGN: Randomized controlled trial. SETTING: A tertiary referral fertility clinic. PATIENT(S): Women with anovulatory infertility secondary to clomiphene-resistant polycystic ovary syndrome. Inclusion criteria were age of <39 years, body mass index of <35 kg/m(2), failure to ovulate with 150 mg of clomiphene citrate for 5 days in the early follicular phase, >12 months of infertility, and no other causes of infertility. INTERVENTION(S): Laparoscopic ovarian diathermy versus three cycles of urinary or recombinant gonadotropins. MAIN OUTCOME MEASURE(S): Cumulative pregnancy and miscarriage rates. RESULT(S): Cumulative pregnancy rates were 28% at 6 months for laparoscopic ovarian diathermy and 33% for three cycles of ovulation induction with gonadotropins. There were three miscarriages in each group. Women in the laparoscopic ovarian diathermy arm of the study had four additional spontaneous pregnancies 6 to 12 months after surgery. CONCLUSION(S): There was no statistically significant difference in pregnancy or miscarriage rates during the 6-month follow-up period or the three cycles. Laparoscopic ovarian diathermy is a safe and effective alternative to ovulation induction with gonadotropins.     

A randomized, 48-week, placebo-controlled trial of intensive lifestyle modification and/or metformin therapy in overweight women with polycystic ovary syndrome: a pilot study

OBJECTIVE: To obtain data from a pilot randomized trial on the effect of metformin therapy and lifestyle modification on ovulation and androgen concentrations in women with polycystic ovary syndrome (PCOS). DESIGN: Prospective, randomized, placebo-controlled pilot trial. SETTING: Academic medical center. PATIENT(S): Thirty-eight overweight or obese women with PCOS. INTERVENTION(S): All subjects were randomized to one of four 48-week interventions: metformin 850 mg two times per day, lifestyle modification plus metformin 850 mg two times per day, lifestyle modification plus placebo, or placebo alone. MAIN OUTCOME MEASURE(S): Recruitment, dropout, and compliance with a long-term lifestyle intervention in PCOS; preliminary estimates of treatment effect on ovulation, as measured by weekly urinary pregnanediol glucuronide, and on total T and free androgen index. RESULT(S): It was necessary to screen seven women to have one subject randomized. The dropout rate was 39%, with the majority of dropouts occurring within the first 24 weeks. Mean body mass index was >39 mg/kg(2). Modest weight reduction was found in all treatment groups, with the most significant reduction occurring with the combination of metformin and lifestyle intervention. Significant androgen reduction occurred in the combination group only. Ovulation rates did not differ significantly between groups. However, when data were analyzed by presence or absence of weight reduction in subjects, independent of treatment group, the estimated odds ratio for weight loss was 9.0 (95% confidence interval 1.2-64.7) with respect to regular ovulation. If weight loss occurred during metformin therapy, the odds ratio for regular ovulation was 16.2 (95% confidence interval 4.4-60.2). CONCLUSION(S): Key methodologic issues for a large-scale, randomized trial of lifestyle intervention in PCOS include minimizing early dropout from the lifestyle intervention and including a range of body mass index that is not skewed toward severe obesity. Weight reduction might play the most significant role in restoration of ovulation in obese women with PCOS.