Randomized controlled trial comparing laparoscopic ovarian diathermy with clomiphene citrate as a first-line method of ovulation induction in women with polycystic ovary syndrome. A prospective randomized trial comparing the clinical and endocrinological outcome with rosiglitazone versus laparoscopic ovarian drilling in patients with polycystic ovarian disease resistant to ovulation induction with clomiphene citrate. Combined metformin and clomiphene citrate versus laparoscopic ovarian diathermy for ovulation induction in clomiphene-resistant women with polycystic ovary syndrome: a randomized controlled trial. Letrozole versus laparoscopic ovarian diathermy for ovulation induction in clomiphene-resistant women with polycystic ovary syndrome: a randomized controlled trial. Prospective parallel randomized, double-blind, double-dummy controlled clinical trial comparing clomiphene citrate and metformin as the first-line treatment for ovulation induction in nonobese anovulatory women with polycystic ovary syndrome. Reproductive outcome after letrozole versus laparoscopic ovarian drilling for clomiphene-resistant polycystic ovary syndrome. Clomiphene citrate plus tamoxifen versus laparoscopic ovarian drilling in women with clomiphene-resistant polycystic ovary syndrome. 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. Comparison of metformin treatment and laparoscopic ovarian diathermy in patients with polycystic ovary syndrome. Metformin increases the ovulatory rate and pregnancy rate from clomiphene citrate in patients with polycystic ovary syndrome who are resistant to clomiphene citrate alone. 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. Ultra-short metformin pretreatment for clomiphene citrate-resistant polycystic ovary syndrome. PCOSMIC: a multi-centre randomized trial in women with PolyCystic Ovary Syndrome evaluating Metformin for Infertility with Clomiphene. Clomiphene citrate and dexamethazone in treatment of clomiphene citrate-resistant polycystic ovary syndrome: a prospective placebo-controlled study. A prospective, double-blind, randomized, placebo-controlled clinical trial of bromocriptine in clomiphene-resistant patients with polycystic ovary syndrome and normal prolactin level.
Laparoscopic ovarian diathermy (LOD) is currently accepted as a successful second-line treatment for ovulation induction (OI) in clomiphene citrate (CC)-resistant women with polycystic ovary syndrome (PCOS). The aim of this study was to test the hypothesis that LOD may be superior to CC as a first-line treatment.
                The study included 72 anovulatory women with PCOS who were randomized to LOD (n = 36) or CC (n = 36). Women who remained anovulatory after LOD were offered CC. Similarly, women receiving CC who failed to ovulate or conceive were offered LOD. Pregnancy rates were compared between the two groups using chi(2) and odds ratio with 95% confidence interval (OR, 95% CI).
                After randomization, six women conceived before starting treatment and another patient postponed treatment. The remaining 65 women received the treatment (33 underwent LOD and 32 received CC). After the primary treatment, more pregnancies (44%) occurred in women receiving CC than in those undergoing LOD (27%), although the difference did not reach statistical significance [P = 0.13, OR 2.1 (0.7 - 5.8)]. After adding the second treatment, the pregnancy rate was still higher, but to a less extent, in the CC group [63% versus 52%, P = 0.2, OR 1.6 (0.6 - 4.2)].
                LOD is not superior to CC as a first-line method of OI in women with PCOS. The trial is registered with ClinicalTrials.gov with an identifier number NCT00220545. Rosiglitazone, an insulin sensitizing agent is used currently in women with clomiphene citrate (CC) resistant polycystic ovarian syndrome (PCOS). Our study proposed to compare the efficacy of rosiglitazone and CC with laparoscopic ovarian drilling (LOD) and CC in terms of biochemical effects, ovulation rate and pregnancy rate in patients of PCOS resistant to CC.
                This prospective randomised trial included 43 patients of PCOS resistant to CC. Twenty-two women were assigned to the rosiglitazone (4 mg twice daily) and CC group and other 21 patients underwent unilateral LOD and then received CC and multivitamins. The treatment continued for six cycles in both the groups. The biochemical response, ovulation rate and pregnancy rate over a follow up period of 6 months were compared.
                Treatment with rosiglitazone and CC or LOD and CC resulted in increased ovulation (80.8 vs. 81.5%) and pregnancy (50 vs. 42.8%), respectively. There was no statistical difference between the two groups in terms of biochemical response, ovulation rate and pregnancy rate.
                To avoid the risk of adverse effects of LOD preference may be given to the use of rosiglitazone and CC therapy in patients of PCOS resistant to CC. To compare the effect of combined metformin and clomiphene citrate (CC) with laparoscopic ovarian diathermy (LOD) meant for ovulation induction in CC-resistant women with polycystic ovary syndrome (PCOS).
                Two-hundred and eighty-two anovulatory women with CC-resistant PCOS were selected in this randomized controlled trial. Patients (n = 138) received combined metformin-CC for up to six cycles or underwent LOD (n = 144) with six months follow up. The outcome measures were: ovulation rate, midcycle endometrial thickness, pregnancy and miscarriage rates.
                Ovulation occurred in 386/576 cycles (67%) in the combined metformin-CC group and 381/558 cycles (68.2%) in LOD group without a significant difference between the groups. Resumption of regular menstruation was similar in both groups. A significant increase in midcycle endometrial thickness was observed in the combined metformin-CC group (9.2 ± 1.2 mm vs 7.6 ± 1.1 mm) (P < 0.05). The pregnancy rate was similar in both groups (15.4% vs 17%), and there were no statistically significant differences regarding the miscarriage rate between both groups. Four twin pregnancies occurred in the metformin-CC group. No ovarian hyperstimulation occurred in either group.
                Combined metformin-CC and LOD are equally effective for inducing ovulation and achieving pregnancy in CC-resistant PCOS patients.
                © 2010 The Authors. Journal of Obstetrics and Gynaecology Research © 2010 Japan Society of Obstetrics and Gynecology. To compare the effect of letrozole with laparoscopic ovarian diathermy (LOD) for ovulation induction in clomiphene citrate (CC) resistant women with polycystic ovary syndrome (PCOS).
                Two hundred and sixty anovulatory women with CC-resistant PCOS were selected in this randomized controlled trial. Group A (n = 128) received 2.5 mg letrozole daily for 5 days for up to six cycles. Group B (n = 132) underwent LOD with 6 months follow-up. Outcome measures were ovulation rate, midcycle endometrial thickness, pregnancy, miscarriage and live birth rates.
                Ovulation occurred in 335/512 cycles (65.4%) in letrozole group and 364/525 cycles (69.3%) in LOD group without significant difference between both groups. Resumption of regular menstruation was similar in both treatment groups. A significant increase in midcycle endometrial thickness was observed in letrozole group (8.8 ± 1.1 mm vs. 7.9 ± 1.2 mm) (P < 0.05). Pregnancy rate was similar in both groups (15.6 vs. 17.5%). There were no statistical significant differences as regards miscarriage and live birth rates between both groups. No multiple pregnancy or ovarian hyperstimulation occurred in either group.
                Letrozole and LOD are equally effective for inducing ovulation and achieving pregnancy in CC-resistant PCOS patients. Although metformin has been shown to be effective in the treatment of anovulation in women with polycystic ovary syndrome (PCOS), clomiphene citrate (CC) is still considered to be the first-line drug to induce ovulation in these patients.
                The goal of this study was to compare the effectiveness of metformin and CC administration as a first-line treatment in anovulatory women with PCOS.
                We describe a prospective parallel randomized, double-blind, double-dummy controlled clinical trial.
                The study was conducted at the University "Magna Graecia" of Catanzaro, Catanzaro, Italy.
                One hundred nonobese primary infertile anovulatory women with PCOS participated.
                We administered metformin cloridrate (850 mg twice daily) plus placebo (group A) or placebo plus CC (150 mg for 5 d from the third day of a progesterone withdrawal bleeding) (group B) for 6 months each.
                The main outcome measures were ovulation, pregnancy, abortion, and live-birth rates.
                The subjects of groups A (n = 45) and B (n = 47) were studied for a total of 205 and 221 cycles, respectively. The ovulation rate was not statistically different between either treatment group (62.9 vs. 67.0%, P = 0.38), whereas the pregnancy rate was significantly higher in group A than group B (15.1 vs. 7.2%, P = 0.009). The difference found between groups A and B regarding the abortion rate was significant (9.7 vs. 37.5%, P = 0.045), whereas a positive trend was observed for the live-birth rate (83.9 vs. 56.3%, P = 0.07). The cumulative pregnancy rate was significantly higher in group A than group B (68.9 vs. 34.0%, P < 0.001).
                Six-month metformin administration is significantly more effective than six-cycle CC treatment in improving fertility in anovulatory nonobese PCOS women. To compare the clinical outcomes of letrozole and laparoscopic ovarian drilling (LOD) in patients with clomiphene-citrate-resistant polycystic ovary syndrome (PCOS).
                In the present prospective randomized trial, 140 women with clomiphene-citrate-resistant PCOS were randomly allocated to receive 5mg letrozole from day 3 to day 7 of menses for 6 consecutive cycles, or to undergo LOD. When a leading follicle of at least 18 mm was present, ovulation was triggered with human chorionic gonadotropin (hCG). The 6-month rates of ovulation, pregnancy, abortion, and live births were evaluated.
                The groups were similar with regard to baseline clinical characteristics and hormonal profiles. The ovulation rate was significantly higher in the letrozole group than in the LOD group (59.0% versus 47.5%). On the days of the hCG injection, women in the letrozole group had a significantly thicker endometrium than those in the LOD group (P<0.0001). Women receiving letrozole had a higher pregnancy rate (35.7% versus 28.6%) and a lower rate of spontaneous abortion (8.0% versus 20.0%, respectively), but these differences were not statistically significant.
                Letrozole seems to be a suitable second-line ovulation-inducing alternative to LOD in women with PCOS who do not conceive with clomiphene citrate.
                Copyright © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. 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).
                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.
                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).
                Clomiphene citrate plus tamoxifen was as effective as laparoscopic ovarian drilling in promoting ovulation and pregnancy. 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. To compare hormone levels and clinical outcomes in patients with polycystic ovary syndrome (PCOS) after metformin therapy or laparoscopic ovarian diathermy (LOD) at 6 months follow-up.
                A randomized trial was conducted in 126 patients with PCOS who had a history of infertility for at least 1 year and resistance to clomiphene citrate (CC). Patients (n=63) received metformin treatment or underwent LOD (n=63).
                Levels of follicle-stimulating hormone did not change in either group after the intervention (P>0.05). Serum levels of testosterone (P<0.001) and luteinizing hormone (P<0.001) were significantly lower after the treatment in both groups. The proportion of women with regular menstrual cycles increased significantly to 35% (P<0.001) in the LOD group and to 49% (P<0.001) in metformin group compared with before the intervention. Although proportion was higher in the metformin group compared with the LOD group, the difference was not significant (odds ratio 1.81; 95% CI, 0.88-3.69, P=0.1). Hirsutism decreased significantly from 100% to 79.37% (P<0.001) in both groups.
                CC-resistant patients with PCOS were treated effectively by both metformin and LOD. To determine whether metformin treatment increases the ovulation and pregnancy rates in response to clomiphene citrate (CC) in women who are resistant to CC alone.
                Randomized, double-blind, placebo-controlled trial.
                Multicenter environment.
                Anovulatory women with the polycystic ovary syndrome (PCOS) who were resistant to CC.
                Participants received placebo or metformin, 500 mg three times daily, for 7 weeks. Information on reproductive steroids, gonadotropins, and oral glucose tolerance testing was obtained at baseline and after treatment. Metformin or placebo was continued and CC treatment was begun at 50 mg daily for 5 days. Serum P level > or =4 ng/mL was considered to indicate ovulation. With ovulation, the daily CC dose was not changed, but with anovulation it was increased by 50 mg for the next cycle. Patients completed the study when they had had six ovulatory cycles, became pregnant, or experienced anovulation while receiving 150 mg of CC.
                Ovulation and pregnancy rates.
                In the metformin and placebo groups, 9 of 12 participants (75%) and 4 of 15 participants (27%) ovulated, and 6 of 11 participants (55%) and 1 of 14 participants (7%) conceived, respectively. Comparisons between the groups were significant.
                In anovulatory women with PCOS who are resistant to CC, metformin use significantly increased the ovulation rate and pregnancy rate from CC treatment. 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.
                Prospective, double-blind, placebo-controlled, randomized study.
                Referral university hospitals.
                Two hundred thirty women with PCOS and normal DHEAS who failed to ovulate after a routine protocol of CC.
                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.
                Follicular development, hormonal status, ovulation rate, pregnancy rate.
                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.
                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. To evaluate the effect of ultra-short (12 days) metformin pretreatment in clomiphene-citrate (CC) resistant polycystic ovary syndrome (PCOS).
                Eighty women with CC-resistant PCOS were randomly allocated to metformin pretreatment or usual treatment. Forty women received 1500 mg metformin daily for 12 days, followed by clomiphene 150 mg daily for 5 days along with metformin. Forty women (control group) received the same dose of clomiphene but no metformin pretreatment.
                In the metformin group, 17 (42.5%) women ovulated, and 6 (15%) conceived. In the control group, 5 (12.5%) women ovulated but none conceived. Compared with the control group, the metformin group had significantly higher ovulation (P = 0.03) and pregnancy rates (P = 0.026).
                Twelve days of metformin pretreatment improves ovulation and pregnancy rates in women with CC-resistant PCOS. Ovulation induction treatment with metformin, either alone or in combination with clomiphene citrate (CC), remains controversial even though previous randomized trials have examined this.
                A double blinded multi-centre randomized trial was undertaken including 171 women with anovulatory or oligo-ovulatory polycystic ovary syndrome. Women with high body mass index (BMI) > 32 kg/m(2) received placebo ('standard care') or metformin; women with BMI < or = 32 kg/m(2) received CC ('standard care'), metformin or both. Treatment continued for 6 months or until pregnancy was confirmed. Primary outcomes were clinical pregnancy and live birth.
                For women with BMI > 32 kg/m(2), clinical pregnancy and live birth rates were 22% (7/32) and 16% (5/32) with metformin, 15% (5/33) and 6% (2/33) with placebo. For women with BMI < or = 32 kg/m(2), clinical pregnancy and live birth rates were 40% (14/35) and 29% (10/35) with metformin, 39% (14/36) and 36% (13/36) with CC, 54% (19/35) and 43% (15/35) with combination metformin plus CC.
                There is no evidence that adding metformin to 'standard care' is beneficial. Pregnancy and live birth rates are low in women with BMI > 32 kg/m(2) whatever treatment is used, with no evidence of benefit of metformin over placebo. For women with BMI < or = 32 kg/m(2) there is no evidence of significant differences in outcomes whether treated with metformin, CC or both. ClinicalTrials.gov number NCT00795808; trial protocol accepted for publication November 2005: Johnson, Aust N Z Journal Obstet Gynaecol 2006;46:141-145. The aim of this work was to evaluate the efficacy of adding dexamethazone (DEX) (high dose, short course) to clomiphene citrate (CC) in CC-resistant polycystic ovary syndrome (PCOS) with normal dehydroepiandrosterone sulphate (DHEAS) in induction of ovulation.
                Eighty infertile women with CC-resistant PCOS were randomly assigned into two groups. Group I: Clomiphene citrate 100 mg/day was given from day 3 to day 7 of the cycle and DEX 2 mg/day from day 3 to day 12 of the cycle. Group II: Same protocol of CC combined with placebo (folic acid tablets) was given from day 3 to day 12 of the cycle. The main outcome was ovulation. Secondary measures included number of follicles >18 mm endometrial thickness and pregnancy rate. Ovarian follicular response was monitored by transvaginal ultrasound. HCG 10,000 U was given when at least one follicle measured 18 mm, and timed intercourse was advised.
                There were no statistically significant differences between groups as regards age, duration of infertility, BMI, waist-hip ratio (WHR), menstrual pattern, hirsutism, serum DHEAS or day of HCG administration. The mean number of follicles>18 mm at the time of HCG administration and the mean endometrial thickness were significantly higher in the DEX group than in the placebo group (P<0.05). Similarly, there were significantly higher rates of ovulation (75 versus 15%) (P<0.001) and pregnancy (40 versus 5%) (P<0.05) in the DEX group. Dexamethazone was very well tolerated as no patients complained of any side effect. There was a significant difference between the responders and non-responders in the presence of oligomenorrhea, amenorrhea or hirsutism.
                Induction of ovulation by adding DEX (high dose, short course) to CC in CC-resistant PCOS with normal DHEAS is associated with no adverse anti-estrogenic effect on the endometrium and higher ovulation and pregnancy rates in a significant number of patients. Induction with DEX appears to be independent on age, period of infertility, BMI or WHR. 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.
                Prospective double-blind, placebo-controlled, randomized.
                Referral university hospitals.
                One hundred women with PCOS and normal PRL who failed to ovulate with a routine protocol of CC.
                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.
                Follicular development, hormonal changes, ovulation rate, pregnancy rate.
                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.
                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.
There was no evidence of a significant difference in rates of clinical pregnancy, live birth or miscarriage in women with clomiphene-resistant PCOS undergoing LOD compared to other medical treatments. The reduction in multiple pregnancy rates in women undergoing LOD makes this option attractive. However, there are ongoing concerns about the long-term effects of LOD on ovarian function.