hCG administration offers no outcome benefit over spontaneous ovulation in anovulatory women treated with clomiphene citrate. A prospective randomized trial comparing clomiphene citrate with tamoxifen citrate for ovulation induction. Reproductive outcome after letrozole versus laparoscopic ovarian drilling for clomiphene-resistant 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. Effects of metformin on ovulation rate, hormonal and metabolic profiles in women with clomiphene-resistant polycystic ovaries: a randomized, double-blinded placebo-controlled trial. A randomized controlled trial of laparoscopic ovarian diathermy versus gonadotropin therapy for women with clomiphene citrate-resistant polycystic ovary syndrome. 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. A clomiphene citrate and tamoxifen citrate combination therapy: a novel therapy for ovulation induction. 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. Does metformin induce ovulation in normoandrogenic anovulatory women? Combined metformin and clomiphene citrate versus laparoscopic ovarian diathermy for ovulation induction in clomiphene-resistant women with polycystic ovary syndrome: a randomized controlled trial.
This randomized controlled trial compared spontaneous ovulation versus hCG-triggered ovulation in anovulatory women treated with clomiphene citrate. No statistically significant differences were observed between the two groups in terms of ovulation and pregnancy rates. To compare the rates of ovulation and pregnancy after tamoxifen citrate (TMX) or clomiphene citrate (CC) among anovulatory women with infertility.
                Prospective randomized trial.
                Infertility clinic in a university teaching hospital.
                Eighty-six anovulatory women under 40 years of age undergoing ovulation induction.
                The women were assigned randomly to receive either TMX or CC on cycle days 5-9.
                Rates of ovulation and pregnancy for the two treatment modalities.
                The overall rate of ovulation in the TMX group was 50 of 113 (44.2%) and in the CC group, 41 of 91 (45.1%). There were 10 pregnancies in the TMX group and 6 pregnancies in the CC group. The cycle fecundity per ovulatory cycle was 20.0% in the TMX group and 14.6% in the CC group.
                The overall rate of ovulation and pregnancy were similar with TMX and CC. TMX is a suitable alternative agent to CC in the management of anovulatory infertility. 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 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. Metformin, an insulin-sensitizing agent, has been used successfully as the first-line drug to induce ovulation in women with polycystic ovary syndrome. There are, however, very few studies evaluating metformin treatment in women with clomiphene citrate (CC)-resistant polycystic ovaries (PCO).
                Twenty infertile Chinese women aged <40 years, who had ultrasound features of PCO and remained anovulatory on CC, were randomized by computer using the sealed envelope method to receive placebo or metformin 500 mg three times a day for 3 months. Hormonal and metabolic profiles were determined before the therapy and were repeated after 3 months for women who failed to become pregnant within this period. Clomiphene was then added for one cycle to those women who did not ovulate after taking placebo or metformin alone.
                The median ovulation rate in the placebo group was 0% (range: 0--50%) after placebo only and 6.9% (range: 0--50%) after placebo and CC, whereas the corresponding rates in the metformin group were 0% (range: 0--22%) and 0% (range: 0--22%) respectively. There was no improvement in the ovulation rate despite a significant reduction of body mass index, serum testosterone and fasting leptin concentrations in the metformin group.
                Metformin treatment may result in successful ovulation only in certain subgroups of these women. To compare the effectiveness of laparoscopic ovarian diathermy with gonadotropin ovulation induction for women with clomiphene citrate-resistant polycystic ovary syndrome.
                Randomized controlled trial.
                A tertiary referral fertility clinic.
                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.
                Laparoscopic ovarian diathermy versus three cycles of urinary or recombinant gonadotropins.
                Cumulative pregnancy and miscarriage rates.
                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.
                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. 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 assess the efficacy of a clomiphene citrate (CC) and tamoxifen citrate (CC/tamoxifen) combination therapy in ovulation induction by comparing with a CC alone therapy.
                A randomized cross-over study with CC alone and CC/tamoxifen combination therapies for 20 normoprolactinemic anovulatory women. Randomly selected 10 of the 20 women (group A) underwent a CC alone therapy (100 mg CC during cycle days 5 to 9) for the initial three consecutive treatment cycles and a CC/tamoxifen combination therapy (50 mg CC and 20 mg tamoxifen during cycle days 5 to 9) for the subsequent three consecutive treatment cycles. The remaining 10 (group B) were treated similarly but with the inverse sequence. Ovulation was documented when a high BBT phase persisted for 11 days or more, when midluteal serum P levels exceeded 7 ng/mL (22.3 nmol/L), or when pregnancy ensued.
                The rates of ovulatory/treated, pregnant/treated, and pregnant/ovulatory cycles were 42 of 56 (75.0%), 3 of 47 (6.4%), and 3 of 35 (8.6%) for CC/tamoxifen, respectively. Those were 25 of 57 (43.9%), 1 of 48 (2.1%), and 1 of 21 (4.8%) for CC, respectively. Clomiphene citrate/tamoxifen was more effective in ovulation induction than CC. All the pregnancies were normal and single. None of the treatments was accompanied by any remarkable side effects.
                Clomiphene citrate/tamoxifen is a novel treatment modality of ovulation induction with high efficacy. 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. This study was undertaken to evaluate the efficacy of metformin in women with anovulation who do not have evidence for hyperandrogenism and classic polycystic ovary syndrome.
                A randomized trial of metformin (1500 mg daily) and placebo in 24 anovulatory women was undertaken for 3 months. Assessments of changes in hormone levels and insulin sensitivity were carried out. Abnormal hormonal values were defined by levels exceeding the range in normal ovulatory controls.
                Anovulatory women had normal androgen levels and luteinizing hormone but had higher serum insulin and lower insulin sensitivity compared with controls. Over 3 months, there were 16 ovulatory cycles with metformin and only 4 with placebo ( P < .05). Success of ovulation did not correlate with changes in androgen, insulin, or insulin sensitivity parameters.
                Metformin may be useful for inducing ovulation in anovulatory women who do not have hyperandrogenism. This effect may be independent of a lowering of androgen or insulin levels. 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.
There is inadequate evidence to recommend or refute the use of urinary hCG, as an ovulation trigger, in anovulatory women being treated with clomiphene citrate. We did not find trials evaluating the use of ovulation triggers in anovulatory women, being treated with other ovulation inducing agents.