The role of metformin in polycystic ovary syndrome: a systematic review.
Topic: Hormone Therapy

This meta-analysis evaluated the effectiveness of metformin in subfertile women with polycystic ovary syndrome (PCOS). Only randomized trials investigating the effectiveness of metformin and PCOS definition consistent with the Rotterdam consensus criteria, were eligible. Primary outcome was live birth rate. A literature search identified 27 trials. In therapy naïve women, we found no evidence of a difference in live birth rate when comparing metformin with clomifene citrate (CC) [relative risks (RR) 0.73; 95% confidence interval (CI) 0.51-1.1] or comparing metformin plus CC with CC (RR 1.0; 95% CI 0.82-1.3). In CC-resistant women, metformin plus CC led to higher live birth rates than CC alone (RR 6.4; 95% CI 1.2-35); metformin also led to higher live birth rates than laparoscopic ovarian drilling (LOD) (RR 1.6; 95% CI 1.1-2.5). We found no evidence for a positive effect of metformin on live birth when added to LOD (RR 1.3; 95% CI 0.39-4.0) or FSH (RR 1.6; 95% CI 0.95-2.9), or when co-administered in IVF (RR 1.5; 95% CI 0.92-2.5). In IVF, metformin led to fewer cases of ovarian hyperstimulation syndrome (OHSS) (RR 0.33; 95% CI 0.13-0.80). This meta-analysis demonstrates that CC is still first choice therapy for women with therapy naïve PCOS. In CC-resistant women, the combination of CC plus metformin is the preferred treatment option before starting with LOD or FSH. At present, there is no evidence of an improvement in live birth when adding metformin to LOD or FSH. In IVF, metformin leads to a reduced risk of OHSS.

PICO
Population: Subfertile women with polycystic ovary syndrome (PCOS)
Intervention: Metformin
Comparison: Clomifene citrate (CC), Laparoscopic ovarian drilling (LOD), FSH, IVF
Outcomes: Live birth rate, Ovarian hyperstimulation syndrome (OHSS)

Included studies:
title: Effects of metformin on insulin resistance, androgen concentration, ovulation and pregnancy rates in women with polycystic ovary syndrome following laparoscopic ovarian drilling.
abstract: To evaluate the effects of metformin on insulin resistance, androgen concentration, ovulation rates and pregnancy rates in infertile women with polycystic ovary syndrome (PCOS).
title: A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain.
abstract: We prospectively estimated the prevalence of the polycystic ovary syndrome (PCOS), as defined by the NIH/NICHHD 1990 endocrine criteria, in a population of 154 Caucasian women of reproductive age reporting spontaneously for blood donation. Anthropometric data; the presence of hirsutism, acne, and androgenic alopecia; and the menstrual history were recorded by a single investigator. In 145 women, blood samples were also obtained for measurement of serum androgen levels. PCOS was defined by the presence of 1) oligomenorrhea, 2) clinical and/or biochemical hyperandrogenism, and 3) exclusion of hyperprolactinemia, thyroid disorders, and nonclassic 21-hydroxylase deficiency. Hirsutism was defined by a modified Ferriman-Gallwey score of 8 or more, acne was considered as a sign of hyperandrogenism when persistent after the second decade of life, and hyperandrogenemia was defined by an increase in circulating testosterone or dehydroepiandrosterone sulfate or an increase in the free androgen index above the 95th percentile of the control values derived from the nonhirsute, nonacneic women having regular menses who were not receiving hormonal therapy. PCOS was present in 10(6.5%), hirsutism was present in 11 (7.1%), and acne was present in 19 (12.3%) of the 154 women. Our results demonstrate a 6.5% prevalence of PCOS, as defined, in a minimally biased population of Caucasian women from Spain. The polycystic ovary syndrome, hirsutism, and acne are common endocrine disorders in women.
title: Ultra-short metformin pretreatment for clomiphene citrate-resistant polycystic ovary syndrome.
abstract: To evaluate the effect of ultra-short (12 days) metformin pretreatment in clomiphene-citrate (CC) resistant polycystic ovary syndrome (PCOS).
title: Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome.
abstract: Obese women with the polycystic ovary syndrome are relatively unresponsive to the induction of ovulation by clomiphene. We hypothesized that reducing insulin secretion by administering metformin would increase the ovulatory response to clomiphene.
title: A randomized controlled trial evaluating metformin pre-treatment and co-administration in non-obese insulin-resistant women with polycystic ovary syndrome treated with controlled ovarian stimulation plus timed intercourse or intrauterine insemination.
abstract: There are few data in the literature regarding the utility of metfomin before and during gonadotrophin administration in women with polycystic ovary syndrome (PCOS). The aim of the present study was to assess the effect of the pre-treatment and co-administration of metformin in infertile PCOS women treated with controlled ovarian stimulation (COS) followed by timed intercourse (TI) or intrauterine insemination (IUI).
title: Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: a prospective study.
abstract: Estimates of the prevalence of the polycystic ovary syndrome (PCOS) in the general population have ranged from 2-20%. The vast majority of these reports have studied White populations in Europe, used limited definitions of the disorder, and/or used bias populations, such as those seeking medical care. To estimate the prevalence of this disorder in the United States and address these limitations, we prospectively determined the prevalence of PCOS in a reproductive-aged population of 369 consecutive women (174 White and 195 Black; aged 18-45 yr), examined at the time of their preemployment physical. Body measures were obtained, and body hair was quantified by a modified Ferriman-Gallwey (F-G) method. All exams were initially performed by 2 trained nurses, and any subject with an F-G score above 3 was reexamined by a physician, the same for all patients. Of the 369 women, 277 (75.1%) also agreed to complete a questionnaire and have additional blood drawn. Subjects were studied regardless of current estrogen/progestin hormonal use (28.5%). PCOS was defined as 1) oligoovulation, 2) clinical hyperandrogenism (i.e. hirsutism) and/or hyperandrogenemia, and 3) exclusion of other related disorders, such as hyperprolactinemia, thyroid abnormalities, and non-classic adrenal hyperplasia. Hirsutism was defined by a F-G score of 6 or more, and hyperandrogenemia was defined as a total or free testosterone, androstenedione, and/or dehydroepiandrosterone sulfate level above the 95th percentile of control values [i.e. all eumenorrheic women in the study, who had no hirsutism (F-G < or = 5) or acne and were receiving no hormonal therapy; n = 98]. Considering all 369 women studied, White and Black women had similar mean ages (29.4 +/- 7.1 and 31.1 +/- 7.8 yr, respectively), although White women had a lesser body mass than Black women (24.9 +/- 6.1 vs. 29.2 +/- 8.1 kg/m2, respectively; P < 0.001). Of these 7.6%, 4.6%, and 1.9% demonstrated a F-G score of 6 or more, 8 or 10, respectively, and there was no significant racial difference, with hirsutism prevalences of 8.0%, 2.8%, and 1.6% in Whites, and 7.1%, 6.1%, and 2.1% in Blacks, respectively. Of the 277 women consenting to a history and hormonal evaluation, 4.0% had PCOS as defined, 4.7% (6 of 129) of Whites and 3.4% (5 of 148) of Blacks. In conclusion, in our consecutive population of unselected women the prevalence of hirsutism varied from 2-8% depending on the chosen cut-off F-G score, with no significant difference between White and Black women. Using an F-G score of 6 or more as indicative of hirsutism, 3.4% of Blacks and 4.7% of Whites had PCOS as defined. These data suggest that PCOS may be one of most common reproductive endocrinological disorders of women.
title: Insulin resistance in clomiphene responders and non-responders with polycystic ovarian disease and therapeutic effects of metformin.
abstract: To evaluate the clinical features, endocrine and metabolic profiles in clomiphene (CC) responders and non-responders with polycystic ovarian disease (PCOD), and to examine the effects of metformin (MTF) on the above parameters of CC resistance.
title: Decreases in ovarian cytochrome P450c17 alpha activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome.
abstract: Insulin resistance and increased ovarian cytochrome P450c17 alpha activity are both features of the polycystic ovary syndrome. P450c17 alpha, which is involved in androgen biosynthesis, has both 17 alpha-hydroxylase and 17,20-lyase activities. Increased activity of this enzyme results in exaggerated conversion of progesterone to 17 alpha-hydroxyprogesterone in response to stimulation by gonadotrophin. We hypothesized that hyperinsulinemia stimulates ovarian P450c17 alpha activity.
title: Sequential treatment of metformin and clomiphene citrate in clomiphene-resistant women with polycystic ovary syndrome: a randomized, controlled trial.
abstract: Recognition of the importance of insulin resistance in clomiphene-resistant women with polycystic ovary syndrome (PCOS) has led to the use of insulin sensitizers.
title: The effects of metformin on insulin resistance, clomiphene-induced ovulation and pregnancy rates in women with polycystic ovary syndrome.
abstract: To evaluate the effects of metformin on insulin resistance, ovarian androgen production, and clomiphene-induced ovulation and pregnancy rates in infertile women with polycystic ovary syndrome (PCOS).
title: Metformin treatment before IVF/ICSI in women with polycystic ovary syndrome; a prospective, randomized, double blind study.
abstract: Our aim was to investigate the effect of pre-treatment with metformin in women with polycystic ovary syndrome (PCOS) scheduled for IVF stimulation.
title: Co-administration of metformin during rFSH treatment in patients with clomiphene citrate-resistant polycystic ovarian syndrome: a prospective randomized trial.
abstract: This study aims to evaluate the impact of metformin on ovarian response when co-administered during recombinant (r)FSH using the low-dose step-up protocol in clomiphene citrate-resistant polycystic ovarian syndrome (PCOS) patients with normal glucose tolerance.
title: The use of metformin for women with PCOS undergoing IVF treatment.
abstract: Metformin appears to improve reproductive function in some women with polycystic ovary syndrome (PCOS). We wished to explore the effect of metformin in women with PCOS undergoing IVF.
title: Metformin therapy improves ovulatory rates, cervical scores, and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome.
abstract: To evaluate the effect of metformin therapy on hyperandrogenism, insulin resistance, cervical scores, ovulation, and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome (PCOS).
title: Medical vs. surgical treatment for clomiphene citrate-resistant women with polycystic ovary syndrome.
abstract: This study was conducted to evaluate the efficacy of metformin compared with ovarian drilling in the treatment of clomiphene citrate (CC) resistant women with polycystic ovary syndrome. A total of 161 infertile, CC-resistant women with PCOS aged 22-34 years (mean 25.5 +/- 4.4) were evaluated prospectively during the period between January 2000 and December 2001. Patients were allocated into two groups; group 1 includes 64 women who received metformin, 850 mg twice daily throughout the cycle, and group 2 which includes 97 women who underwent laparoscopic ovarian drilling. If spontaneous ovulation or pregnancy was not achieved within 3 months after treatment, CC was added with increments of 50 mg (up to 150 mg/day) for both groups. Clinical and menstrual characteristics in addition to the hormonal profile were evaluated before and after the treatment. There were no significant differences between the two groups in terms of age, body weight, BMI, duration of infertility and serum hormone levels (androgens, gonadotrophins, insulin) before starting the treatment. A significant improvement in the regularity of menstrual cycles (P < 0.05) and a significant reduction in the serum levels of testosterone(P<0.01), androstenedione (P<0.01), DHEAS (P <0.05), LH (P<0.01) and LH:FSH ratio (P<0.05) were noted after the treatment. There were no significant differences between the metformin group compared with the drilling group in the rates of ovulation (79.7% vs. 83.5%) and pregnancy (64.1% vs. 59.8%). It is concluded that CC-resistant patients with polycystic ovary syndrome can be treated effectively either by metformin or by laparoscopic ovarian drilling. Menstrual cycle pattern and the rates of ovulation and pregnancy are improved significantly, due most probably to the significant decrease in the levels of androgens and luteinising hormone.
title: Metformin-induced resumption of normal menses in 39 of 43 (91%) previously amenorrheic women with the polycystic ovary syndrome.
abstract: In 43 amenorrheic women with polycystic ovary syndrome (PCOS), 31 (74%) with fasting hyperinsulinemia (> or =20 microU/mL), our aim was to determine whether Metformin (Bristol-Myers Squibb, Princeton, NJ), which reduces hyperinsulinemia, would reverse the endocrinopathy of PCOS, allowing resumption of regular normal menses. A second aim was to assess the effects of weight loss versus other Metformin-induced effects on ovarian function, and to determine if there were different responses to Metformin between those who lost weight and those who did not. A third aim was to assess associations between PCOS, 4G/5G polymorphism in the promoter sequence of the plasminogen activator inhibitor-1 gene (PAI-1 gene), and PAI activity (PAI-Fx). Of the 43 women, 40 (93%) had normal fasting blood glucose and 37 had normal hemoglobin A1C (HgA1C); onlythree (7%) had type 2 diabetes mellitus. Metformin (1.5 to 2.25 g/d) was given for 6.1+/-5.1 months (range, 1.5 to 24), to 16 patients for less than 3 months, to 12 for 3 to 6 months, and to 15 for at least 6 months. On Metformin, 39 of 43 patients (91%) resumed normal menses. The percentage of women resuming normal menses did not differ among treatment duration groups (P<.1) or among dose groups (P>.1). The body mass index (BMI) decreased from 36.4 + 7 Kg/m2 at study entry to 35.1+/-6.7 on Metformin (P=.0008). Of 43 patients, 28 (67%) lost weight (1 to 69 pounds), with nine (21%) losing at least 12 pounds. On Metformin, the median fasting serum insulin decreased from 26 microU/mL to 22 (P=.019), testosterone decreased from 61 ng/dL to 47 (P=.003), and estradiol increased from 41 pg/mL to 71 (P=.0001). Metformin-induced improvements in ovarian function were independent of weight loss (testosterone decrease, P<.002; estradiol increase, P<.0004). The change in response variables on Metformin did not differ (P>.05) between those who lost weight and those who did not, excepting Lp(a), which increased 4 mg/dL in those who lost weight and decreased 9 mg/dL in those who did not (P = .003). The change in response variables on Metformin did not differ among the five quintiles of weight loss, excepting fasting glucose (P<.05), which increased 6 mg/dL in those who lost the least weight on Metformin versus those in the 60th to 80th percentile for weight loss, in whom glucose decreased 33 mg/dL. Although the pretreatment fasting serum insulin was not significantly correlated with testosterone (r=.24, P=.13) or androstenedione (r=.27, P=.09), on Metformin, the change in insulin correlated positively with the change in testosterone (r=.35, P=.047) and with the change in androstenedione (r=.48, P=.01). Patients were more likely than normal controls (83% v 64%, P=.016) to be heterozygous or homozygous for 4G polymorphism of the PAI-1 gene and were also more likely to have high PAI-Fx (> or =22 U/mL, 28% v3%, chi(2)=10.1, P=.001). Metformin reduces the endocrinopathy of PCOS, allowing resumption of normal menses in most (91%) previously amenorrheic women with PCOS.
title: Effects of metformin on gonadotropin-induced ovulation in women with polycystic ovary syndrome.
abstract: To evaluate whether pretreatment with metformin improves FSH-induced ovulation in women with clomiphene-resistant polycystic ovary syndrome (PCOS).
title: Insulin reduction with metformin increases luteal phase serum glycodelin and insulin-like growth factor-binding protein 1 concentrations and enhances uterine vascularity and blood flow in the polycystic ovary syndrome.
abstract: We hypothesized that hyperinsulinemia contributes to early pregnancy loss in the polycystic ovary syndrome by adversely affecting endometrial function and environment. Serum glycodelin, a putative biomarker of endometrial function, is decreased in women with early pregnancy loss. Insulin-like growth factor-binding protein-1 may also play an important role in pregnancy by facilitating adhesion processes at the feto-maternal interface. We studied 48 women with polycystic ovary syndrome before and after 4 weeks of administration of 500 mg metformin (n = 26) or placebo (n = 22) 3 times daily. Oral glucose tolerance tests were performed, and serum glycodelin and insulin-like growth factor-binding protein-1 were measured during the follicular and clomiphene-induced luteal phases of menses. In the metformin group, the mean (+/-SE) area under the serum insulin curve after glucose administration decreased from 62 +/- 6 to 19 +/- 2 nmol/L.min (P < 0.001). Follicular phase serum glycodelin concentrations increased 20-fold from 150 +/- 46 to 2813 +/- 1192 pmol/L (P < 0.001), and serum insulin-like-growth factor-binding protein-1 concentrations increased from 936 +/- 152 to 2396 +/- 300 pmol/L (P < 0.001). Similarly, luteal phase serum glycodelin concentrations increased 3-fold from 3434 +/- 1299 to 10624 +/- 1803 pmol/L (P < 0.001), and serum insulin-like growth factor-binding protein-1 concentrations increased from 1220 +/- 136 to 4916 +/- 596 pmol/L (P < 0.001). Uterine vascular penetration also increased in the metformin group, as did blood flow of spiral arteries, as demonstrated by a 20% decrease in the resistance index from 0.71 +/- 0.02 to 0.57 +/- 0.03 (P < 0.001). These variables did not change in the placebo group. We conclude that insulin reduction with metformin increases follicular and luteal phase serum glycodelin and insulin-like growth factor-binding protein-1 concentrations and enhances luteal phase uterine vascularity and blood flow in the polycystic ovary syndrome. These changes may reflect an improved endometrial milieu for the establishment and maintenance of pregnancy.
title: Impact of metformin therapy on ovarian stimulation and outcome in 'coasted' patients with polycystic ovary syndrome undergoing in-vitro fertilization.
abstract: This study was designed to determine if metformin therapy improves ovarian stimulation and IVF outcomes in coasted patients with clomiphene-resistant polycystic ovarian syndrome (PCOS). A retrospective data analysis was performed on women with clomiphene citrate-resistant PCOS treated with or without metformin, who underwent 72 cycles of IVF-embryo transfer with intracytoplasmic sperm injection (ICSI). In 59 cycles, patients were coasted to allow oestradiol concentrations to drop before human chorionic gonadotrophin administration. In patients undergoing coasting, the outcome of IVF with ICSI was compared in those who were treated and untreated. In patients treated with metformin, follicular fluid concentrations of testosterone and insulin were significantly lower (60.5 +/- 5 versus 79.1 +/- 6 ng/dl; P < 0.05 and 18 +/- 2.5 versus 22 +/- 2.4 micro IU/ml; P < 0.05 respectively), and the mean number of oocytes retrieved (22.3 +/- 2.4 versus 19.7 +/- 1.6) did not differ. The metformin-treated group showed an increase in the mean number of mature oocytes, oocytes fertilized and cleaving embryos (4-cell or greater by 72 h). However, in the group of patients undergoing coasting, maximum oestradiol concentrations and number of days of coasting were all lower in the metformin-treated group with increased clinical pregnancy rates (71 versus 30%, P < 0.05). Therefore, metformin use appears beneficial in improving IVF outcomes in clomiphene citrate-resistant PCOS patients.
title: Effects of metformin on clinical and biochemical parameters in polycystic ovary syndrome.
abstract: To assess the effects of 6 months of metformin therapy on clinical and biochemical parameters in polycystic ovary syndrome (PCOS) and to evaluate those parameters in responders and nonresponders to identify the subjects who respond to an insulin sensitizer in PCOS.
title: Metformin therapy in women with polycystic ovary syndrome.
abstract: To determine the clinical, biochemical, hormonal, and ultrasonographic effects of 6 months of metformin therapy in women with polycystic ovary syndrome (PCOS) and compare with pretherapy parameters.
title: The effect of metformin on ovarian stimulation and in vitro fertilization in insulin-resistant women with polycystic ovary syndrome: an open-label randomized cross-over trial.
abstract: Metformin effectively restores insulin sensitivity in insulin-resistant women with polycystic ovary syndrome (PCOS). We examined whether metformin, given prior to and during ovarian stimulation for in vitro fertilization (IVF), altered follicle stimulating hormone (FSH) requirement and increased the number of collected oocytes in these women. Seventeen insulin-resistant women with PCOS were recruited to our IVF unit to receive two consecutive cycles of ovarian stimulation with or without metformin co-treatment, the order of treatments being randomized using a table of random numbers. Metformin treatment (1500 mg/day) started 3 weeks before downregulation with buserelin acetate and was continued throughout ovarian stimulation with human recombinant FSH. Nine women completed both cycles, the results of eight women being excluded because of pregnancy after the first cycle (n = 4) or because the protocol of the study was not followed (n = 4). Mean total FSH dose was 2301 IU (range 1500-6563 IU) in metformin cycles and 2174 IU (range 1200-3900 IU) in parallel control cycles, while the mean number of collected oocytes was 8.6 (range 2-28) and 4.6 (range 1-16), respectively. Bayesian analysis showed probabilities of 0.05 that metformin reduces FSH requirement by at least 10%, and of 0.61 that at least 10% more oocytes are collected after metformin co-treatment. Co-administration of metformin is therefore likely to increase the number of oocytes collected after ovarian stimulation in insulin-resistant women with PCOS but is unlikely to reduce the requirement for FSH.
title: Effect of clomifene citrate plus metformin and clomifene citrate plus placebo on induction of ovulation in women with newly diagnosed polycystic ovary syndrome: randomised double blind clinical trial.
abstract: To compare the effectiveness of clomifene citrate plus metformin and clomifene citrate plus placebo in women with newly diagnosed polycystic ovary syndrome.
title: Metformin does not enhance ovulation induction in clomiphene resistant polycystic ovary syndrome in clinical practice.
abstract: To determine whether metformin pretreatment has beneficial effects in clomiphene resistant infertile women with polycystic ovary syndrome (PCOS) in an infertility clinic.
title: Role of metformin in correcting hyperinsulinemia, menstrual irregularity and anovulation in polycystic ovary syndrome.
abstract: Previous studies suggest that metformin by reducing hyperinsulinemia is clinically useful in the treatment of polycystic ovary syndrome (PCOS). Our Objective was to observe the role of metformin in correcting oligomenorrhea/amenorrhea and anovulation within six month in hyperinsulinemic women with PCOS. Another aim was to assess the decrease in hyperinsulinemia and body weight by metformin in our population.
title: 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.
abstract: 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).
title: The effect of metformin treatment to ovarian response in cases with PCOS.
abstract: To examine the effect of metformin therapy on ovarian response in clomiphene-resistant PCOS patients.
title: Metformin increases the ovulatory rate and pregnancy rate from clomiphene citrate in patients with polycystic ovary syndrome who are resistant to clomiphene citrate alone.
abstract: 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.
title: Clinical and endocrinological effects of 6 months of metformin treatment in young hyperinsulinemic patients affected by polycystic ovary syndrome.
abstract: Most patients with polycystic ovary syndrome (PCOS) have hyperinsulinemia; thus it has been postulated that insulin-lowering drugs, such as metformin, might be a useful long-term choice. We evaluated the effects of 6 months' administration of metformin on clinical and endocrine indices in PCOS patients. Forty-two hyperinsulinemic women with PCOS were continuously treated with metformin for 6 months. Gonadotropins, androgens (testosterone and androstenedione), insulin, sex hormone binding globulin (SHBG), lipid profile and clinical indices (menstrual length, body mass index (BMI), Ferriman-Gallwey score and waist/hip ratio (WHR)) were studied before and after metformin treatment. All women experienced a normalization of menstrual cycle length (reduction rate, 36.9%), a significant decrease in luteinizing hormone, insulin and androgen levels and an increase in SHBG plasma concentrations, with a concomitant decrease in cycle length and WHR. Significant changes were observed in the lipid profile. According to baseline androgen levels, patients were divided into two groups: 20 normoandrogenic and 17 hyperandrogenic women. The greatest decline of androgens, BMI and Ferriman-Gallwey score was observed in hyperandrogenic patients. Lowering of androgenicity was independent of BMI. Significant changes in lipid profile were observed in both groups after metformin treatment. These results suggest that metformin is effective in decreasing hyperandrogenism, mainly by reducing insulin levels. This leads to an improvement of clinical manifestations of PCOS and, in particular, of hyperandrogenism.
title: The effect of metformin plus clomiphene citrate on ovulation and pregnancy rates in clomiphene-resistant women with polycystic ovary syndrome.
abstract: To study the effect of metformin in combination with clomiphene citrate, as compared with placebo plus clomiphene citrate, on the ovulation and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome.
title: 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.
abstract: 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.
title: Metformin improves ovulation and pregnancy rates in patients with polycystic ovary syndrome.
abstract: We evaluated the fertility promoting effect of metformin in infertile patients with polycystic ovary syndrome. Twenty-nine infertile patients with polycystic ovary syndrome (PCOS) are included in our prospectively designed study and 15 normal menstruating women served as controls for reproductive hormones and ovarian volumes. All PCOS patients received a total of 78 cycles of clomiphene citrate (CC) in the beginning, then patients who could not get pregnant were switched to metformin plus clomiphene citrate. PCOS patients served as their own controls for the ovulation and pregnancy rates. At the end of the CC cycles 4.2% of patients got pregnant and 65.2% of the remaining group got pregnant with metformin plus CC cycles (p=0.0001). We have not observed any serious side effects of metformin. The high pregnancy rate of our study population is consistent with the hypothesis that insulin resistance plays an important role in the pathogenesis of anovulation in patients with PCOS.
title: Metformin administration versus laparoscopic ovarian diathermy in clomiphene citrate-resistant women with polycystic ovary syndrome: a prospective parallel randomized double-blind placebo-controlled trial.
abstract: At present, it is unclear what the role is of laparoscopic ovarian diathermy (LOD) and of metformin administration as second-line treatments for ovulation induction in women with polycystic ovary syndrome (PCOS) after failure of clomiphene citrate (CC) treatment. The aim of the present study was to compare in a randomized double-blind placebo-controlled fashion the effectiveness of LOD with metformin administration in the treatment of CC-resistant women with PCOS. A total of 120 overweight primary infertile anovulatory CC-resistant women with PCOS were enrolled and randomized into two groups of treatment. Group A underwent diagnostic laparoscopy, whereas group B underwent LOD. At hospital discharge, the patients were treated for 6 months with metformin cloridrate (group A; 850 mg twice daily) or with multivitamins (group B). The ovulation, pregnancy, abortion, and live-birth rates were evaluated. At the end of the study, the total ovulation rate was not statistically different between both treatment groups (54.8 vs. 53.2% [correction] in groups A and B, respectively), whereas the pregnancy (21.8 [correction] vs. 13.4%), the abortion (9.3 [correction] vs. 29.0%), and the live-birth (86.0 [correction] vs. 64.5%) rates were significantly (P < 0.05) different between the two groups. Our data show that metformin administration is more effective than LOD in overall reproductive outcomes in overweight infertile CC-resistant women with PCOS.
title: Presentation of polycystic ovary syndrome and its management with clomiphene alone and in combination with metformin.
abstract: This study was carried out to determine the pattern of presentation of Polycystic ovary syndrome (PCOS) in patients presenting at our unit and to compare effects of clomiphene alone and in combination with metformin in management of PCOS.
title: Does metformin induce ovulation in normoandrogenic anovulatory women?
abstract: 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.
title: Early effects of metformin in women with polycystic ovary syndrome: a prospective randomized, double-blind, placebo-controlled trial.
abstract: Metformin is successfully used in the treatment of cycle disorders and anovulation in women with polycystic ovary syndrome (PCOS). No data of the exact point and the impact of insulin resistance (IR) on metformin's efficacy exist.
title: Does metformin modify ovarian responsiveness during exogenous FSH ovulation induction in normogonadotrophic anovulation? A placebo-controlled double-blind assessment.
abstract: To assess whether the addition of metformin to gonadotrophin ovulation induction in insulin-resistant, normogonadotrophic, anovulatory women alters ovarian responsiveness to exogenous FSH.