A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain. Metformin reduces pregnancy complications without affecting androgen levels in pregnant polycystic ovary syndrome women: results of a randomized study. Decreases in ovarian cytochrome P450c17 alpha activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome. The use of metformin for women with PCOS undergoing IVF treatment. 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. Continuing metformin throughout pregnancy in women with polycystic ovary syndrome appears to safely reduce first-trimester spontaneous abortion: a pilot study. Can metformin reduce the incidence of gestational diabetes mellitus in pregnant women with polycystic ovary syndrome? Prospective cohort study Quantitative Synthesis in Systematic Reviews Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. Continuation of Metformin Reduces Early Pregnancy Loss in Obese Pakistani Women with Polycystic Ovarian 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. Metformin reduces abortion in pregnant women with polycystic ovary syndrome
We prospect ively 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 and rogenic alopecia ; and the menstrual history were recorded by a single investigator . In 145 women , blood sample s were also obtained for measurement of serum and rogen levels .  PCOS was defined by the presence of 1 ) oligomenorrhea , 2 ) clinical and /or biochemical hyper and rogenism , 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 hyper and rogenism when persistent after the second decade of life , and hyper and rogenemia was defined by an increase in circulating testosterone or dehydroepi and rosterone sulfate or an increase in the free and rogen 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 BACKGROUND Investigation of a possible effect of metformin on and rogen levels in pregnant women with polycystic ovary syndrome ( PCOS ) . METHODS A prospect i ve , r and omized , double-blind , placebo-controlled pilot study was conducted . Forty pregnant women with PCOS received diet and lifestyle counselling  and were r and omized to either metformin 850 mg twice daily or placebo . Primary outcome measures were changes in serum levels of dehydroepi and rosterone sulphate , and rostenedione , testosterone , sex hormone-binding globulin , and free testosterone index . Secondary outcome measures were pregnancy complications and outcome . Two-tailed t-tests and chi2-tests were used . RESULTS Maternal and rogen levels were unaffected by metformin treatment in pregnant women with PCOS . While none of the 18 women in the metformin group experienced a severe pregnancy or post-partum complication , seven of the 22 ( 32 % ) women experienced severe complications in the placebo group ( P = 0.01 ) . CONCLUSIONS Metformin treatment did not reduce maternal and rogen levels in pregnant women with PCOS . In the metformin-treated group we observed a reduction of severe , pregnancy and post-partum complications .  Metformin treatment of pregnant PCOS women may reduce complications during pregnancy and in the post-partum period BACKGROUND Insulin resistance and increased ovarian cytochrome P450c17 alpha activity are both features of the polycystic ovary syndrome . P450c17 alpha , which is involved in and rogen bio synthesis , 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 . METHODS We measured fasting serum steroid concentrations and the response of serum 17 alpha-hydroxyprogesterone to leuprolide , a gonadotrophin-releasing hormone agonist , and performed oral glucose-tolerance tests before and after oral administration of either metformin ( 500 mg three times daily ) or placebo for four to eight weeks in 24 obese women with the polycystic ovary syndrome . RESULTS In the 11 women given metformin , the mean ( + /- SE ) area under the serum insulin curve after oral glucose administration decreased from 9303 + /- 1603 to 4982 + /- 911 microU per milliliter per minute ( 56 + /- 10 to 30 + /- 6 nmol per liter per minute ) ( P = 0.004 ) . This decrease was associated with a reduction in the basal serum 17 alpha-hydroxyprogesterone concentration from 135 + /- 21 to 66 + /- 7 ng per deciliter ( 4.1 + /- 0.6 to 2.0 + /- 0.2 nmol per liter ) ( P = 0.01 ) and a reduction in the leuprolide-stimulated peak serum 17 alpha-hydroxyprogesterone concentration from 455 + /- 54 to 281 + /- 52 ng per deciliter ( 13.7 + /- 1.6 to 8.5 + /- 1.6 nmol per liter ) ( P = 0.01 ) . The serum 17 alpha-hydroxyprogesterone values increased slightly in the placebo group . In the metformin group , the basal serum luteinizing hormone concentration decreased from 8.5 + /- 2.2 to 2.8 + /- 0.5 mlU per milliliter ( P = 0.01 ) , the serum free testosterone concentration decreased from 0.34 + /- 0.07 to 0.19 + /- 0.05 ng per deciliter ( 12 + /- 3 to 7 + /- 2 pmol per liter ) ( P = 0.009 ) , and the serum sex hormone-binding globulin concentration increased from 0.8 + /- 0.2 to 2.3 + /- 0.6 microgram per deciliter ( 29 + /- 7 to 80 + /- 21 nmol per liter ) ( P < 0.001 ) . None of these values changed significantly in the placebo group . CONCLUSIONS In obese women with the polycystic ovary syndrome , decreasing serum insulin concentrations with metformin reduces ovarian cytochrome P450c17 alpha activity and ameliorates hyper and rogenism BACKGROUND 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 . METHODS A r and omized , placebo-controlled , double-blind study was carried out between 2001 and 2004 . Patients with PCOS undergoing IVF/ICSI treatment using a long GnRH agonist protocol were r and omized to receive metformin ( MET ) , 850 mg , or placebo ( PLA ) tablets twice daily from the start of the down-regulation process until the day of oocyte collection . The primary outcome was to be an improvement in the overall fertilization rate . RESULTS One-hundred and one IVF/ICSI cycles were r and omized to receive metformin ( 52 ) or to receive placebo ( 49 ) . There was no difference in the total dose of rFSH required per cycle ( median dose : MET = 1200 U , PLA = 1300 U ; P = 0.937 ) . The median number of oocytes retrieved per cycle ( MET = 17.2 , PLA = 16.2 ; P = 0.459 ) and the overall fertilization rates ( MET = 52.9 % , PLA = 54.9 % ; P = 0.641 ) did not differ . However , both the clinical pregnancy rates beyond 12 weeks gestation per cycle ( MET = 38.5 % , PLA = 16.3 % ; P = 0.023 ) and per embryo transfer ( MET = 44.4 % , PLA = 19.1 % ; P = 0.022 ) were significantly higher in those treated with metformin . Furthermore , a significant decrease in the incidence of severe ovarian hyperstimulation syndrome ( OHSS ) was observed ( MET = 3.8 % , PLA = 20.4 % ; P = 0.023 ) , and this was still significant after adjustment for BMI , total rFSH dose and age ( OR = 0.15 ; 95 % CI : 0.03 , 0.76 ; P = 0.022 ) . CONCLUSION Short-term co-treatment with metformin for patients with PCOS undergoing IVF/ICSI cycles does not improve the response to stimulation but significantly improves the pregnancy outcome and reduces the risk of OHSS 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 OBJECTIVE To determine whether metformin would safely reduce the rate of first-trimester spontaneous abortion without teratogenicity in 19 women with the polycystic ovary syndrome ( PCOS ) . DESIGN Prospect i ve pilot study . SETTING Outpatient . PATIENT(S ) Twenty-two previously oligoamenorrheic , nondiabetic women with PCOS ; 125 women with PCOS who were not currently pregnant and who had > or = 1 previous pregnancy while they were not receiving metformin .  INTERVENTION(S ) Metformin , 1.5 - 2.55 g/day , throughout pregnancy . MAIN OUTCOME MEASURE(S ) Rates of first-trimester spontaneous abortion and teratogenicity . RESULT ( S ) Before metformin , 10 women had 22 previous pregnancies with 16  first-trimester spontaneous abortions ( 73 % ) . While receiving metformin , these 10 women had 6 normal live births ( 60 % ) , 1 spontaneous abortion ( 10 % ) , and 3 normal ongoing pregnancies ( 30 % ) ( all > or = 13 weeks ; median gestation , 23 weeks ) . Among women receiving metformin , including those with live births and normal pregnancy for at least the first trimester , 1 of 10 ( 10 % ) had first-trimester spontaneous abortion compared with 73 % in 22 previous pregnancies without metformin ( P<.002 ) . To date , the 19 women receiving metformin have had no adverse maternal side effects , and no birth defects have occurred ; 9 ( 47 % ) had normal term live births , 2 ( 11 % ) had normal and appropriate for gestational age births ( one at 33 and one at 35 weeks ) , 6 ( 32 % ) have ongoing normal pregnancies lasting longer than the first trimester , and 2 ( 10.5 % ) had first-trimester spontaneous abortions . Sonography showed normal fetal development without congenital defects in the 6 ongoing pregnancies ( median gestation , 23 weeks ) . Among women who received metformin before conception , reductions in insulin and plasminogen activator inhibitor activity were correlated ( r=0.65 , P=.04 ) . CONCLUSION ( S ) Metformin therapy throughout pregnancy in women with PCOS reduces the otherwise high rate of first-trimester spontaneous abortion seen among women not receiving metformin and does not appear to be teratogenic Background . Women with polycystic ovary syndrome ( PCOS ) are at a high risk to develop Gestational Diabetes mellitus ( GDM ) . We hypothesized that metformin due to its metabolic , endocrine , vascular , and anti-inflammatory effects may reduce the incidence of GDM in PCOS women . Patient and method . We carried out a prospect i ve cohort study to determine the beneficial effects of metformin on PCOS patients during pregnancy . Three-hundred and sixty non-diabetic PCOS patients were included who were conceived on metformin by different treatment modalities . Two-hundred pregnant women continued on metformin at a dose of 1000–2000 mg daily throughout pregnancy ( study group ) and 160 women discontinued metformin use at the time of conception ( control group ) . Results . There is a statistically significant reduction in the incidence of GDM in favor of metformin group ( OR : 0.17 , 95 % CI : 0.07–0.37 ) . There is a statistically significant reduction in the incidence of pre-eclampsia in favor of metformin group ( OR : 0.35 , 95 % CI : 0.13–0.94 ) . Conclusion . Metformin is a promising medication for the prevention or reduction of the incidence of GDM and pre-eclampsia in PCOS women A quantitative systematic review , or meta- analysis , uses statistical methods to combine the results of multiple studies . Meta-analyses have been done for systematic review s of therapeutic trials , diagnostic test evaluations , and epidemiologic studies . Although the statistical methods involved may at first appear to be mathematically complex , their purpose is simple : They are trying to answer four basic questions . Are the results of the different studies similar ? To the extent that they are similar , what is the best overall estimate ? How precise and robust is this estimate ? Finally , can dissimilarities be explained ? This article provides some guidance in underst and ing the key technical aspects of the quantitative approach to these questions . We have avoided using equations and statistical notations ; interested readers will find implementations of the described methods in the listed references . We focus here on the quantitative synthesis of reports of r and omized , controlled , therapeutic trials because far more meta-analyses on therapeutic studies than on other types of studies have been published . For practical reasons , we present a stepwise description of the tasks that are performed when statistical methods are used to combine data . These tasks are 1 ) deciding whether to combine data and defining what to combine , 2 ) evaluating the statistical heterogeneity of the data , 3 ) estimating a common effect , 4 ) exploring and explaining heterogeneity , 5 ) assessing the potential for bias , and 6 ) presenting the results . Deciding Whether To Combine Data and Defining What To Combine By the time one performs a quantitative synthesis , certain decisions should already have been made about the formulation of the question and the selection of included studies . These topics were discussed in two previous articles in this series [ 1 , 2 ] . Statistical tests can not compensate for lack of common sense , clinical acumen , and biological plausibility in the design of the protocol of a meta- analysis . Thus , a reader of a systematic review should always address these issues before evaluating the statistical methods that have been used and the results that have been generated . Combining poor- quality data , overly biased data , or data that do not make sense can easily produce unreliable results . The data to be combined in a meta- analysis are usually either binary or continuous . Binary data involve a yes/no categorization ( for example , death or survival ) . Continuous data take a range of values ( for example , change in diastolic blood pressure after antihypertensive treatment , measured in mm Hg ) . When one is comparing groups of patients , binary data can be summarized by using several measures of treatment effect that were discussed earlier in this series [ 3 ] . These measures include the risk ratio ; the odds ratio ; the risk difference ; and , when study duration is important , the incidence rate . Another useful clinical measure , the number needed to treat ( NNT ) , is derived from the inverse of the risk difference [ 3 ] . Treatment effect measures , such as the risk ratio and the odds ratio , provide an estimate of the relative efficacy of an intervention , whereas the risk difference describes the intervention 's absolute benefit . The various measures of treatment effect offer complementary information , and all should be examined [ 4 ] . Continuous data can be summarized by the raw mean difference between the treatment and control groups when the treatment effect is measured on the same scale ( for example , diastolic blood pressure in mm Hg ) , by the st and ardized mean difference when different scales are used to measure the same treatment effect ( for example , different pain scales being combined ) , or by the correlation coefficients between two continuous variables [ 5 ] . The st and ardized mean difference , also called the effect size , is obtained by dividing the difference between the mean in the treatment group and the mean in the control group by the SD in the control group . Evaluating the Statistical Heterogeneity of the Data This step is intended to answer the question , Are the results of the different studies similar ( homogeneous ) ? It is important to answer this question before combining any data . To do this , one must calculate the magnitude of the statistical diversity ( heterogeneity ) of the treatment effect that exists among the different sets of data . Statistical diversity can be thought of as attributable to one or both of two causes . First , study results can differ because of r and om sampling error . Even if the true effect is the same in each study , the results of different studies would be expected to vary r and omly around the true common fixed effect . This diversity is called the within- study variance . Second , each study may have been drawn from a different population , depending on the particular patients chosen and the interventions and conditions unique to the study . Therefore , even if each study enrolled a large patient sample , the treatment effect would be expected to differ . These differences , called r and om effects , describe the between- study variation with regard to an overall mean of the effects of all of the studies that could be undertaken . The test most commonly used to assess the statistical significance of between- study heterogeneity is based on the chi-square distribution [ 6 ] . It provides a measure of the sum of the squared differences between the results observed and the results expected in each study , under the assumption that each study estimates the same common treatment effect . A large total deviation indicates that a single common treatment effect is unlikely . Any pooled estimate calculated must account for the between- study heterogeneity . In practice , this test has low sensitivity for detecting heterogeneity , and it has been suggested that a liberal significance level , such as 0.1 , should be used [ 6 ] . Estimating a Common Effect The questions that this step tries to answers are , 1 ) To the extent that data are similar , what is their best common point estimate of a therapeutic effect , and 2 ) how precise is this estimate ? The mathematical process involved in this step generally involves combining ( pooling ) the results of different studies into an overall estimate . Compared with the results of individual studies , pooled results can increase statistical power and lead to more precise estimates of treatment effect . Each study is given a weight according to the precision of its results . The rationale is that studies with narrow CIs should be weighted more heavily than studies with greater uncertainty . The precision is generally expressed by the inverse of the variance of the estimate of each study . The variance has two components : the variance of the individual study and the variance between different studies . When the between- study variance is found to be or assumed to be zero , each study is simply weighted by the inverse of its own variance , which is a function of the study size and the number of events in the study . This approach characterizes a fixed-effects model , as exemplified by the Mantel-Haenszel method [ 7 , 8 ] or the Peto method [ 9 ] for dichotomous data . The Peto method has been particularly popular in the past . It has the advantage of simple calculation ; however , although it is appropriate in most cases , it may introduce large biases if the data are unbalanced [ 10 , 11 ] . On the other h and , r and om-effects models also add the between- study variance to the within- study variance of each individual study when the pooled mean of the r and om effects is calculated . The r and om-effects model most commonly used for dichotomous data is the DerSimonian and Laird estimate of the between- study variance [ 12 ] . Fixed- and r and om-effects models for continuous data have also been described [ 13 ] . Pooled results are generally reported as a point estimate and CI , typically a 95 % CI . Other quantitative techniques for combining data , such as the Confidence Profile Method [ 14 ] , use Bayesian methods to calculate posterior probability distributions for effects of interest . Bayesian statistics are based on the principle that each observation or set of observations should be viewed in conjunction with a prior probability describing the prior knowledge about the phenomenon of interest [ 15 ] . The new observations alter this prior probability to generate a posterior probability . Traditional meta- analysis assumes that nothing is known about the magnitude of the treatment effect before r and omized trials are performed . In Bayesian terms , the prior probability distribution is noninformative . Bayesian approaches may also allow the incorporation of indirect evidence in generating prior distributions [ 14 ] and may be particularly helpful in situations in which few data from r and omized studies exist [ 16 ] . Bayesian analyses may also be used to account for the uncertainty introduced by estimating the between- study variance in the r and om-effects model , leading to more appropriate estimates and predictions of treatment efficacy [ 17 ] . Exploring and Explaining Heterogeneity The next important issue is whether the common estimate obtained in the previous step is robust . Sensitivity analyses determine whether the common estimate is influenced by changes in the assumptions and in the protocol for combining the data . A comparison of the results of fixed- and r and om-effects models is one such sensitivity analysis [ 18 ] . Generally , the r and om-effects model produces wider CIs than does the fixed-effects model , and the level of statistical significance may therefore be different depending on the model used . The pooled point estimate per se is less likely to be affected , although exceptions are possible [ 19 ] . Other sensitivity analyses may include the examination of the residuals and the chi-square components [ 13 ] and assessment of the effect of deleting each study in turn . Statistically significant results that depend on a single study may require further exploration . Cumulative Meta- Analysis BACKGROUND The polycystic ovary syndrome is a common cause of infertility . Clomiphene and insulin sensitizers are used alone and in combination to induce ovulation , but it is unknown whether one approach is superior . METHODS We r and omly assigned 626 infertile women with the polycystic ovary syndrome to receive clomiphene citrate plus placebo , extended-release metformin plus placebo , or a combination of metformin and clomiphene for up to 6 months . Medication was discontinued when pregnancy was confirmed , and subjects were followed until delivery . RESULTS The live-birth rate was 22.5 % ( 47 of 209 subjects ) in the clomiphene group , 7.2 % ( 15 of 208 ) in the metformin group , and 26.8 % ( 56 of 209 ) in the combination-therapy group ( P<0.001 for metformin vs. both clomiphene and combination therapy ; P=0.31 for clomiphene vs. combination therapy ) . Among pregnancies , the rate of multiple pregnancy was 6.0 % in the clomiphene group , 0 % in the metformin group , and 3.1 % in the combination-therapy group . The rates of first-trimester pregnancy loss did not differ significantly among the groups . However , the conception rate among subjects who ovulated was significantly lower in the metformin group ( 21.7 % ) than in either the clomiphene group ( 39.5 % , P=0.002 ) or the combination-therapy group ( 46.0 % , P<0.001 ) . With the exception of pregnancy complications , adverse-event rates were similar in all groups , though gastrointestinal side effects were more frequent , and vasomotor and ovulatory symptoms less frequent , in the metformin group than in the clomiphene group . CONCLUSIONS Clomiphene is superior to metformin in achieving live birth in infertile women with the polycystic ovary syndrome , although multiple birth is a complication . ( Clinical Trials.gov number , NCT00068861 [ Clinical Trials.gov ] . ) Background : Polycystic ovarian syndrome ( PCOS ) is the most common cause of anovulatory infertility worldwide . In addition to a poor conception rate , pregnancy loss rates are significantly higher ( 30–50 % ) during the first trimester in women with PCOS . Insulin resistance ( IR ) in this syndrome is not only implicated toward early pregnancy loss ( EPL ) but also pathognomic for various obstetrical complications during pregnancy . We evaluated the role of Metformin in the reduction of EPL in women with PCOS who conceived spontaneously or after induction ovulation with or without Metformin .  Objective : The primary objective was to evaluate the effectiveness of Metformin in the reduction of EPL in women with PCOS . Secondary outcomes like gestational diabetes , pregnancy-induced hypertension and intrauterine growth restriction were also analyzed at the end of the study . Material and Methods : This case-control study was conducted from March 2005 to March 2008 in the infertility and antenatal clinics of the Department of Obstetrics and Gynecology of Aga Khan University Hospital , Karachi , Pakistan . A total of 197 infertile women with PCOS were included . ‘ Cases ’ were women with PCOS who conceived while taking Metformin and it whom it was continued throughout pregnancy . ‘ Controls ’ were women in whom Metformin was either stopped in first trimester after confirmation of pregnancy ( by serum βHCG or by ultrasound ) or they conceived spontaneously without the use of Metformin . Results : All 197 women in this study had a confirmed diagnosis of PCOS ( Rotterdam criteria ) . These women were followed till the final outcome of pregnancy was achieved . Both groups were compared for risk of EPL . It was found that continuation of Metformin during pregnancy reduces EPL , i.e. 8.8 vs. 29.4 % in cases and controls , respectively ( p < 0.001 ) . In the subset of women with a prior history of miscarriage , the pregnancy loss rate was 12.5 % in the Metformin versus 49.4 % in control group ( p = 0.002 ) . Conclusion : Metformin continuation during pregnancy significantly reduces EPL in women with PCOS . IR may play a significant role in EPL CONTEXT 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 . OBJECTIVE 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 . DESIGN We describe a prospect i ve parallel r and omized , double-blind , double-dummy controlled clinical trial . SETTING The study was conducted at the University " Magna Graecia " of Catanzaro , Catanzaro , Italy . PATIENTS One hundred nonobese primary infertile anovulatory women with PCOS participated . INTERVENTIONS 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 . MEAN OUTCOME MEASURES The main outcome measures were ovulation , pregnancy , abortion , and live-birth rates . RESULTS 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 ) . CONCLUSIONS Six-month metformin administration is significantly more effective than six-cycle CC treatment in improving fertility in anovulatory nonobese PCOS women Background . Women with polycystic ovary syndrome ( PCOS ) are considered to be at increased risk of miscarriage . Since metformin has beneficial effects on the risk factors contributing to first-trimester abortion in PCOS patients , we hypothesized that metformin – owing to its metabolic , endocrine , vascular and anti-inflammatory effects – may reduce the incidence of first-trimester abortion in PCOS women . Material s and methods . A prospect i ve cohort study was set up to determine the beneficial effects of metformin on PCOS patients during pregnancy . Two hundred non-diabetic PCOS patients were evaluated while undergoing assisted reproduction . One hundred and twenty patients became pregnant while taking metformin , and continued taking metformin at a dose of 1000–2000 mg daily throughout pregnancy . Eighty women who discontinued metformin use at the time of conception or during pregnancy comprised the control group . Results . Both groups were similar with respect to all background characteristics ( age , body mass index , waist/hip ratio , follicle-stimulating hormone , luteinizing hormone , estradiol and dehydroepi and rosterone sulfate levels ) . Rates of early pregnancy loss in the metformin group were 11.6 % compared with 36.3 % in the control group ( p < 0.0001 ; odds ratio = 0.23 , 95 % confidence interval 0.11–0.42 ) . Conclusions . Administration of metformin throughout pregnancy to women with PCOS was associated with a marked and significant reduction in the rate of early pregnancy loss
PURPOSE Some previous studies have found that continued metformin use is beneficial in the management of polycystic ovary syndrome ( PCOS ) in pregnant women .
A systemic review and meta- analysis were needed to more fully assess the effects of metformin on pregnant PCOS patients .