Metformin reduces pregnancy complications without affecting androgen levels in pregnant polycystic ovary syndrome women: results of a randomized study. Pharmacokinetics and pharmacodynamics of metformin in healthy subjects and patients with noninsulin-dependent diabetes mellitus. Metformin should be considered in the treatment of gestational diabetes: a prospective randomised study Pretreatment and co-administration of oral anti-diabetic agent with clomiphene citrate or rFSH for ovulation induction in clomiphene-citrate-resistant polycystic ovary syndrome. Efficacy predictors for metformin and clomiphene citrate treatment in anovulatory infertile patients with polycystic ovary syndrome. 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. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. Metformin vs. insulin in gestational diabetes. A randomized study characterizing metformin patients needing additional insulin. Does metformin affect the ovarian response to gonadotropins for in vitro fertilization treatment in patients with polycystic ovary syndrome and reduced ovarian reserve? A randomized controlled trial. Metformin and insulin in the management of gestational diabetes mellitus: preliminary results of a comparison. Comparison of Newborn Outcomes in Women with Gestational Diabetes Mellitus Treated with Metformin or Insulin: A Randomised Blinded Trial Effects of metformin-diet intervention before and throughout pregnancy on obstetric and neonatal outcomes in patients with polycystic ovary syndrome Uterine effects of metformin administration in anovulatory women with polycystic ovary syndrome. PCOSMIC: a multi-centre randomized trial in women with PolyCystic Ovary Syndrome evaluating Metformin for Infertility with Clomiphene. How Metformin Acts in PCOS Pregnant Women Pregnancy outcomes among women with polycystic ovary syndrome treated with metformin. Height, weight, and motor-social development during the first 18 months of life in 126 infants born to 109 mothers with polycystic ovary syndrome who conceived on and continued metformin through pregnancy. Effect of metformin on miscarriage in pregnant patients with polycystic ovary syndrome. Continuation of metformin in the first trimester of women with polycystic ovarian syndrome is not associated with increased perinatal morbidity Pregnancy Loss, Polycystic Ovary Syndrome, Thrombophilia, Hypofibrinolysis, Enoxaparin, Metformin Metformin in the treatment of clomiphene citrate-resistant women with polycystic ovary syndrome undergoing in vitro fertilisation treatment: A randomised controlled trial Efficacy of metformin versus insulin in the management of pregnancy with diabetes. Continuing metformin throughout pregnancy in women with polycystic ovary syndrome appears to safely reduce first-trimester spontaneous abortion: a pilot study. Prevention of gestational diabetes by metformin plus diet in patients with polycystic ovary syndrome. Effects of in-utero exposure to oral hypoglycaemic drugs Metformin, pre-eclampsia, and pregnancy outcomes in women with polycystic ovary syndrome. Can metformin reduce the incidence of gestational diabetes mellitus in pregnant women with polycystic ovary syndrome? Prospective cohort study Pregnancy in women with Type 2 diabetes: who takes metformin and what is the outcome? 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 Prevalence of insulin resistance in the polycystic ovary syndrome using the homeostasis model assessment. Metformin versus metformin plus rosiglitazone in women with polycystic ovary syndrome. The administration of metformin during pregnancy reduces polycystic ovary syndrome related gestational complications. Metformin compared with insulin in the management of gestational diabetes mellitus: a randomized clinical trial. Metformin--a convenient alternative to insulin for Indian women with diabetes in pregnancy. Teratology Information Services in Europe and Their Contribution to the Prevention of Congenital Anomalies Metformin increases the ovulatory rate and pregnancy rate from clomiphene citrate in patients with polycystic ovary syndrome who are resistant to clomiphene citrate alone. Continuation of Metformin Reduces Early Pregnancy Loss in Obese Pakistani Women with Polycystic Ovarian Syndrome Metformin compared with insulin in the treatment of pregnant women with overt diabetes: 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. Metformin improves ovulation and pregnancy rates in patients with polycystic ovary syndrome Metformin administration versus laparoscopic ovarian diathermy in clomiphene citrate-resistant women with polycystic ovary syndrome: a prospective parallel randomized double-blind placebo-controlled trial. Metformin during pregnancy reduces insulin, insulin resistance, insulin secretion, weight, testosterone and development of gestational diabetes: prospective longitudinal assessment of women with polycystic ovary syndrome from preconception throughout pregnancy. Randomized trial of metformin vs insulin in the management of gestational diabetes. Metformin reduces risk of ovarian hyperstimulation syndrome in patients with polycystic ovary syndrome during gonadotropin-stimulated in vitro fertilization cycles: a randomized, controlled trial. Laparoscopic ovarian diathermy vs clomiphene citrate plus metformin as second-line strategy for infertile anovulatory patients with polycystic ovary syndrome: a randomized controlled trial. Enoxaparin-metformin and enoxaparin alone may safely reduce pregnancy loss. Metformin for gestational diabetes in routine clinical practice.
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 This study was conducted to assess the effect of noninsulin-dependent diabetes mellitus ( NIDDM ) and gender on the pharmacokinetics of metformin and to investigate whether or not metformin exhibits dose-dependent pharmacokinetics . The pharmacodynamic effects ( on plasma glucose and insulin ) of metformin in patients with NIDDM and in healthy subjects also were assessed . Nine patients with NIDDM and 9 healthy subjects received 4 single-blind single-dose treatments of metformin HCL ( 850 mg , 1,700 mg , 2,550 mg , and placebo ) and a multiple-dose treatment of 850 mg metformin HCL ( 3 times daily for 19 doses ) . After each single-dose treatment and the final dose of the multiple-dose phase , multiple plasma and urine sample s were collected for 48 hours and assayed for  metformin levels . Plasma sample s were also assayed for glucose and insulin levels . There were no significant differences in  metformin kinetics in patients with NIDDM compared with healthy subjects , in men compared with women , or during multiple-dose treatment versus single-dose treatment . Plasma concentrations of metformin  increase less than proportionally to dose , most likely due to a decrease in percent absorbed . In patients with NIDDM , single doses of 1,700-mg or higher of metformin significantly decrease postpr and ial , but not prepr and ial , glucose concentrations and do not influence insulin concentrations . With multiple doses , both prepr and ial and postpr and ial glucose concentrations and prepr and ial insulin concentrations were significantly lower than with placebo . The effect of metformin on glucose level is correlated with the average fasting plasma glucose level without drug . In healthy subjects , single and multiple doses of metformin showed no effect on plasma glucose , but significantly attenuated the rise in immediate postpr and ial insulin levels Please cite this paper as : Ijäs H , Vääräsmäki M , Morin‐Papunen L , Keravuo R , Ebeling T , Saarela T , Raudaskoski T. Metformin should be considered in the treatment of gestational diabetes : a prospect i ve r and omised study . BJOG 2011;118:880–885 AIM The objective of this study was to explore the result of pretreatment and concomitant use of metformin with clomiphene citrate ( CC ) and rFSH for ovulation induction in clomiphene-citrate-resistant polycystic ovary syndrome ( PCOS ) . MATERIAL AND METHODS This r and omized controlled trial was done in the Dhaka Medical College and Hospital and the Infertility Care and Research Centre , Dhaka , Bangladesh . A total of 165 infertile patients with CC-resistant PCOS who attended for treatment were the target population for this study . Patients were divided into three groups : groups A and B were given metformin and group C was the control . Along with metformin , group A received CC and group B received rFSH . Group C was treated with only rFSH . Metformin was given 1500 mg daily for 4 weeks . Afterwards CC or rFSH were added for induction of ovulation along with metformin . Six ovulatory cycles were assessed . Treatment was terminated when there was no response with maximum dose of CC and rFSH or after six ovulatory cycles without pregnancy or after achieving pregnancy . A P-value of < 0.5 was considered as significant . RESULTS Ovulation ( 89.09 % ) and pregnancy ( 54.55 % ) rates were higher in group B. Ovulation ( 74.55 % ) and pregnancy ( 29.09 % ) rates were also satisfactory in group C but a dose of rFSH requirement was significantly higher ( P = 0.000 ) . In group A , both ovulation and pregnancy rate were much lower than the other two groups ( 27.27 % and 12.73 % , respectively ) . CONCLUSIONS Use of metformin increases the response of ovulation-inducing agents and can be used safely in PCOS OBJECTIVE To evaluate ovulation and pregnancy predictors in infertile polycystic ovary syndrome ( PCOS ) patients who received clomiphene citrate ( CC ) and metformin as first-line ovulation inductors . DESIGN Prospect i ve controlled study . SETTING Departments of Obstetrics and Gynecology , Universities Magna Graecia of Catanzaro and Federico II of Naples , Italy . PATIENT(S ) Eighty infertile anovulatory PCOS patients allocated in two groups matched for body mass index ( BMI ) and age . INTERVENTION(S ) Metformin ( 1700 mg/day for 6 months ) or CC ( 50 mg/day , increasing doses up to 250 mg/day ) . MAIN OUTCOME MEASURE(S ) Baseline clinical and biochemical parameters categorized according to interventions response . RESULT ( S ) The BMI was statistically significantly lower in patients who ovulated under both treatments . Insulin sensitivity indexes were statistically significantly worse in patients who ovulated under metformin and statistically significantly better in patients who ovulated under CC . And rogen levels and free and rogen index ( FAI ) were statistically significantly lower in ovulatory patients than in anovulatory ones who received CC . Age , BMI , infertility duration , and insulin sensitivity indexes were statistically significantly different between patients who achieved and those who did not achieve a pregnancy under both treatments . And rogens levels and FAI were statistically significantly lower in patients who achieved a pregnancy under CC . CONCLUSION ( S ) Insulin-resistant PCOS patients with low BMI are more likely to respond to metformin whereas CC treatment is more effective in less hyper and rogenic and insulin-resistant PCOS patients with low BMI BACKGROUND 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 ) . METHODS Seventy insulin-resistant primary infertile women with PCOS were r and omized to receive metformin cloridrate ( 850 mg twice daily ; group A ) or placebo tablets ( two tablets daily ; group B ) for 3 months . Three trials of COS using highly purified urinary FSH ( hpFSH ) plus TI/IUI were performed . Number of ampoules of gonadotrophin used , duration of the ovarian stimulation , cycle cancellation , ovulation , pregnancy , abortion , live birth , mono-ovulatory cycles , multiple pregnancies and ovarian hyperstimulation syndrome ( OHSS ) rates were assessed . RESULTS No difference between groups was detected in ovulation , cycle cancellation , pregnancy , abortion , live birth , multiple pregnancies and OHSS rates . The mono-ovulatory cycle rates were significantly ( P = 0.002 ) more frequent in group A than in group B , whereas the days of stimulation for non-cancelled cycles and the number of vials of gonadotrophins used were significantly ( P < 0.001 ) higher in group A than in group B. CONCLUSION In insulin-resistant women with PCOS  , metformin pre-treatment and co-administration with hpFSH increases the mono-ovulatory cycles BACKGROUND We conducted a r and omized clinical trial to determine whether treatment of women with gestational diabetes mellitus reduced the risk of perinatal complications . METHODS We r and omly assigned women between 24 and 34 weeks ' gestation who had gestational diabetes to receive dietary advice , blood glucose monitoring , and insulin therapy as needed ( the intervention group ) or routine care . Primary outcomes included serious perinatal complications ( defined as death , shoulder dystocia , bone fracture , and nerve palsy ) , admission to the neonatal nursery , jaundice requiring phototherapy , induction of labor , cesarean birth , and maternal anxiety , depression , and health status . RESULTS The rate of serious perinatal complications was significantly lower among the infants of the 490 women in the intervention group than among the infants of the 510 women in the routine-care group ( 1 percent vs. 4 percent ; relative risk adjusted for maternal age , race or ethnic group , and parity , 0.33 ; 95 percent confidence interval , 0.14 to 0.75 ; P=0.01 ) . However , more infants of women in the intervention group were admitted to the neonatal nursery ( 71 percent vs. 61 percent ; adjusted relative risk , 1.13 ; 95 percent confidence interval , 1.03 to 1.23 ; P=0.01 ) . Women in the intervention group had a higher rate of induction of labor than the women in the routine-care group ( 39 percent vs. 29 percent ; adjusted relative risk , 1.36 ; 95 percent confidence interval , 1.15 to 1.62 ; P<0.001 ) , although the rates of cesarean delivery were similar ( 31 percent and 32 percent , respectively ; adjusted relative risk , 0.97 ; 95 percent confidence interval , 0.81 to 1.16 ; P=0.73 ) . At three months post partum , data on the women 's mood and quality of life , available for 573 women , revealed lower rates of depression and higher scores , consistent with improved health status , in the intervention group . CONCLUSIONS Treatment of gestational diabetes reduces serious perinatal morbidity and may also improve the woman 's health-related quality of life AIMS We compared metformin with insulin as treatment of gestational diabetes mellitus ( GDM ) . Furthermore , we aim ed to characterize  metformin-treated patients needing additional insulin to achieve prespecified glucose targets . METHODS We conducted a single centre r and omized controlled study with non-inferiority design comparing metformin and insulin in the treatment of 217 GDM patients having birth weight as primary outcome variable . RESULTS There were no significant differences in mean birth weight expressed in grams [ + 15 ( 90 % confidence interval ( CI ) : -121 to 89 ) ] or SD units [ + 0.04 ( 90 % CI : -0.27 to 0.18 ) ] between the metformin and insulin groups . There were no significant differences in neonatal or maternal data between the groups . Only 23 ( 20.9 % ) of the 110 patients in the metformin group needed additional insulin .  Compared with the patients on metformin only , those needing additional insulin  were older ( p = 0.04 ) , their oral glucose tolerance test had been performed earlier and diabetes therapy started earlier in gestation ( p = 0.01 and p = 0.004 , respectively ) . The risk for additional insulin was 4.6-fold in women with baseline serum fructosamine concentration above median compared with those below median . CONCLUSIONS Metformin is an effective alternative to insulin in the treatment of GDM patients . Serum fructosamine may help in predicting the adequacy of metformin treatment alone OBJECTIVE To evaluate the effects of metformin on the ovarian response to gonadotropins given for in vitro fertilization ( IVF ) programs in patients with polycystic ovary syndrome ( PCOS ) and reduced ovarian reserve . DESIGN Prospect i ve , parallel , r and omized , double-blind , placebo-controlled clinical trial . SETTING Academic departments of obstetrics and gynecology , and a private IVF center . PATIENT(S ) Primary infertile patients with PCOS older than 35 years and /or with a basal follicle-stimulating hormone ( FSH ) level higher than 10 IU/L who were scheduled for IVF cycles . INTERVENTION(S ) Gonadotropin-releasing hormone agonist flare-up protocol and high starting doses of recombinant FSH plus metformin or placebo tablets . MAIN OUTCOME MEASURE(S ) Primary end point : cancellation rate for low ovarian response . Secondary end-points : other clinical , biochemical , and reproductive data . RESULT ( S ) Enrollment was stopped after 88 participants had been r and omized and analyzed due to an unacceptable increased risk of poor ovarian response in the metformin arm . Statistically significant differences between the metformin and placebo groups were observed in the dose of gonadotropins used , peak estradiol levels , and the number of dominant follicles , retrieved oocytes , and metaphase II oocytes . CONCLUSION ( S ) In patients with PCOS and reduced ovarian reserve , metformin worsened the response to gonadotropins , and its administration should be stopped before the start of controlled ovarian hyperstimulation for IVF programs . CLINICAL TRIALS IDENTIFICATION NUMBER : NCT01208740 OBJECTIVE To compare glycemic control and neonatal outcomes in women with gestational diabetes mellitus ( GDM ) treated with metformin vs. insulin . STUDY DESIGN Women with GDM not controlled with diet and exercise were r and omized to metformin ( n = 32 ) or insulin ( n = 31 ) . The levels of glycemic control as well as maternal/neonatal complications were evaluated . RESULTS The mean ( + /- SD ) fasting and 2-hour postpr and ial blood glucose did not differ statistically between the 2 treatment groups . No patient failed metformin and required insulin . The majority ( 27/32 ) were easily controlled on the initial dosage ( 500 mg twice a day ) . Gestational age at entry and delivery ( p = 0.077 , 0.412 ) were similar . The difference in the rate of cesarean delivery was not statistically significant between the 2 groups ( p = 0.102 ) . Neonatal statistics were also not different between the metformin and insulin groups : birth weight , Apgar score at 5 minutes , respiratory distress syndrome , hyperbilirubinemia , neonatal hypoglycemia and neonatal intensive care unit admission ( p = 0.144 - 0.373 ) . CONCLUSION Based on these preliminary data , metformin appears to be an effective alternative to insulin in the treatment of GDM Background : Few studies have been done on the use of metformin in pregnancy and their results were not similar , therefore this research is performed to compare neonatal outcomes of metformin and insulin in the treatment of gestational diabetes . Methods : In this prospect i ve r and omized trial , 200 pregnant women within their 24th to 34th weeks of gestation with gestational diabetes , single fetus pregnancy , and in need of hyperglycemia treatment were entered and grouped as either metformin or insulin . Data related to maternal and neonatal outcomes were recorded and analyzed . Results : Considering data recorded of HbA1c at the beginning of pregnancy , pregnancy induced hypertension , preeclampsia , birth weight , dystocia , first and 5th min APGAR , neonatal sepsis , rout of delivery , liver function tests of neonate , hypoglycemia , anomaly , and still birth , there were no significant statistical differences between groups . The end pregnancy HbA1c , maternal weight gain during pregnancy , preterm labor , neonatal jaundice , respiratory distress and hospitalization of infants were higher in insulin group . Conclusions : Considering data from this study , metformin is efficient to control hyperglycemia in pregnancy . It is suggested performing more studies to evaluate long term side effects of metformin in pregnancy with higher sample size and longer follow-up of newborns Abstract Objective : Prospect ively assess whether metformin/diet pre-conception and throughout pregnancy would safely reduce first trimester miscarriage and improve pregnancy outcomes in women with polycystic ovary syndrome ( PCOS ) . Research design and methods : In 76 PCOS women , first pregnancy miscarriage and live birth were compared before and on metformin/diet , started 6.8 months ( median ) before conception , continued throughout pregnancy . On metformin 2–2.55 g/day , low glycemic index diet , first pregnancy outcomes in PCOS were compared with 156 community obstetric practice women ( controls ) . Main outcome measures : Live births , miscarriage , birth < 37 weeks gestation , gestational diabetes , pre-eclampsia , fetal macrosomia . Results : In 76 PCOS women before  metformin-diet , there were 36 miscarriages ( 47 % ) and 40 live births vs. 14 ( 18 % ) miscarriages and 62 live births on metformin-diet 6.8 months before conception and throughout pregnancy , p = 0.0004 , OR 3.99 , 95 % CI 1.91–8.31 . On metformin-diet , PCOS women did not differ ( p > 0.08 ) from controls for birth < 37 weeks gestation , gestational diabetes , pre-eclampsia , or fetal macrosomia .  Conclusions : Metformin-diet before and during pregnancy in PCOS reduces miscarriage and adverse pregnancy outcomes . Study limitation : individual benefits of the diet alone and diet plus metformin could not be assessed separately . R and omized , controlled clinical trials now need to be done with a larger number of patients BACKGROUND Metformin has been shown to improve fertility in anovulatory patients with polycystic ovary syndrome ( PCOS ) , inducing not only a high ovulation and pregnancy rate but also reducing the incidence of miscarriages . The aim of the present study was to evaluate the uterine effects of metformin in patients with PCOS who ovulated under metformin .  METHODS Thirty-seven non-obese primary infertile anovulatory patients with PCOS and another 30 age- and body mass index-matched healthy women ( control group ) were studied . PCOS patients were treated with metformin ( 850 mg twice daily ) for 6 months , whereas the control group did not receive any treatment . In these PCOS patients who ovulated whilst under metformin treatment ( PCOS group ) and in controls , uterine , sub-endometrial and endometrial blood flow , and endometrial thickness and pattern were evaluated using serial ultrasonographic assessment s. RESULTS Before treatment , uterine , sub-endometrial and endometrial blood flows were significantly lower in patients with PCOS than in the control group . All indexes of uterine vascularization were significantly improved in the PCOS group with metformin treatment and were not different from the controls . Nor was any difference in endometrial thickness and pattern detected between PCOS and control groups . After grouping the data of PCOS patients who ovulated under metformin for cycles with favourable/unfavourable reproductive outcome , no difference in any parameter was observed . CONCLUSIONS Metformin improves all surrogate markers of endometrial receptivity in PCOS patients , without difference between patients who had favourable or unfavourable reproductive outcome BACKGROUND Ovulation induction treatment with metformin , either alone or in combination with clomiphene citrate ( CC ) , remains controversial even though previous r and omized trials have examined this . METHODS A double blinded multi-centre r and omized 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 ( ' st and ard care ' ) or metformin ;  women with BMI < or = 32 kg/m(2 ) received CC ( ' st and ard care ' ) , metformin or both . Treatment continued for 6 months or until pregnancy was confirmed . Primary outcomes were clinical pregnancy and live birth . RESULTS 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 . CONCLUSIONS There is no evidence that adding metformin to ' st and ard 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 . Clinical Trials.gov number NCT00795808 ; trial protocol accepted for publication November 2005 : Johnson , Aust N Z Journal Obstet Gynaecol 2006;46:141 - 145 OBJECTIVE Metformin has been reported to reduce the risk of gestational diabetes ( GD ) in women with polycystic ovarian syndrome ( PCOS ) . However , little is known about the mechanisms of action of this drug during pregnancy . In the attempt to fill this gap , we performed a prospect i ve longitudinal study providing a detailed examination of glucose and insulin metabolism in pregnant women with PCOS undergoing metformin therapy .  RESEARCH DESIGN AND METHODS We enrolled 60 women with PCOS who conceived while undergoing metformin treatment .  An oral glucose tolerance test and a euglycemic-hyperinsulinemic clamp were performed at each trimester of gestation in 47 ongoing pregnancies . RESULTS Twenty-two of the study subjects had development of GD despite the treatment . At baseline , insulin sensitivity was comparable between women who had development of GD and women who did not . A progressive decline in this parameter occurred in all subjects , independently of the trimester of GD diagnosis . Insulin secretion was significantly higher during the first trimester in patients with an early failure of metformin treatment . Women with third trimester GD and women with no GD exhibited a significant increase in insulin output as gestation proceeded . All newborns were healthy and only one case of macrosomia was observed . CONCLUSIONS Women with PCOS who enter pregnancy in a condition of severe hyperinsulinemia have development of GD earlier , independently of metformin treatment . The physiologic deterioration of insulin sensitivity is not affected by the drug and does not predict the timing and severity of the glycemic imbalance . Despite the high incidence of GD observed , the drug itself or the intensive monitoring probably accounted for the good neonatal outcome BACKGROUND We sought to determine whether metformin , which had facilitated conception in 72 oligoamenorrhoeic women with polycystic ovary syndrome ( PCOS ) , would safely reduce the rate of first trimester spontaneous abortion ( SAB ) and increase the number of live births without teratogenicity . METHODS Seventy-two oligoamenorrheic women with PCOS conceived on metformin ( 2.55 g/day ) . They were prospect ively assessed in an outpatient clinical research centre . Outcome measures included number of first trimester SAB , live births , normal ongoing pregnancies > or=13 weeks , gestational diabetes ( GD ) , congenital defects ( CD ) , birthweight and height , as well as weight , height , and motor and social development during the first 6 months of life . RESULTS Of the 84 fetuses , to date there have been 63 normal live births without CD ( 75 % ) , 14 first trimester SAB ( 17 % ) , and seven ongoing pregnancies > or=13 weeks with normal sonograms without CD ( 8 % ) . Previously , without metformin , 40 of the 72 women had 100 pregnancies ( 100 fetuses ) with 34 ( 34 % ) live births and 62 ( 62 % ) first trimester SAB . In current pregnancies on metformin in these 40 women ( 46 pregnancies , 47 fetuses ) , there have been 33 live births ( 70 % ) , two pregnancies ongoing > /=13 weeks ( 4 % ) , and 12 SAB ( 26 % ) ( P < 0.0001 ) . There was no maternal lactic acidosis , and no maternal or neonatal hypoglycaemia . Fasting entry serum insulin was a significant explanatory variable for total ( previous and current ) first trimester SAB , odds ratio 1.32 ( for each 5 micro U/ml rise in insulin ) , 95 % CI 1.09 - 1.60 ( P = 0.005 ) . On metformin , GD developed in 4 % of pregnancies versus 26 % of previous pregnancies without metformin , P = 0.025 . There have been no major CD in the 63 live births or CD by sonography in the seven fetuses < or=13 weeks . In the 63 live births , neither weight nor height differed from the normal neonatal population . At 6 month follow-up , height was greater ( P = 0.008 ) and weight did not differ from the normal paediatric population ; motor and social development were normal . CONCLUSIONS Metformin therapy during pregnancy in women with PCOS was safely associated with reduction in SAB and in GD , was not teratogenic , and did not adversely affect birthweight or height , or height , weight , and motor and social development at 3 and 6 months of life BACKGROUND We prospect ively assessed growth and motor-social development during the first 18 months of life in 126 live births ( 122 pregnancies ) to 109 women with polycystic ovary syndrome ( PCOS ) who conceived on and continued metformin ( 1.5 - 2.55 g/day ) through pregnancy . METHODS The lengths and weights of PCOS neonates were compared with gender-specific Centers for Disease Control and Prevention ( CDC ) infant data . Gestational diabetes ( GD ) and pre-eclampsia in women with PCOS were compared with 252 healthy women without PCOS who had > or=1 live birth ( 262 live births ) . RESULTS There were 101 out of 126 ( 80 % ) term ( > or=37 gestational weeks ) PCOS births , which was not significantly different ( P = 0.7 ) from controls , 206 out of 252 ( 81.7 % ) . There were two ( 1.6 % ) birth defects . GD occurred in nine out of 119 PCOS pregnancies ( 7.6 % ) versus 40 out of 251 ( 15.9 % ) controls , P = 0.027 . The prevalence of pre-eclampsia did not differ in PCOS versus control pregnancies ( 4.1 versus 3.6 % , P = 0.8 ) . The birth length and weight of the 52 male neonates did not differ ( P > 0.05 ) from those of CDC males ; the 74 female neonates were shorter than CDC females ( 48.9 + /- 5.4 versus 50.6 + /- 2.7 cm , P = 0.006 ) and weighed less ( 3.09 + /- 0.85 versus 3.29 + /- 0.52 kg , P = 0.04 ) . There were no systematic differences in growth between PCOS and CDC infants over 18 months . At 3 , 6 , 9 , 12 and 18 months , of a potential 100 % motor-social development score , scores ( + /-SD ) were 95 + /- 13 , 98 + /- 8 % , 95 + /- 10 , 97 + /- 8 and 94 + /- 16 % ; no infants had motor-social developmental delays . CONCLUSIONS Metformin reduced development of GD , was not teratogenic and did not adversely affect birth length and weight , growth or motor-social development in the first 18 months of life BACKGROUND This study was performed with the aim of evaluating the effect of metformin in reducing miscarriage when continued until the end of the first trimester of pregnancy in patients with polycystic ovary syndrome ( PCOS ) and infertility . SUBJECTS AND METHOD From January 2004 to December 2005 , a total of 75 pregnant women with PCOS were studied in three different groups . In Group A , metformin administration ( 500 mg three times daily ( TDS ) ) was stopped immediately after diagnosis of pregnancy ( 5 - 6 weeks gestation ) , in Group B , metformin was administered until the end of 8 weeks gestation and in Group C until the end of 12 weeks gestation . The results of this study were then assessed using chi-square McNemar 's , ANOVA Kruskal Wallis and logistic regression tests . RESULTS There was a significant statistical difference between previous and current miscarriage in the current pregnancy with a decline in Group B from 40 % to 8 % and in group C from 32 % to 4 % . In spite of the reduced rate of miscarriage seen in Group A , from 20 % to 4 % , this difference was not statistically significant . Fetal anomalies were absent in all three groups . CONCLUSION According to the current findings , it seems that continuing metformin during the first trimester of pregnancy has beneficial effects in patients with PCOS This study aim ed to assess the perinatal outcome , especially foetal growth , following the continuation of metformin during the first trimester of pregnancy . All women with polycystic ovary syndrome ( PCOS ) treated with metformin in the first trimester and who delivered a baby weighing 500 g or more between 2003 and 2005 were studied . Subjects were matched for age and parity with r and omly selected controls . The perinatal outcomes studied were : growth parameters , gestational age , congenital defects , hypoglycaemia and neonatal unit admission .  Sixty-six pregnancies were compared with 66 controls ; all had singleton deliveries . There was no difference in mean birth weight between the metformin and the control groups ( p = 0.84 ) . The percentage of small ( < 10th centile ) and large ( > 90th centile ) for gestational age babies was lower in the metformin group . In the metformin group , there were no major congenital malformations and 24 % of the babies were admitted to the neonatal intensive care unit ( NICU ) compared with 27 % of the babies in the control group ( non-significant ) . Neonatal hypoglycaemia was less common in the metformin group ( 18.5 % vs. 24.5 % ) and fewer babies required intravenous glucose therapy ( 6.3 % vs. 12 % ) . We found no evidence that the continuation of metformin in the first trimester of pregnancy was associated withan adverse foetal outcome Thrombophilia , hypofibrinolysis , and polycystic ovary syndrome ( PCOS ) are associated with  recurrent pregnancy loss ( RPL )  and  spontaneous abortion  ( SAB ) alone and concurrently . The efficacy and safety of combined enoxaparin-metformin was prospect ively assessed in women with PCOS with one or more previous SAB , thrombophilia , and /or hypofibrinolysis . Twenty-four white women with PCOS were studied ; 23 with previous pregnancies , seven with RPL of unknown etiology ( ≥ three consecutive pregnancy losses < 20 weeks ’ gestation ) , two with two consecutive SABs , 13 with one SAB , and one with one live birth ( HELLP syndrome ) . Prospect ively , metformin ( 1.5 to 2.55 g/day ) was administered before and throughout gestation , with concurrent enoxaparin ( 60 mg/day ) throughout gestation . The 24 cases differed from 93 normal white female controls for the factor V Leiden mutation , 17 % vs. 2 % , Fisher ’s p [ pf ] = .016 , and for the 4G4 G mutation of the plasminogen activator inhibitor-1 ( PAI-1 ) gene ( 46 % vs. 24 % , Chi-square 4.63 , p = . 031 ) . The patients also differed from 44 normal white female controls for high levels ( > 21.1 U/mL ) of the PAI-1 gene product , plasminogen activator inhibitor activity ( PAI-Fx ) ( 33 % vs. 8 % , pf = . 018 ) , and for high factor VIII ( > 150 % ) ( 22 % vs. 0 % , pf = .037 ) . Of the 24 women , 23 had 65 previous pregnancies without metformin or enoxaparin , with 18 live births , 46 SAB ( 71 % ) , and one elective abortion . On metforminenoxaparin , the same 23 women had 26 current pregnancies ( 28 fetuses ) , with 20 live births , two normal pregnancies 13 weeks or longer , and six SAB ( 21 % ) , 3.4-fold lower than previous gestations ( McNemar ’s S = 33.6 , p < . 0001 ) . There were no adverse maternal or fetal therapy effects . Enoxaparin-metformin  reduces pregnancy loss in women with PCOS with one or more previous SAB , who also have thrombophilia and /or hypofibrinolysis Summary This study was conducted to determine the efficacy of metformin vs placebo in women with polycystic ovary syndrome ( PCOS ) undergoing IVF treatment . A total of 66 CC-resistant patients were studied prospect ively . The women were r and omly assigned to receive 850 mg of metformin ( n = 34 ) or placebo ( n = 32 ) twice daily that started 1 month before commencing the IVF treatment and continued to the day of the pregnancy test . Compared with the metformin-treated group , women who received a placebo had a significant increase in terms of days of stimulation with HMG , number of HMG ampoules , number of follicles > 14 mm , number of oocytes retrieved , number of mature eggs , fertilisation rate and oestradiol level on the day of hCG administration . Similarly , women in the placebo group showed a significant increase in poor quality embryos , cancellation rate and the rate of ovarian hyperstimulation syndrome , as compared with the metformin-treated group . On the other h and , women who received metformin showed a significantly higher number of good quality embryos and implantation rate when compared with the placebo controls . Despite the transfer of a similar number of embryos , an insignificant increased in the pregnancy rate along with significant reduction in the abortion rate was observed in the metformin-treated group as compared with the placebo controls . No fetal abnormalities were encountered in the babies born in the metformin-treated group . It is concluded that metformin affects positively the quality of both oocytes and embryos without a significant increase in the pregnancy rate . It decreases significantly the rates of abortion and ovarian hyperstimulation syndrome OBJECTIVE To compare the efficacy of metformin with insulin in the management of  pregnancy with diabetes .  STUDY DESIGN R and omized clinical trial . PLACE AND DURATION OF STUDY Department of Obstetrics and Gynaecology , Maternal and Child Health Centre ( MCH ) , Pakistan Institute of Medical Sciences , Islamabad , from May 2010 to January 2011 . METHODOLOGY A total of 68 pregnant patients with diabetes were included in this study . Patients were r and omly divided in to two groups of each 34 patients based on table of r and om numbers . One was labelled as group-A and other was labelled as group-B. Group-A received insulin and group-B received metformin for the management of diabetes . RESULTS The mean age was 29.82 ± 4.58 and 29.35 ± 4.97 years in groups-A and B respectively . Fasting blood sugar level after 1 month was controlled in 22 ( 64.7 % ) patients in group-A and in 27 ( 79.4 % ) in group-B ( p > 0.05 ) . Fasting blood sugar level at term , remained controlled in 30 ( 88.2 % ) patients in group-A and 27 ( 79.4 % ) in group-B ( p > 0.05 ) . Comparison of r and om blood sugar levels within normal limits after 1 month in 25 ( 73.5 % ) in group-A and in 24 ( 70.6 % ) in group-B. At term , r and om blood sugar level was controlled in 28 ( 82.4 % ) and 27 ( 79.4 % ) patients in group-A and B , respectively . Comparison of post-treatment HBA1C level depicts that diabetes controlled in 27 ( 79.4 % ) patients in group-A while in 28 ( 82.3 % ) patients of group-B. The efficacy of metformin and insulin in controlling diabetes was equal in two groups . CONCLUSION There was no marked difference in efficacy of metformin and insulin in controlling diabetes in pregnant patients in two groups 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 OBJECTIVE To prospect ively assess whether metformin diet safely provides primary and secondary prevention of  gestational diabetes ( GD ) . DESIGN Assess development of GD on metformin diet . SETTING Outpatient clinical research center . PATIENT(S ) One hundred forty-two nondiabetic women with polycystic ovary syndrome ( PCOS ) who had at least one live-birth ( LB ) pregnancy on metformin diet ( 172 pregnancies , 180 LBs ) . INTERVENTION(S ) Women were given 26 % protein , 44 % carbohydrate diets , without calorie restriction during pregnancy . Metformin ( 2 - 2.55 g/d ) was given preconception , through pregnancy . MAIN OUTCOME MEASURE(S ) Development of GD . RESULT ( S ) On metformin , GD developed in 12 ( 7 % ) of 172 LB pregnancies . Forty-seven women had at least one previous LB pregnancy ( n = 64 ) without metformin , with GD developing in 19 ( 30 % ) . Subsequently , on metformin , these 47 women had 50 LB pregnancies , developing GD in 6 ( 12 % ) , which was a statistically significant difference . Of 15 women who had previous GD without metformin , GD developed in 5 ( 31 % ) of 16 subsequent pregnancies on metformin . Of 32 women who were previously free of GD without metformin , GD developed in 1 ( 3 % ) of 34 subsequent pregnancies on metformin .  Previous GD without metformin was the only statistically significant explanatory variable for current GD on metformin . CONCLUSION ( S ) Metformin diet during pregnancy in women with PCOS facilitates primary and secondary prevention of GD The observation that several Mexican-American women were taking oral hypoglycaemic agents while pregnant led to a study to confirm reports of associations between these agents and congenital abnormalities . 20 non-insulin-dependent ( NIDDM ) pregnant diabetic women with exposure to oral hypoglycaemic drugs during embryogenesis and 40 pregnant NIDDM women matched for age , race , parity , weight , and glycaemic control but not exposed to oral hypoglycaemic drugs were followed up . 10 infants ( 50 % ) in the exposed group had congenital malformations , compared with only 6 ( 15 % ) in the control group ( p less than 0.002 ) . 5 ( 25 % ) infants in the exposed group had ear malformations , anomalies not commonly described in diabetic embryopathy . Hyperbilirubinemia ( p less than 0.04 ) , polycythaemia , and hyperviscosity requiring partial exchange transfusions ( p less than 0.03 ) were commoner among babies in the exposed than in the control group . 3 babies in the exposed group but none in the comparison group had severe prolonged neonatal hypoglycaemia lasting 2 , 4 , and 7 days ; 2 of the 3 had been exposed for 22 and 28 weeks during gestation , whereas the third had been exposed throughout the first trimester . Although exposure to oral hypoglycaemic drugs during fetal life seems to be associated with congenital malformations and neonatal hypoglycaemia , a large , prospect i ve study is needed to exclude the confounding effect of maternal metabolic derangement secondary to diabetes AIMS Was metformin during pregnancy in women with polycystic ovary syndrome ( PCOS ) associated with pre-eclampsia , and was it safe for mother and neonate ? METHODS In the current study , pre-eclampsia and other pregnancy outcomes were prospect ively studied in 90 women with PCOS who conceived on metformin 1.5 - 2.55 g/day , and had > or = 1 live birth ( 97 pregnancies , 100 live births ) compared with 252 healthy women ( not known to have PCOS ) with > or = 1 live birth , consecutively delivered in a community obstetrics practice . RESULTS Women with PCOS were older than controls ( 33 + /- 5 vs. 29 + /- 6 years , P < 0.0001 ) , more likely to be > 35 years old at conception ( 23 vs. 13 % , P = 0.028 ) , much heavier ( 93 + /- 23 vs. 72 + /- 18 kg , P < 0.0001 , BMI 33.8 + /- 7.8 kg/m2 vs. 25.6 + /- 5.9 , P < 0.0001 ) , and more likely to be Caucasian ( 97 vs. 90 % , P = 0.05 ) , but there were similar numbers with preconception Type 2 diabetes mellitus [ 2/90 ( 2.2 % ) vs. 1/252 ( 0.4 % ) , P = 0.17 ] . Pre-eclampsia in PCOS ( 5/97 pregnancies , 5.2 % ) , did not differ ( P = 0.5 ) from controls ( 9/252 , 3.6 % ) , nor did it differ ( P = 1.0 ) in PCOS vs. control primigravidas [ 2/45 ( 4.4 % ) vs. 4/91 ( 4.4 % ) ] . Development of gestational diabetes in PCOS did not differ from controls [ 9/95 pregnancies ( 9.5 % ) vs. 40/251 ( 15.9 % ) , P = 0.12 ] . Of the 100 live births to 90 women with PCOS , there were no major birth defects . Mean + /- sd birth weight of the 80 live births > or = 37 weeks gestation in women with PCOS ( 3414 + /- 486 g ) did not differ from controls ' 206 live births > or = 37 weeks ( 3481 + /- 555 g ) , P = 0.34 , nor did the percentage of > or = 37 week gestation neonates > or = 4000 g ( 12.5 vs. 17.5 % , P = 0.3 ) or > or = 4500 g ( 1.3 vs. 2.9 % , P = 0.7 ) . CONCLUSIONS Metformin is not associated with pre-eclampsia in pregnancy in women with PCOS , and appears to be safe for mother and fetus 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 AIMS To review pregnancy outcomes in women with Type 2 diabetes ( Type 2 DM ) , comparing women treated with those not treated with metformin . METHODS Data were collected by case-note review for all pregnancies in women with Type 2 DM over a 6-year period ( 1998 - 2003 ) at the National Women 's Hospital . Two hundred and fourteen pregnancies were included , metformin was taken in 93 pregnancies and continued until delivery in 32 ; the remaining 121 pregnancies comprised the control group . The principal outcome measures were preeclampsia , perinatal loss and neonatal morbidity . RESULTS Baseline characteristics differed between groups : women in the metformin group had greater mean ( SD ) body mass index [ 35.5(7.6 ) vs. 33.5(6.6 ) kg/m2 , P < 0.05 ] , more chronic hypertension ( 19 % vs. 7 % , P < 0.05 ) and higher mean ( SD ) first trimester glycated haemoglobin ( HbA1c ) levels [ 8.3(1.9)% vs. 7.5(1.7)% , P < 0.005 ] . There was no difference between metformin and control groups , respectively , in the rate of preeclampsia ( 13 % vs. 14 % , P = 0.84 ) , perinatal loss ( 3 % vs. 2 % , P = 0.65 ) or neonatal morbidity , including rate of prematurity ( 23 % vs. 22 % , P = 0.7 ) , admission to the neonatal unit ( 40 % vs. 48 % , P = 0.27 ) , respiratory distress ( 9 % vs. 18 % , P = 0.07 ) and treatment with intravenous dextrose ( 20 % vs. 31 % , P = 0.08 ) . CONCLUSIONS Pregnant women with Type 2 DM who were treated with metformin had more risk factors for adverse pregnancy outcomes , but no differences in outcomes were seen compared with women not taking metformin . We need r and omized trials to address potential benefits of metformin treatment in this population that may be masked by current practice Abstract Objective To compare the effectiveness of clomifene citrate plus metformin and clomifene citrate plus placebo in women with newly diagnosed polycystic ovary syndrome . Design R and omised clinical trial . Setting Multicentre trial in 20 Dutch hospitals . Participants 228 women with polycystic ovary syndrome . Interventions Clomifene citrate plus metformin or clomifene citrate plus placebo . Main outcome measure The primary outcome measure was ovulation . Secondary outcome measures were ongoing pregnancy , spontaneous abortion , and clomifene resistance . Results 111 women were allocated to clomifene citrate plus metformin ( metformin group ) and 114 women were allocated to clomifene citrate plus placebo ( placebo group ) . The ovulation rate in the metformin group was 64 % compared with 72 % in the placebo group , a non-significant difference ( risk difference − 8 % , 95 % confidence interval − 20 % to 4 % ) . There were no significant differences in either rate of ongoing pregnancy ( 40 % v 46 % ; − 6 % , − 20 % to 7 % ) or rate of spontaneous abortion ( 12 % v 11 % ; 1 % , − 7 % to 10 % ) . A significantly larger proportion of women in the metformin group discontinued treatment because of side effects ( 16 % v 5 % ; 11 % , 5 % to 16 % ) . Conclusion Metformin is not an effective addition to clomifene citrate as the primary method of inducing ovulation in women with polycystic ovary syndrome . Trial registration Current Controlled Trials IS RCT N55906981 [controlled-trials.com][controlled-trials.com ] OBJECTIVE To determine the prevalence of insulin resistance ( IR ) in a large population of patients with the polycystic ovary syndrome ( PCOS ) . DESIGN Prospect i ve , case-control . SETTING University medical center . PATIENT(S ) Two hundred seventy-one PCOS patients and 260 eumenorrheic , non-hirsute , control women . INTERVENTION(S ) History and physical examination and blood sampling . MAIN OUTCOME MEASURE(S ) Total T , free T , DHEAS , sex hormone-binding globulin , and fasting glucose and insulin levels ; homeostatic model assessment values for IR ( HOMA-IR ) and percent beta-cell function ( HOMA-%beta-cell ) . RESULT ( S ) Patients with PCOS and controls differed significantly in all parameters studied , except fasting glucose . Because the HOMA-IR and HOMA-%beta-cell values were variably associated with race , age , and body mass index , the HOMA-IR and HOMA-%beta-cell values were then adjusted for these cofounders . After adjustment , 64.4 % of PCOS patients were noted to be insulin resistant , and 2.6 % had beta-cell dysfunction . Compared with PCOS patients without IR ( n = 96 ) , patients with IR ( n = 174 ) were more obese and had higher beta-cell function . CONCLUSION ( S ) In patients with PCOS , the prevalence of IR was 64 % according to the HOMA-IR measurement , after adjustment . Patients with IR were more clinical ly affected . Although IR is a common abnormality in PCOS , it does not seem to be a universal feature BACKGROUND Hyperinsulinemia and insulin resistance are present in the majority of women with polycystic ovary syndrome ( PCOS ) . Both metformin and rosiglitazone can improve the ovulation and endocrine disorders of the patients . How about the combination of the two ? It is rarely reported . This study aim ed to compare the therapeutic efficacy of metformin versus metformin plus rosiglitazone in patients with PCOS . METHODS Fifty-eight women with PCOS were r and omly assigned to two groups . Metformin group ( 29 ) was treated with metformin mono-therapy and metformin plus rosiglitazone group ( 29 ) was treated with metformin plus rosiglitazone for 6 months . Treatment was discontinued once pregnancy was diagnosed . RESULTS Fasting insulin , postpr and ial insulin , the homeostatic model assessment of insulin resistance ( HOMA-IR ) , luteinizing hormone ( LH ) , triglyceride , lower density cholesterol and testosterone level decreased significantly in both groups ( P < 0.05 ) . Metformin plus rosiglitazone had a better effect than metformin mono-therapy . Body mass index decreased by 7.8 % in metformin group while no significant change in metformin plus rosiglitazone group . There were eight pregnancies , six in metformin plus rosiglitazone group ( one abortion ) and two in metformin group . There was no congenital anomaly at birth and seven infants developed well at one year 's follow-up . CONCLUSIONS Metformin can improve insulin resistance and imbalance of endocrine hormones . Metformin plus rosiglitazone has a more pronounced therapeutic effect and achieved more pregnancies than mono-therapy with metformin . The use of metformin and rosiglitazone before pregnancy has no obvious side effect on the development of the infants . Our study might suggest that metformin is the better choice in PCOS patients with serious obese and rosiglitazone plus metformin would be more effective in patients with severe insulin resistance or those do not respond to metformin OBJECTIVES To prospect ively evaluate the safety of metformin administration during pregnancy in a group of PCOS patients by assessing its effect on the prevalence of gestational complications and neonatal outcome . STUDY DESIGN Our prospect i ve , single centre study included 98 pregnant women with PCOS treated with metformin throughout pregnancy and 110 normal pregnant controls . All PCOS patients were hyperinsulinemic and received metformin ( 1700 - 3000 mg/day ) before conception and until 37 weeks ' gestation . RESULTS Metformin treatment in the pregnant PCOS patients result ed in significant decrease in miscarriage rate ( 9.1 % vs 20 % ; p<0.05 ) , gestational diabetes ( 0 vs 13 % ; p<0.005 ) , and gestational hypertension ( 0 vs 11 % ; p<0.005 ) and a non-significant decrease in pre-eclampsia ( 0 vs 3 % ; p=.24 ) , compared to the control group . Mean neonatal Apgar score , weight and length were comparable between the two groups . CONCLUSIONS Continuing metformin therapy throughout pregnancy result ed in significant reduction in pregnancy complications with concomitant improved neonatal outcome , with no serious deleterious side effects AIMS To evaluate the effect of metformin and insulin in glycemic control and compare pregnancy outcome in women with gestational diabetes mellitus ( GDM ) . METHODS This r and omized controlled trial was conducted in GDM women with singleton pregnancy and gestational age between 20 and 34 weeks who did not achieve glycemic control on diet were assigned r and omly to receive either metformin ( n=80 ) or insulin ( n=80 ) . The primary outcomes were maternal glycemic control and birth weight . The secondary outcomes were neonatal and obstetric complications . RESULTS Two groups were comparable regarding the maternal characteristics . Two groups were similar in mean FBS ( P=0.68 ) and postpr and ial measurements ( P=0.87 ) throughout GDM treatment . The neonates of metformin group had less rate of birth weight centile > 90 than insulin group ( RR : 0.5 , 95 % CI : 0.3 - 0.9 , P=0.012 ) . Maternal weight gain was reduced in the metformin group ( P<0.001 ) . Two groups were comparable according to neonatal and obstetric complications ( P>0.05 ) . In metformin group 14 % of women needed to supplemental insulin to achieve euglycemia . CONCLUSION Metformin is an effective and safe alternative treatment to insulin for women with GDM . This study does not show significant risk of maternal or neonatal adverse outcome with the use of metformin OBJECTIVE To compare the use of metformin with that of insulin for the treatment of gestational diabetes mellitus ( GDM ) and type 2 diabetes mellitus ( T2DM ) unresponsive to diet therapy . MATERIAL S AND METHODS In this prospect i ve observational study , maternal  glycemic control and perinatal outcome in diabetic pregnancies were compared between 2 obstetric units , one using insulin therapy and the other using metformin therapy . Baseline pretreatment glycemic profile was done and then repeated weekly throughout pregnancy . The outcome measures studied were glycemic control , maternal complications and perinatal outcome . RESULTS Sixty women with gestational and type 2 diabetes were enrolled , 30 each for metformin and insulin .  Both groups were comparable with respect to age , body mass index ( BMI ) , parity and pretreatment plasma glucose levels . Glycemic control was better with metformin after 1 week of therapy and also throughout gestation ( P = 0.03 - 0.007 ) . There were no major complications or perinatal deaths in this study . Mean gestational age and birth weight ( 2.9 + /- 0.4 kg versus 3.1 + /- 0.4 kg , P = 0.30 ) were comparable . However , there was a significant increase in neonatal intensive care unit ( NICU ) admission and stay for babies born in the insulin group . The cost of treatment was tenfold higher in thethe insulin group . CONCLUSION Metformin is clinical ly effective , cheap and a safe alternative to insulin therapy in pregnant diabetic women Objectives : To inform on Teratology Information Services ( TIS ) in Europe , their history , function and activity in preventing congenital malformations . Conclusions : Clinical teratology tries to identify human teratogens . TIS play an important role in public health by providing counsel on known reproductive risks and conducting specific research . This has led to a reduction in unnecessary fears of pregnant women and pregnancy terminations , as well as to better , more appropriate drug selection to treat acute or chronic disease . In addition , TIS units also conduct prospect i ve studies and inform the public and physicians of the possible effects of environmental agents on the developing embryo and fetus OBJECTIVE 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 . DESIGN R and omized , double-blind , placebo-controlled trial . SETTING Multicenter environment . PATIENT(S ) Anovulatory women with the polycystic ovary syndrome ( PCOS ) who were resistant to CC . INTERVENTION(S ) 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 . MAIN OUTCOME MEASURE(S ) Ovulation and pregnancy rates . RESULT ( S ) 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 . CONCLUSION ( S ) In anovulatory women with PCOS who are resistant to CC , metformin use significantly increased the ovulation rate and pregnancy rate from CC treatment 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 OBJECTIVE To compare the safety and tolerability of metformin to insulin for glycemic control among women with preexisting type 2 and early A2 gestational diabetes . STUDY DESIGN Women with preexisting type 2 diabetes and those diagnosed with gestational diabetes who required medical management prior to 20 weeks were r and omly assigned to metformin or insulin . Glycemic control , defined as > 50 % capillary blood glucose within target range , was compared between groups . Other outcomes included patient tolerance , neonatal and obstetric complications , maternal weight gain , neonatal cord blood C-peptide , and patient satisfaction with therapy . RESULTS Twenty-eight women completed the study , with 14 in each group . Of the 15 women assigned to metformin , 100 % continued to receive metformin until delivery , although 43 % required supplemental insulin to achieve glycemic control . Glucose measures did not differ between the groups , and the proportion who met fasting and postpr and ial glycemic target values did not differ between the groups . Women treated with metformin had significantly fewer subjective episodes of hypoglycemia compared with those using insulin ( 0 % versus 36 % ; p = 0.04 ) as well as reported glucose values < 60 mg/dL ( 7.1 % versus 50 % ; p = 0.03 ) . CONCLUSION Metformin should be considered for treatment of overt diabetes and early A2 gestational diabetes in pregnancy 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 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 prospect ively design ed 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 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 r and omized 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 r and omized 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 BACKGROUND In a prospect i ve observational study of 42 pregnancies in 39 Caucasian women ( age 30 + /- 4 years ) with polycystic ovary syndrome ( PCOS ) , we examined effects of metformin on maternal insulin , insulin resistance ( IR ) , insulin secretion ( IS ) , weight gain , development of gestational diabetes ( GD ) , testosterone and plasminogen activator inhibitor activity . We assessed the hypothesis that diet-metformin ( MET ) lessens the physiological gestational increase in IR and reduces gestational weight gain , thus reducing GD . METHODS Preconception , in an out-patient clinical research centre , MET 1.5 ( eight pregnancies ) to 2.55 g/day ( 34 pregnancies ) was started . Women with body mass index < 25 or > or=25 kg/m(2 ) were given a 2000 or 1500 calorie/day , high-protein ( 26 % of calories ) , low-carbohydrate ( 44 % ) diet . Calorie restrictions were dropped after conception . RESULTS On MET , GD developed in three out of 42 pregnancies ( 7.1 % ) . Median entry weight ( 94.5 kg ) fell to 82.7 on MET at the last preconception visit ( P = 0.0001 ) , fell further to 81.6 during the first trimester , was 83.6 in the second trimester , and 89.1 kg in the third trimester . Median weight gain during pregnancy was 3.5 kg . The median percentage reduction in serum insulin was 40 % on MET at the last preconception visit ; insulin did not increase in the first or second trimesters ( P > 0.05 ) , and rose 10 % in the third trimester . The median percentage reduction in HOMA IR was 46 % on MET at the last preconception visit ; IR did not increase ( P > 0.05 ) in the first , second or third trimesters . HOMA insulin secretion fell 45 % on MET at the last preconception visit , did not increase in the first trimester , rose 24 % in the second trimester , and rose 109 % in the third trimester . Testosterone fell 30 % on MET at the last preconception visit ( P = 0.01 ) and then rose 74 , 61 and 95 % during trimesters 1 , 2 and 3 ; median testosterone during the third trimester did not differ from pre-treatment levels . CONCLUSIONS By reducing preconception weight , insulin , IR , insulin secretion and testosterone , and by maintaining these insulin-sensitizing effects throughout pregnancy , MET-diet reduces the likelihood of developing GD , and prevents and rogen excess for the fetus OBJECTIVE To evaluate glycemic control in women receiving metformin or insulin for gestational diabetes , and to identify factors predicting the need for supplemental insulin in women initially treated with metformin . STUDY DESIGN Women with gestational diabetes who failed to achieve glycemic control with diet and exercise were r and omized to receive metformin ( n = 47 ) or insulin ( n = 47 ) . Criteria for inclusion were singleton pregnancy , diet , and exercise for a minimum period of 1 week without satisfactory glycemic control , absence of risk factors for lactic acidosis , and absence of anatomic and /or chromosome anomalies of the conceptus . Patients who were lost to prenatal follow-up were excluded . RESULTS Comparison of mean pretreatment glucose levels showed no significant difference between groups ( P = .790 ) . After introduction of the drug , lower mean glucose levels were observed in the metformin group ( P = .020 ) , mainly because of lower levels after dinner ( P = .042 ) . Women using metformin presented less weight gain ( P = .002 ) and a lower frequency of neonatal hypoglycemia ( P = .032 ) . Twelve women in the metformin group ( 26.08 % ) required supplemental insulin for glycemic control . Early gestational age at diagnosis ( odds ratio , 0.71 ; 95 % confidence interval , 0.52 - 0.97 ; P = .032 ) and mean pretreatment glucose level ( odds ratio , 1.061 ; 95 % confidence interval , 1.001 - 1.124 ; P = .046 ) were identified as predictors of the need for insulin . CONCLUSION Metformin was found to provide adequate glycemic control with lower mean glucose levels throughout the day , less weight gain and a lower frequency of neonatal hypoglycemia . Logistic regression analysis showed that gestational age at diagnosis and mean pretreatment glucose level were predictors of the need for supplemental insulin therapy in women initially treated with metformin OBJECTIVE To test whether metformin administration reduces the incidence of ovarian hyperstimulation syndrome ( OHSS ) in infertile high-risk patients with polycystic ovary syndrome ( PCOS ) who have been treated with gonadotropins for IVF . DESIGN Parallel , r and omized , double-blind , placebo-controlled clinical trial . SETTING Academic departments , general hospital , and IVF centers . PATIENT(S ) One hundred twenty patients with PCOS at high risk for OHSS . INTERVENTION(S ) Gonadotropins ovarian stimulation for IVF and metformin ( 500 mg three times daily ) or placebo tablets ( three times daily ) . MAIN OUTCOME MEASURE(S ) The primary end point of the current clinical trial was the rate of OHSS . Anthropometric and reproductive data were evaluated . RESULT ( S ) The total OHSS and cancellation rates were significantly reduced in patients treated with metformin . The relative risk for OHSS was of 0.28 ( 95 % confidence interval , 0.11 - 0.67 ) . With metformin the stimulation length and the total amount of gonadotropins used were significantly increased , whereas the peak E(2 ) levels were significantly reduced . CONCLUSION ( S ) In patients with PCOS who are at high risk for OHSS and who have been stimulated with gonadotropins for IVF cycles , metformin reduces the risk of OHSS by modulating the ovarian response to the stimulation . REGISTRATION ID NUMBER FROM CLINICAL TRIALS.GOV : NCT01233206 OBJECTIVE The purpose of this study was to compare the effectiveness of laparoscopic ovarian diathermy ( LOD ) vs clomiphene citrate ( CC ) plus metformin in infertile patients with CC-resistant polycystic ovary syndrome ( PCOS ) . STUDY DESIGN Fifty primary infertile patients with CC-resistant PCOS were assigned r and omly to receive LOD followed by a 6-month observation ( group A ) or 6-cycle course of CC plus metformin ( group B ) . Reproductive and safety outcomes were analyzed . RESULTS No significant difference between 2 groups in pregnancy ( 15/92 women [ 16.3 % ] vs 14/107 women [ 13.1 % ] ; P = .521 ) and live-birth ( 13/92 women [ 14.1 % ] vs 12/107 women [ 11.2 % ] ; P = .536 ) rates per cycle was observed . With the use of a Cox regression analysis , patients under medical treatment , compared with patients who received surgical treatment , had a relative risk of pregnancy of 1.2 ( 95 % confidence interval , 0.61 - 2.44 ; P = .582 ) and a relative risk of live-birth of 1.4 ( 95 % confidence interval , 0.63 - 2.96 ; P = .425 ) . CONCLUSION LOD and CC plus metformin seem to be 2 effective approaches to treat infertility in patients with CC-resistant PCOS Polycystic ovary syndrome ( PCOS ) , thrombophilia , and hypofibrinolysis are associated with recurrent pregnancy loss ( RPL ) and spontaneous abortion ( SAB ) .  In 28 Caucasian women , 21 women with PCOS ( 4 with previous thrombosis , 18 with 1 SAB or more , and 20 with 1 coagulation disorder or more ) , and 7 women with coagulation disorders-thrombi , we speculated that prospect i ve treatment with enoxaparin-metformin or enoxaparin alone would successfully and safely promote healthy live births compared with previous untreated pregnancies . In 21 women with PCOS , metformin ( 1.5 - 2.55 g/day ) was given before and during pregnancy with concurrent enoxaparin ( 60 mg/day ) . Of 21 PCOS women , 19 women had 40 previous untreated pregnancies , 7 had live births ( 18 % ) , 3 had elective abortions ( ABs ) ( 8 % ) , and 30 had SABs ( 75 % ) . On enoxaparin-metformin , these 19 women had 24 pregnancies , 20 live births ( 83 % ) , and 4 SABs ( 17 % ) ; the SAB rate was 4.4-fold lower than previous untreated pregnancies ( McNemar 's s = 20.8 , P < 0 . 0001 ) . Two women with PCOS without previous pregnancies , but with previous thrombosis , had 2 pregnancies on enoxaparin-metformin and 2 live births . Of the 7 women with coagulation disorders-thrombi , 4 had 15 previous pregnancies without enoxaparin , with 6 live births ( 40 % ) , 8 SABs ( 53 % ) , and 1 elective AB ( 7 % ) . On enoxaparin , these 4 women had 4 pregnancies , with 4 ( 100 % ) live births ( McNemar 's s = 8.0 , P = 0.005 ) . The other 3 women with coagulation disorders-thrombi had 4 pregnancies on enoxaparin with 4 live births . No adverse maternal-fetal side effects were reported on enoxaparin alone or enoxaparin-metformin . Enoxaparin-metformin reduces pregnancy loss in women with PCOS-coagulation disorders and in women with coagulation disorders-thrombi AIMS To compare maternal and neonatal outcomes in women with gestational diabetes treated with diet , metformin and /or insulin  in routine clinical practice in a single centre . METHODS We analysed prospect ively collected data from the National Women 's Health data base for all women with gestational diabetes who delivered between January 2007 and December 2009 . Since June 2007 , women requiring medication have been given a choice of either metformin or insulin treatment , except women with a fetal abdominal circumference less than the 10th percentile , who were not offered metformin . RESULTS There were 1269 women with gestational diabetes ; treatment was diet  in 371 , insulin in 399 and metformin in 465 ( 249 metformin alone , 216 metformin and insulin ) . Women treated with metformin and /or insulin had significantly higher BMI s compared with those in the diet group ( P < 0.001 ) and had a higher fasting glucose at diagnosis ( p < 0.001 ) . Women treated with insulin had higher rates of Caesarean delivery ( 45.6 % insulin , 37 % metformin , 34 % diet , P = 0.02 ) than women treated with metformin or diet . They also had higher rates of preterm births ( 19.2 % insulin , 12.5 % metformin , 12.1 % diet , P = 0.005 ) , customized large-for-gestational-age infants ( 18.5 % insulin , 12.5 % metformin , 12.4 % diet , P = 0.02 ) , neonatal admissions ( 18.7 % insulin , 12.7 % metformin , 14.0 % diet , P = 0.04 ) and neonatal intravenous dextrose use ( 11.1 % insulin , 5.1 % metformin , 7.4 % diet , P = 0.004 ) . Neonatal outcomes were similar between diet- and metformin-treated women . CONCLUSIONS In routine practice , use of metformin in gestational diabetes was associated with fewer adverse outcomes compared with insulin , but baseline differences between treatment groups may have contributed to this
BACKGROUND Metformin is generally considered a non-teratogenic drug ; however , only a few studies specifically design ed to assess the rate of congenital anomalies after metformin use have been published in the literature .
The objects of the present study were to review all of the prospect i ve and retrospective studies reporting on women treated with metformin at least during the first trimester of their pregnancy and to estimate the overall rate of major birth defects .