Congenital malformations in pregnancies complicated by NIDDM. Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome. Metformin therapy throughout pregnancy reduces the development of gestational diabetes in women with polycystic ovary syndrome. Pregnancy outcomes among women with polycystic ovary syndrome treated with metformin. Co-administration of metformin during rFSH treatment in patients with clomiphene citrate-resistant polycystic ovarian syndrome: a prospective randomized trial. Metformin therapy improves ovulatory rates, cervical scores, and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome. 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. Effects of in-utero exposure to oral hypoglycaemic drugs Troglitazone improves ovulation and hirsutism in the polycystic ovary syndrome: a multicenter, double blind, placebo-controlled trial. Metformin does not enhance ovulation induction in clomiphene resistant polycystic ovary syndrome in clinical practice. High serum luteinizing hormone and testosterone concentrations do not predict pregnancy outcome in women with recurrent miscarriage. Metformin increases the ovulatory rate and pregnancy rate from clomiphene citrate in patients with polycystic ovary syndrome who are resistant to clomiphene citrate alone. The effect of metformin plus clomiphene citrate on ovulation and pregnancy rates in clomiphene-resistant women with polycystic ovary syndrome. Polycystic ovaries and recurrent miscarriage--a reappraisal.
OBJECTIVE To determine whether the use of oral hypoglycemic agents during early pregnancy is associated with a risk of congenital malformations in infants of mothers with non-insulin-dependent diabetes mellitus ( NIDDM ) independent of maternal metabolic control . RESEARCH DESIGN AND METHODS From a prospect ively collected data -base of pregnancies complicated by diabetes at a large urban medical center , we identified 332 consecutive infants born to women with NIDDM who did not participate in a preconceptional diabetes care program . Stepwise logistical regression was used to identify maternal characteristics that were independently associated with risks of major and minor congenital malformations in infants . RESULTS Overall , 56 ( 16.9 % ) of the 332 infants were born with congenital anomalies ( 11.7 % major anomalies and 5.1 % minor anomalies ) . Analysis of data from subgroups of women who were treated with diet therapy , exogenous insulin , or sulfonylurea compounds during the first 8 weeks of gestation did not reveal statistically significant differences in major or minor malformation rates among the three groups . Stepwise logistic regression analysis revealed two maternal characteristics that were independently associated with major malformations in infants : maternal HbA1c at initial presentation for care ( direct relationship ; P = 0.0007 ) and the maternal age at onset of diabetes ( inverse relationship ; P = 0.009 ) . The risk of major malformations was unrelated to the mode of antidiabetic therapy during early pregnancy . No relationship was found between maternal glycemia or treatment modality and rates of minor congenital anomalies . CONCLUSIONS These data indicate that , in the absence of special preconceptional care , NIDDM is associated with a risk for major congenital anomalies that is in the range reported for pregnancies complicated by insulin-dependent diabetes mellitus . Moreover , the risk in individual patients appears to be related to maternal glycemic control rather than to the mode of antidiabetic therapy during early pregnancy BACKGROUND Obese women with the polycystic ovary syndrome are relatively unresponsive to the induction of ovulation by clomiphene . We hypothesized that reducing insulin secretion by administering metformin would increase the ovulatory response to clomiphene . METHODS We performed oral glucose-tolerance tests before and after the administration of 500 mg of metformin or placebo three times daily for 35 days in 61 obese women with the polycystic ovary syndrome . Women who did not ovulate spontaneously were then given 50 mg of clomiphene daily for five days while continuing to take metformin or placebo .  Serum progesterone was measured on days 14 , 28 , 35 , 44 , and 53 , and ovulation was presumed to have occurred if the concentration exceeded 8 ng per milliliter ( 26 nmol per liter ) on any of these days . RESULTS Twenty-one women in the metformin group and 25 women in the placebo group were given clomiphene because they did not ovulate spontaneously during the first phase of the study . Among the 21 women given metformin plus clomiphene , the mean ( + /-SE ) area under the serum insulin curve after oral glucose administration decreased from 6745+/-2021 to 3479+/-455 microU per milliliter per minute ( 40.5+/-12.1 to 20.9+/-2.7 nmol per liter per minute , P=0.03 ) , but it did not change significantly in the 25 women given placebo plus clomiphene . Nineteen of the 21 women ( 90 percent ) who received metformin plus clomiphene  ovulated ( mean peak serum progesterone concentration , 23.8+/-3.4 ng per milliliter [ 7.6+/-10.9 nmol per liter ] ) . Two of the 25 women ( 8 percent ) who received placebo plus clomiphene  ovulated ( P<0.001 ) . Overall , 31 of the 35 women ( 89 percent ) treated with metformin  ovulated spontaneously or in response to clomiphene  , as compared with 3 of the 26 women ( 12 percent ) treated with placebo . CONCLUSIONS The ovulatory response to clomiphene can be increased in obese women with the polycystic ovary syndrome by decreasing insulin secretion with metformin OBJECTIVE To assess whether metformin safely reduced development of gestational diabetes in women with the polycystic ovary syndrome ( PCOS ) . DESIGN Prospect i ve and retrospective study . SETTING Outpatient clinical research center . PATIENT(S ) The prospect i ve study included 33 nondiabetic women with PCOS who conceived while taking metformin and had live births ; of these , 28 were taking metformin through delivery . The retrospective study included 39 nondiabetic women with PCOS who had live birth pregnancies without metformin therapy .  INTERVENTION(S ) Metformin , 2.55 g/d , throughout pregnancy in women with PCOS . MAIN OUTCOME MEASURE(S ) Development of gestational diabetes in women with PCOS . RESULT ( S ) Before metformin therapy , after covariance adjustment for age , the two cohorts did not differ in height , weight , basal metabolic index , insulin , insulin resistance , or insulin secretion . Both cohorts had high fasting insulin , were insulin resistant , and had high insulin secretion . Among the 33 women who received metformin  , gestational diabetes developed in 1 of 33 ( 3 % ) pregnancies versus 8 of 12 ( 67 % ) of their previous pregnancies without metformin . Among the 39 women who did not take metformin  , gestational diabetes developed in 14 of 60 ( 23 % ) pregnancies . When all live births were combined , gestational diabetes occurred in 22 of 72 pregnancies ( 31 % ) in women who did not take metformin versus 1 of 33 pregnancies ( 3 % ) in those who took metformin . With gestational diabetes as the response variable and age at delivery and treatment group ( metformin or no metformin ) as explanatory variables , the odds ratio for gestational diabetes in women with metformin versus without metformin was 0.093 ( 95 % CI : 0.011 to 0.795 ) . With gestational diabetes in 93 pregnancies as the response variable and age at delivery and treatment group ( metformin no metformin ) as explanatory variables , the odds ratio of gestational diabetes in pregnancies in women taking metformin versus without metformin was 0.115 ( 95 % CI : 0.014 to 0.938 ) . CONCLUSION ( S ) In PCOS , use of metformin is associated with a 10-fold reduction in gestational diabetes ( 31 % to 3 % ) . It also reduces insulin resistance and insulin secretion , thus decreasing the secretory dem and s imposed on pancreatic beta-cells by insulin resistance and pregnancy 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 This study aims to evaluate the impact of metformin on ovarian response when co-administered during recombinant (r)FSH using the low-dose step-up protocol in clomiphene citrate-resistant polycystic ovarian syndrome ( PCOS ) patients with normal glucose tolerance . METHODS AND RESULTS Thirty-two patients were r and omized to metformin  ( n = 16 ) and placebo  ( n = 16 ) groups . Hormonal assessment , a 75 g oral glucose tolerance test ( OGTT ) and a frequently sample d i.v . glucose tolerance test ( FSIGTT ) were performed before and after oral administration of metformin ( 850 mg twice daily ) or placebo for 6 weeks . Recombinant FSH treatment was undertaken , thereafter , in women who did not ovulate on metformin ( n = 10 ) or placebo ( n = 15 ) . There was no significant change in all insulin sensitivity indices in both groups . The only change noted was a decline in mean serum free testosterone concentration in the metformin group ( P = 0.049 ) . One patient on placebo and six patients on metformin  ovulated spontaneously ( P < 0.05 ) . All parameters of ovarian response were comparable between the two groups during rFSH treatment . Combining the 6 week placebo or metformin-only period with a single rFSH treatment cycle , the overall ovulation rates were 75 and 94 % in the placebo and metformin groups respectively ( P > 0.05 ) . The respective figures for pregnancy were 6.3 and 31.3 % ( P > 0.05 ) . CONCLUSIONS Metformin may restore ovulation with no improvement on insulin resistance in clomiphene citrate-resistant PCOS patients with normal glucose tolerance , but has no significant effect on ovarian response during rFSH treatment OBJECTIVE To evaluate the effect of metformin therapy on hyper and rogenism , insulin resistance , cervical scores , ovulation , and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome ( PCOS ) . DESIGN Prospect i ve , r and omized , double-blind , placebo-controlled study . SETTING Infertility clinic of a tertiary referral center . PATIENT(S ) Fifty-six women with clomiphene citrate-resistant PCOS . INTERVENTION(S ) Two cycles of oral metformin therapy ( 850 mg , twice daily ) in group I and placebo therapy ( twice daily ) in group II . Clomiphene citrate ( 100 mg/day ) on cycle days 3 - 7 of the second cycle in both groups . MAIN OUTCOME MEASURE(S ) Insulin , T , DHEAS , FSH , LH , body mass index ( BMI ) , waist-to-hip ratio , endometrial thickness , cervical score , ovulation , and pregnancy rates in clomiphene-induced cycles after metformin therapy . RESULT ( S ) Metformin therapy result ed in a significant decrease in total T , LH level , LH/FSH ratio , insulin resistance , and mean BMI . No difference in waist-to-hip ratio , DHEAS level , and fasting insulin level was observed . Clomiphene citrate induction result ed in higher ovulation rates and thicker endometrium in the metformin group than in the placebo group . There was higher cumulative pregnancy rate in the metformin group ; however , there was no significant difference in the pregnancy rate between the two groups . CONCLUSION ( S ) Metformin therapy not only decreases hyper and rogenism and insulin resistance but also improves ovulation rates , cervical scores , and pregnancy rates in clomiphene citrate-resistant women with PCOS 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 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 We hypothesized that the administration of troglitazone , an insulin-sensitizing agent of the thiazolidinedione class , would improve the ovulatory dysfunction ,  hirsutism  , hyper and rogenemia , and hyperinsulinemia of polycystic ovary syndrome ( PCOS ) patients . Four hundred and ten premenopausal women with PCOS in a multicenter , double blind trial were r and omly assigned to 44 weeks of treatment with placebo ( PBO ) or troglitazone [ 150 mg/day ( TGZ-150 ) , 300 mg/day ( TGZ-300 ) , or 600 mg/day ( TGZ-600 ) ] . We compared changes in ovulatory function ( by monitoring the urinary level of pregnanediol-3-glucuronide daily ) , hirsutism ( by a modified Ferriman-Gallwey scoring method ) , hormonal levels ( total and free testosterone , and rostenedione , sex hormone-binding globulin , LH , FSH , and the LH/FSH ratio ) , and measures of glycemic parameters ( fasting levels of glucose , insulin , hemoglobin A(1c ) , and the glucose and insulin areas under the curve during an oral glucose challenge ) among study groups . Of the 410 patients recruited , 305 ( 74.4 % ) met evaluability criteria and were included in the analyses . The patients ' baseline characteristics were similar across all treatment arms . Ovulatory rates were significantly greater for patients receiving TGZ-300 and TGZ-600 than for those receiving PBO ( 0.42 and 0.58 vs. 0.32 ; P < 0.05 and 0.0001 , respectively ) . Of PCOS patients treated with TGZ-600 , 57 % ovulated over 50 % of the time compared with 12 % of placebo-treated patients . There was a significant decrease in the Ferriman-Gallwey score with TGZ-600 compared with PBO ( 0.22 + /- 0.53 vs. -2.21 + /- 0.49 ; P < 0.05 , respectively ) . Free testosterone decreased and sex hormone-binding globulin increased in a dose-related fashion with troglitazone treatment , and all three troglitazone treatment groups were significantly different from placebo . Nearly all glycemic parameters showed dose-related decreases with troglitazone treatment . The total number and severity of adverse events ( including elevations in liver enzymes ) and the proportion of patients withdrawn from the study due to the development of adverse effects were similar between treatment groups . Troglitazone improves the ovulatory dysfunction , hirsutism , hyper and rogenemia , and insulin resistance of PCOS  in a dose-related fashion , with a minimum of adverse effects AIMS To determine whether metformin pretreatment has beneficial effects in clomiphene resistant infertile women with polycystic ovary syndrome ( PCOS ) in an infertility clinic . METHODS This was a r and omized placebo controlled double-blind crossover study of 3 months metformin ( 1500 mg day-1)/placebo , followed by 3 months metformin/placebo together with clomiphene ( 50 - 100 mg for 5 days ) for three cycles in clomiphene resistant women with PCOS . The primary outcomes were restoration of spontaneous menses , ovulation induction ( spontaneous or clomiphene induced ) and pregnancy . Secondary endpoints were changes in biochemical parameters related to and rogens and insulin . RESULTS Twelve women completed the metformin arm and 14 the placebo arm .  Spontaneous menstruation resumed in five metformin treated patients and in six placebo treated women , P=0.63 . No women given metformin  spontaneously ovulated , although one patient given placebo did , P=0.30 . There was no difference in the efficacy of clomiphene  between the two groups with ovulation being induced in five ( out of 12 ) metformin treated women and four ( out of 14 ) placebo treated women , P=0.63 . Pregnancy occurred in three ( out of 12 ) women given metformin and two ( out of 14 ) women given placebo , P=0.59 . CONCLUSIONS Metformin is not always beneficial when given to clomiphene resistant infertile women with PCOS in clinical practice OBJECTIVE To investigate the relationship between Day 8 serum luteinizing hormone ( LH ) and testosterone ( T ) concentrations , and body mass index ( BMI ) with pregnancy outcome in women with recurrent miscarriage . DESIGN Prospect i ve observational study . SETTING National recurrent miscarriage clinic . PATIENT(S ) Three hundred forty-four women ( median age 32 years ; range 18 - 44 ) with a history of recurrent first trimester miscarriage ( median 4 ; 3 - 14 ; < 12 weeks gestation ) who conceived spontaneously and who received no pharmacological treatment during pregnancy were studied . All women were antiphospholipid antibody negative and had a normal peripheral karyotype as did their partners . INTERVENTION(S ) Outcome of untreated pregnancies . MAIN OUTCOME MEASURE(S ) Day 8 serum LH and T concentrations and BMI were correlated with pregnancy outcome . RESULT ( S ) One hundred and ninety-two ( 55.8 % ) women had a live birth and 152 ( 44.2 % ) women miscarried .  Polycystic ovarian morphology was diagnosed in 174 women ( 50.6 % ) . There was no significant relationship between follicular phase LH concentrations and pregnancy outcome . Pregnancy outcome was similar in women with normal and high serum T concentrations . BMI value was not significantly different between women who had a live birth and those who miscarried . CONCLUSION ( S ) The analysis of this large cohort of women with recurrent miscarriage demonstrates that prepregnancy Day 8 serum LH and T concentrations , and BMI do not have a statistically significant relationship with pregnancy outcome 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 OBJECTIVE To study the effect of metformin in combination with clomiphene citrate , as compared with placebo plus clomiphene citrate , on the ovulation and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome . METHODS This study was carried out at King Hussein Medical Center , Amman , Jordan , during the period January 2001 through to July 2001 . Twenty-eight clomiphene citrate-resistant polycystic ovary syndrome women were evaluated prospect ively for 6 treatment cycles by receiving metformin , 850 mg twice daily throughout the cycle along with 50 mg clomiphene citrate , starting on day 5 - 9 of the same cycle ( N=16 ) , or by taking placebo with clomiphene citrate ( N=12 ) . During cycles 2 - 6 , clomiphene citrate was added with increments of 50 mg ( up to 200 mg/day ) for both groups . Progesterone level on day 21 and 28 > 5ng/dl was indicative of ovulation . RESULTS A statistically significant increase in the rates of ovulation ( 68.6 % versus 25 % , p<0.05 ) and pregnancy ( 56.3 % versus 16.6 % , p<0.05 ) were observed in the metformin-clomiphene citrate group as compared with the placebo-clomiphene citrate controls . Insignificant increase in the rate of ovarian hyperstimulation was noted in the placebo-clomiphene citrate group . CONCLUSION Metformin-clomiphene citrate regimen in resistant-clomiphene citrate polycystic ovary syndrome women significantly increases the ovulation and pregnancy rates , and decreases the occurrence of ovarian hyperstimulation syndrome The prevalence of polycystic ovaries ( PCO ) was established amongst 2199 consecutive women ( median age 33 years ; range 19 - 46 ) with a history of recurrent miscarriage ( median 3 ; 3 - 14 ) . A diagnosis of PCO was made if the ovarian volume was enlarged ( > 9 ml ) , there were > /=10 cysts of 2 - 8 mm in diameter in one plane and there was increased density of the stroma . In a cohort study , the prospect i ve  pregnancy  outcome of 486 of the women scanned who were antiphospholipid antibody negative and who received no pharmacological treatment during their next pregnancy was studied . The prevalence of PCO was 40.7 % ( 895/2199 ) . The livebirth rate was similar amongst women with PCO ( 60.9 % ; 142/233 ) compared to that amongst women with normal ovarian morphology ( 58.5 % ; 148/253 ; not significant ) . Neither an elevated serum luteinizing hormone concentration ( > 10 IU/l ) nor an elevated serum testosterone concentration ( > 3 nmol/l ) was associated with an increased miscarriage rate . Polycystic ovarian morphology is not predictive of pregnancy loss amongst ovulatory women with recurrent miscarriage conceiving spontaneously . The search for a specific endocrine abnormality that can divide women with PCO into those with a good and those with a poorer prognosis for a future successful pregnancy continues
PURPOSE OF REVIEW The use of insulin sensitizing drugs such as metformin in polycystic ovary syndrome has been increasingly popular and vali date d by systematic review s. There has also been an interest in the use of metformin for gestational diabetes .
However , administration of metformin to prevent miscarriage is controversial and widespread use of this drug in early pregnancy requires investigation .
RECENT FINDINGS There are cl aims that miscarriage and gestational diabetes are more common in polycystic ovary syndrome and that use of insulin sensitizers improves outcomes dramatically .