human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE : To evaluate whether myo-inositol supplementation , an insulin sensitizer , reduces the rate of gestational diabetes mellitus ( GDM ) and lowers insulin resistance in obese pregnant women . METHODS : In an open-label , r and omized trial , myo-inositol ( 2 g plus 200 micrograms folic acid twice a day ) or placebo ( 200 micrograms folic acid twice a day ) was administered from the first trimester to delivery in pregnant obese women ( prepregnancy body mass index 30 or greater . We calculated that 101 women in each arm would be required to demonstrate a 65 % GDM reduction in the  myo-inositol  group with a statistical power of 80 % ( & agr;=0.05 ) . The primary outcomes were the incidence of GDM and the change in insulin resistance from enrollment until the diagnostic oral glucose tolerance test . RESULTS : From January 2011 to April 2014 , 220 pregnant women at 12–13 weeks of gestation were r and omized at two Italian university hospitals , 110 to myo-inositol and 110 to placebo .  Most characteristics were similar between groups . The GDM rate was significantly reduced in the myo-inositol group compared with the control group , 14.0 % compared with 33.6 % , respectively ( P=.001 ; odds ratio 0.34 , 95 % confidence interval 0.17–0.68 ) . Furthermore , women treated with myo-inositol showed a significantly greater reduction in the homeostasis model assessment of insulin resistance compared with the control group , −1.0±3.1 compared with 0.1±1.8 ( P=.048 ) . CONCLUSION : Myo-inositol supplementation , started in the first trimester , in obese pregnant women seems to reduce the incidence in GDM through a reduction of insulin resistance . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT01047982 OBJECTIVE It was previously shown that higher concentrations of myo-inositol in human follicular fluid improve oocyte and embryo quality , whereas D-chiro-inositol seems to worsen oocyte quality and ovarian response in polycystic ovary syndrome patients . Our study was the first one aim ing to test whether different myo-inositol and D-chiro-inositol concentration in follicular fluids correlate with blastocyst quality in healthy young women . PATIENTS AND METHODS Eight egg donors and eleven couples undergoing in vitro fertilization , were involved in a prospect i ve observational study . Myo-inositol/D-chiro-inositol ratio was calculated in the follicular fluids and associated with different blastocyst grade s. Donors were homogeneous and followed the same st and ard stimulation protocol . RESULTS The ratio between myo-inositol and D-chiro-inositol was significantly higher in the specimens rated as good quality blastocysts , compared to those rated as poor- quality blastocysts . In this study , almost all the transferred blastocysts were grade d as good quality and were correlated to lower D-chiro-inositol content in the follicular fluid ; the implantation rate and pregnancy rate were satisfying . Our data suggest that the reduction of such ratio in follicular fluid seems to play a negative role in follicular development . CONCLUSIONS We found a correlation between myo-inositol/D-chiro-inositol ratio in follicular fluid and blastocyst quality . The value of this ratio may represent a new biomarker for estimating the good features of blastocysts , and a prognostic factor of embryo implantation and pregnancy success . Moreover , the pre-treatment with myo-inositol in women undergoing in vitro fertilization ( IVF ) may improve oocyte quality and ART outcome . CLINICAL TRIAL REGISTRATION NUMBER NCT03055442 ( Clinical Trials.gov registry ) CONTEXT Lifestyle modification is recommended in women with polycystic ovary syndrome ( PCOS ) prior to conception but there are few r and omized trials to support its implementation or benefit . OBJECTIVE This study aim ed to determine the relative efficacy of preconception intervention on reproductive and metabolic abnormalities in overweight/obese women with PCOS . DESIGN , SETTING , AND PARTICIPANTS This was a r and omized controlled trial of preconception and infertility treatment at Academic Health Centers in women with infertility due to PCOS , age 18 - 40 y and body mass index 27 - 42 kg/m(2 ) . INTERVENTION Women were r and omly assigned to receive either 16 weeks of 1 ) continuous oral contraceptive pills ( OCPs ) ( ethinyl estradiol 20 mcg/1 mg norethindrone acetate ) ( " OCP " ) ; 2 ) lifestyle modification consisting of caloric restriction with meal replacements , weight loss medication ( either sibutramine , or orlistat ) , and increased physical activity to promote a 7 % weight loss ( " Lifestyle " ) ; or 3 ) combined treatment with both OCP and lifestyle modification ( " Combined " ) . After preconception intervention , women underwent st and ardized ovulation induction with clomiphene citrate and timed intercourse for four cycles . Pregnancies were followed with trimester visits until delivery . MAIN OUTCOME MEASURES Weight , ovulation , and live birth were measured . RESULTS We consented 216 and r and omly assigned 149 women ( Lifestyle : n = 50 ; OCP : n = 49 ; Combined : n = 50 ) . We achieved significant weight loss with both Lifestyle ( mean weight loss , -6.2 % ; 95 % confidence interval ( CI ) , -7.4 - -5.0 ; and Combined ( mean weight loss , -6.4 % ; 95 % CI , -7.6 - -5.2 ) compared with baseline and OCP ( both P < .001 ) . There was a significant increase in the prevalence of metabolic syndrome at the end of preconception treatment compared with baseline within OCP ( odds ratio [ OR , 2.47 ; 95 % CI , 1.42 - 4.27 ) whereas no change in metabolic syndrome was detected in the Lifestyle ( OR , 1.18 ; 95 % CI , 0.63 - 2.19 ) or Combined ( OR , 0.72 ; 95 % CI , 0.44 - 1.17 ) groups . Cumulative ovulation rates were superior after weight loss : OCP , 46 % ; Lifestyle , 60 % ; and Combined , 67 % ( P < .05 ) . Live birth rates were OCP , 12 % ; Lifestyle , 26 % ; and Combined , 24 % ( P = .13 ) . CONCLUSIONS A preconception weight loss intervention eliminates the adverse metabolic oral contraceptive effects and , compared with oral contraceptive pretreatment , leads to higher ovulation rates BACKGROUND Obese women with polycystic ovary syndrome ( PCOS ) manifest impaired insulin-stimulated release of a d-chiro-inositol-containing inositolphosphoglycan ( DCI-IPG ) insulin mediator during oral glucose tolerance testing ( OGTT ) , which appears to be restored by the administration of metformin . This suggests that either obesity or PCOS is associated with a defect in the coupling of the stimulation of the insulin receptor by insulin to the release of the DCI-IPG mediator . The objective of this study was to compare the release of bioactive DCI-IPG between normal nonobese women and obese PCOS women during stimulation with two different concentrations of insulin when glucose levels are clamped . METHODS We performed a cross-sectional case-control study at the clinical research center of an academic medical center . A two-step euglycemic-hyperinsulinemic clamp was carried out in 8 nonobese normal and 8 obese PCOS women , during which DCI-IPG bioactivity was monitored . RESULTS At baseline , PCOS women were significantly more obese , hyperinsulinemic , and insulin resistant than the controls . During the clamp studies , DCI-IPG bioactivity increased significantly over the first 45 min of the low-insulin step of the clamp in normal nonobese women ( P = 0.046 ) and then decreased to baseline levels ; DCI-IPG increased again after initiation of the high-insulin step ( P = 0.029 ) . Despite higher insulin levels during the clamp in PCOS women , DCI-IPG bioactivity remained flat throughout both insulin steps and was thus significantly lower than in controls during the initial periods of both steps . CONCLUSIONS The coupling between insulin action and the release of the DCI-IPG mediator is selectively impaired in obese PCOS women , which may contribute to the insulin resistance in these women OBJECTIVES Nuclear and cytoplasmic competence of human oocyte is critical for future competence of the embryo upon which ultimately depends the outcome of an ART ( Assisted Reproductive Technology ) treatment . Follicular microenvironment in which the oocyte develops is crucial , and this must be taken into account particularly with the use of hormonal ovarian stimulation protocol s. Inositol is an important element of the follicular environment and data support that its higher level in follicular fluid correlates with the development of a good oocyte . Aim of this study is to underst and the effects of treatment with inositol on oocyte quality in a sample of patients undergoing ICSI ( Intracytoplasmic Sperm Injection ) . PATIENTS AND METHODS Assessment of oocyte/embryo quality and pregnancy rates in 149 patients divided , according to a controlled r and omized pattern , into two groups : study group 1 treated with folic acid and inositol and control group 2 treated with folic acid alone . RESULTS The number of patients with excellent and good oocyte quality appears to be significantly higher in group 1 ( p = 0.02 ) , as shown , they significantly increased the number of embryos of grade A transferred in the group 1 ( p = 0.02 ) compared to group 2 , despite being completely similar averages of total embryos transferred ( total mean ± SD = 2.4 ± 0.8 , group 1 mean ± SD = 2.4 ± 0.8 , group 2 mean ± SD = 2.4 ± 0.8 ) . There is not any significant difference between groups 1 and 2 in the number of positivity to β-hCG and in the number of biochemical pregnancies detected although it has a tendency to increase in the first and to decrease in the second for group 1 . The increase in percentage of clinical pregnancies in group 1 was statistically significant ( p = 0.02 ) , whereas there was no apparent significance in the difference between the biochemical and clinical pregnancies in the two groups despite the positive trend in the study group . CONCLUSIONS Relying on " inositol help " to solidify our efforts , seems to be an easy path to help to deepen the effectiveness of its use in all patients still under 40 but with prior failed attempts at ICSI or diagnosed with PCOS or as " poor responders " 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE : To evaluate whether myo-inositol supplementation , an insulin sensitizer , reduces the rate of gestational diabetes mellitus ( GDM ) and lowers insulin resistance in obese pregnant women . METHODS : In an open-label , r and omized trial , myo-inositol ( 2 g plus 200 micrograms folic acid twice a day ) or placebo ( 200 micrograms folic acid twice a day ) was administered from the first trimester to delivery in pregnant obese women ( prepregnancy body mass index 30 or greater . We calculated that 101 women in each arm would be required to demonstrate a 65 % GDM reduction in the  myo-inositol  group with a statistical power of 80 % ( & agr;=0.05 ) . The primary outcomes were the incidence of GDM and the change in insulin resistance from enrollment until the diagnostic oral glucose tolerance test . RESULTS : From January 2011 to April 2014 , 220 pregnant women at 12–13 weeks of gestation were r and omized at two Italian university hospitals , 110 to myo-inositol and 110 to placebo .  Most characteristics were similar between groups . The GDM rate was significantly reduced in the myo-inositol group compared with the control group , 14.0 % compared with 33.6 % , respectively ( P=.001 ; odds ratio 0.34 , 95 % confidence interval 0.17–0.68 ) . Furthermore , women treated with myo-inositol showed a significantly greater reduction in the homeostasis model assessment of insulin resistance compared with the control group , −1.0±3.1 compared with 0.1±1.8 ( P=.048 ) . CONCLUSION : Myo-inositol supplementation , started in the first trimester , in obese pregnant women seems to reduce the incidence in GDM through a reduction of insulin resistance . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT01047982 OBJECTIVE It was previously shown that higher concentrations of myo-inositol in human follicular fluid improve oocyte and embryo quality , whereas D-chiro-inositol seems to worsen oocyte quality and ovarian response in polycystic ovary syndrome patients . Our study was the first one aim ing to test whether different myo-inositol and D-chiro-inositol concentration in follicular fluids correlate with blastocyst quality in healthy young women . PATIENTS AND METHODS Eight egg donors and eleven couples undergoing in vitro fertilization , were involved in a prospect i ve observational study . Myo-inositol/D-chiro-inositol ratio was calculated in the follicular fluids and associated with different blastocyst grade s. Donors were homogeneous and followed the same st and ard stimulation protocol . RESULTS The ratio between myo-inositol and D-chiro-inositol was significantly higher in the specimens rated as good quality blastocysts , compared to those rated as poor- quality blastocysts . In this study , almost all the transferred blastocysts were grade d as good quality and were correlated to lower D-chiro-inositol content in the follicular fluid ; the implantation rate and pregnancy rate were satisfying . Our data suggest that the reduction of such ratio in follicular fluid seems to play a negative role in follicular development . CONCLUSIONS We found a correlation between myo-inositol/D-chiro-inositol ratio in follicular fluid and blastocyst quality . The value of this ratio may represent a new biomarker for estimating the good features of blastocysts , and a prognostic factor of embryo implantation and pregnancy success . Moreover , the pre-treatment with myo-inositol in women undergoing in vitro fertilization ( IVF ) may improve oocyte quality and ART outcome . CLINICAL TRIAL REGISTRATION NUMBER NCT03055442 ( Clinical Trials.gov registry ) CONTEXT Lifestyle modification is recommended in women with polycystic ovary syndrome ( PCOS ) prior to conception but there are few r and omized trials to support its implementation or benefit . OBJECTIVE This study aim ed to determine the relative efficacy of preconception intervention on reproductive and metabolic abnormalities in overweight/obese women with PCOS . DESIGN , SETTING , AND PARTICIPANTS This was a r and omized controlled trial of preconception and infertility treatment at Academic Health Centers in women with infertility due to PCOS , age 18 - 40 y and body mass index 27 - 42 kg/m(2 ) . INTERVENTION Women were r and omly assigned to receive either 16 weeks of 1 ) continuous oral contraceptive pills ( OCPs ) ( ethinyl estradiol 20 mcg/1 mg norethindrone acetate ) ( " OCP " ) ; 2 ) lifestyle modification consisting of caloric restriction with meal replacements , weight loss medication ( either sibutramine , or orlistat ) , and increased physical activity to promote a 7 % weight loss ( " Lifestyle " ) ; or 3 ) combined treatment with both OCP and lifestyle modification ( " Combined " ) . After preconception intervention , women underwent st and ardized ovulation induction with clomiphene citrate and timed intercourse for four cycles . Pregnancies were followed with trimester visits until delivery . MAIN OUTCOME MEASURES Weight , ovulation , and live birth were measured . RESULTS We consented 216 and r and omly assigned 149 women ( Lifestyle : n = 50 ; OCP : n = 49 ; Combined : n = 50 ) . We achieved significant weight loss with both Lifestyle ( mean weight loss , -6.2 % ; 95 % confidence interval ( CI ) , -7.4 - -5.0 ; and Combined ( mean weight loss , -6.4 % ; 95 % CI , -7.6 - -5.2 ) compared with baseline and OCP ( both P < .001 ) . There was a significant increase in the prevalence of metabolic syndrome at the end of preconception treatment compared with baseline within OCP ( odds ratio [ OR , 2.47 ; 95 % CI , 1.42 - 4.27 ) whereas no change in metabolic syndrome was detected in the Lifestyle ( OR , 1.18 ; 95 % CI , 0.63 - 2.19 ) or Combined ( OR , 0.72 ; 95 % CI , 0.44 - 1.17 ) groups . Cumulative ovulation rates were superior after weight loss : OCP , 46 % ; Lifestyle , 60 % ; and Combined , 67 % ( P < .05 ) . Live birth rates were OCP , 12 % ; Lifestyle , 26 % ; and Combined , 24 % ( P = .13 ) . CONCLUSIONS A preconception weight loss intervention eliminates the adverse metabolic oral contraceptive effects and , compared with oral contraceptive pretreatment , leads to higher ovulation rates BACKGROUND Obese women with polycystic ovary syndrome ( PCOS ) manifest impaired insulin-stimulated release of a d-chiro-inositol-containing inositolphosphoglycan ( DCI-IPG ) insulin mediator during oral glucose tolerance testing ( OGTT ) , which appears to be restored by the administration of metformin . This suggests that either obesity or PCOS is associated with a defect in the coupling of the stimulation of the insulin receptor by insulin to the release of the DCI-IPG mediator . The objective of this study was to compare the release of bioactive DCI-IPG between normal nonobese women and obese PCOS women during stimulation with two different concentrations of insulin when glucose levels are clamped . METHODS We performed a cross-sectional case-control study at the clinical research center of an academic medical center . A two-step euglycemic-hyperinsulinemic clamp was carried out in 8 nonobese normal and 8 obese PCOS women , during which DCI-IPG bioactivity was monitored . RESULTS At baseline , PCOS women were significantly more obese , hyperinsulinemic , and insulin resistant than the controls . During the clamp studies , DCI-IPG bioactivity increased significantly over the first 45 min of the low-insulin step of the clamp in normal nonobese women ( P = 0.046 ) and then decreased to baseline levels ; DCI-IPG increased again after initiation of the high-insulin step ( P = 0.029 ) . Despite higher insulin levels during the clamp in PCOS women , DCI-IPG bioactivity remained flat throughout both insulin steps and was thus significantly lower than in controls during the initial periods of both steps . CONCLUSIONS The coupling between insulin action and the release of the DCI-IPG mediator is selectively impaired in obese PCOS women , which may contribute to the insulin resistance in these women OBJECTIVES Nuclear and cytoplasmic competence of human oocyte is critical for future competence of the embryo upon which ultimately depends the outcome of an ART ( Assisted Reproductive Technology ) treatment . Follicular microenvironment in which the oocyte develops is crucial , and this must be taken into account particularly with the use of hormonal ovarian stimulation protocol s. Inositol is an important element of the follicular environment and data support that its higher level in follicular fluid correlates with the development of a good oocyte . Aim of this study is to underst and the effects of treatment with inositol on oocyte quality in a sample of patients undergoing ICSI ( Intracytoplasmic Sperm Injection ) . PATIENTS AND METHODS Assessment of oocyte/embryo quality and pregnancy rates in 149 patients divided , according to a controlled r and omized pattern , into two groups : study group 1 treated with folic acid and inositol and control group 2 treated with folic acid alone . RESULTS The number of patients with excellent and good oocyte quality appears to be significantly higher in group 1 ( p = 0.02 ) , as shown , they significantly increased the number of embryos of grade A transferred in the group 1 ( p = 0.02 ) compared to group 2 , despite being completely similar averages of total embryos transferred ( total mean ± SD = 2.4 ± 0.8 , group 1 mean ± SD = 2.4 ± 0.8 , group 2 mean ± SD = 2.4 ± 0.8 ) . There is not any significant difference between groups 1 and 2 in the number of positivity to β-hCG and in the number of biochemical pregnancies detected although it has a tendency to increase in the first and to decrease in the second for group 1 . The increase in percentage of clinical pregnancies in group 1 was statistically significant ( p = 0.02 ) , whereas there was no apparent significance in the difference between the biochemical and clinical pregnancies in the two groups despite the positive trend in the study group . CONCLUSIONS Relying on " inositol help " to solidify our efforts , seems to be an easy path to help to deepen the effectiveness of its use in all patients still under 40 but with prior failed attempts at ICSI or diagnosed with PCOS or as " poor responders " 
    Output:
    