Lipid profile in nonobese pregnant women with polycystic ovary syndrome: a prospective controlled clinical study.

Alterations in lipid pattern and increased risk for obstetric/neonatal complications have been observed in patients with polycystic ovary syndrome (PCOS). Pregnancy leads to physiologic changes in lipoprotein metabolism, and alterations in lipid profile have been related with adverse pregnancy outcomes. Based on these considerations, the aim of the present prospective controlled clinical study was to test the hypothesis that the changes in the lipid profile in patients with PCOS during pregnancy are characteristic and potentially related to the increased risk of obstetric/neonatal complications. One hundred and fifty nonobese PCOS women and 150 age- and body mass index (BMI)-matched healthy controls were enrolled. Serum lipids, glucose, insulin, and androgens levels were serially assayed in all subjects before and throughout pregnancy. Serum low-density lipoprotein (LDL) and triglyceride (TG) concentrations were significantly (P<0.05) higher in PCOS group than in healthy controls at each assessment. Throughout pregnancy, serum LDL and TG levels increased significantly (P<0.05) in both groups, although the change from pre-pregnancy values was significantly (P<0.05) greater in PCOS patients than in healthy controls. A significant (P<0.05) relationship was observed between serum LDL and TG changes and changes in both insulin sensitivity indexes and androgen levels in PCOS patients alone. After adjusting for maternal age, pre-pregnancy BMI and lipid levels, body weight gain, and insulin-resistance markers, serum TG concentrations during pregnancy were directly and independently associated with obstetric complications in both groups, whereas serum LDL levels only in PCOS patients. We can conclude that nonobese PCOS patients had specific changes in lipid profile during pregnancy, and that the lipid pattern typical of PCOS may account for the more frequent adverse pregnancy outcomes. PCOS-related hormonal and metabolic features, such as insulin resistance and high androgen levels, may mediate this phenomenon.

Early trophoblast invasion and placentation in women with different PCOS phenotypes.

This study evaluated the impact of different phenotypes of polycystic ovary syndrome (PCOS) on early trophoblast invasion and placentation. Pregnant patients with different PCOS phenotypes and healthy pregnant women, matched for age and body mass index, were enrolled. Histological analysis of trophoblastic and decidual tissue and macroscopic and microscopic assessment of the placentas were performed. Implantation-site vessels with endovascular trophoblast differed significantly among PCOS phenotypes. Placental weight, thickness, density and fetal-placental weight ratio were significantly different in the full-blown and non-polycystic ovary (PCO) phenotypes versus the ovulatory and non-hyperandrogenic phenotypes. The incidence of macroscopic placental lesions was only significantly different between controls and the full-blown and non-PCO phenotypes. The overall incidence of microscopic placental lesions was significantly different among PCOS phenotypes and was significantly higher in the full-blown and non-PCO phenotypes than in the ovulatory and non-hyperandrogenic phenotypes. The rates of chorionic villitis and intervillositis were significantly higher in full-blown and non-PCO phenotypes than in ovulatory and non-hyperandrogenic phenotypes. In conclusion, alterations in early trophoblast invasion and placentation observed in PCOS vary widely according to phenotype.

Low-grade chronic inflammation in pregnant women with polycystic ovary syndrome: a prospective controlled clinical study.

CONTEXT: Polycystic ovary syndrome (PCOS) and pregnancy are conditions characterized by an increased low-grade chronic inflammation state. A higher incidence of pregnancy complications has been detected in pregnant PCOS women. OBJECTIVE: The objective of the study was to test the hypothesis that the low-grade chronic inflammation state typical of PCOS patients persists during gestation and is exacerbated by pregnancy and contributes to the increased risk of obstetric/neonatal complications. DESIGN: This was a prospective controlled clinical study. SETTING: The study was conducted at the Academic Department of Obstetrics and Gynecology of the "Pugliese-Ciaccio" Hospital of Catanzaro (Catanzaro, Italy). PATIENTS: One hundred fifty pregnant PCOS women and 150 age- and body mass index-matched healthy pregnant controls participated in the study. INTERVENTIONS: INTERVENTIONS included serial clinical, biochemical, and ultrasonographic assessments before and throughout pregnancy. MAIN OUTCOME MEASURES: Serum levels of white blood cell count (WBC), C-reactive protein (CRP), and ferritin were measured. RESULTS: Pregnant women with PCOS had higher WBC, CRP, and ferritin levels at study entry and at all gestational ages than controls. Changes in serum WBC and ferritin levels were significantly higher in PCOS than in controls starting from the 12th week of gestation whereas those in CRP from the 20th week of gestation. By multivariable Cox proportional hazard analysis, in the PCOS group, a significant association with the risk of adverse obstetric/neonatal outcomes was found for WBC [hazard ratio (HR) 1.52, 95% confidence interval (CI) 1.31-1.64; P = .010], CRP (HR 1.19, 95% CI 1.06-1.34; P = .019), and ferritin levels (HR 1.12, 95% CI 1.03-1.26; P = .011). CONCLUSIONS: In PCOS patients, the low-grade chronic inflammation persists during gestation and is exacerbated by pregnancy, and it is associated with adverse pregnancy outcomes.

A randomized controlled trial comparing three single-incision minislings for stress urinary incontinence.

INTRODUCTION AND HYPOTHESIS: Studies have observed a significant heterogeneity in efficacy data for single-incision minislings (SIMS) as surgical treatment for female urinary incontinence (UI). Our study aim was to test the hypothesis that different vaginal kits for SIMS have different long-term outcomes. METHODS: One hundred and twenty women with stress (SUI) or mixed (MUI) UI were enrolled in a multicenter randomized clinical trial (registration number NCT00751088) and treated with three different SIMS (Ajust, MiniArc, or TVT Secur System). Duration of follow-up was at least 24 months from surgery. The primary outcome was the subjective cure rate at 24 months from surgery; secondary outcomes were rates of total failure and reoperations for UI. RESULTS: At study end, no difference was detected between groups in terms of total subjective cure rate [21 (52.5%) vs. 26 (65.0%) vs. 21 (52.5%), in Ajust, MiniArc, and TVT Secur System group, respectively; P = 0.412] or in terms of total failure rate [24 (60.0%) vs. 22 (55.0 %) vs. 27 (67.5 %), in Ajust, MiniArc, and TVT Secur System group, respectively; P = 0.432]. The proportion of patients who received a second surgery for UI was also not significantly different between groups [13 (32.5%) vs. 10 (25.0%) vs. 13 (32.5%), in Ajust, MiniArc, and TVT Secur System, respectively; P = 0.831]. CONCLUSION: The long-term efficacy of SIMS does not differ between the vaginal kits examined.

Single-incision mini-slings versus retropubic tension-free vaginal tapes: a multicenter clinical trial.

STUDY OBJECTIVE: To compare single-incision mini-slings (SIMSs) and retropubic tension-free vaginal tape (r-TVT) in terms of the long-term efficacy and safety for the treatment of female stress (SUI) or mixed urinary incontinence (MUI). DESIGN: Prospective multicenter cohort trial (registration number NCT00751088) (Canadian Task Force II). SETTINGS: Department of Obstetrics and Gynecology, Italy. PATIENTS: Two hundred-forty women with SUI/MUI. INTERVENTIONS: SIMS or r-TVT. MEASUREMENTS AND MAIN RESULTS: The operative time and the use of analgesic tablets were significantly (p < .001) higher and lower, respectively, in the r-TVT group versus the SIMS group. After 24 months of follow-up, no difference between the study arms was observed in terms of the complication rate (30/120 [25%] vs 19/120 [15.8%] for the r-TVT and SIMS arms, respectively; relative risk = 1.58; 95% confidence interval, 0.94-2.65; p = .083), whereas the subjective cure rate was significantly lower in the SIMS arm than in the r-TVT arm (57/103 [55.3%] vs 89/106 [84.0%] for the r-TVT and SIMS arms, respectively; relative risk = 0.66; 95% confidence interval, 0.54-0.80]; p < .001). The proportion of retreated patients for SUI/MUI was significantly higher in the SIMS arm than in the r-TVT arm (37/103 [34.9%] vs 12/106 [11.3%] for SIMS and r-TVT arm, respectively; p < .001). CONCLUSION: SIMS has no advantage in terms of safety over r-TVT and was found to be less effective than r-TVT. Thus, its use in the clinical practice should be questioned.

Pervasive developmental disorders in children of hyperandrogenic women with polycystic ovary syndrome: a longitudinal case-control study.

OBJECTIVE: Foetal exposure to high testosterone concentrations seems to be involved in the development of mammalian brain and related to pervasive developmental disorders (PDDs). The aim of the current study was to test the hypothesis that children born from hyperandrogenic women with polycystic ovary syndrome (PCOS) are at higher risk of PDDs. DESIGN: Longitudinal case-control study. PATIENTS: Thirty pregnant PCOS patients with hyperandrogenaemia and other 45 pregnant healthy women were followed during pregnancy. All women had a healthy baby. MEASUREMENTS: Clinical evaluations and biochemical assays of the mothers during pregnancy and after delivery were performed. The children's versions of the Autism-Spectrum Quotient (AQ-C), the Empathy Quotient (EQ-C) and Systemizing Quotient (SQ-C) tests were administered. RESULTS: Total AQ-C and communication scores were significantly higher for children of PCOS patients. Stratifying our population according to sex, total AQ-C, communication and attention switching subscores were significantly higher only for daughters of PCOS patients. EQ-C and SQ-C scores resulted in significantly lower and higher scores, respectively, only in daughters of PCOS patients in comparison with those of healthy non-PCOS controls. AQ-C, EQ-C and SQ-C scores, irrespective of the studied group and/or subclassification by gender, were significantly influenced by amniotic testosterone levels. CONCLUSIONS: Daughters of mothers affected by hyperandrogenic PCOS seem to have a higher risk for PDDs probably due to an unbalanced prenatal exposure to high levels of testosterone.

A randomized controlled trial comparing three vaginal kits of single-incision mini-slings for stress urinary incontinence: surgical data.

OBJECTIVE: Single-incision mini-slings (SIMS) are new minimally invasive devices used for female stress urinary incontinence (SUI). To date, several SIMS are available, but few and uncontrolled comparative data have assessed their safety and feasibility. The aim of the present clinical study was to compare three different SIMS in an ambulatory setting. STUDY DESIGN: One hundred and twenty patients with SUI were randomized to receive three SIMS: Ajust, MiniArc, and TVT Secur System. Surgical data were compared. RESULTS: Significantly (P<0.05) lower surgical difficulty and higher patient satisfaction were detected in the MiniArc group when compared to the Ajust and TVT Secur System groups. A significantly (P<0.05) higher feasibility under local anesthesia and in ambulatory setting was also detected for the MiniArc group. The overall complication rate was significantly (P<0.05) lower in the MiniArc group than in the TVT Secur System group. CONCLUSIONS: MiniArc is simpler to insert under local anesthesia and in an ambulatory setting. It is safer than the TVT Secur System, and is related to higher patient satisfaction.

Decidual endovascular trophoblast invasion in women with polycystic ovary syndrome: an experimental case-control study.

CONTEXT: Previous experimental and clinical data suggest impaired decidual trophoblast invasion in patients with polycystic ovarian syndrome (PCOS). OBJECTIVE: The objective of the study was to test the hypothesis that decidual endovascular trophoblast invasion in pregnant patients with PCOS is impaired and to clarify the potential mechanisms involved. DESIGN: This was an experimental case-control study. SETTING: The study was conducted at the academic Departments of Obstetrics and Gynecology and the Unit of Pathology (Italy). PATIENTS: Forty-five pregnant subjects screened from a wide population of women waiting for legal pregnancy termination were included in the final analysis. Specifically, 15 pregnant patients with PCOS were enrolled as cases and another 30 age- and body mass index (BMI)-matched healthy pregnant women without any feature of PCOS were enrolled as the controls. INTERVENTION: Interventions included the collection of trophoblastic and decidual tissue at the 12th week of gestation. MAIN OUTCOME MEASURES: Clinical, ultrasonographic, and biochemical data as well as the histological analysis of decidual endovascular trophoblast invasion. RESULTS: The rate of implantation site vessels with endovascular trophoblast invasion (ratio between total number of implantation site vessels and total number of vessels with endovascular trophoblast invasion) and the extent of endovascular trophoblast invasion (proportion between immunoreactive areas to cytokeratin 7 and to CD34) were significantly lower in patients with PCOS compared with healthy non-PCOS controls. Endovascular trophoblast invasion data were significantly and indirectly related to the markers of insulin resistance and testosterone concentrations in PCOS patients. CONCLUSIONS: Pregnant patients with PCOS patients have impaired decidual trophoblast invasion. Further studies are needed to evaluate the exact mechanisms through which insulin resistance and hyperandrogenemia exert this effect.

The risk of a persistent glucose metabolism impairment after gestational diabetes mellitus is increased in patients with polycystic ovary syndrome.

OBJECTIVE: To test the hypothesis that the risk of persistent glucose impairment after gestational diabetes mellitus (GDM) is increased in patients with polycystic ovary syndrome (PCOS). RESEARCH DESIGN AND METHODS: The prospective case-control study included 42 pregnant patients with PCOS and GDM and 84 pregnant control patients with GDM but without clinical and biochemical hyperandrogenism, polycystic ovaries, and oligo-anovulation. The case and control subjects were matched one to two for age and BMI. The glycemic profiles were studied in all subjects 6 weeks, 12 weeks, and 18 months after delivery. The incidence and the relative risk (RR) were calculated for overall persistence of an abnormal glycemic pattern and for each specific alteration, i.e., impaired glucose tolerance (IGT), impaired fasting glucose (IFG), and diabetes mellitus (DM). RESULTS: At 18 months after delivery, the incidences of IFG, IGT, and IFG-IGT were significantly (P < 0.05) higher in the cases than in the controls. At the 18-month follow-up, the RR for the composite outcome of glucose metabolism impairment in PCOS women was 3.45 (95% CI 1.82-6.58). CONCLUSIONS: Patients with PCOS are at increased risk for a persistent impaired glucose metabolism after GDM.

Metformin administration in patients with polycystic ovary syndrome who receive gonadotropins for in vitro fertilization cycles: 10-year experience in a large infertile population.

The study aim was to evaluate our personal experience regarding the use and the reproductive effect of metformin administration in a large population of infertile patients with polycystic ovary syndrome (PCOS) undergoing gonadotropins ovarian stimulation for in vitro fertilization (IVF). Infertile patients with PCOS undergoing gonadotropins ovarian stimulation with (metformin group, n = 191) or without (control group, n = 187) metformin and IVF were evaluated. Treatment characteristics, patients' data and reproductive outcomes were evaluated. In all cases, metformin with an immediate-release formulation was administered, and in most of cases it was given as pre- and co-treatment (74.9%) and at a dosage of 1700 mg/day (59.7%). Stimulation length and gonadotropins doses were significantly (p < 0.05) higher in metformin group than in control group. The number of dominant follicles on day of ovarian maturation triggering and peak oestradiol levels were significantly (p < 0.05) lower in metformin group than in control group. Cycle cancellation rate under metformin resulted significantly influenced by interaction with body mass index (BMI), age and basal follicle-stimulating hormone (FSH) levels. Notwithstanding, metformin use in infertile PCOS patients who receive gonadotropins for IVF is not standardized, it seems to modulate the ovarian response to stimulation. This effect may benefit or harm on the basis of ovarian reserve and patients' characteristics.

Metformin reduces risk of ovarian hyperstimulation syndrome in patients with polycystic ovary syndrome during gonadotropin-stimulated in vitro fertilization cycles: a randomized, controlled trial.

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, randomized, 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 CLINICALTRIALS.GOV: NCT01233206.

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.

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: Prospective, parallel, randomized, 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 randomized 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.

Changes in androgens and insulin sensitivity indexes throughout pregnancy in women with polycystic ovary syndrome (PCOS): relationships with adverse outcomes.

BACKGROUND: Given the high rate of pregnancy and perinatal complications recently observed in patients with polycystic ovary syndrome (PCOS) and the lack of data on the serum variations in androgens and insulin sensitivity indexes in pregnant women with PCOS, the current study was aimed to assess these changes and their potential effect on pregnancy outcomes in a population of women with PCOS. METHODS: Forty-five pregnant patients with ovulatory PCOS (PCOS group) and other 42 healthy pregnant women (control group) were studied assaying serum androgen levels and insulin sensitivity indexes throughout pregnancy serially, and recording obstetrical outcomes. RESULTS: Serum androgen levels and insulin resistance indexes were significantly (p < 0.05) higher in PCOS than in control group at study entry, these differences were sustained throughout pregnancy, and their changes resulted significantly (p < 0.05) different between PCOS and control group. In PCOS patients, women who had a complicated pregnancy showed serum androgen levels and insulin sensitivity indexes significantly (p < 0.05) worse in comparison to subjects without any pregnancy and/or neonatal complications. CONCLUSIONS: PCOS patients have impaired changes in serum androgen levels and insulin sensitivity indexes during pregnancy. These alterations could be implicated in the pregnancy and neonatal complications frequently observed in women affected by PCOS.

Serum and follicular anti-Mullerian hormone levels in women with polycystic ovary syndrome (PCOS) under metformin.

BACKGROUND: No data regarding metformin effects on follicular fluid anti-Müllerian hormone (AMH) levels were to date available in literature. The aim of the present study was to evaluate in patients with polycystic ovary syndrome (PCOS) whether metformin administration affects serum and follicular AMH levels, and whether this is related to ovarian response to the treatment. METHODS: Twenty young patients with PCOS who had received metformin were enrolled. Ten patients were anovulatory (Met-anov group), whereas the other 10 were ovulatory (Met-ov group) but had failed to conceive. Further untreated PCOS (PCOS controls, n. 10) and healthy controls (non-PCOS controls, n. 10) who were scheduled for laparoscopic surgery were enrolled. In each subjects, clinical and biochemical evaluations were performed. AMH concentrations in blood and antral follicular fluid were assayed. RESULTS: In both Met-anov and Met-ov groups, and without difference between them, serum androgens and AMH, and indices of insulin resistance were significantly (p < 0.05) improved after treatment. On the other hand, significant differences (p < 0.05) between the two groups were detected with respect to the same biochemical parameters in antral follicular fluid. In the Met-anov group, no significant correlation was observed between AMH concentrations in the follicular fluid and variation in serum androgens, AMH and insulin resistance indexes; whereas in Met-ov group significant correlations were detected between AMH levels in the follicular fluid and variation in serum androgens, AMH and insulin resistance indexes. CONCLUSIONS: Metformin administration in patients with PCOS exerts a differential action on the ovarian AMH levels on the basis of ovulatory response. Changes in AMH levels in antral follicular fluid during metformin treatment could be involved in the local mechanisms mediating the ovulatory restoration.

Ultra-conservative fertility-sparing strategy for bilateral borderline ovarian tumours: an 11-year follow-up.

BACKGROUND: This is a prospective long-term extension study of a randomized controlled trial aimed to assess the risk-benefit ratio of an ultra-conservative fertility-sparing approach in patients with bilateral borderline ovarian tumours (BOTs). METHODS: The experimental group (n = 15) was treated with an ultra-conservative surgical approach consisting of bilateral cystectomy, whereas the control group (n = 17) received a less conservative surgery consisting of oophorectomy plus controlateral cystectomy alone. All patients received a complete laparoscopic staging followed by a fertility enhancement programme. Patients who completed childbearing were treated with a non-conservative standard treatment at the first recurrence. RESULTS: After a follow-up period of 128 (9 interquartile range (IQR); 115-150 range) and 132 (7 IQR; 117-152 range) months for the experimental and control groups, respectively (P = 0.25), the time to first baby-in-arm (P < 0.02) and the relative rate (RR) of baby-in-arm (8.05 [95% confidence interval (CI), 1.20-9.66; P < 0.01]) were significantly lower and higher, respectively, for the experimental compared with the control group. Although the time to first recurrence was significently (P < 0.01) shorter for the experimental group, in the regression analysis the difference did not reach the statistic significance (P = 0.14), and the RR of recurrence (1.23 [95% CI, 0.62-3.17; P = 0.41]) was not significant. Finally the number needed to treat for pregnancy was three, the number needed to harm for radical surgery was only two. CONCLUSIONS: The ultra-conservative fertility-sparing approach is more effective than the standard approach in terms of reproductive outcomes, but presents a higher oncological risk.

Randomized controlled study comparing the Gynecare Morcellex and Rotocut G1 tissue morcellators.

STUDY OBJECTIVE: To evaluate the effectiveness of the Gynecare Morcellex tissue morcellator (Ethicon, Inc., Somerville, NJ) in laparoscopic supracervical hysterectomy and myomectomy. DESIGN: Randomized controlled trial (Evidence I). SETTING: University department of obstetrics and gynecology. PATIENTS: Seventy-four patients with symptomatic uterine myomas scheduled for laparoscopic supracervical hysterectomy or myomectomy. INTERVENTIONS: Laparoscopic supracervical hysterectomy and myomectomy followed by tissue morcellation using the Gynecare Morcellex (experimental group) or the Rotocut G1 morcellator (Karl Storz GmbH & Co. KG, Tuttlingen, Germany) (control group). MEASUREMENTS AND MAIN RESULTS: Patient characteristics and surgical data were noted for both groups. No difference was detected between groups in any parameters assessed, whereas a significant difference (p <.05) in handling score was detected in the experimental group compared with the control group. CONCLUSION: The Gynecare Morcellex is an effective instrument with excellent safety and handling.

Systemic and local effects of metformin administration in patients with polycystic ovary syndrome (PCOS): relationship to the ovulatory response.

BACKGROUND: Several data have demonstrated the efficacy of metformin in inducing ovulation in patients with polycystic ovary syndrome (PCOS), however, the exact mechanism by which this drug acts remains unknown. The aim of the present study was to evaluate whether the efficacy of the drug in patients with PCOS is related to a systemic hormonal-metabolic improvement, or to a local action on the ovary. METHODS: Twenty-four normal weight patients with PCOS, who were treated with metformin, were enrolled. Of these, 12 subjects were anovulatory (Group A1), whereas the other 12 were ovulatory but had failed to conceive (Group A2). A further 24 untreated subjects who were scheduled for laparoscopic surgery were enrolled as controls, 12 anovulatory patients with PCOS scheduled for laparoscopic myomectomy (Group B1) and a further 12 non-PCOS participants were scheduled for diagnostic laparoscopy (Group B2). Clinical assessments and biochemical evaluations in blood and antral follicular fluid were performed in each participant. RESULTS: In 1/12 and 9/12 participants from Groups A1 and A2, respectively, the ovarian morphology was changed, and a significant (P < 0.05) reduction in the ovarian dimensions was observed only in Group A2. In both of these groups, and without difference between them, serum androgens and indices of insulin resistance improved significantly (P < 0.05) after metformin treatment. On the other hand, significant differences (P < 0.05) between the two groups were detected with respect to the same biochemical parameters in antral follicular fluid. In Groups A1 and A2, levels of androgens and indices of insulin resistance in the antral follicular fluid were significantly (P < 0.05) better than in Group B1, but worse than in Group B2. CONCLUSIONS: Irrespective of its systemic effects, the efficacy of metformin in the induction of ovulation is probably due to a direct action on the ovary, and the ovulatory response to the drug seems to be related to local sensitivity or resistance to the drug.

Laparoscopic ovarian diathermy vs clomiphene citrate plus metformin as second-line strategy for infertile anovulatory patients with polycystic ovary syndrome: a randomized controlled trial.

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 randomly 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.

Effects of metformin with or without supplementation with folate on homocysteine levels and vascular endothelium of women with polycystic ovary syndrome.

OBJECTIVE: To evaluate whether the administration of metformin exerts any effects on serum homocysteine (Hcy) levels in patients with polycystic ovary syndrome (PCOS) and whether supplementation with folate enhances the positive effects of metformin on the structure and function of the vascular endothelium. RESEARCH DESIGN AND METHODS: A total of 50 patients affected by PCOS, without additional metabolic or cardiovascular diseases, were enrolled in a prospective nonrandomized placebo-controlled double-blind clinical study. They were grouped into two treatment arms that were matched for age and BMI. Patients were treated with a 6-month course of metformin (1,700 mg daily) plus folic acid (400 microg daily; experimental group, n = 25) or placebo (control group, n = 25). Complete hormonal and metabolic patterns, serum Hcy, folate, vitamin B12, endothelin-1 levels, brachial artery diameter at the baseline (BAD-B) and after reactive hyperemia (BAD-RH), flow-mediated dilation, and intima-media thickness in both common carotid arteries were evaluated. RESULTS: After treatment, a significant increase in serum Hcy levels was observed in the control group compared with the baseline values and the experimental group. A beneficial effect was observed in the concentrations of BAD-B, BAD-RH, flow-mediated dilation, intima-media thickness, and serum endothelin-1 in both groups. However, the results were improved more significantly in the experimental group than in the control subjects. CONCLUSIONS: Metformin exerts a slight but significant deleterious effect on serum Hcy levels in patients with PCOS, and supplementation with folate is useful to increase the beneficial effect of metformin on the vascular endothelium.

Pregnancy in women with polycystic ovary syndrome: the effect of different phenotypes and features on obstetric and neonatal outcomes.

OBJECTIVE: To test the hypothesis that the risk of adverse obstetric or neonatal outcomes varies according to different phenotypes of polycystic ovary syndrome (PCOS), and to evaluate the clinical impact of the main features of PCOS. DESIGN: Prospective controlled clinical study. SETTING: Academic Departments of Obstetrics and Gynecology, and of Endocrinology, Italy. PATIENT(S): Ninety-seven pregnant women with PCOS and 73 healthy pregnant subjects were recruited as cases and controls, respectively. INTERVENTION(S): Clinical, biochemical, and ultrasonographic evaluations. MAIN OUTCOME MEASURE(S): Obstetric and neonatal outcomes. RESULT(S): The relative risk (RR) for adverse obstetric or neonatal outcomes was increased (1.7, 95% confidence interval [CI] 1.12-2.96) in patients with PCOS and varied according to the PCOS phenotype (1.93, 95% CI 1.12-2.96; 2.23, 95% CI 1.21-3.15; 0.54, 95% CI 0.09-1.63, and 0.48, 95% CI 0.31-0.78 for full-blown, nonpolycystic ovaries [PCO], nonhyperandrogenic, and ovulatory phenotypes, respectively). The RRs were 1.57 (95% CI 0.85-2.52) and 0.48 (95% CI 0.31-0.78) for oligoanovulatory and ovulatory patients with PCOS, respectively. The risk for adverse obstetric or neonatal outcomes was affected significantly by ovarian dysfunction and biochemical hyperandrogenism, whereas no significant effect was detected for clinical hyperandrogenism and PCO. CONCLUSION(S): The increased risk for adverse obstetric and neonatal outcomes that was observed in patients with PCOS varies widely according to the different phenotypes and features of PCOS.