Efficacy of combined metformin–letrozole in comparison with bilateral ovarian drilling in clomiphene-resistant infertile women with polycystic ovarian syndrome

Objectives

To compare the hormonal-metabolic profiles and reproductive outcomes between women receiving metformin plus letrozole and women undergoing bilateral ovarian drilling in clomiphene citrate (CC)-resistant women with polycystic ovary syndrome (PCOS).

Methods

In this randomized study, 146 patients were randomly allocated into group 1 (n = 73) who received metformin plus letrozole, and group 2 (n = 73) who underwent bilateral ovarian drilling. Comparison was done between the basal and after treatment biochemical values for each group, in addition reproductive outcomes after treatment were compared between both groups.

Results

There was significant reduction in testosterone (p ≤ 0.001), fasting insulin (p ≤ 0.001), and fasting glucose/fasting insulin ratio (p = 0.029) in metformin plus letrozole group, while there was significant reduction in FSH, LH and LH/FSH ratio in bilateral drilling group (p ≤ 0.001, 0.001 and 0.001). No significant difference in cycle regularity (p = 0.82), ovulation (p = 0.24), pregnancy rate (p = 0.32) and abortion rate (p = 0.51) between both groups.

Conclusion

Both metformin plus letrozole and bilateral ovarian drilling are similarly effective as second-line strategies for the treatment of women with PCOS who do not conceive with CC.     

二甲双胍治疗耐克罗米酚多囊卵巢综合征23例临床分析

目的探讨二甲双胍在多囊卵巢综合征(PCOS)治疗中的作用.方法对23例耐克罗米酚PCOS患者的临床资料进行回顾性分析,比较二甲双胍治疗前后各项内分泌代谢指标的变化及其对恢复月经、促排结局及妊娠的影响.结果二甲双胍治疗前后比较,血清睾酮、空腹胰岛素水平下降,胰岛素敏感性指数上升(P<0.01).6例(26.09%)的患者恢复月经,4例(17.39%)恢复自然排卵,2例妊娠. 二甲双胍加促排治疗共26个周期,排卵周期率为61.54%(16/26),妊娠周期率为23.08%(6/26). 结论二甲双胍可以降低雄激素水平及胰岛素水平,改善PCOS妇女对克罗米酚促排的反应.     

Evaluation of ultrasonographic and Anti-Müllerian Hormone (AMH) changes as predictors for ovarian reserve after laparoscopic ovarian drilling for women with polycystic ovarian syndrome

Background and aim of the studyLaparoscopic ovarian drilling (LOD) is considered one of the effective tools for treatment of women with polycystic ovarian syndrome. The aim of this work was to evaluate the effects of laparoscopic ovarian drilling on ovarian reserve assessed by Anti-Müllerian hormone assay and ultrasonography.Study designThe current prospective controlled study included 70 (n = 70) primary anovulatory women with PCOS who are allocated to undergo LOD (n = 40), who are clomiphene citrate (CC) resistant, and another group receiving incremental doses (50–150 mg) of CC (n = 30) and 20 healthy age-matched women with a regular menstrual cycle and normal ovaries (confirmed with ultrasound examination) as the control group.Materials and methodsFor the LOD group, standard laparoscopy ovarian drilling was done just after the end of the menstruation using a monopolar electrocautery needle. For the CC group, clomiphene citrate was given in incremental doses (50–150 mg) for up to six cycles from days 2–6 of a menstrual cycle or after a progestin withdrawal bleeding. Evaluation for the ovarian reserve was done using the following tests: (1) AMH level in the third cycle day, (2) antral follicle count (AFC) by TVS, and (3) summed ovarian volume (SOV) by transvaginal ultrasound examination (TVS).ResultsIn the current study, among the (40) PCOS women having LOD, 30/40 (75%) had regular cycles in the 6-month period after LOD, while the ovulation rate was 24/40 (60%) and the pregnancy rate was 11/40 (27.5%) in the 6-month period after LOD. Those rates were not statistically different in the PCO women group treated with CC. There were statistically significant differences between AMH levels and antral follicle count before and after LOD (p = 0.001 and 0.009 respectively) and this might indicate a possible diminished ovarian reserve.ConclusionAMH and AFC are reliable markers for assessment of the ovarian reserve and measuring them for women with anovulatory PCOS undergoing LOD may provide a useful tool in evaluating the outcome of LOD.     

二甲双胍对多囊卵巢综合征患者纤溶系统、内分泌、代谢的影响及对耐氯米芬的作用

目的：评估二甲双胍对多囊卵巢综合征（PCOS）与耐氯米芬患者的治疗作用。方法：31例PCOS患者（8例为耐氯米芬者）,用二甲双胍375mg/次、3次／d,治疗12－16周,观察服药前后血纤溶酶原激活物抑制物－1（PAI－1）及组织型纤溶酶原激活物（tPA）水平,月经、生殖内分泌激素,糖、脂代谢,卵巢体积的变化及副反应。服用二甲双胍未恢复正常月经、耐氯米芬的患者,再加用氯米芬促排卵,观察排卵情况。非耐氯米芬未恢复正常月经的患者,二甲双胍加量至500mg／次、3次／d,至少8周,观察月经情况。结果：二甲双胍治疗后,PAI－1、黄体生成素／促卵泡激素（LH／FSH）、睾酮、雄烯二酮、低密度脂蛋白胆固醇、总胆固醇、胰岛素、胰岛素曲线下面积、舒张压明显下降,下降幅度分别为3％、41％、25％、34％、28％、14％、27％、23％、7％;左侧卵巢体积缩小59％,右侧卵巢体积缩小41％;雌二醇和FSH水平分别上或42％、58％（P＜0．05－0．01）。二甲双胍375mg/次、3次／d治疗后,61％（19／31）的患者恢复正常月经,2例妊娠;12例恢复正常月经周期,其中6例伴耐氯米芬者再用氯米芬,5例（12／18周期）排卵,2例妊娠,余6例二甲双胍加量至500mg／次、3次／d,1例恢复月经并妊娠。结论：二甲双胍可改善PCOS患者的纤溶系统,生殖内分泌激素,糖、脂代谢,月经失调等,增强耐氯米芬患者对氯米芬的敏感性。     

Metformin improves ovulation and pregnancy rates in patients with polycystic ovary syndrome

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 prospectively designed 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.     

Unilateral ovarian drilling in polycystic ovarian syndrome: a prospective randomized study

Ovarian drilling is a well-accepted intervention for ovulation induction in clomiphene citrate-resistant polycystic ovarian syndrome (PCOS) patients. The aim of this study was to evaluate the effect of unilateral and bilateral ovarian drilling by electrocautery in PCOS women. In this prospective randomized clinical study, 87 patients with ovulation failure as a result of PCOS were randomly allocated to either unilateral (group A; n = 43 patients) or bilateral (group B; n = 44 patients) laparoscopic ovarian drilling by electrocautery. The average time required for unilateral ovarian drilling was shorter than for bilateral drilling. In patients who ovulated after drilling, there was a significant fall in serum LH concentration (group A, P < 0.05, group B, P < 0.05). Ovulation, pregnancy and miscarriage rates were similar in both groups. It seems that unilateral ovarian drilling in PCOS is effective, less time-consuming and probably associated with fewer complications.     

l-Carnitine plus metformin in clomiphene-resistant obese PCOS women,reproductive and metabolic effects: a randomized clinical trial

To evaluate the reproductive and metabolic effects of L-carnitine plus metformin in clomiphene citrate (CC) resistant obese polycystic ovary syndrome (PCOS) women. A double-blinded randomized controlled clinical trial, clomiphene-citrate resistant obese women were allocated randomly to receive CC plus metformin and L-carnitine (n?=?138) or CC plus metformin and placebo (n?=?136). The primary outcome was clinical pregnancy rate. The secondary outcomes were hormonal and metabolic profile changes in addition to ovulation and first trimester (13 weeks) miscarriage rates. Clomiphene-citrate, L-carnitine, and metformin group showed significant improvement in the menstrual regularity, ovulation rate, and pregnancy rate compared to CC plus metformin and placebo group (29% vs. 9%, 34.7% vs.11%, and 28.2% vs. 6.6%, respectively). No statistically significant difference in the miscarriage rate between the two groups (p?=?.08). After three months of treatment, the reduction in body mass index (BMI) was non-significant (p?=?.061) between both groups. The hormonal and metabolic parameters were more significantly improved in the L-carnitine group compared with the placebo group. l-Carnitine may act synergistically with metformin for improvement of reproductive performance, insulin resistance, and lipid profile in clomiphene-resistant obese PCOS women.     

Effects of low-dose metformin in Japanese women with clomiphene-resistant polycystic ovary syndrome

Background and Aims  The aim of the present prospective observational study was to evaluate the effects of low-dose, short-term metformin, in combination with domiphene (CC), in CC-resistant infertile Japanese women with polycystic ovary syndrome (PCOS). Methods  Metformin therapy was administered orally (one 250 mg tablet, twice daily) to 15 CC-resistant infertile patients with PCOS, beginning on the third day of progestin-induced withdrawal bleeding, and was continued for 14 days in the first cycle. In the event of anovulation, 100 mg/day of CC was given during subsequent cycles on days 5–9, in addition to the aforementioned dose of metformin. Hormonal and metabolic parameters were measured on the second or third days of the first cycle and also the fourth cycle, following an overnight fast. Results  None of the 15 women successfully ovulated during the first cycle with metformin treatment alone. After two subsequent cycles with the combination of CC and metformin, ovulation was confirmed in 17 of 29 cycles (61%) and in 13 of 15 patients (87%). Two women became pregnant within 2 months of therapy (13%). There were no cases of ovarian hyperstimulation syndrome. Following three cycles of metformin therapy, a slight reduction in serum levels of luteinizing hormone (LH), free testosterone, androstenedione, dehydroepiandrosterone sulfate, hemoglobin Alc and total cholesterol was seen, while serum LH/follide-stimulating hormone ratio and serum level of low-density lipoprotein cholesterol were significantly decreased. Although there were no significant differences between the responder (n = 11) and non-responder (n = 2) groups at baseline, the levels of plasma fasting insulin was significantly higher and fasting glucose/insulin ratio was significantly lower in the non-responder group compared with the responder group after three cycles. Conclusion  Low-dose, short-term metformin, combined with CC, can improve ovulation rates in CC-resistant infertile Japanese women with PCOS.     

Polycystic Ovary Syndrome: Fertility Management

Polycystic ovary syndrome (PCOS) is characterized by a series of symptoms, including oligomenorrhea or amenorrhea anovulation or infertility; it is associated with insulin resistance and compensatory hyperinsulinemia. Several treatment options are available for women with anovulatory infertility related to PCOS. Clomiphene citrate (CC) is the first-choice for induction of ovulation in PCOS patients. Laparoscopic ovarian drilling (LOD) or gonadotropin ovarian stimulation can be offered after failure of CC to achieve pregnancy. Hyperinsulinemia related to PCOS can be corrected by weight loss or insulin-sensitizing agents, such as metformin, which alone or in combination with other agents are capable of restoring ovulation. Only very limited clinical data are available on the use of letrozole at present, so letrozole cannot be recommended for routine use in ovulation induction. When all treatments fail, in vitro fertilization and embryo transfer (IVF/ET) can be tried and can have excellent results. Many treatment options available today ensure that the majority of women who are subfertile due to PCOS can be treated successfully.     

Three decades after Gjönnaess’s laparoscopic ovarian drilling for treatment of PCOS; what do we know? An evidence-based approach

Background

The introduction of laparoscopic ovarian drilling (LOD) by Gjönnaess in 1984 as a substitute for ovarian wedge resection created opportunities for extensive research given its worldwide application for ovulation induction in women with polycystic ovary syndrome (PCOS).

Purpose

To critically evaluate and summarize the current body of literature regarding the role of LOD for the management of PCOS entailing its different preoperative, operative and postoperative aspects. In addition, long-term efficacy, cost-effectiveness, patient preference and health-related quality of life issues will be evaluated together with other available alternatives of ovulation induction treatments.

Methods

A PubMed search was conducted looking for the different trials, reviews and various guidelines relating to the role of LOD in the management of PCOS.

Results

LOD whether unilateral or bilateral is a beneficial second-line treatment in infertile women with clomiphene citrate (CC)-resistant PCOS. It is as effective as gonadotrophin treatment but without the risk of multiple pregnancy or ovarian hyperstimulation and does not require intensive monitoring. Increased responsiveness of the ovary to CC especially in patients who remain anovulatory following LOD is another advantage. Recent evidence suggests that relatively novel oral methods of ovulation induction, e.g. CC plus metformin, CC plus tamoxifen, rosiglitazone plus CC and aromatase inhibitors represent a successful alternative to LOD in CC-resistant PCOS. Meanwhile current evidence does not support LOD as a first-line approach in PCOS-related anovulation or before IVF.

Conclusion

LOD is currently recommended as a successful and economical second-line treatment for ovulation induction in women with CC-resistant PCOS.     

Metformin versus laparoscopic ovarian drilling in clomiphene- and insulin-resistant women with polycystic ovary syndrome

Objective

To compare the hormonal-metabolic profiles and reproductive outcomes in clomiphene-resistant patients with polycystic ovary syndrome and insulin resistance between women receiving metformin and those undergoing laparoscopic ovarian drilling.

Methods

A total of 110 eligible participants were randomly allocated to diagnostic laparoscopy plus metformin therapy (group 1, n = 55) or laparoscopic ovarian drilling (group 2, n = 55). The t test was used for mean comparisons of hormonal-metabolic parameters and OGTT values before and after treatment. The χ² test was used for comparisons of ovulation, pregnancy, and abortion rates.

Results

Groups 1 and 2 showed a significant decline in testosterone, insulin-like growth factor-1 (P < 0.001 vs P < 0.001), and luteinizing hormone (P < 0.05 vs P < 0.001), while the glucose to insulin ratio was significantly increased (P < 0.001 vs P < 0.05) compared with baseline. Group 2 patients had more regular cycles and higher rates of ovulation and pregnancy compared with group 1: 76.4% [42/55] vs 58.2% [32/55], P < 0.04; 50.8% [131/258] vs 33.5% [94/281], P < 0.001; and 38.2% [21/55] vs 20.0% [11/55], P < 0.03, respectively. The difference in the early abortion rate between the groups was not statistically significant.

Conclusion

Although metformin results in a better attenuation of insulin resistance, laparoscopic ovarian drilling is associated with higher rates of ovulation and pregnancy.     

A prospective randomized trial comparing the clinical and endocrinological outcome with rosiglitazone versus laparoscopic ovarian drilling in patients with polycystic ovarian disease resistant to ovulation induction with clomiphene citrate

Objectives  

Rosiglitazone, an insulin sensitizing agent is used currently in women with clomiphene citrate (CC) resistant polycystic ovarian syndrome (PCOS). Our study proposed to compare the efficacy of rosiglitazone and CC with laparoscopic ovarian drilling (LOD) and CC in terms of biochemical effects, ovulation rate and pregnancy rate in patients of PCOS resistant to CC.     

Anti-Müllerian hormone in polycystic ovary syndrome and normo-ovulatory women: Correlation with clinical,hormonal and ultrasonographic parameters

BackgroundAlthough the ultimate pathogenesis of polycystic ovary syndrome (PCOS) remains obscure, the distinctive feature is failure of follicular maturation resulting in anovulation and accumulation of preantral and small antral follicles which contribute significantly to the production of anti-Müllerian hormone (AMH).ObjectivesTo compare serum AMH levels between PCOS and normo-ovulatory women; and to investigate whether AMH correlates to clinical, hormonal and ultrasonographic parameters in both groups.DesignComparative observational cross-sectional study.SettingDepartment of Obstetrics and Gynecology, Kasr El-Aini Teaching Hospital, Faculty of Medicine, Cairo University.SubjectsThirty-five women with PCOS according to the Rotterdam consensus; and 35 normo-ovulatory-matched controls with male, tubal or unexplained infertility.MethodsSerum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, androstenedione, estradiol, fasting insulin and AMH were measured in the early follicular phase (day 3–4) of natural cycle or progestin-induced withdrawal bleeding (in PCOS); together with transvaginal sonography for detection of the number of small follicles (<10mm) and calculation of ovarian volume.Main outcome measuresCorrelation between AMH and clinical, hormonal and ultrasonographic parameters in both groups.ResultsAMH was significantly higher in the PCOS group. In the whole group of patients and in each group separately, AMH was positively correlated to LH, LH/FSH, number of follicles <10mm and ovarian volume; and negatively correlated to FSH. No correlation was found between AMH and age, BMI, estradiol or fasting insulin. Testosterone and androstenedione were positively correlated to AMH in the PCOS group exclusively (r=0.557; P=0.001 and r=0.451; P=0.007, respectively). Multiple regression analysis demonstrated that testosterone was the only determinant for AMH level (r=0.485; P<0.001).ConclusionsHyperandrogenism is associated with increased AMH secretion in PCOS patients, possibly due to increased number of small antral follicles. Assessment of AMH levels before and after the treatment of hyperandrogenism should be recommended in the plan of management of PCOS.     

Combined pioglitazone–metformin and clomiphene citrate versus metformin and clomiphene citrate in induction of ovulation in women with clomiphene citrate-resistant polycystic ovary syndrome

ObjectiveTo compare the efficacy of pioglitazone + metformin and clomiphene citrate (CC) with metformin and CC in women with CC-resistant polycystic ovary syndrome (PCOS).DesignRandomized clinical trial (RCT).SettingA university teaching hospital in Cairo, Egypt.PatientsOne hundred women with CC-resistant PCOS.MethodsFifty women received pioglitazone 15 mg + metformin 850 mg once daily from the first day of the cycle for 10 days, and 50 women received metformin (500 mg three times daily). Clomiphene citrate 100 mg from the third day of the cycle for 5 days was added to each group. Treatment was continued for three cycles.Main outcome measure(s)Ovulation rate and pregnancy rate.ResultsOvulation rate was significantly higher in the pioglitazone + metformin and CC group than the metformin and CC group (69.8% versus 48.8%) (p: 0.002). Significantly higher serum E₂ on day 12 and thicker endometrium were found in the pioglitazone + metformin and CC group in the three follow up cycles. Also, cummulative pregnancy rate was significantly higher in the pioglitazone + metformin and CC group than the metformin and CC group (58% versus 34%) (P: 0.027).ConclusionThe use of pioglitazone/metformin and CC is more effective than metformin and CC as regards ovulation and pregnancy rates in anovulatory women with CC-resistant PCOS.     

Effect of Metformin on Sleep Disorders in Adolescent Girls with Polycystic Ovarian Syndrome

ObjectivePatients with polycystic ovarian syndrome (PCOS) have a high prevalence of sleep disorders. Metformin is an antidiabetic drug that may have a role in treatment of the manifestations of PCOS. The aim of this study was to assess the presence of sleep disorders in adolescent girls with PCOS and to study the effects of using metformin on sleep disorders in these girls.MethodsThis study was carried out on 90 adolescent girls aging from 12 to 18 years who were divided into 3 equal groups: control untreated group, untreated PCOS group, and PCOS + metformin group. Body weight, height, body mass index, hirsutism score, fasting and postprandial blood glucose, fasting serum insulin, Homeostatic Model Assessment (HOMA) index, sleep disturbances scale, and Epworth sleepiness scale were measured.ResultsMetformin administration resulted in significant decrease in the body weight, body mass index, hirsutism score, fasting and postprandial blood glucose, fasting serum insulin, HOMA index, sleep disturbances scale, and Epworth sleepiness scale compared to the untreated PCOS group.ConclusionMetformin can reduce the incidence of sleep disorders and excessive daytime sleepiness in adolescent girls with PCOS.     

Follicular fluid lipid fingerprinting from women with PCOS and hyper response during IVF treatment

PurposePolycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder that leads to lower natural reproductive potential and presents a challenge for assisted reproductive medicine because patients may exhibit immature oocyte retrieval and a higher risk of ovarian hyper stimulation syndrome during in vitro fertilization (IVF) treatment. This study aimed to identify potential lipid biomarkers for women with PCOS and a hyper response to controlled ovarian stimulation.MethodsFollicular fluid samples were collected from patients who underwent IVF, including normal responder women who became pregnant (control group, n = 11), women with PCOS and a hyper response to gonadotropins (PCOS group, n = 7) and women with only hyper response to gonadotropins (HR group, n = 7). A lipidomic analysis was performed by electrospray ionization mass spectrometry, and candidate biomarkers were analyzed by tandem mass spectrometry experiment.ResultsThe lipid profiles indicated particularities related to differences in phosphatidylcholine (PCOS and HR), phosphatidylserine, phosphatydilinositol and phosphatidylglycerol (control), sphingolipids (PCOS) and phosphatidylethanolamine (control and HR).ConclusionsThese findings contribute to the understanding of the molecular mechanisms associated with lipid metabolism in the PCOS-related hyper response, and strongly suggest that these lipids may be useful as biomarkers, leading to the development of more individualized treatment for pregnancy outcome.

Electronic supplementary material

The online version of this article (doi:10.1007/s10815-014-0375-0) contains supplementary material, which is available to authorized users.     

Unilateral Versus Bilateral Laparoscopic Ovarian Drilling Using Thermal Dose Adjusted According to Ovarian Volume in CC-Resistant PCOS,A Randomized Study

Objective

This study aimed to evaluate the efficacy of unilateral laparoscopic ovarian drilling versus bilateral laparoscopic ovarian drilling with thermal dose adjusted according to ovarian volume in clomiphene citrate (CC)-resistant PCOS patients in terms of endocrine changes, menstrual cycle resumption, ovulation and pregnancy rates.

Patients and Methods

This study was conducted in the Department of Obstetrics and Gynecology, Zagazig university hospitals. One hundred CC-resistant PCOS patients were divided into two groups. Group (I) (50 patients) underwent unilateral laparoscopic ovarian drilling with thermal dose adjusted according to ovarian volume (60 J/cm³ of ovarian tissue), and group (II) (50 patients) underwent bilateral laparoscopic ovarian drilling using the same previously mentioned thermal dose. Endocrinal changes and menstrual cycle resumption were assessed within 8 weeks postoperatively, but the ovulation and pregnancy rates were estimated after 6-month follow-up period.

Results

There was no statistically significant difference between the two groups as regards demographic data (p > 0.05). As regards menstruation cycle resumption (62.5 vs. 81%) (p = 0.047), total ovulation rate (54.2 vs. 78.7%) (p = 0.011) and cumulative pregnancy rate (33.3 vs. 55.3%) (p = 0.031), there was statistically significant difference between both groups. After drilling, there were highly statistically significant decrease in the mean serum levels of luteinizing hormone (LH) and significant decrease in the mean serum levels of testosterone in both groups. Mean serum level of follicle stimulating hormone (FSH) did not change significantly in both groups after drilling.

Conclusion

Bilateral laparoscopic ovarian drilling with thermal dose adjusted according to ovarian volume is more effective than the right-sided unilateral technique with thermal dose adjusted according to ovarian volume in terms of menstrual cycle resumption, ovulation and cumulative pregnancy rates in CC-resistant PCOS patients.

     

Effects of metformin on insulin resistance, androgen concentration, ovulation and pregnancy rates in women with polycystic ovary syndrome following laparoscopic ovarian drilling

AIM: To evaluate the effects of metformin on insulin resistance, androgen concentration, ovulation rates and pregnancy rates in infertile women with polycystic ovary syndrome (PCOS). METHODS: Forty-two infertile women with PCOS were selected in this randomized clinical study. Basal steroid and gonadotropin levels were measured, and oral glucose tolerance test (OGTT) was performed. The patients were randomly divided into group 1 (n = 21) and group 2 (n = 21). Group 1 patients were treated with laparoscopic ovarian drilling (LOD). Group 2 patients underwent laparoscopic ovarian drilling (LOD) and received 1700 mg per day of metformin for 6 months. LOD was performed in women with PCOS using a unipolar electrode. Serum progesterone (P) level > 5 ng/mL was considered as a confirmation of ovulation. Ovulation and pregnancy rates were determined after six cycles. RESULTS: Serum androgens and insulin response to OGTT decreased significantly after metformin therapy. Mean serum P levels and endometrial thickness were significantly higher in cycles treated with metformin plus LOD (34.6 +/- 25.4 ng/mL, 8.4 +/- 1.1 mm) than in those treated with LOD alone (26.2 +/- 24.7 ng/mL, 7.9 +/- 2.8 mm) (P < 0.05). The ovulation (56 of 65 cycles, 86.1% vs 29 of 65 cycles, 44.6%) and pregnancy rates (nine of 21 women, 47.6% vs four of 21 women, 19.1%) were significantly higher in group 2 than in group I. CONCLUSIONS: Metformin improves insulin resistance, reduces androgen levels and significantly increases the ovulation and pregnancy rates in infertile women, following LOD.     

Evaluation of unilateral versus bilateral ovarian drilling in clomiphene citrate resistant cases of polycystic ovarian syndrome

Objectives  Laparoscopic ovarian drilling (LOD) has been put forward as the treatment of choice in women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS), with tubo-ovarian adhesion formation as the major disadvantage. Our study proposed to compare the efficacy of laparoscopic unilateral ovarian drilling with bilateral ovarian drilling in terms of ovulation and pregnancy rate with the expected advantage of decreasing postoperative adhesion rate and change in fimbiro ovarian relationship with unilateral drilling. Methods  This prospective randomized study included 44 patients with anovulatory infertility due to PCOS. Twenty-two patients underwent unilateral ovarian drilling in group-I and 22 patients underwent bilateral ovarian drilling in group-II between June 2005 and June 2007. The number of drilling site in each ovary was limited to five. The clinical and biochemical response, ovulation and pregnancy rates over a follow-up period of 1 year were compared. Tubo-ovarian adhesion rate was compared during cesarean section or during repeat laparoscopy. Results  There was no statistical difference between the two groups in terms of clinical and biochemical response, ovulation rate and pregnancy rate. Postoperatively, tubo-ovarian adhesions could be assessed in 36.3% of the patients and no adhesions were found in a single case in either group. Conclusion  Unilateral drilling cauterization of ovary is equally efficacious as bilateral drilling in inducing ovulation and achieving pregnancy. Unilateral ovarian drilling may be a suitable option in clomiphene citrate resistant infertility patient of PCOS which can replace bilateral ovarian drilling with the potential advantage of decreasing the chances of adhesion formation.     

Update in polycystic ovary syndrome: new criteria of diagnosis and treatment in Japan

Polycystic ovary syndrome (PCOS) is the most frequent endocrine disorder in women of reproductive age. In 2006 the Japanese Society of Obstetrics and Gynecology (JSOG) proposed new, revised diagnostic criteria that in the future could also be valued internationally. Based on the new diagnostic criteria, the JSOG has also proposed the revised treatment criteria in 2008. In PCOS obese patients desiring children, weight loss and exercise is recommended. Nonobese patients, or those obese women who do not ovulate after lifestyle changes, are submitted to ovulation-induction therapy with clomiphene citrate (CC). Obese CC-resistant patients who have impaired glucose tolerance or insulin resistance are treated with a combination of metformin and CC. If these treatments options are unsuccessful, ovulation induction with exogenous gonadotropin therapy or laparoscopic ovarian drilling (LOD) is recommended. A low-dose step-up regimen is recommended with careful monitoring in order to reduce the risk of ovarian hyperstimulation syndrome (OHSS) and multiple pregnancies. Alternatively, with LOD high successful pregnancy rates of around 60 % are expected with a low risk of multiple pregnancies. If ovulation induction is unsuccessful, IVF-ET treatment is indicated. In high OHSS-risk patients, systematic embryo freezing and subsequent frozen embryo transfer cycles are recommended. In nonobese, anovulatory PCOS patients not desiring children, pharmacological treatments such as Holmström, Kaufmann regimens or low-dose oral anticonceptives are used to induce regular withdrawal bleeding. These treatments are especially important for preventing endometrial hyperplasia and endometrial cancer. These new diagnostic and treatment criteria hopefully will contribute to an improved care of PCOS patients in Japan.