Two treatment methods of infertility associated with polycystic ovarian syndrome

OBJECTIVES: 30 patients treated for infertility associated with PCO were analyzed. Anovulatory cycles and US scans of ovaries were taken as criteria for PCO. MATERIALS AND METHODS: Patients were treated either by the laparoscopic electrocauterization (n = 16) of ovaries or by the ultrasonographic punction of follicles (n = 14). Number of ovulatory cycles, cumulative pregnancy rate and hormonal changes were analyzed. RESULTS: We observed the same efficacy of both methods in terms of ovulatory cycles and pregnancy rates. The cumulative pregnancy rate was 37.5% in laparoscopic and 35.7% in ultrasonographic groups during the 3 months' observation. CONCLUSIONS: Ultrasonographic punction has appeared to be easier to do and safer for the patient and have the same pregnancy rate. It also gives opportunity for in vitro culture and maturation of obtained oocytes.     

Metformin for the treatment of polycystic ovary syndrome

OBJECTIVE: To familiarize obstetrician-gynecologists with the use of metformin for the treatment of polycystic ovary syndrome (PCOS). DATA SOURCES: Using OVID, 94 English-language articles published after 1966 indexed with the key words "metformin" and "polycystic ovary syndrome" were identified. METHODS OF STUDY SELECTION: Studies were excluded if they did not have a control group, did not use the National Institutes of Health definition of PCOS, did not have a clinical outcome as an end point, and were not in the English language. Reviews were also excluded, leaving 21 articles for inclusion. TABULATION, INTEGRATION, AND RESULTS: Three clinical trials reported that for the treatment of anovulatory infertility caused by PCOS, metformin plus clomiphene is more effective than clomiphene alone in inducing ovulation. For the treatment of irregular menses caused by PCOS in women not attempting conception, metformin therapy may restore ovulatory menses in the majority of women. However, most women will require 4-6 months of metformin therapy before they achieve ovulatory menses. In obese women, metformin plus a low-calorie diet may be associated with more weight loss than a low-calorie diet alone. CONCLUSION: Polycystic ovary syndrome is a common gynecologic endocrine disorder. Obstetrician-gynecologists should be familiar with the indications and contraindications for the use of metformin in their practice.     

Metformin for the treatment of the polycystic ovary syndrome

The polycystic ovary syndrome (PCOS) is characterized by increased secretion of LH, insulin and androgens. The main clinical complaints of women with PCOS include: oligo- or amenorrhea, dysfunctional uterine bleeding, hirsutism, obesity and/or anovulatory infertility. The first line treatment for these problems include: 1) estrogen-progestin therapy for oligomenorrhea and dysfunctional uterine bleeding; 2) estrogen-progestin therapy and/or antiandrogens for hirsutism; 3) lifestyle changes such as diet and exercise for obesity and 4) weight loss or clomiphene for anovulatory infertility. However, clinical trials have indicated that metformin is effective second line therapy when first line therapy has not been effective, is not acceptable to the patient or is medically contraindicated. The addition of metformin to the armamentarium of the gynecological endocrinologist represents an important advance.     

Metformin versus rosiglitazone in the treatment of polycystic ovary syndrome

OBJECTIVE: The aim of our study is to investigate and compare the clinical, biochemical and hormonal changes during application of insulin-sensitizers from two different groups. STUDY DESIGN: This prospective, open clinical study lasted 3 months and included 30 women with PCOS, divided in two groups of 15 women each. Group 1 received 850 mg metformin twice a day and group 2 was treated with rosiglitazone 4 mg a day. Serum levels of testosterone, immune reactive insulin (IRI), sex hormone binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS) and lipid metabolism parameters were measured before the treatment, and on the 3rd month. Free androgen index (FAI) and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. Body mass index (BMI) and waist-to-hip ratio (WHR) were assessed at baseline and at the end of therapy. RESULTS: Two parameters change significantly in the 3rd month in our study--testosterone and insulin. Much better decrease in the level of testosterone and free androgen index was established in group treated with metformin, while the indices of insulin resistance were better influenced in the group treated with rosiglitazone. CONCLUSION: Application of insulin sensitizers from both groups has a favorable influence on the basic hormonal deviations in PCOS--the hyperandrogenemia and the insulin resistance. In cases with PCOS metformin treatment influences better hyperandrogenemia, while rosiglitazone affects more pronouncedly insulin resistance and hyperinsulinemia.     

Metformin treatment in different phenotypes of polycystic ovary syndrome

Background

The aim of this study was to evaluate the effectiveness of Metformin on ovulation and eventual clinical pregnancy in different phenotypes of polycystic ovary syndrome (PCOS).

Materials and methods

A total of 359 subjects who had proven PCOS according to Rotterdam criteria were prospectively selected. Patients’ PCOS phenotypes were determined and recorded. All patients were younger than 35 years. Clinical and biochemical assays in all patients were initially obtained. Then patients were divided into two separate groups. One group received both 1,500 mg of Metformin and 1 mg of folic acid per day and the other group received only 1 mg of folic acid for a total of 2 months. Subsequently, all patients underwent ovulation stimulation with 5 mg of Letrozole per day for 5 days followed by an intra-uterine insemination. Finally, ovulation and pregnancy rates were evaluated for all four PCOS phenotypes. Effect of Metformin therapy was evaluated for each group and each phenotype.

Results

The pregnancy rate in Metformin and non-Metformin groups were, respectively, as follows: in phenotype A (39.2 vs. 33.7 %, p = 0.270), phenotype B (43.8 vs. 20 %, p = 0.210), phenotype C (44 vs. 20 %, p = 0.064), and phenotype D (36.5 vs. 28.6 %, p = 0.279).

Conclusion

Although there was a little improvement in ovulation and pregnancy rates among patients with B and C phenotypes, there was not a statistically significant difference between the two groups. Based on our study, Metformin therapy does not change the ovulation and pregnancy rate.     

Metformin in polycystic ovary syndrome

PURPOSE OF REVIEW: Metformin has become an established treatment for women with polycystic ovary syndrome, although controversy remains as to how effective it is and in which populations it should be used. This review examines the recent literature in order to ascertain the evidence for the benefits and disadvantages of using metformin in women with polycystic ovary syndrome. RECENT FINDINGS: A Cochrane systematic review and metaanalysis examined the evidence for metformin in treating polycystic ovary syndrome. Since this was published there have been a number of new trials, some of which have been reasonably large involving participants from many different countries. SUMMARY: Evidence shows that metformin is effective in inducing ovulation, has some marginal benefit in improving aspects of the metabolic syndrome, improves objective measures of hirsutism, and seems to be effective in both obese and lean individuals. However, it has significant side effects, and the high levels of effectiveness that were reported by some early trials have not been replicated. Metformin should always be used as an adjuvant to general lifestyle improvements, and not as a replacement for increased exercise and improved diet.     

Assisted reproduction in the treatment of polycystic ovarian syndrome

Treatment of patients with polycystic ovary syndrome (PCOS) with assisted reproductive techniques is a great challenge for the infertility specialist. Patients with PCOS demonstrate many problems, such as excessive body weight and hyperinsulinaemia, that render management more complex. Prior to treatment with IVF, the PCOS patient should be thoroughly evaluated for disclosure of endometrial neoplasia, hyperinsulinaemia, and other general health related problems. Ovarian stimulation for IVF carries the risks of overstimulation and severe hyperstimulation, which should be avoidable in most cases with preventive measures. The outcome in terms of pregnancy and implantation rates is similar for patients with PCOS when compared with patients undergoing IVF for other indications. There are some questions regarding oocyte and embryo quality in women with PCOS. This manifests itself in lower fertilization rate and decreased embryo quality in some studies. However, increased numbers of oocytes available for insemination or ICSI compensate for decreased fertilization rates and embryo quality. More recent studies suggest higher cumulative conception rates in women with PCOS when compared with controls. In-vitro maturation (IVM) of oocytes retrieved from non-stimulated or minimally stimulated cycles represents a viable option that should be considered seriously when assisted conception is attempted. Results of IVM, however, should be improved further and generalized before the technique can be advocated as the initial treatment approach in these patients.     

Co-involvement of psychological and neurological abnormalities in infertility with polycystic ovarian syndrome

Objective  

To investigate psychological distress, serum levels of monoamine neurotransmitters and their metabolites, as well as their correlation with polycystic ovarian syndrome (PCOS).     

Metformin therapy in polycystic ovary syndrome

Polycystic ovarian syndrom (PCOS) affects 5% to 10% of women of reproductive age, and is the most common reason of anovulation in infertile women. It is multi-symptom disease. A drug which is used to induce ovulation in women with PCOS is clomiphene citrate. After clomiphene treatment, ovulation is achieved in 56%-73% of women. The rest of them has different level of opportunity to therapy. Clomiphene does not have influence on elementary factor in PCOS which seems to be opportunity to insulin. The drug which can have positive effect is metformin, derivative from biguanid. Its influence on percent of ovulation, pregnancy and live births was evaluated based on randomized trials. Many trials have reserched this so far, but their results are divergent. In this article, we are aiming to systemize results of randomized trials concerning the role of metformin in PCOS therapy.     

Revisit of metformin treatment in polycystic ovarian syndrome

Polycystic ovary syndrome (PCOS) is a common endocrinopathy in women; its traditional pharmacological therapy mainly addresses short-term symptom control and does not correct the associated long-term metabolic risks. Recently, there has been increasing evidence that insulin resistance has an important implication in the pathogenesis of PCOS and that insulin-sensitizing drugs are a useful therapeutic approach. Therefore this review aims to discuss the current evidence on the use of metformin, a commonly used insulin-sensitizing agent, in treating both the short-term and the long-term problems of women with PCOS.     

The treatment of infertility in polycystic ovary syndrome: a brief update

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. Lifestyle change alone is considered the first-line treatment for the management of infertile anovulatory PCOS women who are overweight or obese. First-line medical ovulation induction therapy to improve fertility outcomes is clomiphene citrate, whilst gonadotrophins, laparoscopic ovarian surgery or possibly metformin are second line in clomiphene citrate-resistant PCOS women. There is currently insufficient evidence to recommend aromatase inhibitors over that of clomiphene citrate in infertile anovulatory PCOS women in general or specifically in therapy naive or clomiphene citrate-resistant PCOS women. IVF/ICSI treatment is recommended either as a third-line treatment or in the presence of other infertility factors.     

Association of metabolic syndrome in polycystic ovarian syndrome: an observational study

Objectives

To find out the prevalence of metabolic syndrome (MBS) in women with PCOS and assess their strength of association. Methods: Total 50 apparently healthy non-pregnant PCOS subjects of 15 to 35 years were studied for having the features of MBS from May 2006 to April 2007. MBS was diagnosed by National Cholesterol Education Program’s Adult Treatment Panel III 2001 criteria. Student’s t test & Mann-Whitney U test were used for statistical analysis.

Results

21 subjects out of 50 (42%) met criteria for the MBS. 15(71.5%) belonged to 26–35 years and six (20.7%) in 15–25 years. Prevalence of waist circumference > 88 cm were noted in 34%, HDL cholesterol< 50 mg/dl in 50%, triglycerides ≥ 150 mg/dl in 40%, BP ≥130/85 mm Hg in 50% and FBS≥ 110 mg/dl in 16%. Women with higher insulin resistance and free testosterone levels significantly (P<0.01) correlated with higher prevalence of MBS.

Conclusion

The metabolic syndrome and its individual components are common in PCOS, particularly among women with hyperinsulinemia and hyperandrogenism.     

Surgical treatment of polycystic ovary syndrome associated with infertility

Laparoscopic ovarian drilling is a relatively simple procedure performed by minimal access and usually on an outpatient basis. It provides an alternative treatment option for polycystic ovary syndrome (PCOS) patients anovulatory to clomiphene citrate. The mechanism of action of laparoscopic ovarian drilling is unclear; its beneficial effect is apparently due to destruction of the androgen-producing stroma. The procedure appears to have little or no effect on insulin sensitivity and lipoprotein profile. The majority (56-94%) of PCOS patients who are clomiphene citrate resistant ovulate after drilling, and at least half of them go on to achieve a pregnancy. Predictive factors for pregnancy are younger age and lower body mass index. The endocrine changes resulting from ovarian drilling last for an extended period of time. Exogenous gonadotrophin treatment and laparoscopic ovarian drilling appear to yield comparable ovulation and pregnancy rates; however, multiple pregnancy is rare with drilling. There are several complications associated with the procedure, including post-operative periadnexal adhesion formation. Alternative treatment options, including lifestyle modification (diet and exercise) and metformin, may well reduce the need for ovarian drilling in well-selected cases. Progress in understanding of this complex syndrome and effective new treatments will further diminish the need for surgery.     

Factors affecting the outcome of laparoscopic ovarian drilling for polycystic ovarian syndrome in women with anovulatory infertility

Objective To describe and analyse the factors affecting the pregnancy rate of laparoscopic ovarian drilling for polycystic ovarian syndrome in women with anovulatory infertility.
Design A retrospective study.
Setting A specialist infertility clinic based at a teaching hospital in England.
Population One hundred and eighteen women, for whom hospital records and follow up data were available, with polycystic ovarian syndrome who underwent laparoscopic ovarian surgery for anovulatory infertility over a five year period, between January 1991 and December 1995.
Main Outcome measures Ovulation and pregnancy rate.
Results The cumulative conception rate 12 months after the treatment was 54%. Women who conceived following the surgery had a shorter duration of infertility, were treated with diathermy (rather than laser), had higher pre-operative luteinising hormone levels, were younger and were more likely to have ultrasonographic evidence of polycystic ovarian disease. Logistic multiple regression analysis showed that the duration of infertility, modality used in treatment (laser or diathermy) and the preoperative levels were the main determinants of the outcome.
Conclusion Women with polycystic ovarian syndrome respond favourably to laparoscopic ovarian drilling. The success rate in women with infertility duration of less than three years, treated with diathermy, in whom the pre-operative level was more than 10 IU/L reached 79%.     

Consensus on infertility treatment related to polycystic ovary syndrome

The treatment of infertile women with polycystic ovary syndrome (PCOS) is surrounded by many controversies. On the basis of the currently available evidence, a group of experts reached a consensus regarding the therapeutic challenges raised in these women. Before any intervention is initiated, preconceptional counseling should be provided emphasizing the importance of lifestyle, especially weight reduction and exercise in overweight women, smoking, and alcohol consumption. The recommended first-line treatment for ovulation induction remains the anti-estrogen clomiphene citrate (CC). Recommended second-line intervention, should CC fail to result in pregnancy, is either exogenous gonadotropins or laparoscopic ovarian surgery (LOS). The use of exogenous gonadotropins is associated with increased chances for multiple pregnancy, and, therefore, intense monitoring of ovarian response is required. Laparoscopic ovarian surgery alone is usually effective in less than 50% of women, and additional ovulation induction medication is required under those circumstances. Overall, ovulation induction (representing the CC-gonadotropin paradigm) is reported to be highly effective with a cumulative singleton live-birth rate of 72%. Recommended third-line treatment is in vitro fertilization (IVF). More patient-tailored approaches should be developed for ovulation induction based on initial screening characteristics of women with PCOS. Such approaches may result in deviation from the above mentioned first-line, second-line, or third-line ovulation strategies in well-defined subsets of patients. Metformin use in PCOS should be restricted to women with glucose intolerance. Based on recent data available in the literature, the routine use of this drug in ovulation induction is not recommended. Insufficient evidence is currently available to recommend the clinical use of aromatase inhibitors for routine ovulation induction. Even singleton pregnancies in PCOS are associated with increased health risk for both the mother and the fetus.     

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.