An algorithm for treatment of infertile women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a common condition with both a reproductive and metabolic phenotype. Women with PCOS often seek care because of infertility or menstrual cycle irregularities that result from chronic anovulation interspersed with occasional ovulatory cycles. Initially, it is important to delineate a differential diagnosis for oligo- or amenorrhea and to evaluate for disorders that may “masquerade” as PCOS. If fertility is a desired goal, then it is critical to optimize health conditions that impact fertility and gestation. Lifestyle modifications, including nutritional counseling and weight loss, should be a part of all treatment plans. Even minimal (5%) weight loss in obese women with PCOS improves both ovulation and pregnancy rates. The first line of treatment for ovulation induction remains the selective estrogen receptor modulator (SERM) clomiphene citrate. The role of insulin sensitizers, particularly metformin, remains unclear. A recent consensus panel recommended against its routine use in the absence of an elevated glucose or hemoglobin A1c. If a woman fails to achieve pregnancy after a trial of weight loss and six ovulatory cycles induced by clomiphene citrate, then ovulation induction with exogenous gonadotropin, with or without timed intrauterine insemination, or in vitro fertilitization, is a reasonable next step. Women with PCOS are particularly prone to excessive follicle development and are at increased risk for ovarian hyperstimulation syndrome (OHSS). Although limited data exist comparing approaches to ovulation induction or controlled ovarian stimulation in women with PCOS, the American Society for Reproductive Medicine recommends the use of “step-up” or “step-down” protocols in which a low dose of exogenous FSH or combined gonadotropins are employed in an attempt to constrain ovarian responsiveness. In vitro fertilization allows for the transfer of only one embryo or for cryopreservation of all embryos with subsequent transfer of a single embryo in a subsequent cycle without ovarian stimulation. Countless questions regarding pathogenesis and treatment of PCOS create opportunity for basic and clinical research and for refinement of existing therapeutic approaches.     

Insulin-sensitizing agents in women with polycystic ovary syndrome

Improvement of insulin resistance and, consequently, hyperinsulinemia is one of the main procedures for treating the polycystic ovary syndrome. The improvement of insulin resistance and the decrease in insulin concentration can be achieved in different ways: (1) by lifestyle modifications; (2) by using insulin sensitizing agents; and (3) by using antiandrogens.     

多囊卵巢综合征不孕患者辅助生殖治疗临床效果分析

目的 探讨多囊卵巢综合征(PCOS)不孕患者辅助生殖治疗的临床效果及方案选择.方法 回顾性分析2003年1月至2007年11月间,在山东大学附属省立医院生殖医学中心就诊的PCOS不孕患者的临床资料,根据治疗方案不同,分为药物治疗[分别用来曲唑(LE组,58个周期)或枸橼酸氯米芬(CC组,45个周期)]、体外受精-胚胎移植(IVF-ET)治疗、经阴道B超未成熟卵泡穿刺治疗、未成熟卵体外成熟(IVM)治疗等方案,分析其临床效果.结果 (1)药物治疗者中,LE组排卵率为66%(38/58),Cc组为47%(21/45);人绒毛膜促性腺激素(hCG)注射日平均子宫内膜厚度,LE组为(0.89±0.13)cm,CC组为(0.78±0.08)cm;hCG注射日宫颈黏液评分,LE组为(11.9±1.8)分,CC组为(9.9±1.8)分;平均成熟卵泡数,LE组为(1.08±0.28)个,CC组为(1.73±0.59)个;hCG注射日平均雌二醇水平,LE组为(983±138)pmol/L,CC组为(1676±372)pmol/L,两组各项指标比较,差异均有统计学意义(P<0.05);LE组周期妊娠率为14%(8/58),CC组为13%(6/45),两组比较,差异无统计学意义(P>0.05).(2)IVF-ET治疗者中,1584例PCOS不孕患者(PCOS组)促性腺激素(Gn)总用量[(980±1192)IU]低于对照组[(1194±1389)IU,同期因输卵管因素行IVF-ET治疗者1615例],但两组使用Gn平均天数[分别为(9.6±1.8)、(9.5±1.8)d]、hCG注射日平均雌二醇水平[分别为(15 752±6206)、(9675±4818)pmol/L]、平均获卵数[分别为(21±6)、(9±3)个]、平均受精数[分别为(15±6)、(7±3)个]、平均卵裂数[分别为(12.9±5.7)、(5.7±2.8)个]和重度卵巢过度刺激综合征(OHSS)发生率(分别为4.86%、1.67%)比较,PCOS组均明显高于对照组,差异均有统计学意义(P<0.05).但两组临床妊娠率(分别为44.7%、45.0%)比较,差异无统计学意义(P>0.05).(3)109例经阴道B超未成熟卵泡穿刺治疗患者的睾酮和黄体生成素水平均较治疗前明显下降,卵巢基础窦卵泡计数随穿刺次数增加而减少.穿刺治疗后应用尿促性腺激素促排卵治疗时,OHSS发生率很低,穿刺治疗后妊娠率达50%以上.(4)IVM治疗的286例PCOS不孕患者,取卵周期304个,平均每周期取卵12.3个,有76例患者获得临床妊娠.结论 PCOS不孕患者治疗的选择方案较多,上述4种治疗方案均有效,应结合患者具体情况给予个体化处理.     

Strategies for the use of insulin-sensitizing drugs to treat infertility in women with polycystic ovary syndrome

OBJECTIVE: Insulin resistance and its compensatory hyperinsulinemia play a key pathogenic role in the infertility of the polycystic ovary syndrome. Numerous studies indicate that insulin-sensitizing drugs can be used to enhance spontaneous ovulation and the induction of ovulation in the syndrome. The aim of this review is to summarize the studies in which insulin-sensitizing drugs were used to increase ovulation rate or improve fertility in women with the PCOS and to translate the information into practical guidelines for the use of these drugs by reproductive endocrinologists. DESIGN: Review and critique of studies in which an insulin-sensitizing drug was used to increase ovulation rate or improve infertility in women with the polycystic ovary syndrome. MAIN OUTCOME MEASURE(S): Ovulation rate and pregnancy rate. RESULT(S): Studies have demonstrated that insulin-sensitizing drugs can increase spontaneous ovulation, enhance the induction of ovulation with clomiphene citrate, and increase clinical pregnancy rates. CONCLUSION(S): An algorithmic approach is provided for the use of insulin-sensitizing drugs to treat the anovulation and infertility of women with the polycystic ovary syndrome.     

Laparoscopic ovarian drilling as first line of treatment in infertile women with polycystic ovary syndrome.

Laparoscopic ovarian drilling (LOD) is used as a first line of treatment, as a second line of treatment after patients have proved resistant to clomiphene or as a third line of treatment after failed ovulation induction with gonadotropins. We present the postoperative pregnancy rates of 57 women to evaluate a potential optimal time of LOD together with the other treatment regimens of infertile women with polycystic ovary syndrome (PCOS). Data on the preoperative and operative treatment, and background data were evaluated for their influence on pregnancy rates. The pregnancy rate was 61% among women with PCOS who had LOD. No difference was found in the clinical data between the women who became pregnant and those who did not. Likewise, no difference was found between the women who had pre- and/or postoperative medical ovulation treatment and those who had none. The median time to pregnancy after LOD was 135 days. LOD alone resolves infertility within 4-6 months in 50-60% of couples. A strategy with diagnostic laparoscopy and LOD as the first line of treatment of infertility in women with PCOS will shorten the time to pregnancy for many women, reduce the need for medical ovulation induction and enable diagnosis of those women with anatomic infertility, who can achieve pregnancy only by in vitro fertilization treatment.     

Marital satisfaction and social support in infertile women with and without polycystic ovary syndrome

Background and objective

Few studies have evaluated marital satisfaction and social support in infertile women with polycystic ovary syndrome (PCOS). The aim of this study was to assess and compare marital satisfaction and social support among infertile women with and without PCOS.

Therapeutic strategies for ovulation induction in infertile women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder characterized by hirsutism, obesity, hyperandrogenism and insulin resistance. The syndrome is often accompanied by infertility because of anovulation. Many approaches have been proposed to solve this problem, with the most commonly used therapies being ovarian drilling and pharmacological ovulation induction. Ovarian drilling is a procedure in which a laser fiber or electro-surgical needle punctures the ovary four to ten times. Side-effects are rare and often related to surgery itself. Pharmacological strategies include administration of metformin and insulin-sensitizing agents, clomiphene citrate (CC), gonadotropins and aromatase inhibitors. Metformin appears valuable in increasing ovulation rate, menstrual cyclicity and pregnancy rate. CC is an oral estrogen antagonist that raises circulating concentrations of follicle-stimulating hormone (FSH) and induces follicular growth in most women with PCOS and anovulation. Failure to respond is associated with high body mass index and high androgen levels. Aromatase inhibitors mimic the central reduction of negative feedback through which CC works. Ovulation induction with recombinant FSH has proved successful, but treatment requires skill and experience to avoid multiple pregnancies and ovarian hyperstimulation syndrome. The hypothetical deleterious effects of the high luteinizing hormone concentrations observed in PCOS patients seem to be related to the concomitant hyperinsulinemia (and/or insulin resistance). A thorough understanding of the syndrome and a careful assessment of each patient are the mainstays for choosing an appropriate treatment regimen.     

Unilateral laparoscopic ovarian diathermy in infertile women with clomiphene citrate-resistant polycystic ovary syndrome

We evaluated the efficacy of unilateral versus bilateral laparoscopic ovarian diathermy in infertile women with clomiphene citrate-resistant polycystic ovary syndrome. Recall follow-up 18 to 48 months after laparoscopic ovarian diathermy showed that unilateral ovarian diathermy was as effective and long lasting as bilateral ovarian diathermy in the resumption of menstruation and pregnancy rates.     

Choice of treatment for women with polycystic ovary syndrome

Polycystic ovary syndrome presents with many different symptoms and signs, for which different therapies are indicated. However, for the majority of women, the metabolic disorder requires diligence in management, regardless of the presenting complaint.     

Fertility management experiences of women with polycystic ovary syndrome in Australia

Abstract

Background: Women with polycystic ovary syndrome (PCOS) are usually told that the condition is associated with fertility difficulties. However, little is known about their fertility management including contraceptive use, childbearing desires, and pregnancy outcomes.

Aim: To compare the fertility management experiences and outcomes of Australian women with and without PCOS.

Method: The 2013 Australian electoral roll was used to identify a random sample of 18- to 50-year-old women who were sent the Understanding Fertility Management in Australia survey to be completed anonymously. Factors associated with fertility management and outcomes were identified in multivariable analyses.

Results: Among the 1543 women who completed and returned the survey, 113 (7.3%) reported having PCOS. Women with PCOS reported a similar rate of current contraceptive use as women without PCOS (50.4% vs. 52.6%, p?=?.66). However, they were significantly younger at first pregnancy (24.9 vs. 26.8 years, p?=?.015), more likely to have consulted a health professional about fertility management (OR: 3.86, 95% CI: 2.50–5.96, p?<?.001), and perceive that it would be difficult to conceive (OR: 2.31, 95% CI: 1.41–3.79, p?=?.001) than women without PCOS. There were no significant differences in the number of desired children, unintended pregnancies, live births, abortions or miscarriages between women with and without PCOS.

Conclusion: These findings indicate that women with PCOS need more nuanced information about their fertility potential. While they may experience fertility difficulties because of their condition, they should also be informed that they can conceive spontaneously and need reliable contraception to avoid pregnancy when it is not wanted.     

Metabolic syndrome in women with polycystic ovary syndrome

The prevalence of the metabolic syndrome in polycystic ovary syndrome (PCOS) is high across all age groups. Dyslipidemia, particularly a decreased high-density lipoprotein cholesterol level, also is common in women with PCOS.     

Preptin in women with polycystic ovary syndrome

Introduction: Polycystic ovary syndrome (PCOS) patients, frequently develop metabolic complications, such as insulin resistance (IR), impaired carbohydrate metabolism, dyslipidemia, obesity. Among the new markers responsible for metabolic disorders, preptin seems to be of great significance.

Material: One hundred and thirty-four women aged 17–45 were enrolled. PCOS was diagnosed in 73 women on the basis of ESHRE-ASRM criteria. Non-PCOS group consisted of 61 women with regular menstruation matched for nutritional status.

Methods: All women underwent anamnesis, physical examination, anthropometric measurements, the abdominal ultrasound examination, and dual energy X-ray absorptiometry (DXA). Serum adropin levels were determined by ELISA. Biochemical and hormonal (testosterone, androstenedione, LH, FSH, estradiol) measurements were also performed. Insulin resistance indices (HOMA, QUICKI, Matsuda) and free androgen index (FAI) were calculated with the test results according to the standard formula. For all comparisons, statistical significance was defined by p?≤?.05.

Results: Serum preptin levels were significantly higher in the PCOS group. No significant correlations between preptin level and metabolic and hormonal markers were observed. The logistic regression analysis demonstrated that serum preptin level was an independent factor differentiating the two groups.

Conclusions: Serum preptin levels were significantly higher in women with PCOS compared with controls. This peptide might be an independent predictor of PCOS in the future.     

N-acetyl-cysteine treatment improves insulin sensitivity in women with polycystic ovary syndrome

Objective: To evaluate the effect of N-acetyl-cysteine (NAC) on insulin secretion and peripheral insulin resistance in subjects with polycystic ovary syndrome (PCOS).

Design: Prospective data analysis.

Setting: Volunteer women in an academic research environment.

Patient(s): Six lean and 31 obese subjects, aged 19–33 years.

Intervention(s): Patients were treated for 5–6 weeks with NAC at a dose of 1.8 g/day orally. A dose of 3 g/day was arbitrarily chosen for massively obese subjects. Six of 31 obese patients with PCOS were treated with placebo and served as controls.

Main Outcome Measure(s): Before and after the treatment period, the hormonal and lipid blood profile and insulin sensitivity, assessed by an hyperinsulinemic euglycemic clamp, were evaluated and an oral glucose tolerance test (OGTT) was performed.

Result(s): Fasting glucose, fasting insulin, and glucose area under curve (AUC) were unchanged after treatment. Insulin AUC after OGTT was significantly reduced, and the peripheral insulin sensitivity increased after NAC administration, whereas the hepatic insulin extraction was unaffected. The NAC treatment induced a significant fall in T levels and in free androgen index values (P<.05). In analyzing patients according to their insulinemic response to OGTT, normoinsulinemic subjects and placebo-treated patients did not show any modification of the above parameters, whereas a significant improvement was observed in hyperinsulinemic subjects.

Conclusion(s): NAC may be a new treatment for the improvement of insulin circulating levels and insulin sensitivity in hyperinsulinemic patients with polycystic ovary syndrome.     

The role of metformin in the management of polycystic ovary syndrome

PURPOSE OF REVIEW: The purpose of this review is to provide a critical summary of recent studies on the clinical effects of metformin in polycystic ovary syndrome. RECENT FINDINGS: After the recognition that hyperinsulinaemia is a fundamental disturbance in polycystic ovary syndrome, a novel and promising form of therapy in the form of insulin-sensitizing drugs has been introduced. Among these, metformin is the most widely used. This therapeutic intervention has been shown to exert beneficial effects on the endocrine and metabolic disturbances that characterize the syndrome and, more recently, to improve the reproductive outcome in women with polycystic ovary syndrome. With rapid progress in this area, metformin use has also been extended to the management of lean polycystic ovary syndrome patients. SUMMARY: Although most studies are nonrandomized trials, current data provide a rationale for metformin as first-line management for women with polycystic ovary syndrome, alone or in combination with conventional treatments. Controversy still exists, however, regarding the mechanisms by which metformin exerts its beneficial effects in polycystic ovary syndrome.