Search

Objective: To compare the effectiveness of alternative first line treatment options for women with WHO group II anovulation wishing to conceive., Design: Systematic review and network meta-analysis., Data Sources: Cochrane Central Register of Controlled Trials, Medline, and Embase, up to 11 April 2016., Study Selection: Randomised controlled trials comparing eight ovulation induction treatments in women with WHO group II anovulation: clomiphene, letrozole, metformin, clomiphene and metformin combined, tamoxifen, gonadotropins, laparoscopic ovarian drilling, and placebo or no treatment. Study quality was measured on the basis of the methodology and categories described in the Cochrane Collaboration Handbook. Pregnancy, defined preferably as clinical pregnancy, was the primary outcome; live birth, ovulation, miscarriage, and multiple pregnancy were secondary outcomes., Results: Of 2631 titles and abstracts initially identified, 54 trials reporting on 7173 women were included. All pharmacological treatments were superior to placebo or no intervention in terms of pregnancy and ovulation. Compared with clomiphene alone, both letrozole and the combination of clomiphene and metformin showed higher pregnancy rates (odds ratio 1.69, 95% confidence interval 1.33 to 2.14; 1.71, 1.28 to 2.27; respectively). Letrozole led to higher live birth rates when compared with clomiphene alone (1.67, 1.11 to 2.49). Metformin led to lower multiple pregnancy rates compared with clomiphene alone (0.22, 0.05 to 0.93)., Conclusions: In women with WHO group II anovulation, letrozole and the combination of clomiphene and metformin are superior to clomiphene alone in terms of pregnancy. Compared with clomiphene alone, letrozole is the only treatment showing a significantly higher rate of live birth., Systematic Review Registration: PROSPERO CRD42015027579., Readers' Note: This is the second version of this paper. The original version was corrected following the retraction of two studies and removal of another which were ineligible (references 40, 41, and 75 of the original paper). These studies are not shown in this version. A tracked changes version of the original version is attached as a supplementary file to the correction notice, which explains the issue further., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Unlabelled: BACKGROUND Recent studies suggest that metformin may be more effective in women with polycystic ovary syndrome (PCOS) who are non-obese. The objective here is to determine and compare the effectiveness of metformin and clomiphene citrate for improving fertility outcomes in women with PCOS and a BMI < 32 kg/m(2) (BMI 32 kg/m(2) was used to allow for international differences in BMI values which determine access to infertility therapy through the public health system). METHODS Databases were searched for English language articles until July 2011., Inclusion Criteria: women of any age, ethnicity and weight with PCOS diagnosed by all current criteria, who are infertile; at least 1000 mg of any type of metformin at any frequency, including slow release and standard release, compared with any type, dose and frequency of clomiphene citrate., Outcomes: rates of ovulation, live birth, pregnancy, multiple pregnancies, miscarriage, adverse events, quality of life and cost effectiveness. Data were extracted and risk of bias assessed. A random effects model was used for meta-analyses of data, using risk ratios (relative risk). RESULTS The search returned 4981 articles, 580 articles addressed metformin or clomiphene citrate and four randomized controlled trials (RCTs) comparing metformin with clomiphene citrate were included. Upon meta-analysis of the four RCTs, we were unable to detect a statistically significant difference between the two interventions for any outcome in women with PCOS and a BMI < 32 kg/m(2), owing to significant heterogeneity across the RCTs. CONCLUSIONS Owing to conflicting findings and heterogeneity across the included RCTs, there is insufficient evidence to establish a difference between metformin and clomiphene citrate in terms of ovulation, pregnancy, live birth, miscarriage and multiple pregnancy rates in women with PCOS and a BMI < 32 kg/m(2). However, a lack of superiority of one treatment is not evidence for equivalence, and further methodologically rigorous trials are required to determine whether there is a difference in effectiveness between metformin and placebo (or no treatment) or between metformin and clomiphene citrate for ovulation induction in women with PCOS who are non-obese. Until then, caution should be exercised when prescribing metformin as first line pharmacological therapy in this group of women.

Though widely used, there is uncertainty about the effectiveness and adverse effects of metformin and clomiphene citrate (CC) for infertility in polycystic ovary syndrome (PCOS). A systematic review (SR) of the best available evidence suggests that both CC and metformin are better than placebo for increasing ovulation and pregnancy rates, but CC is more effective than metformin for ovulation, pregnancy and live-birth rates, in PCOS patients with body mass index (BMI) >30. A combination of CC and metformin is superior to either metformin alone or CC alone, depending on the BMI and CC sensitivity of the patient. This SR provides key messages to guide clinicians and consumers on the use of these interventions in different subgroups of women with PCOS., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

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., (© 2012 The Authors ANZJOG © 2012 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

The present paper reports a single department's retrospective case series of all clomiphene citrate (CC) combined with intrauterine insemination (IUI) treatment cycles for ovulatory infertility performed during 2002. Thirty-eight couples with unexplained, endometriosis, male or unilateral tubal factor infertility had undergone 71 cycles of CC and IUI. The clinical and ongoing cycle pregnancy rates were 20 and 17%, respectively. Seven percent of the clinical pregnancies were multiple pregnancies, with all multiple pregnancies being twin gestations. The current use of CC and IUI is an effective early treatment option in couples with ovulatory infertility presenting to our department.

Background: Controlled ovarian hyperstimulation (COH) with clomiphene citrate (CC) combined with intrauterine insemination (IUI) is often used as treatment for ovulatory infertility which includes unexplained, male, cervical, endometriosis, and tubal infertility., Aims: To review the effectiveness of CC and IUI in ovulatory infertility., Methods: Systematic review of pertinent randomised controlled trials (RCT) using the bibliographic databases MEDLINE and EMBASE. References of selected articles identified were hand-searched for additional relevant citations., Results: Six published RCT were included in the overall review. Meta-analysis demonstrated a higher cycle pregnancy rate (CPR) with CC and IUI compared to timed intercourse in the natural cycle (P < 0.001 and odds ratio = 4.6, 95% CI = 1.9-11.3). Treatment with gonadotrophins and IUI results in a higher CPR compared to CC and IUI (P = 0.005 and odds ratio = 2.9, 95% CI = 1.3-6.2). Further RCT are required comparing CC and IUI with IUI or CC alone before one can make firm conclusions., Conclusions: Clomiphene citrate combined with IUI is more effective than timed intercourse in the natural cycle at achieving pregnancy in couples with ovulatory infertility. However, treatment with gonadotrophins and IUI is superior to CC and IUI.

Objective: To determine whether a spontaneous luteinizing hormone (LH) surge influences the pregnancy and miscarriage rate in women with unexplained infertility undergoing controlled ovarian hyperstimulation (COH) without in vitro fertilization., Design: Retrospective cohort study., Setting: Ovulation Induction Clinic, Royal Hospital for Women, Sydney, Australia., Patients: 145 patients with unexplained infertility who underwent 374 cycles of COH., Methods: Two types of ovarian stimulation protocols were used: human menopausal gonadotrophin (hMG) alone or hMG and clomiphene citrate (CC). A spontaneous LH surge occurred in 54% of the total cycles. All patients received human chorionic gonadotrophin, whether or not a spontaneous LH surge occurred. All cycles were covered by natural intercourse., Main Outcome Measures: Cycle pregnancy rate and miscarriage rate in cycles with or without a spontaneous LH surge., Results: The cycle pregnancy rate of the LH surge group was significantly higher than that of the no LH surge group for CC/hMG cycles (16.4% and 4.3% respectively, p = 0.02) but not for hMG alone cycles (12.8% and 10% respectively, P > .05). The miscarriage rate was not significantly different between the LH surge group and no LH surge group in either the CC/hMG cycles (30% and 75% respectively, P > .05) or the hMG alone cycles (22% and 38% respectively, P > .05)., Conclusions: In women with unexplained infertility undergoing COH with CC/hMG, the occurrence of a spontaneous LH surge is a favorable event associated with a significantly increased pregnancy rate. The data showed a lower miscarriage rate, but there was insufficient power to confirm or refute this result.