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Long versus short course treatment with Metformin + Clomiphene Citrate for ovulation induction in women with PCOS

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among women of reproductive‐age. Apart from infertility, women with PCOS often have other endocrine disorders, including insulin resistance, hyperinsulinaemia and hyperandrogenism. Metformin combined with clomiphene citrate (CC), has been shown to be more effective in ovulation induction than clomiphene citrate alone. The optimal duration for metformin pretreatment before initiation of clomiphene citrate, however, is unknown. There have been no trials conducted to determine the effectiveness of short‐course (less than four weeks) metformin plus clomiphene citrate compared to the conventional long‐course (four weeks or more) metformin plus clomiphene citrate with regard to ovulation and achievement of pregnancy in infertile women with polycystic ovary syndrome.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2012

Use of clomiphene citrate in IVF treatment

Gonadotrophin injections are commonly used in an IVF treatment to stimulate the ovaries to increase the number of available eggs, which can then be mixed with sperm in the laboratory to create embryos for transfer back into the uterus. However, the injections are expensive, inconvenient and are associated with side effects. Calls for patient friendly stimulation regimens have generated interest in using clomiphene, which is a tablet, in these treatments to reduce the burden of injections. Presently it is not known whether use of clomiphene is associated with similar pregnancy rates. The aim of this review was to compare regimens with clomiphene versus gonadotropins alone for stimulation of the ovaries during IVF treatment. A total of 12 studies, with 2536 participants, were included in the analysis. The evidence from this review suggests that use of clomiphene along with gonadotropins leads to similar pregnancy rates as those occurring after the use of gonadotropins alone. However, the evidence was limited as all studies included in this review were old. Further evidence is required to determine the clinical and cost effectiveness of stimulation regimens using clomiphene citrate with gonadotropins versus gonadotropins alone.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2012

Clomiphene citrate for unexplained subfertility in women

Clomiphene citrate is a fertility drug that can increase the number of eggs released for possible fertilisation. It is used by women who do not ovulate regularly and by some who do but still have not become pregnant. Clomiphene citrate does not appear to increase the chance of pregnancy in women who ovulate regularly but have failed to conceive after more than a year of unprotected intercourse and so are considered to be subfertile. An associated risk of treatment with clomiphene citrate is a 10% chance of multiple pregnancy. The results of this review of trials should be used with caution due to the heterogeneity between some of the studies.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2010

Clomiphene and other antioestrogens for subfertility associated with anovulation

Subfertility due to the absence of ovulation is a common problem in women. Medical treatment may help these women ovulate. For example, oral antioestrogens such as clomiphene cause increased stimulation of the ovaries and aid ovulation.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2017

Does metformin combined with clomiphene citrate improve fertility related outcomes in clomiphene resistant women with PCOS: a systematic review

Bibliographic details: Gill S, Gemmell A, Colleran R, Bt Zanuri N, O'Brien H, Poobalan A.  Does metformin combined with clomiphene citrate improve fertility related outcomes in clomiphene resistant women with PCOS: a systematic review. Middle East Fertility Society Journal 2014; 19(2): 81-88 Available from: http://www.sciencedirect.com/science/article/pii/S1110569014000326

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2014

N-acetylcysteine for treating women with clomiphene citrate resistant polycystic ovary syndrome: a systematic review

Bibliographic details: Wang AH, Li XL, Feng X.  N-acetylcysteine for treating women with clomiphene citrate resistant polycystic ovary syndrome: a systematic review. Chinese Pharmaceutical Journal 2014; 49(20): 1860-1863 Available from: http://caod.oriprobe.com/articles/43192545/N_Acetylcysteine_for_Treating_Women_with_Clomiphene_Citrate_Resistant_.htm

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2014

[Systematic review and meta-analysis of the reproductive system effects of metformin alone or in combination with clomiphene citrate in patients with polycystic ovary syndrome]

Bibliographic details: Costello M F.  [Systematic review and meta-analysis of the reproductive system effects of metformin alone or in combination with clomiphene citrate in patients with polycystic ovary syndrome]. [Revision sistematica y metanalisis de los efectos de la metformina sola o en combinacion con citrato de clomifeno sobre el sistema reproductivo en pacientes con sindrome de ovario poliquistico.] Salud(i)Ciencia 2007; 15(5): 852-855

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2007

Is ultrasound monitoring of the ovaries during ovulation induction by clomiphene citrate essential? A systematic review

The study objective was to investigate whether ultrasound (US) monitoring is essential during treatment with clomiphene citrate (CC) for ovulation induction, as recommended by the Royal College of Obstetricians and Gynaecologists (RCOG) and the National Institute for Clinical Excellence (NICE). We performed a systematic review of all studies investigating the effects of US in the treatment of ovulatory dysfunction with CC. The main objective of this review was to investigate whether US monitoring during CC treatment reduced multiple pregnancy rates. There was insufficient evidence to suggest that US monitoring reduces multiple pregnancy rates or improves pregnancy rates. On the other hand, no indication that treatment with CC is safe without US monitoring was identified. The small number of relevant studies and the heterogeneity observed in the methodologies of each study prohibit reliable conclusions to be drawn. There is currently no basis for amending the evidence base (good-practice points) used in the RCOG and NICE guidelines, which recommend the use of US to monitor the ovaries during stimulation with CC.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2011

Clomiphene combined with gonadotropins and GnRH antagonist versus conventional controlled ovarian hyperstimulation without clomiphene in women undergoing assisted reproductive techniques: systematic review and meta-analysis

PURPOSE: To compare the effectiveness and safety of controlled ovarian hyperstimulation (COH) using clomiphene citrate associated with gonadotropin and GnRH antagonist (CC + Ant) versus conventional COH without clomiphene citrate (Non-CC) for women undergoing assisted reproductive techniques (ART).

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2013

[Therapeutic effect of metformin for clomiphene-resistant infertility patients with polycystic ovary syndrome: a systematic analysis]. [Chinese]

OBJECTIVE: To evaluate the efficacy of metformin (MTF) in treatment of clomiphene (CC)-resistant patients with polycystic ovary syndrome (PCOS).

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2012

Insulin‐sensitising drugs for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility

Women with polycystic ovary syndrome (PCOS) typically have infrequent or absent periods and increased hair growth and acne. Women with PCOS are also at risk of developing metabolic syndrome, such as diabetes, high blood pressure and high cholesterol levels. High insulin levels are thought to play a role in PCOS and are generally worse with obesity. Insulin‐sensitising drugs considered in this review are metformin, rosiglitazone, pioglitazone and D‐chiro‐inositol. This updated review showed that the use of medications to lower insulin levels, such as metformin either alone or in combination with drugs to induce ovulation (for example clomiphene citrate), does not increase the chance of having a live birth. Metformin was also associated with increased gastrointestinal symptoms such as nausea and diarrhoea.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2012

Use of medicines to help release eggs in women with infertility being treated with medicines to increase the growth of eggs

In women being treated with medicines to help eggs to grow (called ovulation induction), Cochrane authors wished to know whether adding medicines (called ovulation triggers) that help to release the egg (ovulation) would lead to more women having babies without causing harm compared with not giving them ovulation triggers. We found two randomised studies.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2014

Gonadotrophins for ovulation induction in women with polycystic ovarian syndrome (PCOS)

To compare the effectiveness and safety of gonadotrophins as a second‐line treatment to stimulate ovulation in women with PCOS who do not respond to clomiphene citrate (CC).

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2015

Chinese herbal medicines for subfertile women with polycystic ovarian syndrome

We reviewed the evidence about the effect of Chinese herbal medicines (CHM) on rates of live birth pregnancy and adverse events in subfertile women with polycystic ovarian syndrome (PCOS).

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2016

Acupuncture for polycystic ovarian syndrome

PCOS is where women have small cysts on their ovaries (organs that produce eggs) and is characterised by the clinical signs of infrequent or very light menstruation (periods), failure to conceive (become pregnant) and excessive hair growth. The current standard western medical treatments for women with PCOS are prescription medicines, surgery and lifestyle changes. There has been evidence suggesting acupuncture may influence ovulation (release of the egg) by affecting levels of various hormones. Acupuncture is a Chinese therapy where fine needles are inserted into the skin in certain places. Various non‐randomised studies (an experimental study in which people are allocated to different treatments using methods that are not random) of acupuncture in PCOS suggested that there were low rates of side effects, no increased risk of multiple pregnancy (e.g. twins) and that it was comparatively inexpensive to administer. However, it should be emphasised that these conclusions were made based on the findings of non‐randomised controlled studies alone and, therefore, may not reliably support the effectiveness and use of acupuncture in this area.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2016

Aromatase inhibitors for subfertility treatment in women with polycystic ovary syndrome

Review question: Cochrane authors examined the evidence about aromatase inhibitors for subfertile women with polycystic ovary syndrome (PCOS).

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2014

In vitro fertilisation (IVF) compared to other options for unexplained subfertility

Review question: Cochrane review authors investigated whether IVF leads to more live births than other management options in women with unexplained subfertility.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2015

Meta-analysis of letrozole versus clomiphene citrate in polycystic ovary syndrome

The aim of this study was to systematically compare the clinical efficacy and safety of letrozole with clomiphene citrate for ovulation induction in women with polycystic ovary syndrome (PCOS). The Cochrane Central Register of Controlled Trials, PubMed, EMbase, CBMdisc and CNKI were searched for eligible randomized controlled trials (RCT) comparing letrozole with clomiphene citrate in PCOS patients. Two reviewers independently extracted information and evaluated methodological quality according to the Cochrane Handbook 5.0. Meta-analysis was performed with the fixed-effects model or random-effects model according to the heterogeneity. Six eligible RCT involving 841 patients were included. Letrozole was associated with a number of lower mature follicles per cycle (standardized mean difference (SMD) -1.41; 95% confidence intervales (CI) -1.54 to -1.28; P<0.00001) compared with clomiphene citrate. There were no significant differences in pregnancy rate (relative risk (RR) 0.97; 95% CI 0.79 to 1.18), abortion rate (RR 1.38; 95% CI 0.48 to -3.96) and multiple pregnancy rate (RR 0.34; 95% CI 0.07 to -1.72) between the two groups. The evidence from ovulation rates was not enough to support either letrozole or clomiphene citrate. In conclusion, letrozole is as effective as clomiphene citrate for ovulation induction in patients with PCOS.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2011

Laparoscopic ovarian electrocautery versus gonadotropin therapy in infertile women with clomiphene citrate-resistant polycystic ovary syndrome: a systematic review and meta-analysis

BACKGROUND: Some trials have compared laparoscopic ovarian drilling (LOD) with gonadotropins but, because of variations in study design and small sample size, the results are inconsistent and definitive conclusions about the relative efficacy of LOD and gonadotropins cannot be extracted from the individual studies.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2014

Chinese herbal medicine and clomiphene citrate for anovulation: a meta-analysis of randomized controlled trials

OBJECTIVES: The study objective was to investigate the efficacy of Chinese herbal medicine for improving standard infertility treatments.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2011

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