Does Metformin combined with Clomiphene Citrate improve fertility related outcomes in Clomiphene resistant women with PCOS: a systematic review

Sabraj Gill, Ailsa Gemmel, Rebecca Colleran, Nurhazwani Bt Zanuri, Helen O’Brian, Amudha Poobalan

Research output: Contribution to journalArticle

2 Citations (Scopus)
4 Downloads (Pure)


Polycystic Ovary Syndrome (PCOS) is clinically associated with infertility. Many women are resistant to Clomiphene Citrate and the addition of insulin sensitisers may help to overcome this challenge.

This review aims to assess if Metformin added to Clomiphene Citrate improves pregnancy outcomes in patients with PCOS and are resistant to Clomiphene Citrate.

Search strategy
A systematic search was conducted on four electronic databases published until May 2013.

Selection criteria
Studies evaluating the use of Metformin in combination with Clomiphene Citrate resistant patients with PCOS compared to placebo. Outcomes assessed were ovulation rate, pregnancy by ultrasound, Sex Hormone Binding Globulin (SHBG), BMI, fasting insulin and testosterone levels.

Data collection and analysis
The reviewers carried out data extraction of specific outcomes and evaluated each study according to the sign guidelines.

Main results
In total 40 citations were identified however only four were eligible for analysis. Two studies were found to have a statistically significant improvement in ovulation and pregnancy rates in the intervention group compared to the control group. These studies used the highest dose of Metformin and Clomiphene Citrate. In two studies we found statistically significant reductions in testosterone concentrations and BMI values.

Authors’ conclusions
Metformin and Clomiphene Citrate have been shown to improve ovulation and pregnancy rates in the treatment of infertile patients with PCOS who are Clomiphene resistant. However, the optimal treatment regime remains ambiguous and needs further investigation with larger sample sizes of adequate power.
Original languageEnglish
Pages (from-to)81-88
Number of pages8
JournalMiddle East Fertility Society Journal
Issue number2
Early online date5 May 2014
Publication statusPublished - Jun 2014



  • clomiphene citrate resistance
  • metformin
  • polycystic ovary syndrome

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