Clomiphene Citrate, Metformin or Aromatase Inhibitors for Anovulatory Infertility in Women with Polycystic Ovary Syndrome (PCOS): A Systematic Review of Meta-analyses and Randomized Controlled Trials
Stefano Palomba, Angela Falbo and Giovanni B.L. Sala
Affiliation: Unit of Obstetrics and Gynecology, Arcispedale “Santa Maria Nuova”, Viale Risorgimento 80-42123 Reggio Emilia, Italy.
Background: Several drugs are actually used for treating women with polycystic ovary syndrome (PCOS).
These included mainly clomiphene citrate (CC), metformin or aromatase inhibitors (AIs). Objectives: To review systematically
the literature for meta-analyses and randomized controlled trials (RCTs) in order to clarify evidence based indications
for the use of CC, metformin and AIs in the treatment of infertility in anovulatory patients with PCOS. Search Strategy:
We searched and reviewed until September 2012 the main databases available. Selection Criteria: Meta-analyses and
RCTs. Live-birth rate was considered as primary end-point. Data Collection and Analysis: Authors independently reviewed
and extracted the data. Main Results: Fourteen meta-analyses and nine additional RCTs were analyzed showing
heterogeneous results for several treatment comparisons. Conclusions: In infertile obese PCOS patients, the CC should be
still considered the drugs of choice for inducing ovulation. Letrozole, even if is the only AI supported by evidence-based
data, is not better than CC in therapy naïve patients. In patients with CC resistance, metformin plus CC improves significantly
the reproductive outcomes, with particular regard for obese subjects.
Keywords: Aromatase inhibitors, clomiphene citrate, infertility, letrozole, meta-analysis, metformin, PCOS, RCT, sterility.
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