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#Grand Rounds

Cochrane Review: Letrozole vs Clomiphene Citrate for the Treatment of infertility in Women with PCOS

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BACKGROUND AND PURPOSE: 

  • PCOS leads to subfertility, related to anovulation  
  • Clomiphene citrate has been the standard fertility treatment but letrozole, an aromatase inhibitor, appears to be effective for ovulation induction in women with PCOS  
  • Franik et al. (Cochrane Reviews, 2018) updates a previous review on the effectiveness and safety of aromatase inhibitors to treat infertility in women with (PCOS)

METHODS: 

  • Systematic review and metaanalysis  
  • Review included RCTs of aromatase inhibitors used alone or with other therapies for ovulation induction in women with anovulatory PCOS 
  • To avoid bias, two authors independently selected trials, extracted data, and assessed risk of bias 
  • Quality of evidence assessed using GRADE methods 
  • Primary outcomes  
    • Live birth  
    • Ovarian hyperstimulation syndrome (OHSS)  
  • Secondary outcomes 
    • Clinical pregnancy | Miscarriage | Multiple pregnancies

RESULTS: 

  • 16 studies were added to the previous review, totaling 42 RCTs and 7935 women 
  • Each study used letrozole as the aromatase inhibitor 

Comparing letrozole to clomiphene citrate 

  • Live birth rate was increased 
    • Odds ratio (OR) 1.68, 95% CI 1.42 to 1.99 (moderate-quality evidence) 
  • Pregnancy rate was increased 
    • OR 1.56, 95% CI 1.37 to 1.78 (moderate-quality evidence) 
  • There was no significant difference in  
    • OHSS rate  
    • Miscarriage rate  
    • Multiple pregnancy rate  

Comparing letrozole to laparoscopic ovarian drilling 

  • Live birth rates are similar  
    • OR 1.38, 95% CI 0.95 to 2.02; (low-quality evidence) 
  • Pregnancy rates are similar  
    • OR 1.28, 95% CI 0.94 to 1.74; (moderate-quality evidence)

CONCLUSION: 

  • The authors do not feel studies of letrozole vs placebo is required as letrozole performs better than clomiphene citrate which has been proven to be superior to placebo  
  • More RCTs are warranted to investigate five- or 10-day administration protocol and day 3 to 5 or day 5 to 9 administration of letrozole 
  • Compared to clomiphene citrate, letrozole is associated with an increased likelihood of live birth, and appears to comparable to ovarian drilling when it comes to outcomes  
  • Letrozole is an effective and comparatively safe fertility treatment in women with PCOS

Learn More – Primary Sources: 

Aromatase inhibitors (letrozole) for subfertile women with polycystic ovary syndrome

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Related ObG Topics:

PCOS: Targeting Treatments to Improve Reproductive Outcomes and Reduce CVD
Polycystic Ovary Syndrome: Making the Diagnosis
Secondary Amenorrhea: Workup and Diagnosis  

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