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

Related ObG Topics:

PCOS: Targeting Treatments to Improve Reproductive Outcomes and Reduce CVD

Polycystic Ovary Syndrome: Making the Diagnosis

Secondary Amenorrhea: Workup and Diagnosis