Co-treatment with letrozole during ovarian stimulation for IVF/ICSI: a systematic review and meta-analysis

Nathalie Søderhamn Bülow*, Marianne Dreyer Holt, Sven Olaf Skouby, Kathrine Birch Petersen, Anne Lis Mikkelsen Englund, Anja Pinborg, Nicholas Stephen Macklon

*Corresponding author for this work
5 Citations (Scopus)


Letrozole reduces serum oestradiol by inhibiting the aromatase enzyme and has growing clinical indications in fertility. The available evidence of letrozole's role in ovarian stimulation for IVF and intracytoplasmic sperm injection (ICSI) and clinical outcomes was assessed. Medline, Cochrane, and databases were systematically searched up until August 2021, including 31 studies (n = 16 randomized controlled trials [RCTs]; n = 15 observational studies). Live birth rate (LBR) in poor responders significantly increased by 7% (95% CI, 1% to 13%, P = 0.03) with letrozole co-treatment. Concomitantly, the gonadotrophin consumption was significantly reduced, without decreasing the number of retrieved oocytes. In normal responders, number of oocytes increased with 1.8 oocytes (95% CI 0.35 to 3.27, P = 0.01) with letrozole co-treatment. No significant effect on LBR, clinical pregnancy rate (CPR), or ovarian hyperstimulation syndrome rate was demonstrated. Only two studies reported on high responders and revealed no effect on LBR or CPR. Overall, the endometrium thickness was slightly affected, where as the, miscarriage rate and cancellation rate were unaffected by letrozole co-treatment. None of the included studies reported on neonatal outcomes. The quality of evidence was high or moderate in the RCTs and low in the observational studies. In conclusion, poor responders may benefit from co-treatment with letrozole during ovarian stimulation for IVF, whereas letrozole for normal and high responders requires further investigation with larger, high-quality studies.

Original languageEnglish
JournalReproductive BioMedicine Online
Issue number4
Pages (from-to)717-736
Number of pages20
Publication statusPublished - Apr 2022


  • Female
  • Fertilization in Vitro
  • Humans
  • Letrozole/therapeutic use
  • Live Birth
  • Ovulation Induction
  • Pregnancy
  • Pregnancy Rate
  • Sperm Injections, Intracytoplasmic


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