TY - JOUR
T1 - Co-treatment with letrozole during ovarian stimulation for IVF/ICSI
T2 - a systematic review and meta-analysis
AU - Bülow, Nathalie Søderhamn
AU - Dreyer Holt, Marianne
AU - Skouby, Sven Olaf
AU - Birch Petersen, Kathrine
AU - Englund, Anne Lis Mikkelsen
AU - Pinborg, Anja
AU - Macklon, Nicholas Stephen
N1 - Publisher Copyright:
© 2021 Reproductive Healthcare Ltd.
PY - 2022/4
Y1 - 2022/4
N2 - 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 ClinicalTrials.gov 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.
AB - 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 ClinicalTrials.gov 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.
KW - Female
KW - Fertilization in Vitro
KW - Humans
KW - Letrozole/therapeutic use
KW - Live Birth
KW - Ovulation Induction
KW - Pregnancy
KW - Pregnancy Rate
KW - Sperm Injections, Intracytoplasmic
UR - http://www.scopus.com/inward/record.url?scp=85124735406&partnerID=8YFLogxK
U2 - 10.1016/j.rbmo.2021.12.006
DO - 10.1016/j.rbmo.2021.12.006
M3 - Review
C2 - 35183444
AN - SCOPUS:85124735406
SN - 1472-6483
VL - 44
SP - 717
EP - 736
JO - Reproductive BioMedicine Online
JF - Reproductive BioMedicine Online
IS - 4
ER -