Pregnancy Outcomes Following Letrozole Use in Frozen-thawed Embryo Transfer Cycles: A Systematic Review and Meta-analysis

Abstract

While widely used for ovulation induction in assisted reproductive technology, the clinical efficacy of letrozole for endometrial preparation prior to frozen-thawed embryo transfer (FET) cycles remains yet to be elucidated. We performed a meta-analysis to compare pregnancy outcomes after letrozole use with those of other endometrial preparation protocols in patients undergoing FET. PubMed, Scopus, Embase and the Cochrane Library were searched for eligible studies. Clinical pregnancy rate (CPR), live birth rate (LBR) and birth defect rate (BDR) were analysed using odds ratio (OR) and 95% confidence interval (CI). A total of 10 studies representing 75 968 FET cycles were included. Comparable CPR and LBR were observed when comparing letrozole administration with natural cycle (OR 1.24, 95% CI: 0.69 – 2.24; OR 1.18, 95% CI: 0.60 – 2.32), artificial cycle (OR 1.46, 95% CI: 0.87 – 2.44; OR 1.39, 95% CI: 0.77 – 2.52), and artificial cycle with gonadotropin-releasing hormone agonist suppression (OR 1.11, 95% CI: 0.78 – 1.59; OR 1.18, 95% CI: 0.82 – 1.68). Pooled results of the limited studies comparing letrozole with human menopausal gonadotropin demonstrated a similar CPR between groups (OR 1.46, 95% CI: 0.29 – 7.21, two studies), but the letrozole group had a statistically lower LBR (OR 0.67, 95% CI: 0.52 – 0.86, one study). No increased BDR was observed in the letrozole group compared to natural cycles or artificial cycles (OR 0.98, 95% CI: 0.60 – 1.61; OR 1.39, 95% CI; 0.84 – 2.28). This pooled analysis supports the use of letrozole as an efficacious and safe alternative to mainstream regimens for endometrial preparation in FET cycles.

Zusammenfassung

Obwohl Letrozol oft in der assistierten Reproduktionstechnik zur Einleitung der Ovulation eingesetzt wird, ist die klinische Wirksamkeit von Letrozol bei der Vorbereitung des Endometriums vor Transferzyklen von konservierten/aufgetauten Embryos (FET) noch unklar. Wir führten eine Metaanalyse durch, um das Schwangerschafts-Outcome nach dem Einsatz von Letrozol mit denen anderer Protokolle zur Vorbereitung des Endometriums bei Patientinnen, bei denen ein FET vorgenommen wurde, zu vergleichen. Die Datenbanken von PubMed, Scopus, Embase und the Cochrane Library wurden nach passenden Studien durchsucht. Die klinische Schwangerschaftsraten (SR), Lebendgeburtenraten (LGR) und Geburtsfehlerraten wurden mithilfe von Odds Ratio (OR) und 95%-Konfidenzintervallen (KI) analysiert. Insgesamt wurden 10 Studien, die 75 968 FET-Zyklen darstellten, in die Analyse aufgenommen. Die SR und die LGR für Letrozol waren statistisch vergleichbar mit den Werten für natürliche Zyklen (OR 1,24; 95%-KI 0,69 – 2,24 bzw. OR 1,18, 95%-KI 0,60 – 2,32), künstliche Zyklen (OR 1,46; 95%-KI 0,87 – 2,44 bzw. OR 1,39; 95%-KI 0,77 – 2,52), sowie künstliche Zyklen mit Gonadotropin-Releasing-Hormon-Agonisten-Suppression (OR 1,11; 95%-KI 0,78 – 1,59 bzw. OR 1,18; 95%-KI 0,82 – 1,68). Die gepoolten Ergebnisse der begrenzten Anzahl an Studien, die Letrozol mit humanem Menopausengonadotropin verglichen, zeigten eine ähnliche SR für beide Gruppen (OR 1,46; 95%-KI 0,29 – 7,21, 2 Studien), wobei die Letrozol-Gruppe eine statistisch niedrigere LGR aufwies (OR 0,67; 95%-KI 0,52 – 0,86, 1 Studie). Die Geburtsfehlerrate in der Letrozol-Gruppe war nicht erhöht verglichen mit den Geburtsfehlerraten für natürliche Zyklen bzw. künstliche Zyklen (OR 0,98; 95%-KI 0,60 – 1,61 bzw. OR 1,39; 95%-KI 0,84 – 2,28). Diese gepoolte Analyse weist darauf hin, dass Letrozol eine wirksame und sichere Alternative zu den Standardprotokollen bei der Vorbereitung des Endometriums in FET-Zyklen darstellen könnte.

Key words

endometrium - embryo transfer - letrozole - meta-analysis - treatment outcome

Schlüsselwörter

Endometrium - Embryotransfer - Letrozol - Metaanalyse - Behandlungs-Outcome

^* Dongjia Chen and Xiaoting Shen contributed equally to this work, and both should be considered as first authors.

Publication History

Received: 08 October 2019

Accepted after revision: 17 June 2020

Article published online:
14 August 2020

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