Preparation of endometrium for frozen embryo replacement cycles: a systematic review and meta-analysis

Abstract

Purpose: The purpose of this study was to evaluate the best protocol to prepare endometrium for frozen embryo replacement (FER) cycles.

Methods: This study is a systematic review and meta-analysis. Following PubMed and OvidSP search, a total of 1166 studies published after 1990 were identified following removal of duplicates. Following exclusion of studies not matching our inclusion criteria, a total of 33 studies were analyzed. Primary outcome measure was live birth. The following protocols, including true natural cycle (tNC), modified natural cycle (mNC), artificial cycle (AC) with or without suppression, and mild ovarian stimulation (OS) with gonadotropin (Gn) or aromatase inhibitor (AI), were compared.

Results: No statistically significant difference for both clinical pregnancy and live birth was noted between tNC and mNC groups. When tNC and AC without suppression groups are compared, there was a statistically significant difference in clinical pregnancy rate in favor of tNC, whereas it failed to reach statistical significance for live birth. When tNC and AC with suppression groups are compared, there was a statistically significant difference in live birth rate favoring the latter. Similar pregnancy outcome was noted among mNC versus AC with or without suppression groups. Similarly, no difference in clinical pregnancy and live birth was noted when ACs with or without suppression groups are compared.

Conclusions: There is no consistent superiority of any endometrial preparation for FER. However, mNC has several advantages (being patient-friendly; yielding at least equivalent or better pregnancy rates when compared with tNC and AC with or without suppression; may not require LPS). Mild OS with Gn or AI may be promising.

Keywords: Assisted reproduction; Endometrial preparation; Frozen embryo replacement; Meta-analysis; Thawed embryo transfer.

Figures

Fig. 1

PRISMA flow diagram depicting the study selection

Fig. 2

True natural cycle (tNC) versus modified natural cycle (mNC): pooled results of all studies and subgroup analysis based on luteal phase support (LPS). Asterisk donates random effect

Fig. 3

True natural cycle (tNC) versus artificial cycle (AC) without suppression: pooled results of all studies and subgroup analysis based on luteal phase support (LPS). Asterisk denotes fixed effect

Fig. 4

True natural cycle (tNC) versus artificial cycle (AC) with suppression: pooled results of all studies and subgroup analysis based on luteal phase support (LPS)

Fig. 5

Modified natural cycle (mNC) versus artificial cycle (AC) without suppression: pooled results of all studies and subgroup analysis based on luteal phase support (LPS). Asterisk denotes fixed effect

Fig. 6

Modified natural cycle (mNC) versus artificial cycle (AC) with suppression: pooled results of all studies

Fig. 7

Artificial cycle (AC) with versus without suppression: pooled results of all studies

Fig. 8

Natural cycle versus mild ovarian stimulation with gonadotropin (OS with Gn): pooled results of all studies and subgroup analysis based on type of NC. Asterisk donates random effect

Fig. 9

Artificial cycle versus mild ovarian stimulation with gonadotropin (OS with Gn or AI): pooled results of all studies