Embryo transfer strategy and therapeutic options in infertile patients with thin endometrium: a systematic review

Abstract

Human endometrium has a key role in implantation process. The measurement of endometrial thickness is the most commonly used in clinical practice. Managing patients with thin endometrium still represents a major challenge for clinicians. The objective of this systematic review was to investigate all available interventions to improve endometrial thickness (EMT) in women with history of thin endometrium undergoing fresh or frozen-thawed embryo transfers (ET). We performed a comprehensive search of relevant studies from January 1978 to February 2018. The different strategies were categorized as hormonal, vascular, and growth factor approaches and specifically analyzed according to the type of ET. Thirty-one studies were included. Overall, quality of the evidence ranged from very low to moderate, with only few randomized controlled trials that support the use of either GnRH analogues in fresh ET or sildenafil in frozen ET for enhancing endometrial growth. Besides, intensified estradiol administration is a common approach that might improve EMT in frozen ET. The present review evidences the paucity of reliable data regarding the efficiency of different interventions aiming at increasing EMT before fresh or frozen-thawed ET. Robust and high-quality randomized controlled trials are still needed before guidelines can be established.

Keywords: Embryo transfer; Endometrial thickness; In vitro fertilization; Pregnancy.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1

Flow diagram of study selection

Fig. 2

Hormonal therapeutic options for thin endometrium before an embryo transfer. Blue background with frozen flake identifies FET cycle. Timing for treatment introduction and ending is specified (D, day; i.e., D2, 2nd day of menstrual cycle). Administration route is represented: subcutaneous in yellow, vaginal in red, and oral in dark yellow. ET, embryo transfer; OR, oocyte retrieval

Fig. 3

Vascular therapeutic options for thin endometrium before an embryo transfer. Blue background with frozen flake identifies FET cycle. Timing for treatment introduction and ending is specified (D, day; S, stimulation day; i.e., D1, 1st day of menstrual cycle). Administration route is represented: vaginal in red, oral in dark yellow, and electrostimulation in orange. ET, embryo transfer; HRT, hormonal replacement therapy

Fig. 4

Growth factor therapeutic options for thin endometrium before an embryo transfer. Blue background with frozen flake identifies FET cycle. Days of intrauterine perfusions (D, day; i.e., D12–13, 12th or 13th day of cycle) and total dose of growth factors are specified. Administration route is represented: intrauterine perfusion in green, with a white border when facultative. ET, embryo transfer; HRT, hormonal replacement therapy; OR, oocyte retrieval

Fig. 5

Summary of proposed strategies in case of thin endometrium according to fresh or frozen embryo transfer. In dark purple, treatments with low to moderate evidence. In light purple with dotted border, strategies with unclear effect. In pale purple without border, interventions with no evidence of benefit