A Review of Luteal Support Protocols for Single Embryo Transfers: Fresh and Frozen

Abstract

Assisted reproductive technologies result in an abnormal luteal phase and additional support protocols are needed to ensure satisfactory implantation and ongoing pregnancy rates. This objective is especially crucial following single embryo transfer. Progesterone is the main component of luteal-phase support (LPS) therapy, and there is no significant difference in the efficacy of vaginal or intramuscular preparations regarding pregnancy rates. In the past, hCG was commonly used in luteal support regimes, but its use has declined due to concerns arising from an increased incidence of ovarian hyperstimulation syndrome (OHSS). The use of supplemental estrogen in LPS protocols remains controversial, and although some studies have suggested a benefit, the overall conclusion from available evidence does not indicate a definite improvement in outcome. A segmented approach to stimulation and transfer can be employed to antagonist protocol cycles using a GnRH agonist trigger in order to reduce the risk of OHSS in patients considered to be at high risk of this complication. This strategy employs elective cryopreservation of all embryos and delayed transfer in a subsequent cycle. Initial fresh transfers after the introduction of a GnRH agonist trigger protocol were associated with poor pregnancy rates. Recent studies have shown that intensive LPS regimes can achieve pregnancy rates comparable to standard hCG-triggered cycles, while maintaining an acceptable OHSS risk in certain patients. Frozen embryo transfer cycles bring different challenges for management of the luteal phase. Current data suggest no difference in outcome between hormonally medicated protocols or natural cycles and that no benefit is gained by adding progesterone to the luteal phase of modified natural treatment cycles. There is a shortage of data from prospective randomized trials to assess LPS in frozen–thawed treatment cycles, so additional research is needed to inform the decision-making process.