Introduction

Since the first successful conception via in vitro fertilization (IVF) 40 years ago, advances in protocols have resulted in increasing success rates. Among them, improvements in culture conditions that allow a higher number of fertilized oocytes to reach the blastocyst stage and the development of vitrification techniques with excellent frozen-thawed blastocyst survival rates with no impact on the implantation potential are the most important. Nowadays, in the era of personalized medicine, the practice of fixed protocols is becoming outdated and defining individualized parameters for each situation is now considered more appropriate for obtaining higher success rates (i.e., ongoing pregnancy rates [PRs]) and fewer adverse effects (i.e., multiple pregnancies) of IVF.
These advances have allowed the evolution of two practices in assisted reproductive technology (ART): freeze-only strategy and single-embryo transfer (SET). The freeze-only strategy, in which all available good-quality embryos are frozen and transfers are delayed for a more physiologic cycle (natural or hormone replacement cycle), has been increasingly used. Previous studies have suggested that frozen-thawed embryo transfers (FETs) in the absence of ovarian stimulation allow better synchrony between blastocyst and endometrium maturation (1), which is an essential step in the interaction between an implantation-competent blastocyst and a receptive endometrium (2, 3). Hence, transferring embryos in a more physiological uterine environment could hypothetically improve the overall outcomes (4). The freeze-only strategy is being used for patients at a risk for ovarian hyperstimulation syndrome (OHSS) (5) and those undergoing preimplantation genetic testing for aneuploidy (6). However, there is no evidence supporting the widespread use of the freeze-only strategy for all patients undergoing IVF and a number of additional questions need to be answered (7-9).
The SET is another practice who have been increasing applied after the improvement in embryo vitrification techniques. SET is the best choice to reduce multiple pregnancies and the associated risks, as preterm labour and birth, gestational hypertension, gestational diabetes, premature birth, premature rupture of membranes, etc (10-12). However, SET is not always practiced, although there is recommendations for a reduction in the number of embryos transferred (ET) (13). Double embryo transfer (DET) is the most common practice worldwide and multiple pregnancies remain the most important iatrogenic complication of assisted reproductive technology (ART) (14). Efforts has been towards to stimulate SET. Studies demonstrate the transfer of two embryos in sequential SET cycles results in similar cumulative live birth rates compared to DET, with reduced multiple pregnancy (15, 16). Studies from our group also confirmed that SET is a valuable practice for good prognosis patients (17-19), as those younger than 38 years of age, good ovarian response (at least 4 oocytes collected) and without severe male factor (20, 21).
Based on the theory that patients at risk of OHSS should undergo freeze-only approach and at the same time the increased number of oocytes characterize those patients as good prognosis, which is one of the indications for SET, we hypothesized that high responder patients undergoing freeze-only strategy to avoid the OHSS, the use of consecutive elective single embryo transfers can result in the most efficient approach in terms of higher pregnancy success rates and less complications. To answer our question, we assessed retrospectively the clinical outcomes of IVF cycles of high responder patients who underwent freeze-only strategy and SET in the last 9 years in our centre. As control group, we included patients with the same characteristics who underwent freeze-only strategy and DET.