Why we should transfer frozen instead of fresh embryos: the translational rationale

Abstract

Epidemiologic studies have shown an increased rate of adverse perinatal outcomes, including small for gestational age (SGA) births, in fresh in vitro fertilization (IVF) cycles compared with frozen embryo transfer cycles. This increase is not seen in the donor oocyte population, suggesting that it is the peri-implantation environment created after superovulation that is responsible for these changes. During a fresh IVF cycle, multiple corpora lutea secrete high levels of hormones and other factors that can affect the endometrium and the implanting embryo. In this review, we discuss both animal and human data demonstrating that superovulation has significant effects on the endometrium and embryo. Additionally, potential mechanisms for the adverse effects of gonadotropin stimulation on implantation and placental development are proposed. We think that these data, along with the growing body of epidemiologic evidence, support the proposal that frozen embryo transfer should be considered preferentially, particularly in high responders, as a means to potentially decrease at least some of the adverse perinatal outcomes associated with IVF.

Increased risk of large-for-gestational age birthweight in singleton siblings conceived with in vitro fertilization in frozen versus fresh cycles

“…[31]. In recent years, there has been a growing interest in frozen embryo transfers, with clinical papers and editorials suggesting a freeze-all approach [32][33][34][35]. The clinical rationale to support this technique is that the supraphysiological hormone levels resulting from ovarian hyperstimulation in the 1st trimester in fresh transfers are associated with a significantly increased risk for low birthweight (LBW, <2500 g), SGA [36], and preterm delivery [37].…”

Agonist depot versus OCP programming of frozen embryo transfer: a retrospective analysis of freeze-all cycles

“…However, if FET is going to replace fresh ET universally for reasons of better periimplantation outcomes [13], we will first have to address the concerns raised in a number of perinatal studies reporting large for gestational age, extreme preterm birth, and vascular dysfunction in off-spring conceived after FET [27][28][29]. Even with the reassurance that other FET perinatal outcomes are more optimal than after fresh ET and very similar to those of natural conceptions, further studies are necessary to investigate the possible mechanisms involved in the epigenetic modifications that might result from extended embryo culture and cryopreservation.…”

“…The rationale to use so-called segmented-ART treatment has been the avoidance of iatrogenic complications related to controlled ovarian stimulation (COS), such as, ovarian hyperstimulation syndrome (OHSS) and premature progesterone rise [3,5]. In the latter case, deferring fresh transfer, freezing all embryos, and transferring frozen-thawed embryos in a subsequent physiologically normal cycle has been shown to potentially result in improved embryo implantation and placentation and consequently improved perinatal and neonatal outcomes [1][2][3][6][7][8][9][10][11][12][13]. However, segmented treatment also has complications, i.e., the management of an increased number of confounding variables and an increase in the treatment duration.…”

Fresh vs Frozen Embryo Transfer

“…Perinatal sonuçları olarak; SGA, düşük doğum ağırlığı, preeklampsi prevalansında artış. 7 Yukarıdaki tartışmaların sonucunda, taze sikluslarda meydana gelen birtakım değişikliklerin, endometriyumu olumsuz etkileyerek implantasyonu bozduğu, plasentasyonda defekt meydana getirerek embriyo-endometriyum diyaloğunu bozduğu ileri sürülmektedir.…”