BOARD INVITED REVIEW: Post-transfer consequences of in vitro-produced embryos in cattle

Abstract

In vitro embryo production (IVP) in cattle has gained worldwide interest in recent years, but the efficiency of using IVP embryos for calf production is far from optimal. This review will examine the pregnancy retention rates of IVP embryos and explore causes for pregnancy failures. Based on work completed over the past 25 yr, only 27% of cattle receiving IVP embryos will produce a live calf. Approximately 60% of these pregnancies fail during the first 6 wk of gestation. When compared with embryos generated by superovulation, pregnancy rates are 10% to 40% lower for cattle carrying IVP embryos, exemplifying that IVP embryos are consistently less competent than in vivo-generated embryos. Several abnormalities have been observed in the morphology of IVP conceptuses. After transfer, IVP embryos are less likely to undergo conceptus elongation, have reduced embryonic disk diameter, and have compromised yolk sac development. Marginal binucleate cell development, cotyledon development, and placental vascularization have also been documented, and these abnormalities are associated with altered fetal growth trajectories. Additionally, in vitro culture conditions increase the risk of large offspring syndrome. Further work is needed to decipher how the embryo culture environment alters post-transfer embryo development and survival. The risk of these neonatal disorders has been reduced by the use of serum-free synthetic oviductal fluid media formations and culture in low oxygen tension. However, alterations are still evident in IVP oocyte and embryo transcript abundances, timing of embryonic cleavage events and blastulation, incidence of aneuploidy, and embryonic methylation status. The inclusion of oviductal and uterine-derived embryokines in culture media is being examined as one way to improve the competency of IVP embryos. To conclude, the evidence presented herein clearly shows that bovine IVP systems still must be refined to make it an economical technology in cattle production systems. However, the current shortcomings do not negate its current value for certain embryo production needs and for investigating early embryonic development in cattle.

The incompletely fulfilled promise of embryo transfer in cattle—why aren’t pregnancy rates greater and what can we do about it?

“…As many as 72% of IVP blastocysts were reported to exhibit mixoploidy ( Viuff et al, 1999 ). Following transfer, there are reports of compromised trophoblast elongation, loss of the embryonic disk, changes in placental function, and dysregulation of fetal development (reviewed by Ealy et al, 2019 ). Most important for the current discussion, a smaller percent of transferred IVP embryos result in pregnancies than when MOET embryos are transferred ( Ealy et al, 2019 ).…”

“…Following transfer, there are reports of compromised trophoblast elongation, loss of the embryonic disk, changes in placental function, and dysregulation of fetal development (reviewed by Ealy et al, 2019 ). Most important for the current discussion, a smaller percent of transferred IVP embryos result in pregnancies than when MOET embryos are transferred ( Ealy et al, 2019 ). Clearly, technical procedures to produce a transferrable embryo in vitro have not yet been optimized.…”

“…There are two pathways for making a better embryo—that for the MOET embryo and that for the IVP embryo. Focus on the IVP embryo may be more fruitful because embryo competence for pregnancy establishment is lower ( Ealy et al, 2019 ), and there are probably more opportunities to manipulate the production system than for MOET. Moreover, transfer of IVP embryos is growing worldwide while that of MOET embryos is relatively stable ( Hansen, 2020 ).…”

“…MOET will continue to be an important method for producing embryos for transfer because few laboratory resources are required and P/ET is superior to that achieved with IVP embryos ( Ealy et al, 2019 ). Research continues to improve superovulatory protocols with the goal of increasing blastocyst yield ( Bó and Mapletoft, 2020 ), and some of these methods may also affect embryo competence for pregnancy.…”

A review of simulation analyses of economics and genetics for the use of in-vitro produced embryos and artificial insemination in dairy herds

“…Risk of abortion and stillbirth was at least twice as high in calves made by IVP as from AI. A recent review on post-transfer consequences of IVP embryos in cattle revealed lower conception rates compared with AI (Ealy et al, 2019).…”