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

Hansen, Peter J.

doi:10.1093/jas/skaa288

Cited by 74 publications

(60 citation statements)

References 176 publications

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“…In this regard, biomarkers that differed in their abundance between pregnancy endpoints could be predictive of specific embryo developmental competence. Miscarriage is a difficult topic to investigate because of obscure etiology, low incidence, and the influence of conditions such as cryopreservation and the presence of serum [ 3 ]. The cases of dimethyl adipate (and, to a lesser extent, p-cresol), highly pregnancy predictive for Day-40 and Day-62, but with low predictive ability at birth, are consistent with their pregnancy and miscarriage identification in the general dataset.…”

Section: Discussionmentioning

confidence: 99%

“…Accurate selection of competent in vitro produced (IVP) embryos for transfer to recipients is essential to maximize pregnancy and birth rates. Currently, the selection of viable IVP embryos is based on morphology and development stage, subjective criteria that rarely allow birth rates over 45% with either fresh or cryopreserved embryos [ 1 , 2 , 3 , 4 , 5 ]. The interest in identifying reliable markers of embryonic viability is higher in IVP, and mainly with respect to cryopreserved embryos, because of their intrinsic reduced viability to term.…”

Section: Introductionmentioning

confidence: 99%

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The Metabolic Signature of In Vitro Produced Bovine Embryos Helps Predict Pregnancy and Birth after Embryo Transfer

et al. 2021

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In vitro produced (IVP) embryos show large metabolic variability induced by breed, culture conditions, embryonic stage and sex and gamete donors. We hypothesized that the birth potential could be accurately predicted by UHPLC-MS/MS in culture medium (CM) with the discrimination of factors inducing metabolic variation. Day-6 embryos were developed in single CM (modified synthetic oviduct fluid) for 24 h and transferred to recipients as fresh (28 ETs) or frozen/thawed (58 ETs) Day-7 blastocysts. Variability was induced with seven bulls, slaughterhouse oocyte donors, culture conditions (serum + Bovine Serum Albumin [BSA] or BSA alone) prior to single culture embryonic stage records (Day-6: morula, early blastocyst, blastocyst; Day-7: expanding blastocyst; fully expanded blastocysts) and cryopreservation. Retained metabolite signals (6111) were analyzed as a function of pregnancy at Day-40, Day-62 and birth in a combinatorial block study with all fixed factors. We identified 34 accumulated metabolites through 511 blocks, 198 for birth, 166 for Day-62 and 147 for Day-40. The relative abundance of metabolites was higher within blocks from non-pregnant (460) than from pregnant (51) embryos. Taxonomy classified lipids (12 fatty acids and derivatives; 224 blocks), amino acids (12) and derivatives (3) (186 blocks), benzenoids (4; 58 blocks), tri-carboxylic acids (2; 41 blocks) and 5-Hydroxy-l-tryptophan (2 blocks). Some metabolites were effective as single biomarkers in 95 blocks (Receiver Operating Characteristic – Area Under the Curve [ROC-AUC]: 0.700–1.000). In contrast, more accurate predictions within the largest data sets were obtained with combinations of 2, 3 and 4 single metabolites in 206 blocks (ROC-AUC = 0.800–1.000). Pregnancy-prone embryos consumed more amino acids and citric acid, and depleted less lipids and cis-aconitic acid. Big metabolic differences between embryos support efficient pregnancy and birth prediction when analyzed in discriminant conditions.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Metabolic Signature of In Vitro Produced Bovine Embryos Helps Predict Pregnancy and Birth after Embryo Transfer

et al. 2021

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“…Morphological evaluation (114), widely used both in humans and farm animals to select embryos before transfer due to its non-invasive nature, is certainly useful, as pregnancy rates are higher when better-quality grade embryos are transferred (115)(116)(117)(118). However, embryo grade is a subjective criterion; it does not always reflect competence to establish pregnancy (119), and it does not necessarily infer proper development of embryonic lineages. For instance, early mouse mutant embryos lacking a specific cell lineage cannot be visually distinguished from their wildtype counterparts, although they hardly progress beyond implantation (37, [120][121][122][123].…”

Section: Lineages Specification Markers To Assess Embryo Quality In Farm Animalsmentioning

confidence: 99%

Lineage Differentiation Markers as a Proxy for Embryo Viability in Farm Ungulates

et al. 2021

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Embryonic losses constitute a major burden for reproductive efficiency of farm animals. Pregnancy losses in ungulate species, which include cattle, pigs, sheep and goats, majorly occur during the second week of gestation, when the embryo experiences a series of cell differentiation, proliferation, and migration processes encompassed under the term conceptus elongation. Conceptus elongation takes place following blastocyst hatching and involves a massive proliferation of the extraembryonic membranes trophoblast and hypoblast, and the formation of flat embryonic disc derived from the epiblast, which ultimately gastrulates generating the three germ layers. This process occurs prior to implantation and it is exclusive from ungulates, as embryos from other mammalian species such as rodents or humans implant right after hatching. The critical differences in embryo development between ungulates and mice, the most studied mammalian model, have precluded the identification of the genes governing lineage differentiation in livestock species. Furthermore, conceptus elongation has not been recapitulated in vitro, hindering the study of these cellular events. Luckily, recent advances on transcriptomics, genome modification and post-hatching in vitro culture are shedding light into this largely unknown developmental window, uncovering possible molecular markers to determine embryo quality. In this review, we summarize the events occurring during ungulate pre-implantation development, highlighting recent findings which reveal that several dogmas in Developmental Biology established by knock-out murine models do not hold true for other mammals, including humans and farm animals. The developmental failures associated to in vitro produced embryos in farm animals are also discussed together with Developmental Biology tools to assess embryo quality, including molecular markers to assess proper lineage commitment and a post-hatching in vitro culture system able to directly determine developmental potential circumventing the need of experimental animals.

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confidence: 99%

“…However, technical aspects of embryo transfer procedures remain to be optimized (Hansen, 2020). Human chorionic gonadotropin (hCG) has a potent luteinizing hormone (LH)-like effect in cattle.…”

mentioning

confidence: 99%

Inducing ovulation with human chorionic gonadotrophin improves the pregnancy rate in lactating dairy cows receiving an in vitro‐produced embryo

García-Ispierto

Llobera-Balcells

López‐Gatius³

2021

Reprod Domestic Animals

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The global use of in vitro-produced embryos (IVP) in dairy cattle has increased over the last twenty years (López-Gatius & Hunter, 2019).However, technical aspects of embryo transfer procedures remain to be optimized (Hansen, 2020). Human chorionic gonadotropin (hCG) has a potent luteinizing hormone (LH)-like effect in cattle.Unlike with GnRH, the ovulation-inducing effects of hCG are mediated by an increase in progesterone (P4) synthesis extending the life span of the corpus luteum (De Rensis et al., 2010). As far as we know, no study has explored the possible benefits of hCG treatment for oestrus synchronization in embryo transfer procedures. The present study was designed to compare the effects of inducing ovulation using hCG or GnRH at the end of a 5-day P4-based oestrous synchronization protocol on the pregnancy rate in lactating dairy cows subjected to IVP embryo transfer. | MATERIAL S AND ME THODSThis study was performed on two commercial Holstein-Friesian dairy herds kept on farms 1 km apart in northeastern Spain. During the study period (January 2018-September 2019), mean numbers of lactating cows in the herds were 212 (Herd 1) and 1,244 (Herd 2), respectively. As pregnancy rates following IVP embryo transfer were not significantly different between herds, data were grouped as derived from a single herd and 'herd' considered as a factor in binary logistic regression procedures. Mean annual milk production was 11,120 kg per cow. The mean annual culling rate was 30%. In each herd, cows were grouped according to age (primiparous plus secundiparous versus multiparous), milked three times daily, and fed complete rations. Herd management included the use of fans and water sprinklers. Except cows receiving an IVP embryo, all cows were artificially inseminated (AI) approximately once every two months and

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

Cited by 74 publications

References 176 publications

The Metabolic Signature of In Vitro Produced Bovine Embryos Helps Predict Pregnancy and Birth after Embryo Transfer

The Metabolic Signature of In Vitro Produced Bovine Embryos Helps Predict Pregnancy and Birth after Embryo Transfer

Lineage Differentiation Markers as a Proxy for Embryo Viability in Farm Ungulates

Inducing ovulation with human chorionic gonadotrophin improves the pregnancy rate in lactating dairy cows receiving an in vitro‐produced embryo

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