Abnormal embryo cleavage linked to early pregnancy loss in mares

CURRENT FULL VERSION: A new Equine Veterinary Journal study adds a sharper screening tool to equine assisted reproduction: abnormal cleavage patterns in the first mitotic division of in vitro-produced embryos were associated with substantially higher early pregnancy loss after transfer. In the retrospective analysis, embryos showing abnormal cleavage had a 53.3% total early pregnancy loss rate, versus 22.6% for embryos with normal cleavage, while embryos that reached the blastocyst stage earlier were more likely to establish pregnancy by day 14 and less likely to be lost by day 25. (pubmed.ncbi.nlm.nih.gov)

That matters because equine in vitro embryo production has advanced quickly, but embryo grading still lacks the kind of standardized classification criteria many clinicians would like. The paper’s authors note that IVP embryos remain associated with higher early loss than in vivo-derived blastocysts. UC Davis has been building toward this kind of assessment for several years through time-lapse imaging work aimed at identifying early developmental events that predict embryo competence. (pubmed.ncbi.nlm.nih.gov)

In the new study, investigators analyzed archived time-lapse material and clinical records from 70 transferred IVP embryos with known outcomes, alongside 114 embryos that arrested during development. Using those images, they classified abnormalities during the first cleavage division and recorded time to vitrification or arrest. Their regression analysis found two main signals: cleavage pattern and developmental speed. Abnormal cleavage both reduced the odds of pregnancy and increased the odds of early loss, while earlier vitrification, used here as a proxy for faster blastocyst formation, improved pregnancy odds and lowered pregnancy loss through 25 days. (pubmed.ncbi.nlm.nih.gov)

The findings fit with earlier equine literature suggesting that embryo kinetics carry prognostic value. A 2018 study on cryopreserved IVP equine embryos found that time from ICSI to blastocyst formation was among the embryo-related factors examined in pregnancy and embryonic loss after transfer. A 2020 study similarly reported that day-7 IVP blastocysts had better foaling outcomes than day-8 blastocysts, with the highest pregnancy and foaling rates seen when embryos were transferred into recipient mares on day 4 after ovulation. More recently, a large retrospective clinical study of 2292 IVP blastocyst transfers found that slow in vitro embryo development, poor embryo grade after thawing, advanced donor mare age, and later-season embryo transfer all negatively affected pregnancy rate after transfer. That same study also found that IVEP was generally efficient overall: 85% of successful sessions produced at least one pregnancy, with the chance rising from 78% when only one blastocyst was produced to 91% with two and 98% with at least three. (pubmed.ncbi.nlm.nih.gov)

That broader dataset also helps put genetics and donor effects in context. Variation in pregnancy rates between most individual donor mares and stallions was relatively small, around 20%, suggesting identity alone usually has a limited effect. But the mare-stallion combination was not always trivial: for some underperforming mares, the likelihood of pregnancy varied by as much as 50% depending on which stallion was used for ICSI. In other words, embryo morphokinetics may be one useful layer of selection, but not the only one. (pubmed.ncbi.nlm.nih.gov)

Direct outside commentary on this specific paper was limited, but the broader expert view is consistent: embryo loss after transfer is multifactorial, and better non-invasive markers are needed. UC Davis’ veterinary assisted reproduction program says time-lapse imaging can help define cleavage and later developmental milestones without disturbing embryos in culture, while also noting that mare age, stallion effects, aneuploidy, and culture conditions may all contribute to failure. That context is important, because the new paper does not suggest cleavage pattern is the only driver of outcome, but rather that it may be a clinically useful early signal. (vetart.vetmed.ucdavis.edu)

Why it matters: For veterinarians and reproduction specialists, this study supports a more objective embryo selection workflow in equine IVP programs. If first-cleavage abnormalities can be scored consistently, clinics may be able to prioritize embryos with better odds of maintaining pregnancy, reduce the number of lower-potential transfers, and give pet parents more realistic expectations after ICSI-derived embryo transfer. The work also complements recent evidence that donor mare age, embryo development speed, embryo quality after thawing, and transfer timing all shape pregnancy likelihood after transfer of IVP embryos, while mare-stallion interactions may matter in selected cases. Taken together, that reinforces that embryo assessment and recipient management have to be considered alongside donor and sire factors, not in isolation. (pubmed.ncbi.nlm.nih.gov)

There are still limits. This was a retrospective study, and the authors note that a larger transfer dataset could reveal additional interactions among morphokinetic traits. Just as importantly, early pregnancy maintenance is not the same as live foal production. Practices will want prospective data showing that adding time-lapse cleavage assessment improves decision-making in real-world commercial programs, ideally alongside standardized protocols for recipient synchronization and follow-up pregnancy monitoring. (pubmed.ncbi.nlm.nih.gov)

What to watch: Expect follow-up work to focus on prospective validation, integration of time-lapse grading into routine IVP lab protocols, and whether these early morphokinetic markers can ultimately predict live foal outcomes across different mares, stallions, and culture systems.