Abnormal early cleavage may flag higher pregnancy loss in horse embryos

CURRENT FULL VERSION: Abnormal cleavage during the first mitotic division of equine in vitro-produced embryos appears to be more than a laboratory curiosity. In a new retrospective study, researchers reported that embryos showing abnormal cleavage patterns had markedly higher early pregnancy loss after transfer than embryos that cleaved normally, adding a potentially useful early selection signal for equine assisted reproduction programs. The study was published online ahead of print in Equine Veterinary Journal on July 31, 2025. (pubmed.ncbi.nlm.nih.gov)

The work lands at a time when equine in vitro embryo production is becoming more established in clinical practice, especially through oocyte aspiration, ICSI, embryo culture, vitrification, and transfer. UC Davis says its IVEP workflow typically takes 9 to 11 days, with about 66% of collected oocytes maturing and roughly 30% developing into embryos within 7 to 9 days. That growth in use has increased pressure on labs and clinicians to identify which embryos are most likely to hold a pregnancy, particularly because standard morphology-based grading systems borrowed from cattle have known limitations in horses. (cehhorsereport.vetmed.ucdavis.edu)

According to the PubMed abstract, the investigators reviewed time-lapse images and clinical records from 70 transferred IVP embryos with known pregnancy outcomes, alongside 114 arrested embryos. Their analysis focused on morphokinetic characteristics during first cleavage and early development. The key finding was a sharp difference in early pregnancy loss: 53.3% in embryos with abnormal cleavage patterns versus 22.6% in embryos with normal cleavage. The authors concluded that morphokinetic characteristics from the first mitotic division could serve as classification criteria to help identify higher-quality embryos for transfer. (pubmed.ncbi.nlm.nih.gov)

That conclusion fits with a broader body of equine embryo research suggesting that early developmental behavior matters. A 2023 study in Reproduction, Fertility and Development found that day of blastocyst development was a major factor associated with foaling rate in equine IVP embryos, while some conventional morphology features were less predictive than expected. More recently, a large retrospective Equine Veterinary Journal study of 2,292 IVP blastocyst transfers found that slow in vitro embryo development, poor embryo grade after thawing, advanced donor mare age, and embryo transfer later in the breeding season all reduced pregnancy rate. That study also found donor mare and stallion identity had relatively low overall impact in most cases, with pregnancy-rate variation around 20% for most individual mares and stallions, but some underperforming mares showed as much as a 50% swing depending on the stallion used. At the IVEP-session level, 85% of successful sessions produced at least one pregnancy; when a single blastocyst was produced, 78% of sessions yielded a pregnancy, rising to 91% with two blastocysts and 98% with three or more. Together, those studies suggest that embryo competence in horses may be better captured by dynamic developmental markers than by static visual grading alone, while still being influenced by donor, seasonal, and post-thaw factors. (pubmed.ncbi.nlm.nih.gov)

Direct outside commentary on the new EVJ paper was limited, but UC Davis has already highlighted the clinical promise of live embryo monitoring. In its 2025 Horse Report, the university said its time-lapse system can help determine the normal timeline for equine embryo development and predict which embryos are likely to progress appropriately, and it specifically cited the Martin-Pelaez study as showing that developmental characteristics can predict pregnancy loss. That institutional framing stops short of a formal clinical recommendation, but it signals that the authors see practical translational value, not just an academic observation. (cehhorsereport.vetmed.ucdavis.edu)

There may also be a biologic explanation behind the signal. UC Davis-affiliated researchers have separately reported that chromosomal abnormalities are common in equine pregnancy loss, and the same 2025 Horse Report states that duplicated or deleted chromosomes, or chromosome segments, account for early pregnancy loss in 22% of cases, citing De Coster et al. A 2024 UC Davis Veterinary Genetics Laboratory news release, summarizing a separate study, said chromosomal abnormalities were present in more than half of equine pregnancy losses before 110 days of gestation. The new cleavage-pattern study did not, based on the abstract, establish causation between abnormal cleavage and aneuploidy, but it supports the inference that visibly abnormal early division may be a useful non-invasive marker of underlying developmental instability. (cehhorsereport.vetmed.ucdavis.edu)

Why it matters: For equine practitioners, theriogenologists, and IVEP laboratories, the practical takeaway is that embryo selection may need to move earlier and become more data-driven. If abnormal first cleavage reliably flags embryos at higher risk of loss, clinics could use time-lapse monitoring to improve transfer decisions, counsel pet parents and breeders more accurately about prognosis, and potentially reduce the cost and disappointment associated with failed pregnancies. It also reinforces that pregnancy outcome after IVEP is shaped by multiple interacting factors, including embryo kinetics, cryopreservation effects, donor mare age, seasonality, and in some cases specific mare-stallion combinations, so no single grading metric is likely to be enough on its own. (pubmed.ncbi.nlm.nih.gov)

What to watch: The next step is likely prospective validation in larger commercial populations, ideally with parallel genetic testing to determine whether abnormal cleavage is tracking chromosomal error, culture stress, or both. If that evidence builds, time-lapse morphokinetic scoring could become a more standard part of equine embryo transfer workflows, especially at referral centers already offering ICSI, biopsy, and vitrification. It will also be worth watching whether clinics combine cleavage-pattern data with established predictors such as development speed, post-thaw grade, donor mare age, timing within the breeding season, and mare-stallion pairing to build more practical embryo-selection models. (cehhorsereport.vetmed.ucdavis.edu)