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Pregnancy loss in the mare: what are the risks and your diagnostic options?

Knowing the underlying cause of pregnancy loss allows you to take steps to reduce the chance of repeat losses

09 July 2020, at 8:30am

Pregnancy loss in the mare is a relatively common condition faced in veterinary practice. Nevertheless, it can also be very frustrating to manage on both an individual mare and a herd level. In this article, we will review the frequency of pregnancy loss in the mare in the UK, which mares pose a higher risk profile for the condition and diagnostic options available to you to identify the cause.

How common is pregnancy loss?

Improvement in clinical approaches have led to high conception rates in the mare of around 60 to 70 percent per oestrous cycle. Given we also know from studies on research mares that rates of pregnancy loss between conception and first scan can be as high as 20 to 30 percent, we are now at a point where true “conception” rates in well-managed naturally bred mares are estimated to reach around 90 percent. Not bad! With the pregnancy now confirmed, how likely is the mare to go on and lose that pregnancy?

Pregnancy loss encompasses three main periods: early pregnancy loss (EPL) (15 to 65 days), abortion (65 to 300/315 days) and stillbirth (300/315 to parturition). EPL includes the embryonic period to 35 days (often referred to as early embryonic death) and the implantation period (40 to 65 days). In the horse, early pregnancy is the most common period pregnancies fail, which is not surprising given it also coincides with major foetal and placental developmental events. In most of the common breeds in the UK, you should expect 8 to 12 percent of confirmed pregnancies to be lost prior to 65 days. The majority (approximately 90 percent) of these are single event EPLs.

In our study across two seasons, only 0.9 percent of mares experienced two EPLs and 0.1 percent three or more EPLs, representing less than 10 percent of all EPLs (Rose et al., 2018). The incidence of abortion (approximately 5 percent) in the UK is approximately half of that of EPL, a figure that has been relatively stable over recent decades (Allen et al., 2007; Roach et al., 2018). Stillbirths are less frequent again, representing around 1.5 percent of pregnancies that fail to produce a live foal.

These UK figures, subject to year-to-year, regional, breed and cohort variation, form a baseline to enable veterinary surgeons to assess the performance of mares under their management. A higher incidence may not necessarily be a cause for concern but does warrant further investigation.

An increase may merely represent an older mare population under management, or alternatively could be an early indicator of a problem. If you don’t monitor, you will never know!

Risk factors for pregnancy loss

Risk factors for pregnancy loss can be divided into those which are intrinsic to the mare (Box 1), the stallion or the developing pregnancy and external factors such as therapeutics, nutrition and other environmental exposures. Whilst wherever possible, management should aim to minimise the exposure to these risks, many of the risks intrinsic to the mare can’t be reduced. Therefore, they need to be considered in the clinical management of mares, in advising owners of the likelihood of a mare suffering pregnancy loss and by stud farms when considering herd composition required to maintain profitability.

BOX (1) Risks for pregnancy loss
BOX (1) Risks for pregnancy loss

Mare-level risks

Nutrition is vitally important to supporting the pregnant mare, with mares with a BCS of less than 5 at significantly increased risk of both EPL and abortion (Miyakoshi et al., 2012). Similar to other species, increasing mare age increases the risk of pregnancy loss (Allen et al., 2007; de Mestre et al., 2019). Independent of age, maiden mares are at a reduced risk of EPL. The risks associated with foal heat breeding and pregnancy loss are unclear with overseas studies showing an increased risk for EPL when mares were bred before day 13 postpartum, but UK studies not repeating this observation. Foal heat breeding is relatively uncommon in the UK which might explain this difference. Uterine conditions are also linked with EPL risk. Two studies indicate uterine cysts increase the risk of EPL (Miyakoshi et al., 2012; de Mestre et al., 2019). Surprisingly presence of uterine inflammation/infection at the time of cover is not associated with a modified risk for either EPL or pregnancy loss to term demonstrating that endometritis present around the time of cover doesn’t necessarily negatively impact on pregnancy outcome if managed appropriately.

Pregnancy-level risks

Conceptus position within the uterus and vesicle size at the first scan but not the number of conceptuses (twin pregnancies) at initial examination increase risk for EPL. In a small study, Jobert et al. (2005) showed that caudal uterine body pregnancies experienced very high rates of early pregnancy loss with 13/21 (62 percent) pregnancies confirmed in the caudal uterine body subsequently lost prior to day 42. These observations stress the importance of vigilant monitoring of the position and size of the developing conceptus and termination of caudal body pregnancies carefully considered.

Diagnostic options for investigating underlying cause of pregnancy losses

Knowing the underlying cause of pregnancy loss allows you to take steps to reduce the chance of repeat losses within a mare and put in place mechanisms to reduce the possible impact on other mares in the same herd, and also helps guide breeding choices that minimise the chance of it occurring again.

Our review of clinical records suggests approximately 60 percent of mares suffering EPL present with no conceptus. In these cases, it is often difficult to do anything beyond a thorough reproductive examination and take an endometrial swab which is recommended at the next oestrus to exclude bacterial infection, responsible for approximately 10 to 15 percent of EPLs. If the embryo is visualised by ultrasonography prior to the loss, the clinician can obtain additional information, such as location of the embryo within the uterus (see risks of caudal body pregnancies above), presence of fluid indicative of inflammation and endometritis, and assess the anatomical development of the embryo/foetus. Whilst not a standard diagnostic technique yet, clinicians across the UK and Ireland have additionally been flushing out EPL conceptuses and submitting them to our laboratory (Figure 1A). Assessment of the first 100 submissions have so far resulted in the identification of a number of conditions such as gross morphological abnormalities of the foetus, in particular the cardiovascular system (Figure 1B) and the central nervous system (Figure 1C), known to explain EPL in other species. Gross genetic abnormalities such as aneuploidy, a loss or gain of a whole chromosome, commonly described as a cause of human pregnancy loss, have also been identified.

Investigation of the underlying cause of abortion and stillbirth requires a combination of a thorough veterinary examination and examination of the abortus material, and if pathological findings support it, genetic tests can also be performed. In our review of over 3,000 pregnancies, we found that abortus material was available for assessment in approximately 70 percent of cases of abortion (Roach et al., 2018). Further, if this material was submitted to a diagnostic laboratory, a diagnosis of an underlying cause of abortion was reached in 75 percent of cases. Overall, this supports the value in seeking a diagnosis for abortion, so do persist with your submissions as over time it will be rewarding for both you and your clients. There are a vast number of possible causes of abortion that might be identified but by far the most common in the UK is umbilical cord pathologies representing approximately 50 percent of laboratory investigated cases, followed by infectious placentitis and EHV1, each representing around 10 percent of cases. At the time of writing this article, it is also worth noting that many of the emerging causes of abortion found overseas – including equine amnionitis and foetal loss, mare reproductive loss syndrome (both caused by ingestion of caterpillars) and Chlamydia psittaci infection – have not been identified in the UK.

Whilst we are often tempted to reach to progesterone assays in the case of investigating a pregnancy loss, particularly in the first two months, these assays are frequently not helpful. Progesterone insufficiency is not a common cause of pregnancy loss and further, if a low progesterone is detected at the time of the loss, in most cases it is nearly impossible to determine whether the progesterone dropped due to the failure or was the cause of the failure.

Genetic testing

There has been an explosion in genetic research in the horse over the last decade and this is starting to filter through to stud medicine with growing applications in clinical practice. For example, our unpublished work discussed above indicates aneuploidies are associated with pregnancy loss, and it is hoped that tests associated with this genetic condition will be available very soon. In the meantime, there are a few options already available. It is recommended that mares with a history of recurrent pregnancy loss or failure to conceive are karyotyped to rule out chromosomal abnormalities such as translocations (Lear et al., 2008). Whilst this testing is currently not available in the UK, blood samples can be shipped using established export/import protocols to the Cytogenetics Laboratory at Texas A&M, USA.

Warmblood fragile foal syndrome (WFFS) is a relatively newly described genetic disease caused by a mutation in the procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (PLOD1) gene. The phenotype of the condition is variable but usually involves significant skin defects and abnormal joint flexibility resulting in late gestation abortion, stillbirth or perinatal death (Aurich et al., 2019). WFFS can be confirmed by testing for homozygosity for the C2032G > A mutation in PLOD1. Whilst the condition has to date only been described in Warmbloods, other breeds such as Thoroughbreds have been shown to be carriers of the allele so testing of all breeds that present with cases involving skin defects and hyperflexibility is warranted. This test is also strongly recommended for both mares and stallions prior to breeding to screen for carrier status enabling mating choices that avoid the condition.

References
Author Year Title
Allen, W., Brown, L., Wright, M. and Wilsher, S. 2007 Reproductive efficiency of Flatrace and National Hunt Thoroughbred mares and stallions in England. Equine Veterinary Journal, 39, 438-445
Aurich, C., Müller-Herbst, S., Reineking, W., Müller, E., Wohlsein, P., Gunreben, B. and Aurich, J. 2019 Characterization of abortion, still-birth and non-viable foals homozygous for the Warmblood Fragile Foal Syndrome. Animal Reproduction Science, 211, 106202
de Mestre, A., Rose, B., Chang, Y., Wathes, D. and Verheyen, K. 2019 Multivariable analysis to determine risk factors associated with early pregnancy loss in thoroughbred broodmares. Theriogenology, 124, 18-23
Hanlon, D. W. 2012 Reproductive performance of Thoroughbred mares in the Waikato region of New Zealand: 1. Descriptive analyses. New Zealand Veterinary Journal, 60, 329-334
Jobert, M. L., Leblanc, M. M. and Pierce, S. W. 2005 Pregnancy loss rate in uterine body pregnancies. Equine Veterinary Education, 17, 163-165
Lear, T. L., Lundquist, J., Zent, W. W., Fishback, W. D. Jr. and Clark, A. 2008 Three autosomal chromosome translocations associated with repeated early embryonic loss (REEL) in the domestic horse (Equus caballus). Cytogenetic and Genome Research, 120, 117-122
Miyakoshi, D. 2012 Factors influencing the frequency of pregnancy loss among Thoroughbred mares in Hidaka, Japan. Journal of Equine Veterinary Science, 32, 552-557
Roach, J. M., Verheyen, K. L. P., Smith, K. C., Molyneux, M., Bryan, J., Foote, A. and de Mestre, A. M. 2018 Incidence and pathology of abortions associated with umbilical cord torsions. Journal of Equine Veterinary Science, 66, 230
Rose, B., Firth, M., Morris, B., Roach, J., Wathes, D., Verheyen, K. and de Mestre, A. 2018 Descriptive study of current therapeutic practices, clinical reproductive findings and incidence of pregnancy loss in intensively managed thoroughbred mares. Animal Reproduction Science, 188, 74-84

Mandi de Mestre, BVSc (Hons), PhD, MRCVS, FHEA, is a reader in reproductive immunology and head of the equine pregnancy laboratory at the RVC. Her laboratory studies the epidemiology, pathology and genetics of early pregnancy loss and abortion. She lectures at national and international conferences on clinical aspects and the underlying science behind pregnancy loss in the mare.

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