Copyright Robert Foster
Department of Pathobiology
University of Guelph
The conceptus is the products of conception. It includes the embryo or fetus and the membranes.
The embryo is the 'young', 'organism' or 'component' that becomes the independently viable animal. The embryo becomes the fetus at a time point that is defined differently by different groups. Some say it is when the organism can be identified as to species. Others say it is when the organism begins independent movement. In humans some believe it is at the end of the first trimester.
Failure of Pregnancy (FOP) encompases a loss of pregnancy at any stage in gestation. It includes embryonic mortality, abortion, stillbirth, early pregnancy loss, midterm pregnancy loss, late term pregnancy loss, late term abortion and a variety of other terms with overlap in their definitions.
Embryonic mortality is when pregnancy is lost in the embryonic stage of gestation.
Abortion is an active noun derived from the latin past participle aboriri which is to miscarry, fail, disappear, pass away (see etymonline.com). It is a compound word used in Latin for deaths, miscarriages, and sunsets. Ab means amiss and oriri means appear, be born, or arise. It can refer to embryo or fetus.
Stilbirth is the death of an independently viable organism/fetus at or before the normal time of birth.
Is there a public health issue?
Many infectious causes of pregnancy loss are zoonotic. Some are highly infectious or indicate contamination of the farm/premises. Coxiella burnetti is a highly infectious organism.
Is there really a problem?
A problem of failure of pregnancy in a herd, flock, kennel, cattery or mob is recognised when the number of pregnancies that fail is above the normal for the species or is above a level attainable for that situation.
Cost benefit analysis
Cost
What can be achieved?
Many people believe that diagnostic evaluation and particulary laboratory evaluation is the 'be all and end all'. It is only part of the evaluation.
There are published laboratory success rates for many species - particulary for horses, ruminants and pigs. This provides some guidance for probability of determining infectious causes of FOP.
Sporadic vs outbreak? The probability of determining the cause of FOP is much higher in an outbreak situation. This is because there is a change in circumstance that lead to this FOP and it is easier to find a change.
What will you do about it?
If you are not going to do anything, there is little point, from a financial perspective, to spend money for no benefit.
Discuss Quarantine
About one half of FOP are infectious and quarantine is often an effective way to slow the spread of infectious disease.
General Principles
There are 2 parallel lines of investigation to solve a problem of failure of pregnancy. Determine if the cause is infectious or not, and are there lesions of the mother, fetus or placenta to explain the FOP.
The causes of failure of pregnancy are usually divided into two main groups - the infectious and the non-infectous causes. Infectious causes are usually the easiest to recognise because the lesions in the fetus or placenta can be recognised. Veterinarians with some experience can usually identify the lesions and recovery or identification of the causative agent or agents can be done with relative ease. Diagnostic laboratories are particularly skilled at this, and it is these laboratories that produce the figures of prevalence of disease. Those FOP without a recognised cause (usually without lesions or lacking an infectious cause) are usually labelled 'idiopathic abortion' or 'cause unknown'.
Diagnostic laboratories provide data on their known causes of failure of pregnancy. The laboratory success rate varies with the species and with their experience and committment. The data from diagnostic laboratories is skewed or 'biased' based on what is submitted. It is fair to say that about 50% of cases sent to the laboratory are infectious. At the individual or farm level this is likely to be lower, as there is a tendency for people to send in material that has a lesion such as placentitis. It is also likely that outbreaks garner more attention and material from these are more likely to be sent to laboratories - outbreaks are often the result of infectious disease.
Diagnostic Process
Clinical history and interview
Obtain signalment and history
Identify current complaint
Identify previous diagnoses
Determine current medications and actions
Take precautions to prevent zoonotic disease
Determine common diseases
Previous diagnoses, common diseases for the area based on experience and diagnostic laboratory information, and emerging diseases.
Examine Mother, Fetus and Placenta
Diagnostic testing
Is the cause infectous or not?
Collect samples according to Guide provided by the Diagnostic Laboratory which is based on what are common diagnoses. You must determine if results are relevant.
Non infectious disease is often management related and should be further investigated.
Final diagnosis
Treatment or recommendations.
Exposure of a pregnant female two high temperatures is known to result in failure of pregnancy. The mechanism of action includes effects on both the endometrium and the fetus.Experiments done in rabbits suggests high temperatures altar messenger RNA gene expression in embryos and endometrial tissue, particularly OCT-4. VEGF is also upregulated and interferon-gamma is down regulated.
It is likely that changes in hormonal and metabolic actions alters the generation of reactive oxygen species that results in pregnancy failure.
Marco-Jiménez F, Naturil-Alfonso C, Peñaranda DS, Jiménez-Trigos E, García-Diego FJ, Vicente JS.Maternal exposure to high temperatures disrupts OCT4 mRNA expression of rabbit pre-implantation embryos and endometrial tissue. Reprod Domest Anim 2013; 48: 429-434.
There are several recognised causes of generalised edema in fetuses. these include
- primary cardiac failure
- absence of the ductus venosis and high throughput cardiac failure
- hypoproteinemia
Some breeds, strains or lines of animals have differing birthrates. Failure of pregnancy can be as high as 100% in some mutant mice. Mice, rabbits and pigs I recognised as having genetic differences in prenatal losses. In most cases fertilisation rate is very high but many of the losses are at the embryonic stage.
Both embryonic and maternal genotype affects embryo and fetal survival. Experiments involving embryo transfer between strains of animals with different fetal survival rates indicates that the fetal genotype influences placental weight and maternal genotype influences embryo and fetal survival and add some maternal genotypes have greater receptivity during implantation.
Vicente JS, Llobat MD, Jiménez-Trigos E, Lavara R, Marco-Jiménez F (2013) Effect of embryonic and maternal genotype on embryo and foetal survival in rabbit.
Reprod Domest Anim 2013; 48: 402-406
Infectious agents including viruses, bacteria, protozoa and others cause pregnancy in a variety of ways. Some result in lesions in the mother, or fetus, or placenta or any combination. Others do not have recognisable lesions. Many of those without lesions create a cascade of inflammation resulting in cytokine injury and oxidative stress that result in fetal loss. These are the more difficult to diagnose.The initiating inflammatory change maybe small, inapparent or in a location that cannot be readily examined (such as the endometrium).
Multiple experiments using lipopolysaccharide injection into the amniotic fluid show a systemic pro-inflammatory reaction in the fetus from the lung and skin/amnion with an acute phase response and inflammation of the liver and spleen.
Adams Waldorf KM, McAdams RM. Influence of infection during pregnancy on fetal development. Reproduction. 2013; 146: R151-162.
Kemp MW1, Kannan PS, Saito M, Newnham JP, Cox T, Jobe AH, Kramer BW, Kallapur SG. Selective exposure of the fetal lung and skin/amnion (but not gastro-intestinal tract) to LPS elicits acute systemic inflammation in fetal sheep. PLoS One. 2013; 8(5):e63355