romagnoli - proceeding papers forbangkok apvc 2012

8/10/2019 ROMAGNOLI - Proceeding Papers ForBangkok APVC 2012

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PRACTICAL USE OFHORMONES INSMALL ANIMAL

REPRODUCTIONProf. Stefano Romagnoli, DVM, MS, P.D, Di!l. ECAR

Department of Animal Medicine, Production and Health,

University of Padova, Agripolis, Legnaro, 3500 !PD"

[email protected]

PROSTA"LANDINS

Prostaglandin #alpha !P$#" compounds have %een availa%le for over 30 years as

veterinary compounds for use in food animals and horses& 'heir luteolytic and

uterotonic actions ma(e them uni)ue, and very useful also in small animals, although

no pharmaceutical company has yet even ta(en into consideration mar(eting aprostaglandin product for use in dogs and cats& P$# compounds can %e used in small

animals *ith the folli*ng indications+

#$ earl% !regnan&% termination in 'it&e(

'he a%ortifacient efficacy of prostaglandins !P$#" involves induction of luteolysis,

stimulation of uterine contraction and cervical dilation& f these, the luteolytic effect

is the most important in the %itch, *hile the cervical dilating action has never )uite

%een demonstrated in this species& -n dogs, the progesterone supporting pregnancy is

entirely from the corpora lutea throughout gestation& P$# *ill induce luteolysis and

depress progesterone concentrations to nearly non.detecta%le levels very easily after

day 5 or 30, although also earlier in pregnancy& 'he later in the cycle P$# is

administered, the easier and more rapidly the induction of luteolysis& Use of P$#

re)uires su%cutaneous administration or 3 times a day, for / days or longer& o

P$# products are mar(eted *ith an indication for use in dogs or cats& 'he dosage

varies depending on the type of P$#+ natural P$# should %e given a ma1imum

dosage of 20.00 mcg4(g t*ice daily, starting gradually *ith 43 to the dose for

the first day !or the first administrations", *hile cloprostenol is currently %eing used

at a dose of mcg4(g !once every 6.62 hour intervals" and *hile alphaprostol must

%e used at the dose of 0 mcg4(g t*ice daily for several days li(e natural P$#& 7ide

effects !*hich include emesis, salivation, defecation, urination and slight tachipnea"are dose dependent !displayed in 859 of %itches using doses of 50 mcg4(g and only

in 59 of %itches using doses of 50 mcg4(g" and self.limiting, decreasing in intensity

*ith repeated dosing&

)$ late !regnan&% termination in 'it&e( an* +een(

:anine late pregnancy termination is generally adopted as a treatment *hen either a

mismating *as not o%served,the female *as not in the ovulatory phase or fertility of

the male is un(no*n& -n cats, the result of a serum progesterone assay done on a

%lood sample collected *ithin 3.8 days follo*ing mismating can %e used as an

indrecet indication of pregnancy, as ovulation is induced in this species& Dosage ofP$# compounds is the same as for early a%ortion, the only difference %eing that

treatment must %e continued until verification of efficacy %y ultrasound as partial

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a%ortion of litters can occur if treatment is discontinued prematurely&


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ANTIPROLACTINICS

Prolactin secretion %y the lactotroph cells of the anterior pituitary gland is regulated

%y multiple neuro.transmitters and hormones, *ith the ma?or control mechanism

%eing the activation of prolactin.inhi%iting dopaminergic neurons in the

hypothalamus& Prolactin is a ma?or luteotrophic hormone and appears to %e ana%solute re)uirement for canine and feline progesterone secretion %y day 30 after

ovulation& Dopamine agonists li(e %romocriptine or ca%ergoline are ergot al(aloids,

*ith strong dopamine D.receptor agonist activity, and thus can reduce prolactin

secretion there%y suppressing progesterone levels& 'he seretonin antagonist

metergoline stimulates endogenous dopamine secretion and thus can inhi%it prolactin

secretion as *ell&

:a%ergoline has a slo* clearance, *hich allo*s for a single oral daily administration&

#urthermore, its action is longer than 62 hours due to its particularly long !minimum62 hours" half.life at the hypophyseal level& @ecause of its more specific D.type

action, ca%ergoline presents only fe* side effects *hen used at clinical dosages&

@romocryptine mesylate inhi%its P;L secretion during relatively short periods of

time !half.life+ 6./ hours" and in a dose.dependent mode& -n order to effectively

inhi%it P;L tone in a continuous fashion for therapeutic purposes, %romocryptine

should %e administered at least t*ice a day, administered orally at doses 0.50 Bg4(g&

-ts lac( of specificity leads to side effects on the cardiorespiratory system, causing

hypotension due to vasodilatation !adrenergic type effect", or emesis due to

stimulation of the :hemioreceptive 'rigger Cone !:'C"& Attemps to improve sideeffects %y gradually increasing an initially lo* dose, or %y pre.treating *ith an anti.

emetic drug have proved only partially effective& Although its effectiveness has

never %een )uestioned, %romocryptine is not approved in most countries as an anti.

P;L in small animals and its e1tra.la%el use has not caught on, in spite of its *orld.

*ide availa%ility as a human drug&

Metergoline is essentially a serotoninergic antagonist *ith dopaminergic agonist

properties *hen used orally at doses of 0& mg4(g @-D& -ts shorter half.life re)uires

at least administrations t*ice a day& -ts antiserotoninergic properties can induce

mar(ed central effects such as depression, nervousness, increased e1cita%ility,

changes in appetite !anore1ia or %ulimia", psychotic effects !escaping from home,

aggressiveness"& $astrointestinal side effects due to stimulation of the :'C are

evaluated %y the emetic dosage in 509 of the %itches or D50& 'he D50 of

ca%ergoline and %romocryptine are identical& Ho*ever, *hen considering dosages

commonly used in a clinical setting, the emetic effect of %romocryptine is almost

al*ays present *hile it is negligea%le *ith ca%ergoline& 'he D50 of metergoline is

much higher, %ut it is very close to the therapeutic dosage& 'herefore, emetic effects

are sometimes o%served *hen using metergoline, especially *hen overdosing it&


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Antiprolactinic drugs can %e used in the %itch and the )ueen *ith three indications+

pseudopregnancy, induction of a%ortion and induction of estrus&

#$ P(e*o!regnan&%

'he anti.lactogenic action of %oth metergoline and ca%ergoline is *ell (ino*n& 'heir

administration for 6.5 days at pharmacological doses is effective in treatingpseudopregnancy signs and reducing mil( production& ccasional failures can %e

dealt *ith %y repeating the treatment protocol and e1tending it to 2 to 0 days, and

also %y administering at the same time metergoline !at the usual antigalactogenic

dosage of 00 mcg4(g @-D" or %romocriptine !0.0 mcg4(g @-D" !see ta%le nE "&

Antiprolactinics are currently considered the treatment of choice for

pseudopregnancy& Until the last part of last century, *hen antiprolactinics %ecame

commercially availa%le, progestogens *ere thought to %e an appropriate treatment for

false pregnancy due to their lo*ering action on P;L concentrations at the end of the

luteal phaseF infact, progestogen administration is clinically demonstrated to %eeffective in preventing the occurrence of lactation and of pseudopregnancy as *ell as

in eliminating related clinical signs& Ho*ever, a re%ound effect is fre)uently

o%served follo*ing treatment *ithdra*al, similarly to *hat occurs at the end of a

normal luteal phase, *hen the progesterone decline triggers a P;L pea(& 'herefore,

progestins should not %e used as a treatment for false pregnancy&

Anti!rola&tini&

*rg

Dail% *o(age in te

'it&1+een

Si*e effe&t(

2in&i*en&e$

Commer&ial name,

Com!an%

:a%ergoline 5 mcg4(g M-D mesis, anore1ia !09" $alastopG, :evaetem

@romocriptine 0.30 mcg4(g @-D

!I"

mesis, anore1ia !509" ParlodelG, ovartis

Metergoline 00 mcg4(g @-D

!I"

mesis, anore1ia

!09", %ehavioral

changes

:ontralacG, ir%ac

Ta'le n3 #J Daily dosages, side effects and commercial name !in urope" of the 3

antiprolactinics most commonly used in small animals+ ca%ergoline !$alastop

,:A.'M, a veterinary compound" and %romocriptine !Parlodel, ovartis, a

human compound" are dopamine agonists !they increase the concentration of

dopamine, a P;L.inhi%iting factor" *hile metergoline !:ontralac, ir%ac, a

veterinary compound" is a serotonine antagonist !it lo*ers the concentration of

serotonine, a P;L.stimulating factor"& !I" 'here is no scientific information

availa%le for the )ueen&

)$ In*&tion of a'ortion

'he a%ortion induction properties of antiprolactinic drugs have %een *ell studied for

ca%ergoline, *hile not as much is (no*n for metergoline& :a%ergoline is effective

in terminating pregnancy in dogs *hen administered at mid.gestation !as prolactin


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secretion starts around day 5" or later& ing action on the main P;L inhi%itor dopamine causes a po*erful, al%eit

indirect stimulus to P;L release !for a revie* see Cuppa et al&, 00" *ith reported

high efficacy rates especially *hen metoclopramide is associated *ith o1ytocin

Excerpts of this paper are taken from the article Control of mammary function in the bitch and queen from Romagnoli S. and Lopate C. inpress Clinical !heriogenology "#$"


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nasal spray& -n lactating *omen, metoclopramide is transferred to %reast mil(

*here it )uic(ly %ecomes more concentrated than in plasma !mil(.to.plasma ratio

of &2+", although this is not regarded as critical for %a%ies since the mil( level is

%elo* pharmacological doses& Metoclopramide acts also as an antagonist of

serotoninergic receptors !although this does not prevent P;L.releasing action", andhas some cholinergic effects on smooth muscle& Maternal side effects include

tiredness, headache, an1iety, nervousness and intestinal disorders& At higher doses

!.5 mg4(g" the drug may penetrate the %lood.%rain %arrier and e1trapyramidal

signs !an1iety, agitation, movement disorders, dystonic reactions, ata1ia" are

reported&

Metoclopramide is also normally used in dogs as an antiemetic drug at oral dosages

%et*een 0&.0&6 and . mg4(g divided in .3 administrations !ohnson et al&,

==6"& -t has %een used also to stimulate canine P;L secretion, although scientificdata *ith pre. and post.treatment P;L concentrations are availa%le only for male

dogs, in *hich a significant increase in serum P;L concentration is reported

follo*ing treatment *ith 0& mg4(g 3 times daily !Noivisto et al&, 00="& Use of

metoclopramide in %itches *ith agalactia is anecdotal, *ith protocols varying from

lo* !0&.0&5 mg4(g 7: or P, @-D or '-D . , 00" to high dose regimens !.5 mg4(g %eginning P or 7:, every /.2

hrs . Linde.#ors%erg 008"& fficacy seems to %e ade)uate *ith !su%?ective"

improvement of mil( production in O509 of cases, although no data on P;L

concentrations pre. and post. treatment is availa%le& 1trapyramidal signs mayoccur in canines, and are a concern in nursing %itches, therefore higher dosages

should %est %e avoided& -mprovement in mil( production is generally noticea%le

*ithin 6 J 62 hours& 'o minimi>e side effects, it is advisa%le to start at a lo*er

dose !0&5 J mg4(g4day divided '-D" for the first 6.62 hours and then if there is

no improvement gradually increase the dose every other day until an effect or

a%normal clinical signs are noted, at *hich point the dose is dropped to the prior

days dose or discontinued& 1trapyramidal signs are much more common at doses

a%ove mg4(g4day& @itches should %e monitored carefully *hen %eing treated *ith

metoclopramide to ensure in?ury to the pups does not occur& 'reatment should %e

continued for at least .3 days %eyond *hen mil( production appears to %e resulting

in ade)uate daily *eight gain for the pups *ithout supplementation&

Domperidone is a peripheral dopamine receptor antagonist developed as an

antiemetic agent and used for the treatment of nausea and vomiting& -n *omen,

domperidone significantly increases P;L secretion there%y enhancing %reast mil(

production, and is therefore used !off.la%el" as a galactogogue in most


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not use domperidone, after *hich the drug *as su%se)uently *ithdra*n from the

U7 human mar(et& 7u%se)uent research has sho*n that domperidone is safe *hen

used %y lactating mothers !see :amp%ell.eo et al&, 00 for a revie*"& 'he

ma1imum approved treatment protocol of domperidone in lactating *omen is 0

mg given 6 times daily, although most authors advice using doses of 0 mg orally'-D for . *ee(s& Ho*ever, the minimum effective dose and the minimum

duration of therapy have not %een identified yet& Domperidone causes a significant

increase in serum P;L concentrations and mil( production in treated vs control

mothers, *hich has %een estimated at 859 in a recent meta.analysis !sadchy et

al&, 0"& Unli(e metoclopramide, domperidone is less permea%le to the %lood.

%rain %arrier and is transferred in moderate )uantities to maternal mil( !mil(.to.

plasma ratio of 0&.&", due to its high molecular *eight and its =09 %inding to

plasma proteins !Cuppa et al&, 00"& o side effects are reported in infants of

mothers ta(ing domperidone, *hile side effects in mothers include oral mucosaldryness, s(in eruption, itch, headache and gastrointestinal disordersF e1trapyramidal

effects have %een o%served !dystonia" %ut are rare& o difference in mil( )uality of

mothers treated *ith domperidone is reported, e1cept for significant increases in

car%ohydrate and calcium !:amp%ell.eo et al&, 00"&

arly e1perimental use of domperidone has %een reported in the dog, *ith data on

pharmaco(inetics and e1cretion and meta%olism in @eagle dogs& Ho*ever, there is

a lac( of scientific as *ell as anecdotal information on clinical use of domperidone

in small animals *ith lo* mil( production& 'his is surprising given the positiveresults and the lac( of side effects of this drug ma(ing it pro%a%ly the %est treatment

for increasing mil( production in lactating mothers& Domperidone is (no*n among

small animal clinicians %y Q*ord of mouthR to %e effective in improving mil( yield

at doses of &5.&0 mg4(g in )ueens, and & mg4(g in %itches, per os for .3 *ee(s&

'reatment should %e continued for at least .3 days %eyond *hen mil( production

appears to %e resulting in ade)uate daily *eight gain for the pups *ithout

supplementation& -n our e1perience, results of domperidone in increasing mil(

production in agalactic %itches and )ueens appear to %e positive, %etter than those

o%tained *ith metoclopramide and devoid of e1trapyramidal effects& Diarrhea is

the most common side effect in the %itch, although there are anectodal reports of

%ehavior changes in some %itches %eing medicated&

Anti!(%&oti&(

:hlorproma>ine is an antagonist of D dopaminergic hypothalamic receptors,

commonly used for the treatment of human psychosis including schi>ophrenia and

depression& -t is considered the prototype of the phenothia>ine class of drugs& -ts

action on dopaminergic receptors causes P;L release, *hich is the reason for its

off.la%el use in %reastfeeding mothers& -t is transferred to mil( in lo* )uantities

!mil(+plasma ratio of 0&5", and its recommended dosage for galactogogic effect is5 mg orally '-D for one *ee( !Cuppa et al&, 00"& :hlorproma>ine has a *ide


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action on different :7 receptors producing also anticholinergic, antihistaminic, as

*ell as *ea( antiadrenergiceffects& 'he main side effectsof chlorproma>ine in

psychotic patients !*ho are treated *ith higher doses than lactating mothers" are

mostly due to its anticholinergic properties and include sedation, slurred speech,

dry mouth, constipation, urinary retention, possi%le lo*ering of the sei>urethreshold, increased appetite and impaired glucose toleranceleading to increase in

*eight& ot much is (no*n a%out side effects of chlorproma>ine in %reastfeeding

mothers and their infants !$entile, 002", although lethargy, sleepiness and reduced

activity have %een reported in a fe* %a%ies !AAP, 00"& #or these reasons, the

American Academy of Pediatrics !AAP" in 00 stated that chlorproma>ine is

included in the list of drugs *hose effects on nursing infants may %e of concern

!AAP, 00", and some authors advice monitoring of infants *hose mothers are

under chlorproma>ine treatment !@riggs et al&, 00/"&

-n small animals, chlorproma>ine is used as a second choice antiemetic drug *hen

metoclopramide does not *or( and %lood pressure is normal !7impson, 008"&

7uggested antiemetic dosage is 0&.0&5 mg4(g every /.2 hrs& nly anecdotal

information on the use of chlorproma>ine in cases of agalactia is availa%le for small

animals !ohnston, ;oot.Nustrit> and lson, 00"& 7ome authors advice the use of

aceproma>ine at 0&5.0&5 !amide used as an antipsychotic drug for the treatment

of human psychosis including schi>ophrenia and depression& -t is a strong

antagonist of serotoninergic receptors as *ell as of muscarinic, alpha.adrenergic

and histaminic receptors& -ts administration !off.la%el" to %reast.feeding *omen in

galactogenic doses of 50 mg orally .3 times4day for .6 *ee(s produces a strong

P;L.releasing effect *ith P;L reaching serum concentrations *hich may %e up

=09 higher than in the control group and infants of treated mother gaining

significantly more *eight than control ones& 7ignificant increases in mil(

production are reported only for primiparous mothers, not multiparous& Mil( of

treated mothers sho*s presence of the drug, although the mil(+plasma ratio of

transfer is lo*er than *ith metoclopramide or chlorproma>ine& Although side

effects are e1tremely rare in mothers and have never %een reported in infants of

treated mothers, the AAP advises against use of sulpiride in %reastfeeding *omen

as it does *ith all neurotropic drugs&

PRO"ESTERONE ANTA"ONISTS

Antiprogestins can %e used for+

" early and late pregnancy termination in %itches and )ueens

" open and closed.cervi1 pyometra in %itches and )ueens J :onservative medicaltreatment of %itches *ith pyometra can %e achieved *ith the administration of 0
http://en.wikipedia.org/wiki/Anticholinergichttp://en.wikipedia.org/wiki/Antihistaminichttp://en.wikipedia.org/wiki/Antiadrenergichttp://en.wikipedia.org/wiki/Adverse_drug_reactionhttp://en.wikipedia.org/wiki/Constipationhttp://en.wikipedia.org/wiki/Glucose_tolerance_testhttp://en.wikipedia.org/wiki/Anticholinergichttp://en.wikipedia.org/wiki/Antihistaminichttp://en.wikipedia.org/wiki/Antiadrenergichttp://en.wikipedia.org/wiki/Adverse_drug_reactionhttp://en.wikipedia.org/wiki/Constipationhttp://en.wikipedia.org/wiki/Glucose_tolerance_test


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mg4(g of aglepristone on days , , 2 and then also 5 and 2 depending on the

clinical situation in %itches *ith %oth open cervi1 and closed.cervi1 pyometra

!;omagnoli et al&, 00/"& 'he use of aglepristone should %e associated *ith

anti%iotics if necessary, and can also %e associated *ith P$# provided that cervical

opening has occurred& -n %itches *ith closed cervi1 pyometra, administration ofaglepristone is often follo*ed %y cervical opening *ithin 6.62 hrs& 'here is no

information on the effect of aglepristone on pyometra in the )ueen, %ut efficacy for

this indication is thought to %e the same as in dogs&

3" -nduction of parturition

6" treatment of feline mammary hypertrophy . @enign mammary hypertrophy is a

%enign fi%roglandular proliferation of one or more mammary glands *hich typically

occurs in young )ueens at their first luteal phase& 'he proliferation of the mammary

gland is due to an e1cessive response to the action of progesterone *hich is present

in presuma%ly normal concentrations in affected animals& Mammary glands *illstart s*elling rapidly and *ithin .3 days all glands %ecome very s*ollen, firm and

nodular& -f left untreated, the pro%lem may disappear on its o*n *ithout any

complication in most cases& 'reatment *ith prostaglandins or antiprolactinic is not

effective, *hile removal of ovaries or administration of aglepristone can %e

curative&


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Urinar% in&ontinen&e

see the paper on Medical treatment of canine urinary incontinence

Un6ante* !regnan&%7everal estrogenic compounds have %een used for this purpose, %ut for most of them

the ris( of side effects has discouraged their clinical application& nly estradiol

%en>oate, *hen given at lo* doses has proven to %e fairly efficacious and relatively

safe& A compound *ith estradiol %en>oate is mar(eted for veterinary use in mismated

%itches in several uropean countries, *hich is to %e administered at the dose of 0

mcg4(g 7: on day 3, 5 and 8 post %reeding& o short.term side effects have %een

reported follo*ing this protocol& -n a retrospective study done in the UN the

incidence of pyometra in the 6 months after the administration of lo* doses of

estradiol %en>oate *as 2&89, *hereas the incidence of that condition in a practicesituation *as estimated to %e S &09 !

and P lson ds& ler MA J :anine postpartum disorders& -n+ Nir(Ks :urrent eterinary'herapy V-& @onagura and D '*edt ds,


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"&.


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CLINICAL USE OF"NRH A"ONISTS INSMALL ANIMAL

REPRODUCTION)

Prof. Stefano Romagnoli, DVM, MS, P.D, Di!l. ECAR

%epartment of Animal Medicine, !roduction and &ealth,'ni$ersity of !ado$a, Agripolis, (egnaro, )*++ -!%

[email protected]

Despite their vital role for reproduction, endogenous se1 steroids may have negative

effects on fertility and general health&:yclical stimulation of mammary glands or

endometrium *ith endogenous estrogens and progesterone is (no*n to predispose the

female to develop conditions such as mammary tumors and endometritis4pyometra&Androgens are (no*n to predispose male dogs to prostatic hypertrophy as *ell as

contri%ute to the gro*th of prostatic carcinoma and perianal gland tumors& 'herefore

gonadectomy has al*ays %een advocated as a mean to avoid the ris( of developing

uterine or mammary diseases in females and prostatic or perianal diseases in males&

Ho*ever, %oth spaying and castration are irreversi%le modifications *hich in some

countries are considered not accepta%le on cultural or psychological grounds& Also,

surgical neutering carries the ris( of increased incidence of health pro%lems such as

urinary incontinence, o%esity, change of temperament, dermatological pro%lems !7ociety

for 'heriogenology, 0"&

A recent development in the field of control of the reproductive cycle in carnivores is the

use of gonadotropin.releasing hormone !$n;H" and especially its long acting agonists&

$onadorelin is a synthetic form of $n;H, *hile compounds such as %userelin,

deslorelin, goserelin, triptorelin, leuprorelin and nafarelin are synthetic analogues *hich

are availa%le as human as *ell as veterinary compounds& #or instance, leuprorelin !also

(no*n as leuprolide acetate", triptorelin and goserelin are almost e1clusively availa%le

as human drugs, nafarelin is currently studied for its potential use4s in controlling

reproduction in small animals *hile deslorelin is already mar(eted for veterinary use in

most *estern countries as a & mg, 6&8 mg and =&6 mg implantF the & mg implant is

mar(eted for use in horses !vuplantW", %ut its e1tra.la%el use in dogs is rather

common, *hile the 6&8 !7uprelorinW" and =&6 !7uprelorin W" mg implants are

currently mar(eted in urope and ceania for the control of fertility and aggressiveness

in male dogs %ut their e1tra.la%el use in cats is currently %eing evaluated& 'his paper

*ill revie* current and potential clinical applications of $n;H agonists in small animal

reproduction&

1cerpts of this paper are ta(en from the article Q:linical usage of $n;H agonists in small animal reproductionR from ;omagnoli7, accepted for pu%lication on the ?ournal :linical 'heriogenology

;eproduction
mailto:[email protected]:[email protected]


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POTENTIAL CLINICAL APPLICATIONS OF "nRH A"ONISTS

$n;H agonists act %y initially over.stimulating and su%se)uently do*n.regulating

$n;H receptors at the gonadotropes in the pituitary, there%y suppressing the function of

the HP$ a1is& 7uch a suppressing action on the release of luteini>ing hormone !LH" and

follicle stimulating hormone !#7H" leads to an arrest of secretion of gonadal steroids as*ell as their %y.products& 7uch %loc(ade of steroidogenesis can %e used in dogs and

cats for a variety of indications in prepu%eral and adult animals& 7ome clinical

applications have already %een tested and demonstrated useful and effective, *hile

others are ?ust the result of *or( in progress or have not %een put into practice yet %ut

are theoretically feasi%le %ased on the results of e1perimental studies&

INDICATIONS FOR PREPU7ERAL ANIMALS

Po(t!onement of !'ert%

7u%cutaneous administration of an early $n;H agonist to prepu%ertal male and femaledogs daily for 3 months partially or completely suppressed dehydroepiandrosterone

!DHA", andostenedione, ', dihydrotestosterone, 5.X androstanes and estrogens in

males, and DHA and estrogens in females !Lacoste et al&, =2=a"& 'reatment caused a

reduction in testicular and prostatic volume, a%sence of secondary follicles in the ovary

and atrophy of pituitary LH.secreting cells in %oth se1es& After a recovery period of 6

months %oth male and female dogs sho*ed pu%erty and their fertility *as normal

thereafter !Lacoste et al&, =2=a"& A>agly.nafarelin at the dose of 2 mg in a single depot

device *as administered su%cutaneously to 0 prepu%eral %eagle %itches and left in situ

for year& one of the %itches came in heat or ovulated *hile the 0 control %itchescame in heat regularly during the study period !;u%ion et al&, 006"& 'here *as no

difference in %ody *eight and gro*th rate %et*een treated and control animals, and

pu%erty in treated %itches resumed randomly and in a non.synchroni>ed manner after the

device *as removed !;u%ion et al&, 006"&

$n;H agonists can %e used to postpone pu%erty in cats&


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and 82 days in treated and control )ueens, respectively, *hile there *as no

difference in *eight at the end of the study& ne treated )ueen sho*ed clinical and

ultrasonographical signs of pyometra = days after implantation and *as immediately

spayed&

$n;H agonists are evidently capa%le of suppressing the hypothalamic.pituitary.gonadal

a1is of prepu%eral dogs and cats leading to postponement of pu%erty for a prolonged

period of time& -n dogs, use of deslorelin in young animals sho*s an age.dependent

response, *ith pups of 6 months sho*ing no estrus follo*ing implantation *hile all

pups implanted after 8 months of age *ill sho* pu%erty *ithin a short time& nly

prepu%ertal administration is capa%le of avoiding implantation.induced oestrus response

!'rigg et al&, 006"& Ho*ever, detailed information on onset of suscepti%ility to

e1ogenous $n;H around the time of pu%erty is not availa%le for dogs and cats& ation and a rise in testosterone in prepu%ertal )ueens andtomcats, respectively, follo*ing administration of a 6&8 mg deslorelin implantF ho*ever,

these signs *ere not follo*ed %y pu%erty, *hich *as instead delayed %y the implant&

Use of $n;H agonists can %e considered as a safe method to postpone pu%erty in dogs

and )ueens, *hile more data are necessary in tomcats to dra* the same conclusion

!although a similar effect is li(ely to occur"&

In*i&ation( for a*lt female(

Contra&e!tion

'he gonadal %loc( conse)uent to the suppression of the HP$ a1is achieved *ith a$n;H agonist causes onset of anestrus in the %itch& An implant of goserelin acetate

!$oserelin acetate, Ceneca, Milan, -taly", administered 7: at the dose of /0 Yg4(g every

days for months suppressed cyclicity in = adult %itches reducing circulating levels

of estradiol and P6 !Lom%ardi et al&, ==="& 'reatment of adult %itches *ith 3, / or

mg deslorelin !7uprelorinW, Peptech Animal Health, Australia" suppressed heat for

periods varying %et*een 0 !3&0 mg dose" and 0 !/ or mg doses" months !'rigg et

al&, 00"& Administration of deslorelin during anestrus or in the early stages of

proestrus *ill inevita%ly %e follo*ed %y induction of estrus *ithin 6.2 days after

implantation !'rigg et al&, 00, ;omagnoli et al&, 00=", *hile administration in

diestrus is not generally follo*ed %y heat induction !;omagnoli et al&, 00="& Ho*ever,

although a serum P6 concentration of 5 ng4ml is reported as a potential threshold a%ove

*hich estrus is not induced !'rigg et al&, 00", #ontaine et al& !00" have o%served

estrus induction in 642 %itches treated in diestrus&


19/75

6 *ee(s to cause do*n.regulation, there%y leaving enough time for normal *helping of

live fetuses to occur& 'he =&6 mg deslorelin implant has %een used in a fe* %itches,

*ith interval treatment.return to heat of months !;omagnoli et al&, 00="&

-n order to avoid inducing estrus follo*ing treatment *ith deslorelin, ler et al&, 00F

00F ol(mann et al&, 00/aF Nut>ler et al&, 00=F ;omagnoli et al&, 00=F #ontaine

et al&, 0"& -nterval from onset of proestrus until ovulation and onset of

cytological diestrus may %e shorter in %itches induced *ith deslorelin than in

spontaneous cycles !ol(mann et al&, 00/aF Nut>ler et al&, 00=+ #ontaine et al&,

0"& Leaving the implant in situ e1poses treated %itches to the ris( of pregnancy

loss occurring around mid.gestation due to premature arrest of luteal function

!ol(mann et al&, 00/aF Nut>ler et al&, 00=F #ontaine et a&, 0"& Administration

of 50 -U human chorionic gonadotropin !h:$" at day 6 post.LH does not solve

this pro%lem as after an initial stimulatory effect on serum P6 a drastic decline is

o%served over the ne1t fe* days !ol(man et al&, 00/%"&


20/75

easily accessi%le places such as the vesti%ular mucosa, the medial side of the leg or

the post.um%ilical region !Nut>ler et al&, 00=F ler et al&, 00=" or at

ovulation !#ontaine et al&, 0"& Although comparative evaluations of differentremoval times have not %een performed, if one considers reproductive parameters of

various studies no clear advantage has %een identified in this respect& -n %itches

induced to cycle *ith deslorelin ovulation rate3, conception rate6pregnancy rate5and

rate of premature luteal regression/*ere studied %y+

a" comparing treated and control %itches using a &05 mg !half of an vuplantW" or

the entire & mg implant administered into the vesti%ular mucosa !M" !ol(man

et al&, 00/a" Z ovulation rate *as not calculated, all other parameters did not

differ&

%" comparing the M vs the 7: !%et*een the shoulder %lades" administration usingthe & mg implant !Nut>ler et al&, 00=" Z conception rate *as either e)ual or

significantly %etter and a clear trend for a %etter pregnancy rate and a lo*er rate of

premature luteal regression *ere evident for M !//&89 and /&89, respectively"

vs 7: %itches !38&59 and 38&59, respectively"& A control, non.treated group *as

not used for this study&

c" comparing treated and control %itches using the 6&8 mg implant !


21/75

treatment !e&g& even if the %itch has not ovulated yet" in order to avoid unnecessary

ovarian stimulation !#ontaine et al&, 0"&

Pre0ention of mammar% tmor meta(tati& *i(ea(e

'he role of gonadal steroids in the development of mammary tumors is *ell esta%lished&eoplastic transformation of normal cells is thought to %e effected %y an QinitiatorR,

after *hich a%normal gro*th is stimulated %y a QpromoterR& 'he mitogenic action of

estrogens on canine mammary epithelium has %een descri%ed !@attistacci et al&, =86F

Hellmen, ==3"& strogens are considered potential initiators of neoplastic gro*th in

different species, often in con?unction *ith other hormones& #or instance, the

QinitiatingR role is played %y estrogens and prolactin in the rat and mouse, %y estrogen

plus a placental factor and perhaps a novel pituitary hormone in mon(eys and humans&

-n the %itch, the action of gonadal steroids, especially P6, can create a highly

proliferative environment in *hich an important initiating role is pro%a%ly played %ygro*th hormone !Mol et al&, ==8"& Under the influence of endogenous or e1ogenous

P6, $H can %e secreted %y the canine pituitary, and if the progestational stimulus is

prolonged $H can %e secreted %y the mammary gland as *ell& 'herefore, gonadal

steroids can have a direct as *ell as an indirect stimulatory action on the canine

mammary gland through the production of their needed co.factor, $H&

ormal and neoplastic mammary tissue features receptors for estrogen, P6, epidermal

gro*th factors and prolactin& 'he amount of such hormonal receptors decreases

proportionately to the increase in the degree of differentiation of neoplastic mammarytissue, *ith malignant mammary tumors having less hormonal receptors than %enign

mammary tumors !;utteman and Misdorp, ==3"& 'he use of $n;H agonists has

proven effective %oth in rats *ith hormone.dependent dimethyl%en>anthracene.induced

mammary tumors as *ell as in pre.menopausal *omen suffering from advanced %reast

cancer !@a((er et al&, =2=F @a?etta et al&, ==6"& A recent study loo(ed at the effect of

goserelin in %itches *ith spontaneous hormone.dependent mammary neoplasia

!Lom%ardi et al&, ==="& #ollo*ing assessment of presence of estrogen4P6 receptors on

a %iopsy of mammary tissue, 2 %itches *ith hormone.dependent lo%ular4invasive

mammary carcinoma *ere selected and assigned to a control !no drug" or treated

!goserelin" group& 'he = treated %itches received an implant of goserelin acetate

!$oserelin acetate, Ceneca, Milan, -taly", administered 7: at the dose of /0 Yg4(g every

days for months& $oserelin treatment reduced circulating levels of estradiol and

P6 and reduced the si>e of mammary tumors after 3 months in all treated %itches, *ith

229 of them sho*ing a relapse.free survival time of years !Lom%ardi et al&, ==="&

Although these results a*ait confirmation, the use of $n;H agonists for the treatment of

canine mammary tumors loo(s promising provided that clinical cases can %e selected on

the %asis of tumor type and presence of steroid receptors&


22/75

Treatment of !o(t8(!a%ing rinar% in&ontinen&e

'he involuntary loss of urine *hich may occur follo*ing spaying in the %itch has a

multifactorial origin, as demonstrated %y the fact that no single treatment !*hether

medical or surgical" achieves 009 efficacy& 'he chronic gonadotropin elevation *hich

inevita%ly occurs after neutering !%ecause of a%sence of gonadal steroid negativefeed%ac(" has %een considered as a potential cause of urinary incontinence in castrated

%itches& 'he hypothesis that a do*n.regulation of gonadotropins using $n;H agonists

may improve or fully cure urinary incontinence *as initially considered valid follo*ing

clinical trials in *hich ovariectomi>ed %itches refractory to the use of .agonists *ho

*ere successfully treated *ith a $n;H agonist !leuprorelin, %userelin, triptorelin or

deslorelin" !;eichler et al&, 003"& @ecause of the initial increase in #7H.LH release,

some protocols included also administration of .agonist treatment for the first 3 *ee(s

!;eichler et al& 00/"& ;esults have %een )uite positive *ith periods of continence

varying from to some months follo*ing a single treatment *ith different $n;Hagonists !revie*ed %y Arnold et al&, 00="& Although chronic administration of a $n;H

analogue decreases plasma LH and #7H to %asal values, in incontinent %itches there is

little if any correlation %et*een the effect on gonadotropin levels and the response to

treatment !;eichler et al&, 006"& 7erum concentration of gonadotropins appears to %e

involved, directly or indirectly *ith the pathophysiology of canine post.spaying urinary

incontinence, *ith a greater role played %y #7H& Ho*ever, the e1act pathophysiology

of this condition has not %een clarified yet&

Administration of deslorelin has no significant effect on urodynamic parameters, even*hen %itches respond positively to the treatment, %ut rather seems to modulate %ladder

function allo*ing for a larger %ladder filling volume at the same %ladder pressure

!;eichler et al&, 00/aF 00/%"& :urrent clinical information suggests that *hen treated

*ith a 6&8 mg deslorelin implant, previously incontinent %itches *ill sho*

appro1imately a 509 recovery rate, *ith another 0.09 of %itches sho*ing incomplete

response characteri>ed %y a reduction in the fre)uency of incontinence episodes and4or

an improvement in the response to pharmacological treatment *ith . agonists or estriol

!Arnold et al&, 00="&


23/75

ng4ml" follo*ed %y a decrease to castration levels for a prolonged time& 7imilar results

*ere later o%tained *ith implants of /&/ mg %userelin !;iesen%ec( et al&, 00", 2&5 mg

a>agly.nafarelin !Lud*ig et al&, 00/", or 6&8 mg deslorelin !;omagnoli et al&, 005F

unaidi et al&, 008" & Dogs treated *ith implants of /&0 mg deslorelin typically sho*

initially an acute increase in concentration of LH and ', *ith %oth hormones %ecomingundetecta%le after a%out t*o *ee(s !unaidi et al&, 00=a"F histologically, disruption of

seminiferous tu%ules and epithelial atrophy are evident as early as day / and 6,

respectively !unaidi et al&, 00=%"F clinically, they start %ecoming infertile *ithin a /.

*ee( period and resume normal fertility only after several months !;iesen%ec( et al&,

00"& A chronic treatment *ith a 6&8 mg deslorelin implant causes a progressive loss

of pituitary responsiveness to $n;H over a period of 6 *ee(s *ith a lac( of response to

stimulation of the HP$ *ith $n;H or LH already evident at 3 *ee(s and %eing

complete at 60 days post implantation !unaidi et al&, 008"& 'he decrease in testicular

si>e may vary from a 0.309 reduction during the first fe* months up to 50./09 at /months post.treatment !;iesen%ec( et al&, 00F ;omagnoli et al&, 005F Lud*ig et al&,

00/"&

-n male dogs treated *ith a deslorelin implant, complete sterility is thought to occur

*ithin a .month period !;iesen%ec( et al&, 00"&


24/75

implant is effective is reducing li%ido and aggressiveness in male dogs, although

occasional failures are encounteredF these are pro%a%ly due to the fact %oth these aspects

of a dogKs temperament are not fully dependant on serum ' concentration, %ut there is

also a role of e1perience in their development&

Treatment of an*rogen8*e!en*ent *i(ea(e(

@enign prostatic hyperplasia !@PH" is the most common canine prostatic disorder, *ith

more than 509 of intact dogs developing histologic evidence of @PH after 5 years of

age& Hyperplasia is pro%a%ly due to an altered androgen+estrogen ratio, and re)uires the

presence of the testes to start and continue to develop& Dihydrotestosterone !DH'"

*ithin the prostate gland pro%a%ly serves as the main hormonal mediator for

hyperplasia& :astration is commonly considered the %est treatment as the drastic

decrease in androgen secretion causes a 809 decrease in prostatic si>e !due to atrophy"

*ithin = *ee(s !@arsanti e #inco, ==5F @arsanti, ==8"& #ollo*ing administration of a$n;H agonist, prostatic si>e decreases in parallel *ith the decrease of ' !Lacoste et al&,

=2=%F Ponglo*hapan et al&, 00F ;iesen%ec( et al&, 00F Lud*ig et al&, 00/"& ed %y presence of a round, irregular .

6 cm diameter mass *hich had developed over the last . months& -n %oth cases,

administration of an implant of 6&8 mg deslorelin acetate *as sufficient to cause a long


25/75

lasting regression of the perianal mass *ithout any additional treatment !;omagnoli,

unpu%lished data"

7I7LIO"RAPH4 an* SU""ESTED READIN"S

& Arlt 7P, 7pan(o*s(y 7, Heu*ieser < . #ollicular cysts and prolonged oestrus in afemale dog after administration of a deslorelin implant& e* Cealand eterinary

ournal, 5=+, 28.=

& Arnold 7, Hu%ler M&, ;eichler - J Urinary incontinence in spayed %itches& e*

insights into the pathophysiology and options for medical treatment& ;eprod Dom

Anim 66 !7uppl "+ =0.=, 00=

3& @a?etta , :elio L, Cilem%o , @ono A, $allu>>o D, Campino M$, Longhi A,

#errari L, @u>>oni ;+ ==6& varian function suppression *ith the

gonadotrophin.releasing hormone analogue goserelin in premenopausal advanced

%reast cancer& 'umori /++ 2.36& @a((er $H, 7etyono.Han @, Portengen H, De ong #H, #oe(ens , Nlin $M+

=2=& ndocrine and antitumor effects of com%ined treatment *ith an

antiprogestin and antiestrogen or luteini>ing.hormone releasing hormone agonist

in female rats %earing mammary tumor& ndocrinology 0*+ 5=3.5=2

5& @arsanti A, #inco D; J Medical management of canine prostatic hyperplasia&

-n+ @onagura D, Nir( ;


26/75

7& Antonio, 'e1as, U7A, April 002http+44***&accd&org46th907ymposium

90#iles4#ontaine]Useof$n;H&pdf$ Accessed April 0

3ontaine , Mir #, annier #, $erardin A, Al%ouy M, avarro :, #ont%onne A, .

-nduction of fertile oestrus in the %itch using Deslorelin, a $n;H agonist&

'heriogenology 8/ !0", 5/.5//6oresta :, @ettella A, ;ossato M, La 7ala $, De Paoli M, Ple%ani M+ ===&

-nhi%in @ plasma concentrations in oligo>oospermic su%?ects %efore and after

therapy *ith follicle stimulating hormone& Human ;eprod 03+ 0.08

5oresta :, @ettella A, 7polaore D, Merico M, ;ossato M, #erlin A+ 006&

7uppression of the high endogenous levels of plasma #7H in infertile men are

associated *ith improved 7ertoli cell function as reflected %y elevated levels of

plasma inhi%in @& Human ;eprod 04!/"+ 63.638

/&unaidi A, ler M+ 005& -nduction and synchroni>ation of estrus in dogs&

'heriogenology 23+8//.885

3&Nut>ler M, 7tang @,


27/75

5&Lacoste D, La%rie #, Du%^ D, @^langer A, 'ice ', $illey ;M, Pladger NL+ =2=%&

;eversi%le inhi%ition of testicular androgen secretion %y 3.& 5. and /.month

controlled.release microsphere formulations of the LH.;H agonist D.'rp, des.

$ly.H LH.;H ehtylamide in the dog& 7teroid @iochem ))!5"+008.00

/&Lom%ardi P, #lorio 7, Paganini U, :rispino A, Avallone L+ ===& varian#unction suppression *ith a $n;H analogue !$oserelin" in hormone.dependent

canine mammary cancer& et Pharmacol 'herap + 5/./

8&Lud*ig :, Desmoulins P, #lochlay.7igognault A, Driancourt MA, Hoffman @+

00/& 'reatment *ith a su%cutaneous $n;H agonist.containing implant do*n.

regulates the hypothalamo.pituitary gonadal a1is of male dogs& Proceedings 5th

:ongress uropean eterinary 7ociety for 7mall Animal ;eproduction, @udapest,

Hungary, 8.= April, pp 38

2&Ma?dic $, Mceilly A7, 7harpe ;M, vans L;, $roome P, 7aunders 'N+ ==8&

'esticular e1pression of inhi%in and active su%units and follistatin in the rat andhuman foetus and neonate and during postnatal development in the rat&

ndocrinology 0)/+3/.68

=&Massoud $, Perrin P, Daumont M, ;uffion A Discovery of

a pituitary adenoma follo*ing a gonadotropin.releasing hormone agonist in a

patient *ith prostate cancer&-nt Urol& 00/ 3!3"+303.6

30&Mol A, 7elman P, 7prang PM+ ==8& 'he role of progestins, insulin.li(e

gro*th factor !-$#" and -$#.%inding proteins in the normal and neoplastic

mammary gland of the %itch+ a revie*& ;eprod #ert 7uppl *0+33=.366

3&Pisu M:, ;omagnoli 7 . -mpiego clinico di un impianto di deslorelin nel gatto&eterinaria, Anno / !", #e%ruary+ .8, 0

3&Ponglo*hapan 7, Lohachit :, 7*angchanutai ', 'rigg '+ 00& 'he effect of the

$n;H agonist deslorelin on prostatic volume in dogs& Proceedings :ongress

uropean eterinary 7ociety for 7mall Animal ;eproduction, Liege, May 0.,

p 50F

33&;eichler -M, Hu%ler M, ochle


28/75

38&;eichler -M, @arth A, Pich^ :, ochle t=-!/"+5.50

3=&;isso A, :orrada , @ar%eito :, Dia> D, $o%ello : J Long.term release $n;H

agonists postpone pu%erty in domestic cats& ;eprod Dom Anim doi+0&4?&

63=.053&0&0==6&1

60&;omagnoli 7, :oncannon P


29/75

50& 'ammela ', 006 J ndocrine treatment of prostate cancer& 7teroid @iochem Mol

@iol 4!6"+28.=5

5& 'aniyama H, Hirayama N, a(ada N, umagami N, aosa(a , Naga*a ,

->umisa*a , a(ade ', 'ana(a , il August 6./, pp 6=.556& 'rigg ', Doyle A$, ler MA, ler MA, , Lam% 7+ 006&

#ailure of h:$ to support luteal function in %itches after estrus induction using

deslorelin implants& 'heriogenology //+ 50.50/, 00/%58& , 'hompson -, 005+ Luteini>ing hormone.releasing

hormone agonist effects on s(eletal muscle+ ho* hormonal therapy in prostate

cancer affects muscular strength& Urol&01)!6"+0/8.8

52&


30/75

CLINICAL APPROACH TOINFERTILIT4 INTHE7ITCH


%epartment of Animal Medicine, !roduction and &ealth,

'ni$ersity of !ado$a, Agripolis, (egnaro,

)*++ -!%[email protected]

:anine infertility can %e due to *rong %reeding management, reproductive cycledisorders, non.infectious uterine disease, poor semen )uality, failure of the male to

achieve a complete %reeding, infectious disease of the reproductive tract, or ovarian

;eproduction


31/75

diseaseF also, non.reproductive or systemic causes may also limit fertility, such as

hypothyroidism, or advanced age of the %itch& #rom a practical standpoint, fertility

means achieving conception, then esta%lishing a pregnancy through implantation

and carrying the pregnancy to term& As things can go *rong in each one of these

phases, this paper *ill %riefly revie* the most common factors influencingconception, the esta%lishment of pregnancy as *ell as the successful carrying of a

pregnancy to term in canines&

FACTORS INFLUENCIN" CONCEPTION AND PRE"NANC4 IN THE

7ITCH

rrors in %reeding management, anovulatory cycles and ovarian4uterine pro%lems

are fre)uently encountered as a cause of infertility in %itches of all ages, *hile poor

semen )uality is often a feature of adult to older male dogs& 'he most common

factors influencing conception and the esta%lishment of a normal canine pregnancyare listed in order of incidence in 'a%le nE &

Ca(e of Con&e!tion or

Pregnan&% Failre

Un*erl%ing &a(e

@reeding Management Breeding early or late

;eproductive cycle disorders and

ovarian diseases

Anestrus, short cycles, failure to o$ulate,

o$arian cysts or tumors

on.infectious uterine Disease "ystic endometrial hyperplasia, pyometra

Poor 7emen [uality !rostate disease, testicular disease or

degeneration#ailure to Achieve a ormal

Mating

(ac5 of e6perience,no coital loc5, poor female

recepti$ity

-nfectious disease of the

reproductive tract

Br. canis, &erpes Virus canis, 7acterial

infections

on.infectious causes of

em%ryonic.fetal death

8ndocrine disease, chromosomal a7normalities,

improper use of drugs

Ta'le n3 #+ 'he most common factors influencing conception and the esta%lishment

of pregnancy in dogs& #actors are listed in order of incidence&

A complete data%ase of information !'a%le nE " should %e recorded for all previous

seasons for *hich information is availa%le& -nformation collected through history

can %e used %y the clinician to decide *hether or not the %itch is cycling normally,

*hether or not she *as %red4inseminated at the appropriate time and *hether or not

reproductive disease is present& ach of the )uestions on ta%le nE addresses a

specific issue *hich may %e relevant for understanding the cause of failure to

conceive&

7ree*ing management


32/75

As most %itches ovulate on day of their season, there is a *idespread tendency

of o*ners to assume that day is the ideal %reeding day for all %itches& As a

matter of fact, some %itches ovulate early !such as on day 2, or / or even 6 from the

onset of proestrus" *hile others may ovulate as late as on day 8, = or .6& ne

should never assume that a given %itch *ill ovulate on day unless proven& Also,incidence of early or late ovulation is pro%a%ly higher in the those %itches *ho are

ta(en to the veterinarian *ith a presenting complaint of infertility *ith respect to

the normal canine populationF %itches ovulating on day from the onset of

proestrus *ill al*ays conceive at the first mating and therefore *ill almost never %e

ta(en to the veterinarian %ecause of fertility pro%lems& Managing a canine %reeding

re)uires the client ta(ing the %itch to the veterinary clinic as soon as the first signs

of proestrus are displayed !vulvar discharge, male attractiveness" for a first chec(,

and then coming %ac( every .3 days to monitor ho* )uic(ly the female is

progressing to*ards ovulation through vaginal smears and serum progesteroneassays& aginoscopy and ovarian ultrasound can %e very helpful clinical tools in

identifying and monitoring the ovulation process&


33/75

Ta'le n3 )J [uestions to %e as(ed *hen collecting reproductive history for

cases of canine female infertility and reasons for their importance&

Provided that vaginal a%normalities !strictures, %ands of tissue, hymen" are ruled

out, serum P6 as *ell as using different male dogs !to rule out male preference" are

helpful in such cases, although some %itches %ecome receptive to mating only in

mid to late estrus& vulation should al*ays %e timed using serum P6 assay every .

3 days and the %itch should %e %red *hen a high P6 value is o%served !O5&0 ng4ml"&

aginal cytology should also %e used to confirm serum P6 data !serum P6 (its

*hich use a semi.)uantitative colorimetric system are only 209 accurate" during

and !most importantly" after %reeding until the first day of cytological diestrus !D"

is identified, *hich occurs /.2 days after ovulation& aginal endoscopy is also a

helpful tool to stage the estrous cycle& stradiol stimulation causes vaginal mucosa

to %ecome edematous, therefore during proestrus and early estrus vaginal folds

THEINFORMATION

ON>

ISIMPORTANTFOR>

Date of onset of

proestrual %leeding

stimating ovulation !in most %itches occurs on day

after onset of proestrus"

Date of onset of firstreceptivity

stimating ovulation !in most %itches occurs daysafter start of receptivity"

@reeding4s+ dates,

out4inside tie, A-, fresh

vs fro>en semen

stimating on potential fertility as %reedings *ith

outside tie may not %e fertileF fro>en semen must %e

placed into the uterus days after ovulation

Date of first refusal of

mating

:orrelation *ith onset of cytological diestrus, *hich

is helpful to estimate ovulation

Male fertility, age,

semen colture

Assessing male responsi%ility+ prostatic disease

!common in adult.older dogs" and

orchitis4epididymitis may alter semen )uality@rucella canis anti%ody

status !%itch T dog"

valuating presence of @& canis role in infertility

!-mportant in countries *here it has %een isolated"

Pregnancy status at 2

days

Assessing *hether conception too( place

Previous normal

*helping4s, litter4s

Assessing *hether fertility *as previously present or

if it may %e a congenital pro%lem

Previous signs of false

pregnancy

;uling in4out ovulation !false pregnancy occurs only

after ovulation"

Previous reproductivedisease

Assessing *hether or not previous pathologicconditions of the reproductive tract may affect fertility

Previous non.

reproductive disease

Assessing *hether clinical signs of other system may

have relevance on fertility !(ennel cough may %e due

to herpes virus"

Previous hormonal

therapy

Assessing potential negative effect of of previous

administration of progestogens


34/75

appear round and s*ollen *ith some %lood.tinged fluid in %et*een them& As soon

as follicular estrogen production stops fluid is resor%ed from the vaginal mucosal

lining and therefore vaginal folds suddenly %ecome *rin(led !a process called

QcrenulationR"& As the *rin(ling process is associated *ith a decrease in estradiol

rather than an increase in progesterone, the crenulation is only an indirect indicatorof ovulation& 'herefore, vaginal endoscopy is a good *ay of identifying and

monitoring the estradiol curve, %ut cannot %e used to identify ovulation directly+

serum progesterone remains a vital indicator in this respect&

Re!ro*&ti0e &%&le *i(or*er( an* o0arian *i(ea(e(

Prolonged lac( of heat or anestrus is sometimes o%served especially in older %itches&

#re)uent cycling !3.6 heats4year" is also o%served in %itches of all ages, and has

%een associated *ith infertility, although the mechanism involved is not yet clear&

Anovulatory cycles occur fairly fre)uently !although there is not enoughinformation on their incidence" %oth at pu%erty as *ell as in the adult %itch&


35/75

insufficiency and other endocrine diseases may affect foetal via%ility& 'he improper

use of drugs may also have an adverse effect on pregnancy& :hromosomal

a%normalities are *idely descri%ed as a cause of em%ryonic4fetal death in the dog&

:ollecting a *hole %lood sample and su%mitting it to a la%oratory for (aryotype

should never %e overloo(ed *hen dealing *ith an a%ortion case& Lutealinsufficiency is a recogni>ed cause of failure to carry a pregnancy to term in the

%itch&

Poor (emen +alit%

Dogs e?aculate 500.000 million spermato>oa diluted in .50 cc of seminal plasma&

[uantity of spermato>oa as *ell as of seminal plasma varies according to %ody

*eight and testicular si>e, *ith or(shire terriers and $reat Danes producing an

average of .3 and 0.30 cc of e?aculate, respectively& 7emen )uality depends on

)uantity of spermato>oa present, their motility and morphology& Assessing semen)uality is an easy tas( *hich can %e performed in any veterinary clinic, provided

that the male dog is accustomed to the techni)ue or a %itch in heat is availa%le to

help him concentrate on e?aculation& 7emen collection is generally performed *ith

manual stimulation of the dogKs penis through an artificial vagina !a late1 cone

connected to a plastic tu%e" or ?ust *earing a late1 glove in one hand and a smooth

glass or plastic container in the other hand& nce collected, the semen must %e (ept

in a *arm environment !holding the tu%e in oneKs hands is enough" *hile it is %eing

chec(ed for motility !under a light microscope at 00V", morphology !under light

microscope at 00.600V follo*ing staining *ith any cytological stain such as Diff[uic(, haemato1ylin.eosin or Leishman %lue" and num%er of spermato>oa !using a

haemocytometer such as a ie%auer cham%er, 'homas cham%er or Ma(ler

cham%er"& Poor semen )uality can %e found in adult to older male dogs, especially

if suffering from prostate disease or follo*ing orchitis4epidydimitis or scrotal

trauma& Poor semen )uality can %e due to also to in%reeding causing early testicular

degeneration&

Failre to a&ie0e a normal mating

oung stud dogs at their first attempts at %reeding may sometime apparently loo(

not capa%le of mounting properly, e&g& they may approach the female from her flan(

or from her head, or may spend a considera%le amount of time pelvic thrusting

*ithout achieving an intromission& Although this should %e considered part of the

normal process of learning reproductive %ehaviour in young animals, it is

considered a%normal *hen displayed %y adult male dogs& 7ometimes a male dog

may achieve an incomplete intromission in *hich the %ul%us glandis *ill engorge

outside of the vulva& oa outside the vulva or to ahigher degeneration rate of spermato>oa due to the acidic pH of the vagina& ot


36/75

achieving an inside tie in the dog may %e due to lac( of e1perience, disease of the

penis or lac( of li%ido&


37/75

mm and4or persisting for more than .3 days should %e considered a%normalF canine

ovarian cysts respond poorly to $n;H, %ut a course of 3.5 day treatment *ith 3.5

in?ections4day should %e enactedF the dose is 40 of the dose for treating ovarian

cysts in dairy co*s& Anovulatory cycles can %e diagnosed %y lac( of progesterone

secretion after the end of estrusF there is no information on treatment for thisconditions, %ut it generally does not occurs t*ice in a ro*& @itches in prolonged

anestrus can %e treated *ith a .6 *ee( course of ca%ergoline at the regular anti.

galactogenic dose !5 mcg4(g" once dailyF the treatment should %e stopped once a

%loody vulvar discharge is o%served indicating the onset of proestrus&

Non8infe&tio( terine *i(ea(e

'he clinical approach to hypoluteoidism includes assessing maternal and fetal

conditions, ruling out other possi%le causes of a%ortion and repeatedly measuring

serum progesterone !P6" concentrations& -n a %itch *ith a history of infertility due toa suspected luteal insufficiency, P6 monitoring should start 5.to.8 days after the last

%reeding and should %e done once4*ee(& 'reatment includes administration of a

natural or synthetic P6 compound to support pregnancy as long as needed& 'he use

of synthetic P6 compounds prior to day 30 of gestation should %e avoided since it

may induce malformation of the genital system of female foetuses& Protocols used in

%itches *ith luteal insufficiency include daily administration of Allyl.tren%olone,

0&022 mg4(g, orally, Medro1yprogesterone acetate !0& mg4(g", orally, or natural

progesterone 00 mg @-D orally& 'reatment should %e *ithdra*n no later than

gestation day /0, as a prolonged P6 administration may inhi%it the mechanism ofparturition& Ho*ever, there is not enough data to advice a specific time interval prior

to the e1pected date of *helping during *hich P6 administration should %e

*ithdra*n, and treated %itches very often end up in having a :.7ection& Progestin

administration during pregnancy may negatively affect the canine lactation&

Poor (emen +alit%

'here is little if any treatment that can %e done to improve semen )uality in male,

unless this is due to a treata%le contingent cause !such as orchitis4epidydimitis,

prostatic condition, fever, systemic disease"& oospermic dogs improvements in semen )uality are anecdotally

reported using P$#a 0& mg4(g 5 minutes prior to semen collection, or using

gonadorelin 3&3 mcg4(g -M once *ee(ly for 6 months !Hess, 00/", or a $n;H

agonist !Na*a(ami, et al&, ==2"&

Failre to a&ie0e a normal mating

nce *rong %reeding management is ruled out, the vagina should %e e1amined

digitally, then using endoscopy and, if nothing is o%served, using a retrograde

vaginography& Minor vaginal4vesti%ular restrictions !fairly common" can %eresolved manually %y gentle manipulation, *hile partial persistent hymen often


38/75

resolves on its *on at parturition& More relevant anomalies !large septa, complete

hymen, vaginal neoplasia or hyperplasia" should %e dealt *ith on a case.%y.case

%asis, surgically if necessary& Mate preference or %ehavioural pro%lems can %e

solved using artificial insemination&

Infe&tio( *i(ea(e of te re!ro*&ti0e tra&t

-nfectious diseases causing a%ortion *ill %e dealt *ith in the chapter on

Q:omplications in canine pregnancyR& @itches infected *ith Herpes irus should %e

vaccinated *ith the Herpes accine t*ice !once 0 days after mating and again /

*ee(s later"& @itches infected *ith @rucella canis should %e eliminated from the

%reeding (ennel, and %est ovariohysterectomi>ed& @itches suffering from any other

type of infection during the previous cycle should %e chec(ed early in proestrus

performing %acteriology of the cranial vagina, and treated *ith specific anti%iotics

until ovulation&

7I7LIO"RAPH4 an* SU""ESTED READIN"S

& $orlinger 7, $alac 7, Nooistra H7, ((ens A:, 005 . Hypoluteoidism in a

%itch& 'heriogenology /6, 3J=&

& Hess M J Documented and anecdotal effects of certain pharmaceutical agents

used to enhance semen )uality in the dog& 'heriogenology //+/3./8, 00/

3& Na*a(ami , Hori ', 'sutsui '& :hanges in plasma LH and testosterone

levels and semen )uality after a single in?ection of h:$ in t*o dogs *ith

spermatogenic dysfunction& et Med 7ci ==2F/0+8/5J86& Nustrit> M;, 00+ Use of supplemental progesterone in management of

canine pregnancy& -n+ :oncannon P M, lson P7 J :linical approach to canine

infertility& -n+ :anine and #eline 'heriogenology& ditors 7D ohnston, M

;oot.Nustrit> and lson P7,


39/75

0&'homas P$A, Per(ins ; J History ta(ing and diagnostic assessment of

the su%fertile %itch& Austr et Pract 3+36.63, ==3

&'i%old A and 'huroc>y . Progesterone, oestradiol, #7H and LH

concentrations in serum of progesterone.treated pregnant %itches *ith

suspected luteal insufficiency& ;eprod Domest Anim&00= ulF 66 7uppl+=.3&

&;amsey -, Herrtage M . Distinguishing normal, sic( and hypothyroid

dogs using total thyro1ine and thyrotropin concentrations& :anine Practice

+63.66, ==8

3&;eimers ' J ndocrine testing for infertility in the %itch& -n+ Nir( ;< ed,

:urrent et 'herapy ---,


40/75

COMPLICATIONS INCANINE PRE"NANC4 ANDTHEIRCLINICAL

APPROACH


Department of Animal Medicine, Production and Health,University of Padova, Agripolis, Legnaro, 3500 !PD"

[email protected]

-n the %itch as in most other species death of conceptus can occur at any stage of

pregnancy, resulting in partial or total resorption, partial or total a%ortion or

retention of foetuses *hich can %ecome mummified or %e coloni>ed %y %acteria

causing a pyometra& 'he type of outcome depends on *hat has causedem%ryonic4fetal death, the stage of pregnancy and fetal4maternal

immunocompetence& A%ortion is often difficult to diagnose as the %itch rarely

sho*s *ell defined clinical signs !often no signs at all or ?ust a short lasting malaise

or anore1ia" %ut it can in rare instances %ecome a life.threatening situation leading

to shoc(& A relevant clinical pro%lem is the lac( of an early pregnancy test *hich

*ould allo* to monitor em%ryonic *ell.%eing and diagnose em%ryonic death& Also,

the availa%ility of a histopathological diagnosis on a%orted fetuses is fre)uently

hampered %y lac( of o*ner colla%oration as *ell as %y the fact that %itches often

devour or hide dead fetuses& A%orted fetuses and4or placentae !the more the %etter"should refrigerated at J6E: and shipped to the diagnostic la%oratory *ithin 6 hours

of death&

-ncidence of canine em%ryonic resorption or spontaneous a%ortion is not *ell

defined& n laparotomy it has %een o%served a 5.39 difference %et*een nE of

corpora lutea and nE of fetal vesicles& n ultrasound em%ryonic death is

characteri>ed %y lac( of vesicle gro*th, reduction of volume of the em%ryo mass,

loss of vesicular roundness, reduction of volume and ecogenicity of em%ryonic

fluids& Death of one or more em%ryos may not %e detrimental to survival of the

other em%ryos even on the same uterine horn& :linical signs at this stage are

fre)uently a%sent& A%ortion is characteri>ed more fre)uently than resorption %y

general clinical signs !from very mild signs to one or more fo the follo*ings+

anore1ia, fever, depression, vomition, a%dominal pain, shoc(" especially if not all

dead fetuses are e1pelled& #etal mummification can occur in a%sence of %acterial

contamination, *hich is . again . often not accompanied %y clinical signs, *ith

mummified fetuses occasionally found une1pectedly during a laparotomy or a

survey a%dominal radiograph&

;eproduction
mailto:[email protected]:[email protected]


41/75

Death of conceptus can %e due to developmental defect,maternal

endocrine4meta%olic im%alance, infectious disease of the reproductive tract, trauma,

improper use of drugs&

De0elo!mental *efe&t(Naryotype a%normalities reported in the %itch *hich may %e responsi%le for death of

the conceptus include monosomy and trisomy of the V chromosome, translocations

and chimerism& -t is generally %elieved that chromosomal anomalies are very rare

as a cause of em%ryo4fetal death, %ut there is a paucity of data due to the fact that it

is often difficult to find a la%oratory *hich performs (aryotyping, and the test in

itself can %e )uite e1pensive& 'he true incidence of this phenomenon in the canine

could %e higher than e1pected, and most researchers agree that the reduction in

fertility o%served in highly in%red populations is due to developmental defects& -n

case of a spontaneous a%ortion, (aryotyping should al*ays %e performed& -ncidenceof congenital anomalies and spontaneous a%ortion is directly proportional to the

degree of in%reeding&

Maternal en*o&rine im'alan&e

H%!ot%roi*i(m

'hyroid insufficiency, a relatively fre)uent endocrine disease in *omen, is

associated *ith an increased ris( of spontaneous a%ortion& Hypothyroidism is also

relatively common in dogs and a relationship *ith lo* fertility in the canine,

although still not yet confirmed, is strongly suggested& As in *omen, canine '3, '6and thyroid %inding glo%lulin are higher during pregnancy& 7pontaneous a%ortion

in dogs could %e related to hypothyroidism& Hypothyroid %itches should %e

considered to %e at a higher ris( of spontaneous a%ortion& @itches *ith a history of

a%ortion should have their thyroid function chec(ed, and the thyroid function of

those undergoing thyroid treatment should also %e carefully evaluated during

gestation&

Lteal in(ffi&ien&%

-n *omen luteal insufficiency !*hich is characteri>ed %y short cycles, lo* serum

progesterone concentration during the luteal phase and insufficient endometrial

development" is reported as a cause of spontaneous a%ortion& Luteal insufficiency

!or hypoluteoidism" occurs also in other*ise normal *omen and can %e successfully

treated *ith a repositol progesterone treatment& Progesterone is the (ey hormone for

endometrial development, uterine secretions, endometrial gro*th, esta%lishment and

maintenance of placental attachments, inhi%ition of uterine motility, elimination of

leu(ocyte responsiveness in the uterus and development of mammary glands

!Nustrit>, 00F #eldman and elson, 006"& -n polyestrous species, P6

concentrations can %e used to rule out a pregnancy& Ho*ever, this cannot %e done in

the dog as P6 concentrations are similar in %oth pregnant and non.pregnant %itches!:oncannon et al&, =85"&


42/75

Diagno(i(

'he diagnosis of luteal insufficiency is %ased on the demonstration of a very lo*

progesterone concentration during pregnancy in the a%sence of any other sign of

disease& 'his %ears clinical relevance as it should %e noted that a lo* serumprogesterone concentration in a %itch *ith an impending or recently occurred

a%ortion, may not necessarily mean that a%ortion is due to a primary luteal

insufficiency !Nustrit>, 00"& #etal distress may cause a decrease in progesterone

concentration as a normal physiologic response !ohnston et al&, 00"& 'herefore, it

is important to rule out %acterial or inflammatory conditions of the uterus *hich

may cause a decline in the progesterone level %y stimulating the release of

prostaglandin from the endometrium& #urthermore, also, non.infectious causes !such

as the genetic a%normalities of the pups, systemic diseases of the %itch or trauma"

should %e ruled out !Nustrit>, 00"&

-n order to confirm a diagnosis and administer a treatment,serum4plasma

progesterone concentrations should %e measured *ith a ;-A or chemiluminence

since the degree of accuracy of semi.)uantitive in.house assays is not relia%le for a

diagnosis of luteal insufficiency !Nustrit>, 00F $rlinger et al., 005"& @itches

*ith a history of a%ortion or failure to conceive after several matings should %e

closely monitored after onset of proestrus& aginal cytology as *ell as serial LH and

progesterone measurements should %e performed to determine accurate timing of

the ovulation and to confirm luteal insufficiency& Ho*ever, dystocia, pyometra orsepticemia may occur during treatment if miscarriage is due to a fetal a%normalities,

placentitis or intrauterine infection& @ecause of this reason, it is imperative that

diagnosis of luteal insufficiency is confirmed %efore treatment& Unfortunately there

is a lac( of information on *hat is the serum progesterone concentration for each

stage of the canine pregnancy& 'a%le nE sho*s a compilation of serum

progesterone concentrations throughout the canine pregnancy %ased on differrent

studies&


43/75

Days

7tudy

LH

7urg

e

v

ulat

ion

.6

/.2

!implanta

tion"

2.55.

35

35.

65

65.

5555./5

7mith

and

McDon

ald,

=86

. .

0.30

ng4ml

!Day

0"

35.60

ng4ml

60.50

ng4ml

!Days

0.5"

5.

60

ng4

ml

5.

30

ng4

ml

0.

0

ng4

ml

5

ng4ml

!Day

/5"

:oncan

non et

al&,

=85

&6.

&2

ng4m

l

.

8.

ng4ml

!Day

0"

.

0./

ng4ml

!Day

5"

. . .

0,8.

0,=

ng4ml

nclin

and

ersteg

en,

==8

&2.

&0

ng4m

l

. .30 ng4ml

!Day /"33.32 ng4ml .

&5.

&0

ng4ml

!Day

/6"

:oncan

non,

000

. . .5.20 ng4ml

Days 5.30. .

3.

5

ng4

ml

Day

s

50.

/0

bng4

ml

Day

/5

Ta'le n3 #. Different values of P6 concentrations during various stages of canine

pregnancy& Datas are standardi>ed and counted from ovulation !compiled and

e1trapolated from 7mith and McDonald, =86F :oncannon et al&, =85F nclin and

erstegen, ==8F :oncannon, 000"

Treatment

Luteal insufficiency has %een treated %y supplementation *ith a suita%le

progesterone or progestagen chosen %ased on the stage of pregnancy !Nustrit>,

00F $rlinger et al., 005"& Progestagens are compounds *hich act li(e

progesterone in preparing or maintaining the female reproductive tract forimplantation and pregnancy, and are commonly used for the treatment of


44/75

%ehavioural disorders or for the control of reproduction in small animals

!;omagnoli and :oncannon, 003"& 'he progestational properties of many such

compounds have %een *ell documented in all species, including the %itch !$oyings

et al&, =88, Purs*ell, ==F ilts, ==F on @er(y and 'o*nsend, ==3F ilts et

al&, ==6"&Prior to the progesterone4progestogen supplementation, it is crucial to verify

presence of live fetuses %y ultrasonography& Progesterone supplementation in a

pregnant %itch *ith non.via%le fetus may inhi%it uterine contractions and a%ortion

!Memon and Mic(elsen, 000F Nustrit>, 00" *hereas it may induce

masculini>ation of female fetuses if administered during organogenesis, *hich in

the %itch is complete around day 5 post.ovulation, as o%served %y :urtis and $rant

!=/6" in a @o1er %itch treated *ith norethindrone during pregnancy 6 *ee(s after

the last mating& Accurately staging pregnancy is very important for deciding *hich

compound to use and *hen to *ithdra* the treatment since the half.life of eachprogestagen is different& Long acting progestagens such as medro1yprogesterone

acetate or proligestone have longer half.lives *hereas others such as megestrol

acetate or natural progesterone have a faster meta%olism !Loose.Mitchell and

7tancel, 00"& A long.acting compound may prevent parturition causing the %irth of

still%orn pups and even maternal health pro%lems if administered in late pregnancy,

*hereas ending a treatment too early may result in the %irth of immature pups&

'herefore, the period of pregnancy should %e determined prior to the treatment %y

ultrasonography, radiography or progesterone measurements&

A fe* natural4synthetic progesterone compounds have %een used *ith success in the

treatment of hypoluteoidism, such as progesterone at the dose of mg4(g

intramuscularly on days 50 and 53 of pregnancy, ally.tren%olone, at the dose of

0&022 mg4(g4day !from mid.term on, follo*ing ovariectomy" and

medro1yprogesterone acetate, orally, )6 hours, at a dose of 0& mg4(g, %et*een

days 6.52 of pregnancy !Purs*ell, ==F ilts et al& ==6F $rlinger et al&, 005"&


45/75

*hich may !especially in dia%etic patients" cause intrauterine death& Hypoglycemia

during pregnancy in humans can cause hypoglycemic coma around the th*ee(

and dia%etic coma around the 0th*ee( !%ecause of an increased need of insulin"&

-n *omen, a *orsening of dia%etic conditions during pregnancy carries an increased

ris( of hypertension, eclampsia, urinary tract infections and placental detachment&$lycaemia.related pregnancy disorders share some similarities in the canine and

humans species& -n the %itch !as in *omen and in a fe* other species" a serum

progesterone rise is follo*ed %y a rise in serum gro*th hormone !$H"

concentration& 7uch an increased $H concentration !due to progesterone.induced

activation of $H.secreting foci in the mammary glands " causes insulin resistance

and hyperglycemia& -n the pregnant %itch insulin re)uirements increase during

pregnancy %ecause of the rise in serum progesterone and the conse)uent rise in

serum $H& -nsulin re)uirements also have a pea( at parturition and then su%due in

the postpartum period&

'he increased ris( of neonatal mortality in dia%etic %itches is due to an increased

ris( of fetal malformations, respiratory diseases as *ell as neonatal hypoglycemia&

Dia%etic %itches have %een reported to *help macrosomic foetuses !causing an

increased ris( of dystocia", *hich could %e due to an increased secretion of fetal

insulin in response to the increased glucose availa%ility in the maternal circulation&

:onversely, in the pregnant %itch use of a diet *ith lo* caloric content is associated

*ith smaller litter si>e

Dia%etic (etoacidosis !DNA" has %een reported in the %itch& -n dogs, the aetiology

of the condition is un(no*n ho*ever progesterone, estradiol, gro*th hormone and

placental cyto(ines are %elieved to %e involved in the pathogenesis of the disease

!ohnson 002"& -n a retrospective study %y #all et al& !002", a %reed predisposition

to*ard ordic 7pit> %reeds to $DM has %een reported due to the num%er of dogs

involved ! of 3"& ed %y a high incidence of fetal death *hen

treatment is not performed during pregnancy& Although no information is availa%le

in the dog concerning incidence of fetal death in %itches *ith hypo. or


46/75

hypercorticalism !also %ecause these dogs are not generally %red", adrenal pathology

should al*ays %e ruled out *hen considering a case of fetal death&

Infe&tio( *i(ea(e( of te re!ro*&ti0e tra&t

7r&ella &ani(

Li(e all other %rucella infections, @rucella canis infection causes endometritis,

placentitis and late a%ortion in the female, epididymitis in the male& #ollo*ing

infection !characteri>ed %y mild clinical signs" @& canis proliferates in lymphnodes,

spleen, %one marro* and Peyer patches, after *hich it invades the reproductive tract

!uterus, epididymis, prostate"& Pregnant %itches *ill either a%ort %et*een 30 and 58

days gestation !sho*ing prolonged %loody vulvar discharge" or have a highpostnatal mortality& #ertility of %reeding (ennels may fall from =09 to 309 during

the first year after an epidemic& Diagnosis is achieved through isolation of @& canis

from the %lood !leu(ocyte fraction" a%orted fetuses, vulvar discharge, seminal fluid

and various lesions of dogs *ith clinically evident disease& 'he ;apid 7lide

Agglutination 'est is sensitive %ut not very specific, therefore all positive

individuals must %e rechec(ed *ith the 'u%e Agglutination 'est, immunodiffusion,

complement fi1ation or P:;& 'reatment consists of associations of anti%iotics

!tetracycline streptomicine, minocycline streptomicine or o1itetracycline and

streptomicine" %ut it is long and efficacy is not 009& #ollo*ing complete

recovery a dog may %ecome infected again& @ecause of costs, length and degree of

efficacy of treatments, in the U7 it is recommended that affected dogs of %reeding

esta%lishments are euthani>ed& @& canis infection has %een reported in #rance in

==/&

Her!e( Vir( &ani(

-"&V. :H is a DA.virus *hose gro*th is stimulated at temperature !'" of 35.

38 E:, and inhi%ited at ' O 3=E:& -t generally causes disease only in immuno.

compromised individuals in *hich it is responsi%le for late a%ortion, neonatal

septicemia and urogenital as *ell as respiratory !(ennel cough" diseases& -n adultsdogs the virus replicates at the point of entry !genital or respiratory system" causing

a mild disease !(ennel cough or vaginitis" *hile pregnant %itches may a%ort

sho*ing signs of placentitis and fetal4neonatal infection& #etuses may contract the

infection *hile passing through the %irth canal& 'he immaturity of the

thermoregulatory mechanism of canine neonates creates optimal condition for the

development of :H& :H causes a *ea( and short.lasting immunologic response

after *hich, similarly to other herpes viruses %ecomes latent in sensory ganglia& '.

lymphocytes are very important for the hostKs defense mechanism, therefore

*henever their function is depressed !i&e& during a parvovirus infection, animmunosuppressive treatment, pregnancy, the perinatal period, or during stress"

:H may %ecome clinically evident&


47/75


48/75

a%orted fetuses include & coli, '& gondii, :ampylo%acter, %.haemolitic

streptococcus, :hlamydia spp& and salmonella&

Trama

Death of conceptus can %e caused %y a direct uterine trauma or indirect trauma tothe mother or %y an a%dominal surgery, all of *hich may cause death of conceptus

either directly !trauma on the conceptus" or undirectly through an early placental

detachment& -n pregnant *omen laparotomy may cause a%ortion especially if

surgery is on the uterus or on contiguous organs& Although such a ris( is possi%le

in pregnant %itches as *ell, one should have chec(ed fetal via%ility prior to the

trauma as this may also precipitate an already compromised situation& A surgical

procedure has %een reported in *hich some canine fetuses are removed and the

remaining one are carried normally to term through administration of progesterone

-M days pior to surgery !Lo*ry, =85"&

Drg(

'he most delicate period of the canine pregnancy is the first month during *hich

organogenesis ta(es place& Prior to day 0. follo*ing ovulation !*hen

implantantion occurs and placental development starts" canine em%ryos are

surrounded %y Quterine mil(R, a protein endometrial secretion *hich is in

homeostatic e)uili%rium *ith the %lood compartment, i&e& any su%stance that arrives

in the %loodstream reaches the endometrium& 'herefore, use of any su%stance

during this time carries the potential ris( of harming em%ryonic development eventhough there is no ris( associated for the mother& After placental development

fetuses %ecome more resistant to to1ic insults as most su%stance cannot reach the

placental circulation unless they are present in

romagnoli - proceeding papers forbangkok apvc 2012

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