Pathologies of the waiting period in the cow

Pathologies of the waiting period in the cow

● Placental retention

● Anoestrus

● Metritis

 Acute metritis

 Clinical endometritis

 Subclinical endometritis

 Pyometra

● Uterine involution delay

● Ovarian cysts

 Follicular cysts

 Luteinized cysts

The placental retention in

the cow

Cotyledon (fœtal part)

Caroncula

(maternal part)

Cotyledonary placentation (+/- 100 caroncula)

Uterine wall

Photo Lopez-Gatius Lleda 2008

Maturation and placental expulsion

Leucocytes : synthesis of collagenases P4 decrease:

activation of collagénase PGF increase

Oxytocin

Myometrial

contractions

Cow’placenta

Definitions

Stage 3 or parturition

Placentophagy

Placental retention : definition

● = Non expulsion of the placenta during the first 24 hours postcalving

 Primary retention

 Secondary retention

● Frequency

 3 à 32 %

 Average : < 7 %

Fréquence de la rétention placentaire

Expulsion delay (871 cases of placental expulsion)

3 6 9 12 15 18 21 24 h

0 10 20 30 40 50 60 70 80 90 100

Symptoms

ENVA

Placental retention and hypocalcemia

Etiology

Etiology

● Determining factors

 Decrease or increase of pregnancy lenght

 twinning

 dystocia

 Milk fever

 Lox BCS

 Calf mortality

● Predisposing factors

 Heavy calf

 Male

 Increase of parity

 Dairy vs suckling cow

 Carences : Vit A, E, Se

Treatments

In case of placental retention …

● First step (after 24 hours)

 General exam (T° )….

 Genital tract examination

• Hygienic

• Identification of lesions

• Differential diagnosis between primary or secondary placental retention

● Step 2 :

 Manual extraction if possible : quickly and complete

 If not : general antibiotherapy

 No effects of oxytocine or PGF2a

● Step 3 :

Uterine involution in the cow and delay of uterine

involution

Uterine involution: definition

● = anatomical, histological, bacteriological,

hormonal and biochemical modifications of the uterus observed during the post-partum

● Duration (anatomical criteria) : 30 days

Uterine involution delay : definition

●Definition

 identification after day 30 by manual

palpation of one or two uterine horn with a diameter more than 5 cm associated or not with an uterine infection and

independently of the position of the uterus in the abdominal cavity.

●Frequency : 7 % (d30-d50)

Anatomical aspect of uterine involution

● Parameter : Diameter Weight Lenght

 At calving : 40 cm 10 kgs 1 m

 « Half-live : 5 jours 7 jours 15 J

● d15 : palpation of the all uterus

A noter l’aspect plissé de la surface utérine

Bacteriological aspects of uterine involution

<15 16-30 31-45 46-60

0 10 20 30 40 50 60 70 80 90 100

Cellular

Neutrophiles : phagocytose

Lymphocytes : immunity

Hormonal Oestrogens Oxytocin

Progesterone PGF / PGE

LTB4 Bacteria

Lipopolysaccharides Endotoxines

Factors involved in uterine involution

Risk factors of uterine involution delay (Hanzen et al. 1995)

Meat Dairy

--- ---

Increase of number of lactation + +

Acute metrtis + +

Increase of pregnancy lenght + +

Dystocia T -

Placental retention + +

Milk fever +

Twinning + +

Calf mortality + +

---

Specific treatment ?

Uterine infections in the

cow

Definition and symptoms

Definition and symptoms

● Many terms (15) in the litterature to define the same pathology

● Consensus proposed by Sheldon en 2006

(Sheldon IM, Lewis G, LeBlanc S, Gilbert RO.

Defining postpartum uterine disease in cattle.

Theriogenology, 2006, 65, 1516-1530).

● Acute or puerperal metritis : < 21 days PP

● Clinical endometritis : > 21 days

● Pyometra

● Subclinical endometritis

Contamination = physiological process

Infection = pathological process

Acute or puerperal metritis

●< 21 days PP

●General symptoms :

 decrease of appetite and milk production

 Increase of T° > 39.4-39,5°C

 Acetonemia, mastitis, abomasum displacement…

●Local symptoms :

 fetid red-brown watery uterine discharge

Acute metritis : discharge

ENVA

Clinical endometritis

● Generally, absence of general symptoms

●> 21 days postpartum

●Purulent or mucopurulent or pus flakes discharge

●Delayed uterine and or cervical involution

Clinical endometritis

Purulent discharge

Pyometr a

● ccumulation of purulent or mucopurulent material within the uterine lumen

● distension of the uterus,

● presence of an active corpus luteum

● pathological anoestrus by suppression of

endometrial syntheis of PGF2a

Pyometr

a

Subclinical endometritis

● endometrial inflammation of the uterus

● absence of purulent material in the vagina

● diagnosed by cytological analysis (neutrophils)

 J 21 à J 33 : > 18 %

 J 34 à J 37 : > 10 %

 J 28 à J 41 : > 8 %

 J 40 à J 60 : > 5 %

Diagnostic methods

Le diagnostic : stratégies

● Approche individuelle = sous-estimation

 les seuls cas de rétention placentaire

 les cas observés par l’éleveur

 les repeat-breeders

● Approche systématique = objectivation

 Importance du choix d ’une méthode de diagnostic

 Importance du choix d ’un moment de

diagnostic : Inv utérine

Methods of diagnostic

• Anamnese

• General examination and local inspection

• Rectal palpation

• Vaginoscopy

• Echography

• Bacteriology

• Cytology

• Anatomopathology

• Biochemistry (haptoglobine, P4)

Echography and metritis

Cytology (http://www.be.fishersci.com/ )

(Deguillaume 2007)

L’examen cytologique (Deguillaume 2007)

Erythrocy te

Cellule épithéliale

Neutrophile

Frequenc

y

(Sheldon et al. Biol Reprod 2009, 981,1025)

30

%

Etiology

Etio-pathogeny of uterine infections

Determing factors

Bacteria

Gram - : < 7 days PP

Gram + : > 7 days PP

Predisposing factors

NL, season, Defense mechanisms

Cellular :

phagocytose (neutrophiles),

lymphocytes (immunology)

Main bacteria isolated in endométritis (Louis et

Dohmen 1994)

Economical consequences of uterine infections

● Drillich et al. JDS 2001 84,2010-2017

 By case : 292 Euros

● At european level

 24.146.000 dairy cows (Ataide Dias et al.

www.eds-destatis.de )

 1,4 billion d’Euros (Sheldon et al. Biol Reprod 2009,81,1025-1032)

● At american (USA) level

Treatment

s

Preliminary remarks

● No standard method for diagnosis

● No general method to quantify the problem

● Infleuenc factors are not taken in account to evaluate the efficacy of the treatments

● No comparison with non treated animals

● Results based on clinical and not

Strategy of treatment

Quantification of the problem

Individuel

Her d

Curative approach : choice of

- Treatment : Ab, AS, PGF2a

- the moment of treatment

Preventive approach :

relation with risk

factors Identification de la

Which way : IM route

● IM Injection Avantages

 Best concentrations il all the genital tract

 Distibution not influenced by uterine content

 No adverse reactions on phagocytosis

 No risk of lesions of the genital tract

● IM injection disadvantages : DIY possible

● Exemples

 Pénicillines, 20 à 30.000 UI/Kg, IM, 2X/J

 Céftiofur, 1mg/Kg, 2X/J pdt 3 SC

Which way : Intra uterine injections

● Difficulty to obtain an effect on all the uterus and oviduct

● Negative effect on phagocytosis

● Residus in milk (as by IM route)

● Very few Ab registered for such injections

● Very low efficacy of preventive and systematic treatments

ENVA

Some specialities (Belgium)

(http://www.cbip-vet.be/fr/texts/FIUTOOL1AL2o.php

● CHLORTETRACYCLINE 2000 U-BATON ERNST (Friedrich Ernst)

 chlortétracycline chlorhydrate: 2.000 mg bâton iu

 Posologie: Bo: 1000 - 2000 mg/animal

 Viande: 10 j, Lait: 4 j

● EMDOMETRIN 2000 (Emdoka)

 chlortétracycline chlorhydrate: 2.000 mg bâton iu

 Posologie: Bo: 1.000 - 2.000 mg

 Viande: 10 j, Lait: 4 j

● METRICURE (Intervet)

 céfapirine (benzathine): 500 mg suspension iu (Céphalosporine)

 Posologie: Bo: 500 mg

 Viande: 2 j, Lait: 0 h

● METRICYCLIN (Kela Laboratoria)

 chlortétracycline chlorhydrate: 1 g comprimé (oblet) iu

 Posologie: Bo: traitement préventif: 1 g traitement curatif: 1 - 2 g

 Viande: 10 j, Lait: 4 j

● OBLETS GYNECOLOGIQUES (VMD)

● As soon as possible : importance of early detection

 Temperature if placental retention

 Systematic involution control

● If possible : when the cow is under oestrogenic influence and never under progesteronic

influence

 Interest of PGF2a to induce an oestrogenic

When to treat

Ovarian cysts in

the cow

Definiti

on

mm

2 8 10 12 14 16 18

4 6

Growth phase :

puberty, pregnancy, postpartum

Preovulatory phase Post-partum

Reproduction period Puberty

Reproduction

periods and

anovulation

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22

mm

0 2 4 6 8 10 12 14 16 18

Follicular reserve

1st group : recruted follicles 4rd group :

Preovulatory follicle

3rd group :

dominant follicle

Ovulation Follicul ar cyst

Luteini zedfolli cular cyst

Cyst = abnormal follicular growth

2^nd group : selected follicles

Three evolutions : - Atresia

- Ovulation

- Cyst

So, the cyst is an abnormal ovarian structure …

 In 30 to 40 % of cases : cyst coexists with a CL

1. Absence of corpus luteum

 Duration of dominance : 5 to 6 days

2. More than 1 week

 In the cow, ovulation between 13 to 19 mm

3. Diameter more than 20 to 24 mm

Frequenc

y

Frequency of ovarian cysts amongst different studies (1974 to 1994)

*

Frequency of ovarian cysts

● Fourichon et al., 2000 : meta-analysis (20.000 cows in 196 dairy herds) : 12 % (3 to 29 %)

● Lubbers 1998 (Holland) : 12.626 lactations

during 10 years in 39 herds 7,2 % (1,9 to 11,3

% amongst herds)

● Erb et Martin, 1980 and Kinsel et Etherington, 1998 (Canada) 24.356 lactations : 9,3 %

More than 10 % : herd problem

Diagnosis

- Manual palpation - Ultrasonography - Hormones

- Ethology

Manual / US diagnosis

Follicular cyst

Luteinized cyst

Diameter : 31 ± 4 mm to 33

± 7 mm

(if > 24 mm : Hanzen and Bascon 2007)

Easily

depressed

Thin wall (< 3 mm)

Cavity

anechogenous Ovary

Cavity less large (24 to 49 mm)

and anechogenous

Diameter : 35 ± 7 mm to 39

± 9 mm

(if > 24 mm : Hanzen and Bascon 2007

Thick wall (3 to 9 mm) Less easily

depressed

Caracteristics of

cysts

Caracteristics of cysts (ultrasonography)

20 mm

20 mm

Luteinized cyst an corpus luteum with

cavity

Diagnosis (hormones)

« high » : 1,08 et 10,4 ng/ml low : 0,13 et 2,1 ng/ml

Progestérone

Oestradiol low or high low

Anoestrus or nymphomania FC LC

> 0,5 or 1 ng/ml

Etio-pathogeny

Risks factors of ovarian cysts and their interrelationships in the cow

Negative energy balance Nutrition

Follicular wall

Environm Hypothalamo- ent

hypophysis complex

Animal

Low

progesteronemia

Modification

of – FB of oestradiol on cyclic LH

Lack of tonic LH

inhibition Modification of oestradiol receptors

Abnormal production of growth factors

Abnormal production of proteines by cellular matrix

Number of lactation Milk production Stage of postpartum

Puerperal diseases Genetic

Decrease of leptine IGF1 decrease Hypoglycemia

Hypoinsulinemia

Cortisol

LH

inhibition Season

Stress

Hormonal

pathogeny of ovarian cyst in the cow

Tonic LH

Hypothalamus

Progesterone

(0.1 à 1 ng) Growth stimulation

Hypophysis

Wave 1

Oestradiol Inhibine

1 2

3

4

Cycli c LH

5

Impaired ovulation

6

9

Cyst

FSH

7

8 _{New wave}

Frequency (%) of cysts according to stage of postpartum (days)

(Whitmore et al. 1974, Wiltbank et al. 1953, Whitmore et al. 1979, Erb et White 1981, Kirk et al. 1982)

10 15 20 25 30

Treatments

- To treat or not to treat ?

- Non hormonal curative treatments - Hormonal curative treatments

- individual approach

- hormonal associations

To treat or not to treat : that’

the question

● Stage of the postpartum period

 Lenght of the waiting period decided

 Diagnosis during the reproduction period

● Spontaneous regression of cysts

 28 to 80 % before d60 of postpartum

● Accuracy level of the diagnosis : follicular vs luteinized

● Efficacy of the treatment : different parameters

 Interval treatment-pregnancy

 Fertility index after treatment

● Cost of the treatment

Non hormonal curative treatments : manual rupture

Lopez-Gatius personal communication

Effect of manual

rupture of a cyst on the oestrus return rate in the 14 days after treatment (388 dairy cows)

GnRH and MP PGF2a and MP MP 0

5

10

15

20

25

30

35

40

Non hormonal curative treatments : manual rupture

Lopez-Gatius personnal communication

● Effect of manual rupture of a cyst on the pregnancy rate at first AI after treatment (10.634 lactations)

● Oestrus observed 6,8 days after

treatment in 36 % of cows

22

24

26

28

30

32

34

Hormonal curative treatments : general objective

To obtain as soon as possible a new

follicular growth with expulsion

of a mature oocyte

Hormonal curative treatments : three steps

to obtain a P4 phase

to assume ovulation of the dominant

follicle to stop the P4 phase

and assume

the final follicular growth

hCG GnRH

PRID CIDR

PGF2a Remote of PRID

hCG GnRH

1 2 3

Hormonal treatment steps of a follicular cyst Endogenous synthesis of P4

hCG or GnRH

CL

3

?

2 1

LH effect

Luteinizati on

if

receptors

Ov

Ov PGF2a

7 to 14 d

Oestrus

GnRH

Increase of P4 7 to 20 days

70 to 90 % of cases

2 to 5 d

Hormonal treatment steps of a follicular cyst Effect of an exogenous administration of P4

6 to 24 h

1

Oest R HPTH

- _GnRH

+

LH

+

New wave and

2 DF ?

Increase of

oestradiol and LH receptors

3

4

Oestrus (0 to 66 %)

Ovu

Hormonal treatment steps of a luteinized cyst

PGF2a

Oestrus

GnRH

2 to 5 d

Hormonal associations

Justifications :

- difficulty to make a differential diagnosis between cysts ?

- decrease time between treatment and

pregnancy ?

Some hormonal associations

1. hCG or GnRH (d0) – PGF2a (d7 or d14) 2. GnRH and PGF2a (d0) – PGF2a (d14)

3. hCG (d0) – PGF2a (d7 to d12) – GnRH (d9 to d14)

4. hCG or GnRH(d0) – Progesterone (d7 to d14 or d16) – PGF2a (d14 or d16) – GnRH (d16 or

d18)

5. Ovsynch : GnRH (d0) – PGF (d7) – GnRH (d9)

Hormonal association : GnRH-PGF-GnRH (Ovsynch)

16 – 24 h AI

GnR

0 7

PGF2a

9

GnRH

Ovsynch and treatment of ovarian cysts (8 studies and 792 cases of cysts between year 2000 and 2008)

1 2 3 4 5 6 7 8 Total 0

5 10 15 20 25 30

% of pregnancy rate

Comparison of hormonal treatments of cysts (Hanzen et al. 2008)

Treatment N PR (%)

PRID (12d) + OB 63 14 to 28

GnRH (J0)-PGF(J14) 62 8 to 16

GnRH-PGF (J0)-PGF(J14) 65 22 to 36

OVSYNCH 791 17

GnRH(J0)-Ovsynch(J8) 89 30