prevalence and risk factors for postpartum anovulation in dairy cows
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Prevalence and Risk Factors for Postpartum Anovulation in Dairy Cows. Robert Walsh November 30, 2006. Outline. Resumption of Ovarian Activity Identification of at Risk cows Cow-level risk factors Herd-level risk factors Questions. Outline. Resumption of Ovarian Activity. - PowerPoint PPT PresentationTRANSCRIPT
Prevalence and Risk Factors for Postpartum Anovulation in Dairy
Cows
Robert Walsh
November 30, 2006
Outline
• Resumption of Ovarian Activity– Identification of at Risk cows
– Cow-level risk factors
– Herd-level risk factors
• Questions
Outline
• Resumption of Ovarian Activity
0 5 10 15 20 25 30 35 Calving Ovulation
DIM
16
14
12
10
8
6
4
2
0
Fol
licle
dia
met
er (
mm
)Resumption of Ovarian Activity
All follicles present at birth
Follicle development divided into 3 stagesStage Size Duration
Recruitment < 0.13mm birth - Slow phase 0.16 – 3 mm 10 – 40 daysFast phase > 4 mm 8 - 10 days
(Lussier et al. 1987)
0 5 10 15 20 25 30 35 Calving Ovulation
DIM
16
14
12
10
8
6
4
2
0
Fol
licle
dia
met
er (
mm
)Resumption of Ovarian Activity
Atresia or ovulation IGF-1, IGFBP, E2, ….
Deviation Luteinizing Hormone (LH)
Emergence Follicle Stimulating Hormone (FSH)
0 5 10 15 20 25 30 35 Calving Ovulation
DIM
16
14
12
10
8
6
4
2
0
Fol
licle
dia
met
er (
mm
)Resumption of Ovarian Activity
33.8 days (1106 Lactations; Petersson et al. 2005)
27.4 days (>1200 Records; Royal et al. 2004)
28.7 ± 14.6 days (2503 Lactations, Lamming and Darwash 1998)
29 days Control line vs. 43 days Select (Lucy et al. 2001)
43 days First Estrus (1398 Lactations, Thatcher and Wilcox, 1973)
Resumption of Ovarian Activity
Reference Location DIM DOV1 ALL
Lopez et al. 2004 Wisconsin 70 28.5%
Cerri et al. 2004 California 65 25.7%
Moreira et al. 2001 Florida 63 23%
Opsomer et al. 2000 Belgium 50 21.2%49%
Lamming and Darwash 1998 England 10.9% 38%
Shrestha et al. 2004 Japan 24.1% 57%
Archbald et al. 1990 Florida 30 30%
McDougal and Compton 2005 NZ 20.9%
Thatcher and Wilcox 1973 Florida 60 25.9% (Estrus)
5 10 15 20 25 Days In Milk
16
14
12
10
8
6
4
2
0
Fol
licle
dia
met
er (
mm
)
(Wiltbank et al. 2002)
Anovulation
Follicular Growth to Deviation
Consecutive waves of follicle growth initiated by FSH
Insufficient LH to support deviation
Communication failure between ovary and hypothalamus
5 10 15 20 25 Days In Milk
16
14
12
10
8
6
4
2
0
Fol
licle
dia
met
er (
mm
)
(Wiltbank et al. 2002)
Anovulation
Follicles Larger than Ovulatory Size
LH release supports deviation
Elevated E2 concentration
Failure of ovulation
The presence of large follicles does not precludeNormal ovarian activity and function
Outline
• Resumption of Ovarian Activity
– Identification of at Risk cows
Objectives
• Determine prevalence of anovulation
• Assess consequences of anovulation
• Identify cow-level risk factors– herd-level risk factors
Observational Protocol
Milk Ketotest™
BCS
HH visit BCS, Lameness
Milk P4
Collect Reproduction and Culling Data
0 4 11 38 52 60
Record peripartumdisease
Data presented from 1341 cows
AnestrusBoth samples
<1ng/ml
Calving
Descriptive Data
Tiestall Freestall Herds Cows Herds Cows
Herd Size < 100 cows 9 404 3 178> 100 cows 1 65 5 694
Milk Frequency
2 Times/day 9 404 4 2183 Times/day 1 65 4 654
TAI First Service > 90 % 5 236 1 61
0 to 50% 5 233 7 775Rumensin
CRC 2 82 2 427 Premix 6 292 3 308Both 2 95 3 137
Study Population
• Enrolled 20 herds (lost 2)– Total calving 2645
– Culled prior to 52 DIM 277
– Total eligible 2368
– Two Milk Samples1 1575
– Met Inclusion criteria 1341 (56.7%)
• Herd specific inclusion ranged 33 – 90%
• Disease under-reported in cows not sampled
• No significant difference in parity distribution, first milk projection, days dry between included and excluded cows
• Excluded cows more likely culled (P < 0.001)
1 Excluded if milk sample protocol violated or use of hormones
Cow Level Prevalence of Anovulation
19.5% (95% CI 17.4 – 21.7%)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 180.0
0.1
0.2
0.3
0.4
0.5
Herd Number
An
estr
us (
%)
VWP 45-60 d
Calving
No Estrus Activity
Ovarian Activity ??
Impact of Anovulation
• 1 in 5 cows • Herd Repro Management
• Heat Detection • Timed Insemination protocols
Time to First Insemination
Herd ReproProgram Factor AI HR P 95% CI
Heat Anovular 80b 0.7 <0.0001 0.6 to 0.8Detection1 Cycling 72a Referent
Timed Anovular 78ab 0.67 0.19 0.1 to 1.2AI2 Cycling 76b Referent
Multiparous 0.84 0.04 0.7 to 0.9Retained Placenta 0.75 <0.001 0.6 to 0.8
1 Insemination at Observed Estrus in >50% of herd (12 herds 79% of cows)2 Timed Insemination in > 90% of herd (6 herds, 21% of cows)
Probability of Pregnancy after First Insemination
Herd ReproProgram Factor FSCR OR P 95% CI
Heat Anovular 20.3b 0.6 0.007 0.4 to 0.6Detection1 Cycling 30.5a Referent
Timed Anovular 29.7ab 0.67 0.19 0.1 to 1.2AI2 Cycling 35.9a Referent
Multiparous 0.73 0.02 0.6 to 0.9
1 Insemination at Observed Estrus in >50% of herd (12 herds 79% of cows)2 Timed Insemination in > 90% of herd (6 herds, 21% of cows)
Time to Pregnancy
0.00
0.25
0.50
0.75
1.00
Surv
ivor
Fu
nction
(Pro
port
ion n
ot
Pre
gna
nt)
0 50 100 150 200 250 300 350 400
Days in Milk
CyclingAnestrus
Kaplan-Meier survival estimates, by anest156
126
Time Adjusted HR 81 0.56123 0.74165 0.89
Adjusted HR = HR*TVCln(t)
Diagnosis of Anovulation
• Rectal Palpation1 (2 palpations 14-days apart)
• Sensitivity 65.4%• Specificity 68.6%• Positive Predictive value 31.9%
1 gold standard circulating progesterone
Diagnosis of Anovulation using Pedometry (HDR ~ 60%)
0
10
20
30
40
50
60
70
1 21 41 61 81 101
Mil
k (K
g/d
ay)
0
100
200
300
400
500
600
Ste
ps/
ho
ur
0
10
20
30
40
50
60
1 21 41 61 81 101
Mil
k (k
g/d
ay)
0
100
200
300
400
500
600
700
800
900
Ste
ps/
ho
ur
•Sensitivity 83.0%•Specificity 68.0%•Positive Predictive value 34.0%
Diagnosis of Anovulation Assumption 100 cows, True Prevalence of 20%
Test Detail Sensitivity Specificity Apparent Prevalence
(%)
Anovular and treated
(n)
Anovular and not treated
(n) Once 60 DIM1
0.41 0.75 28 8 12 Palpation
Twice 14d apart1
0.65 0.68 38 13 7
Once2
0.88 0.83 31 17 3
Ultrasound
+ no visible estrus3
0.86 0.88 27 17 3
Pedometry HDR ~ 60%4
0.83 0.68 42 17 3
1 Walsh et al. (Unpublished)2 Sprecher et al. 1989; Theriogenology3 McDougal and Rhodes, 1999; NZVJ (Apparently Anestrus cows)4 Core et al. (Unpublished)
Outline
• Resumption of Ovarian Activity
– Identification of at Risk cows
– Cow-level risk factors
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 180.0
0.1
0.2
0.3
0.4
0.5
Herd Number
An
estr
us (
%)
Univariable Risk Factor Analysis Factor Class n OR 95% CI
Twins 49 2.3** 1.27 to 4.22 Calving
Dystocia 113 1.8** 1.17 to 2.79 Retatined placenta 119 2.0*** 1.31 to 2.97 Displaced abomasum 42 2.3** 1.24 to 4.39 Disease Lame (back arch) 87 1.8* 1.36 to 2.90
BCS 2.75 (60 7 DIM) 529 1.5** 1.12 to 2.12 Week 1 100 271 1.7** 1.21 to 2.39 Week 2 100 265 1.5* 1.05 to 2.07
Milk BHBA
Week 2 200 132 1.6* 1.03 to 2.57 < 9500 522 0.98* 0.96 to 0.99 First
305ME 9500 819 1.0 0.98 to 1.01 Spring 255 Summer 277 Fall 417
Season
Winter 392
Controlling for fresh season (* P < 0.05; ** P < 0.01; *** P < 0.001)
Final Risk Factor Model Factor Class n OR 95% CI
Twins 49 2.15* 1.15 to 4.01 Calving
Dystocia 113 1.70* 1.07 to 2.72 Retained placenta 119 1.35 0.84 to 2.20 Displaced abomasum 42 2.4* 1.17 to 4.90 Disease Lame (back arch) 87 1.5 0.93 to 2.61
BCS 2.75 (60 7 DIM) 529 Week 1 100 271 1.49* 1.04 to 2.15 Week 2 100 265
Milk BHBA
Week 2 200 132 < 9500 522 0.98* 0.96 to 0.99 First
305ME 9500 819 1.0 0.99 to 1.02 Spring 255 1.12a 0.45 to 1.75 Summer 277 0.87ab 0.56 to 1.35 Fall 417 0.54*b 0.41 to 0.99
Season
Winter 392 Referent
(* P < 0.05; ** P < 0.01; *** P < 0.001)
Prevalence of anovulation by Parity
Data Table-3
1 2 30.0
0.1
0.2
0.3
Parity is an inconsistent risk factor for anovulation
Lameness• 238 Animals, 11% DOV
• Lameness (Median day of diagnosis = 15 DIM)
– 42% Moderately Lame– 17% Lame
• Relative to animals never classified as lame controlling for calving season, lactation, ketotsis*and Milk Production (305ME)*– Moderate Lameness 2.14 odds of DOV (95%CI = 0.7 , 6.14)
– Lame 3.5 increased odds of DOV (95% CI = 1.0 , 12.7)
Calving Lameness Score (1-5)
Milk P4
Garbarino et al. 2004
Lameness and Reproductive Performance
• 65 Cases, 130 Controls• Controlling for parity, calving season, and milk yeild
(305ME)– Non-lame cows 4.22 times more likely to conceive at first
service (95% CI 1.59 , 11.2)– Lame cows 2.63 times more likely to have an occurrence of
an ovarian cyst
• Using Survival analysis – Lame cows HR 0.43
(95% CI 0.28 , 0.66)
Melendez et al. 2003
Body condition Loss
• Lopez-Gatius et al. Theriogenology 2003
• 4529 cows from 11 studies
• Relative to BCS 2.5-3.5
• <2.5 at parturition + 6 DOPN
• >3.5 at parturition – 6 DOPN
• Relative to BCS change <0.5 units between parturition and first AI
• Loss >1 +10.6 DOPN
• Not significant in all studies
• Ruegg et al. 1995
• Domecq et al. 1999
Milk ProductionStudy Milk Measure Delayed OvulationOpsomer et al. 2000 100d & 305d FCM ns
Shrestha et al. 2004 305d FCM ns
Santos et al. 2004 Proj 305 ME 0.21(0.05 to 0.98) high vs. Med
Time to PregnancyGröhn and Rajala-Schultz
2000 60d Milk HR 0.92 (highest vs. lowest)
Outline
• Resumption of Ovarian Activity
– Identification of at Risk cows
– Cow-level risk factors
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 180.0
0.1
0.2
0.3
0.4
0.5
Herd Number
An
estr
us (
%)
Cow Level Prevalence of Subclinical Ketosis Week 1
26.2% (95% CI 23.5 to 28.9 %)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 180.00
0.25
0.50
0.75
1.00
Herd Number
Su
bc
lin
ica
l K
eto
sis
(%)
Energy Balance and DOV• 54 Multiparous HF cows calculated energy
balance
Item ER LR NRNumber 25 (46%) 14 (26%) 15
(28%)
4% FCM (kg/d) 33.4 31.7 28.5
DMI (kg/d) 18.8 17.7 15.2
Day to Ovulation 21.9 43.1
Days Open 133 88 200
Calving7 14 21 28 35 42 49 56 63
Progesterone Profile ER LR NR
Staples et al. 1990
Estimating Energy Status• Significant correlation
between ketone body concentration and CLA (Reist et al. 2000)
• Milk Acetone week 3-6 not associated with FSCR (Plym-Forshell, 1991)
• Increased DOPN, Increased culling risk (Cook et al. 2000)
• 1400 mol/ml HBA cutpoint used for disease status
Impact of subclinical ketosis on the probability of pregnancy at first service and time to pregnancy
Objectives• Is SCK early in lactation associated with the
probability of pregnancy at first insemination?• Which week postpartum has the most impact?• Does the duration of SCK impact probability of
pregnancy at first insemination or time to pregnancy?
Impact of subclinical ketosis on the probability of
pregnancy at first service and time to pregnancy
Serum SampleStore samples and analyze for
HBA
BCS
Observe for estrus and breed
PD
-3 0 1 2 3 6 9
Calving
BCS
25 Herds (25-160 cows)
1010 cows
Exclusion criteria
806 records for analysis
Rumensin CRC study 1995-1996 (Duffield et al. 1999)
Distribution of serum BHBA
0
50
100
150
200
250
300
350
500 800 1000 1100 1300 1500 1700 1900 1901
BHBA Concentration (Week 1 vs. Week2)
Nu
mb
er o
f C
ow
s
16% week 1 (132/806 cows)
19% Week 2 (152/806 cows)
Mean Serum BHBA Sorted by Pregnancy
Diagnosis to First Insemination
-3 -2 -1 0 1 2 3 4 5 6 7 8 9600
650
700
750
800
850
900OpenPregnant
Week Relative to Calving
LS
Mea
n Se
rum
BH
BA
Investigation of Cutpoints
Week BHBA
cutpoint n
% Pregnant
below cutpoint
n
% Pregnant
above cutpoint
OR P-
value
1000 508 37.9 288 29.2 0.73 0.04 1200 606 36.6 190 28.9 0.78 0.16 1 1400 670 36.1 126 27.7 0.75 0.21
1200 601 37.5 206 28.9 0.87 0.42 1400 651 37.0 151 22.5 0.60 0.01 2 1600 685 37.9 117 18.8 0.48 0.002
Impact of Subclinical Ketosis in the Second Week Postpartum on the Probability of
Pregnancy at First Insemination
0.1
.2.3
.4
Pro
ba
bili
ty o
f P
reg
na
ncy
0 2000 4000 6000 8000
Week 2 serum BHBA concentration (mmol/L)
Effect of Prolonged Elevation of Serum BHBA on the Probability of Pregnancy at First Insemination
15
20
25
30
35
40
45
0 1 >1
Number of Weeks Above BHBA Cutpoint
Pro
bab
ility
of P
regn
anc
y (%
)
OR = 0.83P = 0.2 OR = 0.47
P = 0.003
Impact of duration of subclinical ketosis on time to pregnancy
0.00
0.25
0.50
0.75
1.00
Sur
viva
l Fun
ctio
n (
Pro
port
ion
Not
Pre
gnan
t)
0 100 200 300 400
Days in Milk
Not Ketotic
Ketotic week 1 or week 2
Ketotic both week 1 and 2
Time Adjusted HR 81 0.62 0.63123 0.75 0.84165 0.85 1.02
Adjusted HR = HR*TVCln(t)
Median time to Pregnancy
108124130
Cow-level Summary
• Diagnosis is problematic
• Calving history / periparturient disease
• Subclinical ketosis
Dry Period Length
• >77days vs. <63 days 2.9 times more likely to experience DOV(Opsomer et al. 2000)
• DD associated with increase risk of longer DOPN (Moss et al.
2002)
(Gümen et al. 2005)
Milking Frequency
• 3X vs 2X majority of studies show no difference (Weiss et al. 2004; Barnes et al. 1990; Amos et al. 1985*)
• 3X vs 2X associated with 6d increase DOPN (Smith et al. 2002)
• 3X vs. 6X for 3 weeks increased DOPN (Bar-Peled et al. 1995)
Herd-Season Anovulation Prevalence
• 34 herd-seasons from 18 herds (Fall vs. Other)
• Linear regression of herd-level prevalence
• Relative to Tie-Stall barns the prevalence of anestrus
• ↓ 7.2% in 3-Row Freestalls (P = 0.1)
• ↓ 11.0 % in 2-Row Freestalls (P = 0.007)
• ↑ 2.1% for every 10% ↑in herd-season prevalence of SCK
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 180.0
0.1
0.2
0.3
0.4
0.5
Herd Number
An
estr
us (
%)
Herd-Season Anovulation Prevalence
• Things to Consider– Stocking density– Number of ration or group changes– Dry period length
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 180.0
0.1
0.2
0.3
0.4
0.5
Herd Number
An
estr
us (
%)
Questions ?
Acknowledgement
AdvisorsDrs. Leblanc, Leslie, Duffield, Kelton and Walton
VeterinariansAlmonte, Bay of Quinte Veterinary Services, Embrun, Ferguson, Grenville-Dundas, Kirkton, Linwood, Listowel, Navan, New Hamburg,
Tavistock
AABP ResearchAssistantship