Designing Research to Assess Health Outcomes
After Assisted Reproduction
Barbara Luke, ScD, MPHDepartment of Obstetrics, Gynecology, and Reproductive Biology, and
Department of Epidemiology
Michigan State University
Year # Clinics ART Cycles # Deliveries # Live Babies
1997 335 71,826 17,054 24,582
2007 430 142,415 43,408 57,564
Increase +28% +98% 155% +134%
International Comparison of ART
Country Cycles IVF Clinics ART Deliveries ART Infants National Births % ART Infants
Belgium 19,109 18 2,320 2,596 109,588 2.4
Denmark 11,518 21 2,152 2,616 62,741 4.2Finland 9,204 18 1,562 1,589 55,065 2.9
France 69,746 100 10,460 12,664 745,634 1.7Germany 56,813 120 8,458 10,270 643,822 1.6
Iceland 316 1 64 81 4,065 2.0
Norway 6,078 10 1,219 1,512 54,392 2.8
Slovenia 2,725 3 522 611 17,902 3.4
Sweden 12,871 15 2,545 2,711 93,998 2.9
United Kingdom 39,981 74 8,338 10,301 655,745 1.6
United States 127,977 391 36,760 49,458 4,021,726 1.1
Anderson et al, ART in Europe, 2004. Human Reproduction, 2008; 23:756‐771
Contribution of Multiple Births from ART
Singletons Twins Triplets+ Singletons Twins Triplets+
All US Births, 2004 ART Births, 2004
96.6% 3.2% 0.2% 67% 3%30%
Birth rate among women
aged 40‐44 has increased 70% since 1990.
Among women aged 45‐49,
the birth rate has increased fourfold since 1990.
Among women aged 50 and
older, there has been a 15% annual increase since this
category was added in 1997.
Births by Maternal Age ≥35 yrs and Plurality
4.5
8.8
14
6
11.5
23
5.5
17.4
31
0
5
10
15
20
25
30
35
1980 1990 2006
Pe
rce
nt
Singletons Twins Triplets+
Births by Maternal Age ≥40 yrs and Plurality
0.71.2
2.6
0.81.3
5.2
0.50.9
7
0
1
2
3
4
5
6
7
8
1980 1990 2006
Pe
rce
nt
Singletons Twins Triplets+
Research Using the SART CORS
•
Embryonic or fetal loss
•
Single embryo transfer
•
Race, ethnicity, and female obesity
•
Male factor infertility
•
Birth defects
•
Risk of childhood cancer
•
Linking ART cycles
Singleton Preterm Birth Rate
0
5
10
15
20
25
30
35
US Singletons One Two Three+
Perc
ent
10.8
15.5
23.6
28.6
*
*p
Singleton Low Birthweight
0
5
10
15
20
25
US Singletons One Two Three+
Perc
ent
6.38.6
16.0
20.5
*
*p
AOR* of Birthweight Z‐Score
Likelihood of Pregnancy and Live Birth (Adjusted for age, #embryos transferred, and diagnosis)
0.4
0.5
0.6
0.7
0.8
0.9
1
1.1
1.2
Adjusted Odd
s Ratio (9
5% CI)
Pregnancy Live Birth
WHITE ASIAN BLACK HISPANIC
1.00Reference
0.860.90
1.09
0.62
1.06
0.87
*p
Likelihood of Preterm Birth
Likelihood of Birthweight Z-score
Likelihood of Pregnancy as Treatment Outcome (Adjusted for age, race, and infertility diagnoses)
0.80.9
11.11.21.31.41.51.61.71.81.9
22.1
Adj
uste
d O
dds
Rat
io (9
5% C
I)
1.00Reference
1.3
OneEmbryo
TwoEmbryos
ThreeEmbryos
≥
FourEmbryos
1.11.0
*
*p
Likelihood of Singleton Live Birth as Treatment Outcome (Adjusted for age, race, and infertility diagnoses)
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
1.1
Adj
uste
d O
dds
Rat
io (9
5% C
I) 1.00Reference
0.6
OneEmbryo
TwoEmbryos
ThreeEmbryos
≥
FourEmbryos
0.5
0.4
*
*p
Likelihood of Twin Live Birth as Treatment Outcome (Adjusted for age, race and ethnicity, and infertility diagnoses)
0
5
10
15
20
25
30
35
40
45
Adj
uste
d O
dds
Rat
io (9
5% C
I)
1.00Reference
26.6
OneEmbryo
TwoEmbryos
ThreeEmbryos
≥
FourEmbryos
23.722.6
*
*p
Maternal Obesity Adversely Affects Assisted Reproductive Technology (ART)
Pregnancy Rates and Obstetric Outcomes
Barbara Luke, Morton B. Brown, Judy E. Stern,
Stacey A. Missmer, Victor Y. Fujimoto, Richard Leach
A SART Writing Group
65th annual meeting, American Society for Reproductive Medicine,
Atlanta, Georgia, October 17‐21, 2009
Maternal Weight by BMI Group
60
90
120
150
180
210
240
270
Under Wt Nl Wt Over Wt Class I Class II Class III
Pou
nds
110131
191
221
250
161
Not Pregnant as the Treatment Outcome
4344454647484950515253
Under Wt Nl Wt Over Wt Obese I Obese II Obese III
Per
cent
46.9
48.1
51.352.3
Reference
46.6
49.0
Failure to Achieve Clinical Intrauterine Gestation
0.85
0.95
1.05
1.15
1.25
1.35
1.45
1.55
1.65
Adjusted Odd
s Ratio (9
5% CI)
Autologous Donor
Under Wt Over Wt Obese‐I
1.02 1.031.06
1.60
0.89
1.16
1.03
1.13
1.00
1.35
Obese‐II Obese‐III
* * *
Failure to Achieve Live Birth
0.50.60.70.80.91
1.11.21.31.41.51.61.71.81.92
Adjusted Odd
s Ratio (9
5% CI)
Autologous Donor
Under Wt Over Wt Obese‐I
0.93
1.18
1.90
1.50 1.55
0.55
1.301.39
1.45 1.44
Obese‐II Obese‐III
* * ** * *
National ART Cycle Linkage (2004‐08)Cycles
of ART
Live Birth Deliveries
in Each Cycle (N)
Number of Women
at Risk in Each Cycle
(N)
Live Birth Delivery
Rate at Each Cycle
(%)
Cumulative Live Birth
Delivery Rate Per
Woman (%)
1 110,019 306,565 35.9 35.9
2 36,518 122,669 29.8 47.8
3 14,810 50,863 29.1 52.6
4 5,800 21,293 27.2 54.5
5 2,355 9,145 25.8 55.3
6 1,100 4,142 26.6 55.6
≥7 725 3,819 19.0 55.9
Current Grants, Contracts, and Projects
•
Upstate Kids
•
Assisted Reproduction and the Risk of Birth Defects
•
Child Health After Assisted Reproductive Technology: A Population‐based Study
•
To determine whether infertility treatments adversely affect the growth, motor, and social
development of children from birth through age three years
•
To validate infertility data from self‐reports and the birth certificate with the SART CORS
•
Linking ART cycles to evaluate the effect of treatment parameters on childhood growth and development
•
Matched cohort design of 1,500 case families and 4,500 control families
Assisted Reproduction and the Risk of Birth Defects
•
National Birth Defects Prevention Study includes
Massachusetts, Texas, New York, Utah, Arkansas, North Carolina, Iowa, California, and Georgia (CDC)
•
Linkage of the SART CORS with the National Birth Defects
Prevention Study (8,100 cases and 2,700 controls)
Child Health After Assisted Reproductive Technology: A Population‐Based Study
•
Collaborative study between Boston University School of
Public Health, Massachusetts Department of Public Health, SART, and CDC.
•
Massachusetts Pregnancy to Early Life Longitudinal Data
System (PELL) between 2004 and 2011, including longitudinal data on pregnancy, births, deaths, hospitalizations, birth
defects, and participation in the Early Intervention Program linked to the SART CORS.
•
The resulting database will track reproductive and child
health outcomes to age 3 for 18,000 children born after ART, 5,000 children born to subfertile women, and 354,000
children born to fertile women.
Pending Grants & Contracts
•
Assisted Reproduction and the Risk of Childhood Cancer
•
Women’s Health After Assisted Reproductive Technology: A Population‐Based Study
Assisted Reproduction and the Risk of Childhood Cancer
•
Linking live births from the SART CORS for 2004 to 2012 to the birth and cancer registries of 19 States and New York City to create cohorts of:
•
27 million children, including more than
•
380,000 children conceived by ART and
•
42,000 children conceived with non‐ART treatments
Women’s Health After Assisted Reproductive Technology: A Population‐Based Study
•
Collaborative study between Boston University School of
Public Health, Massachusetts Department of Public Health, SART, and CDC.
•
Massachusetts Pregnancy to Early Life Longitudinal Data
System (PELL) between 2004 and 2012, including longitudinal data on pregnancy, births, deaths, hospitalizations, and
cancer linked to the SART CORS.
•
The resulting database will track health outcomes for 47,000
women treated with ART, 6,000 subfertile women, and more than 400,000 fertile women.
Designing Research �to Assess Health Outcomes �After Assisted Reproduction Slide Number 2International Comparison of ARTSlide Number 4Contribution of Multiple Births from ARTSlide Number 6Slide Number 7Births by Maternal Age ≥35 yrs�and PluralityBirths by Maternal Age ≥40 yrs�and PluralitySlide Number 10Slide Number 11Slide Number 12Research Using the SART CORSSlide Number 14Singleton Preterm Birth RateSingleton Low Birthweight�AOR* of Birthweight Z-Score
