your environment: your fertility · demographers’ definition of fertility: –average number of...
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Your environment: Your fertility
Strong Fertility Center Education SeriesSeptember 25, 2008
Shanna H. Swan, PhDProfessor
Obstetrics & Gynecology University of Rochester School of Medicine
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Has fertility declined?
The answer depends on the definition of fertility
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Demographers’ definition of fertility: – Average number of children per woman– By this measure fertility has declined dramatically worldwide since 1965
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If you are not fertile are you infertile?
• Not necessarily– You may have chosen
• Not to have a child• Not to have a child• To delay childbearing
• So, what defines infertility?
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Impaired fecundity• A woman has “impaired fecundity” if:
– It is difficult or physically impossible for her to conceive and bring a child to term or
– Impossible for her husband to conceive a child orchild or
– She was continuously married or cohabiting and had not used contraception without conceiving for the prior 3 years.
By this measure, infertility is increasing
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But, by another definition…
A woman has 12-month infertility if she did notconceive (with or without treatment) during thepreceding 12 months, and was:
• 15-44 and married• Sexually active• Not sterilized• Not using any contraceptives
By this measure, infertility is declining
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Two measures of infertility: Two answers
Chandra et. al. NSFG 2002. Vital Health Stat 23(25), 2005
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Time to Pregnancy (TTP)
TTP: number of months (cycles) of unprotected intercourse until conception
Strengths of TTP compared to other measures:
• More precisely defined• More consistently used• Most suitable for cross-study
comparisons(Joffe, 1996)
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Planning or “wantedness” of pregnancy
• TTP Most useful for couples planning pregnancy
• TTP poorly defined for unplanned pregnancies
• But 49% of pregnancies in the US (not ending in miscarriage) in 1994 were unplanned (Henshaw 1998)
All these factors make TTP very variable
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Range: 2.8% to 31.8%Mean 12.8% (median 11.7%)
Distribution of Percent Subfertile(TTP>=12 months)
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Prospective studies of pregnancy planners
UNITED STATES EUROPE
Sample Size 611 221 200 430
Study Years 1963-68 1983-85 1994 1992-95
Study Area United States North Carolina Washington, DC DenmarkStudy Area United States North Carolina Washington, DC Denmark
Rate of clinically-recognized pregnancy after:3 cycles .60 .56 .51 .40
6 cycles .76 .69 .71 .70
9 cycles .83 .70 .78 N/A
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Infertility
• Inability to become pregnant after 12 months of unprotected intercourse– Ovulation disorders 27%– Semen abnormality 25%– Semen abnormality 25%– Tubal defect 22% – Unexplained 17%– Endometriosis 5%– Other 4%
Barbieri. In: Yen and Jaffe’s Reproductive Endocrinology 2004
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Infertility
• 10 to 15% of couples trying meet definition– Over 7 million in the United States
• Frequency may increase with delayed childbearingchildbearing– Mean age at 1st and 2nd pregnancy has
increased by about 4 years over the past 3 decades.
• Few modifiable risk factors for infertility known
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Possible environmental factors
• Environmental = non-genetic• Includes:
– Lifestyle factors (smoking, drinking, stress)– Diet, nutrition and exercise– Diet, nutrition and exercise– Chemicals in our food, water air
• At home, work and elsewhere
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Nonchemical agents
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BMI and ovulatory infertility
Rich-Edwards JW et al. Epidemiology 2002
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Fatty acid intake
-7
-14
-25
9
All fats for carbs, 5% of energy
Saturated fat for carbs, 5% of energy
MUFAs for carbs, 5% of energy
PUFAs for carbs, 5% of energy 9
73
79
131
-100 0 100 200 300
PUFAs for carbs, 5% of energy
trans fat for carbs, 2% of energy
trans fat for n-6 PUFAs, 2% of energy
trans fat for MUFAs, 2% of energy
Percent Change in Risk of Ovulatory infertility
Chavarro et al. Am J Clin Nutr 2007
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Protein intake
19
22All protein for carbs,5% of energy
Animal protein forcarbs, 5% of energy
-58
-43
-100 -50 0 50 100
carbs, 5% of energy
Vegetable protein forcarbs, 5% of energy
Vegetable for animalprotein, 5% of energy
Percent Change in Risk of Ovulatory infertility
Chavarro et al. Am J Obstet Gynecol 2008
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Frequency of multivitamin use
Chavarro et al. Fertil Steril 2007
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Low-fat dairy foods
1.851.711.86
1.24
2
2.5
3
Relative Risk (95%
CI)
1.24
0
0.5
1
1.5
< 1 / week 1 / week 2 – 6 / week 1 / day ≥ 2 / day
Frequency of Intake
Relative Risk (95%
CI)
P, trend =0.002
Chavarro et al. Hum Reprod 2007
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High-fat dairy foods
0.730.76
1.051
1.5
Relative Risk (95%
CI)
0.730.76
0
0.5
< 1 / week 1 / week 2 – 6 / week ≥ 1 / day
Frequency of intake
Relative Risk (95%
CI)
P, trend =0.01
Chavarro et al. Hum Reprod 2007
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Lowest risk exposure levels1. Vigorous physical activity: > 30 min/day2. Body mass index: 20 – 24.93. Animal protein: < 10% of energy4. Vegetable protein: >7% of energy5. Blood sugar: bottom 10% of distribution5. Blood sugar: bottom 10% of distribution6. Iron: > 40 mg/day7. Low fat dairy: < 1 serving/week8. High fat dairy: ≥ 1 serving/day9. Multivitamins: ≥ 6 tablets/week
Chavarro et al.
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How much can be prevented
21 (12 – 29)0.64 (0.53 – 0.78)54BMI 20 – 24.9
21 (0 – 40)0.78 (0.58 – 1.05)14Physical activity > 30 min/day
PAR% (95% CI)RR (95% CI)%Characteristic
66 (29 – 86)0.31 (0.14 – 0.70)45+ factors
55 (36 – 70)0.40 (0.27 – 0.59)144+ factors
46 (29 – 60)0.48 (0.35 – 0.67)19Diet score Q5
21 (12 – 29)0.64 (0.53 – 0.78)54BMI 20 – 24.9
Chavarro et al. Obstet Gynecol 2007
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BMI and reproductive potential
BMI Testis Size (mL)
Semen Volume (mL)
Sperm concentration (%)
Sperm count (%)
< 20 -2.0 * - 0.24 * -28.1 * -36.4 *
20–24.9 Ref Ref Ref Ref
≥ 25 0.1 -0.003 - 21.6 * - 23.9 *
Jensen et al. Fertil Steril 2004
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Chemicals in the Environment
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Carlsen et. al. 1992
• Meta-analysis of 61 studies published 1938-1991(included 14,947 men)
• Found a significant decrease in sperm density:density:– 1940: 113 x 106/mL– 1990: 66 x 106/mL Average decline: 1%/yr (-0.93 x 106/mL)
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Carlsen et al. 1992
Circles proportional to log sample size
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Chemicals in the environment
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Swan et al. 2000
• New literature search: 1934-1996• Analysis included 101 studies• North America: 44• Europe: 34• Europe: 34• Other: 23
Average decline: 1%/yr (-0.94 x 106/mL)
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Swan et al. 2000
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• Overall sperm density appears to have declined.
• Not explained by obvious confounders.• Rate of decline varies geographically.• Mean density varies geographically.• Mean density varies geographically.• Though significant, decline was not
convincing.A new approach was needed
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The Study for Future Families (SFF)
Designed to examine geographic variation in geographic variation in semen quality
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Semen Quality by Center
*
* P-Value for MO vs. all other centers <.001
**
*
Swan et al 2003
*
*
*
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MO – 57% MN – 19%
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Nested Case-Control Study in Missouri
• Cases: Poor semen quality– Mean concentration: 32.4 x 106/mL
• Controls: Normal semen quality• Controls: Normal semen quality– Mean concentration: 72.2 x 106/mL
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Pesticides Detected More Often in Cases Than Controls
Percent above LOD
Diazinon
Metolachlor
Alachlor
Malathion
Atrazine
2,4-D
Percent above LOD
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Chemicals and diet might act together
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Xenoestrogens and sperm quality
• Maternal beef consumption
• Dairy foods
• Processed beef • Processed beef consumption
Swan et al. Hum Reprod 2007 Mendiola et al. Fertil Steril in press
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Diet: Another possible source of geographic variation in semen quality
• Hypothesis: Mother’s beef consumption during pregnancy can affect her son’s semen qualityquality
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Background
• Diethylstilbestrol present in US beef from 1954-1979.• Six hormones (anabolic steroids) used in production of US
beef:– Natural steroids: estradiol, testosterone and
progesterone progesterone – Synthetic hormones, zeranol (an estrogen), trenbolone
acetate (a steroid with androgen action) and melengestrol acetate (a progestin)
• Since 1988 no hormone-treated beef sold in the EU
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We examined this hypothesis in our study
• We looked at semen parameters in SFF men in relation to amount of beef their mothers ate while pregnant.
• Mothers’ beef consumption was also analyzed in relation to her son’s history of previous subfertility.relation to her son’s history of previous subfertility.
• Regression analyses controlled for son’s age, abstinence time, and alcohol consumption.
• Definition:Eating >1 beef meal a day = “High beef consumer”
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Results (1)
• Sperm concentration was inversely related to mothers’ beef meals per week (P = 0.041).
• Sons of “high beef consumers” vs. others:– Sperm concentration reduced 24.3% – Sperm concentration reduced 24.3%
(P = 0.014) – 17% had sperm concentration < 20 x 106/ml
compared to 5.7% of others (P = 0.002)
(Swan et al. 2007)
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Results (2)
• History of previous subfertility twice as frequent among sons of high beef consumersfrequency (p = 0.016).
• Sperm concentration was not significantly • Sperm concentration was not significantly related to:– the mother’s consumption of other meat– the man’s consumption of any meat
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Sperm Production Unlikely to be Effected in Isolation
• If sperm decline is real, we would expect trends in related parameters, such as steroid hormones.
• If geographic variability in semen quality is • If geographic variability in semen quality is real, we would expect variability in other endpoints reflecting testicular development.
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Total Testosterone: Declined 1.2% /yr (1980-2004)
Travison 2006
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Conclusion (1)
• Sperm concentration shows significant declines in some areas of the world.
• Semen quality shows significant geographic variation.geographic variation.
• Environmental factors (such as pesticides and anabolic steroids) are suspect but not proven causes.
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Conclusions (2)
Fertility can be influenced by a mixture of exposures at different developmental stages:– In utero exposures including environmental
endocrine disruptors (e.g. pesticides, endocrine disruptors (e.g. pesticides, hormones in beef)
– Early postnatal development (e.g. BPA in infant formula)
– Adult exposure (e.g. pesticides, phthalates)
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Useful websites and groups to “Google”
• Shaping Our Legacy: Reproductive Health and the Environment (http://www.prhe.ucsf.edu/prhe/pubs/shapingourlegacy.html
• Our Stolen Future (http://www.environmentalhealthnews.org)• Our Stolen Future (http://www.environmentalhealthnews.org)
• Environmental Health News
• Environmental Working Group
• National Geographic Green Guide
• National Resources Defense Council
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Final Slide
Thank you