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Cigarette smoking and infertility

Cigarette smoking and infertility. de Mouzon Jacques, MD, MPH, INSERM U822, Le Kremlin-Bicêtre, France. Introduction. Cigarette smoking associated to many pathologies Cancer : Lung, Stomach, Bladder, etc. Cardiovascular disease, lung insufficiency, etc.

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Cigarette smoking and infertility

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  1. Cigarette smoking and infertility de Mouzon Jacques, MD, MPH, INSERM U822, Le Kremlin-Bicêtre, France

  2. Introduction • Cigarette smoking associated to many pathologies • Cancer : Lung, Stomach, Bladder, etc. • Cardiovascular disease, lung insufficiency, etc. • First cause of preventable mortality in France (65000 deaths) • Among women, well established role in pregnancy • Pre-eclampsia,, Placenta praevia, Abruptio placentae • Fetus : birth weight (150-200g), small for gestational age • Increasing concern in human reproduction • For natural fertility (woman and man) • For ART • Several hypotheses for action mode

  3. I / Natural fertility

  4. Normal fertility • On average, • 85% of couples conceive within 12 months • 90 % within 18 months • What about cigarette smokers ?

  5. Diminution of probability to conceiveFrench study (Gefco) 1887 couples, planned pregnancies de Mouzon J, Spira A, Schwartz D. Int J Epidemiol 1988,17:378-384

  6. Increase in TTPEuropean study (7 countries) * TTP > 9,5 months % * * Cigarettes / day • General population : 3187 planned pregnancies • Maternity hospitals : 2587 planned pregnancies Infertility duration multiplied by : 1.2 pour 1 - 10 cigarettes (1.1-1.4) 1.5 pour > 10 (1.3-1.8) Bolumar F, Olsen J, Boldsen J et al. Am J Epidemiol 1996,143:578-587

  7. Increase in TTP (2)England(Avon county) % 8515 planned pregnancies Hull MGR, North K, Taylor H et al. Fertil Steril 2000,74:725-733

  8. Increased risk of TTP≥ 12 months Male and female smoking cigarettes 8515 planned pregnancies English study Hull MGR, North K, Taylor H et al. Fertil Steril 2000,74:725-733

  9. Male and female smokingCanadian study OR for fecundibility Ontario Farm Family Health Study:2607 planned pregnancies Woman +, Man +,Both man and woman ++ Curtis KM, Savitz DA, Arbuckle TE Am J Epidemiol 1997,146:32-41

  10. In utero exposition to smokingOdds-ratios for fecundibility Prospective study, CO stopping, 423 couples, multivariate analysis Jensen TK, Henriksen TB, HjollundNHI et al. Am J Epidemiol 1998,148:992-997

  11. In utero exposition to smoking Danish study (2) • Jensen et al, Int J Androl. 2006 • National cohort of twins born 1931 - 1952 • 1653 women / 1598 men, with TTP • Exposition in utero to cigarette smoking • Fecundibility Odds Ratios, whole cohort • Women : FOR = 0.81; 95% CI 0.67-0.99 • Men : FOR = 1.12; 95% CI 0.89-1.40 NS • Selection of twins of opposite sex • Women : FOR = 0.65; 95% CI 0.47-0.91 • Men : FOR = 0.97; 95% CI 0.60-1.55

  12. Cigarette smoking and female fertilityOther aspects • Increase in short / irregular cycles • Younger menopausal age (2 years) • Increase % of earlymenopauses (<40 yrs) • Related to level and duration of smoking • Multiplied by 3 fo 20 cig / day, 20 years • ± reversible Willett W, Stampfer MJ & Bain C et al. Cigarette smoking, relative weight, and menopause. Am J Epidemiol 1983,117: 651-8

  13. Cigarette smoking and male fertilitySemen • Künzle 2003, infertile smokersNon smokers p • n 655 1131 • Concentration : 68 (66)80 (75) 0.001 • Motility A : 37.1 (18.6)38.7 (17.7) 0.07 • Normal forms: 21.2 (14.6)23.7 (15.5) 0.001 • Trummer 2002, infertile: n=478 517 109 ExS • Round cells (106) : 3.5 (5.3) 2.7 (3.4)2.6 (3.4) 0.01 • Saleh 200212 Infert S21 Infert NS13 Donors NS Leucocytes (106) 1.8 (0.6-4.4)0.0 (0.0-0.4)0.1 (0.0-0.2) 0.01 S=Smokers; NS=Non Smokers; ExS= Ex Smokers

  14. II / Assisted Reproduction

  15. Woman cigarette Smoking and IVF. Retrospective cohort Van Voorhis BJ, Dawson JD, Stovall DW et al. Obstet Gynecol 1996;88:785-791

  16. Woman cigarette Smoking and IVF. Tubal infertility Smoking classified according to follicular cotinine (ng/ml) Sterzik K, Abt M, Strehler E et al. Human Reprod 1995,10:3213-3217

  17. Woman cigarette Smoking and oocyte quality Zenzes MT, Wang P, Casper RF (Human Reprod 1995,10:3213-3217

  18. Couple cigarette smoking and IVF failure OR N=221 Klonoff-Cohen H., Natarajan L., Marrs R., Yee B. Human Reprod 2001,16 :1382-1390

  19. Woman cigarette smoking and Pregnancy rate Belaisch-Allart J, El-Akoum ., Mayenga JM, et al. Fertil Steril 1996,66:679-689

  20. Woman passive cigarette smoking and Pregnancy rate All NS Neal MS, Hughes EG, Holloway AC et al.Hum Reprod 2005,20:2531-5

  21. Woman passive cigarette smoking and Pregnancy rate (2) • Cumulative embryo score • ** p<0.05 Neal MS, Hughes EG, Holloway AC et al.Hum Reprod 2005,20:2531-5

  22. Cigarette smoking and implantation: oocyte donation S.R.Soares, Human Reproduction 2006 785 oocyte donations, Valence, man no-smoker, transfer D3 2.1 embryos on average (identical in the groups) *: p<0.05

  23. Meta-analysis 1 (EG Hugues) • 13 studies on natural fertility (n=55000) • All odds-ratios or relative risks of fertility lower than 1 except 1 : from 0.3 to 1 • 7 studies on ART (n=1700) • All odds-ratios of fertility lower than 1 • Mean estimate, 0.57 (0.42-0.78) • Hugues EG, Brennan BG. Fertil Steril 1996,66:679-689

  24. Meta-analysis 2 (Augood) • 13 studies on natural fertility • Mean estimate of risk of infertility among smokers: OR =1.60(1.34-1.91) • Mean estimate of risk of TTP >1yr among smokers OR = 1.42(1.27-1.58) • 9 studies on ART Mean estimate of risk pregnancy among smokers OR = 0.66 (0.49-0.88) Augood C, Duckitt K, Templeton. Human Reprod 1998,13 :1532-1539

  25. Cigarette smoking and infertility Hypotheses • Nicotine • Hypothalamo-pituitary-ovarian axis • Early menopause, Estradiol, oocytes number • local : • cervical mucus, tubal motility, ciliary function • Other compounds :Cadmium (diploid oocytes ?) • Hypoxia: oxydative stress on follicle • Marker for tubal infertility • Van Voorhis BJ et al. Tubal infertility in IVF cohort : No smoker 34 %, Ex smoker 57 %, smoker 62 %. • Smoker more sexually active (ACSF)

  26. Conclusion (1) • Decreased fertility (natural and ART) • Probablecausal relationship • Relation dose-effect, duration-effect • Biological plausibility • Reversibility at stopping (±) • Some interesting points • In utero exposure • Probable maternal and paternal effect • Passive exposition

  27. Conclusion (2) • Methodological difficulties in measuring exposition • Questionnaires, but concealed exposures • Biological measurements (cotinine) , expensive • Difficulties to measure duration, level • Carbon monoxyde tester in expired air • No study with large sample in ART

  28. Conclusion (3)French epidemiological study • Objective: association smoking/ Result • Large cohort study (3500 couples) • 14 ART Centres • Measurement of carbon monoxyde • Both members of couples • Criteria • Sperm quality • Oocyte number and quality • Cycle result and pregnancy outcome

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