Smoking - IVF Smoking and ectopic pregnancy -smo ex-smo +smo - PDF document

Lifestyle and infertility Lifestyle and infertility Age, smoking, caffeine, alcohol • Some definitions and male fertility • How big is the problem? • Age and fertility • Smoking Øjvind Lidegaard • Alcohol Dept. Obstetrics & Gynaecology • Caffeine Herlev University Hospital • Male fertility NFS 2005 Li/05 Some definitions Lifestyle and infertility • Infertility: – No pregnancy after one year attempt • Some definitions • Fecundity: • How big is the problem? – The capability to become pregnant and deliver • Age and fertility • Fecundability: • Smoking – Pregnancy chance per cycle (mean: 20%) • Alcohol • Fecundability ratio: • Caffeine - Pregnancy chance among exposed • Male fertility compared with non exposed NFS 2005 Li/05 Total fecundity rate in DK 1901-2001 Infertility: Prevalence Infertility now: Women in fertile age: 10% 4 Infertility ever: Women in fertile age: 15% Infertility life time risk: Couple: 25% 3 Seeking aid for infertility: 10% 2 No children despite wish at 50 years: 4% Is the problem increasing? Yes . Because 1 • More infertile at a certain age • Sooner seeking for aid among infertile 0 1 1 1 1 1 1 1 1 1 1 1 0 1 2 3 4 5 6 7 8 9 0 9 9 9 9 9 9 9 9 9 9 0 • Older age when pregnancy wish arises 1 1 1 1 1 1 1 1 1 1 2 Schmidt L. Hum reprod 1995; 10: 1407-18 Lisbeth B Knudsen, Fertility trends in DK in the 1980s Li/03 Li/04 Danmarks Statistik online. 1

Age at first birth Lifestyle and infertility Denmark 1970-2002 29 • Some definitions 28,5 28 27,7 • How big is the problem? Increase: 1 year/6 years 27 • Age and fertility 26,8 • Smoking 26 • Alcohol 25,2 25 • Caffeine 24,1 24 • Male fertility 23,4 23 1970 1977 1983 1991 1998 2002 NFS 2005 Li/05 Knudsen LB. Fertility trends in DK in the 1980s og DK's Statistik Li/04 What is a woman, and Fecundity according to age what can you expect from her? Live births per cycle 35 34 Couples: 544 North & South Dakota to where the Hutterites Children: 3,846 30 28 immigrated at end of 19th century. Approx. Post-partum 25 24 Amennorrhea: 10 months 215 persons immigrated about 1870. In 1960 Children/woman: 10,8 20 they were 5.450 • No contraception allowed 17 15 • Children have high priority 12 10 • Socially comparable with other couples. 6 • Let’s look at 544 couple, all married and all 5 0,5 0 with at least one child to quantify womans 18 20 25 30 35 40 45 fertility Larsen U et al. Social Biology 2000; 47: 34-50 Why does fertility decrease by age? Donor IUI. Pregnancies/100 cycles 35 Per cent 6,139 IUI-D cycles 30 1,001 treated women • Egg’s get older 25 All during 18 years • Increased risk of 20 15 spontaneous abortion 10 5 0 <22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 >44 Botchan A et al. Hum Reprod 2001; 16: 2298-2304 Li/02 2

Spontaneous fetal loss after living Age and fertility: Conclusion pregnancy week 12-24 (CH). • The dramatic increase in age at first 13,8 delivery through last three decades has 2,534 spontaneously pregnant 50 14 women, all with US verified live increased the risk of infertility substan- 12 pregnancy. 40 tially Per cent 10 • This development is expected to 30 OR 8 continue over the next decades 6 20 • Age at first pregnancy wish is probably 4 2,1 10 the most important life style factor in 1 2 0,7 0,8 0,8 7,8 50 effect 2,9 3,4 3,9 0 3,2 0 <20 20-24 25-29 30-34 35-39 40-45 Hoesli et al. Am J Med Genet 2001; 100: 106-9 Li/02 Naughty girls Lifestyle and infertility Cig/day Drinks/week 10 4 3,187 women 25-44 years old • Some definitions 8,8 European Multicentre Study on 8 3,6 3,6 • How big is the problem? Infertility and subfecundity 3,3 6 • Age and fertility 3,2 5,5 ↑ 214% ↑ 64% • Smoking 4 2,8 3,5 • Alcohol 2,8 2 2,4 • Caffeine 2,3 2,2 • Male fertility 0 2 Cups per day <1 1-2 3-5 >5 NFS 2005 Bolumar et al. Am J Epidemiology 1997; 145: 324-34. Li/05 Li/04 Fertility and smoking Smoking in DK in 1987, 1994 & 2000 Risk of waiting time >9,4 months Women, N=8,494 50 1987 1994 2000 Relative risk 45 2 40 Men Women 35 1,5 30 1 25 1,7 47 46 43 1,4 1 41 0,9 39 20 36 1 34 0,5 29 15 27 27 25 24 10 0 . 5 . 0 1-10 >10 No Yes 0 16-24 25-44 45-66 67+ Bolumar et al. Am J Epidemiology 1996; 143: 578-87. Li/01 Li/203 Sundhed og Sygelighed i DK 2000. SIF 2002 European multicenter study on infertility and subfecundity 3

Smoking - IVF Smoking and ectopic pregnancy -smo ex-smo +smo Odds ratio 3,5 3,5 Case-control study, USA 1988-90 No 499 351 111 37 196 cases, 237 controls. 3 Ø2/FSU U 82 71 60 Adjusted for age, parity, infertility, 2,5 and vaginal douching. 2,3 Oocytes 13.5 13.6 12.6 2 Fertilis. rate 54% 54% 50% 1,7 1,6 1,5 Embryos 8.0 8.2 6.6 1 1 Embr. transf 3.6 3.5 3.6 0,5 Implant. rate 16 16 6.7 0 0 1-5 6-10 11-20 >20 Voorhis et al. Obstet Gynecol 1996; 8: 785-91 Li/01 Li/01 Am J Obstet Gynecol 1998; 178: 393-8 IVF and smoking: Århus 2000-03 IVF and smoking: Results • Observational cohort study at Skejby OR (95% CI) Oocytes Fertilisa- Pregnan- N=777 retrieved tion rate cy rate • Couples undergoing IVF or ICSI from Female January 2000 through December 2003 - smoking 1 1 1 • Confounders included: Coffee, alcohol, + smoking 1.0 (0.7-1.5) 1.2 (0.8-1.7) 1.0 (0.7-1.4) BMI, length of infertility, previous pregn, Male cause of infertility - smoking 1 1 1 • Outcomes: oocytes retrieved, fertilisation + smoking 1.0 (0.7-1.5) 1.0 (0.7-1.4) 1.2 (0.8-1.7) rate, clinical pregnancy rate week 7 (US) Conclusion: No effect of smoking on IVF Rikke Krogh, Kesmodel & Ingerslev. Paper in preparation. Li/05 Rikke Krogh, Kesmodel & Ingerslev. Paper in preparation. Li/05 Smoking: Selection bias Smoking: Selection bias Pregnancy Pregnancy Smoking Smoking attempt (home) attempt (home) women women Organic cause Organic cause Smoking women Infertile Organic cause Li/05 Li/05 4

Smoking: Selection bias Smoking: Selection bias Infertile GP Infertile GP Smoking Smoking women women Organic cause Organic cause Infertile, IVF clinic Smoking women Organic cause Endometriosis, high BMI, PCO+-S, tubal occlusion, myomas, polypes etc. Smokers (%) according to length of Smoking: Selection bias infertility (months) Diagnosis % smokers 40 % smokers All women (n=1,441) 32% Anovulation 18% 35 Endometriosis 20% Other 25% 30 Idiopatic 28% Male factor 32% Length of infertility Tubal factor (22%) 44% 25 0-12 13-24 25-36 37-48 49-60 61+ Rikke Krogh, Kesmodel & Ingerslev. Paper in preparation. Li/05 Li/05 Smoking and fertility Lifestyle and infertility Impeded ciliary function : Pick-up function ↓ • Some definitions Implantation rate ↓ • How big is the problem? • Age and fertility • Smoking Ud/Li/2001 • Alcohol Impeded placental function, low E2, hCG • Caffeine • Male fertility Abortion rate ↑ ↓ progesterone E2-production ↓ in granulosa cells NFS 2005 Li/05 Shiverick et al: Placenta, 1999; 20: 265-72 5

Fertility and alcohol Alcohol and fertility Fecundability odds, 95% CI Does small amounts of alcohol have an 1,6 Odds for pregnancy impact on natural fertility? 1,4 • Only few studies Women Men 1,2 • Danish prospective study 1992-94 with 430 1,02 1 1 1 0,91 couples, 20-35 years, trying to become 0,76 0,83 0,8 pregnant for the first time 0,6 0,61 0,55 • Alcohol intake was recorded in detail 0,4 0,34 0,34 through 6 cycles 0,2 • Control for smoking, BMI, and semen count Drinks per week 0 0 1-5 5-10 11-15 >15 0 1-5 6-10 11-15 >15 Jensen et al. BMJ 1998; 317: 505-10 Jensen TK et al. BMJ 1998; 317: 505-10. Waiting time to pregnancy in months Alcohol and time to pregnancy and drinks per week Cross sectional study DK 1997-2000 including 100% 39,612 pregnant women (Danish birth cohort). 29,933 planned pregnancies included. 80% >12 Included: 60% of invited = 1/3 of all pregnant. 6-12 60% Asked about alcohol habits before pregnancy, 3-5 0-2 40% which was correlated to time to pregnancy. Included confounders: Smoking (in 20% pregnancy), BMI, parity and age. 0% Drinks per Outcome measure: Subfecundity odds ratio <0,5 0,5-2 2,5-7 7,5-14 >14 week Confounders: Age, Smoking, BMI, parity Juhl M et al. Human reprod 2002; 16: 2705-9. Li/02 Li/02 Time to pregnancy, age, alcohol & Subfecundity OR and drinks per week smoking Risk of waiting time >12 months 1,5 Risk of increase in waiting time 1,48 3,5 3,4 1,4 2,8 3 1,3 2,4 No smo 2,5 1,2 + smo 2 1,9 30-34 1,1 1,7 1,6 1,6 1,5 >34 1 1 1,2 1,2 0,94 0,92 1 1,2 0,9 1,1 1 0,86 0,5 0,8 0 0,5-14 >14 0 0,5-2 2,5-7 7,5-14 >14 Li/02 Li/02 Juhl M, et al. Human Reprod 2002; 16: 2705-9 6