DANSKE MÆNDS SÆDKVALITET - EN OPDATERING Niels Jørgensen Afdeling for Vækst og Reproduktion Rigshospitalet
Sædkvalitet Lavere end 2-3 generationer siden I Europæiske lande Kun 25% har optimal sædkvalitet 20-30% i risiko for forlænget ventetid til graviditet (TTP) 10-15% i risiko for at få behov for fertilitetsbehandling Andre betydninger Markør for helbred?
Evidence for decreasing quality of semen during past 50 years Historiske data Primært Europa and USA 50% nedgang over 50 år Carlsen et al: BMJ, 1992
Sperm density (10 6 /ml) The Question of Declining Sperm Density Revisited: An Analysis of 101 Studies Published 1934-1996 Historiske data North America Europe Other Forskellige trends i Europa og USA Year of sample collection
Session, Danmark, 1917 Danske Øjeblikke. Danske pressefotos i 100 år, ed. L. Davidsen.
Table 1.1: Physical appearance and self-reported information of men from the general population in the Copenhagen area, Denmark. Physical appearance Difference between the 3 groups Mean (SD) Median (5-95) Mean (SD) Median (5-95) Mean (SD) Median (5-95) Mean (SD) Median (5-95) p-value Age (years) a 19.4 (1.2) 19.0 (18.4-21.7) 19.6 (1.4) 19.0 (18.5-22.4) 19.3 (1.1) 18.9 (18.4-21.3) 19.4 (1.2) 19.0 (18.4-21.8) <0.0005 A Height (m) 1.81 (0.06) 1.81 (1.71-1.92) 1.81 (0.07)) 1.81 (1.71-1.92) 1.81 (0.07) 1.81 (1.70-1.91) 1.82 (0.06) 1.82 (1.71-1.93) <0.0005 A Weight (kg) 75.1 (11.5) 73.5 (59.4-96.4) 75.2 (11.7) 73.6 (59.0-97.5) 74.9 (11.5) 73.3 (59.2-97.0) 75.5 (11.2) 74.1 (60.1-96.0) 0.15 A BMI (kg/m2) 22.9 (3.1) 22.4 (18.7-28.8) 22.9 (3.2) 22.4 (18.8-28.9) 22.9 (3.2) 22.4 (18.7-29.0) 22.8 (3.1) 22.4 (18.7-25.6) 0.8 A Testis size (ml) b 20 (5) 20 (13-28) 20 (5) 20 (12-28) 20 (5) 20 (13-28) 22 (5) 23 (14-29) <0.0005 A Testis size (ml), US 15 (4) 14 (9-22) 15 (5) 15 (9-24) 14 (4) 14 (9-22) 14 (4) 14 (9-21) <0.0005 A Life style Cigarettes daily, all men 4.1 (6.7) 0.0 (0.0-20.0) 5.0 (7.4) 0.0 (0.0-20.0) 3.9 (6.5) 0.0 (0.0-20.0) 3.7 (6.2) 0.0 (0.0-18.0) 0.004 A Cigarettes daily, smokers only 9.9 (7.1) 10.0 (1.0-20.0) 11.7 (7.1) 10.0 (1.0-20.0) 9.9 (6.9) 10.0 (1.0-20.0) 8.1 (6.9) 7.0 (0.1-20.0) <0.0005 A Alcohol consumption (units) c 14 (14) 11 (0-40) 13 (13) 11 (0-38) 14 (14) 11 (0-37) 15 (16) 12 (0-42) 0.1 A Ejaculation abstinence (hours) 81 (117) 63 (37-155) 86 (95) 63 (35-168) 81 (137) 62 (38-135) 77 (96) 63 (37-134) 0.1 A % % % % Taken medication d 12.5 14.6 9.7 15.1 <0.0005 B Smoker 41.7 42.5 39.1 45.4 0.001 B Previous smoker 3.1 2.0 2.3 5.8 <0.0005 B Never smoker Median alder 55.2 19 år 55.6 58.6 48.7 <0.0005 B Mother smoked in pregnancy 38.0 36.2 38.3 29.1 <0.0005 B Been diagnosed as having Investigation period 1996-2010, total (N=4,867) 1996-00 (N=1,339) 2001-05 (N=2,254) 2006-10 (N=1,274) 4,867 mænd fra Københavnsområdet Undersøgelse 1996 til 2010 Varicocele 0.6 0.5 0.7 0.4 0.4 B Epididymitis 0.3 0.3 0.5 0.2 0.3 B Sexual transmitted disease e 4.3 2.2 4.6 6.2 <0.0005 Undersøgte mænd er repræsentative for normalbefolkningen B af unge B Cystitis 2.4 1.4 2.4 3.6 0.002 B Diabetes 0.02 0.0 0.04 0.0 0.6 B Thyroid disease 0.04 mænd 0.0 0.05 0.08 0.001 B Been treated for Varicocele 0.4 0.0 0.7 0.4 0.004 B Testicular torsion 0.8 1.0 0.6 0.9 0.4 B Testicular cancer 0.02 0.0 0.0 0.1 0.2 B Cryptorchidism f 6.1 3.9 8.0 5.0 <0.0005 B Hypospadias 0.1 0.0 0.0 0.3 0.004 B Phimosis 3.9 5.4 2.7 4.6 <0.0005 B Inguinal hernia 3.4 3.8 4.8 0.5 <0.0005 B Has had cryptorchidism g 8.3 4.4 11.2 6.9 <0.0005 B experienced fertility problems h 0.6 1.7 0.2 0.2 <0.0005 B caused a pregnancy i 6.4 7.4 5.6 6.8 0.08 B Subgroup 80.6 84.6 77.8 81.2 <0.0005 B Jørgensen et al: BMJ Open, 2012
Sperm concentration (mill/ml) 45 mill/ml 43 mill/ml 45 mill/ml 48 mill/ml 200 180 160 140 120 100 80 60 40 20 0 Year of investigation Jørgensen et al: BMJ Open, 2012
Total sperm count (mill) 143 mill 132 mill 146 mill 151 mill 700 600 500 400 300 200 100 0 Year of investigation Jørgensen et al: BMJ Open, 2012
Morphologically normal spermatozoa (%) 6.5% 16 7.0% 6.0% 7.0% 14 12 10 8 6 4 2 0 Year of investigation Jørgensen et al: BMJ Open, 2012
% of men % of men 50 45 40 35 30 25 70 60 50 40 20 15 10 5 0 30 20 10 0 Sperm concentration (million/ml) Total sperm count (million) Men from infertile couples (1940-1943) Men from general population (1996-2010) Jørgensen et al: BMJ Open, 2012
4,867 mænd fra Københavnsområdet Resultater forenelige med nedgang siden begyndelsen af 1940 erne Lille stigning i sædcellekoncentration og totat sædantal, 1996-2010 Er det aktuelle niveau problematisk?
% of men % of men % of men 12 10 8 45 mill/ml 61 mill/ml Men from the general population (1996-2010) Fertile men (1996-1998) 6 4 2 0 30 25 143 mill 215 mill 20 Sperm concentration (million/ml) 15 40 35 6.5% 8.5% 10 5 30 25 0 20 15 Total sperm count (million) 10 5 0 0 >0-2 2-5 5-9 9-12 12-15 >15 Morphologically normal spermatozoa (%) Jørgensen et al: BMJ Open, 2012
Sandsynlighed for graviditet / menstruationscyklus % Sædcellekoncentration, mill/ml Bonde et al.: Lancet, 1998.
Nedsat sandsynlighed for graviditet Sperm conc. Total count Motile Normal (mill/ml) (mill) (%) (%) Bonde <40 - <70 - Guzick <48 - <63 <12 Slama <55 <145 - <19 Bonde et al: Lancet, 1998. Slama et al: Hum Rep, 2002 Guzick et al: NEJM, 2001
No improvement in semen quality with increasing age of young men 158 young Danish men, median 19 years Delivered 1,838 semen samples during 4 years No change in semen parametres Poor semen quality of young Danish men is unlikely to be the result of immaturity Carlsen et al: Hum. Reprod. 2005
Impact of morphology on fecundity Guzick et al.: N. Engl. J. Med., 2001;345:1388 Fertile and subfertile population - Fertile range > 12% - Indeterminate 9-12% - Subfertile range < 9% Van Waart, Krüger et al.: Hum Reprod. Update, 2001;7:495 Intrauterine insemination - Reduced pregnancy rate < 5%
4,867 mænd fra Københavnsområdet Resultater forenelige med nedgang siden begyndelsen af 1940 erne Lille stigning i sædcellekoncentration og totalt sædantal, 1996-2010 Kun 23% med sædcellekoncentration >40 mill/ml OG >9% morfologisk normale sædceller 15% med sædcellekoncentration sv.t øget risiko for behov for fertilitetsbehandling og 27% i risiko for forlænget ventetid til graviditet
Finland High and unchanged sperm counts of Finnish men M. Vierula, M. Niemi, A. Keiski, M. Saaranen, S. Saarikoski and J. Suominen International Journal of Andrology, 19;11-17:1996
Normal young men Sperm conc. (mill/ml) 41 43-48 44 55 67 48 63 63 55 Jørgensen et al (2002, 2011), Richthoff et al (2000), Axelsson et al (2011) Punab et al (2002), Tsarev et al (2003), (62) Paasch et al (2008) Fernandez et al (2010)
Investigation period, 2006-07 Infertile men, N=341 Fertile men, N=293 Results controlled for age, BMI and education
Sædkvalitet Nedsat sædkvalitet er risikofaktor for fertilitetsproblem Nedsat sædkvalitet er risikofaktor for Nedsat kapacitet til testosteronproduktion Testikelcancer Morbiditet generelt og mortalitet? Skal nedsat sædkvalitet også opfattes som advarsel om kommende generelle helbredsproblemer?
Sædkvalitet Lavere end 2-3 generationer siden I Europæiske lande Kun 25% har optimal sædkvalitet 20-30% i risiko for forlænget ventetid til graviditet (TTP) 10-15% i risiko for at få behov for fertilitetsbehandling Andre betydninger Markør for nedsat helbred?