HUMAN SEMEN QUALITY IN THE NEW MILLENIUM: A MATTER OF CONCERN?

Rigshospitalet

Copenhagen

Denmark

Niels Jørgensen, Ulla N. Joensen, Tina K. Jensen, Martin B.

Jensen, Kristian Almstrup, Inge A. Olesen, Elisabeth Carlsen,

Jørgen H. Petersen, Jorma Toppari and Niels E. Skakkebæk

Semen quality a matter of concern

• Lower than two-three generations ago

• In European countries

• Only 25% have optimal semen quality

• 20-30% at risk of prolonged waiting time to pregnancy

• 10-15% at risk for need of fertility treatment

• Other implications

• Marker of reduced general health status?

Carlsen et al: BMJ, 1992

Historical data

• Mainly European and US

• 50% decrease in 50 yrs

Evidence for decreasing quality of semen during past 50 years

0

20

40

60

80

100

120

140

160

180

200 S

perm

co

nc

en

trati

on

(m

ill/m

L)

Jørgensen et al: BMJ Open, 2012

45 mill/mL

43 mill/mL 45 mill/mL 48 mill/mL

Year of investigation

0

5

10

15

20

25

30

35

40

45

50

% o

f m

en

Sperm concentration (million/mL)

0

10

20

30

40

50

60

70

% o

f m

en

Total sperm count (million)

Men from infertile couples (1940-1943) Men from general population (1996-2010)

Jørgensen et al: BMJ Open, 2012

0

2

4

6

8

10

12

% o

f m

en

Sperm concentration (million/mL)

0

5

10

15

20

25

30

% o

f m

en

Total sperm count (million)

0

5

10

15

20

25

30

35

40

0 >0-2 2-5 5-9 9-12 12-15 >15

% o

f m

en

Morphologically normal spermatozoa (%)

Jørgensen et al: BMJ Open, 2012

Fertile men (1996-1998)

Men from the general population (1996-2010) 45 mill/mL 61 mill/mL

143 mill 215 mill

6.5% 8.5%

Bonde et al.: Lancet, 1998.

Probability of pregnancy within one menstrual cycle

Sperm concentration, mill/ml

%

4,867 men from Copenhagen area in Denmark

Results compatible with decrease since early 1940’s

Slight increase in sperm concentration and total sperm

count 1996-2010

Only 23% had sperm concentration >40 mill/ml AND

>9% morphologically normal spermatozoa

Approx. 15% had a sperm concentration that indicate a

high risk of needing future fertility treatment, and

another 27% will be at risk of a prolonged waiting time

to pregnancy

41

Normal young men

Sperm conc. (mill/ml)

55 63

63

55

44

43-48

67 48

(62)

Jørgensen et al (2002, 2011),

Richthoff et al (2000),

Axelsson et al (2011)

Punab et al (2002),

Tsarev et al (2003),

Paasch et al (2008)

Fernandez et al (2010)

Semen quality studies

Decrease in Finnish men (and maybe also in French)

Geographical differences, lowest levels in Norway,

Denmark, Germany (and maybe Switzerland)

High frequency of men with low sperm counts in all

(investigated) European countries

Many men at risk of impaired fertility

Also low among young Americans?

Other male genital health problems

Testicular Cancer

”Association of Nordic Cancer Registries” and ”Cancer in Germany”

0

2

4

6

8

10

12

1943

1947

1951

1955

1959

1963

1967

1971

1975

1979

1983

1987

1991

1995

1999

2003

Inc

ide

nc

e r

ate

s (

pe

r 1

00

,00

0),

WS

P

Denmark

Norway

Germany

Sweden

Finland

Semen quality

• Reduced semen quality may cause fertility problems

and have an impact on fertility rates

• Semen quality is a risk factor for

• reduced capacity for testosterone production

• testicular cancer

• morbidity and mortality?

Should reduced semen quality be seen as a warning

of general health problems?

Testicular Dysgenesis Syndrome

TESTICULAR

DYSGENESIS

DISTURBED

SERTOLI

CELL

FUNCTION

DECREASED

LEYDIG CELL

FUNCTION

IMPAIRED

GERM

CELL

DIFFEREN-

TIATION

ANDROGEN

INSUFFICIENCY

REDUCED SEMEN

QUALITY

TESTICULAR

CANCER

HYPOSPADIAS

TESTICULAR

MALDESCENT

Environmental factors

incl. endocrine

disrupters

Genetic defects

incl. 45,X/46,XY and

point mutations

CIS

Prenatal period Postnatal period

Prenatal vs. adulthood exposures

TESTICULAR

DYSGENESIS

REDUCED SEMEN

QUALITY

Environmental factors

incl. endocrine

disrupters

Genetic defects

incl. 45,X/46,XY and

point mutations

Prenatal period Adulthood

Environmental factors

incl. endocrine

disrupters

Irradiation

Chemotherapy

Occupational events

(toxic events)

Postnatal period

?

TESTICULAR

CANCER

HYPOSPADIAS

TESTICULAR

MALDESCENT

CIS

Conclusions

• Semen quality has approached levels that may

impair fertility

• Testicular cancer incidence is increasing in

many European countries

• Genital malformations of newborn boys have

increased in some European countries

• May all be symptoms of a Testicular

Dysgenesis Syndrome (TDS) of fetal origin