Male fertility disorders

Transcription

1 Male fertility disorders Etiology diagnosis therapeutic approaches Dr. Cornelia Roggenbuck September 29, 2009 Orthomol pharmazeutische Vertriebs GmbH Content Fertility Facts and figures Factors of influence The male reproductive system Tips and information Micronutrients Conclusions 1

2 Facts and figures Reproductiveness = Fertility Situation in Germany 15% (1.5 million) of all couples are involuntarily childless 3-4% of all German males are infertile In 40% of the cases there is no cause detectable (idiopathic infertility) * 2 million at least temporarily General factors of influence Alcohol Stress Age Smoking Underweight Environment: pollutants, estrogens Fatherhood Overweight 2

3 The age factor Sperm density remains almost normal Sperm motility and proportion of normally shaped sperms decreases BUT: Generally fertility and spermatogenesis remain into old age Problem: decreasing number of sperms Analysis of 61 studies Observation period: 1938 to 1991 Sperm density is decreasing Sperms (n x 10 6 /ml) 1938: 113 m/ml 1990: 66 m/ml Ejaculate volume is decreasing Possible causes: Softeners in packaging material Estrogens in the potable water???? Year Carlsen E, et al. BMJ 1992;305:

4 Male reproductive system Bladder Spermatic duct (Vas deferens) Urethra Seminal vesicle Prostate gland Epididymides Testes Sperm cell formation and maturation Per second approx. 1,000 sperms are produced, 3 4 million per hour approx. 78 days Time 4

5 Mature spermatozoon (sperm cell) Cap (acrosome) Nucleus Midpiece (rich in mitochondria) Tail Head: contains DNA Cap: enzymes facilitating the penetration into the egg cell Midpiece: cell organelles (mitochondria) supply energy for the forward motion Tail: generates motion Normal spermiogram Criteria Reference values Ejaculate volume >2 ml Sperm density 20 million/ml Motility: - Forward progression > 50% - Rapid linear motility > 25% Normal morphology > 30% Quality of sperms is essential for successful fertilization. 5

6 Diagnosis Spermiogram (after 5 days of abstinence) Quantity Motility Morphology Vitality Hormone analyses (blood) FSH level Testosterone level Ultrasonic examination (testicles) Varicocele (unilateral is very common) Obstruction of sperm ducts Causes of male infertility Hormonal causes Low testosterone values Less frequent: dysfunction of the thyroid gland Diseases of the testicles Undescended testicles Varicoceles Diseases/inflammation of the testicles, epididymis and seminal duct Immunological causes Antisperm-antibodies 6

7 Causes of male infertility Idiopathic infertility At least in 32% of the cases Exclusion process -> no organic cause detectable, but reduced sperm quality Other causes Varicocele (varicose veins) 19%, infections 9%, hormonal causes 9%, abnormal testicle position (cryptorchidism) 9% In many cases there has been very little chance so far of improving an insufficient sperm quality 7

8 Micronutrients Now there is a dietary therapeutic option. Oxidative stress Studies demonstrate the negative effects of oxidative stress on sperm quality 1,2 Infertile patients have a higher concentration of free radicals than healthy controls 3 Patients with fertility disorders have a diminished antioxidant status 4 Men with increased DNA strand breaks also have lower fertility rates 5,6 1 Tremellen K. Human Reprod Update 2008; Agarwal A, et al. Fertil Steril 2003;79(4): Agarwal A, et al. Fertil Steril 2005;84(4): Khosrowbeygi A et al.bmc Clin Pathol 2007;7:6. 5. Cocuzza, et al. Int Braz J Urol 2007;33(5): Agarwal, A, et al. Reprod Biomed Online 2004;8(6):

9 Antioxidant status influences sperm quality Antioxidant capacity correlates positively with sperm quality (r=0.45) and sperm morphology (r=0.45) 8-isoprostane (marker for oxidative stress) correlates negatively with sperm motility and sperm morphology Antioxidant status and oxidative stress in the seminal plasma of fertile and infertile men Antioxidant capacity Oxidative Stress -> Lower concentration of antioxidants in the seminal plasma is a significant factor in the etiology of male fertility disorders Khosrowbeygi et al. BMC Clin Pathology; 2007; 7:6. Vitamin E Occurs naturally in oils and nuts Antioxidative effect Protects the cell membrane of the sperms against free radicals 1 Positive effect on sperm motility 2 1 Agarwal 2005 J Androl 2005;26(6): Suleiman SA, et al..j Androl 1996;17(5):

10 Vitamin E intervention study Randomized, placebocontrolled n=52 men with asthenozoospermia 6-month administration of vitamin E -> oxidative stress marker (MDA) -> sperm motility Lower MDA concentration and higher sperm motility after administration of vitamin E 1 Before intervention After intervention MDA= malonic dialdehyde Suleiman, et al. J Androl 1996; 17: Vitamin C Occurs naturally in citrus fruit, bell peppers, califlower, tomatoes Antioxidative effect Protects the genetic information (DNA) of the sperms against free radicals Oxidative damage to the sperm DNA leads to impaired sperm function, infertility and congenital defects Regenerates vitamin E Positive effect on sperm motility, normal sperm shape and sperm density 10

11 Oxidative stress / vitamin C (2/2) 13 men with oligospermia, 1000 mg/d vitamin C, 2 months % share 80 million/ ml Motility Morphology Sperm density before intervention after intervention p<0,001 Akmal, et al., WAJM 2006;23(4): Carotenoids Occurs naturally in carrots, tomatoes, collard greens, lamb s lettuce Antioxidative effect Protects the genetic information (DNA) of the sperms against free radicals Positive effect on sperm density and the number of forward progressing sperms 11

12 Vitamin B 6, B 12, folic acid Occurs naturally in green leafy vegetables, meat, fish, sauerkraut Important for the degradation of homocysteine, a metabolite High homocysteine concentration means deterioration of embryo quality according to IVF/ ICSI (Ebisch et al., 2006) 1 An increased homocysteine level is thought to be related to reproduction problems 2 Homocysteine Vit B 6 Cysteine Folic acid Vit B 12 Methionine 1. Ebisch et al., Hum Reprod Update 2006; 21(7): Forges T, et al. Hum Reprod Update 2007; Wallock LM, et al. Fertil Steril 2001;75(2): Folic acid study A recent study shows that men s eating habits play an important role: Study with 97 men / nutrition survey incl. supplements The men with the highest uptake of folic acid ( µg/d) had up to 30 percent fewer sperms with various forms of aneuploidy (genome mutation) This often leads to miscarriages or diseases such as Down s syndrome or Turner s syndrome Young SS, et al. Hum Reprod May;23(5):

13 Omega-3 fatty acids Occurs naturally in fish Omega-3 fatty acids are an important component of the sperm membrane They improve the elasticity of the sperm membrane important for successful fertilization Sperm membranes play an active part in capacitation and acrosome reaction L-Carnitine / Coenzyme Q 10 Occurs naturally in meat (L-carnitine), fish, eggs (coenzyme Q 10 ) L-Carnitine: Supports the transport of long-chain fatty acids to the mitochondria 1,2 -> important function in the sperms energy generation Positive effect on sperm motility 2 Coenzyme Q 10 : Powerful antioxidant and radical scavenger 3,4 Positive effect on sperm motility and forward motility 4 1. Balercia G, et al. Fertil Steril 2005;84(3): Zhou X, et al. Asia Pac J Clin Nutr 2007;16(1): Balercia G, et al. Fertil Steril 2004;81(1): Littaru GP, et al. Mol Biotechnol 2007;37:

14 L-Carnitine - Metaanalysis Evaluation of 4 studies Forward Motility * Intensity (95% CI) Administration of L-carnitine Forward motility Proportion of atypical shapes -> L-carnitine improves sperm quality significantly -> Higher pregnancy rate (p<0.0001) Favors control Favors test * Zhou X, et al. Asia Pac J Clin Nutr 2007; 16 (Suppl 1): N-Acetylcysteine Occurs naturally in beans, eggs, fish, meat Component of an antioxidative enzyme (glutathione peroxidase) with an important function in the seminiferous tubules and sperm cells Protects the sperm cell membranes Promotes sperm molitily and increases the proportion of normally shaped sperms 14

15 Zinc Occurs naturally in meat, eggs, milk, cheese Important component of antioxidative enzymes also present in the sperms Together with the fibrous sheath of the sperms it forms a complex which protects the fibrous sheath against oxidation and thus stiffening Zinc shortage: reduced testosterone level and diminished number of sperms 2 1. Wroblewski. (Med. Dissertation); Selenium Occurs naturally in meat, fish, eggs, asparagus Cofactor of glutathione peroxidase Enzyme activity influences the vitality, normal shape and motility of the sperms Selenium protein (PHGPx) acts as a structural protein in the mitochondrium of mature sperms PHGPx correlates with sperm motility Proportion of motile sperm (%) Foresta C, et al. Biol Reprod 2002;67:

16 Micronutrient combination Study: Effect of folic acid and zinc on fertility 103 patients Duration: 6.5 months Increase in sperm density (see fig.) and normal sperm shape Sperm density (million/ml) 74% increase week 0 week 26 Wong WY, et al. Fertil Steril 2002;77(3): Orthomol Fertil plus Composition Micronutrient daily portion Micronutrient daily portion Vitamins and trace elements Vitamin E 120 mg Vitamin C 250 mg Folic acid 800 µg Vitamin B 6 3,5 mg Vitamin B 12 9 µg Mixed carotenoids 3 mg Trace elements Zinc 40 mg Selenium 60 µg Copper 1000 µg Other micronutrients Omega-3 fatty acids 170 mg L-Carnitine 440 mg Coenzyme Q mg N-Acetylcysteine 80 mg 16

17 Orthomol Fertil plus Orthomol Fertil plus, the dietary food for special medical purposes, improves sperm motility, sperm density and normal sperm shape, i.e. the decisive parameters of sperm quality 17