Male infertility (2)

Male infertility (2)

1. MALE INFERTILITY 1

2. CONTENTS Introduction Spermatogenesis Causes Evaluation Management What’s new in male infertility 2

3. INTRODUCTION INFERTILITY - one year of unprotected intercourse without conception SUBFERTILITY- couples who exhibit decreased reproductive efficiency FECUNDABILITY - probability of achieving pregnancy within a single menstrual cycle FECUNDITY - probability of achieving live birth within a cycle . Speroff 15 th ed. 3

4. SPERMATOGENSIS During embryogensis , there are a pproximately 300 thousand spermatogonia in each gonad. Each undergoes mitotic division, and by puberty 600 million in each testis. 4

5. Sperm production takes place in seminiferous tubules within testis. Spermatogenesis takes about 70 days Adult males produce 100-200 million sperm each day. Leydig cells produce testosterone (which along with FSH , stimulates spermatogenesis). Maturation of sperms takes place in epididymis . Transport of sperms – vas deferens Speroff 15 th ed. 5

6. 1.Plasma membrane 2.Outer acrosomal membrane 3.Acrosome 4.Inner acrosomal membrane 5.Nucleus 6.Proximal centriole 7.Rest of the distal centriole 8.Thick outer longitudinal fibers 9.Mitochondrion 10.Axoneme 11.Anulus 12.Ring fibers A.Head B.Neck C.Mid piece D.Principal piece E.Tail 6 SPERM STRUCTURE

7. Physiology of Semen after Ejaculation Liquefaction Capacitation Acrosome reaction Cortical reaction 7

8. Relative prevalence of the etiologies of infertility Percentage Male Factor 20-30 Both male & Female 10-40 Female Factor 40-55 Unexplained Infertility 10-20 8

9. SEMEN ANALYSIS Abstinence for 2-3 days (Not less than 2 days & not more than 7 days) Abnormal sperm count - analysis at least after 4 weeks. Analysis : Volume, number , motility, morphology 9

10. Short intervals of abstinence- decreases the sperm density and semen volume. Longer abstinence intervals - increase in the proportion of dead, immotile and morphologically abnormal sperms. Semen specimen should be collected in a clean container. Semen can also be collected in a silastic condom, which does not contain any antispermicidal agents. Semen sample should be examined within an hour after collection 10

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12. Parameters Normal Reference Values Lower Reference Limits Volume 1.5-5.0 mL 1.5 (1.4-1.7) mL P H >7.2 Viscosity <3 Sperm Concentration >20 million/mL 15 (12-16) million/mL Total sperm number >40 million/ejaculate 39 (33-46) million/ejaculate Percent motility >50% 40 (38-42)% Forward progression >2 (scale 0-4) 32 (31-34)% Normal morphology >15,30,50% normal 4(3-4)% Round cells <5 million/mL Sperm agglutination <2 (Scale 0-3) 12

13. Semen analysis Ejaculate volume and pH: Low or absent – CBAVD, ejaculatory duct obstruction, hypogonadism , retrograde ejaculation. High volume (>5ml)- Inflammation of accessory gland Seminal vesicle secretions are alkaline and contains fructose. EDO- semen is acidic (prostrate secretions), and has no sperm or fructose. 13

14. Sperm concentration and total sperm count: Azoospermia , Oligospermia OBSTRUCTIVE : blockage in ductal system ( CBAVD, scrotal or inguinal surgery) NON OBSTRUCTIVE: primary testicular failure, endocrinopathies that suppress spermatogenesis. Endocrine and genetic evaluation indicated in men with severe oligospermia . Total sperm count is the product of multiplying semen volume and sperm concentration. 14

15. Abnormalities of sperm Oligozoospermia - reduced sperm count Asthenozoospermia – reduced sperm motility Teratozoospermia - increased abnormal sperms Oligoasthenoteratozoospermia – sperm variables are subnormal Azoospermia - no sperm in semen Aspermia – no ejaculate Leucocytospermia – increased WBC Necrozoospermia – all sperms are nonvaiable and motile. 15

16. Causes of Male I nfertility Hypothalamic pitutary disorders (1-2%) Primary gonadal disorders (30-40%) Disorders of sperm transport (10-20%) Idiopathic (40-50%) 16

17. Hypothalamic pitutary disorders Idiopathic isolated gonadotropin deficiency Kallmann syndrome Single gene mutations Hypothalamic and pitutary tumours Infiltrative disease Hyperprolactinemia Drugs Chronic systemic illness and malnutrition Infections Obesity 17

18. Primary gonadal disorders Klinefelter syndrome Y chromosome deletions Cryptorchidism Varicoceles Infections Drugs Radiation Environmental gonadotoxins Chronic illness 18

19. Disorders of sperm transport Epididymal obstruction or dysfunction Infections causing obstruction to vas deferns Vasectomy Kartagener syndrome Ejaculatory dysfunction Young syndrome 19

20. CAUSES PRE TESTICULAR TESTICULAR POST TESTICULAR ENDOCRINE: Hypogonadotropic hypogonadism Hypothyroidism Hyperprolactinaemia Diabetes COITAL DISORDERS: Erectile dysfunction Ejaculatory failure GENETIC: Klinefelter syndrome Y chromosome deletion Immotile cilia syndrome CONGENITAL: Cyptorchidism Infective Antispermatogenic agents heat, irradiation, drugs, chemotherapy VASCULAR : Torsion Varicocele IMMUNOLOGICAL IDIOPATHIC OBSTRUCTIVE: Epdidymal congenital infective Vasal Genetic: cystic fibrosis. Accquired : Vasectomy Ejaculatory duct obstruction Accessory gland infection Immunological Idiopathic post vasectomy 20

21. Evaluation of male infertility To Identify and correct specific cause To identify the individuals whose fertility cannot be corrected but could be over come by IUI and ART. To identify- Genetic abnormality To identify any medical condition that requires specific attention To identify the individuals whose infertility can neither be corrected or overcome with ART, in whom adoption or donor sperm are considered. 21

22. HISTORY Duration of infertility and previous infertility Coital frequency and sexual dysfunction Any previous evaluation or treatment of infertility Childhood illness and developmental history Previous surgery and its outcome, systemic medical illness History of exposure to STD Exposure to environmental toxins Current medications and allergies Occupational exposure to tobacco, alcohol and other drugs 22

23. Physical examinations Examination of penis, Palpation of testes and measurement of their size Presence and consistency of both vasa and epididymides Presence of any varicocele Secondary sexual characteristics, hair distribution, and breast development Digital rectal examination 23

24. Other investigations Absence of fructose: Congenital absence of seminal vesicle, Partial duct obstruction. Semen culture (If pus cells in microscopy) Urologic evaluation Endocrine evaluation - FSH, LH, Testosterone. Transurethral or transcrotal USG Renal ultrasonography Testis biopsy- azoospermia Vasography 24

25. Endocrine evaluation: Indications: Abnormal semen analysis S erum FSH,LH and testosterone Hypogonadotropic gonadism - FSH,LH,testosterone low Abnormal spermatogenesis- FSH normal/increased, LH& testosterone normal Testicular failure- high FSH and LH, low /normal testosterone 25

26. Genetic evaluation 1) Mutations within cystic fibrosis transmembrane conductance regualtor (CTFR gene) 2) Chromosomal anomalies resulting testicular dysfunction – klinefelter syndrome 3) Y chromosome deletions associated with abnormalities of spermatogeneis . 26

27. Transrectal ultrasonography: less invasive indicated in diagnosis s evere oligospermia or azoospermia . Renal ultrasonography: unilateral or bilateral vasal agenesis. Trans scrotal ultrasonography : To confirm physical findings. Detect non palpable varicocele . 27

28. Testis biopsy : diagnostic purpose in azoospermic men. when the testicular biopsy shows normal spermatogenesis obstruction to the vas deferens is suspected. 28

29. Drugs that impair male infertility 29

30. Treatment Hypogonadotropic hypogonadism : Pulsatile GnRh , hCG , hMG , Testosterone, Clomiphen citrate, Tamoxifen Hypergonadotropic hypogonadism : IVF/ICSE, Donor sperm, Adaptation Androgen, FSH, Clomiphen Hyperprolactinemia - Dopamine agonists Strict control of DM, Hypothyroid 30

31. Pretesticular Erectile dysfunction- PDE5 Inhibitor (Sildenafil) For ejaculatory problems(Retrograde ejaculation): Imipramine , Pseudoephedrine/Ephedrine , Phenylpropalamine Retrograde ejaculation, Neurogenic impotence, Severe Hypospadias Intrauterine insemination (IUI) 31

32. Post testicular Prior vasectomy (most common cause)- microsurgical vasovasostomy (better if less than 5 years) Epididymal or vasal obstruction MESA PESA TESE TESA/FNA ICSI 32

33. Surgical treatment for male infertility Vasovasotomy Vasoepididymostomy Transurethral resection of ejaculatory ducts Varicocele repair Orchiopexy Vibratory stimualtion and electro ejacualtion 33

34. surgical management Cryptorchidism- Orchidopexy at 2-3 year of age Varicocele - High ligation of internal spermatic vein Gonadal failure- Surgical retrieval of spermatozoa, followed by ICSI 34

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