1. Male infertility General Practice Perspective Siya Sharma Consultant Gynaecologist & Obstetrician Kings Lynn GP Update on Women’s Health 14-9-2013 1

2. My Interest Areas Infertility Management, Reproductive Medicine, IVF Laparoscopic & Hysteroscopic Surgery Ovulatory and Menstrual disorders 2

3. Aims of the session To discuss Male infertility aspects relevant to general practice Diagnosis and Treatment options 3

4. Q - Permanently sterile men ? A – 1% Do We Know? 4

5. Myths 1.A man with azoospermia cannot become a biological father - “donor sperm or adoption are the only choices” 2.A man who has had chemotherapy before, is sterile and cannot father a child 3.“Your FSH is too high: we will never find sperm” 4.A man with oligo-astheno-teratozoospermia (OAT) does not need to see a urologist / andrologist –“his sperm can be used for IVF and ICSI” 5

6. Infertility – Factors & Incidence 6 (Hull MG, et al. BMJ 1985;291:1693–7. School of Public Health, University of Leeds, The management of subfertility. Effective Health Care 1992;1(3):1–240. Thonneau P, et al. Hum Reprod 1991;6:811–6.

7. Male Infertility Incidence Male infertility is a factor in ¼ to ½ (25 - 50%) of subfertile couples Main reasons  abnormal semen quality - sexual dysfunction 7

8. Male Infertility-Specific Causes 8 Seminiferous tubule dysfunction 60-80% Post-testicular abnormalities, defect & blocks 10-20% Primary hypogonadism 10-15% Secondary hypogonadism (Hypothalamic-pituitary disorders) 1-2%

9. Male Infertility - Aetiology CategoryExamples Primary gonadal disorders CongenitalAcquired Y-chromosome abn. Klinefelter syndrome Androgen insensitivity 5  -reductase deficiency Haemochromatosis Cryptorchidism Anorchia Varicocoele Viral orchitis Epididymo-orchitis Drugs / toxins Radiation Hyperthermia Trauma / torsion Immunological Systemic illness 9

10. CategoryExamples Hypothalamic-pituitary disorders CongenitalAcquired Kallmann syndrome IHH – idiopathic hypogonadotropic hypogonadism Multi-system disorders: - Prader-Willi syndrome - Laurence-Moon-Biedl syndrome Haemochromatosis Pituitary tumours Hypothalamic tumours Hormone-related: - Hyperprolactinaemia - Androgen - Estrogen - Cortisol Infiltrative disorders Vascular Drugs Chronic illness Nutritional deficiency Obesity Male Infertility - Aetiology 10

11. Testosterone concentration in testis/testes Q – More or Less than blood A - More Q – How many times more A - 20-100 times more Brain Storming 11

12. Sexual function Pubertal development Coitus – Frequency (2-3/week), timing Libido – do you have desire for coitus? Erectile function – do you have normal erections ? Ejaculatory function – do you ejaculate ? 12

13. Past Surgical History 13 Varicocoele Cryptorchidism Trauma Torsion Inguinal SurgeryScrotal

14. Medical history Diabetes mellitus Neurological disease Hypothalamic-pituitary disorders Cancer survivors Viral orchitis 14

15. Medical history Hyposmia / anosmia – Kallmann Syndrome Headaches/visual disturbance – Prolactinoma Recurrent respiratory infections – Cystic Fibrosis 15

16. MechanismExamples Gonadotoxins (impair spermatogenesis) Sulfasalazine Methotrexate Cytotoxic chemotherapy Colchicine Nitrofurantoin Erectile dysfunctionBeta-blockers Thiazide diuretics Metoclopramide Ejaculatory failureAlpha-blockers Anti-depressants Phenothiazines AntiandrogenicSpironolactone Cimetidine Hypothalamic-pituitary suppression Testosterone Anabolic steroids Drugs →  prolactin GnRH analogues Drugs of misuseCannabis Heroin Cocaine Drugs Impairing Male Fertility 16

17. Personal History Alcohol > 3-4 units/day detrimental to semen quality Smoking - reduces semen quality - impact on male fertility is uncertain 17

18. Environmental factors Heavy metals Organic solvents Pesticides / herbicides Phytoestrogens Radiation Heat 18

19. Male – Physical Examinations General Genitalia –Meatus normal? –Any scars? –Testes – size/volume, consistency, location/symmetry, masses –Can you feel vas deferens? –Is epidiymis full? –Does the patient have a varicocoele? DRE – Digital rectal examination for prostate 19

20. Male - Anatomy 20

21. Laboratory investigations of infertile male 21

22. Semen analysis –Abstinence 3-5 days –Specimen pot –Transportation to lab –Repeat analysis if abnormal (need minimum of two analyses, three months apart) Male – Lab Investigations 22

23. WHO 2010 Semen Analysis CriteriaLower Reference Value (5 th percentile, 95%CI) Semen volume (mls)1.5 (1.4–1.7) Total sperm number (10 6 per ejaculate) 39 (33–46) Sperm concentration (10 6 per ml)15 (12–16) Total motility (PR + NP, %)40 (38–42) Progressive motility (PR, %)32 (31–34) Vitality (live spermatozoa, %)58 (55–63) 23

24. WHO 2010 Semen Analysis CriteriaLower Reference Value (5 th percentile, 95%CI) Sperm morphology (normal forms, %)4 (3.0–4.0) pH≥7.2 Peroxidase-positive leukocytes (10 6 per ml) <1.0 MAR test (motile spermatozoa with bound particles, %) <50 Immunobead test (motile spermatozoa with bound beads, %) <50 Seminal zinc (ųmol/ejaculate)≥2.4 Seminal fructose (ųmol/ejaculate)≥13 Seminal neutral glucosidase (mU/ejaculate) ≥20 24

25. 25

26. Q – What % of men have sperm quality below the threshold thought compatible with normal fertility (conception within one year) ? A - 20% Quiz 26

27. Azoospermia

28. What to do next if azoospermia is revealed Endocrine assessment – FSH – Testosterone (8-9 am, circadian cycle) 28

29. Consider following when azoospermia is revealed Genetic screen in NOA - no spermatogenesis – Karyotyping, – Y deletions – CF – CBAVD – Hypogonadotrophic hypogonadism – Haemochromatosis – erectile disorders, loss of libido 29

30. Consider referral in azoospermia Whom to refer ? Andrologist or Urologist with andrology interest Geneticist when indicated 30

31. Azoospermia With low volume With normal volume 31

32. Azoospermia Obstructive Obstructive Non-Obstructive Non-Obstructive 32

33. Low volume, acidic azoospermia Volume < 1cc Ph < 7.2 Azoospermia 33

34. Low volume acidic azoospermia Testes - normal in size & consistency FSH - normal Spermatogenesis - normal (OA) Low vol indicates no SV contribution Diagnosis by: - Vasal palpation - TR USS - Fructose assay not required EDO CBAVD

35. Normal Volume Azoospermia Seminal Vesicles are present Ejaculatory ducts are open Differential diagnosis - Non Obstructive Azoospermia (NOA) (spematogenic failure) - Obstructive Azoospermia (OA) (Blockage of vas or epididymis) 35  ✔

36. Normal volume Azoospermia Making a diagnosis of OA Testis - normal in size & consistency Epididymes – full & firm NOA Testis - small in size Epididymes – Normal 36

37. Azoospermia Azoospermia - semen volume and pH are the key for diagnosis –Low volume, acidic pH CBAVD, EDO –Normal volume alkaline NOA, blockage of vas or epididymis 37

38. Male Infertility Treatment Options Conservative Medical Surgical ART 38

39. Treatment in azoospermia Non Obstructive - spematogenic failure,variable - Sperm extraction (testicular biopsy) Obstructive - Blockage of vas or epididymis - Reconstruction - Sperm aspiration 39 

40. Q -Infertile couples undergoing IVF - male factor is solely implicated in ? A - 20% of cases Q – and is contributory in up to ? A - 50% Quiz 40

41. Any Questions Please? 41