1. Fawaz Edris MD, ARDMS, AAACS, FRCSC, FACOG

2. Background  Definition: 1 yr unprotected coitus without conception  10-15% couples affected  Etiology Couples: ○ 35% Tubal and pelvic pathology ○ 35 % Male problems ○ 15% Ovulatory dysfunction ○ 10% Unexplained ○ 5% unusual causes

3. Background  Etiology Women: ○ 40% Tubal and pelvic pathology ○ 40% Ovulatory dysfunction ○ 10% Unexplained Infertility ○ 10% Unusual causes  Normal couple: 25-30% chance of pregnancy per ovulatory cycle  Fertility decreases with age

4. Infertility Time of Exposure % Pregnant 3 months60% 6 months70% 1 year85% 18 months 90%

5. Approach to Infertility  DDX  Hx  Px  Tests/Inv  Dx  Rx

6. Approach to Infertility  Production  Storage  Delivery

7. Male Infertility 1. Production: Hypothalamus Anterior Pituitary Testes

8. Hypothalamic-Pituitary-Gonadal Axis

9. Male Infertility  1. Production Hypothalamus ○ Congenital abnormalities of hypothalamus e.g. Kallman’s syndrome ○ Starvation, stress or severe illness ○ Tumors (craniopharyngioma, metastatic tumor) ○ Head injury ○ Inflammation (sarcoidosis) ○ Infection (tuberculosis) ○ XRT ○ Drugs: marijuana,

10. Male Infertility  1. Production: Pituitary ○ Endocrine: thyroid, prolactin ○ Tumors ○ Inflammation: sarcoidosis, meningitis ○ Infiltration ○ Infarction ○ Trauma/XRT ○ Drugs: anabolic steroids

11. Male Infertility  Production: Testes: ○ Congenital: Klinefelters (XYY), developmental disorders ○ Disorders of gonadal steroidgenesis ○ Infection: chlamydia, prostatitis, mumps orchitis ○ Autoimmune ○ Cryptorchidism ○ Tumors; chemo/XRT ○ Drugs / alcohol ○ Vascular: testicular torsion

12. Male Infertility  2. Storage: Temperature ○ Rise in scrotal temperature ○ Occupation ○ Varicocoele

13. Male Infertility  3. Delivery: Impotence/Ejaculation ○ Neurogenic: medications (α-blockers, methyldopa) ○ Endocrine: diabetes ○ Congenital: absence vas deferens (CF) ○ Genetic: cystic fibrosis ○ Primary ciliary dyskinesia: Kartagener syndrome ○ Hypospadia ○ Vasectomy

14. Male Infertility  History: Previous children Infections: prostatitis, STD, mumps orchitis Trauma to head or testicles Surgery to testicles or hernia Occupation (sitting, bio hazards, XRT) Chemo or Radio therapy Ethanol or Smoking Medication Medical history (DM, HTN) Previous investigations

15. Male Infertility  Physical Anatomy (meatus) Testicular size Varicocele (valsalva) Rectal exam (protatitis, discharge)

16. Male Infertility  Investigations: semen analysis ○ Abstain 2-4 days prior ○ At least 2 samples over different period of time If abnormal: ○ Blood work: FSH, LH, TSH, testosterone, PRL ○ Testicular U/S ○ Chromosomal analysis

17. Male Infertility  Semen analysis: WHO (1992) ○ Volume> 2.0 mL ○ Sperm> 20 million/mL ○ Motility> 50% forward progression or > 25% rapid progression within 60 min ○ Morphology> 30% normal forms ○ WBC< 1 million/mL

18. Male Infertility  Tx / Interventions: Treat underlying causes Intrauterine Insemination (IUI) Intracytoplasmic Sperm Injection (ICSI)

19. Female Infertility  Fecundability: probability of achieving a pregnancy within 1 menstrual cycle (25%)  Fecundity: ability to achieve a live birth within 1 menstrual cycle (6%)

20. Female Infertility  Production  Storage  Delivery

21. Female Fertility  Production: Hypothalamus Pituitary Ovary

22. Hypothalamic-Pituitary-Gonadal Axis

24. Female Infertility  Hypothalamus: Stress Exercise Eating disorders Psychogenic Congenital/genetic: Kallman’s syndrome (hyposmia & hypoplasia olfactory lobes of brain) Starvation/stress or severe illness Tumors (craniopharyngioma, metastatic tumor) Head injury Inflammation (sarcoidosis) Infection (tuberculosis) XRT Drugs

25. Female Infertility  Pituitary: Sheehan syndrome Tumors: Pituitary adenoma, metastatic Empty sella syndrome Inappropriate gonadal steroid feedback: ○ estrogen excess: obesity/ tumors ○ estrogen deficiency: aromatase deficiency/ ER gene mutation ○ androgen excess: adrenal or ovarian ○ PCOS Testicular feminization (46 XY) - absence androgen receptors

26. Female Infertility  Ovary Gonadal dysgenesis - Turner’s Syndrome 45XO or mosaics 46 XX/45 XO Testicular feminization XRT / Chemo for childhood malignancies Premature ovarian failure

27. Female Infertility  Storage (R.P.L. unless severe) Uterine abnormalities Mullerian Agenesis: Mayer-Rokitansky- Kuster-Hauser syndrome Asherman’s syndrome Leiomyoma Luteal phase deficiency

28. Female Infertility  Delivery: Uterine abnormalities Vaginal septum Tubal Disease ○ Infections/ STD/PID ○ Ruptured appendix ○ Septic abortion Endometriosis

29. Female Infertility  History: Age GTPAL Regulatory of period Prolactin S/S Thyroid S/S Infections, Surgeries Medication, Smoking, Ethanol Medical history Previous investigations

30. Female Infertility  Examination: Thyroid Breast (milk) Abdomen (masses, scars) Vaginal (abnormalities) Bimanual (Uterus, masses)

31. Investigations  Blood work: TSH PRL D3 FSH D3 LH Luteal phase Progesterone  Imaging: Pelvic Ultrasound HSG  Diagnostic Laparoscopy (later)

32. Treatment  Treat the underlying cause  Medical  Surgical

33. Treatment  Anovulation: Clomiphene induction  IUI Gonadotropin  IUI  IVF Bilateral tubal disease Unexplained infertility after Gonadotropin + IUI failure. Failure of the above  ICSI Male factor Unexplained infertility

34. Take Home Points  DDx – Hx – Px – Inv - Rx  Age is important factor for female  Hypothalamic-Pituitary-Gonadal axis central in working up both male and female infertility  Investigations: Male: Sperms Female: Tubes (HSG) + Ovaries (FSH, LH, PRL, TSH)

35. Thank you