1. Managing unwanted childlessness Dr Jodie Semmler fertility SA Dr Louise Hull Senior lecturer in reproductive medicine WCH, University of Adelaide and fertility SA

2. ‘For unflagging interest and enjoyment, all other forms of success lose their importance in comparison to a household of children’ Theodore Roosevelt

3. Age makes a difference

5. Lifestyle Advice Intercourse every 2-3 days optimises conceptionIntercourse every 2-3 days optimises conception Fertile times of the cycleFertile times of the cycle Moderate alcohol intake (no binges)Moderate alcohol intake (no binges) Stop smokingStop smoking Optimal BMI between 19 and 25Optimal BMI between 19 and 25 Avoid DrugsAvoid Drugs Avoid occupational exposures to solvents etcAvoid occupational exposures to solvents etc Folic acid, Vit B 6 and 12 supplements, Omega 3Folic acid, Vit B 6 and 12 supplements, Omega 3 Vitamin supplementation (Vit E and Selenium)Vitamin supplementation (Vit E and Selenium)

6. Causes of difficulty conceiving Eggs Sperm Need to meet

7. EGGS!

8. Assessing Ovulation Are your cycles regular?Are your cycles regular? Mid luteal prog – day 21 if day 28 cycle, day 28 if 35 day cycle (timing critical)Mid luteal prog – day 21 if day 28 cycle, day 28 if 35 day cycle (timing critical) Basal body temperatureBasal body temperature LH kitsLH kits Cycle trackingCycle tracking

9. Ovarian Reserve Ovarian reserve may be reduced even if ovulatory if ovulatory Assess with egg timer test day 3-5 FSHAMH ovarian volume and antral follicle count If low ovarian reserve –prompt referral for fertility advice. Associated with poor response to gonadotrophins, possibly poor oocyte and embryo quality if markedly reduced, ?increased miscarriage

10. Anovulation Hypothalamic dysfunction (normal FSH/LH)Hypothalamic dysfunction (normal FSH/LH) Hypogonadotrophic hypogonadism (low FSH/LH)Hypogonadotrophic hypogonadism (low FSH/LH) Premature menopause (high FSH/LH)Premature menopause (high FSH/LH) Hyperprolactinaemia (high PRL)Hyperprolactinaemia (high PRL) Abnormal thyroid function (high TSH)Abnormal thyroid function (high TSH) Polycystic ovarian syndromePolycystic ovarian syndrome Tests- day 3 FSH, LH, PRL, TSH, androgens if suspect PCOSTests- day 3 FSH, LH, PRL, TSH, androgens if suspect PCOS USS pelvis –ovarian reserve, PCOSUSS pelvis –ovarian reserve, PCOS

11. Hypothalamic Dysfunction Simple Environmental CausesSimple Environmental Causes Exam/ other stressExam/ other stress TravelTravel PerimenarchalPerimenarchal Weight related CausesWeight related Causes Anorexia/malnutritianAnorexia/malnutritian Exercise induced amenorrhoeaExercise induced amenorrhoea PsychiatricPsychiatric DepressionDepression Organic Causes (pan hypopit)Organic Causes (pan hypopit) Brain tumors –need MRIBrain tumors –need MRI Endocrine disordersEndocrine disorders

12. Ovarian Failure high FSH and LH and low E2, normal prolactin and thyroid Further Investigations may include: chromosomes autoantibody screen bone mass lipids Treatment – donor oocyte programme donor oocyte programme estrogen replacement therapy estrogen replacement therapy counselling counselling

13. Prolactin Elevated prolactin on 2 occasionsElevated prolactin on 2 occasions Galactorrhoea, breast discomfort, visual field abnormalitiesGalactorrhoea, breast discomfort, visual field abnormalities MRI/CT pituitaryMRI/CT pituitary Treat with Carbergoline (0.5mg weekly)Treat with Carbergoline (0.5mg weekly)

14. Thyroid disorders TSH to screen SymptomsSymptoms Goitre/thyroid enlargementGoitre/thyroid enlargement Referral to endocrinologist/surgeon for treatment and ongoing care.Referral to endocrinologist/surgeon for treatment and ongoing care.

15. Polycystic ovarian syndrome 2 out of 3 of: Oligo/ammenorrhoeaOligo/ammenorrhoea Clinical and/or biochemical signs of hyperandrogenismClinical and/or biochemical signs of hyperandrogenism UltrasoundUltrasound And exclude other causes of anovulationAnd exclude other causes of anovulation PCOS consensus agreement ESHRE/ASRM (Rotterdam) 2003 Hum. Reprod, (2004) 19,1:41-47

16. PCOS Investigations PCOS Investigations Investigations: Insulin resistance (blood glucose) Lipids Lipids Endometrial thickness

17. PCOS fertility treatment Weight lossWeight loss ClomipheneClomiphene MetforminMetformin Ovulation Induction with FSHOvulation Induction with FSH Ovarian drillingOvarian drilling IVF –risk of OHSSIVF –risk of OHSS

18. Ovulation Induction

19. Sperm

20. Male Factor Disorder HistoryHistory –Previous surgery/trauma –Congenital problems –Infections (mumps orchitis/STDs) –Other illnesses (cancer/chemotherapy) –Smoking, drinking, drugs –Occupational exposures

21. Semen Analysis More than 1 semen Analysis usually required (3 months apart) Normal SANormal SA >20 million per ml>20 million per ml >50% forward motility>50% forward motility >3% normal morphology (WHO strict criteria)>3% normal morphology (WHO strict criteria)

22. Other sperm defects Kruger et al 1986 (strict morphological criteria)Kruger et al 1986 (strict morphological criteria) <15% normal morphology (old criteria) associated with reduced IVF fertilisation even with normal counts. No data yet with new reference ranges, 4% normal shapes is 5 th centile, may be fertilisation issue if less than eg 8% <15% normal morphology (old criteria) associated with reduced IVF fertilisation even with normal counts. No data yet with new reference ranges, 4% normal shapes is 5 th centile, may be fertilisation issue if less than eg 8% ICSI restored fertilisation ratesICSI restored fertilisation rates

23. Investigation of an abnormal semen Analysis If semen Analysis abnormalIf semen Analysis abnormal - repeat S.A. - repeat S.A. If mild/ moderate oligozoospermic (majority)If mild/ moderate oligozoospermic (majority) - IUI/IVF/ICSI - IUI/IVF/ICSI If azoospermic/severe oligozoospermiaIf azoospermic/severe oligozoospermia -further investigations

24. Investigations of Severe Semen Defects FSH/LH/testosterone/PRL/TSH If abnormal then MRI pituitary USS testes (tumour) Chromosomes/CF mutations/Y chromosome deletions

25. Management Hypogonadotrophic hypogonadism -FSH treatment Mild sperm defects -IUI Testicular failure -ICSI/TESA/donor sperm Obstructive azoospermia -PESA/TESA

26. Intrauterine Insemination 15-40% chance of pregnancy over 3 cycles (very dependent on patient selection) FSH Injections to ensure 1 or 2 eggs present at insemination Need patent fallopian tubes Risk of multiple pregnancy Low sperm morphology, unexplained and endometriosis patients do poorly

27. PESA/TESA

28. ICSI IVF+/- ICSI approx 50% chance of pregnancy in 1 cycle if < 38yrs

29. Meeting up

30. Assessing Sexual dysfunction (5%) Male history importantMale history important –How often do you make love? –Do you get erections? –Can you penetrate your partner deeply? –Do you reach orgasm? –Do you ejaculate?

31. Assessing Tubal Damage Have you had tubal surgery, endometriosis, painful periods, appendicitis or infections like chlamydia?Have you had tubal surgery, endometriosis, painful periods, appendicitis or infections like chlamydia? If no- HSG (reliable indicator of tubal patency not obstruction)If no- HSG (reliable indicator of tubal patency not obstruction) If yes- consider laparoscopy and dyeIf yes- consider laparoscopy and dye History of Tubal ligation/reversal – high chance tubal issuesHistory of Tubal ligation/reversal – high chance tubal issues Congenital anomalies - best assessed by MRI, 3D ultrasound, Hy Cosi or saline sonogram. HSG not as accurate for thisCongenital anomalies - best assessed by MRI, 3D ultrasound, Hy Cosi or saline sonogram. HSG not as accurate for this

32. Endometriosis Tubal damage, Oxidative damage to oocytes/embryos Eutopic endometrial changes (implantation problems) Painful intercourse Management: Surgery, GnRH agonists before IVF

33. Unexplained Failed Fertilisation (5-10% IVF cycles) Implantation Failure Recurrent Miscarriage Other causes

34. IVF

35. Who needs referral?

36. Referral to Fertility Services All couples concerned about fertility should be offered a consultationAll couples concerned about fertility should be offered a consultation Further investigation should be offered after 1 year of failing to conceiveFurther investigation should be offered after 1 year of failing to conceive Earlier investigation should be offered to:Earlier investigation should be offered to: –Women >35 years –History suggestive of anovulation, tubal disease, pelvic surgery, endometriosis or male factor problems –Family history of early menopause

37. The goal of treatment A single healthy baby born at term