1. “My biological clock is running out, doctor” Max Brinsmead MB BS PhD April 2014

2. Hannah 38 and Barry 36 Have been living together for 6 years without contraception but Hannah has never conceived. She now seeks your advice because: “My biological clock is running out, doctor” WHAT ARE THE POSSIBLE CAUSES?

3. Hannah & Barry Differential Diagnosis Female Factors Anovulation Genital tract pathology – tubes & cervix Implantation failure Male Factors Failure of sperm generation Genital tract pathology – epididymis, vas and ejaculatory duct Sperm delivery problems

4. Hannah & Barry with 6 years of infertility Seek your advice because Hannah believes that time is running out WHAT ADDITIONAL INFORMATION DO YOU REQUIRE?

5. History required of Hannah & Barry with 6 years of infertility Previous conceptions, either partner General health, drugs, smoking, exercise etc Past health and any operations Previous STDs Menstrual history Coital history

6. Hannah & Barry with 6 years of infertility Previous conceptions? General health, drugs, smoking, exercise etc Past health and any operations Previous STDs Menstrual history Coital history Hannah TOP at age 18. Barry’s previous wife no conception in 4 years Barry smokes 10-15/day Barry had a “hernia operation” in infancy Hannah suffers recurrent thrush. Was treated for CIN at age 28 Periods every 26-29 days. Mild dysmenorrhoea Coitus 2-3 x per week, no problems

7. Hannah & Barry with 6 years of infertility Do you examine either partner? What tests would you request? Any other advice?

8. Possible Tests for Hannah & Barry Semen analysis Hormone test for ovulation STD screen Antenatal screen especially Rubella & Varicella Basal body temperature chart (BBT) Gene testing for cystic fibrosis, maybe Recommend smoking cessation (Barry) and Folic acid for Hannah (Hysterosalpingogram) (Laparoscopy, hysteroscopy and dye studies)

9. Test Results for Hannah & Barry Semen analysis Routine AN tests BBT Volume 1 ml (NR>2) Count 20) Motility 30% (NR>50) Normal 0% (NR>15) AN tests NAD but non immune to Varicella BBT biphasic but coitus not as frequent as claimed

10. Hannah, 38 & Barry, 36 with 6 years of infertility have a severe male problem What do you do now? Examine either or both? Repeat the semen analysis Do more tests on Hannah? Do more tests on Barry?

11. Hannah & Barry further evaluation Examine Barry Repeat the semen analysis Blood tests for B Blood tests for H Ultrasound female pelvis R. testis 15 ml. L testis small & soft. Epidiymis & vas deferens NAD Much the same, but volume 2 ml FSH, Testoserone, PRL, antisperm antibodies Day 2 FSH, LH & E2 Day 21 Progesterone Normal endometrium, myometrium & ovaries

12. Hannah, 38 & Barry, 36 with 6 years of infertility have a severe male problem What do you do now? Barry wants to know if there is anything that he can do about his sperm count Is Hannah’s biological clock running out?

13. Hannah & Barry are advised to seek assisted conception with an IVF Clinic What sorts of assisted conception are there? What do they need to know?

14. Assisted conception options for Hannah & Barry AIH +/- ovarian stimulation DI GIFT IVF ICSI Ovarian stimulation with Clomid or FSH then intrauterine insemination with washed & concentrated husband’s sperm Insemination with donor sperm Ovarian stimulation, egg collection then fallopian tube transfer of eggs and sperm Ovarian stimulation, egg collection, in vitro fertilisation then uterine transfer of embryo(s). Ovarian stimulation, egg collection, sperm microinjection in vitro then uterine transfer of embryo(s).

15. Hannah & Barry need to understand: What is done What are the risks Side effects of drugs Pituitary suppression with GnRHa, FSH stimulation of ovaries, vaginal egg collection with ultrasound, IVF or ICSI, culture to blastocysts then uterine transfer. Extra embryos can be frozen for later attempts. 1-5% risk of OHSS, 1% risk of egg collection mishap. No risk of ovarian Ca, premature menopause etc. Few side effects of these physiological hormones used in pharmacological doses

16. Hannah & Barry need to understand: Success rates Possible cycle outcomes Possible pregnancy outcomes Cost 30 – 40% chance of pregnancy per embryo transfer. Depends on female age. Cycle cancellation 10%, failed egg collection 1%, failed fertilisation 5-10% Miscarriage, ectopic (2-fold increased risk), 3% risk of chromosomal abnormality with ICSI but not IVF Medicare eligible but most IVF programs have out of pocket costs

17. Endometriosis is: Ectopic endometrium i.e. “internal menstruation” Requires laparoscopy +/- biopsy for diagnosis Activity is more important than appearance Symptoms do not always correlate with grading

18. Symptoms of Endometriosis The Classic Triad… Dysmenorrhoea Dyspareunia Infertility

19. Symptoms of Endometriosis But consider also… Pre menstrual staining Pain with defaecation during menstruation Intermenstrual pain Disordered cycles Family history

20. Diagnosis of Endometriosis A Careful History (The most important) Rule out other Causes of Symptoms (The next most important) Examination (not much help) Ultrasound (of little value) MRI (useful for rectovaginal deposits) Laparoscopy (The gold standard) Serum CA125 (Lacks sensitivity) Iridology (a good guess!)

21. Differential Diagnosis: Primary Dysmenorrhoea Irritable Bowel Syndrome Ovulation Pain Pelvic Inflammatory Disease Psychosexual Problems

22. Aetiology Two Main Theories: Retrograde menstruation Peritoneal metaplasia Predisposing Factors Familial predisposition Disordered immunity Environmental toxins Recurrent ovulation Infertile partner Obstructed menstrual flow

23. Principles of Management: When the Problem is Pain – Use Medical Rx When the Problem is Infertility – Use Surgical Rx When there is no Problem – Use no Rx

24. Medical Therapy Options Progestins COC (best in continuous form) Provera or Norethisterone The Mirena IUS Danazol & Gestrinone GnRH agonists +/- Add Back Therapy A question of side effects