1. APPROACH TO INFERTILITY Nissi Wei PGY-1 June 2016

2. CASE #1 Sarah is a healthy 30 year-old woman new to your practice. She has never been pregnant but is desiring pregnancy with her husband. They have been trying for almost a year with no success. She is worried that she may be infertile. How would you respond?

3. DEFINITION Infertility: no conception after 1 year of unprotected intercourse if < 35 years old (or 6 months if older than 35) primary infertility = never pregnant secondary infertility = previous pregnancy by this definition, 15% couples are infertile … this means 85% of couples become pregnant within the first year, and 95% within two years – ergo, do not investigate too early (after 3 consecutive SAB, 55-60% chance of successful birth, 70% if previous liveborn)

4. (BRIEF) PRIMER ON INFERTILITY male factor = 25-40% ovulatory dysfunction = 21% tubal factor = 14% endometriosis = 6% uterine/tract abnormality = 3%

5. OVULATORY DYSFUNCTION WHO classification type I (10%) = hypothalamic failure – low FSH, low estrogen anorexia, weight loss, stress type II (85%) = HPO axis dysfunction – normal FSH, low estrogen PCOS, hyperprolactinemia type III = ovarian failure – no menses, high FSH, no estrogen – IVF only POI, Turner’s systemic: hyperprolactinemia, hypothyroid, systemic illness androgen excess: PCOS, CAH, androgen-secreting tumors

6. TUBAL DISEASE/ENDOMETRIOSIS pelvic inflammatory disease tubal ligation endometriosis?

7. UTERINE ABNORMALITY fibroids (especially submucosal) polyps Asherman’s syndrome Cervical factor (ex. recurrent LEEPs)

8. MALE FACTOR testicular: varicocele*, post-infectious (mumps, STI) iatrogenic: radiation, drugs (THC) structural: previous surgery (hernia repair, vasectomy) erectile dysfunction (neuro, DM, hormonal, depression) other: retrograde ejaculation, antisperm-ab, hyperprolactinemia, hypothyroid *if abnormal semen analysis, high likelihood of varicocele but not vice versa

9. CASE #1 CONTINUED … You decide to take a more detailed history. Sarah and her husband John are both healthy with no significant medical history. John has a child from a previous relationship. They’ve talked about getting pregnant for the past year, but have only been “seriously trying” for the past six months. Do you investigate?

10. WHAT IF SARAH HAS … BMI > 35? multiple partners? irregular periods? painful periods? previous pregnancy losses?

11. INDICATIONS FOR EARLY WORK UP After 6 months … age 35-40 irregular/absent menses history of PID pelvic surgery, ?ruptured appendix Immediately … > age 40 previous chemo, radiation advanced endometriosis suspected uterine/tubal disease male partner – groin surgery, adult mumps, chemo etc. not physically able to have children previous sub-fertility

12. HISTORY Interview both parties separately, then together Menstrual history, GTAPL Past medical history – “SPICE” Surgeries Previous fertility testing, family history Infections – STI, mumps, PID Childhood growth/ sexual development Exposures: EtOH, radiation, steroids, chemo, medications Coital frequency + habits ROS: s/s androgen excess, perimenopause

13. PHYSICAL women skin: hirsutism, acne, acanthosis nigricans, vitiligo breasts: galactorrhea pelvic: clitoromegaly, infection BMI men testosterone deficiency: gynecomastia, hair loss pelvic exam: varicosity, testis size, hypospadias

14. BACK TO OUR CASE … You reassure Sarah that she is likely to get pregnant within the next 6 months and there is no need for investigations right now. But before she leaves your office, you offer her some practical parting advice.

15. GENERAL FERTILITY ADVICE most fertile day 9-16 – aim for intercourse q2-3 days aim for BMI < 27 smoking + EtOH cessation lubricants - ?impair motility (consider mineral oil or “preseed”) no evidence for home ovulation kits ?limit caffeine ?boxers folic acid varicella + rubella Don’t forget to explore psychosocial factors … marital stress) Contraception PRN.

16. 9 MONTHS LATER Sarah and John return tearfully to your office. They’ve followed your advice completely but have not yet conceived. How do you investigate?

18. SYSTEMIC PCOS Intra-ovarian androgen excess + insulin resistance Symptoms: hyperandrogenism, menstrual irregularities, metabolic syndrome Diagnosis: androgen excess, polycystic ovaries, oligo-/anovulation Investigations: serum androgens, transvag u/s, TSH, b-HCG, FSH, luteal phase progesterone HYPERPROLACTINEMIA Etiology: drugs, malignancy, pregnancy, nipple stimulation Symptoms: galactorrhea, menstrual irregularities, low bone density Investigations: prolactin, MRI HYPOTHYROID TSH, FT4

19. INVESTIGATIONS ovulation Regular periods – day 21 progesterone Irregular periods – test 7d before presumed cycle, then weekly until menses Ovarian failure – FSH >30, low estradiol (high day 3 FSH may indicate low ovarian reserve) STI testing

20. STRUCTURAL hysterosalpingogram – fluoroscopy – uterus + tube abnormalities (day 6-10) hysteroscopy – directly visualize uterus only sonohystogram – saline to distend uterus during ultrasound fluid in cul de sac suggests at least one patent tube transvaginal ultrasound laparoscopy.

21. SEMEN ANALYSIS morphology, motility, count, vitality, volume collect after 2-3 days of abstinence repeat after 6 weeks if abnormal

22. OTHER CONSIDERATIONS comorbid anxiety + depression quite common infertility is a couple-family problem, not entirely medical unexplained infertility – do need contraception if decide no longer desire pregnancy consider referral to fertility specialists, genetic counselling PRN

23. ADOPTION discuss adoption early (when appropriate) private, public, or international takes 6-12 months to be “adopt ready” 30 000 kids waiting for homes – 8000 in Ontario

24. ABBRV. OBJECTIVES Take an appropriate history Describe likelihood of fertility Look for signs of menstrual abnormalities and investigate appropriately Follow up at an appropriate time, earlier if older Discuss adoption

25. SAMP 28 year olds Amy and Mark are in your office seeking fertility advice as they want to start trying to get pregnant. Name three lifestyle interventions that can increase their likelihood of success. Weight loss, smoking + EtOH cessation, coital frequency, folic acid

26. SAMP When do you want them to follow up with you if they are unsuccessful? What factors would make you want to investigate sooner? Name three. Age > 35, irregular periods, severe endometriosis, chemo/radiation, suspected tubal/uterine abnormality, pelvic surgery, previous subfertility

27. QUESTIONS?

28. RESOURCES Uptodate Medscape Toronto notes NMS textbook AAFP