Fertility for the Primary Care Provider

1. Fertility for the Primary Care Provider Lora K. Shahine, M.D., F.A.C.O.G. Pacific NW Fertility and IVF Specialists 2/28/12

2. What We Will Cover • Introduction • What is infertility and how common is it? • Causes of infertility • Basic evaluation • Who to test and What to order? • When to refer • Treatment Basics • For the primary care provider • For the infertility specialists • Myths/Mistakes I have seen

3. Basics • Infertility Definition • Inability to conceive after 12 months or more of unprotected intercourse (or inability to carry a pregnancy to full term) • 85% couples will conceive within the first 12 cycles of trying • Common • In the U.S. 7.3 million women (12% of reproductive age women) have infertility • 1/10 couples

4. Causes of Infertility

5. Evaluation • Who Should Have Fertility Testing? • Anyone unable to conceive if trying for at least one year • Couples with a female partner 35 years old or older who have been unable to conceive after 6 months

6. What about age and fertility?

7. Fertility Evaluation • Detailed history • Female anatomy • Eggs (Ovarian reserve/egg supply) • Sperm (Semen analysis)

8. Fertility Evaluation - History • Detailed history • Chronic disease • Thyroid disease and miscarriage • Uncontrolled diabetes and miscarriage • Lupus and infertility/miscarriage • Painful menses ?endometriosis • Family history of infertility, miscarriage, early • STDs – risk of tubal disease • Surgical history • Abdominal surgery – risk of tubal disease • Menstrual cycle history • Regular cycles – ovulating • irregular cycles – likely not ovulating on a regular basis

9. Fertility Evaluation – Female Anatomy • Pelvic Ultrasound • Fibroids • Ovarian cysts/endometriosis • Antral follicle count • Hysterosalpingogram • Tubes • Uterine cavity

10. Fertility Evaluation: Ovarian Reserve Testing • Antral follicle count • 12-20 follicles total • FSH and estradiol • AMH FSH Estradiol AMH

11. Fertility Evaluation: FSH • Follicle stimulating hormone (FSH) • Cycle Day 3 (ok to do CD2, 3, or 4) • FSH <10 mIU/mL = normal ovarian reserve • FSH >10 decreased ovarian reserve – refer • Must be done with estradiol • Estradiol <50 pg/dL normal for CD3 • Estradiol >80 pg/dL • Likely falsely lowers FSH level (inaccurate FSH result) • Independent indicator of decreased ovarian reserve • Changes cycle to cycle • Only as good as your highest FSH

12. Fertility Evaluation: AMH • Antimullerian hormone • Protein produced by granulosa cells in the ovary and controls the formation of primary follicles • Benefits • direct reflection of follicle/egg status • Not influenced by estradiol/other hormones • Consistent throughout menstrual cycle (can test on any day or while patient on OCPs) • Limits • We do not know exactly how to interpret the information and counsel patients • My Advice: Do not order In General: 25 y.o. AMH 3.0-3.5 ng/mL 35 y.o. AMH 2.0-2.5 ng/mL 40 y.o. AMH 1.0 ng/mL

13. Semen Analysis • Normal sperm parameters: • Volume 2.0-5.0 mL • Count: >20 × 106/mL • Motility: >50% • Morphology: >14% • Stain approximately 200 sperm • <4% = bad • Abnormal sperm = fertilization issue • Most important: TMC Total motile count goal = 10 million motile sperm (volume mL X count Milliom/mL X % motile) = TMC

14. Preconception counseling • Thyroid and fertility/pregnancy • TSH >2.5 increased risk of miscarriage, poor obstetric outcome • Prolactin - elevated prolactin associated with decreased implantation, miscarriage, anovulation • CBC, Blood type, Rubella titer, Varicella titer • Preconception counseling visit • Chronic medical issues – especially cardiovascular, liver, kidney disease – refer to perinatologist

15. Fertility Evaluation for PCP • Cycle Day 3 FSH, estradiol • TSH • Prolactin • CBC, Blood type, Rubella and Varicella titers • Semen analysis • Pelvic ultrasound • ?HSG – can be out of pocket expense for patients, may reserve for patients with risk factors for tubal disease (abdominal surgery, STDs, endometriosis)

16. Fertility Treatment for PCP • Optimize natural fertility • Provide reassurance to anxious couples • Do the basic fertility work up • Abnormal results - refer • Normal results – Counsel, advise, consider ovulation induction with clomid • But know clomid’s limits and side effects

17. Treatment: Optimizing Nature • Most fertile day = day before ovulation • Egg viable for 12-24 hours • Sperm viable for up to 72 hours • In general, start intercourse around CD10 and have IC every other day for a week • Ovulation predictor kits • Expensive, can increase anxiety • May reassure some patients, but can have false results so would not limit IC to positive OPK timing • Basal body temperatures • Temperature increases after ovulation (do not use to time IC) • Can increase anxiety and be a daily reminder of infertility • Can be helpful if trying to follow cycles and determine fertile window

18. Treatment: Counseling and Realistic expectations

19. Treatment: Clomid • Clomiphene • SERM • Anti-estrogen • Increasing endogenous FSH levels FSH Estradiol

20. Clomid • Benefits • Best for patients who are not ovulating – helps recruit an egg for ovulation • May help select the ‘best’ egg to ovulate in a cycle and support a ‘strong’ follicle with better progesterone support • Side effects • Increased risk of twins/multiples – (5-8%) • Mood swings, hot flashes, vision changes • Thin endometrial lining (implantation issues) • Ovarian cysts and hyperstimulation syndrome – especially if used for multiple cycles in a row

21. Clomid • Ovulating patients • Clomid 50mg tabs, One tab by mouth CD3-7 • Try for 3 cycles then refer • Anovulatory patients • Starting dose as above • Confirm ovulation • Monitoring ultrasound • CD21 progesterone >3 • If patients get menses within 35 days of taking clomid – then they likely responded and continue same dose • If no evidence of ovulation and no menses by CD35 – induce menses with Provera after negative pregnancy test then increase to clomid 100mg (2 tabs CD3-7) • Refer if no response or no conception with 3 ovulatory cycles

22. Fertility Treatment – Fertility Specialist • Ovulation induction • Clomid, Femara, gonadotropins • Ultrasound monitoring • Intrauterine insemination • Male factor • Cervical factor • Timing

23. Fertility Treatment – Fertility Specialist • Donor sperm IUI • In vitro fertilization • Tubal disease, endometriosis, severe male factor • Unexplained infertility • Donor egg IVF • Surrogacy

24. Fertility Treatment – Fertility Specialist • Preimplantation genetic diagnosis • Genetic testing on embryos after IVF before pregnancy • Fertility preservation • Freezing sperm • Freezing eggs • Freezing embryos

25. Fertility Treatment – Fertility Specialist • Premature ovarian failure • PCOS • Recurrent pregnancy loss

26. Referring patients – dispel myths • All we do is IVF • We will give patients twins • All treatment is expensive

27. Myths or Mistakes • Order estradiol with FSH • Do not give testosterone to a man trying to conceive – no matter what • It is equivalent to giving birth control pill (estrogen) to a woman and will shut down sperm production • Using clomid for over 6 cycles • Starting fertility treatment without a semen analysis

28. Myths or Mistakes • Wash out period after OCPs – no need • Eggs age – no matter how healthy or young we feel, the ability to conceive declines with age • Providing false reassurance to patients with normal ovarian reserve testing despite their age

29. Future topics • IVF • PCOS • Recurrent pregnancy loss