Infertility: the role of the family doctor

1. Infertility: the role of the family doctor Carroll Haymon, M.D. January 7, 2002

2. Definitions • Infertility = Inability of a couple practicing frequent intercourse and not using contraception to fail to conceive a child within one year. • Infertility affects 15-20% of couples, or 11 million reproductive age people in the U.S.

3. Causes of infertility • Tubal pathology 35% • Male factor 35% • Ovulatory dysfunction 15% • Unexplained 10% • Cervical/other 5%

4. Counsel patience! • In normal young couples: • 25% conceive after one month • 70% conceive after six months • 90% conceive by one year • Only an additional 5% will conceive in an additional 6-12 months

5. Fecundity and Age • In a federal survey: • Impaired fertility in women < 25y is 11.7% • Impaired fertility in women > 35y is 42.1% • In another study: • 74% of women < 31y conceived in one year. • 54% of women >35y conceived in one year. • Our challenge: presenting data in a supportive, non-judgmental manner

6. Congenital anomalies Tubal occlusion Evaluated by: hysterosalpingogram laparoscopy hysteroscopy May occur as sequelae of PID endometriosis abdominal/pelvic surgery peritonitis Tubal/ Pelvic pathology

7. Male factor • Male partner should be evaluated simultaneously with female • Causes of male infertility: • reversible conditions (varicocele, obstructive azoospermia) • not reversible, but viable sperm available (ejaculatorydysfunction, inoperative obstructive azoospermia) • not reversible, no viable sperm (hypogonadism) • genetic abnormalities • testicular or pituitary cancer

8. Ovulatory dysfunction • Causes 15% of infertility • Diagnosed by menstrual irregularities, basal body temperature charting, ovulation prediction kits, serum progesterone levels.

9. Ovulatory Dysfunction - 2 • Causes of ovulatory dysfunction: • polycystic ovary syndrome • hypothalamic anovulation • hyperprolactinemia • premature and age-related ovarian failure • luteal phase defect (theoretical)

10. Polycystic Ovarian Syndrome • Oligomenorrhea/amenorrhea and hyperandrogenism • Prevalence: 5%. Among women with O.D., 70% have PCOS. • Clinical evidence: hirsutism, acne, obesity • Lab evidence: elevated testosterone, elevated DHEA-S. • “Polycystic ovaries” supportive, not diagnostic

11. PCOS: Treatment Approach • Weight loss if BMI>30 • Clomiphene to induce ovulation • If DHEA-S >2, clomiphene + glucocorticoid (dexamethasone) • If clomiphene alone unsuccessful, try metformin + clomiphene. • Source: ACOG Bulletin, #34, “Management of Infertility caused by Ovulatory Dysfunction” Feb 2002.

12. Hypothalamic Anovulation • Low levels of GnRH, low of normal levels of FSH/ LH, low levels of endogenous estrogen. • Associated factors: low BMI (< 20), high-intensity exercise, extreme diets, stress. • Treatment: lifestyle modification.

13. Hyperprolactinemia • Causes: pituitary adenoma, psych meds. • Test for: pregnancy, thyroid disease. • Imaging: MRI for macro vs microadenoma • Treament: Bromocriptine (dopamine agonist). After correction, 80% of women will ovulate, 80% will get pregnant. • Discontinue treatment once pregnancy established.

14. What Can I Do? Infertility Evaluation for the Family Doctor

15. History menarche, puberty menstrual hx preganancies, abortions, birth control dysparenunia, dysmenorrhea STD’s, abdominal surg, galactorrhea Weight loss/gain Stress, exercise, drugs, alcohol, psychological Physical weight/BMI thyroid skin (striae? Acanthosis nigracans?) pelvic (vaginal mucosa, masses, pain) rectal (uterosacral nodularity) History and Physical - Female

16. History prior fertility medications h/o diabetes, mumps, undescended testes genital surgery, trauma, infections ED drug/alcohol use, stress underwear, hot tubs, frequent coitus Physical habitus, gynecomastia sexual development testicular volume (5x3 cm) epididymis, vas, prostate by palpation check for varicocele History and Physical - Male

17. Trouble in Paradise • Don’t wait a year if: • irregular menses; intermenstrual bleeding • h/o PID • h/o appy with rupture • h/o abdominal surgery • dyspareunia • age > 35 • male factors

18. On your first visit: • Semen analysis • Confirm ovulation • basal body temperature charting • ovulation predictor kits (detect LH surge) • consider serum progesterone on day 21 • Labs: • TSH and prolactin. DHEA-S if concern for PCOS. • FSH & estradiol on cycle day 3 if >35y. • Cervical cultures prn.

19. Three months later • Hysterosalpingogram • evaluates tubal patency and uterine cavity shape • noninvasive but involves a tenaculum • performed by radiology with gynecology supervision • diagnostic and therapeutic

20. Sorry, no data for... • Postcoital test • endometrial biopsy • immune testing for antisperm antibodies • routine cervical cultures

21. Clomiphene citrate • Effective for anovulatory patients. • Also used in unexplained fertility, but no data to support. • Most effective for women with nomal FSH and estrogen, least effective in hypothalamic amenorrhea or elevated FSH. • Induces ovulation by unknown mechanism • Most pregnancies occur in first 3 cycles. 80% will ovulate, 40% will become pregnant in 3 cycles.

22. Clomiphene - complications • 7% twin gestations, 0.3% triplet gestations • Miscarriage rate = 15% • Birth defect rate unchanged from controls • Side effects: hot flashes, adnexal tenderness, nausea, headache, blurry vision • Contraindications: pregnancy, ovarian cysts.

23. Clomiphene - Administration • 50 mg po qd, cycle day 3 through 7. Induce bleeding first with progesterone if amenorrheic. • Intercourse QOD cycle days 12 - 17. • Track ovulation with BBT or ovulation detection kits. • Increase dose to 100 qd, then 150, if no ovulation occurs.

24. Bibliography • Bradshaw, Karen. Evaluation and Management of the Infertile Couple. Ob/Gyn vol 5, chapter 50, 1998. • Penzias, Alan. Infertility:Contemporary office-based evaluation and treatment. Obstet& Gynecol Clinics, vol 27, no 3, Sept 2000. • ACOG Practice Bulletin. Management of Infertility Caused by Ovulatory Dysfunction. Number 34, February 2002. • Royal College of Obstetricians and Gynecologists, The Management of Infertility in Secondary Care: National Evidence-Based Clinical Guidelines. www.rcog.org.uk.

25. Case 1 • A 24 year old couple comes to see you. They have been trying to get pregnant for 8 months. • What questions do you ask?

26. Case 1 • The woman tells you she has never been pregnant. She has a regular 28 day cycle and bleeds for 4 days each month. Her medical history is unremarkable except she “got really sick” when she was 16 and had “nasty stuff coming from down there” • what do you do next?

27. Case 2 • A 35 year old woman and her 31 year old male partner come to see you. They have been trying to get pregnant for 6 months. • What do you ask?

28. Case 2 • She says her periods have been irregular since she went off the pill a year ago. She has never been pregnant. He has fathered a child by another woman several years ago. • What do you look for on exam? • What lab tests do you order today? • Do you give them homework?

29. Case 2 • They come back 3 months later with BBT charts showing no discernable pattern. Lab tests, including semen analysis, were all normal. • What is the diagnosis? • What do you do next?

30. Case 2 • You begin discussion of clomiphene. They want to know the side effects, and if this means they’ll have sextuplets and get a free house like the folks on TV. • What do you tell them? • How do you administer the clomiphene?

31. Case 2 • They come back in one month. She feels “like a total bitch - excuse me, doctor” on the clomiphene. She is not pregnant. BBT charting shows a mid-cycle temperature rise. • What happens next?