1. INFERTILITY: ROLE OF FAMILY PHYSICIAN SUSHIL JAIN 3 RD YEAR B.H.M.S

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

3. Causes of infertility n Tubal pathology35% n Male factor35% n Ovulatory dysfunction15% n Unexplained10% n Cervical/other5%

4. Counsel patience! n In normal young couples: – 25% conceive after one month – 70% conceive after six months – 95% conceive by one year n Only an additional 5% will conceive in an additional 6-12 months

5. Fecundity and Age n In a federal survey: – Impaired fertility in women < 25y is 11.7% – Impaired fertility in women > 35y is 42.1% n In another study: – 75% of women < 31y conceived in one year. – 58% of women >35y conceived in one year. n Our challenge: presenting data in a supportive, non-judgmental manner

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

7. Male factor n Male partner should be evaluated simultaneously with female n 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 n Causes 15% of infertility n Diagnosed by menstrual irregularities, basal body temperature charting, ovulation prediction kits, serum progesterone levels.

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

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

11. PCOS: Treatment Approach n Weight loss if BMI>30 n Clomiphene to induce ovulation n If DHEA-S >2, clomiphene + glucocorticoid (dexamethasone) n If clomiphene alone unsuccessful, try metformin + clomiphene. – SOURCE- MIMS 2012

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

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

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

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

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

17. Trouble in Paradise n 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: n Semen analysis n Confirm ovulation – basal body temperature charting – ovulation predictor kits (detect LH surge) – consider serum progesterone on day 21 n 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 n Hysterosalpingogram – evaluates tubal patency and uterine cavity shape – noninvasive but involves a tenaculum – performed by radiology with gynecology supervision – diagnostic and therapeutic

20. ADDITIONAL TEST. n Postcoital test n endometrial biopsy n immune testing for antisperm antibodies n routine cervical cultures n T.O.R.CH PCT ENDOMETRIAL BIOPSY ANTISPERM ANTIBODY CERVICAL SMEAR TORCH

21. Clomiphene citrate n 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. n Induces ovulation by unknown mechanism n Most pregnancies occur in first 3 cycles. 80% will ovulate, 40% will become pregnant in 3 cycles.

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

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

24. Bibliography n Bradshaw, Karen. Evaluation and Management of the Infertile Couple. Ob/Gyn vol 5, chapter 50, 1998. n Penzias, Alan. Infertility: Contemporary office-based evaluation and treatment. Obstet& Gynecol Clinics, vol 27, no 3, Sept 2000. n ACOG Practice Bulletin. Management of Infertility Caused by Ovulatory Dysfunction. Number 34, February 2002. n 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 n 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 n 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 n 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 n 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 n 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 n 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 n 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?