Office Management of Infertility

1. Office Management of Infertility Christopher R. Graber, MD Salina Women’s Clinic 10 Dec 2010

2. Overview • Definitions and Numbers • Indications for evaluation • Causes of infertility • Ovulatory dysfunction • Tubal and pelvic • Male factor • Laboratory evaluation • Treatment with Clomid • When to refer

3. Definitions • Infertility – 1 year of unprotected intercourse without conception (10-15% of couples) • Fecundability – probability that a single cycle will result in pregnancy (20-25% if normal)

4. Lies, Damn Lies and Statistics • Time required for conception in couples who will attain pregnancy • Exposure% Pregnant 3 mo 57 6 mo 72 1 yr 85 2 yr 93

5. Indications for Evaluation • Education should be offered to any couple who seeks it – even without trying first • Any couple who is infertile • Any woman older than 35yo with irregular or infrequent menses • Women with a history of PID • Men with known or suspected poor quality semen

6. Causes of Infertility • Ovulatory dysfunction – 15-20% • PCOS, ovarian failure • Tubal and peritoneal pathology – 30-40% • Congenital malformations, fibroids, tubal scarring, intrauterine adhesions (Asherman’s) • Male factors – 30-40% • Unexplained – 10-15%

7. Ovulatory Dysfunction • 20% of infertile women have ovulatory disorders • The cause of anovulation will guide treatment • Symptoms • polymenorrhea, oligomenorrhea, amenorrhea • Regular menstrual cycles (22-35d) with presence of premenstrual symptoms is highly suggestive of ovulation (~95%)

8. Ovulatory Dysfunction • Differential diagnosis • PCOS (70%) • Hypothalamic amenorrhea (10%) • aka hypogonadotropi c hypogonadism • Low GnRH, LH, FSH, Estrogen • Hyperprolactinemia (10%) • Can be caused by hypothyroid (TRH acts as PRF) • Premature ovarian failure/insufficiency (10%) • aka hypergonadotropic hypoestrogenic anovulation

9. PCOS • Must have 2 of 3 diagnostic criteria • “polycystic ovaries” on sono • Clinical or lab evidence of increased testosterone • Oligo- or amenorrhea • Diagnosis of exclusion • thyroid/prolactin disorders • Testosterone secreting tumor, non-typical congenital adrenal hyperplasia (CAH), Cushing’s syndrome

10. Other Ovulatory Dysfunction • Hypothalamic amenorrhea • aka hypogonadotropic hypogonadism • Low GnRH, LH, FSH, Estrogen • Frequently found in athletes and women with very low BMI – consider eating disorders • Hyperprolactinemia • Can be caused by hypothyroid (TRH acts as PRF) • MRI to look for prolactinoma of pituitary

11. Other Ovulatory Dysfunction • Premature ovarian failure/insufficiency • aka hypergonadotropic hypoestrogenic anovulation • Premature if less than 35 to 40yo • Usually not complete “failure” • High FSH and LH but low estrogen levels • Signs that the ovaries are not responding • Rule out chromosomal abnormalities • Y chromosome, Turner’s syndrome, Fragile X

12. Ovulatory Dysfunction Eval • Physical exam (after a very thorough history) • Galactorrhea, thyroid eval • Acanthosis nigricans, hirsutism, acne • BMI (>30 or <20) • Laboratory evaluation for ovulation • Basal body temperature • Urine testing for LH surge (seen after ovulation) • Pelvic sono

13. Tubal and Peritoneal Pathology • Cervical factor – post-coital test not common • Uterine factor • Fibroids: size, symptoms, sono • Intrauterine adhesions – Asherman’s syndrome • Painful, short menses • Classically after a D&C, may also be after infection

14. Tubal and Peritoneal Pathology • Tubal factor • History of PID (or untreated STI) • Abdominal/pelvic surgery • Endometriosis – painful menses

15. Tubal and Peritoneal Pathology • Evaluation • Pelvic sono • Hysterosalpingography (HSG) • Sonohysterography (SHG) • Hysteroscopy • Laparoscopy with tubal dye instillation

16. Male Factor • Semen analysis • Volume 1.5 – 5ml • pH > 7.2 • Concentration > 20 mil/ml • Total number > 40 mil • Percent motile >50% • Normal morphology – lab: 14%, 30%, or 50% • If abnormal, repeat then refer if still abnormal

17. Laboratory Evaluation • For ovulatory dysfunction • Basal body temperature, urinary LH • TSH • Prolactin (ideal conditions if first test abnormal) • Cycle day 3 labs • FSH, Estradiol • Consider other screening • Pap, Rubella, STI, genetics

18. Clomiphene Citrate • Clomid – estrogen agonist and antagonist • Binds to nuclear estrogen receptors • Circulating estrogen levels perceived as low • Stimulates increased pituitary gonadotropins • Increases ovarian follicular development • Side effects • Antiestrogenic • Multiples: 7% twins, 1% triplets

19. Clomiphene Citrate • Who to give • Anovulatory woman with • normal TSH, PRL • Normal estradiol or menstrual response to progesterone challenge • Unexplained fertility • How to give • 50mg PO qday on cycle days 3-7 (or 5-9) • New prescription every month • Scheduled intercourse QOD days 10-18

20. Clomiphene Citrate • When it fails (no menses and not pregnant) • Double check a pregnancy test (usually CD 33-35) • Induce menses with progesterone challenge • Provera 5mg PO qday x 5 days • Increase dose of CC by 50 mg • Max dose 150 mg – 250 mg • How long to give • 3 to 6 to 9 months – patient and provider specific

21. Other options • Insulin sensitizers • Metformin 500 – 875 mg, BID to TID • Letrozole (Femara) • Aromatase inhibitor • 2.5 mg PO on cycle days 3-7 • Laparoscopic ovarian drilling • Injectible gonadotropins

22. When to refer • Right away • Advanced age • Previous treatment • Upon patient request • Non-ovulatory dysfunction • Tubal or peritoneal factory, male factor • When Clomid doesn’t work • 3 to 6 to 9 months

23. Questions?