5/5/2010. Infertility FINANCIAL DISCLOSURE. Infertility Definition. Objectives. Normal Human Fertility. Normal Menstrual Cycle

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1 Infertility FINANCIAL DISCLOSURE I HAVE NO FINANCIAL INTEREST IN ANY OF THE PRODUCTS MENTIONED IN MY PRESENTATION Bryan K. Rone, M.D. University of Kentucky Obstetrics and Gynecology I AM RECEIVING COMPENSATION FOR PARTICIPATION IN THE CONTINUING EDUCATION COURSE May 5, 2010 Objectives Infertility Definition Define infertility Discuss normal human fertility Discuss diagnosis and treatment of the causes of infertility < 35 y/o: >12 months of unprotected intercourse without pregnancy > 35 y/o: > 6 months of unprotected intercourse without pregnancy Normal Human Fertility Normal Menstrual Cycle Cycle Number of couples in cycle Number of pregnancies Per cycle rate of pregnancy (%) % of couples will become pregnant within 12 months 7% of remaining couples will become pregnant over the next 36 months Zinaman, MJ, Clegg, ED, Brown, CC, et al. Estimates of human fertility and pregnancy loss. Fertility & Sterility 1996; 65:503 Day 1 = First day of bleeding Ovulation occurs on days for most women 1

2 Optimal Fertility Recipe for a baby every other day from Day BMI between No sexual position is better than another Stop smoking Exercise: < 7 hrs/week No alcohol Caffeine intake < 200mg/day Causes of Infertility Sperm Male factor 23% Ovulatory factor 18% Tubal factor 14 % Endometriosis 8% factor 5% Cervical factor 3% Unexplained 28% Timing, Frequency Absent, low sperm count, abnormal motility and morphology Anovulation, endometriosis, maternal age, premature failure PID, endometriosis, surgical adhesions, abnormal motility Mullerian abnormalities, fibroids, synechia Endometriosis Pelvic Inflammatory Disease 2

3 Uterine Abnormalities Infertility Evaluation History Exam Diagnostic Studies Infertility Evaluation: History Infertility Evaluation: Exam Timing, Frequency, Technique, Psychosocial barriers Erection, Ejaculation, Previous pregnancy, Undescended testicle, Scrotal mass Menstrual history, Pelvic pain Hx of STD/PID, Pelvic pain, Surgical hx, Smoking, Other cilliary disorders Menstrual hx, Dysmenorrhea, Pelvic Pain, Surgical hx, Confirm normal female anatomy Perform male genital exam, look for testicular masses, varicocele Identify any focal tenderness or an ovarian mass Identify any areas of focal tenderness or mass Identify any uterine irregularities or masses Semen Analysis Semen volume: ml concentration: >15 million/ml motility: >40% motile morphology: >4% normal 3

4 Anovulation labs (TSH, Prolactin, FSH), Ovarian Reserve, Day 21 Progesterone, Ultrasound, Laparoscopy Tests for Ovarian Reserve Use for women > 35 years old Tests for sufficient ovarian function Day 3 FSH/E2 FSH < 15 is normal FSH is borderline FSH >20, <4% chance of pregnancy with fertility treatments E2 <80 for FSH value to be relevant Clomid Challenge Test Day 3 and Day 10 FSH Clomid 100mg daily on cycle day 5 9 Day 3 E2 <80 for FSH values to be relevant Tests for Ovulation Ovulation Predictor Kits OTC Accurate Measures LH surge in urine which peaks at 24 36hrs prior to ovulation Day 21 Progesterone Serum progesterone on Day 21 of cycle Measures progesterone in the luteal phase of the cycle If > 3, then ovulation occurred Anovulation labs (TSH, Prolactin, FSH), Ovarian Reserve, Day 21 Progesterone, Ultrasound, Laparoscopy HSG, Laparoscopy Tubal Evaluation: HSG Tubal Evaluation: Laparoscopy 4

5 Uterine Evaluation: HSG and SHG Anovulation labs (TSH, Prolactin, FSH), Ovarian Reserve, Day 21 Progesterone, Ultrasound, Laparoscopy HSG, Laparoscopy HSG, Hysteroscopy, 3D Ultrasound, SHG, MRI, Hysteroscopy, Laparoscopy Uterine Evaluation: 3D Ultrasound and MRI Uterine Evaluation: Hysteroscopy and Laparoscopy Infertility Causes Timing, Frequency Absent, low sperm count, abnormal motility and morphology Anovulation, endometriosis, maternal age, premature failure PID, endometriosis, surgical adhesions, abnormal motility Mullerian abnormalities, fibroids, synechia Review optimal timing and frequency Discuss any cultural, religious, or personal barriers to intercourse Azoospermia: Treat underlying cause, testicular aspiration Low sperm count/abnormal morphology/low Motility Intrauterine Insemination (IUI) Sperm Bank In vitro fertilization with intracytoplasmic sperm injection IVF with ICSI 5

6 IVF with ICSI Anovulation: Treat underlying cause, Clomid, Gonadotropins Endometriosis: Laparoscopic ablation Maternal age: Clomid, Gonadotropins, IUI, IVF if passes Day 3 FSH If fails Day 3 FSH, discuss donor egg (fresh or frozen) IVF Premature ovarian failure: Donor egg IVF clomiphene citrate Indications: Anovulation, Oligomenorrhea, Unexplained infertility Selective estrogen receptor modulator Estrogen receptor agonist and antagonist depending on target tissue Hypothalamus: Blocks estrogen receptors Prevents negative feedback from ovarian estrogen production End result: Increased FSH/LH production by pituitary Uterus: Estrogen antagonist at doses > 100mg Thins endometrial tissue Thickens cervical mucous Protocol Await menses or induce a progesterone withdraw bleed (Provera 20mg for 10 days) Cycle Day 1 = First day of bleeding Cycle Day 5 9 take Clomid 50mg daily Cycle day have intercourse every other day Cycle day 21 obtain a Day 21 Progesterone to assess ovulation status Home ovulation predictor kits are an acceptable alternative Cycle day 28 35: Await menses..if no bleeding by day 35 then take a pregnancy test. If negative, then induce withdraw bleed and repeat cycle Protocol If Day 21 progesterone >3 patient ovulated on current dose, continue up to 6 months If no ovulation, then increase Clomid by 50 mg/day Maximal a dose is 250mg/day FDA approves up to 100mg/day ACOG recommends maximum of 150mg/day Precautions Side Effects Hot flashes, N/V, Abd distention, Abd pain, Breast tenderness Multiples Twins: 7% Triplets: 0.5% Ovarian cancer Uncertain association with Clomid use for > 12 cycles and epithelial ovarian cancer Recommend no more than 6 Clomid cycles 6

7 PID: Prevention, prompt treatment (preferably non surgical) if diagnosed, lysis of adhesions, drainage of hydrosalpinx Endometriosis: Laparoscopic ablation Surgical adhesions: Lysis of adhesions, use of adhesion prevention materials Abnormal motility: IVF Mullerian abnormalities Septum: Hysteroscopy resection Didelphys: Usually unable to take only one out Fibroids: Surgical removal Synechia: Hysteroscopic resection If infertility persists after treatment, then IVF. Infertility Referral Comfort level and scope of practice Uncertain diagnosis Diagnostic modalities are not in scope of practice Treatment modalities are not in scope of practice Treatment failure Initial consultation $100 $150 HSG $500 $1000 Ultrasound $100 $200 $200 Clomid $4 Semen Analysis $200 Laparoscopy $3000 $5000 Hysteroscopy $2000 $3000 Infertility Cost $200 $500/sample IUI $500 $1000/cycle IVF $10,000 $15,000/cycle $15,000/cycle IVF with ICSI $15,000 $20,000/cycle IVF with fresh donor egg $25,000 $30,000/cycle Adoption $25,000 $30,000?? Questions?? Waimea Canyon Kauaʹi, Hawaii 7