Infertility

1. Infertility UNC School of Medicine Obstetrics and Gynecology Clerkship Case Based Seminar Series

2. Objectives for Infertility • Define infertility • Describe the causes of male and female infertility • Describe the evaluation and initial management of an infertile couple • List the psychosocial issues associated with infertility

3. Definition • Failure of a couple to conceive after 1 year of regular intercourse without use of contraception • Primary infertility – No prior pregnancies • Secondary infertility – Prior pregnancy

4. Prevalence • Infertility affects 10-15% of reproductive-age couples in the U.S. • Approx. 85% of couples achieve pregnancy within 1 year • Conception rate (fecundability) • 25% conceive within 1 mo. • 60% conceive within 6 mo.’s • 75% conceive within 9 mo.’s • 90% conceive within 18 mo.’s

5. Etiology Successful conception requires a specific series of events: • Ovulation of competent oocyte • Production of competent sperm • Juxtaposition of sperm and oocyte in a patent reproductive tract • Fertilization • Generation of a viable embryo • Transport of the embryo to the uterine cavity • Implantation of the embryo into the endometrium

6. Etiology • Major causes of of infertility: • Female factor – 60% • Ovulatory dysfunction • Abnormalities of female reproductive tract • Peritoneal factors • Reproductive aging • Male factor – 20% • Abnormal semen quality • Abnormalities of male reproductive tract • Idiopathic – 15% Infertility in ~ 20-40% of couples has multiple causes

7. Infertility: History • Female • Duration of infertility and prior evaluation or therapy • Menstrual cycle (length and characteristics) • Symptoms associated with ovulation (e.g. breast tenderness, bloating, mood changes) • Full OBHx and GynHx • Prior pregnancies, surgeries, or STD’s • Sexual history (frequency of intercourse) • Chronic medical illness • Family history (infertility, birth defects, genetic disorders) • Social history (smoking, EtOH, drugs)

8. Infertility: History • Male • Prior children • Genital tract infections • Genital surgery or trauma • Chronic medical illness • Medications (e.g. Furantoins, CCB) • EtOH, drugs, or smoking • Sexual history (frequency of intercourse)

9. Infertility: Physical Exam • Female • Height, weight , BMI • Pelvic exam • Masses • Tenderness (Adnexa, Cul-de-sac) • Structural abnormalities (Vagina, Cervix, or Uterus) • Male (Urologist referral) • Evidence of androgen deficiency • Structural defects (e.g. varicocele, hernia)

10. Male factor: Evaluation

11. Male factor: Evaluation • Semen analysis • Following 2-4 day period of abstinence • Repeated x1 for accuracy

12. Male factor: Evaluation • Urologic evaluation • Physical Exam • Varicocele • Congenital absence of vas deferens (CAVD) • Transrectal ultrasound • Vasography, Seminal vesiculography • Epididymal sperm aspiration (PESA or MESA)

13. Male factor: Evaluation • Endocrine evaluation • Indication: Oligospermia (< 10million/mL) or sexual dysfunction (decreased libido, impotence) • FSH, LH, testosterone • Genetic evaluation • Indication: Azoospermia (no sperm) • CFTR mutation • Karyotype (Klinefelter’s, Y chromosome deletion) • Testicular biopsy • Indication: Nonobstructiveazoospermia • Palpable vasa • Normal testis volume • Normal FSH/LH

14. Female factor: Evaluation

15. Female factor: Menstrual Cycle

16. Female factor: Evaluation • Ovulation • Initial evaluation: • Basal body temp – rise for > 10 days indicates ovulation • Ovulation predictor kit – detects LH surge in urine • Further evaluation: • Mid-luteal phase progesterone level - level > 3 ng/mL provides qualitative evidence of recent ovulation • Endocrine testing (TSH, prolactin, FSH, LH, Estradiol, DHEA-S) • Endometrial biopsy • Not routinely performed

17. Female factor: Evaluation • Reproductive tract • Initial evaluation: • Hysterosalpingogram (HSG) • Detect uterine anomalies (septate or bicornuate uterus, uterine adhesions, uterine leiomyoma) • Detect patency of fallopian tubes (occlusion, hydrosalpinx, salpingitis) • Ultrasound – alternative to HSG to evaluate uterus

18. Female factor: Evaluation • Reproductive tract • Further evaluation: • Saline-infusion sonography (SIS) • Hysteroscopy • Laparoscopic chromotubation

19. Female factor: Evaluation • Peritoneal factors • Laparoscopy • Endometriosis • Pelvic/adnexal adhesions

20. Female factor: Evaluation • Reproductive aging • Indications: • > 35 years of age • 1st degree relative with early menopause • Previous ovarian insult (surgery, chemotherapy, radiation) • Smoking • Poor response to ovarian stimulation • Unexplained infertility • Candidate for IVF

21. Female factor: Evaluation • Reproductive aging • Cycle day 3 serum FSH and estradiol • Abnormal (“diminished ovarian reserve”) • FSH > 10 IU/L • Estradiol > 75-80 pg/mL • Clomiphene citrate challenge test • Cycle day 10 serum FSH • Serum antimullerian hormone (AMH)

22. Idiopathic Infertility • Prevalence ~ 15% • Factors that cannot be identified • Sperm transport defects • Inability of sperm to fertilize egg • Implantation defects

23. Infertility: Management • Male Factor • Avoidance of alcohol • Scheduled intercourse • Ligation of venous plexus for significant varicocele • Intrauterine insemination (IUI) with washed sperm • Intracytoplasmic sperm injection (ICSI) + IVF • Donor sperm insemination

24. Infertility: Management • Anovulation • Oral medications: • Clomiphene citrate • Dopamine agonists (Bromocriptine) - hyperprolactinemia • Injectable medications: • Gonadotropins (FSH/hMG, hCG) • Laparoscopic “ovarian drilling” • Complications: Ovarian hyperstimulation, Multiple pregnancy

25. Infertility: Management • Reproductive tract abnormality • Uterine: Myomectomy, Septoplasty, Adhesiolysis • Tubal: Microsurgical tuboplasty, Neosalpigostomy • Peritoneal: Laparascopic treatment of endometriosis, Adhesiolysis • Idiopathic infertility • Ovarian stimulation + IUI • Clomiphene or gonadotropins (hMG, hCG) • IVF

26. Infertility: Management (IVF) • Used for: • Severe male factor • Tubal disease • Couples who failed other treatments • Requires • Controlled ovarian hyperstimulation • Retrieval of oocytes • In vitro fertilization and embryo transfer • Procedures • IVF + embryo transfer (IVF-ET) • Intracytoplasmic sperm injection + embryo transfer (ICSI-ET) • Donor egg IVF + embryo transfer

27. Psychological • The psychological stress associated with infertility must be recognized and patients should be counseled appropriately.

28. Bottom Line Concepts • Infertility is defined as one year of unprotected coitus without conception. Infertility may be primary or secondary. • Multiple causes must be considered for infertility diagnosis and treatment. • Male and female reproductive tract anatomy and physiology should be reviewed in order to generate a full differential diagnosis. • Components of an initial infertility workup include a thorough history and physical examination. Laboratory investigations include a semen analysis, documentation of ovulation, and hysterosalpingogram. • Dysfunction of the hypothalamic-pituitary-ovarian (HPO) axis and medical illness, including thyroid disease and pituitary tumors, can cause ovulatory disturbances. • Success rates with IVF depend on the etiology of infertility and the age of the female partner.

29. References and Resources • APGO Medical Student Educational Objectives, 9th edition, (2009), Educational Topic 48 (p102-103). • Beckman & Ling: Obstetrics and Gynecology, 6th edition, (2010), Charles RB Beckmann, Frank W Ling, Barabara M Barzansky, William NP Herbert, Douglas W Laube, Roger P Smith. Chapter 38 (p337-346). • Hacker & Moore: Hacker and Moore's Essentials of Obstetrics and Gynecology, 5th edition (2009), Neville F Hacker, Joseph C Gambone, Calvin J Hobel. Chapter 34 (p371-378).