INFERTILITY

1. INFERTILITY Patricia M. Dillon Updated Spring 2009 By Professor Unn Hidle

2. Infertility affects about 5.3 million Americans, or 9 percent of the reproductive age population, according to the American Society for Reproductive Medicine. • Usually 70-80% of couples that do not use any birth control conceive within a year and 80-90% conceive within 2 years.

3. 2002 Statistics from the CDC • Number/Percent of women ages 15-44 with impaired fecundity (impaired ability to have children): 7.3 million or 11.8% • Number of married women ages 15-44 that are infertile (unable to get pregnant for at least 12 consecutive months): 2.1 million • Percent of married women ages 15-44 that are infertile: 7.4% • Number of women ages 15-44 who have ever used infertility services: 7.3 million

4. Definition Unprotected coital exposure for 12 months without conception. (15% - 20% of U.S. Couples) A physician will generally initiate a medical evaluation only if a couple has not conceived after one year of trying, or, if the woman is over 35, after six months. Of note, with the increase in infertility services/clinics in the later years, many physicians will initiate infertility treatments sooner.

5. Age Factor in Infertility • If the woman and man are approximately 25 years old, there is a 50% chance that the couple will conceive within 5 months. After age 35, the ability to become pregnant in the woman decreases noticeably. After menopause the ability to conceive disappears completely • Pregnancy rates for men decrease considerably after age 45. However, unlike women, a man’s sperm can fertilize an egg into senescence (old age).

6. Infertility Management • Assess and treat causes of infertility • Provide accurate information and dispel myths • http://www.ihr.com/infertility/ • Identify expectations and stress • Counsel couples and provide emotional support

7. Etiologic Factors in Infertility • Male Factor 40% • Tubal Factor 40% • Ovulation Problem 10% • Unexplained 10%

8. Male Factors in Infertility • Male infertility most commonly occurs because of: • Anatomical inadequacies • Poor sperm motility • Short lifespan (a normal sperm has a lifespan of about 4 days) • Delivery issue • Inadequate sperm production • No sperm at all.

9. Male Factors in Infertility • Etiological reasons for problems or lack of sperm include: • Endocrine dysfunction • Cryptorchidism, varicocele, hypospadius, and epispadius • Exposure to toxic chemicals or radiation (envirnomental) • Genetic disorders, such as Klinefelter’s syndrome • Testicular exposure to high temperatures such as taking frequent, long, hot tub baths, occupations that increase heat to the testes (i.e. cab driver) and wearing constrictive clothing (i.e. tight jeans) • alcohol, tobacco, or drug abuse • A severe mumps infection as an adolescent or adult.

10. VARICOCELE (incompetent veins along the spermatic cord) Courtesy of: Netter, F.H., The CIBA Collection & Miguel F. da Cunha, Ph.D., The University of Texas – Houston Health Science Center Courtesy ofwww.andrologia.lazio.it/varicocele.jpg

11. CRYPTORCHIDISM Courtesy of UCLA Media book from:www.crump.ucla.edu:8801/NM-Mediabook/figures/REPRODUCTIVE/cryptorchidism.gif

12. HYPOSPADIAS From: Netter, F.H., The CIBA Collection Courtesy: Contemporary Pediatrics® Archive Courtesy: http://www.hypospadias.net/ http://www.rnweb.com/be_core/content/journals/k/data/2001/0202/screen/k2a089f01.jpg

13. Un-repaired Adult Male Courtesy of: http://www.epispadias-info.com/photos.html EPISPADIAS From: Netter, F.H., The CIBA Collection MALE infant FEMALE infant Infants Curtesy of: http://cai.md.chula.ac.th/lesson/atlas

14. MALE FACTORS

15. Male Factors PhysiologicalAbnormalities • Retrograde ejaculation (semen reflux into the bladder) due to • Spinal Cord Damage resulting in paralysis • Beta blockers • Diabetic neuropathy • Early ejaculation • Inability to maintain an erection due to • Blood pressure medications • Diseases such as Diabetes, Peyronie’s Disease • Anti-sperm antibody production • Damage to genitalia from infections of accessory glands or radiation therapy

16. Male Clinical Evaluation Basic Assessment Procedures: • Physical examination • A semen analysis to check for the number and quality of sperm • Blood tests to check for infections from sexually transmitted diseases and for a hormone imbalance (endocrine profile: T, LH, FSH, PRL) • Cultures of fluid from the penis to check for infections.

17. 1) Volume 2) pH 3) Sperm concentration4) Morphology 5) Viability 6) Forward motility 7) Forward progression rate 8) WBC >2 ml 7.2-7.8 >20x10(6)/ml >30% Normal >60% @ 1hr >50% are motile >3+ (Scale: 0-4) <1x10(6)/ml Semen Analysis Values

18. Male Clinical Evaluation Adjunctive Procedures: • Postcoital test • Optimized Sperm Penetration Assay • Testicular biopsy • Antisperm antibody test

19. FEMALE FACTORS

20. Disorders of Ovulation • Anovulation / Amenorrhea Causes: • Psychological dysfunction • Emotional stress • Genetic abnormalities • A menstrual cycle that is too brief • Nutritional deficiencies (anorexia, bulimia, etc.) • Endocrine problems (hormone imbalance) or CNS disease • Decreased progesterone production • Excessive body weight • Excessive exercise • Abuse of alcohol, drugs, tobacco, coffee, tea, or other products containing caffeine.

21. Other Female Factors • Cervical mucus dysfunction • Damaged fallopian tube or uterus • psychological dysfunction • previous infection (pelvic inflammatory disease or STDs) • birth defects • previous uterine/adenexa surgery (adhesions and scar tissue) • other conditions such as endometriosis, fibroids, or an abnormally-shaped or tipped uterus. • Rare antigen-antibody reaction to sperm • Natural decline with age

22. Female Factors:Clinical Evaluation • Postcoital test: evidence of: • Quality, quantity and mobility of semen and quality of cervical mucus • adequacy of coital technique and anatomy • http://www.universityobgyn.com/postcoit.htm • BBT recording: evidence of ovulation • http://www.early-pregnancy-tests.com/bbt-basal-body-temperature.html • Endometrial biopsy and profile forprogesterone

23. Female Factors:Clinical Evaluation • Tests on a sample of cervical mucus and a sample of tissue from the lining of your uterus to determine if ovulation is occurring • Urine and blood tests on both to check for sexually transmitted infections and hormonal imbalance • Assays on female to check the evidence of sperm antibodies for semen allergy (http://www.womenshealth.org/a/semen_allergy.htm)

24. Basal Body Temperature • After ovulation every month, the ovary produces a large amount of natural progesterone, which acts to increase a woman’s body temperature . • The basis of checking basal body temperature (BBT) = • The increase can be very subtle, only one to two degrees Fahrenheit; • taken immediately upon awakening in the morning, since any activity can also raise the BBT. • Since the BBT can be affected so easily: • the use of over-the-counter ovulation predictor kits tend to be more accurate and easier to perform. They measure the Leutinizing Hormone, which is made in the pituitary gland and spikes 24 to 48 hours prior to ovulation.

25. Female Factors:Clinical Evaluation Tubal/peritoneal/uterine diagnostic tests: • Hysterosalpingography • http://www.radiologyinfo.org/en/info.cfm?PG=hysterosalp • Laparoscopy • http://www.ivf.com/laprscpy.html • http://www.nhs.uk/conditions/Laparoscopy/Pages/Introduction.aspx?url=Pages/What-is-it.aspx • Hysteroscopy • http://www.gynalternatives.com/hsc.htm

26. Tubal/peritoneal/uterine diagnostic tests: Adjunctive Procedures: • Follicular ultrasound • Thyroid panel • Prolactin • FSH

27. Summary of Diagnostic Tests ADJUNCTIVE TESTS TESTS • Male: • Semen analysis • Female: • Ovulation history • Progesterone • BBT • Endometrial biopsy • Hysterosalpingography • Laparoscopy • Hysteroscopy Postcoital test Antisperm antibodies Sperm penetration Follicular ultrasound Prolactin Thyroid panel FSH

28. Endometriosishttp://www.ivf.com/endohtml.html Definition: “Growth of endometrial ectopic tissue” • Transformation of intra-abdominal tissue into endometrial-like tissue • Distant sites • Abdominal cavity

29. Endometriosis Myths: • Only affects women over 30 • Only affects white women • Does not occur before menarche • Confined to nulliparous women

30. Endometriosis Manifestations: • Dysmenorrhea • Diffuse pain (bladder, rectum areas) • Low back pain • Premenstrual spotting • Dyspareuria (pain with intercourse)

31. Endometriosis and Infertility • With ovarian problems as a result of adhesions • Without ovarian involvement from: • Increased prostaglandins = • Decreased tubal motility, or • Impaired follicular maturation, or • Impaired corpus luteum function

32. Treatment of Endometriosis: Hormonal Approachhttp://www.mayoclinic.com/health/endometriosis/DS00289/DSECTION=treatments-and-drugs • Principle: estrogen stimulates growth • Approach: anti-estrogenic agents • Until late 70s: oral contraceptives • Modern approach: Danazol • Results (Danazol): • Hypoestrenism --> stops growth of implants • Amenorrhea --> stops new bleeding

33. Treatment of Endometriosis:Adverse Events (Danazol) • Weight gain • Fatigue • Decreased breast size • Acne and oily skin • Deepening of voice • Hot flushes • Muscle cramps • Emotional lability • Liver damage Occur in 80% of women, but only 10% consider them significant enough to stop treatment

34. Other hormonal treatment approaches • Hormonal contraceptives: • Birth control pills, patches and the vaginal ring • Control the hormones responsible for the buildup of endometrial tissue • Using hormonal contraceptives can reduce or eliminate the pain of mild to moderate endometriosis. • Gonadotropin-releasing hormone (Gn-RH) agonists and antagonists: • Block the production of ovarian-stimulating hormones • Prevents menstruation and dramatically lowers estrogen levels • Causes endometrial implants to shrink • Gn-RH agonists and antagonists can force endometriosis into • These drugs create an artificial menopause that can sometimes lead to troublesome side effects, such as hot flashes and vaginal dryness.

35. Other hormonal treatment approaches • Medroxyprogesterone (Depo-Provera): • Injectable drug effective in halting menstruation and the growth of endometrial implants • Relieves the signs and symptoms of endometriosis • Aromatase inhibitors: • Known for their effectiveness in treating breast cancer • May be useful for endometriosis • Work by blocking the conversion of hormones such as androstenedione and testosterone into estrogen and by blocking the production of estrogen from endometrial implants • This deprives endometriosis of the estrogen it needs to grow. • Early studies suggest that aromatase inhibitors are at least as good as other hormonal approaches and may be better tolerated.

36. Treatment of Endometriosis:Surgical Approach • Recommended if > 1cm • Goal is to restore anatomy & destroy growths • Conservative & Radical Approaches • Danger is still developing adhesions!

37. TREATMENT SUCESS AFTER SURGICAL REPAIRSTATISTICS COURTESY OF : Miguel F. daCunha, Ph.D.The University of Texas - HoustonHealth Science Center • Varicocele repair • 50-70% • Probability of pregnancy: Probability of semen improvement 25-50% • Vasoepididymostomy • Patency rates: 60-70% • Probability of pregnancy: >30% • Vasovasostomy • Overall pregnancy rate: 50-60%

38. TREATMENT OUTCOMESwith ejaculatory problems • Ejaculatory disorders: • Sympathomimetic drugs: 20-30% • Retrograde ejaculation: • Sperm rescue from urine: variable success rate • Antisperm antibody: • Immunosuppressive drugs: variable success

39. ASSISTED REPRODUCTIVE TECHNIQUEShttp://www.nlm.nih.gov/medlineplus/infertility.html • IUI (intrauterine insemination) • http://www.mayoclinic.com/print/intrauterine-insemination/MY00104/METHOD=print&DSECTION=all • IVF (in vitro fertilization) • http://www.ivf.com/ivffaq.html • ZIFT (zygote intrafallopian transfer) • http://www.monlezun.com/art-5.htm • GIFT (gamete intrafallopian transfer) • http://www.monlezun.com/art-4.htm • ICSI (intracytoplasmic sperm injection) • http://www.asrm.org/Patients/FactSheets/ICSI-Fact.pdf • Of note, ZIFT, GIFT and ICSI are very rarely used

40. Food For Thought…… • Ethical issues • “Designer Babies” • Sperm donation • Preserving ovum • “Wombs For Hire” • Surrogacy • Insurance issues • And more……….

41. THE END