Infertility Treatment: Public Health and Primary Care Perspectives

1. Infertility Treatment:Public Health and Primary Care Perspectives Joseph B. Stanford, MD, MSPH Division of Epidemiology, Statistics, and Prevention Research National Institute of Child Health and Human Development Department of Health and Human Services 2005/11/17

2. Outline • Definition • Incidence and Prevalence • Public Health Issues • Primary Care Issues • Evaluation and Treatment Options • Effectiveness • Research Suggestions • (Clinical case study)

3. Definition: infertility • Inability to conceive despite 1 year of intercourse without contraception. • “Trying”? • Cycles “at risk”? • Excludes incomplete or sporadic use of contraception • Primary: no previous pregnancy • Secondary: previous pregnancy • Syndrome, not diagnosis!

4. Related (confused) terms • Infertility • Subfertility • Sterility • Infertility + recurrent miscarriage = subfecundity (epidemiology) • Or visa versa (demography)

5. Definition: infertility • What about spontaneous abortion? • Most definitions of infertility do not include recurrent miscarriage • Association between infertility and miscarriage • From clinical and public health standpoints, the pertinent issue is inability to have a live birth.

6. Definition: infertility • WHO recommends 2 years • Ongoing discussion in the literature about optimal definition- multidimensional? • Time, (presumed) etiology, prognosis • Infertility plus impaired fecundity • Some are suggesting a new definition: 6 months of adequately timed intercourse. • Within 6-day fecund window prior to and including ovulation.

7. Dunson, Colombo et al, Obstet Gynecol 2004 Estimated time to pregnancy by age of woman

8. Couple Heterogeneity

9. Etiology of Infertility • Male Factors 30-50% • Ovarian Causes 30-70% • PCOS 15-30% • Age, Diminished Reserve ? • Anatomic Obstruction 20-30% • Endometriosis 5-75% • Mucus Factors 5-80% • Coital Issues 5-10% • Luteal Phase Defects 10-55% • Lifestyle issues 10-40% • Unexplained 10-30%

10. Etiology of Infertility • Wide variation in diagnostic evaluation • Strong trend towards minimal evaluation! • Issue of cause versus association of diagnostic abnormalities • e.g., male factor • Multiple factors are common • Prioritization, classification? • Independent, or reflect underlying process? • e.g., limited cervical mucus and ovarian dysfunction

11. Incidence • Incidence • German study (2004): 10.4% • 1 year trying and “at risk” • Population basis: unknown

12. Prevalence: Ascertainment • One (two) year(s) sexually active without contraception • One (two) year(s) trying • Consulted physician • Physician diagnosed problem • Self-report of difficulty conceiving

13. Prevalence • Marchbanks: 6-33% lifetime prevalence • USA age-adjusted, n=4754, early 1980s • Larsen: 6-12% point prevalence • Northern Tanzania, n=1125, 2003 • Developed countries: 5-21% • 1970s-80s

14. Prevalence- NSFG, USA

16. Public Health Issues • Delaying of initial childbearing • Reduction in fecundity • Over 35: immediate evaluation and treatment • Time pressure and sense of crisis • May extend to younger ages

17. Public Health Issues • Treatment of age-related infertility is a race against a biologic time clock, rather than treatment of an underlying disorder. • “Except for oocyte donation, [treatments for age-related infertility] are intended to accelerate the time to conception rather than directly affect oocyte or embryo quality.” ASRM 2004, emphasis added

18. Infertility: Lifestyle risk factors • Alcohol • Tobacco • Up to 13% attributable risk • Also impairs ART treatment • Caffeine • Marijuana, Cocaine • Odds ratios 1.2 to 2.0

19. Infertility: Risk factors • Sexually transmitted infection • Chlamydia • 20-90% sensitivity for tubal occlusion • Pelvic inflammatory disease • Overweight • Ovulatory infertility (RR 2-3) • PCOS • Underweight • Ovulatory infertility (RR 1.5-4.5)

20. Infertility as a Risk Factor • Woman • Diabetes, cardiovascular (PCOS) • Pelvic pain and GI problems (endometriosis) • Endometrial, ovarian, breast cancer (hormonal) • Pregnancy • Miscarriage • Prematurity, pre-ecclampsia, gestational diabetes • Man (?) • Child

21. Public Health Issues • Access to care • Insurance coverage • Providers • Approximately 400 ART centers USA (2000) • Approximately 100,000 ART procedures • 7.9 million women with fertility problems • 19,750 women per center • 0.013 procedures per woman

22. Public Health Issues • Rapid development and adoption of new treatments • Beyond initial indications • Although the rapid and widespread introduction of IVF, ICSI, and related technologies into the clinic has been technology-driven rather than evidence-based, ART has become the gold standard with which other treatments are compared…ART has become widely used without comprehensive assessment of its efficacy and safety. • JL Evers, Lancet, 2002

23. Public Health Issues • Cost • IVF over $12,000 per cycle (average)

24. Public Health Issues • Multiple gestation • Multiple gestation- iatrogenic • Twins increased 50% from 1980-2001 • Higher older multiples increased 4x from 1980-2001 • Estimated 70% due to ART and ovulation induction • Pressure to maximize per-cycle success incentivizes multiple embryo transfers in ART and superovulation in ovulation induction without ART

25. Public Health Issues • Adverse outcomes of ART, independent of multiple gestation • Low birth weight • Prematurity • Perinatal mortality • Birth defects (9% versus 4%) • Aneuploidy (1-2%) • Angelman’s syndrome (rare, but increased) • Others?

26. Public Health Issues • What are optimal evaluation and treatment strategies for infertility? • Is ART currently over-used or under-used?

27. Primary Care Issues • Common problem • Couples problem- both woman and man • Chronic condition • Chronic versus acute disease management model • Lifestyle and preconception issues • Psychosocial dimensions • Cultural, ethical, and cost issues • Importance of patient preferences and values

28. Levels of care for infertility • Prevention • Primary detection, basic medical evaluation, and management • Secondary full medical evaluation and management • Tertiary medical management

29. A rational and complete approach to infertility needs to address it at the levels of public prevention and primary care as much as at the tertiary care level.

31. Evaluation and Treatment Options • Assisted Reproductive Technology (ART) • Bypass one or more parts of the natural process and perform it in the lab, “in vitro” • Natural Procreative Technology (NPT) • Restore or establish natural reproductive function • fertilization occurs in vivo from sexual intercourse

32. Infertility Treatment Options • Assisted Reproductive Technology • Artificial insemination (partner or donor) • Super-ovulation, usually with artificial insemination • In vitro fertilization • Intracytoplasmic sperm injection (ICSI)

33. Infertility Treatment Options • Restore or establish natural reproductive function • Disease-specific treatment • eg, treat polycystic ovarian disease, thyroid disease, correct anatomical abnormalities • Ovulation induction, correction of follicular and luteal hormonal/functional deficiencies • Fertility tracking • Systematic approach: NPT

34. Natural Procreative Technology (NPT) • A systematic approach to normalize and optimize reproductive function in women and men. • Components • Health education: Creighton NaPro Tracking • Biomarkers: vaginal bleeding and mucus discharge • Medical evaluation and management • Surgical correction of anatomic abnormalities, if indicated

35. www.naprotechnology.com

36. Creighton Model NaPro Tracking:Vaginal discharge biomarkers • Highly correlated with ovulation • Changes precede ovulation • Maximizes time available for intercourse to try to conceive • Gives information about sperm survival • Easily observed by women

37. Estrogen/Progesterone curves

38. Type E and G mucus at cervix

39. Fertility Charting of Vaginal Discharge (Creighton Model NaProTracking)

40. What are the best days to conceive?

41. Probability of Clinical Pregnancy

42. Creighton Model NaPro Tracking is optimal for timing intercourse to achieve pregnancy. AND it provides key information to guide diagnostics and adjust therapy.

43. NaProTracking makes the couple an equal participant in their own fertility evaluation and treatment. They are as much an expert in their own fertility as is the doctor.

44. NPT • Use NaPro Tracking to time diagnostic tests accurately • hormone levels, endometrial biopsy • follicular ultrasound • Use NaPro Tracking to time treatments to improve ovulatory function and cervical mucus production, and to monitor and adjust treatment. • Goal is to facilitate in vivo conception over 12 effective cycles.

45. NPT Infertility Protocol • Initial Medical Consultation • NaProTracking for 2 cycles • Blood Tests & Seminal fluid analysis • Medical Review - 3rd or 4th cycle • Basic Anatomic Evaluation • +/- Ultrasound Follicle Tracking • Consider Diagnostic Laparoscopy - 6th cycle • 12 effective cycles of medical treatment

46. Illustrative CrM cycles in infertility

47. Irish clinic diagnoses ART vs. NPT (n=95)

48. Twelve effective cycles • Adequate mucus flow (CrM chart) • Repeated intercourse during days with mucus flow (fertile days) (CrM chart) • Optimal progesterone and estradiol levels on 7th day after peak (CrM chart) • Attention to manage stress appropriately • Other medical/surgical issues identified and addressed (CrM chart)

49. Case History

50. Case #1 • 26 y/o P0010, previous SAB in 2 years’ trying • BMI 18.2, healthy habits, no comorbid conditions • Usual cycles 40-45 days • Husband good health • No STDs or GYN surgeries • Normal exam