1. NaProTechnology An Integrated Approach to Infertility Joseph B. Stanford, MD, MSPH Health Research Center University of Utah Hospital and Medical School USA 13 December 2004

2. Dr. Phil C. Boyle, Ireland Dr. Tracey Parnell, Canada Dr. Kevin McCarthy, UK Dr. Amanda Lamont, Australia Dr. Thomas W. Hilgers, USA

3. s Background: Infertility s The NaProTechnology approach –Creighton NaPro Tracking –NPT Evaluation –NPT Intervention s NPT Diagnoses –Patients who failed IVF, conceived with NPT s Success rates –Per cycle versus cohort –Live Births –Multiple Gestation s Illustrative case study s Comments

4. Infertility is a common problem s 10-15% of couples s Couples problem- both woman and man s Need for an integrated primary approach

5. NaProTechnology (NPT) s Natural Procreative Technology s A systematic approach to normalize and optimize reproductive function in women and men. –Conception occurs naturally, in vivo. s Components –Health education: Creighton NaPro Tracking –Medical evaluation and management –Surgical treatment, as indicated

6. NPT Development s Developed in USA (centered at Creighton University) s 1980 Creighton NaPro Tracking s 1991 first monograph on systematic medical approach s 2004 textbook published on medical and surgical aspects –1244 page, 90 chapters, over 2000 references

7. www.naprotechnology.com

8. Most of the medical and surgical techniques have been used previously, but NPT integrates these in a fertility charting system (Creighton Model NaPro Tracking) that empowers the patient and provides key information to guide investigation and treatment.

9. Creighton Model NaPro Tracking is the cornerstone, foundation, and unifying framework for NPT. A Standardised Modification of the Billings Ovulation Method Taught by trained health educators (FertilityCare Teachers)

10. 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

11. Estrogen/Progesterone curves

12. Type E and G mucus at cervix

13. Coronal section of cervix: the biological valve

14. Estrogenic and progestogenic mucus- light microscopy

15. Type E mucus and sperm transport

17. Probability of Clinical Pregnancy

18. Creighton Model NaPro Tracking is optimal for timing intercourse to achieve pregnancy. Better than BBT, urine LH, calendar calculations

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

21. NPT DiagnosisFUNCTIONAL s Hormone deficiency - Follicular or Luteal? s Ovulatory defect - Anovulation, Luteinised Unruptured Follicle Syndrome, Partial follicular rupture. s Limited Cervical Mucus Flow s Male FactorSTRUCTURAL s Surgical - Endometriosis, PCOD, Fibroids, Polyp, Uterine Septum, PID.

22. NPT TreatmentFUNCTIONAL s Luteal Phase Support - HCG, Progesterone s Mucus Enhancers - Vitamin B6, Mucolytics, Antibiotics s Stress Management s Male Treatment s Ovulation Induction - Clomiphene, HCG, FSHSTRUCTURAL s Surgical - Endometriosis, Ovarian Diathermy, Fibroids, Polyp, Uterine Septum, PID.

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

24. NPT Infertility Protocol s Initial Medical Consultation s NaProTracking for 2 cycles s Blood Tests & Seminal fluid analysis s Medical Review - 3rd or 4th cycle s Ultrasound Evaluation s Ultrasound Follicle Tracking s Consider Diagnostic Laparoscopy and Hysteroscopy - 6th cycle s 12 effective cycles of medical treatment

25. 45 MINUTES per CONSULTATION Review of CrM chart, labs, and adjustment of medical treatment. Attention to psychosocial issues with appropriate referral

26. Diagnostic categories

27. NPT diagnostic categories 95 couples, failed IVF, conceived with NPT Data from practice of Dr. Phil C. Boyle, Galway, Ireland

28. Prior diagnostic categories

29. NPT diagnostic categories

30. NPT treatments

31. Time to pregnancy with NPT

32. Effectiveness in infertility s Per cycle success rates are not appropriate for NPT –Can be misleading for any infertility treatment s Cohort-based measures are appropriate. s Crude rates will underestimate effectiveness. s Traditional life tables will overestimate effectiveness to an unknown extent.

33. National ART registries s All data in terms of treatment cycles –Unknown number of women, cycles per woman, or centers per woman s USA 2001 –38% pregnancy per transfer –25% live birth per cycle of treatment

34. Very few RCTs of IVF The effectiveness of IVF relative to other treatment options for unexplained infertility remains unproven. Adverse events and the costs associated with the interventions compared have not been adequately assessed. Pandian Z, Bhattacharya S, Nikolaou D, Vale L, Templeton A.. In vitro fertilisation for unexplained subfertility (Cochrane Review). In: The Cochrane Library, Issue 4, 2003. Chichester, UK: John Wiley & Sons, Ltd.

35. Stolwijk et al 1996 s IVF for up to 6 cycles. s Estimated life table rates –Crude rate 29.5 –Traditional life table 56.0 –Adjusted life table 34.4 s Two other cohorts with similar results.

36. Irish NPT Study s Over 1239 couples –Entered treatment Feb. 1998 through Jan. 2002 s Average Female age 36.1 yrs. s Average time trying to conceive 5.2 yrs. s 28.6% with history of unsuccessful IVF

37. Irish NPT Study s Crude live birth rate 25.5 s Lifetable live birth rate 46.3 –Lifetable is at 24 months, which corresponds roughly to 12 effective cycles.

38. Irish NPT Study s No prior IVFcrudeLT –Age <= 37 yrs32.053.6 –Age >=38 yrs20.343.8 s Prior failed IVF –Age <= 37 yrs21.638.8 –Age >=38 yrs15.125.3

39. NPT neonatal morbidity s Preterm birth rate <6% s Low birth rate <8%

41. NPT Twins s 4.1 %, compared with 28% IVF (HFEA) s Less prematurity, low birth weight, morbidity, mortality and cost