NaProTechnology Natural Procreative Technology A multifactorial approach to the chronic problem of Infertility Dr. Phil C. Boyle MICGP, MRCGP, CFCMC Galway Clinic, Ireland Prof. Joseph Stanford MD, University of Utah, USA 03 Sept 2011
Outline Abstract Summary 3 Case Presentations Discussion points
Illness can be Acute Sudden onset Shorter duration May resolve spontaneously Tend to have single or few causes May be cured by single intervention or treatment Chronic Gradual onset Longer duration Rarely resolve spontaneously Usually have multiple causes Outcomes improved with multiple sustained interventions
Health conditions Acute Appendicitis Respiratory viral infection Fractured bone Chronic Asthma Diabetes Degenerative arthritis
Infertility (subfertility) is a chronic health condition.
Infertility Gradual, unknown, or early onset Ongoing issues Potential for recurrence Syndrome, not diagnosis Many possible causes Usually, more than one cause or factor present
Infertility Rarely completely cured by single intervention Can be treated with multiple interventions Rarely resolves spontaneously
Chronic vs Acute approach NaProTechnology Infertility indicates the presence of disease with the challenge to diagnose and treat for optimum health. ART Infertility presents a technical challenge to bypass the dysfunctional process.
Chronic vs Acute approach NaProTechnology Seeks to identify longterm health conditions and improve them over a reproductive lifetime Chronic perspective ART Long term health conditions are considered less important for shortterm treatment. Acute perspective
Description Infertility is usually a consequence of multiple chronic conditions rather than a single acute condition. We propose that it is erroneous to apply acute medical interventions to a condition that is chronic in nature.
Diet & Nutrition Low Hormones Limited Mucus Infection Low Endorphins Infertility & Miscarriage Immunological Surgical Male Factor Adrenal Fatigue Others To be discovered
Possible Diagnoses from NaProTechnology Evaluation Hormonal Ultrasound Surgical Other Low Progesterone Immature follicle Endometriosis Limited (hostile) Mucus Low Oestradiol Partial rupture Pelvic Adhesions Adrenal Fatigue Poor Follicular Function Corpus Luteum Insufficiency Luteinised unruptured follicle Delayed Rupture Blocked Fallopian Tubes Hydrosalpinx Chronic Endometritis Endorphin Deficiency * Polycystic Ovaries Afollicularism Fibroid Food Intolerance Reduced ovarian reserve Absent Cumulus Oopherous Polyp Nutritional Deficiency Hypothyroidism Uterine Septum Immune dysfunction *Although these diagnoses are hormonally mediated, at least in part, the diagnosis and management is not based on direct hormonal testing at this time. Fig. 3
Method Retrospective analysis of 3 case studies which demonstrate the multifactorial and chronic nature of infertility that were previously managed unsuccessfully with acute intervention using IVF (in Vitro Fertilisation) or ART (Assisted Reproductive Technology).
Results Demonstration of the multifactorial approach and 3 successful singleton live births using NPT (Natural Procreative Technology or NaProTechnology).
Conclusion Infertility can be treated successfully with a multifactorial approach which takes into account the chronic nature of infertility and targets treatment to manage multiple factors responsible for the condition.
Discussion Infertility is not a diagnosis but is often the expression of several underlying ill health conditions which if diagnosed and treated correctly will result in restoration of normal reproductive function.
Discussion - Continued Physicians ought to consider broader diagnostic possibilities in their evaluation of infertile couples. A multifactorial treatment strategy for the chronic condition of infertility may be more effective than the widespread acute strategy employed by ART.
Discussion - Continued Future studies looking at NPT and ART outcomes Must be cohort studies and Compare populations with similar patient characteristics
3 Case Presentations 1. Case A 2. Case B 3. Case C
Case A Gravida 0 Para 0, Female aged 41, Male aged 40, Trying to conceive for 2 years, Unexplained infertility, 3 failed IUI and 2 failed IVF.
Case A Presented for treatment March 2009 Unexplained Infertility Lap and Dye normal 2007 Semen analysis normal 2007 IUI x 3 FSH/LH and HCG - June 2008 IVF x 2 3 Embryos transferred Aug 2008 & March 2009
Case A NPT Diagnoses Chronic Endometritis Progesterone deficiency poor follicular function & corpus luteum insufficiency Hostile Cervical Mucus Clinical endorphin deficiency Mild food intolerance
Case A NPT Treatments Clinical endorphin deficiency Naltrexone 2mg nocte Mild food intolerance (IgG) Egg yolk and soya www.camnutri.com
Case A NPT treatment Progesterone deficiency poor follicular function & corpus luteum insufficiency Letrozole 2.5mg 10 tabs on day 3 HCG 10,000 iu mid cycle HCG 2,500 iu Peak +3,5,7
Case A NPT Treatments Hostile Cervical Mucus Cabroceistine 375mg tid x 7 days, day 11 Amoxycillin 500mg tid x 5 days, day 11 PreSeed Vaginal Lubricant
Case A NPT Treatments Chronic Endometritis Metronidazole 400mg BD x 3 weeks Clarithromycin 500mg BD x 3 weeks Pro biotic for 6 weeks Start day 14 of cycle
10 F 10 F H H H H Antibiotic treatment Positive Test!
Case A 42 years old at conception. Hormone support with cyclogest 400mg pv. twice daily until 8 weeks Cyclogest 400mg pv nocte until 16 weeks gestation
Case A She delivered a healthy baby boy by Caesarean section in November 2010, weighing 3180g.
Case A CrMS Chart was critically important to the process Timing of blood tests Timing of HCG injections Identify hostile mucus Identify Brown Bleed Chronic Endometritis
Case A IVF which attempted to solve the symptom of infertility through bypassing the natural process of conception was inappropriate and ineffective as she had several chronic conditions that needed to be treated in a targeted fashion to restore normal reproductive function
Case B Gravida 1 Para 0 Female aged 37 Male aged 39 7 years trying to conceive Mildly polycystic ovaries and recurrent implantation failure 3 failed IVF cycles, 3 fresh & 1 frozen transfer.
Case B Presented on April 2009 Trying to conceive since Jan 2002 Cycle 32 to 25 days Unplanned miscarriage at 11 weeks 1999 Diagnosis Mild PCOD by ultrasound
Case B Normal investigations Laparoscopy 01 & 08, Hysteroscopy 09 Semen analysis several tests 01-08 Day 3 bloods Thrombophillia Screen Immunological testing Chicago Bloods
Case B Treatments Clomiphene 50mg daily for 5 days, from day 3 of cycle x 4 100mg daily for 5 days, from day 3 of cycle x 4 150mg daily for 5 days, from day 3 of cycle x 4 12 cycles in total previously
Case B Treatments IVF x 3 stimulated cycles Feb 2006 March 2009 Embryo transfer 3 fresh and 1 frozen 2 3 embryos each time Additional Aspirin, Enoxaparin, Prednisolone 25mg with last IVF cycle despite normal testing
Case B NPT Diagnoses Progesterone deficiency with corpus luteum insufficiency - Dramatic chart! Polycystic Ovaries with poor follicular function Clinical endorphin deficiency Clinical Adrenal fatigue
6 7 9 6 10F H H H H H 12
Case B NPT Treatments Progesterone deficiency with corpus luteum insufficiency - Dramatic chart! Polycystic Ovaries with poor follicular function HCG 2,500iu P+3,5,7,9 Letrozole 2.5mg 16 tabs day 3 HCG 10,000 iu mid cycle
10F H H H H 12 10F H H H H 14 10F H H H H 17
Case B NPT Treatments Clinical endorphin deficiency Naltrexone 3mg nocte Clinical Adrenal fatigue Hydrocortisone 5mg 7am & 12 noon Supplements Vitamin D3 2,400iu daily Omega 3 2000mg daily plus Folic acid
Case B NPT Outcome With treatment we achieved a normal appearing CrMS chart, with proven follicle rupture by ultrasound, and a healthy happy patient. She conceived on her 5th cycle of treatment (second effective cycle) in April 2010
16F H H H H Positive Test!
Case B NPT Pregnancy treatment Cyclogest 400mg pv twice daily until 36 weeks gestation Aspirin 75mg daily until 30 weeks Prednisolone 25mg daily until 12 weeks
Case B NPT Pregnancy Outcome She had a normal vaginal delivery of a healthy baby boy, 3.130 Kg in January 2011 Mother was 38 years old at delivery
16F H H H H Positive Test!
Case B Comments Immediately identified Corpus luteum insufficiency & confirmed restoration of normal function with treatment. Patient s well being improved with naltrexone and cortisol treatment. When this happens, we often find our treatment is more successful.
Case B Comments Although we did not feel aspirin or prednisolone were necessary we conceded to the patients request to give these medications as recommended by her previous doctor
Case C Gravida 1 (with IVF), Para 0 Female age 38, Male age 38 Oligoasthenozoospermia, progesterone deficiency and endometriosis. 12 cycles of clomiphene 3 IUI 3 IVF cycles
Case C Presented in January 2008, female aged 38 Never conceived naturally since trying in February 2003. 28 to 32 day cycle Laparoscopy 2003 Mild Endometriosis Unclear if this was treated
Case C Semen Analysis Oligoasthenozoospermia Count 6 to 17 million per ml Motility 25 37%.
Case C Previous Treatments 12 cycles of ovulation induction with clomiphene, 3 attempts at IUI 3 failed IVF attempts between Dec 2005 and April 2007 2 embryos replaced x 3 IVF cycles Miscarriage at 9 weeks after first attempt
Case C NPT Diagnoses Endometriosis Oligoasthenozoospermia Clinical endorphin deficiency Low progesterone and oestradiol combined poor follicle function and corpus luteum insufficiency Obvious from Chart Food Intolerance to eggs
Pre-menstrual Spotting with low progesterone levels
Case C NPT Treatments Clinical endorphin deficiency Naltrexone 4.5mg nightly Food Intolerance to eggs Change in diet
Case C NPT Treatments Endometriosis Laparoscopy and diathermy June 2008 Oligoasthenozoospermia CoEnzyme Q10 200mg daily Tamoxifen 20mg daily FertilityPlus for men Lifestyle (cigarettes, alcohol, caffeine, stress)
Case C NPT Treatments Low progesterone and oestradiol combined poor follicle function and corpus luteum insufficiency Clomiphene 150mg daily x 3 days, starting on day 3 of the cycle with HCG 5000 iu mid cycle to facilitate follicle rupture and HCG 2,500 iu on days 3, 5 and 7 after ovulation
Laparoscopy
Laparoscopy Positive Test!
Case C NPT Pregnancy Treatments Positive pregnancy test in September 2008 Cyclogest 400mg pv nocte until 14 weeks Naltrexone 4.5mg nocte until 38 weeks
Case C NPT Pregnancy outcome They had a healthy baby boy by normal vaginal delivery weighing 3.400kg in June 2009, when mum was 40 years old.
Case C repeat attempt Second attempt in February 2010 Same treatment approach successfully conceived by September 2010. Healthy baby boy delivered 19th May 2011 when mum was 42 years old.
Case C Comments CrMS chart demonstrated premenstrual spotting indicating a problem with endometrial integrity in the luteal phase of the cycle It is important to adequately treat mild endometriosis as this has been shown to improve pregnancy and live birth rates
Case C Comments We continued Naltrexone throughout pregnancy in this case because the patient felt dramatically better preconception with treatment. It appears she had significant endorphin deficiency which needed ongoing treatment Over 100 pregnancies with naltrexone
Appropriate Diagnosis NaProTechnology Seeks to diagnose all underlying causes. Seeks to identify all possible exacerbating and mitigating factors. ART Less concerned about diagnosis except for factors that may directly impact effectiveness of IVF treatment.
Appropriate Treatment NaProTechnology Seeks to optimize health of baby, mother, father ART Acute approach- do something to get pregnant as quickly as possible, almost at any cost
Impact on health of the baby NaProTechnology Expected lower miscarriage rates Low birth weight rates under 5% Expected lower rates of prematurity, perinatal mortality ART High miscarriage rates Low birth weight rates 30%+ Also higher rates of prematurity (2.0x), perinatal mortality (2.2x), and birth defects (2.0x) J Amer Board Fam Med, 2008 Obstet Gynecol 2004 NEJM 2002
Appropriate evidence Chronic approach Cumulative outcomes over time Cohort analysis Full picture Acute approach Short-term outcomes only No context for cumulative outcomes over time Misleading
Appropriate evidence Case C - 3 failed IVF Miscarriage at 9 weeks Recorded as Success with IVF Clinical pregnancy following embryo transfer A Cohort analysis would not do this
National Registries for ART USA- SART and CDC Europe- ESHRE UK- HFEA All have data in terms of treatment cycles Unknown number of women Unknown cycles per woman
Cochrane evaluation of IVF Outcomes should be reported as pregnancy rates per woman or couple, because repeat cycle data are not statistically independent and are less relevant to the patient. Pandian et al. Cochrane Database Sys Rev 2005
Cochrane evaluation 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 et al. Cochrane Database Sys Rev 2005
Cumulative pregnancy rates In couples without clear indications for IVF, the main benefit of early IVF may be to shorten time to pregnancy, a benefit that must be weighed against costs and potential adverse outcomes. Stanford JB, et al. Fertil Steril 2010
Cumulative live birth rates Per couple, not per cycle Adjusted live birth rates Couples who drop-out of treatment are no longer counted after they drop out Crude live birth rates Include all couples who start treatment, whether or not they continue (intention to treat)
Cumulative live birth ratesexample 100 couples 50 drop out after 3 months 50 get pregnant after 9 months Crude live birth rate: 50% Adjusted live birth rate: 100% True value somewhere in between
Appropriate evidence Accounts for population characteristics that impact the prognosis
Comparing cohorts- NPT and ART Ireland NPT Netherlands ART JABFM 2008 Hum Reprod 2007
Comparing cohorts- NPT and ART Ireland NPT N=1072 Mean female age=35.8 Duration infertility=5.6 yrs Prior ART=33% Prior pregnancy=47% 2 years Adjusted=52.8% BIRTH Crude=25.5% BIRTH JABFM 2008 Netherlands ART N=1351 Mean female age=32.8 Duration infertility=3.6 yrs Prior ART=0% Prior pregnancy=47% 1 year Adjusted=64.7% pregnancy Crude=42.4 pregnancy Hum Reprod 2007
Comparing cohorts- NPT and ART Ireland NPT N=1072 Mean female age=35.8 Duration infertility=5.6 yrs Prior ART=33% Prior pregnancy=47% 2 years Adjusted=52.8% BIRTH Crude=25.5% BIRTH JABFM 2008 Netherlands ART N=1351 Mean female age=32.8 Duration infertility=3.6 yrs Prior ART=0% Prior pregnancy=47% 1 year Adjusted=64.7% pregnancy Crude=42.4 pregnancy Hum Reprod 2007
Comparing cohorts- NPT and ART Ireland NPT Netherlands ART Twins 4.5% Birth < 2500 grams 4.5% Twins 22% Birth < 2500 grams Not reported JABFM 2008 Hum Reprod 2007
Spiritual dimensions NaProTechnology Partnership between CFCP, CFCMC, couple Acknowledges God inherently Goal is healthy baby, mother, father ART Technological accomplishment of the physician Promotes mastery of man Goal is a baby, quickly, at almost any cost
Spiritual dimensions NaProTechnology Profound respect for human life from its earliest stages of development ART Embryonic stages of life are treated instrumentally as a means to an end
Summary Infertility is a chronic health condition, and should be diagnosed and treated accordingly. The diagnostic evaluation should search for all underlying causes and contributing factors. Treatment should address all known causes and contributing factors, in order to maximize health of the baby, mother, and father.
Summary Evaluation of infertility treatment outcomes should be done on a cohort basis, over time. Comparisons between studies need to account for differences in study populations.
Summary NaProTechnology has comparable live birth rates to ART, with healthier babies. NaProTechnology seeks to maximize the longterm health outcomes for baby, mother, and father.
NaProTECHNOLOGY Any Questions? Dr. Phil Boyle