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 Summary3 Case PresentationsDiscussion points

Illness can be ……

Acute

Sudden onsetShorter durationMay resolve spontaneously Tend to have single or few causesMay be cured by single intervention or treatment

Chronic

Gradual onsetLonger durationRarely resolve spontaneously Usually have multiple causesOutcomes improved with multiple sustained interventions

Health conditions

Acute

AppendicitisRespiratory viral infectionFractured bone

Chronic

AsthmaDiabetesDegenerative arthritis

Infertility (subfertility) is a chronic health condition.

Infertility

Gradual, unknown, or early onsetOngoing issuesPotential for recurrenceSyndrome, not diagnosisMany possible causesUsually, more than one cause or factor present

Infertility

Rarely completely “cured” by single interventionCan be treated with multiple interventionsRarely resolves spontaneously

Chronic vs Acute approach

NaProTechnologyInfertility indicates the presence of disease with the challenge to diagnose and treat for optimum health.

ARTInfertility presents a technical challenge to bypass the dysfunctional process.

Chronic vs Acute approach

NaProTechnologySeeks to identify long-term health conditions and improve them over a reproductive lifetimeChronic perspective

ARTLong term health conditions are considered less important for short-term 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.

Infertility & Miscarriage

Infection

Low Endorphins

Diet &Nutrition

Surgical

Immunological

Male Factor

AdrenalFatigue

Low Hormones

OthersTo be discovered

Limited Mucus

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

FunctionLuteinised unruptured

follicleBlocked Fallopian

TubesChronic Endometritis

Corpus Luteum Insufficiency

Delayed Rupture Hydrosalpinx Endorphin Deficiency *Polycystic Ovaries Afollicularism Fibroid Food Intolerance

Reduced ovarian reserve

Absent Cumulus Oopherous

Polyp Nutritional Deficiency

Hypothyroidism Uterine Septum Immune dysfunction

Fig. 3

*Although these diagnoses are hormonally mediated, at least in part, the diagnosis and management is not based on direct hormonal testing at this time.

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 andCompare populations with similar patient characteristics

3 Case Presentations

1. Case A2. Case B3. 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 2009Unexplained Infertility

Lap and Dye – normal 2007Semen analysis – normal 2007

IUI x 3 – FSH/LH and HCG - June 2008IVF x 2

3 Embryos transferred – Aug 2008 & March 2009

Case A – NPT Diagnoses

Chronic EndometritisProgesterone deficiency

poor follicular function & corpus luteum insufficiency

Hostile Cervical MucusClinical endorphin deficiencyMild food intolerance

Case A – NPT Treatments

Clinical endorphin deficiencyNaltrexone 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 3HCG 10,000 iu mid cycle HCG 2,500 iu Peak +3,5,7

Case A – NPT Treatments

Hostile Cervical MucusCabroceistine 375mg tid x 7 days, day 11Amoxycillin 500mg tid x 5 days, day 11PreSeed Vaginal Lubricant

Case A – NPT Treatments

Chronic EndometritisMetronidazole 400mg BD x 3 weeksClarithromycin 500mg BD x 3 weeksPro biotic for 6 weeks

Start day 14 of cycle

Positive Test!

Antibiotic treatment10 F

10 F

H H H H

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 testsTiming of HCG injectionsIdentify hostile mucusIdentify 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 failure3 failed IVF cycles, 3 fresh & 1 frozen transfer.

Case B

Presented on April 2009Trying to conceive since Jan 2002Cycle 32 to 25 daysUnplanned miscarriage at 11 weeks – 1999Diagnosis – Mild PCOD by ultrasound

Case B – Normal investigations

Laparoscopy ’01 &’08, Hysteroscopy ‘09Semen analysis several tests – ’01- ’08Day 3 bloodsThrombophillia ScreenImmunological testing “Chicago Bloods”

Case B – Treatments

Clomiphene 50mg daily for 5 days, from day 3 of cycle x 4100mg daily for 5 days, from day 3 of cycle x 4150mg 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 2009Embryo transfer – 3 fresh and 1 frozen

2 – 3 embryos each timeAdditional 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 functionClinical endorphin deficiencyClinical Adrenal fatigue

6 7

9

6

10F H HHHH 12

Case B – NPT Treatments

Progesterone deficiency – with corpus luteum insufficiency - Dramatic chart!Polycystic Ovaries – with poor follicular function

HCG 2,500iu P+3,5,7,9Letrozole 2.5mg – 16 tabs – day 3HCG 10,000 iu mid cycle

H H

H HHH

H

HH

H HH10F

10F

10F

17

14

12

Case B – NPT Treatments

Clinical endorphin deficiencyNaltrexone 3mg nocte

Clinical Adrenal fatigueHydrocortisone 5mg – 7am & 12 noon

SupplementsVitamin D3 – 2,400iu dailyOmega 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 HHH

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 HHH

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 0Female age 38, Male age 38Oligoasthenozoospermia, progesterone deficiency and endometriosis. 12 cycles of clomiphene3 IUI 3 IVF cycles

Case C

Presented in January 2008, female aged 38Never conceived naturally since trying in February 2003.28 to 32 day cycleLaparoscopy 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 cyclesMiscarriage at 9 weeks after first attempt

Case C – NPT Diagnoses

EndometriosisOligoasthenozoospermiaClinical endorphin deficiencyLow progesterone and oestradiol –combined poor follicle function and corpus luteum insufficiency Obvious from ChartFood Intolerance to eggs

Pre-menstrual Spotting with low progesterone levels

Case C – NPT Treatments

Clinical endorphin deficiencyNaltrexone 4.5mg nightly

Food Intolerance to eggsChange in diet

Case C – NPT Treatments

EndometriosisLaparoscopy and diathermy June 2008

OligoasthenozoospermiaCoEnzyme Q10 200mg dailyTamoxifen 20mg dailyFertilityPlus for menLifestyle – (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

Positive Test!

Laparoscopy

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 cycleIt 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 treatmentOver 100 pregnancies with naltrexone

Appropriate Diagnosis

NaProTechnology

Seeks to diagnose all underlying causes.Seeks to identify all possible exacerbating and mitigating factors.

ARTLess 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

ARTAcute approach- do something to get pregnant as quickly as possible, almost at any cost

Impact on health of the baby

NaProTechnologyExpected lower miscarriage rates Low birth weight rates under 5%Expected lower rates of prematurity, perinatal mortality

ARTHigh miscarriage ratesLow 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 timeCohort analysisFull picture

“Acute” approachShort-term outcomes onlyNo context for cumulative outcomes over timeMisleading

Appropriate evidence

Case C - 3 failed IVF

Miscarriage at 9 weeksRecorded as “Success” with IVFClinical pregnancy following embryo transferA Cohort analysis would not do this

National Registries for ART

USA- SART and CDCEurope- ESHREUK- HFEAAll have data in terms of treatment cycles

Unknown number of womenUnknown 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

Stanford JB, et al. Fertil Steril 2010

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.

Cumulative live birth rates

Per couple, not per cycleAdjusted live birth rates

Couples who drop-out of treatment are no longer counted after they drop out

Crude live birth ratesInclude all couples who start treatment, whether or not they continue (intention to treat)

Cumulative live birth rates-example

100 couples50 drop out after 3 months50 get pregnant after 9 monthsCrude 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

Hum Reprod 2007JABFM 2008

Comparing cohorts- NPT and ARTNetherlands ARTN=1351Mean female age=32.8Duration infertility=3.6 yrsPrior ART=0%Prior pregnancy=47%1 year

Adjusted=64.7% pregnancyCrude=42.4 pregnancy

Ireland NPTN=1072Mean female age=35.8Duration infertility=5.6 yrsPrior ART=33%Prior pregnancy=47%2 years

Adjusted=52.8% BIRTHCrude=25.5% BIRTH

Hum Reprod 2007JABFM 2008

Comparing cohorts- NPT and ARTNetherlands ARTN=1351Mean female age=32.8Duration infertility=3.6 yrsPrior ART=0%Prior pregnancy=47%1 year

Adjusted=64.7% pregnancyCrude=42.4 pregnancy

Ireland NPTN=1072Mean female age=35.8Duration infertility=5.6 yrsPrior ART=33%Prior pregnancy=47%2 years

Adjusted=52.8% BIRTHCrude=25.5% BIRTH

Hum Reprod 2007JABFM 2008

Comparing cohorts- NPT and ARTNetherlands ART

Twins 22%Birth < 2500 grams

Not reported

Ireland NPT

Twins 4.5%Birth < 2500 grams

4.5%

Hum Reprod 2007JABFM 2008

Spiritual dimensions

NaProTechnology

Partnership between CFCP, CFCMC, coupleAcknowledges God inherentlyGoal is healthy baby, mother, father

ARTTechnological accomplishment of the physicianPromotes mastery of manGoal is a baby, quickly, at almost any cost

Spiritual dimensions

NaProTechnology

Profound respect for human life from its earliest stages of development

ARTEmbryonic 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 long-term health outcomes for baby, mother, and father.

NaProTECHNOLOGYAny Questions?

Dr. Phil Boyle