NaProTechnology after previous IVF Galway, Ireland

NaProTechnology after previous IVF 2004-2012 Galway, Ireland Salt Lake City, July 2012 Dr. Phil Boyle MICGP, MRCGP, CFCP

IVF Report.. Sunday Times 2009 1 in 6 couples - Infertility 1.25% (1 in 80) have IVF Birth 50% of women who try IVF do not need it! They could conceive naturally! Dr. Sami David New York s first IVF baby

Analysis of all couples Previous IVF attending the Galway Clinic Jan 2004 - Jan 2012 405 new couples attempted NaProTechnology with a history of previous IVF (Jan 2004-2010) 6 years, all treatment concluded by Jan 2012. Total of 839 previous IVF attempts Average of 2.1 IVF attempts per couple

Analysis of all couples Previous IVF attending the Galway Clinic Jan 2004 - Jan 2012 405 Couples Previous IVF 4% 21% 17% 58% Never conceived Live birth natural Live birth IVF Miscarriage 79% No previous Live Birth

Analysis of all couples Previous IVF attending the Galway Clinic Jan 2004 - Jan 2012 405 Couples Previous IVF - Female Age 140 120 100 80 60 40 20 0 127 109 89 52 29 <34 35-37 38-40 41-42 43+ Years old Average Female Age 37.1 years

Analysis of all couples Previous IVF attending the Galway Clinic Jan 2004 - Jan 2012 Years trying to conceive 180 160 140 120 100 80 60 40 20 0 166 93 70 46 30 <2yrs 3-4yrs 5-6yrs 7-9yrs >10yrs 5.8 years Trying to conceive

Analysis of all couples Previous IVF attending the Galway Clinic Jan 2004 - Jan 2012 Exclusion Criteria (112 couples) Those who attended for only 1 medical consultation = 104 couples Irreversible Severe Male factor 8 couples

Analysis of all couples Previous IVF attending the Galway Clinic Jan 2004 - Jan 2012 ESHRE European Society for Human Reproduction and Embryology Average success rates for all of Europe Ireland 21% Live Birth rate

Analysis of all couples Previous IVF attending the Galway Clinic Jan 2004 - Jan 2012 In addition.. Consider how many people with a Respiratory Tract Infection respond favorably to antibiotic treatment 2 days of treatment 3 days 4 days 5 days. Highest success

Analysis of all couples Previous IVF attending the Galway Clinic Jan 2004 - Jan 2012 405 couples attempted NaProTechnology with previous IVF 130 Conceptions (from 106 couples) 299 Did not conceive 106 / 405 = 26.2% crude conception rate 77/ 405 = 19.0% crude live birth rate

Analysis of all couples Previous IVF attending the Galway Clinic Jan 2004 - Jan 2012 26.2 % crude conception rate 19% crude live birth rate Includes all couples of all ages who had 2 or more medical consultations Not a fair reflection on true success rate for couples who use NaProTechnology to its full potential

299 couples Discontinued Group Jan 2004- Jan 2012 # Consults Quit Early NPT failed Total 2 63 (83%) 13 (17%) 76 3 54 (70%) 23 (30%) 77 4 39 (51%) 37 (49%) 76 5 8 (23.5%) 26 (76.5%) 34 6 0 23 (100%) 23 7 0 13 (100%) 13 164 135 299

Analysis of all couples Previous IVF attending the Galway Clinic Jan 2004 - Jan 2012 130 Conceptions (from 106 couples) 299 Did not conceive 164 Quit treatment too Early (55%) 135 NaPro Treatment Ineffective

Reasons for Ineffective NaPro Treatment Severe non responsive male factor Unresponsive Anovulation Ovarian Failure Persistent LUF Non Reparable Blocked Tubes Completely Dry Cycle

299 couples Discontinued Group Jan 2004- Jan 2010 # Consults Quit Early NPT failed Total 2 63 (83%) 13 (17%) 76 3 54 (70%) 23 (30%) 77 4 39 (51%) 37 (49%) 76 5 8 (23.5%) 26 (76.5%) 34 6 0 23 (100%) 23 7 0 13 (100%) 13 164 135 299

Analysis of all couples Previous IVF attending the Galway Clinic Jan 2004 - Jan 2012 106 Conceptions from 405 couples 299 Did not conceive - 2 or more consults 106/405 = 26.2% per couple conception rate 236 couples (299 63) 3 or more consults 106 / 106+236 (342) = 30.9% per couple conception rate 182 couples (236 54) 4 or more consults 106 / 106+182 (288) = 36.8% per couple conception rate

405 Couples Previous IVF NaPro Conception and Live Birth Rates all ages Jan 2004 - Jan 2010 # Consults Conception Rate Live Birth Rate 2 (299) 3 (236) 4 (182) 5 (143) 106/405 26.2 % 106/342 30.9 % 106/288 36.8 % 106/249 42.6 % 77/405 19.01% 77/342 22.5% 77/288 26.7% 77/249 30.9% Conception rate - based on 106 conceptions Live Birth rate - based on 77 Live Births

405 Couples Previous IVF NaPro Conception Rates Female age Jan 2004 - Jan 2010 # consults < 34 35-37 38-40 41-42 43 + 2 (299) 25/64 = 89 28.1% 39/88 = 127 30.7% 24/84 = 109 22.0% 13/39 = 52 25.0% 5/24=29 17.2% 3 (236) 25/55 = 80 31.3 % 39/68 = 107 36.4% 24/62 = 87 27.6% 13/33 = 46 28.3% 5/18= 23 21.7% 4 (182) 25/43 = 68 36.8 % 39/48= 87 44.8% 24/48 = 73 32.9% 13/28 = 41 31.7% 5/15=20 25.0% Conception rate - based on 106 conceptions

405 Couples Previous IVF NaPro Live Birth Rates Female Age Jan 2004 - Jan 2010 # consults < 34 35-37 38-40 41-42 43 + 2 (299) 18/64 = 89 20.2% 30/88 = 127 23.6% 16/84 = 109 14.7% 10/39 = 52 19.2% 3/24=29 10.3% 3 (236) 18/55 = 80 22.5 % 30/68 = 107 28.0% 16/62 = 87 18.3% 10/33 = 46 21.7% 3/18= 23 13.0% 4 (182) 18/43 = 68 26.5 % 30/48= 87 34.5% 16/48 = 73 21.9% 10/28 = 41 24.4% 3/15=20 15.0% 5 (143) 18/36 =61 29.5% 30/36= 75 40.0% 16/35 = 60 26.7% 10/22 = 35 28.5% 3/14=19 15.8%

405 Couples Previous IVF NaPro Miscarriage Rates Per couple Jan 2004 - Jan 2010 < 34 35-37 38-40 41-42 43 + Total 7/18 = 25 28.0% 9/30 = 39 23.1% 8/16 = 24 33.3% 3/10 = 13 23.1% 2/3=5 40.0% 29/77=106 27.3% Including 2 Ectopic 2/106 = 1.8% 106 couples conceived 77 achieved 1 successful pregnancy 13 achieved 2 successful pregnancies 1 achieved 3 successful pregnancy 29 couples end result was miscarriage

So how do we Compare with IVF data?

DIAGNOSTIC CHALLENGE Total 100%

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 Male Factor Uterine Septum Immune dysfunction *Although this diagnosis is hormonally mediated, at least in part, the diagnosis and management is not based on direct hormonal testing at this time. Fig. 3

Infertility Diagnoses 250 200 150 100 50 0 6 1 173 210 127 26 95 69 64 29 27 15 26 IVF Dx NaPro Unexpl. Inf Unexpl Misc Endometriosis low Prog low oestrogen anovulation hostile mucus male PCOS Fibroids PID tubal low ov. Res

DIAGNOSTIC CHALLENGE Total 100% NaPro 5% 85% 15% 70% 5% 30% 50% 1% 90% 95% NTP is a multifactorial approach of male and female factors and our totals exceed 100%

Live Birth Rate 57.7% 38.2% 43.8% 13.3%

Live Birth Rate 57.7% 38.2% 43.8% 13.3% 41% Multiple pregnancy rate

13.3% # consults < 34 35-37 38-40 41-42 43 + 5 (143) 18/ 61 29.5% 30/ 75 40.0% 16/60 26.7% 10/35 28.5% 3/19 15.8%

Total IVF cycles = 99,467 Multiple pregnancies 27,668 27.8% overall 14,191 6,132 5,065 1,821 Twins 24,787 24.9% Triplets 2,881 2.9% 1,085 662 804 303

Multiple Pregnancy Rate 2 out of 77 Live Births = 2.6% 2 out of 106 conceptions = 1.9% No Triplet pregnancy

Prematurity Rate <35 weeks 35weeks 36weeks 37+weeks 1 (1.3%) 1 (1.3%) 6 (8.1%) 66 (89.2%) 2.6% of Babies born prior to 36 weeks Almost 90% of babies were born at 37 weeks or later

Birth Weights <1500g 1500-2500g >2500g Nil 6 70 Average Birth weight = 3,400g (7lbs 8 oz ) 92% of babies were over 2500g (5lb 8 oz)

Birth Defects None were reported

ESHRE, Istanbul, July 2012 98,737 Danish women with infertility between 1973 and 2008. Women with Failed fertility treatment alcohol and substance increased by 103% schizophrenia increased by 47% Dr. Baldur-Felskov

ESHRE, Istanbul, July 2012 FET is more successful by 30% Pregnancy rate 38% in fresh transfer cycles, 50% in the FET cycles. Endometrial receptivity is better in un-stimulated cycles Prof. Checa, Barcelona

Simple cost analysis NPT approach $1,500 IVF approach $10,000 6.67 fold difference Difference in cost is almost 7 times higher for IVF babies in the general population..but in this study

Simple cost analysis NPT approach 405 x $1,500 = $607,500 resulting in 91 live births Cost per baby =$6,676 IVF approach 839 cycles x $10,000 = $8,390,000 resulting in 17 live births. Cost per baby = $493,529 Difference in cost is 74 times higher for IVF babies in this study This is without taking into account the 10 fold higher incidence of multiple pregnancies and the costs associated with premature births

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

3 Case Presentations 1. Case A 2. Case B 3. Case C

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. The estimated date of delivery is 19th May 2011 when mum will be 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

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.

(IIRRM) International Institute for Restorative Reproductive Medicine Dr. Joe Stanford Dr. Tracey Parnell

NaProTECHNOLOGY Any Questions? Dr. Phil Boyle