Update on iNEST and

Status of IIRRM Research Joseph B. Stanford, MD, MSPH, CFCMC

Director of Research, IIRRM

Professor and Director, Office of Cooperative Reproductive Health Department of Family and Preventive Medicine

University of Utah

2014 July 12

Faculty Disclosure

I have no financial interest/arrangement that would be considered a conflict of interest.

Objectives l To present current results from the iNEST

study. l To give an overview of ongoing research

sponsored and endorsed by the IIRRM. l To discuss the key role of research for the

future of restorative reproductive medicine. l To discuss possible future research directions

in RRM.

l Background l Gap l iNEST

¡ Methods ¡ Current results

l Ongoing projects l How can you help? l Future

Background

Restorative reproductive medicine l Restorative Reproductive Medicine (RRM)

addresses reproductive health problems exclusively by using investigations and treatments to identify and correct abnormalities of reproductive function, restoring or optimizing normal function.

Conventional reproductive medicine l Conventional reproductive medicine, including

artificial contraception and assisted reproductive technology, employs techniques to prevent, suppress or bypass natural reproductive processes.

RRM l Infertility indicates the

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

ART l Infertility presents a

technical challenge to bypass the dysfunctional process.

Contrasting approaches to infertility

Long-term health issues

RRM l Seeks to identify long-

term health conditions and improve them over a reproductive lifetime

ART l Focuses on short-term

treatment outcomes.

Respect for human life

RRM l Profound respect for

human life from its earliest stages of development

ART l Embryonic stages of life

are treated instrumentally as a means to an end

Creighton Model FertilityCare (CrM)

l Teaching women and couples to understand and interpret the biomarkers of their own fertility ¡ Vaginal discharge of cervical fluid and bleeding ¡ Standardized observational routine ¡ Vaginal discharge recording system ¡ Standardized algorithms for identifying days of fertility

and infertility ¡ Standardized teaching, assessment, and case

management

Natural Procreative Technology (NaPro)

l Medical protocols applied to CrM charting or women in pregnancy ¡ Various levels of evidence ¡ Rapidly evolving!

l Surgical protocols to restore reproductive integrity and function

Creighton Model charting

CrM- normal fertility

From: Pope Paul VI Institute for the Study of Human Reproduction, 2004

CrM- infertility

From: Pope Paul VI Institute for the Study of Human Reproduction, 2004

From: Pope Paul VI Institute for the Study of Human Reproduction, 2004

Gap

What is the volume of evidence? PubMed (NLM, USA)

l Natural family planning ¡ 450 ¡ ~1/month since 1975

l Natural procreative technology ¡ 3

l Cooperative reproductive ¡ 9 (all basic science)

l RRM ¡ 7 (all not related)

l Contraception ¡ 21,897 ¡ ~36/month since 1963

l Hormonal oral contraception ¡ 4523 ¡ ~13/month since 1986

l In vitro fertilization ¡ 27,688 ¡ ~66 month since 1979

Two published studies of NaProTechnology

Galway 2009

Toronto 2012

Number of couples 1072 108 Mean age women (yrs) 35.8 35.4 Mean years trying 5.6 3.2 Crude live birth rate (per 100) 25.5 38.0 Adjusted live birth rate 52.8 66.0

International NaProTechnology Evaluation and Surveillance of Treatment for subfertility and

miscarriage iNEST

iNEST design

l Prospective cohort of couples l NPT practice-based initiation l Follow all couples for 3 years regardless of

treatment continuation or discontinuation l Obtain treatment data from NPT physician l Main outcome = live birth

iNEST: current results

Enrollment characteristics

Clinic location* # enrolled

mean age mean yrs trying

prior preg.

prior IVF

Clinton, NJ, USA 161 34.7 2.6 52.8% 8.7% Salt Lake City, UT, USA 85 31.6 2.5 30.6% 2.4% Gardner, MA, USA 45 32.7 2.8 48.9% 4.4% Leamington Spa, UK 150 36.5 4.0 16.7% 14.0% Etobicoke, Ontario, Canada 104 33.5 2.4 44.2% 6.7% Baton Rouge, LA, USA 17 32.2 3.3 47.1% 0% Charlottesville, VA, USA 14 31.9 1.9 50.0% 0% TOTAL 599 34.2 2.7 37.4% 7.7% Missing from total na 1.2% 31.4% 36.4% 31.6%

*Clinics in the following sites have each contributed <10 patients to date: St. Louis, MO, USA, Winston Salem, NC, USA, New Brunswick, NJ, USA, Lublin, Poland

Events in study

Clinic location* Repro surgery

# clinic visits

Preg Birth

Clinton, NJ, USA 8.4% 1.5 46.0% 37.3% Salt Lake City, UT, USA 9.4% 6.7 48.2% 38.8% Gardner, MA, USA 13.3% 8.5 26.7% 24.4% Leamington Spa, UK NR NR 19.3% 19.3% Etobicoke, Ontario, Canada 13.5% 7.5 46.2% 39.4% Baton Rouge, LA, USA 0% NR 35.3% 35.3% Charlottesville, VA, USA 7.1% 5.6 7.1% 7.1% TOTAL 8.7% 5.0 35.4% 30.4% Missing from total 80.8% 33.9% 40.2% 39.9%

*Clinics in the following sites have each contributed <10 patients to date: St. Louis, MO, USA, Winston Salem, NC, USA, New Brunswick, NJ, USA, Lublin, Poland

Conception leading to live birth by time previously trying to conceive

Conception leading to live birth by prior IVF

Conception leading to live birth by prior intrauterine insemination

Conception leading to live birth by prior live birth

Conception leading to live birth by surgery during NaPro treatment

Conception leading to live birth by surgery anytime-before or during NPT tx

iNEST levels of involvement

l (Retrospective audit of charts) l Enter basic tracking data and consent l Use iNEST online initial questionnaires l Send CrM charts to DCC l Enter dates of visits, surgeries, diagnoses,

investigations l Send follow-up questionnaires (usually DCC) l Future: cycle tracking

Involvement in research improves your practice! l Retrospective audit l Prospective tracking (iNEST)

iNEST immediate future l Get additional funding l Get more clinics active l Analyze birth outcomes l Publish initial outcomes l Add investigations checklist

iNEST next few years l More sites and couples l Electronic charting l Cycle reviews online l Methods work for sorting out contribution of

NaPro to pregnancies in complex actual histories

l Plan appropriate randomized trials

Ongoing projects

Studies of NaProTechnology (infertility)

Lead clinician(s) Location Year published

Hilgers Omaha, Nebraska 2004 Boyle Galway, Ireland 2008 Tham Toronto, Canada 2012 Pingitore Switzerland pending Carpentier, Rollo New England pending Horodenchuk Ukraine pending Barczentiwicz Lublin, Poland pending Boyle (post IVF) Galway and Dublin, Ireland pending Many Many (iNEST) pending

Ongoing IRM-sponsored research

l Retrospective NPT audits l iNEST l Infertile and fertile women fertility charting

comparison (CrM) l  Contact: Joseph Stanford, MD, joseph.stanford@utah.edu

Ongoing IRM-endorsed research

l Pregnancy Achieving Trials: a group of randomized trials for sympto-thermal charting ¡ Infertility and normal luteal phase ¡ Infertility and luteal phase defect ¡ Infertility and anovulation

l Stop Threatened Outcomes with Progesterone Trial (STOP) ¡ Patients who present in early pregnancy with

threatened miscarriage l  Contact: Luke McLindon, MD, lukemclindon@bigpond.com

Ongoing IRM-endorsed research

l Critical evaluation and rating of Fertility Awareness or Natural Family Planning apps

l Conducted by the consortium of Fertility Awareness Collaborative to Teach the Systems (FACTS)

l  Contact: Marguerite Duane, MD, mduanemd@gmail.com

How can you help?

Every kind of support makes a difference!

l Become a member of IIRRM l Do a retrospective audit of your practice l Work with iNEST l Work with PAT or STOP l Review an app for FACTS l Give a webinar l Present to physicians in your area l Sponsor an IIRRM conference in your area

Every kind of support makes a difference!

l Develop a research question or protocol l Help seek research funding l Donate to a project l Help tell your friends l Publicize our work l Help with our online presence l Mentor a colleague l Mentor a student

Future

The big picture

l Synergize practice and research ¡ NPT (and broadly, RRM)

l Systematically observe practice and outcomes l Improve practice and outcomes l Become the new evidence-base

The opportunity l Shape the future, develop the evidence l Collaborate l Be recognized l Be misunderstood

¡ Ridiculed, attacked

l Make options available for women/couples that otherwise would never be available.

l Open a door for mainstreaming.

The challenges

l Time l Funding l Publication l Communication l Integration

¡ Clinicians, teachers, researchers

Building learning communities

In the current biomedical research system, it takes an average of 17 years for 14% of new discoveries to be incorporated into practice.

The research engine of the future must combine an enthusiasm for discovery with a desire to make the world a better place.

Researchers are consultants in this process in which everyone must have a stake.

James Mold, MD

2004 “last slide”

l NPT/RRM has a bright future. l Ongoing research is essential to

survival and expansion of NPT/RRM ¡ Replication ¡ Publicizing ¡ Validating ¡ Increased understanding

l We all have the opportunity to play an important role in this new reproductive science.