Update on iNESTand

CrM chart comparison studyJoseph B. Stanford, MD, MSPH, CFCMC

Director of Research, IIRRM

Professor and Director, Office of Cooperative Reproductive HealthDepartment of Family and Preventive Medicine

University of Utah

2015 July 15

iNESTPurposeMethodsEnrollmentRecent resultsFuture

CrM chart review studyPurposeMethodsOpportunity

iNEST

international NaProTechnology Evaluation and Surveillance of Treatment

iNEST purpose

Evaluate outcomes (“success rates”) of NaProTechnology treatment for couples seeking treatment to have a live birth.Take advantage of natural variation in practice

to assess the impact of the use and timing of different interventions.

iNEST methods

Prospective cohort of couplesNPT practice-based initiationMultiple centers, multiple countries

Follow all couples for 3 years regardless of treatment continuation or discontinuationObtain treatment data from NPT physicianMain outcome = live birthSecondary outcomes = low birthweight, preterm birth

iNEST enrollment

Currently 672 couples!Last year 599

Enrollment characteristics (2014)

Clinic location* #enrolled

mean age mean yrstrying

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

Events in study (2014)

Clinic location* Reprosurgery

# clinicvisits

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

Conception leading to live birth by time previously trying to conceive

Conception leading to live birthby prior live birth (2014)

Birth weight by treatment at conception (n=189)

Gestational age by treatment at conception (n=193)

Live births and newborn hospital stay (n=333 and n=195, respectively)

0

10

20

30

40

50

60

70

80

90

100

Live Birth/Total Pregnancies Newborn Hospital Stay > 7 Days

Perc

ent (

%)

Pregnancy Outcomes

Follow-up questionnaire response rates

2014 2015Qnrs sent to women 117 34Women’s response rate 61% 50%

Qnrs sent to men 113 34Men’s response rate 42% 24%

Women, % pregnant 52% 65%

Follow-up questionnaire response rates

2014 2015Qnrs sent to women 117 34Women’s response rate 61% 50%

Qnrs sent to men 113 34Men’s response rate 42% 24%

Women, % pregnant 52% 65%

2014: compensated2015: not compensated

iNEST current and future

No funding currently!Actively pursuing additional fundingLong-term sustainability?

iNEST proposed revamp

Rename and broadenLevels 1, 2, 3, 4

Rename and expand

Any restorative reproductive medicine approachMore comparative data

Same or similar acronym?eNEST = extended natural evaluation of

systems of treatment (?!)

Level 1 basic outcome data

Yearly reporting of core dataFor each couple starting treatmentAge of woman and manTime attemptingPrior treatments (yes/no)Prior live birth and pregnancy (yes/no)Surgery (date and basics)Pregnancy dates and outcomes

Level 1: basic outcome data

Does not require individual consent of couplesAnnual report (individual clinics not identified)Analogous to SART, HFEA, ESHRE, othersHolding our profession (RRM) accountable to

ourselves and to the public

Web-based or spreadsheet reportingCould be facilitated by RRM-EMRCould be expanded to other RRM outcomes

eventually

Level 2: prospective enrollment

Consent individual couples prospectivelyLevel one data, plusDetailed questionnaire data at enrollment and at

follow-upLearn what happened to patients who disappeared!

This is the current iNEST study designCould be facilitated by RRM-EMR

Level 3: cycle-based data

Enroll couples prospectivelyLevel 1 and 2 data plusCycle-specific treatments used, charting, and

online cycle reviews shared between patient and clinician, with automatic data transferCould be greatly facilitated by RRM-app

Level 4: randomized trials

Level 2 or 3 plus Invite suitable patients to enroll in randomized

trials, e.g., Early versus delayed surgical interventionLetrozole versus clomiphene without PCOSDietary intervention (specific or general)etc.

How to fund this?Level 1: participating physicians and clinicsLevel 2: external funding for follow-up

questionnairesLevel 3: fees from app users?Level 4: requires major external funding

Funding to date

Atlas FoundationUniversity of Utah internalPrimary Children’s Medical Foundation,

Salt Lake City, UTSt. Augustine FoundationMary Cross Tippmann FoundationWomen’s Reproductive Health

Foundation

Creighton Model chart review study (clinical validation)

CrM charts reflect underlying fertility status

Figure 1. CrMS chart of a cycle from a woman with normal fertility.

Figure 2. CrMS chart of a cycle from a woman with infertility.

CrM chart comparison purpose

Evaluate sensitivity, specificity, positive predictive value, negative predictive value, and proportion of subfertility correctly predicted by expert Creighton Model chart reviewers (medical consultants, practitioners, and educators).Proof of principle

Chart study methods

Approximately 30 matched pairsiNEST = subfertile or “infertile”CEIBA = normally fertileMatched by age, parity

First 100 days of charting (without intercourse)Randomly ordered

Chart study methods

Volunteers review via online questionnaireFirst answer questions about training and

experience with Creighton Model charting and other types of chartingOptional anonymous or acknowledged

Then review each chart blindlyQualitatively assess specific parametersClassify each as subfertile or normally fertile

We estimate total review time = 6 hours

Chart study analysis

Analyze with 2x2 tables for sensitivity, specificity, etc.We will also look objectively at each parameter

statisticallyMenstrual flow scoreMucus cycle scoreNumber of days of brown bleedingDuration of postpeak phaseetc.

Watch for email announcement!

Every kind of support makes a difference!

Review for the chart studyBecome a member of IIRRMGive a webinarWork on a committeePresent to physicians in your areaSponsor a conference in your areaDonateMentor

Office of Cooperative Reproductive Health

Update on iNEST�and�CrM chart comparison studySlide Number 2iNESTiNEST purposeiNEST methodsiNEST enrollmentEnrollment characteristics (2014)Events in study (2014)Conception leading to live birth �by time previously trying to conceiveConception leading to live birth�by prior live birth (2014)Birth weight by treatment at conception (n=189)Gestational age by treatment at conception (n=193)Live births and newborn hospital stay (n=333 and n=195, respectively)Follow-up questionnaire response ratesFollow-up questionnaire response ratesiNEST current and futureiNEST proposed revampRename and expandLevel 1 basic outcome dataLevel 1: basic outcome dataLevel 2: prospective enrollmentLevel 3: cycle-based dataLevel 4: randomized trialsHow to fund this?Funding to dateCreighton Model chart review study (clinical validation)CrM charts reflect underlying fertility statusCrM chart comparison purposeChart study methodsChart study methodsChart study analysisWatch for email announcement!Every kind of support makes a difference!Slide Number 34Office of Cooperative �Reproductive Health