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International research in preventing and treating infertility
Joseph B. Stanford, MD, MSPH, DFPMTracey Parnell, MD, Fam Med, UBC
Kristi Panchuk RN, MN, Fam Med, UBCMary Ellen Haggerty, MD, Edmonton, Alberta
22 January 2010
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AcknowledgmentsKirsten Stoesser, MD
UU DFPM
Bernie LaSalleUU Center for Clinical Translational Science
Xiaoming Sheng, PhDUU Pediatrics
Phil Boyle, MBGalway Clinic, Ireland
International Institute of Restorative Reproductive Medicine
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Funding
Funding for iNEST provided bySt. Augustine FoundationUniversity of Utah Health Studies FundUniversity of Utah Primary Care Research CenterAtlas Foundation
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BackgroundSensitivity and specificity of the Creighton
Model chart for identifying female infertilityClinical observations and questionDesign
International practice-based research in treating infertility (iNEST)Design, progress, lessons, next steps
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Questions for you
What would make these two studies more interesting and attractive to potential funders?
What would improve the science?What would facilitate the logistics?
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Background
What does infertility have to do with primary care and public health?
What is natural procreative technology (NPT)?
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Infertility and primary care
Common problem: 10-15% of couplesonly half of these seek treatment
Couples problem- both woman and manChronic conditionOther health implicationsLifestyle issuesPsychosocial dimensionsSound primary approaches needed
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Infertility and public health
Cost, access of treatmentCultural acceptability of treatmentPreventionChild outcomes
Multiple gestation, low birth weight, birth defects, developmental delay
Risk factor for cancer and other conditions
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Natural Procreative Technology (NPT)
A systematic cooperative approach to optimize reproductive function- primarily in women. Health education: Creighton NaProTracking
Biomarkers to guide evaluation and treatmentVaginal bleeding and cervical mucus discharge
Medical evaluation and managementSurgical correction, if indicatedGoal is to facilitate in vivo conception over 12
optimized cycles.Applied in Family Medicine and OBGYN practices
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Sensitivity and specificity of the Creighton Model FertilityCare chart for identifying female infertility
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Creighton Model chart review study
Basic premise: underlying physiologic abnormalities of infertility are reflected in the woman’s standardized observations and charting.Not systematically demonstrated
ExamplesResearch questionDesign
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PCOS, prior failed ARTThis patient, who previously lost sextuplets from an ART procedure, shows herCrMS chart which is strikingly consistent with polycystic ovarian disease (From:Pope Paul VI Institute).
Hilgers TW: The Medical & Surgical Practice of NaProTechnology. Pope Paul VI Institute Press, Omaha, NE, 2004.Hilgers TW: The Medical & Surgical Practice of NaProTechnology. Pope Paul VI Institute Press, Omaha, NE, 2004.
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34 yo, endometriosis, infertility
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Recurrent miscarriage, variable PPP, abnormal bleeding, split peak
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Objective
To determine the specificity and sensitivity of NaProTracking to discriminate between patients with known infertility and known fertility, through expert assessment based on standardized assessment algorithm.
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Design- CrM chart review study
Toronto CrM centerNew patients charting who subsequently
successfully conceive and have a live birthNew patients charting who have a history of
infertilityMatched 1:1 by age and prior gravidity
Or just select those with no prior pregnancy
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Design- CrM chart review study
Blind review of charts by NPT-trained physicians5 independent reviewers
Rate parameters: mucus score, abnormal bleeding, length of post-peak phase
Classify as likely fertile or infertile
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CrM chart review study- analysis
Sensitivity and specificity: 2x2 tableInter-rater (and intra-rater?) reliability with
kappa statisticAssociation of specific chart characteristics with
fertility status: logistic regression
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Questions
Other centers?Miscarriage patients as an additional
component?
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International NaProTechnology Evaluation and Surveillance of
Treatment for Infertility and MiscarriageiNEST
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Cumulative pregnancy rates for different treatment strategies
Stanford JB, et al. Fertil Steril 2009 Mar 26 epub
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Comparing cohorts
Netherlands ARTN=1351Mean female age=32.8Duration infertility=3.6 yrsPrior ART=0%Prior pregnancy=47%Pregnancy rate at 1 year
Crude=42.4%Lifetable=64.7%
Ireland NPTN=1072Mean female age=35.8Duration infertility=5.6 yrsPrior ART=33%Prior pregnancy=47%Live birth rate at 2 years
Crude=25.5%Lifetable=52.8%
Lintsen et al. Hum Reprod 2007 Stanford et al. JABFM 2008
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Comparing cohorts
Netherlands ARTTwins 22%Birth < 2500 grams
Not reported
Ireland NPTTwins 4.5%Birth < 2500 grams
4.5%
Lintsen et al. Hum Reprod 2007 Stanford et al. JABFM 2008
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32yo, longstanding amenorrhoea, then dry cycles, eventually ovulatory cycles
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iNEST rationale
Document outcomes for peer-reviewImprove outcomes
Outcomes = live birth, health pregnancies, healthy babies, healthy children
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iNEST Objectives
Improve NaPro treatment outcomes by systematically tracking the relationships between patient characteristics, diagnosis, and treatments.
Enhance efficiency and improve quality in the clinical practice of NaPro.
Provide guidance for future targeted randomized trials for the future.
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Synergy between research and practice
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Learning from each other
Care delivery is undergoing constant changes, many of whichconstitute natural experiments from which we could learnimportant lessons. These care changes, however, usually comeup too quickly to allow the usual approach to development andfunding of a research proposal that could evaluate their effects, and there are rarely research-practice connections that could coordinate the design and implementation of studies of theseinnovations.
Solberg LI et al. Ann Fam Med 2009;7:164-9
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Learning from each other
[We should] convert the paradigm from “translate research into practice” to “optimize health and health care through research and quality improvement.”
[We should] develop and facilitate more partnerships among clinicians, researchers, and care delivery leaders for engaged scholarship in both research and quality improvement.
Solberg LI et al. Ann Fam Med 2009;7:164-9
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iNEST Design
Prospective cohortCouples based
NPT practice-based initiationPatient follow-up independent of practiceFollow all couples regardless of treatment
continuation or discontinuationObtain treatment data from NPT physician
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iNEST Design
Synergize study procedures with practice procedures
Provide added value for both practices and patients
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iNEST Sites
Jean Golden-Tevald, Morningstar Family Health Care, New Jersey, began enrolling patients Feb. 2006
Joseph Stanford, University of Utah, began enrolling patients July 2007
Paul Carpentier, In His Image Family Medicine, began enrolling February 2009
Ira Winter and Anne Carus, Life FertilityCare Center, Leamington Spa, UK, April 2009
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More iNEST practices
Practices with research ethics approval already in placeBoyle, Galway, IrelandTham, Toronto, Canada
Practices very closeParker, Ohio, USAKho and Rota, Perth, AustraliaStegman, Pennsylvania, USA
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Participating patients
Written informed consent is obtained for 3-year follow-up with option for more.
Initial clinical questionnaire facilitates the clinical evaluation.
Future: if they enroll in the study, they can track their own cycles of evaluation and treatment online.
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Main Outcome
Live birth up to 3 years after beginning NPTExamine in terms of baseline characteristics
and treatment choices
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Interim progress
87 couples enrolled27 conceived (31%)
Online tracking and entrance questionnaire developed
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Online system
Tracking log of eligible patients and those enrolled in study
Patients can complete initial evaluation questionnaire online:Data released to study only when consent received
Some flexibility for implementation based on individual practice needs
Future: track cycles of treatment, and hormonal support of pregnancy
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Proposed modifications to iNEST
Only one detailed follow-up questionnaire at one year after entry
Add cycle review trackingAdd general health questions to the entrance
and follow-up questionnairesAdd diet assessment or tracking
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Next stepsMethods paper describing study design
and web-based innovationsAddition of practicesAdditional fundingKeeping the cohort going!
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Big picture
Potentially high pay-off studyFMB has played essential role in start upPotential for longitudinal cohort
Child outcomes
Data, experience, and infrastructure for randomized trial
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Big picture
NPT has a potentially important role in infertility in relation to public health and primary care.OutcomesAccessCost
iNEST can provide key quality improvement data to improve the practice and outcomes of NPT internationally.