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Landmarks growth miscarriagehandout

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					                                                 Landmarks <28 days


                                         • Empty uterus
   Landmarks in early pregnancy,         • Thickened
                                           hyperechogenic
 growth and diagnosing miscarriage         endometrium


           Dr Cecilia Bottomley MRCOG
                                         • Corpus luteum
                  BMUS Study Day
                  20 February 2009




         Landmarks 28-35 days                    Landmarks > 35 days


                                         • Visible yolk sac



• Visible gestation
  sac


                                         • Visible embryo




                                                 Measurements of embryonic
         Landmarks >49 days
                                                 and fetal size


 • Visible amniotic sac                 • 80 patients with certain
 • Cephalocaudal                          dates
   distinction from 52                  • 214 TA USS measurements
   days (single ventricle)              • 6-14 weeks
 • Limb buds from 56                    • Reproduced by Hadlock (TV
   days                                   and TA)
 • Embryonic period                     • Assume uniform growth in
   complete from 70                       first trimester
   days


                                                              Robinson H. British Medical Journal 1973 4, 28-31
             Measurements of embryonic
                                                            Optimal time to date a pregnancy
             and fetal size

• Greatest length <6 weeks
                                                      When the measurement is most accurate and
• Neck rump length <8 weeks                           repeatable
                                                      when the growth of the fetus is greatest
• Crown rump length >8 weeks
                                                      with little biological variability
                                                      but before the fetal movements and flexion or
                                                      extension introduce further potential error.
                                                      This has been suggested to be between eight
                                                      and 12 weeks




             Factors associated with poor                   CRL discrepancy prior to
             first trimester growth                         miscarriage


•    Miscarriage

•    Trisomy 18, XO (Turner’s), sex
     triploidies (e.g. XXY)                                                                                   Expected mean CRL
                                                                                                              +2SD
                                                                                                              -2SD

•    Early onset IUGR                                                                                         Viable
                                                                                                              Non viable



•    Age, ethnicity, BMI, smoking

                                                                          Mukri et al. BJOG. 2008 Sep;115(10):1273-8.




                                                            Twins: CRL discrepancy

                                                                    Median      Interquartile
                                                                    discrepancy range
• 61% that miscarried had CRL at least 2 SD
  below expected                                   Single
                                                   embryonic          37.4%            10.7-64.3%
                Ongoing    Miscarriage             demise                                                     P=0.0012
                 viable                            Ongoing viable
               pregnancy
                                                   twins               5.9%             2.3-12.4%
    Mean z       -0.82       -2.42       P<0.000
    score      (SD 1.46)   (SD 1.31)     1


                                                                      CRL 39mm                       CRL 29mm

                                                                                                           n = 57 (DCDA twins)
                                                                                                           Bora et al 2008
                                                                                                                                         Functional linear discriminant analysis -
            Growth rate prior to miscarriage                                                                                             comparison with ‘z score’
                                                       2
                                                                 class 1 certain
                                                      1.8        class 1 uncertain
                                                                 class 2 certain
                                                                                                                               Prediction of miscarriage
                                                      1.6
                       growth slope of CRL (mm/day)




                                                      1.4                                                                               TP   FN   TN      FP        Acc       Sens Spec PPV NPV
                                                      1.2

                                                       1
                                                                                                                              FLDA      17   11   459     34        91.4      60.7 93.1          33.3 97.7
                                                      0.8

                                                      0.6                                                                     z-score   15   13   355     137       71.2      53.6 72.2          9.9      96.5
                                                      0.4                                                                     (1st
                                                      0.2                                                                     scan)
                                                       0
                                                            40     50           60           70          80        90
                                                                                gestational age (days)

Slope (increase in CRL when GA increases with 1 day) for patients from class 1                                                                Bottomley et al. Hum Rep 2008 (epub ahead of print)
with certain dates (•), patients from class 1 with uncertain dates (•) and patients
from class 2 with certain dates (•)




                                                                                                                                         Early growth and late
                   Rate of change in CRL in Class 2
                   pregnancies (miscarriage)                                                                                             pregnancy outcome
                                                                            class 2 - curves
                  80



                                                                                                                                  CRL below expected at 11-14 week
                  70


                  60                                                                                                              ultrasound scan is associated with
                                                                                                                                  greater risk of IUGR, preeclampsia and
                  50
                                                                                                                                  premature delivery
            CRL




                  40


                  30


                  20
                                                                                                                                                     Källén. Ultrasound Obstet Gynecol. 2004 Jul;24(1):30-4
                                                                                                                                                                 Thorsell et al. BJOG. 2008 Apr;115(5):585-9
                  10                                                                                                                                         Smith et al. N Engl J Med 1998;339:1817–1822
                                                                                                                                                                           Bukowski et al. BMJ 2007;334:836
                  0
                   30                                       40    50         60         70          80        90        100
                                                                            gestational age




…Redating is not as simple as it seems

       Think about miscarriage risk
       Think about chromosome analysis
       (check NT date)
       Think about long term adverse
       outcome risk

                                                                                                                                                                   Bukowski et al. BMJ 2007;334;836
                                                                                            Background


                                                                                • Diagnosis of miscarriage:

                                                                                        mean gestational sac diameter (MSD) > 20mm, with
                                                                                        no visible fetal pole
                                                                                   or
          Diagnosis of miscarriage                                                      crown rump length (CRL) > 6mm, with no visible FH
                                                                                        pulsation


                                                                                                    RCR/RCOG Guidance on ultrasound procedures in early pregnancy
                                                                                                                                                   RCOG Press 1995
                                                                                   Hately et al. Establishing the death of an embryo by ultrasound: report of a public
                                                                                        inquiry with recommendations. Ultrasound Obstet Gynecol 1995;5(5):353-7.




                                                                                                            Optimal timing
                                                                                Theory
                                                                                • Intrauterine gestation sac from 31 days
• Pregnancy of ‘uncertain viability’ (IPUVI):                                   • Fetal pole from 36 days
        intrauterine sac (<20mm mean diameter) with) no                                 Yeh 1986, Rossavich 1988,Timor-Tritsch 1990, Jurkovic 1995
        obvious yolk sac or fetus
   or                                                                           Reality
        fetal echo <6mm crown–rump length with no                               • Uncertain or wrong dates
        obvious fetal heart activity                                            • Slow growing abnormal pregnancies
                                                                                • Technical limitations (fibroids)
In order to confirm or refute viability, a repeat scan at a
                                                                                Consequence
minimal interval of 1 week is necessary
                                                                                • High anxiety and financial cost of follow up hCG
                                                                                  and ultrasound
                     Hately et al. Ultrasound Obstet Gynecol 1995;5(5):353-7.




               Frequency of diagnostic outcome
            according to gestational age (n=1442)


                                                                                                                                             Increase in likelihood of
                                                                                                                                             making diagnosis for each
                                                                                                                                             one day increase in
                                                                                                                                             gestational age:

                                                                                                                                             <49 days: 20.0% per day
                                                                                                                                             (95% CI 16.5-23.7%)

                                                                                                                                             >49 days: 2.3% per day
                                                                                                                                             (95% CI 0.8-3.9%)



                                                                                                                                             Symptomatic: 25% lower
                                                                                                                                             odds of making a diagnosis
                       Ectopic pregnancy and scan timing


      • Incidence 2.0% (29/1442)
      • Median gestation at presentation 45 (19-81)
        days

                                            >49 days                           >49 days                                   Intrauterine pregnancy of uncertain
                                                                                                                                    viability (IPUVI)
      Asymptomatic                          2/177*                             1/200
                                            (1:89)                             (1:200)
      Symptomatic                           19/505                             7/560
                                            (1:27)                             (1:80)
                      * Both had history of previous ectopic pregnancy




                       Methods                                                                                                        Results: ultrasound findings
      • 493 women with TVS findings of:
         – an empty GS <20mm                                                                                                          Classification                    n            Viable at initial follow up
         – GS <25mm containing yolk sac (YS) only*
         – fetal pole <6mm without fetal heartbeat (FH)                                                                   Empty sac (<20mm)                       296 (60.5%)                    59.7%
                                                                    *Hurwitz SR. J Ultrasound Med 1986;5(8):435-8
      • Multivariate logistic regression analysis to predict ongoing
                                                                                                                          Small CRL (<6mm) with no FH              30 (6.1%)                     6.7%
        pregnancy viability

      • Main outcome measures                                                                                             Yolk sac only (MSD <25mm)               165 (33.5%)                    77%
          Viability at initial 7-14 day follow up
          Viability at 11-14 weeks
                                                                                                                          Ultrasound measurements (mm)                 mean                      range

                                                                                                                          Mean sac diameter (MSD)                      9.2                    (2.3-29)

                                                                                                                          Mean yolk sac diameter                       3.4                   (1.5-9.9)

                                                                                                                          Crown rump length (CRL)                      4.3                   (1.8-5.7)




                       Results: multivariate analysis                                                                                 Results: simple rules

                                                                                                                                        Visible Yolk sac
                                                                                                                    Gestational age
       Variable                                         P value               OR (95% CI) for viability                                    with mean         Any reported          Probability of ongoing first
                                                                                                                     less than 42
                                                                                                                                         diameter less     vaginal bleeding?           trimester viability
                                                                                                                        days?
                                                                                                                                         than 4.6mm?
       Gestational age <42 days by LMP                 <0.0001                  6.345 (3.141-12.816)
                                                                                                                                                                                Viable at 7-14     Viable at 11-14
                                                                                                                                                                                     days              weeks
       Bleeding score                                  <0.0001                  0.279 (0.165-0.472)                       No                   No                Yes                3.7%                 3.5%
                                                                                                                          No                   No                 No               17.7%                 14.4%
       Presence of a yolk sac (YS)                      0.0084                   2.722(1.293-5.728)                      Yes                   No                Yes               44.1%                 17.2%
                                                                                                                          No                   Yes               Yes               46.0%                 39.9%
       Mean yolk sac diameter (MYD)                     0.0034                  0.097 (0.021-0.462)                      Yes                   No                 No               81.4%                 48.7%
                                                                                                                          No                   Yes                No               82.5%                 75.3%
                                                   <7mm: <0.0012                 1.601(1.204-2.130)
       MSD-MYS difference                                                                                                Yes                   Yes               Yes               94.5%                 79.0%
                                                   >=7mm: 0.0003                 0.811(0.718-0.916)
                                                                                                                         Yes                   Yes                No               99.0%                 94.5%
Not significant: age, ethnicity, previous miscarriage, parity, certainty of dates, pain, subchorionic haematoma


                    Test data set: multivariate regression model AUC = 0.81                                                                  Test data set: Simple rules AUC = 0.79
             Objectives in EPU


  Offer woman certainty regarding miscarriage,
  or hope of ongoing pregnancy

But

  Avoid inadvertent termination of a potentially
  viable pregnancy

				
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Description: Landmarks growth miscarriagehandout