1 st TRIMESTER PREGNANCY FAILURE - PowerPoint Presentation

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1st TRIMESTER PREGNANCY FAILUREShortened to emphasize medical student curriculum requirements

Carlos M. Fernandez, M.D

Department of Obstetrics and Gynecology

Advocate Illinois Masonic and Medical Center

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Ultrasound diagnosis of intrauterine pregnancy

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Diagnosis of IUP“Double decidual sign” at 4½ to 5 wksGestational sac + yolk sac at 5 wks (a definitive sign of IUP)GS + yolk sac + embryo at 5½ to 6 wks

CRL >5 mm – fetal cardiac activity present

Seeber BE and Barnhart KT. Obstet Gynecol 2006;107:339-413

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Tips for Students

IUP=intrauterine pregnancyCould include a live intrauterine pregnancy, a threatened abortion, an inevitable abortion, an incomplete abortion, or a missed abortionDoes not include ectopic pregnancy, completed miscarriage, or a molar pregnancyGestational ageThe age of the pregnancy in weeks since the last menstrual periodAbout 2 weeks longer than the embryonic age

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Tips for Students

Try to memorize the gestational ages at which the markers of an intrauterine pregnancy appear….But more importantly, you should understand what is required to confirm an intrauterine pregnancyThis is how we rule out ectopic pregnancies and molar pregnanciesIf there is any possibility of an intrauterine pregnancy, you cannot give methotrexate or cytotecyou

could cause an elective abortion

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Gestational sacDouble

decidual signThe first sign of an intrauterine pregnancy

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First sign of IUP: double decidual signEarliest finding is the “double decidual sign” (arrows)

seen around 4½-5 wks gestation

initially eccentric in location

It excludes pseudogestational sac (free fluid or blood within endometrium)

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Double-decidual sign ( 5 weeks' menstrual age). The decidua vera (dv) can be discerned from the decidua capsularis (dc) and chorion laeve surrounding the gestational sac. A small subchorionic hemorrhage(*) is present between the unopposed layers of decidua vera.

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Gestational Sac (confirmed by double

decidual sign)Grows 1 mm per dayUsually seen by 4 ½ to 5 weeks of gestationDiscriminatory ß-hCG with TVUS (the level of ß-

hCG

above which you

should

be able to see a gestational sac on

transvaginal

ultrasound):

Usually quoted 1000 - 2000 ß-

hCG

IU/L

At AIMMC, we use 1500 IU/L

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Gestational SacDiscriminatory ß-hCG with transvaginal ultrasound

:

1000 - 2000

ß-hCG IU/L

Discriminatory

ß-hCG

with

trans-abdominal ultrasound

:

≥ 6500

ß-hCG IU/L

Bhatt & Dogra, Radiol Clin N Am 45 (2007) 549-560

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Long axisShort axis

The gestational sac diameter is used to calculate gestational age

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Yolk sac

Second sign of intrauterine pregnancy

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Second sign of IUP: Yolk SacFirst structure visualized within the gestational sacRound , bright ring

A definitive sign of IUP

Involutes after 11 weeks

Can be seen half a week before normal embryo is seen

When enlarged (“hydropic”), solid or duplicated, it is a very poor prognosis sign

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Gestational sac and yolk sac (5 weeks' menstrual age). A normal yolk sac is visualized. The embryo is not identified. The decidua vera (dv) and decidua capsularis (dc) (double-decidual sign) are identified.

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Fetal pole

Third sign of intrauterine pregnancy

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Third sign of IUP: GS + yolk sac + embryo

GS + yolk sac + fetal pole at 5½ to 6 wks

The fetal pole (arrow) is better seen on the zoomed in image

GS grows 1mm/day

Embryo grows 1mm/day

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Cardiac activtiy

Fourth sign of intrauterine pregnancy

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Fourth sign of IUP: GS + YS + embryo + cardiac activity

Double decidual sign +yolk sac+ fetal pole +cardiac activity

Cardiac activity confirms a

live

intrauterine pregnancy (rules out a miscarriage)

Cardiac activity is usually detected at 5 ½ to 6 weeks from last menstrual period

CRL ≥5 mm – fetal cardiac activity present

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Bhcg and progesterone in early pregnancy

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Serum concentrations of ß-hCG in 443 normal pregnancies

Braunstein G D, et al.

Am J Obstet Gynecol

1976

; 126:678-81.

ß-hCG is

first detected

in maternal serum

6 to 9 days after conception

. The levels rise in a logarithmic fashion,

peaking 8 to 10 weeks after the last menstrual period,

followed by a decline to a

nadir at 18 weeks

, with subsequent levels remaining

constant until delivery

Second International Standard ß-hCG

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Serial ß-hCG

The doubling time for a normal IUP is 2 daysß-hCG peaks at ~10 weeks gestation

It can get as high as 100,000 IU/L

Doubling of ß-hCG is

less reliable after 10 weeks gestation.

At this time, pregnancy is better evaluated with U/S

15% of normal IUPs

can demonstrate an

abnormal rise of ß-hCG

Kadar N, et al. Obstet Gynecol 1981;52:162-6

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ß-hCG up to 10000 mIU/ml

The minimal rise in ß-hCG for a viable pregnancy is

53%

in 48 hours

The

minimal decline

of a

spontaneous abortion

is

21-35%

in 48 hours

A

rise or fall

in serial ß-hCG values that is slower than this is

suggestive of an ectopic pregnancy

Seeber BE and Barnhart KT. Obstet Gynecol 2006;107:339-413

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Hypothetical illustration of the rise, or fall, of serial hCG values in women with an EP

Seeber BE and Barnhart KT. Obstet Gynecol 2006;107:339-413

53%

21-35%

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Serum Progesterone

Progesterone level of <10 ng/ml is consistent with an abnormal pregnancyProgesterone level of > 20 ng/ml is consistent with a normal pregnancy

McCord ML, et al. Fertil Steril 1996; 66:513-16

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Spontaneous abortion: background, etiology

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Spontaneous abortion or miscarriageSpontaneous abortion is a fetal loss before 20 weeks gestation80% of miscarriages occur in the first trimester (first twelve weeks)Biochemical pregnancy:

A woman has a positive pregnancy test, but does not miss a period

(her period might come a few days late)

The pregnancy has miscarried

very early

(~3wks gestation)

Ferri: Ferri's Clinical Advisor 2012, 1st ed

.

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Trophoblast plugging of maternal spiral arteries with invasion of the decidua and superficial myometrium in the central area of the normally developing placenta

There is a shallow trophoblastic invasion and the plugs are loose, allowing premature entry of maternal blood (arrows)

Normal first-trimester pregnancy

Miscarriage

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Background

Miscarriage is the most common serious pregnancy complication affecting approximately 30% of biochemical pregnancies and 11–20% of clinically recognized pregnanciesThe diagnosis of miscarriage is made most commonly by trans-vaginal ultrasound (TVS) assessmentAfter a diagnosis of miscarriage, half of women undergo significant psychological effects

Cecilia Bottomley, Tom Bourne. Diagnosing miscarriage.

Best Practice & Research Clinical Obstetrics & Gynecology

2009

; 23:463-77

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Etiology

Approximately 50–60% of first-trimester spontaneous abortions have karyotype abnormalities

Igor N Lebedev, Nadezhda V Ostroverkhova, Tatyana V Nikitina, Natalia N Sukhanova and Sergey A Nazarenko. Features of chromosomal abnormalities in spontaneous abortion cell culture failures detected by interphase FISH analysis.

European Journal of Human Genetics

2004; 12:513–20

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Etiologies

The most frequent type of chromosomal abnormalities detected are:Autosomal trisomies ─ 52 %Monosomy X ─ 19 %Polyploidies ─ 22 %

Other ─ 7 %

Hsu, LYF. Prenatal diagnosis of chromosomal abnormalities through amniocentesis. In: Genetic Disorders and the Fetus, 4th ed, Milunsky, A (Ed), The Johns Hopkins University Press, Baltimore 1998. p.179

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Classification of miscarriage

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Clinical classification of spontaneous abortionTypeDefinitionThreatened abortionVaginal bleeding

during the first 20 weeks of pregnancy and

no evidence of cervical

dilation.

<50

% of threatened

abortions will

progress to loss of

pregnancy.

Missed abortion

Intrauterine demise

of the

embryo

without either vaginal bleeding or expulsion of the products of

conception

. Includes both an embryo with no heart tones (>7mm) or an empty gestational sac (>20mm).

Incomplete abortionVaginal bleeding with dilation of the cervix and partial expulsion of products

of conception

.

Complete abortion

Vaginal bleeding with expulsion of all of the products of

conception.

Inevitable abortion

Abortion in progress

with

cervical dilation but

the

products of conception have not been expelled.

Laifer-Narin SL. Ultrasound for Obstetrics Emergencies.

Ultrasound Clin

. 2011; 6: 177-193

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Threatened AbortionPregnant patient who is symptomatic with:Vaginal bleedingMild abdominal crampsClosed cervical osComplication affecting 16-25% of pregnant patientsIncreases her chance of spontaneous abortion, but <50% progress to pregnancy loss

Chung TKH. Aust N Z J Obstet Gynaecol 1999; 39:443-447

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Differential Diagnosis ofThreatened AbortionUndetermined or physiologic (implantation related)

Ectopic pregnancy

Sub-chorionic bleed, found in ~20% of threatened Ab

Gestational

trophoblastic

disease (molar pregnancy)

Impending spontaneous miscarriage

Cervix, vaginal or uterine pathology

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Ultrasound diagnosis of miscarriage

This section is too in-depth for most medical students; read it for background, but you don’t necessarily have to memorize!

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Comparison of international criteria

Different organizations use different cutoffs to diagnose miscarriage…

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TVS features of pregnancy failureNon visualization of the yolk sac by the time the mean sac diameter is 13 mm, orNon visualization of the embryo by the time the mean sac diameter is 20 mm, orNon visualization of cardiac activity by the time the embryo is 5 mm in length (~7wks gestation).

Specificity for diagnosis of nonviable pregnancy is 100%

Levine D. Radiology 2007; 245:385-397

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Royal College of Obstetricians and Gynaecologists. The Management of Early Pregnancy Loss. Green-Top Guideline No. 25. October 2006Miscarriage:Mean sac diameter greater than 20 mm and no embryonic contents, or

Embryo crown-rump length > 6 mm with no heart beat, or

If sac remains empty after at least one week or still no cardiac activity 1 week after initial ultrasound

How to define miscarriage using ultrasound-comparing and contrasting national guidelines

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The Institute of Obstetricians and GynaecologistsRoyal College of Physicians of Ireland

How to define miscarriage using ultrasound-comparing and contrasting national guidelines

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What is the evidence to support the cut-offs used to diagnose miscarriage?UOG 2011 November,

Jeve

Y et al.

Systematic review of ultrasound diagnosis of miscarriage

Problems: studies are 15–20 years old, small study numbers, and various cut-off values used (4

–

6mm for CRL, 13

–

25mm for MSD), making pooling of data impossible

Best (most specific) criteria appeared to be MSD > 25mm with a missing embryo or MSD > 20mm with a missing yolk sac

These criteria had a 95% CI of 0.96

–

1.00,

therefore

up to 4 out of 100

diagnoses of early fetal demise may be wrong.

A

single incorrect diagnosis of miscarriage is one too many

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Abdallah Y, et al. Limitations of current definitions of miscarriage using mean gestational sac diameter and crown–rump length measurements: a multicenter observational study. Ultrasound Obstet Gynecol 2011; 38: 497–502Prospective multicenter study1060 patients of IPUV

Conclusions

In order to minimize the risk of a false-positive diagnosis of miscarriage the following cut-off could be introduced

Empty gestational sac or sac with a yolk sac but no embryo seen with MSD >25 mm

Embryo with an absent heartbeat and CRL > 7 mm

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Summary

SummarySignificant interobserver variability may be associated with a misdiagnosis of miscarriage

This could result in interventions (D&C,

misoprostol

use) that could harm a viable pregnancy

Current

national guidelines should be reviewed to avoid inadvertent

termination of wanted

pregnancy

Large

prospective studies with agreed reference standards are urgently required