1st TRIMESTER PREGNANCY FAILURE

Shortened to emphasize medical student

curriculum requirementsCarlos M. Fernandez, M.D

Department of Obstetrics and Gynecology

Advocate Illinois Masonic and Medical Center

ULTRASOUND DIAGNOSIS OF INTRAUTERINE PREGNANCY

Diagnosis of IUP

1. “Double decidual sign” at 4½ to 5 wks

2. Gestational sac + yolk sac at 5 wks (a definitive sign of IUP)

3. GS + yolk sac + embryo at 5½ to 6 wks

4. CRL >5 mm – fetal cardiac activity presentSeeber BE and Barnhart KT. Obstet Gynecol

2006;107:339-413

Tips for Students

IUP=intrauterine pregnancy Could include a live intrauterine pregnancy, a

threatened abortion, an inevitable abortion, an incomplete abortion, or a missed abortion

Does not include ectopic pregnancy, completed miscarriage, or a molar pregnancy

Gestational age The age of the pregnancy in weeks

since the last menstrual period About 2 weeks longer than the

embryonic age

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 pregnancy This is how we rule out ectopic pregnancies

and molar pregnancies If there is any possibility of an intrauterine

pregnancy, you cannot give methotrexate or cytotecyou could cause an elective abortion

GESTATIONAL SACDOUBLE DECIDUAL SIGN

The first sign of an intrauterine pregnancy

First sign of IUP: double decidual sign

Earliest 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)

Gestational Sac (confirmed by double

decidual sign) Grows 1 mm per day Usually seen by 4 ½ to 5 weeks of

gestation Discriminatory 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

Gestational Sac

Discriminatory 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

Long axis Short axis

The gestational sac diameter is used to

calculate gestational age

YOLK SACSecond sign of intrauterine pregnancy

Second sign of IUP: Yolk Sac

First structure visualized within the gestational sac

Round , 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

FETAL POLEThird sign of intrauterine pregnancy

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

CARDIAC ACTIVTIYFourth sign of intrauterine pregnancy

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

BHCG AND PROGESTERONE IN EARLY PREGNANCY

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

Serial ß-hCG

The doubling time for a normal IUP is 2 days

ß-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

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

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%

SPONTANEOUS ABORTION: BACKGROUND, ETIOLOGY

Spontaneous abortion or miscarriage

Spontaneous abortion is a fetal loss before 20 weeks gestation

80% 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.

Background

Miscarriage is the most common serious pregnancy complication affecting approximately 30% of biochemical pregnancies and 11–20% of clinically recognized pregnancies

The diagnosis of miscarriage is made most commonly by trans-vaginal ultrasound (TVS) assessment

After a diagnosis of miscarriage, half of women undergo significant psychological effectsCecilia Bottomley, Tom Bourne. Diagnosing miscarriage.

Best Practice & Research Clinical Obstetrics & Gynecology 2009; 23:463-77

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

Etiologies

The most frequent type of chromosomal abnormalities detected are:1. Autosomal trisomies ─ 52 %2. Monosomy X ─ 19 %3. Polyploidies ─ 22 %4. 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

CLASSIFICATION OF MISCARRIAGE

Clinical classification of spontaneous abortion

Type Definition

Threatened abortion

Vaginal 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 abortion

Vaginal 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

Differential Diagnosis ofThreatened Abortion

1. Undetermined or physiologic (implantation related)

2. Ectopic pregnancy3. Sub-chorionic bleed, found in ~20%

of threatened Ab4. Gestational trophoblastic disease

(molar pregnancy)5. Impending spontaneous

miscarriage6. Cervix, vaginal or uterine pathology

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!

COMPARISON OF INTERNATIONAL CRITERIA

Different organizations use different cutoffs to diagnose miscarriage…

Royal College of Obstetricians and Gynaecologists. The Management of

Early Pregnancy Loss. Green-Top Guideline No. 25. October 2006

Miscarriage: 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

The Institute of Obstetricians and Gynaecologists

Royal College of Physicians of Ireland

Transvaginal Ultrasound

Embryo > 7 mmNo cardiac

activity

Miscarriage

Gestational sac > 20 mm

No embryo or yolk sac

Miscarriage

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

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

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: 497–502

Prospective multicenter study 1060 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

SummarySummary

Significant 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