Transcript Quantitative Beta-hCg

Approach to Vaginal Bleeding During
the First Trimester of Pregnancy:
Role of the Discriminatory Zone of
Beta-hCG
Beth Froelke
Emergency Medicine
Overview
• Patient Presentation
• Differential Diagnosis
• Diagnostic tools
– Quantitative b-hCG
• What is it?
• Doubling time
• Discriminatory zone
– Ultrasound
• Summary
S.M.
• 27 y o AAF p/w vaginal bleeding x 1 day
– Spotting on two occasion on toilet paper (< 1
pad); Clot in toilet
– No recent trauma
– No abdominal/suprapubic pain; no fever,
chills, N/V/D
– Seen at OSH two days prior for dizziness – dx
with + urine pregnancy test
• Beta-quant reported at 1500 (told ~ 4 weeks
pregnant); no sonogram; no pelvic done
S.M.
• PMH
– Para 1-0-1-1, SVD x 1; TAB x 1
– Menarche age 11; irregular menses since off
of OCP for past four years; LMP ~ October
2005
– Remote h/o Chlamydia, gonorrhea – treated
– DM, HTN
S.M.
• FH: DM, HTN
• SH: denies tob/ETOH/drug use
• Meds
– Metformin
• Allergies: NKDA
Physical Exam
• VSS
• RRR, Lungs CTA
• Abd soft, NT/ND, no suprapubic
tenderness
• Pelvic exam: no blood or fetal parts in
vault; cervical os open ~ fingertip width; no
CMT or adnexal tenderness
Differential Diagnosis
• Normal intrauterine pregnancy
• Ectopic pregnancy
• Miscarriage
– Threatened miscarriage (closed os)
– Inevitable miscarriage (open os)
– Incomplete miscarriage
• (blood or fetal products in cervical canal)
– Missed miscarriage: (fetal products retained in utero
after nonviable); closed os; low b-hCG
• STD
– Chlamydia, gonorrhea, BV
Differential Diagnosis
• 20% of all pregnancies terminate prematurely
– 80-90% of these are first trimester miscarriages
MUST RULE OUT…
• Ectopic pregnancy until proven otherwise!!
– 2% of pregnancies in US
– 10% of maternal-pregnancy related deaths (Seeber &
Barnhart, 2006)
– Classic signs: amenorrhea, abd pain, vaginal
bleeding
Ectopic Pregnancy
• Risk Factors
– Prior h/o ectopic pregnancy
– H/o tubal surgery or pathology
– Genital infections/STD
– Multiple sexual partners
– Smoking
(Taken from uptodateonline.com – Please see ectopic pregancy
article for full list of Risk Factors)
Plan for S.M.
• IV access (2 large bore IV for unstable patients)
• Labs
– Qualitative, quantitative beta-hCG
– BMP, CBC, coags, UA
– Cervical cultures: gonorrhea, chlamydia, trichomonas,
BV
– Type and screen (type and cross for unstable)
– Rh status
• Ultrasound
– Transabdominal and transvaginal
Human Chorionic Gonadotropin
• First key hormone of pregnancy
• Secreted by the syncytiocytotrophoblast
cells (embryonic origin)
• Prevents corpus luteum from regression
until placenta can make its own
progesterone, estrogen
• Alpha and beta subunits
– Alpha ~ TSH, LH, FSH
– Beta unique
beta-hCG
• Gold standard for diagnosis of pregnancy
• Urine or serum markers
• ELISA
– Most sensitive assays can detect approximately 7
days after fertilization
– Qualitative and quantitative markers
• Sensitivity and specificity
– Laboratory: 97 to 100%
– Home pregnancy: variable by test; ~ 75% sensitive
• FNR often due to testing too early since ovulation
• Repeat in a few days if believe pregnant
Doubling Time of hCG
• Beta-hCG levels double ~ 48 hours
– Minimum of 66% rise over 2 days (Kadar et al., 1981)
• Peaks at 100,000 IU/L (8 to 10 weeks since LMP)
then declines to 30,000 from wk 20 to term
• Utility of serial quantitative b-hCG
– Suggestive of normal pregnancy progression versus
abnormal gestation
– Too low or declining: miscarriage, ectopic
– Too high: multiple births, molar pregancy,
Down’s syndrome
Diagnostic Tools
• By about 5 ½ weeks gestational age,
transvaginal US should be able to identify
IUP
• Discriminatory Zone
– Serum hCG level above which ultrasound
expected to detect a viable intrauterine
pregnancy
– 1500 IU/L – 2500 IU/L (Seeber & Barnhart,
2006)
Diagnostic Tools
• Barnhart et al., 1999
– Accuracy of US with quantitative b-hCG > and
< 1500 IU/L
– Results
• 73% of women with b-hCG < 1500 IU/L had nondiagnostic US (versus 6%)
• 29% of women with hCG < 1500 had accurate
preliminary US dx versus 91% of women with hCG
> 1500 IU/L
– Conclusion
• b-hCG > 1500 IU/L associated with more accurate
US diagnoses
• Seeber and Barnhart, 2006 (Obstet and Gyn)
– Redefined/clarified the importance of rise and fall
of b-hCG
– Rise
• Minimum rise for potentially viable pregnancy across
two days is 53% (n > 700; Barnhart et al., 2004)
– Prior evidence have shown a minimum rise of 66% (n = 20)
• Bottom line: Algorithms endorsing D & C when levels do
not rise by atleast 66% over two days may terminate
viable pregnancies
– Decline
• Minimum decline for spontaneous abortion is 21% to
35% in two days and up to 84% in 7 days (Barnhart et
al., 2004)
Seeber and Barnhart, 2006
• Please see important diagrams in:
Suspected ectopic pregnancy. Obstet Gynecol. 2006
Feb;107(2 Pt 1):399-413. Review. PMID: 16449130
[PubMed - indexed for MEDLINE]
Figure 2: Diagnostic Algorithm for Ectopic Pregnancy
Figure 3: Hypothetical Rise and Fall of serial beta-hcg in women with
an ectopic pregnancy
Treatment Options
• Ectopic Pregnancy
– MTX (dihydrofolate reductase inhibitor)
• Indicated for unrupture EP
– Laparascopic surgery
• Ruptured EP
• Patients questionable reliability for follow-up
• Inevitable/Incomplete Miscarriage
– Misoprostol (prostaglandin E1)
– Dilation and curettage
S.M.
• Final US read…
– Abnormal shaped gestational sac diameter
consistent with 9 week gestation
– No fetal parts identified; no cardiac activity
– Fluid in uterus consistent with spontaneous
abortion
• Return to ED that evening for increased
vaginal bleeding…
S.M.
• Quantitative b-hCG
– 1428 (14% drop in 12 hours)
• Repeat US
– Intrauterine gestational sac no longer
identifiable
• Final Diagnosis: Miscarriage
– Spontaneously Resolving
References
• Barnhart KT, Simhan H, Kamelle SA. Diagnostic accuracy of
ultrasound above and below the beta-hCG discriminatory zone.
Obstet and Gynec 1999;94:583-587.
• Barnhart KT, Katz I, Hummel A., Gracia CR. Presumed diagnosis of
ectopic pregnancy. Obstet and Gynec 2002;100:505-510.
• Barnhart KT, Sammel MD, Rinaudo PF, Zhou L, Hummel AC, Guo
W. Symptomatic patients with an early viable intrauterine
pregnancy: hCG curves defined. Obstet and Gynec 2004;104:5055.
• Barnhart KT, Sammel MD, Chung K, Zhou L, Hummel AC, Guo W.
Decline of serum hCG and spontaneous complete abortion: defining
the normal curve. Obstet and Gynec 2004;104:975-981
• Dart RG. Role of pelvic ultrasonography in evaluation of
symptomatic first-trimester pregnancy. Ann Emerg Med
1999;33:310-320.
• Gracia CR & Barnhart KT. Diagnosing ectopic pregnancy: Decision
analysis comparing six strategies. Obstet and Gynec. 2001;97:464470.
• Seeber BE. & Barnhart KT. Suspected ectopic pregnancy. Obstet
and Gynec 2006;107:399-413.
• Up to Date: searches include ectopic pregnancy, spontaneous
abortion, beta-hCG