1. 1st TRIMESTER PREGNANCY FAILURE Shortened to emphasize medical student curriculum requirements
Carlos M. Fernandez, M.D
Department of Obstetrics and Gynecology
Advocate Illinois Masonic and Medical Center

2. Ultrasound diagnosis of intrauterine pregnancy

3. Diagnosis of IUP “Double decidual sign” at 4½ to 5 wks
Gestational 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:

4. 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)

6. Double-decidual sign ( 5 weeks' menstrual age)
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.

8. 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 TVS: usually quoted ß-hCG IU/L. Depends upon:
Skill of the sonographer and image magnification
Frequency (5-10mHz) and resolution of the transducer
Uterine abnormalities, fibroids
Multiple gestation

9. Gestational Sac Discriminatory ß-hCG with TVS : 1000 - 2000 ß-hCG IU/L
Discriminatory ß-hCG with TAS: ≥ 6500 ß-hCG IU/L
Bhatt & Dogra, Radiol Clin N Am 45 (2007)

10. The gestational sac diameter is used to calculate gestational age
Long axis
Short axis

11. Second sign of IUP: Yolk Sac
First structure visualized within the gestational sac
Round , bright ring <6mm
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

12. Gestational sac and yolk sac (5 weeks' menstrual age)
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.

13. 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

14. 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
Cardiac activity is usually detected at 5 ½ to 6 weeks from last menstrual period
CRL ≥5 mm – fetal cardiac activity present

15. Bhcg and progesterone in early pregnancy

16. Serum concentrations of ß-hCG in 443 normal pregnancies
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
Braunstein G D, et al. Am J Obstet Gynecol 1976; 126:

17. Serial ß-hCG
The doubling time for a normal IUP is 2 days, with a range of 1.4 to 2.1 days
Doubling of ß-hCG is less reliable after 10,000 mIU/ml , at this level pregnancy is better evaluated with U/S
15% of normal IUP can demonstrate an abnormal rise of ß-hCG
Kadar N, et al. Obstet Gynecol 1981;52:162-6

18. ß-hCG up to 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:

19. 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
53%
21-35%
Seeber BE and Barnhart KT. Obstet Gynecol 2006;107:

20. Serum Progesterone
Progesterone level of <10 ng/ml is consistent with an abnormal pregnancy
Progesterone level of > 20 ng/ml is consistent with a normal pregnancy
Progesterone level of < 5 ng/ml is % specific of an abnormal pregnancy
92% of the ectopic pregnancies the progesterone level was < 17.5 ng/ml
McCord ML, et al. Fertil Steril 1996; 66:513-16

21. Spontaneous abortion: background, etiology

22. Spontaneous abortion or miscarriage
Spontaneous abortion is a fetal loss before week 20 of pregnancy
Early loss is before menstrual week 12
Late loss refers to losses from weeks 12 to 20
80% of miscarriages occurring in the first trimester
Ferri: Ferri's Clinical Advisor 2012, 1st ed.

23. Normal first-trimester pregnancy
Miscarriage
Diagram representing placentation in (a) a normal first‐trimester pregnancy and (b) miscarriage. Note trophoblast plugging of maternal spiral arteries and trophoblast invasion of the decidua and superficial myometrium in the central area of the normally developing placenta (a). By contrast, in the miscarriage (b) there is a shallow trophoblastic invasion and the plugs are loose, allowing premature entry of maternal blood (arrows).
© This slide is made available for non-commercial use only. Please note that permission may be required for re-use of images in which the copyright is owned by a third party.
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)

24. Miscarriage
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 the women undergo significant psychological effects, which may last for up to 12 months
Cecilia Bottomley, Tom Bourne. Diagnosing miscarriage. Best Practice & Research Clinical Obstetrics & Gynecology 2009; 23:463-77

25. Miscarriage
The crucial role of chromosomal imbalance in abnormal early human development is well established
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

26. Miscarriage
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 p.179

27. Classification of miscarriage

28. Clinical classification of spontaneous abortion
Laifer-Narin SL. Ultrasound for Obstetrics Emergencies. Ultrasound Clin ; 6:
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 conceptus without either vaginal bleeding or expulsion of the products of conception
Incomplete abortion
Vaginal bleeding with dilation of the cervix and partial expulsion of the conceptus
Complete abortion
Vaginal bleeding with expulsion of all of the products of conception
Inevitable abortion
Abortion in progress in which the bleeding is profuse with cervical dilation but a maintained intrauterine pregnancy

29. Threatened Abortion Pregnant patient who is symptomatic with:
Vaginal bleeding
Mild abdominal cramps
Closed cervical os
Complication affecting 16-25% of pregnant patients
SAB rate as high as 50% before ultrasound evaluation of fetal viability
Chung TKH. Aust N Z J Obstet Gynaecol 1999; 39:

30. Differential Diagnosis of Threatened Abortion
Undetermined or physiologic (implantation related)
Ectopic pregnancy
Sub-chorionic bleed, found in ~20% of threatened Ab
Gestational trophoblastic disease
Impending spontaneous miscarriage
Cervix, vaginal or uterine pathology

31. Ultrasound diagnosis of miscarriage (comparing international criteria)
This section is too in-depth for most medical students; use it only for the most interested students!
Ultrasound diagnosis of miscarriage (comparing international criteria)

32. TVS features of pregnancy failure
Non visualization of the yolk sac by the time the mean sac diameter is 13 mm
Non visualization of the embryo by the time the mean sac diameter is 20 mm
Non visualization of cardiac activity by the time the embryo is 5 mm in length
Specificity for diagnosis of nonviable pregnancy is 100%
Levine D. Radiology 2007; 245:

33. How to define miscarriage using ultrasound-comparing and contrasting national guidelines
Royal College of Obstetricians and Gynaecologists. The Management of Early Pregnancy Loss. Green-Top Guideline No. 25. October 2006
Miscarriage:
Miscarriage is defined at first scan when gestational sac with MSD greater than 20 mm an no embryonic contents or CRL > 6 mm with no heart beat
Or subsequently if sac remain empty after at least one week or still no cardiac activity 1 week after initial

34. Transvaginal Ultrasound Gestational sac > 20 mm
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 mm
No cardiac activity
Miscarriage
Gestational sac > 20 mm
No embryo or yolk sac

35. What is the evidence to support the cut-offs used to diagnose miscarriage?
Conclusions
First systematic review of ultrasound diagnosis of miscarriage
Studies are 15–20 years old, small numbers of miscarriage, reference standards were poor (method of miscarriage confirmation)
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
A confidence interval (CI) is a particular kind of interval estimate of a population parameter and is used to indicate the reliability of an estimate.
Jeve Y et al., UOG 2011 Nov

36. Prospective multicenter study 1060 patients of IPUV Conclusions
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
Current definitions used to diagnose miscarriage by ultrasound are potentially unsafe
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

37. Summary Summary
Data from these studies show that current definitions used to diagnose miscarriage are potentially unsafe
Significant interobserver variability may be associated with a misdiagnosis of miscarriage
Current national guidelines should be reviewed to avoid inadvertent termination of wanted pregnancy
Large prospective studies with agreed reference standards are urgently required

38. Ectopic pregnancy

39. Risk Factors for Ectopic Pregnancy
Prior ectopic
Previous tubal surgery
History of tubal ligation
Intra-uterine contraceptive device
History of infertility
History of PID
History of chlamydia or gonorrhea
Smoking

40. TVS Criteria for Ectopic Pregnancy
TVS Findings
Likelihood of ectopic
Extrauterine embryo + heartbeat
100%
Adnexal fluid + Yolk sac
or Embryo without heart beat
Tubal ring
95%
Complex or solid adnexal mass.
No tubal ring, yolk sac, embryo
91.9%
Brown and Doubilet. J Ultrasound Med 1994, 13:

41. Pregnancy of uknown location

42. Pregnancies of unknown location (PUL)
Definition
Positive pregnancy test with no signs of intra- or extrauterine pregnancy on transvaginal sonography (TVS)
The women should have no signs of hemoperitoneum on ultrasound scan
Condous G, Timmerman D, Golstein S, Valentin L, Jurkovic D, Bourne T. Pregnancies of unknown location: consensus statement. Ultrasound Obstet Gynecol 2006; 28:121-2

43. Pregnancies of unknown location (PUL)
It is well accepted that women with a PUL can be safely managed expectantly
Banerjee S, et al. Ultrasound Obstet Gynecol 1999; 14:231-6
Condous G, et al. Int J Gynecol Obstet 2004; 86:351-7
Condous G, et al. BJOG 2006; 113:1-7
Kirk E, et al. Ultrasound Obstet Gynecol 2006; 27:311-5

44. Follow up of PULs ß-hCG levels taken at 0 and 48 h
Kirk E, et al. Hum Reprod 2007;22:
ß-hCG levels taken at 0 and 48 h
TVS on day 1 and repeat TVS on day 7
Still PUL after TVS on day 7
Repeat ß-hCG
Repeat TVS as indicated
All women with PUL were given:
Details of follow up
24-h contact numbers in case of emergency
Return to EPU or ED if increase of pain or vaginal bleeding

45. Final clinical outcome of 363 PULs
Kirk E, et al. Hum Reprod 2007;22:
229 (63.1%) failing PULs
111 (30.6%) IUPs
23 (6.3%) EP
Within 7 days of follow-up, 97.5% (354/363) of PULs had a final diagnosis
Only 1 patient (0.3%) required a diagnostic laparoscopy for pregnancy location

46. Retained products of conception

47. Retained Products of Conception (RPOC)
Oscar Sadan, Abraham Golan, Ofer Girtler, Samuel Lurie, Abraham Debby, Ron Sagiv, Shmuel Evron, Marek Glezerman. Role of Sonography in the Diagnosis of Retained Products of Conception. JUM :371-4
RPOC are well-known and troublesome complications after spontaneous or induced abortion and parturition
Patients usually have abdominal pain, bleeding, fever, and an open cervical external os
The diagnosis is based on the sonographic appearance of intrauterine echogenic material
Retained products of conception are generally treated by D&C to empty the uterine cavity. This exposes the uterus to additional potential trauma, with immediate risks such as bleeding, perforation, and infection and late sequelae such as intrauterine adhesions

48. Retained products of conception
Retained products of conception. Intrauterine heterogeneous, mixed echogenic mass with marked internal vascularity in a patient who recently underwent spontaneous abortion

49. Transvaginal sagittal sonogram of a uterus immediately after repeated D&C. A thin hyperechoic echo is shown, characteristic of an empty uterus.