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

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Presentation on theme: "1 st TRIMESTER PREGNANCY FAILURE Shortened to emphasize medical student curriculum requirements Carlos M. Fernandez, M.D Department of Obstetrics and Gynecology."— Presentation transcript:

1 1 st 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 “Double decidual sign” at 4½ to 5 wks Gestational sac + yolk sac at 5 wks (a definitive sign of IUP) Gestational sac + yolk sac at 5 wks (a definitive sign of IUP) GS + yolk sac + embryo at 5½ to 6 wks GS + yolk sac + embryo at 5½ to 6 wks CRL >5 mm – fetal cardiac activity present CRL >5 mm – fetal cardiac activity present Seeber BE and Barnhart KT. Obstet Gynecol 2006;107:

4 First sign of IUP: double decidual sign 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)

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6 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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8 Gestational Sac (confirmed by double decidual sign) Grows 1 mm per day Grows 1 mm per day Usually seen by 4 ½ to 5 weeks of gestation Usually seen by 4 ½ to 5 weeks of gestation Discriminatory ß-hCG with TVS: usually quoted ß-hCG IU/L. Depends upon: 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 Sa c Discriminatory ß-hCG with TVS : ß-hCG IU/L Discriminatory ß-hCG with TVS : ß-hCG IU/L Discriminatory ß-hCG with TAS: ≥ 6500 ß-hCG IU/L Discriminatory ß-hCG with TAS: ≥ 6500 ß-hCG IU/L Bhatt & Dogra, Radiol Clin N Am 45 (2007)

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

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

15 BHCG AND PROGESTERONE IN EARLY PREGNANCY

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

17 Serial ß-hCG The doubling time for a normal IUP is 2 days, with a range of 1.4 to 2.1 days 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 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 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 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 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 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 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: % 21-35%

20 Serum Progesterone Progesterone level of <10 ng/ml is consistent with an abnormal pregnancy 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 > 20 ng/ml is consistent with a normal pregnancy Progesterone level of < 5 ng/ml is % specific of an abnormal 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 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 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 Late loss refers to losses from weeks 12 to 20 80% of miscarriages occurring in the first trimester 80% of miscarriages occurring in the first trimester Ferri: Ferri's Clinical Advisor 2012, 1st ed.

23 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 pregnancyMiscarriage

24 Miscarriage Miscarriage is the most common serious pregnancy complication affecting approximately 30% of biochemical pregnancies and 11–20% of clinically recognized pregnancies 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 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 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: 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 p.179

27 CLASSIFICATION OF MISCARRIAGE

28 Clinical classification of spontaneous abortion TypeDefinition Threatened 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 abortionIntrauterine demise of the conceptus without either vaginal bleeding or expulsion of the products of conception Incomplete abortionVaginal bleeding with dilation of the cervix and partial expulsion of the conceptus Complete abortionVaginal bleeding with expulsion of all of the products of conception Inevitable abortionAbortion in progress in which the bleeding is profuse with cervical dilation but a maintained intrauterine pregnancy Laifer-Narin SL. Ultrasound for Obstetrics Emergencies. Ultrasound Clin. 2011; 6:

29 Threatened Abortion Pregnant patient who is symptomatic with: Pregnant patient who is symptomatic with: Vaginal bleeding Vaginal bleeding Mild abdominal cramps Mild abdominal cramps Closed cervical os Closed cervical os Complication affecting 16-25% of pregnant patients Complication affecting 16-25% of pregnant patients SAB rate as high as 50% before ultrasound evaluation of fetal viability 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 1. Undetermined or physiologic (implantation related) 2. Ectopic pregnancy 3. Sub-chorionic bleed, found in ~20% of threatened Ab 4. Gestational trophoblastic disease 5. Impending spontaneous miscarriage 6. 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!

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 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 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 Non visualization of cardiac activity by the time the embryo is 5 mm in length Specificity for diagnosis of nonviable pregnancy is 100% Specificity for diagnosis of nonviable pregnancy is 100% Levine D. Radiology 2007; 245:

33 Royal College of Obstetricians and Gynaecologists. The Management of Early Pregnancy Loss. Green- Top Guideline No. 25. October 2006 Miscarriage: 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 How to define miscarriage using ultrasound-comparing and contrasting national guidelines

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

35 What is the evidence to support the cut-offs used to diagnose miscarriage? Conclusions First systematic review of ultrasound diagnosis of miscarriage 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) 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 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 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 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 Jeve Y et al., UOG 2011 Nov

36 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 Prospective multicenter study 1060 patients of IPUV 1060 patients of IPUVConclusions Current definitions used to diagnose miscarriage by ultrasound are potentially unsafe 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 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 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 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 Prior ectopic Previous tubal surgery Previous tubal surgery History of tubal ligation History of tubal ligation Intra-uterine contraceptive device Intra-uterine contraceptive device History of infertility History of infertility History of PID History of PID History of chlamydia or gonorrhea History of chlamydia or gonorrhea Smoking 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 100% 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) 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 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 ß-hCG levels taken at 0 and 48 h TVS on day 1 and repeat TVS on day 7 TVS on day 1 and repeat TVS on day 7 Still PUL after TVS on day 7 Still PUL after TVS on day 7 Repeat ß-hCG Repeat ß-hCG Repeat TVS as indicated Repeat TVS as indicated All women with PUL were given: All women with PUL were given: Details of follow up Details of follow up 24-h contact numbers in case of emergency 24-h contact numbers in case of emergency Return to EPU or ED if increase of pain or vaginal bleeding Return to EPU or ED if increase of pain or vaginal bleeding Kirk E, et al. Hum Reprod 2007;22:

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

46 RETAINED PRODUCTS OF CONCEPTION

47 Retained Products of Conception (RPOC) RPOC are well-known and troublesome complications after spontaneous or induced abortion and parturition 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 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 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 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 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

48 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.


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