Complications of Pregnancy

1. Complications of Pregnancy Lee Graham January 22, 2009

2. What’s Covered • Miscarriage • Ectopic • Hyperemesis • preeclampsia/eclampsia/HELLP • Throboembolus

3. What’s not covered • Abruption • Previa • Amniotic fluid embolism • Surgical disease of pregnancy • Fetal monitoring • Delivery • US

4. Case 1 • 32 yo with vaginal bleeding • ~7/52 pregnant • (positive home preg test 1 week ago) • no prenatal care • Vaginal spotting X 2 days • Diffuse abdominal cramping 2hrs before arrival • Pmed / Pobs / Psurg = non contributory

5. Case 2 • Vitals = 37 C, HR=93, BP=110/70 • Abdo = soft/non-tender • Pelvic = • Cervic closed • Moderate amount of blood at the os • No adenexal mass and mild cervical motion tenderness

6. Case 2 • US - no visible IUP

7. General approach • In all women presenting with: • Abdominal/pelvic pain • Vaginal bleeding • Syncope • Shock • You must consider the dx of Pregnancy • Obtain a Urine hCG

8. Lower abdominal pain and/or vaginal bleeding - urine hCG + urine hCG

9. Diagnosis of pregnancy • Fertilization occurs in the fallopian tube within minutes to hours after follicular ovulation. • Implantation in the endometrium > ~6 days • Trophoblast secretes hCG > ~7 days • Augments corpus luteal production of progesterone until the trophoblastic production of progesterone is capable of maintaining pregnancy

10. hCG • The initial doubling time is fast • attributed to the actual process of implantation. • This is followed by a slower rate of doubling as trophoblast hCG and maternal circulatory hCG equilibrate • hCG levels peak at 7 to 10 weeks of • mean value of 50,000 IU/L • range of 20,000 to 200,000 IU/L

11. Urine Pregnancy Test • Monoclonal antibodies are selected that act against the purified β subunit of hCG • Sensitivity between 25 and 50 IU/L. • Normal hCG levels in men and premenopausal women range from 0.02 to 0.8 IU/L. • Postmenopausal women may have higher levels.

12. Urine Pregnancy Test • hCG testing becomes positive in 98% of patients 7 days after implantation, which coincides with the time of the expected period. • Negative result 1 week from the expected time of the missed period essentially guarantees that a woman is not pregnant. • Doubling time • 4 wk = 2.2 days (sd ± 0.8 d) • 9 wk = 3.5 days (sd ± 1.2 d)

13. False Positive • postmenopausal status • abortion in the first trimester • exogenous hCG for induction of ovulation • hCG-secreting tumor • Molar pregnancy

14. False Negative • Expired test • Too early • Murse (color blind) • Dilute urine? (SG < 1.010, use 20 drop test) • High vitamin C • gross hematuria • protein > 2+

15. “Effect of low urine specific gravity on pregnancy testing” • J Am Coll Health 1998 Nov;47(3):138-9. • Urine pregnancy tests with a low urine specific gravity (<1.015) were compared with a serum specimen. • 410 urine specimens were evaluated. Eighty of the women with a specific gravity under 1.015 had negative urine pregnancy tests with a concomitant serum specimen. 0% False Negative.

16. Signs of Pregnancy • Uterine enlargement • Non pregnant - size of ping pong • 4-6 weeks - size of baseball • 8-10 weeks - size of softball • 12 weeks - symphysis pubis • 16 - 20 weeks - umbilicus • 36 - 38 weeks xiphoid process of the sternum • >38 weeks - fetus descends into the pelvis • Hegar’s sign (6-8 weeks) softening of the lower uterine segment • Chadwick's sign (6-8 weeks) vaginal walls changes from pink to blue to violet

17. Lower abdominal pain and/or vaginal bleeding Workup as non-pregnant - urine hCG + urine hCG

18. Lower abdominal pain and/or vaginal bleeding Workup as non-pregnant - urine hCG + urine hCG Hemodynamicaly unstable Hemodynamicaly stable

19. Lower abdominal pain and/or vaginal bleeding Workup as non-pregnant - urine hCG + urine hCG Hemodynamicaly unstable Hemodynamicaly stable ?Ruptured ectopic pregnancy or hemorrhage Resuscitate, EDTU and surgical consultation

20. Lower abdominal pain and/or vaginal bleeding Workup as non-pregnant - urine hCG + urine hCG Hemodynamicaly stable Cervix open Or Products of Conception History and physical examination Cervix Closed Ultrasound Ultrasound Inevitable or Complete Miscarriage IUP Ectopic Non- Diagnostic Miscarriage or Physiologic Treat

21. Ectopic Pregnancy • Gestation that implants outside the endometrial cavity • Incidence in ED • among women presenting with vaginal bleeding or pain in the first trimester is 10% • 2nd leading cause of maternal death

22. Ectopic Pregnancy • Incidence of ectopic pregnancy is highest in women aged 25 to 34 • The rate is highest among older women and women belonging to minority groups. • Heterotopic pregnancy • Natural birth 1 in 4000 • IVF - 1-4/100

23. Ectopic and hCG • The embryo grows at a slower rate than normal pregnancies • Usually resulting in a low hCG level and rise • Rupture can occur at any level • Documented at less than 100 mIU/mL • Unruptured ectopics documented at 50,000

24. Risk Factors • No risk factors in 50% confirmed ectopics • High Odds Ratio • Previous ectopic pregnancy 9.3 - 47 • Previous tubal surgery 6.0 - 11.5 • Tubal ligation 3.0 - 139 • Tubal pathology 3.5 - 25 • Current IUD use 1.1 - 45

25. Risk Factors • Moderate Odds Ratio • Infertility 1.1 - 28 • Previous cervicitis 2.8 - 3.7 • History of pelvic inflammatory disease 2.1 - 3.0 • Multiple sexual partners 1.4 - 4.8 • Smoking 2.3 - 3.9 • Low • Previous pelvic/abdominal surgery 0.9 - 3.8 • Vaginal douching 1.1 - 3.1 • Early age of intercourse (<18 years) 1.1 - 2.5

26. Symptoms • In one representative series of 147 patients with ectopic pregnancy • Abdominal pain (99%) • Amenorrhea (74%) • Vaginal bleeding (56%) J Reprod Med 1982 Feb;27(2):101-6.

27. Signs • PE often unremarkable in small, unruptured ectopics • Adnexal masses are felt in only 10% to 20% of patients with ectopic pregnancy • Vital signs - • orthostatic changes • occasionally, low grade fever • Mild uterine enlargement • Tenderness • adnexal / cervical motion /abdominal

28. Ectopics and Vaginal Bleeding • Heavy bleeding with clots or tissue usually suggests a threatened or incomplete miscarriage • Endometrial sloughing can be mistaken for passage of fetal tissue (dropping hormone levels) • Passed tissue should be examined in saline

29. Diagnostics • Consider in any female of reproductive age in the ED with • abdo pain • vaginal bleeding • shock • syncope • All women with a positive hCG and these symptoms need an US

30. Ruptured Corpus Luteum Cyst • 1st - trimester bleeding with pain • Corpus luteum normally supports the pregnancy during the first 7 to 8 weeks • Rupture causes pelvic pain and peritoneal irritation • US is helpful if it reveals an IUP (except in patients with in vitro fertilization)

31. Lower abdominal pain and/or vaginal bleeding Workup as non-pregnant - urine hCG + urine hCG Hemodynamicaly stable Cervix open Or Products of Conception History and physical examination Cervix Closed Ultrasound Ultrasound Inevitable or Complete Miscarriage IUP Ectopic Non- Diagnostic Miscarriage or Physiologic Treat

32. Non-diagnostic US Quantitative hCG <1500 >1500

33. Discriminatory zone • Serum hCG level above which a gestational sac SHOULD be visualized by ultrasound examination if an intrauterine pregnancy is present • Institutional dependent • Trans-vaginal 1500 or 2000 IU/L • Trans-abdominal 6500 IU/L

34. Discrimatory zone • -ve US below the discriminatory zone can be • early viable intrauterine pregnancy • ectopic pregnancy • nonviable intrauterine pregnancy • Such cases are termed "pregnancy of unknown location" and 8 to 40 percent are ultimately diagnosed as ectopic pregnancies • Gestatinal sac can be seen as low as 800

35. hCG rises like an IUP 21% EP Minimal rise IUP Abnormal rise hCG 71% EP hCG hCG falls like a SAB 8% EP Minimal fall SAB 0 Day’s after presentation 0

36. Non-diagnostic US Quantitative hCG <1500 >1500

37. Non-diagnostic US Quantitative hCG <1500 >1500 No adnexal mass and no IUP Suspicious mass in adnexa Repeat B-HCG + and US in 2 days Treat as EP IUP No IUP hCG decreasing hCG or plateaued Failed Pregnancy (IUP vs Ectopic) Ectopic

38. hCG > 1500 • i)IUP • Visualiztion of IUP rules out ectopic • Exceptions include • heterotopic pregnancies • misdiagnoses • rudimentary uterine horn • Cornua

39. hCG > 1500 • ii)Adnexal Mass • Embryonic cardiac activity or a gestational sac with a definite yolk sac or embryo at an extrauterine location is certain evidence of an ectopic gestation

40. hCG >1500 • iii) Neither • NO IUP or Anexal Mass • May represent multiple gestations • Repeat US and hCG concentration two days later. • No IUP - ABNORMAL • hCG increasing or plateaued - ECTOPIC • hCG decreasing - failed pregnancy • arrested pregnancy, • blighted ovum, • tubal abortion, • spontaneously resolving ectopic

41. Non-diagnostic US Quantitative hCG <1500 >1500

42. Non-diagnostic US Quantitative hCG <1500 >1500 hCG in 72hr <2X hCG hCG 2X hCG Follow US until IUP or EP US Failed Pregnancy (IUP vs Ectopic) Non-diagnostic EP IUP Failed Pregnancy (IUP vs Ectopic) Weekly hCG until negative

43. Female patient with positive urine BHCG Lower abdominal pain and/or vaginal bleeding Hemodynamicaly stable Hemodynamicaly unstable Cervix open Or Products of Conception History and physical examination ?Ruptured ectopic pregnancy or hemorrhage Cervix Closed Inevitable or Complete Miscarriage Ultrasound Resuscitate, EDTU and surgical consultation IUP Ectopic Non- Diagnostic Miscarriage or Physiologic bleeding Treat

44. Management • Surgical vs Methotrexate • Equivalent outcomes • Approximately 35 percent of women with ectopic pregnancy are eligible for medical treatment

45. Ectopic - Medical • MTX is a folic acid antagonist • Inhibits DNA synthesis and cell reproduction, primarily in actively proliferating cells such as malignant cells, trophoblasts, and fetal cells. • Rapidly renally cleared • With renal insufficiency, a single dose of MTX can lead to death or severe complications • bone marrow suppression • acute respiratory distress syndrome • bowel ischemia.

46. Contraindications to MTX • Hemodynamically unstable • Impending or ongoing ectopic mass rupture (ie, severe or persistent abdominal pain or >300 mL of free peritoneal fluid outside the pelvic cavity) • Hematologic, renal or hepatic disease • (need BW before treatment) • Immunodeficiency, active pulmonary disease, peptic ulcer disease • Coexistent viable intrauterine pregnancy • No post-therapeutic monitoring

47. Relative contraindications • High hCG concentration • A high serum hCG concentration is the most important factor associated with treatment failure • hCG concentration greater than 5000 are more likely to require multiple courses of medical therapy or experience treatment failure • Fetal cardiac activity • Large ectopic size (>3.5cm)

48. Follow up • Patients may require multiple doses • Require frequent bloodwork monitoring • Followed until hCG to zero • Can be 2 to 3 months • Patients still at risk of tubal rupture

49. Surgical • Salpingostomy versus salpingectomy • Laparoscopy versus laparotomy • Indications: • Hemodynamic instability • Impending or ongoing rupture of ectopic mass • Contraindications to use of methotrexate • Coexisting intrauterine pregnancy • No posttreatment follow-up • Desire for permanent contraception • Known tubal disease with planned in vitro fertilization for future pregnancy • Failed medical therapy

50. Surgical • Post surgery persistent ectopic pregnancy reported in case series ranges from 4 to 15 percent • Weekly measurement of serum beta-hCG concentration to r/o persistent disease