1. First Trimester Bleeding and Abortion UNC School of Medicine Obstetrics and Gynecology Clerkship Case Based Seminar Series Gretchen S. Stuart, MD, MPHTM Amy G. Bryant, MD Jennifer H. Tang, MD Erika E. Levi, MD Family Planning Program, Dept Ob/Gyn, UNC-Chapel Hill Updated August 17, 2011

2. Objectives  Develop a differential for first trimester vaginal bleeding  Differentiate the types of spontaneous abortion (missed, complete, incomplete, threatened, septic)  Describe the causes of spontaneous abortion  List the management options for spontaneous abortion  Describe reasons for induced abortion  List methods of induced abortion  Understand the public health impact of the legal status of abortion

3.  Ectopic pregnancy  Normal intrauterine pregnancy  Threatened abortion  Abnormal intrauterine pregnancy Most Common Differential Diagnosis of 1 st Trimester Bleeding

4.  Urine pregnancy test (UPT)  Accurate on first day of expected menses  βhCG  6-8 days after ovulation – present  Date of expected menses (@14 days after ovulation) – βhCG is100 IU/L  Within first 30 days – βhCG doubles in 48-72 hours  Important for pregnancy diagnosis prior to ultrasound diagnosis Diagnosis tools for early pregnancy

5. EGAβhCG (IU/L) Visualization 5 wks>1500Gestational sac 6 wks>5,200Fetal pole 7 wks>17,500Cardiac motion Diagnostic tools for early pregnancy Transvaginal ultrasound Estimated β hCG values and associated findings on transvaginal ultrasound in early pregnancy

6.  SAB/EPF if  Ultrasound measurements are:  5mm CRL and no fetal heart rate  10mm Mean Sac Diameter and no yolk sac  20mm Mean Sac Diameter and no fetal pole  Change in βhCG is  <15% rise in βhCG over 48 hours  Gestational sac growth <2mm over 5 days  Gestational sac growth <3mm over 7 days Diagnosis of Spontaneous Abortion (SAB) or Early Pregnancy Failure (EPF)

7.  Diagnosis made by ultrasound and/or ßhCG – normally growing early pregnancy, but with vaginal bleeding  More formal definition:  Vaginal bleeding before the 20 th week  Bleeding in early pregnancy with no pregnancy loss Diagnosis of threatened abortion

8.  SAB (spontaneous abortion):  Usually refers to first 20 weeks  Abortion in the absence of an intervention  If fetus dies in uterus after 20wks GA  Called a fetal demise or stillbirth Spontaneous Abortion (SAB) Early Pregnancy Failure (EPF)

9.  Complete  Incomplete: cervix open, some tissue has passed  Inevitable: intrauterine pregnancy with cervical dilation & vaginal bleeding  Chemical pregnancy: +βhcg but no sac formed  Blighted ovum/anembryonic pregnancy: empty gestational sac, embryo never formed  Missed: embryo never formed or demised, but uterus hasn’t expelled the sac  Septic: missed/incomplete abortion becomes infected Types of SAB/EPF

10.  Epidemiology  15-25% of all clinically recognized pregnancies  Offer reassurance: probability of 2 consecutive miscarriages is 2.25%  85% of women will conceive and have normal third pregnancy if with same partner  80% in the first 12 weeks  Etiologies  Chromosomal  Non-chromosomal SAB/EPF Epidemiology and etiology

11.  50% due to chromosomal abnormalities  50% trisomies  50% triploidy, tetraploidy, X0 SAB/EPF: Chromosomal Etiologies

12.  Maternal systemic disease  Antiphospholipid antibody syndrome, lupus, coagulation disorders  Infectious factors  Brucella, chlamydia, mycoplasma, listeria, toxoplasma, malaria, tuberculosis  Endocrine factors  DM, hypothyroidism, “luteal phase defect” from progesterone deficiency 50% Non-Chromosomal Etiologies

13.  Abnormal placentation  Anatomic considerations (fibroids, polyps, septum, bicornuate uterus, incompetent cervix, Asherman’s)  Environmental factors  Smoking >20 cigarettes per day (increased 4X)  Alcohol >7 drinks/week (increased 4X)  Increasing age 50% Non-Chromosomal Etiologies

14.  Outcomes  25-50% will progress to spontaneous abortion  However – if the pregnancy is far enough along that an ultrasound can confirm a live pregnancy then 94% will go on to deliver a live baby  Management  Reassurance  Pelvic rest has not been shown to improve outcome Outcomes and management of threatened abortion

15. 1.Uterine evacuation by suction  Manual  Electric 2.Uterine evacuation by medication Management of spontaneous abortion

16. Surgical management SAB/EPF Manual vacuum aspiration  Ensures POCs are fully evacuated  Minimal anesthesia needed  Comfortable for women due to low noise level  Portable for use in physician office familiar to the woman  Women very satisfied with method MVA Label. Ipas. 2007.

17. Creinin MD, et al. Obstet Gynecol Surv. 2001.; Goldberg AB, et al. Obstet Gynecol. 2004.; Hemlin J, et al. Acta Obstet Gynecol Scand. 2001. Electric vacuum aspirator  Uses an electric pump or suction machine connected via flexible tubing Surgical management SAB/EPF Electric Vacuum Aspirator

18.  Aspiration/vacuum  Preparation  Music  Support during procedure  Conscious sedation  Paracervical block  Medication abortion  NSAIDS  Oral narcotics and antiemetics if necessary Pain Management

19. Tissue examination  Basin for POC  Fine-mesh kitchen strainer  Glass pyrex pie dish  Back light or enhanced light  Tools to grasp tissue and POC  Specimen containers Source: A Clinicians Guide to Medical and Surgical Abortion; Paul M, Grimes D, National Abortion Federation, available online Hyman AG, Castleman L. Ipas. 2005 Floating Chorionic Villi

20. Dean G, et al. Contraception. 2003. EVAMVA VacuumElectric pumpManual aspirator NoiseVariableQuiet PortableNot easilyYes AnesthesiaConscious sedation and paracervical block Capacity350–1,200 cc60 cc AssistantNot necessaryHelpful Comparison of surgical management

21. Complication Rate/1000 procedures Prevention Uterine perforation1 Cervical preparation Intra-Op Ultrasound Hemorrhage<12 wks – 0 Efficient completion of procedure Retained products3 Ultrasound Gritty texture Examine POC Infection2.5 Prophylactic antibiotics PO doxy or IV cephalosporin Post-abortal hematometra 1.8 N/a – unpredictable Immediate re-aspiration required EVA and MVA risks and preventing the risks

22.  Misoprostol  Synthetic prostaglandin E1 analog  Inexpensive  Orally active  Multiple effective routes of administration  Can be stored safely at room temperature  Effective at initiating uterine contractions  Effective at inducing cervical ripening Medication management of SAB/EPF

23.  Misoprostol 800 μg vaginally  Repeat dose on day 2 or 3 if indicated  Pelvic U/S to confirm empty uterus  Consider vacuum aspiration if expulsion incomplete Zhang J, et al. N Engl J Med. 2005. Creinin MD, et al. Obstet Gynecol. 2006. Regimen

24. Misoprostol 600 μg vaginally Expectant management (placebo) Success by day 273.1%13.5% Success by day 788.5%44.2% Evacuation needed 11.5%55.8% Bagratee JS, et al. Hum Reprod. 2004. Efficacy: Medication vs. Expectant Management

25. Language:  Termination  Abortion  Elective abortion  Therapeutic abortion  Interruption of pregnancy Definition  The removal of a fetus or embryo from the uterus before the stage of viability Indications  Personal choice  Medical indication (hemorrhage, infection)  Medical recommendation (SLE, Pulmonary HTN, PPROM)  Fetus diagnosed with anomalies Methods  Dependent upon gestational age and provider abilities Induced Abortion/Pregnancy Termination

26.  Any discussion of abortion needs to include some of the legal and political aspects  Providers should be familiar with the abortion laws in their own states  Providers performing abortions must know the laws in their own state Induced Abortion History

27.  1821 – First abortion law enacted in Connecticut  Bars abortion after “quickening”, but definitions vague  1973 – Roe v. Wade  Woman’s constitutional right of privacy  The government cannot prohibit or interfere with abortion without a “compelling” reason  1976 – Hyde Amendment  Forbids use of federal money to pay for almost any abortion under Medicaid  Some states have reinstated state funding (NY, VT, CA among others) Induced Abortion History

28.  1 in 3 women by the age of 44 years  1/3 occur in women older than 24 years  Gestational age:  90% within first 12 weeks  50% within first 8 weeks  Complications  Dependent upon gestational age  7-10 weeks have lowest complication rates  mortality: 1/100,000  Complications are 3-4x higher for second-trimester than first trimester Induced Abortion Epidemiology

29. Gold RB, Richards C. Issues Sci Technol. 1990.; Hatcher RA. Contracept Technol Update. 1998.; Mokdad AH, et al. MMWR Recomm Rep. 2003. IncidentChance of death Terminating pregnancy < 9 weeks1 in 500,000 Terminating pregnancy > 20 weeks1 in 8,000 Giving birth1 in 7,600 Driving an automobile1 in 5,900 Using a tampon1 in 350,000 Putting Induced Abortion into Perspective…

30. Earlier Procedures are Safer Abortions at < 8 weeks = lowest risk of death Bartlet L, et al. Obstet Gynecol. 2004. Gestational Age Strongest risk factor for abortion-related mortality 61% ≤8 weeks 18 10 6 1 4 ≤8 9 to 10 11 to 12 13 to 15 16 to 20 ≥21 Weeks Gestation

31.  Methods:  Uterine evacuation (basically the same as treatment of abortion; however, the cervix is closed)  Manual vacuum aspiration  Electric vacuum aspiration  Medication  Mifepristone and misoprostol Induced Abortion Methods

32.  Mifepristone  19-norsteroid that specifically blocks the receptors for progesterone and glucocorticosteroids  Antagonizing effect blocks the relaxation effects of progesterone  Results in uterine contractions  Pregnancy disruption  Dilation and softening of the cervix  Increases the sensitivity of the uterus to prostaglandin analogs by an approximate factor of five  Takes 24-48 hours for this to occur  Misoprostol  Synthetic prostaglandin E1 analog  Inexpensive  Orally active  Multiple effective routes of administration  Can be stored safely at room temperature  Effective at initiating uterine contractions  Effective at inducing cervical ripening  Used in decreasing doses as pregnancy advances Medical abortion methods

33. Gestational age (days) Complete abortion rate (%) Time to expulsion (after misoprostol) < 4991–97 49%–61% within 4 hours < 5683–95 87%–88% within 24 hours < 6388 1.Mifepristone 200-600 mg orally, administered in clinic 2.Misoprostol 400-800 mcg orally or buccally 24-48h later 3.Evaluate with ultrasound 13-16 days later to confirm completion WHO Task Force. BJOG. 2000.; Peyron R, et al. N Engl J Med. 1993. Spitz IM, et al. N Engl J Med. 1998; Winikoff B, et al. Am J Obstet Gynecol. 1997. Medical abortion protocols

34.  Epidemiology  14 weeks gestation and above  96% done by Dilation and Evacuation (D&E)  4% done by labor induction 2nd Trimester Induced Abortion Epidemiology

35.  Etiology  Social indications  Delay in diagnosis  Delay in finding a provider  Delay in obtaining funding  Teenagers most likely to delay  Fetal anomalies  Genetic such as Trisomy 13, 18, 21  Anatomic such as cardiac defects  Neural tube such as anencephaly 2nd Trimester Induced Abortion Etiology

36.  Discuss pain management  Informed Consent  Discuss contraception – even those with abnormal or wanted pregnancy may not want to follow immediately with another pregnancy  Ovulation can occur 14-21 days after a second trimester abortion; risk of pregnancy is great and must be addressed  Lactation can occur between days 3-7 postabortion  Procedure  Follow-up Nyoboe et al 1990 2 nd Trimester Induced Abortion Counseling

37. Dilation and evacuationLabor induction abortion Two visits in 1-2 daysRequires inpatient hospital stay usually lasting 1-3 days Anesthesia/analgesia requiredAverage time to delivery 13 hrs Procedure room requiredIncreased likelihood of retained placenta resulting in uterine evacuation compared to D&E Skilled surgeonMedication used misoprostol and/or mifepristone Laminaria placement required before procedure 2 nd trimester induced abortion Management

38. Complication Rate/1000 procedures Prevention Uterine perforation1 Cervical preparation Intra-Op Ultrasound Hemorrhage 13-15 wks: 12 17-25 wks: 21 Adequate anesthesia Paracervical block which includes vasopressin 4 units. Efficient completion of procedure Retained products5-20 Ultrasound, Gritty texture Examine POC Infection2.5 Prophylactic antibiotics PO doxy or IV cephalosporin Post-abortal hematometra 1.8 n/a – unpredictable Immediate re-aspiration required D&E risks and prevention

39.  Surgeons skilled and experienced in D&E provision  Adequate pain control options with appropriate monitoring  Requisite instruments available  Staff skilled in patient education, counseling, care and recovery  Established procedures at free standing facilities for transferring patients who require emergency hospital-based care Requirements for a safe D&E Program

40.  Laminaria  Osmotic dilators  Dried compressed seaweed sticks, 5-10mm diameter in size  4-19 dilators can be placed  Slow swelling to exert slow circumferential pressure and dilation  1-2 days prior to procedure  Paracervical block with 20cc 0.25% bupivicaine D&E Step 1 cervical Preparation

41.  Adequate anesthesia  Ultrasound guidance  Uterine evacuation using suction and instruments  Paracervical block with 20cc 0.5% lidocaine and 4U vasopressin to decrease blood loss D&E Procedure

42.  One office visit – then hospital admission  Hypertonic saline amnioinfusion, intracardiac KCl, intra-amniotic digoxin to induce fetal death  Misoprostol or misoprostol and mifepristone to cause contractions and uterine evacuation  20% may require vacuum aspiration for retained placenta Labor Induction Abortion

43.  Patient is awake  Can obtain analgesia for pain  Fetus delivered intact  Often only option for obese women Labor Induction Abortion

44. Bottom Line Concepts  First trimester bleeding occurs in 25% of all pregnancies and 25-50% will progress to a spontaneous abortion  Etiologies of first trimester bleeding include normal pregnancy, spontaneous abortion/early pregnancy failure, or ectopic pregnancy.  Diagnosis of normal vs abnormal early pregnancy made using physical exam and ultrasound and/or ßhCG  50% of spontaneous abortions are the result of genetic abnormalities  Management of spontaneous abortion can be medical or surgical and surgical options can be in the operating room or in the clinic  1/3 women will have an induced abortion  Induced abortion before 8 weeks is safest  Risks associated with induced abortion are less than childbirth or driving a car  Methods for induced abortion include medication or surgical

45.  24yo G1P0 presents to your office and reports spotting dark blood for 4 days.  What are your initial history questions?  What steps will you take to make the final diagnosis? Case No. 1

46.  On the ultrasound exam you note a CRL consistent with 8 weeks but no cardiac motion. – What kind of abortion does she have? – What proportion of clinically recognized pregnancies will end in spontaneous abortion? – What proportions of spontaneous abortions are due to chromosomal abnormalities? – What are some of the non-chromosomal etiologies of spontaneous abortion? – What are her options for management? – What are the advantages of each option? Case No. 1 Continued

47. 32yo G2P1 presents with lower abdominal pain, vaginal spotting, and an LMP 6 weeks ago.  What’s in your differential diagnosis?  What pertinent things about her history would you like to know?  What would you look for on physical exam?  What labs/imaging studies would you order? Case No. 2

48. Her BHCG returns as 3200 and a pelvic ultrasound does not demonstrate an intrauterine pregnancy  What is her likely diagnosis?  What are some risk factors for this diagnosis?  What are her treatment options?  What would you tell her about future pregnancies? Case No. 2 Continued

49. 27yo G5P4 with LMP 8 wks ago presents with fever to 101.4, abdominal pain, and vaginal bleeding  What is in your differential diagnosis?  What are your initial history questions?  What pertinent findings might you look for on physical exam? Case No. 3

50. The patient states that she “took a pill to make her period come down” a couple weeks ago and has had spotting ever since. The fever started last night, and the bleeding has now gotten heavier. On exam, her os is open and she has purulent discharge. She also has fundal tenderness.  What kind of abortion does she have?  What risk factors does she have for this diagnosis?  What are her options for management? Case No. 3 Continued

51. A 38 year-old G1P0 with an IVF pregnancy at 16wks presents to discuss the results of her recent fetal survey, which shows fetal anencephaly. You know that most anencephalic fetuses do not survive birth.  How do you counsel this patient?  What are her options for management?  What questions do you ask her to help her make a decision for management?  How would you counsel the patient if the ultrasound showed features consistent with Trisomy 21 instead of anencephaly? Case No. 4

52. References and Resources  APGO Medical Student Educational Objectives, 9 th edition, (2009), Educational Topic 16 (p34-35), 34 (72-73)  Beckman & Ling: Obstetrics and Gynecology, 6th edition, (2010), Charles RB Beckmann, Frank W Ling, Barabara M Barzansky, William NP Herbert, Douglas W Laube, Roger P Smith. Chapter 13 (p147-150).  Hacker & Moore: Hacker and Moore's Essentials of Obstetrics and Gynecology, 5th edition (2009), Neville F Hacker, Joseph C Gambone, Calvin J Hobel. Chapter 7 (p74-78).