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Miscarriage: 1 st trimester pregnancy loss

Miscarriage: 1 st trimester pregnancy loss. Sonal Patel Gynecology didactics Swedish First Hill Family Medicine February 15, 2011. Goals / Objective. Terms/Definitions for first-trimester bleeding Reviewing causes and risk factors for 1 st trimester losses

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Miscarriage: 1 st trimester pregnancy loss

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  1. Miscarriage: 1st trimester pregnancy loss SonalPatel Gynecology didactics Swedish First Hill Family Medicine February 15, 2011

  2. Goals / Objective • Terms/Definitions for first-trimester bleeding • Reviewing causes and risk factors for 1st trimester losses • How to diagnose a 1st trimester pregnancy loss • Review options for management • How to counsel re: options based on Risks / Benefits

  3. Case - 1 • 43 y/o G3P0020 who presents for initial evaluation based on a positive pregnancy test. • No LOF, (+) mild brown vaginal discharge, no abdominal pain or cramping. • Ambivalent feelings about being pregnant. • Couple mostly had ?’s re: prenatal genetic testing.

  4. Case - 2 • Ob/Gynhx: 2 VTOP, early in pregnancy • PMHx: h/o colon ca - s/p partial colectomy and chemotherapy at age 35 (in 2003) • Meds: none • Social: married, no EtOH/tobacco/drugs, runs restaurant with her husband, uninsured • by LMP was at 7 wks EGA • Dating u/s: ~6 4/7 wks, No cardiac activity seen in embryo. • Quantitative hCG 1 day later in-clinic: ~ 50,000

  5. Definitions • "embryo" ≤10 weeks of gestation • "fetus“ > 10 wks of gestation • Spontaneous abortion: passage of tissue before viable gestational age • Typically corresponds to gestational age of less than 20 (or 24) weeks. • WHO defines this by fetus weighing less than 500 g

  6. Definitions • Occurring at < 20 wks EGA • Threatened abortion – any vaginal bleeding until other causes ruled out • Inevitable abortion – ROM and/or cervical dilation • Incomplete abortion – some (but not all) uterine contents passed early pregnancy loss (EPL) • Missed abortion - retention of failed IUP • Silent miscarriage - intrauterine gestation with embryo > 6 mm and no cardiac activity on ultrasound • Anembryonic pregnancy - missed abortion with gestational sac > 20 mm and no fetal pole on ultrasound • Septic abortion – incomplete abortion with ascending infection (endometritis and/or peritonitis)

  7. Numbers – Incidence/Prevalence • Nearly 25% of all women will experience a miscarriage in their lifetime1 • Around half of pts (57%) with bleeding in first trimester go on to miscarry2 • Most cases occur during first 12 weeks of gestation • highest peak at 6 weeks • second, smaller peak at 10 weeks • Risk of Spontaneous abortion dramatically increasing increases with age: • 8.9% in women aged 20-24 years • 74.7% in women > 45 years old3

  8. Causes and risk factors • Chromosomal abnormalities more likely in 1st trimester (most common) • nondisjunction, • balanced translocation/carrier state • trisomy, triploidy, monosomy • Maternal disease more likely in 2nd trimester miscarriage • Age & risk of loss: • 20 to 30 years (9 -17 %) • ~ age 35 (20 %) • 35 - 40 yrs (40 %) • age 45 (80 %)

  9. Anatomic Causes (7) • leiomyomata uteri (submucosal) • Septate/unicornateuterus • bicornuate uterus • incompetent cervix • abnormality of placentation • intrauterine adhesions - intrauterine synechiae(Asherman's syndrome) • maternal in-utero diethylstilbestrol (DES) exposure – assoc w/ abnormally shaped uterus

  10. Endocrine Causes (5) • Luteal phase defect (insufficient progesterone) • Thyroid disease • Hyperandrogenism • Hyperprolactinemia • PCOS

  11. Infectious (14) • Listeria monocytogenes • Mycoplasma hominis • Ureaplasma urealyticum • toxoplasmosis • syphilis • HSV • chlamydia • HIV • parvovirus B19 • gonorrhea • rubella • CMV • HPV • malaria

  12. Medications & Substances • antidepressants • Paroxetine (adjusted OR 1.75) • Venlafaxine (adjusted OR 2.11) • > 1 med (adjusted OR 1.68) • NSAIDs (adjusted RR: 1.8) • Itraconazole (50-800 mg/day for 1-90 days) • 12.6% vs 4% (no exposure) had SAb’s • Cigarette smoking (>10 cig/d) • Cocaine • EtOH (> 3d / week in first 12 wk) • Heavy caffeine intake (>200mg/d)

  13. Risk factors - Others • Trauma – CVS, amniocentesis, blunt abdominal trauma in second trimester • Occupational Hazards: • exposure to ‘unscavenged anesthetic gases’ for ≥ 1 hour per week (OR: 2.49) • performing > 5 radiological exams per week (OR: 1.82) • pesticide use (OR 1.88) • Low pre-pregnancy BMI < 18.5; hazard ratio: 1.24 • Danish National Birth Cohort , n = 23,821 • Note: sexual activity has NOT been show to elevate risk of SAB

  14. Making the Diagnosis • History: • cramping, bleeding, vaginal discharge - color, odor?; fever? • Physical Exam: • Vitals (hypotensive, tachycardic?) • Abdomen: tenderness, masses, peritoneal signs • Bimanual • Speculum Exam • Listen for doppler tones

  15. Making the diagnosis • Rule out: • physiologic bleeding in normal pregnancy (implantation bleeding) • ectopic pregnancy • hydatidiform mole or other trophoblastic disease • non-obstetrical conditions: • cervical polyp • cervicitis • cervical cancer

  16. Pause for emotional support • Look & Listen for cues (grief, guilt, frustration) • Speak slowly • Explain what you are concerned about • Before jumping into management options, give pause and ask about support system (partner involved? Family/friends?) • Let them know you are still collecting info to diagnose potential loss or cause of symptoms • Give AVS, which should include clear warning signs, and on-call phone number

  17. Work-up / Other Tests • Quantitative beta hCG • Ultrasound • Progesterone level • Blood & Rh type • CBC

  18. Role of beta-hCG • “hCG ratio” • serum hCG48 hours / serum hCG0 hours less than 0.874 • ~93% sensitivity • 91 - 96% specificity for failing pregnancy

  19. Role of ultrasound • Cardiac motion should be seen when embryo reaches 5 mm size (5 – 7 wks EGA, TV) • Predictive value of ultrasound fetal heart beat for fetal survival to 20 weeks • 97% sensitivity • 98% specificity5

  20. Review of gestational timeline

  21. Ultrasound Images 6 weeks 5 weeks 10 weeks 8 weeks

  22. Role of Progesterone level • serum progesterone level ≥ 22 ng/mL • sensitivity 100% • specificity 27% • PPV: 10% • NPV: 100% *Ann Emerg Med 2000 Aug;36(2):95

  23. Rhogam? • Rh-negative, or if unknown: RhoGAM recommended • 50 mcg (250 units) with bleeding at < 12 wks • 300 mcg (1,500 units) if bleeding at > 12 wks

  24. Options for management • Expectant: “watch & wait” method – give warning signs • Medical: oral vs. vaginal misoprostol 800 mcg • May repeat dose if no expulsion on day 3 • Surgical: Manual vacuum aspiration (in-office); D&C • Base management on patient preference and need for intervention (based on Sx)

  25. Management by diagnosis • Incomplete abortion: Expectant is successful in 82-96% of women • within 2 weeks • average time to completion 9 days • Missed Abortion:  expectant management is a lower success rate than medical therapy • 16-76%

  26. Expectant Management • Can wait up to 4 wks for expectant loss to occur • mean number of days of bleeding = 1.3 d6 • For successful outcomes: vaginal bleeding stopped by 3 weeks, products of conception fully expelled by 2 weeks7

  27. Expectant Management - 2 • 7Absence of complications reported in: • 93.6% patients receiving D&C • (1408 patients in 10 studies, 93% when only considering data from 3 RCTs) • 92.5% patients receiving expectant management • 51.5% patients receiving medical management

  28. Medical Management • Vaginal vs. oral vs. sublingual misoprostol • Misoprostol 800 mcg vaginally, repeat dose in 24-48 hours if needed • Warn re: cramping/bleeding typically starts w/in 2-4 hours of admin, worst cramping and bleeding lasting about 3-5 hours • Vaginal miso vs. placebo8 • increased rate of passage of POC within 24 hrs • 800 mcg more effective than 600 or 400. • Symptom management: • Pain control with NSAIDs and/or narcotic analgesics • antiemetics • 800 mcg vaginally has 84% success rate at 1 week9

  29. Medical Management • Oral Miso – usual dose is 600mcg • Fewer benefits than with vaginal • Oral miso (400 mcg) vs. expectant management – no sig difference10 • Mifepristone + oral miso -- no more effective than misoprostol alone • Medical vs Surgical: (???) • rate of needing MVA is 16% vs 3%

  30. Surgical Management • Uterine Evacuation procedures: D&C, suction curettage, MVA = manual vacuum aspiration* • Necessary for incomplete abortion with heavy bleeding • Contraindications: • acute pelvic infection • coagulopathy • fetal demise not proven to patient's or physician's satisfaction

  31. What is a MVA? • a hand-held plastic aspirator providing a vacuum source attached to a cannula (thin tube) and manually activated to suction the uterine contents.

  32. Surgical Management • neither medical nor surgical management economically superior for treatment of miscarriage12 • surgical evacuation reduces rate of unplanned hospital admission but no differences in infection rates13

  33. MIST trial *DynaMed & MIST trial – BMJ 2006 May 27;332(7552):1235

  34. Which should you offer/recommend? • Depends on scenario… • If heavy bleeding, excessive pain or evidence of septic abortion, requires intervention. OR… • If expelled tissue: no bleeding, uterus empty – manage expectantly • Otherwise, base it on pt preference.

  35. What to counsel re: Risks / Benefits

  36. Costs • Net Societal cost per woman: • $1746 for expectant management • $2267 for medical management • $2549 for surgical management

  37. Follow-up • At 2 weeks evaluate for Expectant Management • Grief counseling • Hcg level, trend down to 0 up to 30 days • decrease in beta-hCG of 80% at 1 week following passage of tissue • Repeat u/s (+/-)

  38. Follow - up • 4-6 wks once completed Med/Surg management: • review cause or lack of cause • Perform grief counseling • uterine involution • return of menses • discuss reproductive plans (no ideal inter-pregnancy interval, Rx: PNV)

  39. Grief Counseling • Include partner (if involved/supportive) • Acknowledge and legitimize grief, provide comfort, empathy and ongoing support • reassure about future (no increased risk of future miscarriages with < 3 miscarriages) • counsel patient on how to tell family and friends about miscarriage, consider using designated person • warn patient of “anniversary phenomenon” • not all women are grieved by miscarriage

  40. Grief Counseling • “There are organizations that help support women and their partners during this time” : • The Compassionate Friends (http://www.compassionatefriends.org; telephone: 877-969-0010) • SHARE Pregnancy and Infant Loss Support, Inc. (http://www.nationalshareoffice.com; telephone: 800-821-6819)

  41. Conclusion of case • Preferred expectant management, initially • Planned to monitor serum hCG-levels @ 48 hrs • Quant hCGafteratapprox 7wks EGA: 58,313 mIU/mL • Pt not yet passed products, opted for medical management of missed Ab with misoprostol • 2 wks later, quant hcg: 527 mIU/mL • Would trend Hcg level to 0 • Lost to follow-up

  42. Note re: Infertility • 68 % Follow-up rate after 5 years, in MIST Trial • Rate of live births in this time period was: • 79% in women with expectant manage’t group • 79% in women with medical management • 82% in women with surgical management

  43. Brief word re: Recurrent Loss • 3 or more losses (first or second trimester) • Risk of subsequent loss: • After 1 miscarriage: 20 percent • After 2 consecutive losses: 28 percent • After 3 or more consecutive losses: 43 percent • History – past medical, ob/gyn, surgical, familial/genetic

  44. Consider w/u for Recurrent Loss • Anatomic clues- uterine instrumentation? • Endocrine clues - Are the menstrual cycles normal? Galactorrhea? Thyroid? • Genetic clues --Does the family history display patterns of disease consistent with a strong genetic influence? Is consanguinity present? • Toxin—is  there exposure to environmental toxins, which may be lethal to developing embryos? • Inherited thrombophilia or antiphospholipid syndrome?

  45. Work-up for Recurrent Loss • Most useful tests: • Karyotype: both the parents and the abortus or products of conception (easier to r/o exposures) • Uterine assessment: u/s; hysterosalpingogram • Anticardiolpian Antibodies, lupus anticoagulant • Thyroid function • Ovarian reserve evaluation

  46. Thank you for listening… (& to E-Hutch, for helping prepare )Questions?

  47. References • DynaMed & UpToDate– accessed February 2011 • 1Clin ObstetGynecol 2007 Mar;50(1):67 • 2BMJ 1997 Jul 5;315(7099):32 • 3BMJ 2000 Jun 24;320(7251):1708 • 4BJOG 2006 May;113(5):521 • 5Br J Gen Pract 1996 Jan;46(402):7 • 6 Lancet 1995 Jan 14;345(8942):84 • 7J Am Board FamPract 1999 Jan-Feb;12(1):55 in J FamPract 1999 May;48(5):331 • 8Cochrane Library 2006 Issue 3:CD002253 - last updated 2006 Apr 24 • 9N Engl J Med 2005 Aug 25;353(8):761 • 10Br J ObstetGynaecol 1999 Aug;106(8):804 • 11BJOG 2007 Nov;114(11):l1363, 1368 • 12BJOG 2009 Jun;116(7):984 • 13 MIST Trial BMJ 2006 May 27;332(7552):1235 • Images from: http://www.advancedfertility.com/ultraso1.htm

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