1. RECURRENT AND MID- TRIMESTER PREGNANCY LOSS David L. Berry, M.D. Austin Perinatal Associates Seton Medical Center OB Grand Rounds September 19, 2011

2. “MISCARRIAGE” OR “SPONTANEOUS ABORTION” n Spontaneous loss of a conceptus < 20 weeks n 30% of all pregnancies –1/3 recognized (usu. > 10 weeks) –2/3 isolated elevated hCG and < 10 weeks n Increased with maternal age 35 n Increased with increased # of previous losses n 80% unexplained, 20% explained n Only ½ of explained losses are aneuploidy

3. PSYCHOLOGY OF RECURRENT PREGNANCY LOSS n All patients feel broken and unworthy n All partners feel inadequate and helpless n With 80% unexplained, any theoretic explanation will be sought and grasped onto as gospel n This industry is so poorly understood, there is significant abuse of these desperate patients

4. RECURRENT PREGNANCY LOSS (RPL) n 3 or more consecutive, unexplained spontaneous abortions n Occurs in 1% of couples n Two consecutive losses occur in 5% n Must differentiate timing (early vs. late) n Structural, hormonal, chromosomal, implantation, anomaly, placental, circulatory, cervical

5. RECURRENT PREGNANCY LOSS n Early losses (< 10 weeks) associated with fetal structural/chromosomal abnormalities, uterine defects (scarring/fibroids/septa), and luteal phase defects n Frequently early losses are idiopathic n Phospholipid syndromes associated with 16 – 20 week IUFD’s, PIH and IUGR at < 34 weeks and maternal thrombosis more so than early losses n 5 – 15% of RPL have anti-phospholipid Ab syndrome

6. RECURRENT PREGNANCY LOSS n Uterine malformations (10 – 25%) n Parental balanced translocations (3 – 6%) n Maternal thyroid disease and diabetes n Mycoplasma/Ureaplasma screening are of questionable utility

7. EVALUATION FOR RPL n Historical information is VITAL –Anembryonic and < 10 weeks –+FHR seen followed by bleeding –History of familial disease or previous aneuploid fetus is useful –Previous D&C or Hysteroscopy useful –REMEMBER: Symptoms of miscarriage do not show for 4 weeks post embryonic demise

8. EVALUATION FOR RPL n Anembryonic may be structural uterine or fetal anomaly/aneuploidy n +FHR and spontaneous bleeding and cramping is likely luteal phase defect n Mid-trimester IUFD may be placental, fetal or anti-phospholipid syndrome n Mid-trimester delivery of a well-grown fetus is frequently cervical insufficiency

9. WORK-UP FOR RPL n For < 10 week losses, karyotype on POC’s or on parents, HSG n For losses involving bleeding/cramping, Day 21 Progesterone may help (not predictive of future cycles) n For Mid-trimester IUFD - LAC, ACA, and Beta 2 Glycoprotein I may be helpful –Factor V Leiden and Prothrombin gene mutation are less diagnostic from a fetal standpoint

10. RPL – TREATMENT OPTIONS n If HSG indicates filling defects – Hysteroscopy is indicated n If parental balanced translocation is identified, IVF with PGD ($50 – 100,000) n Consider treatment of both partners for mycoplasma/ureaplasma(?) n For all unexplained losses, consider ASA and progesterone supplements until 12 weeks(?)

11. RPL TREATMENT OPTIONS n For cramping/bleeding history, treat with Progesterone replacement from +UPT until 10 – 12 weeks n Vaginal progesterone 200 mg BID n No need for Progesterone levels n Early (6 – 8 week ultrasound) n Follow up ultrasound q 1 – 2 weeks until 12 weeks of pregnancy

12. ANTIPHOSPHOLIPID SYNDROME n Abnormal aPTT + DRVVT n ACA IgG or IgM (> 40 GPL/MPL units) n Anti Beta-2 glycoprotein I (>99 th centile) n ALL OF THE ABOVE MUST BE + ON TWO OCCASIONS AT LEASE 12 WEEKS APART AND MAY NOT BE THE CAUSE OF PREVIOUS LOSSES!

13. WHO SHOULD BE TESTED FOR APL ANTIBODY SYNDROME? n Any patient with a history of unexplained arterial or venous thrombosis n Any patient with an unexplained fetal death (> 10 weeks) of a morphologically normal fetus on exam or ultrasound n History of < 34 week birth from IUGR or severe preeclampsia/eclampsia n Patient with 3 or more early losses with normal chromosomes and hormones

14. TREATMENT FOR APL SYNDROME n Focus on prevention of thrombosis, 3 rd trimester IUGR and prevention of pre- eclampsia > pregnancy loss n Prophylactic anticoagulation (usu. Lovenox + ASA) until 6 weeks PP n Prednisone, IVIG controversial n Expert opinion support increased AP testing n Observe for future thromboses n Avoid estrogen containing OCP’s

15. MISCONCEPTIONS ABOUT RPL n A single loss or even two early losses are “abnormal” n Low + ACA, + ANA or + FVL or other thrombophilias are CAUSATIVE of RPL n Hysteroscopy will “cure” or “fix” the cause so it will not recur n Frequent progesterone and hCG values are helpful

16. TRUTHS ABOUT RPL n Psychological and emotional support are imperative n Even unexplained losses deserve a “plan” n Treatment of true APL Antibody Syndrome is with Heparin/Aspirin n Treatment of FVL and Prothrombin gene mutations and other thrombophilias are maternal treatments, not fetal

17. CERVICAL INSUFFICIENCY n No known cause of cervical failure n Poor association between prior cervical surgeries and cervical insufficiency n LEEP and CKC more causative of stenosis n ACOG recommends > or = 3 losses with painless dilatation to consider cerclage n ACOG states up to 16.6% complication from elective cerclage

18. TREATMENT OF CERVICAL FAILURE n Simple, easy, outpatient procedure n 12 – 14 week Modified McDonald cerclage n Use 5 mm Mersilene n Do NOT tie over Hegar/Hank’s dilator n As high and as tight as possible n Remove electively at 36 weeks

19. AUSTIN PERINATAL OUTCOMES FOR CERCLAGE n Over 900 procedures performed n One (0.1%) transient anesthetic complication n 0% procedurally related losses n 99% Survival Rate n 96% Term Rate (4% prematurity) n Compared to the uncomplicated term rate is 88% (12% prematurity)

20. RESCUE CERCLAGE n Reserved for specific circumstances n Highly risky (up to 50% complication) n Not clinically proven in controlled study n Patients discovered incidentally n Exclusions include bleeding, contractions, infection, PROM, dynamic changes or > 2 X 2 cm BOW outside the external os

21. TREATMENT OPTIONS FOR MIDTRIMESTER IUFD n Pre-medicate with Cytotec 200mcg q 4 hrs n Cytotec p.o. or p.v. n 200 mcg tabs do not dissolve vaginally n 100 mcg tabs do not dissolve in high pH n 30 cc Foley catheter + high dose Pitocin n Hemabate 250 mcg I.M. q 4 hours n Intra-amniotic Hemabate (10 mL) n D&E