RECURRENT AND MID-RECURRENT AND MID-TRIMESTER PREGNANCY LOSSTRIMESTER PREGNANCY LOSS

David L. Berry, M.D.David L. Berry, M.D.

Austin Perinatal AssociatesAustin Perinatal Associates

Seton Medical Center OB Grand RoundsSeton Medical Center OB Grand Rounds

September 19, 2011September 19, 2011

““MISCARRIAGE” OR MISCARRIAGE” OR “SPONTANEOUS ABORTION”“SPONTANEOUS ABORTION”

Spontaneous loss of a conceptus < 20 weeksSpontaneous loss of a conceptus < 20 weeks 30% of all pregnancies30% of all pregnancies– 1/3 recognized (usu. > 10 weeks)1/3 recognized (usu. > 10 weeks)– 2/3 isolated elevated hCG and < 10 weeks2/3 isolated elevated hCG and < 10 weeks

Increased with maternal age < 18 or > 35Increased with maternal age < 18 or > 35 Increased with increased # of previous lossesIncreased with increased # of previous losses 80% unexplained, 20% explained 80% unexplained, 20% explained Only ½ of explained losses are aneuploidyOnly ½ of explained losses are aneuploidy

PSYCHOLOGY OF RECURRENT PSYCHOLOGY OF RECURRENT PREGNANCY LOSSPREGNANCY LOSS

All patients feel broken and unworthyAll patients feel broken and unworthy All partners feel inadequate and helplessAll partners feel inadequate and helpless With 80% unexplained, any theoretic With 80% unexplained, any theoretic

explanation will be sought and grasped explanation will be sought and grasped onto as gospelonto as gospel

This industry is so poorly understood, This industry is so poorly understood, there is significant abuse of these there is significant abuse of these desperate patientsdesperate patients

RECURRENT PREGNANCY LOSS RECURRENT PREGNANCY LOSS (RPL)(RPL)

3 or more consecutive, unexplained 3 or more consecutive, unexplained spontaneous abortionsspontaneous abortions

Occurs in 1% of couplesOccurs in 1% of couples Two consecutive losses occur in 5%Two consecutive losses occur in 5% Must differentiate timing (early vs. late)Must differentiate timing (early vs. late) Structural, hormonal, chromosomal, Structural, hormonal, chromosomal,

implantation, anomaly, placental, implantation, anomaly, placental, circulatory, cervicalcirculatory, cervical

RECURRENT PREGNANCY LOSSRECURRENT PREGNANCY LOSS

Early losses (< 10 weeks) associated with fetal Early losses (< 10 weeks) associated with fetal structural/chromosomal abnormalities, uterine defects structural/chromosomal abnormalities, uterine defects (scarring/fibroids/septa), and luteal phase defects(scarring/fibroids/septa), and luteal phase defects

Frequently early losses are idiopathicFrequently early losses are idiopathic Phospholipid syndromes associated with 16 – 20 week Phospholipid syndromes associated with 16 – 20 week

IUFD’s, PIH and IUGR at < 34 weeks and maternal IUFD’s, PIH and IUGR at < 34 weeks and maternal thrombosis more so than early lossesthrombosis more so than early losses

5 – 15% of RPL have anti-phospholipid Ab syndrome5 – 15% of RPL have anti-phospholipid Ab syndrome

RECURRENT PREGNANCY LOSSRECURRENT PREGNANCY LOSS

Uterine malformations (10 – 25%)Uterine malformations (10 – 25%) Parental balanced translocations (3 – 6%)Parental balanced translocations (3 – 6%) Maternal thyroid disease and diabetesMaternal thyroid disease and diabetes Mycoplasma/Ureaplasma screening are of Mycoplasma/Ureaplasma screening are of

questionable utilityquestionable utility

EVALUATION FOR RPLEVALUATION FOR RPL

Historical information is VITALHistorical information is VITAL– Anembryonic and < 10 weeksAnembryonic and < 10 weeks– +FHR seen followed by bleeding+FHR seen followed by bleeding– History of familial disease or previous History of familial disease or previous

aneuploid fetus is usefulaneuploid fetus is useful– Previous D&C or Hysteroscopy usefulPrevious D&C or Hysteroscopy useful– REMEMBER: Symptoms of miscarriage do REMEMBER: Symptoms of miscarriage do

not show for 4 weeks post embryonic demisenot show for 4 weeks post embryonic demise

EVALUATION FOR RPLEVALUATION FOR RPL

Anembryonic may be structural uterine Anembryonic may be structural uterine or fetal anomaly/aneuploidyor fetal anomaly/aneuploidy

+FHR and spontaneous bleeding and +FHR and spontaneous bleeding and cramping is likely luteal phase defectcramping is likely luteal phase defect

Mid-trimester IUFD may be placental, Mid-trimester IUFD may be placental, fetal or anti-phospholipid syndromefetal or anti-phospholipid syndrome

Mid-trimester delivery of a well-grown Mid-trimester delivery of a well-grown fetus is frequently cervical insufficiencyfetus is frequently cervical insufficiency

WORK-UP FOR RPLWORK-UP FOR RPL

For < 10 week losses, karyotype on POC’s or on For < 10 week losses, karyotype on POC’s or on parents, HSGparents, HSG

For losses involving bleeding/cramping, Day 21 For losses involving bleeding/cramping, Day 21 Progesterone may help (not predictive of future cycles)Progesterone may help (not predictive of future cycles)

For Mid-trimester IUFD - LAC, ACA, and Beta 2 For Mid-trimester IUFD - LAC, ACA, and Beta 2 Glycoprotein I may be helpfulGlycoprotein I may be helpful– Factor V Leiden and Prothrombin gene mutation are less Factor V Leiden and Prothrombin gene mutation are less

diagnostic from a fetal standpointdiagnostic from a fetal standpoint

RPL – TREATMENT OPTIONSRPL – TREATMENT OPTIONS

If HSG indicates filling defects – If HSG indicates filling defects – Hysteroscopy is indicatedHysteroscopy is indicated

If parental balanced translocation is If parental balanced translocation is identified, IVF with PGD ($50 – 100,000)identified, IVF with PGD ($50 – 100,000)

Consider treatment of both partners for Consider treatment of both partners for mycoplasma/ureaplasma(?)mycoplasma/ureaplasma(?)

For all unexplained losses, consider ASA and For all unexplained losses, consider ASA and progesterone supplements until 12 weeks(?)progesterone supplements until 12 weeks(?)

RPL TREATMENT OPTIONSRPL TREATMENT OPTIONS

For cramping/bleeding history, treat with For cramping/bleeding history, treat with Progesterone replacement from +UPT Progesterone replacement from +UPT until 10 – 12 weeksuntil 10 – 12 weeks

Vaginal progesterone 200 mg BIDVaginal progesterone 200 mg BID No need for Progesterone levelsNo need for Progesterone levels Early (6 – 8 week ultrasound)Early (6 – 8 week ultrasound) Follow up ultrasound q 1 – 2 weeks until Follow up ultrasound q 1 – 2 weeks until

12 weeks of pregnancy12 weeks of pregnancy

ANTIPHOSPHOLIPID SYNDROMEANTIPHOSPHOLIPID SYNDROME

Abnormal aPTT + DRVVT Abnormal aPTT + DRVVT ACA IgG or IgM (> 40 GPL/MPL units)ACA IgG or IgM (> 40 GPL/MPL units) Anti Beta-2 glycoprotein I (>99Anti Beta-2 glycoprotein I (>99thth centile) centile) ALL OF THE ABOVE MUST BE + ON ALL OF THE ABOVE MUST BE + ON

TWO OCCASIONS AT LEASE 12 TWO OCCASIONS AT LEASE 12 WEEKS APART AND MAY NOT BE WEEKS APART AND MAY NOT BE THE CAUSE OF PREVIOUS LOSSES!THE CAUSE OF PREVIOUS LOSSES!

WHO SHOULD BE TESTED FOR WHO SHOULD BE TESTED FOR APL ANTIBODY SYNDROME?APL ANTIBODY SYNDROME?

Any patient with a history of unexplained Any patient with a history of unexplained arterial or venous thrombosisarterial or venous thrombosis

Any patient with an unexplained fetal death Any patient with an unexplained fetal death (> 10 weeks) of a morphologically normal (> 10 weeks) of a morphologically normal fetus on exam or ultrasoundfetus on exam or ultrasound

History of < 34 week birth from IUGR or History of < 34 week birth from IUGR or severe preeclampsia/eclampsiasevere preeclampsia/eclampsia

Patient with 3 or more early losses with Patient with 3 or more early losses with normal chromosomes and hormonesnormal chromosomes and hormones

TREATMENT FOR APL TREATMENT FOR APL SYNDROMESYNDROME

Focus on prevention of thrombosis, 3Focus on prevention of thrombosis, 3rdrd trimester IUGR and prevention of pre-trimester IUGR and prevention of pre-eclampsia > pregnancy losseclampsia > pregnancy loss

Prophylactic anticoagulation (usu. Lovenox Prophylactic anticoagulation (usu. Lovenox + ASA) until 6 weeks PP+ ASA) until 6 weeks PP

Prednisone, IVIG controversialPrednisone, IVIG controversial Expert opinion support increased AP testingExpert opinion support increased AP testing Observe for future thrombosesObserve for future thromboses Avoid estrogen containing OCP’sAvoid estrogen containing OCP’s

MISCONCEPTIONSMISCONCEPTIONS ABOUT RPL ABOUT RPL

A single loss or even two early losses are A single loss or even two early losses are “abnormal”“abnormal”

Low + ACA, + ANA or + FVL or other Low + ACA, + ANA or + FVL or other thrombophilias are CAUSATIVE of RPLthrombophilias are CAUSATIVE of RPL

Hysteroscopy will “cure” or “fix” the cause so it Hysteroscopy will “cure” or “fix” the cause so it will not recurwill not recur

Frequent progesterone and hCG values are Frequent progesterone and hCG values are helpfulhelpful

TRUTHS ABOUT RPLTRUTHS ABOUT RPL

Psychological and emotional support are Psychological and emotional support are imperativeimperative

Even unexplained losses deserve a “plan”Even unexplained losses deserve a “plan” Treatment of true APL Antibody Treatment of true APL Antibody

Syndrome is with Heparin/AspirinSyndrome is with Heparin/Aspirin Treatment of FVL and Prothrombin Treatment of FVL and Prothrombin

gene mutations and other thrombophilias gene mutations and other thrombophilias are are maternalmaternal treatments, not fetal treatments, not fetal

CERVICAL INSUFFICIENCY CERVICAL INSUFFICIENCY

No known cause of cervical failureNo known cause of cervical failure Poor association between prior cervical Poor association between prior cervical

surgeries and cervical insufficiencysurgeries and cervical insufficiency LEEP and CKC more causative of stenosisLEEP and CKC more causative of stenosis ACOG recommends > or = 3 losses with ACOG recommends > or = 3 losses with

painless dilatation to consider cerclagepainless dilatation to consider cerclage ACOG states up to 16.6% complication from ACOG states up to 16.6% complication from

elective cerclageelective cerclage

TREATMENT OF CERVICAL TREATMENT OF CERVICAL FAILUREFAILURE

Simple, easy, outpatient procedureSimple, easy, outpatient procedure 12 – 14 week Modified McDonald 12 – 14 week Modified McDonald

cerclagecerclage Use 5 mm MersileneUse 5 mm Mersilene Do NOT tie over Hegar/Hank’s dilatorDo NOT tie over Hegar/Hank’s dilator As high and as tight as possibleAs high and as tight as possible Remove electively at 36 weeksRemove electively at 36 weeks

AUSTIN PERINATAL OUTCOMES AUSTIN PERINATAL OUTCOMES FOR CERCLAGEFOR CERCLAGE

Over 900 procedures performedOver 900 procedures performed One (0.1%) transient anesthetic One (0.1%) transient anesthetic

complicationcomplication 0% procedurally related losses0% procedurally related losses 99% Survival Rate99% Survival Rate 96% Term Rate (4% prematurity)96% Term Rate (4% prematurity) Compared to the uncomplicated term Compared to the uncomplicated term

rate is 88% (12% prematurity)rate is 88% (12% prematurity)

RESCUE CERCLAGERESCUE CERCLAGE

Reserved for specific circumstancesReserved for specific circumstances Highly risky (up to 50% complication)Highly risky (up to 50% complication) Not clinically proven in controlled studyNot clinically proven in controlled study Patients discovered incidentallyPatients discovered incidentally Exclusions include bleeding, contractions, Exclusions include bleeding, contractions,

infection, PROM, dynamic changes or > 2 infection, PROM, dynamic changes or > 2 X 2 cm BOW outside the external osX 2 cm BOW outside the external os

TREATMENT OPTIONS FOR TREATMENT OPTIONS FOR MIDTRIMESTER IUFDMIDTRIMESTER IUFD

Pre-medicate with Cytotec 200mcg q 4 hrsPre-medicate with Cytotec 200mcg q 4 hrs Cytotec p.o. or p.v.Cytotec p.o. or p.v. 200 mcg tabs do not dissolve vaginally200 mcg tabs do not dissolve vaginally 100 mcg tabs do not dissolve in high pH100 mcg tabs do not dissolve in high pH 30 cc Foley catheter + high dose Pitocin30 cc Foley catheter + high dose Pitocin Hemabate 250 mcg I.M. q 4 hoursHemabate 250 mcg I.M. q 4 hours Intra-amniotic Hemabate (10 mL)Intra-amniotic Hemabate (10 mL) D&ED&E