1. Recurrent Pregnancy Loss
John R. Martinelli
NBIMC Ob/Gyn
11/4/13

2. Case A.A.
10/30/13
HPI
•35yo African-American
•Gravida: G9P21162
•LMP 5/27/13
•GA: 22 + 2 (LMP)
• Confirmed with US
•EDD: 3/3/14
•(-) CTX, LOF, VB
•(-) CP/SOB
•(-) N/V/D
•(-) Fever
•Evaluated in ATU (Antenatal Care Unit)
•s/p KCL injection secondary to complications from sickle cell disease
and subsequent fetal isoimmunization.

3. Case A.A.
PObHx
•G1 – 2000 Elective TOP
•G2 – 2003 Elective TOP
•G3 – 2004 Elective TOP
•G4 – 2005 SAB @ 4wks (?Hx)
•G5 – 2008 FT NSVD (w/o complication)
•G6 – 2008 SAB (?Hx)
•G7 – 2008 SAB (?Hx)
•G8 – 2010 PT C/S 6lbs 1oz (Rh Sensitization)
•G9 – Current SAB @ 22 + 2 wks (SCD & Isoimmunization)

4. Case A.A.
PGynHx
•(-) STD
•(-) PAP
•Irregular Menses 3-4 days (years)
•?Menarche
Allergy
•NKDA/NKA
PMHx
•HgbSS (maternal + paternal carriers)
PSxHx
•C/S x 1, D&C x 3

5. Case A.A.
Meds
•PNV Daily
PFHx
•Non-contributory
PSoHx
•Denies Smoking, EtOH, Drugs
PE
•BP: 100/46
•HR: 67
•Ht: 5’7”
•Wt: 203

6. Case A.A.
PE (cont.)
•HEENT: Unremarkable
•Lungs: CTAB
•CV: S1, S2
•Abd: Soft, Gravid
•Skin: Warm, Dry
•Ext: (-) Edema b/l, (-) Calf Tenderness b/l
•Cervix: C/50/-3
•EFM: (-) Activity
•Toco: Quiet

7. Case A.A.
Lab
•Blood: O Neg
•Ab Screen: Pos
•Anti-D: 1:128
•Rubella: Immune
•HBsAg: Neg
Imaging
•US (10/30/13): Breech, Ant Placenta, Polyhydramnios, (-) FHR
•US (10/23/13): Cephalic, Ant Placenta, FHR 144, AFI 20.4, BPP 8/8
•Doppler (10/23/13): UA WNL, MCA Elevated

8. Case A.A.
Assessment
•35yo G9P21162
•Stable, Afebrile
•GBS unknown
•Multigravida
•HgbSS
•Anti-D Isoimmunization (1:128 titer)
Plan
•Admit L&D
•Toco/EFM
•IVF
•Labs
•Cytotec (Dinoprostone) induction
•Cord Blood CBC, pH

9. Loss of Pregnancy
•50% of conceptions fail (majority unrecognized)
•13-15% of known pregnancies fail in 1st trimester
•10-20% of pregnant women -> 1 spontaneous abortion
•2% pregnant women -> 2 consecutive spontaneous abortions
•0.4-1% pregnant women -> 3 consecutive spontaneous
abortions

10. Recurrent Pregnancy Loss
• 3 consecutive pregnancy losses < 20 week gestation
• Ectopic & molar pregnancies not included
• Consider formal work-up after 2 consecutive losses
• Fetal heart activity had been present
• 35 yo
• History of difficulty conceiving

11. Recurrent Pregnancy Loss
•Primary RPL -> (-) History of Live Birth
•Secondary RPL -> (+) History of Live Birth
•Single sporadic miscarriage -> 80% subsequent success
•Three consecutive miscarriages -> 40%-60% subsequent
success

12. RPL Workup
• Detailed Obstetric History
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Recurrent pregnancy loss
Early pregnancy loss
2nd trimester loss
Still birth
Elective TOP
Malformed fetus
Pre-term birth
Full-term birth

13. RPL Workup
• STI’s
• Environmental
• Smoking
• Toxins/Chemical
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•
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•
•
Lifestyle
Obesity
Daily caffeine (> 300 mg)
Alcohol
Drugs/NSAID’s

14. RPL Etiology
• Etiology determination (50%)
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Uterine
Immunologic
Endocrine
Genetic
Thrombophilia
Environmental

15. UTERINE Etiology
• Acquired or congenital anomalies
• 10-15% in RPL vs 7% overall
• Abnormal placentation
• Irregular Vascularity
• Inflammation

16. UTERINE Assessment
• Ultrasound
• Uterine fibroids
• Renal abnormalities
• MRI
• Septate vs Bicornuate

17. UTERINE Assessment
• Sonohysterography
• Septate vs Bicornuate uterus
• Hysterosalpingogram
• Uterine cavity & Fallopian tubes
• Hysteroscopy
• Gold standard

18. SEPTATE UTERUS
• Most common
• Irregular placentation
• Position
• Endometrial receptivity
• Degeneration/Inflammation
• Loss of Pregnancy > 60%

19. LEIOMYOMA
• Submucosal
• Irregular Placentation
• Position
• Endometrial receptivity
• Degeneration/Inflammation

20. UTERINE Other
• Polyps
• DES exposure
• Vaginal clear-cell adenocarcinoma
• T shaped uterus/uterine fibroids
• Possible cervical incompetence
• Intrauterine adhesions
• D&C (granulation tissue at basalis)
• Asherman’s Syndrome

21. UTERINE Other
• Cervical Incompetence
• Internal OS dilation >1cm
• Cervical length <2cm
•Hx PPROM
•Hx Cervical biopsy
•Hx D&E/Mechanical Dilation
•Hx Trauma
•Hx DES exposure
• Cervical Cerclage
• Surgical risk
• Uterine contraction risk

22. Autoimmune
• Systemic Lupus Erythematosus (SLE)
• 20% risk in 2nd or 3rd trimester
• Anti-Phospholipid Syndrome (APA)
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5 - 15% RPL
Anti-phospholipid antibodies (platelets)
Lupus “anti-coagulant”
Anti-cardiolipin antibodies (+/-)
Micro-thrombi at site of placentation
Vascular compromise

23. Alloimmune
• Pregnancy tolerated by the maternal immune system via
formation of antigen blocking antibodies
• Couples may share similar HLA
• Inadequate formation blocking antibodies
• Mother mounts immune response
• Loss of pregnancy

24. ENDOCRINE
• Polycystic Ovarian Syndrome (PCOS)
• Hyperinsulinemia
• Hyperglycemia
• tPa inhibitor activity
• Diabetes
• Well controlled
•No increased risk
• Poorly controlled
•1st Trimester greatest risk

25. ENDOCRINE
• Thyroid Disease
• Uncontrolled hypo/hyperthyroid
• Infertility & pregnancy loss
• Luteal Phase Defect
• Corpus Luteum defect
• Progesterone key for implantation and maintenance

26. GENETIC
• Fetal Chromosomal Abnormalities
• Egg and/or sperm
• Increased RPL in 1st degree relatives of women with RPL
• Shared HLA types, coag defects, immune dysfunction, others
• 1st Trimester RPL
• Advanced Maternal Age
• Anembryonic
• Malformations

27. GENETIC
• Chromosomal rearrangements
• 3–5% of RPL
• One partner carries a balanced chromosomal translocation
• 5–10% of RPL
• One partner carries an unbalanced translocation
• Monosomy
• Turner (XO)
• Cri-du-chat (5p deletion)
• Trisomy
• 21 (Downs)
• 18 (Edwards)
• 13 (Patau)

28. THROMBOPHILIA
• Maternal Thrombophilia
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Protein C/S deficiency
Factor V Leiden
Pro-thrombin gene mutation
Anti-thrombin III deficiency
• Late Fetal Loss
• Thrombosis on maternal side of the placenta
• IUGR, abruption, or PIH
• Early Fetal Loss
• Specific defects not well understood

29. OTHER
• Environmental chemicals/toxins
• Sporadic spontaneous loss
• ?RPL risk
• Lifestyle
• Obesity, smoking, alcohol, and caffeine
• ?RPL risk
• Exercise
• No risk

30. OTHER
• Maternal
• RPL risk re: quality & quantity of oocytes
• Unexplained RPL have a higher Day3 FSH and E2
• Paternal
• RPL risk re: quality & quantity of sperm
• Advanced paternal age (> maternal)
• Infection
• Listeria, Toxoplasma, CMV, HSV
• Sporadic loss

31. MANAGEMENT
• Anatomic
• Surgical correction
• Endocrine
• Control
• Diabetes, Thyroid, Progesterone (Luteal)
• Anti-phospholipid antibodies
• Aspirin and heparin
• Thrombophilia
• Heparin

32. MANAGEMENT
•Idiopathic RPL Empiric Treatment
• Preconception
• Folic acid
• Correct nutritional deficiencies
• Luteal support
• HCG / Progesterone
• Post-conception
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Toxoplasmosis
APA
Steroid Tx
Frequent NST/US
Prophylactic aspirin
Prophylactic cervical cerclage

33. THANK YOU!