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

10/30/13

HPI
•35yo African-American
•Gravida: G9P21162
•LMP 5/27/13
•GA: 22 + 2 (LMP)
• Confirmed with US

•ED...
Case A.A.
PObHx
•G1 – 2000 Elective TOP
•G2 – 2003 Elective TOP
•G3 – 2004 Elective TOP
•G4 – 2005 SAB @ 4wks (?Hx)
•G5 – ...
Case A.A.
PGynHx
•(-) STD
•(-) PAP
•Irregular Menses 3-4 days (years)
•?Menarche
Allergy
•NKDA/NKA
PMHx
•HgbSS (maternal +...
Case A.A.
Meds
•PNV Daily
PFHx
•Non-contributory
PSoHx
•Denies Smoking, EtOH, Drugs
PE
•BP: 100/46
•HR: 67
•Ht: 5’7”
•Wt: ...
Case A.A.
PE (cont.)
•HEENT: Unremarkable
•Lungs: CTAB
•CV: S1, S2
•Abd: Soft, Gravid
•Skin: Warm, Dry
•Ext: (-) Edema b/l...
Case A.A.
Lab
•Blood: O Neg
•Ab Screen: Pos
•Anti-D: 1:128
•Rubella: Immune
•HBsAg: Neg
Imaging
•US (10/30/13): Breech, An...
Case A.A.
Assessment
•35yo G9P21162
•Stable, Afebrile
•GBS unknown
•Multigravida
•HgbSS
•Anti-D Isoimmunization (1:128 tit...
Loss of Pregnancy
•50% of conceptions fail (majority unrecognized)
•13-15% of known pregnancies fail in 1st trimester
•10-...
Recurrent Pregnancy Loss
• 3 consecutive pregnancy losses < 20 week gestation
• Ectopic & molar pregnancies not included
•...
Recurrent Pregnancy Loss
•Primary RPL -> (-) History of Live Birth
•Secondary RPL -> (+) History of Live Birth
•Single spo...
RPL Workup
• Detailed Obstetric History
•
•
•
•
•
•
•
•

Recurrent pregnancy loss
Early pregnancy loss
2nd trimester loss
...
RPL Workup
• STI’s
• Environmental
• Smoking
• Toxins/Chemical

•
•
•
•
•

Lifestyle
Obesity
Daily caffeine (> 300 mg)
Alc...
RPL Etiology
• Etiology determination (50%)
•
•
•
•
•
•

Uterine
Immunologic
Endocrine
Genetic
Thrombophilia
Environmental
UTERINE Etiology
• Acquired or congenital anomalies
• 10-15% in RPL vs 7% overall
• Abnormal placentation
• Irregular Vasc...
UTERINE Assessment
• Ultrasound
• Uterine fibroids
• Renal abnormalities

• MRI
• Septate vs Bicornuate
UTERINE Assessment
• Sonohysterography
• Septate vs Bicornuate uterus

• Hysterosalpingogram
• Uterine cavity & Fallopian ...
SEPTATE UTERUS
• Most common
• Irregular placentation
• Position
• Endometrial receptivity
• Degeneration/Inflammation

• ...
LEIOMYOMA
• Submucosal
• Irregular Placentation
• Position
• Endometrial receptivity
• Degeneration/Inflammation
UTERINE Other
• Polyps
• DES exposure
• Vaginal clear-cell adenocarcinoma
• T shaped uterus/uterine fibroids
• Possible ce...
UTERINE Other
• Cervical Incompetence
• Internal OS dilation >1cm
• Cervical length <2cm
•Hx PPROM
•Hx Cervical biopsy
•Hx...
Autoimmune
• Systemic Lupus Erythematosus (SLE)
• 20% risk in 2nd or 3rd trimester

• Anti-Phospholipid Syndrome (APA)
•
•...
Alloimmune
• Pregnancy tolerated by the maternal immune system via
formation of antigen blocking antibodies
• Couples may ...
ENDOCRINE
• Polycystic Ovarian Syndrome (PCOS)
• Hyperinsulinemia
• Hyperglycemia
• tPa inhibitor activity

• Diabetes
• W...
ENDOCRINE
• Thyroid Disease
• Uncontrolled hypo/hyperthyroid
• Infertility & pregnancy loss

• Luteal Phase Defect
• Corpu...
GENETIC
• Fetal Chromosomal Abnormalities
• Egg and/or sperm

• Increased RPL in 1st degree relatives of women with RPL
• ...
GENETIC
• Chromosomal rearrangements
• 3–5% of RPL
• One partner carries a balanced chromosomal translocation

• 5–10% of ...
THROMBOPHILIA
• Maternal Thrombophilia
•
•
•
•

Protein C/S deficiency
Factor V Leiden
Pro-thrombin gene mutation
Anti-thr...
OTHER
• Environmental chemicals/toxins
• Sporadic spontaneous loss
• ?RPL risk

• Lifestyle
• Obesity, smoking, alcohol, a...
OTHER
• Maternal
• RPL risk re: quality & quantity of oocytes
• Unexplained RPL have a higher Day3 FSH and E2

• Paternal
...
MANAGEMENT
• Anatomic
• Surgical correction

• Endocrine
• Control
• Diabetes, Thyroid, Progesterone (Luteal)

• Anti-phos...
MANAGEMENT
•Idiopathic RPL Empiric Treatment
• Preconception

• Folic acid
• Correct nutritional deficiencies
• Luteal sup...
THANK YOU!
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Recurrent Pregnancy Loss

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Recurrent Pregnancy Loss

  1. 1. Recurrent Pregnancy Loss John R. Martinelli NBIMC Ob/Gyn 11/4/13
  2. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 12. RPL Workup • Detailed Obstetric History • • • • • • • • Recurrent pregnancy loss Early pregnancy loss 2nd trimester loss Still birth Elective TOP Malformed fetus Pre-term birth Full-term birth
  13. 13. RPL Workup • STI’s • Environmental • Smoking • Toxins/Chemical • • • • • Lifestyle Obesity Daily caffeine (> 300 mg) Alcohol Drugs/NSAID’s
  14. 14. RPL Etiology • Etiology determination (50%) • • • • • • Uterine Immunologic Endocrine Genetic Thrombophilia Environmental
  15. 15. UTERINE Etiology • Acquired or congenital anomalies • 10-15% in RPL vs 7% overall • Abnormal placentation • Irregular Vascularity • Inflammation
  16. 16. UTERINE Assessment • Ultrasound • Uterine fibroids • Renal abnormalities • MRI • Septate vs Bicornuate
  17. 17. UTERINE Assessment • Sonohysterography • Septate vs Bicornuate uterus • Hysterosalpingogram • Uterine cavity & Fallopian tubes • Hysteroscopy • Gold standard
  18. 18. SEPTATE UTERUS • Most common • Irregular placentation • Position • Endometrial receptivity • Degeneration/Inflammation • Loss of Pregnancy > 60%
  19. 19. LEIOMYOMA • Submucosal • Irregular Placentation • Position • Endometrial receptivity • Degeneration/Inflammation
  20. 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. 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. 22. Autoimmune • Systemic Lupus Erythematosus (SLE) • 20% risk in 2nd or 3rd trimester • Anti-Phospholipid Syndrome (APA) • • • • • • 5 - 15% RPL Anti-phospholipid antibodies (platelets) Lupus “anti-coagulant” Anti-cardiolipin antibodies (+/-) Micro-thrombi at site of placentation Vascular compromise
  23. 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. 24. ENDOCRINE • Polycystic Ovarian Syndrome (PCOS) • Hyperinsulinemia • Hyperglycemia • tPa inhibitor activity • Diabetes • Well controlled •No increased risk • Poorly controlled •1st Trimester greatest risk
  25. 25. ENDOCRINE • Thyroid Disease • Uncontrolled hypo/hyperthyroid • Infertility & pregnancy loss • Luteal Phase Defect • Corpus Luteum defect • Progesterone key for implantation and maintenance
  26. 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. 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. 28. THROMBOPHILIA • Maternal Thrombophilia • • • • 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. 29. OTHER • Environmental chemicals/toxins • Sporadic spontaneous loss • ?RPL risk • Lifestyle • Obesity, smoking, alcohol, and caffeine • ?RPL risk • Exercise • No risk
  30. 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. 31. MANAGEMENT • Anatomic • Surgical correction • Endocrine • Control • Diabetes, Thyroid, Progesterone (Luteal) • Anti-phospholipid antibodies • Aspirin and heparin • Thrombophilia • Heparin
  32. 32. MANAGEMENT •Idiopathic RPL Empiric Treatment • Preconception • Folic acid • Correct nutritional deficiencies • Luteal support • HCG / Progesterone • Post-conception • • • • • • Toxoplasmosis APA Steroid Tx Frequent NST/US Prophylactic aspirin Prophylactic cervical cerclage
  33. 33. THANK YOU!

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