recurrent pregnancy loss
DESCRIPTION
TRANSCRIPT
Recurrent Pregnancy LossJohn R. MartinelliNBIMC Ob/Gyn11/4/13
Case A.A. 10/30/13
HPI•35yo African-American•Gravida: G9P21162•LMP 5/27/13•GA: 22 + 2 (LMP)• Confirmed with US
•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.
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)
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
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
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
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
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
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
• 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
Recurrent Pregnancy Loss
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
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
RPL Workup
• STI’s• Environmental• Smoking• Toxins/Chemical
• Lifestyle• Obesity• Daily caffeine (> 300 mg)• Alcohol• Drugs/NSAID’s
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 Vascularity• Inflammation
UTERINE Assessment
• Ultrasound• Uterine fibroids• Renal abnormalities
• MRI• Septate vs Bicornuate
UTERINE Assessment
• Sonohysterography• Septate vs Bicornuate uterus
• Hysterosalpingogram• Uterine cavity & Fallopian tubes
• Hysteroscopy• Gold standard
SEPTATE UTERUS
• Most common
• Irregular placentation• Position• Endometrial receptivity• Degeneration/Inflammation
• Loss of Pregnancy > 60%
LEIOMYOMA
• Submucosal
• Irregular Placentation• Position• Endometrial receptivity• Degeneration/Inflammation
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
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
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
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
ENDOCRINE
• Polycystic Ovarian Syndrome (PCOS)• Hyperinsulinemia• Hyperglycemia• tPa inhibitor activity
• Diabetes• Well controlled
•No increased risk
• Poorly controlled•1st Trimester greatest risk
ENDOCRINE
• Thyroid Disease• Uncontrolled hypo/hyperthyroid
• Infertility & pregnancy loss
• Luteal Phase Defect• Corpus Luteum defect
• Progesterone key for implantation and maintenance
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
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)
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
OTHER
• Environmental chemicals/toxins• Sporadic spontaneous loss
• ?RPL risk
• Lifestyle • Obesity, smoking, alcohol, and caffeine
• ?RPL risk
• Exercise• No risk
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
MANAGEMENT
• Anatomic• Surgical correction
• Endocrine• Control
• Diabetes, Thyroid, Progesterone (Luteal)
• Anti-phospholipid antibodies• Aspirin and heparin
• Thrombophilia• Heparin
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
THANK YOU!