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!