Recurrent Pregnancy Loss Dr. Delani Kotarba – Associate Professor

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Recurrent Pregnancy Loss Dr. Delani Kotarba – Associate Professor

  1. 1. Recurrent Pregnancy Loss Dr. Delani Kotarba – Associate Professor University of Ottawa Ottawa Fertility Centre
  2. 2. Overview 1) Definition of Recurrent Pregnancy Loss 2) Causes of Recurrent Pregnancy loss 3) Investigations 4) Management- Treatable Causes 5) Empiric therapy 6) Conclusions
  3. 3. Definition Three or more consecutive spontaneous pregnancy losses prior to 20 weeks gestation -however, many clinicians would begin investigations after two unexplained losses -actual incidence of recurrent pregnancy loss is between 0.4% and 5% of couples (M. Stephenson ‘00) -approximately 40% of recurrent pregnancy losses will be unexplained
  4. 4. Causes Factor S tephenson ‘96 Genetic 3.5% Endocrine 20% Anatomical 16% Infectious 0.5% Autoimmune 20% Unexplained 43%
  5. 5. Causes 1) Genetic/Chromosomal 2) Anatomical 3) Endocrine 4) Immunological (autoimmune) 5) Environmental Exposures 6) Thrombophyllia 7) Unexplained
  6. 6. Genetic Causes 70% of all early spontaneous abortions (<14 weeks) have chromosomal abnormalities. Most are autosomal trisomies (50%). 2 to 4% of couples with RPL will have some form of chromosomal abnormality on karyotyping. Most are balanced translocations.
  7. 7. Anatomical Factors <ul><li>15 to 16% of women with RPL have uterine abnormalities </li></ul><ul><li>Fibroids, </li></ul><ul><li>endometrial polyps, </li></ul><ul><li>intrauterine adhesions, </li></ul><ul><li>Mullerian Abnormalites (septa, bicornuate, didelphus) </li></ul><ul><li>DES exposure (T shaped uterus, +/- cervical changes) </li></ul><ul><li>Incompetent cervix </li></ul>
  8. 8. Endocrine Causes Mild endocrine diseases are likely not causes for recurrent abortion Significant thyroid disease, poorly controlled diabetes, or significant hyperprolactinemia can result in spontaneous abortion. Patients with PCOS who have elevated serum insulin levels have Been found to have a higher incidence of spontaneous abortion.
  9. 9. Autoimmune Causes (self antigens) Antiphospholipid antibodies : approximately 3% of recurrent miscarriage (Anticardiolipin, Lupus anticoagulant) APA likely induce microthrombi at the placentation site. Altered vascularity affects developing embryo, induces abortion.
  10. 10. Environmental Causes Smoking, alcohol use, and heavy coffee consumption have all been linked to spontaneous abortion. Armstrong ‘92 McGill 11% attributable to smoking 5% attributable to alcohol 2% attributable to coffee Anesthetic gases and dry cleaning fluid (tetrachloroethylene) exposure has been linked to spontaneous abortion.
  11. 11. Thrombophyllic Causes Conflicting studies regarding inheritable clotting disorders and recurrent pregnancy loss.-NOHA study’97 Factor V Leiden mutation (activated protein C resistance) most extensively studied. -? more common with 2nd trimester abortion -definite risk factor for venous clotting in pregnancy, uncertain if treatment with heparin decreases risk of abortion -certainly require heparin for risk of VT during pregnancy
  12. 12. Infectious Causes <ul><li>Quinn et al . Am J Obstet Gynecol 1983 </li></ul><ul><li>84.5% of couples with “pregnancy wastage” were colonized with </li></ul><ul><li>Ureaplasma urealyticum or Mycoplasma hominis </li></ul><ul><li>25.5% of fertile couples were colonized with either or both organisms </li></ul>Poor study-criticized for low success in controls We still culture for mycoplasma/ureaplasma, chlamydia and bacterial vaginosis and treat all positives
  13. 13. Investigations History and Physical Exam Focusing on: a) obstetrical hx- gestational ages, D&Cs, b) galactorrhea, thyroid symptoms c) autoimmune illnesses d) exposures to solvents, drugs, smoking e) family hx of RPL, genetic diseases, autoimmune diseases f) general physical exam with thyroid exam, breast exam g) complete pelvic exam with cultures
  14. 14. Investigations Cervical cultures Infectious Protein C, S, antithrombin III, prothrombin gene, Factor V leiden, Thrombophyllia Lupus anticoagulant, anticardiolipin antibody Immunological TSH, Prol, GTT Endocrine Sonohysterogram, HSG, Hysteroscopy, MRI Anatomical Karyotype the couple Chromosomal Investigation Etiology
  15. 15. Treatment Antibiotics Infectious Heparin Thrombophyllia Heparin & ASA 81 mg Immunological Thyroid replacement (hypo), Bromocriptine (if ↑ prolactin) Metformin (if ↑ insulin) Endocrine Hysteroscopic resection of uterine septum, submucus fibroids, endometrial polyp, lysis of intrauterine adhesions Anatomical Counseling (no treatment) Chromosomal Treatment Etiology
  16. 16. Empiric Treatment Supportive Care Treatment n Success rate of pregnancies No treatment 24 33% TLC 37 86% p<0.001 (psychological support Frequent follow up, Follow up 2 weeks beyond Latest abortion) Small numbers, but low risk/complication treatment. 1984 Stray- Peterson
  17. 17. Conclusions 1) Recurrent pregnancy loss affects up to 5% of couples 2) Approximately 40% of recurrent pregnancy loss is unexplained 3) Investigations should include Karyotype, TSH, Prolactin, APA’s, coagulation studies, cervical cultures and an anatomic uterine study 4) Available treatments are limited. 6) Empiric therapy includes psychological support

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