1. The Diagnostic Evaluation and Treatment of Recurrent Pregnancy Loss
Ashim Kumar, M.D.
Reproductive Endocrinology and Infertility
Clinical Assistant Professor,
UCLA School of Medicine
Fertility & Surgical Associates
of California,
Encino & Thousand Oaks, CA

2. Luteal Support Progesterone +/- Estradiol
Start after ovulation or egg retrieval
Continue until 10 weeks gestational age

3. Early Pregnancy Reassurance Ultrasounds Pelvic rest as needed
As Indicated
Monitor TSH
Monitor BP

4. Prenatal Testing Screening Diagnostic
1st Trimester – Nuchal Fold + Serum
2nd Trimester – Triple/Quadruple Screen
Diagnostic
1st Trimester – Chorionic Villus Sampling
2nd Trimester – Amniocentesis

5. Recurrent Pregnancy Loss
SAB: involuntary loss of pregnancy before 20wk GA
RPL: Three or more pregnancy losses in the first trimester
Indications to evaluate after 2 or more consecutive losses:
+ FCA in prior loss
Normal Karyotype on prior loss
Female > 35yr
Infertility
Emotional Support is critical

6. Risk of RPL in Young Women
# of Prior SAB’s
% Risk of SAB in Next Pregnancy
h/o prior liveborn
12% 1
24% 2
26% 3
32% 4 6
53%
No liveborn
2 or more
40-45%

7. Early Pregnancy Loss Clinically unrecognized (less than 8wk GA)
30-60% of all pregnancies end in SAB
At least ½ are early losses (go unnoticed)
~75% of embryos with chromosomal abnormalities
90% are numerical (aneuploidy/polyploidy)
Rest are structural or mosaicism
2/3 of the remaining 25% with normal karyotype exhibit gross structural abnormalities

8. Etiology Uterine Defect (~30%) Thrombophilia Genetic General Endocrine
Congenital
Acquired
Thrombophilia
Immunologic (~3-5%)
Genetic
Meiotic Nondisjunction
Balanced Translocation (5%)
General Endocrine

9. Uterine Defect Congenital Acquired Septum Bicornuate / Unicornuate
T-Shaped Uterus
Acquired
Submucosal Leiomyoma
Endometrial Polyp
Synechia
Adenomyosis

10. Uterine Evaluation Ultrasound Sonohysterogram (saline ultrasound)
Hysterosalpingogram
MRI
Hysteroscopy

11. Bicornuate or Septate

12. Endometrial Polyp

13. Thrombophilias Congenital Immunologic - Antiphospholipid Syndrome
Factor V Leiden Mutation
Protein C / Protein S Deficiency
Prothrombin Gene Mutation
Methylenetetrahydrofolate Reductase (MTHFR) – homocysteine
Antithrombin III
Immunologic - Antiphospholipid Syndrome
Anticardiolipin Antibodies
Lupus Anticoagulant

14. Virchow’s Triad Stasis (Decrease flow in placental vessels)
Damaged Vasculature
Hypercoagulable State
Cancer
Pregnancy (Elevated Estradiol leads to increased hepatic production of clotting factors)
Congenital
Immunologic

15. Genetic Meiotic Nondisjunction Balanced Translocation (5% of couples)
Risk of miscarriage increases with advancing reproductive age
Balanced Translocation (5% of couples)
Robertsonian
Reciprocal
Others
Mosaicism
Inversion
Chromosomally abnormal sperm do not play a role in RPL

16. Meiotic Nondisjunction

17. Age and Miscarriage Risk
<30 yr %
30-34 yr- 8-21%
35-39 yr %
≥40 yr %

18. Risk of Chromosomal Abnormality in Newborns by Maternal Age
Maternal Fetal Medicine: Practice and Principles.
Creasey and Resnick 1994

19. Preimplantation Genetic Diagnosis

20. Preimplantation Genetic Diagnosis

21. Preimplantation Genetic Diagnosis

22. Robertsonian Translocation

23. Reciprocal Translocation

24. General Endocrine Diabetes (Fasting Glucose) Thyroid Disease (TSH)
Hyperprolactinemia (Prolactin)
Polycystic Ovary Syndrome
Luteal Phase Deficiency (Supplement Everyone)

25. Treatment Provide Emotional Support Uterus Hypercoagulable State
Resect lesion
Hypercoagulable State
Heparin
Aspirin
Folate
Genetic
PGD
General Endocrine
Correct hormonal imbalance

26. What Does Not Work Alloimmune Disorders Genetic Hypercoagulable State
Testing
HLA testing
Mixed lymphocyte culture
Natural killer cell assay
Treatment
Paternal leukocyte immunization
Intravenous immunoglobulins (IVIG)
Genetic
PGD
Hypercoagulable State
Glucocorticoids
Uterus
Metroplasty

27. Conclusion
The likelihood of successful delivery is very high. The challenge is to do it an a cost-effective fashion while being sensitive to the emotional sequelae.