Understanding Recurrent Pregnancy Loss

July 13, 2008

Approximately 50 percent of fertilized oocytes end in spontaneous abortion, most occurring before or at the time of the next expected menses. Of clinically recognized pregnancies, 15 percent result in miscarriage. Recurrent pregnancy loss (RPL) has been defined as three or more spontaneous losses, usually in the first trimester. However, evaluation after two losses (up to 5% of couples) has been recommended due to the similar diagnostic yield following the work-up for two vs. three losses. Etiologies of RPL consist of genetic, anatomic, endocrinologic, immunologic and unexplained. Advanced maternal age, cigarette smoking, alcohol and heavy coffee use have all been associated with RPL. Recently, cocaine and tobacco use have been implicated. No study has established a definite role for infections in RPL.

Genetic analysis of isolated spontaneous abortions is abnormal in 50-60 percent of cases. Genetic etiologies are more common in secondary pregnancy loss rather than primary due to inheritance patterns of translocations. A loss with a normal fetal karyotype has a high chance of a normal karyotype in the subsequent pregnancy, regardless of outcome. Anatomic factors consist of congenital and acquired uterine anomalies. The former involves mullerian malformations, most commonly a septate uterus, as well as in-utero DES exposure and incompetent cervix. Acquired include leiomyomas, endometrial polyps and Asherman’s syndrome (intrauterine adhesions). Asherman’s syndrome most likely results if a D&C is preformed 2-4 weeks post partum.

Hormonal causes of RPL include hyperprolactinemia, antithyroid antibodies, polycystic ovarian syndrome, luteal phase insufficiency and uncontrolled diabetes. A midluteal progesterone above 10ng/ml nearly excludes the possibility of a luteal phase defect. Immune cause of RPL have been classified as autoimmune (against self) and alloimmune (against non-self). The former consists of the antophospholipid antibody syndrome (APS), with fetal loss generally occurring after 10 weeks gestation. Obtaining Lupus anticoagulant and Anticardiolipin antibodies are the standard evaluation. Utilizing aspirin (81 mg/d) and heparin (5- 10,000 units b.i.d) in APS patients with RPL have resulted in an approximate 80 percent pregnancy rate. Thrombophilias have not definitively been associated with 1st trimester RPL. The Factor V Leiden mutation is the most common inherited thrombophilia in Caucasians. Unexplained RPL is the most common diagnosis and accounts for approximately 40 percent of cases. Close monitoring and a supportive staff have been shown to significantly improve outcome.

Treatment should be a direct approach to improved outcome using evidence-based medicine. Patients should use contraception during the period of evaluation and also avoid intercourse during early pregnancy for the theoretical seminal prostaglandin induced uterine contractility.

1. Preimplantation genetic diagnosis for hereditary disorders
2. Operative Hysteroscopy for metroplasty (septum resection) or lysis of adhesions
3. Cervical cerclage for incompetent cervix
4. Utilization of metformin in polycystic ovarian syndrome patients
5. Luteal progesterone support for luteal phase defects
6. Aspirin and heparin for the antiphospholipid syndrome or thrombophilias
7. Empathic and supportive care for all, particularly unexplained cases

Normally, an ultrasound detected fetal heart rate after eight weeks has a more than 95 percent chance for a successful outcome. However, the risk of loss is four to five-fold higher for patients with RPL at this gestational age. Since patients with RPL demonstrate significant stress, positive feedback with a supportive staff and serial ultrasound may improve the outcome during the first trimester.

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