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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. |
