Recurrent miscarriage (RM) is a devastating problem effecting less than five percent of the population. Of the all the patients I see for infertility, those with RM are more psychologically stressed. When most women are rejoicing their positive pregnancy test, a patient with RM is on guard with worry for at least three months of pregnancy, if not longer.
Defined as two or more first trimester losses, RM is unexplained in 50 percent of cases. The accepted causes are: genetic, anatomic, hormonal and thrombophilias. The evaluation is not complicated and should be limited to testing that is supported by solid medical evidence. Unfortunately, RM patients are desperate for an answer and treatment therefore they are at risk of exploitation with excessive testing and unsubstantiated therapy.
1. Folic acid 4mg daily decreases embryo chromosomal abnormalities and miscarriage.
Folic acid in doses of at least 0.4mg daily have long been advocated to reduce spina bifida and neural tube defects. It is optimal to begin folic acid for several months prior to conception attempts. Now there is evidence it may help treat RM by reducing the chance for chromomal errors.
2. Early progesterone support may reduce biochemical miscarriage.
A biochemical pregnancy loss is defined as a miscarriage prior to detection/confirmation by pelvic ultrasound. This type of pregnancy occurs more commonly than realized since many women may experience a “late menses” without performing a pregnancy test. Natural progesterone (unlike synthetic), has long been used to treat and/or prevent miscarriage. Though there is no evidence for its benefit when initiated in pregnancies after five weeks, there may be a therapeutic effect when given in early pregnancy.
3. No benefit of aspirin and/or heparin to treat unexplained RM.
Despite many proponents of this approach, especially on the internet, the use of aspirin and/or heparin has convincingly been shown to not improve live birth rates when the cause of RM is unknown. Other therapies such as white blood cell transfusion and intralipid infusion should also not be prescribed and only offered as part of experimental research protocols after full informed consent regarding the risks.
4. Inherited thromophilias are NOT associated with RM and should not be tested.
Screening for Factor V (Leiden mutation), Factor II (Prothrombin G20210A), and MTHFR (Methylenetetrahydrofolate reductase) have not been shown to cause RM and no treatment, such as aspirin and/or heparin, improves the live birth rate. Only acquired thromophilias (lupus anticoagulant, anticardiolipin antibody, and anti-beta 2 glucoprotein), particularly based on accepted levels, benefit from treatment resulting in improved live birth rates.
5. Close monitoring and empathic care improves outcome.
For unknown reasons, clinics providing close monitoring, emotional support and education to patients with unexplained RM report higher live birth rates compared with patients not receiving this level of care.
6. Behavior changes reduce miscarriage.
Elevations in body mass index (BMI) and cigarette smoking both increase the risk of miscarriage. As a result, a health BMI and eliminating tobacco use reduce the risk of pregnancy loss. Excessive caffeine use (more than two equivalent cups of caffeine in coffee per day) also increases miscarriage.
7. Fertility medications, IUI, and standard IVF do not improve outcome.
When patients are diagnosed with unexplained RM, they often feel compelled to undergo fertility treatment. Unfortunately, medications, intrauterine insemination (IUI) and even in-vitro fertilization (IVF) have not been show to improve the chance for live birth. However, a very exciting option with IVF reduces the miscarriage rate to less than 10 percent. The procedure is called PGS (preimplantation genetic screening) and involves chromosome testing of the embryo prior to being transferred to the patient. By placing a known normal embryo into a patient, the live birth rate is increased while reducing the chance for a loss.
In summary, I recommend obtaining chromosomal testing of the couple, viewing the uterine cavity, blood testing thyroid, prolactin, blood sugar control, and thrombophilias (as above). Fortunately, when the cause is unexplained, the patient/couple have a 70 to 80 percent chance of a spontaneous live birth over the next 10 years from diagnosis. My prayers to all of you struggling with this frustrating problem.
By Mark P. Trolice, M.D., FACOG, FACS, FACE