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Multiple Miscarriages: Causes, Tests and Treatments

By Rafat Abbasi, MD, FACOG
Published in Resolve, for the journey and beyond, Spring 2013 issue

Recurrent pregnancy loss is defined by the loss of two or more clinical pregnancies.(1) It is distinct from sporadic losses before 10 weeks.

A clinical pregnancy is documented by ultrasound or the pathologic diagnosis of the products of conception.

The incidence of spontaneous miscarriage is about 15-20%. Early losses that occur even before a missed period may be as high as 30-50%. In women who have a history of two or more previous losses the risk increases to about 40%. The risk of miscarriage is increased with advancing maternal age. Evaluation should be instituted after 2 losses especially in the infertility population.  About 5% of women will have at least 2 consecutive miscarriages while only 1% experience 3 or more.(2)

Approximately 50% of patients evaluated have a diagnosis. The remainder may never have a definite reason identified for the pregnancy loss.(3)

Causes of recurrent pregnancy loss:

The following factors have been identified as potential causes:

Genetics: Chromosomal abnormalities in the fetus account for about 60% of sporadic losses.(4) Trisomies (an extra chromosome ) is the most frequent and is related to the maternal age. Below the age of 35 the risk of a sporadic miscarriage is between 9-12%. This increases in women at 40 years of age to almost 50%.(5) Parents should undergo chromosomal analysis to rule out any structural rearrangement of chromosomes. Translocations are found in about 2-5% of couples.(6)

When women experience multiple miscarriages, genetic counseling may be recommended. Pre-implantation genetic screening (PGS) to diagnose the abnormality in the fetus is an option. The American Society for Reproductive Medicine (ASRM) does not currently recommend routine preimplantation genetic diagnosis for aneuploid (abnormal number of chromosomes) embryos.

Testing the products of conception is also available but there are some issues with maternal contamination of the tissue.  Maternal blood can be analyzed by reflex DNA testing to differentiate between the fetal and maternal source.(7)

Anatomical Factors: Uterine cavity abnormalities are usually associated with second trimester (after 12 weeks) miscarriages. Congenital abnormalities are present in about 4% of the general fertile population, but in 13% of the recurrent loss patients.(8) The different abnormalities are developmental defects of the uterus. These are an arcuate uterus, a septate uterus, an unicornuate, or bicornuate uterus and a didelphys uterus. These abnormalities can be detected by performing a hysterosalpingogram and confirming with further tests like a MRI and a 3D sonogram. The highest rate of loss occurs in patients with a septate uterus (44%), followed by 36% in those with a bicornuate uterus, and 26% in patients with an arcuate uterus. Surgical correction of a septate uterus is the treatment of choice since it improves the live birth rate.

Patients with other uterine factors include Asherman’s syndrome, ( intrauterine synechiae), submucous fibroids, and polyps.  Surgical correction of these defects is recommended.

Antiphospholipid Syndrome: This syndrome has been known to be associated with recurrent pregnancy loss. In this group of patients, about 8-42% will test positive for antiphospholipid antibodies.(9) Testing should be performed in these patients, after other causes (anatomic, hormonal and chromosomal) have been excluded. The treatment regimen includes low dose aspirin and low dose heparin.

Routine testing of recurrent pregnancy loss patients for inherited thromobophilias is not currently recommended by the ASRM.

Hormonal and Metabolic factors: Thyroid function should be evaluated and treated if abnormal. TSH levels should, be below 2.5 mIU/L.  Uncontrolled diabetes may be associated with pregnancy loss. Elevated prolactin levels can interfere with adequate follicular development and luteal function. This can result in decreased progesterone levels in the luteal phase of the cycle. Treatment with dopamine agonists can correct this. In patients with recurrent losses, progesterone supplementation can improve pregnancy rates.(10)

Infections: There is no current consensus in the literature that infections like Ureaplasma, Mycoplasma, Listeria, Toxoplasmosis or rubella cause recurrent pregnancy loss. Routine testing and treatment with antibiotics is not recommended.

Alloimmune Factors:  Studies have shown inconsistent results when looking at immunological factors, and treatment results have not been reproducible when analyzed. Several trials have concluded that IVIG (intravenous immunoglobulin) is not effective for primary recurrent pregnancy loss.(11)

Lifestyle Factors: Cigarette smoking, alcohol and cocaine use and increased caffeine ( more than 3 cups of coffee a day) have been reported to increase the risk of miscarriage.(12,13)

Unexplained: No cause may be found in 50-75% of patients. In this group of patients the chance of a successful future outcome can be as high as 50-60% depending upon the maternal age. (14)

References:

  1. Evaluation and treatment of recurrent pregnancy loss: a committee opinion.
  2. Stirrat GM. Lancet 1990; 336:673-5.
  3. Jaslow CR et al. Fertil Steril 2010; 93: 1234-43.
  4. Stephenson MD et al. Hum Reprod 2002; 17: 446-51.
  5. Franssen MTM et al. Hum Reprod Update 2011;17: 467-75.
  6. Royal College of Obstetricians and Gynaecologists. Scientific Advisory Committee, Guideline No. 17.
  7. Jarrett KL et al. Am J Obstet Gynecol 2001; 185: 198-203.
  8. Grimbizis GF et al. Hum Reprod Update 2001; 7: 161-74.
  9. ACOG Antiphospholipid syndrome. ACOG Practice Bulletin, No. 118, January 2011.
  10. Oates-Whitehead RM et al. Cochrane Database Syst Rev 2003; 4: CD003511.
  11. Ata B et al. Fertil Steril 2011; 95: 1080-5.
  12. Ness RB et al. N. Engl J Med 1999; 340: 333-9.
  13. Kesmodel U et al. Alcohol 2002; 37: 435-44.
  14. Lund M et al.Obstet Gynecol 2012; 119: 37-43.

Rafat Abbasi, M.D., F.A.C.O.G. completed her residency was at St. Joseph's Hospital in Towson, MD and her fellowship in Reproductive Endocrinology and Infertility at Georgetown University Hospital in Washington, D.C. She is board certified in Obstetrics and Gynecology and Reproductive Endocrinology. Dr. Abbasi served in the United States Army and was the Chief of Endocrinology at Brooke Army Medical Center in San Antonio, Texas. She is a partner at Columbia Fertility Associates in Washington DC. Dr. Abbasi was chosen by her peers as one of the TOP DOCTORS in Washingtonian magazine.

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