Recurrent Miscarriages and Fertility Treatment Options

Why miscarriage occurs

Approximately 15% of pregnancies end in miscarriage, which is defined as the loss of a pregnancy before 20 weeks of gestation. The majority of miscarriages occur within the first 12 weeks of gestation. Most losses are due to a chromosomal abnormality of the embryo. However, a variety of other factors can contribute to continued failure to carry a pregnancy. In some cases, genetic factors can prevent an embryo from developing normally. In other cases, conditions affecting the uterus, metabolic causes, environmental factors, infections, hormonal disorders, and possibly clotting disorders can affect a woman’s ability to carry a pregnancy. It is important to know that the overwhelming majority of women will go on to have a live birth after having one or even two miscarriage(s), although some women require treatment to improve odds of live birth and diminish risk for miscarriage.

Recurrent miscarriage is defined as two or more spontaneous pregnancy losses.

Known etiologies of recurrent pregnancy loss include the following:

Genetics.A genetic problem with a developing embryo or a genetic condition that affects one or both parents may result in recurrent miscarriages.

Approximately 50 to 70% of all early pregnancy losses are believed to be caused by abnormalities in the chromosomal makeup of the embryo. These errors typically occur early in the oocyte (egg) maturation process and less commonly during sperm maturation.

In some cases, one or both parents may have a chromosomal abnormality, resulting in an embryo with too much or too little genetic material. We can evaluate a couple’s chromosomes with a test called a karyotype analysis. While some genetic issues affecting parents are undetectable, we can now test embryos for certain genetic abnormalities before they are transferred to the uterus during in vitro fertilization. This process is called Preimplantation Genetic Testing (PGT).

Conditions affecting the uterus. The process of implantation is hormonally regulated and requires a synchronized interaction between the implanting embryo and the lining of the woman’s uterus (endometrium). Factors that alter this relationship can result in pregnancy losses.

The hormone progesterone, produced by the ovaries in the second half of a woman’s ovulatory cycle, is necessary for the establishment and maintenance of pregnancy. The relationship between the hormonal environment of early pregnancy and implantation is intricate and not very well understood.

Anatomical or structural problems with a woman’s uterus, including polyps, fibroids, or congenital defects, can result in miscarriage or complications later in pregnancy. An ultrasound test (saline sonography) or an X-ray test (hysterosalpingogram, or HSG) can reveal many structural abnormalities of the uterus. Occasionally, additional imaging studies may be required. Fortunately, many abnormalities of the uterus can be corrected through surgery.

Problems affecting the immune system. It is clear that there is a special relationship between the uterus and the immune system, but the exact nature of this relationship is not well understood at this time.

Antibodies including lupus anticoagulant (LAC), anticardiolipin antibodies (ACA), and beta-II-glycoprotein antibodies are believed to promote miscarriage by causing clotting in the early placental circulation or by preventing optimal implantation. Treatment involves the use of low dose aspirin and other anti-clotting medications.

Environmental factors. Women who have had repeated miscarriages often ask about a link between miscarriage and environmental factors such as smoking, caffeine, alcohol use, and exercise. While some studies suggest that environmental factors may cause sporadic pregnancy loss, a link with recurrent pregnancy loss has not been firmly established. We generally advise all pregnant women, but especially those with a history of recurrent loss, to avoid smoking (including second-hand smoke exposure), excessive caffeine intake (more than two cups of coffee/day) and alcohol use.

There is no evidence to suggest that exercise increases a women’s risk of pregnancy loss. However, there are no studies suggesting that strenuous exercise is safe for recurrent loss patients. Therefore, as a precaution, we suggest that women avoid strenuous aerobic exercise. In addition, there is some evidence to suggest that women with a history of miscarriage should avoid exposure to biohazards, solvents or certain industrial chemicals that are known to have an effect on a developing fetus. Your doctor can help you evaluate your risk of exposure to these materials if this is a concern.

Infections. It is believed to be unusual for an infection to cause a miscarriage and it is extremely unlikely that infections cause multiple pregnancy losses. Some suspected but unproven infectious causes of pregnancy loss include the bacteria mycoplasma, ureaplasma and Chlamydia. Screening is done through cultures and/or endometrial biopsy.

Hormonal disorders. Diseases affecting the endocrine system, especially those that are relatively mild, do not appear to increase the risk of miscarriage. However, certain disorders, including uncontrolled diabetes or thyroid disease are known to increase a woman’s risk of miscarriage. In addition, women with Polycystic Ovary Syndrome are at increased risk for sporadic loss, but the condition has no proven association with recurrent pregnancy loss. Based on an individual’s health history, we may recommend an evaluation for an endocrine disorder. In many cases these conditions can easily be managed with medication and should be corrected prior to further attempts at conception.

Clotting disorders. Thrombophilias, the tendency to form blood clots, appear to be associated with a variety of problems in pregnancy, although studies are inconclusive. Research suggests a link between thrombophilias and pregnancy-related problems in the second and third trimester. These include fetal growth problems, fetal death, pregnancy-induced hypertension and placental separation. However, the association between thrombophilias and first trimester loss is controversial. Testing for thrombophilias is based on an individual’s health history. If treatment is required, most cases of thrombophilias can be treated with low dose aspirin and other anti-clotting medications.

Male factors. Although inconclusive, there are recent data that sperm DNA fragmentation can contribute to recurrent pregnancy loss. A semen analysis and a special sperm DNA fragmentation test can help determine if this is an issue. Treatment can include in vitro fertilization with intracytoplasmic sperm injection (ICSI) and the use of a sperm selection device called the ZyMotTM.

Treatment for recurrent pregnancy loss can involve a range of options depending on testing results and can include careful monitoring and pre-natal care, surgery, hormone therapy, antibiotics and the use of procedures such as in vitro fertilization. Appropriate treatment has proved to be both safe and effective for most couples.

Diagnostic tests to determine the causes of miscarriage

Your medical history, a pelvic exam, and one or more of the tests listed below are necessary in diagnosing possible causes of your recurring miscarriages:

  • Karyotype– – a mapping of your chromosomes, used to diagnose genetic defects.
  • Hysterosalpingogram– – a radiology procedure that uses fluoroscopy and a special dye to evaluate the shape of the inside of your uterus and the patency of the fallopian tubes.
  • Saline Sonohysterogram– –a procedure where sterile water is placed into the cavity of the uterus while performing a transvaginal
    ultrasound.  This procedure is useful to look for endometrial cavity abnormalities such as polyps, fibroids, and scar tissue that may increase
    the risk of a miscarriage.
  • Hysteroscopy– – a procedure in which your doctor uses a narrow fiberoptic scope inserted into the uterus to look inside the uterine cavity.
  • Vaginal ultrasound– – a scan that uses high frequency sound waves to detect abnormalities in and around the uterus, ovaries, and fallopian tubes.
  • Blood hormone levels– – blood tests that reveal the levels of certain hormones in your blood, such as prolactin, thyroid stimulating hormone, and progesterone.
  • Endometrial biopsy– – a procedure in which a sample of the endometrial tissue is examined under a microscope to determine if there is an infection present preventing the pregnancy from progressing.
  • Glucose screening– – a blood test used to diagnose diabetes mellitus which, if left uncontrolled increases the likelihood of miscarriage.
  • Antiphospholipid antibody testing– – blood tests used to detect an immune system abnormality.
  • Ovarian reserve testing— Testing of egg quantity and quality may help determine if age-related decline in ovarian function is contributing to pregnancy loss.
  • Sperm DNA fragmentation testing– a test to determine if sperm quality and DNA fragmentation may be contributing to pregnancy loss.

Unexplained recurrent pregnancy loss

Unfortunately, despite a comprehensive medical evaluation, some patients will be left with a diagnosis of unexplained recurrent pregnancy loss. Although this diagnosis can be frustrating, treatment options to lower the risk of miscarriage are available. These options include:

  • Ovulation induction.
  • Progesterone therapy.
  • Low dose aspirin.
  • Injectable blood thinners.
  • Antibiotics for presumed chronic inflammation of the uterus.
  • In vitro fertilization.
  • Preimplantation Genetic Testing for Aneuploidy (PGT-A).
  • Intracytosplasmic sperm injection (ICSI) with the assistance of the
    ZyMotTM device.

As fertility specialists, Dr. John Frattarelli and Dr. Anatte Karmon have evaluated and treated many women in Hawaii and elsewhere for recurrent
pregnancy loss. They have given several invited lectures detailing the current research regarding recurrent pregnancy loss. The Fertility Institute of Hawaii offers state of the art testing and treatment for patients experiencing pregnancy loss.  If you would like more information regarding testing and treatment options for recurrent pregnancy loss, please schedule a consultation with one of our physicians.

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