Recurrent Miscarriage

Recurrent Miscarriage

Jan is a 37 year old patient who presents to her general obstetrician-gynecologist for an early pregnancy ultrasound at approximately 8 weeks gestation. She has been feeling well. Her pregnancy history is notable for having miscarried at this point in pregnancy twice within the past year. Her husband is 39 and otherwise healthy, and he has no children. Jan miscarried both of the previous pregnancies on her own.

Unfortunately, Jan’s obgyn physician diagnoses a third consecutive miscarriage at this visit. Jan and her husband are devastated. Her physician recommends she have a Dilation and curettage (D&C) procedure in order to do genetic testing on the fetus. Her physician also recommends that Jan see a reproductive endocrinology and infertility specialist for further evaluation. Jan feels hopeless as if she will never have a healthy baby.

How is the diagnosis of recurrent pregnancy loss diagnosed?

Recurrent pregnancy loss (RPL) is a distinct disorder characterized by two or more failed clinical pregnancies.* A clinical pregnancy is a pregnancy documented by ultrasound showing a fetus or after-the-fact by a pathologist who examines the pregnancy tissue under a microscope. Studies have shown that fewer than 5% of women will experience two consecutive miscarriages. (Whereas the traditional definition of RPL included three or more miscarriages, currently the definition has expanded to two or more pregnancy losses.)

Why do women have recurrent pregnancy losses?

It is important to note that approximately 50% of the time, there is no clear reason for RPL.

There have been many published recommendations regarding the etiology of recurrent pregnancy losses. Our recommendations are based upon the well-conducted studies based upon true RPL cases and upon the recommendations of the American Society for Reproductive Medicine. Studies focusing on RPL have examined factors related to the following:

  • Genetic abnormalities– Abnormalities in the number of fetal chromosomes (genetic material in cells) or in the structure of fetal chromosomes (such as translocations, when chromosomes break and reseal in abnormal ways) are known causes of RPL.
    • The majority of miscarriages are sporadic and are thought to result by genetic causes, largely influenced by maternal age.
    • Studies have shown that more than half of early pregnancy losses are associated with random chromosomal abnormalities, mostly chromosomal trisomies (where there are three copies of a single chromosome set, rather than the normal two.)  Jan’s physician appropriately wanted to do a D&C to collect fetal tissue so that she could test the fetal chromosomal material. As women age, their risk of a fetal chromosomal abnormality such as a trisomy increases.
    • As an additional evaluation, couples (both the male and female partner) with RPL should undergo chromosomal testing to detect if they are carriers of structural chromosomal abnormalities. If a structural chromosomal abnormality is diagnosed, it is important that a patient meet with a genetic counselor. These patients have different options depending on their history and exact chromosomal abnormality, including expectant management, in vitro fertilization with preimplantation genetic testing, amniocentesis, or chorionic villus sampling.
  • Antiphospholipid Syndrome– The antiphospholipid syndrome is associated with pregnancy loss. Antiphospholipid antibodies are proteins the body makes that attacks phospholipids in one’s own body, leading to various clinical sequelae, such as vascular thrombosis (blood clots) and specific adverse pregnancy outcomes. This syndrome is diagnosed by specific criteria:
    • Clinical criteria: history of blood clots and/or specific adverse pregnancy outcomes, including recurrent pregnancy loss before 10 week
    • Laboratory criteria, including positive results with Lupus anticoagulant testing, Anticardiolipin antibody testing, and Anti-β2 glycoprotein-I antibody.

Treatment for antiphospholipid syndrome includes low-dose aspirin and heparin (blood thinner), which together appear to confer a significant benefit in pregnancies with antiphospholipids and recurrent pregnancy loss.

It should be noted that the diagnosis of Antiphospholipid Syndrome should only be made by a provider with expertise. Failure to follow the exact guidelines for a positive diagnosis will result in a high number of false positive diagnoses and unnecessary treatment.

  • Anatomic Factors – Uterine abnormalities are associated with adverse pregnancy outcomes, and it is recommended patients with first-trimester RPL have a uterine anatomy assessment. This assessment is most commonly done by hysterosalpingogram or hysterosonogram (also known as saline infusion sonogram). Further evaluation with pelvic MRI or 3-D ultrasound may be necessary if a congenital anomaly is suspected. Potential uterine abnormalities can include
    • Congenital uterine anomalies (with which patients are born), such as unicornuate, bicornuate, uterine didelphys, and septate uterus. A reproductive endocrinology and infertility specialist will make specific recommendations depending on the exact anomaly present.
    • Asherman’s syndrome/intrauterine adhesions – Scar tissue inside the uterine cavity can result from prior pregnancies and/or uterine procedures. It is generally recommended these adhesions be treated surgically.
    • Uterine fibroids- If uterine fibroids impinge upon (press upon) the uterine cavity and distort the normal uterine cavity architecture, it is generally recommended they be treated surgically.
    • Endometrial polyps – If endometrial polyps distort the normal uterine cavity architecture, it is generally recommended they be treated surgically.
    • Inherited Thrombophilias – Screening for thromobophilia (predisposition to blood clotting) may be warranted when a patient or a first-degree relative has a history of blood clots. The data regarding hereditary thrombophilia and RPL is conflicting, and at this time it is not recommended women with RPL be screened for inherited thrombophilia.
    • Hormonal and Metabolic Factors- It is generally agreed that women with RPL should be screened and treated for thyroid disease, disorders of prolactin secretion, and Diabetes. The empiric administration of supplemental luteal phase progesterone may be of some potential benefit, although there is not abundant data to support this.
    • Infectious factors – There is no convincing data that infections cause recurrent pregnancy loss.
    • Male factors – Standard semen parameters (as part of a semen analysis) do not appear to predict risk of RPL. Some researchers suggests that sperm with high DNA fragmentation (damaged DNA, due to environmental factors or paternal age) may predispose to risk of RPL, but it should be emphasized that the data pertaining to this is conflicting.
    • Lifestyle Factors – Specific lifestyle factors have been linked with pregnancy loss. Generally in any fertility consultation, a reproductive and endocrinology specialist will inquire regarding these exposures.
      • Cigarette smoking
      • Obesity
      • Cocaine use
      • Alcohol consumption
      • Increased caffeine consumption (>3 cups per day)
    • Alloimmune factors –Studies of human leukocyte antigen (HLA) typing, embryotoxic factors, decidual cytokine profiles, antipaternal antibody levels, HLA-G polymorphism and other immunologic factors are inconsistent. Testing and/or treatment for these factors is not recommended in the setting of RPL.
    •  Psychological Factors – Pregnancy loss can take a significant emotional toll, as seen for pt JAN Patients with RPL are prone to anger, depression, anxiety, and feelings of grief and guilt. However there is inconclusive data that psychological stress causes RPL. Patients with RPL should be offered psychological support services.

    *Defined by the Practice Committee of the American Society of Reproductive Medicine 2012