Recommendations for the Evaluation of Couples With Recurrent Miscarriage
The suggested evaluation and testing of couples with recurrent miscarriage is shown in Figure 1 of the original guideline document. It is important to ascertain the client's primary questions and concerns in order to mutually develop a plan to address these concerns.
- Obtain the Personal Medical and Pregnancy History of the Consultand(s)
- A sample medical and family history intake form is provided in Figure 2 of the original guideline document.
- Thorough pathological evaluation of the fetal tissue and placenta should be pursued when possible according to the recommendations of the College of American Pathologists ("The examination of the placenta," 1991).
- Document Family Medical History
- Using standardized pedigree symbols, obtain first and second degree family history information from the consultand(s) (Bennett, 1999; Bennett et al., 1995). The standardized symbol for a spontaneous pregnancy loss is delta.
- Targeted questions for the family medical history are included in the table below titled "Patient Interview Questions to Help Identify a Family History of Recurrent Miscarriage due to a Genetic Etiology".
- Special attention should be made to first and second degree relatives who may have the history of mental retardation, learning disabilities, progressive muscle weakness, early cataracts, infertility, stillbirth, recurrent miscarriage, and coagulation disorders.
- Record the ethnicity of both sets of grandparents.
- Note any consanguinity; document on the pedigree the exact relationship of unions between relatives.
- Verify reported family history of a genetic diagnosis with medical records, if possible.
- Document results of thrombophilia panels, chromosomal studies, and molecular genetic testing.
- Maintain family history confidentiality with respect to the consultand(s) and extended family members.
- Referrals to other specialists (e.g., maternal fetal medicine, reproductive endocrinology, gynecology) should be considered to exclude maternal causes of recurrent miscarriage.
Patient Interview Questions to Help Identify a Family History of Recurrent Miscarriage due to a Genetic Etiology
Do any of your close biological relatives have a history of:
- Recurrent miscarriage (note gestation and fetal sex if known)?
- Stillbirth/neonatal death (obtain autopsy, as appropriate)?
- Babies born with abnormalities present at birth, failure to thrive, dysmorphic features, needing immediate surgery, decline of health?
- Difficulty in conceiving (infertility)?
- Uterine anomalies (e.g., fibroids, structural defects)?
- Mental retardation or developmental delay?
- Clotting disorder (e.g., thrombophilia)?
- Inherited disorders (e.g., incontinentia pigmenti, Rett syndrome, chondrodysplasia punctata, Aicardi syndrome, focal dermal hypoplasia of Goltz)?
- Diagnosis of alpha thalassemia (particularly for patients of Southeast Asian and Mediterranean ancestry)?
Are you and your partner blood relatives?
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Genetic Evaluation and Testing Recommendations
Couples may have had a prior evaluation with a reproductive endocrinologist, gynecologist, maternal fetal medicine specialist, or other specialists, and testing (e.g., antiphospholipid antibodies, ultrasounds) may have been pursued previously to rule out other causes of recurrent miscarriage. A referral to a genetics specialist is warranted when the prior evaluations yielded normal results, and when the pregnancy, medical, and family history evaluations suggest the possibility of a genetic cause for the couple's recurrent miscarriage (RM), as well as to address any implications for other family members when a genetic etiology is identified. When possible, chromosomal analysis on fetal tissue from products of conception (POC) should be pursued immediately, in addition to a thorough pathological evaluation of the fetus and placenta. Routine karyotyping of each partner is standard and testing the woman for the factor V Leiden and prothrombin G20210A mutations should be considered. Testing for the less common thrombophilias (anticoagulants protein C, protein S, and antithrombin III) should be reserved for women with a personal and/or family history of venous thromboembolism. Testing for methylenetetrahydrofolate reductase (MTHFR) mutations in a woman with recurrent pregnancy loss is not justified, according to currently available studies. Genetic testing for alpha thalassemia is recommended for individuals of Southeast Asian and Mediterranean ancestry with or without a personal or family history of fetal hydrops. The use of specialized chromosomal studies such as comparative genome hybridization, subtelomeric studies, interphase studies on sperm and assays for skewed X-inactivation patterns are not warranted at this time, as their clinical utility has yet to be determined.
Psychosocial Issues
In addition to acknowledging and empathizing with the couple's pregnancy loss, it is also important to recognize the emotional pain that may be experienced by an older child who was anticipating the birth of his or her sibling. Children are affected by their parent's sadness, depression, grief, anger, guilt, sense of shame and stigmatization. Referrals to support groups, and marriage and family therapists should be made, as appropriate.
Psychosocial History of the Consultand(s)
Attempt to build a relationship with the proband and partner by validating, empathizing, and listening. Assess, record, and address the following in the probands and the partners:
- Level of comprehension and communication
- Level of education, employment, and social functioning, as appropriate
- History of depression (e.g., disturbance in sleep pattern, anxiety, changes in appetite, weight gain or loss, fatigue, feelings of hopelessness, loss of libido, suicidal ideation)
- History of alcohol or other drug use (especially a history of using alcohol or other drugs to self-medicate for depression and/or pain)
- Grief reaction and perceived burden of having recurrent miscarriage
- Coping skills
- Family and community support systems
Cultural Issues
Genetic counselors and health care providers should explore and be respectful of beliefs regarding miscarriage, especially when working with patients from various cultures.
It is important to remember that the couple's personal beliefs regarding miscarriage may be different from their perceived cultural beliefs. Counseling and support revolves around the personal significance of the pregnancy loss to the woman and her partner.
Summary
Formulating a unified genetic evaluation and counseling recommendation for all couples with recurrent miscarriage is challenging. As there are several etiologies as well as psychosocial and cultural issues to consider, the assessment involves a team approach including various specialties (e.g., maternal fetal medicine, reproductive endocrinology, gynecology, genetics, psychology).
During the individual/couple's clinic visits, it is essential for the health care professional to obtain detailed pregnancy, medical, and family histories to determine the test that will most likely yield an informative result. Counseling of couples with RM must include acknowledging the profound emotional impact of pregnancy losses, as well as the implications for relatives when a genetic etiology is identified. Genetic counselors and other health professionals should have an awareness of the couple's personal and cultural beliefs regarding miscarriage. Acknowledging the couple's grief and providing realistic assessments of their chance of reproductive success are important even if the underlying cause of the RM is not identified. In addition, referrals to support groups and professional therapists should be made as appropriate.
