What is recurrent pregnancy loss (RPL)?
Recurrent pregnancy loss (RPL) is a difficult and frustrating area of reproductive medicine and is emotionally traumatic to those who suffer from it. There is currently lack of a standard definition for RPL but generally it is defined as 2 or 3 consecutive pregnancy losses. Some definitions stipulate the pregnancy has to be visualized by ultrasound or tissue sample while others include biochemical pregnancies (a pregnancy that ends shortly after implantation, prior to being visible by ultrasound) and ectopic pregnancy (a pregnancy occurring outside the uterus).
What causes RPL?
· The cause of RPL is discovered in only 50% of cases
· Prior pregnancy loss(es) increase risk for subsequent loss however several factors influence this such as gestational age at loss, cause of prior loss, total number of pregnancies, maternal age and prior pregnancy outcomes.
· Uterine factors such as congenital uterine anomalies (malformations of the uterus that a woman is born with), fibroids that protrude into the endometrial cavity (the area where an embryo implants) and intrauterine adhesions (scar tissue) may contribute to RPL. Cervical insufficiency is implicated in mid-pregnancy but not early pregnancy loss. Defective endometrial receptivity is currently under investigation as a cause for RPL.
· Immunologic factors; antiphospholipid syndrome (APS) is the primary autoimmune condition linked to poor pregnancy outcome. APS is characterized by venous and/or arterial blood clots and pregnancy loss. There are other immunologic factors that are not as well defined and require further investigation to determine their significance and treatment in pregnancy.
· Endocrine (hormone) factors may account for 15-60% of RPL. These factors include poorly controlled diabetes, PCOS, hyperprolactinemia and thyroid disease or presence of thyroid antibodies.
· Genetic factors ie abnormalities of fetal chromosome number or structure account for at least 50% of sporadic early pregnancy losses. Additionally 3-5% of couples with RPL have a chromosomal rearrangement such as a translocation or inversion.
· Other factors with less clear associations with RPL include personal habits such as smoking, caffeine, alcohol and obesity, male factor, infection, decreased ovarian reserve, celiac disease, environmental factors and stress and thrombophilia and fibrinolytic factors.
How is RPL Diagnosed?
RPL is diagnosed using testing to rule out the above conditions. A typical RPL workup includes a uterine cavity evaluation such as a hysteroscopy or saline infusion sonohysterogram, a blood draw to determine maternal and paternal karyotype (chromosomal analysis of patient and partner), blood tests to test for antiphospholipid syndrome, blood tests for thyroid function and antibodies and possibly blood tests for blood sugar and prolactin. Less useful tests include those for hypercoagulable state, autoantibodies and immune function, progesterone and endometrial biopsy. Additionally, chromosomal analysis of the fetal tissue from a miscarriage can be helpful.
Is there treatment for RPL?
Treatment options depend on the cause of RPL:
· Couples in whom chromosomal abnormalities are found in one or both partners are referred to genetic counseling and may choose to undergo IVF with preimplantation genetic diagnosis (PGD) and/or prenatal genetic studies such as amniocentesis.
· Uterine abnormalities are managed surgically if the defect is a surgically correctable cause of pregnancy loss such as a uterine septum, adhesions or fibroid.
· Antiphospholipid syndrome may be treated with medication such as aspirin or heparin.
· Thyroid disease and diabetes can be controlled with medication.
· Metformin has been used in women with PCOS to decrease miscarriage risk however this approach is not proven.
· Hyperprolactinemia can be controlled with medication.
· Anticoagulation of women with inherited thrombophilias does not appear to prevent pregnancy loss but may improve maternal outcome by preventing venous thromboembolism.
· IVF with preimplantation genetic screening (PGS) may be helpful in some cases.
· Lifestyle modification such as decreasing alcohol, tobacco, caffeine and lowering body mass index may increase fertility potential but have not been definitively tested in randomized trials.
· Progesterone therapy does not appear to improve live birth rate but there is not universal agreement about its use.
· In some cases, using donor eggs or a gestational carrier may be warranted.
What is the prognosis for RPL?
The prognosis for a successful future pregnancy is generally good: The overall live birth rates after normal and abnormal diagnostic evaluations for RPL are 77 and 71 percent, respectively.
Harger JH, Archer DF, Marchese SG, et al. Etiology of recurrent pregnancy losses and outcome of subsequent pregnancies. Obstet Gynecol 1983; 62:574.
Women with a history of RPL who become pregnant may be at higher risk for developing fetal growth restriction and premature delivery, but not for gestational hypertension or diabetes.
Recurrent pregnancy loss: Definition and etiology
Recurrent pregnancy loss: Evaluation
Recurrent pregnancy loss: Management