Recurrent Pregnancy Loss (RPL) is defined as the loss of two or more consecutive clinical pregnancies before 20 weeks of gestation. While a single loss is common, RPL is a distinct disorder, affecting an estimated 1% to 5% of all couples attempting to conceive. Medical organizations, including the American Society for Reproductive Medicine, recommend a thorough investigation after two losses to identify an underlying cause requiring systematic medical evaluation and management.
Primary Medical Causes
Genetic and Chromosomal Factors
The majority of sporadic pregnancy losses are caused by random chromosomal errors (aneuploidy) in the developing embryo. In RPL, attention shifts to parental genetics, where a structural rearrangement in one parent can be a factor. A balanced translocation, where a piece of one chromosome breaks off and attaches to another, is found in approximately 2% to 5% of couples experiencing RPL. This arrangement can lead to an unbalanced set of chromosomes in the embryo, resulting in pregnancy loss, even though the parent carrying the translocation is typically healthy.
Anatomical Abnormalities
Structural issues within the uterus can impede implantation or restrict fetal growth, contributing to RPL. Congenital uterine anomalies, such as a septate uterus (a wall of tissue dividing the uterine cavity), are the most common defects, present in about 12.6% of RPL patients. Acquired conditions, including large uterine fibroids or polyps that distort the endometrial lining, can also interfere with placental function and cause losses.
Endocrine and Metabolic Issues
Hormonal imbalances can disrupt the environment required for a successful pregnancy. Poorly managed endocrine disorders, particularly uncontrolled diabetes mellitus and certain thyroid dysfunctions, are established causes of RPL. High levels of thyroid-stimulating hormone (TSH) or the presence of antithyroid antibodies have been associated with an increased risk of recurrent loss. While Polycystic Ovary Syndrome (PCOS) is not a direct cause, related metabolic factors like obesity and insulin resistance can elevate the risk.
Hematological and Thrombophilic Disorders
Disorders affecting blood clotting mechanisms can lead to micro-clots in the placental blood vessels, compromising nutrient and oxygen exchange. The most established acquired cause is Antiphospholipid Syndrome (APS), an autoimmune condition producing antibodies like lupus anticoagulant and anticardiolipin antibodies. APS is found in 5% to 20% of women with RPL and can cause both early and late pregnancy losses. Routine screening for inherited thrombophilias, such as Factor V Leiden, is generally not recommended unless other risk factors are present.
Comprehensive Diagnostic Evaluation
The investigation for RPL is a systematic process designed to screen for the established causes. A genetic evaluation begins with parental karyotyping, a blood test that maps the chromosomes of both partners to identify balanced translocations or other structural anomalies. If available, testing the products of conception (POC) from a recent loss can determine if the loss was due to an embryonic aneuploidy.
Assessing the uterine structure is done using specialized imaging techniques to detect anatomical defects. A saline infusion sonography (SIS) or a hysterosalpingogram (HSG) can evaluate the shape of the uterine cavity and the patency of the fallopian tubes. Hysteroscopy, a procedure where a small camera is inserted into the uterus, offers a direct visual inspection to confirm the presence of a septum, fibroids, or scar tissue.
Laboratory testing involves a series of blood tests to screen for hormonal and hematological conditions. Screening for antiphospholipid syndrome requires testing for specific antibodies, including lupus anticoagulant, anticardiolipin antibodies, and anti-β2 glycoprotein I, which often needs to be confirmed with a repeat test several weeks later. Endocrine screening includes checking levels of TSH and prolactin to rule out thyroid and pituitary gland dysfunctions.
Cause-Specific Treatment Protocols
Treatment for RPL is highly individualized based on the specific cause identified. For anatomical defects, surgical intervention is often the definitive treatment. Hysteroscopic surgery, a minimally invasive procedure, can resect a uterine septum or remove submucosal fibroids and polyps that distort the cavity, significantly improving the chances of a subsequent healthy pregnancy.
Pharmacological management is employed for hormonal and thrombophilic issues. Women diagnosed with Antiphospholipid Syndrome are typically treated with a combination of low-dose aspirin and prophylactic heparin, which is started either before conception or upon a positive pregnancy test. For underlying endocrine issues, such as hypothyroidism, treatment involves regulating hormone levels with appropriate medication before and throughout the pregnancy.
In cases where a parental balanced translocation is identified, couples may pursue Assisted Reproductive Technology (ART). In vitro fertilization (IVF) with Preimplantation Genetic Testing for Structural Rearrangements (PGT-SR) allows embryos to be genetically screened before implantation. This process helps ensure that only embryos with a balanced or normal chromosomal complement are transferred, bypassing the risk of miscarriage due to the parental translocation.
Supportive care, involving early and frequent monitoring, is often initiated in the next pregnancy, regardless of the identified cause. This close surveillance provides reassurance and allows for prompt intervention should any complications arise. For some patients with an identified cause, such as a luteal phase defect, empirical treatment with progesterone supplementation is sometimes utilized, though the evidence supporting its routine use is mixed.
Managing Unexplained Cases and Emotional Wellbeing
Even after a comprehensive evaluation, the cause of RPL remains unexplained in a significant percentage of couples, estimated to be between 40% and 50%. For these cases of unexplained RPL, the clinical approach often involves expectant management with supportive monitoring during the next pregnancy. Despite the lack of a definitive diagnosis, the prognosis for a future live birth remains positive for most couples, with success rates often reported between 60% and 80%.
In some instances of unexplained RPL, empirical treatments may be offered, such as progesterone supplementation in the first trimester. Low-dose aspirin may also be considered, particularly for those with late recurrent losses or for women who have tested positive for antithyroid antibodies. The focus is often on providing meticulous monitoring and emotional support, which can independently improve pregnancy outcomes.
The emotional and psychological toll of RPL often leads to anxiety, depression, and grief. Psychological support, including counseling and support groups, is a necessary component of care, regardless of the medical diagnosis. Providing emotional support has been associated with higher rates of successful pregnancies, highlighting its importance alongside medical interventions. Access to mental health resources helps couples navigate the trauma and fear associated with a subsequent pregnancy.