The experience of achieving a positive pregnancy test only to face repeated loss is medically defined as Recurrent Pregnancy Loss (RPL). RPL occurs when an individual experiences two or more consecutive, failed clinical pregnancies before the 20th week of gestation. A clinical pregnancy is confirmed by ultrasound visualization or histopathological examination, excluding losses detected only by hormone tests (biochemical pregnancies). While a single miscarriage is common, affecting 10 to 15% of recognized pregnancies, recurrence warrants a focused investigation. The goal is to systematically explore the reasons behind the body’s inability to sustain the pregnancy, offering pathways for diagnosis and targeted intervention.
Categorizing the Causes of Recurrent Pregnancy Loss
The medical reasons for the failure to stay pregnant are diverse, interfering with either the embryo’s development or its implantation and support within the uterus. While single miscarriages are often due to random genetic errors, RPL involves structural or systemic issues that persist across multiple pregnancies.
Genetic and Chromosomal Factors
Many early pregnancy losses, particularly in the first trimester, are linked to aneuploidy (an abnormal number of chromosomes in the embryo). This random occurrence is influenced by increasing parental age, especially the mother’s, as egg quality declines, leading to a higher rate of chromosomal mistakes. A less common genetic factor in RPL is a balanced translocation. This structural rearrangement in one parent does not cause them problems, but when passed to the embryo, it results in an unbalanced, non-viable set of chromosomes, leading to repeated loss.
Anatomical Issues
Structural anomalies of the uterus can physically impede secure implantation or limit the space and blood flow necessary for fetal development. Congenital malformations, such as a uterine septum (a band of tissue dividing the uterine cavity), are strongly associated with RPL because the septum often lacks the proper blood supply for placental growth. Acquired conditions, including large submucosal fibroids or intrauterine scar tissue (Asherman syndrome), can also disrupt the endometrial lining. These physical obstacles often become more problematic as the pregnancy advances, sometimes leading to second-trimester losses.
Endocrine and Hormonal Imbalances
Systemic medical conditions that affect the hormonal environment can destabilize the uterine lining and placental function. Poorly controlled metabolic disorders, such as diabetes mellitus, and thyroid dysfunction (overt or subclinical hypothyroidism) increase the risk of recurrent loss. Progesterone deficiency is also a consideration. Progesterone is produced by the corpus luteum and is crucial for maintaining the uterine lining during early pregnancy.
Immunological and Thrombotic Factors
A significant identifiable cause of RPL is Antiphospholipid Syndrome (APS). This autoimmune disorder involves the body producing antibodies that attack blood proteins, promoting blood clot formation in the small vessels of the placenta. This disrupts the flow of nutrients and oxygen to the developing fetus, often resulting in pregnancy failure. However, approximately 50% of RPL cases are ultimately classified as unexplained, as a thorough medical evaluation will not identify a clear reason.
Comprehensive Diagnostic Investigations
Identifying the specific cause of RPL requires a systematic, multi-faceted approach involving genetic analysis, blood testing, and advanced imaging. The evaluation typically begins after two consecutive losses to pinpoint the underlying factors.
Genetic Screening
Karyotyping is a primary step, involving a blood test performed on both parents to analyze their chromosomes for balanced translocations. Detecting this rearrangement is vital for understanding the risk of passing an unbalanced chromosome set to future pregnancies, even though the parents are healthy carriers. If tissue from a previous loss (products of conception) is available, genetic analysis can confirm if the loss was due to an isolated random chromosomal error in the embryo.
Blood Work for Systemic Conditions
Extensive blood panels screen for hormonal and immunological issues manageable with medication. Thyroid function tests, measuring Thyroid-Stimulating Hormone (TSH) levels, rule out hyper- or hypothyroidism. The Antiphospholipid Antibody panel checks for Lupus Anticoagulant and Anticardiolipin antibodies, necessary to diagnose APS. These tests identify underlying conditions that interfere with normal pregnancy maintenance.
Uterine Imaging
Specialized imaging of the uterine cavity is performed to assess anatomical issues, evaluating its shape and integrity. While a transvaginal ultrasound provides an initial view, more detailed techniques are often required. Saline Infusion Sonohysterography (SIS) involves injecting sterile saline into the uterus to distend the cavity, allowing clear visualization of polyps, fibroids, or a septum. Hysteroscopy, where a small camera is inserted through the cervix, allows direct visualization and simultaneous correction of structural abnormalities within the uterus.
Treatment and Management Strategies
Once a cause is identified through comprehensive testing, specific medical or surgical interventions can significantly improve the chance of a successful live birth. Treatment is highly personalized based on the confirmed diagnosis.
Addressing Anatomical Issues
For individuals diagnosed with a septate uterus or significant submucosal fibroids, surgical correction is often recommended. Hysteroscopic surgery is a minimally invasive technique used to remove a septum or fibroid, restoring the normal contour and improving the blood supply of the uterine lining. This procedure can increase the rate of subsequent successful pregnancies by optimizing the implantation site.
Hormonal Regulation
Management of endocrine disorders involves optimizing the patient’s underlying health before and during pregnancy. Levothyroxine medication normalizes TSH levels for those with thyroid dysfunction, while individuals with diabetes require rigorous control of blood glucose. Progesterone supplementation, typically administered vaginally in early pregnancy, supports the uterine lining. Its benefit is most clearly established in women with confirmed luteal phase deficiency or those undergoing IVF.
Immunological Treatment
Patients diagnosed with Antiphospholipid Syndrome (APS) are treated with combination therapy to prevent harmful blood clots from forming in the placenta. This regimen typically involves a daily low-dose aspirin alongside an injectable anticoagulant, such as low-molecular-weight heparin. This combination substantially increases the live birth rate in women with confirmed APS.
Genetic Counseling and Advanced Options
If a balanced translocation is identified, genetic counseling is provided to understand the risk of producing an unbalanced embryo. For these couples, In Vitro Fertilization (IVF) coupled with Preimplantation Genetic Testing for Structural Rearrangements (PGT-SR) offers a pathway to a successful pregnancy. This technique allows clinicians to screen lab-created embryos and select only those with a balanced or normal chromosomal complement for transfer, bypassing the risk of another loss. Even in cases of unexplained RPL, lifestyle adjustments, such as maintaining a healthy Body Mass Index (BMI) and cessation of smoking, are advised to improve overall reproductive health.