Experiencing a miscarriage is an emotionally difficult event, and the loss can be compounded by confusion when tests reveal the pregnancy had a normal number of chromosomes. This is known as a euploid miscarriage. Since most early pregnancy losses are due to chromosomal errors, this result raises questions about other potential causes for why a chromosomally normal pregnancy ended.
Understanding Chromosomes in Pregnancy Loss
Chromosomes are strands of DNA that carry genetic instructions. Human cells have 46 chromosomes in 23 pairs, with an embryo receiving 23 from the egg and 23 from the sperm. When an embryo has this correct number, it is called “euploid.”
The most common cause of first-trimester miscarriages is “aneuploidy,” where an embryo has an incorrect number of chromosomes. This random error can disrupt development so significantly that the pregnancy cannot continue. Since aneuploidy accounts for about half of all early miscarriages, a euploid result can be perplexing and shifts the focus from the embryo’s genetics to other health factors.
Investigating the Underlying Causes
When a euploid miscarriage occurs, the investigation turns to maternal and paternal health factors. These causes can range from the uterus’s physical structure to hormonal, immunological, or other imbalances.
Uterine and Structural Issues
Congenital abnormalities, which are structural differences present since birth, can interfere with pregnancy. A common example is a septate uterus, where a band of tissue divides the uterine cavity and may have an inadequate blood supply. Acquired issues like uterine fibroids, polyps, or scar tissue from previous surgeries (Asherman’s syndrome) can also distort the uterine cavity or disrupt blood flow, preventing an embryo from developing.
Hormonal Imbalances
Progesterone prepares the uterine lining for implantation and supports early pregnancy. Insufficient progesterone, a condition known as a luteal phase defect, can make it difficult to sustain a pregnancy. Unmanaged thyroid disorders (both hypothyroidism and hyperthyroidism) interfere with the hormonal balance needed for fetal development. Uncontrolled diabetes can also negatively impact the uterine environment and embryo development.
Immunological Factors
The maternal immune system’s response can sometimes contribute to miscarriage. In autoimmune conditions like antiphospholipid syndrome (APS), the body produces antibodies that cause blood clots in the placenta, cutting off nutrients and oxygen to the fetus. An alloimmune response can also occur, where the mother’s immune system fails to protect the pregnancy and instead treats the embryo as a foreign invader.
Blood Clotting Disorders
Blood clotting disorders (thrombophilias), which can be inherited or acquired, make the blood more prone to forming clots. During pregnancy, tiny clots can form in the placenta’s blood vessels, obstructing blood flow to the fetus. This disruption in placental circulation can prevent a chromosomally normal pregnancy from surviving.
Endometrial Health
The endometrium, or uterine lining, must be receptive for an embryo to implant. Chronic endometritis, a persistent inflammation of this lining, can create a hostile environment for a chromosomally normal embryo. This condition is often subtle and can be a hidden cause of recurrent euploid pregnancy loss.
Paternal Factors
The quality of sperm DNA is a recognized contributor to miscarriage. Standard semen analysis does not assess the genetic integrity of sperm. High levels of sperm DNA fragmentation, which are breaks in the DNA, have been linked to an increased risk of miscarriage by disrupting embryonic development after fertilization.
Diagnostic Evaluation After Euploid Miscarriage
After a recurrent euploid miscarriage, a diagnostic evaluation is recommended to identify underlying causes. This process uses targeted tests to examine uterine structure and maternal immune or endocrine function. The goal is to pinpoint treatable conditions to improve the chances of a successful future pregnancy.
Assessing the uterus’s physical structure helps detect abnormalities, fibroids, or scar tissue. A saline infusion sonohysterogram (SIS) uses saline and an ultrasound for a clear view of the uterine cavity. Another test, a hysterosalpingogram (HSG), is an X-ray that uses dye to visualize the uterus. A hysteroscopy provides a direct inspection of the uterus using a thin, lighted telescope inserted through the cervix.
Comprehensive blood work screens for hormonal, immunological, and clotting disorders. Tests can measure hormones like progesterone and TSH to identify imbalances. To investigate autoimmune issues, doctors may order tests for antiphospholipid antibodies. Screening for inherited thrombophilias, such as Factor V Leiden, is also performed through blood tests.
An endometrial biopsy assesses the health of the uterine lining. During this procedure, a small tissue sample is examined to diagnose chronic endometritis or evaluate the endometrium’s receptivity. This inflammation of the uterine lining can interfere with embryo implantation.
Management Strategies and Future Outlook
Once a cause for a euploid miscarriage is identified, a targeted management plan can be developed. Addressing a specific issue improves the outlook for a future pregnancy. Treatment strategies are tailored to the diagnosis and include surgery, medication, and lifestyle adjustments.
If a structural issue is found, surgery can correct the problem. A uterine septum, fibroids, or polyps can be removed through minimally invasive procedures. This creates a more favorable environment for an embryo to implant and grow, restoring the uterus to a more normal state.
Hormonal imbalances are managed with medication. If low progesterone is identified, supplements may be prescribed to support the uterine lining in early pregnancy. Medication can also regulate thyroid hormone levels. Properly managing conditions like diabetes is also important for improving pregnancy outcomes.
For immunological or blood clotting disorders, medication can reduce miscarriage risk. In cases of antiphospholipid syndrome or certain thrombophilias, low-dose aspirin and heparin may be prescribed. These medications thin the blood and prevent placental clots, ensuring steady blood flow to the fetus.
Even when a specific cause is not found, many individuals who experience a euploid miscarriage go on to have successful pregnancies, sometimes without intervention. Identifying and treating a specific issue provides a clear path forward and offers hope for a healthy, full-term pregnancy.