Recurrent pregnancy loss does not have a single cause, and some couples may have more than one contributing factor.

• Chromosomal Abnormalities in the Embryo
  • Chromosomal abnormalities are an important cause of miscarriage, particularly miscarriage during early pregnancy. It is estimated that approximately 50% of first-trimester miscarriages are associated with chromosomal abnormalities. Embryos with certain abnormalities in the number or structure of chromosomes may not be able to develop normally, which can lead to miscarriage. The likelihood of chromosomal abnormalities in embryos is associated with the woman’s age, particularly as age increases.
• Abnormalities of the Uterus and Uterine Cavity
  • The structure of the uterus and uterine cavity is important for embryo implantation and development. Certain abnormalities, such as a septate uterus, polyps, fibroids in the uterine cavity, or intrauterine adhesions, may be associated with pregnancy loss.
• Certain Immune-Related Conditions
  • One condition associated with recurrent pregnancy loss is Antiphospholipid Syndrome (APS), an autoimmune disorder associated with blood clot formation and pregnancy complications. APS is found in approximately 15% of individuals with recurrent pregnancy loss and is one of the causes that can be treated when appropriately diagnosed and managed.
• Diseases or Medical Conditions in the Woman
  • Certain medical conditions may affect pregnancy, such as thyroid disorders or poorly controlled diabetes.
• Factors Related to the Male Partner
  • Recurrent pregnancy loss is not related only to the female partner. Sperm quality is another factor that may be associated with embryo quality.
    In some cases, doctors may consider evaluating sperm quality, including sperm DNA fragmentation, based on the medical history and clinical indications, as a high level of genetic damage in sperm may be associated with embryo quality and the risk of miscarriage.

When there is a history of recurrent pregnancy loss, doctors do not rely on a single test. Instead, they evaluate multiple factors together to identify potential causes that may be associated with pregnancy loss.
The tests that may be considered include:

1. Chromosome Testing of Pregnancy Loss Tissue
   • If a tissue sample from the lost pregnancy is available, the doctor may consider testing the genetic material of the sample to determine whether the miscarriage was associated with a chromosomal abnormality.
2. Karyotype Testing of Both Partners
   • In some cases, the doctor may recommend Karyotype testing for both the female and male partners.
   • This test helps identify certain chromosomal abnormalities that may not cause noticeable symptoms in daily life for the person carrying the abnormality but may increase the risk of producing eggs or sperm with chromosomal abnormalities.
3. Examination of the Uterus and Uterine Cavity
   • Evaluating the structure of the uterus is another important step in investigating the causes of recurrent pregnancy loss. The method is selected based on the medical history and what needs to be assessed, such as ultrasound or hysteroscopy.
4. Antiphospholipid Antibody Testing
   • For individuals with clinical indications, the doctor may perform blood tests to evaluate for Antiphospholipid Syndrome (APS). Examples of these tests include:
     • Lupus Anticoagulant
     • Anticardiolipin Antibodies
     • beta-2 Glycoprotein I Antibodies
5. Thyroid and Other Health Assessments
   • The doctor may consider evaluating thyroid function, as well as assessing blood sugar levels or other underlying medical conditions based on each individual’s risk factors.
6. Sperm Quality Testing
   • The male partner can start with a Semen Analysis to assess sperm count, motility, and morphology.
     If the doctor considers it clinically indicated, additional testing may be considered, such as Sperm DNA Fragmentation, to evaluate damage to the genetic material in sperm.

In some cases, even after an appropriate evaluation, it may still not be possible to clearly identify the cause of recurrent pregnancy loss. This occurs in approximately 50% of individuals with recurrent pregnancy loss. Not finding a specific cause does not mean that another pregnancy is not possible. Doctors can still evaluate other factors, such as age, overall health, pregnancy history, and reproductive factors, to develop a plan for the next pregnancy.

In some cases, assisted reproductive technologies such as ICSI or genetic testing of embryos before embryo transfer may be considered. This depends on the clinical indications and the suitability for each couple.

Experiencing recurrent pregnancy loss does not mean that you cannot have children. In fact, many individuals with unexplained recurrent pregnancy loss may still have a chance of achieving a successful pregnancy naturally in the next pregnancy. The important step is to systematically evaluate potential contributing factors and select appropriate tests for each individual. When a cause that can be treated or managed is identified, doctors can develop an appropriate treatment plan and prepare for pregnancy accordingly.

If you have a history of recurrent pregnancy loss and are planning to have children again, you should consult a reproductive medicine specialist to assess whether further testing is necessary.
This is particularly important for individuals with a history of:

• Two or more miscarriages
• Miscarriage at a later gestational age
• Previously identified chromosomal abnormalities
• Underlying medical conditions
• Uterine abnormalities
• Previous IVF/ICSI treatment followed by miscarriage
• Wanting to prepare for the next pregnancy