Recurrent Pregnancy Loss

Recurrent Pregnancy Loss (RPL) or Recurrent Miscarriages

Approximately 15% of all known pregnancies end in loss, and recurrent pregnancy loss—defined as two or more consecutive pregnancy losses—affects about 5% of women of reproductive age.

Causes of Recurrent Pregnancy Loss

1. Maternal Age: As maternal age increases, the risk of recurrent pregnancy loss also rises due to a higher chance of chromosomal abnormalities in the fetus.

2. Pregnancy History: A history of repeated losses can increase the risk. For instance, women who experience three consecutive miscarriages have a 40% risk of miscarriage in their next pregnancy.

3. Genetic Factors: Chromosomal abnormalities, particularly in the first trimester, are significant. Testing the chromosomes of both parents is recommended.

4. Anatomical Abnormalities: Uterine structural issues such as congenital septa, double uterus, T-shaped uterus, uterine adhesions, tubal swelling, cervical insufficiency, and fibroids can contribute to RPL. The location, size, and number of fibroids are critical, and in some cases, removing fibroids (myomectomy) has allowed for successful pregnancies.

5. Cervical Insufficiency: Losses occurring after 12 weeks without pain may indicate cervical insufficiency.

6. Endocrine Factors: Although the role of endocrine disorders in RPL is not fully clear, some conditions may contribute:

   • Luteal Phase Deficiency: A lack of progesterone can interfere with pregnancy maintenance.
   • Polycystic Ovary Syndrome (PCOS): Elevated LH and insulin resistance can affect the uterus and ovaries, making insulin-sensitizing treatments beneficial.
   • Diabetes Mellitus: Poorly controlled diabetes increases the risk of early pregnancy complications and congenital anomalies.
   • Hypothyroidism: Severe iodine deficiency and thyroid autoantibodies can increase miscarriage risk.
   • Hyperprolactinemia: Elevated prolactin levels are associated with a higher frequency of miscarriage.

7. Coagulation Disorders: Blood clotting issues can be genetic or acquired:

   • Genetic Factors: While not tested in all cases of miscarriage, specific factors can be assessed, including Protein C and S deficiencies, antithrombin III deficiency, Factor V Leiden mutation, MTHFR mutation (linked to elevated homocysteine levels), and Prothrombin G20210A mutation.
   • Acquired Factors: Antiphospholipid syndrome is a notable cause, often leading to recurrent losses and thrombosis. Tests for antiphospholipid antibodies, anticardiolipin antibodies (ACA) IgG and IgM, and Anti-B2 glycoprotein IgM and IgG can be conducted when this condition is suspected.

8. Autoimmune Factors: Conditions such as lupus and other autoimmune disorders are linked to recurrent miscarriages.

9. Infections in the Cervix and Vagina: The presence of certain bacteria, such as Mycoplasma and Ureaplasma urealyticum, should be investigated and treated if present, as they may contribute to pregnancy loss.

Identifying and addressing these potential causes can improve the likelihood of a successful pregnancy for couples dealing with recurrent losses.

Tests for Recurrent Pregnancy Loss

For couples experiencing RPL, several tests may be performed to identify the potential causes. Here are the main tests generally recommended:

1. Blood Tests:

   • Hormonal and Metabolic Tests: TSH (thyroid-stimulating hormone), mid-luteal progesterone, PRL (prolactin), thyroid autoantibodies, fasting glucose, fasting insulin.
   • Immunological and Coagulation Tests: lupus anticoagulant, anticardiolipin antibodies, antithrombin III, protein C, protein S, Factor V Leiden mutation, prothrombin mutation, homocysteine levels.
   • Nutritional Markers: folate, vitamin B12 levels.
   • Genetic Testing: Genetic tests may not be required for every patient but can be considered if there are suspected chromosomal abnormalities.

2. Ultrasound (USG) and Hysterosalpingography (HSG): These imaging tests can evaluate the structure and condition of the uterus and fallopian tubes, checking for anomalies that could contribute to pregnancy loss.

3. Genetic Testing for Parents: Karyotyping for both partners can help identify chromosomal abnormalities that may affect pregnancy.

4. Additional Tests (If Symptoms Warrant):

   • For patients with unexplained or asymptomatic recurrent pregnancy losses, routine testing for bacteria and viruses, glucose tolerance, thyroid antibodies, and antithyroid antibodies is generally unnecessary.
   • Human Leukocyte Antigen (HLA) Testing: Paternal HLA or maternal anti-paternal antibodies testing is also generally not required unless there are specific clinical indications.

5. Advanced Imaging (If Necessary): Hysteroscopy (H/S) or MRI (magnetic resonance imaging) may be recommended to investigate uterine abnormalities more closely.

These investigations aim to pinpoint possible reasons for pregnancy loss and determine the most effective treatment to help achieve a successful pregnancy.

Treatment for Recurrent Pregnancy Loss

If the cause of recurrent pregnancy loss is identified through tests, a tailored treatment plan can be implemented. When genetic factors are responsible for repeated miscarriages, Preimplantation Genetic Diagnosis (PGD) may be recommended. PGD is an additional procedure used in IVF treatments, allowing for the selection of genetically healthy embryos. Success with this method largely depends on the quality and quantity of eggs in the woman and sperm in the man.

If recurrent miscarriage is due to an anatomical abnormality in the uterus, a treatment plan will be developed to address these issues. Uterine irregularities, or adhesions inside the uterus caused by previous infections, can be a significant cause of recurrent pregnancy loss. In such cases, the doctor will discuss appropriate treatment options with the couple.

Another common cause of recurrent pregnancy loss is blood clotting disorders. If the embryo does not receive an adequate blood supply, it may become oxygen-deprived, resulting in miscarriage. Addressing blood clotting issues thus becomes a key component of the treatment plan. Another potential treatment approach is IVF, which can help mitigate the risk of pregnancy loss and increase the chances of a successful pregnancy.