Recurrent miscarriage investigation

Recurrent miscarriage investigation takes place after 2 or more spontaneous and consecutive pregnancy losses.

  • What is recurrent miscarriage and why do we investigate its cause(s)?

    Loss of a pregnancy at up to 20 weeks of gestation, for more than 2 times, is the clinical definition of recurrent miscarriage. Traditionally, it has been defined as 3 or more pregnancy losses, but advanced knowledge and experience among practitioners has shown that 2 such events provide enough evidence for suspecting an underlying common cause.

    Miscarriage is the most devastating pregnancy complication, and knowing what may have caused it can help us to prevent it in a future attempt. There is a close link between infertility, failed In-Vitro Fertilisation (IVF), pregnancy complications and miscarriage. Whilst the majority of these cases are the result of a random genetic defect in the embryo (due to chromosomal abnormalities), there are additional underlying causes that we can detect and treat.

  • What are the most common causes or risks of recurrent miscarriage and what investigation(s) do we perform?

    • Chromosomal abnormalities: A normal embryo has 46 chromosomes. Any abnormality in the number of chromosomes usually makes the embryo unable to survive and a miscarriage occurs. In these cases, the embryo may have more chromosomes, like in Down syndrome, where there is an extra chromosome 21 (47, XY, +21) or less chromosomes, like in Turner syndrome, where a chromosome X is missing (45X). Other abnormalities that can also take place include chromosomal translocation orinversion, for instance.
    • Uterine anomalies: Many uterine anomalies can be the reason for recurrent miscarriage. Most common are the presence of auterine septum or abicornuate uterus. They can be diagnosed by hysteroscopy, and some of them can be corrected with surgical hysteroscopy.
    • Intra-uterine adhesions (Asherman’s syndrome): Intra-uterine adhesions are remnants of scar tissue that make the uterus’ interior walls to stick to one another. They can be diagnosed and solved by hysteroscopy / surgical hysteroscopy.
    • Endometrial polyps: They are small non-cancerous masses in the lining of the womb. They can be diagnosed by hysteroscopy or ultrasound transvaginal scan, and they are easily excised by surgical hysteroscopy.
    • Submucosal fibroids: They are non-cancerous growths in the muscular wall of the uterus, that protrude into the uterine cavity.They can be diagnosed and excised by surgical hysteroscopy.
    • Thrombophilia(inherited or acquired): A group of conditions that can severely affect blood circulation during pregnancy. In these cases, the blood has an increased tendency to clot and during placenta formation, it affects normal blood circulation to the embryo causing miscarriage. Cases of thrombophilia can be detected with blood testing and specific genetic analyses. Some of the types of thrombophilia are Leiden factor V gene mutation, prothrombin gene mutation (G20210A), anti-phospholipid syndrome, deficit of proteins C and S and anti-thrombin III deficiency.
    • Metabolic and hormone factors: Diseases like diabetes and hypothyroidism (endocrine diseases), for instance, when they are not controlled, can be the reason for recurrent pregnancy loss.
    • Luteal phase defect: It is a condition in which the production of the hormone progesterone is not sustained after ovulation and implantation of the embryo.
    • Infections: Micro organisms like Ureaplasma urealyticum, mycoplasma, chlamydia or Listeria monocytogenes, and viruses like Parvo virus, Rubella, cytomegalo virus orherpes can be the origin of a recurrent miscarriage.
    • Sperm abnormalities: Abnormalities in the number of chromosomes contained in the sperms are responsible for 5-10% of all chromosomal abnormalities in the embryo. These abnormalities can be detected with a FISH on sperm. Currently, there are contradictory data regarding a causal effect between pregnancy loss and sperm DNA fragmentation in IVF cycles. Never the less, it can be the reason for repeated miscarriages in certain cases.
    • Lifestyle and environmental factors: They include cigarette smoking, alcohol and drug consumption, bad diet or exposure to chemicals and pollutants. For instance,increased caffeine(more than 3 cups a day) has been linked to a higher risk of miscarriage. These lifestyle and environmental factors can be found by history-taking information and can be managed, corrected and / or avoided.
    • Immune factors: Many immune analyses have been used to determine the influence of the immune system in recurrent pregnancy loss (studies of human leukocyte antigen (HLA) typing, embryo-toxic factors, blocking or anti-paternal antibody levels and natural killer cells among others). These studies have produced inconsistent data that generally have not been replicated among laboratories. However, here at AAFC, we continue looking and researching for the best and latest techniques and technologies that can help overcome recurrent miscarriage. We perform immunology evaluation and offer treatment, if feasible and available, when everything else has been found normal.
    • Poly-Cystic Ovary Syndrome (PCOS): It is characterized by the presence of cysts in the ovaries and hormonal imbalance. It can be diagnosed by ultrasound scan and blood testing. Women with PCOS have a higher risk of experiencing a miscarriage.
    • No apparent cause: After a comprehensive evaluation, a ‘no apparent causative factor’ can be found in about 30-40% of all couples having recurrent pregnancy loss. It is important to note that, despite this, the chance for a future successful pregnancy can exceed 50-60%, depending on maternal age and parity.
  • How does recurrent miscarriage investigation contribute in achieving a pregnancy followed by live birth?

    If a uterine abnormality is found, corrective surgery may be able to solve the problem. For most of the above mentioned conditions from polycystic ovary syndrome to diabetes, there are treatments or strategies that can ameliorate or treat the symptoms. For instance, if chromosomal abnormalities are found to be the reason for repeated miscarriages, then IVF and embryo selection with Preimplantation Genetic Diagnosis (PGD) and / or Preimplantation Genetic Screening (PGS) will be the way forward. Your doctor will advise how your case can be managed, after having a complete evaluation.

    However, recurrent miscarriage investigation may not be able to find the reason behind pregnancy loss (no apparent cause). There are various other treatments and options for these cases, but without real guarantees that they can tackle undetected causality. Repeated miscarriage can be easily faced if the underlying reason is hypothyroidism, for instance, but it can become a real challenge when it cannot be explained.

    We have seen that close supervision with regular scans and appropriate reassurance throughout a new pregnancy after a previous miscarriage can truly help from a psychological point of view, and lead to a live birth. In any case, despite a recurrent miscarriage history, a woman has a 60-80% chance of conceiving and having a healthy baby.

    Here in AAFC, we perform all possible investigations in order to bypass repeated miscarriages. Our specialist doctors can provide you with further information and consult you on all available / applicable options when necessary.