What is recurrent miscarriage? – Reasons, Tests and Treatment

By (embryologist) and (babygest staff).
Last Update: 01/30/2019

Recurrent miscarriage, also known as recurrent pregnancy loss (RPL) or habitual abortion, consists of having at least two consecutive miscarriages or more than two alternating. It is a common infertility problem, affecting approximately 5% of women of fertile age.

The reasons may be very diverse. It will be essential to carry out the pertinent tests to determine the cause of the miscarriages. In this way, it will be possible to choose the most suitable treatment for each patient.

When do we talk about recurrent miscarriage

According to the World Health Organization (WHO), miscarriage is the spontaneous ending of pregnancy before the fetus is viable, that is, before its weight is 500 grams or more, or before it reaches 20-22 weeks’ gestation.

However, there is no consensus on how many abortions are necessary to be considered recurrent pregnancy loss or whether they should be consecutive or not.

The traditionally accepted definition is that it is considered a recurrent pregnancy loss based on three consecutive clinical miscarriages.

However, nowadays, some scientific organizations such as ACOG (American Congress of Obstetricians and Gynecologists) defend that two consecutive abortions are enough to be considered recurrent pregnancy loss, since the probability of a new loss after two or three abortions is similar.

Therefore, after the second abortion, there may already be a responsible cause that can be treated and it would be helpful to begin studying the possible factors involved in the abortions.

Depending on the cause, it will be recommended to follow one strategy or another to prevent more habitual abortions.

Reasons for Recurrent Pregnancy Loss

The reasons why some women experience recurrent miscarriages are mainly because of the following:

  • Genetic Disorder
  • Problems in the uterine cavity (structural anomalies, fibroids, scar tissue, developmental defects).
  • Other disorders related to blood clotting or Immune Alterations.

The risk of miscarriage is higher in women 35 years of age or older. Most miscarriages occur in the first 12 weeks of gestation, the first trimester. If vaginal bleeding occurs after confirming the existence of a viable fetus, the chance of miscarriage increases by up to 20%.

Approximately 50% of recurrent miscarriages are of unknown cause after relevant tests, which further complicates getting a pregnancy to term.

Below, we will try to explain some of the most common reasons for recurrent miscarriage and what therapeutic options exist in each situation.

Genetic causes

The main known cause of repeated miscarriages are genetic disorders: they are responsible for approximately 50% of cases. The most frequent disorders are chromosomopathies (incorrect number of chromosomes).

Most chromosome problems occur by coincidence. However, sometimes these problems can cause recurrent miscarriages. Generally, these pregnancy losses are not detected because they occur before or at the time menstruation is expected.

Both the karyotype of the fetal tissue and that of both parents can help determine if the abortion is genetically caused. If, after analyzing these karyotypes, it is confirmed that there may be a genetic cause, one of the following strategies should be chosen:

  • Assume the risk and do nothing to avoid repeating the chromosomal alteration, with the possibility of Prenatal Genetic Diagnosis.
  • Analyze the chromosomes of the spermatozoa using FISH (fluorescent in situ hybridization) to assess the probability of it happening again. However, this technique does not allow the selection of euploid sperm (with the correct number of chromosomes), but is only diagnostic.
  • Perform in vitro fertilization (IVF) with preimplantation genetic diagnosis (PGD). Using this technique it is possible to select embryos free of chromosomal alterations.
  • Use gamete donation (oocytes or spermatozoa) in the case that the genetic disorder cannot be identified or if it is not possible to use previously mentioned options. For example, if the ovarian reserve is low, the chances of having a genetically healthy embryo behind the PGD may be very limited and it may be more advisable to opt for egg donation.

It is important to mention that the main cause of abortions due to chromosomal disorders is the age of the woman. Over the years, both the quantity and the quality of the oocytes decrease. The latter considerably increases the probability that the eggs and, therefore, the embryos have an incorrect number of chromosomes.

Uterine Anatomical Abnormalities

About 25% of women with a history of recurrent abortion have an abnormal uterus shape, even though the prevalence and impact of these alterations on abortion is not known exactly.

In order to diagnose the possible uterine causes that could cause these losses and try to assess the impact on gestation, it is possible to resort to:

  • Ultrasound
  • Hysterosalpingography
  • Sonohisterography
  • Hysteroscopy
  • Magnetic Resonance
  • Laparoscopy

A personal evaluation should be made to determine which option may be most useful in each situation. In order to do this, the costs of the technique, the discomfort it may cause the patient, the information it will provide and the tests that have been carried out previously must be considered.

Uterine septum is the uterine abnormality most frequently associated with repeated miscarriage. In these cases, surgical hysteroscopy should be considered to eliminate the problem and increase the chances of successfully carrying the pregnancy to term.

There are several types of uterine malformations that may prevent the normal development of a pregnancy or even make it impossible. Detailed information on this topic can be found in the following post: Uterine Anomalies – Types, Impact on Fertility & Treatment

On the other hand, between uterine factors that can complicate the correct development of the gestation, we also find the uterine fibroids (common tumors, not cancerous), that can interfere in the implantation or the growth of the fetus. Increasing the size of these structures during pregnancy can result in miscarriage. These situations can also be corrected with surgery.

Another uterine factor that can cause recurrent miscarriages is cervical insufficiency: the cervix begins to open prematurely and is too weak to support a pregnancy. Once it is corrected, the probability of miscarriage in the next pregnancy is less and can therefore be completed without problems.

Thrombophilia

Thrombophilia results from an imbalance in the factors responsible for coagulation. Depending on their cause, we can make a distinction between:

Congenital Thrombophilia
The cause is genetic, although they may not be diagnosed until recurrent miscarriages occur.

In this group, there are mutations in Leiden factor V, the prothrombin gene, protein C or S and antithrombin III deficits, and other punctual mutations of genes involved in the coagulation cascade.

Acquired Thrombophilia
It appears later. Its cause may be immunological, such as antiphospholipid syndrome (PAS), which is responsible for 10-15% of recurrent miscarriages. For patients with PAS, blood clots (thrombosis) form in the placenta vessels. This makes fetal development difficult or impossible. It is related to other pathologies such as lupus.

Although there are many factors involved in clotting, the types of Congenital Thrombophilia that have been linked to the most scientific evidence with repeat abortion are Factor V Leiden and the G20210A prothrombin mutation.

Further research is needed on the role of thrombophilia in recurrent miscarriage in order to learn about new factors that may be involved in this pathology and specific treatments that increase the chances of success.

If thrombophilia is diagnosed that complicates pregnancy, the most appropriate treatment is acetylsalicylic acid (Aspirin, Adiro) and heparin.

Immune factors: alloimmune aetiology

Over the last few years, research into recurrent miscarriages due to alloimmune causes is becoming particularly important: the mother’s immune system rejects the paternal antigens expressed by the fetus, and this provokes abortion.

Usually, the mother develops immune tolerance mechanisms during pregnancy to prevent the fetus from being detected as a foreign body and being attacked by the immune system. However, if this system fails, it can lead to rejection and, consequently, abortion.

Rejection is suspected to be responsible for many high order recurrent abortions, that is, those with 5 or more recurrent abortions with no other known cause.

Despite the fact that different mechanisms are known that could explain these abortions, it is necessary to investigate more about possible effective therapies for these patients.

Diagnosis

As mentioned above, there is no consensus on the definition of recurrent miscarriage. As a result, some specialists wait for three pregnancy losses to occur in order to perform the tests necessary to diagnose the cause of recurrent abortions, while others wait for two.

It will also depend on the situation of each patient who begins before or after the test of recurrent miscarriage. For example, if two euploid embryo transfers have been performed (embryos with the correct number of chromosomes have been selected thanks to PGD) and have ended in clinical abortion, there may be some problem with carrying the pregnancy to term, such as thrombophilia.

It seems reasonable to start this type of tests earlier in very anxious couples, as it can be especially hard for them to face a new pregnancy loss.

Usually, the study of recurrent miscarriage includes the following tests:

Karyotype of both partners
consists of studying the number of chromosomes of the parents in order to detect if any alteration may exist and cause the embryo to be aneuploid (incorrect number of chromosomes).
Screening tests in women
to evaluate the morphology and integrity of the uterine cavity. Some of these techniques are ultrasound, hysterosalpingography and hysteroscopy.
Trombophilia testing
especially when there are three or more abortions. The tests are as follows: lupus anticoagulant factor, anti-cardiolipine antibodies, antiphospholipid study, etc.
Hormone analysis in women
prolactin level, progesterone and thyroid gland function.
Male semen analysis
Sperm FISH and TUNEL method to see the DNA fragmentation of sperm.
Immune study
autoantibodies, Natural Killer cells (NK), cytokines, KIR-HLA compatibility, etc.

If all these tests have a normal result and there are no known reasons for recurrent miscarriage, this is a case of recurrent idiopathic or unexplained pregnancy loss. In these situations, the specialists’ recommendation is to carry out a strict control of the next pregnancy, including having access to psychological support from professionals if necessary.

Recurrent miscarriage and surrogacy

Surrogacy is a reproductive technique in which another woman (the pregnant woman) is responsible for maintaining the pregnancy of a couple or single person (the intent parents) who is unable to do so for various reasons.

Recurrent miscarriage without apparent cause, in which a woman has had several pregnancy losses without finding any cause, is one of the main indications that leads these patients to consider surrogacy in order to have a child.

In the same way, women who have suffered several abortions, in which a new pregnancy poses a health risk, can begin to consider surrogacy in order to become mothers without risking their lives.

Surrogacy is probably the most confusing of all infertility treatments. Transparency is a key value for us when it comes to recommending a clinic or agency for intended parents. You can now use this tool to receive a detailed report that will solve any question you may have, and most importantly, to help you avoid potential frauds.

FAQs from users

What is secondary recurrent miscarriage?

By Zaira Salvador (embryologist).

Secondary recurrent miscarriages are those suffered by a woman or couple who has already had a previously healthy child. On the other hand, when recurrent miscarriage is primary, it has not yet been possible to give birth to any baby.

What are the signs and symptoms of recurrent miscarriage?

By Zaira Salvador (embryologist).

Recurrent miscarriage have the same symptoms as any other spontaneous abortion in the first or second trimester: heavy bleeding, decreased beta-hCG hormone, disappearance of pregnancy symptoms, pelvic pain, etc.

What role does hypothyroidism play in recurrent miscarriage?

By Zaira Salvador (embryologist).

There are some hormonal disorders that can cause abortions in women if they are not adequately controlled. Diabetes mellitus and thyroid disorders are some of them, although their repercussion in repeated abortions is very rare, only serious cases of hypothyroidism and hyperthyroidism have been identified.

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References

Authors and contributors

 Zaira Salvador
Zaira Salvador
Embryologist
Bachelor's Degree in Biotechnology from the Polytechnic University of Valencia (UPV). Embryologist specializing in Assisted Procreation, with a Master's Degree in Biotechnology of Human Assisted Reproduction from the University of Valencia (UV) and the Valencian Infertility Institute (IVI). More information about Zaira Salvador
License: 3185-CV
Adapted into english by:
 Marie Tusseau
Marie Tusseau
Babygest Staff
Editorial Director of Babygest magazine in French and English. More information about Marie Tusseau

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