Recurrent Pregnancy Loss

Recurrent Pregnancy Loss is a pregnancy loss is the spontaneous loss of a pregnancy before 24 weeks of gestation .

The loss of a pregnancy after 24 weeks’ gestation is called a stillbirth.

A diagnosis of Recurrent Pregnancy Loss or RPL could be considered after the loss of two or more pregnancies.

This includes pregnancies after spontaneous conception and after assisted reproduction (e.g. IUI and IVF/ICSI).

Ectopic pregnancies and molar pregnancies are not included in RP;  is also sometimes called recurrent miscarriage, although this term should be reserved for cases where all pregnancy losses have been confirmed as intrauterine miscarriages.

Primary RPL is a term used for women who have not had a baby before their pregnancy losses.

Secondary RPL means they have had at least one baby before their losses.

Consecutive pregnancy losses are losses that happen one after the other, without a baby in between losses.

It is estimated that up to 15% of pregnancies result in pregnancy loss.

Which tests should my doctor perform?

Several investigations have been suggested for couples with RPL.

The aim of doing such tests could be to:

• Identify the cause, or likely cause, of the previous pregnancy loss(es)
• Recommend or suggest appropriate treatment, if that is an option
• Help the doctor to estimate your prognosis (the chance of having a baby in the future)

If you (or your family members) have been diagnosed in the past with one of the following medical
conditions, it is important to inform your doctor:
o Congenital abnormalities (Heart defect, Spina Bifida, Down’s Syndrome, other syndromes)
o Thrombophilia, Thromboembolism (blood clotting problems, stroke )
o Polycystic ovary syndrome (PCOS)
o Diabetes or Thyroid abnormalities
o No periods or irregular periods (Amenorrhea or Oligomenorrhea)

Screening for antiphospholipid syndrome (APS)
Thrombophilia is a condition that makes the blood clot more than it should. Thrombophilia can be inherited (passed
down genetically) or it can be acquired (not inherited). When it is acquired, and there is also a history of pregnancy loss, it is called antiphospholipid syndrome or APS.

Testing for antiphospholipid syndrome (APS) is done by a blood test for lupus anticoagulant, and anticardiolipin and maybe also aβ2GPI antibodies.

The results can provide information to:
(1) Make a diagnosis of APS,
(2)Show a contributing factor of the pregnancy losses,
(3) Recommend possible treatment for APS and RPL, and
(4) Help to prevent other pregnancy complications associated with APS (for instance pre –eclampsia)
Screening for thyroid dysfunction
Under-production of thyroid hormones (hypothyroidism) is often found in women with RPL, and may increase the risk for pregnancy loss.
Over-production of thyroid hormones (hyperthyroidism) is associated with several pregnancy complications, although not with pregnancy loss.
Thyroid antibodies, called TPO antibodies, could lead to thyroid dysfunction. TPO antibodies are associated with RPL

The results of screening can provide information to
(1) make a diagnosis of thyroid dysfunction,
(2) show a possible cause or contributing factor for the pregnancy losses,
(3) recommend possible treatment.
Pelvic examination (usually ultrasound)
An ultrasound scan should be done to check the shape of your uterus and to examine it
for any malformations or abnormalities.
Additional investigations that could be considered based on medical and family history:
Genetic analysis
When the genes are combined during conception, errors can occur.
Some of these errors or abnormalities can be significant and result in a fetus that cannot survive.

Genetic testing on both parents (called parental karyotyping) can show a genetic abnormality that does not cause a problem in the parent, but may cause a genetic defect in the fetus.
If you have a family member with a congenital abnormality (Heart defect, Spina Bifida, Down’s
Syndrome, or other syndromes), you may have a higher chance of carrying a genetic abnormality, and your doctor may suggest genetic testing (by means of a blood test) of both parents.
If you do not have any risk family risk factors, there is a very low chance that genetic analysis will show an abnormality.

ANA testing
Antinuclear antibodies or ANA are antibodies in your blood that are directed against your cells.
These antibodies are often detected in patients with autoimmune diseases. Studies have shown that
ANA can also be detected in some patients with RPL, and therefore testing can be considered to explain a possible cause of the pregnancy loss.

Sperm DNA fragmentation
There is now some evidence that damaged sperm could increase the risk of pregnancy loss.
Assessing sperm DNA damage could be considered in couples with RPL in order to provide some information on the role of the father in the pregnancy loss.

What are the options for treatment?

Most couples with RPL have a higher chance of a live birth in their next pregnancy than ofhaving another pregnancy loss, but that does vary depending on maternal age and the number of pregnancy losses and on whether a likely cause has been found. While some treatments are known to reduce the risk of pregnancy loss in certain circumstances, there is nothing
that can remove that risk altogether.

What are the options for treatment of explained RPL?
You have Antiphospholipid syndrome (APS) → Treatment with heparin and low-dose aspirin
There is some research evidence that treatment with heparin and low-dose aspirin increases the
chance of a healthy pregnancy in women with three or more pregnancy losses and APS.
You have been diagnosed with a thyroid dysfunction → Treatment with levothyroxine (but only if you have very low levels of thyroid hormones)
There is some research evidence that treatment with levothyroxine reduces the risk of pregnancy loss in women with very low levels of thyroid hormones (this is called clinical hypothyroidism).

You have a problem with the shape and/or inside of your uterus (uterine malformation) → If you have a septate uterus (e.g. where the uterus is divided by a band of tissue [a septum]), you may be offered septum resection within the context of a clinical trial.

Tests showed a genetic abnormality → Genetic counselling → Information on the available
treatments, including their advantages and disadvantages.
Genetic counselling is recommended for couples with a genetic abnormality.
Treatment options include preimplantation genetic diagnosis (PGD, which would be done as part of an IVF procedure) but there is only limited evidence showing a benefit to reduce the risk of another
pregnancy loss.

Your partner’s sperm showed sperm DNA damage → Cessation of smoking, a normal body weight, limited alcohol consumption and a normal exercise pattern is recommended.
If you have, or are found to have an underlying condition, which could possibly be associated with
pregnancy loss, your doctor will advise you on treatments for the condition. These treatments may
reduce the risk of pregnancy loss.
Examples are:
You have PCOS → Pituitary suppression before induction of ovulation could be an option
You have Hyperprolactinemia → Bromocriptine treatment
You have Hyperhomocysteinemia (high levels of homocysteine in your blood) → Folic acid and
vitamin B6 supplements
What are the options for unexplained RPL?
If none of the tests show a problem or likely cause of your pregnancy losses, you will be diagnosed
as having unexplained RPL.
→ There are no treatments available that are known to improve your chances of a having a baby. →
It is still advisable to try to live as healthy a lifestyle as possible, with a balanced diet, maintaining a
healthy weight, stopping or reducing smoking, avoiding excessive alcohol and avoiding (hard and
soft) drugs.

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