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Recurrent Pregnancy Loss Causes and Testing

What causes recurrent pregnancy loss? Recurrent pregnancy loss is defined as having two or more miscarriages in the first-trimester. The cause is unknown in up to 50% of cases but testing with a fertility specialist can reveal issues that may be the cause of recurrent miscarriages.
Recurrent pregnancy loss - Causes of multiple miscarriages
Recurrent pregnancy loss - Causes of multiple miscarriages
1 in 4 women experience a miscarriage.

While pregnancy loss is unfortunately a common experience, the likelihood of having multiple consecutive miscarriages is relatively low.

Recurrent pregnancy loss (RPL) is the loss of two or more miscarriages in the first-trimester. RPL is a distinct issue which is less common but still not fully understood.

The cause of Recurrent Pregnancy Loss is not known in up to 50% of cases.

However, the current research thus far has found that there are some etiologies that are more prevalent in Recurrent Pregnancy Loss that are the cause of miscarriage.

Here's what we know so far.

What is Recurrent Pregnancy Loss (RPL)?


Recurrent Pregnancy Loss is defined as having two or more clinical pregnancy losses in the first trimester.

A clinical pregnancy means that the pregnancy was confirmed by ultrasound detection of a fetal heartbeat or gestational sac.

It’s estimated that 5% of women experience two consecutive miscarriages and 1% of women will experience three or more losses.

What causes Recurrent Pregnancy Loss (RPL)?


🔎 While no distinct etiology is found in up to 50% of cases, the ASRM committee opinion on evaluation of RPL has listed factors that are associated with the disorder based on studies.

Recurrent Pregnancy Loss may be due to genetic abnormalities, autoimmune disease, uterine malformation, endocrine issues, or lifestyle factors. 

➡️ Genetic abnormalities


📈 Genetic issues are found to be the cause in about 60% of first trimester losses upon testing the tissue from miscarriage.

Aneuploidies such as trisomy for example, in which the cells have an extra chromosome, can increase in occurrence with female age. So older women are more likely to have a higher incidence of chromosomally abnormal embryos that could lead to miscarriage. 

However, in the case of women with Recurrent Pregnancy Loss, it may not be the number of chromosomes that are the issue, but the structure of the chromosomes.
 

Balanced Translocation


A translocation is when genetic material that is meant to appear on one chromosome is mistakenly attached to a different chromosome in the cells.

In a reciprocal translocation, genetic material is interchanged between two specific chromosomes. In cases where the translocation is balanced, it doesn't cause any issues as the genes on the chromosomes aren't affected, they just happen to be located in an unusual place.

However in other cases, this swap of genetic material can cause deletions or gains of genetic material that can affect normal development.

The most common balanced translocation is called a Robertsonian translocation, in which the two long arms of two different chromosomes fuse and the two short arms of these chromosomes are lost. This means that instead of having 46 chromosomes, the cells have 45 chromosomes. These are considered balanced translocations as the genetic material lost from the short arms of the chromosomes contain repetitive genetic material.

The most common type of Robertsonian translocation occurs between chromosomes 13 and 14, occurring in 73% of cases.

Testing for translocations


In this case, karyotyping of both parents would tell you whether there’s an issue with a structural rearrangement of the chromosomes.

A karyotype shows the physical structure of the 46 chromosomes in your cells so that your doctor can check to make sure that they are the correct size.

If there's a rearrangement, such as part of chromosome 7 suddenly appearing attached to chromosome 9, this would show up on the karyotype. 

🧬 Balanced reciprocal translocations & Robertsonian translocations are detected in up to 5% of Recurrent Pregnancy Loss cases. 

Treatment


Some women that are undergoing infertility treatment may choose to do IVF with along with a type of preimplantation genetic testing known as PGT-SR.

This test can identify which embryos are affected by the structural rearrangement versus which embryos have a normal karyotype.

An unaffected embryo could then be transferred during a frozen embryo transfer (FET) cycle to attempt a pregnancy. IVF success rates do vary based on age, so it is a good idea to check what the current IVF success rates are for your age so that you are prepared with some information when discussing your case with your doctor.

However, women that conceive naturally can test the baby by early amniocentesis to check for any genetic issues.

➡️ Autoimmune Disease


Antiphospholipid syndrome is associated with Recurrent Pregnancy Loss occurring in a considerable percentage of RPL cases.

In Antiphospholipid Syndrome (APS) the immune system attacks proteins in the blood that cause clotting issues.

Testing


It’s generally noted that 5-20% of women experiencing Recurrent Pregnancy Loss test positive for antiphospholipid antibodies. 

🧪 Antiphospholipid antibodies are found in 5-20% of women experiencing Recurrent Pregnancy Loss.

However, actual reported ranges can vary as high as 8-42% for RPL cases.

Treatment


Women who carry a pregnancy with antiphospholipid syndrome must work closely with a high-risk OB and will likely be treated with blood thinners such as heparin and aspirin to prevent any clotting issues caused by this condition.

Pregnant women with APS may have to have frequent visits to their OB to check for thrombosis or thromboembolism, severe preeclampsia, or decreased fetal movement. Prenatal visits could be as frequent as every 2-4 weeks until mid-gestation and then 1-2 weeks thereafter.

If managed with the help of your doctor, it’s reported that >70% of women with APS will be able to successfully achieve a live birth.

➡️ Uterine Factor


The anatomy of the uterus could play a factor for some women.

A review of the current literature reported that a uterine malformation was found in 12.6% of RPL cases vs 4.3% of the general population of fertile women. 

🧡 A uterine malformation was found in 12.6% of RPL cases vs 4.3% of the general population of fertile women.

Uterine malformations:
👉Septate
👉Bicornuate
👉Arcuate
👉Unicornuate
👉Didelphic

A septate uterus was the most common issue identified and is responsible for 35% of uterine malformations

Testing


Uterine abnormalities can be identified by HSG (hysterosalpingogram) or a 3D ultrasound.

Treatment 


Some women may need a surgical hysteroscopy to address a uterine issue.

For example, a septate uterus occurs when the uterus has been partitioned into two cavities due to the midline septum running down the middle of the cavity. A physician may choose to resect the septum so that in a future pregnancy, there is more room in the uterus for the baby to grow.

However, some malformations cannot be corrected by surgery.

A 2018 study comparing women undergoing IVF that had a normal uterus to those that has a uterine malformation found that the clinical pregnancy and live birth rate was similar between the two groups.

However, the group of women with uterine malformations had a higher likelihood of pre-term delivery.

It should be noted that in this study the group with uterine malformations were primarily women with an arcuate or subseptate uterus as opposed to the more severe uterine malformations.

So, many women with a uterine factor can still get carry a pregnancy and have a successful live birth, but they have a higher chance of their baby being born premature.

Many women can still carry a pregnancy with a uterine malformation however in some cases, women may need the help of a gestational carrier in order to have a biological child.

➡️ Hormone levels


Your doctor may test for issues with thyroid (TSH) or prolactin (PRL) levels in relation to pregnancy loss, as abnormal levels of these hormones could be associated with miscarriage. 

It has also been noted that uncontrolled diabetes should be evaluated and addressed, as it is associated with pregnancy loss.

➡️ Lifestyle factors


There are certain lifestyle factors that may be associated with increased chance of miscarriage.

So there could be areas within your life that you may want to address to help achieve your fertility goals and have a successful pregnancy. 

🚭 Cigarette smoking was highlighted by the ASRM as being associated with an increased risk of miscarriage.

Other factors that have shown to be associated with increased risk of pregnancy loss are obesity, drug use, alcohol consumption, and high caffeine consumption. 

Recurrent pregnancy loss (RPL) has an unknown cause in up to 50% of cases but in some women may be due to genetic abnormalities, uterine malformation, antiphospholipid syndrome, or other medical conditions. Lifestyle factors may affect risk of miscarriage as well.
Recurrent pregnancy loss (RPL) has an unknown cause in up to 50% of cases but in some women may be due to genetic abnormalities, uterine malformation, antiphospholipid syndrome, or other medical conditions. Lifestyle factors may affect risk of miscarriage as well.

💬👩‍⚕️ What tests are done for recurrent miscarriages?


A fertility doctor, known as a Reproductive Endocrinologist is the best person to seek out if you have suffered multiple miscarriages and are looking for help having a baby.

Aside from the typical fertility workup, they can test for the associated causes of recurrent pregnancy loss such as:

👉Karyotype of both parents
👉Screening for lupus anticoagulant, anticardiolipin antibodies, and anti-b2 glycoprotein I
👉Antiphospholipid antibodies
👉Sonohysterogram, hysterosalpingogram, and/or hysteroscopy
👉Screening for thyroid or prolactin abnormalities
👉Karyotypic analysis of products of conception
👉Hormone levels (TSH, PRL)

It is important to find the right specialist to help test for any issues that could be the cause of recurrent pregnancy loss and manage the issue to help you on your journey to having a child.

👩‍⚕️⭐️ You can check reviews and success rates for fertility doctors in your area using the FertilitySpace clinic search to figure out which provider is the best option for you.

What's my chance of having a baby after multiple miscarriages?


While there are various issues that may cause pregnancy loss, the known causes can be tested for and treated in a variety of ways to help you have a baby. 

The American Society for Reproductive Medicine has reported that even after 3 pregnancy losses, women still have a 60-80% chance of conceiving and carrying a full-term pregnancy.