No matter how far along you are in your pregnancy, miscarriages are heartbreaking. They take an immeasurable toll on your physical and emotional health, and for those pursuing Assisted Reproductive Technology like IVF, there is a financial burden on top of it. 

A miscarriage, generally classified as spontaneous pregnancy loss before 20 weeks, is hard enough to cope with, let alone experience multiple times. Now let’s explore some of the possible reasons for recurrent pregnancy loss, as well as some diagnostic tests and treatment options that are in your control. 

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What is Recurrent Pregnancy Loss?

Affecting roughly 2 million women every year, Recurrent Pregnancy Loss (RPL) is defined as having two or more spontaneous miscarriages. The incidence of RPL becomes higher as a woman ages, and investigations into potential causes begin once a person is "officially" diagnosed with RPL.  

To better understand why multiple miscarriages happen, it’s helpful to think about it in terms of two different categories. The first is the quality of the embryo itself, and the second is the uterine environment where the embryo attaches and develops. In general, almost half of all miscarriages occur because of genetic abnormalities of the embryo. But just as important, and often overlooked, are uterine lining issues. 

Embryo Issues

Unfortunately, even a perfect-looking embryo can have chromosomal abnormalities, either resulting from known parental chromosomal issues or errors that arise during the embryo’s formulation. One example is balanced translocations, where one chromosome ends up being switched with another chromosome during development. Another example is embryos that have an abnormal number of chromosomes (also known as aneuploidy). Sometimes, just a single mutation on a chromosome may affect the viability of the pregnancy. Regardless of the genetic cause, the body often rejects embryos that are not chromosomally “normal.”    

While these factors can be present in any miscarriage, they are more common in couples experiencing recurrent pregnancy loss. For example, translocations are found in 4% to 8% of couples with RPL, and chromosomal rearrangements are present in 12% of couples with RPL. 

If you have experienced two or more miscarriages, your healthcare provider may suggest further genetic testing, including preimplantation genetic testing (PGT) for those undergoing IVF. PGT testing helps fertility specialists choose the most promising embryos for transfer, avoiding embryos with known genetic issues that may result in pregnancy loss.  

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Uterine Issues 

As we know, the first step to a successful pregnancy is embryo implantation, which requires the embryo’s proper development and necessary receptivity in the endometrium. For patients going through IVF, PGT can help minimize embryo issues. So, assuming the embryo transferred is normal, a subsequent miscarriage can suggest the uterine lining may be the probable cause. 

Much like embryo issues, if the endometrial quality is substandard, it can affect implantation. Inflammation of the uterine lining is often the first suspect. Endometriosis, a condition in which cells similar to the uterine lining grow outside of the uterus, is the leading cause of endometrial inflammation that can impair fertility and embryo implantation. Other inflammatory conditions such as endometritis caused by chronic bacterial infection can also affect the endometrium. 

Progesterone is the hormone that activates the normal growth of the endometrium during pregnancy. However, if a condition like endometriosis is present, it can cause progesterone resistance and forgo the body's normal progesterone release. It may also cause resistance to progesterone supplementation (think progesterone-in-oil shots during IVF) until the inflammation is addressed.

Recurrent Miscarriage: What are my options?

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One diagnostic option available before an IVF transfer is a first-of-its-kind test called ReceptivaDx. Using an endometrial biopsy, the test looks for a protein marker called BCL6 that indicates uterine inflammation most often associated with endometriosis. Surprisingly, most women with endometriosis going through IVF are asymptomatic, commonly referred to as “silent endometriosis." The ReceptivaDx test also includes a marker called CD138 that is associated with endometritis. 

If the patient’s ReceptivaDx test indicates high levels of BCL6, most likely from endometriosis, multiple proven treatment options are available. The first is laparoscopic surgery to remove the endometriosis on the uterine lining. The second is hormone suppression therapy to reduce inflammation and allow the uterine lining to develop and thicken for the embryo to attach and grow. 

If the patient’s ReceptivaDx test comes back negative, inflammation is likely NOT the cause of the recurrent pregnancy loss, and your healthcare provider will look for other potential causes.  

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Moving Forward

Enduring recurrent pregnancy loss is draining in more ways than one. Not knowing the reason behind multiple miscarriages can make it all the more difficult. Understanding what is causing the losses can help you and your doctor come up with the best plan of action to help you get and stay pregnant. Whether you are experiencing embryo issues that require in-depth chromosomal screening or PGT testing, or uterine issues like endometriosis that can be detected through ReceptivaDx’s BCL6 test, know that there are options, and there is hope.

Brighid Flynn is a freelance writer based in Philadelphia where she lives with her husband and puppy. She is just beginning her journey toward motherhood.