Up to 75% of women with unknown RPL causes will go on to have a healthy pregnancy.
Your Guide to Recurrent Miscarriage
If you’ve experienced a loss of any kind, we are so sorry. All pregnancy loss is devastating. Please know that no matter the timing, circumstances, or repeated nature of your miscarriages – it’s not your fault. It’s easy to fear you did something wrong, or that you caused the loss in some way. Miscarriage is complex and still, in many ways, misunderstood.
Miscarriage used to be a taboo topic that no one talked about. In recent years, it has become an increasingly open subject. Celebrities and families are opening up about their personal experiences of loss. Still, it is often shrouded in silence and mystery as a part of everyday life. This can lead to difficulty grieving and recovering. This is especially true when someone experiences recurrent pregnancy loss (RPL). This is defined as three or more consecutive miscarriages. Some providers will test and treat for recurrent miscarriage after two backto-back losses.
Miscarriage Rates & Statistics
Miscarriage happens in 10% to 15% of known pregnancies. Most losses occur before 12 weeks. In the second trimester, the miscarriage rate drops to less than 5%.1
About 1% of reproductive-aged women have recurrent pregnancy loss (RPL). Of these women, 50% to 75% of them have unknown causes. Around 65% to 75% of women with unknown causes will go on to have a healthy pregnancy. However, the odds decrease with the number of losses and age of the mother. (2, 3)
When someone experiences even one miscarriage, it’s normal to want to know why. If recurrent miscarriages occur, it becomes critical to understand the cause or causes.
Figuring out the reason(s) for recurrent miscarriage could lead to fewer losses. It can speed up your path to parenthood. It might also help the 25% to 35% of women who aren’t expected to have a healthy pregnancy on their own.
Five Factors Relating to RPL
Many practitioners and researchers recognize a connection between certain health factors and RPL. These include:
- Immune problems
- Blood clotting disorders
- Genetic variants (like MTHFR)
- Thyroid disease or insufficiency
1. The Immune System
Inflammation is a protective response in the body. But ongoing inflammation can be problematic. However, excessive inflammation can interfere and may lead to fetal resorption or miscarriage. This can happen when natural killer cell (NKC) levels are abnormal or too high. These can lead to the over-production of inflammatory proteins called cytokines or tumor necrosis factor-alpha (TNF-a) levels.
Inflammation plays a normal role in the implantation and growth of a healthy pregnancy. Excessive inflammation, however, can interfere and may lead to fetal resorption or miscarriage.(4) This can happen when natural killer cell (NKC) levels are abnormal, or too high. Inflammation can also result from genetic polymorphisms. These can lead to the overproduction of inflammatory cytokines or TNF-alpha levels.
Autoimmune diseases can also increase the risk of abnormal immune function. In turn, it can affect healthy pregnancy development. Some autoimmune conditions that have been associated with recurrent pregnancy loss include:
Celiac disease(5)
Hashimoto’s thyroiditis(6)
Graves’ disease(7)
Systemic lupus erythematosus(8)
While these are the most commonly researched, they are not the only autoimmune issues to consider. Any autoimmune activity can potentially make it harder to conceive or maintain a pregnancy. (9)
The father’s Inflammatory factors can’t be entirely overlooked, either. However, there is less research linking this directly with recurrent miscarriage.
Any autoimmune activity can potentially make it harder to conceive or maintain a pregnancy.
2. Blood Clotting Disorders
Blood clotting disorders are related to inflammation and autoimmunity. Some of them, like anticardiolipin syndrome, have roots in autoimmune dysfunction.
If a woman has clotting disorders on any level, they can become obvious during the early days or weeks of pregnancy. Blood naturally becomes 5 to 10 times thicker during pregnancy due to hormones.
If your blood has a tendency to clot or to be too thick, it can become problematic during pregnancy. It can lead to miscarriage or difficulties with implantation. If a pregnancy does implant, it can interfere with proper placenta formation. This can affect fetal blood supply and nutrient transfer between the placenta and the uterus later. (10) Fetal intrauterine growth restriction (IUGR) or low amniotic fluid levels (oligohydramnios) are possible outcomes as well.
A small blood clotting disorder can become a bigger problem during pregnancy.
Some practitioners believe that clotting disorders can lead to the formation of a subchorionic hematoma (SCH). This is a common cause of vaginal bleeding in early pregnancy. Blood clotting disorders relating to miscarriage include: (11)
- Antiphospholipid syndrome
- Sticky platelet syndrome
- Tissue plasminogen activator deficiency
- Factor V Leiden
- Elevated levels of PAI-1
- Elevated lipoprotein(a)
- Factor II deficiency (prothrombin)
- ApoE2
- PAI-1
- ACE
- MTHFR
This list is not exclusive. Other clotting conditions could be related to recurrent loss. However, these are the most common.
A study of 150 women analyzed clotting factors related to miscarriage. Twenty-five percent of the women had more than one clotting factor present. More than 98% of these women went on to have normal pregnancies when treated with low-dose aspirin and heparin or lovenox to term. (12)
MTHFR is another genetic variant that has been studied in relation to blood clotting and recurrent miscarriage. The risk of RPL increases when both the mother and father have genetic clotting factors. This is true even if individually they would be considered low-risk. (13)
A small blood clotting disorder can become a bigger problem during pregnancy.
3. Methylation
Methylation problems—specifically MTHFR variants—can result in pregnancy complications. Many healthcare practitioners don’t automatically make the connection between MTHFR and miscarriage.
However, the relationship is as distinct as clotting disorders and miscarriage. Methylation is an essential component of healthy cells and DNA. You can’t have viable sperm or eggs without healthy DNA. Methylation can be compromised from dirty genes or unaddressed MTHFR genetic variants. This can lead to poor-quality embryos, resulting in frequent miscarriages.(14)
Solving methylation and optimizing MTHFR isn’t as simple as taking more folic acid. In fact, folic acid can cause many side effects. Similarly, methylation can’t be solved by taking more L-methylfolate or folinic acid. Methylation is a complex process. It requires multiple nutrients, including active B12, active B6, antioxidants, and many others.†
Pregnancy increases the thickness of your blood. Blood can become 5 to 10 times more clotty due to hormones. A small blood clotting disorder can become a problematic one during pregnancy.
4. Thyroid
The thyroid is your body’s master metabolism regulator. This endocrine gland can also influence your overall hormone balance. Pregnancy requires increased levels of hormones that must be balanced. Low thyroid hormone levels and other endocrine factors are estimated to cause up to 12% of all miscarriages. (15)
Unfortunately, most healthcare practitioners only test TSH (thyroid stimulating hormone) to assess whether or not a thyroid is healthy. TSH alone will not paint a full picture of your thyroid health. You also need to run your free T3 and free T4. These are the active and accessible amounts of thyroid hormones. They are far better labs to assess your thyroid function and overall health. These levels can be low even if TSH is normal. Equally important are your thyroid antibody levels. These include thyroid peroxidase antibodies and thyroglobulin antibodies.
Thyroid dysfunction in the early weeks of pregnancy can lead to early miscarriage. Yet many OBGYN’s don’t test thyroid function in pregnant women until between 6 to 12 weeks gestation.
Women with a history of recurrent miscarriages should address their thyroid health early on. Ideally, the thyroid is balanced prior to getting pregnant to rule it out as a potential cause.
Low thyroid may be responsible for up to 12% of miscarriages. Dial-in your thyroid before you get pregnant for a healthy pregnancy from the start.
5. Genetic Health of Mother and Father
60% of all miscarriages are due to chromosome abnormalities that no one can control. This includes losses that are not recurrent and cannot be prevented. They do not occur in subsequent pregnancies. These types of errors do become more common the older a mother gets. (16)
In rare cases, either the mother or the father will have what is known as a translocation. Genetic material passed on from this parent may result in chromosomally abnormal embryos. This contributes to a small percentage of recurrent miscarriages. (17) Fertility specialists can run tests, known as karyotyping, to determine if either parent is a carrier. It is considered rare that translocation in either parent would be the cause of infertility. This is true in both the general population and amongst those experiencing recurrent loss. (18)
Egg and sperm quality matter immensely for a healthy pregnancy outcome. However, there are larger epigenetic factors to consider when it comes to recurrent miscarriage.
Recurrent pregnancy loss is defined as three consecutive losses with the same father. Even the definition excludes the mother’s health alone as the only factor. (19)
Epigenetics describes how your DNA responds to your personal lifestyle, diet, and environment. Epigenetics can influence the health of your eggs or sperm. It can determine how well your body is able to perform methylation. Epigenetics can even turn genes ‘on’ or ‘off.’ This can determine your susceptibility to issues you may be genetically predisposed to. If either partner’s methylation or DNA is not optimally healthy, it can result in passing on compromised genetic material to the embryo.
According to the World Health Organization (WHO), as many as half of all pregnancy losses may be genetically normal (referred to as “euploid”). These may be related to issues that can be resolved to prevent future losses. (20)
Of course, there can be other contributing factors entirely. Nearly one-fourth of all pregnancies end because of random chromosomal abnormalities. Remember, you cannot control or prevent these types of losses. Even if you have recurrent loss, some of your miscarriages will end because of these statistically “normal” reasons. This can make the problem feel that much bigger.
Uterine and other structural abnormalities can also cause recurrent miscarriages. (21)
The bottom line is that if you’re having repeated miscarriages, there isn’t one simple test to run. However, a good place to start is with the list we’ve shared at the end of this document. It will take a careful evaluation of each partner’s health history to reach a resolution and ultimately, a healthy pregnancy
Of all miscarriages, 60% are due to chromosome abnormalities that no one can control. However, up to 50% of all pregnancy losses may be genetically normal. Often, these issues can be resolved to prevent future losses.
How to Get Answers About Your Miscarriages
You don’t have to resign to the fact that you’ll keep having miscarriages. It may take some work, but there are practitioners who will work with you to find the cause(s) of your recurrent pregnancy loss.
It is not normal to have multiple consecutive miscarriages. If a healthcare practitioner is telling you that it is, it’s time to get a second opinion. Look for a practitioner who takes you seriously, and will run the tests you are requesting. If a provider refuses to run your requested lab tests or says that there is no hope for you to hold a pregnancy, then find a different provider.
Types of providers to look for include:
- Maternal Fetal Medicine (MFM) doctors
- Reproductive Endocrinologists (RE)
- OBGYNs versed in recurrent pregnancy loss
- Fertility specialists such as MDs, midwives, and naturopaths
Fertility Testing & Diagnostics
There are a variety of tests available to assess the reasons why you’re having RPL, some of which we’ve mentioned earlier. An advanced workup for those experiencing repeated losses might include:
Physical examinations looking for structural abnormalities in the uterus or fallopian tubes:
- SIS (saline infused sonogram)
- HSG (hysterosalpingogram)
- Hysteroscopy
- Sonohysterosalpingogram
- Transvaginal ultrasound
Lab testing to assess thyroid function:
- TSH (thyroid stimulating hormone)
- Free T3
- Free T4
- TPO (thyroid peroxidase antibodies)
- TGA (thyroglobulin antibodies)
Lab testing to check for autoimmune antibodies
(consult a Rheumatologist)
Lab testing for any signs of clotting disorders
(consult a Hematologist)
Lab testing to look for nutrient or other deficiencies
(consult a Naturopath or Functional Medicine Practitioner)
Lab testing to assess female reproductive hormones:
- Day 3 of the menstrual cycle: estradiol, FSH (follicle-stimulating hormone), LH (luteinizing hormone)
- Day 21 of the same menstrual cycle: Progesteron
- Testosterone (free plus weakly bound)
- Prolactin
Lab testing to assess egg reserve in the mother
[i.e., day 3 FSH, day 3 Inhibin B, AMH (Anti-Müllerian Hormone)]
Sperm analysis to examine sperm health in the father
If you have experienced recurrent miscarriages, Dr. Lynch recommends the following genetic tests:
- Factor V Leiden (FVL)
- Factor II (prothrombin) deficiency (FVL2)
- Plasminogen activator inhibitor (PAI-1)
- Angiotensin-converting enzyme (ACE)
The tests above should be conducted for both the male and female partners. For the mother, Dr. Lynch also recommends:
- Methylmalonic acid (MMA)
- S-adenosylhomocysteine
- Homocysteine
Additional lab tests related to recurrent miscarriage include:
- Anti-nuclear antibody (ANA)
- Anti-paternal leukocyte antibody
- Anti-phospholipid antibody panel (including anti-cardiolipin antibodies)
- Anti-SSA/Ro antibodies
- Anti-thrombin activity
- Cytokines - interferon, interleukin, TNF
- DQ Alpha
- DQ Beta
- Erythrocyte sedimentation rate (ESR)
- Hemoglobin A1c
- Homocysteine
- High sensitivity C-reactive protein (hsCRP)
- Immunophenotype
- Karyotyping
- Leukocyte antibody
- Lupus anticoagulant
- MMA Methylmalonic Acid (MMA)
- Natural Killer Cell Assay (NKC)
- Protein C activitya
- Protein S antigen
- S-adenosylhomocysteine SAH
- 25-hydroxyvitamin D (Vitamin D3)
Your practitioner may suggest additional tests based on your personal health history.
In many cases, you will uncover a diagnosis or perhaps a few different diagnoses. This can help tremendously to direct your treatment. If a clotting disorder is discovered, you may be prescribed medication such as low-dose Lovenox, heparin, or daily baby aspirin. If autoimmune activity is detected, you may be prescribed an immunomodulatory drug, such as Plaquenil or Prednisone. Your fertility specialist will be able to assess your medical history and labs to determine the best fertility treatment for you.
Start Here - Lab Tests to Prioritize
It can help to run ‘all the tests’ in hopes of expediting a diagnosis when time is of the essence. Insurance plans cover most, if not all, of the tests listed in this guide. However, patients paying cash may need to prioritize which tests to run to minimize out-of-pocket expenses.
Most high-risk OBGYNs (MFMs) will order the following labs for a patient after 3+ recurrent losses or following a second- or third-trimester loss. A physical examination, starting with a transvaginal ultrasound, should also be conducted to assess RPL.
It is recommended to start with the following lab tests:
- Thyroid panel (TSH, Free T4, Free T3, thyroid antibodies)
- Antiphospholipid antibody panel
- Lupus anticoagulant with Interp
- MTHFR (can be determined using raw DNA data from StrateGene, 23&Me, or Ancestry)
- Factor V DNA Screen (can be determined with 23&Me)
- Prothrombin (Factor II) mutation (can be determined with 23&Me)
- Plasminogen Activator Inhibitor 1 (PAI-1) 4G/5G Polymorphism
- Protein C
- Protein S
- Homocysteine
Optimize Your Body for Fertility
While you’re working with a practitioner (or waiting to see one), there are many things that you can do on your own. While you can’t treat your own blood clotting disorders or structural problems, there are things you can do to be proactive.
Whether you have MTHFR or other dirty genes, you and your partner can work to support overall health and well-being. Focus on your diet, methylation, lifestyle, and mindset so they are supportive of your overall health. Healthy parents set the stage for all aspects of good health – including pregnancy.
4 proactive steps to support your fertility and health include:
- Read Dirty Genes, and follow the principles in the book that apply to you.
- Practice healthy lifestyle habits. Focus on diet, sleep, stress relief, proper hydration, nose breathing, and having fun.
- Support your mental health by working with a therapist
Additional Resources From Seeking Health®
- Overcoming Recurrent Miscarriage: Interview with Kinsey Jackson, MS, CNS, CFMP
- Recurrent Pregnancy Loss and MTHFR
- Recurrent Miscarriage Goes Beyond the Mother’s Health
- Recurrent Pregnancy Loss – 5 Reasons
- Infertility Causes: 10 Reasons You’re Having Trouble Getting or Staying Pregnant
- 6 Tips When You’re Trying to Conceive (TTC)
- Fertility Diet: How to Eat When You’re Trying to Conceive
- The Devil’s In the Details: Using Ovulation Tracking To Support Fast Conception
- Dirty Genes & Fertility: Cleaning Your Genes When You’re TTC
- How Do Prenatals Support a Healthy Pregnancy?
The Bottom Line
It’s hard to hold onto hope for a healthy pregnancy when you experience RPL. We understand because we have been there. Repeating the same thing over and over often won’t solve the problem. However, getting answers about your personal health and body often will. No one knows better than you, so remember to listen to your intuition along this journey. What is right for one person won’t be for the next.
Happy endings come in many forms. Whether you get pregnant with your own eggs, use donor eggs, opt for a surrogate, adopt, or decide to live a child-free life, remember this: there is no single right way to find your happy ending. Every path is unique and valid. There truly can be a rainbow after the storm. Keep seeking answers, and you will likely find your solution.
We wish you the best of luck, health, and baby dust.
References
- https://www.marchofdimes.org/complications/miscarriage.aspx
- https://www.marchofdimes.org/complications/miscarriage.aspx
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4610348/
- https://pubmed.ncbi.nlm.nih.gov/16682265/
- https://pubmed.ncbi.nlm.nih.gov/19842070/
- https://pubmed.ncbi.nlm.nih.gov/19842070/
- https://pubmed.ncbi.nlm.nih.gov/19842070/
- https://www.ncbi.nlm.nih.gov/books/NBK459481/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4467633/
- https://pubmed.ncbi.nlm.nih.gov/10898270/
- https://pubmed.ncbi.nlm.nih.gov/10898270/
- https://pubmed.ncbi.nlm.nih.gov/10898270/
- https://pubmed.ncbi.nlm.nih.gov/22047507/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6086799/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3603072/
- https://www.acog.org/womens-health/faqs/repeated-miscarriages
- https://www.acog.org/womens-health/faqs/repeated-miscarriages
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4355257/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4610348/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4829626/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4610348/
†These statements have not been evaluated by the Food and Drug Administration (FDA). This product is not intended to diagnose, treat, cure, or prevent any disease.
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