Recurrent miscarriages, also known as spontaneous abortions or early pregnancy losses, are very common. They occur in around 15 to 20 percent of all pregnancies, mostly in the first 3 months of pregnancy. Although one or two early pregnancy losses don’t mean that the woman will have trouble getting pregnant in the future, they can make patients worried and doubting their ability to carry a pregnancy to full term.
In more than 50 percent of cases, couples will end up having a live, healthy baby naturally after suffering two miscarriages. However, you might want to figure out the likely causes if you have been unable to have a live birth and have had multiple pregnancy losses.
What is Recurrent Miscarriage?
Recurrent miscarriage is otherwise known as habitual abortion. It occurs when a woman suffers two or more clinical pregnancy losses one after the other. A clinical pregnancy is one that has clinical evidence of pregnancy, i.e., laboratory or visual signs of the gestational sac (fluid-filled cavity that surrounds the embryo), fetal pole, or placenta on an ultrasound.
Note that clinical pregnancies are not the same as chemical pregnancies, during which a pregnancy loss happens before there’s proof of conception besides a positive blood pregnancy test. As said earlier, just 15-20 percent of all clinical pregnancies result in miscarriages.
Generally, women have a very low chance of recurrent pregnancy losses. Approximately 5 percent of women will suffer two or more successive miscarriages in their lifetimes, and just 1 percent will experience three or more, according to the American College of Obstetrics and Gynecologists (ACOG). However, women who are older than 35 or have suffered previous miscarriages are at increased risk of recurrent miscarriage.
A lot of miscarriage cases go unreported since plenty of women suffered miscarriages before they even realized they were carrying a pregnancy and don’t have symptoms or signs of pregnancy loss at all. But doctors or healthcare providers can tell whether a woman has had a pregnancy by conducting an ultrasound (an imaging technique that uses high-frequency sound waves to take live images from the inside of the body).
Most miscarriages happen due to genetic anomalies in the developing embryo or fetus, like missing or extra sex chromosomes. These are usually random gene mutations that have a very slim chance of recurring. However, in recurrent miscarriages, this is not the case. Often, the physician will check for a certain type of gene mutation known as a balanced translocation. Although a balanced translocation has been linked with recurrent miscarriage, it is still very rare.
Types of Miscarriage
While there are many different causes of miscarriage, they are often classified into two groups:
(i) early miscarriage and
(ii) late miscarriage.
Recurrent early miscarriages are usually caused by chromosomal or genetic issues in the embryo, with about 50 to 80 percent of repeated pregnancy losses having an abnormal number of chromosomes. Structural issues of the womb can also contribute to an early miscarriage.
Recurrent late miscarriage may be due to preterm labor, autoimmune problems, uterine anomalies, or cervical insufficiency (an incompetent cervix).
Finding a Possible Cause
Women with a prior history of recurrent pregnancy losses need to be evaluated, monitored, and managed. At Reproductive Sciences Medical Center (RSMC), we conduct a wide variety of tests on both the pregnant woman, her husband, and the fetal tissue if need be. The tests that can be performed include:
- Genetic testing for autoimmune disorders ( in cases of 3 or more miscarriages)
- Anatomical testing or sonography ( ultrasound test or X-ray)
- Chromosome testing of Intended Parents screening for balanced translocations
- Testing for diabetes, insulin resistance, and other endocrinopathies that have to do with the pituitary and thyroid glands
- Chromosome testing of products of pregnancy after miscarriages ( we can examine the DNA of the fetus from formalin-fixed slides if you already experienced a miscarriage)
- Blood clotting studies ( but only if you have personal or family history of venous thromboembolism)
What are the Causes of Recurrent Miscarriage?
Although the causes of pregnancy loss are often unclear, a lot of patients end up having a healthy third pregnancy. There’s still a 65 percent chance that your third pregnancy will result in a live birth even if you have had two miscarriages.
The issue of pregnancy loss can be easily resolved if a cause is found, and figuring out the reason for the miscarriage can help prevent more losses and emotional stress. A woman who has had two successive miscarriages is said to have called recurrent pregnancy loss. The diagnostic testing above can help them find out if there is a reason for their miscarriages.
The aim of the testing above is to determine the cause of pregnancy loss, but the results usually come back okay without any particular reason for the miscarriage.
Genetic (Embryo or Parents)
Random chromosomal abnormalities in the embryo (fetus) are a common occurrence and are responsible for 50 to 80 percent of all miscarriages that happen in the first trimester of pregnancy. But at times, some chromosomal abnormalities are repeatedly transferred, which may lead to recurrent miscarriages. That is why you and your spouse need to undergo karyotype testing to screen for a balanced translocation if you have suffered two or more miscarriages. The probability of detecting a balanced translocation in one of the Intended Parents is very low (4 percent).
In vitro fertilization (IVF) with preimplantation genetic testing can be considered in some cases of recurrent miscarriage. The reason behind this is that since the pregnancy loss may be due to a chromosomally abnormal embryo, choosing an embryo with normal chromosomes will raise the odds of having a successful pregnancy. This depends on the individual, and you need to consult your doctor about this option before going ahead.
Uterine Abnormalities
Approximately 15 percent of recurrent pregnancy losses are due to a uterine structure issue. A woman can be born with abnormalities of the womb, such as a double uterus, septate uterus, or other genetic conditions.
Some women also have issues like fibroids or polyps. These are unusual growths that can develop anywhere within the womb, which may impact the pregnancy or result in problems.
Miscarriages can also result in intra-uterine scarring. The great news is that most of these issues can be resolved before pregnancy with surgery, improving your odds of a successful pregnancy. Proper medical evaluation is necessary to find out if there is such a problem.
Endocrine Issues
Examples of endocrine issues that call for medical evaluation are diabetes, PCOS (polycystic ovarian syndrome), or disease of the pituitary and thyroid glands.
Luteal phase defect (LPD) indicates that the woman’s ovaries are not functioning correctly, leading to pregnancy loss. Ovulation induction medications, such as clomiphene citrate, are the first line of treatment for women with LPD.
Progesterone therapy used to be very popular for patients with luteal phase defects in the past. But only a few, if any, studies have shown that empiric progesterone therapy helps.
Autoimmune Diseases
Immunological issues result when the mother’s body produces antibodies that lead to clotting in the blood vessels that connect to the growing fetus. Hence, the fetus does not receive enough nutrients and dies in the womb, resulting in a miscarriage.
Several blood tests can be conducted to check for this issue if you have had 3 or more miscarriages. This condition may be treated with the help of medication like aspirin or heparin (a blood anticoagulant). If your physician prescribes daily aspirin therapy, you may be asked to take a small dose of aspirin (81 milligrams) every day.
Heparin is a medication that is often used to treat blood clotting problems. However, it’s best to talk to your doctor about the possible risks linked to heparin use during pregnancy.
Blood clotting disorders were once believed to be the cause of recurrent miscarriage, but not anymore. However, women with a personal or close family history of blood clots (for example, in their lungs or extremities) need to get themselves checked for blood clotting disorders. This is a complicated issue, so you may need a reproductive specialist to help figure out the appropriate testing to undergo.
Blood Clotting Disorders
Blood clotting disorders, including antiphospholipid syndrome and systemic lupus erythematosus (SLE), can result in “sticky” blood and repeated pregnancy losses. These disorders interfere with the flow of blood to the placenta and lead to clots that stop the placenta from working properly. This may prevent the baby from receiving enough oxygen and nutrients, which can cause miscarriage.
Women with recurrent pregnancy losses need to be checked for antiphospholipid antibodies before pregnancy. Treatment can involve using heparin and aspirin, both of which help thin out the blood. Studies have shown that women with repeated miscarriages are more likely to experience blood clotting, preventing the flow of nutrients to the fetus.
Environmental Factors
Exposing yourself to some chemicals, x-rays, medications, etc., can also increase your chances of having a miscarriage. While some of these factors are job-related, others may have to do with your lifestyle. Excessive intake of caffeine or alcohol and smoking by either partner can affect pregnancy outcomes. Obesity has also been linked to a higher risk of pregnancy loss.
Thyroid Problems
Studies have also associated thyroid problems with an increased risk of miscarriage and other pregnancy-related complications. They can be easily checked through a blood test and are usually easy to treat. It’s crucial to have a healthy thyroid function before becoming pregnant.
Thyroid antibodies are small molecules in the blood that target the thyroid gland, preventing it from functioning properly. Elevated levels of antibodies can raise your chances of pregnancy loss. It’s crucial to assess thyroid function in women with these antibodies, especially when carrying a pregnancy.
Cervical Weakness
If you have suffered late pregnancy losses and are believed to be at risk of cervical weakness or cervical incompetence, your doctor may recommend undergoing a scan from 14 weeks of pregnancy to check the length of your cervix. Based on your medical and pregnancy history and results of your scan, a cervical cerclage (a procedure where the doctor places a stitch around your cervix) may be recommended before or during pregnancy.
Natural Killer Cells
Some health experts have linked natural killer cells in the womb to female infertility and pregnancy loss. There are tests you can do to determine your levels of natural killer cells. Talk to your fertility center to see whether they offer these tests.
Age
The chances of early pregnancy loss are highest in couples where the female partner is older than 35 and the male partner is above 40 years of age.
Diagnosing Recurrent Miscarriage
According to the American College of Obstetrics and Gynecology (ACOG), any woman who has a miscarriage at or after the 10th week of pregnancy or suffered 3 successive losses at any gestation age needs to be screened. The doctor will first collect comprehensive information about the patient’s personal, family, surgical, medical, and genetic history. The physician will then carry out a physical exam. The testing may include karyotype analysis of both the male and female partners.
- Karyotype testing: A karyotype refers to an individual’s genetic or chromosomal make-up. The aim of this testing is to check for genetic abnormalities in the parents that can be transferred to their baby, leading to miscarriage.
- Uterus examination: The womb (uterus) and its cavity (inside of the womb) are usually examined. There are many ways to examine the womb cavity, such as an ultrasound, hysterosalpingogram X-ray, magnetic resonance imaging (MRI), and a hysteroscopy (to see the inside of the womb).
- Ultrasound: An ultrasound is the first test that is done. It will provide information about the structure of the womb and whether there are any fibroids (abnormal growths) in there.
- Saline ultrasound: A saline ultrasound is a medical procedure in which a saline solution is injected into the womb cavity so that the doctor can know if there are any abnormalities, such as polyps, fibroids, or scarring, in the womb.
- Hysterosalpingogram: A hysterosalpingogram is a procedure that uses an X-ray to check the uterus and the fallopian tubes. It can help doctors evaluate the womb cavity and find out if the uterine tubes are open or not.
- Hysteroscopy: A hysteroscopy is a minimally invasive procedure where a camera is inserted via the cervix into the womb, so the physician can see the inside of the womb. This enables the physician to get rid of fibroids and polyps as well as scar tissue or septum.
- MRI: A uterine septum, also called a septate uterus, is an abnormality in the shape of the womb that some women are born with. An MRI can be performed to check the location of fibroids and if there are abnormalities in the womb shape.
- Antibodies evaluation: Antiphospholipid antibodies, such as lupus anticoagulant and anticardiolipin antibody, will probably be evaluated. These antibodies have been associated with antiphospholipid syndrome, which can be linked to miscarriage.
- Blood clotting test: Testing for abnormally increased blood clotting should be performed if the patient has a personal history of blood clots linked to risk factors, like surgery, prolonged immunization, or bone fractures. It can also be done if the patient has a sibling or parent with a blood-clotting disease.
- Hormone tests: The doctor may also conduct hormone function tests. These tests evaluate thyroid function and thyroid antibodies. The physician can also measure the levels of prolactin, a hormone that stimulates the production of breast milk in the female body.
- Ovarian reserve tests: Ovarian reserve tests can be done too, which show how well a woman’s ovary is working. Several studies have linked poor ovarian function to chromosomal abnormalities in female eggs.
- Diabetes test: Testing for diabetes can also be conducted if a woman is more likely to develop or is already showing manifestations of the condition.
- Endometrial biopsy: a medical procedure where the doctor takes a sample of the endometrial tissue and checks it under a microscope to find out if there’s an existing infection hindering the pregnancy from progressing.
- Glucose screening: a doctor performs a blood test to screen for diabetes mellitus, which can increase the chances of miscarriage if not controlled.
- Ovarian reserve testing: testing of egg quality and quantity can help find out if an age-linked decline in ovarian function is causing the miscarriage.
- Sperm DNA fragmentation testing: this test checks if DNA fragmentation and sperm quality are leading to the loss of pregnancy.
Treatment for Miscarriage
It is important to speak with your doctor or healthcare provider if you have had two or more miscarriages. A lot of women keep trying to conceive naturally after pregnancy losses. However, in some cases, your doctor can recommend certain treatments to help mitigate your risk for future miscarriage.
Surgery
Most of the problems in the womb (uterus), such as scar tissue, fibroids, or septum ( a tissue that separates the womb), can be fixed with surgery. Rectifying the shape of the inside of the womb can help reduce the risk of pregnancy loss.
Blood-thinning Drugs (Anticoagulants)
Women who have autoimmune or blood clotting issues can be treated with a small dose of heparin and aspirin. These drugs can be used when pregnant to reduce the chances of miscarriage. However, it’sa best to speak with your physician or healthcare provider before taking these drugs.
Correcting Other Medical Issues
Recurrent miscarriage can be due to some medical issues, such as an under or hyperactive thyroid, elevated levels of prolactin, or abnormal blood glucose levels. Treating health conditions like thyroid dysfunction, high prolactin levels, or diabetes can increase the odds of having a successful, healthy pregnancy.
Genetic Screening
In approximately 5 percent of couples with recurrent miscarriage, one of the Intended Parents has a translocation of their chromosomes. A translocation in one parent can result in a fetus with chromosome imbalances that are at higher risk of being miscarried.
The doctor can take the parents’ blood and examine it to check whether they have a translocation. If a chromosomal issue is detected, the physician may advise that the couple undergo genetic counseling. Although couples with translocations can later have a healthy pregnancy unassisted, the doctor may recommend they go for fertility treatments, like IVF (in vitro fertilization).
In IVF, before embryos are transferred into the mother’s or Surrogate’s womb, they can be checked for chromosomal abnormalities (preimplantation genetic screening). This enables the doctor to select embryos without translocations for transfer, increasing the odds of a successful pregnancy.
Lifestyle Choices
Generally, anything that is healthy for a woman increases her chances of a complication-free pregnancy. Quitting smoking and the use of illegal drugs (i.e., cocaine) will mitigate the risk of early pregnancy loss. Reducing caffeine and alcohol consumption can also be beneficial. Studies have associated being overweight with a higher risk of miscarriage, so achieving a healthy weight loss may also help improve pregnancy outcomes. While there is no evidence that anxiety, slight depression, or stress leads to recurrent miscarriage, these are big issues associated with recurrent pregnancy loss.
Mental support and counseling can help parents handle the emotional pain of pregnancy loss and create an ideal environment for conception.
Progesterone & Recurrent Miscarriage
If you are currently experiencing bleeding in your pregnancy and have had one or more miscarriages, new research has found that progesterone can help. The 2019 study (also known as the PRISM trial) was published in the New England Journal of Medicine and suggested the more previous pregnancy losses, the higher the benefit from progesterone treatment
Progesterone is a female hormone that helps increase the thickness of the womb lining and makes the mother’s body more receptive to the developing baby. It is usually administered in the form of pessaries and inserted into the vagina twice per day.
The PRISM trial was a large, multi-center, randomized controlled study, which is the ideal standard of scientific trials.
More than 4000 women with early pregnancy bleeding from 48 clinics in the United Kingdom took part in this research. Nearly 50 percent of the participants were given vaginal progesterone tablets, while the remaining half were given placebo tablets. The researchers found that:
- For women who have never had a miscarriage, the live birth rate was 74 percent in the group that used progesterone and 75 percent in the other group, which means that there’s no significant benefit.
- For women with one or two previous miscarriages, the rate of live birth was 76 percent in the progesterone group and 72 percent in the other group (placebo group), which indicates that there is little benefit.
- For women who have suffered three or more pregnancy losses, the live birth rate was 72 percent in the progesterone group and 57 percent in the placebo group, which suggests that there is a significant benefit.
Note: the researchers did not discover any safety issues from progesterone use in this study.
A Word of Encouragement from RSMC
Sometimes, the causes of recurrent miscarriages are not known. Even if you have had two pregnancy losses, there is still a 65 percent chance that your subsequent pregnancy will result in a healthy, live birth. However, it is important to consult a doctor who specializes in recurrent miscarriages so that you may know the actual cause of this issue.
We offer various surgical and genetic testing procedures that have helped many Intended Parents overcome miscarriage problems and have a successful pregnancy. Schedule a consultation today to learn more.
