Recurrent Miscarriages

Recurrent miscarriage is an aspect of infertility that affects many couples who are trying to conceive. The journey of recurrent pregnancy loss can be devastating; however, with the guidance of a fertility specialist, there is hope for diagnosing the causes of recurrent miscarriage and carrying a pregnancy to term. While most women who miscarry do go on to give birth to a healthy baby, infertility specialists are often called in to find out the cause for recurrent pregnancy loss and recommend treatment.

How common are miscarriages? 

Miscarriages are more common than many people realize. Statistics indicate that about 10-20% of known pregnancies end in miscarriage, most often occurring within the first trimester. Many miscarriages happen early in pregnancy, sometimes even before a woman realizes she’s pregnant. Factors such as age, overall health, and underlying medical conditions can also play a role in miscarriage rates. While these figures might seem concerning, it’s important to understand that most women who have miscarriages will go on to deliver at term with proper care and support from a fertility specialist. If you’ve experienced a miscarriage, know that you’re not alone.

When should patients with recurrent miscarriages seek help?

The American Society for Reproductive Medicine (ASRM) currently recommends that couples who have 2 or more consecutive miscarriages undergo evaluation to determine the reason for the recurrent miscarriages. It has long been believed that – unlike “first” miscarriages, of which a little over half are caused by chromosomal abnormalities – recurrent pregnancy loss has other causes. 

Recent research has demonstrated that when the genetic analysis of the first miscarriage is normal, genetic analysis of the second miscarriage will be normal 70% of the time. Studies have shown that the incidence of chromosomal abnormality in miscarried pregnancies in women under the age of 35 is only 35% as compared with about 50% in older women. Researchers are still debating what causes the remainder. Possibilities include immune system malfunction, hormone imbalances, distortions of the uterine cavity, and pelvic infections. Studies have also linked the use of alcohol, cigarettes, and excessive caffeine consumption to an increased risk of miscarriage.

The risk of miscarriage increases with age, and, in many cases, can be attributed to an abnormal egg. As a woman gets older, the quality of her eggs diminishes resulting, not only in more miscarriages, but also in an increased infertility and genetic abnormalities (such as Down’s syndrome) rates. 

When you seek our care for recurrent miscarriages, our first step is to try to diagnose the cause of your recurrent miscarriages. 

What causes recurrent miscarriage?

The causes of recurrent miscarriages can be complex and multifactorial. In many cases, the exact cause may not be identified, but several potential factors have been associated with recurrent miscarriages:

Genetic Causes of Recurrent Miscarriages

The incidence of chromosomal abnormalities in either spouse is approximately 1-3%. Your doctor may recommend chromosomal analysis for you and your spouse. A genetic study of the miscarriage tissue should be obtained whenever possible.

Uterine Factors of Recurrent Miscarriages

If uterine fibroids or polyps are found, hysteroscopic surgery is advised to correct the problem. Similarly, if a woman has a uterine septum (a congenital condition in which the uterus is partially divided into two compartments), hysteroscopic surgery can also correct this defect. Sometimes, scar tissue within the uterine cavity is responsible for the miscarriage (Asherman’s Syndrome). Removing the scar tissue may improve delivery rates.

Immunologic Factors of Recurrent Miscarriages

Antiphospholipid antibodies (aPL) or Lupus anticoagulant are present in about 15-20% of patients with recurrent miscarriages. Studies have shown that treatment of such patients with aspirin (81mg daily) or heparin improves live birth rates. The treatment has been demonstrated to be successful in about 80% of recurrent miscarriage patients with positive antiphospholipid antibodies or positive Lupus anticoagulant. However, heparin or low dose aspirin treatment of recurrent miscarriage patients without antiphospholipid antibodies has not been shown to be as effective.

Hypothyroidism (low thyroid)

The American Endocrine Society defines hypothyroidism as present when the thyroid stimulating hormone is over 2.5µIU/ml. For women with recurrent pregnancy loss and high TSH level (over 2.5), treatment with thyroid medication is advised to keep the TSH level between 1.0 and 2.5µIU/ml. Patients with hypothyroidism should be screened for antithyroid antibodies (ATA) to rule out thyroid autoimmunity which is often seen in Grave’s disease or Hashimoto’s thyroiditis.

Advanced Reproductive Age

Age has been associated with diminished ovarian reserve and increased rates of miscarriage. After age 40, 30-40% of pregnancies end in miscarriage, most often as a result of an abnormal number of chromosomes in the embryo (aneuploidy).

Celiac Disease

Celiac is an inflammatory disease of the small intestine caused by dietary gluten. Women with this condition have higher risk of miscarriages.

Lifestyle Factors 

Lifestyle factors such as tobacco use, alcohol, obesity, excessive caffeine consumption, and exposure to environmental toxins have been found to cause miscarriages.

Cervical Factor

Incompetent cervix is associated with second trimester pregnancy loss as a result of weakening of the cervical tissue. The treatment involves placing stitches to strengthen the cervix and prevent it from dilating prematurely.

Evaluation for Recurrent Pregnancy Loss

An evaluation for known causes of recurrent pregnancy loss is recommended after two consecutive pregnancy losses and may include the following:

• Genetic factors: Chromosomal analysis (karyotype) of both partners. Genetic analysis of the miscarriage tissue is very important when the result is abnormal.
• Anatomic factors: Hysterosalpingogram (HSG), Saline Infusion Sonography (SIS) or hysteroscopy to make sure that there are no uterine abnormalities.
• Immunologic factors: Antiphospholipid antibodies, lupus anticoagulant
• Endocrine factors: Thyroid, prolactin, Hemoglobin A1c
• Infectious causes: Culture for Ureaplasma organism
• Ovarian reserve evaluation: Day 3 FSH and Estrogen (E2), AMH, Antral Follicle Count (AFC), Fragile X

Currently, there is no indication for routine screening of women with recurrent miscarriages for antinuclear antibodies (ANA). ANA levels are elevated in 20% of reproductive age women. Women with recurrent miscarriages and elevated ANA levels who were treated with low dose aspirin or prednisone did not benefit from the treatment. In fact, they experienced a higher rate of obstetrical complications as compared with women who received no such treatment.

Looking for sperm defects (Sperm DNA fragmentation) has not been shown to be beneficial for patients with recurrent pregnancy loss.

Treatment of Recurrent Pregnancy Loss

Genetic Factors

If the problem is abnormal parental chromosomal analysis, the couple should seek genetic counseling. Depending on the specific parental genetic disorder, Preimplantation Genetic Diagnosis (PGD) can help reduce the risk of a subsequent miscarriage.

When genetic studies of previous miscarriage tissues are abnormal, IVF and Preimplantation Genetic Screening (PGS) have been shown to decrease the risk of another genetically abnormal pregnancy and subsequent miscarriage. Typically, the woman undergoes IVF and the embryos are biopsied at the blastocyst stage (5 days after fertilization). Cells obtained from the embryos can be evaluated utilizing newer genetic screening tests such as Next-Generation Sequencing (NGS). Only biopsy proven, genetically normal embryos are transferred into the uterus. Such treatment can significantly improve the likelihood of a successful pregnancy.

Uterine Disorders

Hysteroscopic or laparoscopic surgery is advised to remove polyps, fibroids, uterine septum or adhesions.

Endocrine Factors

Levothyroxine is prescribed when the thyroid level is low.

When the prolactin level is high, a prolactin lowering medication such as Bromocriptine or Cabergoline can be given to restore normal ovulation.

An elevated level of Hemoglobin A1c is suggestive of high insulin level. A blood sugar lowering medication, such as Metformin, is often prescribed.

Immune Disorders

When the miscarriages are caused by an immune disorder (positive Lupus anticoagulant or positive antiphospholipid antibodies), treatment with heparin and low dose aspirin can increase the odds of a successful outcome.

For patients with celiac disease, a gluten-free diet is advised before attempting pregnancy.

Unexplained Recurrent Pregnancy Loss

When there is no explanation for the miscarriages (unexplained RPL), the couple should work with a fertility specialist to continuously monitor the pregnancy to enhance the chances of maintaining a live pregnancy to term. 

During pregnancy, beta HCG levels should be monitored and progesterone suppositories are commonly prescribed if the progesterone level is less than 15-20ng/ml until the 12 week of pregnancy. Pelvic ultrasound is performed early in pregnancy and repeated weekly until the 12th week of gestation. 

What can I do to prevent another miscarriage?

At Boca Fertility, we recommend maintaining a healthy weight and exercising regularly. Try to avoid caffeine, alcohol and smoking and consider folic acid supplementation. We understand the emotional difficulties that come along with miscarriage and always encourage our patients to seek support from professionals, friends and family. 

If the cause for your miscarriage is known, our fertility specialists will work with you to develop a personalized, specific treatment plan to improve your chances for a successful pregnancy. 

Keep in mind that even if the cause for your miscarriages is unknown, with supportive care, you have about a 70% chance of having a successful outcome with your next pregnancy. We monitor our patients closely to give you the best chance at a successful pregnancy. 

Once you get a positive pregnancy test, we will measure your HCG and progesterone levels to confirm that the pregnancy is progressing well. If the progesterone level is less than 15-20 ng/ml treatment with progesterone suppositories is advised until the 12th week of pregnancy. Early ultrasound is then scheduled to evaluate the pregnancy. If all is well, weekly ultrasounds are scheduled at our clinic until the patient is ready to graduate to their OBGYN.

Some patients consider gestational surrogacy (patient’s embryos implanted into another woman’s womb) in cases of unexplained, high order recurrent pregnancy loss. If you are over 40 with recurrent pregnancy loss, the problem may be attributed to poor egg quality. In such cases, donor egg IVF can be considered.