Recurrent miscarriage – causes & treatments

Miscarriages are mentally and physically traumatizing for anyone, especially if they happen more than a few times. Recurrent miscarriage is the loss of three or more consecutive pregnancies of 13 weeks or less, with the same partner.

American Society of Reproductive Medicine (ASRM) is now considering that the term ‘Recurrent Miscarriage’ may be used even if you’ve lost two pregnancies consecutively.

Miscarriages and early loss of pregnancy are so common that many obstetricians consider it a normal part of reproduction. That doesn’t make the loss easier but the fact that you were able to get pregnant at all should give you hope of having a baby in the future.

How common are recurrent miscarriages?

Even after the confirmation, 15-20% of all pregnancies end in miscarriage, according to the National Infertility Association.

75% of miscarriages happen in the first 12 weeks and many of those women are not even aware that they are pregnant when the loss occurs.

Also known as recurrent pregnancy loss (RPL), recurrent miscarriage is acknowledged when:

You had 3 or more consecutive miscarriages (within 13 weeks of pregnancy), OR
You had 2 late miscarriages (13 – 20 weeks of pregnancy)

1% of all women experience 3 or more miscarriages and around 5% of face 2 consecutive pregnancy losses due to different reasons.

Recurrent miscarriage & successful pregnancy

If you have successfully achieved one pregnancy, you have 80 percent chances of having healthy pregnancies and babies in the future, said Henry Lerner, MD, clinical professor of obstetrics and gynecology at Harvard Medical School and author of ‘Miscarriage: Why it Happens and How Best to Reduce Your Risks.’

However, if you’ve had two or more miscarriages and haven’t had any successful pregnancies, you must consult a fertility specialist ASAP.

Women who have had two or more miscarriages, have a 40% higher chance of having another miscarriage.

Dr. Leong here discusses the common causes of recurrent miscarriage and what can be done to avoid them:

Recurrent miscarriage causes

Finding the possible reason for your recurrent pregnancy loss is crucial before deciding on any treatments.

Causes of recurrent early miscarriages

1. Chromosomal Abnormalities

60% of pregnancy losses are attributed to chromosomal abnormalities in the fetus.

There is 50% risk of miscarriage if you get pregnant after 40 because chances of aneuploidy (addition of extra chromosomes) are much higher. In women under 35, the risk of miscarriage is only around 10%, given all other factors are normal.

The egg quality of women starts to deteriorate as they start aging and that further increases the risk of miscarriage. Pre-implantation genetic screening (PGS) could be helpful, if:

If you are experiencing multiple miscarriages due to chromosomal reasons
If you are aware of a genetic problem in either of the partners
In natural pregnancy or IVF after 40 years of age

2. Anatomical factors

13% of recurrent miscarriage patients are noted to have anomalies in their uterine cavity—arcuate uterus, septate uterus, unicornuate or bicornuate uterus and a didelphys uterus.

A septum in the uterus (septate) is the most common abnormality in which the uterus is separated into two. A hysterosalpingogram can be used for diagnosis, which can further be confirmed with an MRI and a 3D sonogram.

A weak cervix also leads to second trimester miscarriages repeatedly or preterm deliveries. There are several causes for cervical insufficiency and it can be managed with cervical cerclage, in which the doctor will place stitches on the cervix to allow it to hold the pregnancy.

Causes of Recurrent Late Miscarriages

1. Antiphospholipid syndrome

Antiphospholipid Syndrome (aPL) is an auto-immune disease responsible for recurrent miscarriages in around 10-15% of women. Miscarriage at 10 weeks or more of gestation is more strongly associated with aPL than are earlier pregnancy losses.

Testing for antiphospholipid antibodies can be carried out in RPL patients but only after the anatomic, hormonal, and chromosomal causes have been ruled out.

If you test positive, Low doses aspirin and heparin are part of treatment regimen.

2. Immunologic problems

Reduced maternal immune tolerance towards the fetus is considered one of the causes of repeated miscarriage but immunologic factor for recurrent miscarriages have not been conclusively proven by research so far. However, there is evidence that altered levels of maternal immunologic responders are seen in women who’ve had multiple miscarriages.

Other causes

Hormonal and metabolic factors
- Hypothyroidism – Thyroid levels should be evaluated and TSH levels should be below 2.5mIU/L before trying for pregnancy.
- Diabetes – Highly elevated blood sugar can cause loss of pregnancy.
- PCOD – Excessive androgens as in PCOD/PCOS may cause a miscarriage.
- Increased prolactin – Elevated prolactin levels hamper follicular development and luteal function. This leads to reduction in progesterone levels in the luteal phase of the cycle. In patients with repeated miscarriage, progesterone supplements can be given to improve chances.
- Thrombophilia (propensity for blood clots) – About 15% of recurrent miscarriages are attributed to this problem. The doctor may recommend blood tests for Thrombophilia and start a drug called Heparin to prevent blood clots during your pregnancy. However, more research is needed to see if those injections can effectively prevent miscarriage and they might even cause side-effects.
Lifestyle factors

Excessive consumption of alcohol, cigarettes and cocaine use have been reported to raise the risk of miscarriage. Too much caffeine (over 3 cups a day) is also linked to miscarriages.
Unexplained repeated miscarriage

In over 50% of patients, clinicians are unable to find the reason for multiple miscarriages. Unexplained recurrent miscarriages are extremely challenging and frustrating but you must know that the chances of a successful pregnancy in these cases are as high as 50-60%. They have excellent prognosis.

Tests for Recurrent Miscarriages

Recurrent miscarriage tests should be dependent upon an initial understanding of the possible cause.

If, for instance, the miscarriage happened due to a random genetic problem in the baby, you couldn’t have done much and chances are, you could go on to have a normal, healthy pregnancy without really needing any tests.

Scans and investigations for the uterus

Hysterosalpingogram (HSG): This is an x-ray procedure that is done after injecting a dye into the uterus to see if there are any abnormalities that may be interfering with the pregnancy. This test is also done to test the patency of fallopian tubes.
Transvaginal Ultrasound: To check for uterine, ovarian, and endometrial problems that may be causing recurrent miscarriages.
Hysteroscopy: This is done via insertion of a thin telescopic instrument into the uterus to check the insides and get accurate pictures.
ERA test: Endometrial receptivity array is done by taking a biopsy from the uterine lining and checking it for any inconsistencies.

Blood tests for multiple miscarriages

Lupus anticoagulant antibodies and Anticardiolipin antibodies: These are both marker for the antiphospholipid syndrome, which increases the chances of recurrent miscarriage.
Prothrombin Time (PT) and Activated Partial Thromboplastin Time (aPTT): Both of these tests check for the clotting time of blood and any discrepancy may give an indication of hereditary thrombophilia.
MTHFR Gene Mutation: This is known to interfere with folic acid absorption but the US CDC suggests that even if you have MTHFR C677T variant, consuming 400 mg of folic acid each day may help avoid neural tube defects.
Thyroid Panel: Second-trimester miscarriage is sometimes associated with hypothyroidism. Thyroid tests are routinely performed in fertility work-up because abnormal thyroid levels also cause conception problems.
Progesterone: Low progesterone levels could result in repeated miscarriages.
Karyotype testing: This test is performed on both parents to check for genetic problems that cause risks to the pregnancy.

Other tests

Sperm DNA fragmentation analysis: Even with normal semen analysis, there may be genetic problems in the sperm cell, which can be detected with sperm DNA fragmentation testing.
Fetal Tissue Karyotyping: If you end up doing dilation and curettage after the miscarriage, a chromosomal test of the fetal tissue may be done to check for chromosomal anomalies.

It is important that you do not unnecessarily do any or all of these tests under stress. Consult with an experienced doctor to understand your situation, before doing any tests for multiple miscarriages.

Recurrent Miscarriage treatment options

Understanding the cause of recurrent miscarriage is important, so treatment can be tailored accordingly. The below treatments are considered:

In women with anti-phospholipid syndrome or congenital thrombophilia, anticoagulants may increase chances of successful pregnancy.
Certain chromosomal situations call for the usage of PGD testing with IVF to check the genetic makeup of embryos before implanting them in the uterus.
After examination of the shape and size of the uterus, the doctor may check for and remove any abnormal growths, polyps, fibroids, uterine septum or scar tissue that may be interfering with pregnancy.
If the problem is with the uterus, you can opt for surrogacy – an arrangement in which another woman agrees to carry your baby in her womb.
For miscarriages due to thyroid or other endocrine problems, hormonal pills may be given and pregnancy is attempted only after the hormone levels are conducive.
In cases of unexplained recurrent miscarriages, there is no universally acceptable recommendation or any RPL treatment. The chances to conceive after recurrent miscarriages of unknown reason are quite good, but every additional loss worsens the prognosis and increases psychological and physical risk to the mother.

Does IVF help with recurrent miscarriage?

Depending upon the reason for multiple miscarriages, IVF may or may not be helpful.

Unsuccessful IVF or early loss of IVF pregnancy is often attributed to poor genetic condition of the female egg.

The quality of female eggs worsens over time and the chances to get embryos with abnormal genetic makeup are high as you touch your 40s. If you have undergone IVF several times but miscarried early, it is probably due to embryo arrest.

If eggs are the reason, you may talk to your doctor and consider IVF with donor eggs.

Dr. Tan Chong, an experienced IVF specialist in Malaysia, said that most commonly the below three investigations are done for repeated miscarriages:

Thrombophilia screening
Autoimmune screening
Chromosomal screening

Other than this, consider sperm DNA fragmentation testing which is helpful in finding out the integrity of a sperm at the molecular level.

Sperm with damaged DNA may be responsible for recurrent miscarriages.

One of our clients—an Australian couple—underwent eight unsuccessful IVF cycles in over 10 years in several different countries, only to find out eventually that the sperm DNA was responsible for the failure. A simple test could have saved them years of anguish and disappointment.

However, sperm DNA analysis is not advised for everyone. Consult with an experienced fertility expert to understand what may have caused your repeated miscarriages, before you spend any money on IVF.

If you are having trouble conceiving or have been facing recurrent miscarriages, get in touch to consult with some of top fertility doctors on our panel and see if you can find a direction towards completing your family.

To consult with a specialist for recurrent miscarriage and possible treatment options, get in touch via the form on this page.

With contributions from Dr. Tan Chong Seong and Dr. Leong Wai Yew, IVF specialists in KL, Malaysia.

Resources:

Kwak-Kim J, Kim JW, Gilman-Sachs A. Immunology and Pregnancy Losses: HLA, Autoantibodies and Cellular Immunity. In: Madame Curie Bioscience Database [Internet]. Austin (TX): Landes Bioscience; 2000-2013. https://www.ncbi.nlm.nih.gov/books/NBK6615/

Di Prima, F. A., Valenti, O., Hyseni, E., Giorgio, E., Faraci, M., Renda, E., De Domenico, R., & Monte, S. (2011). Antiphospholipid Syndrome during pregnancy: the state of the art. Journal of prenatal medicine, 5(2), 41–53.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279165/

Recurrent Miscarriage, Miscarriage Association: https://www.miscarriageassociation.org.uk/information/miscarriage/recurrent-miscarriage/

Recurrent Pregnancy Loss, Washington University Physicians: https://fertility.wustl.edu/getting-started-infertility/multiple-miscarriages/

MTHFR Gene, Folic Acid, and Preventing Neural Tube Defects, Centers for Disease Control and Prevention: https://www.cdc.gov/ncbddd/folicacid/mthfr-gene-and-folic-acid.html

Miscarriage or Recurrent Pregnancy Loss, American Society for Reproductive Medicine: https://www.asrm.org/topics/topics-index/miscarriage-or-recurrent-pregnancy-loss/