The American Society for Reproductive Medicine (ASRM) has released updated guidance for diagnosing and treating recurrent pregnancy loss (RPL) because of the risk of underdiagnosis of this distressing problem. In the past, a person was only diagnosed with RPL if she had three or more consecutive clinical losses prior to 20 weeks of pregnancy. But anyone who has had a second early loss can tell you this is something we should try to avoid.
Consecutive losses means multiple miscarriages in a row, with no live births in between. However, the problem with this is that some genetic causes of RPL don’t affect every pregnancy, because some pregnancies are still able to be genetically normal. And clinical losses means only losses that were confirmed pregnancies by ultrasound. However, women often miscarry before an ultrasound can be done. This is called a biochemical pregnancy. If you don’t have easy access to first trimester pregnancy care and ultrasound, you could be pretty far along and still meet this definition. Finally, different medical societies have used different cutoffs for when a miscarriage becomes diagnosed as a stillbirth, 20 versus 22 weeks.
The updated definition of recurrent pregnancy loss (RPL) now includes two or more miscarriages before 22 weeks. Key criteria include:
- Non-consecutive losses: You do not need to have miscarriages in a row to qualify.
- Biochemical pregnancies: Losses confirmed only by a positive pregnancy test are included.
- Exclusions: This definition does not include molar or ectopic pregnancies, which have distinct, known causes.
Causes of RPL are generally grouped into four categories:
- Genetic
- Uterine
- Immune
- Medical
The most common genetic cause is aneuploidy, where the egg fertilizes abnormally and has an abnormal number of chromosomes. This causes 50-60% of all losses and can just happen. We recommend testing every miscarriage for chromosome problems if you have had a miscarriage already. This isn’t always possible, but if it is abnormal, it can spare you a lengthy and expensive evaluation. Another cause is called balanced translocation. This is when a piece of one chromosome has broken off and reattached itself to another chromosome. You have all the correct amount of DNA but if you separate the chromosomes to make an egg or a sperm, that egg or sperm will have an abnormal amount of DNA and this causes a 50% miscarriage rate in people who have this. The test for this is a chromosome test on both parents. Genetic diseases can cause miscarriages and these can be tested with genetic carrier screening. Finally, sperm DNA fragmentation is a cause of miscarriage. The embryo has a normal chromosome number (euploid) but other DNA problems affect the ability of the embryo to grow and implant properly.
Uterine causes are diagnosed with imaging of the uterus with a saline sonogram, X-ray dye test of the uterus (HSG), or a scope to look inside the uterus with a camera called hysteroscopy. We can diagnose birth defects of the uterus such as a uterine septum, which can cause recurrent miscarriages. Also, fibroids or polyps may increase the risk of miscarriages when they interfere with the uterine cavity. These can be corrected with surgery. Finally, we can test the uterine lining for chronic infection called chronic endometritis with a biopsy. This is treated with antibiotics.
Immune causes of recurrent miscarriage cause the blood to clot abnormally and are treated with blood thinners. These are checked with a blood test. However, the number of tests we do for this diagnosis has decreased because we have discovered that blood clotting problems that are genetic (familial thrombophilias) are not associated with miscarriages as much as we used to think.
Finally, medical causes can contribute to RPL. Exposures to toxins and endocrine disruptors, microplastics, and other toxic substances can cause miscarriages. Tobacco, nicotine, THC and alcohol are all associated with losses. Obesity, poor diet, chronic inflammation, diabetes, high blood pressure, and lupus are also associated with miscarriage and need to be optimized.
So what is new? First, we now consider two or more losses to be the diagnosis of recurrent miscarriage. Second, these losses don’t need to be consecutive. This means that you can get an evaluation sooner. You don’t need to have three miscarriages to justify testing your next loss for chromosome abnormalities. Likewise, you should be able to get uterine and parental genetic testing after only two losses, especially if these are very early losses or biochemical pregnancies. This is great news, as it allows a faster diagnosis and a shorter time to having a healthy baby.
