9/2024
What is recurrent pregnancy loss (RPL)?
RPL is a condition when an individual has 2 or more clinical pregnancy losses (ie miscarriages) before 20 weeks of pregnancy. Loss of a “clinical pregnancy” is diagnosed by a healthcare provider using ultrasound. In most cases, a pregnancy can be seen with ultrasound as early as 5-6 weeks’ gestational age (or 1-2 weeks after a missed period). It is estimated that fewer than 5% of pregnant individuals will experience two consecutive (back-to-back) miscarriages, and only 1% experience three or more. In 50–75% of people with repeated miscarriages, no cause can be found for the pregnancy losses.
A “biochemical pregnancy” loss is one that has been detected only by urine or blood hormone testing alone and is never identified on ultrasound. Biochemical pregnancy losses are not usually included in making an RPL diagnosis.
What are the causes of RPL?
Genetic:
Many early miscarriages (about 60%) (the ones that happen in the first 3 months of pregnancy) are due to genetic abnormalities in the embryo or fetus. Genetic causes contribute 2 to 5% of RPL cases. Karyotypic (chromosome) analysis of products of conception may be useful in the setting of ongoing therapy for RPL. In addition, referral to a genetic counselor may be beneficial. Finally, as we age, the miscarriage risk due to these genetic abnormalities increases — from 10%-15% in individuals younger than 35 years old to more than 50% in those over 40 years old.
In a small number of people who have repeated miscarriages, one partner has a chromosome in which a piece is transferred to another chromosome. This is called a translocation. People who have a translocation usually do not have any physical signs or symptoms, but some of their eggs or sperm will have abnormal chromosomes. If an embryo gets too much or too little genetic material, it often leads to a miscarriage. A blood test called a “karyotype” can be done to assess the chromosomes of gthe person who contributed the egg and sperm.
Anatomic:
Certain congenital problems of the uterus are linked to repeated miscarriages. Anatomic abnormalities contribute 1.8 to 37.6% (mean 12.6%) of RPL cases. Sonohysterogram, hysterosalpingogram, and/or hysteroscopy can show if a person has a problem with the shape of their uterus. This can be followed-up with an MRI or 3D ultrasound if necessary. Although there are many such anatomic abnormalities, the one that has been more commonly associated with pregnancy loss (44.3%) is a septate uterus. In this condition, the uterus is partially divided into two sections by a wall of tissue. A septate uterus can be managed with resection via hysteroscope. Another anatomic cause involves having a band of tissue inside the uterus, called a septum. This can make the inside of the uterus too small. People born with a septum may have more frequent miscarriages. Finally, an unicornuate, didelphic, bicornuate or arcuate uterus can also be associated with RPL.
Asherman syndrome, in which adhesions and scarring form in the uterus, may be associated with RPL, as can fibroids and polyps, which are benign (noncancerous) growths of the uterus. Fibroids can lead to miscarriages if they grow into or near the uterine cavity. Surgical correction of these abnormalities should be considered, although evidence is lacking that it is a contributor to RPL or will improve pregnancy outcomes.
Lifestyle/Environmental:
- Smoking increases the risk for RPL.
- Using certain recreational drugs, such as cocaine, can alsolead to miscarriage.
- Being overweight has been linked with RPL as well as otherpregnancy complications.
- Excessive alcohol or caffeine intake might be linked withRPL.
Medical:
Antiphospholipid Syndrome
Antiphospholipid syndrome (APS) is an autoimmune disorder in which a person’s immune system mistakenly makes antibodies to certain substances involved in normal blood clotting. APS is associated with repeated miscarriages and fetal deaths, and contributes to 8 to 42% (mean 15%) of RPL cases. A large proportion of pregnancy losses related to anti-phospholipid antibodies occur in the fetal period (greater than 10 weeks of gestation). However, fetal deaths at these gestational ages normally account for only a small proportion of all pregnancy losses in the general population, which occur more frequently before 10 weeks of gestation. Although antiphospholipid antibodies also are not associated with sporadic embryonic pregnancy loss, they have been associated with recurrent embryonic or fetal loss or both. Screening for lupus anticoagulant, anticardiolipin antibodies, and anti-b2 glycoprotein I for APAS.
- Clinical Criteria for Diagnosis:
- 1. Vascular thrombosis:
One or more clinical episodes of arterial, venous, or small vessel thrombosis, in any tissue or organ,
OR
- 2. Pregnancy morbidity:
- One or more unexplained deaths of a morphologically normal fetus at or beyond the 10th week of gestation, with normal fetal morphology documented by ultrasound or by direct examination of the fetus,
OR
- One or more premature births of a morphologically normal neonate before the 34th week of gestation because of eclampsia or severe pre-eclampsia, or features consistent with placental insufficiency,
OR
- Three or more unexplained consecutive spontaneous pregnancy losses before the 10th week of pregnancy, with maternal anatomic or hormonal abnormalities and paternal and maternal chromosomal causes excluded.
Laboratory Criteria: Must occur twice ≥12 weeks apart
- Lupus anticoagulant
- Anticardiolipin IgG or IgM
- Anti-beta2 glycoprotein IgM or IgG'
APL treatment includes:
- Low dose aspirin
- Twice daily heparin
Inherited thrombophilias (Factor V Leiden, Prothrombin, Protein C, Protein S, Antithrombin deficiency)
Testing for these disorders IS NOT recommended routinely for RPL. Testing is ONLY indicated in patients with:
- Personal history of venous thromboembolism (VTE)
or
- First degree relative with known/suspected thrombophilia
Diabetes
Another disease that can lead to miscarriage is diabetes mellitus. In this disease, high levels of glucose are present in the blood. Patients with diabetes, especially those in whom the disease is poorly controlled, have an increased risk of pregnancy loss.
PCOS
Individuals with a condition called polycystic ovarysyndrome also have an increased risk of miscarriage.
Thyroid disease
Untreated medical conditions, such as hyperthyroid disease, can increase the risk for miscarriage.
Elevated Prolactin levels
Unexplained
In over half of RPL cases, doctors cannot find the cause for losses. However, many of these may be due to genetic reasons.
Are there treatments available for RPL?
People with persistent, moderate-to-high titers of circulating antiphospholipid antibodies can be treated with a combination of prophylactic doses of unfractionated heparin and low-dose aspirin. There are surgical treatments for some uterine anomalies. Treating diabetes, thyroid disorders, hyperprolactinemia can improve fertilty.
When considering progesterone, the overall available evidence suggests that progestogens probably make little or no difference in live birth rates for people with threatened miscarriage (ie bleeding in early pregnancy with no history of pregnancy loss). However, vaginal micronized progesterone may increase the live birth rate is patients with a prior early pregnancy loss and vaginal bleeding in the current early pregnancy. Prophylactic progesterone supplementation can be considered in patients who have had ≥3 or more consecutive miscarriages.
Will I be able to have a baby even with a history of RPL?
What should I do if I want to keep trying?
- Take time to recover emotionally before trying again. However, you can ovulate and get pregnant as soon as 2 weeks after an early miscarriage.
- See your ob-gyn for a prepregnancy care checkup.
- Take 400 micrograms of folic acid as a daily dietary supplement.
- Follow a healthy diet and get 30 minutes of exercise on most days of the week.
- Reach a normal weight for your height. Lose weight if you are overweight or gain weight if you are underweight.
- Do not drink alcohol.
- Do not smoke.
- If you have a medical condition, work with your health care team to get your condition under control before trying to get pregnant.
You may also decide not to try to get pregnant again. No choice is right or wrong. You should decide what is best for you.
Pregnancy Loss Support
As someone who has experienced early pregnancy loss, I know first-hand how devastating it can be. No matter if it is a miscarriage, stillbirth, or ectopic pregnancy, there are support groups available to help you. If you have experienced a pregnancy loss, this article in Very Well Family is a tremendous resource in which to find support. You can also go to Resolve.org!
Live Discussion on Early and Recurrent Pregnancy Loss
Joining me to discuss this topic in depth is Dr. Erica Montes, an ObGyn from Phoenix, Arizona. You can connect with her and follow her on Instagram @the.modern.mujer and www.themodernmujer.com.
We cover the many reasons early pregnancy loss can occur. We also discuss whether each loss is considered in a recurrent pregnancy loss workup or not. Physicians do not always include all pregnancy losses in recurrent pregnancy loss workup, but they will still keep it noted in your medical history. Although a full workup may not be done, know that as a patient and parent it is absolutely OK and normal to grieve the loss. If you are concerned about pregnancy loss, have experienced it, or are wanting to understand more about it, this discussion will be very helpful.
Topics Covered:
4:42- Chemical Pregnancy Loss
A chemical pregnancy is when you have a positive pregnancy test right after you miss a period, but the next test is negative or you have a period shortly after. It occurs at less than 5 weeks and is thought to be caused by chromosomal abnormalities. A biochemical or chemical pregnancy is not considered in a recurrent pregnancy loss workup. This is because it was super early before there was ever a viable fetus in the uterus or anything showing up on an ultrasound. However, if there are multiple chemical pregnancies back-to-back, a fertility doctor may do a work-up to see what might be the underlying cause.
9:12- Anembryonic Demise/Pregnancy or Blighted Ovum
It’s thought that these types of pregnancy losses make up about half of all pregnancy losses. These losses are included in a recurrent pregnancy loss workup because there was a sac in the uterus that showed up on an ultrasound at some point.
10:44- Ectopic Pregnancy
When a pregnancy implants anywhere other than the uterine cavity, an ectopic pregnancy has occurred. These losses are not considered in a recurrent pregnancy loss workup. Some factors that can increase the risk for ectopic pregnancy are STD’s like Chlamydia, smoking, tubal ligation or sterilization, age, and IVF.
13:28- Molar Pregnancy
This is a genetically abnormal pregnancy. A patient may present with a larger than normal uterus, possibly with bleeding or pain because there can be cysts on the ovaries. This is not included in a recurrent pregnancy loss workup
16:40- How Common is Early Pregnancy Loss.
We want patients to understand that early pregnancy loss is not caused by one’s own fault in any way. Although early pregnancy loss is common, it can still be devastating.
18:18- Chromosomal Abnormalities
30:00- When will a patient have D&C versus medical management of an early pregnancy loss
32:24- D&C (Dilation and curettage)
34:40- The option to pursue genetic testing on products of conception (to check for chromosomal analysis) after an early pregnancy loss
35:40- How long a patient should wait to get pregnant again after experiencing an early pregnancy loss
40:00- Progesterone supplementation (if, and, or when it is used)
42:06- Recurrent Pregnancy Loss
As always, I hope that this information helps you feel empowered in your journey.
