Q&A: Recurrent pregnancy loss can be overcome

Miscarriage is a common result of pregnancy involving the loss of the fetus before 20 weeks’ gestation, according to Mayo Clinic.

Having two or more of these losses in a row is defined by ACOG as recurrent pregnancy loss. There is no single cause of recurrent pregnancy loss, so clinicians should know how to address the needs of patients with recurrent losses to help them have a successful pregnancy.

Healio spoke with Jeff Chapa, MD, head of the section of maternal-fetal medicine at Cleveland Clinic Children’s Hospital, to learn more about recurrent pregnancy loss and what clinicians should focus on in practice.

Healio: What causes recurrent pregnancy loss and how common is it?

Chapa: Recurrent pregnancy loss is defined as two or more consecutive losses, and in the overwhelming majority of cases the answer is, we don’t know what causes it. Miscarriages, especially early miscarriages, are just a normal part of reproduction, and about 50% to 60% of those result from an underlying chromosome abnormality in the embryo or the conception and the embryo is not compatible with life. These are things that happen sporadically, and they’re not likely to recur again. Other times, there are very severe birth defects in fetuses that we can’t even see on the ultrasound, but they just occur very early. That’s for a lot of miscarriages, but some we don’t exactly know what the cause is. A lot of times, there isn’t any one thing; it’s just chance.

Approximately 15% to 20% of all clinically recognized pregnancies end in miscarriage or loss. So, it’s very common. Then recurrent pregnancy loss — having two or more in a row — if you do the math, 3% to 4% of people are going to have two losses in a row. To have two losses in a row doesn’t mean that there’s actually something going on that’s causing recurrent pregnancy loss.

Healio: Is recurrent pregnancy loss more common for people who have or have not given birth before?

Chapa: It can affect both parous and nonparous people, but the likelihood that there is an underlying cause is probably going to be higher in someone who’s nonparous. In general, if someone’s had a child before, they’re likely to be able to do it again, and it’s more likely that it’s just their losses are due to chance. Sometimes there are reasons, but it’s in nonparous people that we think it’s more likely to be due to an underlying cause.

Healio: What is the likelihood of ever becoming pregnant once you have experienced recurrent pregnancy loss?

Chapa: Very high. The overwhelming majority of people with two consecutive losses are able to get pregnant and have children and have multiple children. I have a patient who had seven straight miscarriages and then she had two kids. We couldn’t find a cause.

Healio: Are there any treatments available or in the pipeline?

Chapa: A good way to frame this is recognize that losses are common — 15% to 20% of pregnancies end in miscarriage. A lot of times, it’s due to a chromosome abnormality or a birth defect or something that’s in the baby, and these are sporadically occurring things that don’t tend to recur. But then, what are the causes of why somebody might continuously have miscarriages. This is part of the evaluation for someone who’s had multiple losses.

No. 1, sometimes there can be an issue inside the uterine cavity, there can be a malformation in the way that the uterus is developed. So, there can be a uterine septum, which is some extra tissue in the lining that makes the cavity not hospitable for implantation, so that people lose pregnancies because the placenta implants on the septum. They can have fibroids, which are benign tumors in the wall of the uterus that kind of impinge on the cavity of the uterus, and they can also lead to poor implantation and losses that way.

There can be diseases in the mother. If there’s thyroid disease that’s not well controlled, or diabetes that’s either unrecognized or very poorly controlled, that can lead to miscarriages. There’s an autoimmune condition called antiphospholipid antibody syndrome. Basically, it’s an autoimmune condition that predisposes to clotting. So, the immune system works and it leads to clotting in the placental circulation and causes pregnancy losses or other adverse pregnancy outcomes. It prevents adequate blood flow to the developing pregnancy because the circulation kind of clots off.

Another cause is luteal phase defect. In the early part of pregnancy, you need progesterone to maintain the pregnancy. Usually that’s made by the ovary, but sometimes, some people don’t make enough progesterone and they lose pregnancies because of that. The problem is that initially in the pregnancy, progesterone is made by the ovary, and if your ovary for whatever reason doesn’t function right and doesn’t make enough progesterone, people continue to lose pregnancies. By about 10 weeks or so, the placenta makes all the progesterone that is needed to continue the pregnancy, but for that early part of pregnancy, that ovaries usually make some progesterone and that’s what’s needed to maintain the pregnancy. They sometimes will treat those patients with progesterone.

Another cause of recurrent pregnancy loss is what’s called a balanced translocation or inversion, which is a chromosome rearrangement in one of the parents. Basically, the genetic material is all there, but it’s arranged in a different way, so parts of one chromosome are stuck to another part of another chromosome. What happens is when you go to have children, the egg and the sperm don’t get equal amounts of the chromosome material, so there’s an unbalanced chromosome arrangement. That is inherited.

The treatments are based on what the underlying cause is. If you think that someone has the luteal phase defect, then they supplement them with progesterone. If you think someone has a uterine anomaly, sometimes there’s surgery done to either remove the septum or the fibroid to allow for a more hospitable environment inside the uterus. If you think they have antiphospholipid antibody syndrome, then the treatment for that is a blood thinner early and aspirin. For thyroid disease and diabetes, it’s just controlling those conditions. Then for the chromosome rearrangement, there’s not a lot you can do, per se, to treat it, but some people have in vitro fertilization and then testing the embryos for their genetic component. Then they only put the ones back that have a normal chromosome complement. So, treatments are tailored toward the underlying cause.

Healio: What work needs to be done to address recurrent pregnancy loss?

Chapa: Most people are able to conceive and have successful pregnancy outcomes. The work that needs to be done is to counsel people to that effect, because I think people have losses and we’re searching for a cause that may not actually be there. It’s hard to tell someone, there’s nothing wrong, just keep going, especially after a couple of losses. Even after three or four losses, the overwhelming majority of people are going to get pregnant and be successful. The work that needs to be addressed is for people to understand how common this is and how well people do, especially if they’ve had a basic workup and everything is normal.

Now, what are things that you can do to improve your chances if you have a history of recurrent pregnancy loss? That’s a good question. There’s not a magic pill, but lifestyle modifications — diet, weight loss. For example, having overweight or obesity is associated with an increased risk for miscarriage. We’re not sure why, but it is. So, getting your health in order — losing weight, eating properly, cutting out things like alcohol and smoking cigarettes or marijuana — those kinds of behavior modifications can go a long way toward improving outcomes.

Healio: Is there anything else you would like to add?

Chapa: The most important thing is that people understand that miscarriages are common. We kind of have a decent idea of why a lot of them occur; some of them, we don’t. But even in folks that have had recurrent losses, there isn’t an identifiable cause for the overwhelming majority, and those people are going to be able to get pregnant and be successful. Sometimes, patients get frustrated because they can’t find a cause. I would say that it’s actually better that we don’t find a cause because their likelihood of being successful in the future is probably higher if they don’t find a cause. That’s somewhat counterintuitive because you’re operating on the assumption that there’s something there, but in general, there isn’t that we know of to date.

Now, could there be causes that we don’t know of? There are lots of things that we don’t know. We don’t know if there’s other immune-mediated mechanisms that occur. Our understanding of how the immune system works in this setting is somewhat limited. All that being said, the outcomes are still really good for most people.

References:

• Pregnancy after miscarriage: What you need to know. www.mayoclinic.org/healthy-lifestyle/getting-pregnant/in-depth/pregnancy-after-miscarriage/art-20044134. Published Oct. 27, 2021. Accessed Feb 2, 2023.
• Repeated Miscarriages. www.acog.org/womens-health/faqs/repeated-miscarriages. Updated January 2023. Accessed Feb. 2, 2023.