Dr. Karenne Fru, MD, PhD
Dr. Fru, for those who aren’t familiar please explain a diagnosis of recurrent pregnancy loss.
As it is implied in the title this means someone who has suffered more than one loss. The number at which that would typically bring someone to clinical attention is two or more losses, especially in the first trimester. So anyone who has had more than one pregnancy loss falls into the category of recurrent pregnancy loss.
What are some of the causes? Is age a factor?
The leading cause is due to chromosomal mistakes which are more likely to happen the older the mother is because the egg is responsible for so much of early embryonic development. The miscarriage rate in the general population rise to over 40% by age 40.
Other causes can be things like structural problems that have not come to light yet in the uterus. It could be structural problems that develop over time like fibroids, or polyps, things that affect the intrauterine cavity but are not congenital. There are other things like congenital uterine anomalies, in particular, septate uterus which is where the uterus starts being formed, and the dividing wall that makes it one unified cavity does not completely resorb like it’s supposed to in development. So you wind up with two chambers and a thin wall that does not have the proper musculature and vasculature to support a pregnancy so if implantation happens on this wall it tends to end in miscarriage. You could have it and have babies and never know it, or you could be unfortunate enough to have it and suffer losses prior to discovering a septum.
Are there other causes related to the mother?
Yes, the other causes I want people to think about are things like metabolic disorders in the mom. So moms with uncontrolled diabetes for example or moms with hyper/hypo thyroid dysfunction can contribute to pregnancy loss so we are typically screening patients for those factors as well. The last category of things we are looking for is Antiphospholipid antibodies Syndrome (APAS) is a clotting pathology that can negatively impact pregnancy. If you have these specific antibodies it causes clotting with the establishment of pregnancy. Pregnancy is largely a vascular process, whereby the embryo invades the wall of the uterus and sets up a system where there is naturally a placenta that acts as an interface between mom and baby. That’s where the baby gets all its nutrients and all the waste gets cleared out. So we get compromised blood flow and either the failure to establish a pregnancy or an early arrest in the development of that pregnancy and you end up with a pregnancy loss.
Can these losses occur anytime over the course of the pregnancy or do they tend to occur during a specific trimester?
People with APAS can manifest with term stillbirth or intrauterine fetal demise in the second trimester, or a first-trimester pregnancy loss. The women who are found to have a positive APAS test have repeated testing 12-weeks later and if that is still found to be positive they are recommended to start a blood thinner with their pregnancies to give them a better chance of continuing all the way through. The other causes of pregnancy loss that I described tend to result in first trimester losses
Does PCOS or Endometriosis affect pregnancy loss?
No, what we are looking for is structural issues. The role of PCOS and endometriosis affects egg quality and ovulation. Once a pregnancy is established neither of them causes an increased risk for pregnancy loss.
What percentage of patients do you see at PREG that have this diagnosis?
It is rare, less than 5% of all patients that we take care of, but for recurrent pregnancy loss, it is the second most likely causal factor so we definitely evaluate patients for congenital structural abnormalities in addition to things that can develop over time like fibroids.
Does family history or genetics affect recurrent pregnancy loss?
Genetic testing is typically to look at karyotype. Most mistakes that occur genetically and result in pregnancy loss are non-repeating mistakes, meaning they are unique to the event of the generation of that embryo when the egg and the sperm come together. However, there are some individuals who have structural rearrangements in their chromosomes which will make it way more likely that they will make a mistake every single time they go to generate a gamete; egg, or sperm. So for those individuals, we check a karyotype which is an analysis of all the chromosomes, and through that, we can detect if there has been something called a translocation, which is when chromosomes swap material, which makes it more difficult for you to wind up statistically with the correct amount of chromosomal material in the resulting embryo.
What are treatment protocols for women who experience translocations?
The treatment for people with balanced translocations or translocations, in general, would be to put them through IVF, generate a good number of embryos, and then genetically screen those embryos to make sure that they chromosomally euploid (we have the right complement of genetic material) understanding that the vast majority are going to be abnormal, but then this is a way to discriminate and only transfer back into the uterus a euploid embryo, which then has a higher probability of becoming a child.
Can you speak to the utter sense of loss and hopelessness these women experience?
There is built-in anxiety that develops over subsequent pregnancies so typically I recommend that they follow up with a mental health specialist who specializes in grief and pregnancy loss because I wish for all my patients who have this diagnosis to be able to celebrate the next pregnancy as a unique genetic event that will never happen again and has never happened before!
Is there a correlation between successful pregnancy outcomes and succeeding failures?
Only in as much if you had a baby in your 20’s that had a lower chance of pregnancy loss and then you waited until your late 30’s to attempt to conceive. With increasing age comes a higher chance of pregnancy loss.
Are OBGYN’s equipped to recognize this in their patients and refer them to infertility treatment?
Most individuals will self-identify as far as the problem that they’ve been pregnant and don’t have a baby to show for it. The statistics are that 20-25% of productive age women will have one pregnancy loss. That number drops to 5% for two pregnancy losses. But if we look at the group that has had three or more pregnancy losses, even without intervention, their chances of taking home a baby on the next pregnancy is 60-70%.
How have technology and science improved this diagnosis and treatment in terms of favorable outcomes previously unavailable?
There is just more awareness around the topic of pregnancy loss. Most people recognize that one loss is about the norm that captures the largest population of women. Most women who’ve had several especially consecutive losses understand that it is not normal and identify themselves to either their OBGYN, or they find a reproductive endocrinologist. So that is really the first thing is kind of putting the pieces of the puzzle together. A woman with three consecutive pregnancies that end in a loss in my mind is a little different from a woman that has had three losses that interspersed three living children. The losses are interspersed with normal pregnancies are generally the result of mistakes. From a technology standpoint, we now have the benefit of IVF to assist with ruling out chromosomal abnormalities for patients in hopes of avoiding another pregnancy loss.
Doesn’t this just stress the critical need for women to have regular and ongoing OBGYN care?
For most women, that is the only doctor they will see all year if they are otherwise healthy. There are several conversations to be had so with each OBGYN visit you get an update on: “Have you been pregnant over the last year?” When I get a new patient one of the first questions I ask is “how many pregnancies have you had and how did each one of those end?” So we are looking to identify the individuals who get pregnant (that is not why they are in my office, it’s not infertility) but have demonstrated difficulty in having healthy babies. Once we identify that we go through the workup to see if there is anything we can correct with say surgery to correct certain structural issues, we can offer IVF to look for chromosomal abnormalities that would be the role of IVF in recurrent pregnancy loss treatment and we can also offer supportive care. If we do absolutely nothing the next pregnancy is unlikely to make it all the way. OBGYN’s being regularly present in the care of their patients is critical so that women can get early and regular ultrasounds to see if things are going well or if they are not. This helps us down the road in infertility treatment and care.
What about the effects of lifestyle behaviors in regard to chances for a successful pregnancy?
Certainly, we are always counseling our patients against lifestyle habits that would be detrimental to the continuation of a pregnancy. Smokers have intrauterine growth restrictions in their babies so there is already a vascular problem there. People at the extremes of BMI (body mass index) are predisposed to miscarriage. I’m usually encouraging patients to modify the things that they do have some control over. I do not wish to give the impression that it is the cause of pregnancy loss because the mother will blame herself. I tell my patients that what we are working on is controlling as much as we can control so that we have a better outcome for the next pregnancy. Weight loss, exercise, smoking cessation, and monitoring drinking or eliminating it if they have a problem with it. Overall we just want to optimize health in these and all of our patients. When we meet a patient it is an opportunity to intervene so that they are set up for a healthier pregnancy with a better outcome.
PREG has IVF Centers and ORs in Greenville, Lowcountry, and Columbia, and satellite offices in Asheville and Spartanburg. We offer highly personalized fertility care and management. Dr. Fru is based at the Columbia, SC, office. For more information on reproductive options call, or contact us today at 866.725.7734, or online at http://www.pregonline.com/contact-us.php
Dr. Karenne Fru, MD, PhD
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