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Renowned fertility specialist Oluyemisi (Yemi) Famuyiwa discusses her article, “When bleeding disorders meet IVF: Navigating von Willebrand disease in fertility treatment.” She explains that von Willebrand disease (VWD), the most common inherited bleeding disorder, affects up to 1 percent of the population and poses unique challenges for women undergoing fertility treatments. Because many women normalize symptoms like heavy menstrual bleeding, VWD often goes undiagnosed until an invasive procedure like IVF egg retrieval reveals the condition. Yemi details the specific risks, including hemorrhage during oocyte retrieval, and outlines a comprehensive management strategy. She emphasizes that while IVF is feasible for women with VWD, it requires a carefully planned, multidisciplinary approach involving both hematologists and reproductive specialists. This includes a thorough pre-IVF workup to determine VWD type and severity, a personalized prophylaxis plan that may include desmopressin or factor replacement, and close monitoring during the procedure and postpartum period to ensure a safe and successful outcome.

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Transcript

Kevin Pho: Hi, and welcome to the show. Subscribe at KevinMD.com/podcast. Today we welcome back Oluyemisi Famuyiwa. She’s a fertility specialist. Today’s KevinMD article is “When bleeding disorders meet IVF: Navigating von Willebrand disease in fertility treatment.” Yemi, welcome back to the show.

Oluyemisi Famuyiwa: Thank you. Thank you. Nice to be here.

Kevin Pho: All right, so we are going to talk about a bleeding disorder as it relates to fertility. Just to get everyone on the same page, before we talk about the article, just tell us what von Willebrand disease is.

Oluyemisi Famuyiwa: So von Willebrand is actually one of the more common inherited blood disorders. When people have it, they do not form blood clots very easily. So when they have even a minor cut, it tends to just bleed more, or they have nosebleeds that just do not stop bleeding.

Kevin Pho: All right, and then tell us about the article and how that relates to fertility treatment.

Oluyemisi Famuyiwa: Yes. So, the reason I wrote that article is because I had a patient who had a history of von Willebrand’s that was undetected. She gave a history of having nosebleeds in the past. She had heavy menstrual periods that lasted days, but they never thought anything of it. So she had been seen in a previous center and had IVF done.

Post-procedure, she simply hemorrhaged. An ambulance had to be called, she was sent to the hospital, had to have a hematologist come in, and they flat out told her, “No way, no how, we are not doing any IVF anymore.” And she came to see me for a second opinion.

So that just piqued my interest and I thought, this is a common enough bleeding disorder. There are a lot of people with it. Why do I not try to shed some light on it?

Kevin Pho: So tell us about some of the bleeding risks when it comes to IVF. For people on anticoagulation or antiplatelet therapy, tell us the bleeding risk. And in general, what type of precautions does one have to take before undergoing a treatment?

Oluyemisi Famuyiwa: The key thing is accurate diagnosis. So, I think when someone gives all those histories that they have had nosebleeds, heavy menstrual cycles, or some people may say, “I delivered a few years ago, and I went into shock. I just did not stop bleeding.” I think the key thing is the accurate diagnosis. Because when you have an accurate diagnosis, you can now set plans in action. The treatment for patients with von Willebrand’s is a multispecialty approach. You cannot do it alone. You need a hematologist in place who understands the disease correctly. They have to understand which type of von Willebrand’s the patient has. There are three types—Type 1, 2, and 3—and one is mild, one can be severe.

So knowing exactly what type they have, putting precautions in place, having things like co-factors, Factor VIII if it is severe, or desmopressin available, certainly not in an outpatient setting, and also having anesthesia be aware of what is involved. So I think it involves a multispecialty approach because these people can bleed internally. After you collect the eggs and everybody goes home, what if they open up and just bleed on the inside? And that could be like a ruptured ectopic; they could die from that. So bleeding at the time of procedure or bleeding post-procedure could be a complication.

And then beyond IVF, these patients are also at risk for miscarriages. So if you have had a long-fought drive to get pregnant, you want to make sure you do not lose it. And now there is some recent scientific evidence that it may also be a risk factor—it is not conclusive yet—it may be a risk factor for the development of endometriosis.

Kevin Pho: So how about for people without von Willebrand’s? Just in general, what is the bleeding risk for IVF procedures?

Oluyemisi Famuyiwa: For normal patients, it is very minimal. OK. Very, very minimal. If you have a normal CBC and a normal PT/PTT, it is very rare that you have a bleeding problem. Knock on wood, I have never had any severe hemorrhage of any of that sort. But I have also seen patients who were aspirated and maybe the surgeon hit a vein. So you have to be very familiar with what the anatomy looks like on the ultrasound when you are doing your egg retrieval. So it is very simple: Do not hit a blood vessel.

Kevin Pho: Now, do people have to hold anticoagulation or antiplatelet therapy before they go through a procedure?

Oluyemisi Famuyiwa: Yes. Absolutely. Some patients may be on Lovenox, OK, because they have a clotting problem. So we usually, in that regard, I like to work with their hematologist and get their suggestions. Lovenox is a blood thinner. It has to be stopped before retrieval, and they tell us exactly how many hours or days they want it stopped and how soon after it can be resumed. So if you are on a blood thinner, we need to work with your hematologist to determine when to stop it. You cannot be on a blood thinner when you are about to go through such a procedure.

Kevin Pho: Now, do you normally screen patients for these genetic hematologic disorders before they go through treatments?

Oluyemisi Famuyiwa: I do not particularly screen for von Willebrand’s. I do an overall genetic carrier testing. The testing that we use tests up to 780-something genes; it is the general genetic screen. So von Willebrand’s is one of the tests that we do. So we usually do genetic testing, period, and determine from that if there is any risk. Then the other test that you would look at is: Does someone have a normal CBC and a normal PT/PTT? If those are normal and they have a normal genetic carrier screen, they should be OK.

I like to use Fulgent carrier screening because it tests for 787 genes. So unlike the past where they would only test 120-something genes or 200-something genes, nowadays we test up to 780-something. So that is what I normally use.

Kevin Pho: OK. So now, getting back to our patient with von Willebrand’s. Correct.

So you mentioned a multifactorial approach. Tell us about some of the things that you mentioned, like DDAVP—that’s desmopressin, correct?—and factor concentrate. Tell us about how those work in terms of treating potential bleeding episodes.

Oluyemisi Famuyiwa: So, with von Willebrand disease, it is the von Willebrand factor that causes the problem. Either you do not have enough—that is Type 1, so it is harder to coagulate—or the ones you have are weak and not as good, or you do not have them, period. Those are the three types. It is either you do not have a sufficient amount of the good one, it takes a little while; you have a defective form, it is not working as well; or you simply do not have it.

So knowing which type you have lets you correctly address what strategy you are going to use to mitigate the circumstances. The von Willebrand factor is responsible for blood clotting for platelets. Let’s say you poke a hole through a blood vessel. Platelets form a little plug that stops blood from pouring out. So with von Willebrand’s, you cannot form those platelet plugs as well, and that is why those patients tend to bleed more.

Kevin Pho: And you mentioned that this has to be done each cycle inpatient with anesthesia and hematology on call?

Oluyemisi Famuyiwa: If they have the diagnosis of von Willebrand’s. If they do not—if they have a normal CBC, PT/PTT, if they have a normal bleeding time, if they do not have such a history that would make you suspect it—then you would not necessarily do all those things. But if you have a history of it, or you have a diagnosis of it, then you have to be cautious.

Kevin Pho: Now how successful—and you do not have to reference this specific patient—but in general, how successful are you with fertility treatments in those with von Willebrand’s disease?

Oluyemisi Famuyiwa: So with the right precautions, the risk with those patients is very minimal. It is the same risk as a normal person. So with the right precautions, there is no untoward aftereffect whatsoever.

Kevin Pho: So after a treatment in a patient with von Willebrand’s, tell us in terms of the aftercare, what kind of precautions do they have to take afterwards to prevent, as you said, a bleeding episode?

Oluyemisi Famuyiwa: As long as you have Factor VIII available and you have desmopressin available, patients do just fine. There is no other risk as long as those mitigations are put in place. They do just as well as any ordinary patient, so they can be successfully treated if the right precautions are in place.

Kevin Pho: So are there any other bleeding disorders outside of von Willebrand’s that you have had to deal with as a fertility specialist?

Oluyemisi Famuyiwa: Von Willebrand’s is the most common one. The other bleeding disorders that we deal with are actually the opposite: it is the clotting, abnormal clotting. So not so much bleeding as clotting. Those are problems such as homocysteine deficiency and all that, Thrombin III deficiency. So more blood clotting issues is what we see.

Kevin Pho: So in terms of von Willebrand’s, that patient came to you for a second opinion after the first opinion said under no circumstances could she do IVF. So there is hope, and there is a protocol for those with von Willebrand’s who want to pursue IVF.

Oluyemisi Famuyiwa: Absolutely. I think that if they have been appropriately treated, they can successfully go through IVF.

Kevin Pho: Do you recommend going to tertiary academic medical centers? Is this available at a community hospital? Tell us about the availability of the support.

Oluyemisi Famuyiwa: I would probably recommend that, or at least a hospital setting. Now, most IVF places are outpatient settings. So if I were to do it, I would either say, “Hey, listen, we have got to take the whole kit and caboodle over to the hospital,” or I would say, “Go to an academic center that can do the procedure in a hospital setting with emergency precautions available.”

Kevin Pho: We are talking to Yemi Famuyiwa. She’s a fertility specialist, and today’s KevinMD article is “When bleeding disorders meet IVF: Navigating von Willebrand disease in fertility treatments.” So Yemi, tell us some take-home messages that you want to leave with the KevinMD audience.

Oluyemisi Famuyiwa: The take-home message is to never overlook minor bleeding histories. Take a deep dive into it. Ask some questions. Look at the patient’s history, what their menstrual cycle is like, and when they started bleeding. I think just being curious, being a Sherlock Holmes about it, is what I would say.

Kevin Pho: Yemi, very educational. Thank you so much for sharing your perspective and insight, and thanks for coming back on the show.

Oluyemisi Famuyiwa: Thank you so much. I appreciate it.