How to Avoid the IVF Catastrophe of OHSS with guest Dr. Nichole Barker
The topic of today’s show is: how to avoid the IVF catastrophe of OHSS. Before we get to the interview, a quick introduction to Dr. Barker:
She is a member of the SRM team since August of 2012 she has special interest in IVF, PCOS, recurrent pregnancy loss and fibroids, She received extensive postgraduate training in minimally invasive surgery to enhance reproductive outcomes. She graduated with honors from John Carroll University in Cleveland, Ohio, with a degree in chemistry, followed by Medical school at Ohio University. She completed her OB-GYN residency and reproductive endocrinology and infertility fellowship at University hospitals, case medical center in Cleveland, Ohio, where she also served as executive chief resident and clinical instructor for Case Western Reserve University.
Dr. Aimee: So tell us a little bit about yourself. Why medicine and more specifically, why fertility?
Dr. Nichole Barker: I think I’m a natural-born caretaker. When I was young, I was always very interested in trying to see if somebody was needing help or hurt. The sight of blood never scared me at all. That, along with my love for science was a great blend.
Yet, reproductive medicine really wasn’t my plan. I fell in love with OB-GYN early in my residency. I loved the idea of helping a couple or person build a family, especially those struggling. I found the idea of that to be very rewarding. I fell in love with all of that as well as just the science of reproductive medicine.
Dr. Aimee: Would you share a little about your personal story?
Dr. Nichole Barker: Sure, I’m not shy about sharing my story. I’ve found that having been a fertility patient, and going through treatment was very informative as a doctor. I always say that being the patient has really allowed me to connect with my patients. I was a fellow when we did our first IVF cycle, and it went pretty well.
We did another round of getting eggs to do a fresh transfer, and I was surprised that I had some trouble. I was older and my estrogen levels weren’t as high. I took forever to stimulate, I wasn’t feeling so hot a few days before my transfer, and I noticed that I was having some epigastric pain. I was having a lot more pain than I did the first time, and I required more pain medication.
On the day before my plan transfer, I was in my office. I scanned myself and saw a bunch of fluid everywhere. After that I called my own doctor, who’s my partner and asked if they could look at the images. I didn’t think I should be doing a transfer the next day. Instead we froze embryos. Luckily, I did not need to be hospitalized or need supportive measures.
I was actually able to keep working. It definitely took about a week to resolve. And, it is not fun. I’d probably say I had a moderate case of OHSS, so I cannot imagine how it would feel for somebody with a severe case.
Dr. Aimee: So what is OHSS?
Dr. Nichole Barker: It’s an unusual situation. Ovarian hyperstimulation is typical in the world of fertility. We want to stimulate ovaries in most cases and get multiple follicles. And so ovarian hyperstimulation is not always bad.
When it becomes pathologic when you develop symptoms. The hallmark of these is that the ovaries are big, and you have lots of follicles, but there’s more going on. For instance, you can have some hyperpermeability of the vasculature.
When you have high estrogen levels, because of the follicles in some people, some serum can leak out and just accumulate into the abdomen. And sometimes it can even back up into the lungs and affect the kidneys. And because of that, the blood can become thick. With that, there’s a higher risk of like blood clots, and obviously in serious cases, stroke. In very serious cases, it can be life-threatening.
Most of the time people get with IVF everybody feels bloated. Everybody’s ovaries are humongous.
There’s actually a very low chance of developing a severe case of OHSS.
Dr. Aimee: You talked a little bit about estrogen levels, but do we know what the cause of OHSS is?
Dr. Nichole Barker: I think some people may have a genetic predisposition. However, there’s not a gene that we can test in our patients.
There are definitely people who are at higher risk right now. There is something called vascular endothelial growth factor (veg F) which we think is probably responsible for this hyperpermeability and fluid overload that happens in these patients.
Dr. Aimee: Is it something that is only specific to IVF or can you get it from any other treatment?
Dr. Nichole Barker: Great question. I’ve seen it with Clomid, which everybody thinks is so benign.
I do think that it’s more common in patients who received the gonadotropins, which are follicle-stimulating hormone and luteinizing hormone. These drugs can be used with timed intercourse or IUI, but we see them more commonly with IVF in higher doses.
Dr. Aimee: I have patients who have read a lot and done their research. Some are really scared about OHSS. And I tell them they don’t have to worry about that because it’s rare. Is there a patient population that doesn’t need to worry about OHSS?
Dr. Nichole Barker: We believe that there are people who are very low risk: those with low egg reserve or people who are not stimulating very robustly.
But the reality is that I’ve even seen a very mild case of patients who take Clomid or gonadotropins, even with those scenarios.
So for me, I feel like anybody could get it. Does everybody get it? No. And, but I think that it’s important that every patient who takes fertility medications is aware of it and knows the symptoms.
Dr. Aimee: I agree. I would say that if the patient is over 40 and has 10 follicles or less, the likelihood of severe OHSS is close to zero. OHSS mostly occurs in younger women or even older women who have a very high AMH. Even with gonadotropins (and not doing IVF per se), you can have it.
What are the symptoms from head to toe, that a patient should be aware of?
Dr. Nichole Barker: I’ve seen it present many different ways. I think the most common is that people feel bloated. Other symptoms include difficulties really taking a deep breath, severe nausea, constipation, and difficulty urinating or stopping urinating. In some cases there’s swelling of the body as well. And there can be chest pain, if there’s fluid that’s backing up into the lungs.
If somebody were to have a stroke or a blood clot, there could be leg pain, headache or visual changes.
But, discomfort and nausea are the most common symptoms.
Dr. Aimee Eyvazzadeh: Are there any other conditions that mimic OHSS?
Dr. Nichole Barker: I consulted on a patient who was a spontaneous pregnancy, who had something called theca lutein cysts. She didn’t have a twin pregnancy. We don’t believe it was associated with a gestational trophoblastic disease (which can also cause that). She had high levels of HCG.
Dr. Aimee: I’ve heard that before: A patient goes to the ER (not my patient) with pain after an egg retrieval. She’s given a diagnosis of ovarian cancer because that poor ER doctor has never seen it before, and they haven’t seen that number of cysts on ovaries. They misdiagnosed the patient.
It’s so important to have an emergency number and know who to call if you’re a fertility patient, so you’re getting answers from the expert. Certainly, things like a ruptured cyst or ovarian torsion can look like OHSS (or it could be a combination of the two). You can have a ruptured cyst and torsion and OHSS so important to talk to the doctor that did your retrieval right away.
Take us through your step by step approach to treating someone who has moderate to even severe OHSS.
Dr. Nichole Barker: If somebody is calling or showing up at the office with symptoms that are suggestive of OHSS, I typically want to see them. I want to lay eyes on them.
It’s definitely very hard to manage patients over a phone call. I ask them to come in to diagnose the situation. I’ll examine them, do vital signs, and do an ultrasound to see how big the ovaries are.
If there’s fluid accumulating, I usually check some laboratory tests as well. With a complete blood count, sometimes you can see that the hemoglobin and hematic are high in these cases, because the blood thickens.
I also look at their electrolytes, because those could be off. Things like sodium, potassium, and looking at the kidney function are important. And so those are usually my first things to do to complement examining the patient, laying my eyes on them. Hearing about their symptoms. Based on their laboratory testing and their exam, many patients can be monitored at home.
If we have to address pain or nausea, we do so, as well as keeping track of how much they’re urinating because it’s a bad sign if you stop peeing. Typically, they are sent home with those instructions, and then we’re checking in on them daily until they start to feel better.
If there’s an extreme amount of fluid that’s accumulating, sometimes we’ll actually remove it. That’s called a paracentesis when you drain fluid from an area. Specifically, it would be the pelvis. Sometimes people even need a drain from the lungs, but we would be sending them off to radiology to do that.
In cases where people can’t keep anything down, or if their labs are really abnormal, they have to be hospitalized and we have to potentially even be monitored for their cardiac status, and be making sure that overall their other systems don’t shut down because of this.
Dr. Aimee: So you’ve provided basically a checklist for people. Check your vitals, talk to someone daily, check your urine output, measure your weight daily. All those things are important for patients to know who might be at higher risk.
I imagine you’re doing all of these, you’re talking to us about how you would treat it, but the reality is you’re probably not seeing that much of it anymore because of all the steps that you take to prevent it.
So, can you talk to us about what you do to prevent this before it even becomes moderate to severe?
Dr. Nichole Barker: First, it’s about identifying the patients at high risk. I do feel like we have been doing a great job of doing that because we’ve seen the incidents.
To do this, I look at their ovarian reserve to understand if they have any of the high risk factors, which would include:
· somebody who’s maybe got PCOS or a really robust ovarian reserve who’s younger
· a low BMI
· having had OHSS previously
From there we talk to those patients upfront and talk to them about how we could avoid OHSS going forward in treatment. For instance, should we plan on maybe not giving HCG for a trigger, but Lupron for a trigger? Or, we could consider freezing embryos. Both of those things can really diminish risk.
Dr. Aimee: Yes, and a couple of other things — and, I’m sure you do this too — get the patient in early, choose a lower dose for the gonadotropins. I imagine you probably see them more often.
And then for the trigger, a couple of things that I found to be really helpful: Femara on the night of the trigger, and even for two to seven days every night afterward, followed by bromocriptine nightly until the period starts. I also suggest adding in whey protein and ganirelix after the egg retrieval.
If you’re someone who’s gone through moderate to severe OHSS, I think one thing that worries people is how is it going to affect me long term? Is it going to make my eggs worse?
Is it going to make me at higher risk for earlier menopause or even cancer? So what are the long-term effects, if there really are any?
Dr. Nichole Barker: It’s typically a self-limiting condition, which means that even though you have to be monitored closely and may be uncomfortable the first two weeks of having it, it does usually go away on its own.
However, I always tell my patients with IVF specifically that you are only stimulating a cohort of follicles and extracting eggs that were destined to not be even used. You will get more follicles and more eggs than that next time. It’s not going to expedite somebody into menopause because it’s not going to take away eggs that they wouldn’t have used.
If an embryo grows and looks to be good quality or is even genetically tested and found to be chromosomally normal, I would not say that that embryo from somebody who developed hyperstimulation would have any decreased chances of getting pregnant.
Dr. Aimee: So you can get pregnant with OHSS, right?
Dr. Nichole Barker: You can, and it’s actually riskier.
If somebody is developing symptoms of OHSS before their transfer we would talk about freezing the embryos. Typically, those patients who are the sickest are the ones who are pregnant. The hormones are even higher at that point. At least from what I’ve seen is that my patients have been the sickest who are pregnant with hyperstimulation.
And it’s hard to tell them, “yes, we want you to be pregnant, but we want you to be healthy and not in the hospital for the first couple of weeks of celebrating pregnancy.”
Dr. Aimee Eyvazzadeh: Right? So sometimes when patients show up for their fresh embryo transfer, you put that ultrasound on their tummy and you’re like, “Oh no, we’re not doing this today. You got to go home and rest.”?
Dr. Nichole Barker: Yes. And you can’t really see, because the ovaries are in the way. That’s a bad sign.
Dr. Aimee: So what would you want every patient to know about OHSS before they start fertility treatments?
Dr. Nichole Barker: I think it’s important for patients to understand their bodies and what their risks are. So asking questions to your provider is first and foremost the most important. Questions like:
· What is my egg reserve?
· Do you think that I will stimulate well?
· And if so, do you think I’m at risk for hyperstimulation?
If a patient has a history of PCOS they want to be questioning their protocol and the plan with their doctor. Trying to avoid OHSS is going to be the number one thing. So asking questions, having patients empower themselves to do that and feel comfortable asking their provider is important. There are definitely ways of decreasing the chances of it happening. It’s important to know that there are things (like the trigger shot and freezing embryos vs a fresh transfer ) that let us navigate this and hopefully minimize the risk.
Dr. Aimee: That’s great advice: asking, “Am I at risk for it? What are you going to do to prevent it?”
Do you see any future novel treatments for OHSS out there coming down the road?
Dr. Nichole Barker: I’ve thought about and I’ve done a little bit of digging in the literature and I don’t know anything new and emerging. I think that the focus in our field is really just trying to identify those patients at risk and preventing it from the beginning as opposed to how do we play, catch up and treat it? How do we prevent it in the first place?
Have you seen anything different?
Dr. Aimee: Not really. I think we’re trying different approaches. A couple of other things that I do are: continue Ganirelix, the night of the retrieval, and the next day.
I’ve always wondered if the medication that’s similar to Orillisa; maybe something like that could just shut down estrogen production very quickly for these patients so that they’re not at risk. Especially for egg donors. Many are just flying in for their egg retrieval and then they leave a day later, and then they don’t have as much supportive care in some places in the world.
Not necessarily in this country, a lot of them are overseas. I feel like there could be some ways to help those patients so that they don’t suffer after they’re giving that gift to another family.
Dr. Nichole Barker: I do think that using a Lupron trigger (as you know, not everybody will respond to that)…in some cases, we must use HCG to trigger. I’ve even seen a case of hyperstimulation with a very minimal dose of HCG. Even a tiny dose of HCG as a trigger can put somebody into hyperstimulation.
I do think that it’s important for us to know about all of these ancillary options. And I think the points that you bring up are great.
Dr. Aimee: I’ve even had one patient in the last 12 years develop moderate to severe OHSS from a Lupron trigger. I’d never thought I would see it, but I have seen it once. So never say never. We never take our patients both for granted.
Thank you, Nicole, for being on today’s show. Tell our audience, where can they find you?
Dr. Nichole Barker: I’m at Seattle reproductive medicine. I work at the Tacoma clinic. We have six different satellites, so that’s where I am. And I do have an Instagram page. It’s FertilitySpecialists_Dr. Barker. I have a lot of fun with that, connecting with people and colleagues and educating.
Dr. Aimee: Well, thank you Dr. Barker for your time today. Thank you everyone for watching today’s show.
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