OHSS: Prevention and Treatment

Have you ever wondered how your REI chose your specific protocol, and how they think about reducing your chances of getting OHSS?
Some people are more at risk for OHSS than others, and a lot can be done on the front end in terms of prevention. 

We have learned so much about OHSS prevention and treatment over the last 10-15 years.
In this episode, I share my thought process when thinking about how to balance safety and success, and how to get people back to living their lives sooner. 

As always, please keep in mind that this is my perspective and nothing in this podcast is medical advice.

If you found this conversation valuable, book a consult call with me using this link:

https://calendly.com/loveandsciencefertility/discovery-call

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Please don’t let infertility have the final word. We are here to take the burden from you so that you can achieve your goal of building your family with confidence and compassion.

I’m rooting for you always.

In Gratitude,

Dr. Erica Bove

Transcript:

Hello, my loves. Let's talk today about ovarian hyperstimulation syndrome, or OHSS for short.

This is something that I actually saw a ton of in my in the early part of my career, like

when I was actually a resident even I did see some of it as a resident, but I did a

lot more fertility specific stuff. Obviously, as a fellow, I would say as a fellow, I probably

rounded on a patient with OHSS about once a month. And like, I will tell you that my fellows today,

like, I don't even know if they've seen a patient admitted with this because our treatments have

gotten a lot better, our prevention has gotten a lot better. And we now have something called

Lupron Trigger, which does almost eliminate all of the ovarian hyperstimulation syndrome. But

no, I think if you're a woman physician who is on the fertility journey, and you're barely able

to make all of this work with your clinics, your hospital duties, your rounding duties,

you do your two weeks of ultrasounds and blood work and monitoring and then the retrieval.

If you are then laid up with another one to two weeks of a complication, like OHSS after that,

and you feel like crap, you're third spacing, I've seen people even like their walk is now a shuffle.

Sometimes people need anticoagulation or hospitalization or IR drains or

basically an egg retrieval, but where you drain the cul-de-sac of fluid instead,

that's really going to cram your style as a physician. And it's also going to just add

more morbidity and time and cost and frustration. And even like VTE risk is higher and miscarriage

risk is higher. So I think this is a really important topic to think about because what

is your REI thinking about as they are preparing to do your IVF cycle and what are some of the ways

to mitigate the side effects of OHSS? So, OHSS is defined actually in terms of mild OHSS, which

I will admittedly say that that's kind of the goal of all IVF is to at least get somebody to

mild OHSS because we are hyperstimulating the ovaries. The whole point is instead of just

ovulating one egg in a given month, that we capture the cohort and in an ideal situation,

you have at least a few follicles to work with. So, yes, we are trying to hyperstimulate the

ovaries, but we're trying to avoid the ovarian hyperstimulation syndrome, which comes with,

like I said, the third spacing and the discomfort and the additional risks. From moderate hyperstimulation,

I mean, that can be defined by a lot of different criteria. One of them is ovarian size. Another is

how much free fluid is in the abdomen. We often see free fluid in the abdomen, even leading up to

a cycle because the capillaries get a little bit leaky. And that's sort of part of my thought

process in terms of the trigger decision, what to trigger somebody with to reduce the risk of OHSS.

And also there's that question, if this person wants to have a fresh embryo transfer, is that

a good idea? Because there's the first wave of OHSS, which is where somebody's ovaries are so vigorous

and usually HCG trigger then makes the vessels leaky and people can be nauseous and even have

vomiting. And every now and again, you see even like mild LFT bumps and creatinine. Nothing,

nothing usually super dramatic, but to the point where, especially if you're in internal medicine,

you're looking at the labs, you're like, oh shoot, this is a physiological alteration, right?

It always gets better. It does. But it's one of those things where yes, in fact,

like OHSS does really affect the system. And so the first wave, if you think about the fact that

the HCG trigger is out of your system in about a week, typically that's when people start to

turn the corner from their symptoms is like, you know, a week after the trigger, which is about

five days after the egg retrieval, the sort of abdominal bloating tends to get better.

The ovaries start to shrink to their normal size. The third spacing starts to get better, unless

somebody is also has, is having an embryo transfer. And I will say some of the worst

hyperstimulation I have ever seen has been in pregnant individuals because you really can't

stop a train once it started, right? So you get the first wave of the OHSS and then the embryo

itself attaches and starts to make beta HCG. And then that then keeps the whole hormonal system

going. So it's really that second wave of OHSS that is think the most morbid. But, you know,

like I said, even the first wave of OHSS can be super pesky and uncomfortable. If you're trying to

get back to work, get back to baseline, a lot of times, you know, if you're taking that time,

blocking patients to get this done, sometimes pre and post, there's kind of like that, like almost

like, you know, when you go on vacation, before you leave for vacation, when you get back on

vacation, there's like those that clustering that happens on either side. So, you know, the goal

really is to sort of get people through this as smoothly as possible and what can be done to

prevent and treat OHSS. So, you know, moderate to severe OHSS is thought to complicate about one to

five percent of IVF cycles. And like I said before, you can see ovarian enlargement, you can see

ascites, you can see hemoconcentration. I've even seen like hematocrites over 50,

hypercoagulability actually, and electrolyte imbalances. So it's really important to think

about the fact that this really can affect physiology and trying to keep this, I always say

safety and success must be balanced and trying to keep this as safe as possible.

You know, with mild OHSS, sometimes people just kind of feel like a little bit bloated,

maybe they gain a few pounds. They even say like, I feel like I'm pregnant, although I know I'm not,

like, you know, sort of the body can kind of feel it. But with severe OHSS, especially if there's a

lot of free fluid in the abdomen, it can push up on the diaphragm. People can have a hard time

sleeping flat. It can really affect like taking a deep breath. People can have chest pain. They can

have pleural effusions because again, all the third spacing of fluid and you know, VTE, I've seen

people have need to be anticoagulated as well. Not even just lower extremity clots, also upper

extremity clots can happen with this as well. So again, not to be taken lightly. severe OHSS can

really lead to some complications, you know, but hopefully your REI can talk with you about that

beforehand. What are some of the risk factors of people who are more likely to have OHSS? Certainly

if you're starting off with a high AMH, that's one of the most important things. I mean, more than

three and a half is usually when I start to think about somebody as increased risk or maybe a high

angel fog account of somebody starting out with a AFC of 30 to 35 already. You know, I usually use

that data to kind of curb the medications. I might start them off a little bit lower than I might,

you know, if everything else was equal. And also just keep that in mind. I usually order a Lupron

trigger ahead of time to make sure that I'm prepared. I will say where I work right now,

I'm very, very, I'll use even the word blessed. I'm very blessed that the downstairs pharmacy just

has it. So like, it's never an issue. But in my other practices, you know, it's sometimes an

overnight shipment. If you don't think about it ahead of time and you realize on the day of

trigger that somebody actually needs it, it can just be kind of a source of panic like, Oh my gosh,

we can't use HGG. She's going to get really sick. And oh my gosh, all we have is HGG. So I think the

sort of the thinking about it ahead of time is a really important part of this picture.

Women under the age of 35 are at increased risk of OHS. It says it's actually 60% of OHS cases are

in women in that demographic. Low BI is actually very controversial, but I will tell you some of

my sickest patients have had a low BMI. And I think that probably it's because the HGG goes farther

in terms of the volume of distribution. But anyway, that is controversial. But I would

say based on my experience, I would say I do think about that in my risk algorithm. Somebody

who has a diagnosis of PCOS is a lot more likely to have to, you know, have a diagnosis of OHS down

the line. People with two will factor because I kind of put that in a different category in my mind,

or even unexplained infertility in black race also for reasons that we're not quite aware of.

We're not quite sure why that is. In terms of ovarian reserve markers, like I said, high

antimalarian hormone, high angiofolic account, those are very good predictors for

hyperstimulation. If you look at like the data, like AMH greater than 3.36, like, okay, fine.

I said three and a half. The data would say angiofolic account over 24. I said like 30 to 35.

Okay, fine. Just so you know the actual numbers of the studies that we look at.

But you know, you can just say like people who, if somebody has an antimal kind of four,

I'm not really concerned that they're going to get OHSs. Also thinking about ovarian stimulation

parameters, like how many follicles are there at the time of retrieval over 25 is a risk factor.

Over 19 large or medium sized follicles at the time of HD trigger, that's definitely

a risk factor. Over 24 OsAs retrieved as a risk factor and also estrogen concentrations greater

than 3,500. Although estrogen does seem to be one of the worst predictors, even though we all freak

out about it, like, oh my gosh, the estrogen is 8,000. We can't give her HGG. It's usually because

those other things are also present. And so just, you know, one of my sickest patients with OHSs

actually had an estrogen of 1,400. So, you know, you just have to be very cautious not to just go

on estrogen alone. We think about different stimulation protocols from the beginning. So

I would say like over the course of my career, we are doing way more antagonist protocols compared

to long Lupron protocols. But when I first started, we were doing a lot more long Lupron in which you

cannot use anything but HGG because your GNRH receptors are downregulated. And then like,

if you give Lupron, then nothing happens because the medication can't talk to the receptors.

So, you know, in a GNRH antagonist protocol, you actually have a Lupron trigger as a possibility,

as long as somebody doesn't have like hypothalamic amenorrhea and they don't have any luteinizing

hormone endogenous to work with. Like usually you can use a Lupron trigger with pretty good results.

But if somebody's on a long Lupron protocol or a microdose flare protocol, then you really

do have to use an HGG trigger just so you know. What are some preventative adjuncts? So some people

have used baby aspirin. I know that's controversial. People ask if that increases the risk of bleeding.

It's not thought to, but it does seem to have an effect on VEGF levels. And that's part of the

pathogenesis of OHSS. If you use a dopamine agonist actually, like starting from the point

of trigger on, after the retrieval, there's good evidence that that can reduce the risk of OHSS.

I love that. Give me a little bit of carburegalin, you know, that's a really nice medication.

Sometimes people have a few side effects like GI, like nausea or sometimes dizziness, so then you

got to pay attention to that. But in general, that does seem to really do a good job in terms of

reducing that third spacing. There's some data that people can actually use metformin, and that can

really help in terms of their, you know, OHSS prevention. Usually that's people with PCOS to

begin with, but that medication in and of itself can have, you know, some side effects. So I don't

usually use that unless somebody has had like a history of bad OHSS and we're really trying to

pull out all the stops. You can like start to decrease the dose of gonadotropins towards the

end of the cycle. That's called coasting. Coasting is truly not giving any gonadotropins, but I kind

of like a slow decrease at the end, and that can try to starve out the little follicles. That's

sort of a philosophy. And then even like, you know, I've used albumin usually in patients before,

but you can use different like IV fluids and agents to help with that as well.

Lettresol, so my personal cocktail, if I get to the point of trigger/ag retrieval and I really

want to shut down the Lueo phase, usually this is in people who are not planning a transfer,

is I like three nights at antagonist, sort of after the retrieval. I like, you know, several days of

Lettresol and several days of kabergaline, you know, eight days of kabergaline per the literature

and five days of Lettresol, but you know, you can sort of make that a little bit more malleable to

who is going to benefit in your practice, and in sort of like just practical aspects. So I like

that combination of things. It does not seem to have any harm. There's actually some data that

it does shut down the Lueo phase faster and reduce the symptoms of OHSS. So, OHSS treatment,

I think, you know, if somebody has moderate OHSS, usually it's supportive care, usually trying to

avoid, you know, a numberio transfer. And if it's truly severe, I mean, sometimes we do manage this

as an outpatient, but you really have to be cautious about ins and outs. Sometimes people need

IV hydration, in which case, from my perspective, they really do need to be in a hospital. And also

anticoagulation is important. I've worked at, you know, different settings where some of my

Parasympathesis was preferred with IR. Sometimes Chaldecenthesis was preferred, you know, because

we can do that in our IVF suite. But there's really only fair evidence for that. And because

people need so much IV fluid repletion, and because, you know, there was not a ton of evidence that

that really does help people get back to baseline quicker, and it is fairly invasive. I usually only

reserve that unless somebody, if somebody's having like short of breath or other, you know, reasons

why I really feel like their physiology is going to be better to do that than I do. But, you know,

I just wanted to say not to be taken lightly. Hopefully, the whole point is, you know, an ounce

of prevention is worth a pound of cure, right? Or something like that. Anyway, so what I would say

is the biggest thing is to identify who's at risk prior to stimulation, to choose a stimulation

protocol that, you know, is appropriate to consider, kabergaline and letrozole and antagonist as

adjuncts, and to avoid a fresh transfer if there's a concern that, you know, somebody really is at

increased risk of OHSS from that second wave of HCG. There's also some things you can do to mitigate,

you know, sort of the side effects after the fact. In addition, like some people like cold packs,

some people like heating packs, I think that sort of mobilizing, getting up and moving is helpful,

both for mobilizing the third space fluid and also, you know, VTE prevention, those things can be very

helpful as well. And also, you know, is a common thread in a lot of my, you know, content and the

way that I practice medicine is really give yourself some grace. Like if you're not feeling well and

you still have an extra 10 pounds of fluid, you know, from your IVF cycle, maybe you do call in,

maybe you do say you need a couple extra days to get back to baseline. And that's really not to be,

you know, ignored. I think that we all need to really give each other permission to create the

space because IVF is not for the faint of heart. And sometimes, you know, there is sort of this

overshooting of like, Oh my goodness, too much of a good thing. And it just takes a little bit

longer to get back to baseline. And I think we all know that if we push through and we ignore those

things, then sometimes it actually takes even longer to recover. So that's always just us in a

nutshell. I'd love to sort of answer more questions if you have them. But hopefully this helps to

understand kind of what your RAI is thinking and things that you can do in your own cycle to

advocate for yourself and to start to feel better sooner. With that, I love you. I'll talk to you

next time. Bye.