Hello, my loves, and welcome back to the Love and Science podcast. Today, we're going to talk about a very common question, which I get asked a lot, which is progesterone levels, interpretation, what do they mean? What can I glean about the potential success or failure of my cycle?

There's so many things to talk about. Okay, so let's start by talking about the physiology of

progesterone. Progesterone is a hormone that is... exclusively in the luteal phase,

which means we ovulate an egg. The follicle that is our dominant follicle starts to make

progesterone. The progesterone level rises. It reaches a peak with corpus luteum production within the first few days of the ovulation event. And then if an embryo implants,

that's fantastic because the HTG from that embryo is in the serum and that stimulates the corpus luteum to keep making more progesterone however if the embryo does not implant then our corpus luteum dies off and then we have the withdrawal of both estrogen and progesterone and the endometrium breaks down and we start to have our period so that is the physiology of progesterone now this is something i didn't appreciate till i was a fellow but progesterone is actually secreted in a pulsatile way and so Interestingly, you can have a progesterone level that varies by like 30 points within even a few hours. You'd have to have an indwelling monitor catheter to be able to really assess true progesterone levels on a minute to minute basis. So when people check a progesterone level, say in the midluteal phase, it's really interesting because the questions that go through my mind as a specialist are. Is that the peak level? Is that the trough level? What are we really looking at? Because if a progesterone level is like seven and that's the peak, well, maybe that's not so great. But if a progesterone level is seven and that's the trough, well, maybe we're not doing so badly, right? And so again, we get one snapshot into time on something that is secreted in a pulsatile way. So I actually tend to look at progesterone secretion as...

know, qualitative, what, excuse me, quantitative instead of qualitative, because it's like, well,

okay, is this a yes or no event, right? Did ovulation happen? If the progesterone's over three,

did ovulation not happen, right? It's more of like a yes or no, but to assign any qualitative value

to that number is really, really hard to do, right? So if I say, oh, that was a good ovulation

event, or that was a crappy ovulation event, it's really hard to make those determinations because

I don't really have much to stand on unless I had like a zillion values over time and nobody's

going to get poked that many times for that blood work. Now I will say another reason why

progesterone, you know, checking is problematic is because it doesn't always reveal the

choreography of the menstrual cycle. So say I see somebody in my office, I'm thinking that they

might have PCOS. Sometimes we get like a progesterone level, right? That's sort of what is.

taught to us in some of our training for the evaluation to get a midluteal progesterone if we know

when somebody might have ovulated. And, you know, what I say is if I catch somebody ovulating,

but they have irregular cycles, I still know that they have ovulatory dysfunction. And so I

actually tend not to get a progesterone in those circumstances because I can tell by the history

alone, if somebody has ovulatory dysfunction, most likely, I mean, If somebody has regular cycles

and if they're really not sure if they're ovulating, sure, we can get a day 21 progesterone, right,

in a 28-day cycle. That will be revealing. But usually if I have the menstrual cycle length data

and people generally know when their LH kids are turning positive or not, with that information

alone, I can usually do just as good, if not better, than if I have progesterone levels to work

with. So again, if I catch somebody ovulating in the context of ovulatory dysfunction, it's not

really going to change how I think about them or how I treat them. Okay. So what about IVF? There's

been a lot of attention with progesterone and progesterone levels recently in IVF. So it's a little

tricky because we have frozen embryo transfer cycles that are programmed where all of the

progesterone comes from the outside world, right? So the ovaries are quiet. All the progesterone is

being given either by progesterone and oil daily or a combination of progesterone and oil and

vaginal progesterone. And the big question is, okay, well, what is an adequate luteal phase

progesterone so that we know that the embryo has everything it needs to stick and stay, right?

Because interestingly, the study that showed vaginal progesterone only didn't have a change in

pregnancy rates, but the ongoing pregnancy rates were lower, which actually suggests that

progesterone is really important in terms of pregnancy maintenance. So, you know, if we are looking

at data and I just reviewed this this week, It seems that a progesterone level of 10 in an IVF

cycle is sufficient to say, yes, in fact, this is a high enough level that we can proceed. Now,

if it's under 10, is that bad? I mean, say some of the proportions coming from vaginal

progesterone, and we know that there is a local absorption effect that is not reflected in the

serum. It's probably not. But I think those of us who do a lot of this work. really don't want that

variable in the mix. And so you might hear your REI say, you know, we want your progesterone level

at usually 15 is what I hear. You know, that's kind of why we continue progesterone until 10 weeks

and not eight weeks because we like that little buffer. You know, that extra five points of

progesterone is probably enough of a buffer that we can say we want the progesterone level to be,

you know, above 15. Now 10 is probably sufficient, but again, that's what most of us say.

Is there such a thing as a progesterone level that is too high in an IVF setting? That's really

controversial. Some studies say no. Other studies say around 30 or 40 that maybe outcomes are

worse. And I think we still haven't really definitively answered that question. It's also a lot

harder in sort of these modified natural FETs because some of the progesterone might be coming from

the ovaries in that pulsatile faction, like we talked about, and maybe some is coming from the

outside world. And so I think it can get really, really tricky in terms of like, um what is the

goal in those sorts of cycles but i i think that if we can come back to physiology and understand

that checking progesterone levels especially in these natural cycles can be very problematic it can

really just say if somebody has ovulated or not and ivf cycles we do our best to stimulate as much

of a menstrual cycle as possible right with the appropriate levels and then we do our best to move

forward um Also just thinking about like recurrent pregnancy loss and luteal phase defect,

the same thing applies. If I think that somebody has a progesterone issue because they're having

premenstrual spotting or their luteal phases are a little short and they keep having miscarriages,

I'll give them supplemental progesterone. And then my patients are like, hey, well, can you check

my progesterone level? And I'm like, well, we can, but the progesterone you're taking is gonna kind

of really cloud the picture. And so I think it can get really tricky, but. really supplementing

with progesterone is not really a big deal. And so if that's something that your REI thinks would

be beneficial for you, just know it can be a little messy, it can be a little cumbersome, but at

the end of the day, sometimes it can really make a big difference for some people. Is there

anything else to say about progesterone? Now, I will say that thinking about progesterone in terms

of like overall pregnancy success, that's something that...

get questions a lot as an REI, especially about like, well, can you check my progesterone level?

I'm newly pregnant. I want to really know if this is a good pregnancy. And the problem with that

though is, you know, under a progesterone level of five, probably not a great pregnancy. If the

progesterone level is like above 25, then maybe that's a good sign, right? Assuming no like

exogenous progesterone exposure, but there's a huge gray zone, right? Between five and 25 can be

very confusing. And so oftentimes if the pregnancy isn't good in and of itself, that will reflect

in poor pregnancy levels. So then it becomes like the chicken or the egg. And so generally

speaking, I don't recommend checking progesterone levels in natural cycle pregnancies because I

don't find that it really helps in any meaningful way. For people who have like bleeding and

they're concerned about pregnancy maintenance, you can give supplemental progesterone in those

situations. Like I said before, also for IVF, we can give it in those situations as well.

But I think that the point is when I think about giving somebody supplemental progesterone,

it's usually based on the clinical history and not so much the serum values. And so try not to get

too bogged down in the actual number. And I think, you know, my patients and my clients do a lot

better under those circumstances, but just because we follow the evidence, we follow the data and

that kind of obsessive checking does not help. So I hope you found this helpful. Stay tuned for

more sciencey episodes until the next time. I love you. Bye.