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Kristyn Hodgdon:
Hi, I'm Kristyn Hodgdon, an IVF mom, proud fertility and women's health advocate, and co-founder of Rescripted. Welcome to Dear Infertility, the first-ever podcast that doubles as an advice column for all things fertility and women's health. This season joined me along with Dr. Nicole Yoder, a fertility specialist at Spring Fertility in New York City. As we explore what to do when you're trying to conceive and feel like nothing is working. From when to seek the help of a fertility specialist to what questions to ask when IVF fails, we'll address all things fertility troubleshooting so you can become your own best reproductive health advocate. Now let's dive in.

Kristyn Hodgdon:
Hi everyone, and welcome back to Dear Infertility. I'm your host, Kristyn, and I'm here with Dr. Nicole Yoder. Hi, Dr. Yoder.

Nicole Yoder:
Hi. Great to be back.

Kristyn Hodgdon:
Yeah. Great to have you back. Dr. Yoder is a fertility specialist and board-certified ob-gyn with Spring Fertility in New York City. And today, Dr. Yoder and I are going to be talking all about IUIs. So intrauterine insemination and how successful are they, really? I often say that the most difficult part of my initial fertility journey before I got pregnant was my IUI journey because I was 27 with PCOS and my only problem was ovulation. So naturally the first step was do IUIs with Clomid and was shocked every time when they didn't work out and really want to touch on who's a good candidate for IUI and how often do they actually successfully end up in a pregnancy.

Nicole Yoder:
Yeah, it's a great talk about and your experience is not an uncommon one and one that we very frequently see. IUIs can be great tools and it can be a great treatment for certain people, but you really have to go in with your eyes wide open about the success rates and be well counseled about that. So I think that's a really good point to start off with when talking about IUIs, because some people, you go through it and you're like, great, I did an IUI; we optimize the thing that was wrong. And oh my gosh, it didn't work. And it can be really like soul-crushing. But you just have to go back to thinking about what do we expect those success rates to be.

Kristyn Hodgdon:
Yeah. And so I know age matters too. But what who is a good candidate for an IUI and what are those success rates?

Nicole Yoder:
Yeah. So when we think about who's a good candidate really, you have to go back to thinking about what an IUI is doing and what we're optimizing there. So with an IUI, basically we are using your own body's egg and sperm and optimizing the timing. So we're helping ovulation one happen and making sure it's at an optimal timing. And then get a good sperm sample as close to that egg as possible. People who IUI are really great for is maybe one, you don't have regular sperm exposure, so this could be single mother by choice. This could be same-sex female couple. So just people who they're not having unprotected intercourse with a male partner on a regular basis, that IUI is a great place to start for those people, other people who it's a good option for are such as yourself, people with PCOS. Maybe you're just not ovulating regularly, which can be PCOS, can just be irregular periods for other reasons. Or maybe you don't get a period for a different reason and we can help you just ovulate and make that egg grow. Make it ovulate. That's another great population that might benefit from starting with an IUI. Another category of people who might be a really good candidate for this is maybe you do ovulate regularly, but maybe the sperm sample is just not quite what we want it to be. Maybe the counts are a little suboptimal. Maybe the motility is a little bit low, but there's sperm there. We just want a more optimal sample. This can be another great population to start with an IUI because if we can just optimize that sperm sample and get it as close as we can to that egg, maybe that's all you need. So those are the people that we think about really benefiting the most and being like really great candidates to start with an IUI.

Kristyn Hodgdon:
And in that population, how much is an IUI sort of increasing the success rates versus trying to conceive at home?

Nicole Yoder:
So this is the main point that you really have to keep in the back of your mind when you're doing IUIs. So an IUI is only going to get you up to the success rates of your age-based fertility. So this is not going to get you higher than we expect for your peers who are ovulating regularly. Say you are 30 years old, and we expect pregnancy rates in the general population trying to conceive to be about 20% chance per month and IUIs probably going to get you maybe close to that 20%, but it's not going to get you higher than that. So you really have to keep in mind that the success rates in their best-case scenarios probably max out around 20% chance per try, and that isn't the best-case scenario in the younger population. As you get older, as the female partner gets older. Those success rates are going to mirror what the fertility rates are for that age. If you're 40 and you're doing IUIs, I expect it's going to be close to the success rates of a 40-year-old. So about 5% chance per month. So you really just have to keep in mind that age-related fertility rates and that's really the max ceiling that we're going to reach with the IUIs.

Kristyn Hodgdon:
I'm curious with IUI versus timed intercourse, how were those two different? Do you ever recommend just monitoring with timed intercourse?

Nicole Yoder:
Yeah, you certainly can start there if we know that the problem is only if there's a lack of ovulation. If we can make that person ovulate and we know that the sperm sample is good, it's robust. We don't really have concerns about either sexual performance or the quantity, quality of sperm from the semen analysis that we can tell you can certainly start with timed intercourse.

Kristyn Hodgdon:
Yeah. No, it makes total sense. I believe I started with timed intercourse, but we only did one cycle and then. Yeah, why not try? If it just increases the chance even a little bit.

Nicole Yoder:
And it does. And doing a combination of both some sort of medication and an IUI is going to have superior rates to doing just medication alone, just IUI alone or just trying on your own.

Kristyn Hodgdon:
Yeah. And so let's talk a little bit about those medications. So the ones I'm aware of Clomid and possibly Gonadotropins like FSH. Are there any that I missed?

Nicole Yoder:
Those are the main ones that we use. Yeah.

Kristyn Hodgdon:
Okay. And what are the difference between those three and what do they differ in success rates? Yeah.

Nicole Yoder:
So generally you're the ones that we usually use as a first-line treatment are going to be the oral medications which are both Clomid and Letrozole, Clomid and Letrozole. The end effect really is to trick your body into thinking that there's not estrogen around, so that your brain says, oh gosh, there's no estrogen. I need to make a follicle in order to produce some estrogen. Their mechanism of action is a little bit different. Clomid works in the brain. Letrozole works a little bit more in the periphery, but the end goal is really the same. Now the difference is between the two. Clomid has been around for much longer. We've used it for forever for ovulation induction and it is FDA-approved for that purpose. But it does have some side effects that can be undesirable. So some people will have some kind of like perimenopausal side effects with it. Some people have hot flashes, insomnia. Some people really don't tolerate Clomid that well, and it can have some negative effects on the lining. So the uterine lining can be a little bit thinner with Clomid. Letrozole again a little bit different mechanism of action, but same end result. Trick your brain into thinking there's no estrogen around. It tends to be a little bit more well-tolerated in terms of side effects. And we've actually seen that in certain populations, like people with PCOS. It actually does have a little bit higher success rates. So I'd say these days more people are leaning toward using Letrozole as a first-line treatment. Although the other thing to know is it's technically not an FDA-approved indication for it. So we do use it off-label, but both of them are. It's a short course, usually about five days of these medications, and they're fairly well tolerated for the most part.

Kristyn Hodgdon:
Is it typical for one or the other to not work? Because I actually Letrozole has never worked for me. It's never.

Nicole Yoder:
Yeah

Kristyn Hodgdon:
Ever helped me ovulate. But Clomid I did have some of those less-than-desirable side effects. So it's like yeah.

Nicole Yoder:
Yeah it can and it can give you headaches too, that I think that's like probably the worst one that people have headaches or vision changes and more severe ones. Yeah. Not fun to have those side effects. I'm sorry you went through that. But certainly, you are correct. Some people just don't respond to one. And it's nice that we have a backup so we can switch to the other just to see. And some people will do very well in Letrozole, some people very well in Clomid. And a little bit of it can be trial and error, so it's good to have that backup plan. The other medication that you mentioned using Gonadotropins. Sometimes we do use that, but we tend to use that only in certain scenarios. Or if you fail to respond to the first two, partially because taking a pill certainly easier than giving yourself an injection. The Gonadotropins are the injectable medications, same ones you use in IVF, but people definitely prefer to just take a pill rather than give himself a shot any day. And I totally understand. The issue with Gonadotropins is that they do have the potential to develop multiple follicles. So our goal is, is to give you one good, healthy pregnancy. And when we're doing IUIs, we have a little less control over how many pregnancies actually take. Yeah. So if you are developing a lot of follicles, which is more common or more, more apt to happen when you're taking those Gonadotropins, there is a higher risk of multiples. So we really monitor you closely if you're using those. And we try to give you the lowest dose possible just because the risk of multiples definitely goes up.

Kristyn Hodgdon:
What about Clomid and Letrozole?

Nicole Yoder:
So those also do have an increased risk of multiples, probably about 6 to 8% I would say. And this is another good reason why it's always, in my opinion, it's always good to at least monitor closely that first cycle to see how many follicles do you develop. Now, if you are young and you don't ovulate and you're 25 and you develop five follicles on these medications, I'm going to say, whoa, whoa, we can't move forward because the risk of multiples is too high. And studies have shown that the pregnancy rates when you have multiple follicles, the pregnancy rates themselves do not go up. But the risk of multiples does. Yeah, we like to have, depending on the scenario, like maybe 2 or 3 follicles based on your age. Sometimes we're comfortable with more if you're older, but definitely a risk of mold with any type of ovulation induction and IUI. But it's higher with the injectables than it is with just the oral medications.

Kristyn Hodgdon:
Okay. And so can you go into a little bit about the process when you're on an ovulation induction medication and then you're having an IUI. What's the timeline what can someone expect?

Nicole Yoder:
Yeah. So the whole timeline for the whole cycle is going to be about a month. So about the same as like your natural cycle would be in theory. So we usually start when you get a period or a cycle day 2 or 3. Now if you don't get periods we can maybe induce one to happen. But starting with that period we're going to have you come in, take a look with the ultrasound, and make sure everything looks good to go. We want to make sure your lining looks thin and want to make sure that there are no big follicles or cysts that we should know about at the start. So we're going to make sure everything looks good to start. Once you do that baseline exam we have, you take five days of that oral medication if you're doing the oral ones. And then usually you'll have you come back in for a monitoring visit sometime around day like nine through 11. Now, if you ovulate really early in general or we think you have the potential to, we might bring you back earlier, but we'll bring you back for that monitoring visit. Usually cycle the 9 to 11 and just see how does the lining look and how many follicles are growing and how big they are. And then you may have a few more monitoring visits until we get to a point where we know your lining is ideally seven millimeters or above, and you have a nice follicle, maybe a couple follicles that are hopefully somewhere around 18mm or above. Now, once we see that you've developed a good follicle, developed a good lining, usually we'll give you a trigger shot to make you ovulate.

Nicole Yoder:
You can do this in a few different ways. You could wait till your body ovulates. But in the interest of timing, we usually will give you a trigger shot to make you ovulate. And then we time the insemination about 24 to 36 hours after that trigger shot happens. So that's when the insemination part comes into play. On the day of the insemination. Either we have frozen sperm that were thawing, or you have a partner who is coming in to give a fresh sample. The lab is going to prepare that sample, wash it down, make it the best sperm sample that we can possibly get. And then you have the IUI procedure. The IUI itself is actually pretty quick for the most part. I think the most uncomfortable thing about it is having a speculum exam, which is not great for anyone for the most part, but clean up the outside of the cervix, and then a little catheter goes through the cervix into the uterus, and that sperm sample is deposited as close to that egg as we can get it. Usually, we have you hang out for five ten minutes. This is not based on science, mostly based on voodoo and superstition, I would say. And then about two weeks later, we have you do a pregnancy test. Okay. Now some people will do progesterone supplementation after. Some may not. That will depend clinic to clinic. Lab to lab. What we think is going on. But that's another variable that can come into play.

Kristyn Hodgdon:
What is Spring typically do. Is it case by case or?

Nicole Yoder:
Yeah, case by case. If we don't have any suspicion that your progesterone would be low, we might just see how the first one goes. Sometimes you might check that progesterone level seven days or about a week after we triggered that ovulation. If it looks a little low, maybe we'll supplement. But typically if you have multiple follicles that have been triggered to ovulate usually the progesterone levels pretty robust.

Kristyn Hodgdon:
Okay. Awesome. So you've had an IUI. It hasn't it didn't end up in a pregnancy. How many do you recommend doing before moving on to the next step?

Nicole Yoder:
Yeah. And this is a really this is a really good question and something it's really good to keep in mind in your overall planning process. The success rates of IUIs are really the highest in the first three months that you do them. The next three months tend to have a little bit lower success rates, and in the next, in the following three months, even lower. I usually tell people to reassess after the first three tries. If we're going to do IUIs. Great. Give it three tries and then reassess where you are. Usually, I will say if you want to keep going on IUIs, maybe try three more up to six. But after six IUIs, the success rate is really going down and most people are like ready to move on to something a little bit more successful. So I'd say reassess after three, maybe up to six depending on the scenario. And after six, usually it's kind of time to start thinking about, is it time for IVF.

Kristyn Hodgdon:
And why do the success rates go down after three? Because you said that the IUIs brings you up to the success rate of your age group. So why after three, does it decrease?

Nicole Yoder:
The people who IUI is helping tend to benefit from it in those first three months. It's mostly the people who are still doing IUIs. We're probably not addressing the true underlying issue. So maybe that there's like a sperm issue, an egg issue, issues with the tubes, something like movement through the tube, something like that. So those people aren't going to be benefiting from IUIs. So the ones who are benefiting are really like they're going to get pregnant a little bit sooner. And the ones who aren't are bringing those rates a little lower.

Kristyn Hodgdon:
Awesome. Yeah. Remember after three IUIs I was pretty.

Nicole Yoder:
It's a that's three months of trying. And it's like emotionally you've been doing it for three months already. You feel like going at it for a while. Yeah. Get over it.

Kristyn Hodgdon:
What I hadn't really realized before going into it was like, you still have to go to those monitoring appointments and take medication. So after three that didn't work out. I was like, okay, is IVF really so bad? You know, it was like it made IVF a little bit more appealing because.

Nicole Yoder:
Totally.

Kristyn Hodgdon:
Because now I have to be in the doctor's office anyway and I have to take the medication anyway.

Nicole Yoder:
Yep. It's less monitoring than IVF, but it's not nothing. You still are coming in, you're still being monitored, you're doing the IUI. It's your time and energy and effort. And after three months of that, most people are like, okay, let's move on.

Kristyn Hodgdon:
Absolutely. So when do you have that conversation or when if someone's listening who might have had two failed IUIs at this point, what would you advise them to do next?

Nicole Yoder:
I always try to encourage people to look at the big picture and like what the overall trajectory is of their journey, and try to have the conversation actually before you even start IUIs to set it up so that, okay, we we'll do this for three, but then we're going to have a discussion about if this doesn't work at three, do you want to keep going. And part of that is like mental stamina. Some people are fine doing more and they're like, nope, I'm perfectly happy and that's fine. But try to set up that conversation like before we even start and revisit it after every cycle goes by. Just so it's always in the back of their mind for future planning.

Kristyn Hodgdon:
Yeah, no, that's a really good call. It's always good to be able to look ahead, even though you sometimes don't want to even go there. It's like, yeah, having that mental preparation.

Nicole Yoder:
Yeah, it's always good to take things one step at a time, but occasionally step back and say, okay, big picture wise, what's the overall map looking like?

Kristyn Hodgdon:
And like we said in a previous episode, if you do know that you want 2 to 3 children, ultimately like that could factor into the decision as well.

Nicole Yoder:
Totally. So yeah, that comes back to the overall big-picture planning of like, how old are you? How many kids do you want? Is IUI the most effective way to make the big picture like entire family happen or after a couple that's not working? Do you want to move on to something like IVF?

Kristyn Hodgdon:
Awesome. Thank you so much, Dr. Yoder. This was awesome. For all of those who might be considering IUI.

Nicole Yoder:
All right, talk to you next time. That sounds great.

Kristyn Hodgdon:
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