Hutchison’s Huddle: Intrauterine Insemination (IUI)

Intrauterine Insemination is a common fertility procedure offered to patients trying to get pregnant. For patients using donor sperm, those who have cervical issues, or some mild forms of male factor, it is often a first step before heading down the path of IVF or other fertility options. On this Hutchison’s Huddle, Dr. Scot Hutchison shares everything you need to know about an IUI. Dr. Hutchison not only explains who might be a good candidate for the procedure, he also shares the steps in the process, as well as shows all of the tools used in the process. Find the video below on Facebook or YouTube. If you have additional questions about IUI, please contact us.

So who do we do intrauterine insemination for? So the main things are donor insemination patients–patients who are using donated sperm either anonymously or from a known donor that’s been qualified to be safe for them to be using. And a lot of, especially the anonymous donor samples, are so expensive now that what we’re trying to do is maximize the efficiency of the of the whole process by getting the sperm higher up into the uterus rather than placing them just into the vagina, which is relatively inefficient, especially when you’re spending about you know, between anywhere from $600-1,000 on a on a semen sample. Semen samples have gotten so expensive because after HIV and other sexually transmitted diseases came along, the Food Drug Administration mandated that the sperm banks do lots of quarantining. So basically donors will be screened for all the bad diseases, then they’ll produce samples sometimes every other day for a month or two for the sperm bank and then those samples are frozen. And then after the bank feels like they’ve had enough sperm stored, then they’ll wait for another few months and at about the six month mark from the original screen, they’ll recheck the donor for all the bad diseases and if they don’t have anything at that point, then they’ll say, Hey, this this guy, his samples can be released for use. But that holding cost and all of the cost of the testing and FDA is mandated that the sperm banks use specialty laboratories that rather than just your local LabCorp Center or Quest for testing of the donors, that is all driven up the cost tremendously. And because the samples have to be frozen, we can’t use fresh ones anymore, those samples, there’s manpower and laboratory cost, and things like liquid nitrogen and media that all have to be paid for and so that has driven up the cost of those samples. So making the process as efficient as humanly possible is the goal. 

So other patients who will need or can use intrauterine insemination are people with cervical facto–so people who have a cervix that’s too narrow. And sometimes that’s just sort of a congenital issue, the patient will have just a narrow cervix from the get-go. That also appears to increase the risk of endometriosis, which then can interfere with people getting pregnant. Obviously, you can dilate the cervix if you need to, either in the office or if that’s difficult in the operating room. But sometimes the cervix doesn’t make a lot of good watery cervical mucus and that’s another potential advantage of the intrauterine insemination because you can get past the cervix up into the uterine cavity with the sample. 

Other patients that just have unexplained infertility. So some you know, some guys have not tons and tons of really progressively mobile or fast swimming sperm and so we will be able to concentrate out the good ones and get those up into the uterine cavity every single month because a guy may have a good semen analysis on one month and then the next month, he may be underperforming and on that second month, if the motility is not great, they would have a very poor chance of getting pregnant and we can actually bring that up to the normal for that person’s age range. 

Then for people with endometriosis, we are trying to super ovulate them. We’re trying to get them to make more eggs than they normally would make to try to get a better chance of getting a normal egg that’s not damaged into play so that we can improve the chance of pregnancy. 

Let’s talk a little bit about IUI. What do people expect on the day of the IUI? Well, first of all, we look with ultrasound. Usually, if people have a 28 day cycle, we like to look around, cycle day 10 to 12. We don’t want to miss it. We don’t want it to, you know, sometimes people will ovulate really early, so we’re trying not to miss their ovulation. Typically speaking, what we tend to see is that when the uterine lining thickness gets up to around eight millimeters, and the uterine lining looks nice and three-layered, and if the lead follicles, depending on the person’s age, are somewhere around 16 to 18 millimeters in diameter, that’s usually day of LH surge. Ovulation then, or release of the egg from the ovary will actually occur about 36 to 44 hours after that. So what we do with our UI cycles and you get in–you know, some places will make this a very cumbersome process, which I think is a waste, because I don’t think it adds to the chance of pregnancy at all. But some practices will start checking hormone levels all the way through, certainly with pill-form fertility drugs, I don’t think that that’s necessary at all. So things like letrozole or clomiphene, we do not draw serial estrodials or typically, if people, if there’s a suspicion that they may need supplemental progesterone, because it’s so inexpensive, we’ll have them start that a couple of days after ovulation, which the ovulation is presumed day of egg release, and then that’s the day that we put sperm in the uterus. 

Also some practices will have people take injectable FSH to try to go from making more than two to three eggs at a time and it’s interesting in that there are a couple of randomised trials that looked at that compared to pill form fertility drug alone and they did not show an improvement in pregnancy rate. They did show an increase in twins and triplets actually came into the picture. So triplets are usually you know less than 1% with pill form fertility drug alone, especially in women over 30, but when you start adding those injectable follicle stimulating hormone or combination follicle stimulating hormone and luteinizing hormone activity injections into there, you’re going to increase your twins rate from about 5-7% to be it could be up as high as 15% and the rate of triplets could be as high as 5%. Multiples, you probably heard me talk about this, multiples are bad because even twins are delivered usually on average about four weeks earlier, so we don’t know that they ever really reached their full intellectual potential. Also, twins have much higher miscarriage risk and about a four to six times increased risk of having something bad happen like cerebral palsy. So then if you go to triplets, it’s even above that by a long stretch. Certainly people can do selective reduction where you go in there and destroy one or both of the extra embryos. The problem with that is it’s basically it’s kind of a brutal process and you’re having to inject the embryo with usually like a potassium solution, and it’s whoever is closest to the needle gets the injection and there is then–you don’t really get–you could have triplets and reduce down to have them. You’re not going to go to the typical 40 week of gestation range for the whole pregnancy, it will be less than that. It’ll be somewhere between the triplet average which is around 31-32 weeks of gestation and then the term. Even taking triplets to twins, you won’t get to 36 weeks from 32, you’ll get to about 34. So selective reduction if someone gets pregnant with triplets is definitely worth considering, but it is a brutal process. And I think that we here consider it our job to try to minimize that risk as much as humanly possible. Certainly, we’ve seen some horror stories of patients coming from other practices where they were given injectable fertility drugs and then they conceived with quintuplets after developing a very hyperstimulation syndrome and even having some multi organ failure. And then losing all five of the babies. I mean, these are horror stories that really nobody needs to go through anymore. So I think it’s worth considering if you can get to ovulate, especially if it’s two or three larger follicles with just pill form fertility drug alone, stick with that. Don’t spend the extra money and it is significant extra money–the cost is about another $600 for the cycle if you’re using injectable fertility drug. 

We tend to look just at the ultrasound, we don’t tend to draw the estradiol levels beforehand. We will have people use an HCG trigger most of the time. I think it’s not necessary. A colleague of mine had a couple babies with this process and then with each time, each kid was a year or two apart, and we were prescribing trigger shots even back then, and she had told me a while ago she said, You know gave me that trigger shot to take with each of my pregnancies, and I said Yeah and she said, Well, I didn’t do either one of them! So, obviously, just getting good sperm in the right place and ovulating is really probably the most important thing because most of the time the patient will get her own LH surge if the ovaries are working predictably.

What do the tools look like? Basically, it’s like having a pap smear. So typically, we use a smaller speculum, so what’s called a Pedersen Speculum. So you put this into the vagina, you open up the speculum so that you can see the cervix at the end of the speculum. And then we use these little–they’re called Norm-Ject syringes. These are mouse embryos tested, there’s not a rubber gasket in there, it’s just purely two pieces of plastic. And so we feel that these are the least toxic to sperm and eggs and embryos and things. So this is the kind that we use. And then that hooks up to–this is our current catheter we use, which is called a Rocket Duo. 

And I like this catheter because these are modeled on embryo transfer catheters and they tend to be pretty soft and atraumatic. So the assembly comes with a little sleeve and you take this, take the catheter out of the sleeve, and then the washed sperm sample will be distilled down to about three tenths of a cc of some sterile nutrient media that the sperm are resuspended in. You hook up your syringe to the catheter assembly and then we’ll draw up the sample–so we’ll pull the plunger of the syringe back, and usually it’s to about there (see 13:25). And then, most of the time, you can just directly insert this flexible catheter up into the uterine cavity without it causing a lot of trouble. And typically, we go to about six and a half centimeters so you know, basically about that far up into the uterine cavity (see 13:48). We’ll get it there. We try not to get all the way at the top of the cavity and bang into the top of the cavity because that actually may decrease and cause more inflammation. And if your uterus is tilted forward or anteverted, which most people probably 80% of people have it tilted forward, having a moderately full bladder will push the uterus flat and so it will make entry of this catheter a little bit easier. Now you can, if the uterus is sharply tilted, you can bend the catheter to acquire the shape and certainly we will use ultrasound from above to guide our way in if we need to. And you can also then back up the outer catheter tip to sort of bolster it so that it can work its way around little corners a little bit better. Having a little bit of cramping and sometimes a little bit of bleeding is normal to see, but with these round tip catheters that have the two side ports, we usually don’t see a lot of bleeding most of the time, we don’t see any. And most of the time we don’t have a whole lot of trickle back, if any. That’s a standard intrauterine insemination catheter. Embryo transfer catheters are very similar to this only, they typically don’t have a rounded tip because you know, sperm,–if we’re losing a few sperm in the residual of the catheter, it’s not a big deal–because we’re looking we’re going for between about 5 million to about 20 million moving sperm. So if you’re leaving some of the sperm in this catheter, it’s not a big deal. Embryo transfer catheters, on the other hand are usually clipped off at the top. They may be a little bit rounded on the edges of the catheter, but it’s just a smooth barrel that goes up into the uterine cavity because you don’t want the embryo to get stuck in the catheter tip. But, very similar configuration and again, just like with embryo transfer catheters, we’re trying to just slide these in as gently as humanly possible to create as little discomfort as humanly possible. Certainly with embryo transfers, now the gold standard is we’d like to make sure–I always ask the people, it wasn’t even perceptible and certainly they’re going to feel the the ultrasound transducer on the abdomen, but they shouldn’t feel my part of the embryo transfer much if at all. The goal is for them to not even feel it at all. 

Here’s another intrauterine insemination catheter. This is one that was called the Select IUI. These are a little stiffer. Oddly enough, these–you know, cost is always a consideration because it has to be passed on to the patient, so we try to make things as inexpensive as we can–and oddly enough, the cost differential between these two catheters was not all that different. And as you can see this other older style catheter, it has a round tip with some fenestrations at the top and like the other catheter, a couple little ones. The difference here is that you can tell this catheter is a little less malleable, a little less soft. And so you know, we had good success rates with these, but they would take a little bit more work to mold into the curve that you wanted. We have, for the most part, switched to the other one. Speculum, you saw before, should be warm and is usually just sort of perceived as a lot of pressure, hopefully, and certainly if it is uncomfortable, you want to give your practitioner feedback about that and let them know if anything is being pinched or is uncomfortable, but usually it takes just about a few minutes–not even a few minutes. We typically will put in little boluses, little aliquots of the seminal plasma. And I like to go kind of slow and then look for any trickle back out through the cervix. And then we’ll just do this over a minute or so and just trickle that sample in very carefully. And if the patient has any cramping, I typically will stop, wait until it’s over, and then keep advancing the plunger until we’ve gotten the sample all the way in. Then I will drop the speculum blades down a little bit, and just back the catheter out and look for any trickle back and if I see any, then I’ll tell the patient, so that they know what to expect because when they get up, they may see some of that fluid either right then or they may see it trickle out down the road. So it’s kind of like a pap. 

We tend to have people stay down for about 15 minutes after doing the insemination because it doesn’t increase their risk of bladder infection the way intercourse does and it might help. And certainly when you’re using a $1,000 donor sample and you see some of the trickle into watery cervical mucus, I always like to give that sperm a chance to swim back up into the uterus. However, in the committee opinion that was published in 2017 about intercourse, staying down after intercourse was of no benefit at all. So it just increases your risk of bladder infection. So I would encourage you to get up and empty your bladder after you have intercourse right away. 

I’ve talked about this on other ones, but every day was also found to be better than every other day with regard to intercourse. Even if you’re doing intrauterine insemination with partner sperm, I strongly recommend that you have intercourse frequently along the way because we don’t want older sperm. We want sperm that are younger and have less DNA fragmentation for the sperm that are going to be fertilizing the eggs. And those are presumably our insemination sample sperm, but some of the good sperm can live in the cervical mucus or upper uterine cavity for sometimes five or six days. So having intercourse frequently is good! Also there are proteins in the seminal plasma, which may improve the chances of implantation. Then, sharing each other’s bacteria can also potentially help the woman become less immuno-aggressive to where she’s more immuno-tolerant. And certainly half of the baby is going to be this foreign genetic material so that that may be of use as well. 

So what are the pregnancy rates like? Pregnancy rates for IUI are a give or take 10%. I think that’s a good general rule of thumb. With the older protocols where we would use the injectables, plus the pill form fertility drug, when we would look at the pregnancy rates year to year, we would hit more like 15 to 18%, sometimes 20%. But again, there were two randomized trials that didn’t show any benefits. So I think you have to look at those randomized trials more than your anecdotal practice numbers.

Are there any risks associated with IUI? Well, I don’t know. I’ve been doing this for 25-28 years and have had none. So pretty, pretty low risk of infection. You can have some pain from the ovulation and certainly if you’re making more than one follicle, you will have some ovulation pain or Mittelschmerz. 

How is the sperm washed–how is the seminal plasma washed? Well, so seminal plasma is about 99% fluid–98% fluid and then about a couple percent sperm cells. So the rest of that fluid, you know, will contain prostaglandins, those transforming growth factors that I talked about earlier that may help with implantation. And the bad part about seminal plasma is really those prostaglandins. Why they’re in the seminal plasma in such high concentration? Who knows, but they’re coming from the prostate gland and that’s why those molecules were first called prostaglandins because that’s where they were first isolated from. Prostaglandins can be used for cervical ripening and induction of pregnancy and that’s why we will always say if people are tired of being pregnant once they’ve reached term and they want to get delivered, even though the last thing they feel like having is sex, but we’ll tell them, go ahead and have intercourse because some of those prostaglandins in the seminal plasma may help move things along. But if you put raw semen up inside the uterine cavity with one of these slick little tubes, you potentially could make the person–well, you will make them cramp super, super badly, and potentially even code. So back in the days where people figured out how to draw these little nifty little plastic tubes–actually the first insemination catheters were a similar material, but they were made for draining cat bladders because sometimes cats will get urinary retention–they thought, wow, I’ve got this really nasty cervix that won’t let sperm through, it’s too narrow. And so let’s just put raw semen up in the uterus with one of these guys. Well, that was a disaster because it’s super painful. So what we do is we will layer the seminal fluid over some nutrient media and then spin that around in a centrifuge and basically the moving sperm will move down to the bottom of the tube. And then you can take the top layer of that seminal plasma, nutrient media and throw that away and then keep doing that until you get a very, very clean sample. So you will have some prostaglandin adsorbed or stuck to the outside of sperm, but typically, it’s a very, very small amount. Here, we don’t like to go over 100 million sperm for an IUI. And if we have a good, really good sample where we’ve got 150 million or sometimes you’ll get–one time we had 300 million moving sperm in a sample–you don’t want to use all those for that. Because the more sperm you put up in there, the more prostaglandin you’re putting in as well, even though they’re just stuck on the sperm and you’ve washed it as clean as it can be. So in those cases, I typically will say, all right, if I’ve got 120 million moving sperm in the sample, I’m going to put, you know, 75% of that up in the uterine cavity or so. Then I’ll back out the catheter into the cervical canal, and then I’ll trickle the last bit into the cervical canal, allowing those sperm to still have a chance to get up into the uterine cavity. 

Do you need to rest after the insemination? The answer is no. You can get up and go ahead and you go back to normal activity. Same with exercise. We do typically recommend that people continue to have intercourse for another couple of days. But again, you do not need to stay down after intercourse at all and you should empty your bladder right away.

So how long after implantation–or how long after the IUI can you detect pregnancy? So the normal deal is from ovulation to menstrual period or positive pregnancy test is usually about two weeks. So it’s 14 days to that luteal phase, or secretory phase as it’s also called, will be just about 14 days plus or minus two days. If it’s a lot shorter than that. If you know that you’ve ovulated say, on cycle day 14 and then you’re getting a period on cycle day 23 or 24 then you may have what’s called a luteal phase defect and you may need to supplement progesterone. But the normal routine is that on the day of ovulation, that’s when the egg is fertilized. Eggs are usually fertilized very quickly, usually within a few hours, that’s why we want the sperm waiting on the egg, not the other way around because you get better embryos that way. The eggs timeout very, very quickly if they’re not fertilized rapidly. Then the embryo makes its way down into the uterine cavity after a period of about five to six days. So you usually are going to get an LH surge and then you’re going to ovulate around cycle day 13 to 15, then five days after that you’ve got an embryo rolling into the uterine cavity and starting to implant and then those cells have to go really quickly and divide rapidly because they need to start making human chorionic gonadotropin, which is pregnancy hormone because that’s the signal that keeps the ovulation cyst making progesterone. If it does not see that signal, about two weeks after that ovulation, that corpus luteum is going to start to implode and will undergo programmed cell death and then the endometrium or uterine lining will then dissolve and be shed. With these new urine pregnancy tests, you can actually pick up a positive pregnancy test sometimes I’ve had patients say even nine to eight days, nine days after ovulation or earlier. I personally wouldn’t do checking that early. I think it’s a waste of money. I typically tell people there are so many biochemical pregnancies, these pregnancies that are really early miscarriages. I don’t know, I guess it’s good information to have that you got some implantation, you get your hopes up kind of. I would wait until around the time that you would be expecting a period before I would go ahead and check a urine pregnancy test. Then after that, we check blood pregnancy tests a couple of days apart and the pregnancy hormone levels should basically double every two to three days. They don’t have to. The rise can be lower than that, but that’s kind of what we’re looking for, for normal pregnancies. 

How many cycles is a good try? Well, there was one paper that showed that about 90% of the pregnancies occurred in the first four cycles. And there was another paper that showed that about 85% occurred in the first three. So somewhere around three to four cycles is a good try. Now if you get pregnant or you have a miscarriage–if you have baby or a miscarriage doing this, then I think it’s reasonable you can keep trying and doing more. But typically, the cost effectiveness with it is about three to four cycles. And then maybe it’s time to move on to something else like IVF.

What else do we have? Oh, mild male factor, I think we talked about that. But guys, keep in mind you know, we see lots and lots of male factor now. I think far more than we used to male semen parameters have fallen by five fold over the last hundred years and that’s probably a combination of pollution, disruptions such as less exercise, less sleep, more junk food. I’ve talked about this before, but you know, in a study from the Netherlands saw that if you gave guys junk food every day that their semen parameters just declined month to month to month. So stay away from junk food, don’t drink alcohol, or use recreational drugs. I’m telling people to avoid CBD oil because at least the samples that have been tested around here usually have one or 2% THC, if not even more. Certainly, I think it is to be avoided for the time being until maybe there’s a more pure form, but I don’t know. I would leave that stuff, you know, way far alone. And tobacco as well, smoking, even being around a lot of industrial fumes is really strongly discouraged if you’re trying to get pregnant and for a whole bunch of reasons. 

Anyway, if anybody has any questions on IUI, feel free to chime in and if we log off before we see your questions, please feel free to contact us and we can try to answer those questions for you. But have a great night and if you have the chance,  enjoy the sunny weather here in southern Arizona in the spring, summer, and fall, but summer is pretty hot!

So have a great day and we will see you on the next Hutchison’s Huddle and feel free to check out the other ones that in our Facebook archive and with some of my collaborators discussing things like endometriosis and polycystic ovary syndrome and all kinds of stuff. And on YouTube! Yeah, it’s on YouTube now, can you believe it? But we’re trying to make social media help our population, not hurt it.

Oh and don’t drink bleach for Coronavirus, please. Don’t believe anybody that says that they sell a little herbal something that can cure Coronavirus either. Wash your hands a lot and be careful going to big events. So, have a great night, stay healthy, and we’ll look forward to seeing you down the road. Thank you!