Fertility Topics Explained from the Experts at SFS
What is IUI with guest Dr. Geoffrey Sher
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This article originally appeared on The Egg Whisperer Show, hosted by Dr. Aimee Eyvazzadeh. You can find her site, along with other episodes like this one at her website: https://draimee.org/blog
Dr. Aimee: Let's get started. What is IUI?
Dr. Geoffrey Sher: First, let me provide context: Up until the mid-1980s, sperm inseminations almost exclusively involved the intravaginal introduction of whole semen, and was not an intrauterine insemination (IUI) procedure. The procedure was largely confined to cases where donor sperm was being used. The results were comparable to the natural conception rate of infertile women (i.e., about 20%). In those cases where IUI was done using whole semen, only a very small amount (about 0.2ml) was inseminated to avoid the common occurrence of severe, and even life-endangering reactions, caused by the intrauterine injection of a large volume of whole sperm. Semen is comprised of 98% milky fluid (plasma) and only 2% spermatozoa. The seminal plasma contains substances known as prostaglandins which upon reaching the uterine cavity, can cause a violent reaction (anaphylaxis) which can be life-threatening. Besides, the pregnancy rate was dismal. Therefore, the intrauterine introduction of whole sperm is now avoided.
In 1982, I and a revered friend and mentor at the University of North Carolina, Chapel Hill, (who was one of the first doctors to be Board Certified in the field of Reproductive Endocrinology) came up with the idea of separating sperm from seminal plasma through centrifugation (a "washing” process), incubating the sperm-rich fraction and injecting the latter via a catheter introduced through the cervical canal directly into the uterine cavity. And so, modern-day IUI was born.
Dr. Aimee: You're telling me that I'm talking to the guy who set up the first IVF practice in the United States and did the first intrauterine insemination, washing sperm to make pregnancy safer for women by IUI?
Dr. Geoffrey Sher: Yes, we published the first paper on IUI in the Journal of Fertility and Sterility back in 1984. The approach soon caught on and is currently used throughout the world.
I had just returned to the U.S.A from visiting with Drs. Steptoe, and Edwards (the fathers of IVF) in the United Kingdom. In 1982, I went on to establish the 1st "Private" (non-university-based) IVF program in the United States. I soon realized that we could better prepare sperm for IUI in the same manner as we did for IVF. This meant separating sperm from seminal plasma by spinning it down through centrifugation, incubating it to enhance the ability of spermatozoa to penetrate the envelopment of the egg ("capacitation”), and then injecting the purified/enhanced specimen directly into the uterine cavity.
I went on to conduct a study which revealed that following controlled Ovarian stimulation with gonadotropins, in cases of "unexplained infertility”, non-immunologic cervical hostility to sperm, and in certain cases of ovulation dysfunction, the use of IUI significantly enhanced utility and success. However, there was absolutely no benefit using IUI in cases of "male infertility"; endometriosis; tubal adhesions; women over 40 years of age, and in cases where the woman had diminished ovarian reserve (DOR).
Concerning the reason for reduced fertility in cases of endometriosis, it is important to bear in mind (regardless of severity) that there is a "toxic" environmental pelvic factor created by the lesions in the pelvis. As sperm passes from the ovary to the tube, through this adverse environment, its ability to penetrate the egg (lying in wait in the Fallopian tube(s) is severely compromised. This reduces the conception rate by at least a factor of 3-4.
I found that for women in their early 40's, the IUI success rate is <3% per cycle and by age 44 years, it drops to about 1:50.
In moderate or severe male factor infertility the use of IUI did not improve the pregnancy rate at all.
In my opinion, the use of IUI should be restricted to cases where the woman has a normal ovarian reserve.
Contrary to popular belief, IUI does NOT improve pregnancy rates per treatment cycle in women who are regular and normal ovulators. Even with the use of fertility drugs, such women rarely release >1 egg at a time. This explains why the incidence of multiple births is also not increased in these women. Conversely, women who have absent or dysfunctional ovulation (e.g., women with irregular or absent periods and those who have a condition known as polycystic ovarian syndrome-PCOS), commonly release several eggs at one time. Accordingly, both COS/IUI success rate as well as the multiple pregnancy rate is much increased in such cases.
Intrauterine insemination is a good procedure when used in combination with COS using gonadotropins for the proper indication. However, it is not a good approach if misused. It is also much less successful when used with the oral fertility agent, clomiphene citrate (Clomid/Serophene) which is an anti-estrogen. The pregnancy rate is about one-third lower in such cases. In my opinion, it is preferable by far to use gonadotropins to prepare for IUI. You get better results that way.
Dr. Aimee: What I would say is I agree with you, but what I don't understand is why is there this misconception out there that IUI is amazing, and it fixes everything? People come in and they're like, "I'm ready, I want to do IUI." Why do you think there is this misunderstanding? When I tell people, "Your pregnancy rate is going to be around 10% with IUI, maybe a maximum of 15% based on your age," why is there this disconnect out there?
Dr. Geoffrey Sher: It is probably because a lot of doctors don't do IVF and prefer to think that IUI and IVF are equivalent. There is the misconception amongst patients that using fertility drugs and then insemination will give them an edge. Many doctors who don't do IVF, still offer their patients IUI. The big tragedy, in my opinion, is that often women delay doing IVF, and in the process their age increases, their ovarian reserve declines. In other words, the biological clock advances, and in the process, their chance of having a baby erodes further.
There is an important fact that most are unaware of. It relates to why normally ovulating women do not have a significant increase in COS/IUI pregnancy rates and do not have an increased incidence of multiple pregnancies, while dysfunctionally ovulating women have an increased incidence of both. Ovulating women may well produce a lot of follicles in response to COS. However, only one will usually grow more rapidly than the other cohorts do. This is the follicle that leads the way (i.e. the "Dominant Follicle"). It is this one that following the hCG "trigger" goes on to ovulate. The others do not grow as fast. It is the Dominant Follicle that ovulates first. The moment the Dominant Follicle releases its egg, the others stop dead in their tracks, they involute, and are ultimately absorbed.
Therefore, when you conduct COS/ IUI in women who are not ovulating, the pregnancy rate is higher, as well as the multiple pregnancy rate per treatment cycle. Conversely, women who do not ovulate functionally (e.g., PCOS patients)., can achieve pregnancy rates of >30% per cycle. However, if you do IUI with fertility drugs in women that are ovulating normally, there is no increase in multiple birth rates. The only time you see an increase in the incidence of multiple birthrates is when it comes to women with absent/dysfunctional ovulation. These women usually produce a large number of follicles and have no identifiable Dominant Follicle. In such cases, numerous follicles rush to the finish line together and simultaneously release their eggs. That is how such women often end up with multiple pregnancies.
Normally ovulating women who undergo COS/ IUI don't have an increased incidence of twins or triplets. However, because the dysfunctionally ovulating women produce far more follicles than their normally ovulating counterparts, they are also at increased risk of developing severe ovarian hyperstimulation syndrome (OHSS)
Dr. Aimee: I think right now with COVID a lot of people are just so stressed out about even having sex, so sometimes IUI can help with that.
Dr. Geoffrey Sher: Yes.
Dr. Aimee: I always say you can take it out of the bedroom and just bring it here, I'll make your sperm sparkle and we'll do your IUI. At the same time, patients just really need to know what their chances are so that if something doesn't work, they're not going to feel misled or misguided, or extremely upset. It's always upsetting when something doesn't work, but if you go on saying most people who do this treatment are not going to be successful, it's just part of human biology when it doesn't work, I think that counseling up front is helpful.
Dr. Geoffrey Sher: Yes, I think it's important for people to avoid the misconception that IUI is this miracle procedure that's going to increase the pregnancy rates above the normal. It may do that if the woman is not ovulating or ovulating abnormally, but not in cases of normally ovulating women.
Dr. Aimee: I think that's a great point. A lot of doctors that do it, for example, are general OBGYNs and they can't do IVF, so patients are kind of stuck in that treatment type because they aren't counseled appropriately about what their diagnosis is, what their prognosis is, and what treatments they can do that will give them a higher chance. They might not understand that they don't have as high of a chance as they thought they did.
I'm stubborn! What I mean by that is that sometimes I'll see a patient and I feel in my gut that IUI should work for this person. Let's say they're resistant to undergoing IVF. I've done six IUIs, nine IUIs, thirteen IUIs. The highest number of IUIs that I've done for one couple is 23. I have 23 gray hairs over all of them.
Dr. Geoffrey Sher: That's a lot.
Dr. Aimee: It is a lot. I'm the godmother of their child. Her picture, an oil painting, sits above my fireplace. Yes, it's a lot. That's only four scenarios where I've gone past maybe three or four IUIs. I can count four and that's it. But I see patients who sometimes they've done 12 IUIs and it's not because they weren't educated people, it's because they weren't given options.
Dr. Geoffrey Sher: There's another thing also…... In my experience, doing IUI in a natural cycle doesn't improve the chance of pregnancy. I recommend strongly against doing IUIs in natural cycles offering false hope of an improved chance of pregnancy. Yes, pregnancy might occur but, in such cases, it would probably have been just as likely to have occurred without it.
It's just a question of being selective and having your patients understand the odds. The greatest travesty of all, as I said earlier, is watching people go through repeated IUIs when you know they need IVF, and you're wasting valuable time that many cannot afford to waste.
Dr. Aimee: I think a lot of it sometimes is the misconceptions associated with IVF and people are so afraid. I just want to implore people out there to talk to an IVF doctor, and we're all IUI doctors as well, to dig into the reasons why you're having trouble conceiving, so you can come up with a great plan with a wonderful doctor like Dr. Sher.
Geoff, is there anything else that you want to add about IUI for our listeners?
Dr. Geoffrey Sher: It's a wonderful procedure done correctly for the right patient. It's often overused and, in my opinion, if undertaken for the right indication and fails to result in a live birth after 3 or perhaps 4 attempts, it is probably time to move on to IVF.
Dr. Aimee: Make sure your tubes are open.
Dr. Geoffrey Sher: Oh, yes, thank you. I've seen so many patients that have gone through IUI only to find out later to have blocked tubes. With blocked tubes, women should always realize the most common cause is tubal inflammation. AND, if one tube is damaged by inflammation, even if the other one is open, it doesn't mean that the patent tube is "competent". Pelvic Inflammatory disease is an equal opportunity problem. If one tube is involved, it usually means that both are damaged.
Dr. Aimee: I jokingly say that when I'm older, not quite, because I don't want to be like the crazy old lady with bumper stickers all over her car, but that's one of the bumper stickers I want on my car, "If one tube is blocked, please assume the other tube is affected." Please don't waste time doing IUI after IUI. In some cases, certainly, you could get pregnant. But if it's very obvious that you're not, don't waste your time.
Dr. Geoffrey Sher: That's a very good message. Make that bumper sticker.
Dr. Aimee: I will. Thank you, Geoff. Thank you for joining us. Thank you for talking about IUI today.
You can find Dr. Geoffrey Sher at Sher Fertility Solutions, or call 702-533-2691 and Patti can help answer your questions.
To learn more about Dr. Aimee, or the Egg Whisperer Show, please visit her website at www.draimee.org
You can also sign up for her Egg Whisperer School by visiting https://draimee.org/the-egg-whisperer-school
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