Thomas A. Masterson, MD
Assistant Professor in Urology at the University of Miami Miller School of Medicine, University of Miami – Miller School of Medicine
I will sort of little deflect, so in my practice, I deal mostly on the male side, so my goal is to try and get sperm, the most advanced sperm, meaning that has the highest quality to be used for whatever the patients are trying to do. In the United States, ICSI is becoming the standard for IVF, different offices have different protocols, but yes, I know that is not the case around the world.
It depends on the reason the patient is having it. For patients who are obstructed, we try to do one good procedure, and if there’s leftover sperm, freeze it for future use. I do have patients who don’t want to go under general anaesthesia or have reasons that they can’t, and I will do the TESE needle biopsy as many times as is needed. I’ve done as many as four for four different IVF cycles.
When it comes to the mTESE, I will do one if we find sperm, and if they have an unsuccessful IVF cycle and are looking to try and do another, I would consider doing a repeat mTESE. In patients where we do not find sperm on the first mTESE, I do not do a second mTESE.
With sperm DNA fragmentation, there can be multiple reasons why patients have it, and if you have an identifiable cause of it, we first try to treat that. There may be patients who come in with a high DNA fragmentation, and no one’s checked their semen for other causes such as infections or high white blood cell counts. If that’s the case, we try to treat the infection, try to treat the leukocytes or the white blood cells and then recheck it.
If a patient has a varicocele, which means dilated veins around the testicle, that’s a surgically correctable cause of high DNA fragmentation. We would treat it. In some patients who have an idiopathic cause, meaning we can’t figure out why their DNA fragmentation is so high, we have some fertility supplements which are that are full of antioxidants, and that’s what we will put them on empirically.
If they’ve had cycles, if none of that has worked, rarely, but we do this, we will do testis biopsy to get the testicular sperm which should have lower DNA fragmentation and do IVF cycles using testicular sperm.
Recovery time is usually about two weeks, so my post-operative instructions are 24 hours of bed rest with plenty of ice, Motrin and Tylenol for the pain, they will wear a jockstrap or scrotal support just tight-fitting underwear.
I recommend that they wear that for at least three days, but most will wear it for up to a week. When it comes to activities, two weeks of no heavy lifting, sexual intercourse, masturbation. After the two weeks, they can reintroduce activities as they feel fit. Certainly, if you’re still having pain take it easy, but again you can get back to running, walking, biking as long as it’s not painful.
This depends on the state and countries. In Florida, insurance doesn’t cover any of these procedures except for rare circumstances. Some states in the U.S. do cover IUI cycles or IVF cycles, but as far as overseas, I don’t know the details of most of the countries and what their national health plans do.
In non-obstructive azoospermia, this is the production defect, what it means is that the testicle itself is not producing a lot of sperm. When we do mTESE, the plan is to do one mTESE, and if we find sperm, we use it and freeze whatever is remaining. If they have an unsuccessful cycle, we’re considering a repeat mTESE, if someone had sperm the first time, if on the first mTESE we did not find sperm, I do not do a second mTESE.
If we were successful the first time on mTESE, we’ll consider a repeat. If we were unsuccessful on the first mTESE, I do not consider it a repeat. As far as conventional testis biopsies, I do not recommend them for patients with NOA, but you can perform multiple. If you didn’t find sperm the first time, your chances of finding sperm on a repeat conventional biopsy are very low.
It sounds like you’re describing a high FSH in small testicles, which is non-obstructive azoospermia. If you have the capability of performing mTESE, I would recommend mTESE in that instance. I think the guidelines from the ASRM, The American Society of Reproductive Medicine in non-obstructive azoospermia, say that mTESE is the preferred technique. If you’re in an area where no one performs that procedure, then a conventional TESE is what you have to go for, and that’s going to be your best bet.
This is a complicated question with many nuances to it, and I don’t want to give you an answer and tell you this is what you should do because there are multiple factors involved, the male side is just half of it. This could also be affected by female parameters. If you do a DNA fragmentation test that shows high fragmentation, again look for causes that may be initially causing it, infection, varicocele. The threshold cut toffs depend on what tests you use.
There are different tests, there’s something called a Comet usually, 30% is about what we use as a cut-off before we would consider, at least initiating some treatment. Before going to a TESE, again we look first for reversible causes before we start trying to use testicular sperm. The reason being testicular sperm having a lower fertilization rate, to begin with. There are risks by going to the testicle and going ejaculated, and I’m assuming ejaculated with sperm was used in these previous ICSI cycles.
This gets into some nuance, for the most part, the patients we see with non-obstructive azoospermia have normal testosterone. There are cases such as Klinefelter patients whose testosterone may be lower, and we do try to optimize their testosterones beforehand. The concept is that testosterone is used to get sperm through that last step of maturation. By potentially optimizing the testicle’s testosterone production, we may be increasing our chance of obtaining sperm. In Klinefelter’s patients, it has been shown to increase your chances of sperm retrieval.
Outside Klinefelter in this sort of idiopathic non-obstructive azoospermia, the results are a little more mixed. If they have a low testosterone level, and it appears to be correctable with medical therapy with Clomid or Anastrozole, I would try to increase their testosterones beforehand. I will not use exogenous testosterone, meaning I will not give testosterone gels, patches or any other form because that will decrease the testicular production of testosterone and lower your chances of finding sperm.
I don’t know that there is a maximum FSH or a maximum LH. If you look at patients who are not obstructive azoospermia, what you’re looking at is potentially a testicular failure. When the testicle’s not making sperm, the brain senses that and gives the signal FSH to the testicle to tell it to make more sperm. Is there a point where the FSH means that signal is so high that we just say to ourselves there’s no chance we’re going to find sperm, and I don’t know if that data exists yet.
I use these numbers to determine what kind of medical therapies I may use to try and boost testosterone production. If the FSH and LH are over 15 to 20, I’m less confident that putting them on a medication like Clomid or hCG is going to affect them. To summarize, there’s not a cut-off of FSH where I would say there’s no chance we’re going to find sperm.
Some of my colleagues are working on this paper, so I won’t give you the big results, but so far, it looks like, with COVID-19, it’s like any other febrile disease, so in times of stress or fever, sperm counts do decline transiently afterwards. It takes about three months for a sperm to grow up from the germ cell to an adult sperm, anything that negatively affects sperm production, say you go into hot tubs every day, that’s going to drop the sperm count almost immediately, but it will recover as long as the offending event is removed, so that’s my teaser for this.
I do not do testicular mapping, I go straight for mTESE. Some people swear by it and think that it will increase your chances of finding sperm, but I trained in a place where we do straight from mTESE, and sperm retrieval rates are similar.
DNA fragmentation should not increase with age, assuming you have a healthy individual. The same thing with semen parameters in patients who do not have a chronic disease, diabetes, high blood pressure, metabolic syndrome, sperm counts should remain and should not be declining. It is typically a chronic disease that causes many of these other abnormalities in sperm.
I don’t have a great answer for it since I don’t do the actual IVF procedures, I don’t think there’s any data to show that the vaccine is harmful to IVF cycles, but I would ask your particular physician what their thoughts are and what they do, but I don’t believe there’s any contraindication.
It’s usually not the volume, but you’re looking more at the numbers of sperm. Something to keep in mind is that in the freeze-thaw cycle of sperm, about 50% of them are going to die off. How much is frozen or what you decide to do depends on multiple factors.
If you’re talking about a patient who had mTESE, and maybe you only found 10 sperm, and you used 5 or 10 of them, or you have some leftover, maybe it’s only 1 or 2, it may be worth trying to save those couple of sperm, it may not be, so really it’s a decision made between you and your physician. Some patients don’t want to freeze any of the sperm, they just want to do one and done, and that’s all. Meanwhile, with ejaculated sperm, you may have millions leftover that you may want to freeze, so it’s not one answer.
To cover what these two things are. Short-acting testosterone is that you take multiple times a day. The two main ones are Nitesto and nasal gel and the new one Jatenzo, which is an oral medication. Compare this to injections which might be once every week to two weeks, pellets which might be once every four to six months.
There is some data to show that the shorter-acting testosterone has less effect on your LH and FSH, as well as semen parameters. Normally, about 60% of guys become azoospermic while on testosterone therapy with the short actings, we don’t see that. We see just small drops in their test in their sperm counts, but they don’t seem to go to zero.
No one has really looked at it. I typically don’t give hCG to men who have normal testosterone. If they’re on the low end of the normal, and they have symptoms of low testosterone, we may consider it.
The reason behind some of this is that hCG mimics LH, so theoretically, it should not drive your testosterone levels as high, it should have less effect on your fertility since you’re not suppressing testicular testosterone production. Long-term HCG use there are not studies, but I can tell you at least anecdotally you know people who go to the gym may be using it, and they seem not to have a ton of ill effects from it.
I screen using just total testosterone if it’s borderline. If the testosterone is around 300, it’s considered to cut off for low. If it’s borderline then I may consider getting free and total on the second since here in the U.S., to get testosterone covered and approved, you need two levels below 300. If there’s any doubt whether it’s low or not, you can get a free to check if the free testosterone is low, and it just supports your diagnosis.
What you’re referring to testicular salvage protocol, one form of treatable non-obstructive azoospermia, so in people with production defect is prior testosterone use. In those patients, we don’t do any of these sperm retrieval techniques we would treat medically to try to get their sperm production back in gear.
It’s non-obstructive azoospermia that’s caused secondary to medical therapy. We take them off of the testosterone, and I then place them on hCG three times a week as well as a medication called Clomid. Clomid causes the natural FSH production to increase, and hCG mimics LH, so you’re getting both of those signals to the testicle to try and increase sperm and intratesticular testosterone production.