Testicular Sperm May Increase Pregnancy Rates After Failed IVF Cycles
Welcome to another episode of The Egg Whisperer Show. I am so excited to have Dr. Blake Evans on today’s show.
Dr. Aimee: Thank you for joining us, Dr. Evans. I know it sounds really weird to be excited about talking about testicular sperm, but I must admit I’m pretty excited about it because it’s possibly something that can help a lot of people by knowing about it. But before we get into that, I want our audience to really get to know you a little bit more. Tell us about yourself.
Dr. Blake Evans: It is great to be here. I am from Oklahoma. I grew up here. I’m married, have two little boys. They are extremely energetic and keep me on my toes always, and they enjoy fighting me and each other always.
I did all of my medical training in Oklahoma, aside from fellowship. I did undergrad and med school and residency at Oklahoma State University. Just finished fellowship recently at the National Institutes of Health. And I’m actually back in Oklahoma at the University of Oklahoma, which is the university rival of where I did all of my training at, so I’m very happy to be here.
Dr. Aimee: I imagine patients probably remind you of that rivalry?
Dr. Blake Evans: They do, but I do have a lapel pin with my alma mater, so everyone understands that I am from Oklahoma State, even though my coat says, “OU physician.”
Dr. Aimee: I love it. Well, thank you for sharing about yourself.
What made you go into medicine, and more specifically fertility medicine?
Dr. Blake Evans: It is funny. When I was doing my rotations in medical school, I said I wanted to do “anything above the waist,” and then of course went into OBGYN. I just really felt drawn to it. I really enjoyed the mixture of surgeries and deliveries, and there’s always excitement, never a dull moment.
But then I found reproductive endocrinology and infertility, and just absolutely loved it. And on a more personal level, my wife and I had to be seen by an REI and go through treatments. I was already undergoing my training and I found out about the specialty.
I just really, really have enjoyed being in a specialty and being able to help families. And there is always so much learning that is going on, and the field’s always changing. And it’s just very exciting to me. I’ve really enjoyed being in this field.
Dr. Aimee: That’s so true. You have published so much great research, and this is not the only time we are going to have you on this show. But today’s show is specifically about a very exciting award-winning paper that was published recently about how to improve IVF pregnancy rates titled, “Does use of testicular sperm improve outcomes in non-azoospermic couples with previous IVF failure using ejaculated sperm?”
That is a lot of stuff there to break down. Can you just break that title down for us?
Dr. Blake Evans: Sure. There are prior studies show that use of testicular sperm may in fact improve IVF outcomes. There’s prior studies that show it could lead to higher implantation rates, clinical pregnancy rates, and live birth rates. Very limited admittedly, and this is kind of a hot button in the field of urology/reproductive endocrinology and infertility.
In our study (which was entirely retrospective, meaning we were looking back at the outcomes that have already occurred), we wanted to evaluate men who have had a prior IVF failure without any obvious reason. They did not have a deficit in their sperm concentrations. We wanted to know if undergoing testicular sperm extraction improved their outcomes for IVF.
Dr. Aimee: How did you enroll patients in this study then, if it was retrospective?
Dr. Blake Evans: I worked on this paper in conjunction with a couple of the urology specialists at Shady Grove Fertility, Doctor Shin and Doctor Tanner Cutt. The patients asked if they wanted their info to be included. Testicular sperm extraction had been offered to these patients if they had failed prior IVF cycles and no obvious etiology. They were not enrolled prospectively. It was just going through and looking through all the data, and seeing which patients had had this treatment, and then looking at the outcomes.
Dr. Aimee: Great. Can you share the difference between extracted and ejaculated sperm?
Dr. Blake Evans: Ejaculate sperm is typically how the sperm is collected prior to doing in vitro fertilization. They have collection rooms as we’ll call them, typically in the clinic, in which the male will collect the ejaculate in a cup, and then that is used subsequently for IVF.
Testicular sperm extraction, it is a surgical procedure where the patient is asleep. There are a couple of different ways in which the sperm can be harvested, whether it be aspiration with the needle versus using a scalpel and excising a little small area of the testicle and looking for sperm under a microscope.
Now, I will say, I am not urology trained, and these are not surgeries that I do. Some of the extractions can be done in office if they are just doing an aspiration with the needle. But by and large, for all the patients in this study, they were asleep.
Dr. Aimee: What were the most important study findings?
Dr. Blake Evans: Now, keep in mind, this study was looking at a prior cycle, where the couples have failed using their ejaculate sperm. And so, now we are moving forward and looking at a new cycle that is using testicular sperm, and then injecting a single sperm into the egg or the oocyte.
And, for these prior cycles — all were considered cycle failures, which we defined as not getting past the stage of the embryo that we call blastocyst. They didn’t have a clinical pregnancy. Therefore, they didn’t have a miscarriage. Therefore, they didn’t have a live birth rate.
In comparison to their prior cycles, there was a statistically higher blastulation rate , or formation of a blastocyst, by about 30%. There was a higher association with blast conversion.
There was a higher association of number of embryos available to freeze. And so, if a patient has an embryo transferred, and they want to try for another child in the future, or the first one did not work, they had at least one to two higher a number of embryos available to freeze.
What is important to note about this study is: we did look at clinical pregnancy rates. We did look at live birth outcomes, which are important aspects of the study. They were higher. It was, about a 40% clinical pregnancy rate, and 32% live birth rate.
We did not statistically compare these to their prior cycles because that would be what we would call regression to the mean, because we didn’t have a control group. And so, that’s the limitation of this study. Something that’s very important to note is there was no control group in this study.
But if you are comparing prior cycles and looking at their next outcomes, is it truly an association with the testicular sperm during IVF, or is it just by chance that we found this increased outcome? We felt it wasn’t right to statistically compare them. That’s something that’s important to note.
Dr. Aimee: I mean, what I would say the most important study findings are that I can now have a bumper sticker on my car that says, “#spermmatters.”
Dr. Blake Evans: Exactly. That is something we should put in the paper.
Dr. Aimee: I agree. Why is it considered controversial that testicular sperm is associated with lower sperm DNA fragmentation? And I know you haven’t talked about that yet, but why don’t you talk to us a little bit about sperm DNA fragmentation? What it is and what’s the controversy all about?
Dr. Blake Evans: There are a few different Sperm DNA fragmentation tests, and different brands that create tests. What is considered is the percent of sperm that has damaged chromatin or the protein within the sperm head has damaged. This has an association with adverse outcomes, such as recurrent pregnancy loss and poor IVF outcomes (those being the main ones), and therefore decreased clinical pregnancy rates, decreased live birth.
The controversy, if you will, is mainly in regard to the available literature that’s out there. A lot of these studies are small in number. They’re retrospective. They may or may not report live birth. They’re very heterogeneous in nature. There is not a good affirmative consensus with all these DNA fragmentation studies.
People are wanting to know more about what else can we test on a male aside from the semen analysis? With the volume of concentration, motility, morphology, there’s got to be something else.
This is an extremely hot topic in the urology field, and in fertility in general. Despite there being a limited availability of literature on the outcomes, there are quite a few clinics that are starting to use it more and more often and finding some associations with positive outcomes and using it more frequently.
The most recent practice committee document from an ASRM, or American Society of Reproductive Medicine, was in about 2012, 2013. It had summarized that the existing literature: it is not consistent, and they do not recommend doing this routinely on all infertile patients because the literature is not consistent. But it has been about seven years or so since it was published, and a lot of people are doing more studies. Hopefully sometime in the near future, we might have an update to that document.
There is a lot that can cause DNA fragmentation in sperm, or cause DNA damage to the sperm. And this fragmentation and damage has been shown to be associated with decreased implantation, miscarriages, and poor IVF outcomes. DNA damage may come from different things intrinsically, like oxidative stress on the sperm. It is possible that at some point, we could have an ability to repair the DNA that has been broken. Or we may need to address external factors such as chronic sauna or hot tub use, or smoking, environmental toxins or cancer related drugs.
The controversy is in regards to the available literature, what to do with the available literature that’s out there. And also, there is good evidence showing that there’s decreased DNA fragmentation and testicular sperm compared to ejaculate. But once again, what do you do with that information? And also, you’re probably not going to find many men that are willing to undergo a prospective trial as to, you can have your testicle cut on, and you don’t, and see who has the better outcome. It’s a little difficult to assess it in that regard.
Dr. Aimee: Yeah. There would have to be some sort of huge incentive for guys to sign up for that I imagine.
Dr. Blake Evans: Yes, absolutely.
Dr. Aimee: Yeah. I mean, that would be a hard clinical trial to recruit for. There’s no doubt about that.
If you know what can cause elevated DNA fragmentation, then guys know what to do to improve their sperm, like eating healthy, exercising most days of the week, sleeping well, decreasing stress, and then also see a urologist.
Dr. Blake Evans: Absolutely. I recommend seeing a urologist. And another thing that’s interesting about DNA fragmentation is the semen analysis itself, it’s been reported to be normal in up to 40% of men that have an abnormal DNA fragmentation. Everything else looks normal on their semen analysis, but they have an elevated DNA fragmentation.
That is certainly something you can discuss with urologists. I have heard of them recommending over the counter vitamins that might help with this. There is not a single tried and true recommended path for what you should do for an abnormal DNA fragmentation. But it’s certainly a point of discussion you can have with your urologist.
Dr. Aimee: That’s a great point. Up to 40% of people who have a normal semen analysis can still have an elevated DNA Fragmentation Index.
Dr. Blake Evans: Correct.
Dr. Aimee: Wow. That is really important for people to know. Before we sign off, can you tell us again where patients can find you?
Dr. Blake Evans: Sure. I am at University of Oklahoma. Ouinfertility.com is our website, and there’s plenty of information about our clinic, and about me on there. I am on Twitter. My handle is @MBlakeEvansDO.
Dr. Aimee: Great, thank you again for your time.
Dr. Blake Evans: Thank you.