Rescripted_S2_E2_The Fertility Workup: Audio automatically transcribed by Sonix

Rescripted_S2_E2_The Fertility Workup: this mp3 audio file was automatically transcribed by Sonix with the best speech-to-text algorithms. This transcript may contain errors.

Kristyn Hodgdon:
Hi! I'm Kristyn Hodgdon, an IVF mom, current IVF patient, and co-founder of Rescripted.

Lucky Sekhon:
And I'm Dr. Lucky Sekhon, a board-certified reproductive endocrinologist at RMA of New York.

Kristyn Hodgdon:
Welcome to Dear Infertility, the first-ever podcast that doubles as an advice column for the millions of people globally who have trouble conceiving.

Lucky Sekhon:
We're here to answer real questions from real fertility patients about what to expect during each stage of the fertility journey and to provide you with the patient-centric advice and guidance you need to be your own advocate when trying becomes trying.

Kristyn Hodgdon:
Now, let's dive in and help you feel more empowered during this overwhelming process.

Kristyn Hodgdon:
Hi everyone, and welcome back to the Dear Infertility Podcast. I'm Kristyn, your host, and I'm here with Dr. Lucky Sekhon. Hi, Lucky.

Lucky Sekhon:
Hi. How's it going?

Kristyn Hodgdon:
I'm doing well. How are you?

Lucky Sekhon:
I'm doing great. Thanks for having me back on.

Kristyn Hodgdon:
Absolutely. I'm really excited to talk today all about the fertility workup. So gone to the fertility clinic for the first time and these are sort of the next step, diagnostic testing, and procedures that all patients sort of need to be aware of as sort of a barrier to entry, to kind of understanding how your body is functioning and what your treatment plan might be.

Lucky Sekhon:
Yeah, and I think it's really confusing because there's so many different tests that people talk about when it comes to fertility. But I always tell patients the basic first step is actually pretty simple, and it can be simple if you think about it as four components that go into establishing a healthy pregnancy. When you think about the sequence of events, you start with sperm entering the reproductive tract and getting into the fallopian tubes, and hopefully meeting an egg that's been ovulated or is about to get ovulated, and that egg will hopefully, successfully fertilize turn into an embryo. That embryo will make its way to the uterine cavity and find a nice, smooth part of the lining of the uterus to implant. So when you think about that sequence of events, you need sperm, you need a good number of sperm, so doing a semen analysis is an easy way to get a lot of insight into male fertility, to make sure the concentration of sperm is sufficient, that there's a good percentage of the sample that's swimming in a forward direction, we call that motility, and a good percentage of the sperm that's shaped normally and formed normally, that's called morphology. And the overall volume of the sample that's provided is important as well to make sure there aren't any strictures or blockages in the male reproductive tract. And then the next step, getting the sperm where it needs to go, are there any blockages or things that are getting in their way in the uterine cavity or in the fallopian tubes? And there's a quick two-for-one test that can be done, the HSG or Hysterosalpingogram, and this is a test that I order, some fertility clinics will do this test themselves, some will outsource it to a radiology office. And you'll want to do this in the first half of your cycle, aka before you ovulate, because we don't want to, in an unintended way, interrupt and implanting pregnancy post-ovulation. So the timing of when you do the HSG is important and you essentially are going to the radiologists and they're putting dye into your cervix and watching it spill into the uterine cavity and hopefully out of either fallopian tube. And the way this is visualized is using an X-ray of the pelvis, and that's going to give us information about the tubes and the contour of the uterine cavity. We can look at the uterus and other ways as well. We can just do a basic ultrasound with or without 3D imaging. And we can also do other types of sonograms, which are more specialized, like a saline sonogram, which is essentially putting fluid into the lining to push the walls apart because your uterine cavity is actually kind of a collapsed cavity, and it's just a space, a potential space. And so pushing the walls apart is what's necessary to really see that inner contour properly. And you're looking for things like polyps or fibroids, things that you can usually rectify if you find them and hopefully, restore normal structure to the uterine cavity and increase the surface area that an embryo has to implant. And then the fourth component are the ovaries, right? There's a couple of different things I care about when it comes to the ovaries. Is someone ovulating regularly? So getting a good history and understanding what's happening with their menstrual cycle, you can also do blood work. A progesterone level on, someone has a 28-day cycle on roughly day 21, should be elevated if that person ovulated appropriately. Doing blood work just to kind of understand someone's ovarian reserve, their AMH level, the higher your AMH level, the more eggs you have. And just looking at other basic hormones to understand your pituitary gland in your brain and how it's driving, functioning of the ovary, your thyroid gland. There's so many different blood tests that I recommend running at the initial visit and then something we talked about last episode, and it's not really fertility-related, but I think every patient should consider this pre-conception, is genetic carrier screening to see what mutations if you, that you or your partner might carry to understand what the reproductive risk is. Is there any chance that the combination of both of your genes could result in having a child with any of a hundred or more disorders that are on those panels. So I think that's really the basic workup that I start with.

Kristyn Hodgdon:
That's really helpful. And so if any of those tests come back normal, that obviously changes the, the plan or the next steps, correct?

Lucky Sekhon:
Yes, sometimes in really clear ways. Examples are if the semen analysis shows that overall, when you combine the volume of the sample, the concentration, and the percent of the sample that's swimming in a normal way and you get the total modal count, if that's less than 10 million, usually we're going to recommend something in the way of at least IUI, if not more aggressive. If it's less than 5 million, then really IVF is the best bet because that's going to give you an opportunity to inject a single sperm directly into the egg, and that can overcome a lot of those types of problems. Similarly, if the tubes are blocked on HSG, the best workaround really is IVF because it will bypass the blockages directly. Fixing the fallopian tubes with surgery is something that's not really done these days, and it's not that effective.

Kristyn Hodgdon:
And what if you suspect PCOS or endometriosis?

Lucky Sekhon:
So ways to figure out someone has PCOS, you know, starting with their menstrual pattern. If they have irregular cycles, that's a sign that they have irregular ovulation. And looking at how their ovaries look on ultrasound is important because they may have very typical appearance where the follicles look really crowded around the periphery of the ovary, and they might have associated symptoms that you need to do blood testing for. Things like excess hair growth or acne, it's not a prerequisite. You don't have to have these symptoms, but some patients will have it. And we always want to rule out that there aren't other things that are masquerading themselves as PCOS, even as serious as tumors that produce testosterone in the adrenal gland or the ovary, and less serious things like just having an overdrive of production of testosterone from the adrenal gland. But you need to rule out that there aren't other reasons why the cycle is irregular, because a lot of things can look like PCOS. So that's the first step, is ruling those things out. If you diagnose someone with PCOS and they have irregular cycles, then that's going to point us in the direction of at a minimum doing something to get their cycles to be more regular because being able to time your attempt around ovulation is going to be much easier if you have a regular predictable cycle and it's also going to give you an adequate number of attempts over a given period of time. If you're only getting a period every 60 to 90 days, that's not very efficient because you can only really then try every 60 to 90 days. So getting the periods to be regular with a medication is called ovulation induction, but it doesn't mean that everyone with PCOS has to do medications with IUI, there is an option to go straight to IVF. So I think it's not just about diagnosis, it's about understanding what your goals are, how old you are when you're starting your journey, how many children you want to have, all of those things should factor into the decision. If you have PCOS and there is lifestyle changes that can be made to help restore normal balance to your metabolism that may help you to ovulate more regularly, so it should really be a multifaceted approach. And I think, obviously we're going to talk about PCOS and problems with ovulation in another episode, but it is a complicated matter, and it requires more than just one simple solution.

Kristyn Hodgdon:
Yeap.

Lucky Sekhon:
In terms of endometriosis, oh, the good news is, is that endometriosis is a condition where the lining of the uterus is found in places it shouldn't be, outside of the uterus, and it can cause inflammation, painful periods, and it can definitely lead to a higher risk of infertility and just making it harder to get pregnant because of that inflammation in the pelvis. And overall, studies have shown that a lot of the treatments that we use in fertility clinics, like Medicated IUI or IVF are usually enough to help overcome the effects of endometriosis. And studies have looked at comparing fertility treatment versus surgical management of endometriosis, and they're considered pretty equivalent. And we've really steered away from surgery as a first-line approach for treatment of endometriosis. There are situations where that might be the right thing to do, but when it comes to improving fertility, a lot of the treatments that will help to improve the overall inefficiency of human reproduction that we all face are going to usually be enough to help overcome the challenges that are posed by endometriosis.

Kristyn Hodgdon:
That's great to know, because it can be such a discouraging diagnosis and painful and all of the above, so it's great to hear. So someone in the community asked, what additional testing would you recommend for recurrent miscarriages?

Lucky Sekhon:
So recurrent miscarriages can be defined as having two or more consecutive miscarriages or pregnancy loss. And there's often a lot of debate that goes back and forth about whether a biochemical pregnancy loss is a true miscarriage. And I think many fertility experts would agree that, I, you know, I count that as a recurrent carriage if someone's had two or more biochemical losses. So if you've had two or more losses, you should do specialized testing just to make sure that there aren't factors that could increase your risk of having a future loss. We know the number one cause of why pregnancies end in miscarriage tends to be that it's very easy for the combination of egg and sperm to result in an embryo that is missing or has extra DNA or chromosomes. Chromosomes are packages of DNA, and you need 46, 23 from the egg, 23 from the sperm. But even if you're looking at the eggs of someone in their twenties, if you turn all of those eggs into embryos, we're expecting at a minimum around 20% of them to be missing or have extra DNA. And that's as good as it gets. And as we get older, that prevalence increases and the proportion increases to about 50% at age 37, 38. Doesn't mean you can't get pregnant, you can still ovulate a normal egg, but the chance of ovulating an abnormal egg increases as we age. And if an embryo doesn't have the right amount of DNA, usually it's going to stop growing before it can implant. You might not get pregnant that month or cycle, but it could implant and then stop growing, and that's the number one mechanism of miscarriage. So if you've had two or more miscarriages, it's possible that it's because you had abnormal embryos implanting. And if you're older, if you're 35 and older, you know that that will be a possible explanation for why you've had that experience. But we don't want to hand wave and make those assumptions because most people haven't got a DNC with definitive information on that pregnancy to confirm whether it was genetically normal or not. And so we don't want to make assumptions and we should look in a very focused fashion. Are there underlying problems with the uterus, you know, having structural issues like having a fibroid or a polyp, which is taking up space in the uterine cavity, almost acting like an IUD, right? And could that be interfering with the proper implantation and establishment of a pregnancy? And if we find something like that, guess what? It's not so hard to fix it. We can do a simple surgery called a historicopy to restore a normal contour to the uterine cavity. So the way we test for this, one of the best ways to look at the uterine cavity is to do a saline sonogram, and that is putting fluid inside the lining and pushing the walls apart to get a nice, clear view of the contour. And then you could also do things like an HSG, and even a simple ultrasound will oftentimes give you a clue that there might be something going on. So definitely need to look at the uterine cavity. I think looking at both sets of chromosomes from each parent, looking for any structural issues because you could be a healthy individual and you have all of the genes that are needed to be a healthy person. But some of us can have rearrangements in the structure of our chromosomes and it can manifest as problems with fertility or recurrent miscarriages. Because when your chromosomes line up to join with the chromosomes of your partner, if there's a structural rearrangement or a section of that DNA that's flipped, it can lead to a higher than expected proportion of abnormal embryos when your DNA is combined. And that could lead to a higher risk of miscarriage and fertility issues. So doing a blood test called a karyotype on both of you and it usually takes about 2 to 3 weeks to come back, will allow us to identify if there's any structural issues with your chromosomes. I think looking at thyroid function, making sure that that's balanced and there aren't any issues there, looking for autoimmune conditions like diabetes, examining whether there are chronic medical conditions that are not well controlled, that could be contributing. Those are really the mainstay. I think looking for blood clotting is controversial, but there are proven conditions like Antiphospholipid syndrome that are definitely warranted. And when you think about the workup, so this is a blood test to look for different antibodies that can lead to an increased risk if they're elevated, and we normally test it twice, 12 weeks apart. And if you have persistent elevations in these antibodies, there's three different antibodies in particular, beta two glycoprotein, anti cardio lupin, and lupus anticoagulant. And those are the things we test for. If they're elevated, there's a solution. Being on baby aspirin while trying and injectable blood thinners like Lovenox, once pregnancy is established can help prevent future miscarriages. So a lot of this testing has a potential action point of something that you could do to minimize the risk of a future miscarriage. And something to be aware if you're going through the workup is that 50% of people will have a completely normal workup. So go into it expecting that nothing is going to be abnormal. Because then.

Kristyn Hodgdon:
Well, that was my next question. What happens if all of my test results come back normal?

Lucky Sekhon:
Nothing. I mean, I think that that's something to expect. You know, 50% of people will have a negative workup and that's okay. It doesn't mean that there isn't a reason, but maybe we just don't have a way or the knowledge of how to directly test for the reason. You know, we also another piece of information or a statistic that I think is really uplifting and to focus on is that studies have shown around 60% of women with recurrent losses, even in the absence of a known diagnosis, if they just keep trying, will eventually get there and have a live birth. So, you know, there's a lot of a lot of this is shrouded in mystery, and we might not get clear answers. But of course, that doesn't mean that you're not going to do anything differently. I think this is where communicating with your doctor and having a clear idea of the potential things that you could switch up or change moving forward and knowing that some of these changes that we recommend might not always based on an abnormal test result or a clear target of treatment. But if it's not something that's harmful or going to cause a lot of side effects, maybe it's worth trying adding it to the plan just to see if it could make a difference, and you'll never know. But I think at the end of the day, the number one causes are the genetics. But it's important to rule out that there isn't something else going on, even if you are older and you're at a higher risk of having miscarriages because of those genetic errors.

Kristyn Hodgdon:
Absolutely. Yeah, it can really help your mental health as well when, when you ask your doctor what you can do differently and they change the plan because you don't want to feel like you keep doing the same thing over and over again and getting the same results. So just being your own advocate in that way and asking all the right questions and, and really seeing if there's anything you can be doing additionally that that won't hurt. That could be something as small as taking baby aspirin or having a hysteroscopy to rule anything out.

Lucky Sekhon:
Exactly. I totally agree.

Kristyn Hodgdon:
So with unexplained infertility, last question, when, if all of your test results come back normal like diagnostic procedures, blood tests, genetic testing, what's sort of the first course of treatment usually?

Lucky Sekhon:
So in that case, we call it unexplained because we didn't identify something abnormal on the testing doesn't mean there isn't an explanation. There are things like, for example, endometriosis, which you mentioned, that doesn't really have a direct way to test for it other than going to surgery and getting a biopsy and sending that off for analysis, which might not be practical. I don't think it makes sense to send everyone off for surgery, I think you can make the diagnosis, you can presume that they have that diagnosis based on their symptoms. And so there really isn't like an ultrasound or a blood test that's going to confirm, yes, you have endometriosis. So I think a lot of patients with unexplained infertility have issues like that. And so it's not to say there isn't a true explanation, but there isn't a specific target to treat. That's a better way to think about it. It's very reasonable to start off with solutions that are very general and nonspecific and just kind of targeting everything that you can. As I mentioned earlier, human reproduction is really inefficient, and I think that that's something to know across the board for everyone, not just patients that are seeing a fertility doctor. There's like a 15% chance each ovulation that you could have a pregnancy. And that's just based on being a human being and knowing that there's a very narrow window of opportunity for sperm and egg to meet in the cycle, and that not every egg is guaranteed to fertilize successfully and turn into an embryo, not every embryo is going to be normal. And even the normal ones, not every single one is going to implant. All of these things have to line up perfectly, and that's just not the most likely thing to happen. So the standard first line treatment for unexplained infertility is essentially just trying to improve the odds and doing things on both the sperm and the egg side, right? On the egg side, we're saying we know that anyone can ovulate abnormal unhealthy eggs with genetic errors in them, so let's give you medication like Clomid, for example, which is a pill that you take for five days at the start of your cycle and it will give your body the opportunity, maybe not a guarantee, but a chance to release more than one egg. And if you're releasing more than one egg, you're improving the odds that at least one of those eggs will be normal and healthy. But we're not just going to focus on the egg because how do we know this isn't something to do with the sperm? So around the time that you're about to ovulate, hopefully more than one egg, we would be planning to do an insemination where we take sperm from your partner and we wash it and we concentrate it and we get the dead sperm out of the sample. So there are things that we do to really optimize the sample and we'll inject it at the top of the uterus so that it's bypassing the cervix and the cervical mucus and getting closer to where the eggs are being released. And that's why realistically Medicated IUI, that combination of two treatment options is not super effective, but it might be the extra push that you individually need to get there. But it's important to go into it realistically and say, look, this is going to bump up my chances above that baseline 15%, but realistically, it's going to improve my chances by 5 to 10% at the most. And so going into that treatment option, you should be prepared to do this more than once because it doesn't make sense to give up after the first try. I mean, obviously, you could and say, I want to move on to something else, this isn't for me, but I think if you're committed to that treatment approach, it makes sense to give it at least a minimum of three cycles. And how long to do that, I think, really depends on what your sense of urgency is and other factors like your age and your family building goals. But studies have shown that couples, patients with unexplained infertility, really there tends to be diminishing returns after the sixth Medicated IUI fails. And that usually means there's something else going on, and it might be better suited for you to do IVF or something more aggressive to try to overcome that inefficiency.

Kristyn Hodgdon:
Wow. Well, this was super helpful. Well, thank you, Dr. Sekhon. And we'll be back next time with some questions on IUI.

Lucky Sekhon:
Awesome. I'm looking forward to it!

Kristyn Hodgdon:
Thank you for tuning into this episode of Dear Infertility. We hope it helps you feel more empowered to be your own advocate on your fertility journey. Whatever you're currently struggling with, Rescripted is here to hold your hand every step of the way. If you like today's episode and want to stay up to date on our podcast, don't forget to click Subscribe. To find this episode, show notes, resources and more, head to Rescripted.com and be sure to join our free fertility support community while you're there.

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