Ep 281: PCOS unfiltered: We Answer Your Questions

Fertility Docs Uncensored is hosted by Dr. Carrie Bedient from the Fertility Center of Las Vegas, Dr. Susan Hudson from Texas Fertility Center, and Dr. Abby Eblen from Nashville Fertility Center. In this episode of Fertility Docs Uncensored, the doctors tackle your most pressing questions about polycystic ovary syndrome (PCOS). Many PCOS patients have high AMH levels, and often that means more eggs at retrieval. However, sometimes a high egg count doesn’t always translate into more embryos or more to transfer, and the Docs explain why quantity doesn’t always equal quality. They also dive into IUI cycles for PCOS patients, including the advantages of combining IUI with ovulation induction. The team recommends limiting ovulation induction + IUI attempts to no more than three or four before considering other options. For those with a history of miscarriage, they emphasize the importance of a thorough recurrent pregnancy loss workup, regardless of PCOS status. Should you move to IVF sooner? The docs explore that too—especially for those wanting multiple children, facing recurrent miscarriage, or when male factor issues are in play. The episode wraps with a discussion of medications like metformin and inositols, and when to consider laparoscopy—typically reserved for symptoms like painful periods or signs of endometriosis. 

This podcast was sponsored by ReceptivaDx.

Transcript

Susan Hudson (00:01)

You're listening to the Fertility Docs Uncensored podcast, featuring insight on all things fertility from some of the top rated doctors around America. Whether you're struggling to conceive or just planning for your future family, we're here to guide you every step of the way.

Susan Hudson MD (00:22)

This podcast is sponsored by ReceptivaDx. ReceptivaDx is a powerful test used to help detect inflammatory conditions on the uterine lining, most commonly associated with endometriosis and may be the cause of failed implantation or recurrent pregnancy loss. Take advantage by learning more about this condition at receptivadx.com and how you can get tested and treated, providing a new pathway to achieving a successful pregnancy. ReceptivaDx, because the journey is worth it.

Carrie Bedient MD (00:53)

Hello everyone and welcome to another episode of Fertility Docs Uncensored. I am one of your hosts, Dr. Carrie Bedient from the Fertility Center of Las Vegas, joined by my two hilarious, happy, heavenly co-hosts, Dr. Susan Hudson from Texas Fertility Center and Dr. Abby Eblen from Nashville Fertility Center.

Abby Eblen MD (01:11)

Hey guys!

Carrie Bedient MD (01:11)

So Abby, you look wonderful and bright and chipper this morning, which is impressive, given your activities. Tell us your stories from this weekend.

Abby Eblen MD (01:19)

Well, I trained in Louisville, Kentucky and I still have a really close friend there. For our Christmas gift this year, they gave us a free trip on the Bourbon Trail. We got to go to one of the Kentucky horse farms. In fact, the largest in the world actually is 1500 acres and it is mares and foals, which are little babies. We got to pet the big horses and feed them. And would you believe I knew horses liked sugar.

But the two things we fed them were carrots and we fed them those peppermint things, those real soft peppermints. They love the When they saw us coming, and we were the only people on the farm. There was like eight of us yesterday and they'd come running with their little ponies and you get to feed them and pet them. And that was really fun. It was just beautiful. I mean, it really looked like what you picture at a horse farm. It had miles and miles of fencing. You couldn't see anything other than horse farms. It was really cool.

And then we topped it off with a trip to Bulleit bourbon. We got to go to the distillery and taste some of the bourbons, some of the bourbons that have rye. The big thing about Kentucky is in order for it to be bourbon, it has to primarily be made of corn. That has to be the biggest ingredient. And then also has barley, which helps the enzymatic reaction. It has wheat. So those are the three components. I'm sorry, rye actually, rye and barley.

I learned a little bit about the distillation process. It gave me a little bit of PTSD though, back to organic chemistry lab, because it's like a big giant organic chemistry lab, how they distill it and they do the mash and the CO2 bubbles off. But it was really fun. It's fun when you can see it in that perspective and not in the organic chemistry lab.

Susan Hudson (02:49)

Exactly.

Carrie Bedient MD (02:50)

Much lower likelihood of something blowing up probably in the well-organized distillery compared to our sophomore organic chemistry lab.

Abby Eblen MD (02:53)

Exactly.

Yeah, and much nicer to drink the product. We never did that in organic chemistry lab, ⁓ That's right.

Carrie Bedient MD (03:03)

That was probably wise. Probably really wise. I remember at one point in Orgo, somebody did something and they exploded a Mercury thermometer. Yeah, yeah. Mercury is fun to play with, but really shouldn't have that opportunity ever. would like to point out I was not the one who exploded the thermometer. Just in case anyone was thinking it, I see you, it was not me.

All right, so today we are going to do a question episode and we have approximately 85,036,002, 36,002 questions on PCOS. So that's what we're going to launch into today. Susan, what you got?

Susan Hudson (03:42)

Okay, our first question is, hello. First, thank you so much for your podcast. Thank you for listening. I'm historically a very nervous patient with most things medical, but have found peace and confidence in being more educated about fertility treatments because of your podcast. My husband and I are about to start IVF after three unsuccessful IUIs and nearly two years of trying to conceive. I'm 32 with an AMH of 3.94 and have polycystic ovaries, but the clinic ruled out PCOS because I have regular periods and no other symptoms. My question is, is there a correlation between polycystic ovaries and a higher quantity of eggs retrieved in an IVF stim? I know maturity is a different story, but curious to hear what your experiences have been. Thanks again. I think this would be a good time to go over what is involved in the diagnosis of PCOS.

Abby Eblen MD (04:34)

So PCOS, there's three different things that you can have to have PCOS, but you really only have to have two to really say that you have it. You've got to have polycystic ovarian ovaries. That means those little tiny black circles, if you've ever gone in for ultrasound, those are called follicles. Roughly if you have over 12, that's considered as a polycystic ovary. That's one thing potentially. The second thing is evidence of male hormone levels. So elevated male hormone levels.

Things like DHEA-S and testosterone are some of the things that we test for that. And the third thing is irregular cycles. See, irregular cycles would be cycles roughly more  than 34 days and less than roughly about 25 days. You don't have that one, but someone who still has the other two things, the polycystic appearing ovaries and the elevated hormone levels can still be diagnosed with PCOS.

Susan Hudson (05:21)

It's important to know that polycystic ovarian syndrome first of all is a poorly named condition. Okay, which we always want to mention. Yes, so it should be poly follicular ovarian syndrome. So cyst to us is something that's greater than two centimeters, that's not supposed to be there at a certain point in time. What women with PCOS have is they have lots of little follicles. Essentially the brain and ovaries aren't communicating with each other very effectively. It is a spectrum meaning that there are some people who have lots and lots of symptoms and there are some people that only have symptoms under certain conditions. Just because you may not fit the diagnostic criteria this moment may not mean you haven't ever or may not in the future meet those criteria. So that's something else important to know.

But back to this listener's question, is there correlation between higher quantity of eggs and polycystic ovaries in a IVF cycle?

Carrie Bedient MD (06:20)

Absolutely. One of the things that we look at is how many follicles do you have at the beginning of a cycle? So we have a guesstimate of what we might get out, and that allows us to plan and it allows us to counsel you so that expectations are reasonable. And someone who has polycystic ovaries where we're seeing a follicle count of 20, 30, 40 or higher means that there's a much higher likelihood that we will get a higher number of eggs during the stim. Some of this is going to depend on what your doc's protocols are because there are some docs who will stim hard and you will get 30, 40, 50 plus eggs. There are others who will not stim as hard and you won't get as many. And you can make a good argument for either depending on what the overall story is. Now with any stimulation, you're going to have a certain percentage of eggs that either don't come out or that do but are not mature. It's equally as important to realize that you may get more eggs but they're not all gonna be mature and that percentage will seem more pronounced because a greater absolute number of them. Meaning if you're getting 20 eggs and six of them are not mature, that's a pretty similar percentage to having 50 eggs with 35 of them being mature and the other 15 not. Percentages are the same, but it feels different because the numbers are different of the actual eggs that are mature. And so you do tend to have a good response from an AFC that's really high when you're going into IVF cycles.

Abby Eblen MD (07:52)

Well, one other thing I would say about that too is sometimes I always caution patients, when we get 30 or 40 eggs, that sounds great, and it is. I would much rather they have too many than too few, but your body's just not equipped to make 40 eggs and do a really good job of it. Alluding to what Carrie was saying, a lot of them can be immature and then, a fair number just don't develop really well. Your body's just not equipped to do that.

So it's not unusual for somebody to get 30, 40 eggs that have PCOS and only have the number we would expect, in terms of ones that are going to go on to develop and grow into genetically normal embryos.

Susan Hudson (08:24)

Also know that we're not going to get an egg out of each of those follicles. So if you're sitting there on your last day of stim and your doctor's busily measuring each of those follicles so the embryologists have a really full clear picture of what they're getting into when we go into egg retrieval so they can prepare appropriately in the embryology lab, understand that if they measure 40 follicles don't go in expecting even 40 eggs and some of those being immature. A lot of those follicles we're going to go into and we're not going to get anything. So that's also something to prepare yourself for.

Susan Hudson (08:59)

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Susan Hudson (10:05)

Ready for the next one? Hello, I 30 have PCOS and my husband 32 have three failed IUIs have recently had our first egg retrieval. On my last ultrasound prior to retrieval, I had 47 follicles, 30 measuring over 16 millimeters. But during my egg retrieval, only 16 of our follicles actually contained eggs.

We ended up with 13 mature, 6 fertilized, and resulted in 1 PGT normal embryo. We are planning to try another retrieval before we transfer, but I can't find much information about having so many empty follicles. My doctor suspects it's all related to my PCOS, but could this be empty follicle syndrome? I have started inositols and CoQ10 to help my quality. Is there anything else that can help?

My BMI is right at 40, so we'll be lowering that prior as well.

Abby Eblen MD (10:56)

Well, over the years, I tend to see people with PCOS have less mature eggs. You almost have to push them an extra day or at least some patients than you would normally to grow their follicles bigger. Because if the eggs are immature, they just don't come out of the follicles. And there's no way that we can see the eggs because they're one cell big. So we don't really know if it's empty follicle or an immature egg. But my guess would be with 47 follicles, you probably had several immature eggs and that's probably the reason that you didn't do quite as well. As far as ways to improve that, I tend to believe adding in LH in the form of menotropins or Menopur can help a little bit. For whatever reason, it helps mature the eggs up. And if the eggs are more mature, then a lot of times we can get more eggs that not only come out of the follicle, but just grow and develop better.

Carrie Bedient MD (11:40)

One of the things that caught my eye about this was not just that she had 30 follicles that were big and only got 13 mature ones, it's that only six of those fertilized because that's a really fairly low percentage of eggs fertilizing from someone who otherwise is normal. And you didn't tell us much about husband's sperm at all, but that might be something where I would consider getting a DNA fragmentation.

Looking at his lifestyle issues, whether BMI, any sort of substances, alcohol, tobacco, nicotine are playing a role in that and optimizing him as well. Because especially when we see fewer fertilize, the question there is, is there something going on with the sperm as well? And I would also look at, was this ICSI, was this conventional insemination? If it was conventional, I might consider switching to ICSI with this next one because ideally, we see more of those fertilized than just half.

Susan Hudson (12:36)

Absolutely. What are your thoughts on empty follicle syndrome? So I'm not a big believer in true empty follicle syndrome. To me, what that implies is there's truly nothing in the follicle, which I don't believe. I think most of that the time it is a receptor issue that somehow there's dysfunctional receptors and true empty follicle syndrome means you go in for an egg retrieval. You have at least a reasonable number of follicles, you go in there and you get nothing. You don't get any cumulus, which are the little cells around the follicles. You just get nothing. What are your thoughts? It's one of those things that I always feel weird when I have somebody come to me as a second opinion about empty follicle syndrome, because to me, there may or may not be things that we can do to change it but I'm not a big believer, especially if it's like, I did get some.

Abby Eblen MD (13:31)

Yeah, I mean, just because you can't see it, don't, I mean, we can't see it. So I tend to believe it's just an undergrown egg that just hasn't developed enough that, because if the eggs are underdeveloped, they're much stickier, they cling more, and we can't see them. I tend to believe it's more just an undergrown egg that's immature and eggs just not coming out.

Carrie Bedient MD (13:48)

Once you asked that question, Susan, I started thinking about, in the past roughly 13 years of doing retrievals, how many times have I gone in and truly gotten zero?

Abby Eblen MD (14:00)

Yeah, it's not wrong. Yeah. Yeah.

Susan Hudson (14:00)

And it wasn't due to a failed trigger.

Carrie Bedient MD (14:02)

And it wasn't due to a failed trigger, because a failed trigger is a big deal. You will get empty follicles if you have a failed trigger, because the maturity won't be there and you won't get anything out. And this is not counting the patients where you only have one, two, three, four follicles where there's a legitimate chance that they're not making anything anyway from the outset. When I look at people who are outside of those exclusionary zones, I can't think of one person where I have not gotten a decent percentage of eggs. One person's experience isn't everything, but you would figure over a long career that you would have seen something.

Susan Hudson (14:39)

I can think of one person in my career and like I said, we tried everything and she had beautiful looking ovaries, multiple types of trigger and we literally would get nothing. To me, it's kind of a catchall of this doesn't make sense and no one's going to go and remove your ovary and do pathology to cut open your follicles and see if there's an egg. Like I said, in this situation, we were pretty sure it was some sort of unusual receptor issue, which is what was contributing to her infertility. it's one of those things that we sometimes throw at people. I hardly ever use this diagnosis, obviously. But I do think that there are some times this...quote, diagnosis is thrown at people because people just don't know what it is and they want to throw a label on it other than idiopathic infertility, which means we don't know. Just be be wary of that diagnosis, because I do find it to be something that I would consider exceptionally, exceptionally, exceptionally rare.

Carrie Bedient MD (15:43)

We have a decent number of people who come to us for second or third IVF cycles after they've been other places and it hasn't worked. And I have seen several people who've come in with a diagnosis of empty follicle syndrome, but have never experienced it myself in those people. I think some of it is just we're learning by the prior stims that have been done and in every stim gives you information. It's not just therapeutic, it's diagnostic as well. There's always the hindsight that you get from being the second or third or fourth or in some cases, eighth person a patient's seeing and we take that information and we run with it. So I question that diagnosis.

Susan Hudson MD (16:22)

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Susan Hudson (16:51)

All right, our next one is IUI cycle had one dominant follicle only 31.5 millimeters. The rest were six millimeters. History of PCOS tried unmonitored letrozole last year for 12 cycles. This is a monitored IUI cycle. Cycle day 11 follicle is so huge, I thought it would be a canceled cycle, but I triggered same day and then IUI the next afternoon.

Having a hard time finding information on large follicles. What are your thoughts? Thanks.

Carrie Bedient MD (17:21)

Do we have an age?

Susan Hudson (17:22)

No.

Abby Eblen MD (17:22)

So it's 3.5 centimeters, and that was the only follicle she had with a cycle of medication, ovulation-induction cycle? Okay.

Susan Hudson (17:29)

Right, letrozole. So I think that one important thing to understand is that when we are looking at doing ovulation induction for IUIs, our goal is generally one to three follicles. We're trying to get you to normal, not to super normal. And that's the difference between what we call ovulation induction and super ovulation.

With that being said though, if you've done 12 cycles of letrozole or any medication, you need to potentially look at different avenues. That's the nicest way I can put that one.

Carrie Bedient MD (18:04)

Yeah, if nothing's worked after 12 cycles, assuming that there's not a sperm problem, and this is where doing a Sperm QT might be helpful because you may find that even despite a completely normal sperm analysis, you've got an abnormal QT, which means that fertilization is more impaired, even though you can't necessarily see it on the semen analysis results. By the time you get to 12 cycles, it's very much diminishing returns.

You're most likely to have success in the first three cycles of ovulation induction and then six cycles. And by the time you get beyond six cycles, the rate of return is really quite low. I would not spend a whole lot of time, money, energy on doing IUIs, particularly if the sperm count has been totally normal, because I don't think you're gaining a whole lot by doing that.

Abby Eblen MD (18:51)

I think to address the question about the follicle, it's hard to know what it is because it could have been leftover from previous cycle. I don't really know where in your cycle they were looking, but if they weren't looking every month, this could have been a leftover follicle that's just gotten bigger. It could either have already ovulated the egg and closed back up again because sometimes even if blood is in the sac, it can look clear sometimes. It's hard to know if it's a hemorrhagic cyst where we see blood in there after ovulation. So it's really hard to know without having some idea of where you were in your cycle. Generally, if say this was your second cycle or your first cycle with ovulation induction, you had a follicle that was that big and we truly thought it was a follicle on day 13 or 14 that contained an egg. What I might consider in a subsequent cycle, once I know that you've ovulated and if you have not gotten pregnant and that cyst has gone away, the sac around the egg has gone away, then I would think about maybe bringing you in a little bit earlier and triggering you sooner with a Ovidrel or something like that.

Because sometimes the follicles can get bigger. I don't know what happens to the egg. It may continue to get bigger. It may become atretic at some point. Ultimately, if somebody truly has an egg in there, if you can trigger them earlier, then that prevents them from having a leftover egg or leftover follicle over time.

Carrie Bedient MD (20:01)

When we did the follicle studies a few years now, we looked at the size of follicles and it was in the context of IVF, not IUI, but we measured out until our largest group was greater than 28 millimeters. And we found that the quality of the eggs coming out of those was just fine. So the thought that there is a post-mature egg is really not born out by that. We do see higher rate of return from some of the smaller eggs, but the ones that do come out are just fine. The thing that I would wonder is, did you start with a bigger follicle in that cycle to begin with? Are you someone who would benefit by either birth control pills going into the cycle to help suppress that, or having an earlier follow-up ultrasound? Maybe you finished your meds day seven and you come back day nine or 10 rather than 11 or 12. Those are some of the things that I would think about, but truly after 12 unmonitored letrozole cycles where there's a decent likelihood that you were ovulating, particularly if you were checking that with ovulation predictor kits or day 21 progesterone levels, things like that, I would say cut your losses, move on, be way more aggressive with IVF because I don't think you're going to get a whole lot from doing IUIs. So don't waste your valuable energy and money and good humor if you've got any of it at this point.

Susan Hudson (21:20)

For our listeners also, if you're in a situation where a lot of times when people are doing these, 12 cycles, it's because they're doing it with their OB-GYN. And one thing to be aware of, and one thing I always ask is when somebody is like, I did 12 cycles of letrozole or Clomid with my OB-GYN and I have PCOS, the most important question was, did you spontaneously start a period after each of those cycles or did you have to take provera or medroxyprogesterone acetate or some other form of progesterone to make you have a period. Because if you did quote, did all these cycles and you never spontaneously had a period, you never had ovulation for the most part. And so that also is a very different part of the story versus I did 12 ovulatory cycles. Whether we use one pill of letrozole, which is 2.5 milligrams or one pill of Clomid, which is 50 milligrams, or even if he used 150 milligrams of Clomid, if you didn't spontaneously start a period, you probably didn't ovulate, which means that wasn't an effective treatment. All right. Okay. Next one. Hello. I am 30 with one child who's four. No issues getting pregnant that time, but had had irregular cycles since age 14 which I now learned was PCOS. We haven't used protection since having my son, but actively started trying two years ago. Once I got my PCOS diagnosis, first round of letrozole ended in a pregnancy of unknown location. After that, tried four more rounds of letrozole and two Clomid cycles with no luck. Since moving to REI, we have done one IUI, which ended in a chemical, starting number two soon. Two HSGs done and both normal, no male factor issues.

Is IUI still a good path given my PCOS, secondary infertility and age? We only want one more child, but wondering if we should start looking into IVF given this journey we have been on.

Abby Eblen MD (23:12)

I think it depends on frustration level, pocketbook, how quickly you want to have a child. But based on what I heard, you've done quite a few, even with your REI, cycles of letrozole and IUI. so typically, Carrie said a minute ago, four to six is about the max. And beyond that, you probably need to move on to something more aggressive. And that more aggressive thing would be to do IVF at this point.

Carrie Bedient MD (23:33)

I would agree with that. The other thing that I would consider is doing a pregnancy loss workup because with the biochemical and pregnancy of unknown location, that starts to get more into the issue of is there something else going on that we haven't seen. The pregnancy of unknown location can indicate a couple of things. One is that it can be just a loss that occurred very early, no sac developed, and so it wasn't able to be pinpointed exactly where it was.

On the one hand, if it's a loss and you've had two losses now with the biochemical and the unknown location, then it's reasonable to start the RPL workup and make sure that everything looks good. The other thing to consider is that if the pregnancy of unknown location was actually an ectopic pregnancy where it tried to implant in a place that it has no business implanting, that indicates that your tubes might be compromised and continuing to do IUIs may be not only an exercise in frustration, but potentially more damaging or more dangerous for you if a pregnancy decides it's going to lodge in a location where it ought not be and try and grow inside of a spaghetti noodle when you really need manicotti or some sort of bigger pasta to grow inside. And so that would be another thing that I would look at. I think that it's reasonable to maybe do some of that additional blood work and to really think, all right, is this worth continuing to pursue because you have done a solid six cycles monitored with your REI and like we've been talking about, there's a point of diminishing returns and so take care of all of the other things, all of the other resources you have as well.

Susan Hudson (25:08)

Another thing to mention is that you said that your partner had a normal evaluation and in a lot of places a normal evaluation is only a semen analysis and there are some more in-depth testing that's available now. We mentioned earlier DNA fragmentation testing, but in our upcoming book, the IVF Blueprint, we also talk a little bit about SpermQT and SpermQT is a test that tells us even with normal sperm parameters, if the sperm know what to do when they get to the egg. So essentially you have genes within the sperm that can become what we call dysregulated or abnormally turned on or off. And if you have a high percentage of these dysregulated genes within the sperm, the sperm essentially get to the door and don't know how to press the doorbell. And so you could be doing all of these cycles and have millions and millions and millions of sperm, they get to the egg and they don't know what to do. Whereby looking at things like IVF and ICSI, where we inject the best looking sperm into each egg, then we can significantly increase your chances. And with things like IUI, those chances are pretty slim.

Okay, let's do another couple of questions. So how about this one? Hi, I absolutely love your podcast and listen to it to and from work every day. Thank you for listening. Thank you for everything that you are all doing. I've had two back to back miscarriages since late 2023 and haven't been able to get pregnant since I've done two letrozole cycles, but no positive pregnancies.

I have since started to see an RE. I'm 34, husband is 35. I have PCOS, LH 12, FSH 6.8, AMH 5.53, TSH normal, prolactin normal, insulin normal, normal BMI. We've had genetic testing done, normal karyotype, normal carrier screening, semen analysis is also normal, waiting on HSG. My RE is suggesting trying IUI then moving to IVF.

My question is, given my age and past failed letrozole cycles, would I be better off going straight to IVF?

Abby Eblen MD (27:18)

You could go directly to IVF. It'd be a little bit more successful, but the American Society for Reproductive Medicine back in 2020 looked at the available treatments that we have. And they said that you have about twice the success rate if you do oral ovulation induction and IUI. And that rate is still very low. So it goes from maybe 5 % to maybe 10%. And so they actually recommended that as physicians, what we really should tell patients is, probably the best treatment is letrozole and IUI. And I don't think you've done that yet. I think you've just done the ovulation induction. Based on your age, it wouldn't be terrible to try three cycles of letrozole and IUI. If you get lucky, get pregnant, win the ball game, then you don't have to do IVF. If you were 39 or 40, I probably wouldn't recommend the same thing. But at your age, don't think there's two or three months and the whole scheme of things is not a big deal. So if you were my patient, I would tell you it's probably reasonable to do either.

Carrie Bedient MD (28:08)

I think all of the other surrounding circumstances are particularly important in this case because this is one where it sounds like, if I'm reading this or hearing this correctly, that you don't have any other children. So this is not a case of we just want one more where doing an IUI and just getting that one more is really helpful. This is something where if you are thinking, hey, we want two, three, four, however many kids.

IVF becomes a little bit more valuable for a few reasons. One is because you can bank embryos. Two is because you can do genetic testing on those embryos. And granted, we don't know the exact reason why you had those two losses before, but one of the most common reasons is genetic abnormality, where there are too many or too few chromosomes. And in that case, IVF with PGTA in particular can be very helpful because it helps you to identify in advance which embryos are never gonna make it so that you can plan accordingly. And those considerations play a large role, as does what does your insurance cover? If you've got a plan that covers six IUIs and none of IVF, that is a different calculus than a plan that doesn't cover anything at all or gives you a lump sum to play with where you use it however you want and once you're done, you're done. So I think those other considerations are very important to think about when you are planning what's our next step.

Susan Hudson (29:26)

It's also important to understand that recurrent pregnancy loss is often what we call multi-factorial. So there are some people who have just one reason why they're having miscarriages, but there's a lot of people, about 30 % of people with a history of recurrent pregnancy loss actually have multiple things going on. And you've had a lot of the evaluation, you had your chromosomes. As Carrie mentioned, the most common reason for us to have miscarriages is because the embryo is developing abnormally chromosomally. But we also want to make sure you've had antiphospholipid antibody studies. Potentially going into IVF, some additional studies you may look at are looking at DNA fragmentation in the sperm. There is some correlation between recurrent pregnancy loss and that, as well as considering a test called Receptiva, which looks for a chemical called BCL6 that can be in the lining of the uterus that can increase the risk of miscarriages.

Just making sure you truly have had that complete evaluation. And then again, looking at what your reproductive goals are for your lifetime. Are we wanting one child or are we wanting a children? And, considering you're currently 34, time is important. Time usually hasn't run out. And the good thing about recurrent pregnancy loss is most people are eventually going to be successful, but we can't tell you without interventions, is that going to be the next pregnancy or four pregnancies down the road? And a lot of that decision is where your heart and your mind come together.

Carrie Bedient MD (30:53)

Agreed.

Susan Hudson (30:54)

All right, ready for another? Hello, my husband and I have been trying to conceive for three years. I'm 26 years old and my husband has normal sperm counts. Diagnosed with PCOS at my first appointment with my fertility specialist. Placed on letrozole five milligrams. Did six cycles of naturally trying to conceive with letrozole. After that failed, we did four rounds of IUI, which failed. Then my doctor suspected endometriosis due to my symptoms, so I went through...with the surgery and we found stage 1-2 endometriosis mild. Now we are back on letrozole for another 5-6 rounds trying naturally after the endometriosis removal. My biggest concern is even though I am getting positive LH surges, how do I know that I am truly ovulating? I have never done mid-cycle ultrasounds or blood work to confirm this.

Abby Eblen MD (31:40)

How old is she?

Carrie Bedient MD (31:41)

26. She with an RE or an OBGYN?

Susan Hudson (31:45)

She's with an RE. I would say that you need to shake this up a notch.

Abby Eblen MD (31:45)

Yeah, agreed, yes.

Carrie Bedient MD (31:52)

Yes.

Susan Hudson (31:54)

And if this is a very, very conservative line of treatment that I can say that none of the three of us would have done. As we mentioned earlier, usually about three cycles, and if we're not successful, then we need to be changing tacts. And if the conservativeness of this treatment, essentially taking baby steps is because that's what you're comfortable with, then that's completely fine.

But you also may be losing some of the effectiveness of the surgery that you had. Realize that with all treatments with endometriosis, most endometriosis is going to come back. It usually comes back at the same stage and it's usually gonna come back within six to 12 months.

Abby Eblen MD (32:33)

Think you need to be more aggressive for sure.

Carrie Bedient MD (32:35)

I'm curious as to what the underlying motivation was behind doing the surgery because sometimes people do it because there's a symptom that's driving it, particularly pain. Other times people do it because they don't want to move on to something more aggressive. And oftentimes that's a patient choice because I think most REs at this point have moved more away from the surgical realm, not because it's not useful, but because some of the other treatments are far more useful and far more effective in particular. And that ends up being better for our patients because it's not just how you get there, it's the time that it takes and everything you're going through and effectiveness and surgery holds quite a few other risks because most of the time you're gonna be fine during surgery, but the times that you're not, it tends to be a bigger negative than the negatives that you encounter during an IVF cycle. Now, everybody has a different experience and so not everyone's gonna agree with that and that is just fine. But I think at this point, you have given yourself more than enough opportunity, even considering your young age, to do this conservatively and the time has come to be more aggressive because...And I see as you're 26, there's a really good chance you do one cycle of IVF and you're done and you have done the surgical routes. You've done the timed intercourse. You've done the letras, all you've done the IUI. You've done all the stuff leading up to it. Just move forward and.

Abby Eblen MD (34:05)

Yeah, and I would say too, there's lots of reasons why people either do or don't want to do IVF. Just reading between the lines and I have, I don't know if this is true for this listener or not, but I know when I was in my late 20s, I was in residency training and somebody told me I had to shell out X amount of dollars to do IVF. I would have been like, I don't have that kind of money. And so I don't know, but I suspect, you know, younger you are generally less money you have. And so, look around at your HR, talk to them, see what coverage you have.

I know in our neck of the woods, a lot of companies like AT &T and Microsoft and several large hospitals, employers, particularly large employers, Walmart, Target, have some coverage. So just think about that. If that's what's holding you back, look at your coverage and figure out what you have and figure out if you can make a lateral move or a better, for even a better job in a different place and have better coverage.

Susan Hudson (34:54)

Very good points. Very good points. Let's do one more. Okay. 28 year old female. I've always had irregular periods, missing it for a year when I went to the gynecologist and the NP prescribed birth control and no tests were done saying come back in a year later and request metformin. That should also help with weight loss. I accepted this because my period was coming in monthly. After moving cities and having issues transferring my pills, my period was absent again.

This year I was diagnosed with PCOS and a prolactinoma. I've been on metformin, cabergoline and vitamin D for four to five months. My prolactin level is back to normal. I'm five foot three and went from 221 pounds to 198 and my fatigue has improved, but I'm concerned I still haven't had a period, just some dark brown spotting. Is there something else at play or is more time needed for my cycle to regulate?

Carrie Bedient MD (35:45)

So she said metformin, cabergoline, was there a third med in there?

Susan Hudson (35:48)

Vitamin D.

Carrie Bedient MD (35:49)

Vitamin D, okay. So it looks like she's tackling a lot of the big obvious things. So on the cabergoline treating the prolactinoma, I would do a check to make sure that your prolactin levels are truly low, because sometimes we have to play with the doses of cabergoline and go up a little higher, go to a slightly higher frequency. And so that's low hanging fruit that I would definitely check.

Looking at your symptoms as well. Do you have any nipple discharge, those types of things. The metformin, I'm glad, is working for you with the weight loss because that has a huge impact on cycle regularity. What most women don't realize is that fat cells are endocrine organs. They produce hormones as well. And so in many respects, it's like having a built-in birth control because you produce a very weak estrogen from adipose cells or fat cells. And when you've got a lot of them, that means that you're getting more estrogen and that functions as birth control. And so keep going on the path that you're going with the weight loss because that will oftentimes be really helpful. And even if you're not seeing continued loss, that exercise that you may have picked up along the way or increased or adjusted can be very helpful in sensitizing the cells to insulin so that they function better, so that you're more likely to ovulate.

So I think a lot of the adjacent stuff you're doing is very good and very helpful. Even if you're not seeing your period come back immediately, I think keep doing all of those things. Make sure that you are getting the most out of those medications and there don't need to be any adjustments with your A1C levels, your prolactin levels, those types of things. Consider, especially because you're young, if you do need to lose more weight, do the injectable medications like Ozempic, trizepizide, Mounjaro and the zillion brand names that go along with those, maybe that's something that is worthwhile. I think making sure that you're totally optimized will be helpful.

Abby Eblen MD (37:43)

But I think at this point, if you've been at this for about a year or so, I think she said, I think it's reasonable to go to somebody to help put you on medication to help you ovulate because presumably, provided they've checked, the one thing I didn't hear is if they've checked your egg number, provided that looks good, you should be able to ovulate and probably with all the great work you've done in terms of weight loss and getting your prolactinoma under good control. Like Carrie said, you've set yourself up for success and I think probably you have a pretty high likelihood of ovulating on ovulation induction, just oral medicine, about 80 % chance with one of the dosages. So definitely at this point, we'd go see an REI if you've not already. And also consider doing IUI along with ovulation induction, because both of those together work better than either one of them separately.

Susan Hudson (38:27)

I'd like to dovetail onto a couple of things that were mentioned. So as to other things to help improve your outcomes, you may want to try some supplements called inositols. Inositols do have some evidence in the right 40 to one ratio of improving menstrual cyclic control as well as improving ovulation. Metformin tends to do good at helping people have periods, but really the pregnancy rates are relatively dismal with only the metformin. Okay. And then the other thing Abby alluded to about getting your egg count. I can't tell you the number of people who have come to all of our clinics who have had a presumed diagnosis of PCOS because of irregular or absent periods and then come to find out they actually have the extreme opposite, which is not enough eggs. Although, PCOS is very common and it sounds like you have some of the other things that tend to go along with PCOS, we really need to truly make sure that is your diagnosis because if you actually have diminished ovarian reserve instead of PCOS, you definitely need to be seeing a reproductive endocrinologist and really focusing on those reproductive goals as soon as possible.

Carrie Bedient MD (39:42)

Definitely agreed. All right, any last thoughts, questions, concerns, or funny jokes about PCOS or any of questions that we have been through today? I think we hit the majority of it.

Abby Eblen MD (39:48)

Yeah.

The one positive note I would say is I do tend to see in older patients, they tend to have more eggs. It doesn't necessarily counterbalance the genetic component of eggs, but the positive PCOS as you get older is you tend to have more eggs, I think, than a lot of women your same age.

Carrie Bedient MD (40:08)

Many of us, when we're looking at a patient who comes in with the diagnosis of PCOS that's been confirmed and true and all of that, we are all doing silent little happy dances in our heads because we know that the likelihood that this is gonna work eventually and you're gonna get that kiddo is pretty high and that is a wonderful feeling, not just for you guys, but for us as well because we want more than to see you succeed and...run into you in Costco with your baby, dancing all over the cart, a couple of years down the line. So, all right. Well, excellent. So to our audience, thank you so much for listening. Subscribe to Apple Podcasts to have next Tuesday's episode pop up automatically for you. Be sure to subscribe to YouTube as well. That really helps us spread reliable information and help as many people as possible.

Abby Eblen MD (40:36)

Visit Fertilitydocsuncensored.com to submit specific questions you have and sign up for an email list. And don't forget about our book, IVF Blueprint, that's coming out in the fall, September.

Susan Hudson (41:02)

As always, this podcast is intended for entertainment and is not a substitute for medical advice from your own physician. Subscribe, sign up for emails, and we'll talk to you soon. Bye.

Carrie Bedient MD (41:11)

Bye!

Carrie Bedient  MD (41:12)

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