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Deborah Howell (Host): Unexplained infertility can be a very frustrating diagnosis for couples trying to conceive. Dr. Allison Rodgers, a reproductive endocrinologist here at FCI, is with us to help us better understand unexplained infertility and some treatment options that are now available.

This is The Time To Talk Fertility Podcast. I'm your host, Deborah Howell. Dr. Rodgers, so nice to have you on with us today.

Allison Rodgers, MD: Thank you so much, Deborah.

Deborah Howell (Host): And if it's all right with you, let's just dive right on in. Shall we?

Allison Rodgers, MD: Perfect.

Deborah Howell (Host): What is unexplained infertility?

Allison Rodgers, MD: So unexplained infertility is when we don't have a clear understanding of why somebody is not getting pregnant. And this is a situation where you're ovulating, there's at least one open fallopian tube, and there is a good quality of sperm and the patient is still not getting pregnant. So we don't have a good explanation for why they are not getting pregnant.

Deborah Howell (Host): Okay. Fair enough. What could be the cause or the reason for this unexplained infertility?

Allison Rodgers, MD: You know, it's so interesting because so much happens inside our body to be successfully pregnant. We think about multiple things, right? So it can be that the fallopian tubes are open, but not functioning. That's a big one I think, that the fallopian tubes have these little finger-like projections that have to pick up the egg and bring it back into the uterus. And if they're not functioning, because of scar tissue or things like endometriosis, then it may not be able to pick up the egg. We can see a situation where women have eggs and are ovulating, but they're abnormal for whatever particular reason, they either are genetically abnormal or are otherwise abnormal and not able to make a baby and that's not necessarily something we can test for in advance. Sometimes we can see some subtle hormone imbalances where you're not having strong ovulations, you're not producing enough progesterone and it's not supporting a pregnancy if one were to come along. We see sperm quality issues where a sperm might not be able to get into the egg, and this can be a sperm issue, but we also think it could be an egg issue. If the egg has sort of a hard outer shell, the sperm may not be able to get in. And then, we also think cervical issues. So maybe there's a cervical mucus that the sperm has to cross to get someone pregnant if you're having a natural intercourse cycle. And if there's something toxic about that, then the sperm cannot get through it.

Deborah Howell (Host): Wow. A host of reasons. How common is unexplained infertility?

Allison Rodgers, MD: Believe it or not, 30% of patients with infertility will have unexplained infertility, and it's so it's very, very common. Now, sometimes we can identify some things that we think may, you know, be the cause, but truly those patients are then diagnosed as unexplained.

Deborah Howell (Host): Got it. Now, does unexplained infertility affect certain age groups more than others?

Allison Rodgers, MD: You know, not really. We know that as people get older, the quality of eggs drops. And so truly by the time women are in their mid-30s, egg quality drops significantly. And by the time women are in the 42 to 44-year-old range, there's very few, if any, healthy eggs. And so we know that egg quality is related to age, but from an unexplained infertility, like we don't have an explanation, that can occur at any age.

Deborah Howell (Host): Okay. And what are some tests you can perform to diagnose unexplained infertility?

Allison Rodgers, MD: So really, we need to make sure, number one, is a semen analysis from a partner with sperm to make sure that there is adequate sperm to produce a pregnancy. We want to do evaluation of the uterus and fallopian tubes. So we either do a hysterosalpingogram, which is an x-ray of the fallopian tubes, or we often will do a three-dimensional saline sonogram, which is an ultrasound where we take a look at the uterus, as well as the fallopian tubes. We want to make sure there's an open tube and a uterus that looks healthy, that's number two. And the third is evidence of ovulation. And a lot of times we can get this just from the history of talking to the patient and having normal cycles. Sometimes patients will be doing ovulation kits, to see if they're ovulating with the urine ovulation kits, looking for the luteinizing hormone or LH, so if those are positive from home. But a lot of times evidence of ovulation is documented by a patient's history of their menstrual cycles. We often also can do luteal progesterone level to document that, but it's not necessarily needed for the diagnosis.

Deborah Howell (Host): So I'm thinking about couples who are actually diagnosed with unexplained infertility. Should they continue trying to conceive on their own or seek treatment?

Allison Rodgers, MD: So really because it's such a variety of things that can cause infertility with unexplained, then it's really hard to sort of know what their chances of success are. You know, we want to see women and people who are trying to get pregnant, who are 34 years and younger. If they're trying for a year without success on their own, it's time to start treatment. And for people who are trying to get pregnant who are 35 years old and older, after six months, it's time to start treatment if they're not successful.

Deborah Howell (Host): That's great advice. Now, what are the treatment options for unexplained infertility?

Allison Rodgers, MD: So this is so fascinating. There's been a lot of research looking at people in the unexplained infertility group and what treatment works. So typically, we start with either Clomid or Letrozole, which are both pills, tablets, and intrauterine insemination, where we put the sperm inside the uterus. And if patients are, you know, in their mid to late 30s, typically at 38, we recommend going directly to IVF with genetic testing because so many of the eggs are abnormal at that age.

Now, they've done some really eloquent studies looking at things like, you know, having a natural cycle and just doing the insemination or alternatively taking pills and doing intercourse, thinking that maybe just increasing the number of eggs really will just help and then you can have intercourse also. And what they found is that did not help people, which is so fascinating, in this patient population group.

So if you have male factor, natural cycle and insemination might be helpful. If you're having trouble ovulating, ovulation induction with intercourse might be helpful. But in unexplained infertility, we need to increase both the number of eggs with medicine and the number of sperm that can get to that egg with insemination to really help patients be successful. The other treatments besides medication, ovulation induction with insemination or IVF, other things that are less than that, are not going to be successful.

Deborah Howell (Host): Well, you're right. This is fascinating. So how do you determine which treatment option is best for an individual or couple with unexplained infertility?

Allison Rodgers, MD: So, this really is an individualized approach. So I take a full history, we do the fertility testing. And a lot of it is how old is the patient, what does their egg quality look like now, and what's their goal. You know, if it's a patient or couple, what are their goals? How many children do they want and how do they want to get there? And so it's really individualized treatment that really depends on the particular couple and the particular situation in terms of what is right for each individual.

Deborah Howell (Host): You know, and I'm thinking couples listening right now are wondering one question, what are my chances of getting pregnant if I have unexplained infertility, or if we have unexplained infertility as a couple?

Allison Rodgers, MD: So it is great actually. I think there's a lot of people who are very frustrated with this diagnosis because they feel like there's got to be something wrong with them because they're not getting pregnant and they want us to find what's wrong so we can fix it, right? And so they have been told, "We don't know. It's unexplained." can be really frustrating for patients. But typically, for patients like this who are trying on their own, it's not zero, right? It's about 1% to 2% per menstrual cycle, which is not real high if they're trying on their own. So that's why fertility treatment with medicine within insemination or IVF can dramatically increase their chances. Depending on the age of the patient, it really depends on the particular situation, but it's probably around 10% to 15% per cycle with, for example, Clomid and insemination, and, you know, it might be like 60% or 65% with IVF. So really good chances of being successful with treatment

Deborah Howell (Host): Wow. Well, you sort of answered my next question, but I'll ask it anyway, maybe you can expand. Is there anything someone diagnosed with unexplained infertility can do to improve their chances of conceiving?

Allison Rodgers, MD: So I wish it was like something as easy as changing their diet, right? I think that we all need to do everything we can to have the healthiest body ready for conception as possible. So limiting caffeine to under 300 milligrams, so I usually tell people not more than about 20 ounces of coffee. You know, avoiding things like nicotine, marijuana and trying to eat as healthy as possible, including trying to limit processed foods or chemicals. I think those are all things that we have control over.

What we don't have control over is a lot of the function of our, you know, uterus, our ovaries, our, you know, testicles. We don't have a whole lot of control over the function of that. And so this is where treatment is really the number one thing you can do to increase your chance of conceiving.

Deborah Howell (Host): Okay. Now, you mentioned marijuana. What about uses of, you know, CBD oils and balms?

Allison Rodgers, MD: So that's a great question. So one of the things is, you know, CBD does not sort of cause you to become high because it doesn't cross your blood into your brain, right? And so I don't think we know enough really to truly know if it has an effect. We do know that marijuana can cause a lot of constriction of blood vessels, increased risks for vascular issues. So I would recommend if you're trying to get pregnant, avoiding any toxins, whether it's something like CBD, or something like marijuana.

Deborah Howell (Host): Good advice. Does insurance cover treatment for unexplained infertility diagnosis? I know every case is different, but does it usually cover it.

Allison Rodgers, MD: Yeah. So, especially in the state of Illinois, where many of our patients have coverage through their employer or through the state of Illinois that has coverage, if you have coverage for infertility treatment, then it it's a covered diagnosis. So, obviously, if you don't have any infertility coverage, you're not probably not going to have it for this. But it is considered a known and treatable diagnosis for infertility and it should be covered if you have infertility coverage, which is great news.

Deborah Howell (Host): As you mentioned before, that is great news. Unexplained infertility can be so frustrating as a diagnosis. What advice do you give to those who are diagnosed with unexplained infertility?

Allison Rodgers, MD: So if you're going to be diagnosed with infertility, it's certainly one of the better diagnoses to have. I will tell you that I personally went through infertility treatment. I was able to have my first child without any issues and then suffered a secondary infertility, which was completely unexplained. I was having cycles every month. My husband's sperm was fine. My tubes were open and I wasn't getting pregnant. And as frustrating as it is because people kind of get fixated at fixing something that's wrong, the good news is that a lot of the things that we find wrong with people are not fixable, right? Problems with the uterus problems, with the fallopian tubes, not having enough eggs issues, you know, there's lots of issues with sperm. Some of those things certainly they're treatable, but a lot of them are really, truly not fixable. Whereas unexplained infertility has a fantastic prognosis. And typically, patients do very, very well with treatment. I went on to have the family of my dreams and, you know, had infertility in the rear view mirror at this point. And I think that as disappointing as it is to be told you have unexplained, meaning I think people think we can't figure it out, so that's a bad thing, but actually it's the best diagnosis to have.

Deborah Howell (Host): Got it and congratulations. And I'm so glad you've reached your happiness factor with your complete family. Anything else you'd like to add to our conversation today, Dr. Rodgers?

Allison Rodgers, MD: Well, I think patients out there should really trust their gut. It's important to really listen to their gut, make sure they're, you know, getting all of the information they need, it's really important to make sure you have a doctor and a medical team that you feel like you can communicate with. And it's important to advocate for yourself, do treatment, and eventually you'll have your family. This journey will end with a baby.

Deborah Howell (Host): Well, it's such great information and it gives so many so much hope, Dr. Rodgers. Thank you so much for being with us today to share your expertise.

Allison Rodgers, MD: Thank you so much for having me.

Deborah Howell (Host): Our pleasure .That was Dr. Allison Rodgers, a reproductive endocrinologist here at FCI. You can schedule an appointment to talk to a fertility specialist at 877-324-4483 or visit FCI online.com for more info. And if you enjoyed this podcast, you can find more like it in our podcast library, and be sure to give us a like and a follow if you do. This has been The Time To Talk Fertility podcast. I'm your host, Deborah Howell. Have yourself a terrific day.