Melanie Cole (Host): Many couples are told that they have unexplained or idiopathic infertility meaning doctors cannot seem to find anything wrong with either the male or the female after analysis of sperm and fallopian tubes or uterus. My guest today is Dr. William Ziegler. He’s a specialist in reproductive endocrinology and infertility and is the medical director of the Reproductive Science Center of New Jersey. Welcome to the show, Dr. Ziegler. So, people hear unexplained infertility. Let’s just start with --what is standard infertility testing? What does that involve?

Dr. William Ziegler (Guest): Well, when a couple are seen within our office, we want to get to an etiology behind what is causing their subfertility. We look at mainly three specific areas. One of them – or the first or the easiest -- is basically looking at the sperm to identify whether there is a male factor issue. That’s easily tested for by just getting a semen analysis and from that we can identify whether there is a low count, concentration of sperm as well as whether there is a low number of moving sperm or even the shape of the sperm -- there’s a low number of normal-looking sperm that in which that could be an issue.

Another area we look at is – looking at a woman’s ovarian age -- that even though somebody has a chronological age of let’s say 34 years old, their ovaries may be acting 44. So, biological age or ovarian age could be different than their chronological age. We also look for other issues such as thyroid problems, other hormonal imbalances and which can affect a woman’s – just – ovulation.

The third issue is looking at the uterus and looking at the fallopian tubes. We want to make sure that the uterine contour is normal in which there is nothing like a fibroid, which is a smooth muscle tumor within the uterine wall, or an endometrial polyp which can actually – those two things can act like an IUD and can stop implantation, and we also want to make sure the fallopian tubes are open. Many of the testing which we have -- hysterosalpingogram or even something like a sonohysterogram -- that we can actually put bubbles through the fallopian tubes and see whether they are open. It tells us they’re open. It doesn’t tell us whether they're working. It doesn’t tell us where they are either which is a good screening tool to identify if there is any other pelvic factors that we need to maybe investigate before we go on for treatment.

Melanie: So, you’ve tested all of these things, and it's a great description that you gave of all of the different things that you look for in a woman, and what if they all come back negative? What if they all come back with nothing – they show you nothing. Then, what do you tell the woman?

Dr. Ziegler: Well, then we have to say, okay, there’s something going on which is affecting your fertility, and basically we run into unexplained infertility in around 20% of our cases -- that we cannot identify a just an obvious cause. So, then what we look at is, okay, based on a woman’s age we’ll then determine we need to, let’s say, improve their ovulation and to improve egg quality and try to maximize the exposure of an egg to sperm and based on a woman’s age we’ll determine what course of therapy in which we proceed with -- whether it is an oral medication like Clomid or something like Letrozol which could improve a woman’s ovulation by increasing their own natural production of follicle-stimulating hormone to stimulate the follicle to grow, and we can monitor it through ultrasound to make sure it’s getting to the mature size so we can be somewhat certain that it should have a mature egg inside. We cause it to ovulate with another medication called HCG and then we do it along with an insemination, so we, again, we try to time the fertile window of the egg and the fertility and then of the sperm. So, we can maybe increase their chances. If a woman fails that type of therapy, or if they are older, we can move on to stronger fertility medications such as follicle stimulating hormone. There’s ones out there -- there's Follistim, there's Gonal-F, there's Menopur, there's different ones out there in which we can use and that’s basically giving back more FSH to maybe improve egg quality, and again, we do that along with insemination.
And then the final -- is basically going directly to in vitro fertilization, but if a couple fails to conceive with conservative treatment with doing insemination, there is a higher probability that there could be some pelvic issues that we did not identify prior because of the testing that we did were not sensitive enough to detect that. So, if a couple goes through conservative treatment – like let’s say Clomid or Letrozol with insemination – and they go through three cycles, and they fail to conceive, then we also talk about possibly doing something called a laparoscopy. We look inside the pelvis to see if there is any adhesions. Some women have – may could have had a prior pelvic infection and never knew that or they have endometriosis, which can actually cause scar tissue and even though the fallopian tube is open, it may not be in its anatomical location to be able to pick up an egg and therefore, the problem in which they have is basically a pelvic issue or a tubal issue that again was not identified on prior studies.

Melanie: So, you mentioned three cycles, Dr. Ziegler. So, how long does a woman or a couple try these conservative measures before they do speak to you about IVF?

Dr. Ziegler: Well, we usually will go through – it really depends on a few factors. We talk about various treatment options, but the decision is really made based on two factors. One of them is insurance coverage. Some patients have coverage for inseminations, and some don’t. Some have coverage for IVF, and some don’t. Also, besides that, there is a stronger variable here – a stronger drive -- and that’s basically a woman’s frustration. By the time a woman is seen in our office, they are frustrated, and they don’t feel light at the end of the tunnel, so we have to really take into account their emotional battery. If their battery energy is running low, then we get aggressive, and maybe it's time to go to in vitro fertilization. If a treatment option is utilized such as insemination, after three cycles, there really no clear cut benefit to continue with that course of therapy. It’s time to change treatment, but each cycle – it gives a certain percentage, a certain pregnancy rate, but then again, that plateaus and then after three cycles, so now it's time to move on to something different.
After we do the Clomid or something conservative, we do discuss possibly going for surgery to take a look inside and see if there is an anatomical problem, or we get aggressive with the injectable fertility drugs with inseminations, but I always have my reservations with doing that because whatever stopped them from getting pregnant with the conservative treatment could stop them from getting pregnant with the more aggressive treatment, or we go directly to in vitro fertilization. So, we take into account the dynamics of the couple also. If it’s causing a lot of turmoil between partners, then it is time to take that next step and maybe go directly to in vitro fertilization.

Melanie: Dr. Ziegler, and you mentioned that you do take into account how the woman is feeling going through all of this and her frustration levels. Is there anything to the fact of some, you know, some doctors say, oh just relax and have lots of sex, and you’ll get pregnant. If this is unexplained infertility could stress play a role and do you ever say to a woman, well, you know, try some of these methods like we've spoken about on the show before – yoga and meditation and acupuncture, all these things? Does it sometimes come to those discussions?

Dr. Ziegler: We always discuss stress, but it's very difficult on how to relieve that stress and really what does – the role that stress plays with infertility treatment. We do entertain other ways to reduce the anxiety of going through fertility treatment. We don’t use that and then as a sole method, we will use it in conjunction with medical treatment, but again we do discuss the psychological as well as the physical stresses and how going through the whole process or even dealing with the condition of infertility of how it is affecting their interpersonal relationships and even with friends and family.

Melanie: So, is it ever a possibility that unexplained infertility could be explained during such things as IVF? Do – can you sometimes find out what was going on after the fact?

Dr. Ziegler: Yes. Even in going through the fertility treatments themselves, even though we get screening tests to try and help identify a cause those tests don’t identify everything. So, even going through either Clomid cycles or injectable cycles or even going for in vitro fertilization, we can identify – there is a possibility of identifying a cause whether it is an ovulation issue. Maybe their ovaries are not acting the way we think they are or even the egg quality. Once we retrieve the eggs, maybe the eggs are not as good as we think they are, or they don’t fertilize well. In some cases, the eggs look great, and the sperm looks great, and then when we do standard insemination, we get no fertilization. So there is something going on there that we have now identified, and the way we overcome that is we do a procedure called intracytoplasmic sperm injection – actually put the sperm directly right inside the egg. In some cases that we find eggs where the shell or the zona pellucida around the egg is very thick, and it could also be very hard and that could also be a reason why things are not working despite all of our screening tests being normal.

Melanie: So, wrap it up for us, Dr. Ziegler, and what do you tell couples when you’ve done all of these tests, and you come up with this term unexplained infertility, and what they can do – what’s their next step and why they should come to the Reproductive Science Center of New Jersey for their care?

Dr. Ziegler: I think in those patients that have unexplained infertility, I think there is a cause – we just have not identified it yet, and we basically need to take into account how aggressive these couples want to proceed, and that’s part of what we do here at the Reproductive Science Center of New Jersey, is that we try to take into account a couple’s frustrations, and we take into account their insurance, and we take into account many factors to help them proceed through fertility treatment and try to decrease their anxiety because a lot of patients they don’t know what their coverage is and even though they want to do IVF, they may not have coverage for that so what else can we do? Or maybe they don’t know they have coverage for IVF, and that’s what they actually want to do, and we can find that out for them. But, I think it's really coming up with a game plan that the couple are comfortable in proceeding with that’s addressing all of their needs – from their medical need to their psychological need, and their family-building desires.

Melanie: Thank you so much for being with us today, Dr. Ziegler. You're listening to Fertility Talk with the Reproductive Science Center of New Jersey. For more information, you can go to fertilitynj.com. That's fertilitynj.com. This is Melanie Cole. Thanks so much for listening.