The Microbiome and Human Reproduction: Current Research and Future Developments

Kaitlin Searfoss:
Hi everyone. Welcome to this podcast from Cambridge Healthtech Institute for the Advances in Microbiome Diagnostic Symposium taking place on August 26, 2016 as part of the Next Generation DX Summit. I'm Katelyn Searfoss, Conference Producer. We have with us today one of our speakers, Dr. Jason Franasiak, who is an attending physician at the Reproductive Medicine Associates of New Jersey. Thanks for joining us today, Dr. Franasiak.

Jason Franasiak:
It's an absolute pleasure to be here with you, thank you.

Kaitlin Searfoss:
Let's get started. Can you tell us a little bit about how the microbiome affects reproduction and how this information may be useful in future diagnostics?

Jason Franasiak:
Absolutely. There's some very fascinating connections for the microbiome to human reproduction. In fact, one of my favorite stories about the microbiome and, in fact, germ theory and hand washing which dates all the way back to the 1800s is actually tied to human reproduction. This story goes back to a Hungarian Ob/Gyn and his name was Dr. Semmelweis and his lived from 1818-1865. Back at that point, we didn't even actually understand that hand washing as physicians was an important thing. He studied in Vienna a syndrome called child bed fever which was essentially these women would come into the maternity hospital, deliver their child, and then come down with these terrible fevers, nobody knew what was going on, and they would ultimately in 10-35% of the cases which is unbelievably high, these women would actually die of this disease.

He noted that in the physician's ward ... There were two wards, a Ward A and a Ward B in the Physician's Ward. The mortality rates of these women was actually three times that of the midwives. After careful study, he found that the difference between the physicians and the midwives was that the physicians did autopsies on cadavers in the afternoon and then would come back and round on the patients and, again, hand washing wasn't a thing. The physicians would bring back, unbeknownst to them, what were termed cadaveric particles but were really truly microbes and would actually infect these women. It ultimately resulted in a higher mortality.

He instituted hand washing and this dramatically reduced the mortality rate of these women. His work laid the ground work for eventual determination of germ theory and many other things as time went on. All of this kind of goes back to the reproductive world in Obstetrics and Gynecology and Dr. Semmelweis and his observations. We have seen that the microbiome's impact on human health and particularly human reproduction has really become prominent in the past several decades. In fact, there is work to show that in all aspect of human reproduction the microbiome has influence.

For example, when men are producing sperm we do know that abnormalities in their microbiome cause things like asthenospermia, oligospermia or leukospermia. These are all abnormalities in spermatogenesis. Similarly, as women are producing the eggs, where the sperm will go and meet the eggs in the Fallopian tube for a successful fertilization and ultimately implantation we see impaired folliculogenesis. The eggs don't end up coming along as well as we might anticipate with alterations of the microbiome.

It is particularly of interest in the area of implantation. Once the embryo has traveled through the Fallopian tube and is implanting inside of the uterine cavity there's a very complex interaction that goes on. Essentially, as many know who are listening to this, it involves essentially a foreign body invading a host. That's essentially what the embryo is, is a foreign body invading the host. There has to be very interesting and complex alterations of the immune system in order for this to happen successfully. Alterations in the microbiome, we know for certain that there is microbiota in the uterine cavity and that they impact and can impair and influence the way the immune system interacts.

Then as time goes on we can see in human reproduction, once we have gone through all these complexities of forming eggs and sperm and having them meet successfully and implant inside of the uterus, we can see that the microbiome has significant impacts on the developing fetus. We can see increases in late pregnancy losses with alterations, we can see intra-amniotic infections where abnormalities of the microbiome inside of the amniotic fluid sac causes problems for the fetus and for the mother. Things like pre-term birth or intrauterine growth restriction which ultimately results in having delivered small babies.

We also know that there's some physiologic and pathophysiologic processes that happen at the time of delivery. You can have the neonate which is colonized at the time of delivery and there's some fascinating work that's being done with Cesarean sections and how actually there's some difference in colonization for babies born via Cesarean section versus vaginal delivery. The microbiome and human reproduction, both normal human reproduction and abnormal reproduction, is vast and we are just now understanding this better.

Kaitlin Searfoss:
How could scientists studying different microbiomes utilize your research and findings and apply it to their own studies?

Jason Franasiak:
Well, the thing that we are focusing on in particular in our research has to do with looking at the microbiome at the time of an embryo transfer in patients that are undergoing in vitro fertilization. These are patients who are infertile and they're infertile for a number of different reasons, one of which may be their microbiome. Typically, they have been classified as infertile for one reason or the other or unknown infertility and are undergoing in vitro fertilization where we have grown embryos in the laboratory and are now placing them back into the uterine cavity. That's done with a sterile catheter. We're looking at the sterile catheter as our sample and characterizing differences in the microbiomes in women who have successful pregnancies and in those that don't.

Some of the things that are interesting about this project are that it does involve the utilization of samples which have traversed into the uterine cavity. There are many mechanisms which are in place to alter or change what type of microbiome exists inside of the uterine cavity. This is of interest in and of itself to understand better what type of microbiome exists at the time of embryo transfer. That may be in and of itself informative. In addition, we are looking at samples that have very low bacterial loads and read counts and so we've had to vary the way that we look at the hyper-variable regions as well as the protocol utilized in order to appropriately get read cause that can be mapped and that we can get adequate sample characterization.

Some of those things may be of interest as well as we better understand how to process reliably those samples which have relatively low bacterial loads as oppose to some of those which may come from the oral pharynx or from the gastrointestinal tract.

Kaitlin Searfoss:
Well, I know I'm excited to see your presentation at the conference but what are you most excited to learn?

Jason Franasiak:
I'm really excited about the entirety of the lineup that we have at this Next Generation Summit, particularly as we're talking about all these advances in microbiome diagnostics. I think some of the most important challenges we have in this area have to do with being able to have reliable sample characterization. A lot of this, while the science is robust in many areas and we're learning a lot from the NIH's Human Microbiome Project, there are still some areas where we're having issues with standardization of obtaining different types of samples, of the way that those samples are processed. There are a couple of really fantastic presentations which deal with just the nuts and bolts of learning how to study various environments adequately and accurately.

Then subsequent to that we really do need to be thinking about how we can put these new tests into clinical use. The second half of the conference really talks about some really fascinating ways that people are looking at the clinical implications of this once we have been able to find a way to accurately and adequately characterize these specimens. How can these specimens actually impact the patients that we're taking care of on a day-to-day basis? Ultimately, that's the most important part of all this research.

Kaitlin Searfoss:
Thank you for your time and your insights today, Dr. Franasiak.

Jason Franasiak:
Thank you. It was a pleasure.

Kaitlin Searfoss:
That was Dr. Jason Franasiak, attending physician at the Reproductive Medicine Associates of New Jersey. He'll be speaking at the Advances in Microbiome Diagnostic Symposium, part of the Next Generation DX Summit taking place this August 26. I'm Katelyn Searfoss, thank you for listening.