Mass General Fertility Center 30th Anniversary Webinar

This year, the Massachusetts General Hospital Fertility Center is celebrating 30 years of care. Our clinical work and cutting-edge research across the field of reproductive health and fertility has helped thousands of people across New England and beyond. As we reflected on the past 30 years during this virtual celebration, our team shared their commitment to furthering research and clinical innovation to improve outcomes for future generations.

Video Transcript

John Petrozza, MD: Good morning and welcome to the Mass General Fertility Center webinar. Thank you for joining us. I'm Dr. John Petrozza, the Director of the Fertility Center and Chief of the Division of Reproductive Medicine and IVF. I am pleased to be here with you to celebrate the 30th anniversary of the Fertility Center. 

Over the past 30 years, we have made incredible strides in reproductive care, from technological advancements to groundbreaking research and clinical innovation. These include surgical devices, surgical procedures, egg freezing techniques, reporting some of the first human data on the impact of chemicals on reproductive health. Hormonal use during the midlife transition, the potential use of AMH as more than just an ovarian reserve marker, but a modulator of ovarian function, early views into placental function in women going through IVF, point of care testing for semen analysis, using your smartphone and the use of artificial intelligence in the embryology laboratory to help us select the best embryo to transfer.

These are phenomenal things, and we hope to continue to advance these fertility innovations and care over the next 30 years and beyond. These include continuing our commitment to educating the next generation of reproductive endocrinologists, improving access to care, including those who cannot afford it and our LGBTQ population, making point of care testing easier and more reliable, creating new therapies to modulate ovarian function, especially in patients who have limited ovarian function, bringing artificial intelligence into the operating room to assist with reproductive surgery to make it safer, and using wearable devices to monitor reproductive health. Just to name a few of the many things that we're currently working on. 

There are many opportunities to help support the Fertility Center in achieving these goals. And it's with philanthropic support that these initiatives can be successful. So please feel free to reach out if you're interested in learning more.

I now have the great privilege of introducing my wonderful colleagues who are here and joining us to answer some of the questions about their areas of expertise. Thank you once again for being here today. 

We'll start with Dr. Shruthi Mahalingaiah. Shruthi is the Director of our Clinical Research. She's also the Director of the Polycystic Ovarian Syndrome Clinic. She has a dual appointment here at Massachusetts General Hospital and also has an appointment at the Harvard School of Public Health. Shruthi, thank you for being here today.

Shruthi Mahalingaiah, MD, MS: Thank you, John. It's a pleasure to be here and engage in this 30th anniversary celebration. 

Dr. Petrozza: So Shruthi, you are involved in the Apple Women's Health Study. Can you explain what this study is and how certain demographic and lifestyle factors could have an impact on menstrual cycles and infertility?

Dr. Mahalingaiah: Absolutely. The Apple Women's Health Study is a collaboration between Apple, the company, the National Institute for Environmental Health Science, and Harvard. It is currently enrolling, and it's longitudinal, which means that we hope to continue being in contact with our study participants for at least 10 years or more. 

The requirements to participate including being of consenting age and having ever menstruated. The study is very unique in that it provides a platform on your iPhone for consented participants to securely share their menstrual tracking information and answer survey questions as well as contribute sensor data from either their phone or their watch, such as step counts. And we are very excited to share discovery on how factors, including everyday exposures and behaviors can impact the menstrual cycle and reproductive health.

Dr. Petrozza: That's wonderful and really groundbreaking to be able to use these wearables in a way that really sort of gives us a lot of information. Now, you are our Clinical Research Director. You do a lot of clinical research. Can you explain why participating in clinical research is so important?

Dr. Mahalingaiah: Well, firstly, I'd like to thank all the participants who participated in studies, whether they be surveys, base studies, or clinical research. One of the main points here is that research in women's health has been historically under-researched, and women have been underrepresented in clinical trials across the board. Only recently has the menstrual cycle been considered a vital sign and important to be included in drug trials and other studies. 

I think participating in clinical research is so important in order for us to fill major gaps so we can move from filling these gaps into our goals, which is health and healing. I'm excited to be able to share not only the digital and virtual studies but clinical studies in partnership with our division as well as with Harvard Chan School of Public Health.

Dr. Petrozza: That's wonderful. Thank you so much. Dr. Mahalingaiah.

Dr. Mahalingaiah: Thank you.

Dr. Petrozza: So next on our panel is Dr. Mary Morris. Dr. Morris has worn many hats in our division over the years that she's been on staff with us. She's currently the Medical Director for the Clinic for Reproductive Health and Cancer. So Mary, can you talk a little bit about what oncofertility is? That's a common word that we hear. And how does this clinic, the clinic that you actually manage, how does it work with your patients?

Mary Morris, MD, PhD: I've been at MGH my whole life, my entire medical career. And so the word oncofertility comes from two words, oncology, which is cancer care, and fertility, which is obvious. So as women, in the past, nobody spoke much of this topic. But as cancer care has improved and people are surviving longer, this has become the single most important topic for adolescents and young adults who have cancer. 

So essentially, what happens is that many cancer care options like chemo and radiation can destroy the ovaries or ovarian function and impair people's ability to become pregnant after they're done with their treatment. So often, what happens is the oncologist will refer the patient to me, and I see them and expedite whatever they want done. And currently, our technologies allow people to freeze eggs, sperm freezing has been around a long time, freeze embryos and freeze ovarian tissue. And we're working on developing medications. Hopefully, that will maybe avoid all of these treatments from being needed, that they can just get done with their cancer care, and then their ovaries would work fine.

Dr. Petrozza: That's fabulous. I mean, one of those things I've noticed over the last 10 years and definitely under your guidance with this clinic is sort of more awareness amongst the oncology specialists that, "Hey, I have a young patient with cancer. I need to reach out to the fertility center and at least give that patient an opportunity to hear the discussion, to hear what their options are." Do you agree with that?

Dr. Morris: Yeah, absolutely. And there's a lot of outreach that I've done and really is a team effort. I work with the oncologist and try to understand what the timeframe is and what the goals are. So, yeah, absolutely. It's grown a lot.

Dr. Petrozza: So, Mary, you're also doing some really groundbreaking research looking at antimullerian hormone (AMH). Antimullerian hormone for people who are going through testing, and for those in the field, has really become a fabulous marker of ovarian function, but you're looking at it in a different way. And I was hoping you could talk a little bit more about some of the groundbreaking stuff you're doing.

Dr. Morris: Yeah, that's right. Thank you. I'm lucky to be at MGH because I have a lot of great collaborators. And so it turns out that AMH was first cloned at MGH, and the person who cloned it is still here. She's the head of pediatric surgery, she's in her 80s, and she's just amazing. But they have worked on the role of AMH and the ovary, and it turns out that AMH, high AMH holds all the follicles back in a very primordial stage and protects them, holds them at bay. And so what we're trying to do is be able to use AMH as a medication that will do that function when people are going through their chemotherapy so that the eggs won't be damaged.

Dr. Petrozza: Yeah. Thank you so much, Mary. We're going to move on and go to Dr. Mitch Rein. Dr. Mitch Rein, he's a Reproductive Endocrinologist. He's also the Chief Medical Officer at North Shore Medical Center. He's been a stalworth of reproductive care in the North Shore area here in the Boston region and has really been a fabulous resource to us in many different ways. 

Now, Mitch, you see a lot of patients in our satellite office, in the North Shore up in Danvers. Can you speak to the value of these satellite offices, especially for consultations, procedural visits, and monitoring?

Mitchell Rein, MD: Sure. So let me just say hey to everybody. It's great to virtually see you all. And for me, I just want to reinforce that it's been a real privilege and joy to be part of this specialty and part of the Mass General Fertility Center for many, many years. I've been practicing, I think, for 35-plus years. 

John's question about satellite functions, I've watched so many developments over the decades, and this is one that has been around for a bit. And I do think it has been an important innovation in terms of care. We're lucky to have three satellite offices. Our initial satellite was at Newton Wellesley Hospital. And then, in 2009, we launched our North Shore satellite at the Danvers Mass General facility. And more recently, we're at the Mass General West facility in Waltham.

If I was to really just highlight the two big advantages of satellite monitoring, whether it's for visits or for procedures, convenience is really what first comes to mind, and for our patients, they're obviously mostly young, reproductive age, busy, have careers, having convenience is exceptionally important. And over the years, traveling into metropolitan areas, whether it's Boston, New York, San Francisco, has become more challenging. 

Then the other big advantage that I think has been somewhat evidence-based is it allows us to minimize the stress associated with these procedures. And we've been able to demonstrate that a whole host of stress-reducing activities improve outcomes. So convenience and stress reduction, John, I would say are the two big advantages.

Dr. Petrozza: Thank you, Mitch. One of the things of having satellites and running a fertility center that has a lot of moving parts is communication. And I think we all agree communication is key. With our new electronic medical records, there's a lot more communication that happens through the Patient Gateway system. We're very cognizant of the questions that are coming in from patients. We're very cognizant of the shared decision-making that goes into a lot of the protocols and treatments that we offer. Can you talk a little bit more about that, Mitch?

Dr. Rein: Sure. So shared decision-making is exactly what it says, and it's really been around for a long time, but I think has become more widespread and popular in the last 10 to 15 years. And the concept is that we make almost all, if not all, decisions with our patients, and generally, this is some sort of couple that we're taking care of as well.

The idea that we will really be the educators, and we try and help our patients understand, particularly in the treatment space, what their options are, what the advantages and disadvantages of the different options are. And then we make our decisions together in a shared fashion. It's often an iterative process where there's a lot of back and forth. We like to make ourselves available for questions and really just lends my final comments to John's more broader comments around communication.

Communication is so important in all we do in healthcare, but it's extremely important in fertility care. And we have a couple of things in place. John mentioned our Patient Gateway and the expansion of electronic applications. The current generation of reproductive-age couples frankly expect all the technology, and this is something we've been able to leverage. I think my colleague, one of my colleagues, is going to talk about telemedicine later, but I will just mention through the pandemic, virtual visits have also become an extremely important part of our communication approach. And it also adds to that convenience and stress reduction for many couples. And then I like to make the comment that there's no great doctor without a great nurse. And so our nursing staff is also just so important in terms of our approach to communication.

We're often busy doing different things during the day, and operating rooms, et cetera, but our nurses are not only available on a really full-time basis, but they’ve also done just a great job getting back to patients in a timely fashion. I'll just end with reinforcing that there's no such thing as a silly or stupid question. If you're worried about anything, we want to hear from you, and there's always someone that will be available to communicate and answer what's on your mind.

Dr. Petrozza: Thank you, Mitch. Great comments and a great lead-in to Dr. Jan Shifren. Dr. Jan Shifren is probably our longest-tenured physician here on our staff. She's also the Director of the Midlife Women's Health Center and endowed professor here in our department and at the Harvard School of Medicine. 

Jan, Mitch talked a little bit about telehealth. I'm hoping you can talk a little bit about what telehealth has meant to us, to our patients, especially during the COVID pandemic, and what value you think telehealth has moving forward.

Jan Shifren, MD: Terrific. First, John, thanks for that nice introduction. And most importantly, thanks to all of you for joining us today. It is very exciting to be 30 years old. Mitch, you and I go back and forth about longevity, but I've actually been a physician in this group for almost 30 years. I joined the program just after it had started. So it's very exciting. It's changed so much. It's changed in wonderful ways. Of course, we now have this terrific group. In the beginning, I wasn't working with any of these wonderful docs, so it's always been a great group of clinicians, great group of, as Mitch said, nurses and embryologists, we have a wonderful team, and it's been that way for three decades, although it's changed a lot. So thanks so much for joining us as we celebrate this really special milestone.

Telehealth has, I think, been wonderful for our practice. There are a lot of really awful things to say about a COVID pandemic, but if you have to look for some silver linings, one of them is we all became much more comfortable, very quickly, both patients and clinicians with telehealth. And we hope it is here to stay because it has, just as Mitch said, we don't need to tell our patients that fertility is really stressful and time-consuming and it's very disruptive to work and personal life. And so, everything we can do to reduce that stress and disruption is really our goal. 

Telehealth allows us to connect with patients often from home and from work. We do a lot of visits in cars. If you're at work and really want privacy, we have a lot of people who just head to the parking lot. And as long as you're not driving, we're really happy to do these visits from cars as well to keep them private. But I'd say most of our patients are typically in their comfortable office or in their comfortable home. And that alone reduces stress. And, of course, you've just saved the time. And the expense, gas is very expensive right now, of getting to the hospital or the satellite. Satellites are great, they help a lot with that stress, but virtual is even a step beyond that. And, of course, saves money. You're not paying to park and travel and all of that. And, of course, there is that reduction in exposure to infectious agents. Clearly, all of our virtual patients are typically also seeing us on site as needed, whether it's for blood tests or ultrasounds, or procedures.

We have a very safe onsite environment for our patients, but you know what? It's nice not to have all that exposure, not just at the hospital but on your way to the hospital. If you're taking public transportation or walking through a parking lot, we do think we're keeping our patients safer by reducing their exposure, not only to COVID-19 but to all the flus and colds that we all get regardless of COVID-19.

The other thing I found is that it makes it really easy for partners to join us. Now, of course, not all of our patients are partnered, but if a patient is partnered, their partner can join us with literally just clicks on the virtual link. We then let them into the visit. It's quite secure. No one can enter the visit unless we let them in. I've had one patient who's in one place, and their partner can join from work or even out of state, or believe it or not, even out of the country, if the partner wants to join the visit. So that's been a wonderful addition as well. 

I think one of the things I love most about virtual visits is I think back to the old days where docs used to go into people's homes, and there is something about patient care in your home which is different. And I like being in people's homes. I like inviting you into my home. I'm actually here at Newton Wellesley today, but I like to use my home office as my virtual background because I do think it's cozier and homier, and it's where I live. I think if you're letting me into your home, I like to let you into mine. It's been wonderful, I've met terrific pets, I've seen wonderful artwork, both that you've purchased or that you've done, patients have done. I think a nice way for us to share our homes as well. So thanks a lot, John. It's a great question. And I think telehealth has been wonderful for both us and our patients.

Dr. Petrozza: Yeah. Thank you so much. I can't agree more. I met more dogs and cats with virtual visits, and it's wonderful to see sort of that home life that people have. Now, your other hand is, you're the Director of the Midlife Women's Health Center. Being part of a big academic reproductive, endocrine practice. We do a lot of things, and one of the things that you really are an expert in is sort of this transition during the midlife phase of a woman's reproductive life. Why is this important?

Dr. Shifren: Thanks for asking, John, it's really a wonderful part of my practice and career, and I've really enjoyed it. Essentially, the MGH Midlife Women's Health Center the goal is to just help women make those midlife years, the years beyond menopause, as healthy and productive as possible. 

I think a lot of women don't realize that here in the developed world, we are really fortunate, but we'll be spending about a third of our lives beyond menopause. And there are symptoms, the most common symptoms that women come to see us for typically vaginal dryness or painful sex and hot flashes. But when a woman comes to us with symptoms, our goal is to all of a sudden make them stop and reassess how they want that next third of their lives to be. As we all know, there are a lot of medical conditions that are more common with aging. Heart disease and osteoporosis are ones that we spend a lot of time focusing on.

It's really a great time to take stock. This is a time when we encourage women to be the healthiest weight they can be, to maybe start an exercise regimen if they haven't been doing it before, to make sure if they have underlying medical problems like high cholesterol or high blood pressure that they get those managed well, to reduce that cardiovascular risk, a time to think about stress reduction, that's common at all times of life. 

In addition to treating symptoms, we do try to really encourage women to focus on that next chapter of life and make it as healthy as possible. We talk a lot about adequate calcium and vitamin D in the diet, regular weight-bearing exercise, reducing osteoporosis risk. There's just so much we can do with lifestyle to keep our lives healthy at all ages, but especially at midlife.

When we are really specifically talking about treating a symptom, let's say hot flashes or vaginal dryness, we want to make sure that women are aware of all the potential options. Clearly, there are alternatives, there are non-hormonal options, and there are a lot of very safe and effective hormone therapy options. And so a lot of what we do is just education about what's available, risks and benefits. And then, it's a terrific time of life to have shared decision-making everything that we may suggest may have some benefits, have some risks, and it's a really great chance for women to really decide what they want fully informed.

The other thing that we do in addition to providing patient care is the midlife center. And please check out our website if you just google MGH midlife. It's a wonderful resource for clinicians and patients. We do a lot of education. So every year, we have a conference, we have a CME conference for clinicians. That's a certified medical education conference, and we also have a conference for the community, which is free. And I'm really sad to say that we have not done it for two years because of COVID because it's kind of an onsite conference with a lot of interaction.

When we move it virtually one year, we really hope to reinstate that conference, but that conference is always videotaped. So if you go to our website, you will be able to see these really wonderful presentations from experts in the community on all aspects of midlife women's health, whether it's osteoporosis prevention, stress reduction, heart disease, risk reduction, treating the general normal menopause.

You'll see a lot of really great, very short 15-minute presentations from our community conferences. So education is a real part of what we do as well. So thanks so much. It's always a pleasure to talk about our Midlife Women's Health Center.

Dr. Petrozza: Thank you, Jan. I can hear the passion in your voice and how much you've meant to this area of midlife health. Before I move on to the next panelist, I do want to give a shout-out to two of our colleagues who can't be here today. Jill Attaman, MD, who's the Director of our IVF Unit, unfortunately, has clinical responsibilities and sends her apology. She's an invaluable resource to our practice and Irene Dimitriadis, MD, who is taking some much-needed vacation, who is the Director of our third-party reproduction clinic. So I just wanted to make you aware that we do have other people than those that are on the panel.

I'm going to move on to Dr. Irene Souter. Dr. Irene Souter has been with us for almost 20 years. She also wears multiple hats. She's the Director of our Preimplantation Genetic Testing (PGT) Program. And probably one of her biggest roles is coordinating, running our Reproductive, Endocrine and Infertility Fellowship Program. So Irene, glad to have you here. As a teaching hospital, education is always a priority, and what are some of the ways that we train the next generation a reproductive endocrinologists?

Irene Souter, MD: So John, first of all, thank you for the opportunity to be here today. I'm very excited to be part of our 30th-year celebration. It has been an honor for me for the 18 years I have been at MGH to have helped so many couples build their families. You all know I have a very big collection of baby photos in my office with big smiles, and that's always a very nice way to start my day. 

So as you said, I have been involved in the Fellowship from the very beginning. I served as the Associate Program Director for over 10 years, and I have been the program director since 2017. For me, it is definitely one of the most fascinating and inspiring characteristics of this department. We have the opportunity to train the next generation of experts in reproduction, endocrinology and infertility, leaders in OB/GYN. And we do all this in a very innovative environment that fosters meaningful collaborations in clinical care, in research, and in medical education.

Our mission is to train great clinicians, but also visionary thinkers and innovative researchers and leaders committed to the goal of advancing women's health. Our fellows are extremely qualified individuals that undergo a very rigorous process of selection. We only select one out of 80 applicants every year. So they're very highly qualified, and it's a three-year program that includes training in research in reproduction, endocrinology, and infertility, but also in andrology in urology, in minimally invasive surgery, in subspecialties of endocrinology to include pediatric endocrinology, menopause. And they also get exposure to pathology as well. But the two main components of their training is research and also the clinical training that involves IVF, reproduction, endocrinology, and minimally invasive surgery.

In research, I have to say they are trained by some of the brightest scientific minds in state-of-the-art research facilities provided either by the pediatric surgical research laboratories or the Vincent Center for Reproductive Biology, as well as the Harvard School of Public Health, mostly the departments of nutrition and environmental health. 

The innovative work has been published in renowned journals and presented in national and international conferences. In a few weeks from now, in early July, our fellows will have the opportunity to participate in the international conference, the European Society for Human Reproduction and Embryology, and they have some groundbreaking presentations. We're very proud of the work they produce.

In the clinical arena, they're guided by very dedicated teachers and astute clinicians, and they learn to deliver top-quality patient-centric care in the management of male and female infertility, oncofertility, third-party reproduction, cryopreservation, as we said, latest innovations in ART, PGT, artificial intelligence, and also very specialized techniques in reproductive surgery. 

I would say that at the end of the day, it is a great honor for all of us that these highly qualified individuals have entrusted their training to us for three years. They are highly qualified OB/GYNs that are board eligible. So they could have been out there in practice delivering obstetrical and routine gynecologic care, but they're very dedicated to the era of fertility, and they have decided to invest another three years of their life in training in order to be able to take care of our patients.

Dr. Petrozza: No, thank you, Irene. No, we're fortunate to have three of our fellows who've joined our practice. We have Mary Morris. We have Irene Dimitriadis. We have Jill Attaman, and I think that's a testament to the great teaching. They've been provided over the years and the skills they've acquired. I'm going to put you on the spot a little bit because I know you have a fantastic memory. Can you list the states where our fellows are currently located?

Dr. Souter: Yes. We have fellows that are in Florida. We have fellows that are in Virginia and D.C. We have fellows in Wisconsin. We have fellows in New Jersey. We have fellows in Massachusetts, and we have fellows in New York and Hawaii.

Dr. Petrozza: And Hawaii, I was going to get to Hawaii.

Dr. Souter: Actually the New Yorkers are in Hawaii. You're absolutely right.

Dr. Petrozza: Fabulous. So your other hat, Irene, is you're the director of the Preimplantation Genetic Testing Program. If you can talk a little bit about what the goals of this program are and has preimplantation genetic testing been the game changer that we all anticipated that it would be?

Dr. Souter: Yes. So the goal of our program of our preimplantation genetic testing program, which in abbreviation called PGT, is to help families that are at risk of having a child with a genetic abnormality decrease that risk.

Our first embryo transfer for PGT took place in 2005. And our first PGT baby was born in April of 2006. I have a photo of him and his brothers up there as well. So there are two types of PGT. One is called PGT-M, and it's addressing the needs of couples that are carrying an unwanted genetic trait, the mutation to decrease the chance of passing on that unwanted genetic trait to their offspring. And PGT-A, which stands for the word aneuploidy that helps couples select embryos that have a higher chance of successful implantation. Our patients will probably be more familiar with the PGT-A, the PGT for aneuploidy. 

Aneuploidy is a condition that is associated with extra and missing genetic material that everybody is at risk for. We all make aneuploidy embryos at early conception, but as women age and as male age as well, the risk increases. It is more obvious for women over age 35, but everybody's at risk. 

PGT, over the last 20 years, has helped many couples build healthy families, but as is the case for most technologies, it also has its limitations. And due to its limitations, it's not indicated for all couples, and it is not the standard of care. So to use the word that you use, the game changer, it's not exactly a game changer. It's an extra technology available to us that can help particular couples at need address those challenges. 

Before I talk about the limitations, I would like to mention the advantages. So as I said, we suspect that many times failure in IVF is associated with aneuploidy, and aneuploidy can lead to IVF failure or miscarriage. So this extra and missing genetic material can lead to failure, whether that's failure to conceive or failure to carry the pregnancy to term. Both of those conditions are devastating for our patients, and we try through PGT to select embryos that are called "euploid," which means they have the correct amount of genetic material so that they can achieve the highest chance of having a successful conception in live birth.

As I mentioned, just like all technologies, it has its weaknesses. The first weakness is the fact that it's an invasive technology. So it is a safe technology. We've used it for many, many years, but nevertheless, it's invasive. The embryos need to undergo manipulation, cryopreservation, and thawing, but most of the mutations are related to the fact that early embryos can be mosaic. In other words, they can contain more than one population of cells.

So we think that's a lot more common than we think in very early embryos. And as the embryo evolves, eventually, it selects, if you wish, preferably those cells that are destined to give rise to a healthy individual. So we worry that we intervene very early in the process of the embryo development, and as a result, we might have some embryos that might be misclassified. If you think about it, we only pick from the embryo five to eight cells. So it's a very small sample that might not accurately represent the entire embryo. Those embryos that are mosaic are often excluded from transfer. And there are some reports if you wish that some of those mosaic embryos have been successful and have given rise to healthy live births.

On top of it, though, what I usually mention to my patients is that in medicine, we never really rely on one test only to make big decisions. So if you think about it, normally, at the end of the first trimester, our patients will get a battery of tests. Some of those are ultrasound. Some are blood tests. They have the ability to undergo an amnio or chorionic villus sampling.

Our colleagues in high-risk obstetrics will put all this information together before they make a recommendation to continue or terminate a pregnancy that is at risk. Unlike our colleagues in high risk OB, we only have one test available to us, which is the PGT, which is performed at the very early stage. And we have to rely on that. So although it's a very safe and highly accurate test, just like all other tests, it's not 100%. So people need to talk to their physicians to see whether the test is indicated for them. And they should just carefully weigh advantages and disadvantages before they decide whether they want this to be incorporated in their treatment plan. 

So it's work in progress. I'm sure that over the years, we will develop better technologies that are less invasive and probably more accurate and will be able to help our couples, even at these very early stages in their attempts to conceive.

Dr. Petrozza: Well, thank you, Irene. Thank you very much. Very, very informative. We're at the question-and-answer phase of our webinar. I do see a couple of comments in our chats, our question-and-answer area. So if any of the viewers have any questions they'd like to ask of our panelists, this is a great opportunity to do that.

I do see a question. And I'm just going to ask it to the panel, and then they can answer rather than me just directing it for somebody else. So the question is, can you speak a little bit about platelet-rich plasma (PRP) and its use in conjunction with IVF to stimulate ovaries to optimize spontaneous conception. And I know that we've all heard about this, and there's a little bit of research out there. I do know there's a big randomized controlled trial that's being done in Europe to look at this. I can tell you it's not commonly used, but would any of them like to speak about this? Maybe I'll ask Dr. Mahalingaiah, who's Director of our clinical research program.

Dr. Mahalingaiah: Thank you. I think this is a really interesting question. And I think this question also reminds me of other questions around the use of a novel intervention such as new supplement or treatment like this. And I would say I don't currently offer this in my practice for supporting spontaneous conception. I think the little that has been written might show promotion of a variety of things that would support fertility. 

One of the things that I share with my patients that a lot of these add-ons, or kind of special additional things, including supplements, sometimes can help, but they can also sometimes harm. And as the cost increases for some of these things, including PRP, we have to be careful what we recommend. 

I think this is a really interesting question, and I think that it can be really challenging to know where to invest your time and effort, especially around the goal of achieving a healthy conception. I know that's kind of a non-answer, but I open it up to the rest of the panel to give some thoughts on specifically PRP but also IVF add-ons or fertility treatment add-ons.

Dr. Petrozza: I think you know, Dr. Shifren had emailed this group here about an upcoming speaker who's talking about some of these novel, new things in the world of reproductive medicine and when is it appropriate to utilize them. Platelet-rich plasma has been used for lots of things. They've used it for intrauterine adhesions, for example, to see if it can stimulate endometrial growth. But a lot of these studies are case series, small case series, small case reports. Thankfully there's this large randomized controlled trial that's going to be done in Europe to look at this. At what point, maybe I'll direct this to Jan. At what point do you take something that's novel? Because a lot of our patients are wanting something new, wanting something different, especially if they've experienced multiple failures. At what point do you take something new, or do you wait for more convincing evidence?

Dr. Shifren: It's a great question from our participant, and you phrased it really thoughtfully too, John. Actually, the speaker was last night, and it was terrific. She is part of the Cochrane collaboration, which is this group of researchers who try to give us evidence, meaning when do we have what are called randomized trials, where instead of just choosing a treatment, the participants are randomized to receive treatment A or treatment B, and that's really the way to get good data. If you let people choose a treatment, there's a lot of what we call bias, and the results won't be good. So she's part of this collaboration, and she has now taken on looking at what we call add-ons, as Dr. Mahalingaiah called them.

One of the first they did is something called endometrial scratching. And this first study out of Israel looked amazing. They took these patients with a limited prognosis chance for pregnancy, and they did some endometrial biopsies in advance of their transfer. And, oh my goodness, 10 out of 10 got pregnant. And so the next thing we knew, every media, internet site, and every office was offering endometrial biopsies in advance of your transfer. And you could argue it wasn't crazy expensive. It was a few hundred dollars, not thousands and thousands of dollars, like many of these add-ons, and it's uncomfortable to have a biopsy but not really dangerous. Again, some of these other things could be much more dangerous, and it took off.

And this group in Australia did a randomized, carefully controlled trial with enough women to have what's called the power to show a difference, and guess what? No difference. And of course, we saw dramatic declines in the use of scratching because neither patients nor clinicians want to be doing something that won't help our patients get pregnant, especially if it's costly and uncomfortable.

I thought that was a perfect way to start. And then when she talked about a lot of the other add-ons, unfortunately, they haven't undergone the same kind of rigorous testing you just talked about, Shruthi. So I would say buyer beware if it's very expensive, if there are potential risks, and there aren't good evidence from a randomized study, probably better to wait till we have more evidence.

Dr. Petrozza: Great, great, great answers, ladies. Thank you so much. The next question, I think I'll direct this to both Dr. Souter and Dr. Morris, is 10 years from now, what will be new and different in our field?

Dr. Souter: That's a good question. So I think that to start with, cryopreservation will be a lot more prevalent. So probably, if not all women, many women will be considering it. If we already saw the trend 10 years ago, I would have 40-year-olds coming considering also cryopreservation. I have 30, 32-year-olds that are now coming asking about the procedure. And there are definitely patients in their 20s that are asking about it as well. And although we always look at which time do you make your investment, at which age do you make your investment? And we usually say 37 is the age where you usually make you money for your investment. If you have not had the baby by 37, there is a pretty good chance you're going to need frozen eggs. The truth of the matter is if you're going to do it, and you're going to invest the time and energy, you might as well cryopreserved the younger eggs, and the younger, the better.

I can see a lot more parents and young women asking questions about when would be appropriate for their daughters to freeze eggs. As Dr. Morris will say, there'll be a lot more volume freezing as well. There is plenty of work that is happening right now in that arena. And Dr. Morris has been working closely with some of our colleagues at Brigham to start the program as well as MGH.

I think there will be innovations in preimplantation genetic testing. We have acknowledged the limitations, and we're working on addressing them. There will be a lot more non-invasive preimplantation genetic testing. And I believe that we're going to try to combine technologies potentially, or we will try to combine the information we get from this with other markers so that we have a higher level of confidence when we make decisions about the destiny of our embryos.

I am pretty sure that cryopreservation of all sides will also further improve. So we will have higher efficiency from the technology. For the present time, we're doing very well, but there's definitely room for improvement. And I think we will make improvements in self-monitoring to a certain degree or monitoring at the point of care where it's actually going to be usually at home or at work so people don't have to come in and don't have to take time off work in order to be able to do treatments.

I think in oncofertility, there might be some, and I'm going to let Dr. Morris talk about it since that's her area of expertise.

Dr. Morris: Well, thanks. But that wasn't the first thing in my head. I was just thinking about when I  started medical school, which was long ago, somebody said to me, they're two important words that you have to learn. One is iatrogenic. That means I messed up, and the other is idiopathic. And that means I don't know. And I think so many things in our field are idiopathic. A good 20, 25% of our couples, the heterosexual couples, will get diagnosed with idiopathic infertility; and those with recurrent loss, it's about 50%, which is staggering. And it's very, very hard to say to a patient I don't know. That is the most honest thing you can do, though, because people do start grabbing at things and treatments that aren't proven, and you have to reassure them that they will go on hopefully to achieve their goal.

But I think conquering those portions of our field that are unexplained. I think there'll be a lot of work in the immunology space and the immune space about this because our immune system performs such an important task in our body. And obviously, when you're pregnant, there's something that's half not you that your immune system ignores. So I think we'll have to learn a lot more about that and other things.

I spoke a little bit about another novel thing, which was AMH. And this is a project that we are collaborating with now with biotech. And we are getting to the phase we're almost in preclinical trials as an onco protectant, but also it could be used as an adjuvant for routine infertility. For example, if somebody goes through IVF and they get three eggs, and they go through IVF, and they get three eggs, and they go through IVF and get three eggs, this AMH, when given to mice, will keep all of those at bay, if you take it for a given amount of time, and then when you go to do IVF, you'll get the nine eggs because everything's been sort of put at the starting gate together. And if this does come to fruition in the next 10 years, maybe, I think that's going to be a real novel advancement. And I hope that there are other medications that are developed that are tolerable to patients.

Dr. Petrozza: Thank you.

Dr. Souter: I was going to say, John, she mentioned how we have witnessed some of the changes. So two things I'll say on that one, I remember in 1978, reading the newspaper and reading about the first IVF baby ever be born. I'm not going to tell you how old I was, but I was old enough to read the newspaper. Little did I know this is what I was going to be doing for the rest of my life. But the second thing I remember very vividly is being an intern in the call room and reading about PGT for the first time ever.

I remember this was in Steven Gaby's textbook back then. And I thought, "Wow, that's wild. We can do this," but you see, 27 years later, we are somewhere else. And we have all witnessed changes from day three to day five, transfers from improvements in cryopreservation. And I think that's what's fascinating in our field, how fast it's moving and how technology is being more and more incorporated. And we can do more and more things for our patients.

Dr. Petrozza: Yeah. Thank you both. I mean, that's great. I do want to sort of get to this next question, which I think is a great lead from Mary about this, which is idiopathic or unexplained infertility. I'm going to direct this to Mitch because Mitch was around back when we used to diagnose unexplained infertility, Mitch, everybody had their testing. Everybody had a diagnostic laparoscopy because you weren't going to call someone idiopathic unless you confirmed there wasn't anything in the pelvis like endometriosis or adhesions. 

So the question from one of our viewers is, is there anything new in the way care is given, any new ways that we can diagnose things to really give this in this realm of unexplained infertility?

Dr. Rein: Well, it's a great question. Frankly, it's a little bit of a challenging question. Because my quick answer would be not so much that we have actually focused more on outcomes and improving healthy babies as outcomes than the actual diagnostic testing. That being said, there are some things on the horizon that I think are beginning to help us understand the unexplained population a little more deeply as IVF continues to get more sophisticated. And some of the other panelists have talked about the genetic components. I do think that is one "breakthrough." 

It may not be the game changer in terms of unexplained, but we haven't talked yet about the concepts of artificial intelligence, and in our laboratory, we do have some cutting edge work that's happening using kind of that combination of whether it's computer-generated or machine learning with us as "the people piece" of the technology.

And I guess the last piece that I'll mention it tags a little bit to the last question, too, is the impact of the environment. And John, you had mentioned in your introduction that we've been leaders in this area as well. And I think we're just starting to pay more attention to the environment in the ways that many of us would like to see not only for ourselves but for future generations to come. And we know that it impacts reproduction both on the male and the female side. So I think we'll continue to see some advancements in that space as well.

Dr. Petrozza: Thank you, Mitch, great answer. Jan, did you want to make a comment on what Irene and Mary had spoken about?

Dr. Shifren: Very small comment, but if we really want to date ourselves, and I won't tell you how old I was in college, but I was very interested in medical ethics, and believe it or not, my research paper was on the ethics of IVF because at that point there was concerns about eugenics and slippery slope and believe it or not, it was really even questionable. And now we're like, "What in the world, this is a wonderful way to help people build families." And of course, as with any new technology, we have to be careful and look at ethical considerations, but I thought that was really dating myself, but fascinating. It just shows how over time, things change as technology changes, ethics change. So thanks a lot.

Dr. Petrozza: Awesome. I think we have time for maybe one more question. Thank you, everybody, for the wonderful questions in the Q&A area. One of the questions from the viewers, and I'll direct this to Dr. Mahalingaiah, is what is the latest science on inflammation and its role in infertility. And do you think anti-inflammatories might be helpful, especially during an IUI process?

Dr. Mahalingaiah: I think this is a really interesting question, and some of our clinicians have talked a lot about the role of the immune system overall in pregnancy establishment. There's also a huge role that the inflammatory system plays during ovulation. And we know that the pathways that over-the-counter medications like ibuprofen can actually be involved in some of the similar pathways that we need for ovulation.

In terms of when one is undergoing an IUI process and intrauterine insemination, there is an internal shift in our immune systems, kind of modulation by estrogen as well as after ovulation progesterone. I don't believe that there is a role to give anti-inflammatory drugs or proinflammatory drugs during an IUI cycle for patients in general, but some patients may have underlying conditions that include dysregulation of the immune system and then will have to take an individualized personal approach to understanding when and how to administer those medications.

So, I think that in terms of other factors like environment and lifestyle, Mitch Rein had mentioned before the impact of stress and kind of overall systemic inflammation kind of from our day-to-day lives. I do think that engaging in lifestyle factors that can reduce stress, either perceived or real. And stress is really hard to gauge because sometimes our bodies react to stress and have inflammatory reactions that we can't specifically measure, and things like meditation, calming physical activity, as well as physical activity that leads to breaking a mild sweat, I think can promote overall health and support the process.

Dr. Petrozza: Wow. Well, thank you, guys. This has been wonderful. What a great way to start our 30th-anniversary celebration, which will be continuing through the spring and into the summer, and into the fall. So thank you to my colleagues for sharing your thoughts today.

A big shout-out and thank you to the audience for your thoughtful questions. We appreciate you joining us to celebrate our 30th anniversary. If you would like to keep tabs on us, you can find us on social media. We do regularly post stories to our accounts and on our website so you can continue to follow us throughout this milestone year. 

If we didn't get to your question, I apologize. And if you would like to learn more about ways you can support the fertility center, some of our initiatives and priorities, and research, please contact my colleague, Meghan Gibbons, in the development office by emailing megibbons@partners.org. Thank you once again for joining us to commemorate our 30th anniversary, and I hope you have a fabulous day. Thank you.