By Casey Berna, MSW
​How many incomplete surgeries and rounds of “medical management” need to occur until an endometriosis patient gets a diagnosis and the expert, multidisciplinary treatment they need to improve quality of life and fertility? How many pregnancy losses does a patient have to endure for their doctor to change course? How many fertility treatments have to occur without a desired ending? How much money has to be spent? How many years have to go by without answers? How much physical, emotional, and financial devastation has to happen before a patient is given more resources to learn more about their health? Reproductive Immunologists can be a crucial part of the multidisciplinary care team that can find fertility answers sooner, lessening diagnostic delay, leading patients to the individualized treatments that can help alleviate the challenges of family building. 

I, like so many other patients, endured incomplete endometriosis surgeries and experienced multiple fertility treatments, that either didn’t result in a pregnancy or soon resulted in a miscarriage, before understanding why my body was having so much trouble doing something society touts as “natural”. Trying to conceive did not feel at all natural or easy for me. At the time, I was in my early thirties and my doctor continued to explain away my challenges as simply bad luck because “everything looked great.” I kept hearing, “You are young. It will be fine.” 

It took so many years of failed treatments for someone to even consider endometriosis as a part of my problem. No one ever checked me for BCL6, a marker of inflammation commonly associated with endometriosis. People with positive ReceptivaDX tests, a measure of these markers are 5 times more likely to have failed IVF cycles. Endometriosis was an incredible burden on my life and on my fertility.

Through diagnostic laparoscopy, my reproductive endocrinologist found and ablated what he referred to as a “mild” endometriosis. After surgery, we continued to try and conceive on our own and he was befuddled as to why it wasn’t working. We started with clomid and then proceeded to IUIs. I eventually got pregnant and had my daughter. We tried conceiving again as soon as it was safe. Clomid cycles led to multiple IUIs, which led to multiple IVFs. After transfering a pristine looking, “textbook embryo,”  I had my third miscarriage in the span of 5 months with still no answers. While I was incredibly lucky to have insurance that covered my treatments, I was quickly reaching my limit for how many more covered treatments I could pursue as my doctor continued trying to “figure things out.”

On a hunch, the physician’s assistant in my reproductive endocrinologist’s practice took me aside privately and told me that I may have a balanced translocation, the same miscarriage causing genetic issue her college roommate had.  My doctor was skeptical, but I fought to get tested and tests showed it was the reason I kept miscarrying. Heartbroken, I had to come to terms with the fact that because of my endometriosis, much of which remained in my pelvis post operatively,  and my balanced translocation, all of the treatments I went through were most likely to fail and some of my miscarriages possibly avoided if I had been treated by a doctor who specializes in endometriosis and reproductive immunology. 

The field of reproductive immunology fills in the gaps that many reproductive endocrinologists miss. As an endometriosis patient, I had no idea that my endometriosis can not only cause anatomical challenges to family building, but it can also cause inflammation that impacts egg quality or prevents fertilization or implantation. While I do not have an autoimmune disease, some patients do which can also impact fertilization and pregnancy viability. The immune system serves an important role in fertilization and implantation that often goes overlooked by reproductive endocrinologists. While up to 20% of pregnancies end in miscarriage, the chance of miscarrying again after experiencing two pregnancy losses increases to 40%.  I didn’t realize that once I had two pregnancy losses, my rate of continuing to miscarry became significantly higher and that the immune system plays a vital role in accepting the embryo, allowing for implantation, and ensuring the continued growth of the fetus. 

Knowing what I know now, I wish I could have gotten diagnosed and treated for my endometriosis as a teenager. Not only would my quality of life have been vastly improved, I could have been mindful and proactive regarding potential fertility challenges which would have given me more options. Having a reproductive immunologist as part of my team from the beginning would have saved time, money, and fertility treatment resources, most of which were spent before we even knew what health challenges I was facing. The recommendation is that a patient should seek care if they have suffered two pregnancy losses. But, by the second loss, the chance of staying pregnant dwindles. Why not give patients access to information, testing, and needed treatment at the start of their journey with pelvic pain or infertility? Why not work to identify all possible causes right away? All too often it feels like the hopes, dreams, and health of patients are deferred due to current standards of care and the lack of information for patients and providers alike. 

I am excited to be a part of the upcoming Reproductive Immunology Summit because they are working to put the power back in the hands of the community by presenting the latest research and information. Reproductive immunologists thoroughly investigate the patient’s genetics, reproductive health, and immune system to understand how they are each working together, or maybe working against one another, with respect to family building. 

Our time is precious. Our health is precious. Our resources are precious. The more we know about our bodies, the more empowered we are to make decisions about our health and our future. We hope you join us!
Register for Virtual Fertility Weekend with an entire day on Reproductive Immunology here. 
https://www.theendometriosissummit.com/virtual-fertility-weekend.html

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By John F. Dulemba, MD, FACOG
Gynecologist specializing in minimally invasive robotic surgery 
The Women’s Centre, Denton, Texas
 When I first meet with patients who have endometriosis, they often cry. It’s usually the first time a doctor has really listened to them, validating complaints that have been brushed off for years or explaining why hormone treatments and surgeries haven’t worked in the past. After I’ve listened, I offer a clear plan to help. 
I perform CO2 laser (AcuPulse DUO, Lumenis) excision with the robot, which many consider to be the gold-standard surgery for endometriosis. The procedure is not inexpensive—the robot and the laser may add to the costs of surgery—but a truly effective procedure is cheaper than having repeated treatments that do not work. The highest-priced surgery is one that’s ineffective, requiring additional surgery, more out-of-pocket expenses and lost work or school days for patients, as well as the high emotional toll of continued pain, frustration and depression. Patients all deserve to get treated for endometriosis and move on with their lives, and that is possible—and most economical—with the right surgery.
 
CO2 Laser Excision with the Robot
To treat endometriosis effectively, we need to perform surgery to remove the abnormal cells. How well we do that will determine whether surgery is a long-term success. If we leave cells behind, there will be greater inflammation, pain and damage to adjacent tissues, as well as greater need for further surgery in the future.
In CO2 laser excision with the robot, the robot allows the key function of 3D and 10-times magnification, which in turn permits me to see all of the endometriosis (I need to see the cells to remove them). Once visualized, the work of removing the endometriosis is accomplished using the CO2 laser energy through the FiberLase waveguide. I can remove the endometriosis very precisely, damaging adjacent tissue at a thickness of less than one cell, as opposed to the harmonic scalpel, which can easily damage thousands of cells next to the disease I’m trying to remove. As a result of laser use, there is minimal damage to the nerves, blood vessels, organs, fallopian tubes or ovaries.
The laser also cauterizes as it cuts, so there is very little bleeding, which makes it easy to always see the endometriosis and keep track of where I am. And by reducing bleeding and collateral tissue damage, we reduce pain and limit stimulation of the body’s inflammatory response, which would trigger an increase in formation of scar tissue and adhesions that could cause additional pain and repeat surgeries. All of these advantages make CO2 laser excision with the robot well worth the additional cost, as well as the most cost-effective choice long term.
 
Less Chance of Additional Surgery
After CO2 laser excision, a patient is less likely to need a repeat procedure compared to other surgical options, but it is possible. We can only remove the cells we can see, and hormones (natural and artificial) can stimulate more cells to become active and visible later. In addition, even with such a precise procedure, there can be some adhesions as the body heals. I want my patients to understand that if they have a problem with endo or adhesions, we can address it with a repeat procedure, but they will not be having an endless series of ineffective treatments. 
This gold-standard surgical approach offers patients the best opportunity to feel good with the fewest surgeries possible, so they won’t always keep paying the exorbitant price of managing endo. I hope to see more people with endometriosis find doctors who are performing CO2 laser excision so they can experience the best long-term outcomes for their health and quality of life.

Here Dr Dulemba present on the role of adhesions in endometriosis on March 7, 2021 at Endo Summit 2021, held VIRTUAL. 

Why might an individual experience unexplained infertility, IVF failure, or recurrent pregnancy loss? Why might someone with endometriosis not be able to conceive even after expert excision? What can help someone have a baby, even when they have tried everything and still don’t know what’s happening?
Reproductive Immunology studies the interactions between the immune and reproductive systems. Reproductive Immunology may help answering these key questions.
         30% of infertile couples worldwide are diagnosed with unexplained or idiopathic infertility. The problem is defined as the lack of an obvious cause for a couple's infertility and their inability to get pregnant after at least 12 cycles of unprotected intercourse or after six cycles in for those above 35 years of age for whom all the standard evaluations are normal. The American Society for Reproductive Medicine has defined recurrent pregnancy loss (RPL) as “a distinct disorder defined by 2 or more failed clinical pregnancies.” For those experiencing the issue, even one loss is challenging, filled with grief, and disheartening. IVF failure can be devastating for people trying to conceive. It is frustrating and discouraging.
         Pregnancy could be considered as a triad involving the embryo, the endometrium, and the immune system. The maternal immune system may play a pivotal role during pregnancy, protecting the mother and the fetus from deleterious environmental pathogens. During pregnancy, the maternal cellular immune responses need to be modulated to prevent embryo rejection.
For a viable pregnancy to occur, a mediation switch must flip- the maternal immune system needs to move toward a more tolerant, low inflammatory state. This decreases the production of inflammatory cytokines and increases the production of cytokines that are more regulatory. Cytokines are any of a number of substances, such as interferon, interleukin, and growth factors, which are secreted by certain cells of the immune system and have an effect on other cells. There are good cytokines and bad cytokines and each will affect implantation and pregnancy. If the mediation switch does not flip or if there are too many of either kind of cytokines, pregnancy will not happen, be it naturally or through IVF. Often times, this reaction is slowed due to many factors from endometriosis, to uterine inflammation and abnormalities, to sperm issues, to genetic translocations. 
Some people with infertility may have a challenged immune system from underlying conditions such as an autoimmune disease, PCOS, silent endometriosis, or any form of endometriosis- excised or not. Systemic inflammation may damage oocyte quality, prevent embryo implantation and increase miscarriage and pregnancy loss. For those with unexplained low AMH it is important to explore the immunological causes of why, while doing everything that can be done to increase pregnancy success rates. 
         Reproductive Immunology explores these issues. Additionally, tools have been created in recent years to assess embryo quality and the embryo’s potential to develop. The receptivity of the endometrial lining to allow implantation can be evaluated. The evaluation of the immune system continues to be a work in progress. 
         No one should have their childbearing decisions made for them by their bodies. Anyone who wants a child or does not want a child should be able to make that decision themselves, not because of “unexplained” factors, a condition, or a disease made it for them. Reproductive Immunology is a unique field of reproductive science to help you understand why pregnancy, either naturally or through IVF, may not be happening. 
 
 Worldwide Leaders in the field- those who have paced the reproductive world will head The Endometriosis Summit’s Reproductive Immunology Day during Virtual Fertility Weekend. Do not miss this opportunity to learn why you may be able to encourage pregnancy, improve IVF implantation rates, and avoid pregnancy loss. 
Tickets are on sale https://www.theendometriosissummit.com/virtual-fertility-weekend.html

 Scheduled to Appear- Dr. Ole Bjarne Christensen, Dr. Henriette Svarre Nielsen, Dr Fabio Scarpelini, Dr. Bruce Lessey, Dr. John Zhang, Dr. Melvin Thornton, Dr. Robert Klitz, Dr. Joanne Kwak-Kim, Dr. Jonathan Scher, Dr. Antonio Gargiulo, Dr. Patrick Yeung, Dr. Mona Orady, Casey Berna, Jessica Drummond, Christopher Butler, April Christina, Perijat Deshpande, Brandon Johnson, Shervonne Coney, Dr Nadera Mansouri-Attia, Michele McGurk and your hosts Dr Andrea Vidali  and Sallie Sarrel. 
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