One of those doctors is Diana Alecsandru, a reproductive immunologist based at IVI-RMA Global in Madrid, Spain. To say that Diana is doing big things in the field of reproductive immunology is an understatement – she is forging a new path, taking on exciting research about the genetic compatibility between uterus and embryo that could have major implications for IVF success in the future.
RMANJ’s coming together with IVI last year didn’t just make us the leading infertility clinic in the world – it also connected us with a new group of innovative doctors with which to share research, treatment breakthroughs and success.
Dr. Alecsandru visited RMANJ’s Basking Ridge office recently to meet her U.S. counterparts. We sat down with her to hear more about her research. Here’s what she said.
1: So what is reproductive immunology?
Dr. Alecsandru: It’s a branch of immunology, and immunology is about making sure your immune system is functioning properly. Immunologists are often treating patients with autoimmune disorders, which is when your body attacks healthy cells. Our immune systems are important for several reasons: to defend against pathogens, to tolerate and not attack our own tissue, and, for women, to help our reproductive system in the uterus tolerate a genetically different fetus.
2: What do you do as a reproductive immunologist?
Dr. Alecsandru: When functioning normally, uterine immune cells will be able to tell the difference between a normal and abnormal embryo, select the normal embryo and help it implant inside the uterine wall. When it’s not functioning normally, it’s usually due to one of two reasons: either you have a reproductive auto immune disorder like APS, or antiphospholipid syndrome (where the immune system produces antibodies that attack the placenta and cause miscarriage, second trimester complications, premature delivery or stillbirth) or your immune system is preventing embryo implantation for some other reason. That’s where I come in.
3: What happens during embryo implantation?
Dr. Alecsandru: When an embryo is inside the uterus – whether it’s been implanted through in vitro fertilization (IVF) or arrived there naturally – the embryo will show its ‘tags’ to the uterus. Once that happens, the maternal immune cells inside the uterus will decide whether to allow the embryo to implant into its walls.
4: How can that go wrong?
Dr. Alecsandru: This is what I’ve been researching for several years – exactly how and why does implantation fail? In short, we’ve discovered that it may be as simple as being a match or not – a genetic match. If the ‘tag’ is a match, like a lock and key, then implantation can happen. If there is no match, there is no implantation, or a partial implantation that causes miscarriage or complications such as preeclampsia, premature birth or stillbirth. My research has focused on trying to understand the interaction between the maternal immune system and the embryo.
5: Are you saying that some embryos could be a right fit, genetically, for women, while others just can’t?
Dr. Alecsandru: Yes. Let’s get back to the ‘tags’ so I can explain. The embryo will present two tags – one from the mother, familiar to the uterus, and one from the father, unfamiliar to the uterus. Because the uterus is already familiar with the mother’s genes, it will pay special attention to the father’s genes. We believe that if the paternal genes in the embryo and the mother’s uterine cells match, the uterus will welcome the embryo to begin implantation. That’s also when the immune system gets involved: the uterus, having agreed to the tags and allowed the implantation to begin, may send signals to the immune system telling it not to attack the embryo.
6: When did you discover this about the compatibility between the uterus and the embryo?
Dr. Alecsandru: The first time we published research about this was 2014 – before that, this was completely unknown. Now we think this incompatibility may be responsible for some cases of embryo implantation failure. My team in Madrid and I are continuing our research into this.
7: So just to make sure I understand – the cause of this mismatch is not an autoimmune disorder or an abnormal embryo – it’s just a genetic mismatch.
Dr. Alecsandru: Exactly.
8: What’s next?
Dr. Alecsandru: Once we complete our research (we are currently working on more studies) we hope to begin using genetic compatibility testing to improve our live birth rates after IVF. Hopefully we will have a lot to celebrate.
9: What is your favorite part of this work?
Dr. Alecsandru: All of it! I don’t see it as work – I see it as my passion. I feel incredibly lucky to be able to pursue my calling.