Welcome to the Egg Whisperer Show. I’m excited to have one of my dearest fertility doctor friends on today’s show: Dr. Gayane Ambartsumyan.
Dr. A (as she’s called by her patients) is one of the top fertility doctors working at one of the top fertility centers in California. We’re here to talk about the best strategies to achieve IVF success.
Dr. A’s background: She completed her residency in OB GYN and fellowship in reproductive endocrinology and infertility at UCLA. Prior to that, she received a doctorate, a PhD in STEM cell biology at UCLA. She’s board certified in both OB GYN and fertility, and she has been awarded or was awarded a prestigious clinical investigator grant two years in a row from California’s Institute of regenerative medicine.
Dr. Aimee: I love hearing from other fertility doctors about why they went into medicine and why they chose fertility medicine specifically.
Dr. A: I thought I would be a musician, or I thought maybe I would be a surgeon (because doing operations sounded so cool.) And then my family moved to the U.S. and that made it so I could no longer pursue music. I went to college and science really inspired me, because you can use science to actually help people and heal people.
And initially, I wasn’t really interested in fertility, but then when I did my fertility rotation, finally, something clicked and I was like, “Aha! This is what I want to do.”
Dr. Aimee: Would you share how you approach IVF care and what you do to help your patients achieve success?
Dr. A: I approach each patient, each retrieval and each baby, each individual person one at a time. I look at the big picture. I make sure they’re prepared to embark on this journey. I make sure that we have looked at all their blood work, and completed their evaluation.
I also want to make sure they’re ready emotionally, physically, and spiritually. So, we talk about nutrition, stress reduction, yoga, relaxation…whatever is going to help that particular woman to go through the journey.
Dr. Aimee: I want to throw out some scenarios for you to guide us through. How do you decide which protocol you should put a patient on? And I’ll give you the patient example. A 25 year old egg freezing patient with an AMH of 4.0 what is your protocol of choice and why?
Dr. A: When I’m treating someone who is young, and has a good number of good quality eggs,and has good AMH: I generally go a gentler route.
And it’s a fine balance. Because if I go gentle, then we’re not maximizing the number of eggs we’ll retrieve eggs to be frozen. At the same time, if we go too harsh and use too many medications, then we run the risk of hyper-stimulation. And that’s not going to be a pleasant experience, which may impact egg quality.
Dr. Aimee: It sounds like you do a lot of handholding, guiding the patient and making sure she stays safe from start to finish.
Let’s change the scenario a little bit. Let’s say you have a 37 year old with an AMH of 0.6 what would your protocol of choice be in that type of situation?
Dr. A: This is a little bit more of a challenge. The first question I have is why is the AMH so low?
It’s important as a doctor to manage expectations. If someone has lower egg reserve (potentially with that AMH), I tell them, “Look, you’re not going to get 20 eggs like your friend. You’re probably going to get. Maybe six or eight.”
With this category of patients, we do something called mild stimulation IVF. It seems counterintuitive. Basically, we give patients less medication, because the high doses of medications puts too much pressure on the body. So I usually do a combination of Clomid for about five days, and a maximum of hundred and 50 units of gonadotropins.
Dr. Aimee: You can still achieve and get a patient’s maximum number of eggs that they have to give you using less drugs?
Dr. A: Absolutely.
Dr. Aimee: Yeah. And I think we’re just conditioned to think that you take more drugs and you take more meds, you’re going to have a higher egg count, but it just doesn’t work like that.
What would your advice be for this 37 year old AMH is 0.6 — How would you counsel her about her chances of success and what she should expect from her first cycle?
Dr. A: This is all about managing expectations. The patient needs to understand they will get about six to eight eggs on average. Ultimately, our success rates are determined by your age.
This patient may need to do more than one cycle to get one, or two, or three good embryos, depending on the family size they want.
Dr. Aimee: So let’s go to this 25 year old. You just froze her eggs, but a lot of the eggs didn’t look so good. There are physical characteristics that the embryologist described to you as misshapen. What do you do to counsel the patient?
Dr. A: It’s a challenging situation because most people don’t know that we can grade eggs. Even if eggs don’t look as pretty as they’re “supposed” to look, it doesn’t necessarily mean they won’t result in pretty embryos or eventually, pretty babies.
The only true way of knowing the quality of these eggs is to create embryos.
The other important thing: you don’t want to wait 20 years to use eggs. If a patient waits until they are 45, only to discover the eggs aren’t good, they’ve missed the chance to do something about it.
Dr. Aimee: I want to go through some scenarios with the 37 year old patient that we talked about with an AMH is 0.6. Let’s say you went through the cycle and there were no blastocysts.
(A blastocyst is an embryo that has hundreds of cells by definition, and it’s an embryo that’s usually formed five or six days after the eggs are fertilized.)
What would you do at that point if there were no blasts? You had fertilized eggs, but they didn’t make it past day three.
Dr. A: Sadly, we are not going to know how good the eggs are until we go through IVF. IVF is a treatment of course, but a lot of times it also acts as a diagnostic process.
The first thing I do is I look back and I look at the grading of the embryos, because you can get a lot of clues from looking at what happens on day one. We assess embryos on day three, when they are called cleavage stage, and they usually have about six to 10 cells on average.
During the first three days when the embryo is developing, it is primarily based on the mom’s genomes. After that the paternal genome kicks in. If I saw that the patient had beautiful day three embryos and that none of them made it to the blastocyst stage, then I start looking at the sperm. Let’s not blame it all on the egg.
If I haven’t already done additional sperm testing, I’d recommend the DNA fragmentation index.
The key thing I tell women (especially women in their thirties) is that I refuse to believe that there are no good eggs left in their ovaries. As long as we’re persistent, and learn from the past cycles, then we should be able to modify the protocol.
Dr. Aimee: Say that same patient has blastocyst and they’re beautiful. But we did genetic testing and we looked at the chromosomes, but none of the chromosomes were normal. What would you do?
Dr. A: I’m really interested to see what chromosomal abnormalities there are and how many are present.
My advice after the first cycle, would be to not use those embryos. I always discuss everything with the patient to make sure we’re on the same page. Unfortunately, it’s a numbers game with a 37 year old. At that age, I would expect maybe one out of three embryos to be chromosomally normal. So I would tell that patient, “Look, you have three. I was hoping that at least one was going to be good, but unfortunately none are good.”
It doesn’t mean that none are good in general, it just means this month we weren’t able to find normal embryos for you.
Dr. Aimee: OK, similar situation: you have blastocyst, but now they’re normal, but the quality is really low. So , when we grade embryos, let’s just make it simple for our audience. Let’s just say good, fair, and poor quality.
Let’s say you have the two embryos that have normal chromosomes, but the quality is poor. How would you counsel your patient?
Dr. A: I think a lot of that is lab dependent. Every reproductive endocrinologist should know their own experience in terms of what they’re poor quality embryos mean.
Unfortunately there’s not one universal way of grading embryos. When it comes to the embryologists and their method of grading embryos, it’s very subjective. I do tell patients (especially if the embryo is poor quality)that the chance of implantation with these embryos are probably lower.
If the patient did get pregnant, it does not mean that the child would have abnormalities or that this puts you at a higher risk for any other birth defects. On average, we see about 65- 70% pregnancy rates per chromosomally normal embryo. That number may be cut in half with this embryo.
Dr. Aimee: Quality does matter, and it’s important to ask these questions. How do you get the uterus ready for transfer? Which protocols do you think help your patients prep for transfer the best and why?
Dr. A: Transfer is what I call the second phase. (First we concentrate on embryos.) Second, let’s concentrate on getting the patient ready for a transfer. Before a transfer, we want to make sure that the patient’s uterus is okay. We make sure there are no polyps or scar tissue or subtle things that would be missed on a regular ultrasound. I usually either do a 3d saline sonogram to make sure that the walls of the uterus are okay. Sometimes I also do diagnostic hysteroscopy.
Once I know the uterus is okay and the woman is ready, we talk about yoga, and their diet and nutrition.
And then for the medical protocol, I usually start with medicated cycles. This involves taking estrogen for about two weeks, which is a way of mimicking our natural cycle. And once the lining is ready, then we start progesterone.
To test the readiness for implantation, I will use the endometrial receptivity assay to correct timing, to decide if that patient needs more or less progesterone.
Dr. Aimee: so let’s go back again. It’s the 25 year old again. So now she’s 45 and she met Brad Pitt and he wants more kids. He’s 76 now, right? How do you prepare her for that? What do you do to give someone their best chance of pregnancy with their frozen eggs? And the trick here is, the challenging part is, especially when the partner is in their seventies.
Dr. A: My first worry would be that the patient may have waited 20 years to use the eggs. That said, it seems this patient has waited because she was waiting for Brad Pitt…
We’d start with a regular semen analysis. And when I have couples coming in with an older male partner, I definitely would use the DNA fragmentation index to make sure that the DNA status of the sperm is okay.
If the patient has a lot of eggs frozen from age 25 (especially given that he’s 76 and we don’t know exactly what his true sperm quality is), we might just thaw half of her eggs.
A lot of times thawing only half is a cost issue, but if it’s Brad Pitt, he can afford it.
And then for her, because she’s 45, I would make sure that health wise, she’s ready for pregnancy. So make sure she’s had her mammogram and pap smear. We’d check that her thyroid is good, and that she doesn’t have high blood pressure. And then I would do a uterine evaluation: the camera test, and the endometrial receptivity assay.
If I suspect she has endometriosis or adenal meiosis, I’d also do the ReceptivaDX test to make sure that there’s no increased markers of inflammation and endometriosis.
Dr. Aimee: Okay, so now your 37 year old patient, she’s ready to transfer. My question for you is, would your preparation be different if you knew she had four embryos versus two embryos?
Dr. A: Basic testing is the same. I may not do the ERA test. If someone has a good number of embryos, then I would be willing to perhaps skip the ERA. But other than that, everything else is the same.
Dr. Aimee: So let’s say she did the ERA, she transferred one embryo and it didn’t work. What would you do then?
Dr. A: If I’ve done all of the tests we’ve already discussed, then we start down the route of determining if there are any other factors that are perhaps impacting this all embryos ability to implant. There could be immune factors. One of the big topics that’s come up recently is natural killer cells. The reality is that there’s not a lot of actual scientific data on this.
I might check that angle, and I do have a special immune sauce that I use with some patients if needed.
Dr. Aimee: You tell us what that immune sauce is?
Dr. A: I use intralipd infusion. The patients would usually do intralipid infusion, a week before transfer and hopefully if they are pregnant, then they would do it again about three weeks later. From there we go on baby aspirin, and blood thinners. Lovenox and prednisone.
Dr. Aimee: And I would love for you to share with our audience again, where can they find you?
Dr. A: I’m with Reproductive Partners in Redondo Beach. We have three locations. The others are in Beverly Hills, and Long Beach.
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