When it comes to DOR, aka Diminished Ovarian Reserve, I will forever be reminding you, your friend, your friend’s mom and anyone else who will listen: “diminished” does not mean “zero”!
That’s why I’m so happy to have Dr. Geoffrey Sher back on the show to talk all about egg stimulation specifically for women with a diminished ovarian reserve.
I know when patients hear “diminished” when it comes to their eggs, they think it’s all over. They imagine they’ve gone from having a whole bunch of gorgeous, high-quality eggs right to having none at all.
The truth is, every ovulating human on earth is going to go through DOR. And when it happens, it happens slowly, over time. There’s no emergency “eggs-it” that all your eggs run through all of a sudden, taking all your fertility journey goals with them.
Just because you may have gotten a DOR diagnosis does not mean your fertility journey ends here. In fact, there are still many ways that you can work with your doctor to give your remaining eggs the best chance at success. Like I always say: all it takes is one good egg!
Dr. Sher had so many excellent insights to share in this episode. Here are just a few things we talked about in this amazing conversation:
- What you need to know about egg quality and how it declines over time
- What we can do to give eggs the best chance during IVF
- Why you might choose birth control (you read that right!) in this situation
If you or someone you care about is wondering what to do after a DOR diagnosis, tune in to this episode of the podcast at the link in my profile. I promise, there’s still so much hope for you and your dreams.
Resources:
- Dr. Sher’s book: In Vitro Fertilization: The Art of Making Babies
- Download Dr. Sher’s free ebook “From In Vitro Fertilization to Family: A Journey with Sher Fertility Solutions“
- Download Dr. Sher’s Free ebook: “Recurrent Pregnancy Loss and Unexplained IVF Failure: The Immunologic Link” (on immunology and recurrent pregnancy loss).
- Contact Dr. Sher’s assistant Patti at concierge@sherivf.com or call 702-533-2691 for inquiries.
Full Transcript:
Dr. Aimee: I am so excited to have Dr. Sher back on to talk about follicle and egg stimulation considerations for women with diminished ovarian reserve. Recently, Dr. Sher joined me to talk about preventing poor embryo quality in IVF. I asked him to come back and share a little more, very specifically about what we need to consider when doing ovarian stimulation in women with diminished ovarian reserve.
Dr. Geoffrey Sher: Thank you.
Dr. Aimee: Let’s start with some context here. What do we need to know about egg quality and how it declines over time?
Dr. Geoffrey Sher: Let’s give some statistics. If you take a woman in her early 30s, two out of every three eggs in her ovaries before they are even subjected to a natural cycle of stimulation have the potential to produce good quality competent embryos that are chromosomally euploid, meaning all 46 chromosomes are present, because she’s young. Through wear and tear, the older she becomes, fewer and lower percentage of those eggs have that potential. These are just guesstimates, but at the mid-30s, maybe one in two or three are normal. When you get to 40, maybe one in five. When you get to 45, maybe one in twenty. There’s a downward slope through wear and tear.
An egg from a woman of 45 that looks normal under the microscope doesn’t make it normal. Beauty is but only skin deep. You can’t tell whether an egg is competent by looking at it. Yes, you can see which ones are decrepit, but those that look normal could still very easily be abnormal because of the impact of age. We have to be aware that we don’t shuffle the deck when we stimulate a woman with drugs, nor do we deal the hand. We simply play the hand we are dealt. We must treat every hand as if it has the potential to have winning cards. It’s really important to do that.
From my perspective, I regard every woman as having the potential to produce good eggs. Which brings me back to the issue of what can we do to give those eggs that are in that particular batch of eggs in the antral follicles that are going to be available in the cycle of stimulation the best chance if they’re normal ones to come out being euploid, because euploid eggs will make euploid embryos. Chromosomally normal eggs will make chromosomally normal embryos.
Dr. Aimee: In doing stimulation during IVF, what can we do to give the eggs the best chance at being normal?
Dr. Geoffrey Sher: You can’t use a one-size-fits-all recipe approach to stimulation. Different strokes for different folks. It’s really important to do your very best to avoid over-exposure to LH induced testosterone. That is why when I stimulate patients, many of my patients, especially those that are older or have diminished reserve, and therefore because of the diminished reserve will have increased LH activity and ovarian testosterone, I put them onto a birth control pill to start their cycle. I don’t do it for everybody. I used to, but I don’t do it for everybody any longer.
Dr. Aimee: Can you explain for those listening or watching why you would choose birth control in this kind of situation?
Dr. Geoffrey Sher: I put them on a birth control pill because that immediately lowers LH, that gives the ovaries a breather and gives the ovaries an opportunity to get ready for the cycle. I then overlap my patients, all of them, with Lupron or Buserelin, or whatever GnRH agonists that you can use because that increases antral follicle production by boosting the FSH. Unfortunately, it also boosts the LH. It causes the pituitary to produce more LH. It’s almost like you have an outstretched hand with a waterlogged sponge, when you give the Lupron, it’s like squeezing that sponge, it all hits the circulation en masse in a couple of hours. I continue with the Lupron, it’s like keeping that hand clenched, and allowing the LH to dry up. By the time the period comes, which it will come six to eight days later, the moment she has her period, she has the antral follicles from the boost in FSH, but her LH is at rock bottom. At that point, the stimulation begins. I either continue on the agonist or I personally switch to the antagonist.
Dr. Aimee: How do you decide to move to the antagonist type cycle, what factors are involved and what else do you consider?
Dr. Geoffrey Sher: In women with diminished reserve and older women, I prefer to start the GnRH antagonist, which is Cetrotide, Ganirelix, and Orgalutran, as examples. They’re all the same. I will start the antagonist on the very first day of stimulation, switching from the agonist to the antagonist, from the Lupron to the Cetrotide or Ganirelix. Then they will continue on it and I’ll boost them with FSH-dominated gonadotropins. I will use the recombinant. It’s not pure FSH, but it’s a 95% FSH, as compared to Menopur, which is roughly 50/50 LH and FSH. I use a limited amount of that, especially to older women and women with diminished reserve.
I start stimulating at the high level. Three days later, I drop the FSH level down by about one-third and continue with the Menopur. If you’re going to use an antagonist, you have to add some LH component because there will be nothing left, and without LH there’s no testosterone, without testosterone there’s no estradiol and there is no follicle growth and development. I always add that, up to 75 units of Menopur. For people in Canada, there are other alternatives of pure LH that you can use. Menopur is fine, as long as you don’t take the dosage too high.
Then I continue on that reduced dose of FSH recombinant and the Menopur for about another four days. Then I start doing daily ultrasound examinations and blood estradiol levels. I watch the estradiol level go up, watch the follicle growth together. Ordinarily, you’d expect each follicle over 15 millimeters to contribute 150 picograms to the total estradiol, maybe 200. But if you’re on an antagonist alone, it can be lower – and falsely lower. You have to watch follicle growth and the trend in the rise of estradiol. When I get a couple of follicles that are 18 to 22 millimeters, but not more, with the rest of the follicles, half of them being over 15 millimeters, I then trigger.
Dr. Aimee: What triggers do you use in these situations and why?
Dr. Geoffrey Sher: I trigger with HCG recombinant or HCG. I do not use Lupron triggers on women with low ovarian reserves. There’s no need. The whole reason for using Lupron to trigger, or Buserelin, is because you want to avoid ovarian hyperstimulation syndrome, which it does do. The problem is when you give something like Lupron, you don’t know how much the LH the pituitary is putting out, because that’s how it triggers myosis. The pituitary surges the LH and then you start getting the maturational division with the reduction in the chromosome number. What I do is I try my best to limit the use of Lupron to women who we know are at risk of severe ovarian hyperstimulation syndrome. Even then, I often prefer to use coasting.
Dr. Aimee: How do you use Lupron?
Dr. Geoffrey Sher: Use a small amount of HCG with it, don’t give the Lupron alone. That will protect the woman against OHSS, but at the expense of egg quality, therefore embryo quality. I prefer to give them HCG. The only time I’m concerned is if the estradiol is through the roof or there are more than 25 follicles. Then I might coast or I might use some Lupron with the HCG. Otherwise, I use HCG alone. I tell women if they don’t have too many follicles, they’re not going to get OHSS. If they do, it will be mild and it’s self-limiting. Since we test the embryos to see if they’re normal anyway, they’re not going to have the transfer in the same cycle, they’re not at risk of developing OHSS that is lingering and dangerous.
Dr. Aimee: What do you think is the most important thing a fertility patient can take from our conversation today?
Dr. Geoffrey Sher: I can’t emphasize enough, from everything we talk about today, basics are basics, but in most cases that I deal with – and like you, I’m pretty busy – it is the egg that is the issue. You can do a lot for the sperm, most of it is dealt with through selecting the sperm properly and doing ICSI. If you do that, you can get away with most. Your focus, unfortunately, needs to be more upon how to protect the eggs during the developmental process, during the cycle of stimulation. You can’t make better eggs. With the PRP, you can make the eggs better. Using things like growth hormone may improve mitochondrial activity in the egg. I use it liberally in all of my patients I stimulate.
Starting about a week or two before the cycle begins, I give them human growth hormone. I think it’s very helpful and it doesn’t do any harm for the short-term use. I use growth hormone in combination with stimulation, but it is the protocol used for ovarian stimulation. The important point is to use a judicious and individualized protocol aimed at avoiding over-exposure to LH-induced testosterone.
Another bad mistake people make, in my opinion, is overdosing their patients with HCG. Like LH, that is only going to make more testosterone get formed in the ovary, especially if the woman has diminished reserve. I don’t use HCG supplementation during stimulation and I don’t use testosterone supplementation that some people get given. I think that’s a major mistake.
I try to use the birth control pill to keep the LH at bay, overlap with Lupron to get follicles, to form antral follicles, and keep the LH low, and then supplement back with some Menopur to give a little bit of LH when they go onto the antagonist cycle. Using that, you get far better egg quality, you get more eggs, you get better results. I use a lot of that because my practice is 70-80% women who have diminished reserve or who have failed repeatedly because of poor egg quality. I’m sure yours is, too.
Dr. Aimee: Yes. Is there anything else you’d like to add today?
Dr. Geoffrey Sher: I can’t think. If you have anything in mind that you’d like to throw at me?
Dr. Aimee: No.
Dr. Geoffrey Sher: I do want to say this to you because you deserve it; I think you’re a wonderful doctor, and anybody who has you as a doctor is very fortunate because you give so much.
Dr. Aimee: Thank you.
Dr. Geoffrey Sher: It’s always a privilege and a pleasure to be with you, to talk to you, and to exchange ideas and learn from you.
Dr. Aimee: Same. I love to learn from you, always. Where can people find you and how can they work with you?
Dr. Geoffrey Sher: If they want to reach me, they can email my assistant Patty by going to Concierge@SherIVF.com or call her directly at 702-533-2691. Patty will always respond.
Dr. Aimee: Thank you again, Geoff. Thank you for joining me today. The information that you share is invaluable. Thank you so much. You’re such a blessing to all of us around you. Thank you for your time.
