Photo of Dr. Greenberg with black shirt, arms crossed and smiling, purple background and evolve logo

Fertility 101 Webinar For Family Physicians

Dr. Greenberg, Reproductive Endocrinology & Infertility Specialist (REI), at EVOLVE and TRIO kicks off the first webinar of our series for family physicians who want to learn more about infertility, egg freezing and more. To register for upcoming webinars, please contact tavia@evolveeggfreeze.com

Transcript (note although we strive for accuracy with the transcription, please allow for some errors)

Tavia:
Welcome everyone. We will get started here. Thank you for joining us. I know we have a few more people that will be trickling in, but I wanted to get started to leave you with time if you have questions for Dr. Greenberg after. My name is Tavia and I work at EVOLVE. I am the director of events and educational aspects. I kind of champion our educational outreach for patients in the community, for businesses and for healthcare practitioners at EVOLVE. And so we are here tonight to start our speaker series with the first talk being with Dr. Cassandra Greenberg. Hopefully, you can join us throughout this series, which runs all the way until June where we’ll be covering a range of topics on fertility and infertility and mental health and many different issues surrounding this topic.

Tavia (01:05):
So tonight we’re starting with fertility 101 and a little bit on egg freezing. We have Dr. Greenberg here. So a little bit of a background on Dr. Greenberg. She graduated with honors from University of Western with a bachelor’s medical science. She went on to do her medical degree at the University of Toronto and then trained in her obstetrics and gynecology there and subsequently completed her fellowship in gynecologic and reproductive endocrinology and infertility at McMaster. She has a written a bunch of articles since doing her fellowship and practicing on egg freezing and mental impacts of fertility treatments and she divides her time. We’re lucky enough, she divides her time between the new EVOLVE Clinic, which is for egg freezing and then TRIO Fertility. She’s a fellow of Royal College of Physicians and Surgeons of Canada. She’s a member of the Canadian Fertility and Andrology Society.

Tavia (02:06):
She’s a member of the American Society for Fertility and also the Society of Obstetrics and Gynecologist. So without further ado, I’ll pass it over to her. I do want to say if there are questions that come up throughout, please throw them in the chat and I will pose them to Dr. Greenberg at the end or as they go along. And I believe at the end we’ll also pause and I think I can unmute your mics and if you have some questions you wanna address then and by all means go ahead. So over to you.

Dr. Greenberg (02:41):
Thank you Tavia for that introduction. So as Tavia mentioned, the talk tonight will really be focusing on just fertility basics, fertility 101 with a little bit on egg freezing. So I’ll spend about half an hour or so kind of going through these topics and at the end, I’m happy to answer any questions that anybody has. So just to start off with the definition of infertility. This is defined by women who are under the age of 35 who are not able to get pregnant after 12 months of regular unprotected intercourse and that decreases down to six months once women are over the age of 35. And just to give you some stats here, about 15 to 20% of couples do meet the definition of infertility. And kind of looking at that a different way, one in six couples will struggle with infertility. When we look at the distribution of causes of infertility, we kind of break them down into causes from the female partner, from the male partner or both.

Dr. Greenberg (03:36):
When you look at the distribution, depending on whichever resource you look at, these numbers might be slightly different. But in general, we find female causes of infertility about 37% of the time. Male factor infertility can be up to 40% of the time. But also important to remember that there are causes on both sides, both female and male factor infertility and about 35% of the time. So whenever we’re seeing couples in the clinic, I always do testing for both partners at the same time because even if the history is suggesting that there might be a problem on one or either side, that doesn’t necessarily exclude a potential barrier. On the other partner’s side as well, there is also unexplained infertility which can account for up to 25% of couples. Unexplained infertility is technically defined by [patients] having regular ovulatory cycles, having at least one open tube on imaging and having a normal semen analysis.

Dr. Greenberg (04:32):
Now when we talk to couples who come to our clinic who have been having difficulty getting pregnant, one of the first things that we talk about are how they’ve been trying to get pregnant. So having regular unprotected intercourse. I also focus on lubricant use as well. So a lot of the commercially available over-the-counter lubricants are actually not safe for couples trying to conceive. They can impact sperm parameters, sperm motility. I often counsel patients to switch their lubricant use so that to not interfere with sperm motility. We also focus on the frequency of intercourse as well. So research has shown that once intercourse goes down to about once a week you are actually significantly reducing the likelihood of conception and then timing as well. So talking about things like the fertile window, making sure that intercourse is occurring around the time of ovulation as well.

Dr. Greenberg (05:21):
Now when we focus on female history specifically things like gynecologic or obstetrical history, we wanna know obviously the regularity of cycles. So how often a woman is getting a cycle, the timing of the cycle isn’t necessarily as important as whether or not she’s getting a regular monthly cycle. As long as there’s a cycle each month, that’s generally a good predictor of regular ovulation. We also focus on pain symptoms, so things like painful periods or painful intercourse, things that could potentially indicate the presence of endometriosis, which we know is associated with subfertility or infertility. We also wanna know history of any abdominal or pelvic surgeries which might increase the risk of things like pelvic adhesions or pelvic inflammation. I often specifically ask about a history of appendicitis and a history of an appendectomy, specifically if the appendix has been ruptured in the past that has been shown to be associated with adhesions and inflammation that could affect tubal patency.

Dr. Greenberg (06:19):
We also ask quite a bit about contraceptive history. This doesn’t necessarily impact infertility or subfertility, like whether or not someone has been on a birth control pill for a long period of time. But it actually is more related to the safety of fertility treatment. So if I have a patient who’s had side effects or like migraines with aura for example on a birth control pill, we’re going to want to make sure that it’s actually safe before we do something like hormonal stimulation. And then over at the top here, obstetrical history is also quite important. So I we always ask of a complete obstetrical history, how many pregnancies they’ve had before, whether or not those pregnancies are with their current partner or with a previous partner, any complications in the pregnancies, how long it’s taken them to get pregnant for each of those pregnancies. And I also specifically ask about any histories of any DNCs.

Dr. Greenberg (07:08):
So whether that’s for terminations, miscarriages, retained products after delivery because we know that could impact things like the development of [undistinguisable] or intrauterine adhesions as well. Other things that we talk about with our female patients, things like weight and exercise, particularly if there’s a history of irregular cycles or specifically anemia. Also a very complete social history as well. So lifestyle things that have been shown to impact female fertility, smoking. So cigarette smoking, decreases egg reserve has been shown to be associated with an earlier age at menopause and associated with higher obstetrical complications. So that could be things like miscarriage, ectopic pregnancies or other obstetrical complications throughout pregnancy. We also talk about alcohol use and I always tell patients to minimize their alcohol use and recreational drug use as well. So most patients are actually surprised to find that marijuana use does have an impact on female fertility and I tell patients to completely stop any kind of marijuana or THC or CBD products while they’re trying to get pregnant.

Dr. Greenberg (08:13):
We also talk about things like work and travel, particularly for things like exposure to Zija virus or any exposures that they could potentially have with their job and on the male side of things. So we wanna know a full reproductive history for our male patients, whether or not they’ve had pregnancies with their current partner or previous partners. Also screening for sexual dysfunction, which could obviously play a role in trying to get pregnant. And then a surgical history as well, particularly focused on any groin surgeries, things like Varicocele surgeries, history of a vasectomy or hernia repair and a complete medical history as well, which also can have an impact on male fertility. So some of the things, things that we also focus on for our male patients medications. So things like any medications for hair loss or testosterone use has been shown to impact male fertility. I also screen for any kind of vitamins or supplements, have had some male patients taking supplements that are marketed as testosterone boosters. I don’t know exactly the impact of those, but I always counsel patients to not take anything that could potentially increase their testosterone because that could impact things like sperm production, history of descended testicles or testicular injury. And particularly we also ask about a history of mumps as a child or as a teenager.

Dr. Greenberg (09:35):
And then as well the social history for males is also very important in terms of sperm quality. So we always screen for things like their occupation, whether or not they have exposure to toxins or travel history, which could make cycle monitoring and things like fertility treatment, difficult cigarette smoking, clear association with reducing sperm counts and sperm quality alcohol use also has a pretty significant impact on sperm quality as well, particularly if they’re in the kind of higher levels of alcohol intake. I have seen patients before where they, they have about, you know, 20 alcoholic drinks a week or so. Their semen analysis has been seriously abnormal. There’s no treatment available to them except for IVF and purely by just decreasing their alcohol intake, their semen analysis has gone completely back to normal. So this can actually have a pretty significant impact on sperm quality and recreational drug use as well. So specifically marijuana can impact things like sperm count, but also sperm motility as well.

Dr. Greenberg (10:35):
Now when we start with investigations for a couple that’s been struggling to get pregnant, some of our physicians will divide it into things like macro fertility and micro fertility. Macro fertility are basically those big picture things that you can see and that we can test for our patients. So things like ovulation, having regular cycles, tubal patency, uterine cavity and sperm quality are all things that we can test for. Micro fertility refers to things that are happening at a microscopic level, things that we can’t necessarily see with our investigations. So things like what’s happening when egg and sperm are coming together at the time of fertilization, what’s happening with embryo development, what’s happening at the time of implantation, these are things that could potentially be a barrier that are happening in the background that we can’t actually see with testing.

Dr. Greenberg (11:24):
So when we’re focusing on our macro fertility investigations, ovulation is obviously one of those things that we wanna look at most of the time we can get at whether or not ovulation is happening purely based on a woman’s history. So again, regular monthly cycles is all we really need to know to see if a woman is ovulating. On occasion we will sometimes do serum hormones to see if a woman is ovulating. Previously we would do diagnostic cycle monitoring just to see what’s happening in a natural cycle. We tend to veer away from that. Now, cycle monitoring is obviously a big part of fertility treatment but we don’t necessarily use it as part of diagnostics initially. And so there are ways for women to monitor their own ovulation. So lots of things out there like basal body temperature, cerval, cervical mucus production, those are not necessarily the best ways to monitor ovulation.

Dr. Greenberg (12:13):
Basal body temperature is notoriously very finicky, not really the best way for women to pick up the fertile window. Cervical mucus is not really the most acceptable way for patients to monitor ovulation. Ovulation predictor kits can be very helpful but they don’t necessarily work for every single patient. Now another way besides a woman just monitoring for ovulation, another easier way for couples to make sure that their timing is appropriate is intercourse every other day from day 10. I usually say for approximately a week or so, but could be up to day 20. Research has shown that intercourse every other day is perfectly appropriate and not any less successful than intercourse every day. And as long as they’re starting from day 10 and intercourse every other day for about a week or so, probably going to capture the fertile window.

Dr. Greenberg (13:00):
And then looking at things like tubal status, we generally look at tubal patency with a sonohysterogram. We also have other testing here listed things like [undistinguisable], which isn’t very frequently ordered anymore. Laparoscopy for very obvious reasons we don’t do routinely for patients, but if they are having laparoscopy for other reasons like endometriosis for example, tubal patency can be assessed at the time of surgery. But generally a sonohysterogram is enough for us to see whether or not the tubes are open. And then assessing the uterine cavities, looking for things like polyps or fibroids or intrauterine adhesions. sonohysterogram is one of our best tests to actually look at the cavity of the uterus if needed. Sometimes we will progress to a hysteroscopy if there’s treatment that’s recommended in sometimes a diagnostic hysteroscopy is also done. And then the other test that we do is a semen analysis.

Dr. Greenberg (13:51):
So the semen analysis can be done at places like Life Labs or flow labs, but we also do it in-house at TRIO, a very basic semen analysis. We’ll look at general things like volume of the sample concentration or sperm count motility morphology like the appearance of the sperm under the microscope. The numbers that are listed here I believe are the numbers that are used at Life Labs whenever a semen analysis is done. When a semen analysis is done at TRIO, we use the WHO strict criteria. So the numbers are slightly different than what you see here. Also, in addition, whenever a SE analysis is done at TRIO we often add on DNA fragmentation. Essentially you can think about DNA fragmentation, the way I explain it to patients is the rate of DNA damage in the sperm.

Dr. Greenberg (14:35):
So higher levels of D fragmentation associated with higher rates of DNA damage and research has shown that that does have an impact on things like male fertility. So fertility does decrease as D F I increases. And also the likelihood of miscarriage or recurrent miscarriage also increases as DNA fragmentation increases. So we often do this routinely for a lot of our couples. It is important to note that a male can have a completely normal semen analysis, meaning normal sperm count, normal motility, normal morphology, but still have an elevated DNA fragmentation which could be playing a role in fertility. Now just as an aside, DNA fragmentation is often not covered by oip. So at trio to do a DNA fragmentation, it does cost patients about $300 or so.

Dr. Greenberg (15:24):
Now in terms of causes of DNA fragmentation, the majority of the time this is related to things like lifestyle. So not only does you know cigarette smoking, marijuana use, high alcohol use impact basic sperm parameters like count and motility, but it can also impact DNA fragmentation. So usually an adjustment in lifestyle factors can bring the DFI down. So smoking cessation stop using marijuana, decreasing alcohol use, but also things like heat exposure to the testicles. So sometimes we have patients using regular saunas, regular steams or regular hot tubs. These are all things that could impact sperm quality and stopping any of those things that could increase heat exposure. Could also bring the DFI down. Other things that people don’t necessarily think about in terms of heat exposure, laptops on the lab, heated car seats, sometimes those can also play a role. Generally an elevated DFI is associated with a normal CARO types. This doesn’t necessarily mean there’s a genetic abnormality with the male, it just means there is higher rates of DNA damage in the sperm within the testicle. With lifestyle changes, usually this improves but sometimes also fertility supplements are enough to improve the DFI. So we actually give fertility supplements to a lot of our male patients and this helps improve some of the sperm parameters.

Dr. Greenberg (16:40):
Now once we’ve done kind of the initial investigations with our patients, some of the ways that we help improve our patient success rate for conception are things just making sure that their timing is appropriate. So talking about things like timing of natural fertility and the fertile window. And we spend a lot of time talking about these lifestyle changes, the smoking, alcohol, marijuana use. If there is a history of irregular cycles, sometimes all that’s needed is ovulation induction. Majority of the time that’s with oral medication. So most commonly we use things like letrozole less commonly. Now Clomid is used on occasion we might use object injectable hormones to actually induce ovulation for example if they don’t respond to oral medications. We have surgery listed here as a way for ovulation induction. This is technically something that was done probably more often in the past.

Dr. Greenberg (17:28):
Things like laparoscopic ovarian drilling or ovarian wedge resection really fallen out of favor. I don’t know too many people who offer those procedures anymore. Generally this is really just accomplished with medications either orally or subcutaneous injections. If there is a sperm abnormality, we do try and improve sperm quality. Again, with those lifestyle changes or fertility supplements, sometimes a referral to urology is required as well to help improve sperm quality. And then obviously things like assisted reproductive technologies or a r t can help boost up success rate for couples if they aren’t having success naturally. So when we talk about a r t, this really encompasses majority of our fertility treatments. Most are based on the idea of superovulation. So using medications for female patients to increase the number of eggs that they’re ovulating more so than just the one egg that’s ovulated. Each month we try and increase this to two or three with some of our more conservative treatments with many more eggs with more aggressive treatments like IVF.

Dr. Greenberg (18:29):
So a R T will encompass things like insemination or IUI, which usually involves some fertility medication again just to kind of boost up the success rate also includes things like IVF and ICSI, which is a way of fertilizing eggs in our lab. And egg freezing would also technically fall under a r t as well more so as a fertility preservation method than a treatment to try to get pregnant. So that’s kind of a nice segue into the impact of age on fertility. And most of the time when we talk about age and its relation to fertility, we’re talking about our female patients. So we know that fertility or infertility increases as women get older and the rate of miscarriage also increases as women get older as well. So usually we talk about the decline in fertility kind of in the later thirties, like after the age of 35 or 37 fertility starts to go down and then in the forties, very high rates of fertility as women are reaching their forties.

Dr. Greenberg (19:27):
Now when we talk about age and the decline in fertility with age, that’s really really focusing on things like egg quantity and egg quality. So we do know that egg quantity declines over time different for each woman, but the pattern is still the same. The egg numbers that are in the ovaries are gonna decrease as women age and then the quality of the eggs also declines over time. So even if you have a woman that’s technically slightly older, like later thirties or early forties and has a good ovarian reserve or a good egg quantity, that’s not telling you anything about the quality of the eggs, which also has a significant impact on fertility. And when we talk about natural fertility or fertility treatment age specifically, female age is by far the most important prognostic factor for success. And then you see here we have some notes here that in people between the ages of 30 and 35, there is that decline in fertility over time. But at the age of 40 there is a sharp decline in fertility.

Dr. Greenberg (20:26):
This is kind of the same idea just shown in graph form. So on the left you can see a graph here showing that the egg quality does decrease over time. So it’s a little bit of a slower decline kind of in the late twenties, early thirties. But as women get to their later thirties and early forties, that is much more of a steep decline in the quality of the eggs. And then also looking at egg count, you do see that again slow decline in egg number over time with a sharp decrease after the age of 40.

Dr. Greenberg (20:55):
Now when we talk about the decrease in egg quality over time, that’s generally referred to aneuploid eggs or eggs with abnormal numbers of genetics, mostly trace back to dysfunction in myosis. And once you have eggs that have a higher number of aneuploidy, then you end up having higher numbers of embryos with chromosomal abnormalities and then that leads to decrease infertility. But also we know that the number one cause of miscarriage is having an aneuploid embryo. So we start to see decreases infertility as eggs become more and more abnormal and the rate of miscarriage also increases as you have more and more aneuploid embryos.

Dr. Greenberg (21:35):
Now some of the ways that we test for egg reserve or egg quantity or egg reserve, we look at this a couple of different ways, but one of our bigger tests that patients are often Googling or researching about is AMH, which is just a blood test that we do routinely for most of our patients. AMH is secreted into circulation by granulosa cells. So it’s not secreted directly by the eggs but more so the cells that are around the eggs. And it gives us a measure of high, medium or low egg reserve. So it doesn’t tell us exactly how many eggs are in the ovaries, but we can basically compare a patient’s AMH level to what the typical level would be for that woman’s age. So is their AMH level consistent with the average at their at their age lower than what’s expected for their age or higher than what’s expected for their age? And you start to see AMH correlated with egg number. So a higher AMH would be considered higher egg reserve lower AMH would be consistent with a lower egg reserve. Now AMH can actually be measured at any point in the cycle. We tend to do it along with our day three hormone blood work, but it’s not actually required. You can do it at any point in the menstrual cycle and it’s still accurate.

Dr. Greenberg (22:46):
Now in terms of trends with AMH, so we do see AMH numbers declining with age, which you see what you would expect as age increases egg number decreases and you see the AMH values go down. There are some conditions where we see higher AMH levels. So in particular women with PCOS do tend to have much higher AMH values consistent with higher ovarian reserve and women with PCOS now AMH only tells us about egg quantity. It doesn’t tell us anything about the quality of the eggs, it also doesn’t correlate with natural fertility. So even if a woman has a low AMH number or a low egg reserve, we can’t actually use that number to say whether or not she would have difficulty getting pregnant. We can’t use the information that way. Really egg reserve just tells us about how a woman would respond to fertility treatment. So for example, if AMH is low or egg reserve is low and they do something like an egg freezing cycle or an IVF cycle, they’re not going to get as many eggs with a lower ovarian reserve compared to if their ovarian reserve was higher but it doesn’t actually mean they would have difficulty or not conceiving.

Dr. Greenberg (23:55):
So that’s a nice segue as well into egg freezing. So just going to go over egg freezing briefly here. So just to give a little bit of history around egg freezing — egg freezing has actually been around for quite a long time. The first live birth reported from a frozen egg was back in 1986 and this was with a slow freeze technique. So a little bit of an older technique of freezing eggs. Slow freeze has generally been replaced by vitrification in most fertility centers. Vitrification is essentially flash freezing, it’s where the egg is frozen very quickly and ends up being frozen into like a glass-like state which really improves outcomes with egg freezing because you really decrease the rate of ice crystal formation and that decreases the amount of damage that you have to the eggs. So once vitrification kind of replaced slow freeze, particularly for egg freezing, we started to see our success rate with egg freezing increase significantly.

Greenberg (24:46):
Now in the past, egg freezing was considered experimental but slowly over time that label was removed from egg freezing. So ESRA in Europe was the first one to remove that experimental label back in 2012 from egg freezing. ASRM in the US followed about a year after that. So egg freezing was no longer considered experimental in the US in 2013 and then Canada followed last. So CFAS removed that label in 2014 and we’ve seen a steady increase in women pursuing egg freezing kind of since that time. It’s become more and more popular and we’ve — I’m sure you guys have seen it in practice as well — we have definitely seen an increase in popularity in egg freezing in our practices. Now the idea behind egg freezing, it’s essentially exactly the same as an IVF cycle just with egg freezing.

Dr. Greenberg (25:29):
We’re stopping at an earlier step compared to a couple doing IVF for the purpose of trying to get pregnant. So it involves stimulation and an egg retrieval to remove the eggs from the ovaries. We then freeze whatever mature eggs we’re able to extract from the ovaries and then women can use them at a later date. The real benefit of egg freezing is that once the eggs are frozen they retain their quality. So if a woman is going to freeze eggs at a younger age and she decides to come back and use them 10 years later, the success rate of fertility treatment is going to be the same as when she froze the eggs. So as an example, if a woman freezes eggs at 33, she comes back to use those eggs at 40, her natural fertility will be decreased purely based on her age, but using those frozen eggs, she’s going to retain the same success rate as a 33-year-old using those eggs.

Dr. Greenberg (26:18):
So they do not age with women over time and they can be stored forever. There’s no expiry date for egg freezing in our lab. They can basically be frozen for however long women want to freeze them for. Some women never come back and use their eggs if they’re actually able to get pregnant on their own, but we can keep them for as long as women want to. Now in terms of reasons to freeze eggs, as you can see here, there are a lot of reasons why people decide to freeze eggs but by far the number one reason is either women do not have a partner or they don’t have the right partner and they want to preserve their fertility for the future. Other very common reasons are things like educational goals or career goals or sometimes just personal goals. They don’t feel ready to have a family and they want to delay that family building until later on, potentially when their natural fertility is going to be much lower.

Dr. Greenberg (27:07):
Other medical conditions, why women might choose to freeze eggs, things like endometriosis which we know will be associated with subfertility or infertility. If they have a family history of early menopause, if they have any like chronic medical conditions or genetic conditions, they might choose to freeze eggs for example if they want to test embryos in the future before transfer. Sometimes other medical conditions like oncology patients might want to freeze eggs before they do any kind of chemotherapy, which we know can be toxic. We don’t actually offer oncology at TRIIO, but many other fertility centers will offer this for oncology patients. And also increasing in popularity are patients undergoing gender transition. So they want to freeze their eggs before doing any kind of hormonal therapy or Lupron even to suppress regular cycles to freeze eggs before they start any hormone treatment to retain their fertility. For some people egg freezing does offer them the ability to preserve fertility, without the ethical or sometimes religious dilemma of freezing embryos.

Dr. Greenberg (28:07):
So not everybody feels comfortable freezing embryos they have, they feel more comfortable freezing eggs and also if someone wants to retain their autonomy in the future. So for example, if they have a partner right now but they’re not sure that’s the partner that they want to try and conceive with, it allows them to retain their reproductive autonomy so they don’t necessarily have to freeze embryos with their partner, which would then legally belong to both them and their partner. Freezing eggs allows them to make decisions on their own about the eggs without their partner in the future.

Dr. Greenberg (28:39):
So in terms of the process, very similar to an IVF cycle, we use injectable hormone medications which essentially consist of both FSH and LH. Those injectable hormones stimulate multi follicular growth. So we’re hoping for a group of follicles developing at a time so that we can extract them later. The average time that women are doing fertility injections are about 10 to 12 days, could be a day or so less could be a little bit more. Everything is really dependent on how any individual person responds to stimulation, but the average time is about 10 to 12 days while they’re doing those injections. We do monitoring, so basic cycle monitoring, blood work and ultrasounds every couple days in the mornings just to monitor response and allow us to time the egg retrieval appropriately. We also add on a GnRH antagonist to suppress ovulation until egg retrieval.

Dr. Greenberg (29:28):
So we don’t want ovaries releasing the eggs, we want to keep them in the ovaries until the time of retrieval. The egg retrieval happens in our clinic. It’s a minimally invasive procedure. It’s done completely guided by a transvaginal ultrasound. Takes 20 or 30 minutes or so, it’s really not very long and it’s done under conscious sedation. [After the retrieva], they hang out in our recovery area up to an hour or so and they go home the same day. So it’s really not too long and there’s no overnight stay or anything like that. Generally people feel a little bit uncomfortable for about a day or so. They’re generally starting to go back to their regular activities after about a day or two after egg retrieval.

Dr. Greenberg (30:09):
Now just to give you some stats here about egg freezing. [The] ideal time for egg freezing is when you’re younger, when egg quantity is higher and egg quality is higher. So generally think about kind of later twenties, early thirties are really the better time to freeze eggs as women get older. Both quantity and quality are gonna decline with time. In terms of this success rate with frozen eggs. So the likelihood of having a live birth from each frozen egg is a range anywhere between 2% to 12%. That’s going to be very variable [from] woman to woman. So that might depend on age, egg reserve, egg quality. So it is different depending on an individual situation. Egg freezing is generally not covered by OHIP or any Ontario funding. So the average cost of a cycle would include cost of a treatment cycle and cost of fertility medications if they don’t have any drug coverage.

Dr. Greenberg (31:05):
So anywhere between about $8.000 to $12,000 is what the cost is per cycle. So this can be pretty prohibitive for a lot of patients. Now, ideally for most patients want to freeze somewhere between 10 to 15 eggs but obviously the more the better. A lot of our patients, depending on their egg reserve and how they respond to medications, can’t necessarily get their goal of eggs with one cycle. I would say it is not uncommon for our egg freezing patients to do more than one cycle to bank the number of eggs that they have. Not every one of our patients can really get their goal of egg numbers just with one cycle. Now in terms of live birth rate per embryo transfer, so once they use the frozen eggs they end up having an embryo. The likelihood of pregnancy or live birth from each embryo transfer can range anywhere between 45% depending on age, egg quality, embryo quality can go up to things like 75%, particularly if they’re doing genetic testing on their embryos. And we’re really selecting out genetically normal embryos that significantly increases success rate not appropriate for every single patient doing an embryo transfer, but we do recommend it in some situations. And then just to give you kind of an overall number, the number of live births that have happened from frozen eggs since 2015 — this is actually an old stat — over 5,000. It’s actually probably even more now cause this is from a couple years ago.

Dr. Greenberg (32:31):
So this is a graph that I present to all of my egg freezing patients because it really helps kind of wrap your head around what the success rate is of egg freezing. So this was a study done, it was published back in 2016 and this group used some data from their clinic to try and predict what the success rate is from egg freezing. So each of these graphs represents a different age group. So on the X axis you see the number of eggs frozen and then on the Y axis is the probability of success and then each of those lines represents the number of children. So really just focusing on that blue line there, which is the probability of having at least one child. This really highlights the decrease in success rate with age. So if we kind of focus on that top left corner there, just as an easy example, if a woman between the ages of 30 to 34 is able to freeze about 10 eggs based on this research that would predict an approximately 60% chance of having a baby in the future, one baby in the future with those 10 eggs if age then goes up a little bit and you’re freezing those same 10 eggs.

Dr. Greenberg (33:32):
But now between the ages of 35 and 37, you’ve now decreased your success rate by 10%. So the likelihood of having a baby is now about 50%. As women get even older, those same 10 eggs really only give you about a 40% chance of success. So you can see here that the older you are the more eggs that we need to freeze to give patients a reasonable chance of success. And you can see even significantly decreased success rate as women get over the age of 40. So only about a 20 to 30% of chance of success in kind of in those early forties.

Dr. Greenberg (34:06):
Now in terms of things that you can do for your patients even before they come to the fertility clinic. So just reminding patients of the relationship between age and fertility. So encouraging patients if it’s appropriate for them to try and conceive sooner rather than later because we know of that decline in fertility with age and also not delaying a couple’s treatment. So for couples that have been trying to get pregnant for long periods of time a year to a year and a half, their natural fertility really does decrease over time. So better to refer patients sooner rather than later so we can start getting them into treatment to improve their chances of success. And also particularly for our female patients, reminding patients that fertility is not an on off switch, female fertility is gonna decrease significantly over time and just other things that can be done even before patients get into the fertility clinic.

Dr. Greenberg (34:55):
Improving lifestyle factors. So again, really harping on those like smoking, alcohol, drug use and then if a woman is not ovulating you can refer them to the clinic kind of right away. They’re not having regular cycles that doesn’t give them too many opportunities to try naturally they probably need some kind of medication to induce ovulation to help them try. And then also just having a basic understanding of some of our fertility treatments, like a basic understanding of IUI or IVF or egg freezing. We’re gonna give them all of their complete information when they come to us but they are gonna ask you some questions about these even before they come to see us. So that’s all I have for our talk today. I have my email address here. I’m very happy for anybody to send me any questions that they have about just kind of general questions or particular cases but I’m also happy to open it up to questions right now.

Tavia (35:45):
I have a few people have posed some questions and if other people also want to speak up then please I think you have to raise your hand and then I have to unmute you. But there were some questions right off the bat there was which lubricant do you recommend to patients that are trying?

Dr. Greenberg (36:04):
Yeah, so generally the one I recommend is pre-seed. You can, you can get that at like the grocery store or the pharmacy. It’s just in that kind of regular aisle. Pre-Seed.

Dr. Greenberg (36:13):
Pre-Seed. Yeah there are other ones that I’ve seen that patients have used. I think there’s a brand called Good Clean Love and they have one that’s called fertility-friendly lube. Basically you just want to make sure that it’s appropriate for couples trying to get pregnant but when in doubt precede is totally fine.

Tavia (36:29):
Okay. great. I, sorry I’m just trying to, and if I get this wrong please chime in if this is yours. Who does the male workup, does that need to come from the male GP or is that done at TRIO?

Dr. Greenberg (36:52):
So we actually, we do the basic male workup at TRIO. So we see the couple together. So both the male and the female are our patients. So we’ll do the initial blood work for the male as well as the semen analysis. If the semen analysis is very abnormal or needs kind of additional workup by urology, we will refer them to urology so the GP or the family doctor doesn’t actually have to do any workup before the male comes to see us.

Tavia (37:15):
Okay. That was their follow up question. Okay, so the urologist workup comes and then just to tag onto that is there specific work you need to be or would like to be having done on the female patient as well or do you do all that workup as well?

Dr. Greenberg (37:31):
We do the full workup on the female. So if you wanna start the workup for the patient, particularly if they want information sooner than it’s going take for them to get into our clinic, that’s fine, but you actually don’t have to do any initial blood work before they come to see us. Just the referral is completely fine. Truthfully most of the time we actually end up repeating a lot of the workup anyway, like those day three hormones, the ultrasound, we end up doing a lot of that ourselves so you don’t actually have to do anything before they come to see us.

Tavia (37:58):
Okay. what else do we have here? It’s a DNA fragmentation question. How do you know, oh I guess it’s a little more lab-based. So ICSI helps with DNA fragmentation. How do you know that you’re choosing the right sperm I guess is the general gist of the question; how does the lab know that they’re choosing the right sperm? Is there a workup done on the sperm before they do ICSI?

Dr. Greenberg (38:30):
There’s not, it’s actually, it’s a, it’s kind of funny when you see the lab selecting out the sperm because they will actually look under the microscope as they’re selecting sperm for each egg and they will look for sperm that looks morphologically normal. So they will scan through the slide until they find a normal looking sperm. You can’t actually do DNA fragmentation testing on sperm that you’re going to use for fertility treatment because just the process of doing DNA fragmentation testing actually damages the sperm and renderers them unusable. But a normal appearing sperm is correlated with a normal DNA fragmentation. So the lab will just kind of search for that normal looking sperm and use each one of those to inject the eggs. They’re looking at like millions of sperm a day so they’re able to pick out which ones look normal and and abnormal.

Tavia (39:16):
All right. Another one on and this one will tie in actually to our next talk with Conceived Health I believe, but what are the fertility supplements for males and females that you recommend offer suggests and where can they be purchased?

Dr. Greenberg (39:32):
So for female patients, whether or not they’re trying to get pregnant or even for egg freezing patients, honestly, [you] recommend a prenatal vitamin or just folic acid on their own just to help improve egg quality. Other supplements that can be helpful for egg quality are things like co-enzyme Q10, which again can just be purchased at any pharmacy or grocery store. The dose that’s helpful for co-enzyme Q10 for egg quality is 600 milligrams a day. So that often means multiple tablets a day. They don’t usually come as 600 milligrams. And then vitamin D as well, which I imagine everybody’s recommending to their patients anyway, especially at this time in the year with the winter for all of our Canadian patients. But those three are generally are my main recommendations for egg quality. I don’t always tell male patients to take supplements right off the bat, but as soon as I’m seeing any kind of abnormality on the semen analysis, which truthfully is more often than not, the one that I generally like to recommend is Fertile Pro for men. We sell that at the TRIO pharmacy, but I also tell patients they can buy it online as well.

Tavia (40:33):
The next one I can kind of start the answer actually and then if you wanna hop in, it’s why can’t patients no longer freeze their eggs at TRIO [and] which patients can still freeze their eggs at TRIO. EVOLVE [is] the first Canadian clinic in Canada to solely do egg freezing But this is been going on for a long time to have solely egg freezing clinics in the United States and actually in Australia where they are a little bit ahead [with the] fertility model so to speak in those countries. And so EVOLVE was launched to cater to that unique patient that has very different needs than the patients that are coming into a fertility clinic.

Tavia (41:26):
So the thought was that a lot of these eggs freezing patients want different things. They want to be in and out, they want to be on their own schedule. They [also] have a lot more questions. They’re not desperate for a baby right now. They want, they have a lot more questions about egg freezing and the clinic there, I like to call it more spa-like, it’s definitely a different group of people. They’re [also] in a more spa-like environment. One benefit of having EVOLVE and being partners with TRIO and part of the family is it also takes those egg freezing patients out of the wait list at TRIO. So for you doctors that are referring IVFs or patients that are having problems with fertility or patients that solely want egg freezing, we can kind of take those egg freezing patients off the doctors and nurses docket so to speak for the day. So it frees up a little bit more time to decrease the wait list at TRIO and your egg freezing patients can be seen a little quicker at or very quickly at EVOLVE. Do you, do you agree with my thoughts there?

Dr. Greenberg (42:33):
The only thing that I would add in is actually like some feedback that I’ve gotten from my egg freezing patients, both from those coming through EVOLVE and those coming through TRIO is they describe the vibe of the clinic. So for an egg freezing patient, they’re coming more from a place of empowerment and taking control of their fertility. [They do] like to be separate from the fertility patients. It does make them feel better. It is preferred and the research has backed that up as well, that egg freezing patients do want to be separate from routine fertility patients who are trying to get pregnant.

Tavia (43:15):
Great. The last question that I have so far in the, in the bank here, unless other people have one they want to add is how do egg transfer rates compare to IVF rates? So I’m assuming this means I guess you, you can take it at that, I’m assuming it means if you were to freeze eggs at 30 and then the person uses ends up using their eggs to become pregnant, how does that compare to the rate of if they were just to go through IVF?

Tavia (43:50):
Think that’s my take on the question.

Dr. Greenberg (43:52):
So, so whoever’s question this is, let me know if I’m answering this appropriately, but I think we can kind of answer it in two parts. So one thing that patients always ask is should they freeze eggs or should they freeze embryos? Because most people have heard that freezing embryos is better than egg freezing because of that advancement in vitrification. Our success rate with egg freezing has gotten so good that embryo freezing doesn’t actually improve pregnancy rates. So I always tell patients that if they don’t want to freeze embryos, rather like whatever angle that comes from, they want to retain their autonomy or sometimes from a financial standpoint, there’s no actual reason to freeze embryos unless they want that additional information — it’s not gonna improve their pregnancy rate. And then in terms of things like doing egg freezing earlier versus doing IVF later when you need it, I always encourage patients if they’re emotionally and financially ready to do egg freezing then earlier is always better. You’re going to have better success rates if you freeze eggs at a younger age purely because of that egg quantity and quality decline over time. [The] success rate is not going to be as good if you wait to do IVF in the future when you need it, should you need it.

Tavia (45:04):
Great. I there was no, oh let me just double. Are eggs genetically tested?

Dr. Greenberg (45:12):
No. So there’s no ability to test the eggs genetically. There’s no PGT for eggs when or if patients do decide to create embryos, we can offer genetic testing once the embryos are created. But genetic testing, depending on the kind of genetic testing that’s done, but generally what most people are looking for is PGTA, which only screens for aneuploidy in the egg. So we’re really just looking at chromosome number. It’s not kind of a broad looking at every single genetic condition out there. We look at chromosome number.

Tavia (45:47):
To add to this, do you want to talk about what they look at before they do freeze eggs? Like they do kind of rate them and look at their maturity though, correct?

Dr. Greenberg (45:56):
So when we do an egg retrieval, patients will get the total number of eggs at the time of retrieval, but later on in the day, the lab actually strips the cells off the outside of the eggs and that allows the lab to assess which eggs are mature or immature. Immature eggs don’t actually offer patients any benefit in terms of the ability to create embryos or a pregnancy in the future. So depending on the appearance of the eggs, the lab will be able to see which eggs are mature and we only freeze mature eggs. So that’s why some patients might have 15 eggs retrieved, but only 11 frozen for example. So 11 outta 15 might be frozen. And then in terms of looking at the quality of the eggs, so I had mentioned earlier in the talk that there’s [no] way to look at egg quality with things like blood work and ultrasound.

Dr. Greenberg (46:47):
Really the only ways to get a sense of egg quality are either a woman’s age, which we really just assume in terms of egg quality or when the lab like looks at the eggs under the microscope. So there’s no necessarily validated score for egg quality. But the lab will look at certain features as they’re looking at the eggs at the time of freezing to really determine if they’re like good quality or if they’re signs of poor quality. Also either through TRIO or through EVOLVE. We do have a company that generates something called the Violet report, which we do for every single egg freezing cycle. And that gives patients a little bit of an idea of their success rate specific to their frozen eggs. So it kind of gives it patients an estimate of like, number of embryos that this AI program predicts that they’ll get from their frozen eggs or what their probability of live birth will be. This is all based on like AI and stats, but it’s kind of a general idea of success rate, which kind of is indirectly related to things like egg quality.

Tavia (47:43):
This is great. Thank you everyone for joining us. We’ll be sending you a link for the next talk in our series, which I believe is February 22nd. It’s in February. Again, it’s 7:00 PM and it is with kind of on the whole nutraceuticals and ways naturopathically that maybe we can increase male and female fertility. So I invite you or encourage you to let anyone else that you think might be interested to to join our talk. And that is all for us for this evening. So thanks for joining us and have a great evening.