Knocked Up Podcast - Fertility and Peri/Menopause Part 1
We’re having children later in life than ever before, often this can mean we encounter perimenopause or menopause on the way. What does this mean in terms of our fertility?
In part one of understanding our fertility and peri/menopause, we unpack why fertility becomes more challenging as we approach perimenopause. Dr Raelia explains how shifting hormones, irregular cycles, and declining egg quality combine to make conception more difficult in our 40s. From understanding AMH and ovarian reserve to recognising the impact of age on egg health and miscarriage risk, this conversation explores what’s really happening to fertility in the decade before menopause and the options available for those still hoping to conceive.
TRANSCRIPT
Jordi Morrison: Hi, Jordi here. In today's episode, we had so much to talk about that rather than chop it up too much, we decided to bring you two episodes. Part two will be out in two weeks.
Hello, and welcome to Knocked Up, the podcast about fertility and women's health. You are joined as always by me, Jordi Morrison, and Dr. Raelia Lew, CREI Fertility Specialist. Welcome, Raelia.
Dr. Raelia Lew: Thanks, Jordi. How are you doing?
Jordi Morrison: I'm great, thank you. As a woman in perimenopause, I'm quite excited about this topic. And as you would see in your practice, we are waiting longer to have children. And often this will mean we encounter perimenopause whilst we are trying to conceive.
Dr. Raelia Lew: Yeah, that's right. And I, without obviously breaching any patient confidentiality, I can tell you I saw a patient yesterday in this very situation. She said to me... she'd been with her partner for a really long time actually, many years, but they weren't at the stage in life where they felt ready to have a baby until their late 30s. And when she tried to conceive, her period started to be irregular and she went to her doctor and her AMH was less than one and her hormones were in a pattern that was consistent with perimenopause. And that can be super stressful. Firstly, because people are trying to conceive at a time where their prognosis for conception is much lower. But also, even when trying naturally, one of the things that is important in being able to try is knowing when you're ovulating. And if your cycles are irregular, that can be very difficult.
So women in perimenopause who are trying to conceive have really the triple whammy of... getting the timing right often and being frustrated because they don't know when they're ovulating or going to ovulate. They can have luteal phase deficiency because we often get cycle shortening in the perimenopause and so we don't properly support the endometrium for conception. And we have low egg number, meaning that assisted reproductive treatments can be less effective for women and couples, as well as poor egg quality associated with advancing maternal age. And that starts to kick in around 35. So it's very stressful when you're trying to conceive in perimenopause.
Jordi Morrison: And I think many of us now know that our fertility drops off a cliff at 35, but we aren't usually in perimenopause at 35.
Dr. Raelia Lew: No, definitely. Most women start perimenopause around the age of 40 and we tend to say perimenopause tends to last about a decade, a stage of life rather than a condition per se. And the first subtle sign is when our menstrual cycles just start to shorten a little bit. And that may be quite subtle and it can be usually going from say a clockwork 28 day or 30 day cycle down to a 26 day cycle and then maybe a 25, 24 day cycle gradually over a period of years. But that is in fact the first sign that ovarian reserve is depleting significantly and perimenopause may be starting in a subtle way. This is really common for women in our 40s and for some people it happens a little bit younger. And one of the things we've noted in society is women are having their first child later in life, and the age that we have our first baby is going to influence the age we are when we're having subsequent children. And the time frame that women are now trying to conceive does overlap significantly with perimenopause and for some women even menopause.
Jordi Morrison: Let's start with what happens to our fertility as we move through our 40s. And we are going to reference the 40s and peri because that's generally the issue. What happens to our fertility as we move through our 40s?
Dr. Raelia Lew: I'm just going to preface what I'm going to say by defining what is menopause, just so people are aware what menopause and perimenopause refer to. Menopause is a retrospective diagnosis and it's when somebody has not had a period at all for more than a year and the likelihood is they will never have another period. Now we say menopause is premature. So another term we sometimes use is premature ovarian insufficiency, and it used to be premature ovarian failure. We say menopause is premature if it happens under the age of 40. If menopause happens at the age of 40, that is considered in medical terms, the lower end of the normal spectrum, the normal physiological spectrum. It's not a disease. It's just that some women have smaller ovaries and a shorter reproductive lifespan naturally. And that when it is a reality for someone who's delayed their family planning and who wants a baby can be extremely emotionally challenging.
Perimenopause refers to the decade that predates menopause. So when the period stopped forever, perimenopause is when they start to go from completely normal to misbehaving on the way to stopping forever. The initial phase is when the cycles shorten and then the cycles become irregular and then they become sporadic, and then they stop forever. And during that time, periods can misbehave. We also develop different pathologies as we get older that we didn't have when we were younger. Things like fibroids, things like adenomyosis, which is a condition where the muscle of the womb becomes boggy and gland infiltrated as we get older. And so quite often this menstrual dysfunction that happens around perimenopause can also be associated with things like heavy menstrual bleeding and out of control periods.
In terms of fertility, as we age, we have multiple issues that do develop. So one of the issues that develop as we age is just that those other conditions have time to impact us. So conditions we didn't have when we were younger, we may now have. If we are prone to things like endometriosis, it's had time to get worse. Fibroids have had time to grow and cause trouble. Adenomyosis has had time to progress. So those kind of conditions, just by virtue of having lived a life, develop more commonly over time and affect older women compared to younger women.
We also have the physiology of the ovary, which is different between women. Ovaries are different between men and testes. Men make sperm their whole life consistently from puberty until death, whereas women make all the eggs we're ever going to make when we are a fetus. And before we're born, we have them all. And egg cells in waiting have a metabolic reserve. I call it the metabolic picnic basket that is packed at the beginning and that depletes as we age. And the egg is a critical cell when it comes to making a baby. And while paternal and maternal DNA contributions are equal, the cellular contribution to making an embryo is overwhelmingly dominated by the egg and the health of the egg. So one of the problems that women have as we get older and that women do experience in perimenopause is egg quality decline. And that manifests in a lower chance of making a healthy embryo, so a lower chance of getting pregnant. And if we do get pregnant, a higher chance of having a miscarriage or a baby with a chromosome error, because chromosome errors that are spontaneous are more likely to occur over the age of 35.
And because of those two facts, infertility is much more common in older women. So we see that a lot of our patients seeking intervention are in the age bracket of perimenopause, particularly women who are trying to have babies in our 40s. And on top of that, our egg count peaks when we are young and depletes over time. So we do run out of eggs completely around menopause, but that is a process. And one of the ways that assisted reproductive treatments can help women who are struggling to conceive is to try and encourage their ovaries in IVF to mature multiple eggs in the same month so that we have the choice of different embryos, some of which will fail and hopefully some of which will succeed. And so we have a better statistical probability of finding a healthy embryo that has the potential to make a healthy baby. As women get older and as our egg count relatively declines, what that means is we can't make as many eggs in an egg collection for IVF as other people or even compared to ourselves at a younger age. And therefore per cycle of assisted reproductive treatment we have a lower chance of creating that healthy embryo that may make a healthy baby. So those are the challenges to fertility in perimenopause.
Jordi Morrison: Indirectly, you've mentioned this, but a question I have is can you explain the difference between perimenopause and menopause in the context of fertility?
Dr. Raelia Lew: Yeah, absolutely. So menopause means that we don't have menstrual cycles and we don't have eggs anymore that can make a baby that we release currently. It doesn't actually mean that you can't have a baby. I know that sounds really strange, but it's true. So let's just say you have gone through menopause and you haven't yet had your family or you haven't completed your family and you would still like to have another baby. You can still carry a pregnancy potentially if you're healthy and well, but you can't make the hormones to help you do that. And you can't currently make the egg that's going to contribute to that pregnancy.
In earlier stages of your life, if you created eggs or embryos that are frozen and that can be warmed and replaced to your body, you may still, even though menopausal, be able to have a baby with your own egg. And that is really one of the great, enlightening and amazing facts behind egg freezing and embryo freezing. And an example that is actually unfortunately not uncommon is when someone has a cancer. And they have to have life-saving chemotherapy to cure them of their cancer, such as a breast cancer. But that chemotherapy makes them menopausal by poisoning the egg cells in their ovary to the point where they won't be able to regain function. So what we do is if we have a young patient and we have the ability to help them before they have cancer treatment, we will often offer them fertility preservation through freezing eggs or embryos. And we can keep those on ice until they are healthy and able to conceive, and even if they are menopausal, we can create artificially the hormonal environment to support a pregnancy even post-menopause.
And the way we do that is what we call an artificial cycle, where we give a combination of estrogen and progesterone support to ready the uterus for conception. And I often, you know, think that the uterus is a muscle and it's a very special muscle lined with glands. What it needs to become receptive is the right hormonal messaging. And we can give those signals artificially. They don't have to come from the ovary. This is also how we help women have a donor egg-derived pregnancy. So if a woman can't, because she's menopausal or just because her egg quality is so poor with advancing age, create a pregnancy with her own egg anymore, she can still have a baby with a donated egg through an artificial cycle. So we can restore the hormones that are required even if a woman is menopausal.
Jordi Morrison: What hormonal changes occur in perimenopause that start to affect fertility?
Dr. Raelia Lew: Quite often as the cohort of eggs available to recruit in a cycle, a natural menstrual cycle, reduces, the cycle becomes shorter. So the hormonal swings are more profound. Follicle stimulating hormone and luteinizing hormone become quite elevated in the early follicular phase. And ovulation happens a bit earlier in the cycle. And that often is a problem for fertility because the lining of the uterus hasn't had ample time to grow and thicken and become receptive by the time the ovulation occurs.
Paradoxically, though, in the perimenopausal period, that early FSH, follicle-stimulating hormone, peak actually can be associated with an increased risk of, or chance of, multiple birth. And twins are more common in our 40s for that reason naturally, that the elevated follicle-stimulating hormone, because of ovarian depletion, can in some women result in double ovulation. It's nature's way of a last hurrah for fertility for some women and we do see more natural twins in this age bracket for that reason.
Jordi Morrison: Also, if your cycle is changing, that would mean when you are ovulating is changing and would you be more likely to miss it if you're counting the traditional, say, 12 days?
Dr. Raelia Lew: I would also say that your cycle is more likely to be different month to month because there will be intra-cycle variation and that will be more profound. And so one thing I would say to women trying to conceive... if their cycle is not clockwork, is don't rely on an app. I think compared to a decade ago, when I saw very few patients tracking their cycle on an app, now it's very common practice. It's important to contemplate that what the app does is make a series of assumptions in order to offer a future prediction. And if those assumptions are wrong, then the prediction can be very inaccurate. And if you're basing when you're trying to conceive on wildly inaccurate predictions, then you're more likely to have mistimed sex.
It's harder to prospectively know when you're going to ovulate in perimenopause because of the very fact that cycles are quite irregular. And one thing that is useful to understand... that you don't have to have sex on the day you're ovulating to get pregnant. And in fact, it's much more important to make sure that there's sperm waiting in the female reproductive tract in advance than to have sex on the day when you are ovulating. So I always say to my patients who are experiencing cycle irregularity and perimenopause that regular sex from really when your period starts to finish, every couple of days, is your best bet rather than trying to time sex with ovulation. And particularly this is relevant to women in perimenopause with short cycles when ovulation timing month to month may vary considerably.
Jordi Morrison: You mentioned that we develop pathologies as we age and things change in our bodies. How does our egg quality change as we age? And this is really important, isn't it?
Dr. Raelia Lew: Yes. So my friend and colleague, Eve Feinberg, who is the host of the Fertility and Sterility podcast, put it really nicely. In IVF and infertility, age is queen. Age is the most important factor in how fertile someone is as a woman. And egg quality is not a medical term, but it is a term used by doctors and patients to describe how likely an egg may be to be able to make a baby. We see that eggs are of high quality when we are young and the quality of eggs, their metabolic potential, their cellular damage levels and their ability to function without error declines consistently as we get older.
Egg quality peaks in our early 20s actually. Teenagers, egg quality is not as good as in our early 20s, which is surprising, but it's true. When we look at studies, we see chromosome abnormalities more commonly in women in their teens having babies than later. And in our early 20s, that's when we're the most fertile. So there is a degree of maturity required, but then eggs do become post-mature.
We also see in IVF as we get older, an increased chance that a follicle seen on an ultrasound scan before an egg retrieval is more likely to be empty. So the risk of oocyte atresia or cell death of the egg within the follicle increases as we get older. So what we see on ultrasound when we do an ultrasound of the ovary is the follicle count. And that's what I like to say is the house the egg lives in, the structure where the egg is. The egg itself is a microscopic cell that's a thousand times smaller than a poppy seed. And you cannot see it on an ultrasound. In fact, you cannot see it with the naked eye. So when we do an egg retrieval in IVF, we put a needle into a follicle and we aspirate the fluid. And then a scientist uses a microscope to find the eggs. And we hope that each follicle may have one egg inside. But as we get older, we note that a higher proportion of follicles have, over the years of our lifetime, lost their egg. And of the eggs we find, a higher proportion of eggs are showing signs of cellular degeneration, which is what we see in the stages before cell death. So eggs do have a finite lifespan. And much like eggs on the supermarket shelf, they have a use-by date.
So sometimes we can find someone who is older and trying to have a baby, and they still have lots of eggs, but those eggs are poor quality. And that's a big challenge. And unfortunately, ovarian rejuvenation and improvements in egg quality still is something that IVF is not very good at. And one of the ways that we help women at an advanced age in IVF is by a numerical advantage, trying to find the special egg that doesn't make an error.
Another frustrating fact for women trying to get pregnant later in life is that the errors that eggs make are not inborn and they are not necessarily prescriptive in that we don't know that an egg's going to make a mistake before it makes it. And you can have a perfect egg meet a perfect sperm in the IVF lab and then make a terrible mistake as an embryo. There is a degree of luck and chance involved in a good egg making a good embryo. And the likelihood that the egg will trip up and make an error is proportional to how tired that egg is to begin with and how metabolically depleted. And that is a function of age.
Jordi Morrison: So for women in their early 30s, for women in their early 40s who are still getting periods, possibly perimenopausal, possibly not, there's still a chance of natural conception, isn't there?
Dr. Raelia Lew: Definitely. And a good egg can come along naturally just as it can come along in IVF. But we know that when you are young, your chance of getting pregnant per month is about one in five. At 40, it's about one in 20. So that's why we say to women and couples that if you've been trying for six months and you're over 35, come quickly. And I think we all in our society are guilty of really a bit of... sounds very harsh to say self-delusion, but that's really what it is. We don't want to recognize that 35 is old. We think 35 is young.
Jordi Morrison: Oh, my goodness. Imagine looking back when we were 35.
Dr. Raelia Lew: Exactly. So in many aspects, it is in life, in career, in the trajectory of what you can achieve. It feels young, but actually from a reproductive perspective, particularly for women, is considered old. And the terminology that used to be used at 35 was geriatric pregnancy. That's what actually was the medical terminology. And so I guess I think what I would love is for women to, without taking it personally, just get it that 35 is not young from an egg perspective. From an egg perspective, 35 is old and 45 is very old. And with egg freezing, you should do it when you're young. 25 is not too young to freeze your eggs. Certainly 30 is a great age to freeze your eggs. And 35 is getting a little bit old to freeze your eggs. You can still do it. But the point of egg freezing is to bottle that younger fertility before it's compromised.
And likewise, for my patients who need an egg donor, nobody wants an egg donor. No woman wants to have an egg donor. That's nobody's first choice. When women have an egg donor, it's because they can't have a baby with their own egg and they haven't created, or they've utilized resources and it hasn't translated to be able to do that. If you choose an egg donor, they should be under 35. I have patients who come to me, and this is really actually quite common because our friends are generally, as a generalization, similar age to us. And so if we need a donor egg, the people we feel closest to are generally in our similar age cohort. Of patients offer them an egg, which is the kindest, most giving thing. And I have patients who come to me and say, oh, my friend's offered me an egg, she's 43. And it breaks my heart to say, that's so her, but that's not your egg donor. Because for your egg donor to have a good prognosis in going through treatment and to result in the birth of a child, the cold calculated facts of the matter are that you want a young egg donor who has healthy eggs, not an older egg donor who has unhealthy eggs. There's no point doing that.
Jordi Morrison: I want to come back to donor, but just to finish up what we were saying before, we talked about women in their early 40s and spontaneous conception. Is this still possible in your mid to late 40s?
Dr. Raelia Lew: Personally, the oldest patient I've ever been able to help use their own eggs to have a baby in IVF, and that's an outlier, was 45 and 11 months. It's possible, but at the same time, in quoted success rates per cycle initiated with own egg at 45, an IVF doctor looking at Australian statistics has to tell their patient that your chance of having a baby is roughly 2%, which is not very high.
Jordi Morrison: And this is using IVF? This is not spontaneous conception?
Dr. Raelia Lew: Yeah, that's throwing the kitchen sink at it. The thing is that if you flip that statistic, you're telling someone that they're 98% plus likely to fail having an IVF cycle with their own egg. It's very confronting. Now, if that person had frozen eggs from a decade earlier, the stats would be much different for them. And also if they were using an egg donor. It is the egg. It is the age. And that is the barrier, unfortunately.
Jordi Morrison: You mentioned about the errors in the egg or the embryo. That makes me think about miscarriage risk and how that would also change with age.
Dr. Raelia Lew: Yeah, definitely. So your miscarriage risk when you're younger is about one in five pregnancies, which is heartbreaking. But most women who get pregnant will have a baby, not a miscarriage. When you are 40, your risk of miscarriage, if you become pregnant, is 50%. And if you're 45, it's 90%. So those are very sobering figures, but that's the facts.
Jordi Morrison: They are, and I think that's when we talk about the errors multiplying in the egg and the embryo. It's not that the baby will necessarily be born with a genetic defect. It's more that you are likely to miscarry before it could even become a viable pregnancy.
Dr. Raelia Lew: Yeah, that's much more common than things like Down syndrome and other chromosome abnormalities, which are common as well, relatively common compared to at a younger age. But the majority of chromosomal errors result either in pregnancies not working or being lost.
Jordi Morrison: Are there any markers or tests that can help gauge fertility potential? I would think if you are tracking your periods and they're still around the 28-day mark, that would make you think you've got good ovarian reserve, but is that true and what else could we be looking for? Are there many tests?
Dr. Raelia Lew: So the tests we have look at egg quantity, not egg quality. We can do an AMH test, we can do a hormonal profile, but there's no test short of an IVF cycle and looking at your eggs down a microscope and seeing how they interact with sperm and checking embryos for DNA normality to look at egg quality. There will be a variance of quality between women in terms of their eggs. There are women who are more likely to conceive later in life than others. Just like some women look younger at the same age than others, some women's egg quality is better. And that's just, it's not fair, but biological variation is never fair. It would be nice to be a C cup rather than an A cup, I think. But you are what you are, right? You can't really help that too much.
Jordi Morrison: In terms of... you can, but not genetically.
Dr. Raelia Lew: Correct. You can help yourself in non-genetic ways. And it's the same, I guess, in a way with assisted reproduction. We can help ourselves. We can't stop ourselves getting older. We can't stop our egg quality declining. We can be proactive. We can plan for the future. We can freeze eggs. We can freeze embryos. We can plan to have our children at an earlier life stage, recognizing that fertility is not infinite and that other things that we sometimes prioritize earlier in life could be deferred to later in life without compromise. So to some degree, it's a perspective and also being in the right position. And not everyone has a partner. Not everyone wants to have a baby without a partner. It's complicated. Just having a good understanding and having the knowledge is very powerful.
And the biggest thing I can say to listeners out there who may be in this kind of peri phase of life is if you want to still have a baby, don't pass go, get help. Get checked out at an early stage because there is nothing more depressing than someone walking into the fertility doctor's office and they are really in the last throes of potential fertility and they tell me they've been trying to conceive for two to three years. And if they had come to me at the six month mark, I could have helped them much more successfully than if they wait and only come as a last resort. If you're trying to have a baby in the last vestige of your fertile years, don't be shy to seek help, because that might make the difference between success or not.
Hosted by Dr Raelia Lew and Jordi Morrison
Dr Raelia Lew is a RANZCOG Board Certified CREI Fertility specialist, Gynaecologist and the Director of Women’s Health Melbourne.
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