The Life of An Egg – Folliculogenesis And Oogenesis

I’ve been doing a TON of research over the last two days. Given the fertility clinic had no new ideas, and even suggested it might be time to call it a day as our chances with IVF were so uncertain, I think we are really on our own here.

So, we’ve formed a plan, but before that I want to go into great detail about the actual process of egg development – because I had misunderstood what actually happens at a cellular level and I think it has impacted my approach.

Feel feel to skip this if you’re not into the nitty gritty details.

There are two processes that are important with regards to creating an egg that can be fertilised into a healthy baby (and I’m deliberately ignoring the sperm side of the equation here, although healthy sperm obviously do play a large part).

  1. Folliculogenesis – the development of the follicle within the ovary
  2. Oogenesis – the development of the egg within the follicle

Part 1: Oogenesis

Chromosome abnormalities occur in eggs during a very, very brief window (again, excluding meeting with the sperm where the second set of chromosomes are added). These abnormalities happen during a process called meiosis, which is the division of the egg cell to create an ovum that contains only 23 chromosomes – half the amount needed to make a new human.

Now, meiosis is really interesting because it actually starts when you are in the womb. Meiosis is divided into two phases – meiosis 1 and meiosis 2. When you are born, all your eggs are suspended in the prophase of meiosis 1. What this means is that the cell division has started, but has effectively been frozen.

Years later, when you enter puberty, these eggs are recruited during a menstrual cycle to complete meiosis.

Only the dominant follicle (the egg you actually ovulate with) completes meiosis 1 (i.e. splitting into two to halve its chromosome number) and this happens in reaction to the LH surge before ovulation. The splitting process in meiosis 1 is very complex, involving crossover of the chromosomes to make two genetically different cells. One of the two new cells is very small and remains with the egg as the polar body (all polar bodies eventually degenerate).

The window for chromosomal abnormalities is therefore in the final days before ovulation.

Once that division has occurred, and the egg bursts out of the follicle, the chromosomal contribution from the mother is complete. Meiosis 2 only occurs if the egg is fertilised by a sperm. This chromosome “dance” however is more straightforward – it is an alignment of maternal and paternal chromosomes followed by a simple division (akin to normal cellular division, or mitosis).

The egg (and the polar body, although not always), divide to make 2 cells each.

The result is one fertilised egg, and three polar bodies.

That egg will (hopefully) grow into a blastocyst, implant, and turn into a healthy baby.

So here’s the important part of this process:

The egg is “frozen” at birth and although it grows in size (it takes nutrients from the follicle – see below), the actual change from frozen-birth-egg to egg-we-ovulate occurs in response to the LH surge. i.e. in the days before ovulation.

The egg cell requires energy to complete meiosis – a huge amount of energy. This energy is supplied by tiny “organs” in our cells called mitochondria. Mitochondria basically turn our food into cellular energy (ATP). That’s it. What we eat fuels mitochondria either well, or badly.

And once your egg bursts out of the ovary and gets fertilised, if the mitochondria can’t make enough energy, that egg is not going to be able to divide and grow like it should.

So this brings me to my first ah-ha moment.

Because of our repeat losses, and my coeliac diagnosis and my focus on immune issues up until now, I have been extremely careful in the two week wait – the window of implantation. That is my time when I don’t drink, I try to eat really healthily and I try to get enough sleep each night. Before the two week wait, I was assuming everything was ticking along happily. I thought my problems started when the egg actually got out of the ovary.

But actually, it makes more sense that the week before ovulation is the crucial one. That goes some way to explaining why older women can carry a pregnancy with (younger) donor eggs, but can’t carry a pregnancy with their own eggs, even via IVF.

What if, in the week before ovulation, I stopped having the odd glass of wine, and rushing about, and eating on the run?

What if all the green smoothies and healthy food I’ve tended to focus on in the two week wait was just too late?

What if I changed my approach to look after my body very, very carefully in the days before I actually ovulate? When my body is using up vast quantities of cellular energy to create a healthy egg? What if I flooded my body with good food and nutrients in the week before ovulation?

It’s something I haven’t tried before.

Okay, onto Part 2

Part 2 – Folliculogenesis

Now, it turns out that the “improve your egg health in 90 days” thing comes from what happens to the follicle not the egg.

Follicles start out as primordial follicles in the womb, and just like the eggs they contain, they don’t do much of anything until puberty.

At this point, they are recruited into a growth stage, many at a time. The initial growth phase lasts around 300 days (!). Interestingly, this period of very slow growth is hormone independent – so it doesn’t matter how out of whack your cycle is, the hormone craziness is not affecting the follicle.

Then, about 65-70 days before ovulation, the follicles become early antral follicles that are hormone dependent. Antral follicles have a small pocket in them which is filled with follicular fluid (this is absent before this point).

For the next 50 days, they grow at a new, faster rate, providing a support structure that actually feeds the egg inside, with nutrients and hormones, and removes waste products from the egg. Kind of like the placenta that will develop and support a growing baby.

At the end of a menstrual cycle, about 15-20 days before the next ovulation, and a few days before your period arrives, the follicle enters a new, even faster growth stage which takes it to maturity – the point at which the egg is released.

Now, not all follicles develop – the death of growing eggs is called atresia, and is very high.

It’s estimated that around 1,000 eggs are lost each month (and this number decreases with age, because less follicles are recruited to enter the growing phase as we get older).

Since only one egg makes it to ovulation, and follicles are constantly being recruited out of the primordial pool, that means about 35 follicles are recruited to grow each day (and a similar number die off each day).

The process of selecting which eggs make it and which don’t is poorly understood. I would like to think (and I would imagine nature would intend that) the healthiest eggs are the ones that stay the course.

Now here is the next thing that just blows my mind – because I didn’t understand it before.

In preparation for IVF, FSH injections are given in the early part of the cycle so that the FSH level never declines, as it would normally. This sustained elevation of FSH, which is all that the administration of ovulatory stimulation hormones amounts to, sustains almost all of the thirty or so antral follicles so that no single follicle can gain dominance over the others. Therefore, the number of eggs retrieved in a hormonal stimulation cycle for IVF is directly reflective of your antral follicle count, and your antral follicle count is directly reflective of your total remaining number of eggs. [Source]

So, essentially, every single egg that you collect for IVF comes from an already formed antral follicle on the day you start the injections. Every egg is the product of the previous 65-ish days worth of growth. Your body would have rejected all but one of those eggs, yet IVF takes them all (or, as many as it can get).

And the most amazing thing of all is they can still make healthy babies!

Anyway, I’m getting off topic a little bit.

The big ah-ha for me regards folliculogenesis is that if you count back from the day of ovulation, the eggs in your ovaries truly are a product of your lifestyle in the preceding 70 days. And most importantly in the preceding 15-20 days, when the follicle undergoes the most rapid growth spurt and the remaining eggs are the ones already deemed to be the best by your body at that stage.

Follicular Fluid

I mentioned follicular fluid above, which is present in the hormone dependent growth stage, in each follicle.

The rate of follicular fluid formation in the final days before ovulation rises about 50-fold above that of the previous phase, and substances in our body can flow freely into and out of the fluid cavity in the follicle. In fact, hormones flow into the fluid in order to influence the growth (or atresia) of the follicle – hence why the follicle is not hormone dependent before the antral follicle stage.

Studies have shown that BPA makes it into follicular fluid, as does caffeine, cadmium (smokers), the broken down products of alcohol, and glucose (which is toxic to the body unless it is used by cells for energy).

Basically, what we eat, and what we are exposed to, finds it way in microscopic form right up to the nutrient delivery system of our growing eggs.

Conclusions?

I think I’ve been focusing far too heavily on the two week wait, and early pregnancy. Given I get pregnant and keep losing them, I suppose this is understandable – why would I have thought there was an issue with what was happening before fertilisation took place?

But I hadn’t realised the complexities of what goes on to create an egg – especially in the two weeks before ovulation and the vitally important days leading up to ovulation.

I know that at least one of our losses was chromosomal, and I suspect my missed miscarriage was too, because the consultant at the time said the sac and baby did not look normal (stopped growing three weeks earlier).

Saying that, I have had one loss tested which was chromosomally normal, although I was still eating gluten at the time and I know my body had a high level of systemic inflammation back then.

I’m pretty sure there isn’t a single answer that will cover all my losses, but going forward, and given my rapidly advancing maternal age (ha ha), care of my eggs should be a priority at this point.

Which leads me onto my next post: what we’re going to do now.

PS If you’ve read this far, you deserve a medal.

Sources

Physiological factors underlying the formation of ovarian follicular fluid

How does the biological clock work?

Folliculogenesis (Wikipedia)

Ovulation (Human Embryology)

Oogenesis (Human Embryology)

Follicle growth and development

13 thoughts on “The Life of An Egg – Folliculogenesis And Oogenesis

  1. Very interesting, thanks for sharing, Rose! I read your last post, but haven’t had a chance to comment yet. I think that “line in the sand” comment is BS! Obviously you don’t want to draw a line in the sand, that’s why you were there. People need to think before they speak, especially doctors!

  2. Yay! Medal for me even though it is my bedtime I read ll the way. lol

    I love this quote:
    “It’s estimated that around 1,000 eggs are lost each month”

    Well that explains what happens to all the eggs we get at birth. I honestly always wondered about that. Where did they all go? Especially when stimulation doesn’t bring hundreds of them.

    This is all really helpful for me moving forward and really confirms that whole thought process for me that “food is medicine”. if you can keep it clean and healthy for a prolonged period of time then you chances of success are higher. I truly believe that.

    Thanks for this super informative post. Now off to bed x

    • Yep – same here – I truly think, now more than ever, that what we eat and drink, along with our environment is the best way of swinging the odds in our favour. Extra large medal for you for reading it all AND so late at night!! Xxx

  3. Thank you for this Rose! I too, used to focus on the TWW more as the limiting phase of TTC, until the recurrent losses, and then I started to wonder about egg quality. One loss we were able to test, and it was a chromosomally normal girl. I also have celiac disease, and was super clean last year when I was undergoing our first IVF. I was however, exercising like a fiend. I think I was lifting weights and doing spin classes daily, as well as playing hockey once a week until day 6 of stims. That’s what I’ve done differently this time, plus the supplements. I can’t wait to read the next part of your post! This was well written and informative, and this is coming from a person who has taken grad school courses in embryology and molecular genetics!

    • Oh my goodness, thank you 🙂 I’m a bit of an OCD information collector to be honest. I didn’t realise you were ceoliac – how did I miss that? That is a lot of exercise though – I think you are doing the right thing easing off this time around. It’s so easy to get obsessed with the two week wait – I feel like I’ve been a bit naive. Hang on – am going to switch from phone to computer as more to type…

    • Interesting that you also had normal chromosome report back from fetal testing. I’m beginning to wonder if the chromosomes themselves are only half the story and the actual quality of the egg cell, regardless of chromosomes, also plays a large part in whether it can divide and grow properly. I don’t know – it’s just so complex, and our lives are so far removed from what we evolved to be like. I WISH I had more answers, I really do. I’ve searched and searched, but everything I try is based on best guess. It’s so hard!

      • I think that for me, the egg quality and embryo quality were okay, but that my body is always so inflammed. I generally don’t tolerate stress very well (my blood levels reflect it almost immediately), and my NK cytokines are abnormally high- indicating that I have usually high levels of inflammation. I’m trying to be careful of what I eat, as beyond the celiac, I think that I have IBS (food intolerances beyond the gluten). I myself only had one miscarriage though. My wife miscarried twice (4 amazing quality blastocysts), and we suspect that it was her body and not the embryos. Really though, we haven’t a clue, so I’m just doing my best to be stress-free and inflammation-free throughout this process.

        • Stress is such a strain on the body – I’ve had to work really hard over the last couple of years to reduce stress. It’s been an emotional process! It doesn’t help that TTC is so stressful in itself. I feel so much better when I’m not on the verge of yelling all the time though. Two mcs with excellent blastocysts must be so hard to bear :-(. I think like you say, all we can do is try our hardest to make our bodies as hospitable as possible. It really gets on my nerves that others can eat whatever they want, drink smoke and still have kids. Although, if I’m honest, I haven’t heard of any hard-drinking, hard-smoking, crap-eating 40 year olds getting pregnant recently – it tends to be reserved for the young – so maybe it’s not that unfair 🙂

          • Yeah. Time is a real bitch. It flies before we know what we have missed, and we will it away when we can’t bear to stand the pain of the present. I too am angry at the unfairness of who gets pregnant so easily. I try to curb it, but when my next door neighbour’s deadbeat chain-smoking-throughout-pregnancy grandson and gf move in, or my teenage teammate has her SECOND accidental pregnancy that she doesn’t even know the father of (and played hockey 2-3x per week throughout her pregnancy until she was delivering), I lose my faith in there being a greater good. But you’re right- they’re all young.

  4. Wow. I knew part of this info from going to vet tech school, I guess I just never really thought of it in this aspect of my life. Some amazing info, thanks so much for sharing!!

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