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

My Chart and My Health Check Results

My temperature went back up today, hurrah! So I think I really have finally ovulated, but we’ll see when fertility friend gives me my crosshairs.

What I will say is that my boobs feel like two great big rocks on my chest, so I know my hormones are sky high.

I know I shouldn’t, but I am really holding out hope for this month. I think it’s just because I managed to have my son like this, straight after a miscarriage, that it feels somehow like it might do the trick. I think DH is relieved that my temperature has gone back up again, ha ha.

In other news, I visited the doctors this morning for my 40-74 year old health check. This is a nationwide scheme the NHS are rolling out here to screen for risk of diabetes, kidney disease, heart disease, stroke and dementia.

I was a little worried there might be something unexpected (I really love my cheese and wine), but it was great. My blood work is, without wanting to sound too far up my own backside, awesome. Ha ha! The nurse said she’d never seen someone with such a low calculated risk of cardiovascular disease.

This is especially important to me, because the last blood test I had done, two years ago, showed I was clinically deficient in blood serum potassium and blood serum calcium, had extremely high inflammatory markers (reactive C protein) and was generally pretty crap.

Not only that, but I dug out a blood panel I had done in 2006 and compared the results – I am better in every way than I was in 2006 – almost 9 years ago. My thyroid function has improved incredibly (TSH from 4.5 to 1.98!), my cholesterol is lower now than when I was 31 (and is now less than half the average level in this country). Even my kidney function has improved (which apparently it isn’t supposed to be able to do).

I think I was probably living with the consequences of coeliac disease for far longer than I realised.

I notice now how much faster I recover after exercise, and how much energy I have in general throughout the day. My aches and pains have all pretty much disappeared and my joints no longer complain about doing things. And most of all, since going gluten free, I have been so much happier. When your health is sub-par it affects everything, even your mood.

It’s taken me a long, long time to get to this point, but now I am so pleased that for all these years I have persevered with slowly moving to a diet that contains more raw food, less caffeine, less refined sugar, and consistently trying (and often failing) to make exercise a normal part of my life. Best of all I have never taken any medication – I have done it all through eating better and moving more.

So… given my glowing report, and how good I feel these days, there’s only one thing left for me to put behind me.

Recurrent pregnancy loss.

One good egg. That’s all I need.

My Chart So Far

So, this morning my temperature shot up.

Now… this could be a coincidence…

But all my ovulation signs are there – fertile cm that dried up yesterday, pain/twinges in my ovaries, sore boobs, and two days of positive opks, followed by a negative opk. Also, my spotting has stopped completely today.

My pregnancy test this morning was the equivalent of an evaporation line – the kind of test that if you get during the two week wait, you spend hours contemplating and wondering if it actually means anything. I’ve marked it as positive, because I know that the teeny shadow I can see means there is a tiny amount of HCG still leaving my body. I’m certain it will be officially negative tomorrow.

decchart

Note the temp I’ve ignored on 1st January? That’s because I drank loads the night before which always affects my reading in the morning. Hic.

Anyway, so I think I’ve ovulated. Nine days after my full-on bleed.

I also think that the sac came away inside when I had all the bleeding, but just didn’t make it’s way out of my body until Saturday. I didn’t get any bleeding when it finally (and so surprisingly) came out, which would imply it had just been sitting there for a while.

If this is true (which I really hope it is), then it means I am back in the two week wait. Hurrah! DH and I talked about it this morning and we decided we’re not going to be disappointed if nothing comes of this (well, okay, I will be, but whatever).

I’m really pleased about this – shall I tell you why?

Of course I will.

I’m super-pleased about this because TTC is all about

WAITING

That’s just what we do. We wait, we wait, and we wait some f*cking more. Nothing ever happens quickly. Ever.

So to suddenly be faced with the prospect of sailing into a two week wait when I was still vaguely wondering what had happened inside my body with the miscarriage is quite simply, awesome.

And not only that, but when I got pregnant with my first son it was immediately following a miscarriage at 6w5d. I ovulated then on day 12. So I feel kind of lucky at the moment. And you know how everyone always tells you you are more fertile after a loss.

Now, you watch as my temp plummets tomorrow and the universe laughs at my pain. Hah!

No. That’s not going to happen.

Good thoughts only!

This morning’s POAS adventures

I’ve been checking my pregnancy test results over the last week, waiting for a clear negative, because I thought that meant we’d be back to square one with regard to trying again.

However, yesterday evening, even though I am still spotting from the miscarriage, it was (TMI warning!) very stretchy and shiny – i.e. my body seemed to be producing fertile cervical mucus.

So this morning at about 10:30am I did a pregnancy test AND an ovulation test at the same time. Yeah, I know. It’s crazy to be peeing on two different kinds of tests during one wee, right?

And this is what I got:

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The top test is for LH – a definite positive. The bottom test is for HCG – a faint positive.

I didn’t think you could ovulate until the HCG cleared your system*. I’ve read that you can get a positive OPK when you are pregnant (apparently the difference between LH and HCG is down to a few amino acids and LH tests can detect HCG, but HCG tests cannot detect LH – weird eh? Never tested this myself, but that’s the theory). Anyway, my pregnancy test result is clearly very faint – so I wouldn’t expect it to affect the OPK so much. I’d put myself on cycle day 8, given my temp/bleeding pattern so this is a bit of a mystery.

I do have a bit of ovary pain, which I’d assumed was post-miscarriage stuff, but actually it is the same swollen feeling I usually get during ovulation.

Well, we let the kids watch a movie and dtd anyway, just in case. It’s not like I’ve got any time to waste. I’ll see what my temperature does over the next couple of days.

*Although, thinking about it, don’t fertility clinics use HCG as a trigger to prompt ovulation? If that’s the case, then HCG should exacerbate the ovulatory response, not inhibit it?

97.9

That was my temperature this morning.

It is the most ambiguous temperature in my cycle. Historically it tends to be the first post-O temp that I get. But it also makes an appearance a few times before ovulation. It’s like the mid-point of my body temperature, and my pre and post ovulation temps pivot around that point.

Which means that I am never really sure if I have ovulated when I get this reading in the middle of the month and so, we never really know whether we need to BD that evening or not.

It’s just annoying. Why can’t it just do a great big jump up to 98-something so I know for sure what’s going on?

So, here we are, CD16, trying not to obsess (but clearly failing), and wondering if I am going to be able to step away from ovulation next month.

I’ve been thinking a lot about this blog too, and wondering if a small part of my difficulty in moving on is because I love to write on here. It’s the only place, in the whole wide world, where I can sit and pour my heart out without fear of judgement or pity. It’s just a matter of fact record of what’s going on with me, and I like that a lot. It’s the only place I can write about my obsessions and fixations and not have to listen to people saying “don’t you think it’s time to let go?” or “it’s all for the best, just think how lucky you already are!”. I know these things, but that doesn’t change the way I think and the time that it takes to genuinely move on from these things without ending up in the loony bin.

So, to recreate this environment, I have been thinking about blogging more personal things under my real name, because I really do love to write about what I’m doing. But my main problem with that is that I don’t want my family and friends to read it.

Bah.

I have this need to talk about my feelings and to connect with others, but I can’t do it in real life. Crazy.

Yeah.

So that’s me on this rainy autumn morning.

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