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).
- Folliculogenesis – the development of the follicle within the ovary
- 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.
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.
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.