IVF卵子成熟度解析：GV、MI、MII、2PN与3PN

今天我们聊聊卵子成熟度，也就是当胚胎学家说卵子是GV、M1或M2时，到底是什么意思。我是医生。

Today we talk about egg maturity what it means when your embryologist says an egg is either a GV, an M1 or an M2 I'm Doctor.

马克·阿莫斯，这里是TacoBoutFertility周二节目。

Mark Amols and this is TacoBoutFertility Tuesday.

取卵之后，通常第二天你会接到电话，告诉你有多少卵子受精了。但在受精之前，这些卵子来自卵泡。

One of the things that happens after you undergo an egg retrieval is you usually get a call the next day, telling you how many of your eggs fertilized, but before they can fertilized those eggs refers follicles.

如果你有，比如说，14个卵泡，可能取到了14个卵子。

And if you had, let's say 14 follicles, maybe you got 14 eggs retrieved.

大家可能会想，那这些卵子应该都是成熟的吧。

And the thought is that maybe then all will be mature.

但成熟到底是什么意思呢？

But what does that mean?

成熟。

Mature.

好，今天的节目，我们要来详细讲讲成熟度是什么意思，如果卵子不成熟又意味着什么，还有GV、M1、M2这些，对你和你的卵子质量有什么影响。

Well, today's episode, what we're going do is break down what it means by maturity and what it means if they're not mature and things like GV and M1 to M2, what does that mean for you and your egg quality?

因为当你取了14个卵子，被告知10个是成熟的，只有7个正常受精时，很自然地，下一个问题就是：等等，那另外7个怎么了？

Because when you have 14 eggs retrieved and you're told 10 were mature and that only seven fertilized normal, understandably, the next question is, wait a minute, what happened to the other seven?

然后你就会开始想，是不是那些卵子质量不好？

And then you start thinking things like, well, were they bad eggs?

是不是医生操作失误了？

Did the doctor mess up?

是不是我的夜针打得不好？

Was my trigger not well?

其实答案很简单。

And the answer is pretty simple.

实际上有很多原因。

It's actually many things.

因为试管婴儿不是单一事件。

Because IVF is not one event.

它是一系列关卡。

It's a series of checkpoints.

卵子得先取出来，得成熟，得受精，然后发育成胚胎。

The egg has to be retrieved, has to be mature, has to fertilize, then develop into an embryo.

然后这个胚胎得发育到囊胚阶段。

Then that embryo has to reach the blastocyst stage.

到了囊胚阶段的胚胎，染色体还得是正常的。

And then that embryo that reached the blastocyst stage has to be chromosomally capable.

然后它得着床，最后希望能长成宝宝。

Then it has to implant and then hopefully become a baby.

所以你看，今天我们只是简单看看这个过程的一部分。

So as you can see, today, we're gonna take a small glimpse at one part of this process.

在接下来的几期播客里，我们会聊聊其他部分。

And over the next few podcasts, we're gonna talk about the other parts as well.

接下来要说的事情挺神奇的。

So here's the wild part.

其实，在女性还没出生之前，她很多未来的卵子就已经开始了减数分裂的过程。

Before a woman's even born, many of her future eggs have already started the process of meiosis.

当你在妈妈肚子里的时候，数百万个卵子会经历一个叫做减数分裂的过程。

While you're in your mother's womb, millions of eggs undergo a process called meiosis.

减数分裂有点像有丝分裂的亲戚。

Meiosis is kind of like the family member to mitosis.

有丝分裂就是细胞分裂。

Mitosis is when cells divide.

减数分裂是一种特殊的细胞分裂方式，精子和卵子会把染色体数量减半。

Meiosis is a special type of division where the eggs and the sperm reduce the number of chromosomes by half.

所以不是46条染色体，而是变成23条。

So instead of having 46 chromosomes, they go down to 23.

这是因为当它们结合时，又会恢复到46条。

And that's because when they then join together, they go back to 46.

对于精子来说，你有一个原始细胞，然后会发生的是，你把它分裂。

Now for sperm, you take one original cell, And then what happens is you split that.

然后分裂出来的部分再翻倍，这样你就得到四个真正的精子。

And then that part that split doubles, that gives you four actual sperm.

但卵子就不一样了。

But eggs are different.

卵子在出生前其实并不会完成整个过程。

The egg doesn't actually finish the process before birth.

它开始减数分裂，然后有时会停滞几十年，处于一个叫前期一的阶段。

It starts meiosis and then it pauses for decades sometimes in a stage called prophase one.

只有当前期一重新启动时，减数分裂才会继续进行。

And then only when prophase one is restarted, meiosis restarts.

刺激的作用就是让它在减数分裂的早期阶段重新启动。

The stimulation is unpausing it in that early part of meiosis.

在治疗过程中，随着卵泡长大，它们最终会达到一个可以成熟的尺寸，然后触发针告诉它们：好了，现在真的该动了。

As the follicle grows during treatment, eventually they get to a size where they're ready to be mature and the trigger shot tells them, okay, now let's really move.

我们用的是HCG，但它模拟的是自然发生的LH高峰。

Now we use HCG, but that makes the natural LA surge that occurs naturally.

然后接下来发生的是，卵子会分裂，但分裂是不均匀的。

And then what happens is the egg will divide, but it divides unevenly.

和精子不一样，精子会产生四个细胞，而这里是一个大细胞加一个很小的极体。

Unlike the sperm where you get four cells, you get one bigger cell and a tiny polar body.

那个小极体就是那23条染色体，它们会被排出去，因为要为大细胞腾出空间。

That small polar body is those 23 chromosomes that are going to be ejected because you're trying to make a bigger cell for the egg.

到了这个阶段，卵子就成熟了。

At this point, this is a mature egg.

它可以和精子结合受精了。

It can fertilize with the sperm.

那我们来说说三种成熟度标签。

So let's start with three maturity labels.

第一种是GV卵，也就是生发泡。

A GV egg, which is a terminal vesicle.

这是一种非常非常不成熟的卵子。

It is a very, very immature egg.

在显微镜下看，你其实能看到卵子的细胞核。

When you look in under a microscope, you actually can see the nucleus of the egg.

如果我们看到这种情况，就知道卵子还停留在减数第一次分裂前期的早期阶段，还没有开始走向成熟。

If we see this, we know the egg is still frozen in the earliest phase of prophase one and has not started towards maturation yet.

接下来是M1期，也就是减数第一次分裂中期。

Next comes M1s, which is metaphase one.

M1期的卵子已经重新启动了减数分裂的过程。

The M1 egg has already restarted the meiosis process.

生发泡现在已经消失了。

The germinal vesicle is now gone.

卵子已经收到了触发针的信号，需要完成减数分裂。

The egg has now gotten the message from the trigger shot that needs to finish meiosis.

但问题是，当你观察卵子时，会发现没有极体。

But the thing is, when you look at the egg, you'll notice that there are no polar bodies.

这是因为它实际上并没有完成减数第一次分裂。

And that's because it doesn't actually finish meiosis one.

它停在中期，具体来说就是第一次分裂的中期。

It stops at metaphase, and specifically that means the first metaphase.

现在，这些M1卵子中的一部分会在接下来的几个小时内继续在实验室里成熟。

Now some of these M1 eggs will continue to mature in the lab over the next several hours.

有些会变成M2，这些被认为是完全成熟的卵子。

Some will become M2, which are considered mature eggs completely.

有些则不会。

Some will not.

而且，即使卵子在实验室里后来成熟了，它的发育潜力也可能不如在卵巢中按时成熟的卵子。

And even when an egg matures later in the lab, it may not have the same developmental potential as an egg that matured on schedule in the ovary.

现在我们来看M2，也就是第二次减数分裂中期。

So now we have M2s, metaphase two.

它已经完成了减数分裂的第一阶段，现在停留在第二次减数分裂中期。

It's completed the first stage of meiosis, and now has stopped at the second stage of metaphase.

这个阶段我们称之为成熟。

This is a stage we call mature.

卵子已经完成了减数分裂一，并排出了第一极体。

The egg has completed meiosis one and pushed out its first polar body.

正是这个极体告诉我们，卵子现在已经准备好接受精子了。

It is this polar body that tells us the egg is now ready for the sperm.

现在要明白，MIIa意味着它已经成熟到可以受精了。

Now it's important to understand that an MIIa means it's mature enough to fertilize.

但这并不代表基因正常。

It does not mean genetically normal.

也不代表质量高。

It doesn't mean high quality.

甚至不保证你一定能得到胚胎。

It doesn't even mean it guarantees that you're gonna get an embryo.

当然更不保证能生出宝宝。

And it definitely does not guarantee a baby.

它只是告诉我们，这是一个准备好的信号，可以受精了，但并不是质量的保证。

It just tells us that it's a ready signal and ready for a fertilization, but not a quality guarantee.

所以有一个问题，为什么卵子必须是M2呢？

So one question is, why does the egg need to be m two?

这里就是DNA变得非常有趣的地方。

Well, this is where the DNA gets very interesting.

在减数分裂开始之前，卵子和其他细胞一样，有46条染色体。

Before meiosis start, the egg has some basic chromosome counts that the rest of my has, which is 46.

它们排列成23对。

And it's arranged in 23 pairs.

在细胞分裂之前，这些染色体会复制DNA并分开。

And before cell division, those chromosomes copy their DNA and split.

但在减数分裂中，就像我提到的，我们把染色体数量减少到23条。

But in meiosis, as I mentioned, we're reducing the number of chromosomes down to 23.

对于卵子来说，这种不均匀的分裂也会不均匀地分配细胞质和细胞器，把主要的留给卵子，然后形成这些较小的极体。

When it comes to the egg, that uneven split also unevenly takes things like the cytoplasm and organelles and keeps it for the main egg and makes these smaller polar bodies.

目前我们还不清楚是什么信号让卵子开始从前期I发育，但我们知道当它处于中期II时，它已经准备好一组染色体来贡献了。

At this time, we don't know what the signal is that makes the egg start growing out prophase I, but we do know that when it's at metaphase II, it then has one chromosome set ready to contribute.

它正好停在那个时刻，等待精子的信号来正确完成第二次减数分裂。

It is paused exactly at the moment where a sperm signal can trigger it to finish meiosis II correctly.

而精子这边呢，进来的时候就已经是23条染色体了。

The sperm on the other hand comes in already at 23 chromosomes.

它不需要再分裂了。

It doesn't need to divide again.

正是精子的进入激活了卵子。

It is the sperm entry that causes the activation of the egg.

基本上，它会产生一个信号，在卵子内部引发钙波。

Basically it creates a signal that causes calcium waves inside the egg.

这些钙波告诉卵子：你已经被受精了。

Those waves tell the egg, you were fertilized.

现在完成第二次减数分裂吧。

Now finish meiosis two.

这时，第二极体被排出，剩下的DNA就形成了雌原核。

At that point, the second polar body is released, And the other piece of DNA creates the female pronucleus.

与此同时，精子的头部开始解包，而精子的DNA是以极其紧密的状态到达的。

At the same time, the sperm head starts to unpack, and then the sperm DNA arrives packed incredibly tight.

然后卵子的细胞质会去掉精子的包装，这样精子的DNA就能变成雄性原核。

The egg's cytoplasm then strips off the sperm packaging and that allows the sperm DNA to turn into the male pronucleus.

这真的很重要，因为不仅仅是成熟度要有正确的染色体数量。

And this is really important because it's not just about maturity having the right chromosome numbers.

细胞质也成熟了，这样精子进入时能激活，完成第二次减数分裂，并产生第二极体。

The cytoplasm also has matured that allows the activation of the sperm when entry, allows for completion of meiosis two, and to create the second polar body.

解开精子的DNA，让它能构建雄性原核。

Unpacking that sperm DNA allows it then to build the male pronucleus.

然后第二天，当他们看那个胚胎，发现确实受精了，就会看到两个原核，一个来自雄性，一个来自雌性。

And then the next day, when they look at that embryo and they see that it did fertilize, they'll now see the two pronuclei, one from the male and one from the female.

在我们讨论这些原核是什么之前，先回到那些极体。

Now before we get into what those pronuclei are, let's go back to those polar bodies.

它们是什么？

What are they?

它们含有卵子故意不保留的染色体物质。

Well, they contain chromosome material that the egg intentionally was not keeping.

就像我说的，它分裂得不均匀，几乎保留了所有的细胞质、线粒体、蛋白质和细胞自身的机制。

As I mentioned, it divides unequally, keeping nearly all the cytoplasm, the myochondria, the proteins, and the cellular machinery itself.

极体只是带有少量细胞质的小块DNA，就是为了把它丢掉。

The polar bodies are just little pieces of DNA with a tiny bit of cytoplasm just to get rid of it.

减数第一次分裂后，卵子还没有极体。

After meiosis one, the aequal didn't have one polar body.

它只完成了一次分裂。

It's undergone one division.

受精后，它激活卵子完成减数第二次分裂，现在就会有两个极体了。

After fertilization, it activates the egg from meiosis two to finish, and now we'll have two polar bodies.

正是这些极体让我们知道卵子是否受精了。

It is these polar bodies that let us know if the egg fertilized or not.

第二天早上，胚胎学家进来，看看你的卵子，然后寻找一些迹象。

Now in the morning, the next day, the embryologist comes in, looks at your eggs, and then they look for a finding.

第一个迹象是，有没有两个极体？

The first is, are there two polar bodies?

如果有的话，我们就知道卵子已经受精了。

If there is, we know that the egg fertilized.

接下来他们要看的是原核。

The next thing they look at are the pronuclei.

他们希望看到两个，一个来自母方DNA，一个来自父方DNA。

They wanna see two, one from the maternal, one from the paternal DNA.

我们称之为2PB和2PN。

We call that 2PB and 2PN.

这种形态只会出现很短的一段时间。

Now this appearance is only there for a short period of time.

这两组遗传物质最终会结合，然后进行第一次细胞分裂。

Both of those packages of genetic material will eventually combine, and then will undergo its first cell division.

如果你有两个极体和两个原核，那是个非常好的消息。

If you have two polar bodies and 2PNs, that's very good news.

这表示它受精了，但并不意味着它会继续发育。

Now it means it fertilized, but it doesn't mean it's gonna keep growing.

有2PN并不代表胚胎的染色体一定正常。

2PN does not mean the embryo is guaranteed to be chromosomally normal.

它只说明在观察的那一刻，受精的模式看起来是正常的。

It means the fertilization pattern looked normal at the moment they looked at it.

看到两个原核也是一样的道理。

The same thing with seeing two pronuclei.

这正是我们想看到的。

That's what we wanna see.

但有时候我们会看到不止一个原核，有时候甚至一个都没有。

But sometimes we see more than one pronuclei or sometimes even less than one.

这个我们待会儿再讲。

We'll talk about that in a minute.

不过先说说极体多的情况吧。

But first let's talk about what about extrapolar bodies?

有时候实验室第二天观察卵子时，会发现多了一个极体，有时候甚至有三个、四个，甚至更多。

Sometimes the lab looks at the egg the next day and notices that there's an extrapolar body, sometimes three, four, even more.

这可能会让人有点困惑，因为你会开始想，这是不是意味着胚胎有多余的染色体，所以才会有多余的极体？

And that could be a little bit confusing because then it starts to wonder, does this mean it has extra chromosomes and that's why there's extra polar bodies?

嗯，有可能，但也不一定就是那样。

Well, can, but it doesn't necessarily mean that.

极体也可能碎裂，看起来很像，但也可能是非典型的非整倍体。

Polar bodies can also be fragment and they can look very similar, but it also could be an atypical of anemiosis.

所以极体数量是个线索，但它不是DNA检测。

So the polar body count is a clue, but it's not a DNA test.

基本上，我们会看整体情况。

Essentially, we look at the whole picture.

我们会看原核的数量、时间、卵子的外观，以及胚胎的发育情况。

We look at the number of pronuclei, the timing, the appearance of the egg, and how the embryo develops.

然后如果最后回顾，我们可以说，哦，我们注意到这些胚胎没有成功，而且它们有额外的极体，那可能就是原因。

And then if we look back at the end, we can say, oh, we noticed these embryos didn't make it, and they had extra polar bodies, that may be why.

但在最开始，我们不能仅仅因为有一个额外的极体就说胚胎会怎么样。

But in the beginning, we can't say anything about what's gonna happen to the embryo just because there's an extra polar body.

有时候，原核不是两个，而是三个，也就是3PN。

Now sometimes the pronuclei, instead of being a 2PN, can be a 3PN.

这意味着这个卵子里面有三套独立的细胞核。

What this means is that there are three separate nuclear packages inside of that egg.

最常见的原因是，如果用常规的试管婴儿技术，可能有两个精子进去了。

And the most common explanation is that if you use conventional IVF, maybe two sperm got in there.

但即使是做ICSI，也有可能精子本身携带了两份DNA。

But there's even the possibility when you put sperm with ICSI that the sperm itself could have had two pieces of DNA in it.

还有一种可能，就是卵子本身没有均匀分裂，它一直带着两份DNA，也就是46条染色体，然后再加上精子带来的23条染色体，就形成了三倍体。

There's even the question that maybe the egg didn't split evenly, and that it always had two pieces of DNA, meaning 46 chromosomes, and then the 23 chromosomes from the egg combined, causing a triploidy.

过去，我们不会移植三倍体胚胎，因为它们不正常。

Now in the past, we would not transfer tripodys because they were abnormal.

但现在有了下一代测序和SNP技术，我们就能判断这些3PN胚胎是不是真的三倍体。

But nowadays with next gen sequencing and SNP technology, we're able to find out if those 3PNs are really triploidy or not.

有时候，我们甚至能移植这些胚胎。

And sometimes we can even transfer these embryos.

那这是不是说它们就不是3PN了呢？

Now does that mean that they aren't 3PNs?

不是的，只是说胚胎在活检之后显示染色体正常，所以我们才能移植它。

No, it just means that eventually the embryo, after being biopsied showed normal chromosome patterns, and that's why we were able to transfer it.

同样的道理也适用于所谓的1PN。

The same thing is with what's called 1PNs.

有时候我们看不到另一个原核。

Sometimes we don't see another pronucleus.

那这是不是意味着它缺少DNA呢？

Does that mean it was missing DNA?

嗯，其实也不是。

Well, again, not really.

原核会出现，然后又会消失。

The pronuclei come and show themselves and then they disappear.

所以有时候你只是错过了另一个原核。

So sometimes you just miss the other pronuclei.

零原核的情况也可能一样。

The same thing can be true for zeropians.

有时候你观察时看到两个极体，你会说，嗯，我们知道它受精了。

Sometimes you look and you see the two polar bodies, you say, well, we know it fertilized.

但之后你只看到细胞质，看不到原核。

But then you only see cytoplasm and you don't see the pronuclei.

这可能意味着受精异常，或者像之前说的，原核像平常一样消失了，你只是错过了那个时间窗口。

Now that could be either abnormal fertilization or like before, the pronuclei could have disappeared like they normally do, and you just missed the window.

然后问题就是，我的胚胎是不是有点异常，所以它的时间窗口不对？

And then the question is, well, is my embryo sort of abnormal and that's why it has a displaced window?

还是说它没有正确受精？

Or did it not fertilize correctly?

或者它完全正常，只是我们错过了那个窗口。

Or is it perfectly normal and we just missed the window.

所有这些可能性都存在。

All those are true.

而且直到几天后我们再看，我们才知道胚胎会怎么样，直到我们看到它。

And until we look days later, we don't know what's gonna happen to the embryo until we see it.

所以下次你取卵后一天拿到胚胎报告，他们说，好的，你有14个卵子，其中7个受精了，6个变成了胚胎。

So next time you get your embryo report, a day after your retrieval and they say, okay, of the 14 eggs you had, seven were fertilized and six became embryos.

现在你可以问这个问题，当你说7个受精了，那其他的卵子有什么问题？

Now you can ask the question, when you say seven were fertilized, what was wrong with the other eggs?

那时他们可能会告诉你它们是GV或M1，他们选择不让它们受精。

And at that point they may tell you they were GV's or M1's and they chose not to fertilize them.

那是合理的。

And that's reasonable.

很多诊所不会让M1受精。

A lot of clinics do not fertilize M1's.

有些会，因为它可能后来成熟，但它们不一定以同样的速度成熟，也不一定以同样的速度受精。

Now some will because it could mature later, but they don't always mature at the same rate and they don't fertilize at the same rate.

但最终你关心的是有多少是两个极体和两个原核。

But in the end what you care about is how many are two polar body and two PNs.

就算你一开始有50个卵子，那也没关系。

It doesn't matter if you start with 50 eggs.

如果只有10个正常受精，那你就只剩下10个胚胎了。

If only 10 fertilize normal, you're down to 10 embryos.

还有一点要记住，有时候当你被告知取了16个卵子，但只有6个受精时，可能会有点沮丧，这确实让人沮丧。

Another point to keep in mind is that sometimes it could be a little bit demoralizing when you're told you get 16 eggs and only six fertilized, and that should be demoralizing.

但关键是，你得问一个问题：有多少是成熟的？

But the thing is you gotta ask the question, how many were mature?

因为如果有一大批都是成熟的，却只有6个受精，那确实令人失望。

Because if a whole bunch were mature and only six fertilized, that's disappointing.

但如果只有6个是成熟的，而且6个都受精了，那这就是完美的受精率。

But if only six were mature and six fertilized, well then that's perfect fertilization.

那就是100%。

That's a 100%.

为什么这很重要呢？因为如果你再做一次周期，你可以利用这些信息来调整下一次周期，帮助提高成熟度和受精率。

And why it matters is because if you do another cycle, you can use that information to make adjustments on your next cycle, to help improve maturation and fertilization.

下周的播客，我们就从这里接着聊，聊聊如果成熟度低怎么办。

Now in next week's podcast, we're gonna leave off right from here and talk about what if the maturity is low?

如果受精率低呢？

What if the fertilization is low?

那时候你需要考虑什么，又是什么原因导致的？

What do you need to be thinking at that point and what can cause that?

是不是医生没有按时给你打夜针？

Did the doctor just not trigger you on time?

我给你个提示。

I'll give you a hint.

其实不总是这个原因。

It's not really always that.

有时候就是人体本身，不同的人卵子发育速度不一样。

Sometimes it's just the human body that develops the eggs at different rates between different people.

甚至夜针有时候也会影响成熟效果，有的效果更好一些。

Even the trigger shot can sometimes cause better maturation than others.

但归根结底，卵子的成熟度告诉我们它是否到达了起跑线。

But in the end, egg maturity tells us whether an egg reached the starting line.

正常的2PM受精说明卵子和精子交接顺利，一切看起来都正常。但这两者都不能告诉我们胚胎的染色体是否正常，或者它能否发育成囊胚、着床，甚至最终成为一个宝宝。

Normal 2PM fertilization tells us that the expected egg and sperm had a good handoff and everything appeared to happen normal But neither one of those tells us whether an embryo is chromosomally normal or whether it will become a blastocyst, implant, or even become a baby.

正如我之前提到的，试管婴儿是一系列检查点。

As I mentioned earlier, IVF is a series of checkpoints.

不是单一的一个评分。

It's not one grade.

也不是单一的一个数字。

It's not one number.

更不是显微镜下的某一个瞬间。

And it's definitely not one moment under the microscope.

所以，如果你正在经历试管婴儿，或者曾经收到过胚胎学报告，心里想：我完全不知道这些是什么意思，你并不孤单。

So if you're someone who's going through IVF or ever received an embryology report and thought, I have no idea what any of this means, you're not alone.

去问问这些数字背后的故事，因为细节很重要。

Ask for the story behind the numbers because the details matter.

如果你喜欢这个播客，像往常一样，请在你最喜欢的平台上给我们一个五星好评。

If you like this podcast, as always mentioned, please give us a five star review on your favorite medium.

告诉你的朋友们关于我们，特别是如果你有朋友正在做试管婴儿，他们也在为胚胎报告感到困惑。

Tell your friends about us, especially if you have friends going through IVF and they're also wondering about their embryo report.

别忘了，我们现在也有一个网站，tacoboutfertility.com，你可以在那里向播客提问，我们会帮你在播客中找到答案。

And don't forget, we also now have a website, tacoboutfertility.com, where you can actually ask the podcast questions and we'll help you find the answers in the podcast.

另外，我很期待大家告诉我你们希望我接下来做什么。

Additionally, I'm looking forward to people giving their views of what they want me to do next.

我会确保把这些建议排上日程，但最重要的是，记得常回来看看。

And I'll make sure to put that in the queue, But most of all, keep coming back.

我期待下周在《聊聊生育》节目中再次与你交流。

I look forward to talking you again next week on Talk About Fertility.