最佳冷冻卵子的年龄是19岁。
The optimal age to freeze eggs is 19

原始链接: https://www.lesswrong.com/posts/dxffBxGqt2eidxwRR/the-optimal-age-to-freeze-eggs-is-19

## 卵子冷冻:不要等到为时已晚 对于考虑推迟生育的女性来说,卵子冷冻提供了一种强大的工具,可以延长生育窗口——有可能在40多岁甚至50多岁生育。然而,目前建议等到30多岁中期或后期再进行卵子冷冻的医疗建议存在重大缺陷。 卵子质量会随着年龄的增长而迅速下降,比子宫下降得更快,而在20多岁初(理想情况下是19-26岁)冷冻卵子可以产生明显更好的结果。这种下降非常显著,以至于37岁冷冻卵子,每个取出的卵子成功生育的几率比25岁时低60%。目前的试管婴儿成功率指标也*低估*了年轻时冷冻卵子的益处,因为它没有考虑到从一次取卵中诞生的多胞胎。 诸如多基因胚胎筛查等新兴技术——允许选择智商和疾病风险等特征——进一步强调了需要更多的卵子储备,而这只有通过年轻时冷冻卵子才能实现。虽然干细胞来源的卵子是一种未来的可能性,但它们可能还需要数年时间才能实现,并且可能存在突变风险。 CNY Fertility等经济实惠的选择与高端诊所并存。最终,积极主动的卵子冷冻,*越早越好*,为未来的家庭计划提供了最佳机会。

一个黑客新闻的讨论围绕着一篇LessWrong的文章,该文章建议19岁是冷冻卵子的最佳年龄。 讨论迅速转向了体外配子生成(IVG)的复杂性——从干细胞中制造卵子。 一个主要担忧是,干细胞会随着年龄增长而积累突变,从而带来当前筛查方法无法完全检测到的遗传疾病风险。 用户们思考自然繁殖如何有效地“重置”缺陷,而人工复制这个过程面临的挑战。 讨论涉及自然选择在过滤遗传问题中的作用,以及现代医学是否干扰了这个过程。 参与者推测,自然繁殖中的“重置”发生在早期发育阶段,而在成年人中复制它则受到组织损伤和癌症风险的阻碍。 一位用户还将这个话题与干细胞疗法联系起来。 同时也分享了一个个人试管婴儿经历的链接。
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原文

If you're a woman interested in preserving your fertility window beyond its natural close in your early 40s, egg freezing is one of your best options. But if you rely on your doctor to tell you when to freeze them, you will likely be doing yourself and your future prospects for a family a disservice.

The female reproductive system is one of the fastest aging parts of human biology. But it turns out, not all parts of it age at the same rate. 

The eggs, not the uterus, are what age at an accelerated rate. Freezing eggs can extend a woman's fertility window by well over a decade, allowing a woman to give birth into her 50s.

In a world where more and more women are choosing to delay childbirth to pursue careers or to wait for the right partner, egg freezing is really the only tool we have to enable these women to have the career and the family they want. 

Given that this intervention can nearly double the fertility window of most women, it's rather surprising just how little fanfare there is about it and how narrow the set of circumstances are under which it is recommended.

Standard practice in the fertility industry is to wait until a woman reaches her mid to late 30s, at which point if she isn't on track to have all the children she wants, it's advised she freeze her eggs.

This is not good practice. The outcomes from egg freezing decline in a nearly linear fashion with age, and conventional advice does a great misservice to women by not encouraging them to freeze eggs until it's almost too late.

The optimal age to freeze eggs varies depending on the source and metric, but almost all sources agree it's sometime between 19 and 26.

Monthly probability of getting pregnant for couples not on birth control. Note that these couples weren't actively trying for pregnancy, which is why the absolute probability is so low. See figure A4 from Geruso et al. for context.

So why has the fertility industry decided to make "freeze your eggs in your mid-30s" the standard advice as opposed to "freeze your eggs in your sophomore year of college"?

Part of the reason is fairly obvious: egg freezing is expensive and college sophomores are not known for being especially wealthy. Nor is the process especially fun, so given a choice between IVF and sex with a romantic partner, most women would opt for the latter.

But another reason is that the entire fertility industry is built around infertile women  in their mid to late 30s and most doctors just don't have a clear mental model for how to deal with women in their mid-20s thinking about egg freezing. 

There are countless examples of this blind spot, but one of the most poignant is the fertility industry almost completely ignores all age-related fertility decline that occurs before the age of 35, to the point where they literally group every woman under 35 into the same bucket when reporting success metrics for IVF.

Average Live Birth Rates Per IVF Cycle by Age. Women under 35 have the highest success rate at 55% per egg retrieval. Women ages 35-37 have a success rate of 41%. Women age 38-40 have a success rate of 27%, women ages 41-42 have a success rate of 13% and women over the age of 42 have a success rate of just 4%.
Yes, you're reading this right. SART literally does not distinguish between 20 year olds and 34 year olds in their success metrics.

This is far from the only issue. We not only ignore differences between 24 and 34 year olds, but the way we measure "success" in IVF is fundamentally wrong, and this error specifically masks age-related fertility decline that occurs before the age of 35.

If you go to an IVF clinic, create five embryos, get one transferred, and that embryo becomes a baby, you can go back two years later and get your second embryo transferred to have another child.

If that works, your second child will be ignored by official statistics. Births beyond one that come from the same egg retrieval are not counted, so these differences in outcomes that come from having many viable embryos literally don't show up in success statistics. This practice specifically masks the benefits of freezing eggs in your mid 20s instead of mid 30s, because most of the decline between those two ages comes from having fewer viable embryos.

What happens if we measure success differently? What if we instead measure the expected number of children you can have from a single egg retrieval, and show how that changes as a function of age?

This figure was generated with a model built by embryo selection company Herasight. You can read their whitepaper on the model's construction here

The answer is the difference between freezing eggs at 25 and freezing them at 37 becomes much more stark: there's a 60% decline in expected births per egg retrieval between those two ages, and no one in the IVF industry will tell you this.

Worse still, by age 35, over 10% of women won't be able to have ANY children from an egg freezing cycle due to various infertility issues which increase exponentially with age. So for a decent portion of egg freezing customers, they will get no benefit from freezing their eggs and they often won't find this out until 5-10 years later when they go back to the clinic and find that none of the eggs are turning into embryos.

Polygenic Embryo Screening

Freezing eggs at a younger age becomes even more important with polygenic embryo screening. We've had genetic screening for conditions like Down Syndrome and sickle cell anemia for decades, but starting in 2019, it became possible to screen your child for risks of all kinds of things. Parents who go through IVF can now boost their children's IQ, decrease their risk of diseases like Alzheimer's, depression and diabetes, and even make their children less likely to drop out of high school by picking an embryo with a genetic predisposition towards any of these outcomes.

But the size of the benefit of this screening depends significantly on the number of embryos available to choose from, which declines almost linearly with age. The expected benefit of embryo screening declines as a result.

These calculations use numbers from Herasight's IQ predictor and assume both parents are of European ancestry. The benefit is slightly smaller for parents of east and south asian and african ancestry. Everyone would like to fix this but we need more data from non-European ancestries to do it.

The father's age actually affects the expected benefit as well! But the decline is slower and most of the biological downsides of an older father show up as increased risk of developmental disorders like serious autism.

It is possible to compensate for this to some degree by doing more IVF cycles, but by the late 30s when the modal woman is freezing eggs, even this strategy starts to lose efficacy.

This is just one more reason why the standard advice to wait until your mid-30s to freeze eggs is wrong.

What about technology to make eggs from stem cells? Won't that make egg freezing obsolete?

More clued in people might point out that there are several companies working on making eggs from stem cells, and that perhaps by the time women who are 20 today reach the age at which they're ready to begin having kids, those eggs will be useless because it will be easy to mass manufacture eggs by that time.

Barring the AI-enabled automation of everything, I don't think stem cell derived eggs are going to be commercially practical for another decade or more.

Companies currently working on this whom I've talked to think we're 6-8 years from human trials. Even after trials conclude there will still be a period where stem cell derived eggs are incredibly expensive as every wealthy woman past her reproductive years rushes to get in line.

Lastly, the stem cells we're planning to use to make these eggs accrue mutations with age, and we don't currently have a good method to fix these before making them into eggs. These mutations will bring additional risk of various serious diseases, only some of which we currently have the genetic screening to detect.

How do I actually freeze my eggs?

Cheapest Option

You can actually freeze your eggs for relatively little money if you know where to go. Clinics like CNY Fertility are about a third the price of a regular IVF clinic and have reasonably similar outcomes for procedures like egg freezing. Including the cost of the retrieval, monitoring, medications, flights, and hotels this will usually come out to about $6000-7000 per retrieval. Storage fees generally run around $500/year.

The downside of CNY is the customer experience is worse than average, and there's much less hand holding than you'll get at a higher end clinic.

The luxury option

If you're rich and money is no object, the best IVF doctor I know is probably Dr. Aimee. She's quite expensive compared to the average IVF doctor (somewhere between $25k and $40k per round with all expenses included), but she has produced some pretty outlierish results for a number of my friends and acquaintances.

For everyone else

If CNY doesn't work for you and Dr. Aimee is too expensive, I'd recommend using Baby Steps IVF to find a clinic. It provides ranked lists of the best clinics all over the United States, and it's completely free. Two friends of mine, Sam Celarek and Roman Hauksson spent the last year and a half building this site. It's probably the best resource on the internet for comparing clinics. Most of the clinics you'll find through this website (and indeed most of the clinics in the country) will cost between $12,000 and $22,000 per round of egg freezing, with annual storage fees usually coming in between $800 and $1200.

Lastly, if you're a California resident, check whether your insurance plan offers coverage for IVF. You may be able to get them to pay for egg freezing, especially if you are already married.

Most women will need 1-3 rounds of egg retrieval to have a high chance of having all the children they want. If you plan to do polygenic embryo selection, 2-5 is a better estimate. If you want more precise numbers, use Herasight's calculator to estimate how many kids you could get from a given number of egg freezing cycles. If you want to do polygenic embryo selection, aim to have enough eggs for >2x the number of children you actually want.

If you're interested in freezing your eggs or you're interested in polygenic embryo selection, send me an email. I'm happy to chat with anyone interested in this process and may be able to add you to some group chats with other women going through the process.

Bottom Line: unless you're literally underage, sooner is almost always better when it comes to egg freezing. If you're one of the few women who visits this site, consider freezing eggs sooner rather than later!

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