What’s next for IVF
What’s next for IVF
试管婴儿(IVF)的未来展望
EXECUTIVE SUMMARY MIT Technology Review’s What’s Next series looks across industries, trends, and technologies to give you a first look at the future. You can read the rest of them here. 执行摘要 《麻省理工科技评论》的“未来展望”(What’s Next)系列旨在纵览各行各业、趋势与技术,为您提供对未来的前瞻性视角。您可以在此处阅读该系列的其他文章。
Forty-eight years ago this July, Louise Joy Brown became the world’s first person born with the help of in vitro fertilization. Millions more IVF babies have entered the world since then. And that’s partly thanks to advances in technology that have made IVF safer and more effective. But it’s still not perfect. The process can be slow, painful, and expensive—and that’s for the lucky people who are able to access it in the first place. And by at least one measure, IVF success rates have been declining in recent years. 今年 7 月,路易丝·乔伊·布朗(Louise Joy Brown)成为世界上首位通过体外受精(IVF)出生的婴儿,距今已有 48 年。自那时起,数以百万计的试管婴儿来到这个世界。这在一定程度上要归功于技术的进步,使得 IVF 变得更加安全和有效。但它仍不完美。整个过程可能缓慢、痛苦且昂贵——这还是针对那些有幸能够获得医疗资源的人而言。而且,至少从某项指标来看,近年来 IVF 的成功率一直在下降。
Reproduction is complex, and there’s a lot that embryologists and gynecologists still don’t know and can’t control. They don’t know why many healthy-looking embryos don’t “stick” in the uterus, for example. They don’t always have an explanation for why their patients can’t get pregnant. And they can’t always account for vast differences in IVF success rates between individuals and between fertility clinics. 生殖过程非常复杂,胚胎学家和妇科医生仍有许多未知和无法控制的因素。例如,他们不知道为什么许多看起来健康的胚胎无法在子宫内“着床”。他们并不总能解释为什么患者无法怀孕,也无法完全解释不同个体之间以及不同生殖诊所之间 IVF 成功率的巨大差异。
Scientists are working on all those questions and more. They’re wrestling with complex ethical questions about how new genetic tools will be used to analyze or even alter embryos. Meanwhile, technologies designed to standardize treatment, eliminate human error, boost success rates, and make IVF more accessible are already beginning to usher in a new era for assisted reproduction—one aided by AI and robots. 科学家们正在致力于解决所有这些问题及更多挑战。他们正在应对复杂的伦理问题,即如何使用新的基因工具来分析甚至改变胚胎。与此同时,旨在标准化治疗、消除人为错误、提高成功率并使 IVF 更易于获取的技术,已经开始引领辅助生殖的新时代——一个由人工智能和机器人辅助的时代。
1. Helping embryos stick
1. 帮助胚胎着床
Some of those technologies are being developed at the Carlos Simon Foundation in Valencia, Spain. When I visited in March, researchers gave me a tour of the labs and showed me a device that had been used to keep a human uterus alive outside the body for the first time. While some members of the team dream of building artificial uteruses that might one day be able to carry a fetus to term, they first want to use such devices to learn more about implantation—the moment at which a fertilized egg makes contact with the lining of the uterus, burrows inside, and essentially “hatches,” triggering the start of a pregnancy. 其中一些技术正在西班牙瓦伦西亚的卡洛斯·西蒙基金会(Carlos Simon Foundation)开发。今年 3 月我访问时,研究人员带我参观了实验室,并向我展示了一种曾首次用于在体外维持人类子宫存活的设备。虽然团队中的一些成员梦想着制造出未来某天能够孕育胎儿至足月的人造子宫,但他们首先希望利用这些设备深入了解“着床”过程——即受精卵接触子宫内膜、钻入其中并本质上“孵化”出来,从而触发妊娠开始的那一刻。
Despite decades of advances in IVF, that process is still poorly understood. Even healthy-looking embryos stick no more than 40% to 60% of the time. In IVF techniques used today, clinics can create early-stage embryos and wait until the uterus is deemed most receptive, but once they insert the embryo into the uterus, it’s on its own. Xavier Santamaria, senior clinical scientist at the Carlos Simon Foundation, and his colleagues are trialing a different approach. They’ve developed a device that, at the press of a button, injects the embryo into the uterine lining. 尽管 IVF 技术已经进步了几十年,但这一过程仍未被充分理解。即使是看起来健康的胚胎,着床率也不过 40% 到 60%。在当今的 IVF 技术中,诊所可以培育早期胚胎,并等待子宫被认为最适宜受孕时再进行移植,但一旦胚胎被植入子宫,就只能靠它自己了。卡洛斯·西蒙基金会的高级临床科学家哈维尔·圣玛丽亚(Xavier Santamaria)及其同事正在尝试一种不同的方法。他们开发了一种设备,只需按下一个按钮,就能将胚胎注入子宫内膜。
In a demonstration I watched with a prototype, Santamaria picked up his speculum and turned to face the vaginal opening of his “patient,” which in this case was just a model of the real thing—a plastic bottom with labia, a vagina, a uterus, and ovaries, two short stumps representing what would normally be a pair of legs held in stirrups. He hunched over and peered inside. “Embryo,” he called. His colleague Maria Pardo, an embryologist, passed him a thin needle containing a mouse embryo she had recently collected from a petri dish. Santamaria’s device allows for the embryo-containing needle to be connected to a delivery tube. This tube also has a camera, a light, and a sensor that lets the doctor know when the needle reaches the uterine lining. Once it has been fed into the uterus, the gynecologist can see the inside of the organ and direct the tube to the lining. 在我观看的原型演示中,圣玛丽亚拿起窥阴器,转向他“病人”的阴道口。在这个案例中,这只是一个真实的模型——一个带有阴唇、阴道、子宫和卵巢的塑料臀部,还有两个短桩代表通常放在脚蹬上的双腿。他弯下腰向内窥视。“胚胎,”他喊道。他的同事、胚胎学家玛丽亚·帕尔多(Maria Pardo)递给他一根细针,里面装着她刚从培养皿中收集的小鼠胚胎。圣玛丽亚的设备允许将装有胚胎的针连接到输送管上。该管还配有摄像头、光源和传感器,可以让医生知道针头何时到达子宫内膜。一旦进入子宫,妇科医生就能看到器官内部,并将管子引导至内膜处。
“When everything is ready, you just press the button,” Santamaria said as he activated it using a foot pedal, allowing the embryo to be injected. “There it goes.” The team has just started a trial of the device; so far, fewer than 10 women have undergone the procedure, and none of those have become pregnant. But foundation director Carlos Simon is hopeful, noting that the inventors of IVF had to perform over 160 cycles before Louise Brown was born (between 1969 and 1978, that team performed 457 cycles in 250 people, resulting in only two live births). “The trial is ongoing,” he says. “当一切准备就绪,你只需按下按钮,”圣玛丽亚一边说,一边用脚踏板启动了设备,让胚胎被注入。“成功了。”该团队刚刚开始对该设备进行试验;到目前为止,不到 10 名女性接受了该手术,且均未怀孕。但基金会主任卡洛斯·西蒙(Carlos Simon)充满希望,他指出,IVF 的发明者在路易丝·布朗出生前进行了超过 160 个周期的尝试(在 1969 年至 1978 年间,该团队在 250 人身上进行了 457 个周期,最终仅有两例活产)。“试验仍在进行中,”他说。
2. Picking the “best” eggs, sperm, and embryos
2. 挑选“最好”的卵子、精子和胚胎
One long-running challenge of IVF has been selection. Say you manage to collect 10 eggs from one partner and a decent-looking semen sample from the other. How do you choose which cells to use? The same question comes up once the resulting embryos have been cultured in a dish for a few days: Which should you transfer to the uterus? Traditionally, these judgments have been made by eye. Embryologists literally pick the ones that look the best in terms of their shape or, in the case of sperm, how they move. But scientists have been working on alternatives. And over the last decade or so, many have turned to genetic testing to hint at which embryos have the best chances of creating a healthy baby. IVF 长期以来的一个挑战是筛选。假设你成功从一方收集了 10 个卵子,并从另一方获得了看起来不错的精液样本。你该如何选择使用哪些细胞?当产生的胚胎在培养皿中培养几天后,同样的问题又出现了:应该将哪一个移植到子宫内?传统上,这些判断都是靠肉眼做出的。胚胎学家实际上是挑选那些在形状上看起来最好的胚胎,或者对于精子而言,挑选那些游动状态最好的。但科学家们一直在研究替代方案。在过去十年左右的时间里,许多人转向了基因检测,以预测哪些胚胎最有可能孕育出健康的婴儿。
The most commonly used test is called PGT-A, which stands for preimplantation genetic testing for aneuploidy. Aneuploidy essentially means having an “incorrect” number of chromosomes, and it is thought that embryos with such characteristics are more likely to be lost through miscarriage or potentially develop into babies with genetic conditions. Once embryologists have created embryos in the lab, they can pinch off a few cells and test them for aneuploidies. The tests are especially beneficial for women over the age of 38, says Alan Penzias, a reproductive endocrinologist at Boston IVF. “You start to see an improvement: more babies and fewer miscarriages,” he says. The tests can shorten the time to pregnancy. This type of genetic testing is possible thanks to multiple advances in technology—not just in genomics, but also in the ability to keep embryos alive in a dish for five to six days and the technique of freezing embryos while the cells undergo testing and thawing them once. 最常用的检测方法称为 PGT-A,即胚胎植入前非整倍体遗传学检测。非整倍体本质上意味着染色体数量“不正确”,人们认为具有这种特征的胚胎更容易因流产而丢失,或者可能发育成患有遗传疾病的婴儿。一旦胚胎学家在实验室中培育出胚胎,他们就可以提取少量细胞并检测是否存在非整倍体。波士顿 IVF(Boston IVF)的生殖内分泌学家艾伦·彭齐亚斯(Alan Penzias)表示,这些检测对 38 岁以上的女性尤其有益。“你开始看到改善:更多的婴儿出生,更少的流产,”他说。这些检测可以缩短怀孕所需的时间。这种基因检测之所以成为可能,要归功于多项技术的进步——不仅是在基因组学方面,还包括在培养皿中维持胚胎存活五到六天的能力,以及在细胞进行检测期间冷冻胚胎并在检测后解冻的技术。