LOS ANGELES – At the annual meeting of the American College of Medical Genetics, held this week in Los Angeles, reproductive biology experts sought to highlight knowledge gaps and potentially faulty assumptions surrounding how chromosomal and genetic abnormalities, aneuploidy and mosaicism in particular, should influence decisions related to .

洛杉矶——在本周于洛杉矶举行的美国医学遗传学学会年会上，生殖生物学专家试图强调围绕染色体和基因异常、非整倍性和嵌合体现象如何影响相关决策的知识空白和潜在错误假设。

in vitro

体外

fertilization (IVF).

体外受精 (IVF)。

Ruth Lathi, director of reproductive endocrinology and infertility at Stanford University, said in a presentation that the fertility field overall has moved towards accepting prenatal genetic testing for aneuploidy (PGT-A) as something of a gold standard for embryo testing and is currently

斯坦福大学生殖内分泌与不孕症科主任拉蒂·鲁思在一次演讲中表示，生育领域总体上已经转向接受产前基因检测非整倍体（PGT-A）作为胚胎检测的某种黄金标准，并且目前正朝着这一方向发展。

the

的

most frequently ordered test

最常见的检查项目

for patients undergoing IVF. Although its perceived benefit is to increase live birth rates, some randomized, controlled trials suggest that it actually does little to this end.

对于接受体外受精的患者。尽管它被认为可以增加活产率，但一些随机对照试验表明，它实际上在这方面作用不大。

One metastudy

一项荟萃研究

even found that it may reduce live birth rates among women with small numbers of embryos.

甚至发现它可能降低胚胎数量较少的女性的活产率。

The American Society for Reproductive Medicine appears to agree. In its

美国生殖医学学会似乎同意。在其

2024 IVF guidelines

2024年体外受精指南

, for example, the organization advised against the routine use of blastocyst biopsy with aneuploidy testing in all infertile patients undergoing IVF treatment.

例如，该组织建议不要对所有接受体外受精治疗的不孕患者常规使用囊胚活检与非整倍体检测。

'We adopted this technology with very little evidence of its benefits,' Lathi said.

“我们采用这项技术时，对其益处的证据知之甚少，”拉蒂说。

This means that potentially healthy embryos get discarded in an unknown number of cases.

这意味着在未知数量的情况下，潜在健康的胚胎会被丢弃。

One recent study

最近的一项研究

, for instance, found that approximately one quarter of segmentally aneuploid embryos –– in which a portion of a chromosome is either missing or gained –– resulted in live births.

例如，发现大约四分之一的片段性非整倍体胚胎——其中一部分染色体缺失或增加——最终导致了活产。

Even when testing shows that an embryo is 'normal,' however, and a euploid embryo is transferred, Lathi said that live births still only occur between 50 and 60 percent of the time.

然而，拉西表示，即使测试显示胚胎“正常”，并且移植了整倍体胚胎，活产率仍然只有 50% 到 60%。

'So does euploid really mean normal?' she asked, noting that 'we're getting live healthy babies from transferring abnormal embryos.'

“所以正常数真的意味着正常吗？”她问道，并指出“我们从移植异常胚胎中得到了活的健康婴儿。”

Lathi stressed, however, that euploid embryo transfers do still result in overall higher birth rates than both aneuploid and mosaic transfers. 'So for patients doing PGT-A,' she said in an email, 'euploid embryos should be transferred first.'

然而，拉蒂强调， euploid胚胎移植的整体出生率仍然高于aneuploid和mosaic移植。 “因此，对于进行PGT-A的患者，”她在电子邮件中说， “应该首先移植euploid胚胎。”

While PGT-A remains useful for ranking embryos

虽然PGT-A在对胚胎进行排序时仍然有用

in patients who produce multiple embryos,

在产生多个胚胎的患者中，

it could,

它可能，

however,

然而，

have implications

具有影响

both in terms of cost and in the potential for discarding viable embryos, which may be a particularly salient consideration in women who do not produce surplus embryos.

无论是在成本方面还是在丢弃可行胚胎的潜力方面，对于不能产生多余胚胎的女性来说，这可能是一个特别突出的考虑因素。

For Kamaria Cayton Vaught, an assistant professor of obstetrics and gynecology at Johns Hopkins, this raises the question, 'Is it really not okay to transfer an aneuploid embryo?'

对于约翰霍普金斯大学妇产科助理教授卡玛里亚·凯顿·沃特来说，这引发了一个问题：“转移一个非整倍体胚胎真的不可以吗？”

Vaught extended the discussion of aneuploidy to mosaicism in her own presentation. Mosaicism refers to cells within the same organism having diverse genetic makeups, typically due to post-zygotic mutations or errors in cell division. The degree of mosaicism observed in human embryos varies widely, with such embryos classified from mosaic-low to mosaic-high and with the complexity of mosaic abnormalities .

瓦特在她自己的演讲中将非整倍性的讨论扩展到了嵌合体。嵌合体是指同一生物体内细胞具有不同的遗传构成，通常是由于合子后突变或细胞分裂错误所致。在人类胚胎中观察到的嵌合体程度差异很大，这些胚胎被分为低嵌合体到高嵌合体，并具有不同程度的嵌合异常复杂性。

increasing with the mother's age

随着母亲年龄的增长而增加

.

。

Vaught explained that genetic testing underpinning embryo transfer decisions typically comes from blastocyst biopsies, which sample such tiny amounts of DNA –– often just picograms —that it is often difficult to draw firm conclusions about the health of that embryo. 'I've had patients [in whom] I transferred a mosaic embryo, and I get beautiful pictures sent to me of their child,' she said.

沃特解释说，作为胚胎移植决策依据的基因测试通常来自囊胚活检，这种活检只能获取极少量的DNA——通常仅为皮克级——因此往往难以对胚胎的健康状况得出明确结论。 “我有患者[他们当中]我移植了嵌合体胚胎，后来他们给我发来了孩子的漂亮照片，”她说。

.

。

As in the case of aneuploid embryos, Vaught said that while euploid embryo transfers typically have higher success rates than mosaic transfer, mosaic transfer should still be considered after counseling about its risks and benefits, particularly for women without euploid embryos.

正如非整倍体胚胎的情况一样，沃特说，虽然整倍体胚胎移植通常比嵌合体移植成功率更高，但在咨询了其风险和益处后，仍应考虑嵌合体移植，特别是对于没有整倍体胚胎的女性。

Lathi, Vaught, and the other speakers who participated in the session were all adamant that an understanding of reproductive genetics is far from complete and that more research is needed. Doing so will involve grappling with legal questions alongside scientific ones.

拉蒂、沃特以及参与该会议的其他演讲者都坚决认为，对生殖遗传学的理解远未完善，还需要进行更多的研究。这样做将涉及在科学问题之外还需应对法律问题。

Anti-abortion laws and legal definitions of when life begins and what constitutes a person have complicated reproductive genetics research and medical procedures such as IVF for generations. As restrictive laws and legal challenges proliferate across the US, IVF and the research contributing to it are likely to face more challenges, with questions that extend from an embryo's viability to its overall health growing ever more prominent..

反堕胎法律以及关于生命何时开始和什么构成人的法律定义，使得生殖遗传学研究和诸如体外受精（IVF）等医疗程序在几代人中变得复杂。随着限制性法律和法律挑战在美国各地激增，IVF及其相关研究可能会面临更多挑战，从胚胎的存活力到其整体健康状况等问题变得越来越突出。

Last year in Alabama, for instance, the fertility field was thrown briefly into disarray when the state Supreme Court ruled that frozen embryos are considered children for legal purposes. This made it possible for IVF clinics to be held liable for the accidental loss of embryos under Alabama's Wrongful Death of a Minor statute, a law that has been on the books since 1872..

例如，去年在阿拉巴马州，当该州最高法院裁定冷冻胚胎在法律上被视为儿童时，生育领域一度陷入混乱。这使得体外受精诊所可能因意外丢失胚胎而依据自1872年以来就存在的《未成年人错误死亡法》被追究责任。

For two weeks following this decision, IVF clinics in Alabama shut down while the professionals employed in those clinics, people seeking –– and in some case already in the process of –– IVF, and activists pressured the state legislature to take action.

在这一决定作出后的两周内，阿拉巴马州的体外受精诊所关闭，而这些诊所的从业人员、寻求体外受精的人（在某些情况下已经在进行过程中）以及活动人士向州立法机构施压，要求采取行动。

'Those were the longest two weeks of my professional life,' said Janet Bouknight, an infertility doctor operating a private practice in Alabama.

“那是我职业生涯中最长的两周，”阿拉巴马州私人诊所的不孕症医生珍妮特·布克奈特说道。

The state Supreme Court's ruling, she said, contained

她说，州最高法院的裁决包含

wording not found in a geneticist's vocabulary, such as 'embryonic children,' and called IVF lab storage facilities 'cryogenic nurseries.' Bouknight pointed out that the ruling also contained several falsehoods, such as claiming that an embryo can be grown into a complete infant inside the lab.

遗传学家的词汇中没有“胚胎儿童”这样的词语，而将试管婴儿实验室存储设施称为“低温托儿所”。布克奈特指出，该裁决还包含若干谬误，例如声称胚胎可以在实验室内长成完整的婴儿。

In the end, the Alabama legislature enacted a bill providing civil and criminal immunity for the death or damage of any embryo to an individual or entity when providing or receiving goods or services related to IVF. 'That is the imperfect solution that Alabama was able to pass, that allowed us to open back up and provide care,' Bouknight said.

最终，阿拉巴马州立法机构通过了一项法案，为在提供或接受与体外受精相关的商品或服务时，对任何胚胎的死亡或损害给予个人或实体民事和刑事豁免。布克奈特说：“这是阿拉巴马州能够通过的不完美解决方案，它让我们能够重新开放并提供护理。”

.

。

One of the changes to Bouknight's practice that followed from that tumultuous episode is that she now keeps all fertilized embryos, out of consideration for potential lawsuits.

布克奈特的那次动荡经历之后，她的做法有所改变，出于对潜在诉讼的考虑，她现在会保存所有受精胚胎。

'It used to be,' she said, 'that the day after the eggs fertilize, you look and say, does this look normal? Is that the right amount of genetic material? Is this a 2pn [referring to the normal number of pronuclei present]? Now we keep everything in culture, even the abnormal fertilizations.'

“以前是这样的，”她说，“在卵子受精后的第二天，你会观察并判断，这看起来正常吗？遗传物质的数量正确吗？这是2pn（指正常的原核数量）吗？现在我们会把所有东西都留在培养皿中，即使是异常的受精情况。”

She also now freezes any and all embryos that blastulate, whereas previously, an embryologist would decide which ones to keep. This has resulted in a new category of embryos to be maintained, incurring greater financial and logistical costs.

她现在还会冷冻所有胚泡化的胚胎，而在此之前，胚胎学家会决定哪些胚胎要保留。这导致了需要维护的胚胎新增了一个类别，带来了更高的财务和后勤成本。

'Quite frankly, we're trying to figure out what to do with them,' she said.

“坦率地说，我们正试图弄清楚该如何处理它们，”她说道。

Lathi is currently recruiting women who wish to consider aneuploid transfer for

拉蒂目前正在招募希望考虑非整倍体转移的女性。

a clinical trial

临床试验

investigating how often embryos reported to be abnormal by preimplantation genetic testing result in liveborn infants, whether pregnancies resulting from those embryos are at higher risk for complications, and whether the resulting babies have higher risk for health or developmental issues in the first five years after birth..

调查通过植入前遗传学检测报告为异常的胚胎最终产生活婴的频率，这些胚胎导致的妊娠是否面临更高的并发症风险，以及出生后五年的健康或发育问题风险是否更高。