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卵子捐赠与代孕:植入不相关胚胎时怀孕风险更高。

Egg donation and gestational surrogacy: Pregnancy is riskier with an unrelated embryo.

作者信息

McCoy Dakota E, Haig David, Kotler Jennifer

机构信息

Department of Ecology and Evolution, The University of Chicago, Chicago, IL 60637, United States of America; Marine Biological Laboratory, Woods Hole, MA 02543, United States of America.

Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02136, United States of America.

出版信息

Early Hum Dev. 2024 Sep;196:106072. doi: 10.1016/j.earlhumdev.2024.106072. Epub 2024 Jul 2.

Abstract

Modern medicine has revolutionized family planning. Remarkably, women can carry to term embryos with whom they share no genetic connection, a feat made possible through egg donation and/or gestational surrogacy. Our reproductive systems evolved to accommodate embryos that are 50% related to the carrier, not 0% related. Here, we apply evolutionary theory to explain how and why pregnancy is riskier with an unrelated embryo. When a woman gestates an unrelated embryo, she is significantly more likely to develop preeclampsia and other diseases above and beyond the known risks associated with advanced maternal age, IVF, multiple gestation, and subfertility. Such "allogeneic pregnancies" are riskier even in fertile, healthy, commercial surrogates and when the egg is donated by a young, healthy donor. We propose that unrelated embryos present a special immune challenge to the gestational carrier, because they have fewer matching genes to the maternal body-therefore exacerbating symptoms of evolutionary maternal-fetal conflict. Indeed, maternal risks seem lower when the embryo is more related to the carrier, e.g., if a sister donates the egg. Finally, we discuss microchimerism in egg donation pregnancies, whereby wholly foreign cells pass from mother to embryo and vice-versa. We conclude with several medical proposals. First, egg donors and surrogates should be informed of the increased health risks they would face. In considerations of risk, these young, fertile women should not be compared to older, infertile women undergoing IVF; the proper comparison group is other young, fertile women. Second, contrary to some medical advice, perhaps genetically-related egg donors and surrogates should be preferred, all else equal. An immunological matching scheme, like what is used for organ transplants, could improve surrogate pregnancy outcomes. Third, more research is needed on microchimerism, sperm exposure, and the long-term impacts of allogeneic pregnancies on maternal and child health.

摘要

现代医学给计划生育带来了变革。值得注意的是,女性能够孕育与自己没有基因关联的胚胎,这一壮举通过卵子捐赠和/或代孕得以实现。我们的生殖系统是为了适应与母体有50%基因关联的胚胎而进化的,而非0%基因关联的胚胎。在此,我们运用进化理论来解释怀有非亲缘关系胚胎时怀孕风险更高的方式及原因。当一名女性孕育一个非亲缘关系的胚胎时,她患先兆子痫及其他疾病的可能性会显著增加,这些疾病超出了与高龄产妇、体外受精、多胎妊娠和生育力低下相关的已知风险。即便在生育能力正常、身体健康的商业代孕女性中,以及卵子由年轻、健康的捐赠者提供时,这种“异基因妊娠”的风险依然更高。我们认为,非亲缘关系的胚胎对妊娠载体构成了特殊的免疫挑战,因为它们与母体的匹配基因较少——因此加剧了进化过程中母胎冲突的症状。事实上,当胚胎与载体的基因关系更密切时,例如如果是姐妹捐赠卵子,母体风险似乎更低。最后,我们讨论了卵子捐赠妊娠中的微嵌合体现象,即完全外来的细胞在母体和胚胎之间相互传递。我们最后提出了几项医学建议。首先,应该告知卵子捐赠者和代孕女性她们将面临更高的健康风险。在考虑风险时,不应将这些年轻、有生育能力的女性与接受体外受精的年长、不育女性进行比较;合适的对照组是其他年轻、有生育能力的女性。其次,与一些医学建议相反,在其他条件相同的情况下,或许应该优先选择有基因关联的卵子捐赠者和代孕女性。一种类似于器官移植中使用的免疫匹配方案,可能会改善代孕妊娠的结果。第三,需要对微嵌合体现象、精子接触以及异基因妊娠对母婴健康的长期影响进行更多研究。

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