目的:是否需要对胚胎培养方案进行非整倍体(niPGT-A)的非侵入性植入前遗传学检测,从而影响临床生殖结局,
结论:实施适应niPGT-A的胚胎培养方案对胚泡活力或妊娠结局没有影响。
背景:最近对废胚泡培养基中胚胎无细胞(cf)DNA的鉴定创造了简化PGT-A的可能性。关注,然而,出现在两个层面。首先,该cfDNA对胚胎真实倍性状态的代表性。第二,试管婴儿实验室在执行niPGT-A时需要实施的后勤变化及其对生殖结局的影响。niPGT-A与侵入性PGT-A的一致率逐渐提高;然而,文化协议变化的影响还没有得到很好的理解。
方法:作为一项试验的一部分,检查niPGT-A与侵入性PGT-A的一致率,IVF诊所实施了特定的niPGT-A胚胎培养方案.简而言之,这涉及在每个实验室标准程序之后直到第4天的受精卵母细胞的初始培养。在第4天,洗涤胚胎并在10μl新鲜培养基中单独培养。在第6天或第7天,对胚泡进行活检,玻璃化,并收集培养基进行NiPGT-A分析。来自先前提到的试验的六个IVF诊所被纳入该分析。在和谐审判中,诊所A将所有胚胎(97个周期和355个胚胎)培养到第6天或第7天,而在其余诊所(B-F)(379个周期),所有囊胚的近四分之一(231/985:23.5%)在第5天进行了活检,其余囊胚按照niPGT-A方案进行活检(754/985:76.5%).同期(2018年4月至2020年12月),IVF诊所也进行了标准的侵入性PGT-A,这涉及胚胎的培养,直到第5、6或7天时,胚泡的活检和玻璃化。
方法:总共,428例(476个周期)患者为niPGT-A研究组。来自1392名患者的胚胎接受标准PGT-A培养方案并形成对照组。从所有患者获得临床信息并进行分析。根据活检的日期在研究组和对照组之间进行统计比较。
结果:平均年龄,卵母细胞数量,受精率,研究组和对照组的胚泡数量没有显着差异。关于总体妊娠结局,对临床妊娠率无显著影响,流产率,或持续妊娠率(≥12周),研究组与对照组相比,当按活检日分层时。
结论:本研究的回顾性性质固有的局限性,以及该研究是在侵入性PGT-A患者中进行的,而不是专门使用niPGT-A病例。
结论:这项研究表明,修改当前的IVF实验室方案以采用niPGT-A对可用于移植的胚泡数量和移植胚胎的整体临床结局没有影响。去除侵入性活检步骤是否会导致妊娠率的进一步改善,有待进一步研究。
背景:本研究由Igenomix资助。C.R.,L.N.-S.,和D.V.是Igenomix的雇员.D.S.在研究期间是Igenomix的科学顾问委员会成员。
背景:ClinicalTrials.gov(NCT03520933)。
OBJECTIVE: Are modifications in the embryo culture protocol needed to perform non-invasive preimplantation genetic testing for aneuploidies (niPGT-A) affecting clinical reproductive outcomes, including blastocyst development and pregnancy outcomes?
CONCLUSIONS: The implementation of an embryo culture protocol to accommodate niPGT-A has no impact on blastocyst viability or pregnancy outcomes.
BACKGROUND: The recent identification of embryo cell-free (cf) DNA in spent blastocyst media has created the possibility of simplifying PGT-A. Concerns, however, have arisen at two levels. First, the representativeness of that cfDNA to the real ploidy status of the embryo. Second, the logistical changes that need to be implemented by the IVF laboratory when performing niPGT-A and their effect on reproductive outcomes. Concordance rates of niPGT-A to invasive PGT-A have gradually improved; however, the impact of culture protocol changes is not as well understood.
METHODS: As part of a trial examining concordance rates of niPGT-A versus invasive PGT-A, the IVF clinics implemented a specific niPGT-A embryo culture protocol. Briefly, this involved initial culture of fertilized oocytes following each laboratory standard routine up to Day 4. On Day 4, embryos were washed and cultured individually in 10 μl of fresh media. On Day 6 or 7, blastocysts were then biopsied, vitrified, and media collected for the niPGT-A analysis. Six IVF clinics from the previously mentioned trial were enrolled in this analysis. In the concordance trial, Clinic A cultured all embryos (97 cycles and 355 embryos) up to Day 6 or 7, whereas in the remaining clinics (B-F) (379 cycles), nearly a quarter of all the blastocysts (231/985: 23.5%) were biopsied on Day 5, with the remaining blastocysts following the niPGT-A protocol (754/985: 76.5%). During the same period (April 2018-December 2020), the IVF clinics also performed standard invasive PGT-A, which involved culture of embryos up to Days 5, 6, or 7 when blastocysts were biopsied and vitrified.
METHODS: In total, 428 (476 cycles) patients were in the niPGT-A study group. Embryos from 1392 patients underwent the standard PGT-A culture protocol and formed the control group. Clinical information was obtained and analyzed from all the patients. Statistical comparisons were performed between the study and the control groups according to the day of biopsy.
RESULTS: The mean age, number of oocytes, fertilization rates, and number of blastocysts biopsied were not significantly different for the study and the control group. Regarding the overall pregnancy outcomes, no significant effect was observed on clinical pregnancy rate, miscarriage rate, or ongoing pregnancy rate (≥12 weeks) in the study group compared to the control group when stratified by day of biopsy.
CONCLUSIONS: The limitations are intrinsic to the retrospective nature of the study, and to the fact that the study was conducted in invasive PGT-A patients and not specifically using niPGT-A cases.
CONCLUSIONS: This study shows that modifying current IVF laboratory protocols to adopt niPGT-A has no impact on the number of blastocysts available for transfer and overall clinical outcomes of transferred embryos. Whether removal of the invasive biopsy step leads to further improvements in pregnancy rates awaits further studies.
BACKGROUND: This study was funded by Igenomix. C.R., L.N.-S., and D.V. are employees of Igenomix. D.S. was on the Scientific Advisory Board of Igenomix during the study.
BACKGROUND: ClinicalTrials.gov (NCT03520933).