目的:体外培养的长度之间是否存在关联,ART模式和最初的内源性hCG上升,
结论:体外培养的长度和ART模式都对单胎妊娠hCG的初始内源性升高有影响。
背景:已经确定了不同的因素来改变妊娠中hCG的动力学。目前的研究表明,关于不同类型的ART(新鲜与冷冻ET(FET))后hCG的动力学,是否包含植入前遗传学检测(PGT),和体外培养时间的长短。
方法:这是一项多中心队列研究,使用从接受IUI的4938名妇女(5524个治疗周期)(周期,n=608)或ART(周期,n=4916)处理,导致通过妊娠早期超声扫描证实的单胎持续妊娠。数据来自丹麦医疗数据中心,由哥本哈根大学医院的三个参与丹麦公共生育诊所使用:Herlev医院,Hvidovre医院,和Rigshospitalet,从2014年1月到2021年12月。
方法:新鲜ET周期包括卵裂期(体外2或3天)和胚泡(体外5天)转移。FET循环包括裂解期(冷冻保存前3天体外)或胚泡(冷冻保存前5或6天体外)转移。IUI循环不代表体外时间。为了达到血清-hCG(s-hCG)的相当间隔,排卵诱导时间相同:取卵或IUI前35-37小时。受孕日被认为是:IUI后怀孕的授精日,新鲜ET取卵日,或转移日减去3或5,适用于第3或5天胚胎的FET。采用多元线性回归分析,包括作为协变量的hCG测量的受孕后天数,并根据女性的年龄进行了调整,不孕的原因,和中心。对于FET,使用敏感性分析来调整子宫内膜准备.
结果:该研究共包括5524个循环:2395个FET循环,2521个新鲜ET周期,和608个IUI周期。关于体外培养的长度,以IUI为参考(在体外培养中没有时间),我们发现新鲜ET(卵裂期ET或胚泡移植)后的妊娠中s-hCG显着降低。S-hCG为18%(95%CI:13-23%,P<0.001)新鲜裂解期ET后降低,和23%(95%CI:18-28%,与IUI相比,新鲜胚泡移植后P<0.001)较低。在FET循环中,s-hCG在胚泡移植后显著高于卵裂期FET,分别,26%(95%CI:13-40%,P<0.001)在体外第5天冷冻保存时更高,为14%(95%CI:2-26%,与第3天相比,当在第6天冷冻保存时,P=0.02)更高。关于ART治疗类型,s-hCG在FET囊胚移植(第5天囊胚)周期后显著升高,33%(95%CI:27-45%,P<0.001),与新鲜ET(第5天胚泡)相比,而裂解阶段FET(第2+3天)和新鲜ET(第2+3天)之间没有差异。S-hCG为12%(95%CI:4-19%,0.005)在PGTFET(第5天囊胚)循环中与没有PGT(第5天囊胚)的FET循环相比更低。
结论:回顾性设计是一个限制,它引入了可能的偏倚和混杂因素的风险,例如胚胎评分,奇偶校验,和卵巢刺激。
结论:本研究阐明了医学辅助生殖治疗的实践与hCG动力学的关系,强调体外培养长度和ART模式对早期胚胎发育和植入的潜在影响。该研究为临床医生提供了知识,即在评估s-hCG对妊娠预后时,所使用的ART类型可能与考虑相关。
背景:本研究未获得资助。美联社收到了咨询费,研究补助金,或来自以下公司的酬金:Preglem,诺和诺德,Ferring制药,GedeonRichter,Cryos,默克A/S,和Organon。AZ已获得GedeonRichter的赠款和酬金。NLF收到了GedeonRichter的资助,默克A/S,还有Cryos.MLG已从GedeonRichter获得酬金或研究资助,默克A/S,和库珀外科。CB已从默克公司获得酬金。MB已获得IBSA的研究资助和酬金。MPR,KM,和PVS都报告没有利益冲突。
背景:该研究由丹麦保护局注册并批准,首都地区,丹麦(Journal-nr.:21019857)。根据丹麦法律,不需要区域伦理委员会的批准。
OBJECTIVE: Is there an association between the length of in vitro culture, mode of ART and the initial endogenous hCG rise, in cycles with a foetal heartbeat after single embryo transfer (ET) and implantation?
CONCLUSIONS: Both the length of in vitro culture and the mode of ART have an impact on the initial endogenous rise in hCG in singleton pregnancies.
BACKGROUND: Different factors have been identified to alter the kinetics of hCG in pregnancies. Current studies show conflicting results regarding the kinetics of hCG after different types of ART (fresh vs frozen ET (FET)), the inclusion or not of preimplantation genetic testing (
PGT), and the length of time in in vitro culture.
METHODS: This was a multicentre cohort study, using prospectively collected data derived from 4938 women (5524 treatment cycles) undergoing IUI (cycles, n = 608) or ART (cycles, n = 4916) treatments, resulting a in singleton ongoing pregnancy verified by first-trimester ultrasound scan. Data were collected from the Danish Medical Data Centre, used by the three participating Danish public fertility clinics at Copenhagen University hospitals: Herlev Hospital, Hvidovre Hospital, and Rigshospitalet, from January 2014 to December 2021.
METHODS: The fresh ET cycles included cleavage-stage (2 or 3 days in vitro) and blastocyst (5 days in vitro) transfers. FET cycles included cleavage-stage (3 days in vitro before cryopreservation) or blastocyst (5 or 6 days in vitro before cryopreservation) transfers. The IUI cycles represented no time in vitro. To attain a comparable interval for serum-hCG (s-hCG), the ovulation induction time was identical: 35-37 h before oocyte retrieval or IUI. The conception day was considered as: the insemination day for pregnancies conceived after IUI, the oocyte retrieval day for fresh ET, or the transfer day minus 3 or 5 as appropriate for FET of Day 3 or 5 embryos. Multiple linear regression analysis was used, including days post-conception for the hCG measurement as a covariate, and was adjusted for the women\'s age, the cause of infertility, and the centre. For FET, a sensitivity analysis was used to adjust for endometrial preparation.
RESULTS: The study totally includes 5524 cycles: 2395 FET cycles, 2521 fresh ET cycles, and 608 IUI cycles. Regarding the length of in vitro culture, with IUI as reference (for no time in in vitro culture), we found a significantly lower s-hCG in pregnancies achieved after fresh ET (cleavage-stage ET or blastocyst transfer). S-hCG was 18% (95% CI: 13-23%, P < 0.001) lower after fresh cleavage-stage ET, and 23% (95% CI: 18-28%, P < 0.001) lower after fresh blastocyst transfer compared to IUI. In FET cycles, s-hCG was significantly higher after blastocyst transfers compared to cleavage-stage FET, respectively, 26% (95% CI: 13-40%, P < 0.001) higher when cryopreserved on in vitro Day 5, and 14% (95% CI: 2-26%, P = 0.02) higher when cryopreserved on in vitro Day 6 as compared to Day 3. Regarding the ART treatment type, s-hCG after FET blastocyst transfer (Day 5 blastocysts) cycles was significantly higher, 33% (95% CI: 27-45%, P < 0.001), compared to fresh ET (Day 5 blastocyst), while there was no difference between cleavage-stage FET (Days 2 + 3) and fresh ET (Days 2 + 3). S-hCG was 12% (95% CI: 4-19%, 0.005) lower in
PGT FET (Day 5 blastocysts) cycles as compared to FET cycles without
PGT (Day 5 blastocysts).
CONCLUSIONS: The retrospective design is a limitation which introduces the risk of possible bias and confounders such as embryo score, parity, and ovarian stimulation.
CONCLUSIONS: This study elucidates how practices in medically assisted reproduction treatment are associated with the hCG kinetics, underlining a potential impact of in vitro culture length and mode of ART on the very early embryo development and implantation. The study provides clinicians knowledge that the type of ART used may be relevant to take into account when evaluating s-hCG for the prognosis of the pregnancy.
BACKGROUND: No funding was received for this study. AP has received consulting fees, research grants, or honoraria from the following companies: Preglem, Novo Nordisk, Ferring Pharmaceuticals, Gedeon Richter, Cryos, Merck A/S, and Organon. AZ has received grants and honoraria from Gedeon Richter. NLF has received grants from Gedeon Richter, Merck A/S, and Cryos. MLG has received honoraria fees or research grants from Gedeon Richter, Merck A/S, and Cooper Surgical. CB has received honoraria from Merck A/S. MB has received research grants and honoraria from IBSA. MPR, KM, and PVS all report no conflicts of interest.
BACKGROUND: The study was registered and approved by the Danish Protection Agency, Capital Region, Denmark (Journal-nr.: 21019857). No approval was required from the regional ethics committee according to Danish law.