Time lapse(胚胎即時監測)常用指標
5 cell 時間----time to division to 5 cells (t5), 
第3次分裂時間----time period of the third cell cycle (CC3), 
2 cell 到 5 cell 時間----time from 2 cell division to 5 cell division (t5-t2) 

Time lapse(胚胎即時監測)仍具相當多盲點，無法取代PGD(胚胎基因染色體診斷)
65%正常染色體胚胎會形成囊胚
60%異常染色體胚胎會形成囊胚

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4915281/

J Hum Reprod Sci. 2016 Apr-Jun;9(2):112-8. doi: 10.4103/0974-1208.183511.

Morphokinetic behavior of euploid and aneuploid embryos analyzed by time-lapse in embryoscope.

Patel DV1, Shah PB1, Kotdawala AP1, Herrero J2, Rubio I2, Banker MR1.

Author information

Abstract

BACKGROUND:

Embryonic aneuploidy may result in miscarriage, implantation failure, or birth defects. Thus, it is clinically necessary to avoid the selection of aneuploid embryos during in vitro fertilization treatment.

AIM:

The aim of this study was to identify the morphokinetic differences by analyzing the development of euploid and aneuploid embryos using a time-lapse technology. We also checked the accuracy of a previously described model for selection of euploid embryos based on morphokinetics in our study population.

MATERIALS AND METHODS:

It is a retrospective study of 29 cycles undergoing preimplantation genetic screening from October 2013 to April 2015 at our center. Of 253 embryos, 167 suitable for biopsy embryos were analyzed for their chromosomal status using array-comparative genome hybridization (CGH). The morphokinetic behavior of these embryos was further analyzed in embryoscope using time-lapse technology.

RESULTS:

Among the analyzed embryos, 41 had normal and 126 had abnormal chromosome content. No significant difference in morphokinetics was found between euploid and aneuploid embryos. The percentage of embryos with blastulation was similar in the euploid (65.85%, 27/41) and aneuploid (60.31%, 76/126) embryos (P = 0.76). Although hard to define, majority of the chromosomal defects might be due to meiotic errors. On applying embryo selection model from Basile et al., embryos falling within optimal ranges for time to division to 5 cells (t5), time period of the third cell cycle (CC3), and time from 2 cell division to 5 cell division (t5-t2) exhibited greater proportion of normal embryos than those falling outside the optimal ranges (28.6%, 25.9%, and 26.7% vs. 17.5%, 20.8%, and 14.3%).

CONCLUSION:

Keeping a track of time interval between two stages can help us recognize aneuploid embryos at an earlier stage and prevent their selection of transfer. However, it cannot be used as a substitute for array CGH to select euploid embryos for transfer.

高齡卵子之粒腺體功能下降是造成品質&受孕率下降眾多原因之一
補充注射高齡卵子之粒腺體並無法有效改善高齡卵子之品質及受孕率

Hum Reprod. 2016 Oct;31(10):2331-8. doi: 10.1093/humrep/dew203. Epub 2016 Sep 2.

Poor embryo development in post-ovulatory in vivo-aged mouse oocytes is associated with mitochondrial dysfunction, but mitochondrial transfer from somatic cells is not sufficient for rejuvenation.

Igarashi H1, Takahashi T2, Abe H3, Nakano H4, Nakajima O4, Nagase S1.

Author information

Abstract

STUDY QUESTION:

Does in vivo aging of mouse oocytes affect mitochondrial function?

SUMMARY ANSWER:

Mitochondrial function was impaired in post-ovulatory in vivo-aged mouse oocytes and microinjection of somatic cell mitochondria did not rescue poor fertilization and embryonic development rates.

WHAT IS KNOWN ALREADY:

The mechanisms underlying the decline in oocyte quality associated with oocyte aging remain unknown, although studies have suggested that the decline is regulated by mitochondrial dysfunction. However, only a limited number of studies have provided direct evidence implicating mitochondrial dysfunction in oocyte quality during the aging of oocytes.

STUDY DESIGN, SIZE, DURATION:

We used post-ovulatory, in vivo-aged mouse oocytes as a model for studying low-quality oocytes in oocyte aging.

PARTICIPANTS/MATERIALS, SETTING, METHOD:

Superovulated oocytes released from the oviduct at 14 h and 20-24 h post-hCG injection were designated as 'fresh' and 'aged' oocytes, respectively. Membrane potentials and oxygen consumption in single oocytes were evaluated as measures of mitochondrial function in fresh and aged oocytes. Mitochondrial transcriptional factor A (TFAM) expression levels were examined by western blotting, and colocalization of mitochondria and TFAM was analyzed by measuring immunofluorescence in fresh and aged oocytes. IVF and blastocyst formation rates were calculated after oocyte microinjection with mitochondria derived from liver cells.

MAIN RESULTS AND THE ROLE OF CHANCE:

The average mitochondrial membrane potential in fresh oocytes was significantly higher than that in aged oocytes (P < 0.05). The average oxygen consumption rate in aged oocytes was significantly lower than that in fresh oocytes (P < 0.05). Although total TFAM expression was unchanged, its colocalization with mitochondria decreased in aged oocytes. IVF and blastocyst formation rates for mitochondrion-injected aged oocytes were not significantly different from those for buffer-injected aged oocytes.

LARGE SCALE DATA:

Not applicable.

LIMITATIONS, REASONS FOR CAUTION:

A limitation of this study is that we did not examine the effects of microinjecting mitochondria from other somatic cell types into aged oocytes on their fertilization and embryonic development rates.

WIDER IMPLICATIONS OF THE FINDINGS:

The results from the present study showed that poor embryonic development was associated with impairment of mitochondrial functions in in vivo-aged oocytes. However, the microinjection of mitochondria from liver cells did not improve the low fertilization and embryonic development rates of aged oocytes. It remains to be demonstrated whether oocyte quality can be rescued by the transfer of cytosolic factors or cellular organelles, such as the endoplasmic reticulum or mitochondria, from specific cell types.

STUDY FUNDING/COMPETING INTERESTS:

This study was supported by Grants-in-Aid for General Science Research to Toshifumi Takahashi (No. 25462550) and Hideki Igarashi (No. 26462474). The funding source played no role in study design in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. The authors have no conflict of interest to disclose.

Day 4 桑葚體胚胎之碎片比例(5%, 5%-20%, or >20%)與胚胎囊胚率( 57.4%, 50%, and 35.6%)有關

Fertil Steril. 2011 Dec;96(6):1473-1478.e2. doi: 10.1016/j.fertnstert.2011.09.015. Epub 2011 Oct 6.

Prediction of human blastocyst development from morulas with delayed and/or incomplete compaction.

Ivec M1, Kovacic B, Vlaisavljevic V.

Author information

Abstract

OBJECTIVE:

To determine the influence of delayed compaction and fragmentation on the developmental capacity of morulas.

DESIGN:

Prospective study.

SETTING:

University IVF center.

PATIENT(S):

Intracytoplasmic sperm injection (ICSI) cycles with compact embryos on day 4 or day 5.

INTERVENTION(S):

The embryos were divided into day 4 (n = 329) and day 5 (n = 256) morulas and graded I, II, or III, according to the percentage of fragmentation (<5%, 5%-20%, or >20%). The embryos were measured using Cronus3 software.

MAIN OUTCOME MEASUREMENT(S):

Blastocyst development rate, blastocoel expansion rate, and optimal blastocyst rate. In an optimal blastocyst: surface area, trophectoderm cell number, inner cell mass (ICM) surface area, ICM volume and ICM shape.

RESULT(S):

Day 4 morulas in classes I-III developed into optimal blastocysts in 57.4%, 50%, and 35.6% of the total, respectively, and day 5 morulas in classes I-III in 43.3%, 29.1%, and 13.6% of the total, respectively. A negative association was identified between the amount of morula fragmentation, the blastocyst ICM size, and the number of trophectoderm cells. A delay of 1 day in compaction was associated with a reduced ICM volume.

CONCLUSION(S):

The measurement of compaction timing and cytoplasmic loss in morulas assists in predicting their ability to develop into optimal blastocysts.

胚胎發育正常速度，符合之囊胚著床率約50%

ICSI後6h應可觀察到2PB
ICSI後12h應可觀察到2PN
2PN直徑差異應<20%，核仁應對稱, 核仁數量差異<3
2PN大軸與最遠PB應<50度
ICSI後26h PN應消失，最好分裂為2 cell(early cleavage)，所有胚葉細胞無多核現像，胚葉細胞大小應一樣‧
ICSI後42-44h應分裂為4 cell，所有胚葉細胞無多核現像，胚葉細胞大小應一樣‧
ICSI後66-68h應分裂為8 cell，所有胚葉細胞無多核現像，胚葉細胞大小應一樣‧
ICSI後94-96h應發育為morula，胚葉細胞應全部參與細胞融合，胚葉細胞與ZP間之空間應擴大，最好形成早期囊胚腔
ICSI後106-108h應發育成熟囊胚(囊胚腔飽滿，ICM細胞多&緻密，TE細胞多)，ZP變薄

http://molehr.oxfordjournals.org/content/early/2016/08/30/molehr.gaw057.full.pdf+html

time lapse胚胎即時監控或許無法明顯提高胚胎著床率
但卻可對胚胎之動態生理學提供更進一步精確之瞭解
包括胚胎分裂立體結構，分裂平面，胚葉細胞相對位置‧
而不僅僅只了解胚胎分裂之速度，胚葉細胞之數量

Cleavage in the preimplantation embryo: it is all about being in the right place at the right time!

1. Denny Sakkas*

+Author Affiliations

1. Boston IVF, 130 Second Avenue, Waltham, MA 02451, USA

1. ↵*Correspondence address. E-mail: dsakkas@bostonivf.com

• Received August 22, 2016.
• Revision received August 22, 2016.
• Accepted August 24, 2016.

 

Next Section

In this special review edition of Molecular Human Reproduction, we examine the impact of cell cleavage timing and morphology on the viability of preimplantation embryos. The concept of cleavage timing and morphology is brought into relevance by initially examining how cleavage planes, position and number in the early cleavage embryo impact developmental potential in different models, from flies to human. Finally, the historical use of cleavage assessment and morphology in human IVF  in addition to the current clinical use of time-lapse imaging is discussed.

Preimplantation embryo morphology and the timing of cleavage has been a mainstay for the clinical embryologist in human IVF. In the first reported case of IVF and embryo development in the human, Rock and Menkin (1944) made the following observation about the developing fertilized embryo: ‘One of these (embryo), when first seen in cleavage, consisted of one large blastomere and two smaller ones, each of the three containing a round, vesicular nucleus. The second egg from this same patient was in a similar stage, but part of the cytoplasm appeared fragmented, and soon proceeded to undergo rapid degenerative changes.’

Since that first observation, embryologists working in the field of IVF have relied largely on examining the morphology and timing of embryo development to select the best embryo.

The underlying importance of these two observations has, however, not always been appreciated and the need of the cells within the embryo to cleave in the correct manner and to be in the right place at the right time has sometimes been overlooked by the clinical embryologist.

The first two reviews (Ajduk and Zernicka-Goetz, 2016; Piliszek et al. 2016) examine the question of ‘Is the way a cell divides and where it goes important?’ In these reviews, we gain a better insight into how cleavage patterns impact molecular expression patterns and subsequent viability in species that have a more definitive animal and vegetal pole. We learn that despite the diversity in cleavage patterns between phyla, the molecular mechanisms regulating early embryonic divisions remain strongly conserved. The concept that cleavage division can lead to cells of not only different sizes but inherently different components is introduced and how this ultimately causes cells to follow distinct developmental paths. The observation of how the viability of a mouse embryo is affected by the pattern of segregation and inheritance of material from the daughter blastomere which undergoes at least one meridional division sheds light on the subtle importance of correct cleavage (Ajduk and Zernicka-Goetz, 2016). Piliszek et al. (2016) also discuss cell fate in mouse and human blastocysts again highlighting the importance of cells being in the correct place at the right time. This impacts the concept of just scoring blastocysts in human IVF and highlights the question: are we missing aspects of their development by just scoring expansion, inner cell mass and trophectoderm? The importance of cell positioning in the blastocyst also leads to questions of how much information we can glean from a trophectoderm biopsy when performing preimplantation genetic screening.

In the third review, Gardner and Balaban (2016), the key features of the human preimplantation embryo are considered in light of historical data on the relationship between morphological characteristics and developmental potential. They argue that these observations have not only taught us about embryo potential, but also inform us about the impact of the culture environment on morphological traits and how key morphological qualities reflect aspects of embryo physiology.

The importance of these observations has been an ongoing discussion for human embryos; however, it has now come under more scrutiny with the advent of video imaging or time-lapse systems. The final review from the group of Meseguer (Motato et al., 2016) discusses how time-lapse systems have provided us with a multitude of data which are now being used to track cleavage patterns and timing more precisely. They show how time-lapse systems have taken the evaluation of embryo morphology and developmental kinetics to another level and how it is starting to impact clinical practice. Unfortunately, however, further studies are required to improve the quality of the current evidence.

Our excitement in being able to visualize the preimplantation human embryo in its first few days of development using time-lapse systems is best summarized by Gardner and Balaban (2016), who stated that ‘it has reopened our eyes and given us a new vantage from which to view the beauty of the initial stages of human life’.

By assessing the scientific evidence in different species that relates the viability of an embryo to its early cleavage planes, timing and position, we hope to enlighten readers to think in novel ways regarding how to approach the use of this information. In many ways, we have tackled the analysis of this data with the concepts that we have used historically, using cell number and time. The non-human studies from the fly to the mouse tell us that it is not only number and time but that other aspects are crucial. A deeper analysis of the time-lapse data will in the future allow us to develop algorithms which assimilate not only cell number and time but more components, including the cleavage plane and position of each cell. This data will help us more accurately predict not only which embryo will lead to a healthy live birth, but also provide insights into the genomic and metabolic tendencies of each individual embryo.

染色體異常是IVF胚胎流產之主因(>50%)
染色體異常種類以 trisomy 21(唐氏症), monosomy X(45XO) and triploidy (三倍體)造成胚胎長度最大

Hum Reprod. 2016 Oct;31(10):2212-8. doi: 10.1093/humrep/dew201. Epub 2016 Sep 9.

Correlation between chromosomal distribution and embryonic findings on ultrasound in early pregnancy loss after IVF-embryo transfer.

Ouyang Y1, Tan Y2, Yi Y2, Gong F1, Lin G1, Li X3, Lu G4.

Author information

Abstract

STUDY QUESTION:

Do early pregnancy losses (EPLs) with and without embryos differ in chromosomal distributions?

SUMMARY ANSWER:

The chromosomal abnormality rate is significantly higher in miscarriages with embryos than without after in vitro fertilization (IVF)-embryo transfer.

WHAT IS KNOWN ALREADY:

Chromosomal abnormalities are the main causes of EPLs, the rate of which is up to 24-30% in the IVF population. Little research has been conducted on the correlations between the chromosomal distributions of EPL and the existence of an embryo or with the postmortem embryonic pole length, and the existing results have been inconsistent.

STUDY DESIGN, SIZE, DURATION:

The data of 2172 women who underwent dilation and curettage (D&C) from January 2008 to December 2013 for missed abortion were analyzed retrospectively. The existence of an embryonic pole and the length of the postmortem embryonic pole of the EPL were evaluated by transvaginal sonography (TVS). Ultrasound findings were compared with karyotype results.

PARTICIPANTS/MATERIALS, SETTING, METHOD:

This analysis included 2172 infertility patients who had singleton pregnancies and experienced EPLs after IVF-embryo transfer. The EPLs were divided into embryonic and anembryonic groups based on TVS diagnosis. The crown-rump length of the fetal pole (observed once) was measured twice for each fetus after confirmation of fetal death, subject to the final measurement before D&C. The karyotype analysis was performed using comparative genomic hybridization (CGH) plus fluorescence in situ hybridization technology.

MAIN RESULTS AND THE ROLE OF CHANCE:

The chromosomal abnormality rate was significantly higher in male miscarriages with an embryo than in those without an embryo (54.14% versus 37.50%, P ≤ 0.001). In the anembryonic group, the abnormal karyotype rate was significantly higher in the yolk sac only than that in the empty sac group (46.11% versus 29.77%, P = 0.001); in the embryonic group, the abnormal karyotype rate in miscarriages with postmortem embryonic pole length >20 mm was significantly lower than that in miscarriages with pole length <10 mm (P = 0.006) and 10-20 mm (P = 0.036). There were significant differences in abnormal karyotype rates among miscarriages of different developmental stages (P ≤ 0.001). The cases with embryonic stages had the highest risk (54.89%) of an abnormal karyotype and those with fetal stages had the lowest risk (18.18%). There were significant differences in the length of postmortem embryonic poles among groups with different karyotypes (P ≤ 0.001). In addition, trisomy 21, monosomy X and triploidy had the longest lengths of postmortem embryonic poles (16, 15.3 and 11.6 mm, respectively).

卵子冷凍前1小時使用glutathione ethyl ester(1mM)共同培養，可提高卵子玻璃化冷凍解凍之存活率與受孕率

Mol Hum Reprod. 2016 Sep 7. pii: gaw059. [Epub ahead of print]

Improved cryo-tolerance and developmental potential of in vitro and in vivo matured mouse oocytes by supplementing with a glutathione donor prior to vitrification.

Trapphoff T1, Heiligentag M1, Simon J1, Staubach N1, Seidel T2, Otte K3, Fröhlich T3, Arnold GJ3, Eichenlaub-Ritter U4.

Author information

Abstract

STUDY QUESTION:

Can supplementation of media with a glutathione (GSH) donor, glutathione ethyl ester (GEE), prior to vitrification protect the mouse oocyte from oxidative damage and critical changes in redox homeostasis, and thereby improve cryotolerance?

SUMMARY ANSWER:

GEE supplementation supported redox regulation, rapid recovery of spindle and chromosome alignment after vitrification/warming and improved preimplantation development of mouse MII oocytes.

WHAT IS KNOWN ALREADY:

Cryopreservation may affect mitochondrial functionality, induce oxidative stress, and thereby affect spindle integrity, chromosome segregation and the quality of mammalian oocytes. GEE is a membrane permeable glutathione donor that promoted fertilization and early embryonic development of macaque and bovine oocytes after in vitro maturation (IVM).

STUDY DESIGN, SIZE, DURATION:

Two experimental groups consisted of: (i) Denuded mouse germinal vesicle (GV) oocytes that were matured in vitro in the presence or absence of 1 mM GEE (IVM group 1), and (ii) in vivo ovulated (IVO) MII oocytes that were isolated from the ampullae and exposed to 1 mM GEE for 1 h prior to vitrification (IVO group 2). Recovery of oocytes from both groups was followed after CryoTop vitrification/warming for up to 2 h and parthenogenetic activation.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Reactive oxygen species (ROS), spindle morphology and chromosome alignment were analyzed by confocal laser scanning microscopy (CLSM) and polarization microscopy in control and GEE-supplemented MII oocytes. The relative overall intra-oocyte GSH content was assessed by analysis of monochlorobimane (MBC)-GSH adduct fluorescence in IVM MII oocytes. The GSH-dependent intra-mitochondrial redox potential (Em GSH) of IVM MII oocytes was determined after microinjection with specific mRNA at the germinal vesicle (GV) stage to express a redox-sensitive probe within mitochondria (mito-Grx1-roGFP2). The absolute negative redox capacity (in millivolts) was determined by analysis of fluorescence of the oxidized versus the reduced form of sensor by CLSM and quantification according to Nernst equation. Proteome analysis was performed by quantitative two dimensional saturation gel electrophoresis (2D DIGE). Since microinjection and expression of redox sensor mRNA required removal of cumulus cells, and IVM of denuded mouse oocytes in group 1 induces zona hardening, the development to blastocysts was not assessed after IVF but instead after parthenogenetic activation of vitrified/warmed MII oocytes from both experimental groups.

MAIN RESULTS AND ROLE OF CHANCE:

IVM of denuded mouse oocytes in the presence of 1 mM GEE significantly increased intra-oocyte GSH content. ROS was not increased by CryoTop vitrification but was significantly lower in the IVM GEE group compared to IVM without GEE before vitrificationand after recovery from vitrification/warming (p < 0.001). Vitrification alone significantly increased the GSH-dependent intra-mitochondrial redox capacity after warming (Em GSH, p < 0.001) in IVM oocytes, presumably by diffusion/uptake of cytoplasmic GSH into mitochondria. The presence of 1 mM GEE during IVM increased the redox capacity before vitrification and there was no further increase after vitrification/warming. None of the reproducibly detected 1492 spots of 2D DIGE separated proteins were significantly altered by vitrification or GEE supplementation. However, IVM of denuded oocytes significantly affected spindle integrity and chromosome alignment right after warming from vitrification (0 h) in group 1 and spindle integrity in group 2 (p < 0.05). GEE improved recovery in IVM group as numbers of oocytes with unaligned chromosomes and aberrant spindles was not significantly increased compared to unvitrified controls. The supplementation with GEE for 1 h before vitrification also supported more rapid recovery of spindle birefringence. GEE improved significantly development to the 2-cell stage for MII oocytes that were activated directly after vitrification/warming in both experimental groups, and also the blastocyst rate in the IVO GEE-supplemented group compared to the controls (p < 0.05).

Day 3 vs Day 5胚胎培養植入

累積懷孕率(含冷凍胚胎植入)無明鮮差異( 52.6% vs 52.5%)

Hum Reprod. 2016 Sep 12. [Epub ahead of print]

Cumulative live birth rates after fresh and vitrified cleavage-stage versus blastocyst-stage embryo transfer in the first treatment cycle.

De Vos A1, Van Landuyt L2, Santos-Ribeiro S2, Camus M2, Van de Velde H2, Tournaye H2, Verheyen G2.

Author information

Abstract

STUDY QUESTION:

Do cumulative live birth rates differ between single cleavage-stage Day 3 transfer and single blastocyst-stage Day 5 transfer?

SUMMARY ANSWER:

Cumulative live birth rates after Day 3 and 5 transfers were similar in young patients when the vitrified embryo transfers were also taken into account.

WHAT IS KNOWN ALREADY:

Previous evidence has shown that the probability of live birth following IVF with a fresh embryo transfer is significantly higher after blastocyst-stage Day 5 transfer. However, because the introduction of vitrification has enhanced the survival of cryopreserved embryos and improved pregnancy rates, the optimal outcome measure for this comparison should now be cumulative live birth rates, as these include the eventual contribution of vitrified-warmed embryos.

STUDY DESIGN, SIZE, DURATION:

Our retrospective study included first IVF/ICSI cycles performed between January 2010 and December 2013 at a tertiary care centre.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

All patients were scheduled for fresh single embryo transfer, either on Day 3 (n = 377) or on Day 5 (n = 623). Both IVF and ICSI cycles were included and the sperm used were either fresh or frozen partner ejaculates, or frozen donor ejaculates. The primary outcome was cumulative live birth (after 24 weeks) rate per started cycle, including the eventual contribution of vitrification until the birth of a first child.

MAIN RESULTS AND THE ROLE OF CHANCE:

Live birth rates per started cycle were significantly lower after transferring the fresh single cleavage-stage embryo, compared to a blastocyst (31.3% and 37.8%, respectively, P = 0.041). Furthermore, the number of embryo transfers necessary until the first live birth was significantly lower for blastocyst-stage embryos (P < 0.001). However, the cumulative live birth rates were 52.6% for cleavage-stage and 52.5% for blastocyst-stage transfers (P = 0.989).

使用長效型排卵針corifollitropin alpha (CFA) vs 使用短效型排卵針(Gona-F, Puregon)
引發早期黃體化(P4>1.5 ng/ml)比率: 5.4% vs 18.3%
長效型排卵針較不會引發早期黃體化

Hum Reprod. 2016 Sep 12. [Epub ahead of print]

Impact of gonadotropin type on progesterone elevation during ovarian stimulation in GnRH antagonist cycles.

Lawrenz B1, Beligotti F2, Engelmann N3, Gates D4, Fatemi HM3.

Author information

Abstract

STUDY QUESTION:

Does hormonal stimulation with corifollitropin alpha (CFA) only, mimicking a step down protocol, result in lower incidence of progesterone elevation on the day of hCGtrigger as compared to sustained stimulation with recombinant FSH (rFSH)?

SUMMARY ANSWER:

The current findings support the concept that sustained FSH stimulus contributes to premature progesterone elevation in stimulated IVF cycles.

WHAT IS KNOWN ALREADY:

Serum progesterone rise during the follicular phase of ovarian stimulation for IVF treatment seems to be related to a poorer reproductive outcome. However, the mechanism by which the rise in progesterone is caused is not yet fully understood.

STUDY DESIGN, SIZE, DURATION:

This study was a post hoc analysis of data from two multi-center, randomized, double-blind, double-dummy, active-controlled, non-inferiority trials, ENGAGE and PURSUE, conducted from June 2006 to January 2008 and from July 2010 to October 2012 respectively.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

In the ENGAGE-study, 1506 women, aged 18-36 years, were allocated to either a single injection of 150 mg CFA or daily injections of 200 IU rFSH in the first week of stimulation, using a standard GnRH antagonist protocol. In the PURSUE-study, a total of 1390 women, aged 35-42 years, were allocated to either a single injection of 150 mg of CFA or daily 300 IU of rFSH for the first week, again using a standard GnRH antagonist protocol. In both trials, daily rFSH was continued until three follicles reached >17 mm in size. All women had a body weight of between 50 and 90 kg, regular menstrual cycles and an indication for ovarian stimulation before IVF. The incidence of progesterone elevation on day of hCG-trigger in patients with CFA only or rFSH stimulation, and triggered on Day 8 of stimulation, was analyzed.

MAIN RESULTS AND THE ROLE OF CHANCE:

Of patients with CFA only stimulation, 5.4% (13/239 patients) showed a progesterone elevation above 1.5 ng/ml on day of hCG-trigger, whereas patients with rFSH stimulation had a significant higher incidence of progesterone elevation (18.3%; 62/339 patients) (P < 0.001).

Day5-6囊胚破卵與否與胚胎植入後活產率無明顯差異(55% vs 50%)

Hum Reprod. 2016 Sep 12. [Epub ahead of print]

Hatching status before embryo transfer is not correlated with implantation rate in chromosomally screened blastocysts.

Rodriguez-Purata J1, Gingold J2, Lee J2, Whitehouse M2, Slifkin R2, Briton-Jones C2, Copperman A3, Sandler B3.

Author information

Abstract

STUDY QUESTION:

Do the reproductive outcomes from the transfer of fully hatched (FH) blastocysts differ from those of not fully hatched (NFH) blastocysts?

SUMMARY ANSWER:

Biochemical pregnancy rate (BPR), implantation rate (IR), live birth rate (LBR) and early pregnancy loss (EPL) rate are similar in FH and NFH single euploid blastocyst embryo transfers.

WHAT IS KNOWN ALREADY:

The use of extended culture and PGS often leads to transfer of an embryo that is well developed and frequently FH from the zona pellucida. Without the protection of the zona, an FH embryo could be vulnerable to trauma during the transfer procedure. To date, no other study has evaluated the reproductive competence of an FH blastocyst transfer.

STUDY DESIGN, SIZE, DURATION:

The retrospective study included 808 patients who underwent 808 cycles performed between September 2013 and July 2015 at a private academic IVF center. Of these, 436 cycles entailed transfer of a NFH blastocyst (n = 123 fresh transfer, n = 313 frozen/thawed embryo transfer (FET)) and 372 cycles entailed transfer of an FH blastocyst (n = 132 fresh, 240 FET). Fresh and FET cycles and associated clinical outcomes were considered separately. LBR was defined as the delivery of a live infant after 24 weeks of gestation.

PARTICIPANTS/MATERIALS, SETTING, METHOD:

Trophectoderm biopsies were performed on Day 5 (d5) or 6 (d6) for embryos meeting morphology eligibility criteria (set at ≥3BC). Morphologic grading was determined using a modified Gardner-Schoolcraft scale prior to transfer. A single euploid embryo was selected for transfer per cycle on either the morning of d6, for fresh transfers or 5 days after progesterone supplementation for patients with transfer in an FET cycle. Embryos were classified as NFH (expansion Grade 3, 4 or 5) or FH (expansion Grade 6) cohorts. The main outcome measure was IR.

MAIN RESULTS AND THE ROLE OF CHANCE:

In the fresh transfer group, IR was similar between NFH and FH cycles (53.7% versus 55.3%, P = 0.99, odds ratio (OR) 0.9; 95% confidence interval (CI) 0.6-1.5). Secondary outcomes were also statistically similar between groups: BPR (65.9% versus 66.7%, OR 1.0; 95% CI: 0.6-1.6), LBR (43.1% versus 47.7%, P = 0.45, OR 1.2; 95% CI: 0.7-1.9) and EPL rate (22.8% versus 18.2%, OR 1.3; 95% CI: 0.7-2.4). After adjusting for age, BMI, endometrial thickness at the LH surge and oocytes retrieved in a logistic regression (LR) model, the hatching status remained not associated with IR (P > 0.05). In the FET cycles, IR was similar between NFH and FH cycles (62.6% versus 61.7%, OR 1.0; 95% CI: 0.7-1.5). Secondary outcomes were similar between groups: BPR (74.1% versus 72.9%, respectively, OR 1.1; 95% CI: 0.7-1.6), LBR (55.0% versus 50.0%, OR 0.8; 95% CI: 0.6-1.1) and EPL rate (18.9% versus 22.9%, respectively, OR 0.8; 95% CI: 0.5-1.2). After adjusting for age, BMI, endometrial thickness at the LH surge and oocytes retrieved in an LR model, the hatching status was not shown to be associated with implantation (P > 0.05).

使用即時監控胚胎time lapse篩選胚胎 vs 傳統胚胎型態篩選胚胎
二者懷孕率無明顯差異(34.3% vs 34.6%)

time lapse無法明顯提高胚胎篩選著床率

Hum Reprod. 2016 Sep 12. [Epub ahead of print]

Embryo selection using time-lapse analysis (Early Embryo Viability Assessment) in conjunction with standard morphology: a prospective two-center pilot study.

Kieslinger DC1, De Gheselle S2, Lambalk CB3, De Sutter P2, Kostelijk EH3, Twisk JW4, van Rijswijk J3, Van den Abbeel E2, Vergouw CG3.

Author information

Abstract

STUDY QUESTION:

Does prospective embryo selection using the results from the Eava Test (Early Embryo Viability Assessment) in combination with standard morphology increase the pregnancy rate of IVF and ICSI patients compared to embryo selection based on morphology only?

SUMMARY ANSWER:

Embryo selection using the Eeva Test plus standard morphology on Day 3 results in comparable pregnancy rates as conventional morphological embryo selection.

WHAT IS KNOWN ALREADY:

Time-lapse monitoring of embryo development may represent a superior way to culture and select embryos in vitro. The Eeva Test records the development of each embryo with a cell-tracking system and predicts the likelihood (High, Medium or Low) that an embryo will form a blastocyst based on an automated analysis of early cell division timings.

STUDY DESIGN, SIZE, DURATION:

This trial was designed as a prospective, observational, two-center pilot study with a propensity matched control group. The analysis involved 280 of 302 enrolled patients who were included in the Eeva Test group in 2013 and 560 control patients who were treated in the years 2011-2013. The majority of transfers (98%) were single embryo transfers.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Two academic hospitals (VUmc Amsterdam and UZ Gent) enrolled patients <41 years old, with <3 previous attempts and ≥5 normally fertilized eggs. Propensity matching was used to identify a propensity matched control group from a cohort of 1777 patients based on age, cycle number, oocyte number and number of fertilized oocytes.

MAIN RESULTS AND THE ROLE OF CHANCE:

There was no difference in patient baseline characteristics between the two groups. The ongoing pregnancy rate (OPR) of patients enrolled in the Eeva Test group (34.3%; 96/280) did not differ significantly from the OPR in the propensity matched control group (34.6%, 194/560; P = 0.92). However, significantly less top quality embryos (eight-cell embryos with ≤25% fragmentation) were transferred in the Eeva Test group compared to the propensity matched control group (70.4% vs. 82.3%; P < 0.001). The transfer of Eeva High and Medium embryos resulted in a significantly higher OPR of 36.8% (89/242) compared to 18.4% (7/38) for Eeva Low embryos (P = 0.02).