2015年2月26日 星期四

什麼是CCS全基因晶片篩檢胚胎?qPCR

什麼是CCS全基因晶片篩檢胚胎?qPCR






試管嬰兒已經進入PGS第三代,
第一代是第三天胚胎切片用螢光原位雜交染色法FISH,因為只有看5個、9個染色體,而且第三天胚胎切片,經由美國紐澤西RMANJ團隊,第三天切片一些會減少39%的胚胎著床率,
PGS第二代是第五天囊胚期胚胎切片,用aCGH也就是微陣列基因晶片,一來第五天切片不傷胚胎,著床率不會受影響,
第五天可以使用的胚胎分析還有SNP單核甘酸多樣性,
和最新的qPCR 3小時,
準確性多達98%,
但SNP時間比較久要24小時,
array CGH目前台灣要2到3天久的話要一個禮拜,國外可以12小時,
因此要冷凍胚胎,在美國紐澤西RMANJ團隊,直接跳過array CGH不用aCGH
他們專利的qPCR -- 24只要3小時有報告,準確率98%,根據Treff崔夫的設計不用96個探針,80幾個探針就可以偵測全基因24染色體,達到CCS;可以新鮮胚胎植入超快速,準確率98%,但有小小的缺點是微片段基因的缺陷抓不出來,
而array CGH一下去就是65萬個探針,平均每個染色體有2500到2700探針,解析度雖高,但有時候會太高,會誤殺胚胎,
第3代的PGS是次世代定序NGS,有三大特色:
(1)全基因診斷、
(2)單基因疾病診斷、
(3)細胞質的粒線體基因診斷,
目前英國針對吵的沸沸揚揚,3個爹娘試管嬰兒其實可以透過次世代定序NGS就可以免去三爹娘試管嬰兒的偵測。
博元婦產科非常有負責的告訴妳:我們已進入PGS第2代的qPCR一條龍的試管嬰兒,我們的PGS不用冷凍胚胎,從打排卵針,取卵,培養囊胚,今天切片,今天或明天就有胚胎染色體報告可以植入健康胚胎,
我們的統計成績已發表在台灣婦產科醫學會年會,
qPCR的好處是:
(1)便宜、
(2)快速、
(3)準確率98%
(4)新鮮胚胎植入,免去冷凍胚胎的費用、
(5)省去妳煎熬等待當父母的漫漫長夜時˙間。
博元試管嬰兒中心以讓父母
少壓力、
少負擔、
少花費,
最快速度達到一圓子望求子的目的,
我們的終極目標是一次植入一個健康的寶寶,
也希望能夠一次成功,
在此告訴妳博元婦產科已經進入PGS第2代正邁向第3代的路上,妳還再冷凍胚胎做CCS嗎?妳還再冷凍胚胎嗎?美國紐澤西RMANJ團隊在最近一次生育與節育期刊發表7個理由,論述胚胎切片全基因檢查應該要新鮮植入胚胎的是世代已經到來見以下言文,
你還在冷凍胚胎苦等報告嗎?妳還再繳冷凍胚胎的費用嗎?

參考:
Comprehensive chromosome screening with

synchronous blastocyst transfer: time for a

paradigm shift*

Recently, the nature of assisted reproductive technology

(ART) laboratory investigation has been shifting. Tradition-
ally, it has focused on optimizing the culture milieu or assur-
ing fertilization; now, a variety of new technologies are

available to assess the reproductive potential of individual

embryos. Perhaps most prominent has been the resurgence

of embryonic aneuploidy screening. The validation of

24-chromosome testing platforms has led to a variety of

studies demonstrating higher implantation and delivery rates.

These findings are now translating to changes in the para-
digm of ART practice.

Caution is prudent in times of change, and methodical

analyses are needed. Evaluation logically focuses on efficacy

in terms of enhanced implantation and delivery rates. Other

factors, such as safety, cost, and accessibility also deserve

thoughtful consideration. Evaluations of these endpoints

should take into account the caliber of the data supporting

the ‘‘new paradigm,’’ in parallel with the data supporting

the current ‘‘standard of care,’’ and both should be evaluated

with the same level of rigor.

Several investigators have recently expressed concerns

about the implementation of comprehensive chromosomal

screening (CCS) in clinical practice. Fortunately, an ever-
growing literature is available to provide clinicians and scien-
tists with the information they need to evaluate many of the

critical issues. Some of the major issues and questions

include:

1. Efficacy of 24-chromosome embryonic aneuploidy

screening. Multiple studies provide class I data demon-
strating higher implantation and delivery rates following

24-chromosome aneuploidy screening. In distinct contrast

to fluorescent in-situ hybridization-based preimplantation

genetic screening studies in which every randomized

controlled trial (RCT) showed either no improvement or

active detriment, every RCT involving 24-chromosome

screening has demonstrated benefit (1–3).

2. What magnitude of improvement in clinical outcomes is

necessary to justify screening? Answering this question

inevitably involves a subjective decision that will be

made by patients after counseling by the clinicians caring

for them. Given that aneuploidy rates vary from 25% in

women in their late twenties to 85% for those in their

mid-forties, the opportunity for enhancing outcomes will

be greatly affected by the age of the female partner and

her intrinsic ovarian responsiveness. It is unlikely that im-
provements will be made in direct proportion to the aneu-
ploidy rate, as many other factors affect delivery rates.

Women with high embryonic arrest rates are unlikely to

attain the full benefit of screening. Still, the magnitude of

the enhanced outcomes seen in the RCTs is substantial.

3. The cost of CCS may be burdensome. Although substantial

costs are associated with CCS, even in proportion, they are

* This is an open access article under the CC BY-NC-ND license (http:// would appear that this type of screening is appropriate

creativecommons.org/licenses/by-nc-nd/3.0/).

660 VOL. 102 NO. 3 / SEPTEMBER 2014

lower than the costs of additional ART cycles. A definitive

cost-effectiveness study has not been published to date.

Although enhanced delivery rates should translate to fewer

treatment cycles, that question must await more detailed

analyses before conclusions may be drawn. Additionally,

savings attributable to decreased pregnancy losses and the

care provided to ongoing aneuploid gestations would need

to be considered. Given that, and the impact on transfer or-
der discussed below, it is unlikely that cost effectiveness will

limit implementation of embryonic aneuploidy screening.

4. Implementation of CCS may actually increase the risk for

multiple gestations unless transfer order is reduced. That

very fact has already been established in a randomized

controlled trial (2). In fact, it is a mathematical certainty.

As implantation rates increase, if there is no decrease in

transfer order, then multiple gestation rates will inevitably

rise. However, it is not reasonable to assume that transfer

order would remain the same. For the first time, there are

class I data demonstrating eSET after CCS is as effective

as double-embryo transfer of unscreened embryos (2).

All prior RCTs comparing elective single-embryo transfer

(eSET) versus double-embryo transfer found poorer per-
transfer outcomes with eSET. If CCS is used, that is no

longer true. Equivalent delivery rates are maintained while

virtually eliminating the risk of twins. The paradigm using

CCS and eSET produced an average gain in birth weight of

approximately 650 grams. No other single intervention in

obstetrics has produced such a dramatic enhancement in

birth weight, which is known to be highly correlated

with the health of the child. Of course, the transfer of

two screened embryos would further increase pregnancy

rates, but at the cost of quite elevated twin rates; thus, it

should be discouraged. Armed with these data, utilization

of eSET in our program has risen from less than 6% to

approximately 60% over a 4-year interval.

5. Embryo cryopreservation is essential to the application of

CCS. This is an excellent point, as it is true in many, but not

all, programs. Analyses can be completed in as little as

4 hours, and several programs now have testing labora-
tories within their facilities. However, that may not be

necessary. Data from RCTs demonstrate equivalent deliv-
ery rates following the transfer of fresh or vitrified CCS

screened blastocysts (2). Furthermore, data now demon-
strate meaningfully better obstetrical outcomes in concep-
tions following the transfer of cryopreserved embryos.

6. Some subpopulations may not benefit from aneuploidy

screening. The studies to date have focused on infertile

normal responders. No class I data address the impact of

CCS in women who are low responders or have recurrent

pregnancy loss. An RCT to determine the impact of CCS

in women at risk for low response to gonadotropin stimu-
lation has been registered (NCT01977144) and is currently

underway. Within the general ART population, individuals

who might typically be considered candidates for two-
embryo transfer should be offered CCS. Given that the

eSET rate was 8.8% in the recently released 2012 Society

for Assisted Reproductive Technology (SART) data, it

Fertility and Sterility®

for very large numbers of patients. Even those patients

who desire eSET attain increased delivery rates if the

euploid embryos are selected for transfer. Although

many of these patients already have excellent delivery

rates, it is difficult to imagine a scenario in which the in-
creases in implantation rates seen in the RCTs done to

date would not be a compelling reason to screen.

7. The need to culture to the blastocyst stage to safely biopsy

embryos increases the number of futile cycles because of

embryonic arrest prior to blastulation. This issue is

extremely important and represents a widely held belief,

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