Day4 胚胎可能尚無自我修復染色體之能力

Day4胚胎有高比例之染色體異常(>50%)

Day4前胚胎可能尚無自我修復染色體之能力

胚胎自我修復染色體之能力可能始自Day5囊胚期

http://humrep.oxfordjournals.org/content/28/6/1716.abstract

17%囊胚期胚胎同時兼具正常與異常染色體

PGD顯示，17%囊胚期胚胎同時兼具正常與異常染色體
這些胚胎仍可能發展成正常胚胎

囊胚期胚胎PGD並非全然準確

Of more significance may be the 17% of blastocysts that contained both diploid and aneuploid cells. The fate of these embryos is unclear. It is possible that the aneuploid cells have a growth disadvantage or are eliminated by processes such as apoptosis, leading to a decline in their numbers as development progresses, ultimately resulting in a normal fetus. If this scenario is correct, some diploid–aneuploid mosaic blastocysts may be viable and might be incorrectly discarded if aneuploid cells were detected following TE biopsy. 

http://humrep.oxfordjournals.org/content/26/2/480.full

植入胚胎有百分之30在著床後12天內流產

植入胚胎有30%順利活產

植入胚胎有30%完全未著床
植入胚胎有30%在著床後12天內流產
植入胚胎有10%在著床後12天後流產

懷孕早期流產有72%染色體異常

http://humupd.oxfordjournals.org/content/8/4/333.full.pdf+html

植入前胚胎染色體有高度不穩定性

植入前胚胎染色體有高度不穩定性，包括
染色體缺損，多套染色體，etc

http://www.ncbi.nlm.nih.gov/pubmed/19396175?dopt=Abstract

3-D sona 於胚胎植入

使用3-D sona 於胚胎植入

http://www.jultrasoundmed.org/content/28/5/573.full

COH劑量150iu vs 225iu 臨床結果類似

非高齡誘導排卵啟始劑量150iu vs 225iu
取卵數&胚胎數較少，但臨床結果類似

http://humupd.oxfordjournals.org/content/17/2/184.full

囊胚期植入子宮收縮頻率明顯下降

囊胚期植入(hCG打後第7天)比Day2胚胎植入(hCG打後第4天)
子宮收縮頻率明顯下降(1.5 contractions/min vs 3.5 contractions/min) 

http://humrep.oxfordjournals.org/content/16/6/1115.long

Day2 vs Day5誘導排卵抽血結果類似

Day2 或 Day5誘導排卵其抽血結果類似，
Day5誘導排卵卵泡數量少於 Day2誘導排卵

http://jcem.endojournals.org/content/96/4/1122.full

低劑量COH懷孕率較一般劑量COH為低

低劑量誘導排卵COH之試管嬰兒IVF療程懷孕率較一般劑量IVF療程為低
(18 vs 29%)

http://humrep.oxfordjournals.org/content/25/11/2678.full

IVF取卵數理想數量為15顆

取卵數15顆為理想數量，
可達最佳懷孕率，
並不提高卵巢過度刺激風險




http://humrep.oxfordjournals.org/content/26/7/1768.full

Laser可提高囊胚冷凍之存活率

玻璃化冷凍前，施行囊胚雷射輔助孵化可提高囊胚冷凍之存活率

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3114962/?report=reader

封閉式vs開放式冷凍載具胚胎存活率類似

玻璃化冷凍載具可分封閉式vs開放式，二者胚胎存活率類似

http://www.ncbi.nlm.nih.gov/pubmed/23315263

紫外光可應用於防止冷凍過程病毒傳染

紫外光可殺死液態氮中之病毒
可應用於防止冷凍過程病毒傳染

http://humrep.oxfordjournals.org/content/24/11/2969.long

Letrozole對於懷孕胚胎早期骨骼發育有不良影響

Letrozole對於懷孕胚胎早期骨骼發育有不良影響
Letrozole抑制cytochrome P450 enzyme aromatase  &抑制estrogen生成

http://humrep.oxfordjournals.org/content/24/11/2688.full

玻璃化冷凍中快速回溫比快速降溫更關鍵

玻璃化冷凍解凍過程中，
解凍過程中之溫度快速回溫比冷凍過程之快速降溫對於胚胎之存活更為關鍵

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2729265/?report=reader

高達百分之15植入胚胎會被子宮收縮排出

胚胎植入後有高達15%胚胎會被子宮收縮排出子宮外

http://humrep.oxfordjournals.org/content/20/1/170.full

Day5冷凍囊胚懷孕率優於Day6

Day5囊胚冷凍解凍懷孕率優於Day6囊胚(39% vs 29%)

http://humrep.oxfordjournals.org/content/18/2/384.full

Zygote arrest與胚胎原核及細胞質型態有關

Day1胚胎受孕後停止分裂(Zygote arrest)
與Day1胚胎原核型態及細胞質型態有關

http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=8394168

Day 1胚胎原核與極體等級與胚胎品質無明顯關連

Day 1胚胎原核與極體等級與胚胎品質無明顯關連

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2902489/?tool=pubmed

Day1&2胚胎細胞核狀況無法有效預測胚胎懷孕率

Day1胚胎原核PN狀況(Z score) & Day2胚胎細胞核狀況無法有效預測胚胎品質與懷孕率

http://www.ncbi.nlm.nih.gov/pubmed/21316045?dopt=Abstract&holding=f1000,f1000m,isrctn

卵子染色體異常率約65%，囊胚染色體異常率約45%

PGD顯示，卵子染色體異常率約65%
囊胚期胚胎染色體異常率約45%

http://www.sciencedirect.com/science/article/pii/S0015028209010784

胚胎原核無法有效預測胚胎品質

Day1胚胎原核PN無法有效預測胚胎品質

http://informahealthcare.com/doi/abs/10.3109/09513590.2010.509829

胚胎分裂速度太慢胚胎染色體常併異常aneuploidy

胚胎分裂速度太慢代表胚胎染色體異常aneuploidy

cell cycle time約 10–12 h 

囊胚染色體異常aneuploidy機率高達50-60%

正常分裂速度

25h+/-2h---2cell

35h+/-2h---3cell

42h+/-2h---4cell

48h+/-3h---5cell

56h+/-3h---8cell

80h+/-4h----compation

95h+/-4h----blastulation

106h+/-4h-- Full blastulation

http://www.sciencedirect.com/science/article/pii/S1472648313000709

time-lapse可取代PGS挑選優質胚胎

使用即時監控time-lapse觀察胚胎可取代胚胎切片基因篩檢PGS挑選出優質胚胎

http://www.sciencedirect.com/science/article/pii/S1472648313002381

配合Day 1 & 3胚胎型態可提高預測胚胎優劣之準確度

可從Day 1胚胎型態(Z score)預估Day3Day 1胚胎型態
配合Day 1 & 3胚胎型態可提高預測胚胎優劣之準確度

http://humrep.oxfordjournals.org/content/18/6/1299.long

Day 1胚胎植入懷孕率略低於Day 2-3胚胎植入

Day 1胚胎植入 vs Day 2-3胚胎植入
懷孕率 36 vs 42%

http://link.springer.com/article/10.1023%2FA%3A1020354318164

Day 3胚胎植入懷孕率優於Day 1胚胎植入

Day 3胚胎植入懷孕率優於Day 1胚胎植入

Day 1胚胎挑選Z score準確度不盡理想

http://humrep.oxfordjournals.org/content/19/3/645.long

Elonva不會造成自體免疫反應

Elonva活產率約21%
Elonva不會造成自體免疫反應

http://humrep.oxfordjournals.org/content/26/8/2200.full?sid=cc9d9992-57cb-4201-96ce-9c7046dbffd2

Elonva無明顯致畸胎作用

長效型排卵針Elonva (corifollitropin alfa)無明顯致畸胎作用

http://humrep.oxfordjournals.org/content/27/7/2177.full?sid=b1c36b3e-756d-4123-a532-1a64eb336a08

letrozole無抑制雌激素副作用之排卵藥

letrozole: 可避免clomid抑制雌激素副作用之排卵藥

http://humupd.oxfordjournals.org/content/14/6/571.long

冷凍卵子懷孕率類似新鮮卵子

冷凍卵子玻璃化冷凍&解凍後施行ICSI，懷孕率類似新鮮卵子

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2794665/?report=reader

低劑量hCG可使用於早期誘導排卵

低劑量 CG (200iu/d)可使用於早期誘導排卵

http://www.rbej.com/content/7/1/91

hMG或rFSH用於誘導排卵懷孕率無明顯差異

hMG vs. rFSH用於誘導排卵懷孕率無明顯差異

http://www.ncbi.nlm.nih.gov/pubmed/21328264

AMH決定排卵針劑量可提高懷孕率

使用AMH決定誘導排卵針劑量可提高IVF懷孕率&減少排卵針劑量

http://humrep.oxfordjournals.org/content/26/9/2353.full

hMG誘導排卵胚胎品質略優於rFSH

使用hMG誘導排卵胚胎品質&懷孕率略優於使用rFSH誘導排卵

http://humrep.oxfordjournals.org/content/22/9/2404.long

nfluence of ovarian stimulation with HP-hMG or recombinant FSH on embryo quality parameters in patients undergoing IVF

BACKGROUND There are limited data on the impact of different gonadotrophin preparations on embryo quality.

METHODS This evaluation was part of a randomized, assessor-blind, multinational trial, conducted in 731 women undergoing IVF after stimulation with highly purified human menopausal gonadotropin (HP-hMG; MENOPUR) (n = 363) or recombinant FSH (rFSH; GONAL-F) (n = 368). Ongoing pregnancy was the primary end-point [HP-hMG 27% and rFSH 22%; odds ratio (OR) (95% confidence interval, CI) 1.25 (0.89-1.75)]. All 7535 oocytes retrieved were evaluated daily until day 3 (embryo transfer) in a blinded manner both by local site embryologists and a central panel of three embryologists.

RESULTS The proportion of top-quality embryos per oocyte retrieved was higher with HP-hMG (11.3%) compared with rFSH (9.0%) (P = 0.044) in the local assessment, but comparable in the central assessment (9.5 and 8.0%, respectively). Significant differences in favour of HP-hMG were observed for number of blastomeres and degree of fragmentation, while uniformity of blastomere sizes, localization of fragments, frequency of multinucleation and homogeneous cytoplasm were comparable between HP-hMG and rFSH. The live birth, ongoing pregnancy and ongoing implantation rates for top-quality embryos were higher with HP-hMG than rFSH [48 versus 32% (P = 0.038), 48 versus 32% (P = 0.038), 41 versus 27% (P = 0.032)]. Both the proportion of embryos with at least 50% surviving blastomeres after cryopreservation and embryos resuming mitosis were more frequent with HP-hMG compared with rFSH.

CONCLUSIONS Composition of gonadotrophin preparations used during ovarian stimulation has an impact on some embryo quality parameters. The capacity to implant of the top-quality embryos derived from stimulation with HP-hMG appears to be improved, although the mechanism needs to be elucidated.

Figure 2:

Summary of clinical outcome of the cryopreserved cycles in the HP-hMG (light bar) and rFSH (dark bar) groups

(a) ongoing implantation rate by blastomere survival rate of the transferred embryos and (b) live birth rate for the first cryo cycle, live birth rate for all cryo cycles, live birth rate by cryo cycle with embryo transfer and live birth rate by patients with thawed embryos

追蹤卵巢反應仍以超音波為主，E2為輔

追蹤卵巢COH反應仍以超音波為主，抽血E2為輔

http://molehr.oxfordjournals.org/content/19/12/799.full

hMG誘導排卵比FSH誘導排卵懷孕率略高

使用hMG誘導排卵比使用FSH誘導排卵懷孕率略高4%

http://humrep.oxfordjournals.org/content/23/2/310.long

月經第8天LH小於1.2 IU/l胚胎較少較差

誘導排卵第7,8天(M 7,8)測LH數值，可評估IVF預後，
 LH<1.2 IU/l，取卵數較少，胚胎品質較差

http://humrep.oxfordjournals.org/content/21/10/2645.long

卵泡較少之病患, P4上升懷孕率較低

卵泡較少之病患, P4>1.5ng/ml懷孕率較低

卵泡多的病患, P4/E2>1懷孕率較低

http://humrep.oxfordjournals.org/content/26/2/498.full

P4>1.5懷孕率較低

施打hCG當天，P4>1.5懷孕率比P4<1.5低
(10顆卵子: 30 vs 48%)
(15顆卵子: 35 vs 55%)

http://humrep.oxfordjournals.org/content/25/8/2092.full

施打rFSH卵泡較多P4易上升

施打rFSH比施打hMG較易造成卵泡較多&P4上升

http://humrep.oxfordjournals.org/content/26/2/498.full?ijkey=3e9e05567fcd24cf6ba5bb18e143987771a222a4&keytype2=tf_ipsecsha

超低劑量RU486 可防止過早黃體化

超低劑量RU486 (40 mg)可用於防止過早黃體化，延遲子宮內膜成熟‧

http://jcem.endojournals.org/content/90/4/2081.long

P4大於1.5建議冷凍胚胎

施打hCG當天P4>1.5，建議胚胎全數冷凍不予植入‧

http://humrep.oxfordjournals.org/content/26/10/2914.full

月經第7天施打GnRHantagonist

月經第3天施打GnRHantagonist vs. 月經第7天施打GnRHantagonist
懷孕率並無明顯差異

http://humrep.oxfordjournals.org/content/28/12/3227.abstract?sid=f2eb2c03-9a8a-4fb3-9cb7-6099559416fe

P4過高會影響子宮內膜之基因表現

P4過高(>1.5 ng/ml )會影響子宮內膜之基因表現，進一步造成胚胎著床率下降‧

http://humrep.oxfordjournals.org/content/26/7/1813.full

IVF適當之取卵數量約6-15顆

IVF適當之取卵數量約6-15顆
>15顆懷孕率並無明顯提高，OHSS機率上升

http://humrep.oxfordjournals.org/content/28/10/2728.abstract

P4越早上升，胚胎著床率越低

P4在誘導排卵過程中越早上升(>1 ng/ml)(，子宮內膜對於胚胎著床率越低

http://humrep.oxfordjournals.org/content/27/7/2036.full

卵巢過度刺激會下降胚胎著床率

卵巢過度刺激OHSS，合併E2過高，會下降子宮內膜接受度及胚胎著床懷孕率

http://humrep.oxfordjournals.org/content/25/3/809.full
http://humrep.oxfordjournals.org/content/25/3/810.full

施打hCG當天E2太高應考慮囊胚植入以讓子宮內膜修復

施打hCG當天，
P4較低(<1.5)，懷孕率較高
LH較低(<1.8)，懷孕率較高
E2太高(>3900)，懷孕率較低

E2太高，應考慮Day5囊胚期胚胎植入以讓子宮內膜修復

http://humrep.oxfordjournals.org/content/24/11/2902.full

身材嬌小無月經病患可能合併染色體異常

身材嬌小之原發性無月經病患可能合併染色體異常
透納氏症候群 Turner syndrom 或其mosaicism

http://www.jhrsonline.org/article.asp?issn=0974-1208;year=2013;volume=6;issue=2;spage=129;epage=132;aulast=Moka

甲狀腺低下，可能併罕見原發卵巢過度刺激

甲狀腺低下，TSH上升，可能併罕見原發卵巢過度刺激

http://www.jhrsonline.org/article.asp?issn=0974-1208;year=2013;volume=6;issue=2;spage=99;epage=105;aulast=Mehta

精蟲處理仍可能合併細菌感染

人工授精之精蟲處理步驟(swim-up, grading), 有可能會合併細菌感染

http://www.jhrsonline.org/article.asp?issn=0974-1208;year=2013;volume=6;issue=2;spage=152;epage=157;aulast=Abeysundara

曲細精管直徑與精蟲取得與否有關

曲細精管seminiferous tubules之直徑與精蟲取得與否有關
直徑<200 um可能無精蟲製造
解剖顯微鏡下找較粗(>250um) &不透明曲細精管施行TESE，較易取得精蟲

http://www.jhrsonline.org/article.asp?issn=0974-1208;year=2013;volume=6;issue=2;spage=111;epage=123;aulast=Ashraf

Letrozole懷孕率略高於clomid

Letrozole懷孕率略高於clomid

http://www.jhrsonline.org/article.asp?issn=0974-1208;year=2013;volume=6;issue=2;spage=93;epage=98;aulast=Kar

植入後第14天hCG值可評估多胞胎之機率

植入後第14天hCG值可用於評估多胞胎之機率
單胞胎 (502 IU/L), 
雙胞胎 (1093 IU/L), 
三胞胎 (2160 IU/L)

http://www.jhrsonline.org/article.asp?issn=0974-1208;year=2013;volume=6;issue=3;spage=213;epage=218;aulast=Singh

孵化囊胚比未孵化囊胚具更高之著床率

已孵化或即將孵化之囊胚期胚胎比未孵化之囊胚期胚胎具更高之著床率及懷孕率

http://www.jhrsonline.org/article.asp?issn=0974-1208;year=2013;volume=6;issue=3;spage=183;epage=188;aulast=Chimote

泌乳素過高常併甲狀腺低下

泌乳素PRL過高常合併甲狀腺低下(TSH上升)

http://www.jhrsonline.org/article.asp?issn=0974-1208;year=2013;volume=6;issue=3;spage=168;epage=175;aulast=Majumdar

Day 5 囊胚植入懷孕率略高於Day 6 囊胚植入

Day 5 囊胚植入懷孕率略高於Day 6 囊胚植入

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3713580/

低劑量誘導排卵可能可提高該次IVF懷孕率

較低劑量之誘導排卵可能反而可提高該次IVF懷孕率 (1450 vs 2664iu)
原計劃施行IUI改為IVF懷孕率可能反而比一般IVF較高(45 vs 34%)

http://www.ncbi.nlm.nih.gov/pubmed/23715874

血清氧化物與抗氧化物濃度與IVF懷孕率有關

血清氧化物與抗氧化物濃度與IVF懷孕率有關
血清氧化物越高，懷孕率越低
抗氧化物越高，懷孕率越高

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3696458/

葡萄胎常由IVF過程中1個卵子與2隻精蟲同時受精造成

葡萄胎partial molar pregnancy，常由IVF過程中，1個卵子與2隻精蟲同時受精造成
使用雙倍染色體之異常精蟲施行ICSI，也可能造成partial molar pregnancy

http://www.ncbi.nlm.nih.gov/pubmed/23640373

AMH可預測不成熟卵子培養成成熟卵子之數量

AMH可用於預測不成熟卵子培養成成熟卵子之數量(IVM)
AMH 1.6約可培養出5顆以上成熟卵子(MII)

http://www.ncbi.nlm.nih.gov/pubmed/23608780

CoQ10可提高精蟲品質

CoQ10可提高精蟲數量與活動力

http://www.ncbi.nlm.nih.gov/pubmed/23912751

退黑激素可提高卵子成熟之機率

低濃度(1nM)的melatonin (退黑激素)可提高不成熟卵子成熟IVM之機率
高濃度(10(6) nM)的melatonin (退黑激素)不利於不成熟卵子成熟

http://www.ncbi.nlm.nih.gov/pubmed/23737216

注射精漿於陰道可能可提高著床率

取卵當日注射0.5ml精漿於陰道可能可提高著床率

http://www.ncbi.nlm.nih.gov/pubmed/23812801

卵子胚胎冷凍相關技術

可預見未來，卵子胚胎冷凍相關技術將日新月益，大幅更新不孕症之治療方向&產生重大影響

http://www.ncbi.nlm.nih.gov/pubmed/23779099

DHEA可提高卵巢反應

DHEA 對於高齡，卵巢功能不佳病患，可提高卵巢反應，卵泡生成

http://www.ncbi.nlm.nih.gov/pubmed/23737215

副睪取精+ICSI可得50%優質胚胎

副睪取精PESA+ICSI可得50%優質胚胎

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3800539/

冷凍胚胎高於新鮮胚胎植入懷孕率

冷凍胚胎植入懷孕率39%高於新鮮胚胎植入懷孕率28%

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2922708/#!po=2.63158

黃體期可取出不成熟卵子

黃體期可取出不成熟卵子，進一步培養IVM形成成熟卵子

http://www.sciencedirect.com/science/article/pii/S1472648310602398

RU486可治療肌瘤

RU486 10mg/d vaginally x 3 月可治療子宮肌瘤, 縮小25%肌瘤體積，降低經血量

http://www.ncbi.nlm.nih.gov/pubmed/24220703

Endometriosis 病患prefer ICSI

Endometriosis IVF病患可能較適合ICSI insemination

http://www.ncbi.nlm.nih.gov/pubmed/23271211

IVF overnight效果類似IVF 2h

IVF overnight效果類似IVF 2h，
控制sperm 濃度(10-20萬/ml)以達最佳狀況

http://www.ncbi.nlm.nih.gov/pubmed/12513887/

IVF 6h去除卵丘細胞可達類似IVF 18h懷孕率

IVF 6h去除卵丘細胞可達類似IVF 18h懷孕率，並可針對未受孕卵子進行rescue ICSI

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3241845/

Time-lapse無法預測胚胎懷孕率

Time-lapse胚胎觀測系統可預測胚胎品質與囊胚比率
但無法預測胚胎植入後之懷孕率

http://humrep.oxfordjournals.org/content/28/10/2643.abstract

取卵flush對IVF懷孕率無明顯助益

取卵flush對於IVF懷孕率無明顯助益，甚至有不良影響

http://humrep.oxfordjournals.org/content/28/11/2990.abstract

適當子宮長度約7-9cm, 過大或過小可能影響IVF孕率

子宮過大或過小可能影響IVF懷孕率
適當子宮長度約7-9cm
子宮長度>9cm 或<7cm, 懷孕率較低
子宮長度<6cm易流產

http://humrep.oxfordjournals.org/content/28/11/3000.abstract

PCO病患施行IVF前不需服用pill

PCO病患施行IVF前不需服用pill

http://www.rbej.com/content/11/1/54

pill可能抑制卵巢reserve與卵泡發育

避孕藥pill會抑制卵巢反應
IVF前一週期建議不一定要使用pill
新型pill含黃體素具抑制androgen，舊型pill含黃體素具類似androgen作用
androgen對於卵泡早期發育有其必要性
新或舊型pill均可能抑制卵巢reserve與卵泡發育

http://www.rbej.com/content/11/1/28

精蟲能承受較鹼性環境，pH低於6.8精蟲無法存活

精液滲透壓(340–380 mOsm)高於血清滲透壓(280-300 mOsm)
精液pH7.2-8.0，精蟲能承受較鹼性環境，可在pH8-9間存活，但pH<6.8精蟲無法存活
精蟲細胞核包覆囊狀結構membrane bound (‘nuclear vacuoles’, more correctly ‘nuclear spaces’)---精蟲品質不佳
健康男性每日可製造數千萬~一億隻精蟲

http://humupd.oxfordjournals.org/content/19/suppl_1/i1.full

一月經週期可能有2-3個卵子挑選波follicle recruitment wave

卵子挑選: 由上週期黃體期挑選一卵子成為優勢卵子
月經第10-12天左右，卵子必須>0.9cm才有可能成為優勢卵子

黃體期仍有基礎濾泡生長，但為黃體壓制
一月經週期可能有2-3個卵子挑選波follicle recruitment wave

http://humupd.oxfordjournals.org/content/18/1/73.full

P4值過高對胚胎著床有不良影響不論卵子之數量

10000 IVF病人施打破卵針當天之P4值顯示:
P4值過高對卵子品質及受孕率無明顯不良影響，
P4值過高對胚胎著床有不良影響，不論卵子之數量&COH之反應

P4值過高 (serum P level of 1.5 ng/mL as the threshold for poor responders, 1.75 ng/mL for intermediate responders, and 2.25 ng/mL for high responders. )----子宮內膜環境可能較不適著床

http://www.ncbi.nlm.nih.gov/pubmed/22494924

使用time-lapse即時觀測囊胚ICM數量預測單絨毛膜雙羊膜同卵雙生

囊胚期植入同卵雙胞胎比例較高,
使用time-lapse即時觀測胚胎可偵測囊胚之ICM數量，
若有2 ICM之囊胚植入後可能行成囊胚monochorionic/diamniotic----最常見之單絨毛膜雙羊膜之同卵雙生

http://humrep.oxfordjournals.org/content/22/suppl_1/i9.full.pdf+html?ijkey=585c21253b2644a26b17a7d5cd20dfe24c87f97f&keytype2=tf_ipsecsha

子宮內膜厚度之測量

子宮內膜厚度之測量,
外層密度較高more echogenic
內層密度較低more hypoechoic, homogenously echogenic
中央為前後子宮內膜interface

http://radiographics.rsna.org/content/32/6/1575.full

黃體化牽涉複雜的賀爾蒙, 分子訊號及血管形成交互作用

黃體Corpus luteum主要由granulosa cell & thecal cell組成
黃體化luteinization 牽涉複雜的賀爾蒙，分子訊號及血管形成angiogenesis交互作用interaction

http://www.biolreprod.org/content/63/1/2.full

黃體化卵泡未排卵卵泡症候Luteinized unruptured follicle syndrome

黃體化卵泡未排卵卵泡症候 Luteinized unruptured follicle (LUF) syndrome
卵泡>1.4cm以上就有可能排卵
施打HCG破卵針後有6-25%仍未破卵

http://humrep.oxfordjournals.org/content/21/8/2110.full

AIH精液取出後30分內進行精蟲處理

人工授孕AIH，取精液最好在診所取，取出後最好30分內進行精蟲處理sperm washing
人工授孕誘導排卵最好使用hMG(取代排卵藥)
取精液後最好90分左右施行AIH

http://www.ncbi.nlm.nih.gov/pubmed/15589871

60000 case研究顯示P4上升IVF懷孕率下降

IVF打HCG當天P4上升(progesterone elevation)
60000 case研究顯示IVF懷孕率下降

但P4上升對冷凍胚胎植入無明顯不良影響

http://humupd.oxfordjournals.org/content/19/5/433.abstract

GnRH antagonist抑制子宮內膜雌激素與黃體素接受體

GnRH antagonist可能會抑制子宮內膜之雌激素與黃體素接受體 (estrogen receptor & progesterone receptor之mRNA expression)

著床窗口 implantation 約為LH上升後第5-10天
window of implantation is described as from Day 5 to Day 10 after the LH surge (Sharkey and Smith, 2003).

http://humrep.oxfordjournals.org/content/22/11/2981.full

陰道給予utrogeston效果類似Crinone

IVF黃體期補充黃體素，
陰道給予utrogeston 600mg/d (200mg tid vaginal usage)，效果類似Crinone

http://humupd.oxfordjournals.org/content/13/6/581.full

AIDS男性可預防性化療chemoprophylaxis再施行AIH

HIV男性施行人工授精最有效之預防方法為清洗精蟲sperm washing(grading, swim-up, wash)
另一方法為預防性化學藥劑治療pre-exposure chemoprophylaxis (PrEP)降低HIV titler

http://humupd.oxfordjournals.org/content/19/2/136.abstract

PCO施行IUI可將多餘卵子取出冷凍保存

多囊性卵巢PCO病患施行人工授精IUI，可考慮將多餘卵子取出冷凍保存

http://humrep.oxfordjournals.org/content/25/5/1213.full

HIV病患AIH採用多次離心法

HIV男性採用多次離心法(45–90% colloidal silica density gradient)+swim-up 清洗精蟲
分離HIV-free sperm from the infected NSC
降低精蟲感染HIV機率
統計顯示感染HIV機率低

http://humrep.oxfordjournals.org/content/25/8/1869.full

IVF提早或延後一日取卵並不明顯影響懷孕率

使用GnRHantagonist COH可提早或延後一日取卵並不明顯影響懷孕率

http://humrep.oxfordjournals.org/content/25/5/1219.full

高達百分之58囊胚染色體有鑲嵌化現象

morula期胚胎高達80%染色體有mosaic現象
blastocyst期胚胎高達58%染色體有mosaic現象

http://humrep.oxfordjournals.org/content/25/8/1916.full

服用葉酸可能不利於卵泡生成

本篇提出另類觀點，服用葉酸可能不利於卵泡生成???
服用葉酸病患卵子數量反而少於不服用葉酸病患卵子數量
葉酸可能影響FSH receptor (FSHR) mRNA表現

傳統 vs. 服用葉酸
preovulatory follicles  (10.6 vs. 7.4; P < 0.01)
median number of retrieved oocytes (12.3 vs. 6.7; P = 0.001)
E2 (傳統>服用葉酸)

http://jcem.endojournals.org/content/96/2/E322.full

非高齡誘導排卵起始劑量可為150iu/d

非高齡小於39歲誘導排卵起始劑量可為150iu/d，懷孕率類似225iu/d

http://humupd.oxfordjournals.org/content/17/2/184.full

M2或M5誘導排卵對懷孕率無差異

月經第2天或第5天誘導排卵COH對懷孕率無明顯差異 (36 vs 36%)

http://jcem.endojournals.org/content/96/4/1122.full

卵巢不佳病患優先考慮GnRHantagonist COH療程

卵巢反應不佳之病患可優先考慮使用GnRHantagonist COH療程

GnRHantagonist COH療程較GnRHagonist 短


http://humrep.oxfordjournals.org/content/26/10/2742.full

Indomethacin對子宮穩定無明顯幫助

Indomethacin對胚胎植入ET前後子宮穩定無明顯幫助

http://humrep.oxfordjournals.org/content/21/2/364.full

Glucophage用於PCO須 glucose intolerance才有效

metformin (glucophage) 使用於多囊性卵巢PCO須針對 glucose intolerance 之PCO病患才有效

http://humrep.oxfordjournals.org/content/27/12/3365.full

低劑量誘導排卵IVF取消機率高達百分之20

<38歲試管嬰兒病人，使用低劑量誘導排卵(FSH 150iu/day，自月經第5天誘導排卵COH )

取消機率高達20%(卵泡>12mm少於3顆)
懷孕率20.7%

http://humrep.oxfordjournals.org/content/22/7/1919.full

根據體重與基礎濾泡數量決定誘導排卵之劑量

人工授孕AIH, 根據體重與基礎濾泡數量決定誘導排卵之劑量
體重越重, 基礎濾泡數量越少劑量越高

http://humrep.oxfordjournals.org/content/24/10/2523.full

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Figure 1

Dosage nomogram for ovulatory IUI patients' first rFSH treatment cycle.

The aim of the stimulation was to achieve two follicles ≥18 mm and maximum one intermediate-size follicle (≥14 and <18 mm) on the day of hCG. The day of hCG was defined as the day the leading follicle reached a diameter of 18 mm. On the basis of a patient's body weight (kg) and total AFC, an individual starting dose can be identified. Reprinted from an article in Reproductive BioMedicine Online by Freiesleben et al. (2008), with permission from Reproductive Healthcare Ltd.

PCO病人體重下降AMH並不明顯下降

PCO病人體重下降，生殖功能改善，

AMH並不明顯下降

http://humrep.oxfordjournals.org/content/24/8/1976.long

pill下降體內男性賀爾蒙濃度

pill可下降體內男性賀爾蒙濃度，機轉包括:
下降卵巢製造男性賀爾蒙
下降腎上腺製造男性賀爾蒙&
提高sex hormone-binding globulin (SHBG)濃度

pill可提高sex hormone-binding globulin (SHBG)濃度
不同種類pill下降體內男性賀爾蒙濃度類似

http://humupd.oxfordjournals.org/content/20/1/76.full

悅己有效改善PCO男性化

Pill Yasmin悅己 (30 microg ethinyloestradiol and 3 mg drospirenone)
服用6month可有效改善PCO男性化

http://www.ncbi.nlm.nih.gov/pubmed/17455042

服用pill造成AMH下降&卵巢反應變差

服用pill可能會造成AMH下降&卵巢反應變差
高齡&體重過重可能會造成AMH下降

http://www.hormones.gr/721/article/article.html

單一成熟卵子活產率約4.5%

23-37歲單一成熟卵子活產率約4.5%
38-43歲單一成熟卵子活產率約3.8%
>43歲單一成熟卵子活產率約0.8%

http://humrep.oxfordjournals.org/content/27/7/2030.full

囊胚冷凍前使用雷射使囊胚腔縮小可提高冷凍存活率

囊胚冷凍前使用雷射或ICSI針穿刺使囊胚腔縮小再冷凍
可能可提高囊胚冷凍解凍存活率

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3660183/

無載具微滴冷凍胚胎

無載具微滴玻璃化冷凍
未來冷凍胚胎卵子之可能發展方向

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3193162/

玻璃化胚胎冷凍保存液僅數ul

玻璃化胚胎冷凍保存液僅數ul (nanoLiter)
已達最快降溫及回溫速度
避免冰晶傷害冷凍胚胎或卵子

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3319864/

卵子解凍後2h施行ICSI

vitrification 優於慢速冷凍
卵子vitrification解凍後2h施行ICSI

http://www.ncbi.nlm.nih.gov/pubmed/19346187?dopt=Abstract

卵子取出2h內冷凍可達不錯懷孕率

卵子取出後，2h內冷凍可達不錯懷孕率

http://www.ncbi.nlm.nih.gov/pubmed/21029612

捐卵數量需4個以上成熟卵子才可達到適當懷孕率

捐卵受卵IVF療程，至少需4個以上成熟卵子才可達到不錯懷孕率

http://www.ncbi.nlm.nih.gov/pubmed/21088879

卵子冷凍步驟

卵子冷凍步驟
BS 1min
ES1 2 min
ES2 2 min
ES3 5min
VS1 20s
VS2 20s
VS3 20s
loading 20s

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3577428/

原核Z-score對預估胚胎懷孕率成效有限

原核PN評估Z-score, 對於胚胎植入後之懷孕率預估成效有限

2PN原核荷仁最好>7
Z1----Fig A----最佳
Z2----Fig B----優
Z3----Fig C,D--中
Z4----Fig E,F--差

http://www.ovarianresearch.com/content/6/1/64

Zygote scoring system of Scott et al. [10]. Z1 includes zygotes with equal number of nucleoli aligned at PN junction (A), Z2 includes zygotes with equal number and size of nucleoli (between 3 and 7) which are equally scattered in the two PN (B), Z3 includes zygotes with either very small/large nucleoli (C and D), and Z4 includes zygotes showing PN separated or different in size and small nucleoli, partially aligned or scattered (E and F).

Nicoli et al. Journal of Ovarian Research 2013 6:64   doi:10.1186/1757-2215-6-64
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Pronuclear morphology evaluation for fresh in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles: a systematic review

Alessia Nicoli, Stefano Palomba^*, Francesco Capodanno, Maria Fini, Angela Falbo andGiovanni Battista La Sala

• *Corresponding author: Stefano Palomba stefanopalomba@tin.it

Author Affiliations

Department of Obstetrics, Gynecology and Pediatrics, A.O. Arcispedale S. Maria Nuova, IRCCS, University of Modena and Reggio Emilia, Viale Risorgimento 80, 42123 Reggio Emilia, Italy

For all author emails, please log on.

Journal of Ovarian Research 2013, 6:64  doi:10.1186/1757-2215-6-64

The electronic version of this article is the complete one and can be found online at:http://www.ovarianresearch.com/content/6/1/64

Received:	5 June 2013
Accepted:	16 August 2013
Published:	12 September 2013

© 2013 Nicoli et al.; licensee BioMed Central Ltd. 

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The current systematic review was aimed to assess the effectiveness of the zygote morphology evaluation in fresh in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles. All available studies reporting on zygote morphology and clinical and/or biological outcomes were analyzed. Forty studies were included in the final analysis. Fourteen different zygote scoring systems were employed. Zygote morphology correlated significantly with embryo quality and cleavage, blastocyst stage, embryonic chromosome status, in a high proportion of the studies which assessed the specific outcome [15/25 (60%), 15/20 (75%), 7/8 (87.5%), 6/6 (100%), respectively]. On the other hand, only a reduced proportion of papers showed a statistically significant relationship between implantation, pregnancy and delivery/live-birth rates and zygote morphology score [12/23 (52.2%), 12/25 (48%), 1/4 (25%), respectively]. In conclusion, our findings demonstrate the lack of conclusive data on the clinical efficacy of the zygote morphology evaluation in fresh IVF/ICSI cycles, even if biological results showing a good relationship with embryo viability suggest a role in cycles in which the transfer/freezing is performed at day 1.

Keywords: 

ARTs; Embryo; ICSI; IVF; Morphology; Zygote

新鮮捐贈卵子與冷凍捐贈卵子懷孕率無差異

新鮮捐贈卵子與冷凍捐贈卵子受孕植入懷孕率無明顯差異‧

http://www.ncbi.nlm.nih.gov/pubmed/17889865?dopt=Abstract

取卵數多不明顯下降該週期懷孕率

取卵數少vs.取卵數多
取卵數較多(n>18)並不會明顯下降該週期之懷孕率‧
取卵數多累積懷孕率較高 (32 vs 58%)‧
長效排卵針corifollitropin alfa效果與短效排卵針daily rFSH懷孕率類似(32 vs 31%)

http://humrep.oxfordjournals.org/content/28/2/442.abstract

HMG於誘導排卵可能提高3-4%懷孕率

含LH針劑包含HMG, uLH, rLH, uhCG, rhCG

使用HMG於誘導排卵COH可能對部分病患提高3-4%懷孕率

http://www.ncbi.nlm.nih.gov/pubmed/19406029

hCG用於誘導排卵

低劑量hCG 200iu可用於誘導排卵COH晚期

http://humrep.oxfordjournals.org/content/25/11/2678.full

取卵前hCG值大於1.2 IU/L懷孕率較高

PCO病患，IVF取卵前抽血顯示hCG值高(>1.2 IU/L)，懷孕率較高

基礎LH值或取卵前LH值與懷孕率無關

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3251000/?report=reader

誘導排卵第6天 P4小於1.5, hCG大於3 懷孕率較高

誘導排卵第6天, P4 <1.5, hCG>3 懷孕率較高‧

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3518295/

卵巢子宮內膜異位瘤切除後AMH 下降

腹腔鏡卵巢子宮內膜異位瘤切除後，造成卵巢功能下降，

AMH 下降(3.8->2)，FSH上升

http://www.ncbi.nlm.nih.gov/pubmed/24269044

含LH之排卵針對施打hCG當天之P4無明顯影響

施打含LH之排卵針(e.g., HMG, r-LH)對施打hCG當天之P4無明顯影響

http://humrep.oxfordjournals.org/content/27/1/232.long

打破卵針當天P4/E2>1懷孕率較低

打破卵針當天P4/E2 比例[P (ng/mL) 1,000/E2 (pg/mL).]-------可預測IVF懷孕率

P4/E2>1代表過早黃體化，通常懷孕率較低


http://www.ncbi.nlm.nih.gov/pubmed/18603501

破卵針12h後E2下降懷孕率較低

打破卵針當天早上抽E2，24h後再抽E2，若第二次E2不升反降，懷孕率較低

http://humrep.oxfordjournals.org/content/27/9/2690.full

P4>1.2是否會影響懷孕率仍具爭議

施打HCG當天P4>1.2即可能為過早黃體化(premature luteinization, PL)，
PL是否會影響懷孕率仍具爭議

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2854984/

cAMP細胞內訊號傳遞與卵細胞發育有關

卵泡發育過程中，卵細胞會分泌inhibin, E2，抑制腦下垂體分泌FSH, LH

FSH會刺激卵細胞之adenylyl cyclase, 引發cAMP製造及細胞內訊號傳遞，及進一步卵顆粒細胞及卵細胞之發育
adenylyl cyclase and the production of cAMP
http://www.biolreprod.org/content/65/3/655.full

PCO病人P4大於1.2與IVF結果可能無明顯相關

過早黃體化----P4>1 or 2, 機率約23%，

PCO病人於施打HCG當天測P4>1.2 or P4<1.2，
卵泡越多，P4可能較高，
P4>1.2與IVF結果無明顯相關

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3401251/

過早黃體化(premature luteinization)

過早黃體化(premature luteinization)---打破卵針當天P4>1.5 ng/ml(1-2 ng/ml)，

可考慮胚胎冷凍保存，或保守植入(少量優質胚胎植入)

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2854984/

過早黃體化(premature luteinization)定義

過早黃體化(premature luteinization)
打破卵針hCG當天 P4>1-2 ng/ml
超音波顯示: 卵泡壁變厚，卵泡液呈irregular echogenic

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2854984/

OHSS病患可使用hCG 1500iu合併GnRHa破卵

卵巢過度刺激OHSS病患可考慮使用hCG 1500iu合併GnRHa破卵可下降OHSS機率並維持高懷孕率

http://humrep.oxfordjournals.org/content/28/9/2529.abstract

GnRHa誘導排卵可能會影響黃體功能

GnRHa誘導排卵可能會影響黃體功能，

需加強黃體期賀爾蒙補充
http://humrep.oxfordjournals.org/content/21/8/2126.full

破卵針易引發血管通透性增加引發腹水形成

破卵針hCG易引發血管通透性增加引發腹水形成‧

http://humupd.oxfordjournals.org/content/17/4/510.full

使用GnRHa誘導排卵容易造成黃體期賀爾蒙缺乏

研究顯示，使用GnRHa誘導排卵容易造成黃體期賀爾蒙缺乏，

http://humrep.oxfordjournals.org/content/21/8/2126.full

卵巢過度刺激之病患可使用腦下垂體抑制劑控制嚴重度

卵巢過度刺激OHSS之病患可使用腦下垂體抑制劑GnRHantagonist控制其嚴重度

研究顯示胚胎植入ET後使用腦下垂體抑制劑，仍可維持不錯懷孕率，
並下降卵巢過度刺激嚴重度

http://humrep.oxfordjournals.org/content/28/7/1929.abstract

長療程卵子比短療程冷凍卵子易長為囊胚

長療程卵子比短療程冷凍卵子，解凍後更易成長為囊胚 (51 vs 27%)

http://www.ovarianresearch.com/content/6/1/15

排卵藥搭配排卵針可達不錯活產率

排卵藥搭配排卵針可達不錯活產率
排卵藥搭配排卵針IVF vs 排卵針IVF活產率 (23% vs. 16-26%)

http://www.ncbi.nlm.nih.gov/pubmed/23152261

因卵巢過度刺激下降破卵針劑量可能干擾懷孕結果

因卵巢過度刺激(OHSS)而下降破卵針劑量(6000-->4000iu)，可能干擾懷孕結果
卵子受孕率FR: 80 vs 71%
臨床懷孕率PR: 65 vs 35%

http://www.ncbi.nlm.nih.gov/pubmed/21824709

胚胎品質不佳冷凍解凍後植入懷孕率不高

胚胎品質不佳冷凍解凍後植入懷孕率不高 (僅10%)

1-2顆以上優質胚胎才可達到不錯懷孕率

http://humrep.oxfordjournals.org/content/28/9/2425.abstract

低氧胚胎培養可能可提高胚胎懷孕率7%

低氧(5%O2)培養胚胎可能可提高胚胎懷孕率7%(30%---->32-43%)

http://www.ncbi.nlm.nih.gov/pubmed/22786519

母血胎兒DNA唐氏症篩檢仍無法完全準確取代羊水檢驗

母血胎兒DNA唐氏症篩檢仍無法完全準確取代羊水檢驗

但可望取代傳統母血唐氏症篩檢

Noninvasive detection of fetal trisomy 21: systematic review and report of quality and outcomes of diagnostic accuracy studies performed between 1997 and 2012

1. E. Mersy1,2, 
2. L.J.M. Smits3, 
3. L.A.A.P. van Winden4,
4. C.E.M. de Die-Smulders1,2, 
5. The South-East Netherlands NIPT Consortium5,†, 
6. A.D.C. Paulussen1,2, 
7. M.V.E. Macville1,2, 
8. A.B.C. Coumans2,4and 
9. S.G.M. Frints1,2,*

+Author Affiliations

1. ¹Department of Clinical Genetics, Reproductive Genetics, Maastricht University Medical Center⁺, PO Box 5800, 6202 AZ Maastricht, The Netherlands
2. ²GROW School for Oncology and Developmental Biology, Maastricht University Medical Center⁺, PO Box 616, 6200 MD Maastricht, The Netherlands
3. ³Department of Epidemiology, Faculty of Health Medicine and Life Sciences, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands
4. ⁴Department of Obstetrics & Gynaecology, Prenatal Diagnosis, Screening and Therapy, Maastricht University Medical Center⁺, PO Box 5800, 6202 AZ Maastricht, The Netherlands
5. ⁵South-East Netherlands NIPT Consortium, Maastricht University Medical Center⁺, PO Box 5800, 6202 AZ Maastricht, The Netherlands

1. ↵*Correspondence address. Tel: +31-4-33-87-78-55; Fax: +31-4-33-87-58-00; E-mail: s.frints@mumc.nl

• Received October 26, 2012.
• Revision received December 20, 2012.
• Accepted January 3, 2013.

Abstract

BACKGROUND Research on noninvasive prenatal testing (NIPT) of fetal trisomy 21 is developing fast. Commercial tests have become available. To provide an up-to-date overview of NIPT of trisomy 21, an evaluation of the methodological quality and outcomes of diagnostic accuracy studies was made.

METHODS We undertook a systematic review of the literature published between 1997 and 2012 after searching PubMed, using MeSH terms ‘RNA’, ‘DNA’ and ‘Down Syndrome’ in combination with ‘cell-free fetal (cff) RNA’, ‘cffDNA’, ‘trisomy 21’ and ‘noninvasive prenatal diagnosis’ and searching reference lists of reported literature. From 79 abstracts, 16 studies were included as they evaluated the diagnostic accuracy of a molecular technique for NIPT of trisomy 21, and the test sensitivity and specificity were reported. Meta-analysis could not be performed due to the use of six different molecular techniques and different cutoff points. Diagnostic parameters were derived or calculated, and possible bias and applicability were evaluated utilizing the revised tool for Quality Assessment of Diagnostic Accuracy (QUADAS-2).

RESULTS Seven of the included studies were recently published in large cohort studies that examined massively parallel sequencing (MPS), with or without pre-selection of chromosomes, and reported sensitivities between 98.58% [95% confidence interval (CI) 95.9–99.5%] and 100% (95% CI 96–100%) and specificities between 97.95% (95% CI 94.1–99.3%) and 100% (95% CI 99.1–100%). None of these seven large studies had an overall low risk of bias and low concerns regarding applicability. MPS with or without pre-selection of chromosomes exhibits an excellent negative predictive value (100%) in conditions with disease odds from 1:1500 to 1:200. However, positive predictive values were lower, even in high-risk pregnancies (19.7–100%). The other nine cohort studies were too small to give precise estimates (number of trisomy 21 cases: ≤25) and were not included in the discussion.

CONCLUSIONS NIPT of trisomy 21 by MPS with or without pre-selection of chromosomes is promising and likely to replace the prenatal serum screening test that is currently combined with nuchal translucency measurement in the first trimester of pregnancy. Before NIPT can be introduced as a screening test in a social insurance health-care system, more evidence is needed from large prospective diagnostic accuracy studies in first trimester pregnancies. Moreover, we believe further assessment, of whether NIPT can be provided in a cost-effective, timely and equitable manner for every pregnant woman, is required.

Key words

• noninvasive prenatal testing
 
• trisomy 21
 
• cell-free fetal DNA/RNA
• QUADAS-2