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不孕不育症的治疗Thehigh-possibilityfertilephase
extendsfrom5daysbefore
ovulation
to
the
day
of精子出发spermatozoacansurviveinthefemalereproductive
tractfor
5–6
days
after
intercourse卵子出发21着床
4子宫——ovulation.相遇
受精输卵管子宫颈阴道3Criteria4thed5thedVolume≥
2.0
mL≥
1.5
mLTotalsperm
number≥
40millions/ejaculate≥
39millions/ejaculateSpermconcentration≥
20millions/
mL≥
15millions/
mLTotal
motility≥
50%≥
40%Progressive
motility≥
25%≥
32%Normal
morphology≥
15%≥
4%(KrugerStrictcriteria)Vitality≥
50%≥
58%pH>7.2>7.2Liquefaction:Completewithin60
minutesatroomtemperatureAppearance:
Homogeneous,gray,andopalescentConsistency:
Leaves
pipetteasdiscretedropletsLeukocytes:
Fewerthan
1
million/mLSemenAnalysisAssisted
Reproductive
Techniques•Intra-Uterine
Insemination(IUI)–
Artificial
Insemination
with
Husband(AIH)–
Artificial
Insemination
with
Donor(AID)•Gameteintra-fallopiantransfer(GIFT)•
Zygoteintra-fallopiantransfer(ZIFT)•In
vitrofertilization(IVF)•Intracytoplasmicsperminjection
(ICSI)•Pre-implantationgeneticdiagnosis(PGD)IUI,配偶人工授孕(AIH)*(一)适应症:男性精虫稀少(每西西一
千万左右),尿道下裂、阴茎畸型、阳萎
、早泄、女性阴道痉挛不能性交、配偶常出差等。*(二)方法:男性将精液取出,经液化后
,将精虫洗涤,去除精液之杂质,在女性
排卵期将精液注入子宫腔。2014/4/24图片来源:我省生殖医学会网站Intra-Uterine
InseminationMale
Factor
Infertility•Bestresultswith
IUIare
achievedwhenTotal
motilespermcount(TMC)
in
theinseminationspecimenexceeds
10million
14%ormore
have
normal
morphology•Highercountsdonot
increase
success•IUI
isseldomsuccessful
iffewerthan
1
milliontotalmotilesperm
are
present.黄X
玉
陈Xj2014/4/24102年第一次医师(二)医学(六)Male
Factor
Infertility•
TMC<
1
million:
ICSI•
TMC>
1
and
<
10
million:IVFcanbe
performed
ifinfertility
durationis2years
or
longer•
TMC>
10
million:
IVF
is
indicated
ifthedurationis3years
or
longer.
Ifthewomanisolderthan36years,
IVF
may
beconsideredearlier.体外授精(试管婴儿)IVF*(一)适应症
:骨盆腔粘连、输卵管堵塞、输卵
管切除、严重度子宫内膜异位、精子稀少(五百
万左右)、精虫产生抗体等。*(二)方法:*(1)用排卵物诱导排卵(2)利用超音波检查卵泡及抽血测E2(3)当卵子成熟,利用阴道超音波,将卵子取出
(4)在实验室将精子与卵子完成受精分裂成胚胎,
再植入子宫腔2014/4/24精虫显微注射
:
(ICSI)应用在合并男性不孕或先前尝试受精率低者IntraCytoplasmicSperm
InjectionMale
Factor
Infertility•
IndicationsforICSITotal
motilespermcount<
1
million<4%
normalmorphologyandTMC
<
5millionNoorpoorfertilizationin
the
first
IVF
cyclewhenTMC<
10
millionNoorpoorfertilization
intwo
IVFcycleswhenTMC>
10
millionEpididymalortesticularspermatozoa.精卵显微授精法(microinjection)(一)适应症:(1)严重精虫稀少(在一百万只左右)、精虫活动
力差、IVF不能受精者。(2)精液检查无精子,但睪丸组织有精子,请泌尿
外科大夫,将精子吸出在实验室处理。*(二)方法:在显微镜下,将一只精子注射入卵子,因注射部
位不同,可分为(A)透明层下注射法(sub-zonal
injection;suzi)
(B)透明层开洞方法(partial
zonal
dissection;
PZD)(C)精子注射入卵细胞浆法(intracytoplasmicsperm
injection
ICSI),因ICSI方法受精机率高,
2014且/4/24怀孕成功机率也高,目前广为世界采用。B男性不孕患者,精液检查总活动数精虫少于
1百万,实施人工协助生殖技术时,下列何
项处置最为有效?A.
透明区穿孔术(zonadrilling)B.卵质内单一精虫注入术(intracytoplasmic
sperminjection)C.透明区下精虫注入(subzonalsperm
injection)D.透明区磨薄术(assistedhatching)93
年第2次专技高考外科学(二)102年第二次专技医师二医学六C一位26岁男性,不孕3年求诊,严格的精液分析
显示:精液量=2.5mL,总精虫数=1×106/mL,
4%直线前进,3%正常外观精子,下列处理何者
较适当?A.
进行子宫腔内受精(intrauterineinsemination)B.进行体外受精(in
vitrofertilization)C.进行卵质内单一精子注入(intracytoplasmic
sperminjection)D.进行睪丸切片取精(testicularspermextraction)*一对夫妻到门诊作不孕症检查,妻子30岁,月经
周期正常,周期第3天
FSH7.2IU/L,双侧输卵管
通畅,先生的精虫数目为
20万/mL,活动力
10%,
先生的染色体为46XY,无Ychromosomemicrodeletion
。你会建议他们作何治疗?A.
人工受精(intrauterineinsemination;
IUI)
B.
传统试管婴儿(invitrofertilization;
IVF)C.
细胞内精虫显微注射(intracytoplasmicsperm
injection;ICSI)D.礼物婴儿(gamete
intrafallopiantransfer;GIFT)C2014/4/24B男性不孕患者,精液检查总活动数精虫少于1百万,实施
人工协助生殖技术时,下列何项处置最为有效?
A透明区穿孔术(zonadrilling)
B卵质内单一精虫注入术(intracytoplasmicsperminjection)C透明区下精虫注入(subzonalsperminjection)
D透明区磨薄术(assistedhatching)A关于不孕症的叙述,何者错误?A做细胞内精虫显微注射(intracytoplasmicsperminjection,
ICSI)的怀孕率比传统试管婴儿(invitrofertilization,IVF)
的怀孕率低B不孕症是指在未避孕的情况下,一年以上没有怀孕C所谓人工生殖技术(assistedreproductivetechnology,
ART)是指各种取卵的介入方法D女性的怀孕能力(fecundability)从30岁后开始下降2014/4/24滤泡发育与诱导排卵2014/4/24负性回馈抑制滤泡刺激素正性回馈增加黄体刺激素*一个dominant
follicle
E2>200
pg/mlfor>50
hrs
会造成positive
feedback,刺激LH大量分泌(LH
surge)并持续四十八小时>200
pg/ml
超过50小时(50-150pg/ml)大幅上升稍许上升雌激素(MetaphaseI)Meiotic
Resumption
(
M
II)just
before
ovulationMeioticArrestatMetaphaseof
Meiosis
IIGV
breakdown(GVBD)=
Meiosis
I
resumes↓
(Metaphase
II)MeioticArrestat
Diplotene,
Prophaseof
Meiosis
IGerminalVesicle
(GV)–intactYenandJaffe’sReproductiveEndocrinology6th
Ed&SperoffClinical
Gynecologic
EndocrinologyandBefore
LHsurgeLH刺激卵子成熟Oocytes25Meiotic
Resumption
(
M
II)LH Plasminogenactivator↑Plasmin
↑Collagenase
↑Ovulation28
ProstaglandinsecretionContractsmooth
muscle
OvulationOocyte(GV
intact)Pre-ovulatoryfollicle
=GraafianfollicleCumulus-OocyteComplex
Granulosa
luteinizationCumulus
cells
(specialize
dgranulosa)Mural
granulosa
cellsOocytefreedfromattachmentLH刺激卵子成熟FollicularfluidCumulusexpansionP4LHsurge1.让卵子由「第一次减数分裂前期(prophase
I)」进展到
「第二次减数分裂间期(metaphaseII)
」
(又称为oocytematuration,在ovulation前就已经发生)2.
卵子卵丘复合体(cumulus-oocytecomplex,简称COC)脱
离滤泡壁(NSAID无法抑制)(此约发生于LH或hCGonset
后34-36小时
,所以是试管婴儿疗程之
取卵时机)3.
Ovulation(足量的NSAID可抑制)4.Ovulation后,滤泡壁上剩下的细胞(granulosacell&thecacell)受到LH(或人工生殖中取代以hCG)作用而luteinization形成「黄体」
--负责供应E&P,使子宫内膜
得以完整地decidualization,开启implantationwindow
俾利胚胎着床LH(或人工生殖中取代LH的hCG)
之四大功能Cumulus-OocyteComplexMeiotic
Resumption(
M
II)Oocyte卵子LHsurge2020/4/8诱导排卵(Controlledovarianstimulation)人工授精
:1~3个滤泡发育試管嬰兒
:8-15个滤泡发育follicles
development(养滤泡)
trigger
final
oocyte
for
7-9
days
or
more
maturation
(破卵)(controlledovarianstimulation
by
rFSH)34-
36
hours(TextbookofART,2nd
Ed.,
2004)取卵黄体期补充人工授精
或自行同房一
次诱发多个滤泡,会加速卵量衰竭?而提早停经吗?DrugsforART
「排卵药」
:提升FSH+/-•
口服:Clomiphenecitrate
or
Letrozole
(
)•皮下注射:
Follicle-stimulating
hormone
(FSH)
Puregon(保妊康)/Gonal-F(果那芬)
/long-actingFSH(Elonva)•皮下注射:
Human
menopausal
gonadotropins(HMG)Menopur(美诺孕)
、rFSH+rLH
Pergoveris(倍孕力)
长大的滤泡吃这个LH•Gonadotropin
releasing
hormoneanalogues
(GnRH
agonist)
Leuplin(柳菩林)/Decapeptyl(弟凯得)•
Gonadotropin
releasing
hormone
an
a一g:o预n防isLtH提早上升
(GnRH
antagonist)Orgalutron(柔妊孕)/Cetrotide(欣得泰)------------------------------------------------------取-代/引发LH•
Human
chorionic
gonadotropin
(hCG)
&卵子最后之
Ovidrel
(克诺得)/Pregnyl(保健宁)
(「破卵针」Leuplin(柳菩林)/Decapeptyl(弟凯得)•GnRH
agonist熟成)诱导排卵(Controlledovarianstimulation)人工授精
:1~3个滤泡发育試管嬰兒
:8-15个滤泡发育*E2>200pg/ml
for>
50
hrs会造成positive
feedback
,刺激LH大量分泌(LH
surge)eachfollicle没有做好做满serumE2就可达带动LH上升「目的」同:让follicle做好做满GnRHagonistvs.GnRH
antagonist:
「用法」异Pulsatile
GnRH
(t
½
:2-4
min)(frequency)
FSHand
LH
in
pituitarygland
Ovary:folliculargrowth,ovulationandcorpus
luteumformation
Estrogenand
ProgesteroneaffectstheendometriumHypothalamus:GnRH•GnRH(GonadotropinReleasing
Hormone)–
半衰期短:2~4min–producedinthearcuate
nucleusofthe
hypothalamus,
inapulsatilefashion–ControlFSH/LH
by
differentfrequency–排卵前强:度短小而密–排卵后强:度高而间隔长(3~4h)–
DecapeptideGnRHandGnRH-R
binding328aminoacidsDeca-peptideGnRH
receptorGnRH610王鹏惠Anim
Reprod
Sci
2005;88:5-28Modifications•
Position6:↓
enzymaticdegradation•
Position
10:↑
potency•
Position6and
10:↑
receptor
affinity受体结合区D-型氨基酸替代点
增强受体的结合
Disulphidebridge:C14-C200;C114-C196内生性酶切除点–临床药物GnRH
agonist--ex.AA
6
modification
Longacting,desensitizeGnRH
receptorsafterdaysofstimulation临•床药物GnRH
antagonist--AA1,2,3,6,8,10
modification2014/4/24GnRH类似物•Ovulationinduction/Controlledovarian
hyperstimulation1.
Oral2.
Injectionsc「排卵药」:提升FSH+/-LH
E2>200
pg/ml
for
>50
hrsHypothalamic
level:
ER
depletion
会造成positive
feedbackDay
2~6
GnRH:
↑frequency↑amplitude
LH
surgeMC
start
↑FSH
↑LH
给完药后5-12天(通常7天)会LH
surge
5days
(建议此时QOD同房)
50~150
mg
HSFolliclegrowth,
E2
rise慢性不排卵(月经不准时,爱爱日好难算!)第一线口服排卵药:
喜妊(Clomiphene)
(健保给付)--可能面临问题:
1.子宫内膜太薄而不利于着床;2.子宫颈黏液较不利于精子进入(自然同房者)
;3.至多六
周期;4.
BMI高;5.胰岛素阻抗高效果差102年第二次专技医师二医学六关于口服排卵药物clomiphenecitrate,下列
叙述何者最正确?A.
需使用于hypothalamus-pituitaryaxis功能
失调的女性B.
具强效的雌激素作用C.会减少GnRH分泌D.会使子宫内膜变薄D2014/4/24103年第一次专技高考医师(一)医学(二)下列有关
clomiphene的药理学作用描述,何者错
误?A.
为一种雌激素受体部分作用剂(partialestrogen
agonist),可以刺激促性腺激素(
gonadotropins)的分泌作用B.
对于排卵功能障碍的妇女具有刺激排卵的作用C.使用时会降低血浆中黄体化激素(LH)
和滤泡
促进素(FSH)的浓度D.容易诱发热潮红(hotflushes)的产生C第二线口服排卵药物:复乳纳Letrozole(自费)•
没有Clomiphene的副作用,而且成功率和Clomiphene并驾
齐驱。•
罹患乳癌却仍想生育的妇女•
可能有些潜在的副作用尚未被发现。但以目前的研究证据看来,Letrozole并没有造成比Clomiphene多的胚胎异常。(Clin.Gynecol.
Endocrinol.Infertil.,6th
Ed.)
(TextbookofART,2nd
Ed.,2004)Two
Cell-TwoGonadotropin
Theory雄性素AromataseInhibitor(AI)女性素2014/4/24人工授精
筛选精虫试管婴儿($$
>,<)输卵管有通,可先尝试自然同房/人工受精自然同房亦要考虑年龄因素(卵子质量的关键所在)输卵管不通/严重精虫问题/前述方式失败精卵相遇的途径
•排卵针帮助排卵的药物↓(Clin.Gynecol.
Endocrinol.Infertil.,6th
Ed.)
(TextbookofART,2nd
Ed.,2004)Two
Cell-TwoGonadotropin
Theory女性素雄性素滤泡萎缩早期黄体化卵子质量受损滤泡正常发育卵子成熟雄性素前躯物不足导致雌激素低下滤泡后期发育不良卵子无法完全成熟在不使用GnRH-a
或GnRH-ant时,FSH诱导排卵约有
20%会发生LH早期
上升下视丘/脑下垂体疾病
或使用GnRH-adepot
,
可能导致LH不足黄体刺激素(LH)在诱导排卵的角色LH
适
当
浓度LH上限~10
mIU/mlLH阈值~1
mIU/mlLH
浓度High
LH
Levels
are
Unfavorable
toReproductiveOutcome•Highendogenous
LH:
increasedincidence
ofinfertilityand
miscarriages•LH
inhibitsgranulosacell
proliferationathighconcentrations,andinduce
atresia
of
follicles•LH
hasa
negativeeffect
on
the
endometriumTo
preventLH
prematuresurge预防LH提早上升(PREMATURE
LUTEINIZATION)各种protocol之介绍Ovulationinduction提升FSH+/-
LH养卵泡诱导排卵(Controlledovarianstimulation)人工授精
:1-3个滤泡发育試管嬰兒
:8-15个滤泡发育*E2>200pg/ml
for>
50
hrs会造成positive
feedback
,刺激LH大量分泌(LH
surge)滤泡还不够熟就发生了!!GnRHagonistvs.GnRH
antagonist:「目的」同:预防LH提早上升「用法」异长疗程(
Long
protocol)(Eur.J.Obstet.Gynecol.,2004;Hum.
Reprod.,2007)MonitoringofPituitarydown-regulation:a)
Menstrualbleedingb)
E2
<
80
pg/mlc)P4
<
1.5
ng/mld)
Endometrialthickness<8
mm抑制剂疗程(Antagonist
protocol)S5Betterstartfrom
MCday2-3
(earlyfollicularphase≤
5th
day,
nodominantfollicular
yet.Theearlier,themorefollicles)93年第一次专技高考基础二有关gonadotropin-releasinghormone
(GnRH)之叙述中,下列何者正确?A.
其由脑下垂体产生B.
为一种多胜
(poly-peptide)组成C.长期大量给与GnRH类似物,会产生生殖
腺官能不足D.持续大量给与GnRH类似物,会使GnRH
接受器之敏感性加强BCC关于目前用于刺激排卵的GnRH-agonist,下列叙述何者正确?A长疗程(longprotocol)乃利用其up-regulation特性B和内生性GnRH比较,只有1个氨基酸不同C半衰期比内生性GnRH长D可口服使用诱导排卵MC
↑MC
↑(TextbookofART,2nd
Ed.,2004;Semin.
Reprod.
Med.,2002
)with
GnRH
antagonistwithGnRH
agonist头三天FSH&
LH
↑,S5MC
↑SOAPControlledovarianhyperstimulation:用药Orgalutron(柔妊孕)/monitoringControlledovarianhyperstimulation:--Receptive
to
blastocyst
implantation
~6
daysafter
ovulation
and
remains
receptive
for4
days.ImplantationWindowProgesterone
effectovulationP>1.5
↓Decidualizationo
A.
Natural
conception:#
LH
surge
→
ovulation
→
oocyte
exposed
to
spermatozoa
→
embryomic
window
of
implantation
(WOI,
blastulation)
#
meaningful
P
shortly
after
LH
surge
↑
→
secretory
transformation
→endometrial
window
of
implantation
(WOI)o
B.
IVF
(lost
of
natural
coordination
=
embryonic-endometrial
dyssynchrony):口
1.
P
↑faster
(16~24
hr)口2.
bastulation
may
be
delayed
(older,
low
responders)natural
conception
invitrofertilization(IVF)Recombinant
Hormoneα-Subunits1Corifollitropinalfa92
aaβ-Subunits2110
aahCG
t½
=40
h92
aa29
aa2t½
corifollitropinalfa=
69
h4aa=amino
acids;t½
=
half
life.1.Adaptedwith
permissionfromStraussJetal.YenandJaffe's
ReproductiveEndocrinology:Physiology,Pathophysiology,andClinicalManagement.
5thedition.Saunders;2004;2.
Fares
FAetal.ProcNatl
AcadSciU
SA.
1992;89:4304–4308;3.
PUREGON®
(rFSH)
summaryofproduct
characteristics,2010.;4.
ELONVA®(corifollitropinalfa)summaryofproductcharacteristics,2010.Corifollitropinalfa(Elonva®
)
Is
at½
rFSH
=40
h3t½
rFSH
=40
hTmax
=
10–12
h3StimulationdaysrFSH=recombinantFSH;t1/2=
half-life;Tmax
=timeto
maximum
concentration.1.Adaptedwith
permissionfrom
FauserBCetal.HumReprodUpdate.2009;15:309–321;2.
ELONVA®(corifollitropinalfa)
summary
of
product
characteristics,2010;3.
PUREGON®
(rFSH)summaryofproductcharacteristics,2010.Comparative
Pharmacokineticst½
corifollitropinalfa=
69
h
Tmax
=36–48
h2Corifollitropinalfa
rFSHFSHactivity1Long
protocol(GnRHagonistdown-regulationprotocol)Flare
upFSH&
LH
↑亦即内生性LHsurge(幅度够,但duration略逊)+FSHsurge(hCGtrigger所缺)Dualsuppresion:2-3weeksof(monophasic)Oral
pills5
daysGnRHantagonistprotocola)
Menstrualbleedingb)E2
<
80
pg/mlc)
P4
<
1.5
ng/mld)
Endometrialthickness<8
mmTrigger:
hCG
orGnRH
agonistMonitoringofPituitarydown-regulation:Trigger:
hCGAntagonist
protocol搭配Dualtrigger:GnRHagonist(Decapeptyl
®
0.2mg)
+
low-dosehCG
(Pregnyl®
)[怕OHSS者hCG只给0~1500IU]Antagonist
protocol搭配Dualtrigger亦可用于不怕OHSS者:6500
IU
hCG(Ovidrel®一支)
+GnRHagonist(Decapeptyl
®0.2mg)
[取其FSHsurge的好处]•
The
LHsurgeiscaused
by
the
increase
in
plasma
E2attheendofthefollicular
phase•
Studiesoncontraceptionhaveshownthatprogesteroneisableto
blockthis
LHsurgeandthereforeovulation•
Experimentsonmonkeyshave
shownthat–
Theadministrationofa
progestin(levonorgestrel)atthebeginning
ofthe
cyclepreventsthe
LHsurgedespitethe
increase
in
E2,foras
longas
it
is
continued–
Theinhibitionofthe
LHsurge
by
progesterone
isa
hypothalamicaction(Massin
N,
Hum.
Reprod.Update,2017)Useofprogestogento
block
LHsurgeantagonistPrevent
LHprematuresurgeGonadotropinfor
follicledevelopmentOVARIAN
STIMULATION
FOR
IVF/ICSIExogenous
PDifferentIVF
ProtocolsFollicularPhaseLuteal
Phase…26
27
28
0102030405
………
10
11
12
1314151617
18
19
20
21
22
……Short
ProtocolG
nRH
Agonist
rFSH
GnRHAntagonistrFSH
or
HMG±GnRH
AntagonistHMG/FSHProvera/Utrogestan/DuphastonTrigger(HCG/Agonist)TransvaginalOocyte
RetrievalPPOSProgestinPrimeOvarianLutealStimulationLong
ProtocolAntagonist
ProtocolrFSH
+
LHLutealGnRH
AgonistrFSH
±
LH83黄体愈旺(luteotrophic
activity↑↑)=着床愈稳但OHSS可能愈严重黄体身负重任,持续分泌P&
E(decidualization之所需)预防卵巢过度刺激的关键在于减少hC的G使用,Why?(Humaidan.
PreventionstrategiesforOHSS.FertilSteril*(hCG:比LH更强的luteotropic
activity)Granulosa-
luteal
cellsTriggerviahCGvs
GnRHa•hCG
trigger
longer
and
stronger
luteotropicactivity•GnRH
agonist
(GnRHa)
trigger
more
rapidluteolysisP.
Humaidan.
Human
Reproduction
Update2011,
17
(4)
:510–524不孕症治疗常见之并发症•
卵巢过度刺激症候群OHSSI/O
、腹围、体重钾可预测谁会发生卵巢过度刺激症候群吗?•
Higher
androgen
levels
(Elder-G-epv
o2b0
y
not
—broad
range–
otherssuggestinggreatergonadotropindose
requirement
(Homburg
1996)•
No
good
way
except
prior
history•就算没有危险因子仍可能潜在过度刺激的风险•每个多囊患者接受排卵针都有风险•只要有多囊型态的卵巢,无论是否符合多囊性卵
巢症候群的诊断标准,风险一样高!
(Kim
YJ2010;
SwantonA2010)C通常需要以剖腹探查来治疗D临床症状通常在人类绒毛膜促性腺激素(hCG)注射后3-7天
开始出现A.一位28岁不孕症妇女在6天前接受取卵手术,共取出20颗卵子,
2天后植入3个胚胎。今天来到急诊,主诉呼吸困难、腹胀以及恶心。超音波发现两侧卵巢肿大约6公分、有大量腹水。下
列那一项处置较不适合?A抽血验CA125,CEA,CA199B抽血验CBC,electrolytes,GPT(ALT),
BUN,creatinineC抽腹水D给予大量normalsaline2014/4/24C有关卵巢过度刺激症候群(OHSS)
的叙述,下列何者错误?A卵巢会肿大B严重时会有腹水Oocyteretrieval(Egg
pick
up)取卵TimingofOocyte
Retrieval•Scheduled
at
about
34-36
h
after
hCG
injection:the
oocytes
are
expected
to
ovulate
at
37
h
post-hCG.•AfterhCG
injection,the
intercellularconnections
betweenthegranulosacellsandthe
oocytes
are
interrupted•
Meiosis
is
resumedandtheoocyte
progressesfrom
prophase
I
to
metaphase
II.103年第一次专技高考
医师二医学六
*取卵的时机一般是在绒毛性腺激素(humanchorionicgonadotropin)注射后几
小时?A.20~24
hrB.
34~36hrC.
40~44hrD.
48~52hrB2014/4/241.
Placethetesttubes,handlingmedium,andthermometerin
a
warmblockonthe
staging
stage2.
Flushtheaspiration
needleand
itstubingwith
medium.3.Singlelumen
v.s.
double
lumen
needle(Thedeadspaceofthe
needle
andtubingis
about
1
ml)PreparationofMaterialsforOocyte
Retrieval(TextbookofART,2nd
Ed.,2004)手术全程保持无菌状态,并在超音波导引下进行取卵经阴道以超音波辅助取卵(TextbookofART,2nd
Ed.,2004)经阴道以超音波辅助取卵不成熟卵子
成熟卵子取得卵子显微镜下结构卵丘卵子复合体精虫之准备卵子体外受精(in
vitro
fertilization)精虫显微注射
:
(ICSI)应用在合并男性不孕或先前尝试受精率低者体外受精及胚胎早期发育D3植入
或继续培养↓四细胞受精卵八细胞两细胞胚胎培养至囊胚期雷射辅助孵化
D5植入桑葚胚囊胚黄体期补充人工生殖中为何要黄体期补充?Abnormal
Luteal
FunctionAfterOvarianStimulationfor
IVF:
Mechanisms•
Continueddown-regulationbyGnRHa
LH
↓•Induction
of
multiple
follicles
perse•Removaloflargequantitiesofgranulosa
cellsatoocyte
retrieval•
SupraphysiologicalE2/P4
in
early
luteal
phase
negativefeedback
LH↓--Receptive
to
blastocyst
implantation
~6
daysafter
ovulation
and
remains
receptive
for4
days.ImplantationWindowProgesterone
effectDecidualizationElements
of
Luteal
Phase
Support•HCG:
1500-2000
IU
i.m.q3dfor4doses
fromoocyte
retrieval•P4:fromoocyteretrievalto
7-10weeks1)progesteronein
oil
25-100
mg
i.m.
qd2)utrogestan200
mg
p.o.orvag.tid-qid3)Crinonegel
90
mgvag.
qd•E2:fromoocyteretrievalto
7-10weeks
E2valerate2
mg
p.o.
bid术后用药+Lutealsupport(药物+monitor)取卵34~36小时
之后破卵Micronized
progesteronecapsuleIntramuscularprogesteroneHCGCrinonevs.Vaginal
P4vs.OralP4ART诱导排卵后黄体期之E与P取卵GnRHatriggerGnRHatrigger取卵破卵破卵•
取卵数:25•
植入囊胚期
胚胎OocyteSpermIntraCytoplasmicSperm
Injection2pronuclei4cell2cell8cellGrade2embryosLessthan
10%fragmentationorUnequal-sizedblastomeresGrade3
embryos10%to50%fragmentation
with/withoutUnequal-sizedblastomeresGrade4embryosMorethan50%fragmentation
with/withoutUnequal-sizedblastomeresMorulaand
Blastocysttheembryo,NO
overallsize
increase.with
slight
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