Icsi preparation

1. ‘‘Preparation of patientsPreparation of patients
for ICSI: an evidence –for ICSI: an evidence –
based approach’based approach’
Dr. Ahmed Abd El AzizDr. Ahmed Abd El Aziz
Professor of Gynecology and ObstetricsProfessor of Gynecology and Obstetrics
Alexandria UniversityAlexandria University

2. AlexandriaAlexandria (c. 300 B.C.)(c. 300 B.C.)

3.  ARTART are sometimes misused to treatare sometimes misused to treat
incompletely-evaluated patients.incompletely-evaluated patients.

4.  The rising pregnancy rates for ICSI mayThe rising pregnancy rates for ICSI may
reflect a change inreflect a change in patient selection criteriapatient selection criteria
and not just an improvement in ART.and not just an improvement in ART.

6. Investigations of infertile coupleInvestigations of infertile couple
Evidence Medicine Based EraEvidence Medicine Based Era
National Evidence-Based Clinical Guidelines
“Assessment and treatment for people with fertility problems
developed by the National Collaborating Centrefor
Women and Children's Health on behalf of
the National Institutefor Clinical Excellence (NICE)”
February 2004

7. Grading – Evidence Based RecommendationsGrading – Evidence Based Recommendations
AA
recommendationrecommendation
I evidenceI evidence
BB
recommendatiorecommendatio
n II evidencen II evidence
CC
recommendationrecommendation
III evidenceIII evidence
DD
recommendationrecommendation
IV evidenceIV evidence
I a-I a- meta-analysismeta-analysis
of RCTs trials,of RCTs trials,
I b-I b- at least oneat least one
RCT.RCT.
II a -II a - at least oneat least one
controlled studycontrolled study
withoutwithout
randomisationrandomisation
II b -II b - at leastat least
one other typeone other type
of quasi-of quasi-
experimentalexperimental
studystudy
non-experimentalnon-experimental
descriptive studies,descriptive studies,
such assuch as
comparativecomparative
studies, correlationstudies, correlation
studies and casestudies and case
control studiescontrol studies
from expertfrom expert
committee reportscommittee reports
or opinions and/oror opinions and/or
clinical experienceclinical experience
of respectedof respected
authoritiesauthorities
• GPP Good practice point : The view of the Guideline Development
Group

8. ICSI PreparationICSI Preparation
uterine
cavity
ovarian
reserve
Chlamydia
Myoma
Hydrosalpinx
Endometriosis
Male
factor
Drugs
&
smoking
History

9. Centers for Disease Control
and Prevention
National Center for Chronic
Disease Prevention and
Health Promotion
Division of Reproductive Health
Atlanta, Georgia
American Society for
Reproductive
Medicine
Society for Assisted
Reproductive
Technology
Birmingham, Alabama

10. Does the cause of infertility affectDoes the cause of infertility affect
the chances of success using ART?the chances of success using ART?
In general, couples diagnosed with :In general, couples diagnosed with :
 unexplained infertilityunexplained infertility
 Ovulatory dysfunction,Ovulatory dysfunction,
 Endometriosis,Endometriosis,
 Male factor,Male factor,
 or Tubal factor,or Tubal factor,
hadhad above-averageabove-average success rates.success rates.

11. TheThe lowest success ratelowest success rate was observed for thosewas observed for those
with diminished ovarian reserve. [Age]with diminished ovarian reserve. [Age]
Below-averageBelow-average success rate was in:success rate was in:
 uterine factor,uterine factor,
 ““other” causes,other” causes,
 or multiple infertility factorsor multiple infertility factors

13. AgeAge

14. Do women who haveDo women who have
previously given birthpreviously given birth
have higher ART success rates?have higher ART success rates?

15. Are success rates different for womenAre success rates different for women
using ART for the first time and thoseusing ART for the first time and those
with failed trials ?with failed trials ?

16. Is there a difference in ART success ratesIs there a difference in ART success rates
between womenbetween women with previous miscarriageswith previous miscarriages
and women who have never been pregnant?and women who have never been pregnant?

17. Does theDoes the sizesize of the clinic affect itsof the clinic affect its
success rate?success rate?

18. Ovarian ReserveOvarian Reserve
 1-Day 3 (FSH) and Estradiol
 2. Basal Antral follicles Count by US
 3. Serum AMH .
 4.Intra-ovarian vascularity by doppler USIntra-ovarian vascularity by doppler US
 5. ovarian volume5. ovarian volume

19. Day 3 (FSH) and EstradiolDay 3 (FSH) and Estradiol
 Day 3 FSH valuesDay 3 FSH values > 15> 15 microIU/LmicroIU/L ;carry a;carry a
poor potential.poor potential.
 Day 3 FSH valuesDay 3 FSH values < 10 microIU/L< 10 microIU/L
represent normal follicular potentialrepresent normal follicular potential
(especially if day 3 estradiol values are less(especially if day 3 estradiol values are less
than 40 pg/mL).than 40 pg/mL).
 ValuesValues between 10 to 15 microIU/Lbetween 10 to 15 microIU/L
probably represent an effect of aging onprobably represent an effect of aging on
fecundity.fecundity.
class: D Evidence.class: D Evidence.

20.  It is possible thatIt is possible that deficient intra-ovariandeficient intra-ovarian vascularityvascularity
may serve as themay serve as the initial markerinitial marker of reduced ovarianof reduced ovarian
reserve which precedes an increased FSH level andreserve which precedes an increased FSH level and
reduction of the ovarian volume .reduction of the ovarian volume .
(Engmann(Engmann et alet al., 1999 ).., 1999 ).
Ovarian ReserveOvarian Reserve

21. Ovarian ReserveOvarian Reserve
A meanA mean ovarian volume of <3 cm3ovarian volume of <3 cm3 have a poorhave a poor
response to exogenously applied stimuli.response to exogenously applied stimuli.
(Syrop(Syrop et alet al., 1995).., 1995).

22. Assessment of the uterineAssessment of the uterine
cavitycavity
 Any lesion of the uterineAny lesion of the uterine
cavity should becavity should be treated priortreated prior
to an IVF cycle to optimizeto an IVF cycle to optimize
reproductive success.reproductive success.
 This would includeThis would include
submucosal myomas,submucosal myomas,
endometrial polyps, a uterineendometrial polyps, a uterine
septum, and intracavitaryseptum, and intracavitary
adhesions.adhesions.

23. The most popular techniques used to identify
lesions in the uterine cavity
Hysterosalpingography
(HSG),
Hysteroscopy
3D Ultrasound

24. HysterosalpingogramHysterosalpingogram

25. IntrauterineIntrauterine
AdhesionsAdhesions

26. Mullerian AbnormalitiesMullerian Abnormalities
Bicornuate uterusBicornuate uterus Septate uterusSeptate uterus
3D ultrasound

27.  The routine performance of a pelvic
ultrasound scan to establish ovarian (and
uterine) morphology is a useful tool to
identify women with risk factors for
pregnancy loss .
RCOG Guidelines : Grade C Recommendation

28. HysteroscopyHysteroscopy
Intrauterine AdhesionsUterine septum

29. Uterine cavityUterine cavity
 Women should not be offered hysteroscopy on its
own as part of the initial investigation unless
clinically indicated, because the effectiveness of
surgical treatment of uterine abnormalities on
improving pregnancy rates has not been
established..
RCOG Guidelines : Grade B Recommendation

30. Many IVF centers now recommend removal of
the septum before assisted reproductive
treatment to reduce the possibility of
miscarriage .

31. Uterine Polyp
Reproductive BioMedicine Online 2006 Vol. 12, No. 2. 205–208Reproductive BioMedicine Online 2006 Vol. 12, No. 2. 205–208
LargeLarge endometrial polyps should be removed.endometrial polyps should be removed.
SmallSmall polyps less than 1.5 cm do not affect ICSIpolyps less than 1.5 cm do not affect ICSI
outcomeoutcome . .

32. Endometrial receptivity
 GoodGood endometrial and subendometrialendometrial and subendometrial blood flowblood flow
assessed by transvaginalassessed by transvaginal Color DopplerColor Doppler before ETbefore ET
is indicative of good endometrial receptivity.is indicative of good endometrial receptivity.
 Poor blood flowPoor blood flow [old women] represents a bad[old women] represents a bad
uterine environment.uterine environment.
(Chien LW , et al 2002 , prospective clinical study.
600 patients undergoung ICSI , FOR PREGNANCY RATE )

33. Chlamydial infectionChlamydial infection
 Women without Chlamydia trachomatis antibodies
have higher implantation rates, higher pregnancy
rates, fewer early abortions, and more normal
deliveries .
 Women with Chlamydia trachomatis antibodies
should be treated before an IVF cycle to give
higher pregnancy rates.

34. TuberculosisTuberculosis
Anti-bacterial treatment of pelvic tuberculosisAnti-bacterial treatment of pelvic tuberculosis
prior to IVF increases the success rate;prior to IVF increases the success rate;
provided that the tuberculous process hasprovided that the tuberculous process has
not destroyed the endometriumnot destroyed the endometrium..

35. Alcohol, smoking and caffeineAlcohol, smoking and caffeine
consumption reduces the successconsumption reduces the success
rate of ICSI .rate of ICSI .
RCOG Guidelines : Grade C Recommendation

36. Characteristics Passive Smokers Non-Smokers
Number of cases 36 38
Number of cycles 50 60
Mean ±SD Mea
n
±SD P
Mature follicles / Cycle 10.3 ±0.87 12.2 ±1.13 <0.001
Oocytes retrived /
cycle
7.2 ±0.73 10.1 ­­±1.19 <0.001
Oocytes Metaphase II/
cycle
4.1 ±0.72 7.8 ±1.22 <0.05
Oocytes fertilized/ cycle 3.2 ±0.83 6.4 ±1.12 <0.001
/ Embryos grade Acycle 2.1 ±0.64 4.1 ±0.878 <0.05
Clinical pregnancy rate
(%)
7(19.4%) 12(31.5%) <0.001
The Outcome ofThe Outcome of ICSI in Passive Smokers & Non Smokersin Passive Smokers & Non Smokers

37. Body weightBody weight
Body mass index [19–30 ]:Body mass index [19–30 ]:
is optimal for ICSI success.is optimal for ICSI success.
RCOG Guidelines : Grade B Recommendation

38. DrugsDrugs
1.1. Metformin .Metformin .
2.2. Aspirin.Aspirin.
3.3. Combined Aspirin andCombined Aspirin and
heparin.heparin.
4.4. Luteal phase supportLuteal phase support ..

39. Metformin TherapyMetformin Therapy
 Metformin therapyMetformin therapy
improvesimproves ovarianovarian
stimulation and IVFstimulation and IVF
outcomes in -resistantoutcomes in -resistant
polycystic ovarianpolycystic ovarian
syndrome (PCOS).syndrome (PCOS).
Jones Institute for Reproductive Medicine, USA , 2002

40. AspirinAspirin
 Low-dose aspirinLow-dose aspirin does notdoes not improve ovarianimprove ovarian
responsiveness or pregnancy rate in IVF andresponsiveness or pregnancy rate in IVF and
ICSI patients:ICSI patients:
in a randomized, placebo-controlled double-in a randomized, placebo-controlled double-
blind study.blind study.
(Päkkilä M(Päkkilä M , et al, et al Hum Reprod. 2005; 20(8):2211-4 )

41. Combined low dose Aspirin & HeparinCombined low dose Aspirin & Heparin
increases success rate in women withincreases success rate in women with
repeated IVF failures .repeated IVF failures .
Pacific Fertility Medical Centers of CaliforniaPacific Fertility Medical Centers of California ,20002000

42. luteal supportluteal support
hCG or progesteronehCG or progesterone is essentialis essential
in women treated within women treated with Gn-RhGn-Rh
agonistsagonists during Ivf & ICSIduring Ivf & ICSI
cycles.cycles.
RCOG Guidelines : Grade A Recommendation

43. HydrosalpinxHydrosalpinx
meta-analyses clearly demonstrated the negative effectmeta-analyses clearly demonstrated the negative effect
of hydrosalpinges on IVF outcomeof hydrosalpinges on IVF outcome
(Strandell(Strandell et alet al., 1994 ),., 1994 ),
(Zeyneloglu(Zeyneloglu et alet al., 1998 ; Camus., 1998 ; Camus et alet al., 1999 ).., 1999 ).

44. Laparoscopic salpingectomyLaparoscopic salpingectomy
Should be considered for all women withShould be considered for all women with
hydrosalpinx who undergo IVFhydrosalpinx who undergo IVF..
Johnson NP Mars ,2002. systematic reviewJohnson NP Mars ,2002. systematic review
(Cochrane review)(Cochrane review)

45. Further research is requiredFurther research is required to assess otherto assess other
pre-IVF surgical interventions,pre-IVF surgical interventions, such as :such as :
 needle aspiration of hydrosalpinx fluidneedle aspiration of hydrosalpinx fluid
 laparoscopic proximal tubal occlusionlaparoscopic proximal tubal occlusion
 laparoscopic salpingostomylaparoscopic salpingostomy

46. Endometriosis
Endometriosis is a commonEndometriosis is a common
finding among infertilefinding among infertile
women.women.

47. Management ofManagement of
endometriosis-associatedendometriosis-associated
infertilityinfertility
1.1. Surgical treatmentSurgical treatment
2. Medical treatment2. Medical treatment
3. Combined medical and surgical therapy3. Combined medical and surgical therapy
4. Controlled ovarian hyperstimulation +/­ IUI4. Controlled ovarian hyperstimulation +/­ IUI
5.5. Assisted reproductive techniquesAssisted reproductive techniques

48. EEndometriosisndometriosis : Mild: Mild
 Surgical ablation or ,or ,
 ovarian stimulation with IUI .ovarian stimulation with IUI .
RCOG Guidelines : Grade A Recommendation

49. Endometriosis :Moderate to SevereEndometriosis :Moderate to Severe
Surgical treatment may improve fertility .
RCOG Guidelines : Grade B Recommendation

50. Endometriosis
 In more advanced stages ofIn more advanced stages of
endometriosis,endometriosis, ARTART is the recommendedis the recommended
treatment.treatment.
 The use ofThe use of GnRH agonistGnRH agonist duringduring
stimulation further improves the outcome.stimulation further improves the outcome.
RCOG Guidelines : Grade A Recommendation

51. Fibroid uterusFibroid uterus
Submucous myomasSubmucous myomas may reduce the likelihood ofmay reduce the likelihood of
successful implantation.successful implantation.

52. Fibroid uterusFibroid uterus
 Patients havingPatients having subserosal or intramuralsubserosal or intramural myomasmyomas
of <4 cm not encroaching on the uterine cavityof <4 cm not encroaching on the uterine cavity
have IVF-ICSI outcomes comparable to those ofhave IVF-ICSI outcomes comparable to those of
patients without such leiomyomas.patients without such leiomyomas.
Oliveira et al , fertil steril , 2004. BrazilOliveira et al , fertil steril , 2004. Brazil

53. Positive factorsPositive factors
1. Younger age of woman .1. Younger age of woman .
2. History of previous pregnancy .2. History of previous pregnancy .
3. History of recurrent miscarriage .3. History of recurrent miscarriage .
4. Non-smoker .4. Non-smoker .

54. Negative factorsNegative factors
1. Old age.1. Old age.
2. Combined male and female infertility .2. Combined male and female infertility .
3. Previous history of failed trials (3 or more3. Previous history of failed trials (3 or more
cyclescycles))

55. Negative factorsNegative factors
4. Uterine abnormality (DES, fibroids) 4. Uterine abnormality (DES, fibroids)
5. Certain types of ovarian dysfunction (High5. Certain types of ovarian dysfunction (High
FSH level) .FSH level) .
6. Hydrosalpinx .6. Hydrosalpinx .

56. Semen analysisSemen analysis
CASA is not superior to conventional semen
analysis
RCOG Guidelines : Grade A Recommendation

57. Semen analysis
Abnormal
Azospermia and
severe oligospermia
Repeat after 3 months Repeat as soon as posible
RCOG Guidelines : Grade B Recommendation

58. Male Subfertility
Oligo/asthenospermia
Gonadotrophin is effective in the
treatment of male hypogonadotrophic
hypogonadism,but ineffective in idiopathic
male infertility.
RCOG Guidelines : Grade B Recommendation

59. Obstructive AzoospermiaObstructive Azoospermia
Microsurgical correction of vas
deferens occlusion and epididymal
blockage can be considered .
RCOG Guidelines : Grade B Recommendation

60. ICSIICSI
Intracytoplasmic sperm injection (ICSI) isIntracytoplasmic sperm injection (ICSI) is
indicated inindicated in
 SSevere deficits in semen qualityevere deficits in semen quality
 OObstructivebstructive azoospermia .azoospermia .
 NNon-obstructive azoospermia .on-obstructive azoospermia .
 PPrevious IVF cyclerevious IVF cycle withwith failed or very poorfailed or very poor
fertilisation.fertilisation.
RCOG Guidelines : Grade A Recommendation

61. Sperm aneuploidy frequency and ICSISperm aneuploidy frequency and ICSI
 Increased frequency is associated with :Increased frequency is associated with :
lower implantation rateslower implantation rates
higher miscarriage rates.higher miscarriage rates.
 Future development of methods to identify geneticallyFuture development of methods to identify genetically
abnormal sperm may allow for better selection and improvedabnormal sperm may allow for better selection and improved
ICSI outcomes.ICSI outcomes.
Nunziatina Burrello, et al .Human Reproduction, Vol. 18, No. 7, 1371-1376, July
2003

62. ICSI PreparationICSI Preparation
uterine
cavity
ovarian
reserve
Chlamydia
Myoma
Hydrosalpinx
Endometriosis
Male
factor
Drugs
&
smoking
History

64. ICSI 3.mpg