It was while performing SUZI that a single spermatozoon accidentally penetrated into the oolemma and provided the hint that a direct sperm injection would be more efficient. 1st successful birth by ICSI took place on Jan 14, 1992.

1. Dr. Jyoti Malik (MBBS, DGO, DNB, MNAMS, FICS)
Designation:
• Medical Superintendent - JJ Institute of Medical Sciences (JJIMS), Bahadurgarh, Haryana.
• Director - Roots IVF & Fertility Institute, JJIMS Bahadurgarh, Haryana.
• Vice- Chairperson- Haryana Chapter of Indian Society of Assisted Reproduction, (H-ISAR 2019-2021).
• Secretary General - Haryana Chapter of Indian Society of Assisted Reproduction, (H-ISAR 2016-2018).
• Joint Secretary - Haryana Association of Gynae Endoscopy (HAGE 2019-2021).
• Joint Treasurer - Haryana Association of Gynae Endoscopy (HAGE 2017-2018).
• Joint Secretary - Delhi chapter, (ISPAT 2016-2018).
• Secretary -Haryana association of registered Obstetricians and Gynaecologists (HARObGyn).
• Secretary - IMA, Bahadurgarh (2019-2020).
• Treasurer - IMA, Bahadurgarh (2016-2018).
• Chairperson - Women Wing, Indian Medical Association, Haryana 2018.
• Vice- Chairperson- Mission Pink Health, Haryana 2019.
• Founder president - Jhajjar Obstetrics & Gynaecological society.
• Life Member of various organizations : FOGSI / AOGD / ISAR /IFS / AMASI / IAGE / MIMA / IMS /DGES / ISPAT / SFM.
Special Awards & Achievements:
• Awarded with “Swasthya Ratan Award 2018” in the field of Medicine & Health by STV Haryana News.
• Awarded with “SIX SIGMA HEALTHCARE EXCELLENCE AWARD as HEALTHCARE ENTERPRENEUR OF THE
YEAR” 2017.
• Awarded with “Nari Shakti Samman” by Honorable Governor of Haryana, in the event organized by JANTA TV in year 2017 .
• Awarded Dr. L M Shah Prize for 4. Awarded “SIX SIGMA HEALTHCARE EXCELLENCE AWARD as WOMAN
ENTERPRENEUR OF THE YEAR” 2015 for outstanding Performance, in the medical field in Haryana among the women of the
District.
• Best presentation on “ENDOMETRIOSIS & CA-125” in Annual conference of ‘BOGS’.
Publication:
• Is co-author of article titled “ Role of TRU-CUT Biopsy in Adnexal Masses “ in international journal of Gynecology &
Obstetrician with Dr. S Seth in 50 (1995) 27 – 31 .
• Published brief communication “ASCITIC TAPPING BY VAGINAL ROUT” in International journal of Gynecology &
Obstetrics 56 (1997) 65 – 66.

2. ICSI FOR ALL ?

3. It was while performing SUZI that a single spermatozoon
accidentally penetrated into the oolemma and provided the
hint that a direct sperm injection would be more efficient.
1st successful birth by ICSI took place on Jan 14, 1992.
Origin of ICSI

4. Indications of IVF
• Tubal disease
• Anovulation
• Unexplained Infertility
• Previous failed IUI

5. Indications of ICSI
• Ejaculatory dysfunction
• Immunological Infertility
• Cancer patients on chemo/radiotherapy
• Fertilization failure
• Low fertilization in previous IVF
• Advanced age(to overcome sperm oocyte penetration issues)
• Low oocyte yield
• Poor quality oocytes
• Unexplained Infertility
• Fertilization of cryopreserved oocytes

6. 57.5 58.6 59.3
42.15
70.7
75.6
0
10
20
30
40
50
60
70
80
USA Australia/New Zeland Europe The Nordic Countries,
Netherlands & UK
(40-44.3%)
Austria, Belgium &
germany (68.5-
72.9%)
Southern European-
Greece, Italy & Spain
(66-81.2%)
Percentage
Countries

7. “ICSI comprised 66% of all aspirations, a
continued increase from 60.6% in 2004 and
62.9% in 2005.

8. Why increase in ICSI cycles
• Declining sperm quality
• Advanced age
• Declining tubal infertility

9. ICSI in male factor
infertility

10. Indications for micro fertilization-
intracytoplasmic sperm injection
Obstructive azoospermia (following MESA/TESA) in patients with
• Obstructive azoospermia (following MESA/TESA) in patients with
• Congenital absence of the vas defense (CAVD)
• Acquired vas obstruction
• Irreparable epididymal obstruction
• Conservatively untreatable ejaculation disturbances
• Failed microsurgical reversal for vasectomy
Non-Obstructive azoospermia (following TESA) in patients with
• Germ-cell aplasia, maturation arrest and tubular sclerosis / atrophy, all with
• Focal spermatogenesis
• Sertoli-cell only syndrome
• Persistent azoospermia post chemotherapy
• A history of orchidopexy
• Spinal cord injury
• Seminiferous tubule dysgenesis (Klinefelter syndrome 47, XXY)
Presence of acrosomeless or immotile spermatozoa.

11. ICSI -Severe male infertility
Post wash total progressively motile sperm count:
• <500,000 progressive motile spermatozoa
• <1 million progressive motile spermatozoa
• SPERM MORPHOLOGY:
• <4 % normal morphology by strict criteria
• ANTI SPERM IMMUNITY:
• High titres of anti sperm antibodies

12. Meta-analysis comparing fertilization in vitro
after conventional IVF and ICSI in patients
with moderate male subfertility.
IVF ICSI RR
Fertilization rate (%) 35.7 62.8 1.9 (1.4-2.5)
Fertilization failure (%) 33.7 3 7.5 (3-20)
The number of ICSI procedures required to avoid a complete fertilization
failure after IVF (number needed to treat, NNT) was 3.1 (95% CI, 2–12)
332 cycles and 4,199 inseminated oocytes
Tournaye. IVF vs. ICSI for male infertility. Fertil Steril 2002.

13. ICSI outcomes in couples with male factor infertility do not
differ from a control group presenting tubal factor
diagnoses
Andrea Abdala, Laura Vargas, Ernesto Gómez Passanante, Sergio Provenzano, Javier Singla
Hospital de Clínicas José de San Martín, University of Buenos Aires, Buenos Aires, Argentina

14. Comparison of fertilization from sibling oocytes
subjected to two protocols of conventional
insemination (IVF) and ICSI i
73 cycles and 986 inseminated oocytes
Cycles
(N)
Fertilization
after IVF,
in (%)
Fertilization
after ICSI
in (%)
Fertilization
failure–IVF,
in (%)
Fertilization
failure–ICSI
in (%)
Pregnancies
in (%)
Protocol A
(5,000 sperm per
oocyte)
35 37.4 64.3 25.7 0 42.8
Protocol B
(20,000 sperm
per oocyte)
38 59.6 67.6 5.3 0 42.1
High insemination concentration can improve fertilization after conventional IVF in cases
with moderate male subfertility and may be an alternative to ICSI.
Tournaye. IVF vs. ICSI for male infertility. Fertil Steril 2002.

15. Proportion of ICSI cycles with diagnosis of male
factor infertility (US - 2006 ART Report, CDC 2008)
99199 fresh-non donor cycles, 62.2 % ICSI
Male Factor
Infertility 48%NO Male Factor
Infertility 52%

16. Fertilization rate in sibling oocytes allocated
to IVF or ICSI in non-male infertility factor
No. Fertilization
rate IVF (%)
Fertilization
rate ICSI (%)
TFF IVF
(%)
TFF ICSI
(%)
Aboulghar et al., 1996 116 64.8 53.3 31.0 32.8
Bhattacharya et al.,
2001
415 58 48 33.0 26.0
Foong et al., 2006), 60 77.2 82.4 50.0 50.0
Jaroudi et al, 2003 124 51.6 61.0 19.2 0.8

17. Results:
No statistically significant differences in reproductive outcomes were noted between
women with no endometriosis and those with minimal to mild (stage I & II) endometriosis
whether conventional IVF or ICSI was utilized. However, ICSI was associated with a
71% decrease in clinical pregnancy rate (OR = 0.29, p = 0.046) and approached
statistical significance for a 69% decrease in live birth rate (OR = 0.31, p = 0.0796) in
women with moderate to severe (stage III & IV) endometriosis.
Conclusion:
The findings of this study suggest that there is no added benefit and it is potentially
detrimental to recommend ICSI in women diagnosed with endometriosis associated
infertility especially in moderate to severe (Stage III & IV) endometriosis.
IVF or ICSI: which is better in women with
endometriosis associated infertility?
L. Tan et al. Fertility Sterlity 2018.

18. ICSI for Tubal Factors
Use of ICSI in IVF cycles in women with tubal ligation does not
improve pregnancy or live birth rates.
Hum Reprod. 2016
Patients who underwent ICSI had no statistically significant improvement in
fertilization rate and actually had a lower likelihood of achieving a clinical
pregnancy and LB

19. Unexplained Infertility

20. A prospective randomized trial of conventional
in vitro fertilization versus intracytoplasmic
sperm injection in unexplained infertility
IVF (n=30) ICSI (n=30)
Fertilization rate 77.2% 82.4%
Fertilization failure 6.7% 0%
Live birth rate 46.7% 50.0%
Foong et al., Journal of Assisted Reproduction
and Genetics, Vol. 23, No. 3, March 2006

21. J Assist Reprod Genet. 1996 Jan;13(1):38-42.
Intracytoplasmic sperm injection and conventional
in vitro fertilization for sibling oocytes in cases of
unexplained infertility and borderline semen.
Aboulghar MA1, Mansour RT, Serour GI, Sattar MA, Amin YM.
CONCLUSIONS:
The study showed that 22.7% of unexplained infertility and 45.8% of patients with
borderline semen would have lost their chance of embryo transfer completely because of
total failure of fertilization if ICSI was not performed on some oocytes in this cycle.
Unexplained Infertility
A
Borderline Semen
B
Fertilization Rate/
Oocyte
Total Fertilization
Failure
Fertilization Rate/
Oocyte
Total Fertilization
Failure
ISCI 63 None 59 None
IVF 50.7 5/22 27 11

22. Reprod Biomed Online. 2004 May;8(5):584-9.
A strategy for treatment of couples with
unexplained infertility who failed to conceive after
intrauterine insemination.
Bungum L1, Bungum M, Humaidan P, Andersen CY.
The policy of splitting the sibling oocytes can effectively minimize complete
fertilization failure while maintaining high chances of achieving a pregnancy. At the
same time, the optimal fertilization method for subsequent treatment cycles can be
determined.
248 Couples
Pregnancy rate / Embryo transfer 57%
Fertilization Rate (P<0.005)
(in%)
Total Fertilisation Failure
(in %)
ISCI
68 4.4
IVF
46 25

23. Intracytoplasmic sperm injection as a treatment for
unexplained total fertilization failure or low
fertilization after conventional in vitro fertilization
Previous IVF with TFF
(N=24)
Previous IVF with low
fertilization (N=17 )
Fertilization rate IVF 29.3% 42%
Fertilization rate ICSI 55.6% 62%
Fertilization after
ICSI only
66.7% 50%
Performing ICSI on at least part of the oocytes will avoid unnecessary total
fertilization failure.

24. J Assist Reprod Genet. 1998 Jan;15(1):18-21.
Treatment policy after poor fertilization in the first
IVF cycle.
Roest J1, Van Heusden AM, Zeilmaker GH, Verhoeff A.
RESULTS:
The recurrence rate of total fertilization failure was high, and poor fertilization frequently
occurred in the second cycle (50-75%).
CONCLUSIONS:
Poor fertilization frequently recurs in the second IVF cycle. The use of intracytoplasmic
sperm injection could be considered after fertilization of 20% or less of oocytes in the first
cycle, irrespective of the number of motile sperm cells per milliliter of semen.

25. Intracytoplasmic sperm injection as a treatment for
unexplained total fertilization failure or low
fertilization after conventional in vitro fertilization
Lucette van der Westerlaken, M.Sc. *,
Fertility and Sterlity March 2005.
Conclusion(s)
Performing ICSI on some oocytes of a cohort may avoid total fertilization failures both
in patients with a history of total fertilization failure and in patients with a history of low
fertilization, as the percentage of fertilization is higher after ICSI compared to IVF

26. Intracytoplasmic sperm injection as a
routine indication in low responder
patients
IVF (n=52) ICSI (n=52)
Fertilization rate 58.8% 56.5%
Fertilization failure 11.5% 11.5%
Pregnancy rate/cycle 17.3% 21.1%
We conclude that the technique of fertilization is not related to
the reproductive outcome of low responders, and the routine
use of ICSI is not indicated.

27. ICSI for Advanced Maternal age
Oocytes retrieved from older women have been theorized to
have structural defects of the zona pellucida or cytoplasm that
might reduce the fertilization rate with conventional insemination.

28. Should ICSI be implemented during IVF to all advanced-age
patients with non-male factor subfertility?
Jacob Farhi, Kfir Cohen, Yossi Mizrachi, Ariel Weissman, Arieh Raziel & Raoul Orvieto
Reproductive Biology and Endocrinology
Conclusions:
This study favors the use of ICSI in the older IVF population in order to
increase both the fertilization rate and the number of top quality embryos that
result per IVF cycle.
52 Patients & 504 Oocytes No. Of Oocytes
Fertilization
rate (%)
ICSI 245 71%
IVF 259 50%

29. ICSI for PGT
The rationale for ICSI use is to ensure monospermic fertilization and eliminate
potential paternal contamination from extraneous sperm attached to the zona
pellucida. While there are no randomized, controlled trials, the concerns of
inaccurate results due to extraneous sperm contamination with PGT justifies the
use of ICSI in this situation.

30. ICSI after IVM
In vitro maturation and fertilization of
immature oocytes: a comparative study of
fertilization techniques.
Hwang JL1, Lin YH, Tsai YL
J Assist Reprod Genet. 2000 Jan;17(1):39-43.
Conclusion:
Cumulus cells are beneficial in the
maturation of human oocytes in vitro and
that ICSI increases the fertilization rate for
the in vitro matured oocytes. The
developmental potential of the fertilized
oocytes, however, is similar irrespective of
the fertilization method or the presence or
absence of cumulus cells.

31. Pregnancy and birth after intracytoplasmic sperm injection of in vitro
matured germinal-vesicle stage oocytes: case report.
Nagy ZP1, Cecile J, Liu J, Loccufier A, Devroey P, Van Steirteghem A
Fertil Steril 1996
Nine of 14 germinal-vesicle stage oocytes matured
to the metaphase II stage after 30 hours of in vitro
culture (64%). Seven of eight injected and intact
oocytes fertilized normally (78%) and five of them
cleaved with < 20% fragmentation (71%). Four
embryos were transferred and a singleton
pregnancy was obtained that ended in the delivery
of a healthy child.
Conclusion:
In vitro maturation of immature oocytes together
with ICSI can result in normal fertilization, embryo
development, pregnancy, and the delivery of
healthy child.

32. ICSI for Cryopreserved
Oocytes
Oocyte cryopreservation involves the removal of the cumulus
cells prior to freezing. This may lead to changes in the zona
pellucida that could reduce fertilization rates with conventional
insemination. For these reasons, ICSI has been the preferred
method of fertilizing cryopreserved oocytes.

33. Safety of ICSI
A prospective longitudinal study of the physical, psychomotor, and intellectual
development of singleton children up to 5 years who were conceived by
intracytoplasmic sperm injection compared with children conceived spontaneously and
by in vitro fertilization.
Isabelle Place, M.Sc.a,*, Correspondence information about the author M.Sc. Isabelle Place
Fertility and Sterility 2003
Results:
Children conceived by ICSI were healthy: no significant
differences appeared in the incidence of combined congenital
malformations (11.3%), health problems (44.1%), surgical
interventions (18.6%), and hospitalizations (6.8%), nor for the
developmental assessments (mean developmental quotient at 9
months: 93.9; at 18 months: 102.0). For the intellectual
assessments, the between-group differences disappeared when
adjusted for levels of parental education (mean intelligence
quotient at 3 years: 97.0; at 5 years: 103.3).
Conclusion:
This pilot study shows that throughout the preschool period,
ICSI-conceived children have psychomotor and intellectual
development similar to that of IVF-conceived and spontaneously
conceived children. These conclusions need to be confirmed by
multicenter studies.

34. The risk of major birth defects after intracytoplasmic
sperm injection and in vitro fertilization.
Hansen M1, Kurinczuk JJ, Bower C, Webb S
N Engl Journal of Medicine 2002
Conclusion:
Infants conceived with use of intracytoplasmic sperm injection or in vitro
fertilization have twice as high a risk of a major birth defect as naturally
conceived infants.

35. Disadvantages of ICSI
ICSI requires technical skills that conventional insemination does not. It is
performed out of the laminar flow hood, on a heated stage outside of the
incubator, and requires an enzymatic / mechanical removal of the cumulus
oophorus. It needs to be performed in a highly regulated laboratory environment
(in fact, early ICSI adopters indirectly improved their pregnancy rates because of
the required adjustments to more stringent laboratory conditions). Most
importantly, ICSI must be performed in an expedited fashion.
ICSI was developed to overcome the shortcoming of the spermatozoon and
should be used only in such conditions or whenever there is a concern for a
reduced ability of the male gamete to penetrate oocyte.

36. ICSI requires additional laboratory experience,
resources, effort, and time.
Thus, expanded use of ICSI increases the complexity
and cost of IVF.

37. Study has shown that in the best scenarios it will only offer
comparable results to conventional in vitro insemination.
Indeed ICSI, because of its sensitivity, is more likely to be
impaired by any fluctuation in laboratory procedural protocols
or media or culture condition aberrations.
Moreover, ICSI requires that the oocyte reaches nuclear and
cytoplasmic maturity to be fertilized in a time-sensitive fashion
one injection is performed.

38. For the reproductive specialist, the tendency to overuse ICSI
is created by situations in which a failure of fertilization may
prove devastating for the infertile woman or couple both
economically and emotionally.
On the other hand, the underuse of ICSI resulting in total
fertilization failure may one day even be perceived as a
liability issue.

39. To Summarize
• ICSI is a safe and effective therapy for the treatment of male factor infertility.
• ICSI can increase fertilization rates when lower than expected or failed
fertilization has previously occurred with conventional insemination.
• ICSI for unexplained infertility does not improve clinical outcomes.
• ICSI for low oocyte yield and advanced maternal age does not improve
clinical outcomes.
• ICSI may improve fertilization rates in a subsequent cycle following total
failed fertilization in a prior IVF/conventional insemination cycle, although
fertilization failure seems to correlate with poor ovarian stimulation.
• ICSI for routine use may decrease the incidence of unexpected failed
fertilization; however, more than 30 couples would have to undergo ICSI
unnecessarily to prevent one failed fertilization.
• ICSI may be of benefit for patients undergoing IVF with PGT, in vitro matured
oocytes, and previously cryopreserved oocytes.

40. THANK YOU