ICSI for all
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Dr. Jyoti Malik is a distinguished medical professional in gynecology and assisted reproduction, holding multiple leadership positions and receiving several awards for her contributions to medicine. She is actively involved in research and has published articles related to intracytoplasmic sperm injection (ICSI) and its implications for various infertility issues. The document also discusses the efficacy of ICSI compared to conventional IVF in several infertility scenarios, highlighting its advantages and limitations.
ICSI for all
- 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
- 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.
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