ICSI Begin en Einde P Devroey ICSI Beginning
ICSI - Begin en Einde? P Devroey
ICSI - Beginning and End? P Devroey
JUST THE SPERM Invited lecture Istanbul ESHRE P Devroey 04 -07 -2012
Pronuclear formation by microinjection of human spermatozoa into human oocytes • Microinjection of a spermatozoon directly into ooplasm • Oocytes from 5 of 11 patients were successful • It promotes the supposition of clinical feasibility by sperm microinjection Lanzendorf et al FS 1988
Beginning… Pregnancies after intracytoplasmic injection of a single spermatozoon into an oocyte Palermo, Joris, Devroey, Van Steirteghem Lancet 1992
Pubmed search • Keyword: ICSI • 14 -06 -2012 • 6209 publications (n) • 24 -09 -2012 • 6369 publications(n) • 15 -10 -2012 • 6395 publications (n) The End…
Surprising ? ICSI - Pub. Med • 6395 publications in 20 years time • 1 publication per day
Innovation – Inspiration - Education • • • Prof. dr. A. Van Assche Prof. dr. I. Brosens Prof. dr. O. Steeno Dr. J. Caudron Prof. dr. R. Schoysman Prof. dr. A. Vansteirteghem
ICMART World Report: ART • 54 countries ( year of collection 2003) • National ART registries globally • 433. 427 initiated cycles resulted in 173. 424 babies • Unfortunately 25% twins and 2% triplets • ART patients benefit from the ICSI technique Nygren et al Fertil Steril 2011
Reproductive technologies and the risk of birth defects • 308. 974 births from natural conception 6163 births from ART • Birth defects • natural conception 5. 8% • ART 8. 3% • OR 1. 47, 95% CI: 1. 33 -1. 62 Davies et al N Engl J Med 2012
Reproductive technologies and the risk of birth defects (continued) • IVF 165 birth defects 7. 2 % • OR 1. 26, 95% CI: 1. 07 -1. 48 • ICSI 139 birth defects 9. 9 % • OR 1. 57, 95% CI 1. 30 -1. 90 • Risk of birth defects with ICSI is increased Davies et al N Engl J Med 2012
Pubmed Search • Keywords: azoospermia ICSI • 14 -06 -2012 • 718 publications (n) • 15 -10 -2012 • 732 publications(n) The End…
Ongoing pregnancies and birth after ICSI with frozen-thawed epididymal spermatozoa Devroey HR 1995
No difference in outcome after ICSI with frozen-thawed epididymal spermatozoa Epididymal sperm Fresh Frozen-thawed ICSI (n) 157 118 Fertilization rate 62% 55% ET (n) 145 100 Implantation rate 15% 12% Ongoing pregnancy rate per ICSI 27% 21% Tournaye HR 1999
Normal fertilization of human oocytes after testicular sperm extraction and intracytoplasmic sperm injection In obstructive azoospermia TESE - testicular sperm extraction Devroey et al Fertil Steril 1994
Normal fertilization of human oocytes after testicular sperm extraction (TESE) and ICSI Patients M-II Embryo 1 22 9 2 14 5 3 9 3 Devroey FS 1994
Story • Mexican engineer (living in the Netherlands) • Blocked tube due to hernia operation as a child : azoospermia • 12 months of donor insemination • No pregnancy in Amsterdam • First TESE pregnant • Child wants to see the lab Fertility and Sterility 1995
Pregnancies after ICSI of sperm collected by fine needle biopsy of the testis Indication obstructive azoospermia Bourn FS 1995
ICSI after FNA versus TESE Retrospective controlled study - obstructive azoospermia FNA TESE ICSI (n) 51 51 COC (n) 691 624 Fertilization rate (%) 64 64 Cleavage rate (%) 72 78 Transfers (n) 49 51 Ongoing pregnancy rate per cycle (%) 20 22 Tournaye HR 1998
Distinct diagnosis • Non-obstructive azoospermia – Congenital • Germ cell aplasia • Maturation arrest • Cryptorchidism • Karyotype abnormalities • Klinefelter syndrome – Acquired • Post chemotherapy • Post radiotherapy Chan COU 2000
Outcome of intracytoplasmic sperm injection with testicular spermatozoa in obstructive and non-obstructive azoospermia • • • 19 couples 264 MII oocytes 58% 2 PN fertilization rate 5/16 ET ( 31% pregnancy rate) 6 healthy babies born Devroey et al Human Reprod 1996
Consecutive sperm retrievals in non -obstructive azoospermia Germ cell aplasia Maturation arrest Rank Recovery rate 1 140/362 (39%) 81/163 (50%) 2 45/58 (78%) 21/30 (70%) 3 15/18 (83%) 8/9 (89%) 4 7/7 (100%) 3/3 (100%) Vernaeve HR 2006
TESE - microdissection improves sperm yield with minimal tissue excision • TESE is a blind procedure not identifying the focal sperm producing area • Microdissection identifies sperm containing regions before their removal by direct identifying seminiferous tubules Schlegel HR 1999
Microsurgical and conventional TESE (patients n = 100) Sibling testes Recovery rate (%) Haematoma on ultrasound (n: 60) at 3 months (%) at 6 months (%) Fibrosis at 3 months (%) at 6 months (%) Microdissection Conventional P 47 30 0. 05 7 0 52 10 0. 05 0 3 2 5 0. 05 Amer HR 2000
Simple and reliable identification of the human round spermatid by phasecontrast microscopy • Only a Nikon inverted microscopy equipped with phase-contrast optics provide a clear image which allows clear recognition of testicular cells • Patients with non-obstructive azoospermia did always reveal the presence of elongated spermatozoa and round spermatids Verheyen HR 1998
Round spermatid injection • Patients (n) • COC (n) 58 1044 • 2 PN fertilization rate • Cleaved embryos 22 (20%) 144 • Blastocyst formation 11 (8%) • None of the patients conceived zero Urman HR 2002
Pubmed Search • Key words: ICSI Klinefelter • 14 -06 -2012 • 85 publications (n) • 15 -10 -2012 • 87 publications(n) The End…
• Syndrome characterized by gynaecomastia, aspermatogenesis without A-leydigism and increased excretion of follicle stimulating hormone Klinefelter JCEM 1942 • Related to 47 XXY karyotype Jacobs Nature 1959 • Incidence is 0. 1% Nielsen HG 1991
ICSI in non mosaic Klinefelter • Authors (n = 12) – PGD 2 – No PGD 10 • Healthy children born (n = 34) • One pregnancy interruption for 47 XXY • Advice: ICSI + PGD or prenatal diagnosis Staessen HR 2003
Clinical pregnancy rate in Klinefelter syndrome FSH (U/L) (mean) TESE (n) Pregnancy Levron (FS 2000) 26 8/20 (40%) 4/20 (20%) Friedler (HR 2001) 38 5/12 (42%) 4/12 (33%) Schiff (JCNM 2005) 33 39/54 (72%) 22/54 (40%) 32. 3 52/86 (60%) 30/86 (35%) Total
TESE-ICSI in patients with Klinefelter syndrome • • Klinefelter syndrome (n=39) Pregnancy rate: 39% Implantation rate: 23% Embryonic genetics: 60% normal karyotypes ( 42/71 embryos ) Yarali et al RBMO 2009
Attitude of Klinefelter men towards TESE-ICSI • Questionnaires (n=260) • 90% positive responses Maiburg et al JARG 2011
Pubmed Search 15 -10 -2012 • Keywords: ICSI frozen testicular sperm • 187 publications (n)
Pregnancies after intracytoplasmic sperm injection with cryopreserved testicular spermatozoa • • 25 patients (n) Cryopreserved TESE in 18 cases Fertilization rate 59% 6 pregnancies (n) Gil-Salom et al Hum Reprod 1996
ICSI using cryopreserved sperm from men with malignant neoplasm yields high pregnancy rates • • • Retrospective consecutive study 118 Couples (n) 169 ICSI cycles (n) Clinical pregnancy rate 59% 96 pregnancies were achieved 126 children were born Hourvitz et al Fertil Steril 2008
Pregnancies and deliveries after injection of vitrified warmed oocytes with cryopreserved testicular sperm • • Vitrified warmed oocytes Thawed warmed testicular spermatozoa 11 patients (n) 4 clinical pregnancies (n) Selman et al Fertil Steril 2010
Birth of healthy boy after cryopreserved oocytes with cryopreserved testicular sperm from a man with Klinefelter syndrome • Injection of 3 oocytes • One embryo replaced • Birth of healthy boy Greco FS 2008
Obstructive azoospermia • • Absence of the vas deference Carrier of cystic fibrosis If partner is carrier PGD
Cumulative delivery rates after intracytoplasmic sperm injection • • • Life-table analysis - < 37 years of age Patients n=498 July 1992 -December 1993 298 deliveries (60%) Average number of cycles: 3. 15 (CI 2. 88, 3. 43) Osmanagaoglu et al HR 1999
Reproductive potential of a metaphase II oocyte retrieved after ovarian stimulation: an analysis of 23 354 ICSI cycles • Assessment of reproductive efficiency of the oocyte • 207 267 oocytes were retrieved • Oocyte utilization rate • In women ≤ 37 years of age : • In women 38 -42 years of age : rate • In women ≥ 43 years of age : 4. 47 % live birth rate 3. 8 % live birth (0. 78% p < 0. 001) live birth rate Stoop et al Human Reprod 2012
ICSI • Beginning or the end? • ICSI by handling gametes induces fertilization • Embryo formation • • • Extinction in the culture medium Extinction in the uterus Extinction during the ectopic Extinction at birth Extinction at 1 at 5 at 20 at 30 at 60 at 80 years …
Conclusion • In the Beginning • • ICSI – TESE Cryopreservation of sperm - testicular sperm Vitrification of eggs and embryos PGD • No end • new science (PUBMED) … • In the End • embryo – culture - uterus - at birth - at any age -… Aknowledgements to Melissa Defreyne
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