The Really First Step SARG –Tel Aviv May 2018
Simon Fishel CARE Fertility Group Ex Ovo Omnia: It all started here…1890
27th April, 1890, Walter Heape transferred rabbit embryos from one mother to another
Why did he undertake this study? “The success of this experiment inclines me to believe a new field of enquiry is opened to students of heredity” Is 1st Oocyte maturation division essential to fertilization?
1935
Normal Fertilization can be secured with eggs removed from follicles! Patrick Steptoe Human: Bob Jean The periodJohn for human oocyteSimon Edwards Purdy Webster Fishel maturation was 12 hours! The very first IVF in humans? ‐ 1944
Bob Jean Patrick John Simon Edwards Purdy Steptoe Webster Fishel
1. Rock, J. and M. Menkin, In vitro fertilization and cleavage of human ovarian eggs, Science, 1944. 100: p. 105–107. 2. Menkin M. and Rock, J. American Journal of Obstetrics and Gynecology Volume 55, Issue 3, 1948, Pages 440-452 11 years later: 1955
Bob Jean Patrick John Simon Edwards Purdy Steptoe Webster72 hours post Fishel insemination 1960 (25 years post Pincus&Enzman):Enter Robert Edwards
• Bob Edwards begins his passion and quest for understanding the ripening of human oocytes
Bob Jean Patrick John Simon Edwards Purdy Steptoe Webster Fishel 1950 –Trinity College Cambridge – Recent PhD student (Edinburgh) 1965 ‐ Pivotal Paper
Edwards R.G. (1965) Maturation in vitro of human ovarian oocytes. Lancet 286:926‐9
Earlier studies (Pincus & Enzmann, and Shetles) “almost certainly erroneous” Findings: • no clear evidence of oocyte maturation and the events 1. germinal vesicle associated with what we understand breakdown (GVBD) up to about fertilization and early 24h; cleavage. 2. diakinesis duration, 25-28h; • Without a record of such events 3. metaphase 1, 36-43h; Edwards stated that there was 4. metaphase 2 and polar always the risk it was body release, 36-43h parthenogenetic activation and Bob Jean Patrick cleavage. John Simon Edwards Purdy Steptoe Webster Fishel Next – Fertilization! 1960‐1969
1965 1968 Edwards travels to USA to work with Howard and Georgiana Jones to get oocytes for fertilising
Edwards and Steptoe meet at a Royal Society of Medicine meeting London, => small research programme at Bob Jean Patrick John Simon Oldham General Hospital Edwards Purdy Steptoe Webster Fishel Eureka! ‐1969 –
Edwards, Bavister, Steptoe Early stages of fertilization in vitro of human oocytes matured in vitro. Nature 221: 632–5.
Edwards and Steptoe announcing fertilisation Bob Barry Bavister as Edward’s PhD Student Edwards Jean Patrick John Simon Purdyno longer necessarySteptoe to recoverWebster sperm Fishel from a patient’s Fallopian tube/reproductive tract! Oldham in Earnest! (1969‐1971 Repeating OM&IVF)
Bob Edwards Jean Patrick John Simon Dr Kershaw’s ‘cottage hospital’ Purdy Steptoe Webster Fishel 1971 First Clinical IVF Begins……
1971‐1975
• Clomid + HCG • Clomid + Pergonal + HCG 150 Cycles –No Success
decried IVF - 1975 1974 US Congressional Hearing demonizing terminology
1976‐1977
• ClomidBob + HCG Jean Patrick John180 Cycles – No Success! • ClomidEdwards + Pergonal +Purdy HCG WebsterSteptoe • + Bromocryptine 1977: Back to Nature: ‘watching the spontaneous cycle’
• 10th November 1977 • Lesley Brown underwent LOR • 26h after the LH surge was detected in her urine. • The left ovary contained a single follicle “~30mm”
Mochida Pharmaceuticals haemagglutination assay kit. ErythrocytesBob sensitizedJean against anti-hCGPatrick John antibodyEdwards Purdy Steptoe Webster Embryo Transfer at 8‐Cell midnight on the 12th November 1977 July 25th 1978 (23:47) ‐ First Successful Delivery!
Bob Jean Patrick Simon Edwards Purdy Steptoe Fishel
Natural Cycle! End of the Beginning ….. Beginning of the Battles!
A second live birth for the team, Allastair MacDonald, was delivered 14 January 1979 in Stobill Hospital, Glasgow.
• January 9th 1971 -August 1st 1978
• 250 patients (0.8%/Patient) • 457 cycles (0.44%/CS) • 112 embryo transfers (1.8%/ET)
September 1978 Steptoe Retires from the NHS ‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐ A new place to continue was needed Jean Purdy Bob Patrick Simon Edwards Steptoe Fishel The Strange Case of the Del Zios…(1973)
• Columbia Presbyterian Hospital, NYC Landrum B Shettles 1909‐2003 • September 12, 1973, Shettles creates an embryo after IVF for the Del Zio couple • Belgium Dr Vande Wiele, ordered Shettles to dispose of the test tube and its contents! • Shettles resigns a month later • Drs persuade Del Zio coupe to sue hospital
• Trial in July 1978 (Del Zio v. Columbia Presbyterian Hospital, U.S. Dist. Lexis 14550 (1978)). • Louise Brown, was born on the seventh day of the trial! Bob Jean Patrick• Judge: JohnColumbia, and Columbia-Simon Edwards Purdy SteptoePresbyterianWebster “had behavedFishel utterly intolerable in a civilized community”. • The jury had awarded $50,000 damages for Doris Del Zio, and $3 to John Del Zio! The Tragic Case of Dr Subhas Mukerji
Pergonal/HCG Colposcopy (gynecologist Dr. Saroj Bob Patrick Kanti Bhattacharya) John Simon Edwards Steptoe Freezing and FET! Webster Fishel Dr Subhas Mukerji
• October 3rd, 1978 • 67 Days after Louise Brown • Kanupriya Agarwal (Knickname ‘Durga’) • Dr Mukerji Ostricised by Indian Scientific Community • 2008 Recognised as world’s 2nd IVF baby
19th June 1981 Suicide! Bob Patrick John Simon Edwards Steptoe Webster Fishel The 2‐Year Wait ‐ and Uncertain Future!
Bourn Hall 1980
Natural Cycle Best Bob Jean Patrick John Simon …..ANDEdwards ALL THEPurdy MYTHS! Steptoe NightWebster‐time TransfersFishel ET in Knee Chest Position! The Original Team
Bob Jean Patrick John Simon Edwards Purdy Steptoe Webster Fishel World First IVF Meeting – 1981: So Much to Learn!
Best Culture Media Sperm Preparation Embryo Development Stimulation Follicular Progesterone Luteal Phase Supplementation
Transfer techniques Nos of embs transferred Timing of ovulation Dealing with the LH surge Bob Jean Patrick Early Pregnancy detection John Simon Edwards Purdy Steptoe Types of infertility Webster Fishel Genetics Ethics ……………….. 1980 =>
23 June 1980 24 February 1982, Paris Melbourne
John Leeton Alex Lopata Carl Wood Ian Johnson Rene Frydman & Jacques Testart August 1982
Dec 1981 1 9 Howard & Georgeanna Jones 8 Bob Jean Simon 7 Edwards Purdy Fishel
December 28, 1981 Joshua Dor & Shlomo Mashiach Science, Medicine, Ethics, – HOSTILITY: Society & Peers
• “only teratogens will The Times 1983 result” • “unethical” • “No self‐respecting Dr should be involved” • “con‐trick” • “Steptoe and Edwards are worse than a Back Street Abortionist in Bangor”
John Bob Jean Webster Edwards Purdy Pa tri ck St ep MURDER!
1984 REPORTS Human chorionic gonadotropin secreted by preimplantation embryos cultured in vitro 1.SB Fishel, 2.RG Edwards, 3.CJ Evans
Bob Jean Patrick John Simon Edwards Purdy Steptoe Webster Fishel 40 Years on…
Jean Purdy Bob Patrick Simon Edwards Steptoe Fishel Ethics and Regulation
Redefined Family Life!
Jean Purdy Bob Patrick Simon Edwards Steptoe Fishel Ultimate recognition
Bob Jean Patrick John Simon Edwards Purdy Steptoe Webster Fishel Fertility and Sterility –July 2018
Jean Purdy Bob Patrick Simon Edwards Steptoe Fishel CARE FERTILITY GROUP OF CLINICS!
Thank you for listening CARE fertility group
www.carefertility.com Natural cycle and Mild Stimulation: Nothing New!
Patrick > 400Bob Cycles of NaturalJean CycleSteptoe IVF => ClomidJohn => Clomid &Simon Pergonal Edwards Purdy Webster Fishel Jean Purdy Bob Patrick Simon Edwards Steptoe Fishel