The Really First StepSARG – Tel Aviv

May 2018

Simon FishelCARE Fertility Group

Ex Ovo Omnia:  It all started here…1890

27th April, 1890, Walter Heape transferredrabbit 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”

Bob Edwards

Jean Purdy

Patrick Steptoe

John Webster

Simon Fishel

Is 1st Oocyte maturation division essential to fertilization?

Human:

The period for human oocyte

maturation was 12 hours!

Normal Fertilization can be securedwith eggs removed from follicles!

1935

Bob Edwards

Jean Purdy

Patrick Steptoe

John Webster

Simon Fishel

The very first IVF in humans? ‐ 1944

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

Bob Edwards

Jean Purdy

Patrick Steptoe

John Webster

Simon Fishel

11 years later: 1955

72 hours post insemination

Bob Edwards

Jean Purdy

Patrick Steptoe

John Webster

Simon Fishel

1960 (25 years post Pincus&Enzman):Enter Robert Edwards

• Bob Edwards begins his passion and quest for understanding the ripening of human oocytes

1950 – Trinity College Cambridge – Recent PhD student (Edinburgh)

Bob Edwards

Jean Purdy

Patrick Steptoe

John Webster

Simon Fishel

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” • no clear evidence of oocyte

maturation and the events associated with what we understand about fertilization and early cleavage.

• Without a record of such events Edwards stated that there was always the risk it was parthenogenetic activation and cleavage.

1. germinal vesicle breakdown (GVBD) up to 24h;

2. diakinesis duration, 25-28h;3. metaphase 1, 36-43h;4. metaphase 2 and polar

body release, 36-43h

Findings:

Next – Fertilization!

Bob Edwards

Jean Purdy

Patrick Steptoe

John Webster

Simon Fishel

1960‐1969

1965 1968

Edwards and Steptoe meet at a Royal Society of Medicine meeting London, => small research programme at Oldham General Hospital

Edwards travels to USA to work with Howard and Georgiana Jones to get oocytes for fertilising

Bob Edwards Jean 

PurdyPatrick Steptoe

John Webster

Simon Fishel

Eureka!  ‐1969 –

Edwards, Bavister, Steptoe  Early stages of fertilization in vitro of human oocytes matured in vitro. Nature 221: 632–5.

no longer necessary to recover sperm from a patient’s Fallopian tube/reproductive tract!

Barry Bavister as Edward’s PhD Student

Edwards and Steptoe announcing fertilisation

Bob Edwards Jean 

PurdyPatrick Steptoe

John Webster

Simon Fishel

Oldham in Earnest! (1969‐1971 Repeating OM&IVF)

Dr Kershaw’s ‘cottage hospital’

Bob Edwards

Jean Purdy

Patrick Steptoe

John Webster

1971 First Clinical IVF Begins……

• Clomid + HCG• Clomid + Pergonal + HCG 150 Cycles – No Success

1971‐1975

• Clomid + HCG• Clomid + Pergonal + HCG• + Bromocryptine

180 Cycles – No Success!

1976‐1977

19751975decried IVF -1974 USCongressional Hearing demonizing terminology

Bob Edwards

Jean Purdy

Patrick Steptoe

John Webster

1977: Back to Nature: ‘watching the spontaneous cycle’

Mochida Pharmaceuticals haemagglutination assay kit. Erythrocytes sensitized against anti-hCGantibody

• 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”

Embryo Transfer at 8‐Cell midnight on the 12th November 1977

Bob Edwards

Jean Purdy

Patrick Steptoe

Simon Fishel

July 25th 1978 (23:47) ‐ First Successful Delivery! 

Natural Cycle!

Bob Edwards

Jean Purdy

Patrick Steptoe

Simon Fishel

End of the Beginning ….. Beginning of the Battles!

• January 9th 1971 -August 1st 1978

• 250 patients (0.8%/Patient)• 457 cycles (0.44%/CS) • 112 embryo transfers (1.8%/ET)

A second live birth for the team, Allastair MacDonald, was delivered 14 January 1979 in Stobill Hospital, Glasgow.

September 1978 Steptoe Retires from the NHS‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐

A new place to continue was needed

Bob Edwards

Jean Purdy

Patrick Steptoe

John Webster

Simon Fishel

The Strange Case of the Del Zios…(1973)

• Columbia Presbyterian Hospital, NYC• 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!

• Judge: Columbia, and Columbia-Presbyterian “had behaved utterly intolerable in a civilized community”.

• The jury had awarded $50,000 damages for Doris Del Zio, and $3 to John Del Zio!

Landrum B Shettles 1909‐2003

Bob Edwards

Patrick Steptoe

John Webster

Simon Fishel

The Tragic Case of Dr Subhas Mukerji 

Pergonal/HCGColposcopy (gynecologist Dr. Saroj Kanti Bhattacharya) Freezing and FET!

Bob Edwards

Patrick Steptoe

John Webster

Simon 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 Edwards

Jean Purdy

Patrick Steptoe

John Webster

Simon Fishel

The 2‐Year Wait ‐ and Uncertain Future!

Bourn Hall 1980 

…..AND ALL THE MYTHS!Natural Cycle BestNight‐time TransfersET in Knee Chest Position!

Bob Edwards

Jean Purdy

Patrick Steptoe

John Webster

Simon Fishel

The Original Team

Bob Edwards

Jean Purdy

Patrick Steptoe

John Webster

Simon Fishel

World First IVF Meeting – 1981: So Much to Learn!

Best Culture MediaSperm PreparationEmbryo DevelopmentStimulationFollicular ProgesteroneLuteal Phase Supplementation

Transfer techniquesNos of embs transferredTiming of ovulationDealing with the LH surgeEarly Pregnancy detectionTypes of infertilityGeneticsEthics ………………..

Bob Edwards

Jean Purdy

Simon Fishel

1980 => 

John Leeton Alex Lopata Carl Wood Ian JohnsonRene Frydman & Jacques Testart

Howard & Georgeanna Jones

23 June 1980Melbourne 24 February 1982, Paris

December 28, 1981

1987

Joshua Dor & Shlomo Mashiach

August 1982

Dec 1981

Bob Edwards

Jean Purdy

Patrick Step

John Webster

Science, Medicine, Ethics, – HOSTILITY: Society & Peers

The Times 1983• “only teratogens will 

result”• “unethical”• “No self‐respecting Dr 

should be involved”• “con‐trick”• “Steptoe and Edwards 

are worse than a Back Street Abortionist in Bangor”

Bob Edwards

Jean Purdy

Patrick Steptoe

John Webster

Simon Fishel

MURDER!

REPORTSHuman chorionic gonadotropin secreted by preimplantation embryos cultured in vitro1.SB Fishel,2.RG Edwards,3.CJ Evans

1984

Bob Edwards

Jean Purdy

Patrick Steptoe

Simon Fishel

40 Years on…

Bob Edwards

Jean Purdy

Patrick Steptoe

Simon Fishel

Ethics and Regulation

Redefined Family Life!

Bob Edwards

Jean Purdy

Patrick Steptoe

John Webster

Simon Fishel

Ultimate recognition

Bob Edwards

Jean Purdy

Patrick Steptoe

Simon Fishel

Fertility and Sterility – July 2018

CARE fertility group

CARE FERTILITY GROUP OF CLINICS!

www.carefertility.com  

Thank you for listening

Bob Edwards

Jean Purdy

Patrick Steptoe John 

WebsterSimon Fishel

Natural cycle and Mild Stimulation: Nothing New!  

> 400 Cycles of Natural Cycle IVF => Clomid => Clomid & Pergonal

Bob Edwards

Jean Purdy

Patrick Steptoe

Simon Fishel