invitro fertilisation

1. HISTORIC PERSPECTIVE OF
IVF

2. OUTLINE
• Introduction
• Historical Background
• 1800
• 1900
• 2000
• Conclusion

3. Introduction
• Infertility is a problem across virtually all cultures and affects an estimated
10-15% of couples.
• IVF and embryo transfer for the treatment of human infertility has now
resulted in the birth of over 5 million babies.
• The technique did not arise as a quantum event but was built on the efforts
of many earlier workers in the field of reproductive endocrinology
• One should remember the famous saying of Isaac Newton: ‘If I have seen
further than most, it is because I have stood on the shoulder’s of giants’

4. Introduction -2
• The early attribution of infertility to women persisted for
centuries and was often considered a divine punishment
• The only solution to infertility was prayer – to Egyptian Isis,
Phoenician Astarte, Greek Aphrodite, or Roman Venus
• First written documentation on infertility may be found in the
Kahoun papyrus (oldest Egyptian medical text), dated to 2200-
1950 BC

5. Introduction-3
• Ethical and moral issues have
always arisen when investigators
study early human development
• Test tube/ Petri dish baby

6. HISTORICAL PERSPECTIVE
The 1800’s
• Fertility treatment mostly consisted of gynecological surgery at that
time.
• Dr. Sims at the Women’s Hospital in New York performed a fresh
intrauterine insemination from the husband’s sperm.
• This resulted in a pregnancy that ended in miscarriage.

7. The 1800’s- contd
• In 1884 Dr. William Pancoast in
Philadelphia performed the first
donor insemination using sperm
from the medical student voted
“best looking” in his class.
• It was anonymous, and both the
husband and wife were not even
informed that a donor was being
used until years later.
• Luckily, the husband was elated
when informed later

8. Early 1900’s
• Early 1900’s much research was done on hormones and how they related to
fertility.
• The first successful attempts to culture preimplantation mammalian
embryos were made in 1913 by Albert Brachet, Director of the Brussels
School of Embryology at the Warocqué Institute of Anatomy
• In 1926 first infertility clinic opened in Massachusetts.
• In 1934 Gregory Pincus performed IVF-like research on rabbits but was
fired from Harvard due to his controversial research.
• In Sydney, 1951, it was discovered that freshly ejaculated spermatozoa
could not immediately fertilize an egg since they require a period of so-
called maturation in the female genital tract.
• The word ‘capacitation’ was coined to denote the phenomenon in 1952

9. 1961
• Palmer from France described
the first retrieval of oocytes by
laparoscopy.

10. 1965
• In 1965, Robert Edwards
together with Georgiana and
Howard Jones at Johns Hopkins
Hospital in the USA attempted to
fertilize human oocytes in vitro

11. Robert Edwards’ contributions
• Edwards and his colleagues published the following key papers that paved
the way for the birth of the first ‘test-tube’ baby:
• Maturation in vitro of human ovarian oocytes’ in The Lancet (Edwards,
1965b).
• (2)‘Early stages of fertilization in vitro of human oocytes matured in vitro’
in Nature (Edwards et al., 1969).
• (3)‘Fertilization and cleavage in vitro of preovular human oocytes’
in Nature (Edwards et al., 1970).
• (4)‘Laparoscopic recovery of preovulatory human oocytes after priming of
ovaries with gonadotrophins’ in The Lancet (Steptoe and Edwards, 1970).

12. 1972
Surgery took place in a hospital in Brooklyn at 8am.
Dr. William Sweeney retrieved five eggs from a female.
The woman’s husband took the eggs in a taxi five miles across town to give
them to Dr. Shettles at Columbia-Presbyterian Hospital.
The husband then went into a collection room and produced a fresh
ejaculate to be used to fertilize the eggs. By 2 p.m.
The hospital chairman learned about the experiment and forbid the embryos
to be transferred back to the mother.
The husband was informed at 4 p.m. that evening and the wife was informed
by 9 p.m. while she was still recovering from surgery.
This would have been the first case of IVF with embryo transfer but it was
stopped prematurely.

13. 1973
• The first IVF pregnancy was
reported by the Monash
research team of Professors Carl
Wood and John Leeton in
Melbourne, Australia.
Unfortunately, this resulted in
early miscarriage

14. 1975
• Steptoe and Edwards published
a report on an ectopic
pregnancy following transfer of a
human embryo at the late
morulae /early blastocyst stage.

15. 1976
• Y. Menezo developed the world's
first B2 culture medium, known
as ‘the French medium

16. 1978
• By 1978, the first successful live birth from IVF was announced by Drs
Edwards and Steptoe in England. Lesley Brown gave birth to her
daughter, Louise Joy Brown.
• Lopata in Melboure described the first cycles stimulated with
clomiphene citrate
• Pregnancy following intrauterine implantation of an embryo obtained
by in vitro fertilization of a preovulatory egg

17. Image -1
1st IVF baby Lesley brown- mother of 1st IVF baby

18. Image - 2
Professor Sir Robert Edwards Patrick Steptoe

19. Second Baby
• In October 1978, it was reported that Subash Mukhopadyay, a
relatively unknown physician from Kolkata, India was performing
experiments and this resulted in a test tube baby, - "Durga" (alias
Kanupriya Agarwal) who was born on 3 October 1978.
• However, state authorities prevented him from presenting his work at
scientific conferences and, in the absence of scientific evidence, his
work is not recognised by the international scientific community.

20. 1979-1980
• Steptoe and Edwards were responsible for the world’s first confirmed
boy conceived by IVF, Alastair MacDonald born on 14 January 1979
in Glasgow.
• Pez et al, began tracking the growth of follicles by ultrasound.
• The first published use of ultrasound to identify growing follicles.
• A team led by Ian Johnston and Alex Lopata were responsible for
Australia's first baby conceived by IVF, Candice Reed, born on 23
June 1980 in Melbourne
• The introduction of culture medium

21. 1981
• The U.S. announced the birth of IVF baby Elizabeth Carr in 1981.
• This first IVF birth in the USA was achieved with the use of hMG.
• Wood and his colleague introduced a foot-controlled fixed aspiration
pressure control, Technique for collecting mature human oocytes for
IVF.
• Introduction of Clomiphene Citrate and hMG in the IVF treatment
protocol
• The Clamart group in France developed an LH assay (LH-SIR0 which
could detect the initial LH rise in plasma allowing accurate prediction
of the ideal time for the retrieval of oocytes.

22. 1982
• The first French IVF birth
occurred in Clamart, France by
the group of Frydman and
Testart.

23. 1982- contd
• The first IVF birth in Sweden by
Hamberger L et al.
• Birth of first Austrian "Test tube
baby" (Twin pregnancy)
• The first demonstration that GnRH
agonists can be used to eliminate
premature luteinisation and control
ovarian stimulation by Fleming et
al.
• The first report of the need for a
delay between oocyte collection
and insemination to allow oocytes
collected to complete maturation.
• Susan Lenz and Jurgen G Lauritsen
demonstrated trans abdominal
transvesical oocyte aspiration using
an ultrasound-guided needle.
• Ian Craft in London reported a
pregnancy from transfer of gametes
to the uterus

24. 1982 contd
• Bourn Hall worlds first IVF
Conference
• Front row, from left to right: Bob
Edwards, Jean Purdy, Patrick
Steptoe, John Webster and
Simon Fishel

25. 1983
• Donor egg: The Monash IVF team achieved the first pregnancy in a woman without
ovaries by using donor eggs.
• Monash IVF team reported on the birth of the first frozen embryo baby.
• First pregnancy after oocyte donation
• First successful delivery following egg donation
• Casper and his colleagues were the first to described the use of low dose hCG for
support of the luteal phase in ART cycles.
• Gleicher and his group reported the first vaginal egg retrieval using an abdominal
ultrasound
• First report on the Canadian IVF baby by the group of Victor Gomel at the University of
British Columbia
• World's first IVF triplets reported by Christopher Chen.
• The first report on human pregnancy following cryopreservation, thawing and transfer
of an eight-cell embryo

26. 1984
• The Government of Victoria established a review of IVF research and
practice which led to the proclamation of the Infertility (Medical
Procedures) Act 1984, the first legislation to regulate IVF and its
associated human embryo research.
• First surrogacy embryo transfer baby born in California
• First report on pregnancy following trans laparoscopic GIFT
procedure
• The world's first IVF quadruplets were born on January 6, 1984, in
Melbourne.

27. 1985 and 1986
• Human pregnancy by in vitro fertilization (IVF) using sperm aspirated
from the epididymis
• First Delivery Resulting From Gestational Surrogacy.
• Monash IVF report on the world’s first pregnancy and birth from the
sperm retrieval operation performed on a patient who had a blocked
sperm duct
• First report on pregnancy after translaparoscopic zygote intrafallopian
transfer
• Delivery of twins from frozen human eggs

28. 1987-1990
• Fertilization of human oocytes by microinjection of a single sperm
under the zona pellucida
• First two babies born after epididymal sperm aspiration for men with
congenital absence of the vas deferens and naming of the technique
MESA
• The death of Dr. Patrick Steptoe -March 21 1988
• First report on biopsy of human preimplantation embryos and sexing
by DNA amplification
• The first report on polar body biopsy, transfer of the embryo and
achieving pregnancy

29. moment Louise Brown, the worlds first IVF baby, met Elizabeth
Carr, the first IVF baby born in the USA

30. 1990s- The following advancements were made:
• Fertility Drugs were improved.
• IVF egg retrievals began to be performed vaginally instead of by laparoscopy.
• Intracytoplasmic sperm injection (ICSI) allowed men with low sperm to become fathers
by 1991.
• Embryo transfers slowly moved from day 1 to day 3 and are now performed on day 5 by
all outstanding fertility centres, as embryology labs became capable of culturing embryos
safely for longer periods of time.
• “live-cam” 24-hour footage became available to monitor cell division.
• Embryo biopsy techniques evolved to safer and a more accurate prediction of the genetic
makeup of an embryo – attempting to improve pregnancy rates and lower the risk of
multiple gestation and miscarriage.
• Comprehensive Chromosome Screening (CCS) of the whole embryo genome (24
Chromosomes).

31. 2000s
• Cryopreserved oocytes and frozen sperm: first ever birth.
• Ongoing twin pregnancy after ICSI of PESA-retrieved spermatozoa into
in-vitro matured oocytes reported by the McGill group
• First report of fertility preservation for cancer patients using IVM and
oocyte vitrification
• Cryopreserved oocytes in cancer patients: first ever birth of healthy
twins after oocyte cryopreservation and bilateral ovariectomy
• Nobel prize in 2010- Robert G Edwards.

32. conclusion
The field of assisted reproductive technique has progressed at an
astounding pace over the past three decades as we have developed new
techniques, medications, testing, and strategies to treat infertile couples.
Now, many previously sterile couples are able to conceive, carry, and
deliver healthy children of their own.

33. References
• Anand Kumar, T.C. Architect of India’s first test tube baby: Dr Subhas Mukerji (16 January 1931 to 19 July 1981). Curr.
Sci. 1997; 72: 526–531
• Biggers, J.D. In vitro fertilization and embryo transfer in historical perspective. in: A. Trounson, C. Wood (Eds.) In Vitro Fertilization
and Embryo Transfer. Churchill Livingstone, London; 1984: 3–14
• John D. Biggers. IVF and embryo transfer: historical origin and development. RBMO August 2012 Volume 25, Issue 2, Pages 118–
127
• Bavister BD. Early history of in vitro fertilization. Reproduction. 2002 Aug;124(2):181-96.
• Perone N. In vitro fertilization and embryo transfer. A historical perspective. J Reprod Med. 1994 Sep;39(9):695-700.
• Sjo¨ gren A, Hillensjo¨ T. Methods for aspiration of human oocytes by various techniques. Acta Med Rom 1982: 20,370 – 378).
• Kretzer D, Dennis P, Hudson B, Leeton J, Lopata A, Outch K, Talbot J, Wood C. Transfer of a human zygote. Lancet, 1973 29;2:728-9.
• Trounson AO, Leeton JF, Wood C, Webb J, Wood J. Pregnancies in humans by fertilization in vitro and embryo transfer in the
controlled ovulatory cycle. Science 1981 8;212:681-2
• Testart J, Frydman R, Feinstein MC, Thebault A, Roger M, Scholler R. Interpretation of plasma luteinizing hormone assay for the
collection of mature oocytes from women: definition of a luteinizing hormone surge-initiating rise. Fertil Steril. 1981 Jul;36(1):50-
4).
• Rao GD, Chian RC, Son WS, Gilbert L, Tan SL. Fertility preservation in women undergoing cancer treatment. Lancet.
2004;363(9423):1829-30).