History and Development of ART Flashcards
Discover the discovery of spermatozoa
Anton Van Leeuwenoek 1677
Father of microbiology, first microbiologist.
First to observe and describe single-celled organism (animalcules)…microorganisms, muscle fibres, bacteria, capillaries and spermatozoa.
Artificial insemination (AI) discovery
John Hunter 1790Appointed as surgeon at St George’s in 1768.
He advised a patient with severe hypospadias to collect the semen which escaped during coitus in a warmed syringe and inject the sample into the vagina. A successful pregnancy resulted.
Hypospadias opening of the urethra develops abnormally, usually on the underside of the penis. Abnormal closure of the urethral fold over the genital groove.
First embryo transfer - in rabbits
Walter Heape Cambridge University 1891Transferred 4 cell embryos from the uterine tubes of Angora rabbits and placed them into the tubes of a recently mated Belgian hare.
2 Angora rabbits (and 4 Belgians) in the resulting litter.
General anaesthetic and the embryos transferred on the point of forceps…they were not transferred to any kind of media.
First to take pre-implantation embryos and transfer them to a gestational carrier without affecting their development.
Discovery for uses of oestrogen and sex steroids
Edward Doisy Harvard Medical School 1929
Extracts from sow ovaries injected into ovarectomized mice, resulted in the production of cornified cells in the vagina – a bioassay. Later isolated estradiol from pig follicular fluid.
Adolf Butenandt University of Göttingen 1929
Isolated estrogen from hundreds of gallons of human pregnancy urine.
Discovery that pituitary produces gonadotrophins
Samuel Crowe 1910
Partial pituitary ablation resulted in gonadal atrophy in dogs and persistence of infantilism in puppies.
Bernard Aschner 1912
Postulated that pituitary function determined by higher centres in the brain (hypothalamus) after observing gonadal atrophy in patients with brain injury.
Sectioned pituitary stalk which resulted in gonadal atrophy and hypothesised that brain/pituitary extracts might affect the gonads.
Identification of FSH and LH
Bernhard Zondek Berlin 1930
Proposed the idea that the pituitary secretes two hormones – Prolan A stimulated follicular growth (FSH) and prolan B stimulated ovulation and formation of the corpus luteum (LH).
He isolated these gonadotrophins from post menopausal blood and urine.
Also isolated hCG from pregnancy urine and injected into mice leading to follicular maturation and ovulation – potential pregnancy test.
Describe the Friedman test- bioassay to test for pregnancy
Maurice Friedman & Maxwell Lapham Pennsylvania 1931
Inject the tested woman’s urine into a female rabbit, then examined the rabbit’s ovaries a few days later… presence of corpus luteum indicated pregnancy.
Hormone responsible is hCG which binds to LH receptors causing luteinisation.
Drawback that the rabbit had to be operated on to examine ovaries.
Later development used the African clawed frog, which responds to hCG by laying eggs and so removing the need for surgery.
Describe the discovery of human IVF
John Rock & Miriam Menkin Harvard 1944
Culmination of 6 years of experiments changing conditions.
Oocytes obtained from patients around 10th day of the menstrual cycle by laparotomy.
Oocytes washed in Locke’s solution and incubated for 27 hours in serum obtained from the egg donor; exposure to a sperm suspension also washed in Locke’s solution for 1 hour.
Transferred to a serum from a post-menopausal patient and observed over the following days where they divided into 2-4 cell embryos. No attempt to transfer the embryos to a recipient.
Describe fertility treatment 1950s-1970s
1st use of hyperstimulation was in mice used crude extracts of PMS, 1950’s
Hypogonadotrophic women treated with crude pituitary extracts & hCG (Gemzel, 1967).
Human menopausal gonadotrophins to treat amenorrhoeic women
(Lunenfeld, 1969).
Anovulatory PCOS patients treated using clomiphene (Kistner, 1972).
Multiple pregnancies. Ovarian Hyperstimulation syndrome (OHSS). Miscarriage. Purity of preparations. CJD...other infectious agents. Virtually no monitoring.
Discovery of laparoscopy in gynaecology
Graduated from St George’s in 1939.
Studied obstetrics and, in 1951 learned the technique of laparoscopy from one of its pioneers Raoul Palmer and promoted its usefulness.
Discovery of fertilisation
Began to study human fertilisation around 1960. Optimised culture media.
Discovered when to collect eggs after hCG trigger using ‘ovulations’ from pieces of ovary and oocyte maturation in vitro, 1965.
In-vitro matured fertilised eggs did not develop, problems with timing egg maturity and sperm capacitation, 1968.
Achieved fertilisation of a human egg in the laboratory 1969.
Next problem was obtaining follicular oocytes from selected patients. To solve this clinical problem, an inspired collaboration was initiated with Patrick Steptoe.
Steptoe and Edwards (measuring urinary oestrogen)
Measured urinary oestrogen in a gonadotrophin stimulated cycle.
Timed collection by laparoscopy IVF and replacement of embryos …..failure 1971.
Decided to give luteal support using Primulot which turned out to be an abortive agent. This wasted 3 years.
Switched to using a natural cycle and achieved 1st pregnancy but it was ectopic, 1977.
List of progress examples in IVF technology
Purer urinary FSH/LH preparations, recombinant gonadotrophins
GnRH agonists/antagonists
Better ultrasound monitoring
Micromanipulation for ICSI, MESA, TESA etc
Cryopreservation of oocytes (vitrification)
Reduction in OHSS less stimulation & GnRH agonist/Kisspeptin triggers
Sequential media for blastocyst culture
Single embryo transfer
Pre-implantation diagnosis or screening
Ovarian tissue cryopreservation
Mitochondrial donation (3 parent family)
In vitro maturation of oocytes
Embryo selection in PGS (pre-implantation genetic screening) and PGD (pre-implantation genetic diagnosis)
Screening of embryos for sex or aneuploidy typically using fluorescence in-situ hybridisation (FiSH).
Count chromosomes and detect chromosomal translocations.
Routine genetic diagnosis from 1 cell of 8 cell embryo, using PCR & DNA microarray chips or DNA sequencing.
Determine whether embryo is homo or heterozygous for a specific point mutation. Identify which alleles for a particular gene the embryo carries.
Describe process of mitochondrial donation
Spindle transfer
Meiotic spindle of donor oocyte removed during MII and replace by patient spindle.
Pronuclear transfer
Pronuclei of fertilised patient egg transferred to fertilised donor egg which has had pronuclei removed.
MST and PNT are cautiously being adopted in clinical practice where inheritance of the disease is likely to cause death or serious disease and where there are no acceptable alternatives.
