Instruct: Given a question, retrieve documents that answer the question.
Query: When was the first embryo transfer performed?
The first ever pregnancy derived from a frozen human embryo was reported by Alan Trounson & Linda Mohr in 1983 (although the fetus aborted spontaneously at ten weeks of gestation); the first term pregnancy derived from a frozen embryo was born in 1984. Since then and up to 2008 it is estimated that between 350,000 and half a million IVF babies have been born from embryos frozen at a controlled rate and then stored in liquid nitrogen; additionally a few hundred births have been born from vitrified oocytes but firm figures are hard to come by. It may be noted that Subash Mukhopadyay from Kolkata, India reported the successful cryopreservation of an eight cell embryo, storing it for 53 days, thawing and replacing it into the mother’s womb, resulting in a successful and live birth as early as 1978- a full five years before Trounson and Mohr had done so. A small publication of Mukherjee in 1978 clearly shows that Mukherjee was on the right line of thinking much before anyone else had demonstrated the successful outcome of a pregnancy following the transfer of a 8-cell frozen-thawed embryo into human subjects transferring 8-cell cryopreserved embryos." (Current Science, Vol .72. No. 7, 10 April 1997)
In 1996 Dolly the sheep was born, the first mammal to be cloned from an adult cell. The process by which Dolly the sheep was cloned utilized a process known as nuclear transfer applied by lead scientist Ian Wilmut. Although other scientists were not immediately able to replicate the experiment, Wilmut argued that the experiment was indeed repeatable, given a timeframe of over a year.
The online edition of "Nature Medicine" published a study on January 24, 2005, which stated that the human embryonic stem cells available for federally funded research are contaminated with non-human molecules from the culture medium used to grow the cells. It is a common technique to use mouse cells and other animal cells to maintain the pluripotency of actively dividing stem cells. The problem was discovered when non-human sialic acid in the growth medium was found to compromise the potential uses of the embryonic stem cells in humans, according to scientists at the University of California, San Diego.
The discovery of adult stem cells led scientists to develop an interest in the role of embryonic stem cells, and in separate studies in 1981 Gail Martin and Martin Evans derived pluripotent stem cells from the embryos of mice for the first time. This paved the way for Mario Capecchi, Martin Evans, and Oliver Smithies to create the first knockout mouse, ushering in a whole new era of research on human disease. In 1995 adult stem cell research with human use, patented (US PTO with effect from 1995). In fact human use published in World J Surg 1991 & 1999 (B G Matapurkar). Salhan, Sudha (August 2011). Textbook of Gynecology. JP Medical Ltd. pp. 625–. .
Bharadwaj, Aditya; Glasner, Peter E. (2009). Local Cells, Global Science: The Rise of Embryonic Stem Cell Research in India. Taylor & Francis. 
^ "Dr.B.G.Matapurkar gets US patent for surgical procedure for organ regeneration - Patents". www.pharmabiz.com.
^ "Method of organogenesis and tissue regeneration/repair using surgical techniques - US Patent 6227202 Claims". patentstorm.us.
Dolly was born on 5 July 1996 and had three mothers: one provided the egg, another the DNA, and a third carried the cloned embryo to term. She was created using the technique of somatic cell nuclear transfer, where the cell nucleus from an adult cell is transferred into an unfertilized oocyte (developing egg cell) that has had its cell nucleus removed. The hybrid cell is then stimulated to divide by an electric shock, and when it develops into a blastocyst it is implanted in a surrogate mother. Dolly was the first clone produced from a cell taken from an adult mammal. The production of Dolly showed that genes in the nucleus of such a mature differentiated somatic cell are still capable of reverting to an embryonic totipotent state, creating a cell that can then go on to develop into any part of an animal. Dolly's existence was announced to the public on 22 February 1997. It gained much attention in the media. A commercial with Scottish scientists playing with sheep was aired on TV, and a special report in "Time" magazine featured Dolly the sheep. "Science" featured Dolly as the breakthrough of the year. Even though Dolly was not the first animal cloned, she received media attention because she was the first cloned from an adult cell.
In 2007 it was shown that pluripotent stem cells highly similar to embryonic stem cells can be generated by the delivery of three genes ("Oct4", "Sox2", and "Klf4") to differentiated cells. The delivery of these genes "reprograms" differentiated cells into pluripotent stem cells, allowing for the generation of pluripotent stem cells without the embryo. Because ethical concerns regarding embryonic stem cells typically are about their derivation from terminated embryos, it is believed that reprogramming to these "induced pluripotent stem cells" (iPS cells) may be less controversial. Both human and mouse cells can be reprogrammed by this methodology, generating both human pluripotent stem cells and mouse pluripotent stem cells without an embryo.
The discovery of the MHC and role of histocompatibility in transplantation was a combined effort of many scientists in the 20th century. A genetic basis for transplantation rejection was proposed in a 1914 Nature paper by C.C. Little and Ernest Tyyzer, which showed that tumors transplanted between genetically identical mice grew normally, but tumors transplanted between non-identical mice were rejected and failed to grow. The role of the immune system in transplant reject was proposed by Peter Medawar, whose skin graft transplants in world war two victims showed that skin transplants between individuals had much higher rejection rates then self-transplants within an individual, and that suppressing the immune system delayed skin transplant rejection. Medawar shared the 1960 Nobel Prize in part for this work.
The discovery of insulin at the University of Toronto in 1921 is considered among the most significant events in the history of medicine. The stem cell was discovered at the university in 1963, forming the basis for bone marrow transplantation and all subsequent research on adult and embryonic stem cells. This was the first of many findings at Toronto relating to stem cells, including the identification of pancreatic and retinal stem cells. The cancer stem cell was first identified in 1997 by Toronto researchers, who have since found stem cell associations in leukemia, brain tumors and colorectal cancer. Medical inventions developed at Toronto include the glycaemic index, the infant cereal Pablum, the use of protective hypothermia in open heart surgery and the first artificial cardiac pacemaker. The first successful single-lung transplant was performed at Toronto in 1981, followed by the first nerve transplant in 1988, and the first double-lung transplant in 1989. Researchers identified the maturation promoting factor that regulates cell division, and discovered the T-cell receptor, which triggers responses of the immune system. The university is credited with isolating the genes that cause Fanconi anemia, cystic fibrosis and early-onset Alzheimer's disease, among numerous other diseases. Between 1914 and 1972, the university operated the Connaught Medical Research Laboratories, now part of the pharmaceutical corporation Sanofi-Aventis. Among the research conducted at the laboratory was the development of gel electrophoresis.
As early in the history of biotechnology as 1990, there have been scientists opposed to attempts to modify the human germline using these new tools, and such concerns have continued as technology progressed. With the advent of new techniques like CRISPR, in March 2015 a group of scientists urged a worldwide moratorium on clinical use of gene editing technologies to edit the human genome in a way that can be inherited. In April 2015, researchers sparked controversy when they reported results of basic research to edit the DNA of non-viable human embryos using CRISPR. A committee of the American National Academy of Sciences and National Academy of Medicine gave qualified support to human genome editing in 2017 once answers have been found to safety and efficiency problems "but only for serious conditions under stringent oversight."
Since the late nineteenth century, breast implants have been used to surgically augment the size (volume), modify the shape (contour), and enhance the feel (tact) of a woman's breasts. In 1895, surgeon Vincenz Czerny effected the earliest breast implant emplacement when he used the patient's autologous adipose tissue, harvested from a benign lumbar lipoma, to repair the asymmetry of the breast from which he had removed a tumor. In 1889, surgeon Robert Gersuny experimented with paraffin injections, with disastrous results.
There is widespread controversy over the use of human embryonic stem cells. This controversy primarily targets the techniques used to derive new embryonic stem cell lines, which often requires the destruction of the blastocyst. Opposition to the use of human embryonic stem cells in research is often based on philosophical, moral, or religious objections. There is other stem cell research that does not involve the destruction of a human embryo, and such research involves adult stem cells, amniotic stem cells, and induced pluripotent stem cells.
Dolly (5 July 1996 – 14 February 2003) was a female domestic sheep, and the first mammal cloned from an adult somatic cell, using the process of nuclear transfer.
In the United Kingdom, the Warnock Committee was formed in July 1982 to consider issues of sperm donation and assisted reproduction techniques. Donor insemination was already available in the UK through unregulated clinics such as BPAS. Many of these clinics had started to offer sperm donation before the widespread use of freezing techniques. 'Fresh sperm' was donated to order by donors at the fertile times of patients requiring treatments. Commonly, infertility of a male partner or sterilisation was a reason for treatment. Donations were anonymous and unregulated.
On July 24, 2009, the first publication of a successful breakthrough in Stem cell research was released, where Chinese researchers from the Shanghai Stem Cell Institute, led by Professor Fanyi Zeng, successfully reprogrammed adult stem cells to be able to differentiate into any body cell, as in the case with standard embryonic stem cells, the cells in question known as "induced pluripotent stem cells" (IPS cells). The IPS cells were obtained by genetically reprogramming the skin cells of mice to acts like embryonic stem cells, which then were able to differentiate into all forms of body tissue. The researchers have managed to use the IPS cells to create every type of cell in a mouse, creating entire mouse pups using the technique. This is the first time the technique has been used to make an entire mouse.
The modern prosthetic breast was invented in 1961, by the American plastic surgeons Thomas Cronin and Frank Gerow, and manufactured by the Dow Corning Corporation; in due course, the first augmentation mammoplasty was performed in 1962. There are five generations of medical device technology for the breast-implant models filled with silicone gel; each generation of breast prosthesis is defined by common model-manufacturing techniques.
The first practical use of blood typing in transfusion was by an American physician Reuben Ottenberg in 1907. And the large-scale application started during the First World War (1914-1915) when citric acid was developed as blood clot prevention. Felix Bernstein demonstrated the correct blood group inheritance pattern of multiple alleles at one locus in 1924. Watkins and Morgan, in England, discovered that the ABO epitopes were conferred by sugars, to be specific, N-acetylgalactosamine for the A-type and galactose for the B-type. After much published literature claiming that the ABH substances were all attached to glycosphingolipids, Finne "et al". (1978) found that the human erythrocyte glycoproteins contain polylactosamine chains that contains ABH substances attached and represent the majority of the antigens. The main glycoproteins carrying the ABH antigens were identified to be the Band 3 and Band 4.5 proteins and glycophorin. Later, Yamamoto's group showed the precise glycosyl transferase set that confers the A, B and O epitopes.
Gene therapy is the use of DNA as a pharmaceutical agent to treat disease. Gene therapy was first conceptualized in 1972, with the authors urging caution before commencing gene therapy studies in humans. The first FDA-approved gene therapy experiment in the United States occurred in 1990, on a four-year-old girl named, Ashanti DeSilva, she was treated for ADA-SCID. This is a disease that had left her defenseless against infections spreading throughout her body. Dr. W French Anderson was a major lead on this clinical trial, he worked for the National Heart, Lung, and Blood Institute Since then, over 1,700 clinical trials have been conducted using a number of techniques for gene therapy.
Hescheler has been working with embryonic stem cells ever since the late 1980s. Beginning with studies on cellular signal transduction, and starting with works on signalling pathways in different cells (g-protein phosphorylation, electrophysiology of channels) he focussed on embryonic stem cells and has since defined many important basic aspects of both fundamental research and clinical applications. He was the first scientist worldwide to perform electrophysiological and functional experiments on stem cells and differentiated phenotypes thereof. He achieved a first functional characterization of cardiomyocytes developed from embryonic stem cells which is an important prerequisite for their subsequent use in regenerative medicine. He thus pioneered the establishment of stem cell research for application in transplantation medicine. In 2002, he was among the first scientists in Germany to obtain permission to work with human embryonic stem cells. In his current position, as Chairman and Director to the Institute for Neurophysiology at the University of Cologne, his research areas include work on embryonic and adult stem cells, induced pluripotent stem cells, mesenchymal stem cells and germline pluripotent stem cells. Among progressing the use of stem cells for translational purposes, aiming at tapping the potential of stem cell biology towards clinical application, Hescheler actively promotes the vision of EPAA through innovative alternative testing strategies, applying stem cells towards toxicity testing. Apart from the rationale of promoting 3R principles it is his goal that coordinating a multidisciplinary research effort undertaken by various projects and consortia led by Hescheler will generate pathway- and evidence-based understanding of long-term toxic effects, thus moving toxicology from a rather descriptive science towards a more mechanistic-driven predictive one. 
Hescheler has been appointed coordinator of various European Consortia such as FunGenES, CRYSTAL, and more recently ESNATS and DETECTIVE. He is also coordinator of the BMBF consortium “iPS and adult bone marrow cells for cardiac repair”. In 2004 he founded and since chaired the German Society of Stem Cell Research (GSZ). He is an active member of the Scientific Panel of the AXLR8 Consortium and a member of steering committee of Stem Cell Network North Rhine Westphalia.
Cell, developmental, and reproductive biology have been a central part of the MBL's programs since the 1890s. Important discoveries in these fields at the MBL reach back to 1899, when Jacques Loeb demonstrated artificial parthenogenesis in sea urchin eggs; to 1905, when Edwin Grant Conklin first identified egg cytoplasmic regions that are programmed to form certain tissues or organs; to 1916, when Frank Rattray Lillie identified circulating hormones that influence sexual differentiation (Lillie, 1944). In the MBL's first two decades, cytologists Edmund Beecher Wilson, Nettie Stevens and others made connections between the chromosomes and Mendelian heredity, while Wilson's colleague at both the MBL and Columbia University, Thomas Hunt Morgan, launched the field of experimental genetics (Pauly, 2000:158). Keith R. Porter, considered by many to be a founder of modern cell biology due to his pioneering work on the fine structure of cells, including the discovery of microtubules, carried out research at the MBL starting in 1937 and directed the laboratory from 1975-77 (Barlow et al., 1993: 95-115).
Nowadays, there are several treatments (still in experimentation) related with stem cell therapy. It is a new opportunity, not only for partners with lack of gamets, but also for homosexuals and single people who wants to have offspring. Theoretically, with this therapy, we can get artificial gamets "in vitro". There are different studies, for both women and men.Stem cell therapy is really new, and everything is still under investigation. However, it could be the future for the treatment of multiple diseases, including infertility. It will take time until these studies can be available for clinics and patients as a regularity.
Later artificial cells have ranged from hundred-micrometer to nanometer dimensions and can carry microorganisms, vaccines, genes, drugs, hormones and peptides. The first clinical use of artificial cells was in hemoperfusion by the encapsulation of activated charcoal.
Embryo rescue was first documented in the 18th century when Charles Bonnet excised "Phaseolus" and "Fagopyrum" embryos and was successful in it , planted them in soil and the cross resulted in dwarf plants. Soon after this, scientists began placing the embryos in various nutrient media. During the period of 1890 to 1904, systems for embryo rescue became systematic by applying nutrient solutions that contained salts and sugars and applying aseptic technique. The first successful "in vitro" embryo culture was performed by Hanning in 1904, he however described problems with precocious embryos that resulted in small, weak, and often inviable plantlets.Depending on the organ cultured, it may be referred to as either embryo, ovule, or ovary culture. Ovule culture or in ovolo embryo culture is a modified technique of embryo rescue whereby embryos are cultured while still inside their ovules to prevent damaging them during the excision process. Ovary or pod culture, on the other hand employs the use of an entire ovary into culture. It becomes necessary to excise the entire small embryo to prevent early embryo abortion. However, it is technically difficult to isolate the tiny intact embryos, so often ovaries with young embryos, or entire fertilized ovules will be used.
Laboratories have developed grading methods to judge oocyte and embryo quality. In order to optimise pregnancy rates, there is significant evidence that a morphological scoring system is the best strategy for the selection of embryos. Since 2009 where the first time-lapse microscopy system for IVF was approved for clinical use, morphokinetic scoring systems has shown to improve to pregnancy rates further. However, when all different types of time-lapse embryo imaging devices, with or without morphokinetic scoring systems, are compared against conventional embryo assessment for IVF, there is insufficient evidence of a difference in live-birth, pregnancy, stillbirth or miscarriage to choose between them. A small prospectively randomized study in 2016 reported poorer embryo quality and more staff time in an automated time-lapse embryo imaging device compared to conventional embryology.
The development of various methods of cryopreservation of bovine embryos improved embryo transfer technique considerably efficient technology, no longer depending on the immediate readiness of suitable recipients. Pregnancy rates are just slightly less than those achieved with fresh embryos. Recently, the use of cryoprotectants such as ethylene glycol has permitted the direct transfer of bovine embryos. The world's first live crossbred bovine calf produced under tropical conditions by Direct Transfer (DT) of embryo frozen in ethylene glycol freeze media was born on 23 June 1996. Dr. Binoy Sebastian Vettical of Kerala Livestock Development Board Ltd has produced the embryo stored frozen in Ethylene Glycol freeze media by slow programmable freezing (SPF) technique and transferred directly to recipient cattle immediately after thawing the frozen straw in water for the birth of this calf. In a study, in vivo produced crossbred bovine embryos stored frozen in ethylene glycol freeze media were transferred directly to recipients under tropical conditions and achieved a pregnancy rate of 50 percent. In a survey of the North American embryo transfer industry, embryo transfer success rates from direct transfer of embryos were as good as to those achieved with glycerol. Moreover, in 2011, more than 95% of frozen-thawed embryos were transferred by Direct Transfer.
The first attempt to edit the human germline was reported in 2015, when a group of Chinese scientists used the gene editing technique CRISPR/Cas9 to edit single-celled, non-viable embryos to see the effectiveness of this technique. This attempt was rather unsuccessful; only a small fraction of the embryos successfully spliced the new genetic material and many of the embryos contained a large amount of random mutations. The non-viable embryos that were used contained an extra set of chromosomes, which may have been problematic. In 2016, another similar study was performed in China which also used non-viable embryos with extra sets of chromosomes. This study showed very similar results to the first; there were successful integrations of the desired gene, yet the majority of the attempts failed, or produced undesirable mutations.