Instruct: Given a question, retrieve relevant passages that can help answer the question.
Query: When was the first embryo transfer performed?
Embryo transfer can be done at day two or day three, or later in the blastocyst stage, which was first performed in 1984.[1]
John Edmond Buster (born July 18, 1941) working at the University of California at Los Angeles School of Medicine, directed the research team that performed history's first embryo transfer from one woman to another resulting in a live birth. It was performed at the Harbor-UCLA Medical Center, reported in July 1983, and culminated in the announcement of the first human birth February 3, 1984. In the procedure, an embryo that was just beginning to develop was transferred from the woman in whom it had been conceived by artificial insemination to another woman who gave birth to the infant 38 weeks later. The sperm used in the artificial insemination came from the husband of the woman who bore the baby.
By 2017, many centers have adopted embryo cryopreservation as their primary IVF therapy, and perform few or no fresh embryo transfers. The two main reasons for this have been better endometrial receptivity when embryos are transferred in cycles without exposure to ovarian stimulation and also the ability to store the embryos while awaiting the results of pre-implantation genetic testing.
Female embryos were selectively transferred in five couples at risk of X-linked disease, resulting in two twins and one singleton pregnancy. Because the Y chromosome region Kontogianni was amplifying contained many repeats, it was more efficient than trying to amplify a unique region. A band on the PCR gel indicated that the embryo was male and the absence of a band indicated that the embryo was female. However, amplification failure or an anucleate blastomere also resulted in absence of a band on the PCR gel. To reduce the risk of misdiagnosis, Kontogianni went on to co-amplify sequences on the X and Y (Kontogianni et al., 1991). At that time nothing was known about allele dropout, cumulus cell contamination, or amplification failure from single cells. During the 1980s, human IVF embryos were exclusively transferred on day two of development as the culture medium used was incapable of reliably growing embryos past this stage. Since the biopsy was to be performed on day three, the first diagnoses were all performed in one day, with transfer of the embryos late on day three. A comparison of day two and day three transfers indicated that this would not adversely affect pregnancy rates. The worry of embryos arresting was so high that some transfers took place in the early hours of day four so that the embryos were removed from culture as soon as possible. There were many evenings at the Hammersmith when a transfer was performed at 1 a.m. on day four and researchers returned to the laboratory at 7 a.m. to start the next case. Winston helped deliver most of the first PGD babies.
PGD is a form of genetic diagnosis performed prior to implantation. This implies that the patient’s oocytes should be fertilized "in vitro" and the embryos kept in culture until the diagnosis is established. It is also necessary to perform a biopsy on these embryos in order to obtain material on which to perform the diagnosis. The diagnosis itself can be carried out using several techniques, depending on the nature of the studied condition. Generally, PCR-based methods are used for monogenic disorders and FISH for chromosomal abnormalities and for sexing those cases in which no PCR protocol is available for an X-linked disease. These techniques need to be adapted to be performed on blastomeres and need to be thoroughly tested on single-cell models prior to clinical use. Finally, after embryo replacement, surplus good quality unaffected embryos can be cryopreserved, to be thawed and transferred back in a next cycle.
No one knows for sure when the first true embryo adoption occurred. The term was used as early as the mid-1980s, in the legal literature. Devroey et al., Dr. Maria Bustillo in Florida, and Dr. Howard Jones in Virginia have reported embryo transfers occurring between 1986 and 1990 that clearly represented adoption of remaining embryos.
The first transfer of an embryo from one human to another resulting in pregnancy was reported in July 1983 and subsequently led to the announcement of the first human birth 3 February 1984.[34] This procedure was performed at the Harbor UCLA Medical Center [35] under the direction of Dr. John Buster and the University of California at Los Angeles School of Medicine.
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.[12] Since 2009 where the first time-lapse microscopy system for IVF was approved for clinical use,[13] morphokinetic scoring systems has shown to improve to pregnancy rates further.[14] 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.[15] 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.[16]
The development of various methods of cryopreservation of bovine embryos[41][42] 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.[43] Recently, the use of cryoprotectants such as ethylene glycol has permitted the direct transfer of bovine embryos.[44][45] 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.[46] 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.[47] Moreover, in 2011, more than 95% of frozen-thawed embryos were transferred by Direct Transfer.[48]
The number to be transferred depends on the number available, the age of the woman and other health and diagnostic factors. In countries such as Canada, the UK, Australia and New Zealand, a maximum of two embryos are transferred except in unusual circumstances. In the UK and according to HFEA regulations, a woman over 40 may have up to three embryos transferred, whereas in the US, there is no legal limit on the number of embryos which may be transferred, although medical associations have provided practice guidelines. Most clinics and country regulatory bodies seek to minimise the risk of multiple pregnancy, as it is not uncommon for multiple embryos to implant if multiple embryos are transferred. Embryos are transferred to the patient's uterus through a thin, plastic catheter, which goes through her vagina and cervix. Several embryos may be passed into the uterus to improve chances of implantation and pregnancy.
Embryo transfer is also used in laboratory mice. For example, embryos of genetically modified strains that are difficult to breed or expensive to maintain may be stored frozen, and only thawed and implanted into a pseudopregnant dam when needed.
In the human, the uterine lining (endometrium) needs to be appropriately prepared so that the embryo(s) can implant. In a natural cycle the embryo transfer takes place in the luteal phase at a time where the lining is appropriately undeveloped in relation to the status of the present Luteinizing Hormone. In a stimulated or a cycle where a "frozen" embryo is transferred, the recipient woman could be given first estrogen preparations (about 2 weeks), then a combination of oestrogen and progesterone so that the lining becomes receptive for the embryo. The time of receptivity is the implantation window. A scientific review in 2013 came to the conclusion that it is not possible to identify one method of endometrium preparation in frozen embryo transfer as being more effective than another.[7]
Direct Frozen Embryo Transfer: Embryos can be frozen by SPF in ethylene glycol freeze media and transfer directly to recipients immediately after water thawing without laboratory thawing process. The world's first crossbred bovine embryo transfer calf under tropical conditions was produced by such technique on 23 June 1996 by Dr. Binoy S Vettical of Kerala Livestock Development Board, Mattupatti
The Pacific angelshark is aplacental viviparous with the unborn young nourished by a yolk sac; reproduction occurs on an annual cycle. Most females have a single functional ovary (on the left side), though some have two; the oviducts are often filled with yolk, which has been speculated to be from unfertilized eggs being resorbed. Young embryos long have translucent skin, protruding eyes, and exposed gill filaments. Spots of pigment have developed when the embryo is long, and the first row of teeth have appeared when the embryo is long. By the time the embryo is long, the mouth has migrated to a terminal position and the color pattern has fully developed; the external yolk sac begins to shrink as the yolk is transferred to an internal yolk sac, which holds it until it can be transferred to the intestine for digestion. The internal yolk sac is fully resorbed before birth; if the pup is released prematurely, it does not feed until this process is complete.
For frozen-thawed embryo transfer or transfer of embryo from egg donation, no previous ovarian hyperstimulation is required for the recipient before transfer, which can be performed in spontaneous ovulatory cycles. Still, various protocols exist for frozen-thawed embryo transfers as well, such as protocols with ovarian hyperstimulation, protocols in which the endometrium is artificially prepared by estrogen and/or progesterone. A Cochrane review in 2010 of randomized studies came to the result that there generally is insufficient evidence to support the use of one intervention in preference to another, but with some evidence that in cycles where the endometrium is artificially prepared by estrogen or progesterone, it is beneficial to administer an additional drug that suppresses hormone production by the ovaries such as continuous administration of a gonadotropin releasing hormone agonist (GnRHa).[6][28] For egg donation, there is evidence of a lower pregnancy rate and a higher cycle cancellation rate when the progesterone supplementation in the recipient is commenced prior to oocyte retrieval from the donor, as compared to commenced day of oocyte retrieval or the day after.[6]
A major issue is how many embryos should be transferred. Placement of multiple embryos carries the risk of multiple pregnancy. In the past, physicians have often placed too many embryos in the hope to establish a pregnancy. However, the rise in multiple pregnancies has led to a reassessment of this approach. Professional societies and in many countries, the legislature, have issued guidelines or laws to curtail a practice of placing too many embryos in an attempt to reduce multiple pregnancies.[22] The appropriate number of embryos to be transferred depends on the age of the woman, whether it is the first, second or third full IVF cycle attempt and whether there are top-quality embryos available. According to a guideline from The National Institute for Health and Care Excellence (NICE) in 2013, the number of embryos transferred in a cycle should be chosen as in following table:[23]
Embryo transfer can be performed after various durations of embryo culture, conferring different stages in embryogenesis. The main stages at which embryo transfer is performed are cleavage stage (day 2 to 4 after co-incubation) or the blastocyst stage (day 5 or 6 after co-incubation).[9]
In current state of the art, early embryos having undergone cryopreservation implant at the same rate as equivalent fresh counterparts. The outcome from using cryopreserved embryos has uniformly been positive with no increase in birth defects or development abnormalities, also between fresh versus frozen eggs used for intracytoplasmic sperm injection (ICSI). In fact, pregnancy rates are increased following frozen embryo transfer, and perinatal outcomes are less affected, compared to embryo transfer in the same cycle as ovarian hyperstimulation was performed. The endometrium is believed to not be optimally prepared for implantation following ovarian hyperstimulation, and therefore frozen embryo transfer avails for a separate cycle to focus on optimizing the chances of successful implantation. Children born from vitrified blastocysts have significantly higher birthweight than those born from non-frozen blastocysts. For early cleavage embryos, frozen ones appear to have at least as good obstetric outcome, measured as preterm birth and low birthweight for children born after cryopreservation as compared with children born after fresh cycles.
Uterine sounding may be performed prior to embryo transfer to determine the uterine depth and how easily an embryo transfer catheter can be passed through the cervix. In this case, it may also be called a "trial transfer".
It is performed prior to insertion of an intrauterine device (IUD) in order to measure the length and direction of the cervical canal and uterus. This reduces the risk of perforating the uterus with the IUD. This may occur when the IUD is inserted too deeply or at the wrong angle.
Almost 42,000 'slow frozen' (as opposed to 'vitrified') human embryo transfers were performed during 2001 in Europe (Andersen et al. 2005). In addition, it is estimated that between 300,000 and 500,000 successful human births have resulted worldwide from the transfer of previously ‘slow frozen’ embryos performed from the mid-1970s to 2006.
The duration of embryo culture can be varied, conferring different stages of embryogenesis at embryo transfer. The main stages at which embryo transfer is performed are cleavage stage (day 2 to 4 after co-incubation) or the blastocyst stage (day 5 or 6 after co-incubation).
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.
Some use the term "embryo donation" to refer strictly to anonymous embryo donation, and "embryo adoption" to refer to an open relationship. Others use the terms interchangeably because, regardless of the relationship, a clinical assisted reproduction procedure is involved, and the recipient couple is preparing to raise a child not genetically related to them. Lawyers who assist those trying to acquire an embryo state the term "embryo adoption" is a misnomer because the transfer of an embryo is handled as property transfer. Abortion rights advocates, advocates of embryonic stem cell research, and members of the fertility industry object to referring to the transfer as an "adoption" because they feel it gives an embryo the same status as a child. Most doctors describe the process as "embryo donation".
The technique of selecting only one embryo to transfer to the woman is called elective-single embryo transfer (e-SET) or, when embryos are at the blastocyst stage, it can also be called elective single blastocyst transfer (eSBT).[24] It significantly lowers the risk of multiple pregnancies, compared with e.g. Double Embryo Transfer (DET) or double blastocyst transfer (2BT), with a twinning rate of approximately 3.5% in sET compared with approximately 38% in DET,[25] or 2% in eSBT compared with approximately 25% in 2BT.[24] At the same time, pregnancy rates is not significantly less with eSBT than with 2BT.[24] That is, the cumulative live birth rate associated with single fresh embryo transfer followed by a single frozen and thawed embryo transfer is comparable with that after one cycle of double fresh embryo transfer.[6] Furthermore, SET has better outcomes in terms of mean gestational age at delivery, mode of delivery, birthweight, and risk of neonatal intensive care unit necessity than DET.[25] e-SET of embryos at the cleavage stage reduces the likelihood of live birth by 38% and multiple birth by 94%.[26] Evidence from randomized, controlled trials suggests that increasing the number of e-SET attempts (fresh and/or frozen) results in a cumulative live birth rate similar to that of DET.[26]
Artificial "embryo splitting" or "embryo twinning", a technique that creates monozygotic twins from a single embryo, is not considered in the same fashion as other methods of cloning. During that procedure, a donor embryo is split in two distinct embryos, that can then be transferred via embryo transfer. It is optimally performed at the 6- to 8-cell stage, where it can be used as an expansion of IVF to increase the number of available embryos. If both embryos are successful, it gives rise to monozygotic (identical) twins.