Embryo transfer
Embryo transfer 123 | |
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MeSH | D004624 |
Embryo transfer refers to a step in the process of
Embryo transfer can be done at day two or day three, or later in the blastocyst stage, which was first performed in 1984.[1]
Factors that can affect the success of embryo transfer include the endometrial receptivity, embryo quality, and embryo transfer technique.
Fresh versus frozen
Embryos can be either "fresh" from fertilized egg cells of the same
There is probably little or no difference between FET and fresh embryo transfers in terms of live birth rate and ongoing pregnancy rate and the risk of
Uterine preparation
In the human, the uterine lining (
Limited evidence also supports removal of
Timing
Embryo transfer can be performed after various durations of
Because in vivo, a cleavage stage embryo still resides in the fallopian tube and it is known that the nutritional environment of the uterus is different from that of the tube, it is postulated that this may cause stress on the embryo if transferred on day 3 resulting in reduced implantation potential. A blastocyst stage embryo does not have this problem as it is best suited for the uterine environment [1]
Embryos who reach the day 3 cell stage can be tested for chromosomal or specific genetic defects prior to possible transfer by
There is a significantly higher odds of
Embryo selection
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.[14] 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.[15] 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.[16] 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.[17] Active efforts to develop a more accurate embryo selection analysis based on Artificial Intelligence and Deep Learning are underway. Embryo Ranking Intelligent Classification Algorithm (ERICA),[18] is a clear example. This Deep Learning software substitutes manual classifications with a ranking system based on an individual embryo's predicted genetic status in a non-invasive fashion.[19] Studies on this area are still pending and current feasibility studies support its potential.[20]
Procedure
The embryo transfer procedure starts by placing a speculum in the vagina to visualize the cervix, which is cleansed with saline solution or culture media. A transfer catheter is loaded with the embryos and handed to the clinician after confirmation of the patient's identity. The catheter is inserted through the cervical canal and advanced into the uterine cavity.[21] Several types of catheters are used for this process, however, there is good evidence that using a soft vs a hard transfer catheter can increase the chances of clinical pregnancy.[22]
There is good and consistent evidence of benefit in ultrasound guidance,[9] that is, making an abdominal ultrasound to ensure correct placement, which is 1–2 cm from the uterine fundus.[23] There is evidence of a significant increase in clinical pregnancy using ultrasound guidance compared with only "clinical touch", as well as performing the transfer with hyaluronic acid enriched transfer media.[24] Anesthesia is generally not required. Single embryo transfers in particular require accuracy and precision in placement within the uterine cavity. The optimal target for embryo placement, known as the maximal implantation potential (MIP) point, is identified using 3D/4D ultrasound.[25] However, there is limited evidence that supports deposition of embryos in the midportion of the uterus.[9][24]
After insertion of the catheter, the contents are expelled and the embryos are deposited. Limited evidence supports making trial transfers before performing the procedure with embryos.[9] After expulsion, the duration that the catheter remains inside the uterus has no effect on pregnancy rates.[26] Limited evidence suggests avoiding negative pressure from the catheter after expulsion.[9] After withdrawal, the catheter is handed to the embryologist, who inspects it for retained embryos.
In the process of zygote intrafallopian transfer (ZIFT), eggs are removed from the woman, fertilised, and then placed in the woman's fallopian tubes rather than the uterus.
Embryo number
A major issue is how many embryos should be transferred, since placement of multiple embryos carries a risk of multiple pregnancy. While the past physicians placed multiple embryos to increase the chance of pregnancy, this approach has fallen out of favor. Professional societies, and legislatures in many countries, have issued guidelines or laws to curtail the practice.[27] There is low to moderate evidence that making a double embryo transfer during one cycle achieves a higher live birth rate than a single embryo transfer; but making two single embryo transfers in two cycles has the same live birth rate and would avoid multiple pregnancies.[28]
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:[29]
Age | Attempt No. | Embryos transferred |
---|---|---|
<37 years | 1st | 1 |
2nd | 1 if top-quality | |
3rd | No more than 2 | |
37–39 years | 1st & 2nd | 1 if top-quality |
2 if no top-quality | ||
3rd | No more than 2 | |
40–42 years | 2 |
e-SET
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).[30] 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,[31] or 2% in eSBT compared with approximately 25% in 2BT.[30] At the same time, pregnancy rates is not significantly less with eSBT than with 2BT.[30] 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.[11] 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.[31] e-SET of embryos at the cleavage stage reduces the likelihood of live birth by 38% and multiple birth by 94%.[32] 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.[32]
The usage of single embryo transfer is highest in Sweden (69.4%), but as low as 2.8% in the USA. Access to public funding for ART, availability of good cryopreservation facilities, effective education about the risks of multiple pregnancy, and legislation appear to be the most important factors for regional usage of single embryo transfer.[33] Also, personal choice plays a significant role as many subfertile couples have a strong preference for twins.[33]
Adjunctive procedures
It is uncertain whether the use of mechanical closure of the cervical canal following embryo transfer has any effect.[34]
There is considerable evidence that prolonges bed rest (more than 20 minutes) after embryo transfer is associated with reduced chances of clinical pregnancy.[35]
Using hyaluronic acid as an adherence medium for the embryo may increase live birth rates.[34] There may be little or no benefit in having a full bladder, removal of cervical mucus, or flushing of the endometrial or endocervical cavity at the time of embryo transfer.[34] Adjunctive antibiotics in the form of amoxicillin plus clavulanic acid probably does not increase the clinical pregnancy rate compared with no antibiotics.[34] The use of Atosiban, G-CSF and hCG around the time of embryo transfer showed a trend towards increased clinical pregnancy rate.[36]
For frozen-thawed embryo transfer or transfer of embryo from
Follow-up
Patients usually start progesterone medication after egg (also called oocyte) retrieval. While daily intramuscular injections of progesterone-in-oil (PIO) have been the standard route of administration, PIO injections are not FDA-approved for use in pregnancy. A recent meta-analysis showed that the intravaginal route with an appropriate dose and dosing frequency is equivalent to daily intramuscular injections.[39] In addition, a recent case-matched study comparing vaginal progesterone with PIO injections showed that live birth rates were nearly identical with both methods.[40] A duration of progesterone administration of 11 days results in almost the same birth rates as longer durations.[41]
Patients are also given estrogen medication in some cases after the embryo transfer. Pregnancy testing is done typically two weeks after egg retrieval.
Third-party reproduction
It is not necessary that the embryo transfer be performed on the female who provided the eggs. Thus another female whose uterus is appropriately prepared can receive the embryo and become pregnant. Embryo transfer may be used where a woman who has eggs but no uterus and wants to have a biological baby; she would require the help of a
History
This section needs additional citations for verification. (February 2018) |
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.[43] This procedure was performed at the Harbor UCLA Medical Center [44] under the direction of Dr. John Buster and the University of California at Los Angeles School of Medicine.
In the procedure, an embryo that was just beginning to develop was transferred from one 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.[45][46]
This scientific breakthrough established standards and became an agent of change for women with infertility and for women who did not want to pass on genetic disorders to their children. Donor embryo transfer has given women a mechanism to become pregnant and give birth to a child that will contain their husband's genetic makeup. Although donor embryo transfer as practiced today has evolved from the original non-surgical method, it now accounts for approximately 5% of in vitro fertilization recorded births.
Prior to this, thousands of women who were
This work established the technical foundation and legal-ethical framework surrounding the clinical use of human oocyte and embryo donation, a mainstream clinical practice, which has evolved over the past 25 years.[45][46]
Effectiveness
Fresh blastocyst (day 5 to 6) stage transfer seems to be more effective than cleavage (day 2 or 3) stage transfer in
• Abdominal ultrasound guidance for embryo transfer
• Removal of cervical mucus
• Use of soft embryo transfer catheters
• Placement of embryo transfer tip in the upper or middle (central) area of the uterine cavity, greater than 1 cm from the fundus, for embryo expulsion
• Immediate ambulation once the embryo transfer procedure is completed[48]
Embryo transfer in animals
Embryo transfer techniques allow top quality female livestock to have a greater influence on the genetic advancement of a herd or flock in much the same way that artificial insemination has allowed greater use of superior sires.[49] ET also allows the continued use of animals such as competition mares to continue training and showing, while producing foals. The general epidemiological aspects of embryo transfer indicates that the transfer of embryos provides the opportunity to introduce genetic material into populations of livestock while greatly reducing the risk for transmission of infectious diseases. Recent developments in the sexing of embryos before transfer and implanting has great potential in the dairy and other livestock industries.[50]
Embryo transfer is also used in
On February 19, 2020, the first pair of Cheetah cubs to be conceived through embryo transfer from a surrogate cheetah mother was born at Columbus Zoo in Ohio.[51]
Frozen embryo transfer in animals
The development of various methods of
References
- S2CID 32746730.
- ^ "Genetics & IVF Institute". Givf.com. Archived from the original on 6 December 2012. Retrieved 22 September 2016.
- PMID 19458318.
- ^ PMID 24916455.
- PMID 20472913.
- ^ PMID 25532533.
- ^ PMID 33539543.
- PMID 23820515.
- ^ PMID 20409543.
- ^ PMID 24480786.
- ^ PMID 30117155.
- PMID 19243755.
- PMID 26951653.
- PMID 20488801.
- PMID 22975113.
- PMID 31140578.
- PMID 27553622.
- ^ "ERICA Embryo Ranking | Artificial Intelligence for Assisted Reproduction".
- .
- PMID 32157183.
- ^ Jain, John (25 March 2015). "Embryo Transfer". Dr. John Jain on Youtube. Archived from the original on 13 December 2021. Retrieved 17 December 2015.
- PMID 35325124.
- PMID 35325124.
- ^ PMID 35325124.
- PMID 16084896..
- PMID 20116786.
- ^ "New Law regarding the number of embryos transferred in Greece". newlife-ivf.co.uk. 22 December 2014.
- PMID 32827168.
- NICE clinical guidelineCG156 – Issued: February 2013
- ^ PMID 19249756.
- ^ PMID 19446806.
- ^ PMID 19446809.
- ^ PMID 20634207.
- ^ PMID 30117155.
- PMID 35325124.
- PMID 35325124.
- PMID 28675921.
- PMID 25281684.
- .
- ^ Khan N, Richter KS, Blake EJ, et al. Case-matched comparison of intramuscular versus vaginal progesterone for luteal phase support after in vitro fertilization and embryo transfer. Presented at: 55th Annual Meeting of the Pacific Coast Reproductive Society; 18–22 April 2007; Rancho Mirage, CA.
- PMID 19523613.
- ^ a b Teman, Elly. 2010. Birthing a Mother: the Surrogate Body and the Pregnant Self. Berkeley: University of California Press.
- ^ Blakeslee, Sandra (4 February 1984). "Infertile Woman Has Baby Through Embryo Transfer". The New York Times. Retrieved 1 May 2010.
- ^ "HUMC – Celebrating 50 Years of Caring". humc.edu. Archived from the original on 3 March 2016. Retrieved 18 January 2009.
- ^ a b Friedrich, Otto; Constable, Anne; Samghabadi, Raji (10 September 1984). "Medicine: A Legal, Moral, Social Nightmare". Time. Archived from the original on 16 February 2009. Retrieved 1 May 2010.
- ^ a b "The New Origins of Life". Time. 10 September 1984. Archived from the original on 14 January 2005. Retrieved 1 May 2010.
- PMID 35588094.
- )
- ^ Embryo Transfer in Cattle Archived 14 May 2008 at the Wayback Machine. Retrieved 21 October 2008.
- ^ Embryo Sexing Technology Archived 2 March 2009 at the Wayback Machine. Retrieved 21 October 2008.
- ^ "First Cheetah Cubs Born as Result of Embryo Transfer". Smithsonian's National Zoo. 24 February 2020. Retrieved 25 February 2020.
- S2CID 46005842.)
{{cite journal}}
: CS1 maint: DOI inactive as of April 2024 (link - bovine embryotransfer. Anim. Reprod., v.10, n.3, p.168-173, Jul./Sept. 2013 173
- AETA, 1998, San Antonio, TX. San Antonio, TX: AETA. pp. 91-98.
- PMID 16727070.
- PMID 16728153.
- in Animal Reproduction
- AETA. pp. 91-98.
- ^ Stroud B (2012). "The year 2011 worldwide statistics of embryo transfer in domestic farm animals". IETS Newslet. 50: 16–25.