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Embryo transfer
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== Timing == Embryo transfer can be performed after various durations of [[embryo culture]], conferring different stages in [[human embryogenesis|embryogenesis]]. The main stages at which embryo transfer is performed are [[human embryogenesis|cleavage stage]] (day 2 to 4 after [[co-incubation]]) or the [[blastocyst]] stage (day 5 or 6 after [[co-incubation]]).<ref name="DarLazer2014">{{cite journal | vauthors = Dar S, Lazer T, Shah PS, Librach CL | title = Neonatal outcomes among singleton births after blastocyst versus cleavage stage embryo transfer: a systematic review and meta-analysis | journal = Human Reproduction Update | volume = 20 | issue = 3 | pages = 439β48 | date = 2014 | pmid = 24480786 | doi = 10.1093/humupd/dmu001 | doi-access = free }}</ref> 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 [https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD002118.pub5/full] Embryos who reach the day 3 cell stage can be tested for chromosomal or specific genetic defects prior to possible transfer by [[preimplantation genetic diagnosis]] (PGD). Transferring at the blastocyst stage confers a significant increase in [[live birth rate]] per transfer, but also confers a decreased number of embryos available for transfer and [[embryo cryopreservation]], so the cumulative clinical pregnancy rates are increased with cleavage stage transfer.<ref name="Farquhar2014">{{cite journal | vauthors = Farquhar C, Rishworth JR, Brown J, Nelen WL, Marjoribanks J | title = Assisted reproductive technology: an overview of Cochrane reviews | journal = The Cochrane Database of Systematic Reviews | issue = 12 | pages = CD010537 | date = December 2014 | pmid = 25532533 | doi = 10.1002/14651858.CD010537.pub3 | editor1-last = Brown | editor1-first = Julie | hdl = 2292/26680 | hdl-access = free }}</ref>{{Update inline|reason=Updated version https://www.ncbi.nlm.nih.gov/pubmed/26174592|date = November 2018}} It is uncertain whether there is any difference in [[live birth rate]] between transfer on day two or day three after fertilization.<ref name="auto">{{cite journal |last1=Farquhar |first1=C |last2=Marjoribanks |first2=J |title=Assisted reproductive technology: an overview of Cochrane Reviews. |journal=Cochrane Database of Systematic Reviews |date=17 August 2018 |volume=2018 |issue=8 |pages=CD010537 |doi=10.1002/14651858.CD010537.pub5 |pmid=30117155|pmc=6953328 }}</ref> [[Monozygotic twinning]] is not increased after blastocyst transfer compared with [[cleavage-stage embryo]] transfer.<ref>{{cite journal | vauthors = Papanikolaou EG, Fatemi H, Venetis C, Donoso P, Kolibianakis E, Tournaye H, Tarlatzis B, Devroey P | title = Monozygotic twinning is not increased after single blastocyst transfer compared with single cleavage-stage embryo transfer | journal = Fertility and Sterility | volume = 93 | issue = 2 | pages = 592β7 | date = February 2010 | pmid = 19243755 | doi = 10.1016/j.fertnstert.2008.12.088 | doi-access = free }}</ref> There is a significantly higher odds of [[preterm birth]] ([[odds ratio]] 1.3) and [[congenital anomalies]] ([[odds ratio]] 1.3) among births having reached the blastocyst stage compared with cleavage stage.<ref name="DarLazer2014" /> Because of increased female embryo mortality due to epigenetic modifications induced by extended culture,<ref>{{Cite journal | doi=10.1073/pnas.1523538113| pmid=26951653| pmc=4812732| title=Impaired imprinted X chromosome inactivation is responsible for the skewed sex ratio following in vitro fertilization| journal=Proceedings of the National Academy of Sciences| volume=113| issue=12| pages=3197β3202| year=2016| last1=Tan| first1=Kun| last2=An| first2=Lei| last3=Miao| first3=Kai| last4=Ren| first4=Likun| last5=Hou| first5=Zhuocheng| last6=Tao| first6=Li| last7=Zhang| first7=Zhenni| last8=Wang| first8=Xiaodong| last9=Xia| first9=Wei| last10=Liu| first10=Jinghao| last11=Wang| first11=Zhuqing| last12=Xi| first12=Guangyin| last13=Gao| first13=Shuai| last14=Sui| first14=Linlin| last15=Zhu| first15=De-Sheng| last16=Wang| first16=Shumin| last17=Wu| first17=Zhonghong| last18=Bach| first18=Ingolf| last19=Chen| first19=Dong-bao| last20=Tian| first20=Jianhui| bibcode=2016PNAS..113.3197T| doi-access=free}}</ref> blastocyst transfer leads to more male births (56.1% male) versus 2 or 3 day transfer (a normal sex ratio of 51.5% male).
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