title: Number of embryos for transfer following in vitro fertilisation or intra-cytoplasmic sperm injection.
abstract: BACKGROUND
  Multiple embryo transfer during in vitro fertilisation (IVF) increases multiple pregnancy rates causing maternal and perinatal morbidity. Single embryo transfer is now being seriously considered as a means of minimising the risk of multiple pregnancy. However, this needs to be balanced against the risk of jeopardising the overall live birth rate.
  
  
  OBJECTIVE
  To evaluate the effectiveness and safety of different policies for the number of embryos transferred in couples who undergo assisted reproductive technology (ART).
  
  
  METHODS
  We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE, from inception to July 2013. We handsearched reference lists of articles, trial registers and relevant conference proceedings and contacted researchers in the field.
  
  
  METHODS
  We included randomised controlled trials (RCTs) comparing different policies for the number of embryos transferred following IVF or intra-cytoplasmic sperm injection (ICSI) in subfertile women. Studies of fresh or frozen and thawed transfer of one, two, three or four embryos at cleavage or blastocyst stage were eligible.
  
  
  METHODS
  Two review authors independently assessed trial eligibility and risk of bias and extracted the data. The overall quality of the evidence was graded in a summary of findings table.
  
  
  RESULTS
  Fourteen RCTs were included in the review (2165 women). Thirteen compared cleavage-stage transfers (2017 women) and two compared blastocyst transfers (148 women): one study compared both. No studies compared repeated multiple versus repeated single embryo transfer (SET). DET versus repeated SETDET was compared with repeated SET in three studies of cleavage-stage transfer. In these studies the SET group received either two cycles of fresh SET (one study) or one cycle of fresh SET followed by one frozen SET in a natural or hormone-stimulated cycle (two studies). When these three studies were pooled, the cumulative live birth rate after one cycle of DET was not significantly different from the rate after repeated SET (OR 1.22, 95% CI 0.92 to 1.62, three studies, n=811, I(2)=0%, low quality evidence). This suggests that for a woman with a 40% chance of live birth following a single cycle of DET, the chance following repeated SET would be between 30% and 42%. The multiple pregnancy rate was significantly higher in the DET group (OR 30.54, 95% CI 7.46 to 124.95, three RCTs, n = 811, I(2) = 23%, low quality evidence), suggesting that for a woman with a 15% risk of multiple pregnancy following a single cycle of DET, the risk following repeated SET would be between 0% and 2%. Single-cycle DET versus single-cycle SETA single cycle of DET was compared with a single cycle of SET in 10 studies, nine comparing cleavage-stage transfers and two comparing blastocyst-stage transfers. When all studies were pooled the live birth rate was significantly higher in the DET group (OR 2.07, 95% CI 1.68 to 2.57, nine studies, n = 1564, I(2) = 0%, high quality evidence). This suggests that for a woman with a 40% chance of live birth following a single cycle of DET, the chance following a single cycle of SET would be between 22% and 30%. The multiple pregnancy rate was also significantly higher in the DET group (OR 8.47, 95% CI 4.97 to 14.43, 10 studies, n = 1612, I(2) = 45%, high quality evidence), suggesting that for a woman with a 15% risk of multiple pregnancy following a single cycle of DET, the risk following a single cycle of SET would be between 1% and 4%. The heterogeneity for this analysis was attributable to a study with a high rate of cross-over between treatment arms. Other comparisons Other fresh cycle comparisons were evaluated in three studies which compared DET versus transfer of three or four embryos. Live birth rates did not differ significantly between the groups for any comparison, but there was a significantly lower multiple pregnancy rate in the DET group than in the three embryo transfer (TET) group (OR 0.36, 95% CI 0.13 to 0.99, two studies, n = 343, I(2) = 0%).
  
  
  CONCLUSIONS
  In a single fresh IVF cycle, single embryo transfer is associated with a lower live birth rate than double embryo transfer. However, there is no evidence of a significant difference in the cumulative live birth rate when a single cycle of double embryo transfer is compared with repeated SET (either two cycles of fresh SET or one cycle of fresh SET followed by one frozen SET in a natural or hormone-stimulated cycle). Single embryo transfer is associated with much lower rates of multiple pregnancy than other embryo transfer policies. A policy of repeated SET may minimise the risk of multiple pregnancy in couples undergoing ART without substantially reducing the likelihood of achieving a live birth. Most of the evidence currently available concerns younger women with a good prognosis.
authors.affiliation: Obstetrics and Gynaecology, Aberdeen Maternity Hospital, Aberdeen, UK. z.pandian@abdn.ac.uk
authors.forename: Zabeena
authors.initials: Z
authors.lastname: Pandian
authors.forename: Jane
authors.initials: J
authors.lastname: Marjoribanks
authors.forename: Ozkan
authors.initials: O
authors.lastname: Ozturk
authors.forename: Gamal
authors.initials: G
authors.lastname: Serour
authors.forename: Siladitya
authors.initials: S
authors.lastname: Bhattacharya
mesh_terms: D001755:Blastocyst; D002970:Cleavage Stage, Ovum / Q000637:transplantation; D004624:Embryo Transfer / Q000009:adverse effects* / Q000379:methods*; D005260:Female; D005307:Fertilization in Vitro; D006801:Humans; D011247:Pregnancy; D018873:Pregnancy Rate; D011272:Pregnancy, Multiple; D016032:Randomized Controlled Trials as Topic; D020554:Sperm Injections, Intracytoplasmic
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