Number of embryos for transfer in women undergoing assisted reproductive technology (ART)

Review question:

How many embryos should be transferred in couples undergoing ART?

Background:

Multiple pregnancy creates serious health risks for the mother (such as premature labour, diabetes and high blood pressure) and for the babies, who are at much higher risk than single babies of problems including premature birth, low birth weight, cerebral palsy and perinatal death. Single embryo transfer is now being seriously considered in order to reduce multiple pregnancies but this needs to be balanced against the risk of lowering the overall live birth rate. Researchers in The Cochrane Collaboration reviewed the evidence about the number of embryos transferred in women undergoing ART. The search is current to July 2013.

Study characteristics:

We found 14 randomised controlled trials with a total of 2165 participants. Most were not commercially funded.

Key findings:

Double versus repeated single embryo transfer

Based on low quality evidence, there was no indication that overall live birth rates differed substantially when repeated single embryo transfer (either two cycles of single embryo transfer or one cycle of single embryo transfer followed by transfer of a single frozen embryo in a natural or hormone-stimulated cycle) was compared with double embryo transfer. The evidence suggested that for a woman with a 42% chance of live birth following a single cycle of double embryo transfer, the chance following repeated single embryo transfer would be between 31% and 44%. The risk of multiple birth was very much lower in the single embryo transfer group: for a woman with a 13% risk of multiple pregnancy following a single cycle of double embryo transfer, the estimated risk following a repeated single transfer was between 0% and 2%.

Double versus single embryo transfer

We found high quality evidence that the chances of live birth were lower after one cycle of fresh single embryo transfer than after one cycle of fresh double embryo transfer. For a woman with a 45% chance of live birth following a single cycle of double embryo transfer, the chance following a single cycle of single embryo transfer was between 24% and 33%. However, the risk of twins was about seven times higher after double embryo transfer.

Conclusion:

Repeated single embryo transfer appears the best option for most women undergoing ART. Most of the evidence currently available concerns younger women with a good prognosis.

Authors' 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.

Read the full 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.

Objectives: 

To evaluate the effectiveness and safety of different policies for the number of embryos transferred in couples who undergo assisted reproductive technology (ART).

Search strategy: 

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.

Selection criteria: 

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.

Data collection and analysis: 

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.

Main 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 single versus repeated multiple embryo transfer (SET).

Repeated SET versus DET

Repeated SET was compared with DET 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 repeated SET was not significantly different from the rate after one cycle of DET (OR 0.82, 95% CI 0.62 to 1.09, three studies, n=811, I2=0%, low quality evidence). This suggests that for a woman with a 42% chance of live birth following a single cycle of DET, the chance following repeated SET would be between 31% and 44%. The multiple pregnancy rate was significantly lower in the SET group (OR 0.03, 95% CI 0.01 to 0.13, three RCTs, n = 811, I2 = 23%, low quality evidence), suggesting that for a woman with a 13% risk of multiple pregnancy following a single cycle of DET, the risk following repeated SET would be between 0% and 2%.

Single-cycle SET versus single-cycle DET

A single cycle of SET was compared with a single cycle of DET in 10 studies, nine comparing cleavage-stage transfers and two comparing blastocyst-stage transfers. When studies were pooled the live birth rate was significantly lower in the SET group (OR 0.48, 95% CI 0.39 to 0.60, nine studies, n = 1564, I2 = 0%, high quality evidence). This suggests that for a woman with a 45% chance of live birth following a single cycle of DET, the chance following a single cycle of SET would be between 24% and 33%. The multiple pregnancy rate was also significantly lower in the SET group (OR 0.12, 95% CI 0.07 to 0.20, 10 studies, n = 1612, I2 = 45%, high quality evidence), suggesting that for a woman with a 14% risk of multiple pregnancy following a single cycle of DET, the risk following a single cycle of SET would be between 1% and 3%. The heterogeneity for this analysis was attributable to a study with a high rate of cross-over between treatment arms.

Other comparisons

Other comparisons were evaluated in four 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, I2 = 0%).