Tuesday, January 22, 2008

Cleavage stage ("day 3") versus blastocyst stage ("Day 5") embryo transfer in assisted conception.

A recent cochrane database review tackled this topic here is a summary of the findings below:



Recent advances in cell culture media have led to a shift in IVF practice from early cleavage embryo transfer to blastocyst stage transfer. The rationale for blastocyst culture is to improve both uterine and embryonic synchronicity and self selection of viable embryos thus resulting in higher implantation rates.


To determine if blastocyst stage embryo transfers (ETs) affect live birth rate and associated outcomes compared with cleavage stage ETs and to investigate what factors may influence this.

Search strategy

Cochrane Menstrual Disorders and Subfertility Group Specialised Register of controlled trials, Cochrane Controlled Trials Register (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE and Bio extracts. The last search date was January 2007.

Selection criteria

Trials were included if they were randomised and compared the effectiveness of early cleavage versus blastocyst stage transfers.

Data collection and analysis

Of the 50 trials that were identified, 18 randomised controlled trials (RCTs) met the inclusion criteria and were reviewed. The primary outcome was rate of live birth. Secondary outcomes were rates per couple of clinical pregnancy, multiple pregnancy, high order pregnancy, miscarriage, failure to transfer embryos and cryopreservation. Quality assessment, data extraction and meta-analysis were performed following Cochrane guidelines.

Main results

Evidence of a significant difference in live-birth rate per couple between the two treatment groups was detected in favour of blastocyst culture (9 RCTs; OR 1.35, 95% CI 1.05 to 1.74 (Day 2/3: 29.4% versus Day 5/6: 36.0%)). This was particularly for trials with good prognosis patients, equal number of embryos transferred (including single embryo transfer) and those in which the randomisation took place on Day 3. Rates of embryo freezing per couple was significantly higher in Day 2 to 3 transfers (9 RCTs; OR 0.45, 95% CI 0.36 to 0.56). Failure to transfer any embryos per couple was significantly higher in the Day 5 to 6 group (16 RCTs; OR 2.85, 95% CI 1.97 to 4.11 (Day 2/3: 2.8% versus Day 5/6: 8.9%)) but was not significantly different for good prognosis patients (9 RCTs; OR 1.50, 95% CI 0.79 to 2.84).

Authors' conclusions

This review provides evidence that there is a significant difference in pregnancy and live birth rates in favour of blastocyst transfer with good prognosis patients with high numbers of eight-cell embryos on Day three being the most favoured in subgroup for whom there is no difference in cycle cancellation. There is emerging evidence to suggest that in selected patients, blastocyst culture maybe applicable for single embryo transfer.

My Comments

I think the key words on the author conclusion are "good prognosis patient". that means somebody who had many eggs and many embryos were created. This allows the option of selecting the very best embryos to transfer and obviously increase the chance of a pregnancy for that cycle (possibly foregoing the chance of subsequent frozen cycles). But in the scenario of somebody with 4 average to poor quality embryos on day 3 , attempting to grow them to blastocyst stage is probably not going to change the overall prognosis. What might happen instead it that the embryos may not grow to the fifth day and the patient may not have a transfer: as frustrating as this experience is this may possibly be a better outcome than having a day 3 transfer and going to the whole 14 days of progesterone injections and get a negative beta.

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