18-01-2012 Effect of age on decisions about the number of embryos to transfer in assisted conception: Lawlor and Nelson in perspective

Peter Braude, Emeritus Professor of Obstetrics and Gynaecology, comments on a recent study into multiple embryo transfer published in The Lancet.

When constructing the report One Child at a Time1 to advise the HFEA, our specialist panel were clear about two factors:

1. That multiple pregnancy, especially triplets, was the biggest threat to the healthy outcome of IVF children,

2. That the decision about how many embryos to transfer in order to maximise pregnancy, but to reduce the escalation in multiple pregnancy, should be left to the clinicians (in consultation with their patients).

In order to achieve this aim it was recommended that single embryo transfer should be considered for those patients who would be most likely to get pregnant from their cycle. This would usually be, but not limited to, those under the age of 35 in their first cycle, or those who had had children previously. It is comforting that in their analysis of over 140,000 IVF cycles from the HFEA database, Lawlor and Nelson2 concluded that the decision to transfer one or two embryos should be based on such prognostic criteria.

It is noteworthy that in this study, that more than two-thirds of IVF patients were below 38, and 90% of the cycles they analysed were first cycles, yet still 83% of patients had two embryos transferred. Bearing this in mind, a single embryo replacement in those young first cycle patients could have had a substantial impact on the 25% multiple pregnancy rate at the time, and thus on the health of the offspring that resulted.

In addition nearly three-quarters of patients had four or more embryos available at the time of transfer. With better freezing methods now available and increasing success with transfer of frozen embryos, those patients who only had one embryo transferred, but failed to become pregnant could have one or more further transfers from the same stimulation cycle.

The effect of cumulative transfer cycles on chances of pregnancy was not examined in the Lawlor and Nelson paper, nor was the improved pregnancy rates that now can be achieved with single blastocyst transfer commented upon.

At the overall multiple pregnancy rate of around 25% quoted, nearly 40% of IVF babies would be born in a multiple birth event3 , which are more complicated and risky for the mother, and which carry a higher incidence of low birth weight and prematurity for the child.

In recognition of this, many health care purchasers (PCTs) are seeking contracts with their provider clinics on the basis of the additional frozen cycles being included in the contract pricing, thus maximizing the chance of pregnancy for each stimulation cycle, reducing the cost of drugs, improving safety, and avoiding the risks of multiple pregnancies to the mother and her baby.

Even if we were able to achieve the current HFEA target maximum of 15% twins; that would still leave one in four IVF children being born in as a result of a multiple birth event, more than 10 times the naturally occurring rate.

The study also reiterated “older women were less likely to have live births than younger women, irrespective of the number of embryos transferred”. However where they do have a multiple pregnancy especially of higher order, the risk to both mother and baby escalates.

Thus the conclusion reached by Lawlor and Nelson, that although women over the age of 40 could consider having two embryos replaced to improve their chances of a live birth the transfer of three embryos would be too risky because of the increased likelihood of triplets without any advantage, and should be avoided at any age. In fact transferring three embryos did not increase the chance of live birth over transferring two embryos.

For the large number of younger woman who undergo IVF, the old adage still stands:
“Of course you can have all your embryos put back, but preferably one at a time”.

Peter Braude, Emeritus Professor of Obstetrics and Gynaecology, King’s College London, formerly chair of the Expert Group on Multiple Births after IVF.

For an abstract of the article see: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61267-1/abstract

1 http://www.oneatatime.org.uk/images/MBSET_report_Final_Dec_06.pdf.

2  Lawlor D & Nelson S. Effect of age on decisions about the numbers of embryos to
transfer in assisted conception: a prospective study. The Lancet, January 12, 2012 DOI:10.1016/S0140-6736(11)61267-1

3 At 25% multiple births, of every 10 babies born, 6 would be as a singleton, and 4 from a multiple birth event.