Favourable Outcomes From 'mild' In-vitro Fertilisation

Main Category: Fertility
Article Date: 02 Mar 2007 - 0:00 PDT

email to a friend   printer friendly   opinions  

In-vitro fertilisation (IVF) has come a long way since the early days of uncertainty, guesswork, and low pregnancy rates. The UK's Human Fertilisation Embryology Authority's (HFEA) guide to infertility1 provides national data for IVF treatments in 2003-04, showing a mean livebirth rate of 28% per cycle in women younger than 35 years. Many cycles of IVF treatment generate embryos that can be frozen for later use in the natural menstrual cycle, giving a cumulative chance of more than 40% for a livebirth per stimulated cycle for women younger than 35 years.

In view of this striking improvement in the efficiency of IVF, attention has increasingly turned to the improvement of safety and quality of care, and the patients' experience of IVF treatment. Patients and their doctors often recall graphic television images of deep intramuscular injections, laparoscopies under general anaesthetic, and extended and stressful courses of treatment. Although many patients find IVF stressful because of the importance of the outcome to their lives, the treatment itself has become gradually but steadily safer and less unpleasant over the past decade.

A landmark publication in 1999 described so-called soft IVF,2 which offered a safer and more acceptable approach, with reduced doses of drugs and shortened treatment duration. Not only would this procedure benefit patients, but it might also improve clinic income by encouraging repeat attempts at IVF.

However, despite the apparent win-win implicit in the soft procedure, many clinicians have continued to adopt a conservative approach, sticking to what they know works. A recent conference in London on natural IVF3 rightly criticised the continued use of high-dose gonadotropins for IVF superovulation. In today's Lancet, Esther Heijnen and colleagues4 provide robust evidence for the efficacy and patients' acceptability of one version of soft IVF.

The researchers show, in an adequately powered randomised trial, that a treatment protocol with an antagonist of gonadotropin-releasing hormone (GnRH) with lowdose gonadotropins and single embryo transfer has the same efficacy and is less unpleasant to patients than a traditional long protocol with GnRH agonist and double embryo transfer.

What are the implications for patients? The antagonist protocol avoids the initial period of 2-3 weeks of pituitary downregulation, during which patients have menopausal symptoms of flushing, sweating, depression, and loss of libido. This situation is hardly ideal preparation for the stresses of IVF and the fact that patients reported less discomfort with the antagonist regimen than with the conservative long protocol is hardly surprising.

What are the implications for health services? The trial also compared livebirth rates after single embryo transfer in the antagonist group with double embryo transfer in the agonist group, with strikingly different rates of resultant multiple births (0•5% vs 13•1%, respectively) despite equivalent 1-year cumulative livebirth rates (43•4% vs 44•7%). The HFEA has recently received the report of its Multiple Birth and Single Embryo Transfer (MBSET) working-group,5 and is about to hold public consultation about future policy for numbers of embryos transferred after IVF.

The report grimly describes the risks of premature birth and other pregnancy complications when women are pregnant with twins after IVF, and suggests several possible policy changes. The report leans heavily on evidence from Scandinavia,6,7 which suggests that transfer of a single embryo plus a subsequent frozen embryo transfer has equal chance of a livebirth compared with double embryo transfer, with greatly reduced risk of twin pregnancy. Heijnen and co-workers report cumulative livebirth rates after 1 year of treatment and support the contention that one fresh embryo plus one frozen embryo transfer equals a double fresh transfer, without most of the resultant twin births. Equivalent numbers of births were achieved in the single embryo transfer group with reduced cost and distress for couples.

An elective policy of single embryo transfer remains controversial in the UK, as shown by media coverage of the MBSET working-group report. Some patients want to complete the procedure as quickly as possible, and see twins as the most desirable outcome.8 While 75% of IVF treatment in the UK continues to be paid for by patients themselves, and the guidance by the UK National Institute for Clinical Excellence in 2004 that all eligible couples are offered three full cycles of IVF9 remains a pipe dream, many couples will opt for double embryo transfer because it is much less costly.

Governments should recognise the long-term benefits to patients, to neonatal and postnatal care, and to the public purse of implementing a policy of single embryo transfer and encouraging adoption of the policy with increased funding for such treatments.

William L Ledger
Academic Unit of Reproductive and Developmental Medicine,
University of Sheffield, Sheffield S10 2SF, UK
I declare that I have no conflict of interest.

1 Human Fertilisation Embryology Authority. Facts and figures. http://www. hfea.gov.uk/cps/rde/xchg/SID-3F57D79B-6350C24C/hfea/hs.xsl/406.html (accessed Jan 3, 2007).

2 Fauser BC, Devroey P, Yen SS, et al. Minimal ovarian stimulation for IVF: appraisal of potential benefits and drawbacks. Hum Reprod 1999; 14: 2681-86.

3 International Society of Natural Cycle Assisted Reproduction. First World Congress on natural cycle/minimal stimulation IVF. London, Dec 15-16, 2006.

4 Heijnen EMEW, Eijkemans MJC, De Klerk C, et al. A mild treatment strategy for in-vitro fertilisation: a randomised non-inferiority trial. Lancet 2007; 369: 743-49.

5 Human Fertilisation Embryology Authority. Multiple births and single embryo transfer review. http://www.hfea.gov.uk/cps/rde/xchg/SID- 3F57D79B-09487768/hfea/hs.xsl/483.html (accessed Jan 3, 2007).

6 Gerris JM. Single embryo transfer and IVF/ICSI outcome: a balanced appraisal. Hum Reprod Update 2005; 11: 105-21.

7 Hamberger L, Hardarson T, Nygren KG. Avoidance of multiple pregnancy by use of single embryo transfer. Minerva Ginecol 2005; 57: 15-19.

8 Newton CR, McBride J, Feyles V, Tekpetey F, Power S. Factors affecting patients' attitudes toward single- and multiple-embryo transfer. Fertil Steril 2006; 87: 269-78.

9 National Institute for Clinical Excellence. Fertility: assessment and treatment for people with fertility problems. Clinical Guideline 11, February 2004. Available at www.nice.org.uk (accessed Feb 26, 2007).

http://www.lancet.com

• Additional
• References
• Citations