BMJ  2004;329:302-303 (7 August), doi:10.1136/bmj.329.7461.302

Editorial

How many eggs?

Ideally, one egg and one offspring

For some, the most crucial part of the question of "How many eggs?" is how many eggs one should put in the same nest. For others, it is how many can one get out of the same nest? Translate nest into incubator, and the study of Pinborg et al in this issue seems to address both.¹

This is the second in a series by Pinborg et al (p 311) on the outcome of 3393 liveborn twins after in vitro fertilisation (IVF) with or without intracytoplasmatic sperm injection (ICSI) compared with 10 239 liveborn control twins in Denmark between 1995 and 2000.^{1 2} The first was based on 3438 twins born after IVF and ICSI and 10 362 naturally conceived twins, but dealt with the neonatal outcome of the 3393 and 10 239 liveborns among them.² The current study deals with the same 13 632 (that is 3393 IVF and 10 239 non IVF and ICSI) liveborn twins. It is remarkably consistent in the reporting of their neonatal outcomes, but a further control group of singletons born after IVF and ICSI is now added to complete the picture.¹ Apparently we are yet to see another study, announced already, based on the same infants from the same nest but without the control twins.³

The current report along with its predecessor seems to bring a much needed positive note on the outcome of twins conceived after IVF and ICSI.^{1 2} A systematic review of controlled studies published earlier this year had shown little difference, if any, in the frequencies of (very) preterm birth, (very) low birth weight, and small size for gestational age between twins born after assisted conception and those conceived naturally.⁴ Unexpectedly, a lower perinatal mortality but a higher rate of neonatal admission to hospital was found among the IVF and ICSI twins.⁴ Pinborg et al, on a much larger cohort, seem to confirm this with a perinatal mortality (stillbirth plus deaths in first week) of 20.7 per 1000 in twins born after IVF and ICSI versus 23.4/1000 in control twins. The same seems to apply to infant mortality (death within the first year after birth) with rates of 10.3/1000 and 15.0/1000, respectively.^{1 2} This, however, does not annihilate the fact that both death rates are substantially higher than the rates for singletons born after IVF and ICSI.¹

Then, how good is the news that neurological disability, including cerebral palsy, occurs with a similar frequency among twins born after IVF and ICSI and among naturally conceived control twins? Does it help to know that the rate was statistically not different from that in singletons born after assisted conception or that low gestational age and low birth weight had a greater influence than either assisted conception or being a twin? After all, the net result of one more egg in the uterus is exactly that—a shorter gestational age and a lower birth weight. This was shown in a classic study more than 50 years ago, and it has not changed since.⁵ We may draw some comfort from learning that IVF with ICSI carries a similar risk of neurological sequelae as conventional IVF. However, that 5% of infants born in Denmark nowadays are the result of IVF techniques and that 40% of them are born as twins, is not comforting.¹

Worldwide, increasing maternal age at conception has resulted in dramatic increases in the rate of twin pregnancies with equally dramatic consequences in terms of perinatal health and cost to families and society.^{6 7} Assisted reproduction is part of that scenario. As a woman's biological clock starts to tick louder so does the urge to do something about it, and mothers using IVF in this study were on average three years older than the mothers of control twins. Although no single mechanism is more secure than IVF to ensure that only a single fertilised egg goes into the uterus, fewer than 2% of all the twins born after IVF and ICSI in this study developed from a single egg (monozygotic) compared with 31% of naturally conceived control twins. How many treatments, other than assisted reproduction, would have lasted for the same length of the time if it appeared that, after 25 years of increasing reliance on it, 40% of its alleged successes are still not successes but overdoses⁸: too many eggs in the same nest.

Department of Obstetrics, Gynaecology and Reproductive Medicine, Flinders University and Flinders Medical Centre, Adelaide, SA 5042, Australia

(f.m.helmerhorst{at}lumc.nl) Department of Obstetrics, Gynaecology and Reproductive Medicine, Leiden University Medical Center, NL-2300RC Leiden, Netherlands

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Papers p 311

Competing interests: None declared.

References

1. Pinborg A, Loft A, Schmidt L, Greisen G, Rasmussen S, Nyboe Andersen A. Neurological sequalae in twins born after assisted conception: controlled national cohort study. BMJ 2004;329: 311-4.[Abstract/Free Full Text]
2. Pinborg A, Loft A, Rasmussen S, Schmidt L, Langhoff-Roos J, Greisen G, Nyboe Andersen A. Neonatal outcome in a Danish national cohort of 3438 in vitro fertilisation/ICSI twins and 10362 non-in vitro fertilisation-ICSI twins born between 1995 and 2000. Hum Reprod 2004:19: 435-41.[Abstract/Free Full Text]
3. Pinborg A, Loft A, Nyboe Andersen A. Neonatal outcome in a Danish national cohort of 8602 children born after in vitro fertilisation (in vitro fertilisation) or intracytoplasmic sperm injection (ICSI): the role of twin pregnancy. Acta Obstet Gynecol Scand 2004 (in press).
4. Helmerhorst FM, Perquin DAM, Donker D, Keirse MJNC. Perinatal outcome of singletons and twins after assisted conception: a systematic review of controlled studies. BMJ 2004;328: 261-5.[Abstract/Free Full Text]
5. McKeown T, Record RG. Observations on foetal growth in multiple pregnancy in man. J Endocrinol 1952;8: 386-401.
6. Keirse MJNC, Helmerhorst FM. The impact of assisted reproduction on perinatal health care. Soz Präventivmed 1995;40: 343-51.[Medline]
7. Blondel B, Kaminski M. Trends in the occurrence, determinants, and consequences of multiple births. Semin Perinatol 2002;26: 239-49.[CrossRef][ISI][Medline]
8. Nyboe Andersen A, Gianaroli L, Nygren KG. Assisted reproductive technologies in Europe, 2000. Results generated from European registers by ESHRE. Hum Reprod 2004;19: 490-503.[Abstract/Free Full Text]

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Neurological sequelae in twins born after assisted conception: controlled national cohort study

Anja Pinborg, Anne Loft, Lone Schmidt, Gorm Greisen, Steen Rasmussen, and Anders Nyboe Andersen
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Rapid Responses:

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All for one?

Prof Ian Craft
bmj.com, 17 Aug 2004 [Full text]

Re: All for one?

Frans M. Helmerhorst, et al.
bmj.com, 22 Sep 2004 [Full text]