Birthweight of singletons after assisted reproduction is higher after single- than after double-embryo transfer

Human Reproduction Vol.21, No.10 pp. 2633–2637, 2006 doi:10.1093/humrep/del247 Advance Access publication June 19, 2006. Birthweight of singletons after assisted reproduction is higher after single- than after double-embryo transfer Petra De Sutter1,3*, Ilse Delbaere1*, Jan Gerris1, Hans Verstraelen1, Sylvie Goetgeluk2, Josiane Van der Elst1, Marleen Temmerman1 and Marc Dhont1 1 3 To whom correspondence should be addressed at: Department of Obstetrics and Gynaecology, University Hospital Gent, De Pintelaan 185, B-9000 Gent, Belgium. E-mail: *These authors contributed equally to this article. BACKGROUND: Single-embryo transfer (SET) has proven efficient in reducing multiple pregnancy rates after assisted reproduction technologies (ART). This study compares outcome of singletons after SET and double-embryo transfer (DET). METHODS: We studied 404 SET and 431 DET patients, who delivered a singleton child of >500 g after fresh embryo transfer in a first, second or third cycle. Preterm birth and low birthweight incidences and gestational age and birthweight were compared between both groups. Adjustments were made for maternal age, parity, cycle rank number, treatment indication, ART method, embryo characteristics and sex of the child. RESULTS: Singletons born after DET have a significantly lower birthweight than that after SET (3204.3 ± 617.5 g versus 3324.6 ± 509.7 g, P < 0.01). Also preterm birth (<37 weeks) [odds ratio (OR) 1.77, 95% confidence interval (CI) 1.06–2.94] and low birthweight (<2500 g) (OR 3.38, 95% CI 1.86–6.12) are significantly more common in DET singletons. CONCLUSIONS: Singleton birth after SET is advantageous compared with DET. This sheds new light on the reasons why singleton births following ART do worse than spontaneously conceived singletons in IVF programs, where double- or multipleembryo transfer is standard. Key words: assisted reproduction/pregnancy outcome/single-embryo transfer/singleton Introduction Elective transfer of one embryo in a selected population is the only effective way to reduce twin pregnancies, which is considered as the most important complication of ART (Luke and Keith, 1992). Merely by their absolute numbers, twin pregnancies still constitute a serious medical problem (Blondel and Kaminski, 2002), leading to a high neonatal mortality and severe short- and long-term morbidity for the children (Bernasko et al., 1997; Elster, 2000). The move from triple- to double-embryo transfer (DET), which was advocated in the late 1990s, had an impact on the reduction of triplets and children of a higher birth order but hardly affected the incidence of twin pregnancies (Staessen et al., 1993; Coetsier and Dhont, 1998; Vilska et al., 1999). The step towards single-embryo transfer (SET) was more difficult to take, because early articles studying pregnancy rates in SETs were discouraging (Elsner et al., 1997). These conclusions were biased, however, because these studies included solely patients who had only one embryo available for transfer. For this reason, a distinction should be made between elective and non-elective SET. When there is only one embryo available for transfer (nonelective), the pregnancy rate is indeed low (Dhont, 2001). In Flanders, Belgium, the percentage of multiple pregnancies because of assisted reproduction dropped from 25% in 2002 to 11.9% in 2004 [Study Centre for Perinatal Epidemiology (SPE), 2004]. This substantial decrease in iatrogenic multiple pregnancies is because of the introduction of the Belgian law on 1 July 2003, which regulates the reimbursement of six IVF cycles up to a maternal age of 43 years (Royal Decree of 4 June 2003) under the condition that SET is performed in first cycles for all patients younger than 36 years. This unique project was the result of extensive research which showed that prevention of twin pregnancies with maintenance of a high overall pregnancy rate is possible, if one high-quality embryo is transferred to a patient with a twin-prone clinical profile, representing at least one-third of the patient population (Gerris et al., 1999; Vilska et al., 1999; Gerris et al., 2001; De Sutter et al., 2003; Tiitinen et al., 2003; Gardner et al., 2004; Martikainen et al., 2004). Reimbursement by the government was granted, because it was demonstrated that SET is a cost-effective alternative to DET, in terms of cost per live-child born (De Sutter et al., 2002; Ombelet et al., 2005). Unfavourable outcomes of pregnancies after assisted reproduction are generally assigned to the higher incidence of twin © The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. 2633 For Permissions, please email: Department of Obstetrics and Gynaecology, University Hospital Gent and 2Department of Applied Mathematics and Informatics, Gent University, Gent, Belgium P.De Sutter et al. Materials and methods Study population The database of the Gent University Hospital Infertility Centre was used for the present study. There are no restrictions for patients to enter the IVF/ICSI programme in this centre, except for HIV-positive patients. Patients older than 43 years are strongly advised against entering the programme. In the period 2000–2004, 5509 IVF/ICSI cycles were performed in our centre, resulting in 1386 ongoing pregnancies and 943 births of a singleton child. All patients undergoing a first, second or third IVF or ICSI cycle between 2000 and 2004 and having obtained a singleton pregnancy after fresh SET or DET, resulting in the live birth of a child of >500 g, were included. Thus, we entered 835 patients, representing 88.5% of the total patient-population who delivered a singleton child following IVF/ICSI. All patients included enjoyed equal obstetric care, irrespective of assisted reproductive method or number of embryos transferred. Clinical and laboratory protocols IVF and ICSI were performed according to accepted standard protocols of pituitary suppression, ovarian stimulation, oocyte retrieval, gamete handling, embryo culture techniques, embryo transfer and luteal supplementation, as was described in previous studies from our group (Laverge et al., 2001; De Sutter et al., 2003). All embryo transfers occurred at day 2 or 3 after oocyte retrieval. Patients younger than 36 years, who entered the program before 1 July 2003, were given the choice between the transfer of one (SET) or two (DET) embryos. Before that date, SET was mainly performed when the transferred embryo was of good quality, which is defined as an embryo with four or five blastomeres on day 2, seven or more blastomeres on day 7 and <20% of fragments and total absence of multinucleated blastomeres at any stage of cleavage (Van Royen et al., 1999). If no high-quality embryo was available, two embryos were transferred, if available. After 1 July 2003, legal prescriptions were followed, meaning that SET was applied at the first IVF/ ICSI attem (...truncated)