Factors affecting obstetric outcome of singletons born after IVF

Antonina Sazonova 2 Karin Ka llen 1 Ann Thurin-Kjellberg 2 Ulla-Britt Wennerholm 0 Christina Bergh 2 0 Department of Obstetrics and Gynaecology, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg University, Sahlgrenska University Hospital/East , Gothenburg, Sweden 1 Department of Reproduction Epidemiology, Tornblad Institute, Institution of Clinical Sciences, Lund University , Lund, Sweden 2 Department of Obstetrics and Gynaecology, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg University, Reproductive Medicine, Sahlgrenska University Hospital , SE-413 45 Gothenburg, Sweden background: Singletons born after IVF have an adverse perinatal outcome when compared with singletons in the general population. This study investigates maternal characteristics and IVF- treatment-related variables, for a possible influence on obstetric outcomes. methods: Data from all IVF clinics in Sweden, including all IVF singletons born after fresh treatment cycles and own oocytes during 2002 - 2006, were included (n 8941) and cross-linked with the Swedish Medical Birth Registry. Four major outcomes were investigated: very preterm birth (,32 weeks), small for gestational age (SGA), placenta previa and placental abruption. Maternal characteristics (age, parity, BMI, smoking and years of infertility) and treatment-related variables (number of oocytes retrieved, number of embryo culture days, number of transferred and cryopreserved embryos, 'vanishing twin') were investigated for independent association with the four selected outcomes. Adjusted odds ratios (AORs) were calculated by logistic regression. results: Primiparity, smoking, BMI and 'vanishing twin' were associated with an increased risk of very preterm birth. Maternal age, primiparity, smoking, BMI and years of infertility were associated with an increased risk of SGA. Maternal age and blastocyst transfer were associated with an increased risk, and primiparity with a decreased risk, of placenta previa. Smoking was significantly associated with placental abruption. conclusions: In singletons born after fresh IVF, certain maternal characteristics and the number of embryos transferred, when there was a 'vanishing twin' affected the obstetric outcome negatively. An increased rate of placenta previa was observed after blastocyst transfer. The results support the use of single embryo transfer and indicate that lifestyle factors are important for obstetric outcome. Introduction Improved perinatal outcome for children born after IVF has been shown in recent studies (Kallen et al., 2010a; Sazonova et al., 2011). In Sweden, this improvement can be attributed, to a certain extent, to single embryo transfer (SET) and thus lower rates of multiple births (Thurin et al., 2004; Thurin-Kjellberg et al., 2006; Kallen et al., 2010a; Sazonova et al., 2011). The increased risks for adverse obstetric outcome in IVF pregnancies cannot, however, be explained entirely by the high incidence of multiple births. In numerous previous studies, it has been demonstrated that not only children in multiple births but also singletons after IVF have a poorer outcome, compared with singletons in the general population (Klemetti et al., 2002, 2006; Helmerhorst et al., 2004; Jackson et al., 2004; McDonald et al., 2009; McGovern et al., 2004; Schieve et al., 2004, 2007). Even after adjustments for maternal factors such as age, parity, duration of infertility, smoking and BMI, known to influence the outcome, significantly higher rates of preterm delivery and low birthweight (LBW) were observed for IVF singletons (Bergh et al., 1999; Sazonova et al., 2011). The cause of this increased risk is not fully understood, but for safety reasons it is of utmost importance to elucidate this question. It has been discussed that the hormonal stimulation in itself and also the in vitro culture could be an explanation. An intriguing finding was that singletons born after the vanishing of one gestational sac have a less favourable obstetric outcome than singletons where only one sac was identified from the outset (Pinborg et al., 2007). Obstetric complications, such as preeclampsia, placental abruption and placenta previa, also occur more frequently in IVF pregnancies, even when only singleton pregnancies are compared with pregnancies after spontaneous conception (Jackson et al., 2004; Kallen et al., 2005a; Shevell et al., 2005; Romundstad et al., 2006; Schieve et al., 2007; Healy et al., 2010; Kallen et al., 2010a) and irrespective of SET or double embryo transfer (DET) (Sazonova et al., 2011). The aim of this study was to investigate maternal and IVF-treatment-related variables, for possible influence on obstetric outcomes in IVF singletons. Materials and Methods Data were collected from all IVF clinics in Sweden, both public and private, for all IVF treatments during the years 2002 2006. Data collected from the IVF clinics included: mother identification, type of IVF treatment (fresh, frozen, IVF, ICSI, ejaculated sperm, epididymal sperm and testicular sperm), donated/own oocytes, number of oocytes retrieved, cleavage stage transfer, blastocyst stage transfer, date of embryo transfer, number of embryos transferred, number of frozen embryos, number of gestational sacs at ultrasound and date for ultrasound, date of delivery and number of children born. All reported IVF singletons from fresh cycles using the couples own gametes were included. Singletons were grouped according to embryo transfer characteristics: elective SET (eSET), non-eSET, DET resulting in one sac and DET resulting in more than one sac, so-called vanishing twin. This subdivision was done from a clinical perspective and on the basis of a discussion in recent years concerning a possible difference in outcome for singletons depending on the number of embryos transferred. eSET was defined as transfer of one fresh embryo, when in the same treatment cycle, at least one embryo was cryopreserved. Non-eSET was defined as fresh cycles when one embryo was transferred and no embryos were cryopreserved. In Sweden, IVF is both publicly and privately funded. Publicly funded IVF is offered to childless couples after investigation, which is performed after at least 1 year of infertility and if no other treatment is considered suitable. Certain age limits exist, usually 40 years for women. Exact rules differ somewhat between different regions. Up to three subsidized cycles with fresh embryos are offered in most regions. After achieving a live birth, no more publicly funded cycles are offered. Using each individuals unique personal identity number, the data from the IVF clinics were cross-linked with the Swedish Medical Birth Registry (National Board of Health and Welfare, 2003) from which obstetric outcomes were retrieved. The Swedish Medical Birth Registry has been found to have high validity and includes virtually all deliveries in Sweden (Cnattingius et al., 1990, National Board of Health and We (...truncated)