View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by SZTE Publicatio Repozitórium - SZTE - Repository of Publications Acta Obstet Gynecol Scand 2003: 82: 850--856 Copyright # Acta Obstet Gynecol Scand 2003 Printed in Denmark. All rights reserved Acta Obstetricia et Gynecologica Scandinavica ISSN 0001-6349 ORIGINAL ARTICLE Obstetric and neonatal risk of pregnancies after assisted reproductive technology: a matched control study 1 2 1 3 1 1 ZOLTA´ N KOZINSZKY ,JA´ NOS ZA´ DORI ,HAJNALKA ORVOS ,MA´ RTA KATONA ,ATTILA PA´ L AND LA´ SZLO´ KOVA´ CS From the 1Department of Obstetrics and Gynecology, the 2Center for Assisted Reproduction, Kaa´li Institute, and the 3Department of Pediatrics, University of Szeged, Albert Szent-Gyo¨rgyi Medical and Pharmacological Center, Szeged, Hungary Acta Obstet Gynecol Scand 2003; 82: 850–856. # Acta Obstet Gynecol Scand 82 2003 Background. The aim of the study was to evaluate the obstetric and neonatal outcome of pregnancies after assisted reproduction technology (ART) in comparison with matched controls from spontaneous pregnancies. Methods. A total of 12 920 deliveries at the Department of Obstetrics and Gynecology, University of Szeged, from 1 January 1995 to 31 December 2001 were subjected to retro- spective analysis. Two hundred and eighty-four singleton, 75 twin and 17 triplet pregnan- cies after ovulation induction (n ¼ 114; 30.3%), intrauterine insemination (n ¼ 33; 8.8%) and in vitro fertilization (n ¼ 229; 60.9%) were evaluated. The pregnancy outcome of the singleton and twin pregnancies was compared with that for controls matched with regard to age, gravidity and parity and previous obstetric outcome after spontaneous pregnan- cies. Results. Twenty-four percent of the assisted reproductive pregnancies were multiple pregnancies. The incidences of singleton intrauterine growth retardation (IUGR) and preterm birth were reasonably similar to those among the controls (IUGR: 6.3% vs. 4.2%; preterm births: 13.0% vs. 9.9%, for the cases and the controls, respectively). As compared with the controls, there was an increased incidence of cesarean section among the singleton (41.2% vs. 34.5%, p ¼ 0.12; OR 1.33; 95% CI 0.95–1.87) and twin assisted reproduction pregnancies (66.7% vs. 60.0%), but without significant differences. Conclusions. Increased obstetric risk could be observed concerning threatened preterm delivery and cesarean section rate in the study group. The perinatal outcome of singleton and twin pregnancies following assisted reproductive techniques is comparable with that of spontaneously conceived, matched pregnancies. Key words: assisted reproduction; perinatal outcome; matched control study Submitted 13 January, 2003 Accepted 04 March, 2003 The incidence of infertility is increasing world- Reports on ART pregnancy outcome indicate wide (1) and a large range of assisted reproduc- that the frequencies of operative delivery, preterm tive technology (ART) methods is available for birth, low birthweight and perinatal death are all the treatment of impaired fertility (2). greater than the general population-based incidences (3,4). Many previous publications have stressed the Abbreviations: higher incidences of prematurity, low birth- ART: assisted reproductive technology; IUGR: intrauterine weight, intrauterine growth retardation (IUGR), growth retardation; IVF-ET: in vitro fertilization–embryo cesarean section, congenital anomalies, placenta transfer; NICU: neonatal intensive care unit; SPSS: Statistical Package for Social Sciences; OR: odds ratio; CI: confidence previa and pregnancy-induced hypertension after interval. in vitro fertilization–embryo transfer (IVF-ET) # Acta Obstet Gynecol Scand 82 (2003) Obstetric and neonatal risk after ART 851 (5–11). Matched controls have also yielded calculated by adding 14 days to the day of ovum adverse results with regard to IVF-ET (8,12–15) pick-up for the IVF-ET group, and by adding and ART (16,17). 14 days to the presumed day of ovulation for the The present retrospective study was designed ovulation induction group. For the spontaneous to compare the perinatal data in singleton and conception group, the first day of the last twin pregnancies resulting from ART with menstrual period was used. IUGR was defined matched naturally conceived pregnancies and to as a birthweight below the 10th percentile for the determine the obstetric risk in triplet pregnancies gestational age, according to the sex and to the following ART. Hungarian data (18). Congenital malformations were diagnosed by Materials and methods the same experienced neonatologist on the basis of physical examination, chest, abdominal or A retrospective analysis of 12 920 pregnancies skull X-ray, and ultrasonography (cardiac, that occurred between 1 January 1995 and abdominal, head, etc.) according to the Hungar- 31 December 2001 was performed. The study ian registration of congenital anomalies (19). group consisted of 376 (2.9% of the total) live Birth defects were classified as major congenital pregnancies (284 singleton þ 75 twin þ 17 triplet malformations (e.g. congenital heart defects, gas- pregnancies) resulting from various ART proced- trointestinal malformations, genitourinary tract ures at the Department of Obstetrics and Gyne- malformations, bone malformations, etc.) or as cology, University of Szeged. The rate of multiple minor anomalies (e.g. hypertelorism, low-set ears, births (24.5%) is higher among ART pregnancies polydactylia, etc.). Babies with major congenital than among naturally conceived pregnancies or structural malformations were admitted to the (1.45%) in our department. Details of the preg- neonatal intensive care unit (NICU) for further nancies and deliveries were obtained from med- observation and treatment. ical records. The distribution of the antecedents of The following antepartum complications the singleton pregnancies was IVF-ET 180, ovu- were examined: gestational diabetes mellitus, lation induction 77 and intrauterine insemination preeclamptic toxemia, pregnancy-induced hyper- 27; and that of the twin pregnancies IVF-ET 37, tension, myoma, placenta previa, malpresenta- ovulation induction 32 and intrauterine insem- tion, malposition, threatened premature labor, ination 6. The matched control group in which placental abruption, premature rupture of the conception was spontaneous was selected on the membranes, intrauterine infection, meconium- basis of similarities in parity, gravidity, maternal stained amniotic fluid, oligohydramnios and age and previous obstetric outcome with regard polyhydramnios. The following intrapartum to singletons and twins. The ratio between the characteristics were assessed: cesarean section, patients and the controls was 1 : 1. fetal distress, cephalopelvic disproportion, Potential controls were selected by systemati- retained placenta, prolonged labor and prolonged cally scanning the obstetric register for women of second stage. suitable age, parity and date of delivery. The con- Statistical analysis was performed with the trol subjects were the next parturients on the list Statistical Package for Social Sciences (SPSS) fullfilling the matching criteria. The relevant med- 8.0 Windows program (SPSS Inc., Chicago, IL, ical records were then retrieved and checked for USA). Univariate comparisons between singleton the other matching criteria. When several patients pregnancies were assessed by the paired t-test and could serve as potential controls, the patient best the w2-test for continuous and categorical vari- matching with regard to maternal height and ables, respectively. Odds ratios (ORs) and 95% weight was chosen. The matching criteria of the confidence intervals (CIs) were also calculated for ART and control women were entered into a form categorical variables. Comparisons between twin and all forms were reviewed by one investigator groups were performed by the Mann–Whitney for approval. To avoid any selection bias, the U-test and the Wilcoxon test for categorical and results of potential control pregnancies remained ordinal variables. The significance level was set at unread before the choice was made. 5%, two-tailed. The triplet pregnancies (IVF-ET 12; ovulation Prematurity was defined as delivery before induction 5) were analyzed without spontaneous 37 weeks of gestation. Intrauterine infection was controls filling the distribution of selected peri- considered to exist when the mother had fever natal characteristics. and leukocytosis and the fetus had tachycardia Deliveries were defined as all liveborn or still- and postnatal symptoms of neonatal infection, born babies delivered after 24 completed weeks e.g. tachypnoe, tachycardia, an oxygen demand of gestation. The gestational age at birth was and positive culturing. Fetal distress was defined # Acta Obstet Gynecol Scand 82 (2003) 852 L. Kova´cs et al. as the presence of repetitive late decelerations, controls. Cephalopelvic disproportion, prolonged severe variable decelerations and persistent fetal labor and prolonged second stage exhibited the tachycardia. Placenta previa was defined as a same frequencies in the two groups. placenta covering the internal os of the cervix Data on the neonatal outcome for the singleton and requiring delivery by cesarean section. pregnancies and the matched controls are listed in Table V. Although the gestational age and Results birthweight were lower, while the rates of preterm birth and IUGR were higher among the induced Table I presents the pattern of pregnancy compli- group, the differences