Journal of Assisted Reproduction and Genetics (2019) 36:2435–2445 https://doi.org/10.1007/s10815-019-01631-6 ASSISTED REPRODUCTION TECHNOLOGIES Obstetric and perinatal complications associated with assisted reproductive treatment in Spain Ana Ballesta-Castillejos1 & Juan Gomez-Salgado2,3 & Julian Rodriguez-Almagro4 & Inmaculada Ortiz-Esquinas5 & Antonio Hernández-Martínez4,5 Received: 20 July 2019 /Accepted: 8 November 2019 / Published online: 18 November 2019 # Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract Background Although most newborns conceived through assisted reproductive treatments are healthy, there are concerns about the safety of reproductive techniques and their effect on foetal/maternal well-being. Objective This study aims to describe the incidence of obstetric and perinatal complications in women undergoing assisted reproductive treatments in the Spanish Health System. Method This is a cross-sectional observational study aimed at women who have been mothers between 2013 and 2018 in Spain. The data was collected through an online survey of 42 items that was distributed through lactation associations and postpartum support groups. In the data analysis, crude odds ratios (OR) and adjusted odds ratios (AOR) were calculated, through a multivariate analysis with binary logistic regression and multinomial logistic regression. Results Five thousand nine hundred forty-two women participated, 2.3% (139) through artificial insemination and 8.2% (486) through in vitro fertilisation (IVF) techniques. Women who underwent IVF had a higher likelihood of suffering problems during pregnancy (OR = 1.71; 95% confidence intervals (95% CI), 1.37–2.13), delivery (OR = 1.43; 95% CI, 1.01–2.02), and post- partum (OR = 1.94; 95% CI, 1.40–2.69) than women with spontaneous pregnancy. No increased likelihood of neonatal problems was observed in this group except for twin pregnancy (OR = 9.17; 95% CI, 6.02–13.96) and prematurity (OR = 1.43; 95% CI, 1.01–2.02). No differences were observed between spontaneous pregnancies and those achieved by artificial insemination. Conclusions Pregnancies achieved through IVF present a higher risk of complications before, during and after delivery. However, there is no increased risk of neonatal problems except for a higher likelihood of twin pregnancy and prematurity. Keywords Reproductive techniques assisted . Fertilization in vitro . Quality of health care . Patient safety . Obstetric labour complications . Morbidity Introduction and 12% at European level [2]. The latest estimates indicate that more than 1.6 million of assisted reproduction cycles Infertility affects approximately 10–15% of the world’srepro- worldwide are carried out each year, and more than 5 million ductive age population [1], with a prevalence of between 10 children have already been born using these techniques [3]. As * Julian Rodriguez-Almagro 1 Department of Obstetrics and Gynecology, Hospital Nuestra Señora [email protected] Del Prado, 45600 Talavera de la Reina, Toledo, Spain 2 Department of Sociology, Social Work and Public Health, University Ana Ballesta-Castillejos of Huelva, 21071 Huelva, Spain [email protected] 3 Juan Gomez-Salgado Safety and Health Postgraduate Programme, Universidad Espíritu [email protected] Santo, 091650 Guayaquil, Ecuador 4 Inmaculada Ortiz-Esquinas Department of Nursing, Ciudad Real Nursing School, University of [email protected] Castilla-La Mancha, 13071 Ciudad Real, Spain Antonio Hernández-Martínez 5 Department of Obstetrics and Gynecology, Mancha-Centro Hospital, [email protected] 13600 Alcázar de San Juan, Ciudad Real, Spain 2436 J Assist Reprod Genet (2019) 36:2435–2445 a result of the advances in these techniques and a better acces- in the Spanish Health as compared with women with a spon- sibility to these services, the number of children born through taneous pregnancy. assisted reproductive techniques (ART) has continued to in- crease [4], resulting in an increase in the number of multiple pregnancies and births [5]. Material and method In 1978, the first baby conceived through artificial insem- ination, Louise Joy Brown, was born in England. Gestation Design and selection of the study subjects was considered of high risk because the mother developed pre-eclampsia and the responsible gynaecologist did not want This is a cross-sectional observational study aimed at women to risk a normal delivery and decided to perform a C-section at who have been mothers between 2013 and 2018 in Spain. The week 38 [5]. This example highlights the fact that gestations survey completion was made between January 2019 and through assisted reproductive techniques are associated with June 2019. This study has received the approval of the increased perinatal risk [5, 6]. Ethics and Clinical Research Committee of Alcázar de San Most newborns conceived through ART are healthy, but Juan, in Spain, with protocol number 92-C. these have also been associated with higher rates of adverse The participants were women over the age of 18, who obstetric and perinatal outcomes [7–9]. Concern about the understood Spanish and who agreed to fill in the question- safety of reproductive techniques and their effect on foetal/ naire. Before filling in the questionnaire, the participants had maternal well-being is growing [10]. It is well documented to read the information sheet about the purpose of the study that pregnancies achieved through ART represent a significant and give their consent to participate in it. Survey recipients increase in the risk of multiple pregnancies and adverse peri- were informed that the overall objective of the study was to natal outcomes. Some studies suggest an increased risk of pre- determine the relationship between complications that occur eclampsia, gestational hypertension, placenta praevia and di- after childbirth, the prevalence of breastfeeding and the factors abetes [6, 11–13]. An increase in the incidence of impaired that may be associated with these phenomena so that their foetal growth, premature births and frequency of intrauterine answers were not conditioned by the fact that they had re- death has been observed regarding perinatal outcomes as com- ceived a fertility treatment. After this, they were provided with pared with the average of all pregnancies [5, 14]. In addition, the necessary information to be able to complete the post-IVF pregnancies have significantly higher rates of in- questionnaire, including a brief explanation in less- duced births and C-sections [5]. technical language of each of the items surveyed. The main factors associated with these adverse outcomes Participants were told that that the questions related to were multiple pregnancies and births [15]. However, as the last pregnancy and the weight reported was expected unique embryo transfers become widespread, these figures to be before pregnancy. Participants could voluntarily decrease, but unique gestations still have a higher incidence provide an e-mail address or phone number through of adverse outcomes as compared with spontaneous pregnan- which they would be contacted in case any additional cies [16]. information related to the study was needed. Different studies conducted at European and North For the sample size estimation, the maximum modelling American levels show the current interest in the use of these criterion that requires ten events for each independent variable techniques and their success rates [17, 18]. However, studies to be included in the multivariate model has been used [20]. focusing on neonatal maternal outcomes of pregnant women We have considered, as a reference event for the sample esti- by assisted reproductive techniques are scarcer, and although mate, twin pregnancy, which amounts to around 3% of the the literature relates ART and maternal and neonatal out- general population [21]. Considering a minimum of ten inde- comes, not all of the studies consider factors such as maternal pendent variables, a minimum of 100 women with twin preg- age and other relevant variables such as obstetric clinical re- nancies would be required, representing a minimum total pop- cords [11], and the underlying cause of these results is still ulation of 3333 women under study within this scenario. being discussed. It is still not clear whether poorest perinatal For data collection, an anonymous online questionnaire outcomes are mainly due to the characteristics of the parents was designed with 42 items (30 yes/no questions and 12 mul- or whether assisted reproductive techniques are a contributing tiple answer questions) on sociodemographic variables, ob- factor in themselves [19]. stetric variables, and complications during pregnancy, deliv- It is undeniable that ART is increasingly present in society, ery and postpartum. The time needed to fill in the question- and this makes it important to know the obstetric and perinatal naire was 12–15 min. The answer options for the pathologies risks involved in order to be able to provide the best assis- were Yes and No. In the instructions, the participants were tance. For these reasons, in this study, we have considered informed of the possibility of stating No in those questions describing the incidence of obstetric and perinatal complica- that raised some doubts. The objective of this procedure was tions in women undergoing assisted reproductive treatments to avoid overstating the pathologies on the one hand, and to J Assist Reprod Genet (2019) 36:2435–2445 2437 Table 1 Sociodemographic and obstetric characteristics