since the first child was born after in vitro fertilization ( ivf ) , more than 30 years ago , ivf and other assisted reproductive technologies ( arts ) have developed rapidly , and the accessibility to treatment has improved . the obvious goals of all such treatments are to achieve a pregnancy and subsequent birth of a healthy infant , but overall ivf pregnancies are often seen as risky [ 2 , 3 ] , mainly due to multiple gestations [ 46 ] . however , even singleton art pregnancies are associated with increased incidences of preterm birth , low birth weight , small - for - gestational - age ( sga ) infants , and obstetric complications such as preeclampsia , placental abruption , and placenta praevia [ 2 , 7 , 8 ] . the increased risks can be partly explained by maternal characteristics such as increased age   and underlying infertility , but the effects of the infertility 's etiology as a potential etiologic factor of obstetric complications and adverse neonatal outcomes have been sparsely investigated . thus , the aim of the presented study was to elucidate associations between indications for art with the incidence of adverse obstetric outcomes among art singleton pregnancies . in this cohort study concerning the outcomes of art , including ivf , intracytoplasmic sperm injection ( icsi ) , and frozen - thawed cycles , first singleton art pregnancies of 255 women were compared with spontaneous singleton pregnancies in the general population during 19962007 at the university hospital of kuopio , finland . in both groups , considered pregnancies were restricted to those that proceeded to delivery ( 22 weeks of gestation or birth weight of at least 500  g ) . in addition , pregnancies with major foetal malformations were excluded , since they carry higher risks of obstetric and neonatal complications . the study group was divided into six subgroups , based on the indication for art : anovulation 27% ( n = 68 ) , endometriosis 19% ( n = 49 ) , male factor infertility 17% ( n = 43 ) , polycystic ovary syndrome ( pcos ) 11% ( n = 27 ) , tubal factor 15% ( n = 38 ) , and unexplained infertility 12% ( n = 30 ) . the aetiology in each case was diagnosed by laparoscopy , ultrasonography , and laboratory parameters ( when appropriate ) , and the sperm of every couple was analyzed . unexplained infertility was defined as infertility lasting at least one year for which no explanatory factor was identified . preconditions for art treatment among women suffering from anovulation , pcos , and unexplained infertility were unsuccessful ovulation induction and three inseminations . the pregnancies and deliveries of the study and reference groups were handled in the same tertiary hospital , and art treatments were carried out in the same unit . the data were collected from kuopio university hospital birth register and databases of the obstetrics and fertility outpatient departments . kuopio university hospital birth register contains information systematically collected from a questionnaire completed by every woman who delivered at kuopio university hospital , with questions concerning maternal characteristics such as marital status , smoking habits , chronic illnesses , and previous pregnancies . in addition , the data were supplemented by information from the women 's case notes which they carry with them , notes made by nurses or doctors during visits to the maternity clinic , and information recorded by the midwife who took care of the birth concerning the birth and neonatal period up to the age of one week . a standard long ivf protocol with gonadotropin - releasing hormone ( gnrh ) agonists and gonadotrophins was used as previously described . in addition to cases of male factor infertility , icsi was used according to our practice in all cases of unexplained infertility when a woman had ovulated after the use of either clomifene or gonadotrophins but failed to become pregnant . if the number of oocytes retrieved was > 10 , icsi was used in half of them . deliveries at < 37 weeks of gestation were defined as premature and low birth weight ( lbw ) as < 2500  g. infants were classified as sga when their birth weight was below the 10th percentile adjusted for our population . preeclampsia was diagnosed if proteinuria exceeded 0.5  g / day and blood pressure exceeded 149/90  mm hg repeatedly , and gestational diabetes if a single abnormal value in oral glucose tolerance tests was recorded . the study was approved by the ethics committee and the institutional review board of our institution . statistically significant differences were determined using the mantel - haenszel  test , fisher 's exact test when n was < 5 , or student 's t - test , as appropriate . multivariate analysis of significant or nearly significant ( p < 0.1 ) correlations between maternal characteristics ( such as age over 35 years , primiparity , marital status , chronic illnesses , and smoking during pregnancy ) and the incidence of obstetric outcomes was based on multiple logistic regression analysis ( sas , institute inc . , cary , nc , usa , version 9.1 ) . odds ratios ( ors ) with 95% confidence intervals ( cis ) were calculated for each subgroup separately and for the pooled ivf / icsi group before and after adjustment for maternal characteristics . the mothers in the art group were older , smoked less , and were more often nulliparous and married than the mothers in the reference group . the mothers in the art group suffered more preeclampsia than those in the reference group , this being a particular problem of the women with tubal factor infertility . furthermore , the pooled study group showed a greater incidence of placenta praevia than the reference group , and in the subgroups , this was particularly the case among mothers with endometriosis and those in the male factor infertility group . after adjustment for confounding factors , preterm birth was found to be particularly a problem for women with endometriosis and those suffering from anovulation . the incidence of sga infants was increased among women in the male factor infertility and unexplained infertility subgroups . the fewest complications appeared among the art mothers who suffered from pcos or tubal factor infertility . the results of the study show that the pooled group of women with singleton art pregnancies had increased risks of preterm birth , lbw , and nicu admission , independently of age and parity , compared to spontaneously conceived women . these findings are in accordance with previous studies [ 2 , 7 ] , although contrasting results have also been presented . however , the main finding of the present study was that the art subgroups did not show a uniform pattern of adverse outcomes . the rate of preterm deliveries was fairly constantly two- to threefold higher across all except the unexplained fertility aetiological subgroups , but sga was mainly associated with couples suffering from male factor or unexplained infertility . the net effects of concomitant sga and prematurity risks in the male factor subgroup in turn resulted in the highest nicu admission rate , whereas no such risk was observed for the unexplained infertility subgroup . these results imply that the obstetric risks associated with ivf should not be pooled , and the aetiology of infertility should be accounted for when its outcomes are considered . in addition , the incidence of chronic illnesses was highest among women with infertility due to anovulation . these , and women with pcos , had more than a twofold risk of preterm birth but no increased sga risk after adjustment for confounding factors . the mean birth weight for these subgroups did not significantly differ from that of the reference group and was even somewhat higher than that of other art pregnancies . women with endometriosis had the highest risk of preterm birth  in accordance with findings of other studies [ 15 , 16]and consequently their infants had the lowest mean birth weight , but interestingly their sga risk was low , and thus their need for intensive neonatal care was comparable to that of the other art subgroups . women with tubal factor infertility had a very similar outcome pattern , although they experienced preeclampsia more often than the reference group . the male factor and unexplained infertility subgroups both had a twofold increased risk of sga , accompanied by increased prematurity risk in the former but not the latter . the nicu admission rate was subsequently highest for the male factor subgroup and lowest for the unexplained infertility subgroup . women with unexplained infertility also had significantly more placental problems such as miscarriages and abruptions than the reference group and lowest mean birth weight , when the mean gestational age was taken into account . similarly , pandian et al .   found that a group of scottish women with unexplained infertility had more preeclampsia , placental abruption , and preterm births than women in the general obstetric population . however , contrasting results have also been reported ; according to another finnish study , ivf pregnancies of women with unexplained infertility had similar outcomes to those of spontaneous pregnancies . the present study was a pilot study with a relatively small sample size with inadequate power to analyse differences between the subgroups , which would have been very interesting . nevertheless , one of the strengths was the extensive database including maternal characteristics and information on the course of pregnancy and delivery collected prospectively enabling wide adjustments for confounding factors . in conclusion , the risk of adverse outcome among art pregnancies varied significantly depending on the cause of infertility . all except the unexplained infertility ivf subgroups had a two- to threefold elevated risk of preterm birth , and the infants of women with male factor infertility had the highest ( ca . if only pooled results had been analysed , the overall sga risk would have remained unnoticed . according to our results , risks of sga were elevated for women with male factor and unexplained infertility , while women with pcos and those with tubal factor infertility had the fewest obstetric complications and the best neonatal outcomes . our results clearly show that women undergoing art are a heterogeneous group , and this should be taken into consideration both when planning ivf / icsi treatment and during antenatal care . further studies are needed to clarify the causes of the wide observed variation in adverse pregnancy outcomes .
in vitro fertilization ( ivf ) is a risk factor for pregnancy , but there have been few studies on the effect of infertility 's aetiology . 
 thus , we have assessed the role of aetiology on ivf pregnancy outcomes in a retrospective cohort study comparing the outcomes of ivf singleton pregnancies with those of spontaneous pregnancies in the general finnish population . 
 the study group consisted of 255 women with births resulting from singleton ivf pregnancies . 
 six subgroups were formed according to the following causes of infertility : anovulation ( 27% ) , endometriosis ( 19% ) , male factor ( 17% ) , tubal factor ( 15% ) , polycystic ovary syndrome ( 11% ) , and unexplained infertility ( 12% ) . 
 the reference group consisted of 26,870 naturally conceived women . 
 adjusted odds ratios ( aors ) , for confounding factors such as age and parity , were estimated using logistic regression analysis . 
 women with endometriosis and anovulation had increased risks of preterm birth ( aor 3.25 , 95% ci 1.57.1 and aor 2.1 , and 95% ci 1.04.2 , resp . ) , while women in couples with male factor infertility had a twofold risk of admission to neonatal intensive care ( aor 2.5 , 95% ci 1.25.3 ) . 
 the findings show that the aetiology of infertility influenced the obstetrics outcome , and that pooling results may obscure some increased risks among subgroups .