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Intrapartum Interventions for Singleton Pregnancies Arising From Assisted Reproductive Technologies

      Abstract

      Objective

      : To assess whether singleton pregnancies conceived by assisted reproductive technology (ART) are associated with an increased use of intrapartum interventions when compared with spontaneous singleton pregnancies.

      Methods

      In total, 1327 ART pregnancies and 5222 spontaneous pregnancies during the period 2004 to 2008 were extracted from BORN (Better Outcomes Registry & Network) Ontario’s information system. The incidences of common intrapartum interventions were compared, and different classification systems for Caesarean section were used to compare the indications for these between singleton pregnancies following ART with or without intracytoplasmic sperm injection and singleton spontaneously conceived pregnancies.

      Results

      Compared with spontaneous singleton pregnancies, the ART group had increased incidences of internal electronic fetal monitoring (OR 1.60; 95% CI 1.37 to 1.87), artificial rupture of membranes (OR 1.39; 95% CI 1.17 to 1.66), oxytocin augmentation of labour (OR 1.51; 95% CI 1.28 to 1.77), induction of labour (OR 1.31; 95% CI 1.14 to 1.50), and Caesarean section (OR 1.40; 95% CI 1.24 to 1.60).

      Conclusion

      Singleton pregnancies resulting from ART were associated with more frequent use of several intrapartum interventions, including Caesarean section.

      Résumé

      Objectif

      Déterminer si les grossesses monofœtales attribuables aux techniques de procréation assistée (TPA) sont associées à une hausse du recours à des interventions intrapartum, par comparaison avec les grossesses monofœtales spontanées.

      Méthodes

      Au total, 1 327 grossesses attribuables aux TPA et 5 222 grossesses spontanées s’étant déroulées au cours de la période 2004-2008 ont été extraites du système informatique BORN (Better Outcomes Registry & Network ou, en français, « bons résultats dès la naissance ») de l’Ontario. L’incidence des interventions intrapartum courantes a été comparée et divers systèmes de classification des césariennes ont été utilisés pour en comparer les indications dans le cadre des grossesses monofœtales attribuables aux TPA (avec ou sans injection intracytoplasmique d’un spermatozoïde) et dans le cadre des grossesses monofœtales spontanées.

      Résultats

      Par comparaison avec le groupe « spontanée », le groupe « TPA » présentait une hausse de l’incidence du monitorage fœtal électronique interne (RC, 1,60; IC à 95 %, 1,37 - 1,87), de la rupture artificielle des membranes (RC, 1,39; IC à 95 %, 1,17 - 1,66), de l’accélération du travail au moyen d’oxytocine (RC, 1,51; IC à 95 %, 1,28 - 1,77), du déclenchement du travail (RC, 1,31; IC à 95 %, 1,14 - 1,50) et de la césarienne (RC, 1,40; IC à 95 %, 1,24 - 1,60).

      Conclusion

      Les grossesses monofœtales attribuables aux TPA ont été associées à une utilisation plus fréquente de plusieurs interventions intrapartum, dont la césarienne.

      Key Words

      ABBREVIATIONS

      ARM
      artificial rupture of membranes
      ART
      assisted reproductive technology
      BORN
      Better Outcomes Registry & Network
      EFM
      electronic fetal monitoring

      INTRODUCTION

      Assisted reproductive technology has been increasingly used for subfertility problems since the first “test-tube” baby was born in 1978.
      • Kamel R.M.
      Assisted reproductive technology after the birth of Louise Brown.
      Worldwide, more than five million babies have been born with ART.
      • Kamel R.M.
      Assisted reproductive technology after the birth of Louise Brown.
      The safety of ART in terms of its effect on maternal, fetal, and infant outcomes has been examined in a number of recent studies.
      • Jackson R.A.
      • Gibson K.A.
      • Wu Y.W.
      • Croughan M.S.
      Perinatal outcomes in singletons following in vitro fertilization: a meta-analysis.
      • Anonymous
      Implementation of the Fertility Clinic Success Rate and Certification Act of 1992: a model program for the certification of embryo laboratories.
      • Maman E.
      • Lunenfeld E.
      • Levy A.
      • Vardi H.
      • Potashnik G.
      Obstetric outcome of singleton pregnancies conceived by in vitro fertilization and ovulation induction compared with those conceived spontaneously.
      • Mukhopadhaya N.
      • Arulkumaran S.
      Reproductive outcomes after in-vitro fertilization.
      Pregnancies achieved with ART, including singleton pregnancies, appear to have an increased risk of obstetric and perinatal complications,
      • Shevell T.
      • Malone F.D.
      • Vidaver J.
      • Porter T.F.
      • Luthy D.A.
      • Comstock C.H.
      • et al.
      Assisted reproductive technology and pregnancy outcome.
      indicating a need for closer surveillance.
      • Allen V.M.
      • Wilson R.D.
      Genetics Committee of the Society of Obstetricians and Gynaecologists of Canada and Reproductive Endocrinology Infertility Committee of the Society of Obstetricians and Gynaecologists of Canada. Pregnancy outcomes after assisted reproductive technology.
      However, there is a lack of evidence regarding the effect of intrapartum interventions used in pregnancies achieved with ART compared with those resulting from spontaneous conception. It is important that this issue be explored. Previous studies have estimated the risk of Caesarean section or induction of labour in ART pregnancies, but few have investigated the roles of other potentially confounding intrapartum interventions, such as fetal surveillance, pain relief, or augmentation of labour, owing to insufficient information in their data sets.
      • Shevell T.
      • Malone F.D.
      • Vidaver J.
      • Porter T.F.
      • Luthy D.A.
      • Comstock C.H.
      • et al.
      Assisted reproductive technology and pregnancy outcome.
      • Kozinszky Z.
      • Zadori J.
      • Orvos H.
      • Katona M.
      • Pal A.
      • Kovacs L.
      Risk of cesarean section in singleton pregnancies after assisted reproductive techniques.
      • Sutcliffe A.G.
      • Ludwig M.
      Outcome of assisted reproduction.
      Second, although pregnancies achieved with ART are at an increased risk of delivery by Caesarean section,
      • Maman E.
      • Lunenfeld E.
      • Levy A.
      • Vardi H.
      • Potashnik G.
      Obstetric outcome of singleton pregnancies conceived by in vitro fertilization and ovulation induction compared with those conceived spontaneously.
      • Sutcliffe A.G.
      • Ludwig M.
      Outcome of assisted reproduction.
      previous studies have not been able to determine what some of the factors driving this risk were. It has been suggested that maternal request or physician preference may be contributing to the increased risk, although no data have been available to support this speculation.
      • Mukhopadhaya N.
      • Arulkumaran S.
      Reproductive outcomes after in-vitro fertilization.
      The objective of this study was to investigate whether singleton pregnancies resulting from ART are associated with an increased risk of intrapartum interventions because of adverse outcomes when compared with singleton pregnancies conceived spontaneously.

      METHODS

      Data included in this study were extracted from BORN Ontario’s database, a web-based information system with manual data entry and uploads from electronic medical records. The database contained perinatal data on hospital births in Ontario from most hospitals and midwifery practice groups, representing between 85% and 98% of total births in Ontario for the period 2004 to 2008. Prenatal information includes maternal demographic characteristics, maternal health behaviours, pre-existing maternal health conditions, types of assisted reproductive technologies, pregnancy complications, intrapartum complications and interventions, and maternal and neonatal outcomes.
      The study included pregnant women who delivered a single live baby with a birth weight of 500g or greater or a gestational age of 20 weeks or greater during the period from March 1, 2004, to December 31, 2008. Excluded were women who had stillbirths (intrauterine fetal death occurring at20 weeks) and women with pre-existing maternal health problems (chronic hypertension, type 1 and type 2 diabetes, heart disease, thyroid disease, systemic lupus erythematosus, alcohol dependence syndrome, asthma, HIV, hepatitis B, or psychiatric disorders).
      The ART group consisted of singleton pregnancies conceived through ART defined as vitro fertilization with or without intracytoplasmic sperm injection. For each ART case, four singleton pregnancies conceived spontaneously were matched by maternal age (within 2 years), parity (nulliparous and multiparous), and hospital level (small community, large community, or teaching hospital) at delivery and randomly selected. A total of 1327 eligible ART pregnancies and 5222 matched spontaneous pregnancies were identified in the BORN Ontario’s database for the study period.
      Between ART pregnancies and spontaneous pregnancies, we examined the differences in fetal surveillance during labour and delivery (external EFM, or internal EFM), augmentation of labour (artificial rupture of membranes, or use of oxytocin or prostaglandin, which was recorded only if labour type was spontaneous), pain relief (epidural analgesia), induction of labour, and Caesarean section.
      To explore the reasons for the differences in Caesarean section between the two study groups, we used the Robson classification system (Table 1), which classifies women in 10 categories according to parity, course of labour and delivery, gestation, previous record of pregnancy, presence of a uterine scar, and type of pregnancy (single or multiple); these categories are mutually exclusive, totally inclusive, prospective, and clinical relevant.
      • Robson M.S.
      Classification of caesarean sections.
      • Robson M.S.
      Can we reduce the caesarean section rate?.
      In addition, the major indications for Caesarean section were further examined using a modified causal model that includes decision rules for assigning multiple indications to a single category (Table 2).
      • Robson M.S.
      Classification of caesarean sections.
      Table 1Description of Robson classification system for women with Caesrean section
      • Robson M.S.
      Classification of caesarean sections.
      • Robson M.S.
      Can we reduce the caesarean section rate?.
      1. Nulliparous women, single cephalic pregnancy, at greater than or equal to 37 weeks’ gestation, spontaneous labour
      2. Nulliparous women, single cephalic pregnancy, at greater than or equal to 37 weeks’ gestation, either had labour induced or were delivered by Caesarean section before labour
      3. Multiparous women, without a previous uterine scar, single cephalic pregnancy, at greater than or equal to 37 weeks, spontaneous labour
      4. Multiparous women, without a previous uterine scar, single cephalic pregnancy at greater than or equal to 37 weeks’ gestation, either had labour induced or were delivered by Caesarean section
      5. All multiparous women, with at least one previous uterine scar, single cephalic pregnancy, at greater than or equal to 37 weeks’ gestation
      6. All nulliparous women, single breech pregnancy
      7. All multiparous women, single breech pregnancy, including women with previous uterine scars
      8. All women with multiple pregnancies, including women with previous uterine scars
      9. All women with a single pregnancy with a transverse or oblique lie, including women with previous uterine scars
      10. All women with a single cephalic pregnancy at less than 37 weeks’ gestation, including women with previous uterine scars
      Table 2Modified causal model with decision rules for major indication for Caesarean section with single and multiple diagnoses
      • Robson M.S.
      Classification of caesarean sections.
      1. Cases having the diagnosis of maternal request were assigned to diagnostic “maternal request” (the diagnosis of maternal diagnosis was defined as Caesarean section required by mother without any medical indications)
      2. Cases having the diagnosis of placenta previa were assigned to diagnostic “placenta previa” that had to be delivered by Caesarean section
      3. All multiple-diagnosis deliveries in which one of the diagnoses was a previous Caesarean section were assigned to the diagnostic class “previous Caesarean section”
      4. Cases having a diagnosis of breech presentation with either dystocia or fetal distress or both were assigned to the diagnostic class ‘breech.’ (This recognized breech presentation as a cause of both dystocia and fetal distress)
      5. Cases having the diagnoses dystocia and fetal distress were assigned to the diagnostic “dystocia” (This recognized dystocia as a cause of fetal distress)
      6. When none of the other five diagnoses appeared in the birth information, cases were assigned to the diagnostic class” fetal distress”
      7. Cases that did not fall into one of the above four classes were classified as “other”
      We used chi-square tests to compare maternal and neonatal baseline characteristics between the two study groups. We then compared the frequencies of intrapartum interventions and the indications for Caesarean section using the Robson classification system and modified causal model. Adjusted odds ratios and 95% confidence intervals were estimated using conditional logistic regression models. All analyses were performed using SAS software version 9.1 (SAS Inc., Cary, NC).
      The study was approved by the Ottawa Hospital Research Ethics Board.

      RESULTS

      Baseline maternal and neonatal characteristics of the two study groups are compared in Table 3. Mothers in the ART group were more likely to be non-smokers, to have initiated prenatal care in the first trimester, and to come from higher income neighbourhoods. Rates of preterm birth, low birth weight, and macrosomia were higher in the ART group than the spontaneous conception group.
      Table 3Maternal and neonatal characteristics of the study population
      Characteristic
      The following characteristics had missing values: smoking (488, 7.45%); initiating prenatal care in the first trimester (1564; 23.88%); birth defect (2152, 32.86%); and previous Caesarean section (34, 0.52%)
      ART group
      Exposed members matched 1:4 with non-exposed members; matching rate, 99.10%
      n=1327 n (%)
      Non-exposed group n=5222 n (%)P
      Maternal age, years0.97
      <2518 (1.36)72 (1.38)
       25 to 29141 (10.63)564 (10.80)
       30 to 34482 (36.32)1928 (36.92)
      35686 (51.70)2658 (50.90)
      Smoking during pregnancy<0.001
       No1176 (95.69)4475 (92.61)
       Yes53 (4.31)357 (7.39)
      Initiating prenatal care in the first trimester<0.001
       Yes952 (90.93)3235 (82.15)
       No95 (9.07)703 (17.85)
      Delivery hospital level0.93
       Small community116 (8.75)464 (8.89)
       Large community832 (62.79)3295 (63.16)
       Teaching hospital377 (28.45)1458 (27.95)
      Parity0.90
       Nulliparous938 (70.69)3700 (70.85)
       Multiparous389 (29.13)1522 (29.15)
      Average neighbourhood income, quintile<0.001
      <20%163 (12.84)1105 (21.80)
       20% to 40%235 (18.85)1033 (20.38)
       40% to 60%281 (22.14)986 (19.46)
       60% to 80%290 (22.85)978 (19.30)
      >80%300 (23.64)966 (19.06)
      Previous Caesarean section0.13
       Yes119 (9.00)402 (7.74)
       No1203 (91.00)4791 (92.26)
      Birth defects0.76
       None809 (97.82)3486 (97.65)
       At least one abnormality18 (2.18)84 (2.35)
      Infant sex0.36
       Male673 (50.72)2721 (52.13)
       Female654 (49.28)2499 (47.87)
      Birth weight, g<0.001
      <150028 (2.11)53 (1.01)
       1500 to 249977 (5.80)226 (4.33)
       2500 to 39991073 (80.86)4397 (84.20)
      4000149 (11.23)546 (10.46)
      Gestational age at birth, weeks<0.001
      <37144 (10.85)345 (6.62)
      371183 (89.15)4863 (93.38)
      * The following characteristics had missing values: smoking (488, 7.45%); initiating prenatal care in the first trimester (1564; 23.88%); birth defect (2152, 32.86%); and previous Caesarean section (34, 0.52%)
      Exposed members matched 1:4 with non-exposed members; matching rate, 99.10%
      Intrapartum interventions in the two study groups are compared in Table 4. High rates of EFM, induction of labour, and Caesarean section were found in both groups. Rates of induction of labour, augmentation of labour with ARM, oxytocin, or both, and internal EFM were significantly higher in the ART group than in the spontaneous conception group. The rate of Caesarean section was 1.4 times higher in the ART group (42.6% vs. 34.2%; OR 1.4, 95% CI 1.2 to 1.6), and the increased risk of Caesarean section in the ART group was seen whether it was performed before labour, during the first stage of labour, or during the second stage of labour. However, no significant difference between the two groups was found in the rate of Caesarean section in women who had induction of labour (Table 4).
      Table 4Comparison of the use of intrapartum interventions between ART pregnancies and spontaneous pregnancies
      Intervention
      The following interventions had missing values: fetal monitoring (263, 4.02%); augmentation (2006, 30.63%); epidural use (92, 1.40%); induction of labour (14, 0.21%); Caesarean delivery (5, 0.08%); Caesarean delivery for women who are induced (1, 0.05%); before labour (17, 0.26%); during first or second stages of labour (1083, 16.55%)
      ART group n=1327 n (%)Non-exposed group n=5222 n (%)Adjusted OR (95% CI)
      OR and 95% CI adjusted for initiating time of prenatal care, smoking during the pregnancy, average neighbourhood income, gestational age at birth, and birth weight
      Fetal monitoring
       Intrapartum EFM1002 (77.55)3865 (77.39)1.00 (0.86 to 1.17)
       External EFM892 (69.04)3652 (73.13)0.81 (0.71 to 0.93)
       Internal EFM320 (24.77)862 (17.26)1.60 (1.37 to 1.87)
      Augmentation
       ARM242 (29.44)877 (23.57)1.39 (1.17 to 1.66)
       Oxytocin359 (43.67)1267 (34.05)1.51 (1.28 to 1.77)
       ARM and oxytocin472 (57.42)1719 (46.20)1.61 (1.37 to 1.89)
       Prostaglandin15 (1.82)57 (1.53)1.36 (0.75 to 2.46)
       Epidural use784 (59.67)3037 (59.05)1.04 (0.91 to 1.18)
       Induction of labour424 (32.10)1404 (26.93)1.31 (1.14 to 1.50)
       Caesarean section566 (42.65)1786 (34.22)1.40 (1.24 to 1.60)
        In women who were induced145 (34.20)452 (32.22)1.09 (0.85 to 1.39)
        Before labour254 (19.23)686 (13.18)1.50 (1.27 to 1.77)
        During first stage of labour168 (15.91)529 (12.01)1.31 (1.08 to 1.60)
        During second stage of labour67 (6.34)215 (4.88)1.38 (1.03 to 1.85)
      * The following interventions had missing values: fetal monitoring (263, 4.02%); augmentation (2006, 30.63%); epidural use (92, 1.40%); induction of labour (14, 0.21%); Caesarean delivery (5, 0.08%); Caesarean delivery for women who are induced (1, 0.05%); before labour (17, 0.26%); during first or second stages of labour (1083, 16.55%)
      OR and 95% CI adjusted for initiating time of prenatal care, smoking during the pregnancy, average neighbourhood income, gestational age at birth, and birth weight
      Analysis according to the Robson classification showed that the risk of Caesarean section was significantly increased in women who conceived after ART in the following categories:
      • 1.
        nulliparous, single cephalic presentation, ≥ 37 weeks, in spontaneous labour;
      • 2.
        multiparous, single cephalic presentation, ≥ 37 weeks (excluding previous Caesarean section), in spontaneous labour; and
      • 3.
        all single cephalic presentations, ≤ 36 weeks (including previous Caesarean section), but among no other categories (Table 5).
        Table 5Comparison of Caesarean section rate between the two study groups based on Robson criteria
        10 categories by Robson criteriaART group n (%)Non-exposed group n (%)Adjusted OR (95%) CI
        1. Nulliparous, single cephalic, ≥ 37 weeks, in spontaneous labour107 (25.91)409 (20.77)1.31 (1.02 to 1.69)
        2. Nulliparous, single cephalic, ≥ 37 weeks, induced or CS before labour185 (51.25)522 (44.62)1.26 (0.98 to 1.62)
        3. Multiparous (excluding prev. CS), single cephalic, ≥ 37 weeks, in spontaneous labour12 (9.76)37 (5.35)2.56 (1.24 to 5.28)
        4. Multiparous (excluding prev. CS), single cephalic, ≥ 37 weeks, induced or CS before labour18 (20.69)50 (17.79)1.24 (0.65 to 2.36)
        5. Previous CS, single cephalic, ≥ 37 weeks84 (89.36)274 (86.98)1.10 (0.51 to 2.36)
        6. All nulliparous breeches55 (94.83)201 (97.10)0.44 (0.09 to 2.12)
        7. All multiparous breeches (including prev. CS)16 (94.12)53 (92.98)0.73 (0.03 to 19.92)
        8. All multiple pregnancies (including prev. CS)00N/A
        9. All abnormal lies (including prev. CS)<613 (68.42)NA
        10. All single cephalic, ≤ 36 weeks (including prev. CS)50 (42.74)84 (30.55)1.92 (1.18 to 3.12)
        Adjusted variables include first trimester visit, smoking during the pregnancy, average neighbourhood income, and birth weight.
        Gestational age at birth was stratified as37 or<37 based on Robson criteria
      Results of the modified causal model analysis showed that in women who conceived with ART, the odds of Caesarean section were significantly increased only in the maternal request group and in women with placenta previa, but not in women with other indications for Caesarean section (Table 6).
      Table 6Analysis of the association between ART and Caesarean section by major indications for Caesarean section
      Indication
      Classification for indications of Caesarean section based on modified causal model with decision rules for Caesarean section with multiple diagnosis. 110 (4.68%) of the values were missing.
      ART group n=545 n (%)Non-exposed group n=1697 n (%)Adjusted OR (95% CI)
      OR and 95% CI adjusted for initiating time of prenatal care, smoking during the pregnancy, average neighbourhood income, gestational age at birth, and birth weight
      Maternal request25 (4.59)59 (3.48)1.69 (1.02 to 2.81)
      Placenta previa29 (5.32)36 (2.12)2.34 (1.38 to 3.98)
      Previous Caesarean section100 (18.35)310 (18.27)1.04 (0.80 to 1.35)
      Breech75 (13.76)221 (13.02)0.96 (0.71 to 1.29)
      Non-progressive labour/descent/dystocia169 (31.01)615 (36.24)0.84 (0.67 to 1.05)
      Non-reassuring fetal status81 (14.86)250 (14.73)0.99 (0.74 to 1.32)
      Others66 (12.11)206 (12.14)0.89 (0.65 to 1.22)
      * Classification for indications of Caesarean section based on modified causal model with decision rules for Caesarean section with multiple diagnosis. 110 (4.68%) of the values were missing.
      OR and 95% CI adjusted for initiating time of prenatal care, smoking during the pregnancy, average neighbourhood income, gestational age at birth, and birth weight

      DISCUSSION

      Singleton pregnancies conceived by ART were associated with an increase in rates of several intrapartum interventions, including internal EFM, ARM, and oxytocin for augmentation of labour, induction of labour, and Caesarean section. The higher incidence of Caesarean section in ART pregnancies, compared with pregnancies conceived spontaneously was observed at all stages of labour (before labour and during both the first and second stages of labour) but not in women who had labour induced, after adjusting for gestational age. Further analysis using the Robson system demonstrated that a significantly increased risk of Caesarean section was seen only in ART pregnancies delivered preterm and in term births after spontaneous labour at37 weeks, but not for term births before labour. Analysis by major indications for Caesarean section indicated that the increased rate of Caesarean section in the ART group was partly attributable to placenta previa and maternal request. Increased maternal age has been found to be associated with an increased rate of Caesarean section.
      • Cleary-Goldman J.
      • Malone F.D.
      • Vidaver J.
      • Ball R.H.
      • Nyberg D.A.
      • Comstock C.H.
      • et al.
      Can we reduce the caesarean section rate?.
      Higher rates of Caesarean section and intrapartum interventions may be attributed to increased maternal age, maternal request, and physician preference.
      To our knowledge, no previous research has investigated the association between pregnancies after ART and the use of EFM and augmentation of labour. We found a significant 1.6-fold increase in the use of internal EFM and a statistically significant reduction in the use of external EFM in women with ART pregnancies. The use of ARM and oxytocin for labour augmentation were also found more frequently in women with ART pregnancies. ART pregnancies are often viewed as “precious” pregnancies, and as a result may be managed differently by physicians or in accordance with maternal request.
      • Allen V.M.
      • Wilson R.D.
      Genetics Committee of the Society of Obstetricians and Gynaecologists of Canada and Reproductive Endocrinology Infertility Committee of the Society of Obstetricians and Gynaecologists of Canada. Pregnancy outcomes after assisted reproductive technology.
      The literature states that the use of intensive intrapartum interventions may more likely be related to physician preference rather than to “hard” indications, such as pregnancy complications.
      • Jackson R.A.
      • Gibson K.A.
      • Wu Y.W.
      • Croughan M.S.
      Perinatal outcomes in singletons following in vitro fertilization: a meta-analysis.
      • Mukhopadhaya N.
      • Arulkumaran S.
      Reproductive outcomes after in-vitro fertilization.
      • Shevell T.
      • Malone F.D.
      • Vidaver J.
      • Porter T.F.
      • Luthy D.A.
      • Comstock C.H.
      • et al.
      Assisted reproductive technology and pregnancy outcome.
      • Blickstein I.
      Does assisted reproduction technology, per se, increase the risk of preterm birth?.
      Rates of intrapartum interventions are also associated with the type of care provider.
      • Symon A.G.
      • Paul J.
      • Butchart M.
      • Carr V.
      • Dugard P.
      Self-rated “no-” and “low-” risk pregnancy: a comparison of outcomes for women in obstetric-led and midwife-led units in England.
      Janssen et al. found that among births in British Columbia there was a decreased likelihood of EFM and Caesarean section among planned home births with midwives compared to planned hospital births with physicians (RR for EFM 0.17; 95% CI 0.16 to 0.19; RR for Caesarean section 0.65; 95% CI 0.56 to 0.76).
      • Janssen P.A.
      • Saxell L.
      • Page L.A.
      • Klein M.C.
      • Liston R.M.
      • Lee S.K.
      Outcomes of planned home birth with registered midwife versus planned hospital birth with midwife or physician.
      In addition, obesity is commonly associated with infertility.
      • Lash M.M.
      • Armstrong A.
      Impact of obesity on women’s health.
      • Zain M.M.
      • Norman R.J.
      Impact of obesity on female fertility and fertility treatment.
      Unfortunately, maternal BMI was available from only about 25% of hospitals in BORN Ontario’s database.
      In concordance with most prior studies,
      • Kozinszky Z.
      • Zadori J.
      • Orvos H.
      • Katona M.
      • Pal A.
      • Kovacs L.
      Risk of cesarean section in singleton pregnancies after assisted reproductive techniques.
      • Källén B.
      • Finnström O.
      • Nygren K.G.
      • Otterblad Olausson P.
      • Wennerholm U.-B.
      In vitro fertilisation in Sweden: obstetric characteristics, maternal morbidity and mortality.
      • Apantaku O.
      • Chandrasekaran I.
      • Bentick B.
      Obstetric outcome of singleton pregnancies achieved with in vitro fertilisation and intracytoplasmic sperm injection: experience from a district general hospital.
      we observed an association between use of ART and an increased incidence of Caesarean section after matching for maternal age, parity, and hospital level, and after adjusting for several additional potential confounders. Most investigators have speculated that the increased incidence of Caesarean section in ART pregnancies is linked with an increase in the number of elective Caesarean sections due to pregnant women’s and obstetricians’ preferences, or to an increase in emergency Caesarean sections from suspected fetal distress.
      • Apantaku O.
      • Chandrasekaran I.
      • Bentick B.
      Obstetric outcome of singleton pregnancies achieved with in vitro fertilisation and intracytoplasmic sperm injection: experience from a district general hospital.
      However, previous studies have not been able to investigate further the underlying reasons for this association because of the limited availability of information on indications for Caesarean section.
      Using the Robson classification system, we found no significant difference in Caesarean section rates in women with cephalic presentation at37 weeks when labour was induced or Caesarean section performed before labour. The analysis from both the Robson classification system and the modified causal model for the indications for Caesarean section showed that a history of Caesarean section and breech presentation were not responsible for the observed increase in Caesarean section rate in the ART group. Rather, it showed that a higher incidence of Caesarean section was observed in women with preterm delivery in the ART group (42.74% in the ART group vs. 30.55% in control subjects). The higher rate of placenta previa in ART pregnancies (5.3% vs. 2.1%) might account for part of this increase, given the results of the analysis of major indications for Caesarean section by the modified causal model. These results were also consistent with previous studies in which ART pregnancies were reported to have a higher incidence of placenta previa
      • Romundstad L.B.
      • Romundstad P.R.
      • Sunde A.
      • Von Düring V.
      • Skjaerven R.
      • Vatten L.J.
      . Increased risk of placenta previa in pregnancies following IVF/ICSI; a comparison of ART and non-ART pregnancies in the same mother.
      and preterm delivery.
      • Blickstein I.
      Does assisted reproduction technology, per se, increase the risk of preterm birth?.
      In pregnancies after spontaneous labour, analysis using the Robson classification system showed that ART pregnancies were associated with a significant increase in the Caesarean section rate in women with cephalic presentation at37 weeks when compared with control subjects. Further analysis using the modified causal model found that non-reassuring fetal status was not a contributing factor to the increased rate of Caesarean section seen with ART pregnancies. Apantaku et al. observed similar results in a study in the United Kingdom in 2008.
      • Apantaku O.
      • Chandrasekaran I.
      • Bentick B.
      Obstetric outcome of singleton pregnancies achieved with in vitro fertilisation and intracytoplasmic sperm injection: experience from a district general hospital.
      In addition, although women with ART pregnancies were more likely to develop fetal macrosomia, no difference was observed between the two study groups in the rate of dystocia. As stated above, the indications for an increased Caesarean section rate in ART pregnancies included placenta previa (which may be responsible for the increased Caesarean section rate in women with preterm birth), maternal request (which might account for the increase of Caesarean section rate in women37 weeks after spontaneous labour), and physician’s preference for intrapartum interventions in ART pregnancies (which was indirectly observed by an increased use of EFM and an increased incidence of maternal request for Caesarean section, which could partly result from physician’s consultation). More education and encouragement for women with ART pregnancies and education and relevant evidence-based guidelines for obstetricians are crucial to reduce the Caesarean section rate. This would assist in encouraging the efficient use of medical resources.
      Our study was large and population-based. The data used in our study reflect routine practice in intrapartum interventions performed for women with ART pregnancies. In addition, extensive information in the database enabled us to investigate the use of several common intrapartum interventions for ART pregnancies in clinical practice, including EFM, oxytocin infusion, ARM, and epidural analgesia. The large study population also enabled us to explore further the reasons for the increased Caesarean section rate in ART pregnancies. Finally, after subjects with major confounders (i.e., pre-existing maternal health problems and stillbirth) were excluded, other important potential confounders were controlled for by matching and regression analysis.
      Several important limitations of this study need to be considered. Firstly, administrative errors can occur in an administrative database. For example, the incidence of missing or incomplete data regarding indication for Caesarean section was 4.7%, and misclassifications were present. However, these errors would be non-differential and less likely to affect the direction of the results. Secondly, intracytoplasmic sperm injection was not separated from IVF in our study, because of the limited number of cases (137) in the database. However, a study by Buckett et al. found that the additional risk for Caesarean section was the same in women after IVF and after ICSI.
      • Buckett W.M.
      • Chian R.-C.
      • Holzer H.
      • Dean N.
      • Usher R.
      • Tan S.L.
      Obstetric outcomes and congenital abnormalities after in vitro maturation, in vitro fertilization, and intracytoplasmic sperm injection.
      Finally, information on obesity, the reasons for undergoing ART, and time to pregnancy was not available in the database. Whether or not a midwife attended the delivery was also not available for this analysis. This information would be helpful because there is a difference in the use of intrapartum interventions between midwives and physicians.
      • Symon A.G.
      • Paul J.
      • Butchart M.
      • Carr V.
      • Dugard P.
      Self-rated “no-” and “low-” risk pregnancy: a comparison of outcomes for women in obstetric-led and midwife-led units in England.

      CONCLUSION

      Women conceiving with ART and their caregivers should be aware of the increased use of intrapartum interventions, including Caesarean section, in these pregnancies. The increased Caesarean section rate in women with singleton pregnancies following ART partly arises from higher rates of maternal request, or possible physician’s preference, and of placenta previa than with spontaneously conceived pregnancies. Further research is needed to assess whether intrapartum interventions are performed effectively and efficiently in women with ART pregnancies.

      ACKNOWLEDGEMENTS

      Data in this study were from the Better Outcomes Registry & Network (BORN) Ontario’s information system. Dr Mark Walker is supported by a University of Ottawa Tier 1 Chair in perinatal epidemiology.

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