title: The periconception maternal cardiovascular risk profile influences human embryonic growth trajectories in IVF/ICSI pregnancies.
abstract: Is the maternal cardiovascular (CV) risk profile associated with human embryonic growth trajectories and does the mode of conception affect this association?
  
  
  
  This small study suggests that the maternal CV risk profile is inversely associated with first trimester embryonic growth trajectories in in vitro fertilization (IVF)/intra-cytoplasmic sperm injection (ICSI) pregnancies, but not in spontaneously conceived pregnancies.
  
  
  
  Maternal high-blood pressure and smoking affect placental function, accompanied by increased risk of fetal growth restriction and low-birthweight. Mothers who experience pregnancies complicated by fetal growth restriction are at increased risk of CV disease in later life.
  
  
  
  In a prospective periconception birth cohort conducted in a tertiary hospital, 111 singleton ongoing pregnancies with reliable pregnancy dating, no pre-existing maternal disease and no malformed live borns were investigated.
  
  
  
  Spontaneously conceived pregnancies with a reliable first day of the last menstrual period and a regular menstrual cycle of 25-31 days only (n = 66) and IVF/ICSI pregnancies (n = 45) were included. Women underwent weekly three-dimensional ultrasound scans (3D US) from 6- to 13-week gestational age. To estimate embryonic growth, serial crown-rump length (CRL) measurements were performed using the V-Scope software in a BARCO I-Space. Maternal characteristics and CV risk factors were collected by self-administered questionnaires. The CV risk profile was created based on a score of risk factors, including maternal age, body-mass index, CV disease in the family, diet and smoking. Quartiles of the CV risk score were calculated. Associations between the CV risk score and embryonic growth were assessed using square root transformed CRL in multivariable linear mixed model analyses.
  
  
  
  From the 111 included pregnancies, 696 3D US data sets were obtained of which 637 (91.5%) CRLs could be measured. In the total group, The CV risk score was inversely, but not significantly associated with embryonic growth (-0.03√mm; P = 0.291). Stratified by mode of conception, the CV risk score was inversely and significantly associated with embryonic growth (β = -0.04√mm; P = 0.025, adjusted for possible confounders) in the IVF/ICSI group. Compared with the first quartile, embryos in the upper quartile were 10.4% smaller at 6(+0) weeks (4.4 versus 4.9 mm) and 3.1% smaller at 12(+0) weeks (56.5 versus 58.4 mm) of gestation. Although the CV risk score was slightly, but significantly, higher in women conceiving spontaneously compared with those undergoing IVF/ICSI treatment [CV risk score = 2.06 (SD: 1.23) and 1.60 (SD: 1.15), respectively], no association was established with embryonic growth in that particular group.
  
  
  
  Participants included in the present cohort are women with a singleton ongoing pregnancy without any pre-existing disease and selected from a tertiary hospital. Hence, they represent a selected group of women. Larger and population-based periconception birth cohort studies are recommended to demonstrate external validity.
  
  
  
  Differences in embryonic growth between pregnancies conceived spontaneously and after IVF/ICSI treatment in relation with CV risk factors substantiate the importance of more investigation into differences in sensitivity of endometrial, endothelial, placental and embryonic tissues.
  
  
  
  Funded by the Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre, Rotterdam, the Netherlands. The authors declare no conflict of interest.
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre, PO Box 2040, Rotterdam 3000CA, The Netherlands.
authors.forename: K P J
authors.initials: KP
authors.lastname: Wijnands
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre, PO Box 2040, Rotterdam 3000CA, The Netherlands.
authors.forename: E M
authors.initials: EM
authors.lastname: van Uitert
authors.affiliation: Department of Internal Medicine, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands.
authors.forename: J E
authors.initials: JE
authors.lastname: Roeters van Lennep
authors.affiliation: Department of Bioinformatics, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands.
authors.forename: A H J
authors.initials: AH
authors.lastname: Koning
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre, PO Box 2040, Rotterdam 3000CA, The Netherlands.
authors.forename: A G M G J
authors.initials: AG
authors.lastname: Mulders
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre, PO Box 2040, Rotterdam 3000CA, The Netherlands.
authors.forename: J S E
authors.initials: JS
authors.lastname: Laven
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre, PO Box 2040, Rotterdam 3000CA, The Netherlands.
authors.forename: E A P
authors.initials: EA
authors.lastname: Steegers
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre, PO Box 2040, Rotterdam 3000CA, The Netherlands r.steegers@erasmusmc.nl.
authors.forename: R P M
authors.initials: RP
authors.lastname: Steegers-Theunissen
mesh_terms: D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000150:complications*; D018568:Crown-Rump Length; D004032:Diet; D047108:Embryonic Development; D005260:Female; D005307:Fertilization in Vitro; D047109:Fetal Development; D006801:Humans; D006973:Hypertension / Q000150:complications; D008423:Maternal Age; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking
keywords: 3D imaging; assisted reproductive technology; cardiovascular disease; crown-rump length; fertility; pregnancy