title: Association between ovarian stimulators with or without intrauterine insemination, and assisted reproductive technologies on multiple births.
abstract: OBJECTIVE
  We sought to quantify the risk of multiple births associated with the use of different modalities of medically assisted reproduction.
  
  
  METHODS
  We conducted a case-control study using a birth cohort from 2006 through 2009. This cohort was built with the linkage of data obtained by a self-administered questionnaire and medical, hospital, pharmaceutical, birth, and death databases in Quebec. Cases were pregnancies resulting in multiple live births (International Classification of Diseases, Ninth Revision/International Statistical Classification of Diseases, 10th Revision codes). Each case was matched, on maternal age and year of delivery, with 3 singleton pregnancies (controls) randomly selected among all Quebec singleton pregnancies. Data on the use of different fertility treatments were collected by a self-administered questionnaire. Multiple logistic regression models, adjusted for body mass index, number of previous live births, ethnicity, family income, place of residence, marital status, subfertility, reduction of embryos, diabetes, metformin treatment, folic acid supplementation, and lifestyle factors, were used to calculate the odds ratios (ORs) and confidence intervals (CIs). We evaluated the associations between each type of fertility treatment (ovarian stimulators used alone, intrauterine insemination [IUI] used with ovarian stimulation, and assisted reproductive technologies [ART]) and the risk of multiple births.
  
  
  RESULTS
  A total of 1407 cases of multiple births and 3580 controls were analyzed. More than half of multiple births following medically assisted reproduction (53.6%) occurred among women having used ovarian stimulation with or without IUI. The use of ovarian stimulators alone and IUI with ovarian stimulation increase the risk of multiple births (adjusted OR, 4.5; 95% CI, 3.2-6.4; and adjusted OR, 9.32; 95% CI, 5.60-15.50, respectively) compared to spontaneous conception. The use of invasive ART was associated with a greatly increased risk of multiple births. Among only the 465 women who used medically assisted reproduction for conception, the use of IUI with ovarian stimulation was associated with an increased risk of multiple births (adjusted OR, 1.98; 95% CI, 1.12-3.49) when compared to ovarian stimulators used alone. Invasive ART were associated with an increased risk of multiple births (adjusted OR, 6.81; 95% CI, 3.72-12.49) when compared to ovarian stimulators used alone.
  
  
  CONCLUSIONS
  Although the risk of multiple births associated with invasive ART can be decreased by elective implementing of single embryo transfer, special attention should be paid to the greatly increased risk associated with ovarian stimulation used alone or with IUI.
authors.affiliation: Research Center and Department of Obstetrics and Gynecology, CHU Sainte-Justine, Montreal, Quebec, Canada; Faculties of Pharmacy, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Sonia
authors.initials: S
authors.lastname: Chaabane
authors.affiliation: Research Center and Department of Obstetrics and Gynecology, CHU Sainte-Justine, Montreal, Quebec, Canada.
authors.forename: Odile
authors.initials: O
authors.lastname: Sheehy
authors.affiliation: University Reproductive Center, Department of Obstetrics and Gynecology, Royal Victoria Hospital, Montreal, Quebec, Canada; Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Patricia
authors.initials: P
authors.lastname: Monnier
authors.affiliation: OVO Fertility Clinic, Montreal, Quebec, Canada.
authors.forename: François
authors.initials: F
authors.lastname: Bissonnette
authors.affiliation: Departments of Pediatrics, Human Genetics, and Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada; Research Institute, Montreal Children's Hospital of the McGill University Health Center, Montreal, Quebec, Canada.
authors.forename: Jacquetta M
authors.initials: JM
authors.lastname: Trasler
authors.affiliation: Dr Fraser is now affiliated with the Department of Obstetrics and Gynecology of the University of Sherbrooke and not with the Research Center CHU Sainte-Justine.
authors.forename: William
authors.initials: W
authors.lastname: Fraser
authors.affiliation: Research Center and Department of Obstetrics and Gynecology, CHU Sainte-Justine, Montreal, Quebec, Canada; Faculties of Pharmacy, University of Montreal, Montreal, Quebec, Canada. Electronic address: anick.berard@umontreal.ca.
authors.forename: Anick
authors.initials: A
authors.lastname: Bérard
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005307:Fertilization in Vitro; D006801:Humans; D007231:Infant, Newborn; D007315:Insemination, Artificial / Q000379:methods / Q000706:statistics & numerical data*; D009099:Multiple Birth Offspring / Q000706:statistics & numerical data*; D016017:Odds Ratio; D010062:Ovulation Induction / Q000706:statistics & numerical data*; D011247:Pregnancy; D011272:Pregnancy, Multiple / Q000706:statistics & numerical data*; D011792:Quebec / Q000453:epidemiology; D027724:Reproductive Techniques, Assisted; D056826:Single Embryo Transfer; D055815:Young Adult
keywords: assisted reproduction; case-control study; epidemiology; intrauterine insemination; in vitro fertilization; ovarian stimulation; risk of multiple births