title: Reduction of multiple pregnancies in the advanced maternal age population after implementation of an elective single embryo transfer policy coupled with enhanced embryo selection: pre- and post-intervention study.
abstract: OBJECTIVE
  Is an elective single-embryo transfer (eSET) policy an efficient approach for women aged >35 years when embryo selection is enhanced via blastocyst culture and preimplantation genetic screening (PGS)?
  
  
  CONCLUSIONS
  Elective SET coupled with enhanced embryo selection using PGS in women older than 35 years reduced the multiple pregnancy rates while maintaining the cumulative success rate of the IVF programme.
  
  
  BACKGROUND
  Multiple pregnancies mean an increased risk of premature birth and perinatal death and occur mainly in older patients when multiple embryos are transferred to increase the chance of pregnancy. A SET policy is usually recommended in cases of good prognosis patients, but no general consensus has been reached for SET application in the advanced maternal age (AMA) population, defined as women older than 35 years. Our objective was to evaluate the results in terms of efficacy, efficiency and safety of an eSET policy coupled with increased application of blastocyst culture and PGS for this population of patients in our IVF programme.
  
  
  METHODS
  In January 2013, a multidisciplinary intervention involving optimization of embryo selection procedure and introduction of an eSET policy in an AMA population of women was implemented. This is a retrospective 4-year (January 2010-December 2013) pre- and post-intervention analysis, including 1161 and 499 patients in the pre- and post-intervention period, respectively. The primary outcome measures were the cumulative delivery rate (DR) per oocyte retrieval cycle and multiple DR.
  
  
  METHODS
  Surplus oocytes and/or embryos were vitrified during the entire study period. In the post-intervention period, all couples with good quality embryos and less than two previous implantation failures were offered eSET. Embryo selection was enhanced by blastocyst culture and PGS (blastocyst stage biopsy and 24-chromosomal screening). Elective SET was also applied in cryopreservation cycles.
  
  
  RESULTS
  Patient and cycle characteristics were similar in the pre- and post-intervention groups [mean (SD) female age: 39.6 ± 2.1 and 39.4 ± 2.2 years; range 36-44] as assessed by logistic regression. A total of 1609 versus 574 oocyte retrievals, 937 versus 350 embryo warming and 138 versus 27 oocyte warming cycles were performed in the pre- and post-intervention periods, respectively, resulting in 1854 and 508 embryo transfers, respectively. In the post-intervention period, 289 cycles were blastocyst stage with (n = 182) or without PGS (n = 107). A mean (SD) number of 2.9 ± 1.1 (range 1-4) and 1.4 ± 0.8 (range 1-3) embryos were transferred pre- and post-intervention, respectively (P < 0.01) and similar cumulative clinical pregnancy rates per transfer and per cycle were obtained: 26.8, 30.9% and 29.7, 26.3%, respectively. The total DR per oocyte retrieval cycle (21.0 and 20.4% pre- and post-intervention, respectively) defined as efficacy was not affected by the intervention [odds ratio (OR) = 0.8, 95% confidence interval (CI) = 0.7-1.1; P = 0.23]. However, a significantly increased live birth rate per transferred embryo (defined as efficiency) was observed in the post-intervention group 17.0 versus 10.6% (P < 0.01). Multiple DRs decreased from 21.0 in the preintervention to 6.8% in the post-intervention group (OR = 0.3. 95% CI = 0.1-0.7; P < 0.01).
  
  
  CONCLUSIONS
  In this study, the suitability of SET was assessed in individual women on the basis of both clinical and embryological prognostic factors and was not standardized. For the described eSET strategy coupled with an enhanced embryo selection policy, an optimized culture system, cryopreservation and aneuploidy screening programme is necessary.
  
  
  CONCLUSIONS
  Owing to the increased maternal morbidity and perinatal complications related to multiple pregnancies, it is recommended to extend the eSET policy to the AMA population. As shown in this study, enhanced embryo selection procedures might allow a reduction in the number of embryos transferred and the number of transfers to be performed without affecting the total efficacy of the treatment but increasing efficiency and safety.
  
  
  BACKGROUND
  None.
  
  
  BACKGROUND
  None.
authors.affiliation: G.EN.E.R.A. Centre for Reproductive Medicine, Clinica Valle Giulia, Via G. De Notaris 2b, 00197 Rome, Italy ubaldi.fm@gmail.com.
authors.forename: Filippo Maria
authors.initials: FM
authors.lastname: Ubaldi
authors.affiliation: G.EN.E.R.A. Centre for Reproductive Medicine, Clinica Valle Giulia, Via G. De Notaris 2b, 00197 Rome, Italy GENETYX, Molecular Genetics Laboratory, E. Fermi, 1 36063 Marostica, Vicenza, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Capalbo
authors.affiliation: G.EN.E.R.A. Centre for Reproductive Medicine, Clinica Valle Giulia, Via G. De Notaris 2b, 00197 Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Colamaria
authors.affiliation: G.EN.E.R.A. Centre for Reproductive Medicine, Clinica Valle Giulia, Via G. De Notaris 2b, 00197 Rome, Italy.
authors.forename: Susanna
authors.initials: S
authors.lastname: Ferrero
authors.affiliation: G.EN.E.R.A. Centre for Reproductive Medicine, Clinica Valle Giulia, Via G. De Notaris 2b, 00197 Rome, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Maggiulli
authors.affiliation: Beishan Industrial Zone, BGI Shenzhen, Yantian District Shenzhen 518083, China.
authors.forename: Gábor
authors.initials: G
authors.lastname: Vajta
authors.affiliation: G.EN.E.R.A. Centre for Reproductive Medicine, Clinica Valle Giulia, Via G. De Notaris 2b, 00197 Rome, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Sapienza
authors.affiliation: G.EN.E.R.A. Centre for Reproductive Medicine, Clinica Valle Giulia, Via G. De Notaris 2b, 00197 Rome, Italy GENETYX, Molecular Genetics Laboratory, E. Fermi, 1 36063 Marostica, Vicenza, Italy.
authors.forename: Danilo
authors.initials: D
authors.lastname: Cimadomo
authors.affiliation: G.EN.E.R.A. Centre for Reproductive Medicine, Clinica Valle Giulia, Via G. De Notaris 2b, 00197 Rome, Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Giuliani
authors.affiliation: G.EN.E.R.A. Centre for Reproductive Medicine, Clinica Valle Giulia, Via G. De Notaris 2b, 00197 Rome, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Gravotta
authors.affiliation: G.EN.E.R.A. Centre for Reproductive Medicine, Clinica Valle Giulia, Via G. De Notaris 2b, 00197 Rome, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Vaiarelli
authors.affiliation: G.EN.E.R.A. Centre for Reproductive Medicine, Clinica Valle Giulia, Via G. De Notaris 2b, 00197 Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Rienzi
mesh_terms: D000328:Adult; D005260:Female; D005307:Fertilization in Vitro; D005500:Follow-Up Studies; D006801:Humans; D008423:Maternal Age; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data*; D011247:Pregnancy; D011272:Pregnancy, Multiple; D019836:Preimplantation Diagnosis / Q000592:standards* / Q000706:statistics & numerical data; D012189:Retrospective Studies; D056826:Single Embryo Transfer / Q000592:standards* / Q000706:statistics & numerical data
keywords: advanced maternal age; comprehensive chromosome screening; elective single embryo transfer; preimplantation genetic screening; vitrification