Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Pediatrics
Published in: BMC Pediatrics 1/2010

Open Access 01-12-2010 | Study protocol

Long term costs and effects of reducing the number of twin pregnancies in IVF by single embryo transfer: the TwinSing study

Authors: Mirjam MJ van Heesch, Gouke J Bonsel, John CM Dumoulin, Johannes LH Evers, Mark AHBM van der Hoeven, Johan L Severens, Ramon HM Dykgraaf, Fulco van der Veen, Nino Tonch, Willianne LDM Nelen, Piet van Zonneveld, Johannes B van Goudoever, Pieter Tamminga, Katerina Steiner, Corine Koopman-Esseboom, Catharina EM van Beijsterveldt, Dorret I Boomsma, Diana Snellen, Carmen D Dirksen

Published in: BMC Pediatrics | Issue 1/2010

Login to get access

Abstract

Background

Pregnancies induced by in vitro fertilisation (IVF) often result in twin gestations, which are associated with both maternal and perinatal complications. An effective way to reduce the number of IVF twin pregnancies is to decrease the number of embryos transferred from two to one. The interpretation of current studies is limited because they used live birth as outcome measure and because they applied limited time horizons. So far, research on long-term outcomes of IVF twins and singletons is scarce and inconclusive. The objective of this study is to investigate the short (1-year) and long-term (5 and 18-year) costs and health outcomes of IVF singleton and twin children and to consider these in estimating the cost-effectiveness of single embryo transfer compared with double embryo transfer, from a societal and a healthcare perspective.

Methods/Design

A multi-centre cohort study will be performed, in which IVF singletons and IVF twin children born between 2003 and 2005 of whom parents received IVF treatment in one of the five participating Dutch IVF centres, will be compared. Data collection will focus on children at risk of health problems and children in whom health problems actually occurred. First year of life data will be collected in approximately 1,278 children (619 singletons and 659 twin children). Data up to the fifth year of life will be collected in approximately 488 children (200 singletons and 288 twin children). Outcome measures are health status, health-related quality of life and costs. Data will be obtained from hospital information systems, a parent questionnaire and existing registries. Furthermore, a prognostic model will be developed that reflects the short and long-term costs and health outcomes of IVF singleton and twin children. This model will be linked to a Markov model of the short-term cost-effectiveness of single embryo transfer strategies versus double embryo transfer strategies to enable the calculation of the long-term cost-effectiveness.

Discussion

This is, to our knowledge, the first study that investigates the long-term costs and health outcomes of IVF singleton and twin children and the long-term cost-effectiveness of single embryo transfer strategies versus double embryo transfer strategies.
Appendix
Available only for authorised users
Literature
1.
RVZ: Zinnige en duurzame zorg. 2006, Zoetermeer: Raad voor de Volksgezondheid en zorg (RVZ)
2.
Kremer JA, Bots RS, Cohlen B, Crooij M, van Dop PA, Jansen CA, Land JA, Laven JS, Kastrop PM, Naaktgeboren N, et al: Tien jaar resultaten van in-vitrofertilisatie in Nederland, 1996-2005. Ned Tijdschr Geneeskd. 2008, 152 (3): 146-152.PubMed
3.
Luke B, Keith LG: The contribution of singletons, twins and triplets to low birth weight, infant mortality and handicap in the United States. J Reprod Med. 1992, 37 (8): 661-666.PubMed
4.
Andersen AN, Goossens V, Ferraretti AP, Bhattacharya S, Felberbaum R, de Mouzon J, Nygren KG: Assisted reproductive technology in Europe, 2004: results generated from European registers by ESHRE. Hum Reprod. 2008, 23 (4): 756-771. 10.1093/humrep/den014.CrossRefPubMed
5.
Nygren KG, Andersen AN: Assisted reproductive technology in Europe, 1999. Results generated from European registers by ESHRE. Hum Reprod. 2002, 17 (12): 3260-3274. 10.1093/humrep/17.12.3260.CrossRefPubMed
6.
Ledger WL, Anumba D, Marlow N, Thomas CM, Wilson EC: The costs to the NHS of multiple births after IVF treatment in the UK. Bjog. 2006, 113 (1): 21-25.CrossRefPubMed
7.
Land JA, Evers JL: Risks and complications in assisted reproduction techniques: Report of an ESHRE consensus meeting. Hum Reprod. 2003, 18 (2): 455-457. 10.1093/humrep/deg081.CrossRefPubMed
8.
Multiple gestation pregnancy. The ESHRE Capri Workshop Group. Hum Reprod. 2000, 15 (8): 1856-1864. 10.1093/humrep/15.8.1856.
9.
Kinzler WL, Ananth CV, Vintzileos AM: Medical and economic effects of twin gestations. J Soc Gynecol Investig. 2000, 7 (6): 321-327. 10.1016/S1071-5576(00)00084-8.CrossRefPubMed
10.
Koivurova S, Hartikainen AL, Gissler M, Hemminki E, Sovio U, Jarvelin MR: Neonatal outcome and congenital malformations in children born after in-vitro fertilization. Hum Reprod. 2002, 17 (5): 1391-1398. 10.1093/humrep/17.5.1391.CrossRefPubMed
11.
Pinborg A, Loft A, Nyboe Andersen A: Neonatal outcome in a Danish national cohort of 8602 children born after in vitro fertilization or intracytoplasmic sperm injection: the role of twin pregnancy. Acta Obstet Gynecol Scand. 2004, 83 (11): 1071-1078.CrossRefPubMed
12.
PRN: Perinatale Zorg in Nederaland 2004. 2007, Utrecht: Stichting Perinatale Registratie Nederland
13.
Glazebrook C, Sheard C, Cox S, Oates M, Ndukwe G: Parenting stress in first-time mothers of twins and triplets conceived after in vitro fertilization. Fertil Steril. 2004, 81 (3): 505-511. 10.1016/j.fertnstert.2003.10.020.CrossRefPubMed
14.
Olivennes F, Fanchin R, Ledee N, Righini C, Kadoch IJ, Frydman R: Perinatal outcome and developmental studies on children born after IVF. Hum Reprod Update. 2002, 8 (2): 117-128. 10.1093/humupd/8.2.117.CrossRefPubMed
15.
Bergh T, Ericson A, Hillensjo T, Nygren KG, Wennerholm UB: Deliveries and children born after in-vitro fertilisation in Sweden 1982-95: a retrospective cohort study. Lancet. 1999, 354 (9190): 1579-1585. 10.1016/S0140-6736(99)04345-7.CrossRefPubMed
16.
Gissler M, Malin Silverio M, Hemminki E: In-vitro fertilization pregnancies and perinatal health in Finland 1991-1993. Hum Reprod. 1995, 10 (7): 1856-1861.PubMed
17.
Liu YC, Blair EM: Predicted birthweight for singletons and twins. Twin Res. 2002, 5 (6): 529-537. 10.1375/136905202762341991.CrossRefPubMed
18.
Bonsel GJ, Eskes M, Birnie E: Eindrapportage Twin Studie [ZonMw subsidienummer 045-12-101]. 2008, Rotterdam: Institute of Health Policy and Management, Erasmus Medical Centre
19.
Pandian Z, Templeton A, Serour G, Bhattacharya S: Number of embryos for transfer after IVF and ICSI: a Cochrane review. Hum Reprod. 2005, 20 (10): 2681-2687. 10.1093/humrep/dei153.CrossRefPubMed
20.
Fiddelers AA, van Montfoort AP, Dirksen CD, Dumoulin JC, Land JA, Dunselman GA, Janssen JM, Severens JL, Evers JL: Single versus double embryo transfer: cost-effectiveness analysis alongside a randomized clinical trial. Hum Reprod. 2006, 21 (8): 2090-2097. 10.1093/humrep/del112.CrossRefPubMed
21.
Gardner DK, Surrey E, Minjarez D, Leitz A, Stevens J, Schoolcraft WB: Single blastocyst transfer: a prospective randomized trial. Fertil Steril. 2004, 81 (3): 551-555. 10.1016/j.fertnstert.2003.07.023.CrossRefPubMed
22.
Gerris JM: Single embryo transfer and IVF/ICSI outcome: a balanced appraisal. Hum Reprod Update. 2005, 11 (2): 105-121. 10.1093/humupd/dmh049.CrossRefPubMed
23.
Lukassen HG, Braat DD, Wetzels AM, Zielhuis GA, Adang EM, Scheenjes E, Kremer JA: Two cycles with single embryo transfer versus one cycle with double embryo transfer: a randomized controlled trial. Hum Reprod. 2005, 20 (3): 702-708. 10.1093/humrep/deh672.CrossRefPubMed
24.
Martikainen H, Tiitinen A, Tomas C, Tapanainen J, Orava M, Tuomivaara L, Vilska S, Hyden-Granskog C, Hovatta O: One versus two embryo transfer after IVF and ICSI: a randomized study. Hum Reprod. 2001, 16 (9): 1900-1903. 10.1093/humrep/16.9.1900.CrossRefPubMed
25.
Thurin A, Hausken J, Hillensjo T, Jablonowska B, Pinborg A, Strandell A, Bergh C: Elective single-embryo transfer versus double-embryo transfer in in vitro fertilization. N Engl J Med. 2004, 351 (23): 2392-2402. 10.1056/NEJMoa041032.CrossRefPubMed
26.
van Montfoort AP, Fiddelers AA, Janssen JM, Derhaag JG, Dirksen CD, Dunselman GA, Land JA, Geraedts JP, Evers JL, Dumoulin JC: In unselected patients, elective single embryo transfer prevents all multiples, but results in significantly lower pregnancy rates compared with double embryo transfer: a randomized controlled trial. Hum Reprod. 2006, 21 (2): 338-343. 10.1093/humrep/dei359.CrossRefPubMed
27.
van Peperstraten AM, Nelen WL, Hermens RP, Jansen L, Scheenjes E, Braat DD, Grol RP, Kremer JA: Why don't we perform elective single embryo transfer? A qualitative study among IVF patients and professionals. Hum Reprod. 2008, 23 (9): 2036-2042. 10.1093/humrep/den156.CrossRefPubMed
28.
Gerris J, De Neubourg D, Mangelschots K, Van Royen E, Van de Meerssche M, Valkenburg M: Prevention of twin pregnancy after in-vitro fertilization or intracytoplasmic sperm injection based on strict embryo criteria: a prospective randomized clinical trial. Hum Reprod. 1999, 14 (10): 2581-2587. 10.1093/humrep/14.10.2581.CrossRefPubMed
29.
Gerris J, De Sutter P, De Neubourg D, Van Royen E, Vander Elst J, Mangelschots K, Vercruyssen M, Kok P, Elseviers M, Annemans L, et al: A real-life prospective health economic study of elective single embryo transfer versus two-embryo transfer in first IVF/ICSI cycles. Hum Reprod. 2004, 19 (4): 917-923. 10.1093/humrep/deh188.CrossRefPubMed
30.
Kjellberg AT, Carlsson P, Bergh C: Randomized single versus double embryo transfer: obstetric and paediatric outcome and a cost-effectiveness analysis. Hum Reprod. 2006, 21 (1): 210-216. 10.1093/humrep/dei298.CrossRefPubMed
31.
Fiddelers AA, Severens JL, Dirksen CD, Dumoulin JC, Land JA, Evers JL: Economic evaluations of single-versus double-embryo transfer in IVF. Hum Reprod Update. 2007, 13 (1): 5-13. 10.1093/humupd/dml053.CrossRefPubMed
32.
Fiddelers AA, Dirksen CD, Dumoulin JC, van Montfoort AP, Land JA, Janssen JM, Evers JL, Severens JL: Cost-effectiveness of seven IVF strategies: results of a Markov decision-analytic model. Hum Reprod. 2009, 24 (7): 1648-1655. 10.1093/humrep/dep041.CrossRefPubMed
33.
Child TJ, Henderson AM, Tan SL: The desire for multiple pregnancy in male and female infertility patients. Hum Reprod. 2004, 19 (3): 558-561. 10.1093/humrep/deh097.CrossRefPubMed
34.
Hojgaard A, Ottosen LD, Kesmodel U, Ingerslev HJ: Patient attitudes towards twin pregnancies and single embryo transfer - a questionnaire study. Hum Reprod. 2007, 22 (10): 2673-2678. 10.1093/humrep/dem173.CrossRefPubMed
35.
Murray S, Shetty A, Rattray A, Taylor V, Bhattacharya S: A randomized comparison of alternative methods of information provision on the acceptability of elective single embryo transfer. Hum Reprod. 2004, 19 (4): 911-916. 10.1093/humrep/deh176.CrossRefPubMed
36.
Newton CR, McBride J, Feyles V, Tekpetey F, Power S: Factors affecting patients' attitudes toward single- and multiple-embryo transfer. Fertil Steril. 2007, 87 (2): 269-278. 10.1016/j.fertnstert.2006.06.043.CrossRefPubMed
37.
Pinborg A, Loft A, Schmidt L, Andersen AN: Attitudes of IVF/ICSI-twin mothers towards twins and single embryo transfer. Hum Reprod. 2003, 18 (3): 621-627. 10.1093/humrep/deg145.CrossRefPubMed
38.
Ryan GL, Zhang SH, Dokras A, Syrop CH, Van Voorhis BJ: The desire of infertile patients for multiple births. Fertil Steril. 2004, 81 (3): 500-504. 10.1016/j.fertnstert.2003.05.035.CrossRefPubMed
39.
Twisk M, van der Veen F, Repping S, Heineman MJ, Korevaar JC, Bossuyt PM: Preferences of subfertile women regarding elective single embryo transfer: additional in vitro fertilization cycles are acceptable, lower pregnancy rates are not. Fertil Steril. 2007, 88 (4): 1006-1009. 10.1016/j.fertnstert.2006.12.004.CrossRefPubMed
40.
Raftery J: NICE: faster access to modern treatments? Analysis of guidance on health technologies. BMJ. 2001, 323 (7324): 1300-1303. 10.1136/bmj.323.7324.1300.CrossRefPubMedPubMedCentral
41.
Ericson A, Nygren KG, Olausson PO, Kallen B: Hospital care utilization of infants born after IVF. Hum Reprod. 2002, 17 (4): 929-932. 10.1093/humrep/17.4.929.CrossRefPubMed
42.
Koivurova S, Hartikainen AL, Gissler M, Hemminki E, Jarvelin MR: Post-neonatal hospitalization and health care costs among IVF children: a 7-year follow-up study. Hum Reprod. 2007, 22 (8): 2136-2141. 10.1093/humrep/dem150.CrossRefPubMed
43.
Klemetti R, Sevon T, Gissler M, Hemminki E: Health of children born as a result of in vitro fertilization. Pediatrics. 2006, 118 (5): 1819-1827. 10.1542/peds.2006-0735.CrossRefPubMed
44.
Koivurova S, Hartikainen AL, Sovio U, Gissler M, Hemminki E, Jarvelin MR: Growth, psychomotor development and morbidity up to 3 years of age in children born after IVF. Hum Reprod. 2003, 18 (11): 2328-2336. 10.1093/humrep/deg445.CrossRefPubMed
45.
Stromberg B, Dahlquist G, Ericson A, Finnstrom O, Koster M, Stjernqvist K: Neurological sequelae in children born after in-vitro fertilisation: a population-based study. Lancet. 2002, 359 (9305): 461-465. 10.1016/S0140-6736(02)07674-2.CrossRefPubMed
46.
Bonduelle M, Ponjaert I, Steirteghem AV, Derde MP, Devroey P, Liebaers I: Developmental outcome at 2 years of age for children born after ICSI compared with children born after IVF. Hum Reprod. 2003, 18 (2): 342-350. 10.1093/humrep/deg061.CrossRefPubMed
47.
Pinborg A, Loft A, Schmidt L, Andersen AN: Morbidity in a Danish national cohort of 472 IVF/ICSI twins, 1132 non-IVF/ICSI twins and 634 IVF/ICSI singletons: health-related and social implications for the children and their families. Hum Reprod. 2003, 18 (6): 1234-1243. 10.1093/humrep/deg257.CrossRefPubMed
48.
Pinborg A, Loft A, Schmidt L, Greisen G, Rasmussen S, Andersen AN: Neurological sequelae in twins born after assisted conception: controlled national cohort study. BMJ. 2004, 329 (7461): 311-10.1136/bmj.38156.715694.3A.CrossRefPubMedPubMedCentral
49.
Pinborg A, Loft A, Rasmussen S, Nyboe Andersen A: Hospital care utilization of IVF/ICSI twins followed until 2-7 years of age: a controlled Danish national cohort study. Hum Reprod. 2004, 19 (11): 2529-2536. 10.1093/humrep/deh474.CrossRefPubMed
50.
ZonMW: [Fertility disorders: chances of more efficient care]. 2005, The Hague: ZonMW
51.
Olivennes F, Golombok S, Ramogida C, Rust J: Behavioral and cognitive development as well as family functioning of twins conceived by assisted reproduction: findings from a large population study. Fertil Steril. 2005, 84 (3): 725-733. 10.1016/j.fertnstert.2005.03.039.CrossRefPubMed
52.
van Kammen J, Jansen CW, Bonsel GJ, Kremer JA, Evers JL, Wladimiroff JW: Technology assessment and knowledge brokering: the case of assisted reproduction in The Netherlands. Int J Technol Assess Health Care. 2006, 22 (3): 302-306. 10.1017/S026646230605118X.CrossRefPubMed
53.
Bartels M, van Beijsterveldt CE, Derks EM, Stroet TM, Polderman TJ, Hudziak JJ, Boomsma DI: Young Netherlands Twin Register (Y-NTR): a longitudinal multiple informant study of problem behavior. Twin Res Hum Genet. 2007, 10 (1): 3-11. 10.1375/twin.10.1.3.CrossRefPubMed
54.
Boomsma DI, de Geus EJ, Vink JM, Stubbe JH, Distel MA, Hottenga JJ, Posthuma D, van Beijsterveldt TC, Hudziak JJ, Bartels M, et al: Netherlands Twin Register: from twins to twin families. Twin Res Hum Genet. 2006, 9 (6): 849-857. 10.1375/twin.9.6.849.CrossRefPubMed
55.
Dolan P: Modeling valuations for EuroQol health states. Medical care. 1997, 35 (11): 1095-1108. 10.1097/00005650-199711000-00002.CrossRefPubMed
56.
Lamers LM, McDonnell J, Stalmeier PF, Krabbe PF, Busschbach JJ: The Dutch tariff: results and arguments for an effective design for national EQ-5D valuation studies. Health Econ. 2006, 15 (10): 1121-1132. 10.1002/hec.1124.CrossRefPubMed
57.
EuroQol--a new facility for the measurement of health-related quality of life. The EuroQol Group. Health Policy. 1990, 16 (3): 199-208. 10.1016/0168-8510(90)90421-9.
58.
Stolk EA, Busschbach JJ, Vogels T: Performance of the EuroQol in children with imperforate anus. Qual Life Res. 2000, 9 (1): 29-38. 10.1023/A:1008923029886.CrossRefPubMed
59.
Feeny D, Furlong W, Torrance GW, Goldsmith CH, Zhu Z, DePauw S, Denton M, Boyle M: Multiattribute and single-attribute utility functions for the health utilities index mark 3 system. Med Care. 2002, 40 (2): 113-128. 10.1097/00005650-200202000-00006.CrossRefPubMed
60.
Oostenbrink JB, Bouwmans CAM, Koopmanschap MA, Rutten FFH: Handleiding voor kostenonderzoek, methoden en standaardkostprijzen voor economische evaluaties in de gezondheidszorg. 2004, Amstelveen: College voor zorgverzekeringen (CVZ)
61.
CVZ: Richtlijnen voor farmaco-economisch onderzoek, geactualiseerde versie 2006. 2006, Diemen: College voor zorgverzekeringen (CVZ)
62.
Ades AE, Lu G, Claxton K: Expected value of sample information calculations in medical decision modeling. Med Decis Making. 2004, 24 (2): 207-227. 10.1177/0272989X04263162.CrossRefPubMed
63.
Claxton K, Cohen JT, Neumann PJ: When is evidence sufficient?. Health Aff (Millwood). 2005, 24 (1): 93-101. 10.1377/hlthaff.24.1.93.CrossRef
64.
Claxton K, Sculpher M, Drummond M: A rational framework for decision making by the National Institute For Clinical Excellence (NICE). Lancet. 2002, 360 (9334): 711-715. 10.1016/S0140-6736(02)09832-X.CrossRefPubMed
65.
Claxton KP, Sculpher MJ: Using value of information analysis to prioritise health research: some lessons from recent UK experience. Pharmacoeconomics. 2006, 24 (11): 1055-1068. 10.2165/00019053-200624110-00003.CrossRefPubMed
Metadata
Title
Long term costs and effects of reducing the number of twin pregnancies in IVF by single embryo transfer: the TwinSing study
Authors
Mirjam MJ van Heesch
Gouke J Bonsel
John CM Dumoulin
Johannes LH Evers
Mark AHBM van der Hoeven
Johan L Severens
Ramon HM Dykgraaf
Fulco van der Veen
Nino Tonch
Willianne LDM Nelen
Piet van Zonneveld
Johannes B van Goudoever
Pieter Tamminga
Katerina Steiner
Corine Koopman-Esseboom
Catharina EM van Beijsterveldt
Dorret I Boomsma
Diana Snellen
Carmen D Dirksen
Publication date
01-12-2010
Publisher
BioMed Central
Published in
BMC Pediatrics / Issue 1/2010
Electronic ISSN: 1471-2431
DOI
https://doi.org/10.1186/1471-2431-10-75

Other articles of this Issue 1/2010

BMC Pediatrics 1/2010 Go to the issue

Research article

Treatment and disease progression in a birth cohort of vertically HIV-1 infected children in Ukraine

Research article

Socio-demographic and behavioural correlates of oral hygiene status and oral health related quality of life, the Limpopo - Arusha school health project (LASH): A cross-sectional study

Research article

Predictors of positive blood culture and deaths among neonates with suspected neonatal sepsis in a tertiary hospital, Mwanza- Tanzania

Research article

Knowledge and information needs of young people with epilepsy and their parents: Mixed-method systematic review

Research article

There is (still) too much aluminium in infant formulas

Study protocol

Physical training in boys with Duchenne Muscular Dystrophy: the protocol of the No Use is Disuse study