Is IVF-served two different ways-more cost-effective than IUI with controlled ovarian hyperstimulation?
OBJECTIVE
What is the cost-effectiveness of in vitro fertilization (IVF) with conventional ovarian stimulation, single embryo transfer (SET) and subsequent cryocycles or IVF in a modified natural cycle (MNC) compared with intrauterine insemination with controlled ovarian hyperstimulation (IUI-COH) as a first-line treatment in couples with unexplained subfertility and an unfavourable prognosis on natural conception?.


CONCLUSIONS
Both IVF strategies are significantly more expensive when compared with IUI-COH, without being significantly more effective. In the comparison between IVF-MNC and IUI-COH, the latter is the dominant strategy. Whether IVF-SET is cost-effective depends on society's willingness to pay for an additional healthy child.


BACKGROUND
IUI-COH and IVF, either after conventional ovarian stimulation or in a MNC, are used as first-line treatments for couples with unexplained or mild male subfertility. As IUI-COH is less invasive, this treatment is usually offered before proceeding to IVF. Yet, as conventional IVF with SET may lead to higher pregnancy rates in fewer cycles for a lower multiple pregnancy rate, some have argued to start with IVF instead of IUI-COH. In addition, IVF in the MNC is considered to be a more patient friendly and less costly form of IVF.


METHODS
We performed a cost-effectiveness analysis alongside a randomized noninferiority trial. Between January 2009 and February 2012, 602 couples with unexplained infertility and a poor prognosis on natural conception were allocated to three cycles of IVF-SET including frozen embryo transfers, six cycles of IVF-MNC or six cycles of IUI-COH. These couples were followed until 12 months after randomization.


METHODS
We collected data on resource use related to treatment, medication and pregnancy from the case report forms. We calculated unit costs from various sources. For each of the three strategies, we calculated the mean costs and effectiveness. Incremental cost-effectiveness ratios (ICER) were calculated for IVF-SET compared with IUI-COH and for IVF-MNC compared with IUI-COH. Nonparametric bootstrap resampling was used to investigate the effect of uncertainty in our estimates.


RESULTS
There were 104 healthy children (52%) born in the IVF-SET group, 83 (43%) the IVF-MNC group and 97 (47%) in the IUI-COH group. The mean costs per couple were €7187 for IVF-SET, €8206 for IVF-MNC and €5070 for IUI-COH. Compared with IUI-COH, the costs for IVF-SET and IVF-MNC were significantly higher (mean differences €2117; 95% CI: €1544-€2657 and €3136, 95% CI: €2519-€3754, respectively).The ICER for IVF-SET compared with IUI-COH was €43 375 for the birth of an additional healthy child. In the comparison of IVF-MNC to IUI-COH, the latter was the dominant strategy, i.e. more effective at lower costs.


CONCLUSIONS
We only report on direct health care costs. The present analysis is limited to 12 months.


CONCLUSIONS
Since we found no evidence in support of offering IVF as a first-line strategy in couples with unexplained and mild subfertility, IUI-COH should remain the treatment of first choice.


BACKGROUND
The study was supported by a grant from ZonMw, the Netherlands Organization for Health Research and Development, (120620027) and a grant from Zorgverzekeraars Nederland, the Netherlands' association of health care insurers (09-003).


BACKGROUND
Current Controlled Trials ISRCTN52843371; Nederlands Trial Register NTR939.
Centre for Reproductive Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
R I
RI
Tjon-Kon-Fat
Centre for Reproductive Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
A J
AJ
Bensdorp
Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
P M M
PM
Bossuyt
Department of Obstetrics and Gynaecology, Máxima Medical Centre, Veldhoven, The Netherlands.
C
C
Koks
Department of Obstetrics and Gynaecology, St. Antonius Hospital, Nieuwegein, The Netherlands.
G J E
GJ
Oosterhuis
Department of Obstetrics and Gynaecology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
A
A
Hoek
Centre for Reproductive Medicine, Vrije Universiteit Medical Centre, Amsterdam, The Netherlands.
P
P
Hompes
Department for Reproductive Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands.
F J
FJ
Broekmans
Department of Obstetrics and Gynaecology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands.
H R
HR
Verhoeve
Department of Obstetrics and Gynaecology, Jeroen Bosch Hospital, 's Hertogenbosch, The Netherlands.
J P
JP
de Bruin
Department of Obstetrics and Gynaecology, University Medical Centre Maastricht, Maastricht, The Netherlands.
R
R
van Golde
Centre for Reproductive Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
S
S
Repping
Department of Obstetrics and Gynaecology, Isala Clinics, Zwolle, The Netherlands.
B J
BJ
Cohlen
Department of Obstetrics and Gynaecology, Albert Schweitzer Hospital, Dordrecht, The Netherlands.
M D A
MD
Lambers
Department of Obstetrics and Gynaecology, Amphia Hospital, Breda, The Netherlands.
P F
PF
van Bommel
Department of Obstetrics and Gynaecology, Catharina Hospital, Eindhoven, The Netherlands.
E
E
Slappendel
Obstetrics and Gynaecology, Medical Centre Leeuwarden, Leeuwarden, The Netherlands.
D
D
Perquin
Department of Obstetrics and Gynaecology, Elisabeth Hospital, Tilburg, The Netherlands.
J
J
Smeenk
Department of Obstetrics and Gynaecology, Scheper Hospital, Emmen, The Netherlands.
M J
MJ
Pelinck
Department of Obstetrics and Gynaecology, Kennemer Gasthuis, Haarlem, The Netherlands.
J
J
Gianotten
Department of Obstetrics and Gynaecology, Medical Spectrum Twente, Enschede, The Netherlands.
D A
DA
Hoozemans
Department of Obstetrics and Gynaecology, Máxima Medical Centre, Veldhoven, The Netherlands.
J W M
JW
Maas
Department of Obstetrics and Gynaecology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
H
H
Groen
Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, The Netherlands.
M J C
MJ
Eijkemans
Centre for Reproductive Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
F
F
van der Veen
The Robinson Research Institute, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA, Australia.
B W J
BW
Mol
Centre for Reproductive Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands m.vanwely@amc.nl.
M
M
van Wely
D000328:Adult; D003362:Cost-Benefit Analysis; D015925:Cryopreservation; D004624:Embryo Transfer / Q000191:economics* / Q000379:methods; D005260:Female; D005306:Fertilization; D005307:Fertilization in Vitro / Q000191:economics* / Q000379:methods*; D006801:Humans; D007248:Infertility, Male / Q000628:therapy; D007315:Insemination, Artificial / Q000191:economics* / Q000379:methods; D008297:Male; D018803:Models, Economic; D009426:Netherlands; D010062:Ovulation Induction / Q000191:economics* / Q000379:methods; D011247:Pregnancy; D011256:Pregnancy Outcome; D018873:Pregnancy Rate; D011379:Prognosis; D056826:Single Embryo Transfer / Q000191:economics* / Q000379:methods
cost-effectiveness; in vitro fertilization; intrauterine insemination; modified natural cycle; single embryo transfer