The INeS study: prevention of multiple pregnancies: a randomised controlled trial comparing IUI COH versus IVF e SET versus MNC IVF in couples with unexplained or mild male subfertility.
BACKGROUND
Multiple pregnancies are high risk pregnancies with higher chances of maternal and neonatal mortality and morbidity. In the past decades the number of multiple pregnancies has increased. This trend is partly due to the fact that women start family planning at an increased age, but also due to the increased use of ART.Couples with unexplained or mild male subfertility generally receive intrauterine insemination IUI with controlled hormonal stimulation (IUI COH). The cumulative pregnancy rate is 40%, with a 10% multiple pregnancy rate.This study aims to reveal whether alternative treatments such as IVF elective Single Embryo Transfer (IVF e SET) or Modified Natural Cycle IVF (MNC IVF) can reduce the number of multiple pregnancy rates, but uphold similar pregnancy rates as IUI COH in couples with mild male or unexplained subfertility. Secondly, the aim is to perform a cost effective analyses and assess treatment preference of these couples.


METHODS
We plan a multicentre randomised controlled clinical trial in the Netherlands comparing six cycles of intra-uterine insemination with controlled ovarian hyperstimulation or six cycles of Modified Natural Cycle (MNC) IVF or three cycles with IVF-elective Single Embryo Transfer (eSET) plus cryo-cycles within a time frame of 12 months.Couples with unexplained subfertility or mild male subfertility and a poor prognosis for treatment independent pregnancy will be included. Women with anovulatory cycles, severe endometriosis, double sided tubal pathology or serious endocrine illness will be excluded.Our primary outcome is the birth of a healthy singleton. Secondary outcomes are multiple pregnancy, treatment costs, and patient experiences in each treatment arm. The analysis will be performed according tot the intention to treat principle. We will test for non-inferiority of the three arms with respect to live birth. As we accept a 12.5% loss in pregnancy rate in one of the two IVF arms to prevent multiple pregnancies, we need 200 couples per arm (600 couples in total).


CONCLUSIONS
Determining the safest and most cost-effective treatment will ensure optimal chances of pregnancy for subfertile couples with substantially diminished perinatal and maternal complications. Should patients find the most cost-effective treatment acceptable or even preferable, this could imply the need for a world wide shift in the primary treatment.


BACKGROUND
Current Controlled Trials ISRCTN 52843371.
Bensdorp
Alexandra J
AJ
Department of Obstetrics and Gynaecology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. a.j.bensdorp@amc.nl
Slappendel
Els
E
Koks
Carolien
C
Oosterhuis
Jur
J
Hoek
Annemieke
A
Hompes
Peter
P
Broekmans
Frank
F
Verhoeve
Harold
H
de Bruin
Jan Peter
JP
van Weert
Janne Meije
JM
Traas
Maaike
M
Maas
Jacques
J
Beckers
Nicole
N
Repping
Sjoerd
S
Mol
Ben W
BW
van der Veen
Fulco
F
van Wely
Madelon
M
D000328:Adult; D004624:Embryo Transfer / Q000191:economics / Q000706:statistics & numerical data*; D005260:Female; D005307:Fertilization in Vitro / Q000191:economics / Q000706:statistics & numerical data*; D005640:Follicle Stimulating Hormone / Q000008:administration & dosage / Q000191:economics; D006801:Humans; D007231:Infant, Newborn; D007246:Infertility / Q000453:epidemiology* / Q000628:therapy; D007315:Insemination, Artificial / Q000191:economics / Q000706:statistics & numerical data*; D008297:Male; D008427:Maternal Health Services / Q000458:organization & administration; D015337:Multicenter Studies as Topic; D009426:Netherlands; D010062:Ovulation Induction / Q000191:economics / Q000379:methods; D011247:Pregnancy; D011272:Pregnancy, Multiple / Q000706:statistics & numerical data*; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D056826:Single Embryo Transfer / Q000191:economics / Q000706:statistics & numerical data*; D016387:Women's Health / Q000191:economics
D005640:Follicle Stimulating Hormone