Home-based monitoring of ovulation to time frozen embryo transfer in IVF.

Frozen-thawed embryo transfer (FET) is at the heart of modern IVF and has been
made possible by -ongoing- improvements in laboratory techniques for freezing
and thawing of embryos (1).The number of FET cycles is increased substantially
over the past decade (Dutch national
IVF results, NVOG 2015 (2)). Currently, 37% of children born from IVF/ICSI
treatments is the result of the transfer of a frozen-thawed embryo in the
Netherlands (www.nvog.nl). It is to be expected that the relative contribution
of FET to the cumulative ongoing pregnancy rates will further increase.

For FET to be effective, the endometrium needs to be synchronized with the
developmental stage of the embryo to allow implantation. There are two methods
to do so: embryo transfer in the natural cycle (NC-FET) with repeated
ultrasound monitoring of the dominant follicle followed by hCG trigger or
embryo transfer in an artificial cycle (AC-FET) with estrogen and progesterone
tablets. A recently performed multicentre non inferiority trial (NTR1586,
ANTARCTICA TRIAL, ), conducted within the Dutch Consortium for Healthcare
Evaluation and Research in Obstetrics and Gynecology, demonstrated that NC-FET
was non-inferior to AC-FET in live birth rates. The economic analysis showed
that NC-FET is the dominant strategy. NC-FET is therefore to be preferred over
AC-FET (4).

During a NC FET cycle the woman has to visit the hospital for ultrasound
monitoring on average three times (unpublished data ANTARTCICA TRIAL). From the
woman*s point of view a more natural approach and less interference with
private and working life is desired (5). Home based monitoring in fresh IVF
cycles indeed improved patient-reported outcomes such as contentedness,
empowerment, discretion and partner participation (6). Therefore, home based
monitoring might be also be the preferred treatment for women in FET cycles.

An alternative to the previously described NC-FET which implies hospital
controlled monitoring, is true natural cycle FET (true
NC-FET) in which the natural ovulation is monitored using urinary LH tests.
This allows women to monitor their natural ovulation
at home, reducing direct costs - of repeated ultrasound visits and medication -
and indirect costs - of transportation to the clinic
and productivity loss-. Because of this advantages, true NC FET is increasingly
being applied in the Netherlands, albeit in the
absence of evidence supporting its (cost-)effectiveness.

Assessing (cost-)effectiveness of home based monitoring with urinary LH tests
(true natural cycle frozen embryo transfer, true NC-FET) versus hospital
controlled monitoring with repeated ultrasound monitoring and hCG trigger
(modified NC-FET) to time frozen embryo transfer in IVF.

Multicentre, non-inferiority RCT with a cost-effectiveness analysis.

INTERVENTION: True natural cycle FET with home-based monitoring of ovulation
with urinary LH tests

USUAL CARE /COMPARISON: Modified NC-FET with repeated ultrasound monitoring of
the dominant follicle followed by hCG
trigger.

As we compare strategies that are already current practices, no additional
risks or burdens are expected from the study.