New Treatment Strategies For Repeated IVF Failures
(Endometrial scratch and use of Granulocyte-colony stimulating factor)
Endometrial Scratch
What is endometrial scratching
The lining of the uterus (the
endometrium) is gently 'scratched' using a thin catheter (a fine, flexible, sterile,
plastic tube) which is passed through the cervix.
Who may benefit from endometrial scratching
Our clinic offers endometrial
scratching to women who have had more than two IVF, ICSI or FET cycles which resulted
in a negative pregnancy test, despite having good quality embryos.
How does scratching help implantation
New research and evidence suggests
that scratching the uterine lining causes a 'repair reaction' which may increase
embryo implantation rates:
OThe repair process releases growth
factors, hormones and chemicals. The new lining which grows after the procedure
is thought to be more receptive to an implanting embryo and so increases the chances
of pregnancy.
Endometrial scratching may 'switch
on' the genes that are responsible for preparation of the endometrium for implantation,
which increases the chances of pregnancy.
When is the best time to have the procedure
The best time to perform the endometrial
scratch is at the 'day 21′ treatment planning appointment, before the IVF, ICSI
or FET treatment cycle begins. In a standard 28 day cycle, 'day 21′comes just after
ovulation, a few days before the woman's period is due. If her periods are infrequent
or irregular, the clinical team will advise on the best time for the procedure.
How is the procedure performed
Sometimes, it may be necessary
to dilate the cervix before performing a scratching. Short acting IV sedation usually
suffices for this minor procedure. A thin flexible catheter is inserted through
the opening of the cervix, and the uterine lining is gently 'scratched'. (Inserting
and moving the intrauterine catheter up and down may cause mild abdominal cramping
similar to period pain.)
Success Rates
Endometrial scratching is a new technique at MFC and we have used it for more than
a 100 patients with repeated IVF failures. The pregnancy rate following this procedure
has been 39% per IVF cycle. Our data suggests improvement in treatment outcomes
in the group of patients who have previously had multiple failed treatment cycles.
Granulocyte Colony Stimulating Factor - Intrauterine Instillation
This drug is relatively new and promoted for use in patients with a very thin lining
of the uterus (endometrium) and patients with repeated implantation failures (repeated
failed IVF cycles).
The mechanism of action is similar to the scratching. Infusion of G-CSF helps in
the regeneration of new endometrium and also stimulates certain factors that help
in embryo implantation.
It is instilled into the uterine cavity with a thin plastic tube – no anesthesia
or cervical dilatation is required. The procedure is similar to an IUI and quite
painless.
It can be infused either on the day of the night trigger of hCG (48 hours before
egg recovery) or during the frozen embryo cycle.
The clinic has used this for a large number of patients with encouraging results.
Platelet rich Plasma (PRP) – Intrauterine instillation
Despite progress in the field of assisted reproductive technology, still multiple
embryos fail to implant. A significant percentage of in vitro fertilization failure
is due to the endometrial receptivity. Implantation requires perfect coordination
between a good quality embryo and a perfectly receptive endometrium (lining of the
uterus). Various approaches have been used as therapeutic strategies in the investigations
and management of Recurrent implantation failures such as local endometrial injury,
changes in stimulation protocols, intrauterine granulocyte colony-stimulating factor
before embryo transfer, blastocyst assisted hatching transfer and pre-implantation
genetic diagnosis for aneuploidy.
Human endometrium undergoes significant changes during implantation. Human endometrial
tissue contains receptors for growth factors, adhesion molecules, cytokines, growth
factors, lipids, and other factors which are thought to enhance endometrial and
embryonic development. PRP contains the growth factors and other cytokines that
have positive effects on local tissue repair and endometrial receptivity. PRP could
be a new treatment used for the improvement of the endometrial thickness in women
with a thin endometrium. The use of PRP is considered safe because it is autologous
and is derived from patient’s own blood.
Local administration of PRP could be a successful treatment in women with recurrent
implantation failure (RIF) especially in cases with a thin endometrium and those
with unexplained recurrent implantation failures.
Freeze-all Policy
A lot of failures with IVF in fresh embryo cycles are because of asynchrony between
the follicles and the endometrium owing to the abnormally high hormone levels during
the stimulation cycle. These patients do well with a freeze all policy where all
embryos are frozen and then transferred in a subsequent unstimulated cycle (where
the endometrium is more like a natural cycle and more physiological). There are
many other indications where frozen embryo transfer gives better results such as
Endometriosis, Polycystic ovaries, thin endometrium, patients with previous miscarriages
or ectopic pregnancies and patients .