Transcript Document

Myomectomy in infertile patients
Prof. Abbas Aflatoonian
14th International Congress on Obstetrics and Gynecology
October 14-17, 2014 - Tehran - Iran
Subjects
•
•
•
•
•
Myoma ,Description and types
Effect on fertility and IVF/ICSI outcome
Myoma and gene expression
Myomectomy, When? Whom?
Conclusions
• Myomas appear to arise from a mutation in a single
myometrial cell
• Regulated factor : estrogen , progesterone , local
growth factors
• Myomas are the most common benign tumors of the
female genital tract and occur in about 20-50% of
women
• They are associated with many gynecological problems
including heavy menstrual bleeding and infertility.
Yoshino O, et al. Human Reproduction 2010;25(10):2475–9.
Types of fibroids
1. Submucos (SM): Fibroid distorting the uterine
cavity:
Type 0: pedunculated without intramural extension
Type I: Sessile with intramural extension <50%
Type II: Sessile with intramural extension >50%
2. Intramural (IM): Fibroid not distorting the cavity
with <50% protrusion into serosal surface
3. Subserosal (SS): >50% protrudes out of the
serosal surface
The European Society of Hysteroscopy, 1993
Myoma and infertility
• Myomas are present in approximately 5%–
10% of women with infertility Fibroids and are
estimated to be the sole cause of infertility in
less than 3% of cases
• Depending on size, number and location in the
uterus, myomas have been implicated in both
recurrent pregnancy loss and infertility
Farquhar C. BMJ 2009;16:338.
• The outcomes of women with any location of
fibroid, clinical pregnancy, implantation, and
ongoing pregnancy/live birth were all
significantly lower in women with myomas
than in control subjects
• The spontaneous abortion rate was
significantly greater in women with fibroids
Pritts et al, Fertile Steril. 2009 Apr;91(4):1215-23.
• The women with SM fibroids, compared with
infertile women without fibroids, demonstrated a
significantly lower clinical pregnancy rate,
implantation rate, and ongoing pregnancy/live
birth rate and a significantly higher spontaneous
abortion rate.
• No difference was seen in rate of preterm
delivery.
• Women with no cavitary involvement had a
significantly decreased implantation rate and
ongoing pregnancy/live birth rate as well as an
increased spontaneous abortion rate compared
with nonfibroid control subjects.
• No significance was seen in preterm delivery rates
Pritts et al, Fertile Steril. 2009 Apr;91(4):1215-23.
• When women with SS fibroids were examined
in comparison with women without fibroids,
no difference was observed for any outcome
measure.
• In contrast, women with IM fibroids produced
significantly lower clinical pregnancy rates,
implantation
rates,
and
ongoing
pregnancy/live birth rates and significantly
higher spontaneous abortion rates. No
difference was seen in the rate of preterm
delivery
Pritts et al, Fertile Steril. 2009 Apr;91(4):1215-23.
• Submucosal fibroids had the strongest
association with lower ongoing pregnancy
rates, through decreased implantation.
• Cumulative pregnancy rates appeared slightly
lower in patients with intramural fibroids
(36.9% vs 41.1%)
• Patients with intramural fibroids also
experienced more miscarriages, 20.4% vs
12.9%.
• There was no conclusive evidence that
intramural or subserosal fibroids adversely
affect fecundity.
• Fertility outcomes are decreased in women with
submucosal fibroids, and removal seems to
confer benefit.
• Subserosal fibroids do not affect fertility
outcomes, and removal does not confer benefit.
• Intramural fibroids appear to decrease fertility,
but the results of therapy are unclear.
• More high-quality studies need to be directed
toward the value of myomectomy for intramural
fibroids, focusing on issues such as size, number,
and proximity to the endometrium.
Myoma and IVF/ICSI outcome
• Live birth as an outcome showed a statistically
significant 21% relative reduction in women with
non-cavity-distorting
intramural
fibroids
compared with women without fibroids
• Clinical pregnancy as an outcome showed a
statistically significant 15% reduction in women
with non-cavity-distorting intramural fibroids,
following IVF treatment
Sunkara et al, Hum Reprod, 2010 Feb;25(2):418-29.
• Result showed statistically non-significant 13%
reduction in IR in women with non-cavitydistorting intramural fibroids
• Miscarriage as an outcome showed a statistically
non-significant 24% relative increase in
miscarriage rate in women with non-cavitydistorting intramural fibroids, following IVF
treatment
Sunkara et al, Hum Reprod, 2010 Feb;25(2):418-29.
• In asymptomatic patients selected for IVF,
small fibroids with a diameter < 50 mm and
not encroaching the endometrial cavity do not
impact on the rate of success of the
procedure. This result should not, however, be
used to conclude that all intramural or
subserosal lesions are unremarkable.
• In fact, current available evidence indicates
that at least some lesions may be deleterious.
• Results suggest that fibroids not encroaching
upon the uterine cavity may not have a strong
adverse effect on IVF/ICSI outcomes.
• A subgroup of IM fibroids with SFD>2.85 cm
was found to have significantly lower DR than
matched nonfibroid controls.
• Type 3 IM fibroids did not portend a poorer
response to IVF/ICSI compared with matched
controls.
• Small IM fibroids with an SFD≤2.85 cm do not
negatively affect the main IVF outcomes
including CPR, MR, and DR.
Myoma and gene expression
• The homeobox (HOX) genes encode transcription
factors that guide embryologic development as
well as regulate d with each menstrual cycle.
• HOXA10 expression is necessary for endometrial
receptivity .
• In the mid-secretory phase at the time of
implantation, HOXA10 messenger RNA(mRNA)
expression is up-regulated in both endometrial
glandular and stromal cells in women.
22
• Result showed statistically significantly decreased HOXA-10
and HOXA-11 transcript levels in infertile patients compared
to controls.
• There was no significant decrease in HOXA-10 protein levels
between these groups.
• A significantly higher level of HOXA-11 protein was reported
in the endometria of infertile patients compared to controls.
• HOXA-10 and HOXA-11 proteins were localized in the nuclei of
the endometrial stromal cells.
• Immunohistochemical analyses did not reveal differences
between amounts of HOXA-10 and HOXA-11 protein levels in
infertility and control groups.
• The results suggest that HOXA-10 and HOXA-11 gene
expression in the endometrium during the implantation
window may not be altered in patients with idiopathic
infertility.
• The study has identified lower expression of
HOXA11,
• LIF and BTEB1 in women with myoma that
may result in inadequate preparation of a
receptive endometrium.
• HOXA11, LIF and BTEB1 mRNA are not the
only molecules responsible for successful
implantation.
Myomectomy
• Hysteroscopic myomectomy is choice for SM myoma
• IM myomectomy may perform via laparoscopy or
laparotomy
• Note: Correct repair in the bed of myoma is essential
• The best time for myomectomy is 3-6 months before
desire pregnancy
• Repeated myomectomy is difficult and may lead to
unwanted hystrectomy
• For SS myoma mostly no surgery unless for very huge
myomas
• If fibroid removal is beneficial, myomectomy
subjects would be expected to have higher
pregnancy rates and lower abortion rates than
those with fibroids in place.
• In those with SM fibroids, clinical pregnancy
rate is indeed higher in the myomectomy
group, but the ongoing pregnancy/live birth
rate fails to reach statistical significance. The
spontaneous
abortion
rate
appears
unchanged.
• In women with IM fibroids, no significant
differences are seen.
Pritts et al, Fertile Steril. 2009 Apr;91(4):1215-23.
Conclusions
• Myoma may interfere with fertility specially
SM and IM myoma
• Treatment perform via surgery, hystroscopy,
laparoscopy or laparotomy
• Repair of bed of myoma is crucial and the best
time is 3-6 months before desire pregnancy
• Molecular and genetic problem due to myoma
may increase Indication for myoma in future