الفهرس 
In vitro FertilizationOnly 14 pages are availabe for public view
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Abstract
Assisted reproductive techniques are an accepted form of
treatment for infertility and the procedures used are generally
assumed to be relatively constant in the way they are
performed between centers. Transvaginal ultrasound guided
oocyte collection is now almost universal (Scott et al., 2001).
In early stages of assisted reproductive technologies
(ART), oocyte retrieval was performed via laparoscopy, a
cumbersome and expensive process requiring general
anesthesia (Lenz et al., 2001). Today, transvaginal oocyte
retrieval for ART is a routine procedure performed under
ultrasound guidance. Double lumen retrieval needles, which
are capable of flushing ovarian follicles, were developed to
overcome the possibility of oocyte retention within the ovarian
follicles and retrieval collection system (Knight et al., 2001).
The place of follicular flushing during oocyte recovery
in ART is still uncertain. The pros of flushing include the
possibility of obtaining more oocytes, and subsequently more
embryos. Whether this translates into a higher pregnancy rate
and live births remains unknown. The cons of flushing are a
longer operative time and larger amounts of required
anaesthetics and analgesics. from a patient’s perspective, it
could also mean higher costs.
The objective of the study was to evaluate the effect of
follicular flushing on IVF cycle outcomes, including the
number of oocytes retrieved, number of mature oocytes,
fertilization rate, number of embryos transferred, implantation
rate, operating room time, pregnancy rate and post operative
adverse event.
The study was a prospective randomized controlled trial.
190 (complete outcome data were available in 185 (97%)infertile women who underwent IVF/ICSI were included in the
study after verbal and written consent. They were recruited
from Assisted Reproductive Technology unit, Ain Shams
University maternity Hospital during the period from
September 2011 to September 2013.
The total sample size was calculated as 190 cases,
randomized using a block randomization method on the day of
oocyte retrieval into two equal groups:
Group 1: this group consisted of 95 (93 completed the
study) cases underwent aspiration alone during oocyte
retrieval.
Group 2: this group consisted of 95 (92 completed the
study) cases underwent aspiration and flushing during
oocyte retrieval.
Patients meeting study requirements were offered
enrollment. Each patient in the study and control groups
subjected to the following:
- Controlled ovarian hyperstimulation using down
regulation with GnRH analogue in mid-luteal phase of
pretreatment cycle as the standard protocol with
Triptorelin acetate (Decapeptyl) 0.1 mg subcutaneous at
day 14 to 16 of pre-induction cycle, followed by ovarian
stimulation with HMG (human menopausal
gonadotropin) at day 3, dosage of HMG depends on the
BMI, age, FSH, and ovarian size by TVUS, At the first
scan, the number, sizes of the follicles were written. If he
size is 12-14 mm allowed two days before next scan, if
14 mm or more next scan was within 24 hours , human
chorionic gonadotropin (choriomon 5000iu, IM
injection) administrated 10000 iu when three or more
follicles were at least 18 mm in largest diameter, Transvaginal follicular aspiration performed 34-36 hours after
hCG trigger as the following:
- During the trial period the following parameters kept
constant, The manufacturer of the aspiration needles
(Wallace Oocyte Recovery Systems; Oocyte Recovery
Needle 33cm x 16), the pump (Pioneer Pro-pump, GenX
International; Guilford, CT) and pressure used set to
maximum of 120 mmHg at aspiration, and up to 200
mmHg at re-aspiration in flushing group, staff involved
in all set procedures, the premises and equipment at
oocyte collection and culture.
In the aspiration alone group, a 16 gauge single
lumen needle used, with suction continue until a small amount
of blood stained fluid appeared in the tubing or flow stop. The
dead space within the needle and tubing suctioned upon
removal from the vagina.
When flushing accompany aspiration of follicular fluid
in the study group, the same needle used with a double-way
tap allowing the same amount of culture medium as the follicle
volume to be circulated through the empty follicle (2 ml) of
Earl’s medium till oocyte retrieved or maximum two times.
The embryologist identifying and collecting the oocytes
remained blinded to the group assignments. The providers
performing the oocyte retrieval remained blinded to the
number of oocytes retrieved until the completion of the
procedure.
The patient kept under observation for two hours to
assess presence of adverse events, including complication rate
for the surgical procedure and during the flushing procedure
(post operative pain (need for diclphen 75 mg im vial, internal
hemorrhage, infection, vomiting and hypotension). Secondary
end-points included recovery rate, total number of matureoocytes, maturity rate, fertilization rate, number of embryos
transferred, implantation rate, on-going pregnancy rate.
Embryo transfer for both groups done in the morning of
day 3 using (Labotect catheter, Germany) while the patient in
Lithotomy position and semi-full bladder, patients instructed
to be resting on their back for at least 30 minute following the
process of embryo transfer.Patients start progesterone
medication after oocyte retrieval. All cases will underwent an
initial serum test for B-HCG two weeks after embryo transfer,
chemical pregnancy is defined when level of B-HCG is higher
than 25 iu, while clinical pregnancy is defined when fetal heart
pulsation could be detected from 6 to 7 weeks by TVUS.
As regard baseline characteristics and cycle outcomes of
both groups, There were no significant differences in age,
BMI, total gonadotropins received, duration of stimulation, the
proportion of ICSI, and the diagnosis between groups. The
long agonist protocol was used in all but one patient (flushing
group) used antagonist protocol. There were no significant
differences between the groups regarding the mean number of
ovarian follicles ≥16 mm.
In our study we found that, Total and differential
retrieved oocytes were significantly higher among flushing
group than non-flushing group. The study observed 60.5 %
oocyte recovery rate with aspiration only (484 oocyte recruited
from 800 follicles), compared with 80.9 % with follicular
aspiration and flushing (670 oocyte recruited from 828
follicles), concluded that 20.4% more oocytes were obtained
with follicular aspiration and flushing than aspiration alone.
The average number of oocytes collected per woman
randomized in study group (7.3±2.3 versus 5.2±2.6, #P< 0.001)
in non flush group, Furthermore, the proportion of mature
oocytes recovered from follicles ≥16 mm was significantlymore with study group than those with control group (5.8±2.1
versus 4.4±2.4, #P< 0.001).
At the same time immature oocyte retrieved were
significantly more in the study group than those in controle
group (#P< 0.001).
Regarding operative time, operative time (minutes) was
significantly longer among flushing group than non-flushing
group. The retrieval time was 1.3 fold higher among those
undergoing follicular flushing, with an estimated increase of 5
minutes (P<0.001).
Regarding total number of produced embryos, total number
of produced embryos were significantly higher among flushing
group than non-flushing group. In addition, oocytes retrieved
by follicular flushing demonstrated a better morphological
quality (top quality embryos 296/423 or 70% versus 189/316 or
60%; P<0.001).
The study observed 39.5% fertilization rate with
aspiration only (316 oocyte fertilized from 800 follicles),
compared with 52.2% with follicular aspiration and flushing
(423 oocyte fertilized from 828 follicles), concluded that
12.7% more embryos were obtained with follicular aspiration
and flushing than aspiration alone.
The average number of produced embryos per woman
randomized in study group (4.7±2.0 versus 3.4±2.2, #P< 0.001)
in non flush group.
Regarding pregnancy outcome, Pregnancy was nonsignificantly
more frequent among flushing group than nonflushing
group. Implantation rates non-significantly more
frequent among flushing group than non-flushing group
(31.6% versus 26.3% , P= 0.424) and ongoing clinicalpregnancy non-significantly more frequent among flushing
group (27.4% versus 21.1% , P= 0.31).
The study failed to follow women up to obtain data on
live births and our pregnancy outcome in general low cause the
Assisted Reproductive Technology unit, Ain Shams University
maternity Hospital accepting cases with bad prognosis and
repeated failed trial of ICSI.
Regarding postoperative adverse events, Postoperative
complications were non-significantly more frequent among
flushing group than non-flushing group. As 62 cases of 92
required post operative Diclophin 75 mg Im. in study group
versus 49 cases of 93 in control group; P = 0.056, and 9 cases
complained of vomiting in the study group versus 4 in control
group; P = 0.151, and 15 cases developed post operative
hypotension in the study group versus 7 cases in control group
P = 0.071.
In conclusion, flushing non-significantly increase
implantation and clinical pregnancy outcome and associated
with a significant increase in the procedure time for oocyte
retrieval, so patient groups where a small number of oocytes
are available for retrieval may represent patients most likely to
benefit from follicle flushing as only one extra oocyte may
affect the outcome. Such patient groups may include poor
responders, natural cycle ART and minimal stimulation ART.