Int J Clin Exp Med 2014;7(7):1853-1859
www.ijcem.com /ISSN:1940-5901/IJCEM0000791
Original Article
Effect of lower than expected number of oocyte on the
IVF results after oocyte-pickup
Süheyla Gonca1, Ismet Gün2, Ali Ovayolu1, Dilek Şilfeler1, Kenan Sofuoğlu1, Özkan Özdamar3, Ali Yilmaz2,
Gülden Tunali1
Department of Obstetrics and Gynecology, Division of Reproductive and Endocrinology Unit, Zeynep Kamil
Education and Research Hospital, Istanbul, Turkey; 2Department of Obstetrics and Gynecology, Gulhane Military
Medical Academy, Haydarpasa Teaching Hospital, Istanbul, Turkey; 3Department of Obstetrics and Gynecology,
Gölcük Military Hospital, Gölcük, Kocaeli, Turkey
1
Received May 14, 2014; Accepted May 27, 2014; Epub July 15, 2014; Published July 30, 2014
Abstract: Objectives: To investigate whether a lower than expected number of oocyte after ≥14 mm follicle aspiration
during OPU has any effect on pregnancy outcomes Methods: This is a retrospective study done between 2010 and
2013 at the IVF Unit of the Zeynep Kamil Women and Children Diseases Education and Research Hospital, dealing
with the medical records of infertile patients who underwent IVF cycle and controlled ovarian stimulation with long
agonist or fix antogonist protocol. The patients included into the study were those diagnosed with a primary infertility, aged between 23 and 39, at a BMI of 22-28 kg/m2 and having received the first or second IVF treatment. Male
factor, presence of uterine anomaly, patients with serious endometriosis and patients with low ovarian reserve were
all excluded from the study. Typically, oocyte pick-up was performed in all the patients 35.5 hours after the hCG
implementation. Single or double embryo transfer was performed, where available. Patients were classified into two
groups. Group 1 consisted of those with no difference between ≥14 mm aspirated follicle number and expected
number of oocyte or with 1 missing number of oocyte at the most. Group 2 consisted of those with at least ≥2 missing number of oocyte between aspirated follicle number and expected number of oocyte. Statistical analysis was
performed using Student’s t test for continuous variables and chi-square test for categorical variables. Additionally,
a Linear regression analysis was conducted between the total number of oocyte and pregnancy. Results: In total,
387 treatment cycles were included into the study. Group 1 consisted of 134 patients and Group 2 consisted of 252
patients. Antral follicle number (12.8 ± 4.3 and 14.5 ± 4.1, P = 0.0007), hCG day E2 value (1990.7 ± 1056.4 and
2515.2 ± 1332.7, P < 0.0001) and the the number of aspirated follicle during OPU (9.1 ± 4.4 and 13.7 ± 5.5, P <
0.0001) were significantly higher in Group 2; whereas on the other hand, daily gonadotropin dose (290.9 ± 79.9
and 273.4 ± 74.4, P = 0.034) and total gonadotropin doses (2545 ± 1031.8 and 2247.7 ± 901.9, P = 0.004) were
significantly higher in Group 1. The pregnancy rate was significantly higher in Group 1 (29.1% and 19.4%, P = 0.041).
No correlation was observed between the number of oocyte and pregnancy (r = 0.082, P = 0.107). Conclusions: The
number of aspirated follicles during IVF treatment being higher than the collected number of oocyte leads to a statistically significant fall in the pregnancy rates. There is no correlation between the number of oocyte and pregnancy.
Keywords: Follicle/egg numbers, oocyte pickup, IVF-ICSI outcome, infertility, ovarian stimulation
Introduction
Today almost 15% of people receive treatment
in in vitro fertilization units (IVF) with a diagnosis of infertility [1, 2]. Even though there has
been a progress in the pregnancy rates over
the last two decades, live birth rates have not
still reached the desired levels. Some researchers examine the reasons underlying infertility
and some others try to find ways to have more
success in treatment and to increase live birth
rates. Nevertheless, there are still problems
waiting to be resolved [3]. There are various factors involved in the formation of pregnancy,
ranging from the age of the woman in question
to the selected treatment protocol and even the
reasons of infertility. Today, a couple of endocrine biochemical markers and ultrasonographic signs are used, which are influential in predicting in vitro fertilization (IVF) outcomes and
determining the gonadotropin doses to be used
in ovarian stimulation (OS) [4]. Among them, the
Lower than expected number of oocyte and IVF results
ones which are used most in practice, having
maximum reliability, are the ultrasonographic
assessment of the primordial antral follicle
pool in the early follicular phase and ovarian
volume [5, 6]. Nonetheless, ovarian reserve
tests are still inadequate in predicting live birth
rates [7, 8].
The primary aim of IVF treatment is to achieve a
term live birth. The main component of assisted reproduction treatment is OS. To know the
factors influencing the success of IVF is crucial
not only for the decision of the patient to begin
treatment, but also for the determination of the
treatment protocol to be selected by the doctor.
If the ovarian reserve is sufficient, the collected
number of oocyte is largely dependent on the
OS protocol to be implemented [9]. Thus, a
series of OS procedures have been implemented until today. Recently, the most frequently
used stimulation protocols have been the combination of long-term GnRH agonists with pituitary suppression and exogen FSH or the combination of exogen FSH and GnRH antagonist
with pituitary suppression [10]. In many studies, no difference was observed between GnRH
agonist and GnRH antagonist protocols in
terms of pregnancy rates [11, 12].
Follicle or oocyte are parameters which have
been frequently studied to achieve success for
IVF treatment. Lan et al. reported that in IVF
patients the right ovarian response was better
[13], Choe et al. reported that there was an
equivalence between the total number of
oocyte collected from both ovaries and the IVF
success [14] and Knopman et al. reported that
large dimensions of follicles extended the duration of treatment, even if they do not change
live birth rates [15]. In a recent study concerning the number of oocyte and live birth, it was
argued that there is a non-linear increase
between the number of oocyte and live birth
[16]; and additionally, that a high number of
oocyte presence leads to high estrogen values,
thus decreasing implantation rates [17-19].
Consequently, it seems that the success of IVF
treatment depends upon a number of factors. A
survey of relevant literature reveals that there
has been multiple studies on this topic, ranging
from IVF treatment protocols to the number of
oocyte and the quality of embryo. It appears
that no study conducted until today has dealt
with the effects of the synchronization between
the number of stimulated follicles after OS and
1854
(≥14 mm) the collected number of oocyte on
pregnancy rates.
The primary aim of this study is to investigate
whether a lower than expected number of
oocyte after follicle aspiration ≥14 mm during
oocyte pickup (OPU) has any effect on pregnancy outcomes in IVF patients who received OS.
The secondary aim of this study is to investigate whether there is a correlation between the
total number of oocyte and the obtained rates
of pregnancy.
Material and methods
This is a retrospective single-centered study
which was conducted between January 2010
and September 2013 over the medical records
of patients who applied to the IVF Unit of the
Zeynep Kamil Women and Children Diseases
Education and Research Hospital. The patients
included into the study were those diagnosed
with a primary infertility, aged between 23 and
39, at a BMI of 22-28 kg/m2 and having
received the first or second IVF treatment. Male
factor (according to the World Health Organization’s the 2010 criteria), presence of uterine
anomaly, patients with severe endometriosis
and patients with low ovarian reserve (FSH>10
or unresponsive in spite of maximum dose)
were all excluded from the study.
Patients received ovulation induction with
either long protocol or antogonist protocol. With
the beginning of the protocol, all patients
received a 100 mg daily dose of baby aspirin
and were reinforced with a 400 mcg of folic
acid. Gonadotropin doses were ascertained in
accordance with the age of the patient, BMI,
follicle number in the early follicular phase,
basal FSH level and the response given to the
previous treatment. During the treatment, ovarian response was assessed with vaginal ultrasonound guided monitoring of follicle growth
and measurement of serum estradiol (E2) levels. When the dominant follicle reached a diameter of 18 mm or in the presence of two follicles
with a diameter of >16 mm, 10,000 IU human
chorionic gonadotropin (hCG) were implemented to all patients. OPU was performed 35.5
hour after the hCG implementation, under
intravenous (iv) sedation and with the guidance
of transvaginal ultrasonography. During OPU
procedure, all patients received a 1 gr single
dose of cefazolin IV (Cefamezin 1000 mg IM/IV
Int J Clin Exp Med 2014;7(7):1853-1859
Lower than expected number of oocyte and IVF results
cal pregnancy; and
six weeks after ET in
Characteristics
Group 1
Group 2
P
an ultrasonic examiAge, year
31.1 ± 4.0
30.9 ± 4.0
0.614a
nation, presence of
Duration of infertility, year
7.5 ± 3.7
7.1 ± 3.9
0.306a
gestational sac was
Basal FSH, IU/L
6.7 ± 1.4
6.4 ± 1.5
0.161a
defined as clinical prBasal E2, pg/ml
49.5 ± 17.6
51.5 ± 16.9
0.330a
egnancy. At the ninth
Basal AFS, n
12.8 ± 4.3
14.5 ± 4.1
0.0007a
week of pregnancy, at
Daily dose/day, IU
290.9 ± 79.9
273.4 ± 74.4
0.034a
the ultrasonography,
the continuing pregDaily usage time, day
8.9 ± 1.6
8.7 ± 1.4
0.397a
a
nancy was defined as
Total daily dose, IU
2545 ± 1031.8
2247.7 ± 901.9
0.004
the presence of fetal
a
hCG day E2, pg/ml
1990.7 ± 1056.4 2515.2 ± 1332.7 < 0.0001
cardiac activity. Patia
hCG day endometrial eco, mm
9.9 ± 1.7
10.1 ± 1.7
0.505
ents were classified
Number of follicles during OPU, n
9.1 ± 4.4
13.7 ± 5.5
< 0.0001a
into two groups. GroTotal oocyte, n
8.5 ± 4.4
8.3 ± 4.5
0.695a
up 1 consisted of thMII oocyte, n
7.1 ± 4.4
6.9 ± 4.3
0.694a
ose with no differenCycle cancellation rate, n (%)
11/134 (8.2%)
14/253 (5.5%)
0.423b
ce between ≥14 mm
ET day
0.092b
aspirated follicle number and expected
3rd day
55.1%
56.7%
number of oocyte or
2nd day
30.8%
30.5%
with 1 missing numPregnancy rate, n (%)
39/134 (29.1%) 49/253 (19.4%)
0.041b
ber of oocyte at the
a
b
Data are presented as mean ± SD and number (percent). Student t test. Chi-square test.
most. Group 2 consisted of those with at
vial, Zentiva) and the same day, 200 mg of doxleast ≥2 missing number of oocyte between
aspirated follicle number and expected number
ycycline (Tetradox 100 mg capsule 2x1, Actavis)
of oocyte. The groups were compared with
and methylprednisolone (Prednol 16 mg tablet
respect to demographic characters, IVF param1x1, Mustafa Nevzat) were orally started, proeters and pregnancy outcomes.
viding all patients with these medicines for 4
days. Beginning from the OPU day onwards,
Statistical analysis
2x1 intravaginal progesteron (Crinone 8% vaginal gel, Merck Serono, UK) was started for luteStatistical analysis was performed using the
al phase support and in case of pregnancy, this
Statistical Package for the Social Sciences for
was continued until the tenth week of the pregWindows 15.0 software (SPSS, Chicago, IL.,
nancy. Following a three days of sexual abstiUSA). Descriptive statistics were given as
nence, the sperms of the male partners were
mean, standard deviation, frequency and percollected and washed on the OPU day. Four-six
centage. Statistical analysis was performed
hours after the OPU, oocytes were fertilized
using Student’s t test for continuous variables
either through routine insemination or intrastoand chi-square test for categorical variables.
plasmic sperm injection (ICSI). Oocyte maturity
When there was a need for a non-parametric
was determined by the presence or absence of
test, Mann Whitney U and Kruskal-wallis tests
the polar body approximately 18 hours after
were performed. In addition, a Linear regresoocyte retrieval. Fertilization was assessed 18
sion analysis was conducted between the total
hours after insemination or ICSI by visualization
number of oocyte and pregnancy. Statistical
of two pronuclei (2PN). All embryo transfers
significance was defined as p < 0.05. A nominal
(ET) were conducted with transabdominal ultratwo-sided P-value was considered for all
sonography guidance after insemination or ICSI
comparisons.
from the embryos in at least two-cell phase at
D2 or D3 or from blastocyst phase at D4 or D5
Results
as single or double embryos. The serum pregBetween January 2010 and September 2013,
nancy test was made twelve hours after the
at the IVF Unit of the Zeynep Kamil Women and
embryo transfer. If the B-hCG values were 20
Children Diseases Education and Research
IU/l and/or above, it was defined as biochemiTable 1. Demographic characteristics of patients and IVF outcomes
1855
Int J Clin Exp Med 2014;7(7):1853-1859
Lower than expected number of oocyte and IVF results
Hospital, a total of 3379 files containing IVF
cycle information were surveyed. 387 treatment cycles were included into the study. There
were 134 patients in Group 1 and 253 patients
in Group 2. Demographic characters, basal hormone values, IVF treatment values and IVF
treatment results are shown in Table 1. In
terms of demographic characters such as age,
BMI and duration of infertility, there was no difference between the groups. Additionally, basal
FSH and E2 levels were similar. However, even
if it has not a clinical significance, the number
of antral follicles were significantly higher in
Group 2 (12.8 ± 4.3 and 14.5 ± 4.1, p =
0.0007). Daily gonadotropin dose (290.9 ±
79.9 and 273.4 ± 74.4, p = 0.034) and total
gonadotropin doses (2545 ± 1031.8 and
2247.7 ± 901.9, p = 0.004) were significantly
higher in Group 1 than in Group 2. hCG day E2
value (1990.7 ± 1056.4 and 2515.2 ± 1332.7,
p < 0.0001) and the number of aspirated follicles during OPU (9.1 ± 4.4 and 13.7 ± 5.5, p <
0.0001) were significantly higher in Group 2
than in Group 1. In terms of the total number of
oocyte (8.5 ± 4.4 ve 8.3 ± 4.5, p = 0.695) and
the number of MII oocyte (7.1 ± 4.4 and 6.9 ±
4.3, p = 0.694), there was no difference
between the groups. Nevertheless, pregnancy
rate were significantly higher in Group 1 (29.1%)
than in Group 2 (19.4%) (p = 0.041). No correlation was observed between the number of
oocyte and pregnancy (r = 0.082, p = 0.107).
Discussion
Despite technological advances, assisted
reproduction methods are not only still expensive, but also tiresome and arduous for patients
on account of the medical effects of the treatment and the ensuing emotinal stresses.
Therefore, knowledge of the factors that would
help predicting the success of IVF is very crucial not only for the decision to begin IVF, but
also for the determination of the suitable OS
method in the process of treatment. Up to the
present, many studies have been done in order
to increase success in IVF, but one of the most
researched structures has been follicle or
oocyte. With respect to the issue at hand, Lan
et al, reported in their studies that in IVF treatment both ovaries do not have an identical
responce and that the right ovary generally has
a better response [13]. These data comply with
the data of the study by Fukuda et al. which
1856
investigated the characteristic of ovulation in
natural cycle [20]. In their study on the dimension of oocyte, Knopman et al. reported that
the postponement of ovulation induction in
order to enhance the dimension of oocyte leads
to financial cost increase and extends the duration of treatment, without increasing the number of embryos and live birth rates [15]. Choe et
al. reported that there is an equivalence
between the total number of oocyte collected
from both ovaries and the IVF success [14],
that the rate of pregnancy increases as the difference decreases, and finally, that the rate of
difference between the total number of oocyte
collected from both ovaries has a predictive
value on IVF cycles. In addition, it was emphasized that the difference between the total
number of oocyte collected from both ovaries is
inversely proportional to the total number of
collected oocyte [14]. In the animal study conducted by Falconer et al. there was a counter
arguement that there is a direct proportion
between the difference and total number [21].
And in our study, too, what was investigated
was whether a difference between the number
of aspirated follicle and expected number of
oocyte had any effect on pregnancy outcomes.
It was seen that in case of a difference between
the number of follicles aspirated independently
of the total number of oocyte and the number
of collected oocyte, pregnanct rates tend to
decrease (29.1% to 19.4%, p = 0.041). Additionally, the number of follicles aspirated during
OPU appeared to be higher in the group where
the number of pregnancy was lesser (p <
0.0001). In other words, the fact that the number of oocyte per follicle is higher in Group 1
and that the pregnancy rate is higher in this
group, supports the data provided by previous
literature, which argued that increases in the
number of oocytes to certain limits also lead to
an increase in the rate of pregnancy [16, 22-24].
The secondary aim of our study was to investigate whether there is any correlation between
the number of oocyte and pregnancy outcomes.
According to the results of our study, there is no
correlation betwen the number of collected
oocyte and pregnancy rates (r = 0.082). Among
the studies about oocyte, the data which we
encounter most is the number of collected
oocyte. For it is believed that an increase in the
number of oocytes enhances the capability to
select the most suitable embryo and that
Int J Clin Exp Med 2014;7(7):1853-1859
Lower than expected number of oocyte and IVF results
obtainment of a few number of oocyte despite
OS represent weak clinical pregnancy outcomes and ovarian aging [25, 26]. There are
also some publications which argue the opposite, i.e., which claim that there is an equivalence between a low number of oocyte presence and high rates of pregnancy [9, 27], or
that there is no correlation between the number of collected oocyte and pregnancy outcomes [28] or that there is no explicit relation
between the two [29]. However, there is no
explicit data about the optimum number of
oocyte in IVF treatment today. The most comprehensive study on this theme is the study
done by Sunkara et al. [16], where they examined the results of 400.135 IVF cycles and
assessed the relationship with live birth rates.
In accordance with these data, it was reported
that the increase in the number of collected
oocyte up to 15 accompanies an increase in
the rate of live birth rates, plateaued between
15 and 20 eggs, and finally declined beyond 20
eggs. Other studies conducted with similar
methods also reported that there is a correlation between the number of oocyte and the
pregnancy rates. Nevertheless, these were
small-scale studies and there were discordances between the data. For example, van der
Gaast et al. reported the optimum collected
oocyte as 9 [24] whereas Ji et al. as between 6
and 15 [22], and Kably Ambe et al. as 10-15
[30]. Even though it seems that the main aim of
in these treatments is to obtain a maximum
number of oocyte, the fact that usage of a high
dose of gonadotropin may effectively damage
the morphology of oocyte and also damage the
embryo transfer by way of increasing the likelihood of chromosomal anomaly should always
kept in mind [31]. In addition, some studies
highlighted that high E2 levels might have negative effects on implantation and development
potential [17-19]. In our study, lower pregnancy
rates in Group 2, might be attributed to the
negative effects of high serum estradiol levels
(1990.7 ± 1056.4 to 2515.2 ± 1332.7, p <
0.0001) arising from a higher number of follicle
(9.1 ± 4.4 to 13.7 ± 5.5, p < 0.0001) upon
embryo implantation.
ences. Second, on account of the density of
volume of work, the information about the operation could not always be recorded on the spur
of the moment and these records were kept by
different doctors. And this might have led to a
decrease in the accuracy of the recorded data.
Third, the patients included into the study were
those who received two separate protocols, but
they were not compared with each other in this
respect. Fourth, on the ground that on hCG day
progesteron values were not routinely monitored, we have no knowledge about the premature luteinization levels. Fifth, we could not
reach the live birth rates of the patients. And
finally, as this is a retrospective study, confusing factors could not be controlled. Nonetheless,
in spite of all these constraints, this is an important study, since it is the first study dealing with
this specific topic in the relevant literature.
There are some weaknesses of our study. First,
although all OPU procedures were conducted in
a single center, the implementation was done
by different doctors. Even if these operations
were standardized by our center as far as possible, there might have been individual differ-
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1857
Consequently, we are not still at the desired levels with regard to IVF treatment. Therefore, it is
crucial to know all the factors that might influence IVF success. Follicular development and
oocyte complex during the IVF treatment is a
complicated process and even if less compared to the past, it still retains its mystery. In
the context of patients receiving IVF treatment,
the number of follicles aspirated during OPU
being higher that the total number of collected
oocytes leads to a statistically significant
decrease in pregnancy rates. There is no correlation between the number of oocyte and
pregnancy. There is a need for larger controlled
studies to analyze how the factor that damages
synchronization leads to a decrease in pregnancy reates.
Disclosure of conflict of interest
None.
Address correspondence to: Dr. Ismet Gün, Department of Obstetrics and Gynecology, GATA
Haydarpasa Training Hospital, 34668 İstanbul,
Turkey. Tel: +90 216 542 20 20; Fax: +90 216 348
78 80; E-mail: [email protected]; drismetgun@
gmail.com
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