Objective
This study investigated whether the average oocyte quality index (AOQI), used as a dysmorphic oocyte scoring system, is higher
in women with ovarian endometrioma than in those with unexplained infertility or diminished ovarian reserve (DOR).
Methods
We included 92 intracytoplasmic sperm injection cycles in which one to five metaphase II oocytes were obtained, and the AOQI
was calculated in each cycle. Cycles were grouped according to the indication for in vitro fertilization: current or recurrent endometrioma (34
cycles), unexplained infertility (26 cycles), and DOR (32 cycles). DOR was defined by a serum anti-Müllerian hormone (AMH) level <1.0 ng/mL.
The AOQI was compared among the three groups, and the relationship between serum AMH levels and AOQI was also analyzed.
Results
The median AOQI value was significantly higher in the endometrioma group (1.50) compared to the unexplained infertility group
(1.00) (p=0.037), but not compared to the DOR group (1.42). Overall, serum AMH level showed an inverse correlation with the AOQI (r=–
0.242, p=0.02). Serum AMH level was also inversely correlated with the AOQI in the endometrioma group (r=–0.429, p=0.011), but not in the
unexplained infertility and DOR groups. Multiple linear regression analysis demonstrated that serum AMH levels remained inversely correlat-
ed with the AOQI (B=–0.176; 95% confidence interval, –0.327 to –0.024; p=0.024), whereas the presence of endometrioma was not a signifi-
cant factor.
Conclusion
The AOQI in the ovarian endometrioma group was higher compared to the unexplained infertility group, and this difference ap-
peared to arise primarily from reduced ovarian reserve rather than the direct impact of endometrioma itself. Serum AMH levels showed an
inverse correlation with AOQI, emphasizing the central role of ovarian reserve in determining oocyte quality.
Keywords
Anti-Mullerian hormone; Endometriosis; Infertility; Oocytes
Introduction
Endometriosis is a chronic inflammatory condition characterized
by endometrial-like tissue located outside the uterus, with ovarian
endometrioma representing one of its most common manifestations
[1]. This disease can significantly affect women’s reproductive health,
particularly in those undergoing in vitro fertilization (IVF), where re-
productive outcomes may be compromised [2 ]. Multiple studies
have demonstrated that the presence of endometrioma may ad-
versely affect ovarian reserve and the response to stimulation during
IVF treatments [3].
There is ongoing debate regarding whether oocyte and embryo
line space, fragmented polar body, and the overall oocyte morpholo-
gy score represented by the AOQI [12].
Despite increasing interest in the impact of endometriosis on re-
productive outcomes, relatively few studies have directly compared
oocyte quality indices between women with ovarian endometrioma
and those with other forms of infertility. Notably, limited research
has examined AOQI differences between women with endometrio-
ma and those with diminished ovarian reserve (DOR) of various etiol-
ogies [13,14]. The relationship between ovarian reserve markers and
oocyte quality in patients with endometrioma also remains unclear,
as current evidence offers conflicting conclusions regarding whether
both oocyte quantity and quality are similarly affected [15].
Therefore, this study sought to analyze AOQI differences in women
with ovarian endometrioma undergoing IVF and to assess its correla-
tion with ovarian reserve. By doing so, it aims to contribute to a more
comprehensive understanding of reproductive outcomes in these
patients and to inform clinical decision-making for treatment optimi-
zation. This study specifically aims to determine whether the AOQI is
higher in women with ovarian endometrioma than in those with un-
explained infertility or DOR. In addition, the association between se-
rum AMH levels and AOQI was also assessed.
Methods
1. Study population
This study was conducted at Seoul National University Bundang
Hospital. We included 92 ICSI cycles (49 women) in which one to five
MII oocytes were obtained between January 2023 and September
2024. The study was approved by the Institutional Review Board of
Seoul National University Bundang Hospital (IRB No. B-2508-989-
109), and the requirement for informed consent was waived because
of its retrospective design.
Each cycle was assigned to one of three groups according to the
primary indication for IVF treatment: current or recurrent ovarian en-
dometrioma (34 cycles), unexplained infertility (26 cycles), and DOR,
defined as a serum AMH level <1.0 ng/mL (32 cycles). Demographic
and clinical information was retrieved from electronic medical re-
cords.
Exclusion criteria included patients with a prior history of endome-
trioma surgery without evidence of current endometrioma, as well
as those undergoing IVF for other indications such as tubal factor in-
fertility or male factor infertility.
2. Ovarian stimulation and IVF procedure
Ovarian stimulation protocols were selected based on patient age,
ovarian reserve, and previous response to stimulation, following
standard clinical practice at our institution [16]. Pituitary suppression
quality are reduced in IVF patients with endometriosis compared to
those with other infertility etiologies. Several studies have explored
correlations between oocyte quality parameters and IVF outcomes
across various patient populations, yet findings remain inconsistent
regarding the specific impact of endometrioma on oocyte compe-
tence [4,5]. A previous study suggested that women with endome-
triosis-associated infertility tend to have reduced oocyte quality
compared to those with other infertility factors, potentially contrib-
uting to lower implantation and pregnancy outcomes [6].
Some have proposed that endometrioma primarily affects ovarian
reserve rather than oocyte quality itself [7]. In a retrospective study
by Benaglia et al. [8], although the number of oocytes collected from
women with endometriosis was smaller, fertilization rates, embryo
quality, implantation rates, pregnancy rates, and live birth rates were
comparable to those in women with other infertility factors. Similar-
ly, Kamath et al. [9] reported that live birth rates per cycle in women
with endometriosis were similar between cycles using donor oocytes
and cycles using autologous oocytes. Based on such findings, endo-
metriosis does not appear to exert a substantial adverse effect on
oocyte or embryo quality.
Nevertheless, previous studies did not directly analyze oocyte
quality, but instead evaluated it indirectly by comparing fertilization
rates. The assessment of oocyte quality is essential for predicting em-
bryo developmental potential and ultimately the success of IVF pro-
cedures. In intracytoplasmic sperm injection (ICSI) cycles, dysmor-
phic metaphase II (MII) oocytes are frequently associated with re-
duced fertilization and cleavage rates. Dysmorphic oocytes exhibit
cytoplasmic granulation, abnormal cytoplasm (including vacuoles,
refractile bodies, or smooth endoplasmic reticulum), abnormal oo-
cyte shape, and alterations of the zona pellucida, perivitelline space,
or polar body.
The average oocyte quality index (AOQI) was introduced as a mor-
phological oocyte scoring system in which the total number of ab-
normalities in MII oocytes is counted, and the index is calculated as
the ratio of abnormalities to the total number of MII oocytes [10]. Si-
gala et al. [10] evaluated abnormalities across seven morphological
categories, including cytoplasmic granularity, irregular shape or
thickened zona pellucida, intracytoplasmic vacuoles, material within
the zona pellucida, anomalies of the first polar body, large perivitel-
line space, and oocyte shape [10].
In one retrospective study, the AOQI was similar between women
with and without endometriosis. However, two specific abnormali-
ties, abnormal oocyte shape and intracytoplasmic vacuoles, were
observed more frequently in women with endometriosis [11]. An-
other retrospective study found that serum anti-Müllerian hormone
(AMH) level was inversely associated with cytoplasmic granulation,
abnormally amorphous oocytes, extended or granulated perivitel-
https://doi.org/10.5653/cerm.2025.084382
Clin Exp Reprod Med [Epub ahead of print]
was performed using either a gonadotropin-releasing hormone
(GnRH) agonist long protocol or a GnRH antagonist protocol. Recom-
binant follicle-stimulating hormone and/or human menopausal go-
nadotropin was administered for stimulation, with dosing individu-
alized to each patient’s characteristics.
Ovulation was triggered with human chorionic gonadotropin
(hCG) once at least two follicles reached a diameter of ≥18 mm.
Transvaginal ultrasound-guided oocyte retrieval was performed 35
to 36 hours after hCG administration. Retrieved oocytes were incu-
bated in culture medium, and ICSI was performed on MII oocytes fol-
lowing standard laboratory procedures.
3. AOQI assessment
The AOQI was calculated for each cycle. First, oocytes were evalu-
ated under a microscope by experienced embryologists, and one or
more dysmorphic features were documented. Dysmorphic features
were categorized into six groups and further classified into 15 de-
tailed items: cytoplasmic granulation (granulation or central gran-
ules), abnormal cytoplasm (vacuoles, refractile bodies, or smooth en-
doplasmic reticulum), abnormal shape (oval, amorphic, or dark), ab-
normal perivitelline space (extended or containing debris), abnormal
polar body (fragmentation, double, or large), and abnormal zona
pellucida (thin or thick) (Figure 1). The AOQI was then determined as
the ratio of the total number of abnormalities to the total number of
MII oocytes in each cycle. Among 251 MII oocytes obtained, 208
(82.9%) had at least one dysmorphic feature.
4. Statistical analysis
Statistical analyses were performed using SPSS ver. 25.0 (IBM
Corp.). Continuous variables were presented as median values with
interquartile ranges. Categorical variables were reported as number
(percentage). The Kolmogorov-Smirnov test was applied to assess
normality. Comparisons among the three groups were conducted
using the Kruskal-Wallis test for continuous variables, followed by
appropriate post hoc tests. Categorical variables were compared us-
ing the chi-square test or Fisher exact test when applicable. The rela-
tionship between serum AMH levels and AOQI was examined using
Spearman’s rho for the overall cohort as well as separately for each of
the three groups. Multiple linear regression analysis was also per-
formed to identify independent factors associated with AOQI, adjust-
ing for the presence of ovarian endometrioma and serum AMH lev-
els.
Results
Women with ovarian endometrioma were significantly younger
than those with unexplained infertility and DOR (p<0.001) (Table 1).
The median serum AMH levels were highest in the unexplained infer-
tility group and lowest in the DOR group (p<0.001 for all comparisons).
The number of MII oocytes retrieved was significantly higher in the
unexplained infertility group compared to the other groups (p<0.05).
The median AOQI value was significantly higher in the endometrioma
group (1.50) than in the unexplained infertility group (1.00) (p=0.037),
although it did not differ significantly from the DOR group (1.42).
With regard to specific oocyte abnormalities, cytoplasmic granula-
tion was most prevalent in the endometrioma group compared to the
other two groups (p<0.05), whereas abnormal cytoplasm was least
prevalent in the endometrioma and unexplained infertility groups
compared to the DOR group (p<0.001) (Figure 2).
Despite these morphological differences, fertilization rates were
comparable across all three groups ( Table 1). The endometrioma
group showed the highest percentage of top-quality embryos
(36.7%), which was significantly higher than that of the DOR group
(0%, p=0.043).
Figure 1. Representative dysmorphic oocyte images categorized
into six feature groups and further detailed by 15 specific items.
www.eCERM.org 3
J H Park et al. Average oocyte quality index and ovarian reserve
Granulation
Vacuoles
Oval
Fragmention
Extended
Thin
Amorphic
Double
Debris
Thick
Dark
Huge
Central granules
Smooth
endoplasmic
reticulum
Refractile body
Table 1. IVF cycle characteristics including the AOQI and distribution of detailed oocyte abnormalities in three groups
Endometrioma
(34 cycles)
a)
Unexplained infertility
(26 cycles)
b)
Diminished ovarian reserve
(32 cycles)
c) p-value Post hoc
Age of female 36 (34–39) 41 (38.5–43.3) 42.5 (40–45.8) 0.001
a),b)
p < 0.001
a),c)
p < 0.001
Serum anti-Müllerian hormone
level (ng/mL)
0.86 (0.59–1.41) 2.03 (1.4–3.29) 0.46 (0.1–0.75) 0.001
a),b)
p < 0.001
a),c)
p < 0.001
b),c)
p < 0.001
Serum estradiol at triggering
day (pg/mL)
707 (476–1,171) 1,687 (965–2,175) 671 (339–948) 0.001
a),b)
p < 0.001
b),c)
p < 0.001
No. of total MII oocytes 2 (2–4) 4 (2.8–4) 2 (1–3) 0.007
a),b)
p = 0.02
b),c)
p = 0.003
No. of dysmorphic MII oocytes 2 (1.8–3) 2.5 (2–4) 2 (1–2.8) 0.022
b),c)
p = 0.009
No. of total abnormalities 4 (2–6) 4 (2–5) 3 (2–4) 0.284
AOQI 1.50 (1.00–2.13) 1.00 (0.75–1.43) 1.42 (1–2) 0.037
a),b)
p = 0.01
From total MII oocytes
No. of fertilized oocytes 2 (1–3) 3 (1–4) 2 (1–3) 0.048
b),c)
p = 0.023
Fertilization rate (%) 100 (66.7–100) 100 (66.7–100) 100 (68.8–100) 0.748
Embryo score at day-3 27.5 (22.6–32) 26.9 (19.4–32) 24 (22.4–30.1) 0.389
Top-quality embryo at day-3
per total MII oocyte (%)
36.7 (0–100) 20 (0–50) 0 (0–50) 0.115
Values are presented as median (interquartile range). Comparisons between the three groups were performed using the Kruskal-Wallis test, followed by the
Mann-Whitney U test.
AOQI, average oocyte quality index; MII, metaphase II.
Figure 2. Distribution of specific oocyte abnormalities in the endometrioma, unexplained infertility, and diminished ovarian reserve groups.
a),b)
p<0.05;
c),d)
p<0.05.
https://doi.org/10.5653/cerm.2025.084384
Clin Exp Reprod Med [Epub ahead of print]
Cytoplasminc
granulation
Abnormal
ctroplasm
Abnormal
shape
Abnormal
perivitelline
space
Abnormal
polar baby
Abnormal
zona
pellucida
Endometriona 46.3% 17.5% 25.0% 32.5% 43.8% 23.8%
Unexplained infertility 29.0% 11.6% 20.3% 23.2% 43.5% 20.3%
Diminished ovarian reserve 28.8% 47.5% 13.6% 47.5% 42.4% 25.4%
50.0%
45.0%
40.0%
35.0%
30.0%
25.0%
20.0%
15.0%
10.0%
5.0%
0%
a)
b) b)
c)
c)
d)
Table 3. Correlation between serum anti-Müllerian hormone levels
and AOQI in three groups
r p-value
Endometrioma –0.429 0.011
Unexplained infertility –0.259 0.201
Diminished ovarian reserve 0.259 0.152
Spearman rho test.
AOQI, average oocyte quality index.
In the overall study population, median serum AMH levels demon-
strated significant positive correlations with both the number of total
MII oocytes and the number of dysmorphic MII oocytes, while show-
ing a significant negative correlation with AOQI (r=–0.242, p=0.020)
(Table 2). When each group was analyzed separately, this negative
correlation between serum AMH level and AOQI was statistically sig-
nificant only in the endometrioma group (r=–0.429, p=0.011) (Table
3). Regression lines illustrating these associations are shown in Figure
3, depicting the relationship between serum AMH levels and AOQI in
the overall study population (Figure 3A) and in the endometrioma
(Figure 3B), unexplained infertility (Figure 3C), and DOR (Figure 3D)
groups.
Because the median AOQI was significantly higher in the endome-
trioma group and a significant negative correlation between serum
AMH level and AOQI was observed in both the endometrioma group
and the overall cohort, a multiple linear regression analysis was per-
formed using two variables: presence of endometrioma and serum
AMH level. Female age was not associated with AOQI (r =–0.164,
p=0.118), and therefore was not included in the multiple linear re-
gression model.
Table 2. Correlation between serum anti-Müllerian hormone levels
and four variables, including the AOQI
r p-value
No. of total MII oocytes 0.473 0.001
No. of dysmorphic MII oocytes 0.403 0.001
No. of total abnormalities 0.216 0.039
AOQI –0.242 0.020
Spearman rho test.
AOQI, average oocyte quality index; MII, metaphase II.
Figure 3. Regression lines depicting the correlation between serum anti-Müllerian hormone (AMH) levels and the average oocyte quality
index (AOQI) in the overall study population (A), the endometrioma group (B), the unexplained infertility group (C), and the diminished
ovarian reserve group (D).
r=–0.242, p=0.02
r=–0.429, p=0.011 r=–0.259, p=0.201 r=0.259, p=0.152
Multiple linear regression analysis showed that serum AMH level
remained a significant independent factor negatively associated
www.eCERM.org 5
J H Park et al. Average oocyte quality index and ovarian reserve
AOQI
AOQI
AOQI
AOQI
4.00
3.00
2.00
1.00
0
3.00
2.50
2.00
1.50
1.00
0.50
3.00
2.50
2.00
1.50
1.00
0.50
0
4.00
3.00
2.00
1.00
0
AMH AMH AMH
AMH
0
0 0 0.20 0.40 0.60 0.80 1.000 0.50
1.00
1.001.00 1.50
2.00
2.002.00
3.00
3.00
4.00
4.00
5.00
5.00
6.00
6.00
AA
BB CC DD
with AOQI (unstandardized coefficient=–0.176; 95% confidence in-
terval, –0.327 to –0.024; p=0.024), whereas the presence of endome-
trioma was not a significant factor (Table 4).
Discussion
Our study addressed an important gap in the current literature by
specifically examining the relationship between oocyte quality and
ovarian reserve in women with endometrioma, comparing them not
only with those who had unexplained infertility but also with those
who had DOR. Previous studies primarily compared endometriosis
patients with normal controls or patients with tubal factor infertility,
without adequately accounting for the potential confounding effect
of DOR, which frequently coexists with endometriosis [17,18].
In our study, women with ovarian endometrioma demonstrated
significantly higher AOQI values (indicating poorer oocyte quality)
compared to those with unexplained infertility. However, we also
observed that higher AMH levels corresponded to better oocyte
quality among women with ovarian endometrioma. This finding
suggests that oocyte quality varies according to ovarian reserve even
among women who share the same diagnosis of endometrioma.
Multiple linear regression analysis further revealed that endometrio-
ma itself was not a significant factor associated with AOQI; instead,
serum AMH level remained the only significant independent factor.
Thus, the elevated AOQI observed in the endometrioma group ap-
pears to be primarily attributable to reduced ovarian reserve rather
than the direct impact of endometrioma.
In our study, female age and AOQI were unrelated, and therefore
age was not included as a variable in the multiple linear regression
analysis. For reference, we also found no correlation between female
age and AMH (r=–0.140, p=0.184). This finding warrants further con-
sideration, particularly given that our endometrioma group included
women with a broad range of AMH levels and our DOR group includ-
ed women across a wide age spectrum. Consequently, within this
study population, there appeared to be no negative relationship be-
tween age and AMH.
In our study, cytoplasmic granulation was the predominant oocyte
abnormality in the endometrioma group, whereas abnormal cyto-
plasm was more prevalent in the DOR group. The higher prevalence
of cytoplasmic granulation among women with endometrioma may
reflect the inflammatory microenvironment associated with endo-
metriotic lesions. Endometriomas are known to produce elevated
levels of inflammatory cytokines, reactive oxygen species, and iron
derived from hemolyzed blood, all of which may diffuse into adja-
cent ovarian tissue and disrupt folliculogenesis [7]. Such oxidative
stress can impair mitochondrial function in oocytes, potentially re-
sulting in cytoplasmic granulation as a morphological indicator of
mitochondrial clustering or dysfunction [6].
Our findings are consistent with several prior studies that have re-
ported altered oocyte morphology in women with endometriosis.
Xu et al. [18] identified a higher incidence of cytoplasmic granularity
and vacuolization in oocytes from endometriosis patients compared
with those from women with tubal factor infertility. Likewise, Goud
et al. [17] observed that oocytes from women with advanced-stage
endometriosis exhibited increased oxidative stress markers and mi-
tochondrial DNA deletions, both of which correlated with abnormal
cytoplasmic appearance.
The major strength of our study lies in its comparative design,
which incorporated three distinct patient groups representing differ-
ent infertility etiologies. Additionally, our detailed assessment of spe-
cific oocyte abnormalities, as opposed to simply categorizing oo-
cytes as normal or abnormal, provided deeper insights into potential
mechanisms by which endometriosis influences oocyte develop-
ment.
Nonetheless, several limitations should be acknowledged. First,
our analysis was limited to cycles in which one to five MII oocytes
were retrieved, which may not fully represent the range of ovarian
responses seen in these populations. It is possible that the effects of
DOR were accentuated by excluding cycles with greater oocyte
yields. Second, final embryo development was evaluated without
distinguishing between embryos derived from dysmorphic versus
morphologically normal oocytes, as our study was not intended to
investigate the specific developmental potential of dysmorphic oo-
cytes. Future research should assess embryo development separate-
ly for dysmorphic and normal oocytes to clarify their respective con-
tributions to reproductive outcomes.
Collectively, the AOQI may serve as a comprehensive marker that
reflects both morphological and cytoplasmic characteristics of oo-
cytes. Our study demonstrates that women with ovarian endometri-
oma exhibit distinct patterns of oocyte morphological abnormalities,
particularly cytoplasmic granulation, compared with those with un-
explained infertility or DOR. Prospective studies with larger sample
sizes and long-term follow-up are needed to further elucidate the re-
lationship between oocyte morphology, developmental compe -
tence, and reproductive outcomes in women with endometrioma.
Table 4. Multiple linear regression analysis of factors influencing
the AOQI in overall population
Unstandardized
coefficient (B) t 95% confidence
Interval p-value
Endometrioma 0.192 1.069 –0.165 to 0.548 0.288
Serum AMH –0.176 –2.303 –0.327 to –0.024 0.024
AOQI, average oocyte quality index; AMH, anti-Mullerian hormone.
https://doi.org/10.5653/cerm.2025.084386
Clin Exp Reprod Med [Epub ahead of print]
Conflict of interest
Byung Chul Jee has served as the editor-in-chief of Clinical and Ex-
perimental Reproductive Medicine since 2018. However, he did not
participate in the selection, evaluation, or decision-making process
for the peer review of this article. No potential conflicts of interest re-
lated to this article have been reported.
Author contributions
Conceptualization: BCJ. Methodology: JHP , BCJ. Formal analysis:
JHP , SKK, BCJ. Data curation: SKK, BCJ. Project administration: SKK,
BCJ. Writing-original draft: JHP , SKK, BCJ. Writing-review & editing:
JHP , SKK, BCJ. Approval of final manuscript: JHP , SKK, BCJ.
ORCID
Ju Hee Park https://orcid.org/0000-0001-5094-1640
Seul Ki Kim https://orcid.org/0000-0002-1647-6711
Byung Chul Jee https://orcid.org/0000-0003-2289-6090
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