Vo
lu
m
e
5,
Ap
ri
l,
20
25
,
M
ED
IC
AL
SC
IE
N
CE
S.
IM
PA
CT
FA
CT
OR
:7
,8
9
UDK 618.14-002-09b2:618.3-08
STUDY OF LIPID PEROXIDATION INDICATORS IN WOMEN WITH
EXTERNAL GENITAL ENDOMETRIOSIS
Saidjalilova D.D., Kuzieva Y.M.
Tashkent medical academy
Annotation:
The article presents the results of a comprehensive clinical and biochemical
study of women with external genital endometriosis (EGE) and infertility, aimed at
elucidating the role of oxidative stress in the pathogenesis of endometriosis-associated
infertility. The study included 117 women: 44 patients with EGE, 19 women with tubal-
peritoneal infertility (comparison group), and 24 healthy women (control group). Analysis of
gynecological and obstetric histories revealed a high incidence of primary infertility (67.4%),
along with a significant prevalence of menstrual cycle disorders and chronic pelvic
inflammatory diseases among women with EGE. Pain syndrome of varying severity was
identified as the leading clinical manifestation of EGE, though it did not consistently
correlate with the extent of tissue damage observed during laparoscopy. Biochemical
analysis of lipid peroxidation (LPO) markers in blood plasma and peritoneal fluid showed a
marked intensification of oxidative processes in women with EGE, especially in advanced
stages (Stage III), compared to the comparison and control groups. Elevated levels of neutral
lipids, lipid hydroperoxides, diene conjugates, and a higher oxidative index indicated a
pronounced oxidative stress and a significant imbalance between pro-oxidant and
antioxidant systems. The findings emphasize the critical role of oxidative stress in the
development of EGE-associated infertility and highlight the potential of targeted antioxidant
therapy as a strategy to improve reproductive outcomes in affected women.
Keywords:
External genital endometriosis (EGE), infertility, oxidative stress, lipid
peroxidation (LPO), pro-oxidant-antioxidant balance, peritoneal fluid, reproductive health,
antioxidant therapy, chronic pelvic inflammation, pain syndrome.
Introduction.
Endometriosis is a chronic gynecological disease characterized by the presence of ectopic
endometrial tissue outside the uterine cavity, often associated with pelvic pain, menstrual
irregularities, and infertility. Among its various forms, external genital endometriosis (EGE)
is one of the most common and challenging to treat, frequently affecting women of
reproductive age. The multifactorial nature of endometriosis, including hormonal,
immunological, genetic, and environmental factors, complicates its pathogenesis and
management.
Endometriosis affects approximately 10% of women of reproductive age worldwide (WHO,
2021), with up to 50% of women diagnosed with infertility. Thus, according to WHO
estimates, at least 190 million women and adolescent girls worldwide currently suffer from
Vo
lu
m
e
5,
Ap
ri
l,
20
25
,
M
ED
IC
AL
SC
IE
N
CE
S.
IM
PA
CT
FA
CT
OR
:7
,8
9
this disease during their reproductive age, although some women may suffer after
menopause [1, 2, 4, 14].
All over the world, external genital endometriosis (EGE) is diagnosed with a significant
delay [1, 4, 8, 12, 14]. Moreover, the first symptoms of the disease (chronic pelvic pain,
dysmenorrhea) appear at an early age: up to 20 years - in 38% of patients, at 20-24 years - in
21% of patients [1, 14]. According to the World Endometriosis Society, on average, EGE is
diagnosed 6.7 years after the appearance of the first symptoms of the disease [1, 14, 15]. The
percentage of recurrence of EGE varies greatly in different studies and ranges from 6 to 67%
[3, 5, 7]. On average, every second woman undergoes repeated surgery after surgical
treatment [6, 13]. According to L.V. Adamyan et al., without subsequent hormonal therapy
within 1 year, the disease recurs in 55% of women, and with each subsequent year, an
episode of endometriosis recurs in 10% of patients [1, 2].
Material and methods of the study:
117 women with infertility who applied to the private
clinic "ProfMedMax" in Karshi were examined for the period from 2022 to 2024. Of these,
38% (n = 44) were diagnosed with EGE, 16.2% (n = 19) - tubal-peritoneal infertility (TPI);
29 (25.2%) were diagnosed with endocrine infertility, and in 20.6% (n = 25) the genesis of
infertility could not be identified. Of the 117 women with infertility, 44 women with EGE
(main group) and 19 women with TPI (comparison group) were included in the study. The
control group consisted of 24 women without infertility and with favorable obstetric and
gynecological history. The criteria for inclusion of patients in the study were: female
infertility associated with EGE, infertility of tubal-peritoneal origin. Exclusion criteria:
malformations of the genitals, oncological diseases of the pelvic organs (including the
ovaries), other genesis of infertility. All patients underwent a complete clinical and
laboratory examination in accordance with the study of female infertility in outpatient
settings. Specially developed examination cards were used, taking into account the somatic
condition, gynecological and obstetric history, and the results of laboratory and clinical
studies. The study of the redox balance of blood plasma and peritoneal fluid was performed
using the immunoassay method on the HUMAN analyzer (Germany). Peritoneal fluid was
aspirated from the Douglas pouch during laparoscopy immediately after the introduction of
additional counter-openings before surgical manipulations. Samples were centrifuged to
remove the cellular fraction, then stored at -20°C until the analytical stage, defrosting of
samples was performed at room temperature.
Results of the research:
The average age of patients with EGE (n=44) was 31.2 ± 2.9 years,
patients with TPI - 32.7 ± 4.2. In the studied women with EGE, primary infertility was
diagnosed in 30 (67.4%) examined, secondary infertility - in 14 (32.6%) (Table 1). Whereas
in the group of women with TPI, the opposite trend was noted and primary infertility was
detected only in =7 (39.5%) women, and secondary infertility in 12 (60.5%) women. When
analyzing the obstetric history, it was found that among patients suffering from
endometriosis-associated infertility, 30 (67.4%) patients had no history of pregnancy, 8
(19.1%) of those observed had given birth through the natural birth canal or by cesarean
section, 6 (13%) patients had a history of abortions (4- artificial abortion and 2 -
spontaneous). Of the 12 (60.5%) patients with TPI who had a history of pregnancy,
childbirth was noted in 8 (73.9%) patients, ectopic pregnancy was observed in 3(26.1%)
Vo
lu
m
e
5,
Ap
ri
l,
20
25
,
M
ED
IC
AL
SC
IE
N
CE
S.
IM
PA
CT
FA
CT
OR
:7
,8
9
patients (all patients underwent unilateral tubectomy), artificial abortion at the request of the
patient was performed in 6 (56.5%) cases, spontaneous termination of pregnancy was
observed in 4 (34.8%) of those examined.
When collecting the gynecological anamnesis, it was established that at least once in 12
(28.1%) patients of the EGE group, the doctor of the antenatal clinic diagnosed an
exacerbation of chronic salpingo-oophoritis, the basis for diagnosing this pathological
condition was complaints of chronic pelvic pain. The second place in frequency of
occurrence was occupied by menstrual cycle disorders, more often of the anovulatory cycle
type, which were observed in 9 (20.2%) women with EGE. Hyperplastic processes of the
endometrium (polyp and hyperplasia), which were detected in 7 (14.6%) patients.
Background diseases of the cervix were noted in the anamnesis of 3 (7.9%) patients with
EGE. The remaining 8 (19.1%) patients with endometriosis-associated infertility had an
uncomplicated gynecological anamnesis.
In 8 (42.1%) patients in the group with TPI, the gynecological anamnesis was complicated
by previous PID, a common cause of which was urogenital infection.
Table 1
Obstetric and gynecological history of the women studied
Anamnesis
Group with infertility and
EGE (n=44)
Group
with
TPI
(n=19)
Control (n=24)
Аbc
%
Аbc
%
Аbс
%
Childbirth
8
19,1**
▲
9
44,7*
24
100
Spontaneous
miscarriage
2
4,5
▲▲
4
21,1**
1
4,2
Abortion
4
9,0
▲▲
6
34,2**
2
8,3
Ectopic pregnancy 2
3,4*
▲▲
3
15,8**
0
0
Primary infertility
30
67,4**
▲
7
39,5**
0
0
Secondary
infertility
14
32,6**
▲
12
60,5**
0
0
Menstrual
cycle
disorders
9
20,2*
▲
2
13,2
3
12,5
IDPO
12
28,1*
8
42,1**
4
16,7
Hyperplastic
processes in the
endometrium
6
14,6**
2
10,5**
0
0
Uterine fibroids
2
4,5*
▲
1
2,6*
0
0
Adenomyosis
3
5,6*
0
0
0
0
Diseases of the
cervix
4
7,9*
▲▲
3
18,4**
1
4,2
Absence
of
gynecological
8
19,1**
2
13,2**
16
66,7
Vo
lu
m
e
5,
Ap
ri
l,
20
25
,
M
ED
IC
AL
SC
IE
N
CE
S.
IM
PA
CT
FA
CT
OR
:7
,8
9
diseases
Notes: * - significant difference in indicators from the control group (*-p<0.05; **-p<0.001);
▲ - significant difference in indicators from the group of women with TPI(▲ -p<0.05; ▲▲
- p<0.001).
The clinical picture of EGE was characterized by a variety of symptoms of the disease. The
most pronounced clinical sign of endometriosis in women was the presence of pain the day
before the onset of menstruation and in the following days of the menstrual cycle. Pain was
also localized in the lower abdomen, lower back, with a pronounced manifestation during
the period of menstruation itself. Complaints of dyspareunia were presented in 5.6% of cases.
Mostly, women had a moderate degree of pain syndrome (59.6%), mild pain was 19.1%, and
severe pain was 21.3% of cases. It should be taken into account that the degree of pain
syndrome was subjective. The psychological component of pain assessment is largely
related to the psycho-emotional state of the woman herself, which may not be related to
actual tissue damage by endometriosis. Often, the volume of tissue damage by
endometriosis, determined later by laparoscopy, did not correspond to the course of the
pathological process and the severity of clinical symptoms. In some cases, with large sizes
of endometrioid cysts, pain syndrome could be present in minimal values, and with
insignificant spread of endometrioid foci to the abdominal surface of the sacrouterine
ligaments and the rectovaginal septum, it could be accompanied by severe pain syndrome.
Ultrasound of the pelvic organs allowed us to specify the location and size of endometrioid
cysts, but did not allow us to identify superficial implants, which were later identified during
laparoscopy. On ultrasound, endometrioid ovarian cysts were round ovoid formations, and
in most cases cysts up to 5.0 cm in size were detected, in 71.9% (n=32) of which a double
contour was detected, in which the thickness of the inner layer corresponded to an average
of 0.12-0.13 cm, but the thickness of the capsule was 0.2-0.4 cm. Often, when pressing with
the sensor, the cyst was displaced. In half of the cases, the cysts were of uniform consistency
in the form of a finely dispersed, non-displaceable suspension; in some cases, there were
thickened formations, mainly oval in shape, and were blood clots. The ultrasound picture of
retrocervical endometriosis was characterized by the formation of a dense consistency
located in the retrocervical retrovaginal tissue, with localization both under the cervix and
above and on the side of the cervix.
To study the relationship between EGE and redox balance in the development of infertility,
we conducted studies of lipid peroxidation indices and their detoxification system in the
women under study. As was stated above, the problem of EGE development from a
pathophysiological point of view has a multicomponent mechanism, which involves many
systems. This dictates the need to search for a mechanism of pathogenetic changes in EGE
leading to infertility. To some extent, such a system can be used to determine the intensity of
lipid peroxidation processes and the antioxidant defense system. To determine the
relationship between the severity of EGE and the processes of lipid peroxidation and
antioxidant protection, we divided 44 women with EGE into 2 subgroups: 1 subgroup - 37
women with EGE of I-II degree; 2 subgroup - 7 women with EGE of III degree.
Vo
lu
m
e
5,
Ap
ri
l,
20
25
,
M
ED
IC
AL
SC
IE
N
CE
S.
IM
PA
CT
FA
CT
OR
:7
,8
9
The study of the indicators of LPO processes in blood plasma between the main subgroups
and the comparison group of women with TPI showed a significant increase in the content
of dien ketones (DK) (P<0.01), and other indicators, such as neutral lipids (NL), lipid
hydroperoxide (LHP) did not have significant changes (P>0.05).
The data presented in Table 2 show that in the groups of women with grades I-II EGE,
significant intensification of the LPO processes in the peritoneal fluid is observed relative to
the comparison group, which is manifested in an increase in NL (P<0.01), GPL (P<0.001),
DK (P<0.001), and OI (P<0.01). In the group of women with grade III EGE, relative to the
values of the comparison group, the value of GPL increases by 5.1 times (P<0.001),
and DK - by 6.4 times (P<0.001), with a smaller increase in NL by 2.1 times (P<0.01),
leading to an increase in the oxidative index (OI) by 2.5 times (P<0.001). The values of
the group of women with TPI were as close as possible to the reference values of the
laboratory.
Table 2.
Values of LPO products in peritoneal fluid in the studied groups of women (M±m)
Indicators lipid
peroxidation
1 subgroup with
EGE I-II (n=37)
1 subgroup with EGE
III (n=7)
Comparison group with
ТPI (n=19)
NL,
еd.оp.pl./ml0
1,724±0,161
2,93± 0,21*
▲
1,374±0,143
LH,
еd.оp.pl./ml
0,721±0,097
2,713±0,371**
▲▲
0,537±0,083
DK,
еd.оp.pl./ml
0,193±0,029*
0,421±0,089**
▲▲
0,066±0,011
OI
0,431±0,081
0,906±0,105*
▲
0,369±0,069
Note: * - significant difference from the indicators of the group with TPI (* - p<0.01; ** -
<0.001); ▲ - significant difference from the indicators of the group of women with grade 1-
2 EGE (▲ - p<0.01; ▲▲ - p<0.001).
Thus, studies of women with EGE and infertility have shown that, despite the presence of
fairly clear clinical symptoms of endometriosis, women differ from each other in the stage
and depth of the lesion, which undoubtedly requires additional diagnostic measures, and
Vo
lu
m
e
5,
Ap
ri
l,
20
25
,
M
ED
IC
AL
SC
IE
N
CE
S.
IM
PA
CT
FA
CT
OR
:7
,8
9
subsequently treatment tactics.It should also be noted that with a full-blown clinical picture
of the disease, the quality of life of patients is significantly reduced, reproductive function
becomes impaired, which does not allow a woman to fully realize her reproductive potential.
The presented data show that women with EGE develop oxidative stress as a result of
changes in the functioning between the processes of lipid peroxidation and the AOP system,
with the prevalence of radical formation processes over their inhibition processes. The
reasons for this are the active inflammatory process in endometrioid foci, peritoneum, and
pelvic organs.
The capabilities of the AOP system in EGE are insufficient to limit oxidative processes
during its prolonged expression. All this creates additional conditions for maintaining
oxidative stress, due to the disruption of lipid regulation by the AOP system and the positive
feedback of the functioning of the pathological cycle between oxidative phosphorylation and
the degree of LPO activity.
Consequently, in women with EGE, various etiological factors cause increased secretion of
lipid-based inflammatory mediators, and with insufficiency of the AOP system, an
inflammatory process develops in endometrioid foci, the peritoneum, and pelvic organs.
Apparently, short intervals between menstrual cycles create favorable conditions for the
action of peroxide radicals, in which the immune system of the female div is unable to
cope with the utilization of menstrual material, which affects and grows on the uterine
appendages, peritoneum and other tissues.
Conclusions:
1.
The frequency of external genital endometriosis in the structure of infertility was
38%.
2.
An important link in the pathogenesis of external genital endometriosis is the
activation of lipid peroxidation and local antioxidant function, which depends on the
severity of the pathology.
3.
All women with EGE, in combination with hormonal and surgical therapy, need to
include antioxidant therapy to reduce the recurrence of the pathology.
Literature:
1.
Адамян Л.В., Логинова О.Н., Соснова М.М., Арсланян К.Н.
Антиоксидантная защита у больных наружным генитальным эндометриозом //
Акушерство, гинекология и репродукция. - 2018. - №3. - C.18-21
2.
Артымук Н.В., Зотова О.А., Шакирова Е.А. и др. Эффективность
комбинированного лечения эндометриом яичников // Эндоскопическая хирургия. -
2019. - №2. - C.35-39.
3.
Борисова А.В., Козаченко А.В., Франкевич В.Е., Чаговец В.В. Факторы риска
развития рецидива наружного генитального эндометриоза после оперативного
лечения: проспективное когортное исследование // Медицинский совет. - 2018. - №7. -
C.32-38.
Vo
lu
m
e
5,
Ap
ri
l,
20
25
,
M
ED
IC
AL
SC
IE
N
CE
S.
IM
PA
CT
FA
CT
OR
:7
,8
9
4.
Волгина Н.Е., Щипицына В.С., Хилькевич Е.Г. и др. Исследование роли
окислительного стресса и уровня IL-6 в перитонеальной жидкости в развитии
эндометриоза // Иммунология. - 2016. - №3. - C.182-184.
5.
Давыдов А.И., Белоцерковцева Л.Д., Таирова М.Б. Эндометриоидные кисты
яичников: обоснование послеоперационной гормональной терапии // Вопросы
гинекологии, акушерства и перинатологии. - 2019. - №2. - C. 122-128.
6.
Дубинская Е.Д., Дутов А.А. Отдаленные результаты лечения пациенток с
бесплодием и эндометриоидными кистами яичников // Тенденции развития науки и
образования. - 2018. - №4. - C.52-56.
7.
Караченцева И.В., Логачева Т.М., Кашоян А.Р. Ранние диагностические
признаки эндометриоза // Архив акушерства и гинекологии им. В.Ф. Снегирёва. - №3.
- C.152-156.
8.
Оразов М.Р., Радзинский В.Е., Хамошина М.Б. и др. Эффективность лечения
бесплодия, обусловленного рецидивирующим наружным генитальным эндометриозом
// Гинекология. - 2019. - T. 21, №1. - C.38-43.
9.
Папышева Е.И., Коноплянников А.Г., Караганова Е.Я. Значимость преграви-
дарной
подготовки
в
повышении
эффективности
экстракорпорального
оплодотворения // Российский вестник акушера-гинеколога. - 2019. - №19. - C.29-37.
10. Покаленьева М.Ш., Нестерова А.М., Соснова Е.А., Проскурнина Е.В.
Оксидативный статус плазмы крови при привычном невынашивании беременности //
Архив акушерства и гинекологии им. В.Ф. Снегирёва. - 2017. - №4. - C.214-220.
