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CLINICAL MANIFESTATIONS OF HPV INFECTIONS IN WOMEN
WITH SECONDARY INFERTILITY
L.R.Agababyan
Z.Sh. Israilova
Department Samarkand State Medical University, Samarkand, Uzbekistan.
https://doi.org/10.5281/zenodo.14227409
Abstract
This article analyzes the main factors of female infertility,
including tubal-peritoneal, endocrine, immunological, infertility caused by
genital diseases, and idiopathic infertility. The etiological aspects are considered,
including the influence of infectious agents on female fertility. Particular
attention is paid to the role of sexually transmitted infections - the human
papillomavirus, in the development of infertility. Data from numerous studies on
the prevalence of HPV and its impact on women's reproductive health are
presented. The article emphasizes the importance of a comprehensive approach
to the diagnosis and treatment of female infertility to improve treatment
outcomes and increase the chances of successful conception.
Keywords
Secondary infertility, papillomavirus infection, condyloma
acuminata, diagnosis of "thin" endometrium
1. Introduction
In the field of reproductive health today, infertility occupies a special place.
According to modern sources, 8 to 12% of married couples have infertile
marriages, in which the woman's share is about 50-80% [3,6,10,29,38].
There are five main groups of factors of female infertility:
Tubal-peritoneal
Endocrine
Infertility caused by genital diseases and anatomical abnormalities
Immunological
Idiopathic (infertility of unknown origin)
Analyzing these factors, it should be recognized that infectious agents can
become a predictor of female infertility in all five groups. Undoubtedly, infection
affects the condition of the fallopian tubes and endometrium, but the
inflammatory autoimmune process contributes to the disruption of the structure
and function of the ovaries. And finally, the disruption of the vaginal microbiota
in connection with the presence of microorganisms with impaired
immunoreactivity contributes to the development of antisperm antibodies and
impaired sperm motility [7, 8, 9, 11, 12,14, 23, 24, 31,34]. In this regard, the
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problem of sexually transmitted infections (chlamydia, ureaplasmosis,
mycoplasmosis, gonorrhea), as predictors of infertility, has already been
sufficiently studied. However, the etiological role of viral sexually transmitted
infections (STIs) in fertility impairment, including human papillomavirus
infection, has not yet been studied. The frequency of human papillomavirus
infections (HPV) in the world, according to various researchers, has increased
more than 10 times over the past decade [2,4,5, 16,20, 21, 22, 27,35, 36]. Almost
all of the reports cited are based on the detection and treatment of oncogenic
HPV strains. However, in practice, clinical manifestations of the human
papillomavirus in the form of condyloma acuminata are increasingly
encountered, which is the main reason for women to seek medical attention, in
whom, upon closer examination, other infections are also detected [17,19, 37,
40]. This state of affairs even led to the need to publish clinical guidelines for the
management of women with condyloma acuminata [32]. Although most
researchers agree that human papillomavirus infection itself does not lead to
infertility in women, but can be the cause of male infertility in her partner
[5,18,25, 26, 30, 39]. the frequent referral of infertile patients with
manifestations of condyloma acuminata served as the reason for conducting this
study.
Objective of the study: To study the condition of the endometrium in infertile
patients with condyloma acuminata.
Materials and methods: Using ultrasound, the condition of the endometrium was
studied in 78 patients with secondary infertility who applied to the private
medical clinic MCHJ "Mama i Ya" in 2022-2023 (main group). The control group
consisted of 50 patients with secondary infertility without condyloma
acuminata.
The inclusion criteria for the study were: age not older than 35 years; absence of
developmental anomalies of the pelvic organs; history of pregnancy; absence of
pregnancy for 12 months without the use of contraceptives; signed informed
consent to participate in the study; condyloma acuminata detected during
genital examination.
Exclusion criteria: age over 35 years; absence of condyloma; congenital
malformations of the pelvic organs; somatic diseases that are contraindications
for pregnancy and childbirth; patient's refusal to participate in the study; alcohol
abuse, drug or drug addiction; male infertility.
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Standard clinical and gynecological research methods were used. In the middle
of the menstrual cycle, an ultrasound examination of the pelvic organs with
Dopplerography was performed on a Sonoscape 3D/4D device.
The obtained results were subjected to statistical processing using methods
presented in the Statistica 6.0 program. To assess the differences between
groups according to quantitatively measured indicators, the parametric
Student's t-test was used. To compare the control and main groups according to
qualitative characteristics, the Fisher's multifunction criterion was used. Using
the χ2 criterion, the frequency of Dopplerometry changes in the groups was
compared. Statistically significant differences were considered at p<0.05 (95%
confidence level).
Results:The patients included in the study were aged 25 to 35 years. We did not
find statistically significant differences in age between the study groups: the
average age of patients in the main group was 30.5±1.2 years, patients in the
control group – 30.2±1.29. When comparing the main characteristics of the
menstrual cycle according to anamnestic data (menarche, duration of the
menstrual cycle, duration and nature of menstruation), it was shown that the
groups are comparable in all these parameters. There were no significant
differences in marital status and education level between the patients in both
groups.
Of the somatic diseases, anemia, which was found with the same frequency in
both groups of women – 50% and 52% respectively, is noteworthy. Mostly it
was chronic iron deficiency anemia of moderate severity.
Particular attention was paid to the obstetric history and gynecological
morbidity in the examined women, as well as to the types of surgical
interventions performed on the pelvic organs (Tables 1, 2, 3).
The presented data demonstrate that both in terms of frequency and structure
of the incidence of gynecological pathology, the groups are comparable (p≥0.05).
It is obvious that the high frequency of endometrial polyps in the structure of
past gynecological diseases (38.5% and 30% respectively), as well as
information from the obstetric history about complications of childbirth and a
high frequency of cesarean section (44.9% and 46% respectively) are quite
understandable, since almost all patients included in the study had a "thin"
endometrium, which can be considered as a predictor of complications that led
to infertility. Laparotomy and laparoscopy on the pelvic organs in the history
were performed in 71% (n=128) of patients in both groups. As can be seen from
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Table 3, in general, statistically significant differences in the frequency of past
surgical interventions between the groups were not revealed (p≥0.05).
Table 1. Obstetric history of observed patient
Indicator
Main
Group
(n=78)
Control Group
(n=50)
P-value
(Level
of
Significance)
Cesarean section
35(44,9%)
23(46%)
p = 1,0
Preterm birth
10(12,8%)
6(12%)
p = 1,0
Manual examination of the
postpartum uterus
19(24,4%)
12(24%)
p = 1,0
Miscarriage (>2)
8(10,3%)
4(8%)
p = 0.764
Postpartum endometritis
11(14,1%)
4(8%)
p = 0.402
Postpartum endometritis
17(21,8%)
11(22%)
p = 1,0
Table 2.
Gynecological morbidity of observed patients (anamnestic data)
Indicator
Main
Group
(n=78)
Control Group
(n=50)
P-value (Level of
Significance)
Pelvic
Inflammatory
Disease
37 (47.4%)
23 (46%)
p = 1.0
Ovarian
Cysts
and
Cystomas
7 (9%)
5 (10%)
p = 1.0
Uterine Fibroids
13 (16.7%)
9 (18%)
p = 1.0
Endometriosis
9 (11.5%)
6 (12%)
p = 1.0
Endometrial Polyps
30 (38.5%)
15 (30%)
p = 0.350
Combined Diseases
18 (23%)
8 (16%)
p = 0.350
The vaginal microflora was disrupted (according to anamnestic data) in 36
patients in both groups, which amounted to 28.1%. Bacterial vaginosis occurred
in 20 (25.7%) patients in the main group and in 5 (10%) patients in the control
group (p≥0.05). Vulvovaginal candidiasis was diagnosed in 8 (10.3%) women in
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the main group and in three (6%) in the control group. The presence of a
sexually transmitted infection (STI) in the history was diagnosed in both groups
of observed patients: chlamydial infection in the history was more than 3 times
more common in patients in the main group – 7.7% (n=6) compared to patients
in the control group – 2% (n=1).
CINI-II was diagnosed 5 times more often in the group of women with
condyloma acuminata compared to the control group (20.5% and 4%
respectively). It should be noted that all patients with condyloma acuminata and
CIN were not vaccinated against HPV.
All patients in this group were prescribed appropriate therapy. Due to the
presence of an inflammatory process of the genital organs, invasive diagnostic
procedures were postponed until the end of treatment.
In the structure of infertility in the main group of patients, the predominant
factor was the violation of the morphological and functional ability of the
endometrium - "thin" endometrium.
The condition of the pelvic organs was assessed according to ultrasound data
(Fig. 1) and
Discussion. Analyzing the data we obtained, we can argue that HPV-
positive patients have prerequisites for the development of infertility. This is
also evidenced by studies conducted by Yu.N. Banashkaeva and co-authors
(2022), which indicate that even in the treatment of infertility using assisted
reproductive technologies, the lowest frequency of pregnancy after
cryoprotocols of IVF was observed in the group of HPV-positive women (33.3%)
compared to HPV-negative (73.9%) and previously vaccinated patients (60.7%);
p<0.05 [1]. The work of Italian researchers showed that in HPV-positive
patients, unsuccessful IVF attempts were almost 3 times more common
compared to HPV-negative (40 and 13.5%) [28]. According to the data of the US
university clinic, when conducting ART programs in women with HPV
persistence, the frequency of pregnancy was significantly lower than in women
without the virus (57 and 23.5%) [15].
The negative impact of HPV on reproductive function is also confirmed in a
number of other works. Thus, a systematic review conducted in Germany
demonstrates a reliable association between spontaneous abortion,
spontaneous preterm birth and the presence of HPV both in the cervix and in the
placenta [13].
Conclusion.
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The combination of condyloma acuminata with "thin" endometrium in
patients with secondary infertility requires further research and determination
of the tactics for managing these women
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