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1. INTRODUCTION
Infertility is defined as inability to conceive after 12 months of
unprotected sex. Infertility is a major social problem, a complex disease
in gynecological diseases, for many reasons. Polycystic ovary syndrome
is one of the causes of ovarian induction infertility as classified by the
World Health Organization. The prevalence of Polycystic ovary
syndrome is from 6% to 10% of all women in childbearing age under the
NIH standard and about 15% under the Rosterdam standard 2003.
Polycystic ovary syndrome is manifested by a variety of clinical
symptoms and laboratory findings. Among them, high LH is always
described as a common symptom and is valuable in the diagnosis and
prognosis of treatment. Fauser (1994) reported a 60% increase in LH
elevations in polycystic ovaries.
According to the WHO, the 2012 ESHRE conference report
addresses the major disorders of Polycystic ovary syndrome: Inability to
induce abnormal LH levels in response to changes in estrogen, LH
receptor blockers, LH / FSH imbalance, relative lack of FSH, no
ovulation, and inappropriate increase of LH. Among these disorders,
most disorders are related to LH.
The first treatment for Polycystic ovary syndrome is clomiphen
citrate alone. However, about 30% of patients did not respond to this
therapy with time to determine whether it was 3 months of continuous
treatment with an increased dose. It is a long time with infertile patients,
greatly affecting the psychological and treatment effect next. According
to an analytical study by Susanne et al. (2012), a total of 28 studies found
that 52-76% of patients with COPD experienced psychological or
depression problems when they knew they had COPD. treatment.
Therefore, the search for identifying prognostic factors shortening
treatment time and improving therapeutic efficacy are always of interest
Studies in Vietnam focus primarily on the results of treatment methods.
The levels of LH released as in Vietnam are associated with elevated LH
levels and low BMI levels in many studies. Some of the comments in the
studies mentioned the link between LH levels, LH / FSH rates and
treatment efficacy, but were not discrete. Therefore, studies of general
neuroscience and our own research in particular are always necessary to
help clinicians gain new insights into management and prognosis when
approaching patients with the Ovarian cysts syndrome.
3. The scientific contributions of the thesis
The thesis reaffirms the role of LH in the prognosis of ovarian
hyperstimulation in patients with polycystic ovary as well as changes in
LH during treatment. In addition, the thesis also offers different
characteristics of patients with bronchial asthma in Vietnam than in other
continents. This helps create a new perspective on access to treatment for
patients with in Polycystic ovary syndrome Vietnam.
4. Structure of thesis
The dissertation consists of 106 pages (excluding annexes and
references) including 2-page introduction, 36-page literature review, 10
pages of research methodology, 25-page study results, 30 pages of
discussion, 2 pages summary and 1 page recommendation.
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Chapter 1
LITERATURE REVIEW
•
1.1. Diagnosis of polycystic ovaries
1.1.1. Clinical symptoms:
Testosterone > 1.5 ng/ml
• Multiple follicular ovaries on ultrasound:
The criteria for determining multiple follicular ultrasound images are
as follows: There are over 12 capsules in size from 2 to 9 mm, or an
ovary volume greater than 10 cm3, without need for follicular
distribution or ovarian tissue density and the above characteristics
expressed in at least one ovary.
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• Insulin resistance or glucose tolerance disorder.
Insulin resistance is an increase in insulin levels or a decrease in
insulin sensitivity to the target organ. Insulin resistance rates vary
between 25 and 70% among ethnic and diagnostic methods in patients
with polycystic ovaries.
1.1.3 Diagnostic standards:
Worldwide, there are 3 NIH / NICHD diagnostic criteria for
diagnosis, ESHRE / ASRM and Androgen Excesse and PCOS Society.
Clinicians use the standard in the Rotterdam Consensus (2003).
Patients were diagnosed with two-thirds of the symptoms
- Menstrual irregularities: amenorrhea or dysmenorrhea.
- Androgens: manifested in clinical or subclinical symptoms.
- Ultrasound: picture of polycystic ovary.
1.2. Mechanism of disease
The mechanism of normal hormonal activity is shown in the
following diagram:
Hypothalamus
Pituitary
ovary syndrome
1.3.1 Weight loss and exercise
1.3.2. Clomiphen citrate
It began to be used in 1961 after the publication of Greenblatt. In
1967 the US FDA approved the use. The drug by taking estrogen in place
in the hypothalamic estradiol receptors leading to estrogen receptors in
the hypothalamic-hypopnegative pituitary gland should increase the
GnRH secretion leading to increased gonadotropin secretion.
Simple CC treatment: Use the 2nd to 6th day of the menstrual period.
Doses of 50 - 150 mg / 24h. The initial dose is 50mg / 24h. If not met the
next cycle will use 100mg / 24h to 150mg / 24h. According to the 2004
NICE standard, when the maximum dose of 150 mg / 24h was not
developed follicle was diagnosed not responding clomiphene citrate.
In the absence of CC, there are a number of further treatments
for continued use of CC: Simple dosing regimens or increased
duration of use or combination regimens with Prednisone, Vit E,
Metformin or additional FSH from the 6th day of the menstrual
cycle at a dose of 50UI / day continuously until maturation.
Co-ordinate regimen: The first 5 days from day 2 to day 7 of the
menstrual cycle followed by the addition of FSH from the 6th day of the
menstrual period at a dose of 50UI / day continuously until matured.
1.4. Study on the relationship
treatment in polycystic ovary
1.4.1. Vietnam
between LH and
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Studies in Vietnam focus on treatment outcomes and treatment
Similarly, Johannes Ott et al. (2009) analyzed over 100 patients who
found a threshold value of LH = 12.1 UI / l for treatment of polycystic
ovaries by means of ovarian firing with sensitivity 88.7%, specificity
75.9%, positive diagnosis 90%, negative diagnosis 73.3%. In addition,
too high or too low LH levels have been shown to affect ovulation
quality, which reduces fertility and increases the risk of miscarriage.
Although there are many opposite views, clinicians hope to find a
"window" value LH to achieve the highest efficiency in the regulation of
reproduction.
Chapter 2
SUBJECTS AND METHODOLOGY
2.1. Location and time of study
- Location: Department of Obstetrics - Central Obstetric Hospital.
- Time: October 2011 to October 2015.
2.2. Subjects
2.2.1. Criteria selection
-
Females, infertility, age of 19 – 35.
To be diagnosed with HCS at the Rotterdam Consensus Meeting (2003)
FSH < 10 UI/l
Pelvic hysterectomy: normal uterus, two catheter tubes, Cotte (+)
Patients with normal semen collection in 1999 or 2010 of the
World Health Organization.
2.2.2. Exclusion criteria
- Infertility patients do not meet the criteria of choice .
- A history of combined oral contraceptives or estrogen , metformin
in the last three months.
- History of treatment to stimulate ovulation, IUI, IVF.
- History of infertility endoscopic surgery.
=14,1
ε = 0,07
n =107 bệnh nhân.
During the study period we obtained 118 patients.
2.3.3 Research process
Patients undergo follow-up procedures under Circular No. 12/2012 /
TT-BYT on the examination and diagnosis of infertility for each
infertility couple.
Treatment of clomiphen citrate
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•
- Starting Conditions:
• Patient satisfaction criteria selection criteria.
• At day 2 ultrasonography does not have residual cysts.
- Use of the drug from day 2 to the 6th day of the menstrual period
with increasing dosage regimen.
- Use Progynova from day 7 to 11 period
- Ultrasound of the vaginal probe on the 10th day of period
- The next ultrasound changes depending on the size of the follicle
at the previous ultrasonography.
- Use Gonadotropin 5000UI, intramuscularly when mature follicle
size (≥ 18 mm).
- IUD or natural Gonadotropin 36 hours after injection
- Get back in 2 weeks.
Record total days of treatment
Record the total dose of FSH.
Study subjects: Divided into two groups:
Group responds to CC treatment: Follicles develop after
doses of CC 50 or 100 or 150 mg / day.
Group does not respond CC: no follicle develops after 3
doses of CC. This group will continue to treat CC + FSH.
2.3.4 Flowchart of the study
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2.3.5. Variables
- Characteristics of subjects: BMI, infertility, menstrual cycle, menstrual
period, longest menstrual period, hairy, acne, ovarian follicular
ultrasonography, average number of follicles.
Pre-treatment hormone levels: Average concentration of LH, FSH,
estrogen, testosterone, oestradiol, progesterone, LH / FSH ratio.
- Hormone levels after treatment: LH, FSH, estrogen, testosterol,
oestradiol, progesterol, LH / FSH ratio.
- Variable treatment response: oocyte number on treatment, response to
treatment.
2.3.6 Data analysis
Epidata software and SPSS 16.0 software were used in data entry,
processing and analysis.
- Descriptive statistics
- Logistic regression analysis is variable and multivariate
- ROC curve
LH/FSH
2,49 ± 1,00
Concentrations of LH ≥ 10 accounted for 81.4%, LH > 14 concentrations
of 52.6%.
- Distribution of LH / FSH
Table 3.4: Distribution of LH / FSH
LH/FSH
< 1,5
1,5 – 2,0
>2
Tổng
N
16
26
76
118
%
13,56
22,03
64,40
100%
Of these, 64.4% had more than 2.
- Comparison of mean LH concentrations according to hair growth:
- Comparison of average LH levels according to acne characteristics:
There was no difference in LH levels when compared to each group.
- Comparison of mean LH levels of patients with infertility I and II:
The patients with the rate of infertility I occupied the majority to 84.75%.
Initial findings showed that the mean LH level of the infertile group was
higher than the inferiority group I. However, the T-test was not
significantly different from p = 0.37.
- Average BMI = 21.27 ± 3.31
In the 118 study participants, only four obese patients were included
in the 41 patients who did not respond to CC alone.
- Clinical features:
• Analyzes of the relationship between hairy hens and testosterone
levels were not associated with p = 0.605 using Fisher's Exact test.
• The relationship between the two clinical characteristics of hair and
acne was not statistically significant with Fisher's Exact test with p = 1.
3.2.2. Subclinical characteristics
Table 3.17: The average hormone level of the group does not
respond to CC
HORMON
Average
LH
14,79 ± 4,92
FSH
6,23 ± 1,57
LH/FSH
2,44 ± 0,78
Testosterone
1,41 ± 0,54
Estradiol
47,05 ± 19,45
Progesterone
1,71 ± 0,89
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- Ultrasonography showed polycystic ovaries: 63.41% of patients
who did not respond to CC showed polycystic ovarian ultrasonography,
3.3.5 Comparison of treatment response according to LH threshold
Vì thế, kiểm định X2 không có sự khác biệt giữa các nhóm giá trị
nồng độ LH với tỷ lệ đáp ứng điều trị CC (p = 0,683).
3.3.6. Linear regression analysis of LH interrelations with factors:
Single-regression analysis revealed a statistically significant
relationship between LH levels and FSH levels, estrogen expressed in the
following equations:
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[LH] = 0,09 x [oestrogen] + 10,06
[LH] = 1,35 x [FSH] + 6,31
3.3.7. Logistic regression analysis:
There is a linear relationship between LH levels and the probability
of not responding to treatment through the following equation:
Ln( = -0,881 + 0,017 x LH
= e -0,881+0,017xLH hay odd = e -0,881+0,017xLH
3.3.8. Changes in LH levels during treatment
The mean initial LH level of the two treatment groups was not
significantly different. After the CC dose of 50mg / 24h, there are 10
patients with non-quantitative LH pregnancy LH, the remaining patients
are measured LH next cycle. Mann Whitney test showed that the
difference in LH levels between the two groups was statistically
significant at p
ovulation occurred in the previous period.
Chapter 4
DISCUSSION
4.1. LH levels in infertile patients have polycystic ovaries
The mean value of LH in our study was 14,475 mUI / ml with a LH
> 10 mUI/ml concentration of 81.4%. According to physiology, the mean
daily blood glucose concentration in day 2 - 3 in the Vietnamese
population is 3.94 - 7.66 IU / L. Thus, the average LH level of the group of
patients with polycystic ovaries is higher than that of normal human LH.
By comparing the mean LH levels with other studies, the mean LH
level was higher than the normal range, but the distribution of LH levels
was not the same in the studies depending on the other clinical features
involved. such as BMI, duration of disability, age, and other clinical
features.
LH is elevated due to three major causes: an increase in the activity
of the pituitary gland due to stimulation from GnRH secreted by the
hypothalamus, due to the inverse harmonic regulation from high levels of
chronic estrogen and metabolic disorders. Obesity changes the LH
pattern. It was found that GnRH did not significantly increase the
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secretion with increased pituitary sensitivity to the hypothalamus or a
change in GnRH secretion. Thus, high LH reflects the degree of
prolonged disturbance of the hypothalamic, pituitary and ovarian systems
due to various causes.
The mean FSH value was 6.06 mUI / ml. The lowest is 3.2 mUI / ml
and the highest is 9.8 mUI / ml within the normal physiological limits of
this indicator. Results of comparative studies with other studies yielded
similar results. There is no specific change in FSH levels in patients with
in weight distribution, nearly 80% of the weight of the patients in the
normal study and most of the weight was abnormal, the BMI in study
20.86 showed the major pathogenic mechanisms in the group The
unrelated study was not related to insulin resistance, but because of
elevated LH levels, the explanation for the mean LH level in the study
was higher than for other studies. Is this a different feature of polycystic
ovarian cancer patients in Vietnam or that different racial traits in the
pathogenesis of polycystic ovaries. Thus, elevated LH is one of the main
and distinct characteristics of the group of patients with polycystic ovary
in Vietnam. Our analysis confirms the role of LH in the prognosis of
polycystic ovaryctomy patients, a distinctive feature of Vietnamese
polycystic ovary patients. The study by Moran C and colleagues in 2014
confirmed that elevated LH in patients with polycystic ovaries of the
BMI group was less than 25 than in the BMI group above 25 and many
other studies confirmed no association. Between LH increases with
increased insulin. Pagan YL et al (2006) also found a negative
association between BMI and LH levels, LH / FSH ratio by increasing
GnRh in PCOS patients, and LH inhibition Get high BMI. Similar linear
correlations between weights and LH concentrations were given for the
inverse relationship between LH levels and the weight of polycystic
ovary patients, Batista MC et al., 2014. Gene detection: rs 1800447 /
rs34349826 LTB TRP28Arg / LL35Thr mutation coding was associated
with increased LH in polycystic ovarian disease and lower LH levels in
the high BMI group.
4.2. Clinical and subclinical patients do not respond to CC alone
The median age for non-response to CC was 14.51 ± 1.75, the
smallest was 11 years and the largest was 18 years. According to the
study of Olga Karapanou (2010), the average age of menstruating of
countries in the world from 12 to 13.5. Thus, the median age of the
polycystic ovary group was higher than the median age of the girls.
nmol / l is a valuable explanation for the high clinical manifestation of
hyperosmotic androgen in patients not responding to CC.
Our hairy hips typically focus on the hips, navel, shoulders, legs and
arms, almost without shagging on the chest, back, buttocks and chin. It is
easy to see that the BMI of the races we have mentioned is very different
in the general community and in the population of polycystic ovaries in
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particular in high BMI, increased testosterone secretion Insulin resistance
increases the clinical manifestations associated with hyperandrogen such
as hair growth, acne. This explains the difference in the distribution rates
obtained in our study.
Continuing with BMI when comparing BMI of patients who did not
respond to CC treatment in our study with domestic and international
studies, we found a significant difference. Ovarian polycystic ovaries of
other countries always have a BMI that is very different from that of
Vietnam, in which case the index varies across regions of the world, very
high in Europe, lower in Europe ASIAN. Our study in the CC group did
not respond to only 4/41 patients with BMI> 25 or 9.75%, and the BMI
not show this abnormality, especially in normal BMI cases.
- Fetal ovary picture: There were 55.1% of patients with polycystic
ovaries with polycystic ovaries on ultrasound, the average number of
cysts on the ovary surface was 10.44. However, when analyzing the
relationship between patients with polycystic ovaries and their response
to CC, the incidence was the same..
4.3. Changes in LH levels in patients responding to and not
responding to CC alone and combination therapy with FSH
The process of monitoring and recording LH levels in successive
stages from the beginning of the patient intake, stimulation of the dose of
CC 50mg, 100mg, 150 mg and combination therapy CC and FSH we
realized when no ovulation or non-response to treatment, the LH level
changed little after the drug with LH levels of 14, IU / l, 13.17IU / l,
13.43IU / l . For ovulatory or treatment-responsive groups, there was a
statistically significant reduction in LH: With the CC dose of 50 mg: the
LH level before treatment was 14.10 IU / l after reduction to 5.94 IU / l,
with a CC100mg dose of LH before treatment of 12.49IU / l after
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reduction to 6.91IU / l, similar to combination therapy with FSH and CC,
respectively: 13.43IU / L and 6,51IU / l.
Table 4.16: Compare LH changes with other studies
Authors
Gustavo (2011)
Bùi Minh Tiến
(2011)
Lisa (2011)
TTT Hạnh
(2017)
13,39±4,71
Treatment Group N
Met
CC 100
PN
K
Châm cứu Chung
PN
CC 50
K
PN
CC100
K
38
37
81
35
46
T test showed that the difference in mean LH level after treatment in
the ovulatory and ovulatory groups was statistically significant in our
study with p
ovaries (13.78 ± 5.76) was lower than that of the normal ovary
group (15,45) ± 4.5).
There is a inverse relationship between LH and weight:
LH = 22,83 – 0,167 x weight (kg)
R = 0,223 R2 = 0,050
2 Comparison clinical characteristics of patients not responding to
olanthetal excitation therapy alone and describing subclinical
characteristics of patients not responding.
Average age of menstruation: 14.51 ± 1.75 (age)
Mean age of study group: 25.79 ± 5.2 (age)
Longest missed period: 139 ± 89 (day)
Average BMI: 21.27 ± 3.31
The clinical characteristics of menstrual disorders, hairy,
acne are 92,68%, 82,93%, 35,59%.
The average hormone level of the group does not meet
CCLH = 14,79 ± 4,92
Mean of FSH = 6,23 ± 1,57
Mean of LH/FSH rate = 2,44 ± 0,78
Mean of Testosterone = 1,41 ± 0,54
Mean of Estradiol = 47,05 ± 19,45
Mean of Progesterone = 1,71 ± 0,89
3 LH changes in patients with IBD with or without CC response
alone or in combination:
Single-variable regression revealed a statistically significant
association between LH levels and FSH levels, estrogen expressed