225
Gladchuk I.Z., Semenyuta O.M., Onyshchenko Y.V.
Definition of efficiency of different approaches in treatment of infertility
for patients with polycystic ovary syndrome and hyperprolactinemia. Journal of
Health Sciences. 2014;04(01):225-232. ISSN 1429-9623 / 2300-665X.
The journal has had 5 points in Ministry of Science
and Higher Education of Poland parametric evaluation. Part B item 1107.
(17.12.2013).
© The Author (s) 2014;
This article is published with open access at Licensee
Open Journal Systems of Radom University in Radom, Poland
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This is an open access article licensed under the
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non commercial use, distribution and reproduction in any medium, provided the
work is properly cited.
Conflict of interest: None declared. Received:
29.11.2013. Revised21.12.2013. Accepted: 05.04.2014.
DEFINITION OF EFFICIENCY OF DIFFERENT APPROACHES IN
TREATMENT OF INFERTILITY FOR PATIENTS WITH POLYCYSTIC OVARY SYNDROME AND
HYPERPROLACTINEMIA
Gladchuk I.Z.1,
Semenyuta O.M.2, Onyshchenko Y.V.1
1. Odessa National Medical
University, Odessa
2. Medical centre " Avicenna
", Melitopol
Abstract. Polycystic
ovary syndrome (PCOS) is one of the most common endocrine disorders in women.
The clinical manifestation of PCOS varies from a mild menstrual disorder to
severe disturbance of reproductive and metabolic functions with severe
long-term health consequences. High-frequency of endocrine-metabolic disorder’s
and anovulatory infertility and also frequent absence of effect from the use of
traditional charts of medicament induction of ovulation resulted in the search
of alternative ways of proceeding in fecundity. The aim of this study was to
evaluate the clinical efficiency of different treatments cancellation and
infertility in women with PCOS and hyperprolactinemia. Materials and
methods. We performed retrospective analysis of 502 consecutive case histories
during 5 years of reproductive results of treatment of women is with
anovulatory infertility, caused by different factors. Aim of the study was to
determine the efficiency of conservative and surgical treatment. Results. Differentiated
application of conservative medical therapy allows to attain the effect of
proceeding in a fertile function in 33, 8% of patients. It is found that
surgical induction of ovulation by ovarian laparoscopic partial degradation is
an option in the management of female infertility associated with PCOS,
especially as a second-line treatment after the failure of 226
clomiphene
citrate treatment, enhancing the efficiency of complex infertility treatment to
40%. It is feasible to develop an algorithm differentiated use of infertility
treatments in women with PCOS and hyperprolactinemia.
Keywords: Polycystic
ovary syndrome (PCOS); reproductive health; hyperandrogenism; infertility;
hyperprolactinemia; hirsutism; menstruation disorders.
Introduction. Demographic
potential of Ukrainian population is burdened with considerable extension of
female infertility [1]. According to local scientists fertility rate in excess
of 10% can be considered as direct reproductive losses that significantly
impair the demographic situation of the country. Many of Ukrainian females have
anovulatory infertility. It has a tendency to spread in the population, with
involvement in the pathogenesis of disorders of ovulation excess synthesis of
androgens and prolactin.
Polycystic ovary syndrome (PCOS) is the most common
endocrine disorder in women. The clinical manifestation of PCOS varies from a
mild menstrual disorder to severe disturbance of reproductive and metabolic
functions [3-5]. Significant progress achieved domestic and foreign scholars
and the development of surgical induction of ovulation in PCOS [6, 7].
However, the results of treatment of anovulatory
infertility associated with PCOS, indicating that the disease is distinguished
not only clinical polymorphism, but also has several pathogenic variants. It is
possible that this group of patients, along with there are other endocrine
disorders that also affect metabolic processes. Thus, the high incidence of
hyperprolactinaemia was found among patients with PCOS deepens dysmetabolic
changes in the patient, involving additional mechanisms in the pathogenesis of
blocking ovulation [8-10]. This can be explained as the influence of prolactin
receptors on ovarian stimulation and compression as β- cells of
the pancreas, leading to the development of insulin resistance. So important is
the optimization approaches to the treatment of patients with PCOS with regard
to the likely role of 227
hyperprolactinemia.
However, to date research on the comparative evaluation of clinical
effectiveness (efficiency) of different methods of multivariate stimulate
ovulation in anovulatory infertility, occur less frequently.
The aim was to evaluate the clinical efficiency of
different treatments cancellation and infertility in women with PCOS and
hyperprolactinemia.
Materials and methods. The survey
was conducted at the department of invasive methods and diagnostics of
university clinic of Odessa National Medical University (Odessa) and
multi-field medical center" Avicenna "(Melitopol). The conducted
retrospective analysis of reproductive results of treatment of women is with
multivariable anovulatory infertility. Retrospective search depth was 5 years.
A total analysis includes 502 case histories
During
the study of data of medical documentation we paid attention to the next
features. PCOS Diagnosed in agreement with criteria of Rotterdam consensus
sponsored in part by the European Society for Human Reproduction and Embryology
and the American Society for Reproductive Medicine (2003), based on the
presence of chronic oligo- or anovulation, clinical and/or biochemical signs of
hyperandrogenism, or polycystic ovaries on ultrasound examination [11].
Patients with hyperprolactinemia were conducted double determination of
prolactin in serum by enzyme-linked immunosorbent assay (ELISA)to exclude
tumours and pituitary hypothalamic syndromes X-ray and/or MRI of the brain were
performed.
In the course of further analysis on the retrospective
phase of the study were identified six groups of patients, depending on the
efficiency of conservative or used surgical treatments.
The first group consisted of 21 (10.7 %) women with an
initial phase of the hypothalamic-pituitary dysfunction with menstrual
disorders and genital infantilism, which became pregnant due to the correction
of hormonal relations by therapy on the type of rebound - effect. 228
Another group
included 27 (13.8 %) women with PCOS who become pregnant during treatment with
standard ovulation stimulation by the medications include clomiphene citrate (a
selective estrogen receptor modulator). One woman had born twins, however one
patient (twice) had ectopic pregnancy.
The third group involved of 23 (11.7 %) women with
PCOS and adrenal hyperandrogenism, without severe symptoms of
hyperprolactinemia who became pregnant by the treatment of derivatives of the
corticosteroid hormones cortisol and aldosterone that are produced naturally by
the adrenal glands (Dexamethasone). All pregnancies resulted in deliveries in
time without conclusions.
The fourth group was composed of 25 (12.8%) patients
with PCOS in combination with adrenal hyperandrogenism and symptoms of
hyperprolactinemia. They were treated with Dexamethasone and a dopamine agonist
ergoline derivative - Bromocriptine, is an in communicating from a minimum dose
to maximal or effective (optimize). In all cases, the patient became pregnant
within six months of beginning treatment after the renewal of ovulation.
The fifth group contained of 18 (9.2%) women who
became pregnant in the ordinary cycle after surgical induction of ovulation by
laparoscopic partial ovarian destruction (that was directed at inefficiency by
applications of medicine correction).
Determinations of authenticity of differences between
the compared groups or subgroups on frequencies of separate clinical indexes or
outputs performed by using 2 test
with Yates correction given for paired comparisons and Bonferoni correction for
multiple comparisons to the control group. Statistical study was performed
using the programmatic complex Statistica 10.0 (StatSoft Inc., USA) [12]. 229
The results. From
the general amount of patients with anovulatory infertility (502 persons) 196
women are selected with verification of PCOS in combined with symptoms of
hyperprolactinemia.
In results of research a variant of multifactor
anovulatory sterility of met in 39. 0 % of cases, this version exceed the
values led by different studies that have been described by other researchers.
In assessing the hormonal profile of patients showed that the levels of
prolactin are higher than the reference value and averaged 18.8 ± 1.1 ng / ml
(Table 1).
According to the data of table, the results of
hormonal profile of inspected women indicate a variability of damages of women
with PCOS and hyperprolactinemia, and PCOS and hyperandrogenism. Patients had
increased fraction of LH / FSH to 2.1 ± 0.1 by increasing LH content (up to
13.2 ± 0.5 IU / l) and decrease in FSH (to (6.5±0.2) mIU/l), hyperandrogenism -
androstenedione level - 4.2±0.2 nmol/l, testosterone -2.8±0.2 nmol/l, DHEA -S -
4.0±0.3 nmol/l), progesterone (8.0 ± 0.5 nmol/l) on a background of moderate
hypoestrogenic state (45.0 ± 2.2 pg / ml). Representative for all patients
where normal levels of AMH (2.7 ± 0.2 ng / ml), indicating a high ovarian
reserve.
Request of surgical induction after the previous
course of hormonotherapy in 82 (41.8%) of women with sterility was not
effective. These women were guided to assisted reproductive technology clinic.
As established in Table 1 the patients of different
groups did not differ on age, middle age in groups had laid down 27.8±0.7. The
investigation of complaints of patients found that and menstrual disorders
prevailed among other conditions, and infertility duration on the average laid
down 5.6±0.4 years. In further study the presence of statistically significant
differences by the hirsute number, free testosterone index in patients with III
and IV groups. Relatively low levels of prolactin (6.9 ± 0.5 ng/ml) were
observed in patients with a preliminary phase of the hypothalamic-pituitary
dysfunction.
Table 1 230
Clinical physiognomies of patients
|
Indices |
² group (n=21) |
²² group (n=27) |
²²² group (n=23) |
IV group (n=25) |
V group (n=18) |
|
Age, year |
27.0±0.4 |
30.0±0.5 |
30.1±0.4 |
26.2±0.3 |
30.0±0.4 |
|
BMI, kg/m² |
22.3±0.4 |
24.9±0.4 |
24.6±0.3 |
20.3±0.4 |
22.3±0.4 |
|
Hirsute number, scores |
6.9±0.1 |
8.7±0.4 |
9.9±0.2* |
7.3±0.2 |
8.9±0.1* |
|
FSH, mIU/l |
9.8±1.5 |
4.2±0.2 |
7.1±0.4 |
11.3±0.3 |
9.8±1.5 |
|
LH, mIU/l |
11.8±1.3 |
12.1±0.3 |
10.0±0.6 |
14.0±0.4 |
14.8±1.3 |
|
LH/FSH |
1.2±0.3 |
3.3±0.5 |
1.7±0.2 |
1.4±0.1 |
1.2±0.3 |
|
Estradiol, pmol/l |
68.2±5.6 |
45.0±2.2 |
50.1±7.0 |
57.9±4.5 |
68.2±5.6 |
|
Progesterone, nmol/l |
1.6±0.1 |
1.2±0.2 |
2.0±0.2 |
1.9±0.2 |
1.6±0.1 |
|
17-ÎÍ progesterone, nmol/l |
1.2±0.2 |
0.8±0.5 |
1.9±0.2 |
1.1±0.1 |
1.2±0.2 |
|
DHEAS, mcmol/l |
3.4±0.3 |
4.0±0.3 |
4.9±0.2 |
4.8±0.3 |
4.4±0.3 |
|
Prolactin, ng/ml |
6.9±0.5 |
11.3±0.4 |
16.4±0.5 |
34.2±1.2* |
16.9±0.5 |
|
TTH, mMI/l |
1.8±0.2 |
1.9±0.2 |
2.6±0.2* |
1.5±0.3 |
2.8±0.2* |
|
Ò4, pmol/l |
4.2±0.2 |
4.0±0.3 |
4.4±0.3 |
4.3±0.2 |
4.2±0.2 |
|
Androstenedione, nmol/l |
4.2±0.2 |
4.0±0.2 |
4.8±0.4 |
3.8±0.2 |
4.2±0.2 |
|
AMH, ng/ml |
2.7±0.2 |
3.1±0.3 |
3.0±0.3 |
2.4±0.3 |
2.7±0.2 |