Pediatrician (St. Petersburg)Pediatrician (St. Petersburg)2079-78502587-6252Eco-Vector1915710.17816/PED10557-65Research ArticlePredictors of the development of cardiac arrhythmias in women after induction of superovulation in vitro fertilizationVakarevaVictoria V.<p>Postgraduate Student, Department of Family Medicine AF and DPO</p>barbora83@mail.ruAvdeevaMarina V.<p>MD, PhD, Dr Med Sci, Professor, Department of Family Medicine AF and DPO</p>Lensk69@mail.ruScheglovaLarisa V.<p>MD, PhD, Dr Med Sci, Professor, Head, Department of Family Medicine AF and DPO</p>shcheglovalar@mail.ruBondarevSergey A.<p>MD, PhD, Dr Med Sci, Associate Professor, Department of Hospital Therapy with Military Therapy and Occupational Medicine Courses</p>sabondarev@yandex.comVoronkovPavel B.<p>MD, PhD, Associate Professor, Department of Family Medicine AF and DPO</p>pbvoronkov@yandex.ruSt. Petersburg State Pediatric Medical University, Ministry of Healthcare of the Russian Federation2812201910557652801202028012020Copyright © 2020, Vakareva V.V., Avdeeva M.V., Scheglova L.V., Bondarev S.A., Voronkov P.B.2020<p>The article presents the results of a clinical and instrumental examination of 80 healthy women (average age 32,313,57 years) in order to assess the heart rhythm disturbances after induction of superovulation during<em>in vitro</em>fertilization. All women were examined twice before and after induction of superovulation during extracorporeal fertilization. Clinical and instrumental examination included: electrocardiography at rest; echocardiography; 24-hour ECG monitoring with heart rate variability analysis; 24-hour blood pressure monitoring. Induction of superovulation is associated with a significant increase in mean daily HR max (<em>р</em>0,01), and consequently with an increase in myocardial oxygen demand. It has been established that induction of superovulation contributes to the development of supraventricular arrhythmias (<em>р</em>0,01) and an increase in episodes of apnea/hypnea (<em>р</em>0,01). Regression analysis revealed predictors of supraventricular arrhythmias after induction of superovulation, including adverse circadian heart rate profile, adverse circadian blood pressure profile, impaired autonomic regulation of heart activity (<em>р</em>0,01). It was shown that the appearance of rhythm disturbances is associated with both the initial functional state of the cardiovascular system and its response to the induction of superovulation. It was established a correlation between the estradiol concentration and the increase of daily average heart rate after induction of superovulation (<em>r</em>=0,30,<em>р</em>0,05), apnea/hypnea index after induction of superovulation (<em>r</em>=0,34,<em>р</em>0,05). Conclusion. Superovulation induction may exacerbate existing chronic cardiovascular diseases. Due to the adverse effect of superovulation induction on the daily heart rate profile, women need to evaluate the functional state of the cardiovascular system during<em>invitro</em>fertilization planning. This will prepare the woman for the upcoming procedure and avoid adverse reactions from the cardiovascular system in response to stimulation of superovulation<em>in vitro</em>fertilization.</p>women’s healthextracorporeal fertilizationrhythm disturbancesrisk of rhythm disturbances in womeninduction of superovulationздоровье женщинэкстракорпоральное оплодотворениенарушения ритмариск нарушений ритма у женщининдукция суперовуляции<p>About 186 million people around the world are infertile, andthe occurrence of infertile couples is 15%17% and tends toincrease [5, 6]. At present, there are about 5 millionchildless families in Russia, and every fifth woman of reproductiveage is not able to conceive a child spontaneously [4].The incidence of female infertility in our country is 164cases per 100,000 women [2]. In the period from 2001to 2014, the number of infertile women increased 1.7 times.Over recent years, female infertility ranked first in the structureof reproductive losses [1].</p>
<p>Studies show that the inability to conceiveis associated with cardiovascular risk, as many nonfertile women havecardiometabolic disorders that potentially increase the risk of cardiovascular disease[3,12]. Moreover, some types of infertility are associated withan increased risk of cardiovascular diseases [7,8, 10,11].</p>
<p>The method of<em>in vitro</em>fertilization (IVF) provides a unique opportunity to implement the ability to give birthin almost all forms of female and many forms ofmale infertility [6]. Although IVF is considered a common andrelatively safe method of treating infertility, the risk of sideeffects in the cardiovascular system still has to be takeninto account [14]. Foreign studies have shown that hormonal therapyof infertility can predispose to cardiovascular diseases[9, 11, 13].However, a small number of studies and their high heterogeneitycannot make firm conclusions about the safety of assisted reproductivetechnologies for the cardiovascular system. In Russia, this problem hasalmost not been studied. In this regard, studies aimed atassessing cardiovascular risk after applying hormonal regimens for the treatmentof infertility in IVF are required.</p>
<p>This study aimed to performa comparative assessment of cardiac rhythm disturbances according to dailyECG monitoring before and after superovulation induction in IVF.</p>
<h2>MATERIAL ANDMETHODS</h2>
<p>Eighty women (average age of 32.31 3.57 years)were examined. All patients underwent an IVF procedure in the Center for ReproductiveTechnologies of the St. Petersburg City Mariinsky Hospital. An indicationfor IVF was a history of primary or secondary female/maleinfertility. Of patients, 21.3% had female infertility factor (<em>n</em>= 17), 37.5% had male infertility factor (<em>n</em>= 30), and 41.3% had mixed infertility factor (<em>n</em>= 33).</p>
<p>Criteriafor inclusion in the study were reproductive age suitable forthe IVF procedure (from 18 to 43years), a historyof primary or secondary female/male infertility, lack of IVF contraindications,and voluntary consent to participate in the study. The studydid not include women with a history of cardiovascular orendocrine system diseases, as well as hormonal disorders.</p>
<ul>
<li>Ovulation induction wasperformed according to a short protocol that consisted of thefollowing phases:</li>
<li>From days 2 to 10 of the cycle, therecombinant human follicle-stimulating hormone Gonal-f (Italy) was administered at adose of 300 IU.</li>
<li>From days 7 to 11, the gonadotropin-releasinghormone antagonist Orgalutran (Netherlands) was administered subcutaneously at a doseof 0.25 mg.</li>
<li>On day 11 at 23:00, the recombinant humanchorionic gonadotropin Ovitrelle (Italy) was administered subcutaneously at a doseof 250 mcg.</li>
<li>On day 11 at 23:00, a synthetic analogof the gonadotropin-releasing hormone Decapeptyl (Germany) was administered subcutaneously ata dose of 0.2 mg.</li>
<li>On day 13, 36 h afterthe last injection, ovarian puncture was performed to obtain anoocyte.</li>
</ul>
<p>According to the results of the one-way analysis of variancetest, age did not affect the changes in daily ECG monitoring indicators (Fishers test<em>F</em>= 0.92336,<em>p</em>= 0.53431);therefore, women were not divided into groups by age.</p>
<p>Thestudy of the functional condition of the cardiovascular system wasperformed twice in a hospital: a day before the startof superovulation induction (day 1 of the cycle) and aftercompletion of the superovulation induction (day 14).</p>
<p>Clinical and laboratory examinationincluded a double study of the general and biochemical analysisof blood (alanine aminotransferase, aspartate aminotransferase, total protein, creatinine, urea,glucose, and total cholesterol), as well as hormonal studies withthe determination of thyroid-stimulating hormone and estradiol levels before andafter stimulation of superovulation in IVF. Venous blood was sampledfor laboratory tests in the morning on an empty stomach.The concentration of total cholesterol, aspartate aminotransferase, alanine aminotransferase, glucose,creatinine, urea, and total protein was determined using an Architectc8000 biochemical analyzer (Abbot, USA). Estradiol concentration was determined ina Cobas e 411 immunochemical analyzer (Roche, Switzerland) using anAlkor-Bio reagent kit (St. Petersburg, Russia). The concentration of thyroid-stimulatinghormone was determined using an Architect i2000 immunochemical analyzer (Abbot,USA). The results of clinical and instrumental examination before andafter the superovulation induction are presented in Table 1.</p>
<p></p>
<p><em>Table1/ </em><em>Таблица</em><em> 1</em></p>
<p>Laboratory indicators before and after induction of superovulation</p>
<p>Лабораторные показатели до и после индукции суперовуляции</p>
<table width="623">
<tbody>
<tr>
<td>
<p>Parameters/ Параметры</p>
</td>
<td>
<p>Beforestimulationsuperovulation,<em>M</em>(<em>n</em>=80) / До индукции суперовуляции,<em>M</em>(<em>n</em>=80)</p>
</td>
<td>
<p>Afterstimulationof superovulation,<em>M</em>(<em>n</em>=80) / После индукции суперовуляции,<em>M</em>(<em>n</em>=80)</p>
</td>
<td>
<p><em>р</em></p>
</td>
</tr>
<tr>
<td>
<p>Total protein,g/l/</p>
<p>Общий белок, г/л</p>
</td>
<td>
<p>74.63 5.83</p>
</td>
<td>
<p>71.92 5.69</p>
</td>
<td>
<p>0.001</p>
</td>
</tr>
<tr>
<td>
<p>Creatinine,mmol/l/Креатинин,ммоль/л</p>
</td>
<td>
<p>72.98 11.31</p>
</td>
<td>
<p>76.76 10.54</p>
</td>
<td>
<p>0.001</p>
</td>
</tr>
<tr>
<td>
<p>Urea,mmol/l/ Мочевина, ммоль/л</p>
</td>
<td>
<p>4.79 1.39</p>
</td>
<td>
<p>5.07 1.47</p>
</td>
<td>
<p>0.001</p>
</td>
</tr>
<tr>
<td>
<p>Cholesterol,mmol/l/ Холестерин, ммоль/л</p>
</td>
<td>
<p>3.70 0.80</p>
</td>
<td>
<p>4.18 0.65</p>
</td>
<td>
<p>0.001</p>
</td>
</tr>
<tr>
<td>
<p>Alanine aminotransferase,IU/l/ Аланинаминотрансфераза, МЕ/л</p>
</td>
<td>
<p>19.01 4.75</p>
</td>
<td>
<p>23.06 4.79</p>
</td>
<td>
<p>0.001</p>
</td>
</tr>
<tr>
<td>
<p>Aspartate aminotransferase,IU/l/ Аспартатаминотрансфераза, МЕ/л</p>
</td>
<td>
<p>24.62 16.55</p>
</td>
<td>
<p>26.37 4.53</p>
</td>
<td>
<p>0.05</p>
</td>
</tr>
<tr>
<td>
<p>Glucose,mmol/l/ Глюкоза, ммоль/л</p>
</td>
<td>
<p>4.02 0.52</p>
</td>
<td>
<p>4.44 0.50</p>
</td>
<td>
<p>0.05</p>
</td>
</tr>
<tr>
<td>
<p>Estradiol,pmol/l/ Эстрадиол, пмоль/л</p>
</td>
<td>
<p>103.42 12.18</p>
</td>
<td>
<p>907.92 150.46</p>
</td>
<td>
<p>0.001</p>
</td>
</tr>
<tr>
<td>
<p>Thyroid-stimulating hormone,mIU/ml/Тиреотропныйгормон,мМЕ/мл</p>
</td>
<td>
<p>1.20 0.47</p>
</td>
<td>
<p>2.47 0.45</p>
</td>
<td>
<p>0.001</p>
</td>
</tr>
</tbody>
</table>
<p></p>
<p>The studywas conducted using a portable cardiomonitor Kardiotechnika (Incart, St. Petersburg).The device was installed in the morning. Continuous ECG recordingwas performed under conditions of unlimited activities of daily livingfor 24 h.</p>
<p>Quantitative variables are presented as arithmetic mean standard deviation (<em>M</em><em></em>) or confidence intervals (CIs). Categorical variables are presented as the frequency of detection and/or as percentageshare. Hypothesis on the equality of two mean values forparametric data was tested using the Student<em>t</em>-test fordependent samples (when comparing the indicators over time). The differenceswere considered statistically significant at<em>p</em> 0.05. To identifythe relationship between quantitative accounting parameters, a correlation analysis wasperformed with the determination of the Pearson correlation coefficient (<em>r</em>). To identify the relationship between quality accounting parameters, the <sup>2</sup>criterion was determined. To identify the relationshipbetween several parameters, a multiple regression analysis was performed withthe step-by-step exclusion of variables. The multiple regression model includedfactors with a significant regression coefficient<em>B</em>(<em>p</em>0.05).</p>
<p>To determine the relative risk of adverse events(AEs), thepatients were divided into two groups: those with the presence of an AE after superovulationinductionand those who had no AE after superovulationinduction.Using the four-field table, the relative risk of an AEwas calculated, which was represented by the emergence of cardiac rhythm disturbances or episodes of apnea-hypopnea after superovulationinduction:</p>
<p><math xmlns="http://www.w3.org/1998/Math/MathML"><mi>OP</mi><mo>=</mo><mfrac><mrow><mi mathvariant="normal">a</mi><mo>/</mo><mo>(</mo><mi mathvariant="normal">a</mi><mo>+</mo><mi mathvariant="normal">b</mi><mo>)</mo></mrow><mrow><mi mathvariant="normal">c</mi><mo>/</mo><mo>(</mo><mi mathvariant="normal">c</mi><mo>+</mo><mi mathvariant="normal">d</mi><mo>)</mo></mrow></mfrac><mo>,</mo></math></p>
<p>where<em>a</em>implies a risk factor and an adverseoutcome,<em>b</em>means no risk factor with an adverse outcome,<em>c</em>implies a risk factor without an adverse outcome,and<em>d</em>means no risk factor without an adverse outcome.</p>
<p>The relative risk indicator was compared with 1 to determine the relationship of thefactor with the outcome. When the value of the relativerisk indicator is 1, it was concluded that the factorunder study did not affect the probability of the outcome(lack of connection between the factor and the outcome). Whenthe value of the relative risk indicator was more than1, it was concluded that the factor increased the frequencyof outcomes (direct correlation). When the value of the relativerisk indicator was less than 1, a conclusion was drawnabout a decrease in the probability of an outcome whenexposed to a factor (feedback).</p>
<h2>RESULTS AND DISCUSSION</h2>
<p>An analysis of theresults of daily ECG monitoring revealed the changes in theparameters of the heart rate (HR) daily profile after stimulationof superovulation compared with the baseline values. According to dailyECG monitoring conducted in women on day 1 after stimulationof superovulation, there was a slight but significant increase inthe average daily (<em>p</em> 0.01) and average nightHR values (<em>p</em> 0.01). The most pronounced increase was registered in theaverage daily HR max (111.8 16.9beats/min before and124.7 11.6 beats/min after; average increase in HR12.9 7.3 beats/min;<em>p</em>0.01). The average daily HR values min (58.1 5.4beats/min before and 64.3 6.6 beats/min after; average HR increase 6.2 5.3beats/min;<em>p</em> 0.01) and average night HR indicators min(50.7 4.4 beats/min before and 57.6 6.5 beats/min after; an increase in HR6.9 4.7beats/min;<em>p</em> 0.01) were found to be more stable (Table 2).A correlation was established between the concentration of estradiol andthe increase in the average daily HR on day 1after the superovulation induction (<em>r</em>= 0.30,<em>p</em> 0.05).</p>
<p></p>
<p><em>Table2/ </em><em>Таблица</em><em> 2</em></p>
<p>Dynamics of the daily profile of the heart rate in women before and after induction of superovulation during extracorporeal fertilization</p>
<p>Динамика суточного профиля частоты сердечных сокращений у женщин до и после индукции суперовуляции при ЭКО</p>
<table width="623">
<tbody>
<tr>
<td>
<p>Timesof day/ Время суток</p>
</td>
<td>
<p>Heart rate,beats/min/ Показатель ЧСС, уд/мин</p>
</td>
<td>
<p>Beforestimulationsuperovulation,<em>M</em>(<em>n</em>=80) / До стимуляции суперовуляции,<em>M</em>(<em>n</em>=80)</p>
</td>
<td>
<p>Afterstimulation of superovulation,<em>M</em>(<em>n</em>=80) / После стимуляции суперовуляции,<em>M</em>(<em>n</em>=80)</p>
</td>
<td>
<p>Difference,<em>M</em>/ Разница,<em>M</em></p>
</td>
<td>
<p><em>р</em></p>
</td>
</tr>
<tr>
<td rowspan="3">
<p>Daytime/ Дневное время</p>
</td>
<td>
<p>Heart rate minimal/ ЧСС минимальная</p>
</td>
<td>
<p>58.1 5.4</p>
</td>
<td>
<p>64.3 6.6</p>
</td>
<td>
<p>6.2 5.3</p>
</td>
<td>
<p>0.01</p>
</td>
</tr>
<tr>
<td>
<p>Heart rate average/ ЧСС средняя</p>
</td>
<td>
<p>75.1 5.9</p>
</td>
<td>
<p>83.1 6.3</p>
</td>
<td>
<p>8.1 5.2</p>
</td>
<td>
<p>0.01</p>
</td>
</tr>
<tr>
<td>
<p>Heart rate maximal/ ЧСС максимальная</p>
</td>
<td>
<p>111.8 16.9</p>
</td>
<td>
<p>124.7 11.6</p>
</td>
<td>
<p>12.9 7.3</p>
</td>
<td>
<p>0.01</p>
</td>
</tr>
<tr>
<td rowspan="3">
<p>Nighttime/ Ночное время</p>
</td>
<td>
<p>Heart rate minimal/ ЧСС минимальная</p>
</td>
<td>
<p>50.7 4.4</p>
</td>
<td>
<p>57.6 6.5</p>
</td>
<td>
<p>6.9 4.7</p>
</td>
<td>
<p>0.01</p>
</td>
</tr>
<tr>
<td>
<p>Heart rate average/ ЧСС средняя</p>
</td>
<td>
<p>65.0 9.0</p>
</td>
<td>
<p>75.6 12.1</p>
</td>
<td>
<p>10.6 7.4</p>
</td>
<td>
<p>0.01</p>
</td>
</tr>
<tr>
<td>
<p>Heart rate maximal/ ЧСС максимальная</p>
</td>
<td>
<p>92.9 13.0</p>
</td>
<td>
<p>103.3 9.1</p>
</td>
<td>
<p>9.1 6.1</p>
</td>
<td>
<p>0.01</p>
</td>
</tr>
<tr>
<td colspan="6">
<p><em>Note.</em>HR heart rate.</p>
<p><em>Примечание</em><em>.</em>ЧСС частота сердечных сокращений.</p>
</td>
</tr>
</tbody>
</table>
<p></p>
<p>After superovulation induction, a decrease in the circadianHR index was registered in female patients (1.18 0.18beats/min before and 1.12 0.17 beats/minafter;<em>p</em>0.05). Similar changes are usually registered with increased activity ofthe sympathetic part of the autonomic nervous system.</p>
<p>In 27.5% ofwomen after the superovulation induction, the frequency of supraventricular extrasystoledecreased, and in 57.5%, it increased compared with the baselinelevel. In 5.0%, supraventricular extrasystole was registered for thefirst time, and in 10.0%, its frequency remained unchanged. Thus,in most female patients, an increase in the total numberof supraventricular extrasystoles after induction of superovulation was noted (<em>p</em> 0.01; Figure 1).</p>
<p></p>
<center>
<div class="preview fancybox" style="text-align: center;"><a title="Fig. 1. Distribution of women in accordance with the dynamics of supraventricular extrasystole after induction ofsuperovulation, %" href="/files/journals/4/articles/19157/supp/19157-55827-1-SP.png" rel="simplebox"><img style="max-height: 300px; max-width: 300px;" src="/files/journals/4/articles/19157/supp/19157-55827-1-SP.png" /></a></div>
</center>
<p><strong>Fig. 1. Distribution of women in accordance with the dynamics of supraventricular extrasystole after induction ofsuperovulation, %</strong></p>
<p><strong>Рис. 1. Распределение женщин в соответствии с динамикой суправентрикулярной экстрасистолии после индукции суперовуляции, %</strong></p>
<p></p>
<p>According to the data obtained, ventricularextrasystoles did not occur in the female patients examined bothbefore and after stimulation of superovulation. There was an increasein the average number of supraventricular extrasystoles over time comparedwith the initial state (2.51 1.61 extrasystoles per hour after before and 3.20 2.95extrasystoles per hour after;<em>p</em> 0.05) and an increasein the average number of apnea-hypopnea episodes (0.23 0.12per hour before and 1.51 0.81 per hour after;<em>p</em> 0.01; Figure 2).</p>
<p></p>
<center>
<div class="preview fancybox" style="text-align: center;"><a title="Fig. 2. The number of supraventricular extrasystoles and episodes of apnea/hypnea in women before and after the induction of superovulation (р0.05)" href="/files/journals/4/articles/19157/supp/19157-55828-1-SP.png" rel="simplebox"><img style="max-height: 300px; max-width: 300px;" src="/files/journals/4/articles/19157/supp/19157-55828-1-SP.png" /></a></div>
</center>
<p><strong>Fig. 2. The number of supraventricular extrasystoles and episodes of apnea/hypnea in women before and after the induction of superovulation (р0.05)</strong></p>
<p><strong>Рис. 2. Количество суправентрикулярных экстрасистол и эпизодов апноэ/гипноэ у женщин до и после индукции суперовуляции (<em>р</em> 0,05)</strong></p>
<p></p>
<p>It should be noted that, ingeneral, an uncritical amount of supraventricular extrasystoles was recorded bothduring the hour and during the day. This was alsotrue for the apnea-hypopnea index, the values of which did not exceed the norm (upto 5 episodes perhour). In the female patients examined, episodes of apnea-hypopnea occurredonly at night. A direct correlation was established between theestradiol concentration and the apnea-hypopnea index after superovulation induction (<em>r</em>= 0.34,<em>p</em> 0.05). It was also revealed that the total number of supraventricular extrasystolesrecorded per day correlates directly with the level of averagedaily HR (<em>r</em>= 0.28,<em>p</em> 0.05, respectively). Therefore,the more significant the increase in the average daily HRis, the greater is the likelihood of supraventricular rhythm disturbances during the inductionof superovulation in IVF. Thus, the data obtained in thestudy indicate that stimulation of superovulation with IVF can bea triggering factor for changes in the heart rhythm. Thepresence of a history of cardiovascular diseases in a womanmay contribute to pathological changes in the heart rhythm. Femalepatients with cardiovascular pathology were not included in our study;therefore, no pathological number of supraventricular extrasystoles was registered afterthe induction of superovulation. However, according to the data obtained,the induction of superovulation is associated with an increase inthe average daily HR max (<em>p</em> 0.01) and, therefore, with an increase in myocardial oxygen demand. The above factors can contribute to the exacerbation of existing chroniccardiovascular diseases, as well as the development of heart rhythmdisorders and more frequent episodes of apnea-hypopnea.</p>
<p>Before stimulation of superovulation,episodes of apnea-hypopnea were registered in 22.5% of female patients,and after manipulation, they were noted in 50.0% (<sup>2</sup>= 15.7,<em>p</em> 0.01; Figure 3).</p>
<p></p>
<center>
<div class="preview fancybox" style="text-align: center;"><a title="Fig. 3. The proportion of women with episodes of apnea/hypnea before and after the induction of superovulation,% (р 0,01)" href="/files/journals/4/articles/19157/supp/19157-55829-1-SP.png" rel="simplebox"><img style="max-height: 300px; max-width: 300px;" src="/files/journals/4/articles/19157/supp/19157-55829-1-SP.png" /></a></div>
</center>
<p><strong>Fig. 3. The proportion of women with episodes of apnea/hypnea before and after the induction of superovulation,% (р 0,01)</strong></p>
<p><strong>Рис. 3. Доля женщин с эпизодами апноэ/гипноэ до и после индукции суперовуляции, % (<em>р</em> 0,01)</strong></p>
<p></p>
<p>It should be noted that after the induction of superovulation,27.5% of female patients experienced episodes of apnea-hypopnea, 22.5% hadmore frequent episodes of apnea-hypopnea, and 50.0% had the baselinenumber of apnea-hypopnea episodes. Inthe subgroup of female patientsin which episodes of apnea-hypopnea were recorded after the inductionof superovulation compared with women without apnea-hypopnea, higher levels ofestradiol (936.44 114.94and817.59 150.23 pmol/L, respectively;<em>p</em> 0.05), cholesterol (4.52 0.47 and 4.08 0.66 mmol/L,respectively,<em>p</em> 0.05), and erythrocyte sedimentation rate (7.42 1.73 and 5.95 2.23mm/h, respectively,<em>p</em> 0.05) were noted.</p>
<p>Using regression analysis, it was found that the determinants of the riskof supraventricular extrasystole after the induction of superovulation can bedeterioration in the daily profile of blood pressure (BP) andHR and disorder of the vagosympathetic balance of the autonomicnervous system (Table 3).</p>
<p></p>
<p><em>Table3/</em><em>Таблица</em><em> 3</em></p>
<p>The results of a step-by-step regression analysis of the influence of the studied variables on the appearance of supraventricular extrasystole after superovulation induction</p>
<p>Результаты пошагового регрессионного анализа влияния изучаемых переменных на появление суправентрикулярной экстрасистолии после индукции суперовуляции</p>
<table width="623">
<tbody>
<tr>
<td>
<p>Independent variables/ Независимые переменные</p>
</td>
<td>
<p>Coefficientregressions<em>B/</em>Коэффициент регрессии<em>B</em></p>
</td>
<td>
<p><em>p</em></p>
</td>
</tr>
<tr>
<td>
<p>Index apnea/hypnea/Индекс апноэ/гипноэ</p>
</td>
<td>
<p>0.40</p>
</td>
<td>
<p>0.01</p>
</td>
</tr>
<tr>
<td>
<p>Average daily heart rate/ Среднедневная ЧСС</p>
</td>
<td>
<p>1.63</p>
</td>
<td>
<p>0.01</p>
</td>
</tr>
<tr>
<td>
<p>Average night heart rate/Средненочная ЧСС</p>
</td>
<td>
<p>1.97</p>
</td>
<td>
<p>0.01</p>
</td>
</tr>
<tr>
<td>
<p>Morning rise of systolic blood pressure/Величина утреннего САД</p>
</td>
<td>
<p>4.76</p>
</td>
<td>
<p>0.01</p>
</td>
</tr>
<tr>
<td>
<p>Morning rise of diastolic blood pressure/Величина утреннего ДАД</p>
</td>
<td>
<p>5.64</p>
</td>
<td>
<p>0.01</p>
</td>
</tr>
<tr>
<td>
<p>24-hour amplitude of diastolic blood pressure/ 24-часовая амплитуда ДАД</p>
</td>
<td>
<p>0.53</p>
</td>
<td>
<p>0.01</p>
</td>
</tr>
<tr>
<td>
<p>12-hour amplitude of systolic blood pressure/ 12-часовая амплитуда САД</p>
</td>
<td>
<p>0.45</p>
</td>
<td>
<p>0.01</p>
</td>
</tr>
<tr>
<td>
<p>12-hour amplitude of diastolic blood pressure/12-часовая амплитуда ДАД</p>
</td>
<td>
<p>0.18</p>
</td>
<td>
<p>0.01</p>
</td>
</tr>
<tr>
<td>
<p>Variability of systolic blood pressure by day/ Вариабельность САД днем</p>
</td>
<td>
<p>0.79</p>
</td>
<td>
<p>0.01</p>
</td>
</tr>
<tr>
<td>
<p>Variability of mean blood pressure by day/ Вариабельность среднего АД днем</p>
</td>
<td>
<p>0.64</p>
</td>
<td>
<p>0.01</p>
</td>
</tr>
<tr>
<td>
<p>Variability of systolic arterial pressure at night/ Вариабельность САД ночью</p>
</td>
<td>
<p>2.67</p>
</td>
<td>
<p>0.01</p>
</td>
</tr>
<tr>
<td>
<p>Variability of diastolic blood pressure at night/ Вариабельность ДАД ночью</p>
</td>
<td>
<p>0.23</p>
</td>
<td>
<p>0.01</p>
</td>
</tr>
<tr>
<td>
<p>Variability of mean blood pressure at night/Вариабельность среднего АД ночью</p>
</td>
<td>
<p>1.83</p>
</td>
<td>
<p>0.01</p>
</td>
</tr>
<tr>
<td>
<p>Index LF/HF day/ПоказательLF/HFднем</p>
</td>
<td>
<p>0.40</p>
</td>
<td>
<p>0.01</p>
</td>
</tr>
<tr>
<td>
<p>SDNNidx/SDNNidx</p>
</td>
<td>
<p>0.22</p>
</td>
<td>
<p>0.01</p>
</td>
</tr>
<tr>
<td>
<p>rMSSD/rMSSD</p>
</td>
<td>
<p>0.23</p>
</td>
<td>
<p>0.01</p>
</td>
</tr>
<tr>
<td colspan="3">
<p>R<sup>2</sup>models = 0.99,F= 4.82;<em>р</em>= 0.001/R<sup>2</sup>модели = 0,99,F= 4,82;<em>р</em>= 0,001</p>
</td>
</tr>
<tr>
<td colspan="3">
<p><em>Note.</em>LF/HF ratio characterizes the balance of sympathetic and parasympathetic effects on the heart; SDNNidx (ms) the average of all standard deviations over the entire recording array (triangular index), characterizes the general state of heart rate variability; rMSSD is the square root of the mean squares of the differences in the values of successive RR intervals, reflects the activity of the parasympathetic link of autonomic regulation.</p>
<p><em>Примечание.</em>Соотношение LF/HF характеризует баланс симпатических и парасимпатических влияний на сердце; SDNNidx (мс) среднее из всех стандартных отклонений по всему массиву записи (триангулярный индекс), характеризует общее состояние вариабельности сердечного ритма; rMSSD квадратный корень из среднего значения квадратов разностей величин последовательных интервалов RR, отражает активность парасимпатического звена вегетативной регуляции. ЧСС частота сердечных сокращений, АД артериальное давление, САД систолическое артериальное давление, ДАД диастолическое артериальное давление.</p>
</td>
</tr>
</tbody>
</table>
<p></p>
<p>Special aspects of the BP daily profilethat affect directly the emergence of rhythm disturbances in women,an increase in BP variability, worsening of the morning BPchanges, an increase in the 12-hamplitudes of systolic and diastolic BP, andan increase in the 24-h amplitudes of systolic and diastolicBP should be noted. In particular, in the subgroup offemale patients with negative dynamics in the form of anincrease in supraventricular extrasystole after induction of superovulation, the morningrise in systolic BP was higher than in the subgroupwithout negative dynamics after induction of superovulation (49.4 4.7and 25.6 6.1mmHg, respectively,<em>p</em> 0.01). This is also truefor the morning increase in diastolic BP (47.1 6.2and 22.8 8.3 mm Hg, respectively,<em>p</em> 0.01). The emergence of supraventricular disturbances of the cardiac rhythm was also influenced by the initial andsubsequent levels of the average dailyand night HR. Thus,in the subgroup of femalepatients who had an increasein the number of supraventricular extrasystoles, the average daily HRwas higher than that in the subgroup of women withoutnegative dynamics (83.7 5.3 and 77.1 9.7 beats/min, respectively,<em>p</em> 0.01). The emergence of supraventricular extrasystole was associated with achange in the vagosympathetic balance both before (LF/HF:<em>B</em>=0.31,<em>p</em> 0.01) and after induction of superovulation (LF/HF:<em>B</em>= 0.40,<em>p</em> 0.01).</p>
<p>The relative risk of supraventricular extrasystole under the influence of superovulationinduction was determined. In female patients with supraventricular extrasystole registeredbefore the induction of superovulation, the relative risk of itsincrease in day 1 after the manipulation was 1.13 comparedwith women who did not initially have supraventricular extrasystole (95%CI 0.572.14). Therefore, the presence of supraventricular extrasystole before theinduction of superovulation increases the risk by 1.13 times inday1 after manipulation. The relative risk of increased episodes of apnea-hypopnea under the influence of induction ofsuperovulation was also calculated. In women with apnea-hypopnea episodes registeredbefore induction of superovulation, the relative risk of increasing theirrate on day 1 after manipulation was 2.82 compared withwomen who did not have apnea-hypopnea before induction of superovulation(95% CI 2.023.94) Therefore, the presence of episodes of apnea-hypopneabefore induction of superovulation increases the risk by 2.8 times after the manipulation.</p>
<h2>CONCLUSION</h2>
<p>Superovulation induction isassociated with a significant increase in the average daily HRmax (<em>p</em> 0.01) and, therefore, with an increase inmyocardial oxygen demand. Induction of superovulation promotes the development ofsupraventricular rhythm disturbances and an increase in episodes of apnea-hypopnea. Predictors of supraventricular rhythm disturbances include unfavorable daily values of HR and BP, as well as disordersof the autonomic regulation of cardiac activity. The emergence ofrhythm disturbances is associated with both the initial functional conditionof the cardiovascular system and its response to the inductionof superovulation. The relative risk of supraventricular extrasystole inpractically healthy women under the influence of superovulation induction inIVF was 1.13 (95% CI 0.572.14). The relative risk ofapnea-hypopnea in practically healthy women under the influence of superovulationinduction in IVF was 2.82 (95% CI 2.023.94). Induction ofsuperovulation can cause an adverse effect on the functional stateof the cardiovascular system of women. In women planning IVF,it is advisable to assess the functional condition of thecardiovascular system using daily monitoring of ECG and BP. Thiswill enable to prepare a woman in advance for theupcoming procedure and avoid adverse reactions in the cardiovascular system.</p>[Землянова Е.В. Потери потенциальных рождений в России из-за проблем, связанных со здоровьем // Социальные аспекты здоровья населения. – 2016. – № 2. – С. 4. [Zemlyanova EV. Potential birth loss due to health-related problems in Russia. Social aspects of public health. Sotsial’nye aspekty zdorov’ya naseleniya. 2016;(2):4. (In Russ.)]][Калачикова О.Н., Шабунова А.А. Репродуктивное здоровье и поведенческие факторы его формирования (на материалах социологического исследования в Вологодской области) // Проблемы развития территории. – 2016. – № 1. – С. 115–129. [Kalachikova ON, Shabunova AA. Reproductive health and behavioral factors in its formation (on the materials of sociological research in the Vologda oblast). Problemy razvitiya territorii. 2016;(1): 115-129. (In Russ.)]][Ротарь О.П., Киталаева К.А., Авдеева М.В., и др. Компоненты метаболического синдрома у женщин, занимающихся преимущественно умственным трудом // Проблемы женского здоровья. – 2009. – Т. 4. – № 2. – С. 17–27. [Rotar OP, Kitalayeva KA, Avdeyeva MV, et al. The components of metabolic syndrome in mentally working females. Problemy zhenskogo zdorov’ya. 2009;4(2):17-27. (In Russ.)]][Сухих Г.Т. ЭКО до сих пор остается самой важной, яркой и наиболее интенсивно развивающейся вспомогательной репродуктивной технологией // Доктор.Ру. – 2007. – № 6. – С. 12–13. [Sukhikh GT. EKO do sikh por ostaetsya samoy vazhnoy, yarkoy i naibolee intensivno razviva-yushcheysya vspomogatel’noy reproduktivnoy tekhnologiey. Doktor.Ru. 2007;(6):12-13. (In Russ.)]][Asemota OA, Klatsky P. 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