Original Article
Anti-müllerian Hormone in Reproductive Age Women With Systemic Lupus Erythematosus
Hormona anti-mülleriana en mujeres en edad reproductiva con lupus eritematoso sistémico
María del Carmen Velarde-Ochoa, Jorge Antonio Esquivel-Valerio, David Vega-Morales
, Cassandra Michele Skinner-Taylor, Dionicio Ángel Galarza-Delgado, Mario Alberto Garza-Elizondo
Corresponding author
Servicio de Reumatología, Departamento de Medicina Interna, Hospital Universitario “Dr. José Eleuterio González”, Universidad Autónoma de Nuevo León, Monterrey, Mexico
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SLE can occur at any age, although its peak incidence is between 15 and 44 years of age, within the reproductive period of women. Therefore, obstetric disease and altered fertility are important.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> Although it has been described that fertility is normal in most patients with SLE,<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> this can be affected by each patient's ovarian reserve. Ovarian failure by low hormone ovarian reserve has, as aggravating factors, the disease activity measured by SLEDAI, the presence of antiovarian antibodies<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> and the use of cytotoxic agents.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Of the latter group, cyclophosphamide is the most studied prodrug due to its gonadal toxicity, damage to the ovarian follicles, follicular maturation and depletion of primordial follicles.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5–9</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In 2002, studies were initiated on the clinical application of determination of serum anti-Mullerian hormone (AMH), making it a marker with high sensitivity and specificity to determine the follicular reserve.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10,11</span></a> This hormone, also called Mullerian inhibitory substance, belongs to the superfamily of transforming growth factor β, is a dimeric glycoprotein with two disulfide bonds, with a molecular weight of 140<span class="elsevierStyleHsp" style=""></span>kDa and is mainly expressed in the granulosa cells.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12–18</span></a> Serum AMH levels correlate with the development of preantral and small antral follicles during reproductive life.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The AMH has been studied in different populations.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13,20–23</span></a> It is known that AMH levels are not altered in women using hormonal contraceptives.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> Some studies have evaluated AMH levels in patients with cancer and chemotherapy.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17,25,26</span></a> Retrospective studies have evaluated the prevalence of ovarian failure in SLE patients treated with cyclophosphamide, determining ovarian failure based on the presence or absence of amenorrhea, which is very sensitive and specific. More recently AMH has been used for measurement in SLE patients with and without immunosuppressants and a relationship has been found with the use of cyclophosphamide, but not with the use of other immunosuppressive agents.<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">27,28</span></a> It has also been studied in Juvenile lupus<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> and a downward trend in the parameters of ovarian reserve was seen, though not statistically significant, related to the use of cyclophosphamide, even when<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> patients were still menstruating. AMH measurements were also used to assess the role of gonadotropins’ agonists in preventing ovarian failure associated with cyclophosphamide.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> It has been reported that AMH may be decreased in SLE patients who never received cyclophosphamide compared with controls, indicating that fertility is itself affected by SLE per se.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">There may be clinical differences in SLE patients of different ethnic backgrounds.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> In the multicenter LUMINA LVIII study, predictors of premature gonadal failure were evaluated in 316 patients with SLE, which was defined by amenorrhea for >6 months and/or menopause before age 40; the study enrolled Hispanic patients, and found a prevalence of 11.7% of developing premature gonadal failure and it was established that the presence of high disease activity, Texas Hispanic ethnicity, and previous use of cyclophosphamide and older age were predictors of premature gonadal failure.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">There is the possibility that differences are not only due to social factors, but molecular and genetic factors only may modify the usefulness of this measurement in our population. For this reason, we studied AMH levels among Mexican women of reproductive age with SLE to assess factors associated with low ovarian reserve.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and Methods</span><p id="par0030" class="elsevierStylePara elsevierViewall">An analytical cross-sectional study from March to August 2011 was performed. We consecutively included 65 women aged 18–40 years, diagnosed with SLE, who fulfilled at least 4 classification criteria of the American College of Rheumatology (ACR), revised in 1997 for SLE,<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> from the Rheumatology Department, Hospital Universitario “Dr. José Eleuterio González” in Monterrey, Nuevo Leon, Mexico. We excluded patients with overlap syndromes, and established diagnosis of ovarian failure and those with a history of ovarian surgery.</p><p id="par0035" class="elsevierStylePara elsevierViewall">After signing informed consent, demographic (age, education level), clinical (disease duration, weight, height, body mass index [BMI], smoking, drug use) and obstetric characteristics (pregnancies, births were obtained abortions, cesarean sections and age at menarche) were collected.</p><p id="par0040" class="elsevierStylePara elsevierViewall">They were given a questionnaire to assess the damage index due to lupus by the <span class="elsevierStyleItalic">Systemic Lupus International Collaborating Clinic</span> (SLICC) validated in Spanish, which was determined in ranges from 0 to 46 points, with activity defined as >4 points.<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">35,36</span></a> The MEX-SLEDAI index was used to evaluate the activity of the disease, which contains 24 specific variables grouped by systems with a maximum of 32 points and which are divided, according to the score, in the inactive condition, mild, moderate or severe activity.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">We performed measurements of serological variables included hemoglobin (normal range 12–14<span class="elsevierStyleHsp" style=""></span>g/dl) and erythrocyte sedimentation rate (ESR) as well as immunological variables: antinuclear antibodies (ANA) by indirect immunofluorescence performed with Hep2 cells (negative<span class="elsevierStyleHsp" style=""></span><1:40), anti-dsDNA antibodies determined by indirect immunofluorescence with <span class="elsevierStyleItalic">Crithidia luciliae</span> (negative<span class="elsevierStyleHsp" style=""></span><1:20), anti-Sm antibodies determined by ELISA (negative<span class="elsevierStyleHsp" style=""></span><15<span class="elsevierStyleHsp" style=""></span>U/ml), anticardiolipin IgM and IgG determined by ELISA (negative<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>11 UMPL and <23 UGPL, respectively), complement levels by nephelometry (C3: 50–120<span class="elsevierStyleHsp" style=""></span>mg/dl, C4: 20–50<span class="elsevierStyleHsp" style=""></span>mg/dl) and lupus anticoagulant by coagulometric method with citrated plasma (Weak: 1.2–1.5/s, moderate: 1.5–2.5/s, strong<span class="elsevierStyleHsp" style=""></span>>2/s).</p><p id="par0050" class="elsevierStylePara elsevierViewall">Serum AMH levels were measured by duplicate in venous blood using ELISA (human anti-müllerian hormone, ELISA Kit TSZ Scientific LLC-Biotang Inc.) using reagents and calibrators provided by the manufacturer. A value <0.35<span class="elsevierStyleHsp" style=""></span>ng/ml was used to define low ovarian reserve, according to Almog et al.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">A database was created in Excel and statistical analysis was done using the SPSS<span class="elsevierStyleSup">®</span> version 19 statistical program. Quantitative variables were expressed as mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD or median and interquartile range, depending on the Gaussian distribution with the Kolmogorov–Smirnov test. The comparative analysis was done for normal quantitative variables with Student's t or Mann–Whitney's test otherwise.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Categorical variables were compared using chi-square or Fisher's exact test, according to the observations distributed in a cuadricelular table. The protocol was registered by the Ethics Committee of the Division of Research of the Faculty of Medicine and the University Hospital “Dr. José Eleuterio González” of the Autonomous University of Nuevo León.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0065" class="elsevierStylePara elsevierViewall">Sixty-five women were included in the study, with a mean age<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD of 28.6<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>6.4 years and a mean disease duration of 5.6<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4.5 years. The average BMI was 25<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>5.9<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span>. Regarding the patient's profession, 43 (66.2%) were unskilled workers, 12 (18.5%) university trained professionals, 9 (9.2%) had technical studies, and 3 (4.6%) (1.5%) were skilled workers. Regarding his educational level, 33 (50.8%) studied secondary school completely, 22 (33.8%) a college career, 8 (12.3%) were illiterate and 2 (3.1%) had incomplete secondary studies. Eight (12.3%) were actively smoking. The drugs used at the time of the study were: prednisone 69.2%, hydroxychloroquine 52.3%, chloroquine 24.6%, methotrexate 20.0%, leflunomide 1.5%, sulfasalazine 1.5%, azathioprine 24.6%, mycophenolate mofetil 6.2%, rituximab 7.7% and cyclophosphamide 25 (38.4%) women, with a mean cumulative dose of 7.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>6<span class="elsevierStyleHsp" style=""></span>g. The median activity index and MEX-SLEDAI fu 1 (IQR 0–3.5) and median SLICC damage index was 2 (IQR 1–3.5).</p><p id="par0070" class="elsevierStylePara elsevierViewall">As for their reproductive background, median menarche was 12 years (IQR 11.5–13.5). Eleven patients (16.9%) had menstrual abnormalities, the median number of pregnancies was 1 (IQR 0–2) and only 4 patients (6.2%) had a history of preeclampsia. Thirty-one patients (47.6%) had no pregnancies.</p><p id="par0075" class="elsevierStylePara elsevierViewall">As for paraclinical variables, mean hemoglobin was 12.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.5<span class="elsevierStyleHsp" style=""></span>g, mean ESR was 24<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>15<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleMonospace">/</span>H; ANA titers showed the following prevalences: 1:80 (38.5%); 1:160 (23.1%); 1:320 or more (7.7%) and were negative (16.9%). The predominant pattern was homogeneous in 47.7% of the titers, followed by speckled pattern in 15.4% and nucleolar pattern in 6.2%.Titers of anti-dsDNA antibodies were positive in 26.2%. Anti-Sm antibodies had a median of 6.1<span class="elsevierStyleHsp" style=""></span>U/ml (IQR 4.4–9.6). The mean complement C3 fraction was 78<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>33<span class="elsevierStyleHsp" style=""></span>mg% and C4 complement fraction of 22<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>11<span class="elsevierStyleHsp" style=""></span>mg%. The mean level of IgM anticardiolipin antibodies was 4.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4.0<span class="elsevierStyleHsp" style=""></span>UMPL and for IgG was 8.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>7.5<span class="elsevierStyleHsp" style=""></span>UGPL.</p><p id="par0080" class="elsevierStylePara elsevierViewall">In our population, the median AMH level was 0.61<span class="elsevierStyleHsp" style=""></span>ng/ml (IQR 0.49–0.74). The prevalence of low ovarian reserve in our study was 3.07% (2 patients). Fifteen patients were between 3 and 25 percentile (0.3879–0.4955<span class="elsevierStyleHsp" style=""></span>ng/ml). There was no correlation between prior use of cyclophosphamide and AMH level (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.88); in turn, the median gestations of patient exposed and not exposed to cyclophosphamide; when compared found 0 (IQR 1) and 1 (IQR 3), respectively, with no significant differences among the patients (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.042).</p><p id="par0085" class="elsevierStylePara elsevierViewall">No correlation between the SLE activity measured by MEX-SLEDAI and AMH levels was found; however, when the ratio of AMH levels and target organ involvement was assessed by SLICC, it was found that in the group with damage measured by SLICC (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>50) it was 0.6425 (IQR 0.28) vs the undamaged group (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>15), which was 0.5260 (IQR 0.16), with a statistically significant difference, with <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.03, using the <span class="elsevierStyleItalic">U</span> test of Mann–Whitney.</p><p id="par0090" class="elsevierStylePara elsevierViewall">Clinical and demographic characteristics of patients with low ovarian reserve are described in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>, where we can see that the first patient with low reserve is 20 years of age, disease duration of 4 years, treated with a dose of prednisone 5<span class="elsevierStyleHsp" style=""></span>mg/day, hydroxychloroquine 400<span class="elsevierStyleHsp" style=""></span>mg/day, a cumulative dose of 3<span class="elsevierStyleHsp" style=""></span>g rituximab, cyclophosphamide cumulative dose of 7.5<span class="elsevierStyleHsp" style=""></span>g, with MEX-SLEDAI 0 and SLICC 6. The second patient with low ovarian reserve is 25 years old, one year since the diagnosis of the disease, treated with prednisone 60<span class="elsevierStyleHsp" style=""></span>mg/day, hydroxychloroquine 200<span class="elsevierStyleHsp" style=""></span>mg/day and methotrexate 15<span class="elsevierStyleHsp" style=""></span>mg/week, received no biological or cyclophosphamide, MEX-SLEDAI was 4 and 3 SLICC. Regarding the obstetric data from both patients, none had menstrual disturbances, only the second patient had two pregnancies, the last one 5 years ago (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). Regarding both patients’ paraclinical variables, no significant data was seen, all being negative, including anti-dsDNA, anti-Sm and anticardiolipin antibody; complement and lupus anticoagulant were normal. The title of the first patients’ AMH was 0.312<span class="elsevierStyleHsp" style=""></span>ng/ml and in the second it was 0.321<span class="elsevierStyleHsp" style=""></span>ng/ml (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0095" class="elsevierStylePara elsevierViewall">This is the first study in our country that evaluates AMH levels in a group of Mexican patients with SLE, with and without cyclophosphamide, which gives importance to work, as this population has negative effects on ovarian reserve, which the can lead to fertility problems.</p><p id="par0100" class="elsevierStylePara elsevierViewall">The behavior of AMH in patients without cyclophosphamide in our population is similar to that described in the nomogram of infertile women published by Almog et al.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> However, they are lower than those reported in the study by Lawrenz et al., which evaluated AMH levels in 33 women with SLE without prior treatment with cyclophosphamide, which may be explained by ethnic and age-based differences, and exclusion of patients with cyclophosphamide; plus <span class="elsevierStyleItalic">the fact that the kit</span> used to measure AMH is different from that used in our study.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> Recently, Morel et al. assessed the probability of pregnancy in 46 SLE patients under 40 years of age with and without exposure to cyclophosphamide compared with control subjects, which found that AMH levels were lower in patients exposed to the drug and in patients older than 30 years. In patients with SLE, 32 of the 38 pregnancies were successful and it was finally settled that the decrease in pregnancy rates is negatively influenced by exposure to cyclophosphamide and age, not AMH<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> levels. We believe that the decline in fertility in our study (which was determined by the number of pregnancies among those exposed to cyclophosphamide or not) was influenced by medical advice to patients not to get pregnant and not secondary to the use of cyclophosphamide.</p><p id="par0105" class="elsevierStylePara elsevierViewall">The utility of AMH measurement to determine ovarian reserves has been studied in control populations, in the study by Tremellen et al., which assessed 238 women. 16 patients had a low ovarian reserve (measured by AMH), with a sensitivity of 80% and a specificity of 85%, positive predictive value 67% and negative predictive value of 97%.<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a> In this study of patients with SLE, the prevalence of low ovarian reserve of 3.07% (2 patients) according to the cutoff value described by Almog et al.</p><p id="par0110" class="elsevierStylePara elsevierViewall">In accordance with data described by Boumpas et al.,<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> both the patient's age and the dose of cyclophosphamide can affect ovarian reserve, which is reflected in the level of AMH of the first patient, with diminished ovarian reserve, who had a 7.5<span class="elsevierStyleHsp" style=""></span>g<span class="elsevierStyleHsp" style=""></span>cumulative dose of cyclophosphamide.</p><p id="par0115" class="elsevierStylePara elsevierViewall">However, in the total study population, we found no correlation between the cumulative dose of cyclophosphamide and level of AMH. The discrepancy with previous studies evaluating ovarian failure in SLE patients treated with cyclophosphamide intravenously<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> is because they define ovarian failure based on more than 12 or 20 months of amenorrhea. Additional factors that can explain are the cumulative dose of cyclophosphamide and patient age, as it is described that the risk of ovarian involvement is dependent on dose and age.</p><p id="par0120" class="elsevierStylePara elsevierViewall">The second patient with low ovarian reserve had not received cyclophosphamide, so low AMH levels could be explained by the presence of other associated factors, including the possible presence of genetic factors, or ovarian antibodies against AMH that could even interfere with the laboratory assay, which is to be determined in future studies. This is in line with that reported by Lawrenz et al., who mentioned that patients with SLE without cyclophosphamide have AMH at lower levels than controls.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">In previous years, regular menstrual periods were a readily ascertainable external parameter of ovarian function. Today, we know that the presence of regular periods is not synonymous with fertility, which can be reflected in the 2 patients with low ovarian reserve in our study who had regular menstrual cycles, something that is consistent with that reported.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Recently, we have studied a subclinical worsening of ovarian reserve in patients with SLE. Ma et al. evaluated 3 groups of patients, all with regular menstrual cycles: SLE without use of cytotoxic drugs, SLE and use of cytotoxic drugs, and a control group, where it was found that AMH levels and antral follicle counts were lower in the 2 groups of SLE, compared with controls, finding no significant difference between them.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> In our population, we found no correlation between the index of SLE activity measured by MEX-SLEDAI and AMH levels, which can be explained because the SLE patients in our study had low disease activity measured by the MEX-SLEDAI; however, due to the characteristics of the sample size, we could not perform a statistical analysis by levels of disease activity.</p><p id="par0135" class="elsevierStylePara elsevierViewall">Our study has several limitations. The first is that you cannot make direct comparisons with other populations, because the <span class="elsevierStyleItalic">kit</span> used was different than that from previous studies. However, the cutoff values in the 3rd percentile (<0.3287<span class="elsevierStyleHsp" style=""></span>ng/ml) correlated with the values described. The second is that the number of subjects with cyclophosphamide was not paired with those who did not receive it, because this was not a case–control study. Finally, a control group was not used.</p><p id="par0140" class="elsevierStylePara elsevierViewall">In conclusion, in our population the median AMH titer was 0.61<span class="elsevierStyleHsp" style=""></span>ng/ml, IQR of 0.49–0.4<span class="elsevierStyleHsp" style=""></span>a. The prevalence of low ovarian reserve in our study is 3.07% (2 patients). There was no correlation between the use of cyclophosphamide, SLE activity and the level of AMH.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Ethical Responsibilities</span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Protection of people and animals</span><p id="par0145" class="elsevierStylePara elsevierViewall">The authors declare that this research did not perform experiments on humans or animals.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Data confidentiality</span><p id="par0150" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of their workplace on the publication of data from patients, and all patients included in the study have received sufficient information and gave written informed consent to participate in the study.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Right to privacy and informed consent</span><p id="par0155" class="elsevierStylePara elsevierViewall">The authors state that no patient data appears in this article.</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Funding</span><p id="par0160" class="elsevierStylePara elsevierViewall">This study used self-resources from the Rheumatology and an unconditional support grant of $60,000 Mexican pesos from the <span class="elsevierStyleGrantSponsor" id="gs1">Mexican College of Rheumatology, AC</span>. The author reports that he does not have any funding to declare.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflict of Interest</span><p id="par0170" class="elsevierStylePara elsevierViewall">The authors have no disclosures to make.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:3 [ "identificador" => "xres436719" "titulo" => "Abstract" "secciones" => array:5 [ 0 => array:1 [ "identificador" => "abst0005" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Material and methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec459954" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres436718" "titulo" => "Resumen" "secciones" => array:5 [ 0 => array:1 [ "identificador" => "abst0030" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivo" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Material y métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec459955" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Material and Methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:3 [ "identificador" => "sec0025" "titulo" => "Ethical Responsibilities" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0030" "titulo" => "Protection of people and animals" ] 1 => array:2 [ "identificador" => "sec0035" "titulo" => "Data confidentiality" ] 2 => array:2 [ "identificador" => "sec0040" "titulo" => "Right to privacy and informed consent" ] ] ] 9 => array:2 [ "identificador" => "sec0045" "titulo" => "Funding" ] 10 => array:2 [ "identificador" => "sec0050" "titulo" => "Conflict of Interest" ] 11 => array:2 [ "identificador" => "xack131207" "titulo" => "Acknowledgments" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2013-11-08" "fechaAceptado" => "2014-03-14" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec459954" "palabras" => array:4 [ 0 => "Hispanic Americans" 1 => "Systemic lupus erythematosus" 2 => "Anti-müllerian hormone" 3 => "Cyclophosphamide" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec459955" "palabras" => array:4 [ 0 => "Latinoamericanos" 1 => "Lupus eritematoso sistémico" 2 => "Hormona anti-mülleriana" 3 => "Ciclofosfamida" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Systemic lupus erythematosus (SLE) is an inflammatory autoimmune systemic and chronic disease. Fertility in SLE patients is considered normal; factors that have been associated in these patients with ovarian failure are: disease activity, autoantibodies, and the use of cytotoxic agents. The anti-Müllerian hormone (AMH) is a marker that helps to determine the follicular reserve.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">The objective was to determine AMH levels in women of reproductive age with SLE.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and methods</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">We included 65 women with SLE classified according to the 1997 ACR criteria, 18–40-years old. We obtained demographic, clinical, obstetric, and gynecological characteristics as well as serum levels of AMH. We performed a bivariate analysis among patients with low ovarian reserve and those with normal ovarian reserve. We also performed a correlation analysis between activity and damage index and between the cumulative cyclophosphamide dose and AMH levels.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">We found a median of serum AMH in SLE patients of .61<span class="elsevierStyleHsp" style=""></span>ng/ml. The prevalence of low ovarian reserve in our study was 3.07%. We found a median MEX-SLEDAI score of 1 point and the median SLICC score was 2 points. Twenty-five patients (38.4%) had used cyclophosphamide and their cumulative average dose was 7.5<span class="elsevierStyleHsp" style=""></span>g.</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">We found a median of AMH of .61<span class="elsevierStyleHsp" style=""></span>ng/ml in our population. The prevalence of low ovarian reserve in SLE patients was 3.07%. We did not find a correlation between AMH levels, the use of cyclophosphamide, and disease activity.</p></span>" "secciones" => array:5 [ 0 => array:1 [ "identificador" => "abst0005" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Material and methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">El lupus eritematoso sistémico (LES) es una enfermedad autoinmune inflamatoria sistémica crónica; se considera que la fertilidad es normal en pacientes con LES, los factores asociados con una baja reserva folicular que condicionan falla ovárica son: actividad de la enfermedad, anticuerpos antiovario y el uso de agentes citotóxicos. La hormona anti-mülleriana (HAM) es un marcador para determinar la reserva folicular.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Determinar los niveles de HAM en mujeres con LES en edad reproductiva.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y métodos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Incluimos a 65 mujeres, de 18 a 40 años, clasificadas como LES según los criterios ACR 1997. Se obtuvieron las características demográficas, clínicas, ginecoobstétricas y niveles séricos de HAM. Se realizó un análisis bivariado entre las pacientes con baja reserva ovárica y aquellas con reserva ovárica normal. Se realizó un análisis de correlación entre los índices de actividad y daño, así como la dosis acumulada de ciclofosfamida y los niveles de HAM.</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">La mediana del título de HAM fue de 0,61<span class="elsevierStyleHsp" style=""></span>ng/ml. La prevalencia de baja reserva ovárica en nuestro estudio fue del 3,07%. La mediana del MEX-SLEDAI fue de 1 punto y la de SLICC 2 puntos. Veinticinco pacientes (38,4%) habían utilizado ciclofosfamida y la dosis promedio acumulada fue de 7,5<span class="elsevierStyleHsp" style=""></span>g.</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">En nuestra población, se encontró una mediana del título de HAM de 0,61<span class="elsevierStyleHsp" style=""></span>ng/ml, similar a lo reportado anteriormente. La prevalencia de baja reserva ovárica fue del 3,07%. No se encontró correlación entre el uso de ciclofosfamida, la actividad de la enfermedad o los niveles de HAM.</p></span>" "secciones" => array:5 [ 0 => array:1 [ "identificador" => "abst0030" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivo" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Material y métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Velarde-Ochoa MdC, Esquivel-Valerio JA, Vega-Morales D, Skinner-Taylor CM, Galarza-Delgado DÁ, Garza-Elizondo MA. Hormona anti-mülleriana en mujeres en edad reproductiva con lupus eritematoso sistémico. 2015;11:78–82.</p>" ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">CPM: cyclophosphamide; MEX-SLEDAI: Mexican Systemic Erythematosus Disease Activity Index; SLICC: Systemic Lupus International Collaborating Clinics damage index.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variable \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Patient 1 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Patient 2 \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Age at time of study, years</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Duration of illness, years</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Weight (kg)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">62 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">77 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Height (cm)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.60 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.62 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Body mass index (kg</span>/<span class="elsevierStyleItalic">m</span><span class="elsevierStyleSup">2</span>) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">24.21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">29.38 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Smoking</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">Medication</span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Prednisone dose (mg/day) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">60 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hydroxychloroquine, dosage (mg/day) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">400 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">200 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Methotrexate dose (mg/week) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Rituximab, cumulative dose, g \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Cyclophosphamide, cumulative dose, g \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Months elapsed after the 1.° CPM application \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>MEX-SLEDAI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>SLICC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab681853.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Demographic and Clinical Characteristics of Patients With Low Ovarian Reserve.</p>" ] ] 1 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variable \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Patient 1 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Patient 2 \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Age at menarche, years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Menstrual disorders \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Months after the last period \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Number of pregnancies \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Number of births \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Number of cesarean sections \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Number of abortions \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Number of deaths \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Preeclampsia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Eclampsia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab681852.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Gynecological and Obstetric Data of Patients With Low Ovarian Reserve.</p>" ] ] 2 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">ACL: anticardiolipin; AMH: anti-Mullerian hormone.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Test \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Patient 1 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Patient 2 \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Hemoglobin (g/dl)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">11.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">ESR (mm/h)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">Antinuclear antibodies</span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Titer \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1–80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1–320 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Pattern \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Nucleolar \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Homogeneous \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Titer anti-native DNA</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Negative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Negative \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Titer anti-SM (U/ml) (0–10)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8.34 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">C3 (mg%) (50–120)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">135.36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">62.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">C4 (mg%) (20–50)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">19.63 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">15.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Titer ACL IgM (WUP) (0–11)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Titer ACL IgG (UGPL) (0–11)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9.18 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Lupus anticoagulant ‘screening’ (s) (29–51)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">43.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">36.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Lupus anticoagulant confirmatory (s) (21–46)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">37.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Ratio (0.95–1.47)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.19 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Titer AMH (ng/ml)</span> 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 6 | 6 | 12 |
| 2024 October | 61 | 40 | 101 |
| 2024 September | 54 | 21 | 75 |
| 2024 August | 64 | 48 | 112 |
| 2024 July | 92 | 34 | 126 |
| 2024 June | 68 | 31 | 99 |
| 2024 May | 102 | 34 | 136 |
| 2024 April | 70 | 30 | 100 |
| 2024 March | 72 | 33 | 105 |
| 2024 February | 60 | 33 | 93 |
| 2024 January | 61 | 26 | 87 |
| 2023 December | 53 | 25 | 78 |
| 2023 November | 83 | 25 | 108 |
| 2023 October | 79 | 38 | 117 |
| 2023 September | 147 | 45 | 192 |
| 2023 August | 102 | 14 | 116 |
| 2023 July | 52 | 30 | 82 |
| 2023 June | 62 | 24 | 86 |
| 2023 May | 84 | 26 | 110 |
| 2023 April | 50 | 20 | 70 |
| 2023 March | 127 | 19 | 146 |
| 2023 February | 77 | 30 | 107 |
| 2023 January | 77 | 20 | 97 |
| 2022 December | 103 | 29 | 132 |
| 2022 November | 72 | 35 | 107 |
| 2022 October | 120 | 22 | 142 |
| 2022 September | 72 | 29 | 101 |
| 2022 August | 71 | 52 | 123 |
| 2022 July | 57 | 42 | 99 |
| 2022 June | 50 | 30 | 80 |
| 2022 May | 75 | 37 | 112 |
| 2022 April | 108 | 54 | 162 |
| 2022 March | 114 | 46 | 160 |
| 2022 February | 94 | 26 | 120 |
| 2022 January | 78 | 44 | 122 |
| 2021 December | 48 | 45 | 93 |
| 2021 November | 53 | 48 | 101 |
| 2021 October | 66 | 56 | 122 |
| 2021 September | 48 | 55 | 103 |
| 2021 August | 84 | 36 | 120 |
| 2021 July | 66 | 37 | 103 |
| 2021 June | 80 | 41 | 121 |
| 2021 May | 83 | 38 | 121 |
| 2021 April | 232 | 113 | 345 |
| 2021 March | 122 | 115 | 237 |
| 2021 February | 83 | 58 | 141 |
| 2021 January | 84 | 47 | 131 |
| 2020 December | 64 | 26 | 90 |
| 2020 November | 63 | 24 | 87 |
| 2020 October | 42 | 17 | 59 |
| 2020 September | 68 | 32 | 100 |
| 2020 August | 55 | 19 | 74 |
| 2020 July | 53 | 15 | 68 |
| 2020 June | 60 | 25 | 85 |
| 2020 May | 57 | 23 | 80 |
| 2020 April | 45 | 19 | 64 |
| 2020 March | 16 | 10 | 26 |
| 2018 May | 5 | 1 | 6 |
| 2018 April | 43 | 13 | 56 |
| 2018 March | 70 | 12 | 82 |
| 2018 February | 28 | 6 | 34 |
| 2018 January | 36 | 8 | 44 |
| 2017 December | 36 | 12 | 48 |
| 2017 November | 48 | 11 | 59 |
| 2017 October | 33 | 8 | 41 |
| 2017 September | 42 | 8 | 50 |
| 2017 August | 65 | 13 | 78 |
| 2017 July | 64 | 10 | 74 |
| 2017 June | 83 | 15 | 98 |
| 2017 May | 88 | 13 | 101 |
| 2017 April | 79 | 5 | 84 |
| 2017 March | 64 | 14 | 78 |
| 2017 February | 31 | 15 | 46 |
| 2017 January | 30 | 12 | 42 |
| 2016 December | 85 | 21 | 106 |
| 2016 November | 69 | 11 | 80 |
| 2016 October | 82 | 20 | 102 |
| 2016 September | 79 | 14 | 93 |
| 2016 August | 84 | 10 | 94 |
| 2016 July | 47 | 11 | 58 |
| 2015 December | 2 | 0 | 2 |
| 2015 November | 1 | 25 | 26 |
| 2015 October | 1 | 20 | 21 |
| 2015 September | 2 | 0 | 2 |
| 2015 August | 2 | 0 | 2 |
| 2015 July | 22 | 8 | 30 |
| 2015 June | 61 | 16 | 77 |
| 2015 May | 80 | 24 | 104 |
| 2015 April | 82 | 36 | 118 |
| 2015 March | 64 | 24 | 88 |
| 2015 February | 11 | 5 | 16 |
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