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Results of IVF-ICSI cycles in low responder patients: An observational study
Resultados de los ciclos de FIV-ICS en pacientes bajas respondedoras: un estudio observacional
Onica Armijoa, Bárbara Alonso-Luqueb,
Corresponding author
Luque.barbara@gmail.com

Corresponding author.
, Sara Vargasc, Enrique Garcíad, Silvia Iniestaa, Alicia Hernándeza
a La Paz University Hospital, Madrid, Spain
b Infanta Leonor University Hospital, Madrid, Spain
c San Carlos Clinical Hospital, Madrid, Spain
d MINIFIV Clinic, Madrid, Spain
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          "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Graphical representation of the pregnancy&#44; abortion&#44; and live birth rates as a function of AMH &#40;in ng&#47;ml&#41; and the overall rate&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="s0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0065">Introduction</span><p id="p0005" class="elsevierStylePara elsevierViewall">One of the main challenges in the field of reproductive medicine is related to patients known as poor responders to ovarian stimulation&#46; It has been estimated that 9&#8211;24&#37; of patients who go through IVF belong to this category &#40;<a class="elsevierStyleCrossRef" href="#bb0100">Venetis et al&#46;&#44; 2010</a>&#41;&#44; and it is noted as well an increase in this number due to delayed maternity and the search for pregnancy in women of advanced age&#46; The retrieval of a low number of oocytes means one of the limiting factors to improve live birth rates&#46;</p><p id="p0010" class="elsevierStylePara elsevierViewall">The definition of poor responder was standardized for the first time in 2011 by The European Society of Human Reproduction and Embryology &#40;ESHRE&#41; according to Bologna criteria &#40;<a class="elsevierStyleCrossRef" href="#bb0040">Ferraretti et al&#46;&#44; 2011</a>&#41;&#44; so that at least two of the following must be fulfilled&#58; advanced maternal age &#40;&#62;<span class="elsevierStyleHsp" style=""></span>40 years&#41; or any other risk factor of low response &#40;ovarian endometriosis&#44; ovarian surgery&#41;&#44; poor ovarian response in a previous treatment &#40;retrieval of &#8804;3 oocytes with a conventional stimulation protocol&#41; and or abnormal ovarian reserve test results &#40;antral follicle count &#40;AFC&#41; by ultrasound &#60;<span class="elsevierStyleHsp" style=""></span>5 or Antim&#252;llerian hormone &#40;AMH&#41; &#60;<span class="elsevierStyleHsp" style=""></span>0&#46;5&#8211;1&#46;1&#8239;ng&#47;ml&#41;&#46;</p><p id="p0015" class="elsevierStylePara elsevierViewall">However&#44; the use of Bologna criteria results in the selection of heterogeneous groups between different studies&#44; making it difficult to unify clinical recommendations for specialized treatment &#40;<a class="elsevierStyleCrossRef" href="#bb0080">Papathanasiou&#44; 2014</a>&#41;&#46; Thus&#44; in 2016 the POSEIDON group &#40;Patient-Oriented Strategies Encompassing Individualized Oocyte Number&#41; proposed a new definition for low response or low reserve patients&#44; stratifying them into four groups depending on age &#40;&#60;<span class="elsevierStyleHsp" style=""></span>35 or &#8805;<span class="elsevierStyleHsp" style=""></span>35 years&#41;&#44; AFC &#40;&#60;<span class="elsevierStyleHsp" style=""></span>5 or &#8805;<span class="elsevierStyleHsp" style=""></span>5&#41;&#44; or AMH &#40;&#60;<span class="elsevierStyleHsp" style=""></span>1&#46;2&#8239;ng&#47;ml&#41; and the ovarian response&#44; provided that there has been a previous stimulation &#40;<a class="elsevierStyleCrossRef" href="#bb0010">Alviggi et al&#46;&#44; 2016</a>&#41;&#46;</p><p id="p0020" class="elsevierStylePara elsevierViewall">Regarding ovarian reserve markers&#44; serum FSH measurement has traditionally been used&#44; considering levels up to 12&#8239;mUI&#47;ml as a low response predictor &#40;<a class="elsevierStyleCrossRef" href="#bb0030">Broekmans et al&#46;&#44; 2006</a>&#41;&#46; However&#44; serum FSH levels just increase when the ovarian reserve is severely diminished &#40;<a class="elsevierStyleCrossRef" href="#bb0065">La Marca et al&#46;&#44; 2012</a>&#41;&#46; For this reason&#44; antim&#252;llerian hormone and antral follicle count are the most recent markers&#46; AMH is a glycoprotein secreted by granulosa cells of antral and preantral ovarian follicles&#46; AFC is performed by ultrasound&#44; counting the identifiable antral follicles from 2 to 10&#8239;mm in both ovaries&#46; Both markers show a high correlation with ovarian reserve &#40;<a class="elsevierStyleCrossRef" href="#bb0015">Baker et al&#46;&#44; 2018</a>&#59; <a class="elsevierStyleCrossRef" href="#bb0045">Fleming et al&#46;&#44; 2015</a>&#41;&#46; For its part&#44; AMH supposes an advantage due to its low inter-and intra-cycle variability&#44; which turns it into a very useful marker in clinical practice&#46;</p><p id="p0025" class="elsevierStylePara elsevierViewall">According to the evidence previously presented&#44; it seems interesting to determine with the information achieved from new studies the relevance of antim&#252;llerian hormone as an ovarian reserve marker and its role as a predictor of pregnancy&#44; as well as the possible age moderating effect on patients considered as poor responders&#46;</p></span><span id="s0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0070">Objectives</span><p id="p0030" class="elsevierStylePara elsevierViewall">The primary objective of this study is to analyze the pregnancy&#44; live birth&#44; and miscarriage rates of the IVF&#47;ICSI cycles that were carried out between 2017 and 2018 in La Paz University Hospital &#40;HULP&#41; in women with low levels of AMH&#44; compared to patients with normal levels of this hormone&#44; taking into account not only the AMH level but the age of the patient and the number of previous cycles performed&#46;</p><p id="p0035" class="elsevierStylePara elsevierViewall">Secondary objectives&#58; to analyze&#44; according to the AMH&#44; the age of the patients&#44; the indications of assisted reproductive technology &#40;ART&#41; &#40;male sterility&#44; failure of artificial insemination of husband&#39;s semen &#40;IAC&#41;&#44; diagnosis of low ovarian response&#44; tubal factor&#44; endometriosis&#44; repeated abortions&#44; sterility of unknown origin&#41;&#44; the percentage variation of oocytes&#44; the rate of blank punctures&#44; the percentage of immature oocytes obtained&#44; number of embryos generated and vitrified&#44; and their quality&#46;</p></span><span id="s0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0075">Material and methods</span><p id="p0040" class="elsevierStylePara elsevierViewall">We carried out an observational&#44; analytical&#44; and retrospective study with the anonymized data of the patients treated in 2017 and 2018 in the Assisted Reproduction Section of the HULP&#46; Data from 912 cycles were collected&#44; including as such the process of ovarian stimulation&#44; follicular puncture&#44; IVF or ICSI&#44; vitrification of embryos and&#47;or transfers of embryos&#44; as well as the diagnosis of pregnancy or abortion&#46;</p><p id="p0045" class="elsevierStylePara elsevierViewall">We included 631 of the 912 cycles recorded&#44; corresponding to those of the low responding patients and the control group&#46; All patients with AMH greater than or equal to 3&#8239;ng&#47;ml were excluded from the study&#44; because it may imply a high response to ART cycles in this subgroup of patients&#46; Low responders were defined as patients with AMH less than 1&#46;1&#8239;ng&#47;ml&#44; and they were subdivided into two groups&#58; AMH &#60;<span class="elsevierStyleHsp" style=""></span>0&#46;5&#8239;ng&#47;ml and AMH<span class="elsevierStyleHsp" style=""></span>&#62; 0&#46;5&#8239;ng&#47;ml and &#60;<span class="elsevierStyleHsp" style=""></span>1&#44; 1&#8239;ng&#47;ml&#46; The control group is formed with normo-responding patients&#44; whose AMH was set between 1&#46;1 and 3&#8239;ng&#47;ml&#46; Smokers were not excluded&#44; and they were represented both in the study and the control group&#46;</p><p id="p0050" class="elsevierStylePara elsevierViewall">The medical records of the patients were reviewed both at the HULP Clinical Station and the HCIS program&#46; The collected data were age&#44; the cycle of ART in which the patients were&#44; the indication of ART &#40;male sterility&#44; IAC failure&#44; low ovarian response&#44; polycystic ovary syndrome&#44; endometriosis&#44; ovodonation&#44; tubal factor&#44; uterine factor&#44; and abortion repetition&#41;&#44; the levels of AMH&#44; the levels of the beta subunit of human chorionic gonadotropin &#40;&#946;-hCG&#41; with which the presence or not of pregnancy was determined&#44; and the follow-up of pregnancy until delivery or abortion&#46;</p><p id="p0055" class="elsevierStylePara elsevierViewall">For the ovarian stimulation&#44; we used GnRH-antagonists stimulation protocols based on recombinant FSH and both FSH and LH&#46; It was used an in vitro immunological test for the quantitative determination of anti-mullerian hormone &#40;AMH&#41; in human serum and plasma by means of the &#34;ECLIA&#34; electrochemiluminescence immunoassay&#46; Serum AMH &#40;ng&#47;ml&#41; levels were measured by endo-pnt-000012 cobas e&#95;601 system&#46;</p><p id="p0060" class="elsevierStylePara elsevierViewall">Data from the embryology laboratory were collected in the SARAplus software application&#46; We included the number of expected oocytes&#44; based on the folliculometry performed by ultrasound scan&#44; the number of oocytes in metaphase II obtained after a puncture&#44; the percentage variation of oocytes &#40;number of oocytes obtained&#47;number of expected oocytes&#41;&#44; the number of oocytes matures and immature and their percentage&#44; number of blank punctures &#40;without any aspirated oocytes&#41;&#44; number of badly fertilized embryos &#40;3 pronuclei&#41;&#44; number of well-fertilized embryos &#40;2 pronuclei&#41; and their quality &#40;good quality&#44; embryos A and B&#44; poor quality embryos C and D according to the ASEBIR criteria&#41;&#44; and the vitrification rate&#46;</p><p id="p0065" class="elsevierStylePara elsevierViewall">With these data&#44; a statistical study was carried out using the IBM SPSS Statistics 23 program&#46; First of all&#44; the variables were codified&#58; age was divided into three ranges&#58; &#60;<span class="elsevierStyleHsp" style=""></span>35 years&#44; between 35 and 38 years and &#62;<span class="elsevierStyleHsp" style=""></span>38 years&#59; and the AMH in four ranges&#58; &#60;<span class="elsevierStyleHsp" style=""></span>0&#46;5&#8239;ng&#47;ml&#44; between 0&#46;5 and 1&#46;1&#8239;ng&#47;ml&#44; between 1&#46;1 and 3&#8239;ng&#47;ml and &#62;<span class="elsevierStyleHsp" style=""></span>3&#8239;ng&#47;ml&#46; We used the Kolmogorov&#8211;Smirnov test to study the normality of the distributions of the variables&#46;</p><p id="p0070" class="elsevierStylePara elsevierViewall">Quantitative variables were expressed by means &#40;x&#175;&#41; and standard deviation &#40;&#963;&#41;&#44; compared with the Kruskal&#8211;Wallis test&#46; Qualitative variables were described with percentages and were compared with the chi-square test and linear by linear association&#46; Likewise&#44; logistic regression was used to study the objective variables&#46;</p><p id="p0075" class="elsevierStylePara elsevierViewall">Results were considered statistically significant when p&#8239;&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#46;</p></span><span id="s0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0080">Results</span><p id="p0080" class="elsevierStylePara elsevierViewall">Data of the 631 cycles of IVF&#47;ICSI carried out between the years 2017 and 2018 in HULP in patients with AMH &#60;<span class="elsevierStyleHsp" style=""></span>3&#8239;ng&#47;ml have been included&#46; <a class="elsevierStyleCrossRef" href="#t0005">Table 1</a> shows the distribution of patients in each study group according to their age and AMH&#46; AMH mean was 1&#46;44&#8239;ng&#47;ml with a standard deviation of 0&#46;72&#44; a minimum of 0&#44; and a maximum of 2&#46;98&#46;</p><elsevierMultimedia ident="t0005"></elsevierMultimedia><p id="p0085" class="elsevierStylePara elsevierViewall">Patients had a mean age of 35&#46;52 years with a standard deviation of 3&#46;07&#44; a minimum of 24&#44; and a maximum of 41&#59; in the AMH group &#60;<span class="elsevierStyleHsp" style=""></span>0&#46;5&#8239;mg&#47;ml the mean was 36&#46;17 &#43; 2&#46;23 years&#44; in the 0&#46;5 to &#60;<span class="elsevierStyleHsp" style=""></span>1&#46;1&#8239;ng&#47;ml &#40;35&#46;98 &#43; 2&#46;98 years&#41; and in the control &#40;35&#46;18 &#43; 3&#46;20 years&#41;&#46;</p><p id="p0090" class="elsevierStylePara elsevierViewall">When the distribution of patients according to their age is analyzed within each AMH group&#44; we observe differences in the range of women under 35 years old&#46; In the group of AMH &#60;<span class="elsevierStyleHsp" style=""></span>0&#46;5&#8239;ng&#47;ml&#44; the youngest ones represent 21&#37; of the total of patients&#44; 26&#37; in the group of AMH 0&#46;5&#8211;1&#46;1&#8239;ng&#47;ml&#44; and 37&#46;5&#37; in the control group&#46; Patients younger than 35 years have a higher prevalence in the control group&#44; compared to the group with low ovarian reserve &#40;BRO&#41;&#46; This does not happen in other age ranges&#46;</p><p id="p0095" class="elsevierStylePara elsevierViewall">At the time of the study&#44; 53&#46;7&#37; of the patients were in the first treatment cycle&#44; 31&#46;3&#37; in the second&#44; and 15&#37; in the third or more&#46;</p><p id="p0100" class="elsevierStylePara elsevierViewall">Looking at indications for treatment&#44; we found that in 309 patients the indication was due to male factor&#44; 229 low ovarian reserve&#44; 136 failure of IAC&#44; 122 endometriosis&#44; 88 tubal factor&#44; 11 uterine factor&#44; 5 polycystic ovary syndrome&#44; 5 with donation&#44; 4 sterility of unknown origin&#44; and 3 for repeated abortions&#46; When we study these indications according to the level of AMH&#44; a significant relationship was found between failure of IAC and low ovarian response &#40;LOR&#41;&#46; The higher the AMH&#44; the greater the failure in IAC &#40;when AMH &#60;<span class="elsevierStyleHsp" style=""></span>0&#46;5&#58; 6&#46;5&#37;&#44; when AMH 0&#46;5&#8211;1&#46;1&#58; 18&#46;8&#37;&#44; and when AMH 1&#46;1&#8211;3&#58; 26&#46;7&#37;&#41;&#44; with a p &#61; 0&#46;001&#46; The lower the AMH&#44; the greater the indication of treatment due to low response &#40;when AMH &#60;<span class="elsevierStyleHsp" style=""></span>0&#46;5&#58; 74&#46;2&#37;&#44; when AMH 0&#46;5&#8211;1&#46;1&#58; 63&#46;6&#37;&#44; and when AMH 1&#46;1&#8211;3&#58; 22&#44; 2&#37;&#41;&#44; with a p &#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#46;</p><p id="p0105" class="elsevierStylePara elsevierViewall">Regarding the variables related to the embryology laboratory &#40;<a class="elsevierStyleCrossRef" href="#t0010">Table 2</a>&#41;&#44; in the study group&#44; the number of expected and obtained oocytes was significantly lower&#44; with a greater percentage variation&#46; The number of mature oocytes and total embryos was also smaller&#46; The number of good-quality embryos did not reach statistical significance&#46;</p><elsevierMultimedia ident="t0010"></elsevierMultimedia><p id="p0110" class="elsevierStylePara elsevierViewall">On one hand&#44; at lower levels of AMH&#44; there were a higher rate of blank punctures and a lower rate of vitrified embryos &#40;<a class="elsevierStyleCrossRef" href="#t0015">Table 3</a>&#41;&#46; Regarding pregnancy&#44; the overall rate reached 32&#46;5&#37;&#44; with significant differences in favor of the control group when comparing to the AMH<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;5 group&#46; The overall abortion rate was 35&#46;3&#37; and the overall live birth rate was 21&#46;2&#37;&#46; When comparing both variables between the study groups&#44; no significant differences were observed&#44; although there is a tendency of linear rise as the AMH increases for the rate of live birth &#40;<a class="elsevierStyleCrossRef" href="#f0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="t0015"></elsevierMultimedia><elsevierMultimedia ident="f0005"></elsevierMultimedia><p id="p0115" class="elsevierStylePara elsevierViewall">On the other hand&#44; the relationship between age and pregnancy&#44; abortion&#44; and live birth rates were also studied &#40;<a class="elsevierStyleCrossRef" href="#f0010">Fig&#46; 2</a>&#41;&#46; At an older age&#44; the pregnancy rate and live birth decreased significantly &#40;p &#61; 0&#46;007 and p &#61; 0&#46;019&#44; respectively&#41;&#46; However&#44; there were no differences found regarding the abortion rate&#46; Nor did they show significant differences when comparing pregnancy&#44; abortion&#44; and live birth rates according to the number of treatment cycle in which the patients were&#46; The pregnancy rate was 32&#46;3&#37; in the first cycle&#44; 32&#46;8&#37; in the second cycle&#44; and 28&#46;1&#37; in the third cycle or higher &#40;p &#61; 0&#46;71&#41;&#46; The abortion rate was&#58; 33&#46;3&#37; in the first cycle&#44; 41&#37; in the second cycle&#44; and 32&#37; in the third cycle &#40;p &#61; 0&#46;568&#41;&#46; The RNV rate in the first cycle was 20&#46;1&#37;&#44; 19&#46;4&#37; in the second cycle&#44; and 24&#46;7&#37; in the third cycle &#40;p &#61; 0&#46;561&#41;&#46;</p><elsevierMultimedia ident="f0010"></elsevierMultimedia><p id="p0120" class="elsevierStylePara elsevierViewall">A logistic regression analysis was carried out to determine the relationship between the levels of AMH and the pregnancy rate according to age &#40;<a class="elsevierStyleCrossRef" href="#f0015">Fig&#46; 3</a>&#41;&#46; In this scenario&#44; the pregnancy rate in the control group versus the AMH &#60;<span class="elsevierStyleHsp" style=""></span>0&#46;5&#8239;ng&#47;ml group &#40;p &#61; 0&#46;001&#41; remains significantly higher&#44; as shown in <a class="elsevierStyleCrossRef" href="#f0015">Fig&#46; 3</a>&#46; Besides&#44; comparing by age ranges&#44; there are differences between the group &#60;<span class="elsevierStyleHsp" style=""></span>35 years and the group of &#62;<span class="elsevierStyleHsp" style=""></span>38&#44; being the highest pregnancy rate in the youngest &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&#46; Regarding abortion and live birth rates&#44; through logistic regression&#44; combining age and AMH&#44; no statistically significant differences were observed&#46;</p><elsevierMultimedia ident="f0015"></elsevierMultimedia><p id="p0125" class="elsevierStylePara elsevierViewall">Finally&#44; the total number of embryos and the percentual variation of oocytes &#40;VPO&#41;&#44; as described and compared in <a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>&#44; were associated with the presence or not of pregnancy &#40;<a class="elsevierStyleCrossRefs" href="#f0020">Figs&#46; 4 and 5</a>&#41;&#46; There were more pregnancies in those with a higher number of embryos&#44; with higher levels of AMH&#44; as well as in those patients with a lower percentual variation of oocytes &#40;VPO&#41;&#46;</p><elsevierMultimedia ident="f0020"></elsevierMultimedia><elsevierMultimedia ident="f0025"></elsevierMultimedia></span><span id="s0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0085">Discussion</span><p id="p0130" class="elsevierStylePara elsevierViewall">The main objective of this study was to analyze the pregnancy&#44; live birth&#44; and miscarriage rates of the IVF&#47;ICSI in women with low levels of AMH&#46; Our results determine that these patients have a lower pregnancy rate compared to patients with a normal ovarian reserve&#44; a situation that is maintained when we adjust the data according to the age of the patients&#46; In line with these results&#44; different studies have led to similar conclusions &#40;<a class="elsevierStyleCrossRef" href="#bb0020">Bozdag et al&#46;&#44; 2017</a>&#59; <a class="elsevierStyleCrossRef" href="#bb0075">Malchau et al&#46;&#44; 2018</a>&#59; <a class="elsevierStyleCrossRef" href="#bb0110">Yakin et al&#46;&#44; 2018</a>&#41;&#46; However&#44; unlike those studies&#44; it has not been possible to demonstrate the relationship with lower RNV rates in our work &#40;<a class="elsevierStyleCrossRef" href="#bb0005">Alson et al&#46;&#44; 2018</a>&#59; <a class="elsevierStyleCrossRef" href="#bb0025">Brodin et al&#46;&#44; 2013</a>&#41;&#46; There is a linear trend&#44; but it does not reach statistical significance&#44; as can be seen in the description of the results in <a class="elsevierStyleCrossRef" href="#t0015">Table 3</a>&#46;</p><p id="p0135" class="elsevierStylePara elsevierViewall">The reason why patients with low ovarian reserve achieve lower pregnancy rates lies in the poor response they present to pharmacological ovarian stimulation&#46; It has been demonstrated that in women with lower levels of AMH the number of oocytes recovered after a puncture is lower than in women with a normal ovarian reserve&#46; Women with lower levels also present a greater percentual variation than the number of oocytes expected according to the previous follicometry&#46; In these patients&#44; there is a greater proportion of blank punctures&#44; as well as immature oocytes&#46; By achieving a smaller number than available oocytes&#44; the amount of embryos is equally lower in this type of patient&#44; as previous studies pointed out &#40;<a class="elsevierStyleCrossRef" href="#bb0070">La Marca et al&#46;&#44; 2009</a>&#41;&#46; With fewer embryos&#44; the vitrification rate was also lower compared to the group with good ovarian reserve&#46;</p><p id="p0140" class="elsevierStylePara elsevierViewall">If the results achieved are adjusted taking age into account&#44; the pregnancy rate remains lower in the LOR group compared to the control group&#46; However&#44; there are significant differences in favor of younger patients when compared with those older than 38 years&#46; The negative correlation between age and fertility is well known &#40;<a class="elsevierStyleCrossRef" href="#bb0050">Gonz&#225;lez-Foruria et al&#46;&#44; 2016</a>&#59; <a class="elsevierStyleCrossRef" href="#bb0090">Su et al&#46;&#44; 2017</a>&#59; <a class="elsevierStyleCrossRef" href="#bb0095">Sunkara et al&#46;&#44; 2014</a>&#59; <a class="elsevierStyleCrossRef" href="#bb0105">Xu et al&#46;&#44; 2018</a>&#41;&#44; not only because of the decrease in the number of oocytes but also for the quality worsening of them&#46;</p><p id="p0145" class="elsevierStylePara elsevierViewall">Looking at the abortion rate&#44; no significant differences were found between the different study groups&#46; It does not happen the same in other works such as <a class="elsevierStyleCrossRef" href="#bb0060">Haadsma et al&#46; &#40;2010&#41;</a>&#44; where they describe a significantly higher abortion rate in women with low response over 36 years than those of normoresponders&#44; but not in younger patients&#44; once again showing the influence of age on oocyte quality&#46;</p><p id="p0150" class="elsevierStylePara elsevierViewall">It is established that the antim&#252;llerian hormone levels&#44; due to their relationship with the growth of the antral follicles&#44; represent a good marker of low ovarian response &#40;<a class="elsevierStyleCrossRef" href="#bb0035">Capecce et al&#46;&#44; 2016</a>&#41;&#46; For this reason&#44; in this study&#44; we have selected as low responding patients those with lower AMH than 1&#46;1&#8239;ng&#47;dl&#46; However&#44; the FAC and the age of the patients could have been also included as in the Bologna criteria &#40;<a class="elsevierStyleCrossRef" href="#bb0040">Ferraretti et al&#46;&#44; 2011</a>&#41;&#46; However&#44; there were only 33 patients with more than 40 years&#44; due to the public health limit of 40 years to access assisted reproduction treatments&#46;</p><p id="p0155" class="elsevierStylePara elsevierViewall">Although AMH has an important role as a marker for ovarian reserve and therefore pregnancy after an IVF cycle&#44; age is the most important factor when determining the success of assisted reproduction treatment &#40;<a class="elsevierStyleCrossRef" href="#bb0055">Goswami and Nikolaou&#44; 2017</a>&#41;&#46; In our study&#44; within the group of patients with low ovarian reserve&#44; the overall pregnancy rate in those under 35 years was 59&#37;&#44; compared to 31&#37; in those over 38 years&#44; findings that are in line with the conclusions established in other studies &#40;<a class="elsevierStyleCrossRef" href="#bb0085">Sefrioui et al&#46;&#44; 2018</a>&#59; <a class="elsevierStyleCrossRef" href="#bb0115">Yang et al&#46;&#44; 2016</a>&#41;&#46;</p><p id="p0160" class="elsevierStylePara elsevierViewall">Therefore&#44; stratifying the patient with low ovarian reserve according to their age is key when we are trying to predict the success of treatment&#46; It is important to unify the criteria that define patients with low response&#44; to create homogeneous study groups that allow us to establish a more accurate prognosis and use treatment guidelines in a more appropriate way for each patient&#46;</p><p id="p0165" class="elsevierStylePara elsevierViewall">Among the limitations of this study&#44; and even when the findings coincide with the main conclusions of previous studies&#44; it would be interesting to achieve bigger homogeneity between the analysis groups&#46; In our case&#44; there were a total of 223 low responders compared to 408 normoresponders&#46;</p><p id="p0170" class="elsevierStylePara elsevierViewall">Likewise&#44; part of the patients studied had not yet been transferred or was still pregnant&#44; and the rates of pregnancy&#44; abortion&#44; and live birth could therefore vary&#46;</p><p id="p0175" class="elsevierStylePara elsevierViewall">It is also important to notice that&#44; since the variables did not follow normality&#44; we had to use non-parametric tests in statistics and it was not possible to draw the significance value between each group&#44; but only between the three of them as a whole&#46;</p></span><span id="s0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0090">Conclusion</span><p id="p0180" class="elsevierStylePara elsevierViewall">In line with the main objective&#44; the results support that patients with low ovarian reserve&#44; defined by AMH levels less than 1&#46;1&#8239;ng&#47;dl&#44; have a lower pregnancy rate compared to patients with a normal ovarian reserve&#46; Besides&#44; this situation is maintained when we adjust the data according to the age of the patients&#46; There are no differences&#44; however&#44; in abortion and newborn rates&#44; although a tendency has been observed suggesting that the higher the AMH the rate of live birth also increases&#46;</p><p id="p0185" class="elsevierStylePara elsevierViewall">Regarding age&#44; pregnancy&#44; and live birth rates decrease as it increases&#44; not observing these differences in abortion rates&#46; Regarding the ART cycle&#44; no relationship has been found with pregnancy&#44; abortion&#44; and live birth rates&#46; In low responders&#44; the number of expected follicles is lower than in normoresponding patients&#44; a smaller number of oocytes is obtained and the number of embryos generated is equally lower&#44; associating this low number of embryos with a lower pregnancy rate</p><p id="p0190" class="elsevierStylePara elsevierViewall">AMH plays a key role as an ovarian response marker in IVF cycles&#44; especially from a quantitative point of view&#44; although age&#44; due to its involvement in oocyte quality&#44; is also one of the factors that should be taken into account&#46;</p></span><span id="s0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0095">Disclosure statement</span><p id="p0195" class="elsevierStylePara elsevierViewall">No potential conflict of interest was reported by the authors&#46;</p></span><span id="s0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0100">Details of ethics approval</span><p id="p0200" class="elsevierStylePara elsevierViewall">Ethical approval was not required&#46;</p></span><span id="s0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0105">Contribution to authorship</span><p id="p0205" class="elsevierStylePara elsevierViewall">All authors were involved in the study&#46; OA was in charge of the conception and planning of the study&#46; Clinical study data analysis was undertaken by SV&#46; The manuscript was written by BAL&#44; with assistance from EG&#44; SI&#44; and AH&#46; All authors approved the final version of the manuscript&#46;</p></span><span id="s0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0110">Funding</span><p id="p0210" class="elsevierStylePara elsevierViewall">None&#46;</p></span><span id="s0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0115">Conflict of interests</span><p id="p0215" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest&#46;</p></span></span>"
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        "resumen" => "<span id="as0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0010">Objectives</span><p id="sp0055" class="elsevierStyleSimplePara elsevierViewall">To analyze the pregnancy&#44; live birth&#44; and miscarriage rates of the IVF&#47;ICSI cycles in women with low levels of AMH&#44; compared to patients with normal levels of this hormone&#46;</p></span> <span id="as0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0015">Methods</span><p id="sp0060" class="elsevierStyleSimplePara elsevierViewall">We carried out an observational and retrospective study with the data of the patients treated in 2017 and 2018 in the Assisted Reproduction Section of La Paz University Hospital &#40;LPHU&#41;&#44; comparing 223 low responder patients &#40;AMH<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;5&#8239;ng&#47;ml and AMH 0&#46;5&#8211;1&#44;1&#8239;ng&#47;ml&#41; with 408 from the control group of normo-responder patients &#40;AMH 1&#46;1&#8211;3&#8239;ng&#47;ml&#41;&#46; Chi-square and Kruskal&#8211;Wallis tests were used&#46;</p></span> <span id="as0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0020">Results</span><p id="sp0065" class="elsevierStyleSimplePara elsevierViewall">Pregnancy rate was lower in the AMH<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;5 group&#40;14&#46;5&#37;&#41;&#44; compared to the control group &#40;35&#46;5&#37;&#41; &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;014&#41;&#46; No significant differences were observed comparing abortion rate and live birth rate between the study groups&#46; At an older age&#44; the pregnancy rate and live birth rate decreased significantly &#40;p &#61; 0&#46;007 and p &#61; 0&#46;019&#41;&#46; At lower levels of AMH&#44; the number of expected and obtained oocytes&#44; mature oocytes&#44; and total embryos were also smaller&#44; there were a higher rate of blank punctures and a lower rate of vitrified embryos&#46;</p></span> <span id="as0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0025">Conclusion</span><p id="sp0070" class="elsevierStyleSimplePara elsevierViewall">Patients with low ovarian reserve have a lower pregnancy rate compared to patients with a normal ovarian reserve&#46; AMH plays a key role as an ovarian response marker in IVF cycles&#44; although age is one of the factors that should be considered&#46;</p></span>"
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        "resumen" => "<span id="as0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0035">Objetivos</span><p id="sp0075" class="elsevierStyleSimplePara elsevierViewall">Analizar las tasas de embarazo&#44; reci&#233;n nacido vivo y aborto de los ciclos de FIV-ICSI en mujeres con bajos niveles de AMH&#44; comparados con pacientes con niveles normales de dicha hormona&#46;</p></span> <span id="as0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0040">M&#233;todos</span><p id="sp0080" class="elsevierStyleSimplePara elsevierViewall">Se llev&#243; a cabo un estudio observacional retrospectivo con los datos de las pacientes tratadas en el Servicio de Reproducci&#243;n Asistida del Hospital Universitario La Paz &#40;HULP&#41;&#44; comparando 223 pacientes bajas respondedoras &#40;AMH<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;5 ng&#47;ml y AMH 0&#44;5-1&#44;1 ng&#47;ml&#41; con 408 del grupo control de pacientes normo -respondedoras &#40;AMH 1&#44;1-3 ng&#47;ml&#41;&#46; Los an&#225;lisis estad&#237;sticos se realizaron mediante Chi cuadrado y Kurskal-Wallis&#46;</p></span> <span id="as0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0045">Resultados</span><p id="sp0085" class="elsevierStyleSimplePara elsevierViewall">La tasa de embarazo fue menor en el grupo de AMH<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;5 &#40;14&#46;5&#37;&#41;&#44; comparado con el grupo control &#40;35&#46;5&#37;&#41; &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;014&#41;&#46; No se encontraron diferencias significativas cuando se compararon las tasas de aborto y reci&#233;n nacido vivo entre los grupos de estudio&#46; A mayor edad&#44; la tasa de embarazo y reci&#233;n nacido vivo disminuye significativamente &#40;p &#61; 0&#46;007 y p &#61; 0&#46;019&#41;&#46; A menores niveles de AMH&#44; el n&#250;mero de ovocitos esperados y obtenidos&#44; de ovocitos maduros y embriones totales fue tambi&#233;n menor&#44; hubo una tasa mayor de punciones en blanco y menores tasas de embriones vitrificados&#46;</p></span> <span id="as0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0050">Conclusi&#243;n</span><p id="sp0090" class="elsevierStyleSimplePara elsevierViewall">Las pacientes con baja reserve ov&#225;rica presentan menores tasas de embarazo comparadas con pacientes con una reserve ov&#225;rica normal&#46; Los niveles de AMH juegan un papel fundamental como marcador en los ciclos de FIV&#44; si bien la edad&#44; tambi&#233;n es uno de los factores a tener en cuenta&#46;</p></span>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleUnderline">&#62;</span><span class="elsevierStyleHsp" style=""></span>0&#46;5 and &#60;<span class="elsevierStyleHsp" style=""></span>1&#46;1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleUnderline">&#62;</span><span class="elsevierStyleHsp" style=""></span>1&#46;1 and &#60;<span class="elsevierStyleHsp" style=""></span>3 &#40;control&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">153&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
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                  \t\t\t\t">325&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleUnderline">&#62;</span><span class="elsevierStyleHsp" style=""></span>0&#46;5 and &#60;<span class="elsevierStyleHsp" style=""></span>1&#46;1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleUnderline">&#62;</span><span class="elsevierStyleHsp" style=""></span>1&#46;1 and &#60;<span class="elsevierStyleHsp" style=""></span>3 &#40;control&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">5&#46;66<span class="elsevierStyleUnderline"><span class="elsevierStyleHsp" style=""></span>&#43;</span><span class="elsevierStyleHsp" style=""></span>2&#46;57&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;45<span class="elsevierStyleUnderline"><span class="elsevierStyleHsp" style=""></span>&#43;</span><span class="elsevierStyleHsp" style=""></span>4&#46;04&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">3&#46;17<span class="elsevierStyleUnderline"><span class="elsevierStyleHsp" style=""></span>&#43;</span><span class="elsevierStyleHsp" style=""></span>2&#46;60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">4&#46;67<span class="elsevierStyleUnderline"><span class="elsevierStyleHsp" style=""></span>&#43;</span><span class="elsevierStyleHsp" style=""></span>3&#46;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;84<span class="elsevierStyleUnderline"><span class="elsevierStyleHsp" style=""></span>&#43;</span><span class="elsevierStyleHsp" style=""></span>3&#46;86&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">oocyte &#37; variation&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">48&#46;79<span class="elsevierStyleUnderline"><span class="elsevierStyleHsp" style=""></span>&#43;</span><span class="elsevierStyleHsp" style=""></span>33&#46;44&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">41&#46;32<span class="elsevierStyleUnderline"><span class="elsevierStyleHsp" style=""></span>&#43;</span><span class="elsevierStyleHsp" style=""></span>29&#46;61&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34&#46;17<span class="elsevierStyleUnderline"><span class="elsevierStyleHsp" style=""></span>&#43;</span><span class="elsevierStyleHsp" style=""></span>25&#46;89&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">0&#46;004&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">n mature oocytes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">2&#46;71<span class="elsevierStyleUnderline"><span class="elsevierStyleHsp" style=""></span>&#43;</span><span class="elsevierStyleHsp" style=""></span>2&#46;50&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3&#46;99<span class="elsevierStyleUnderline"><span class="elsevierStyleHsp" style=""></span>&#43;</span><span class="elsevierStyleHsp" style=""></span>2&#46;38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">5&#46;79<span class="elsevierStyleUnderline"><span class="elsevierStyleHsp" style=""></span>&#43;</span><span class="elsevierStyleHsp" style=""></span>3&#46;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">n immature oocytes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">543&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;68<span class="elsevierStyleUnderline"><span class="elsevierStyleHsp" style=""></span>&#43;</span><span class="elsevierStyleHsp" style=""></span>1&#46;44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">1&#46;05<span class="elsevierStyleUnderline"><span class="elsevierStyleHsp" style=""></span>&#43;</span><span class="elsevierStyleHsp" style=""></span>1&#46;55&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#37; immature oocytes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">17&#46;22<span class="elsevierStyleUnderline"><span class="elsevierStyleHsp" style=""></span>&#43;</span><span class="elsevierStyleHsp" style=""></span>30&#46;73&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#46;87<span class="elsevierStyleUnderline"><span class="elsevierStyleHsp" style=""></span>&#43;</span><span class="elsevierStyleHsp" style=""></span>19&#46;91&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#46;79<span class="elsevierStyleUnderline"><span class="elsevierStyleHsp" style=""></span>&#43;</span><span class="elsevierStyleHsp" style=""></span>21&#46;38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;017&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">n total embryos&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2056&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">2&#46;96<span class="elsevierStyleUnderline"><span class="elsevierStyleHsp" style=""></span>&#43;</span><span class="elsevierStyleHsp" style=""></span>1&#46;93&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">4&#46;39<span class="elsevierStyleUnderline"><span class="elsevierStyleHsp" style=""></span>&#43;</span><span class="elsevierStyleHsp" style=""></span>2&#46;86&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">n good quality embryos&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">0&#46;77<span class="elsevierStyleUnderline"><span class="elsevierStyleHsp" style=""></span>&#43;</span><span class="elsevierStyleHsp" style=""></span>0&#46;98&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">1&#46;10<span class="elsevierStyleUnderline"><span class="elsevierStyleHsp" style=""></span>&#43;</span><span class="elsevierStyleHsp" style=""></span>1&#46;30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">1&#46;28<span class="elsevierStyleUnderline"><span class="elsevierStyleHsp" style=""></span>&#43;</span><span class="elsevierStyleHsp" style=""></span>1&#46;55&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;079&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">n poor quality embryos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">1381&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">1&#46;21<span class="elsevierStyleUnderline"><span class="elsevierStyleHsp" style=""></span>&#43;</span><span class="elsevierStyleHsp" style=""></span>1&#46;30&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">1&#46;65<span class="elsevierStyleUnderline"><span class="elsevierStyleHsp" style=""></span>&#43;</span><span class="elsevierStyleHsp" style=""></span>1&#46;51&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">2&#46;87<span class="elsevierStyleUnderline"><span class="elsevierStyleHsp" style=""></span>&#43;</span><span class="elsevierStyleHsp" style=""></span>2&#46;50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#37; poor quality embryos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">62&#46;51<span class="elsevierStyleUnderline"><span class="elsevierStyleHsp" style=""></span>&#43;</span><span class="elsevierStyleHsp" style=""></span>36&#46;76&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">63&#46;23<span class="elsevierStyleUnderline"><span class="elsevierStyleHsp" style=""></span>&#43;</span><span class="elsevierStyleHsp" style=""></span>35&#46;84&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">67&#46;77<span class="elsevierStyleUnderline"><span class="elsevierStyleHsp" style=""></span>&#43;</span><span class="elsevierStyleHsp" style=""></span>33&#46;50&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">0&#46;454&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleUnderline">&#62;</span><span class="elsevierStyleHsp" style=""></span>0&#46;5 and &#60;<span class="elsevierStyleHsp" style=""></span>1&#46;1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleUnderline">&#62;</span><span class="elsevierStyleHsp" style=""></span>1&#46;1 and &#60;<span class="elsevierStyleHsp" style=""></span>3 &#40;control&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p-value&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">53&#46;3&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
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                  \t\t\t\t">Blank punctures rate&nbsp;\t\t\t\t\t\t\n
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ISSN: 23409320
Original language: English
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es en pt

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