Definition Of Poor Response Research Articles

Inadequate Classification of Poor Response After Total Knee Arthroplasty: A Comparative Analysis of 15 Definitions Using Data From the Dutch Arthroplasty Register and the Osteoarthritis Initiative Database

BackgroundVariations in defining poor response to total knee arthroplasty (TKA) impede comparisons of response after TKA over time and across hospitals. This study aimed to compare the prevalence, overlap, and discriminative accuracy of 15 definitions of poor response after TKA using 2 databases. MethodsData of patients one year after primary TKA from the Dutch Arthroplasty Register (n = 12,275) and the Osteoarthritis Initiative database (n = 204) were used to examine the prevalence, overlap (estimated by Cohen’s kappa), and discriminative accuracy (sensitivity, specificity, positive predictive value, negative predictive value, and Youden index) of 15 different definitions of poor response after TKA. In the absence of a gold standard for measuring poor response to TKA, the numeric rating scale satisfaction (≤ 6 ‘poor responder’) and the global assessment of knee impact (dichotomized: ≥ 4 ‘poor responder’) were used as anchors for assessing discriminative accuracy for the Dutch Arthroplasty Register and Osteoarthritis Initiative dataset, respectively. These anchors were chosen based on a prior qualitative study that identified (dis)satisfaction as a central theme of poor responses to TKA by patients and knee specialists. ResultsThe median (25th to 75th percentile) prevalence of poor responders in the examined definitions was 18.5% (14.0 to 25.5%), and the median Cohen’s kappa for the overlap between pairs of definitions was 0.41 (0.32 to 0.59). Median (25th to 75th percentile) sensitivity was 0.45 (0.39 to 0.54), specificity was 0.86 (0.82 to 0.94), positive predictive value was 0.45 (0.34 to 0.62), negative predictive value was 0.89 (0.87 to 0.89), and the Youden index was 0.36 (0.20 to 0.43). ConclusionsThis study found a lack of overlap between different definitions of poor response to TKA. None of the examined definitions adequately classified poor responders to TKA. In contrast, the absence of a poor response could be classified with confidence.

Definitions of poor outcome after total knee arthroplasty: an inventory review

BackgroundA significant proportion of patients experiences poor response (i.e. no or little improvement) after total knee arthroplasty (TKA) because of osteoarthritis. It is difficult to quantify the proportion of patients who experiences poor response to TKA, as different definitions of, and perspectives (clinician’s and patient’s) on poor response are being used. The aim of this study was therefore to review the literature and summarize definitions of poor response to TKA.MethodsA systematic search was performed to identify and review studies that included dichotomous definitions of poor outcome after primary TKA. The type, amount and combination of domains (e.g. functioning), outcome measures, type of thresholds (absolute/relative, change/cut-off), values and moments of follow-up used in definitions were summarized.ResultsA total of 47 different dichotomous definitions of poor response to TKA were extracted from 2163 initially identified studies. Thirty-six definitions incorporated one domain, seven definitions comprised two domains and four definitions comprised three domains. Eight different domains were used in identified definitions: pain, function, physical functioning, quality of life (QoL), patient satisfaction, anxiety, depression and patient global assessment. The absolute cut-off value was the most common type of threshold, with large variety in value and timing of follow-up.ConclusionsOur inventory review shows that definitions of poor response to TKA are heterogeneous. Our findings stresses the need for an unambiguous definition of poor response to draw conclusions about the prevalence of poor-responders to TKA across hospitals and countries, and to identify patients at risk.

Serum anti-Müllerian hormone and basal serum FSH as predictors of poor ovarian response in assisted conception cycles

The aim of the study was to correlate serum AMH and serum FSH levels with ovarian response to stimulation in IVF–ICSI cycles. This was a prospective observational study conducted in a private assisted conception unit. One hundred and two patients were selected on their first IVF cycle. Basal serum FSH and serum AMH were measured one month before the stimulation cycle. A fixed dose GnRH antagonist protocol was used in all cycles transferring a maximum of three day-3 cleavage stage embryos. We defined poor ovarian response as retrieval of fewer than four mature oocytes in cycles requiring ⩾ 3000 IU of gonadotropins for stimulation or cycle cancellation due to poor response. The correlation between different parameters was expressed as a Spearman’s correlation coefficient. The clinical value of AMH and FSH as predictors of poor ovarian response as well as predictors of pregnancy was evaluated by constructing relevant receiver operator characteristics curves (ROC curves). Of these 102 cycles, 28 fitted our definition of poor response while the remaining 74 cycles all produced an adequate response to stimulation. There was a statistically significant difference between the adequate responders group and poor responders group regarding their mean age (31.5 versus 39.6, p < 0.001), the mean value of AMH (2.84 ng/ml versus 0.9 ng/ml, p < 0.0001) as well as the mean value of basal FSH (7.6 IU/ml versus 9.7 IU/ml, p < 0.0001). Serum AMH level had a positive correlation while serum FSH had a negative correlation with the number of oocytes collected while only serum AMH had a significant positive correlation with the occurrence of pregnancy. ROC curve analysis of our results showed that serum AMH with an optimal cut-off value of 1.2 ng/ml is a reliable predictor of poor ovarian response with an area under the ROC curve of 90.4%. Serum basal FSH with an optimal cut-off value of 8.9 IU/ml was of lower value than AMH as a predictor of poor ovarian response with an area under the ROC curve of 81.9%. However, neither serum AMH nor basal serum FSH was found to able to reliably predict the occurrence of pregnancy with an area under the ROC curve of 59.4% and 58.6% respectively. Our results show that serum AMH level is more reliable than basal serum FSH as a predictor of poor ovarian response to stimulation with a cut-off value of 1.2 ng/ml shown to predict poor ovarian response with a sensitivity of 91.7%.

Identification and management of poor response to growth‐promoting therapy in children with short stature

Growth hormone (GH) is widely prescribed for children with short stature across a range of growth disorders. Recombinant human (rh) insulin-like growth factor-1 (rhIGF-1) therapy is approved for severe primary IGF-I deficiency - a state of severe GH resistance. Evidence is increasing for an unacceptably high rate of poor or unsatisfactory response to growth-promoting therapy (i.e. not leading to significant catch up growth) in terms of change in height standard deviation score (SDS) and height velocity (HV) in many approved indications. Consequently, there is a need to define poor response and to prevent or correct it by optimizing treatment regimens within accepted guidelines. Recognition of a poor response is an indication for action by the treating physician, either to modify the therapy or to review the primary diagnosis leading either to discontinuation or change of therapy. This review discusses the optimal investigation of the child who is a candidate for GH or IGF-1 therapy so that a diagnosis-based choice of therapy and dosage can be made. The relevant parameters in the evaluation of growth response are described together with the definitions of poor response. Prevention of poor response is addressed by discussion of strategy for first-year management with GH and IGF-1. Adherence to therapy is reviewed as is the recommended action following the identification of the poorly responding patient. The awareness, recognition and management of poor response to growth-promoting therapy will lead to better patient care, greater cost-effectiveness and increased opportunities for clinical benefit.

Poor responders: still a problem

The response to ovarian stimulation is the key determinant of ART success, but there are many definitions of poor response and many proposed solutions. The response to ovarian stimulation is the key determinant of ART success, but there are many definitions of poor response and many proposed solutions. The response to ovarian stimulation is a key and major determinant of the outcome of treatment with assisted reproductive technique. Age, antral follicle count, and anti-müllerian hormone level seem to be the best indicators to predict the number (but not the quality) of the oocytes that will be collected. This suggests that most cases of inadequate response to ovarian stimulation can be predicted by a careful appreciation of ovarian reserve. Certainly, there are many unexpected instances of poor ovarian response in young women. In all such cases, we must control the ovarian reserve to make sure that medications have been well administered with respect to weight and other medical history that could interfere with ovarian stimulation. One can decide to modify the protocol, perhaps after assessing polymorphisms in the genes of gonadotropin receptors. Even in “predictable” poor ovarian response, the definition of poor response is a huge problem, leading to difficulties interpreting the results of research protocols. As Paul Devroey will show in a contribution here, there are more than 40 definitions of poor response. The recently published criteria proposed by the Bologna ESHRE meeting are not absent of criticism especially because we do not know the various mechanisms of diminishing oocyte quantity, which can have different impacts on oocyte quality and may not be sufficient to improve the outcomes of various treatments. Findings from very few randomized controlled trials apply to a clearly defined group of patients. What kind of treatment can we propose in this situation? Many controversial propositions can be considered, such as increasing the dose of gonadotropins, prolonged administration of gonadotropins, the use of flare-up and micro flare-up, adjunct use of LH, homogenization of the cohort by E2 in a previous luteal phase, delayed administration of LH, or also to change agonist into antagonist blockage for LH surge. Several authors have proposed different adjuvants like l-arginine, dexamethasone, colony-stimulating factor–1, pyridostigmine, aspirin, or other biological techniques. Three approaches presented in the following commentaries are more likely to be used and of particular interest:1.Kadoch comments on the natural cycle, mainly with the following question: What is the point of trying to stimulate so hard to end up collecting a maximum of two embryos when repeated natural cycles can be realized?2.Growth hormone cotreatment in case of poor COS response has been proposed. De Ziegler and colleagues identified 139 publications over the past 5 years and 3 recent meta-analyses, and they comment on the potential effect on oocyte quality even when GH supplements did not increase the quantity of oocytes retrieved.3.The third proposition that will be analyzed by Fanchin is the use of androgenic supplementation. Based on the excess of small antral follicle number in androgenic diseases such as polycystic ovary syndrome, and the observation of artificial polycystic ovary syndrome in induced transsexual women who want to virilize themselves, different androgenic supplementation by different routes and models have been proposed. Another approach discussed is the use of a small amount of LH to increase the size, number, and perhaps the quality of retrieved oocytes. Certainly, after these interesting contributions, physicians will have the conviction that further trials are urgently needed to define subgroups of poor prognosis with assisted reproductive technique and predict poor response in younger patients. Only this classification will enable us to compare results adequately.

ESHRE consensus on the definition of 'poor response' to ovarian stimulation for in vitro fertilization: the Bologna criteria

The definition presented here represents the first realistic attempt by the scientific community to standardize the definition of poor ovarian response (POR) in a simple and reproducible manner. POR to ovarian stimulation usually indicates a reduction in follicular response, resulting in a reduced number of retrieved oocytes. It has been recognized that, in order to define the poor response in IVF, at least two of the following three features must be present: (i) advanced maternal age or any other risk factor for POR; (ii) a previous POR; and (iii) an abnormal ovarian reserve test (ORT). Two episodes of POR after maximal stimulation are sufficient to define a patient as poor responder in the absence of advanced maternal age or abnormal ORT. By definition, the term POR refers to the ovarian response, and therefore, one stimulated cycle is considered essential for the diagnosis of POR. However, patients of advanced age with an abnormal ORT may be classified as poor responders since both advanced age and an abnormal ORT may indicate reduced ovarian reserve and act as a surrogate of ovarian stimulation cycle outcome. In this case, the patients should be more properly defined as 'expected poor responder'. If this definition of POR is uniformly adapted as the 'minimal' criteria needed to select patients for future clinical trials, more homogeneous populations will be tested for any new protocols. Finally, by reducing bias caused by spurious POR definitions, it will be possible to compare results and to draw reliable conclusions.

Decreased fertility in poor responder women is not related to oocyte morphological status

IntroductionIn women showing impaired fertility, a decreased response to ovarian stimulation is a major problem, limiting the number of oocytes to be used for assisted reproduction techniques (ART). Despite the several definitions of poor response, it is still a matter of debate whether young poor responder patients also show a decrease in oocyte quality. The objective in this study was to investigate whether poor ovarian response to the superstimulation protocol is accompanied by impaired oocyte quality.Material and methodsThis study included 313 patients younger than 35 years old, undergoing intracytoplasmic sperm injection. Patients with four or fewer MII oocytes (poor-responder group, PR, n = 57) were age-matched with normoresponder patients (NR, n = 256).ResultsA higher rate of oocyte retrieval and a trend towards an increase in MII oocyte rate were observed in the NR group when compared to the PR group (71.6 ±1.1% and 74.1 ±1.0% vs. 56.3 ±2.9% and 66.5 ±3.7%; p< 0.0001 and p = 0.056, respectively). A trend toward increased implantation rates was observed in the NR group when compared to the PR group (44 and 24.5 ±2.0% vs. 28.8 and 16.4 ±3.9%; p= 0.0305 and p= 0.0651, respectively).ConclusionsLow response to ovarian stimulation is apparently not related to impaired oocyte quality. However, embryos produced from poor responder oocytes show impaired capacity to implant and to carry a pregnancy to term.