How Can We Predict Success in Poor Responders?

Objectives: The aim of this study was to evaluate how can we predict success in poor responder patients in terms of pregnancy rate and live birth rate. Material and method: This study is a review of the newest papers that have in the center the poor responders undergoing treatment involving assisted reproductive techniques (ART). Outcomes: The results show that the most reliable factors when counseling a poor responder patient are age and Anti-Müllerian hormone (AMH) level. Conclusions: The most important factors that influence pregnancy rate are age and ovarian reserve, but other factors such as male pathology and laboratory techniques must be studied deeper.

ANGI-1 Impact of neoadjuvant bevacizumab on transcriptional factor for stemness, macrophage polarization, and oxygenation of tumor microenvironment in glioblastoma

Background: Previously we reported that bevacizumab (Bev) produces tumor oxygenation with immunosupportive tumor microenvironment (TME) and inhibition of stemness. To confirm whether those effects might contribute prolongation of clinical outcome, in the present study paired samples from same patients with newly diagnosed GBM who received Bev during its effectiveness and refractoriness were investigated by immunohistochemistry. Methods: Eighteen samples from 9 patients with newly diagnosed GBM who received preoperative neoadjuvant Bev (neoBev) followed by surgical operation and chemoradiotherapy in addition to salvage surgery after recurrence were investigated. Expressions of FOXM1, HIF-1, and CD163 were evaluated by immunohistochemistry. Overall survial (OS) were analyzed with the present cohort divided into two groups between good and poor responder (GR and PR, respectively) of Bev defined as tumor regression rate judged by T1 gadolinium enhancement (T1Gd) and fluid attenuated inversion recovery (FLAIR) images. Results: In the group of good responder of T1Gd (T1Gd-GR; defined as >38% of regression rate after neoBev), OS was prolonged compared with T1Gd-PR along with inhibition of FOXM1 expression and HIF-1a. In contrast, in the group of good responder of FLAIR (FLAIR-GR; defined as >54% of regression rate after neoBev), there were no significant differences of OS and FOXM1 expression between GR and PR. HIF-1a expression tended to be elevated in T1Gd-PR of initial tumors, T1Gd-GR of recurrent tumors, and FLAIR-PR of both initial and recurrent tumors.Conclusion: T1Gd-GR after neoBev might attribute to inhibition of FOXM1 and oxygenation. Bev might provide tumor oxygenation, leading to inhibition of stemness and M2 TAM infiltration during its effectiveness. These results suggested that Bev combined with immunotherapy for newly diagnosed GBM might provide clinical benefits including inhibition of stemness and induction of immunosupportive TME, when tumor volume assessed by T1 Gd. was significantly decreased following neoBev.

Applying organisational behaviour theory to aid emergency staff retention

The purpose of this theoretical concept article is to spark a dialogue on the use of organisational behaviour theory to address emergency responder retention. In the United States, emergency medical services (EMS) appear to be burdened with continuing problems of retaining staff. Poor responder retention affects the ability of EMS to deliver high-quality services; without trained, educated and experienced first responders, the EMS system struggles, and what suffers is the ability to provide medical care. The authors set out to construct a pathway for addressing the underlying issues leading to the exodus of professionals using organisational behaviour theory. To develop the idea, an inductive logic approach was used to address underlying negative factors influencing poor retention and discuss the promise of organisational behaviour theory in improving the retention of responders.

Recombinant luteinizing hormone supplementation in assisted reproductive technology: a review of literature

Background Luteinizing hormone (LH) has the main role in ovarian function in both natural and artificial cycles. A normal LH concentration during controlled ovarian hyperstimulation is positively correlated to the number and quality of retrieved oocytes and resulting embryos. Main body of the abstract In this study, we reviewed whether rLH administration, adjunct to the ovarian stimulation regimen, could improve clinical outcomes. The literature review showed that rLH supplementation improves assisted reproductive technology (ART) outcomes among women with hypogonadotropic hypogonadism, and hyporesponsive women to follicle-stimulating hormone monotherapy. Besides, rLH supplementation has advantages for poor responder women 36–39 years of age. Even though the data suggested no priority regarding the LH source for improving ART outcome, women with different LH polymorphisms who did not respond similarly to ovarian stimulation may benefit from adjuvant rLH therapy. Conclusion rLH usage for improving ART outcome should be scrutinized via well-designed studies considering the subgroups of infertile women who benefit the most from rLH adjuvant therapy, the type of ovarian stimulation protocol to which rLH would be added, and also the exact dosage, as well as the proper timing (during or prior to a cycle).

The Effect of Growth Hormone on In Vitro Fertilization Outcomes During Ovarian Stimulation: A Matched Cohort Study

Background. While growth hormone (GH) is commonly used as an adjuvant treatment to controlled ovarian stimulation (COS) for in vitro fertilization (IVF) cycles, the data regarding its efficacy is inconsistent. Design. A retrospective matched cohort study of poor responder patients who underwent COS without the use of GH (COS-GH) subsequently followed by COS cycles that included adjuvant GH (COS+GH) treatment. Materials and Methods. A list of all patients having filled a prescription for GH from January 2018 – March 2020 was obtained. GH was administered daily at 3mg (9IU) starting on the first day of stimulation and ending on the day of trigger. Only women who had documentation of a previous cycle without the use of GH were included in the study. Results. 182 cycles (91 patients) were included in the study, and COS-GH cycles were compared to COS+GH cycles. The total dose of gonadotropins used (5757 vs 4252 mIU, p=0.002), duration of stimulation (10.4 vs 10.1 days, p=-.045), maximum Estradiol (E2) (2411 vs 1932 pg/ml, p=0.010), endometrial thickness (11.2 vs 10.6 mm, p=0.010), number of oocytes retrieved (14.2 vs 11.8, p=0.001), number of mature oocytes (11.1 vs 9.7, p=0.028), number of blastocysts (3.98 vs 2.56, p=<0.001) and number of usable blastocysts (2.5 vs 1.6, p=<0.001) were all significantly greater in the GH group. Conclusions. Adding GH to the COS protocol in poor responder patients may lead to improvements in the number of oocytes retrieved, number of mature oocytes, endometrial thickness, number of blastocysts, the number of usable blastocysts.

Analysis of treatment response about low-dose (0.01%) atropine eye-drops in myopic children

Introduction: Myopia usually commences during primary school and progresses until the mean age of 16 years. Topical low-dose (0.01%) atropine eye-drop appears to be safe and efficacious for myopia control in children. However, in some cases, a higher concentration of atropine is required in some cases because low-dose atropine treatment is not effective. Methods: This is a retrospective study among young myopic children between 5 and 15 years with myopia progression > 0.50 D/year. We selected patients treated with low-dose atropine (0.01%) eye-drops for 12 months and conducted a comparative analysis of the group with good responder and poor responder. Patients were classified as good responders if spherical equivalent refractive error (SE) progression was ⩽ 0.50 D after 12 months of treatment and poor responders if SE progression > 0.50 D. The prognostic factors before and after treatment were analyzed in two groups. Results: A total of 68 eyes were included. Low-dose (0.01%) atropine eye-drops have a good treatment response in 54% of patients. In the good responder group ( n = 37), the mean rate of myopia progression after 12 months of treatment (0.36 ± 0.17 D) was significantly slower compared with the baseline progression ( p < 0.001). Good responders have smaller changes in axial length (AL) elongation and SE than poor responders ( p < 0.001). The only adverse event was temporary near vision difficulty (10%), photophobia (10%), and mild pupil dilation (30%). Discussion: The AL elongation is an important indicator for monitoring the treatment response. Children with a family history of myopia at a young age may not respond well to low-dose (0.01%) atropine eye-drops. In these cases, increasing the concentration of atropine eye-drops should be considered.

P–714 Insulin-like growth factor-I as a mediator of the effect of transdermal testosterone in poor responder patients

Study question Is insulin-like growth factor-I (IGF-I) a mediator of the effect of transdermal testosterone (TT) in poor responder (PR) patients? Summary answer IGF-I might be a mediator of the effect of TT in PR patients who undergo an IVF cycle What is known already Many strategies have been tried to improve the results in PR patients. Androgen supplementation with TT is the only that has significantly increased live birth rate in these patients. The mechanism by which TT might influence on the better results remains unclear but it is likely mediated or facilitated by IGF-I. Testosterone increases the number of primordial follicles, increase IGF-I by threefold and increase IGF-I receptor mRNA by fivehold in primordial follicles in primates. Some studies have suggested that IGF-I could be a parameter that reflects the endocrinological environment of mature follicles, which is correlated with oocyte and embryonic quality Study design, size, duration This prospective cohort study of 93 women PR according Bologna criteria treated with TT and IVF/ICSI was conducted between May 2015 and December 2016 Participants/materials, setting, methods Exogenous andogenization with TT for 5 days prior to ovarian stimulation was carried out. Hormonal parameters were evaluated: basal FSH, LH and Estradiol, AMH, IGF–1 pre and post TT. Ultrasound parameterswere also analysed: antral follicle count (AFC) and number of pre-ovulatory follicles the day of HCGr. We compared these parameters according to the ovarian response: adequate (&gt; 4 oocytes) or insufficient (&lt;3 oocytes), as well as the pregnancy was achieved or not. Main results and the role of chance Baseline characteristics of the patients were: 36.9 years, FSH 11.8, AMH 0.86 and RFA 5.3. In 83% of the patients the oocyte retrieval was carried out, obtaining an average of 3.8 MII oocytes and 2.9 embryos of 2pn with a clinical pregnancy rate per transfer of 33.3%. The FORT Test (AFC/pre-ovulatory follicles x100) was 70%, higher than that observed in other studies with patients with PR without TT (55%). In cases in which an insufficient response was obtained (&lt;3 oocytes) or the cycle was canceled, a higher age and FSH and lower AMH were observed (p &lt; 0.05). There were no differences in the rest of the parameters. Evaluating the hormonal and ultrasound parameters depending on whether or not pregnancy was achieved, a significant increase in IGF1 pre and post-TT was observed in the cases of pregnancy (31.5%) compared to those cases where there was no pregnancy (10.9%) (p = 0’01). There were no differences in the rest of the parameters. A significant correlation was found between AMH, AFC and increase in IGF-I levels (p &lt; 0’05). Limitations, reasons for caution This a prospective cohort study with limited number of patients included. Wider implications of the findings: The significant increase in serum levels of IGF–1 in pregnant patients would indicate the existence of a more favorable clinical setting for the administration of testosterone, probably related to a more favorable ovarian reserve as demonstrated by its correlation with serum levels of AMH and with the AF. Trial registration number Not applicable