Bispecific immunotherapy MEDI5752 or volrustomig and cervical cancer.

MEDI5752 is a monovalent bispecific immunotherapy and is strategically unique as it combines both anti programmed cell death 1 and anti cytotoxic T-lymphocyte-associated protein 4 action. This is one of the first of this kind of molecule. The development of this molecule had been very interesting which is not usually described in regular clinical oncology journals thus losing an important piece of history of an upcoming subject. Only some phase I results in such development is published so far and no full report on this is available till now. This effort will try to record the facts and chain of events which actually occurred in inventing and bringing it in phase III trial.

Comparison of luteal phase stimulation with follicular phase stimulation in poor ovarian response: a single-blinded randomized controlled trial.

BACKGROUND: In the last decade, luteal-phase ovarian stimulation (LPOS) has been suggested as an alternative controlled ovarian stimulation (COS) protocol for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles mainly in women with a history of poor ovarian response (POR). The present randomized controlled trial study aimed to compare the outcomes of follicular phase ovarian stimulation (FPOS) and LPOS protocols in POR cases undergoing ICSI cycles. METHODS: Seventy-eight POR patients who met the Bologna criteria and underwent an ICSI cycle were included. In this study, 39 POR cases were allocated to the FPOS group, and 39 POR cases were allocated to the LPOS group. The primary outcome was the number of metaphase II (MII) oocytes. In addition, the total number of oocytes, number of top-quality day 3 embryo, day 3 embryo development rate, chemical pregnancy and clinical pregnancy rates were defined as secondary outcomes. RESULTS: The obtained results demonstrated that the number of MII oocytes significantly increased in the LPOS group compared to the FPOS group (P = 0.007). However, there was no significant difference between the two groups regarding the number of GV and MI oocytes, number of top-quality day 3 embryos and day 3 embryo development rate among both categories of patients. Also, the number of total and MII oocytes was significantly higher in the LPOS group (P = 0.016). CONCLUSION: These results suggest that LPOS protocol effectively increases the number of mature oocytes in women with a history of POR. TRIAL REGISTRATION: IRCT20210405050852N1 (Registered at Iranian registry of clinical trials; available at https://en.irct.ir/trial/55402 ).

Factors influencing poor response to type 2 targeted therapies in severe asthma: a retrospective cohort study.

BACKGROUND: A significant breakthrough has been made in treating severe asthma, with the recognition of various asthma phenotypes and an updated management guideline. Type 2 targeted therapies, such as benralizumab and omalizumab; have been identified as an effective treatment for severe asthma, improving patient response, lung function tests and asthma symptom control. This study aimed to evaluate factors contributing to poor response to therapy. METHODS: A retrospective single-center cohort study of 162 patients with severe asthma who started biologic therapy; their data were retrieved from medical records for further analysis. Poor responders were patients remained clinically and functionally uncontrolled despite even after augmenting all treatment options. RESULTS: Childhood-onset asthma, bronchiectasis, poor symptom control (ACT below 19), severe airway obstruction (< 60% predicted), and maintenance oral corticosteroid (mOCS) use were significantly associated with poor response to omalizumab and benralizumab; p = 0.0.4 and 0.01; 0.003 and 0.01; 0.01 and 0.001, 0.05 and 0.04; 0.006 and 0.02, respectively. However, chronic rhinosinusitis and IgE < 220kIU/L were associated with higher poor response rates to omalizumab (p = 0.01 and 0.04, respectively). At the same time, female patients and those with blood eosinophils level < 500 cells/mm3 had a higher poor response rate to benralizumab (p = 0.02 and 0.01, respectively). Ischemic heart disease (IHD), bronchiectasis, and continued use of OCS increased the likelihood of poor response to omalizumab by 21, 7, and 24 times (p = 0.004, 0.008, and 0.004, respectively). In contrast, the female gender, childhood-onset asthma and higher BMI increased the likelihood of poor response to benralizumab by 7, 7 and 2 times more, p = 0.03, 0.02 and 0.05, respectively. CONCLUSION: Poor response to omalizumab treatment was independently associated with ischemic heart disease (IHD), bronchiectasis, and a history of maintenance oral corticosteroid (mOCS) use. Conversely, poor response to benralizumab therapy was independently linked to female gender, childhood-onset asthma and higher body mass index (BMI).

Predictors of poor response to oral propranolol in infantile hemangiomas.

BACKGROUND: Propranolol is the first-line treatment for infantile hemangiomas (IH). Cases of propranolol-resistant infantile hemangiomas are rarely reported. The purpose of our study was to investigate the predictive factors for poor response to propranolol. METHODS: A prospective analytical study was conducted between January 2014 and January 2022 including all patients with IH who received oral propranolol therapy at a dose of 2-3 mg/kg/day maintained for at least 6 months. RESULTS: A total of 135 patients with IH were treated with oral propranolol. Poor response was reported in 18 (13.4%) of the patients: 72% were girls and 28% were boys. Overall, 84% of the IH were mixed, and hemangiomas were multiple in three cases (16%), nasal tip hemangiomas accounted for four cases (22%), and 15 patients (83%) had segmental hemangiomas. There was no significant association between the age or sex of the children and type of response to treatment (p > 0.05). No significant association was found between the type of hemangioma and the therapeutic outcome as well as the recurrence after treatment discontinuation (p > 0.05). Multivariate logistic regression analysis revealed that nasal tip hemangiomas, multiple hemangiomas, and segmental hemangiomas were at greater risk of poor response to beta-blockers (p < 0.05). CONCLUSION: Poor response to propranolol therapy has rarely been reported in the literature. In our series, it was approximately 13.4%. To our knowledge, no previous publications have focused on the predictive factors of poor response to beta-blockers. However, the reported risk factors for recurrence are discontinuation of treatment before 12 months of age, mixed or deep type IH, and female gender. In our study, the predictive factors for poor response were multiple type IH, segmental type IH, and location on the nasal tip.

Efficacy, feasibility and tolerability of ketogenic diet for the treatment of poor response to bariatric surgery.

PURPOSE: Poor response to bariatric surgery, namely insufficient weight loss (IWL) or weight regain (WR), is a critical issue in the treatment of obesity. The purpose of our study was to assess the efficacy, feasibility, and tolerability of very low-calorie ketogenic diet (VLCKD) for the management of this condition. METHODS: A real-life prospective study was conducted on twenty-two patients who experienced poor response after bariatric surgery and followed a structured VLCKD. Anthropometric parameters, body composition, muscular strength, biochemical analyses, and nutritional behavior questionnaires were evaluated. RESULTS: A significant weight loss (mean 14.1 ± 4.8%), mostly due to fat mass, was observed during VLCKD with the preservation of muscular strength. The weight loss obtained allowed patients with IWL to reach a body weight significantly lower than that obtained at the post-bariatric surgery nadir and to report the body weight of patients with WR at the nadir observed after surgery. The significantly beneficial changes in nutritional behaviors and metabolic profiles were observed without variations in kidney and liver function, vitamins, and iron status. The nutritional regimen was well tolerated, and no significant side effects were detected. CONCLUSION: Our data demonstrate the efficacy, feasibility, and tolerability of VLCKD in patients with poor response after bariatric surgery.

Idiopathic early ovarian ageing: risk of miscarriage and chance of delivery following ART in a nationwide cohort study.

STUDY QUESTION: Is idiopathic reduced ovarian reserve in young women, quantified as low response to ovarian stimulation in ART, associated with a concomitant loss of oocyte quality as determined by risk of pregnancy loss and chance of clinical pregnancy and live birth? SUMMARY ANSWER: Young women with idiopathic accelerated loss of follicles exhibit a similar risk of pregnancy loss as young women with normal ovarian reserve. WHAT IS KNOWN ALREADY: Normal ovarian ageing is described as a concomitant decline in oocyte quantity and quality with increasing age. Conflicting results exist with regard to whether a similar decline in oocyte quality also follows an accelerated loss of follicles in young women. STUDY DESIGN, SIZE, DURATION: This national register-based, historical cohort study included treatment cycles from young women (≤37 years) after ART treatment in Danish public or private fertility clinics during the period 1995-2014. The women were divided into two groups dependent on their ovarian reserve status: early ovarian ageing (EOA) group and normal ovarian ageing (NOA) group. There were 2734 eligible cycles in the EOA group and 22 573 in the NOA group. Of those, 1874 (n = 1213 women) and 19 526 (n = 8814 women) cycles with embryo transfer were included for analyses in the EOA and NOA group, respectively. PARTICIPANTS/MATERIALS, SETTING, METHODS: EOA was defined as ≤5 oocytes harvested in both the first and second cycle stimulated with FSH. The NOA group should have had at least two FSH-stimulated cycles with ≥8 oocytes harvested in either the first or the second cycle. Cases with known causes influencing the ovarian reserve (endometriosis, ovarian surgery, polycystic ovary syndrome, chemotherapy, etc.) were excluded. The oocyte quality was evaluated by the primary outcome defined as the overall risk of pregnancy loss (gestational age (GA) ≤22 weeks) following a positive hCG and further stratified into: non-visualized pregnancy loss, early miscarriage (GA ≤ 12 weeks) and late miscarriage (GA > 12 weeks). Secondary outcomes were chance of clinical pregnancy and live birth per embryo transfer. Cox regression models were used to assess the risk of pregnancy loss. Time-to-event was measured from the day of embryo transfer from the second cycle and subsequent cycles. Logistic regression models were used to assess the chance of clinical pregnancy and live birth. MAIN RESULTS AND THE ROLE OF CHANCE: The overall risk of pregnancy loss for the EOA group was comparable with the NOA group (adjusted hazard ratio: 1.04, 95% CI: 0.86; 1.26). Stratifying by pregnancy loss types showed comparable risks in the EOA and NOA group. The odds of achieving a clinical pregnancy or live birth per embryo transfer was lower in the EOA group compared to the NOA group (adjusted odds ratio: 0.77 (0.67; 0.88) and 0.78 (0.67; 0.90), respectively). LIMITATIONS, REASONS FOR CAUTION: Only women with at least two ART cycles were included. We had no information on the total doses of gonadotropin administered in each cycle. WIDER IMPLICATIONS OF THE FINDINGS: The present findings may indicate that mechanism(s) other than aneuploidy may explain the asynchrony between the normal-for-age risk of miscarriage and the reduced chance of implantation found in our patients with EOA. The results of this study could be valuable when counselling young patients with low ovarian reserve. STUDY FUNDING/COMPETING INTERESTS(S): The study was funded by the Health Research Fund of Central Denmark Region. The authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Increased versus standard gonadotrophin dosing in predicted poor responders of IVF: an open-label randomized controlled trial.

STUDY QUESTION: Does an increased dosing of FSH improve the live birth rate as compared to standard FSH dosing in expected poor responders who undergo IVF? SUMMARY ANSWER: In this trial, women with an expected poor response allocated to increased FSH dosing did not have a statistically significant increase in cumulative live births as compared to a standard FSH dose. WHAT IS KNOWN ALREADY: Poor ovarian reserve leads to worse IVF outcomes owing to the low number and quality of oocytes. Clinicians often individualize the FSH dose using ovarian reserve tests, including antral follicle count (AFC), and basal plasma FSH or anti-Müllerian hormone level. However, the evidence that increased FSH dosing improves fertility outcomes in women with an expected poor response is lacking. STUDY DESIGN, SIZE, DURATION: We performed a parallel, open-label randomized controlled trial between March 2019 and October 2021 in an assisted reproduction centre. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women <43 years of age with AFC <10 referred for their first IVF cycle were randomized for increased or standard FSH dosing. In participants allocated to increased FSH dosing, women with AFC 1-6 started with 300 IU/day, while women with AFC 7-9 started with 225 IU/day. In participants allocated to the standard care, women started with 150 IU/day. The primary outcome was cumulative live birth attributable to the first IVF cycle including fresh and subsequent frozen-thawed cycles within 18 months of randomization. Live birth was defined as the delivery of one or more living infants ≥24 weeks' gestation. This trial was powered to detect an 11% difference in live birth attributable to the first IVF cycle. Outcomes were evaluated from an intention-to-treat perspective. MAIN RESULTS AND THE ROLE OF CHANCE: We randomized 661 women to start FSH at increased dosing (n = 328) or standard dosing (n = 333). The primary outcome cumulative live birth occurred in 162/328 (49.4%) women in the increased group versus 141/333 (42.3%) women in the standard group [risk ratio (RR) 1.17 (95% CI, 0.99-1.38), risk difference 0.07 (95% CI, -0.005, 0.15), P = 0.070]. The live birth rate after the first embryo transfer in the increased versus standard group was 125/328 (38.1%) versus 117/333 (35.1%), respectively [RR 1.08 (95% CI, 0.83-1.33), P = 0.428]. Cumulative clinical pregnancy rates were 59.1% versus 57.1% [RR 1.04 (95% CI, 0.91-1.18), P = 0.586] with miscarriage rates of 9.8% versus 14.4% [RR 0.68 (95% CI, 0.44-1.03), P = 0.069] in the increased versus standard group, respectively. Other secondary outcomes, including biochemical pregnancy, ongoing pregnancy, multiple pregnancy and ectopic pregnancy, were not significantly different between the two groups both from the first and cumulative embryo transfer. LIMITATIONS, REASONS FOR CAUTION: As this study is open-label, potential selective cancelling and small dose adjustments could have influenced the results. WIDER IMPLICATIONS OF THE FINDINGS: In women with predicted poor response, we did not find evidence that increased FSH dosing improves live birth rates. A standard dose of 150 IU/day is recommended at the start of IVF in these women to reduce potential adverse effects and costs. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the General Projects of Social Development in Shaanxi Province (No. 2022SF-565). B.W.M. is supported by NHMRC (GNT1176437). B.W.M. reports personal fees from ObsEva, and funding from Merck and Ferring outside the submitted work. TRIAL REGISTRATION NUMBER: Registered at Chinese clinical trial registry (www.chictr.org.cn). Registration number ChiCTR1900021944. TRIAL REGISTRATION DATE: 17 March 2019. DATE OF FIRST PATIENT'S ENROLMENT: 20 March 2019.

A CT-based deep learning radiomics nomogram for predicting the response to neoadjuvant chemotherapy in patients with locally advanced gastric cancer: A multicenter cohort study.

Background: Accurate prediction of treatment response to neoadjuvant chemotherapy (NACT) in individual patients with locally advanced gastric cancer (LAGC) is essential for personalized medicine. We aimed to develop and validate a deep learning radiomics nomogram (DLRN) based on pretreatment contrast-enhanced computed tomography (CT) images and clinical features to predict the response to NACT in patients with LAGC. Methods: 719 patients with LAGC were retrospectively recruited from four Chinese hospitals between Dec 1st, 2014 and Nov 30th, 2020. The training cohort and internal validation cohort (IVC), comprising 243 and 103 patients, respectively, were randomly selected from center I; the external validation cohort1 (EVC1) comprised 207 patients from center II; and EVC2 comprised 166 patients from another two hospitals. Two imaging signatures, reflecting the phenotypes of the deep learning and handcrafted radiomics features, were constructed from the pretreatment portal venous-phase CT images. A four-step procedure, including reproducibility evaluation, the univariable analysis, the LASSO method, and the multivariable logistic regression analysis, was applied for feature selection and signature building. The integrated DLRN was then developed for the added value of the imaging signatures to independent clinicopathological factors for predicting the response to NACT. The prediction performance was assessed with respect to discrimination, calibration, and clinical usefulness. Kaplan-Meier survival curves based on the DLRN were used to estimate the disease-free survival (DFS) in the follow-up cohort (n = 300). Findings: The DLRN showed satisfactory discrimination of good response to NACT and yielded the areas under the receiver operating curve (AUCs) of 0.829 (95% CI, 0.739-0.920), 0.804 (95% CI, 0.732-0.877), and 0.827 (95% CI, 0.755-0.900) in the internal and two external validation cohorts, respectively, with good calibration in all cohorts (p > 0.05). Furthermore, the DLRN performed significantly better than the clinical model (p < 0.001). Decision curve analysis confirmed that the DLRN was clinically useful. Besides, DLRN was significantly associated with the DFS of patients with LAGC (p < 0.05). Interpretation: A deep learning-based radiomics nomogram exhibited a promising performance for predicting therapeutic response and clinical outcomes in patients with LAGC, which could provide valuable information for individualized treatment.

Poor Ovarian Response to Gonadotrophins in PCOS Women after Laparoscopic Ovarian Drilling.

Background and Objectives: Polycystic ovary syndrome (PCOS) is a major cause of anovulatory infertility, and ovulation induction is the first-line treatment. If this fails, laparoscopic ovarian drilling (LOD) is used to induce mono-ovulations. There have been implications, that LOD can cause destruction of ovarian tissue and therefore premature ovarian failure. Furthermore, unexpected poor ovarian response (POR) to gonadotrophins can occur in PCOS women after LOD. There have been reports about FSH receptor polymorphisms found in women with PCOS that are related to higher serum FSH levels and POR to gonadotrophins. Materials and Methods: In the present study, we retrospectively analyzed data of 144 infertile PCOS women that had LOD performed before IVF. Results: Thirty of included patients (20.8%) had POR (≤3 oocytes) to ovarian stimulation with gonadotrophins. Women with POR had significantly higher median levels of basal serum FSH (7.2 (interquartile range (IQR), 6.0-9.2) compared to women with normal ovarian response (6.0 (IQR, 5.0-7.4); p = 0.006). Furthermore, women with POR used a significantly higher median cumulative dose of gonadotrophins (1875 IU (IQR, 1312.5-2400) for ovarian stimulation compared to women with normal ovarian response (1600 IU (IQR, 1200-1800); p = 0.018). Conclusion: Infertile PCOS women who experience POR after LOD have significantly higher serum FSH levels compared to women with normal ovarian response after LOD. As these levels are still within the normal range, we speculate that LOD is not the cause of POR. We presume that women with PCOS and POR after LOD could have FSH-R genotypes associated with POR and higher serum FSH levels.

Non-response to psychotherapy for borderline personality disorder: A systematic review.

HIGHLIGHT: This is the first systematic review to investigate non-response to psychotherapy for borderline personality disorder. BACKGROUND: Psychotherapy is the recommended treatment for borderline personality disorder. While systematic reviews have demonstrated the effectiveness of psychotherapy for borderline personality disorder, effect sizes remain small and influenced by bias. Furthermore, the proportion of people who do not respond to treatment is seldom reported or analysed. OBJECTIVE: To obtain an informed estimate of the proportion of people who do not respond to psychotherapy for borderline personality disorder. METHODS: Systematic searches of five databases, PubMed, Web of Science, Scopus, PsycINFO and the Cochrane Library, occurred in November 2020. Inclusion criteria: participants diagnosed with borderline personality disorder, treated with psychotherapy and data reporting either (a) the proportion of the sample that experienced 'reliable change' or (b) the percentage of sample that no longer met criteria for borderline personality disorder at conclusion of therapy. Exclusion criteria: studies published prior to 1980 or not in English. Of the 19,517 studies identified, 28 met inclusion criteria. RESULTS: Twenty-eight studies were included in the review comprising a total of 2436 participants. Average treatment duration was 11 months using well-known evidence-based approaches. Approximately half did not respond to treatment; M = 48.80% (SD = 22.77). LIMITATIONS: Data regarding within sample variability and non-response are seldom reported. Methods of reporting data on dosage and comorbidities were highly divergent which precluded the ability to conduct predictive analyses. Other limitations include lack of sensitivity analysis, and studies published in English only. CONCLUSION: Results of this review suggest that a large proportion of people are not responding to psychotherapy for borderline personality disorder and that factors relating to non-response are both elusive and inconsistently reported. Novel, tailored or enhanced interventions are needed to improve outcomes for individuals not responding to current established treatments.

Letrozole as an adjunct treatment in antagonist cycles that previously failed in poor responders.

OBJECTIVES: To investigate whether adding letrozole in the early follicular phase of a gonadotropin-releasing hormone (GnRH) antagonist (GA) stimulation cycle improves in vitro fertilization (IVF) outcomes in poor responder patients. MATERIAL AND METHODS: To be included in this study, patients had to have had at least one previous GA cycle and a subsequent GA cycle with added early follicular phase letrozole (LzGA). A total of 41 poor responder patients were identified based on the Bologna criteria. RESULTS: The LzGA group had a lower dosage of follicular stimulating hormone (FSH) (p = 0.001), the duration of stimulation days (p = 0.015) and the duration of GnRH antagonist stimulation days (p = 0.033) when compared with controls. Comprehensive analysis of the cycle characteristics showed that the number of oocytes retrieved, the number of MII oocytes retrieved, the number of fertilized oocytes, and the fertilization rate were significantly higher in the LzGA cycle (p = 0.041, p = 0.019, p = 0.008, p = 0.01, respectively). The rate of cycle cancellation was lower in the LzGA group (24.4%) than in the GA group (48.8%), (p < 0.001). Although LzGA administration demonstrated a trend toward improved implantation and clinical pregnancy rates, this was an insignificant trend (p = 1.000, p = 0.177, respectively). CONCLUSIONS: Adjunctive letrozole administration seems to restore an IVF cycle by improving the cycle characteristics and reducing the total gonadotrophin dosage.

Involvement of single nucleotide polymorphisms in ovarian poor response.

PURPOSE: Unpredictability in acquiring an adequate number of high-quality oocytes following ovarian stimulation is one of the major complications in controlled ovarian hyperstimulation (COH). Genetic predispositions of variations could alter the immunological profiles and consequently be implicated in the variability of ovarian response to the stimulation. DESIGN: Uncovering the influence of variations in AMHR2, LHCGR, MTHFR, PGR, and SERPINE1 genes with ovarian response to gonadotrophin stimulation in COH of infertile women. METHODS: Blood samples of the women with a good ovarian response (GOR) or with a poor ovarian response (POR) were collected. Genomic DNA was extracted, and gene variations were genotyped by TaqMan SNP Genotyping Assays using primer-probe sets or real-time PCR Kit. RESULTS: Except for PGR (rs10895068), allele distributions demonstrate that the majority of POR patients carried minor alleles of AMHR2 (rs2002555, G-allele), LHCGR (rs2293275, G-allele), MTHFR (rs1801131, C-allele, and rs1801133, T-allele), and SERPINE1 (rs1799889, 4G allele) genes compared to the GOR. Similarly, genotypes with a minor allele in AMHR2, LHCGR, MTHFR, and SERPINE1 genes had a higher prevalence among POR patients with the polymorphic genotypes. However, further genotype stratification indicated that the minor alleles of these genes are not associated with poor response. Multivariate logistic analysis of clinical-demographic factors and polymorphic genotypes demonstrated a correlation between FSH levels and polymorphic genotypes of SERPINE1 in poor response status. CONCLUSIONS: Despite a higher prevalence of AMHR2, LHCGR, MTHFR, and SERPINE1 variations in the patients with poor ovarian response, it seems that these variations are not associated with the ovarian response.

Improving Reporting of Clinical Studies Using the POSEIDON Criteria: POSORT Guidelines.

The POSEIDON (Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number) criteria were developed to help clinicians identify and classify low-prognosis patients undergoing assisted reproductive technology (ART) and provide guidance for possible therapeutic strategies to overcome infertility. Since its introduction, the number of published studies using the POSEIDON criteria has increased steadily. However, a critical analysis of existing evidence indicates inconsistent and incomplete reporting of critical outcomes. Therefore, we developed guidelines to help researchers improve the quality of reporting in studies applying the POSEIDON criteria. We also discuss the advantages of using the POSEIDON criteria in ART clinical studies and elaborate on possible study designs and critical endpoints. Our ultimate goal is to advance the knowledge concerning the clinical use of the POSEIDON criteria to patients, clinicians, and the infertility community.

Human Menopausal Gonadotropin Commenced on Early Follicular Period Increases Live Birth Rates in POSEIDON Group 3 and 4 Poor Responders.

Human menopausal gonadotropin (hMG) has LH activity, and it may have beneficial effects in terms of oocyte quality and endometrial receptivity similar to recombinant LH supplementation. The aim of this study was to assess the effects of hMG, and its commencement time on the outcome of assisted reproductive technology (ART) cycles of POSEIDON group 3 and 4 poor responders. Data of 558 POSEIDON group 3 and 4 poor responders who underwent ART treatment following a GnRH antagonist cycle at a university-based infertility clinic between January 2014 and December 2019 were reviewed. hMG was commenced at the early follicular phase or mid-follicular phase in the study groups. The control group did not receive hMG stimulation. Live birth rate (LBR) was the main outcome measure. The mean duration of stimulation was significantly shorter in early follicular hMG group than in mid-follicular hMG group (11.9 ± 3.6 days vs. 12.8 ± 4 days, respectively; P = 0.027). The mean numbers of oocytes retrieved and MII oocytes were comparable between the groups. The LBRs per embryo transfer in early follicular hMG, mid-follicular hMG, and control groups were 21.9%, 11.7%, and 11.6%, respectively (P = 0.035). In conclusion, there is a significant association between the commencement time of hMG and live birth chance in ART cycles of POSEIDON group 3 and 4 poor responders. Early initiation of hMG together with rFSH seems to be beneficial in this specific population.

Endometrioma surgery is associated with increased risk of subsequent assisted reproductive technology cycle cancellation; a retrospective cohort study.

The aim of this study was to assess the effect of laparoscopic removal of endometrioma on assisted reproductive technology (ART) outcome. A retrospective cohort study was conducted at a university hospital between January 2014 and December 2017. The ART group consisted of 26 women who underwent 44 ART cycles in the presence of ovarian endometrioma and the surgery group consisted of 53 women who underwent 58 ART cycles after laparoscopic removal of ovarian endometrioma/s. There were no statistically significant differences between the groups regarding demographic parameters and background features including cycle parameters. The live birth rates in the ART and Surgery groups per embryo transfer were 23.7 and 26.1%, respectively (p = .800). The rate of cycle cancellation due to poor response and/or failed oocyte retrieval was significantly higher in the Surgery group than ART group (13.7 vs. 0%, respectively; p = .018). In conclusion, cystectomy significantly increases the risk of cycle cancellation due to poor ovarian response, which might be catastrophic individually. However, it does not seem to affect the live birth rates.IMPACT STATEMENTWhat is already known on this subject? Both the presence of an endometrioma or surgical removal may have deleterious effects on fertility potential.What do the results of this study add? Our results confirm that although cystectomy has no benefit on the number of oocytes collected and live birth rate, it increases the risk of cycle cancellation significantly in assisted reproductive technology cycles following endometrioma surgery.What are the implications of these findings for clinical practice and/or further research? Postponing cystectomy until a freeze-all cycle may be the best option to maximise the number of oocytes retrieved and to maximise the ovarian response.

Early ovarian ageing: is a low number of oocytes harvested in young women associated with an earlier and increased risk of age-related diseases?

STUDY QUESTION: Do young women with early ovarian ageing (EOA), defined as unexplained, and repeatedly few oocytes harvested in ART have an increased risk of age-related events? SUMMARY ANSWER: At follow-up, women with idiopathic EOA had an increased risk of age-related events compared to women with normal ovarian ageing (NOA). WHAT IS KNOWN ALREADY: Early and premature menopause is associated with an increased risk of cardiovascular diseases (CVDs), osteoporosis and death. In young women, repeated harvest of few oocytes in well-stimulated ART cycles is a likely predictor of advanced menopausal age and may thus serve as an early marker of accelerated general ageing. STUDY DESIGN, SIZE, DURATION: A register-based national, historical cohort study. Young women (≤37 years) having their first ART treatment in a public or private fertility clinic during the period 1995-2014 were divided into two groups depending on ovarian reserve status: EOA (n = 1222) and NOA (n = 16 385). Several national registers were applied to assess morbidity and mortality. PARTICIPANTS/MATERIALS, SETTING, METHODS: EOA was defined as ≤5 oocytes harvested in a minimum of two FSH-stimulated cycles and NOA as ≥8 oocytes in at least one cycle. Cases with known causes influencing the ovarian reserve (endometriosis, ovarian surgery, polycystic ovary syndrome, chemotherapy etc.) were excluded. To investigate for early signs of ageing, primary outcome was an overall risk of ageing-related events, defined as a diagnosis of either CVD, osteoporosis, type 2 diabetes, cancer, cataract, Alzheimer's or Parkinson's disease, by death of any-cause as well as a Charlson comorbidity index score of ≥1 or by registration of early retirement benefit. Cox regression models were used to assess the risk of these events. Exposure status was defined 1 year after the first ART cycle to assure reliable classification, and time-to-event was measured from that time point. MAIN RESULTS AND THE ROLE OF CHANCE: Median follow-up time from baseline to first event was 4.9 years (10/90 percentile 0.7/11.8) and 6.4 years (1.1/13.3) in the EOA and NOA group, respectively. Women with EOA had an increased risk of ageing-related events when compared to women with a normal oocyte yield (adjusted hazard ratio 1.24, 95% CI 1.08 to 1.43). Stratifying on categories, the EOA group had a significantly increased risk for CVD (1.44, 1.19 to 1.75) and osteoporosis (2.45, 1.59 to 3.90). Charlson comorbidity index (1.15, 0.93 to 1.41) and early retirement benefit (1.21, 0.80 to 1.83) was also increased, although not reaching statistical significance. LIMITATIONS, REASONS FOR CAUTION: Cycles never reaching oocyte aspiration were left out of account in the inclusion process and we may therefore have missed women with the most severe forms of EOA. We had no information on the total doses of gonadotrophin administered in each cycle. WIDER IMPLICATIONS OF THE FINDINGS: These findings indicate that oocyte yield may serve as marker of later accelerated ageing when, unexpectedly, repeatedly few oocytes are harvested in young women. Counselling on life-style factors as a prophylactic effort against cardiovascular and other age-related diseases may be essential for this group of women. STUDY FUNDING/COMPETING INTEREST(S): No external funding was received for this study. All authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Tumor-infiltrating lymphocytes as a feasible adjuvant immunotherapy for osteosarcoma with a poor response to neoadjuvant chemotherapy.

Aim: To investigate the efficacy of adjuvant chemotherapy plus tumor-infiltrating lymphocytes (TILs) therapy in osteosarcoma patients with a poor response to neoadjuvant chemotherapy. Materials & methods: 40 patients received adjuvant chemotherapy (Group 1) and 40 patients received adjuvant chemotherapy plus TILs therapy (Group 2). Disease-free survival (DFS) and overall survival (OS) were analyzed by Kaplan-Meier analysis. Results: The median DFS (mDFS; 65.3 months) and median OS (mOS; 95.8 months) in Group 2 were significantly prolonged compared with those in Group 1 (55.5 months for mDFS and 80.4 months for mOS). Univariate and multivariate analyses indicated that a greater number of TILs transfused was an independent prognostic factor for both mDFS and mOS. Conclusion: Adjuvant chemotherapy plus TILs therapy may prolong survival of patients with a poor response to neoadjuvant chemotherapy.

Are Repeated Cycles of Intravenous Immunoglobulin Justified in Patients With Poorly Responsive Guillain-Barré Syndrome?

Guillain-Barré syndrome (GBS) is a life-threatening form of inflammatory polyneuropathy. Immunotherapy with intravenous immunoglobulin (IVIG) has been used successfully in the treatment of GBS. In this case report, we present a severe axonal form of GBS that showed improvement after 3 cycles of IVIG. Repeated cycles of IVIG may be an option for treating severe forms of GBS not responding to the first course of such treatment. The recent work suggests that patients who are severely affected and have severe gadolinium enhancement on the magnetic resonance imaging of the spine should be considered for retreatment with IVIG. Although the cost of management was high, the outcome was excellent, which is definitely considered a reasonable approach. This case report is an urgent call for performing large multicenter trials on the use of repeated cycles of IVIG in the management of severe cases of GBS.

Treatment Options for Poor Responders to Bariatric Surgery.

PURPOSE OF REVIEW: This review aims to evaluate the latest evidence on the treatment options for perceived poor responders to bariatric surgery and provide practitioners with a guide on when to consider revisional surgery and when to consider alternatives. RECENT FINDINGS: The use of adjuvant pharmacotherapy has been increasingly described in the literature as an adjunct to primary bariatric surgery, in order to attain more weight loss or better control of obesity-related complications. The newer anti-obesity and anti-diabetes drugs also have cardiorenal benefits, which are shown in recent cardiovascular outcome trials. Revisional bariatric surgery has emerged as a distinctive entity and can be broadly organized into three categories: corrective, conversion, and reversal surgeries. Careful patient selection and preoperative optimization are needed to ensure long-term favorable outcomes. Newer treatment modalities involving the use of anti-obesity medications and endoscopic bariatric interventions provide patients and healthcare providers with more options, when faced with the challenge of poor response after bariatric surgery.