Comparison of Disease Profiles and Three-Month Outcomes of Patients with Neurological Disorders with and without COVID-19: An Ambispective Cohort Study.

Objective: Neurological emergencies saw a paradigm shift in approach during the coronavirus disease-2019 (COVID-19) pandemic with the challenge to manage patients with and without COVID-19. We aimed to compare the various neurological disorders and 3 months outcome in patients with and without SARS-CoV-2 infection. Methods: In an ambispective cohort study design, we enrolled patients with and without SARS CoV-2 infection coming to a medical emergency with neurological disorders between April 2020 and September 2020. Demographic, clinical, biochemical, and treatment details of these patients were collected and compared. Their outcomes, both in-hospital and at 3 months were assessed by the modified Rankin Scale (mRS). Results: Two thirty-five patients (235) were enrolled from emergency services with neurological disorders. Of them, 81 (34.5%) were COVID-19 positive. The mean (SD) age was 49.5 (17.3) years, and the majority of the patients were male (63.0%). The commonest neurological diagnosis was acute ischemic stroke (AIS) (43.0%). The in-hospital mortality was higher in the patients who were COVID-19 positive (COVID-19 positive: 29 (35.8%) versus COVID-19 negative: 12 (7.8%), P value: <0.001). The 3 months telephonic follow-up could be completed in 73.2% of the patients (142/194). Four (12.1%) deaths occurred on follow-up in the COVID-19 positive versus fifteen (13.8%) in the COVID-19 negative patients (P value: 1.00). The 3-month mRS was worse in the COVID-19 positive group (P value <0.001). However, this was driven by higher in-hospital morbidity and mortality in COVID-19 positive patients. Conclusion: Patients with neurological disorders presenting with COVID-19 infection had worse outcomes, including in-hospital and 3 months disability.

Hybrid Workshops During the COVID-19 Pandemic-Dawn of a New Era in Neurosurgical Learning Platforms.

BACKGROUND: During the COVID-19 pandemic, disruption of surgical hands-on training has hampered the skills acquisition by budding neurosurgeons. Online and virtual classrooms have not been able to substitute the hands-on experience and learning via direct interaction with senior colleagues. To overcome these challenges, we organized a hybrid workshop where simulation-based learning modules, and direct and virtual interaction with surgeons during live surgeries or didactic lectures were utilized to help delegates in understanding the nuances of neurosurgery. METHODS: A 3-day hybrid workshop was held in March 2021, which was attended by 133 delegates. A structured questionnaire was utilized to record their feedback. RESULTS: An overwhelming majority of the respondents (94.1%, n = 64) found hybrid conferences to be better than an online conference. Most of the respondents (88.3%, n = 60) rated the utility of direct face-to-face interaction to be more satisfying as compared with online interaction with faculty during a webinar. Again, many the respondents (86.8%, n = 59) believed that similar hybrid events will be the new normal given the current situation of COVID-19 pandemic. A large majority (88.2%, n = 60) of the respondents reported that they will prefer a hybrid event over an online conference. CONCLUSIONS: In this era of the COVID-19 pandemic, "hybrid" microneurosurgery workshops offer unique opportunities to enhance surgical skills acquisition by hands-on simulation-based learning and observing live surgical demonstrations, apart from 2-way interactions with experts under one roof. This may be a stepping stone for what lies ahead in the future of neurosurgical training.

Stroke in India: A systematic review of the incidence, prevalence, and case fatality.

BACKGROUND: The burden of stroke is increasing in India; stroke is now the fourth leading cause of death and the fifth leading cause of disability. Previous research suggests that the incidence of stroke in India ranges between 105 and 152/100,000 people per year. However, there is a paucity of available data and a lack of uniform methods across published studies. AIM: To identify high-quality prospective studies reporting the epidemiology of stroke in India. SUMMARY OF REVIEW: A search strategy was modified from the Cochrane Stroke Strategy and adapted for a range of bibliographic databases from January 1997 to August 2020. From 7717 identified records, nine studies were selected for inclusion; three population-based registries, a further three population-based registries also using community-based ascertainment and three community-based door-to-door surveys. Studies represented the four cities of Mumbai, Trivandrum, Ludhiana, Kolkata, the state of Punjab, and 12 villages of Baruipur in the state of West Bengal. The total population denominator was 22,479,509 and 11,654 (mean 1294 SD 1710) people were identified with incident stroke. Crude incidence of stroke ranged from 108 to 172/100,000 people per year, crude prevalence from 26 to 757/100,000 people per year, and one-month case fatality rates from 18% to 42%. CONCLUSIONS: Further high-quality evidence is needed across India to guide stroke policy and inform the development and organization of stroke services. Future researchers should consider the World Health Organization STEPwise approach to Surveillance framework, including longitudinal data collection, the inclusion of census population data, and a combination of hospital-registry and comprehensive community ascertainment strategies to ensure complete stroke identification.

Management of Dyslipidaemia for the Prevention of Stroke: Clinical Practice Recommendations from the Lipid Association of India.

Stroke is the second most common cause of death worldwide. The rates of stroke are increasing in less affluent countries predominantly because of a high prevalence of modifiable risk factors. The Lipid Association of India (LAI) has provided a risk stratification algorithm for patients with ischaemic stroke and recommended low density lipoprotein cholesterol (LDL-C) goals for those in very high risk group and extreme risk group (category A) of <50 mg/dl (1.3 mmol/l) while the LDL-C goal for extreme risk group (category B) is ≤30 mg/dl (0.8 mmol/l). High intensity statins are the first-line lipid lowering therapy. Nonstatin therapy like ezetimibe and proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors may be added as an adjunct to statins in patients who do not achieve LDL-C goals with statins alone. In acute ischaemic stroke, high intensity statin therapy improves neurological and functional outcomes regardless of thrombolytic therapy. Although conflicting data exist regarding increased risk of intracerebral haemorrhage (ICH) with statin use, the overall benefit risk ratio favors long-term statin therapy necessitating detailed discussion with the patient. Patients who have statins withdrawn while being on prior statin therapy at the time of acute ischaemic stroke have worse functional outcomes and increased mortality. LAI recommends that statins be continued in such patients. In patients presenting with ICH, statins should not be started in the acute phase but should be continued in patients who are already taking statins. ICH patients, once stable, need risk stratification for atherosclerotic cardiovascular disease (ASCVD).

Correlation of DTI-Derived Measures to Therapy-Mediated Recovery after Stroke: Preliminary Findings.

INTRODUCTION: Corticospinal tracts (CST) forms the basis of motor neurophysiology after stroke. Motor skill recovery has been correlated well to the microstructural properties of CST in both hemispheres. Functional imaging has opened up new possibilities of imaging functionality of cortex and fiber tracts in the brain. We studied therapy-induced changes in blood oxygenation level-dependent (BOLD) and DTI imaging on 20 chronic stroke patients at baseline, 8, and 24 weeks. SETTINGS AND DESIGN: All the patients were subjected to MR imaging on a 1.5 T MR scanner. We used block design for BOLD with alternate baseline and activation cycles (repetition time (TR) =4520 ms, echo time (TE) = 44 ms, slices = 31, slice thickness = 4 mm). DTI parameters were as follows: TE = 76 ms, TR = 10,726 ms, EPI factor = 127, resolution = 128 × 128 matrix, field of view = 230 mm and a slice thickness of 4.0 mm. STATISTICAL ANALYSIS USED: The data was analyzed on SPSS software and tractography/DTI processing software (M/s. Siemens Medical Solutions, Erlangen Germany. RESULTS: The mean axial diffusivity (λ[INSIDE:1]) and radial diffusivity (λ[INSIDE:2]) in the affected hemisphere were 0. 30 and 0.18, respectively. The mean number (FN) ratio (± SD) was 0.27 ± 0.14 at baseline, 0.33 ± 0.19 at 8 weeks, and 0.41 ± 0.23 at 24 weeks. Multivariate regression analysis at baseline showed that rFA was well-correlated to the Fugl-Meyer score (regression coefficient: 0.198, F = 10.382, P = 0.001), MI followed by signal intensity. DISCUSSION: All patients had high % signal intensity after 8 weeks of physiotherapy regime with a greater percentage change in rFA as compared at follow-up suggesting that a focused exercise regime in stroke patients helps in the reconnection of neural and myelin networks. CONCLUSION: Clinical and functional recovery after stroke is well-correlated with the DTI and BOLD parameters i.e., rFA ratios, CST involvement fiber numbers, and % signal intensity of the ipsilesional cortex.

Cognitive Capacity Assessment: The Fundamental Element of Neurological Disability Guidelines in India.

BACKGROUND: Disability evaluation as per World Health Organization includes assessment of impairments, activity limitations, and participation restriction, which unfortunately is not assessed by the existing guidelines of disability in India. AIM: The aim of this study wasto comparea new study criterion with the existing guidelines for assessing cognitive disability for chronic neurological conditions. METHODOLOGY: A cross-sectional pilot study was conducted on 41 participants. They were assessed on an existing guideline (Gazette India 200,1 assessing physical domain and Intelligence Quotient[IQ]) and study criterion assessing three aspects of cognitive capacity: IQ, neurocognitive functioning, and QOL. RESULTS: The existing guideline underestimated 84% of cases for disability. The average percentage of disability measured by the study criterion was 33.2% more as compared to existing guidelines with S.D of 26.6. CONCLUSION: Cognitive capacity assessment is an important element to be measured in chronic neurological disability certification. However, a large sample is required to make an affirmative claim for the same.

Multilocus Sequence Typing of Clinical Isolates of Cryptococcus from India.

Cryptococcosis is a life-threatening infection caused by Cryptococcus neoformans and C. gattii species complex. In the present study, to understand the molecular epidemiology of 208 clinical isolates of Cryptococcus from different parts of India, multilocus sequence typing (MLST) using ISHAM MLST consensus scheme for C. neoformans/C. gattii species complex was used. MLST analysis yielded a total of 10 Sequence Types (STs)-7 STs for C. neoformans and 3 for C. gattii species complex. The majority of isolates identified as C. neoformans belonged to molecular type VNI with predominant STs 31 and 93. Only 3 isolates of C. gattii species complex were obtained, belonging to ST58 and ST215 of VGI and ST69 of VGIV. Phylogenetic analysis revealed less diversity among the clinical Indian isolates compared to the global MLST database. No association between prevalent STs and HIV status, geographical origin or minimum inhibitory concentration (MIC) could be established.

Patient Experience of a Neurology Tele-Follow-Up Program Initiated During the Coronavirus Disease 2019 Pandemic: A Questionnaire-Based Study.

Background: Teleneurology consultations can be highly advantageous since neurological diseases and disabilities often limit patient's access to health care, particularly in a setting where they need to travel long distances for specialty consults. Patient satisfaction is an important outcome assessing success of a telemedicine program. Materials and Methods: A cross-sectional study was conducted to determine satisfaction and perception of patients toward an audio call based teleneurology follow-up initiated during the coronavirus disease 2019 pandemic. Primary outcomes were satisfaction to tele-consult, and proportion of patients preferring telemedicine for future follow-up. Results: A total of 261 patients who received tele-consult were enrolled. Satisfaction was highest for domain technological quality, followed by patient-physician dialogue (PPD) and least to quality of care (QoC). Median (interquartile range) patient satisfaction on a 5-point Likert scale was 4 (3-5). Eighty-five (32.6%; 95% confidence interval 26.9-38.6%) patients preferred telemedicine for future follow-up. Higher overall satisfaction was associated with health condition being stable/better, change in treatment advised on tele-consult, diagnosis not requiring follow-up examination, higher scores on domains QoC and PPD (p < 0.05). Future preference for telemedicine was associated with patient him-/herself consulting with doctor, less duration of follow-up, higher overall satisfaction, and higher scores on domain QoC (p < 0.05). On thematic analysis, telemedicine was found convenient, reduced expenditure, and had better physician attention; in-person visits were comprehensive, had better patient-physician relationship, and better communication. Discussion: Patient satisfaction was lower in our study than what has been observed earlier, which may be explained by the primitive nature of our platform. Several variables related to the patients' disease process have an effect on patient satisfaction. Conclusion: Development of robust, structured platforms is necessary to fully utilize the potential of telemedicine in developing countries.

Assessment of Botulinum Neurotoxin Injection for Dystonic Hand Tremor: A Randomized Clinical Trial.

Importance: There is an unmet need for safe and efficacious treatments for upper-extremity dystonic tremor (DT). To date, only uncontrolled retrospective case series have reported the effect of botulinum neurotoxin (BoNT) injections on upper-extremity DT. Objective: To assess the effect of BoNT injections on tremor in patients with upper-extremity DT. Design, Setting, and Participants: In this placebo-controlled, parallel-group randomized clinical trial, 30 adult patients with upper-extremity DT treated at a movement disorder clinic in a tertiary care university hospital were randomized in a 1:1 ratio to BoNT or saline injection, 0.9%, using a computer-generated randomization sequence. Randomization was masked using opaque envelopes. The participant, injector, outcome assessor, and statistician were blinded to the randomization. Participants were recruited between November 20, 2018, and December 12, 2019, and the last follow-up was completed in March 2020. Interventions: Participants received electromyographically guided intramuscular injections of BoNT or placebo into the tremulous muscles of the upper extremity. Injection patterns and doses were individualized according to tremor phenomenologic findings. Main Outcomes and Measures: The primary outcome was the total score on the Fahn-Tolosa-Marin Tremor Rating Scale 6 weeks after the intervention. Outcomes were assessed at baseline, 6 weeks, and 12 weeks. All patients were offered open-label BoNT injections after 12 weeks and reassessed 6 weeks later. Results: A total of 48 adult patients with a diagnosis of brachial dystonia with DT were screened. Fifteen were ineligible and 3 refused consent; therefore, 30 patients (mean [SD] age, 46.0 [18.6] years; 26 [86.7%] male) were recruited, with 15 randomized to receive BoNT and 15 to receive placebo. In the intention-to-treat group, the Fahn-Tolosa-Marin Tremor Rating Scale total score was significantly lower in the BoNT group at 6 weeks (adjusted mean difference, -10.9; 95% CI, -15.4 to -6.5; P < .001) and 12 weeks (adjusted mean difference, -5.7; 95% CI, -11.0 to -0.5; P = .03). More participants in the BoNT group reported global improvement on the Global Impression of Change (PGIC) assessment (PGIC 1, 2, and 3: BoNT: 4 [26.7%], 6 [40.0%], and 5 [33.3%]; placebo: 5 [33.3%], 10 [66.7%], and 0, respectively; P = .047). Subjective hand weakness (BoNT: 6 [40.0%]; placebo: 4 [28.6%], P = .52) and dynamometer-assessed grip strength (mean difference, -0.2 log10[kgf/m2]2/Hz-Hz; 95% CI, -0.9 to 0.4 log10[kgf/m2]2/Hz-Hz; P = .45) were similar in both groups. Conclusions and Relevance: In this randomized clinical trial, botulinum neurotoxin injections were superior to placebo in reducing tremor severity in upper-extremity DT. An individualized approach to muscle selection and dosing was beneficial without unacceptable adverse effects. Trial Registration: Clinical Trials Registry of India (http://ctri.nic.in) Identifier: CTRI/2018/02/011721.

Challenging the Ischemic Core Concept in Acute Ischemic Stroke Imaging.

Endovascular treatment is a highly effective therapy for acute ischemic stroke due to large vessel occlusion and has recently revolutionized stroke care. Oftentimes, ischemic core extent on baseline imaging is used to determine endovascular treatment-eligibility. There are, however, 3 fundamental issues with the core concept: First, computed tomography and magnetic resonance imaging, which are mostly used in the acute stroke setting, are not able to precisely determine whether and to what extent brain tissue is infarcted (core) or still viable, due to variability in tissue vulnerability, the phenomenon of selective neuronal loss and lack of a reliable gold standard. Second, treatment decision-making in acute stroke is multifactorial, and as such, the relative importance of single variables, including imaging factors, is reduced. Third, there are often discrepancies between core volume and clinical outcome. This review will address the uncertainty in terminology and proposes a direction towards more clarity. This theoretical exercise needs empirical data that clarify the definitions further and prove its value.

Calculation of Prognostic Scores, Using Delayed Imaging, Outperforms Baseline Assessments in Acute Intracerebral Hemorrhage.

Background and Purpose- Patients with intracerebral hemorrhage (ICH) are often subject to rapid deterioration due to hematoma expansion. Current prognostic scores are largely based on the assessment of baseline radiographic characteristics and do not account for subsequent changes. We propose that calculation of prognostic scores using delayed imaging will have better predictive values for long-term mortality compared with baseline assessments. Methods- We analyzed prospectively collected data from the multicenter PREDICT study (Prediction of Hematoma Growth and Outcome in Patients With Intracerebral Hemorrhage Using the CT-Angiography Spot Sign). We calculated the ICH Score, Functional Outcome in Patients With Primary Intracerebral Hemorrhage (FUNC) Score, and modified ICH Score using imaging data at initial presentation and at 24 hours. The primary outcome was mortality at 90 days. We generated receiver operating characteristic curves for all 3 scores, both at baseline and at 24 hours, and assessed predictive accuracy for 90-day mortality with their respective area under the curve. Competing curves were assessed with nonparametric methods. Results- The analysis included 280 patients, with a 90-day mortality rate of 25.4%. All 3 prognostic scores calculated using 24-hour imaging were more predictive of mortality as compared with baseline: the area under the curve was 0.82 at 24 hours (95% CI, 0.76-0.87) compared with 0.78 at baseline (95% CI, 0.72-0.84) for ICH Score, 0.84 at 24 hours (95% CI, 0.79-0.89) compared with 0.76 at baseline (95% CI, 0.70-0.83) for FUNC, and 0.82 at 24 hours (95% CI, 0.76-0.88) compared with 0.74 at baseline (95% CI, 0.67-0.81) for modified ICH Score. Conclusions- Calculation of the ICH Score, FUNC Score, and modified ICH Score using 24-hour imaging demonstrated better prognostic value in predicting 90-day mortality compared with those calculated at presentation.

Redefining Hematoma Expansion With the Inclusion of Intraventricular Hemorrhage Growth.

Background and Purpose- Definitions of significant hematoma expansion traditionally focus on changes in intraparenchymal volume. The presence of intraventricular hemorrhage (IVH) is a predictor of poor outcome, but current definitions of hematoma expansion do not include IVH expansion. We evaluated whether including IVH expansion to current definitions of hematoma expansion improves the ability to predict 90-day outcome. Methods- Using data from the PREDICT-ICH study (Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT), we compared a standard definition of hematoma expansion (≥6 mL or ≥33%) to revised definitions that includes new IVH development or expansion (≥6 mL or ≥33% or any IVH; ≥6 mL or ≥33% or IVH expansion ≥1 mL). The primary outcome was poor clinical outcome (modified Rankin Scale score, 4-6) at 90 days. Diagnostic accuracy measures were calculated for each definition, and C statistics for each definition were compared using nonparametric methods. Results- Of the 256 patients eligible for primary analysis, 127 (49.6%) had a modified Rankin Scale score of 4 to 6. Sensitivity and specificity for the standard definition (n=80) were 45.7% (95% CI, 36.8-54.7) and 82.9% (95% CI, 75.3-88.9), respectively. The revised definition, ≥6 mL or ≥33% or any IVH (n=113), possessed a sensitivity of 63.8% (95% CI, 54.8-72.1) and specificity of 75.2% (95% CI, 66.8-82.4). Overall accuracy was significantly improved with the revised definition (P=0.013) and after adjusting for relevant covariates, was associated with a 2.55-fold increased odds (95% CI, 1.31-4.94) of poor outcome at 90 days. A second revised definition, ≥6 mL or ≥33% or IVH expansion ≥1 mL, performed similarly (sensitivity, 56.7% [95% CI, 47.6-65.5]; specificity, 78.3% [95% CI, 40.2-85.1]; aOR, 2.40 [95% CI, 1.23-4.69]). Conclusions- In patients with mild-to-moderate ICH, including IVH expansion to the definition of hematoma expansion improves sensitivity with only minimal decreases to specificity and improves overall prediction of 90-day outcome.

New and expanding ventricular hemorrhage predicts poor outcome in acute intracerebral hemorrhage.

OBJECTIVE: To describe the relationship between intraventricular hemorrhage (IVH) expansion and long-term outcome and to use this relationship to select and validate clinically relevant thresholds of IVH expansion in 2 separate intracerebral hemorrhage (ICH) populations. METHODS: We used fractional polynomial analysis to test linear and nonlinear models of 24-hour IVH volume change and clinical outcome with data from the Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT (PREDICT)-ICH study. The primary outcome was poor clinical outcome (modified Rankin Scale [mRS] score 4-6) at 90 days. We derived dichotomous thresholds from the selected model and calculated diagnostic accuracy measures. We validated all thresholds in an independent single-center ICH cohort (Massachusetts General Hospital). RESULTS: Of the 256 patients from PREDICT, 127 (49.6%) had an mRS score of 4 to 6. Twenty-four-hour IVH volume change and poor outcome fit a nonlinear relationship, in which minimal increases in IVH were associated with a high probability of an mRS score of 4 to 6. IVH expansion ≥1 mL (n = 53, sensitivity 33%, specificity 92%, adjusted odds ratio [aOR] 2.68, 95% confidence interval [CI] 1.11-6.46) and development of any new IVH (n = 74, sensitivity 43%, specificity 85%, aOR 2.53, 95% CI 1.22-5.26) strongly predicted poor outcome at 90 days. The dichotomous thresholds reproduced well in a validation cohort of 169 patients. CONCLUSION: IVH expansion as small as 1 mL or any new IVH is strongly predictive of poor outcome. These findings may assist clinicians with bedside prognostication and could be incorporated into definitions of hematoma expansion to inform future ICH treatment trials.

Independent Validation of the Hematoma Expansion Prediction Score: A Non-contrast Score Equivalent in Accuracy to the Spot Sign.

BACKGROUND AND PURPOSE: The computed tomography angiography (CTA) spot sign is widely used to assess the risk of hematoma expansion following acute intracerebral hemorrhage (ICH). However, not all patients can receive intravenous contrast nor are all hospital systems equipped with this technology. We aimed to independently validate the Hematoma Expansion Prediction (HEP) Score, an 18-point non-contrast prediction scale, in an external cohort and compare its diagnostic capability to the CTA spot sign. METHODS: We performed a retrospective analysis of the predicting hematoma growth and outcome in intracerebral hemorrhage using contrast bolus CT (PREDICT) Cohort Study. Primary outcome was significant hematoma expansion (≥ 6 mL or ≥ 33%). We generated a receiver operating characteristic (ROC) curve comparing the HEP score to significant expansion. We calculated sensitivity, specificity, positive and negative predictive values (PPV/NPV) for each score point. We determined independent predictors of significant hematoma expansion via logistic regression. RESULTS: A total of 292 patients were included in primary analysis. Hematoma growth of ≥ 6 mL or ≥ 33% occurred in 94 patients (32%). The HEP score was associated with significant expansion (adjusted odds ratio [aOR] 1.14, 95% confidence interval [CI] 1.01-1.30). ROC curves comparing HEP score to significant expansion had an area under the curve of 0.64 (95% CI 0.57-0.71). Youden's method showed an optimum score of 4. HEP Scores ≥ 4 (n = 100, sensitivity 49%, specificity 73%, PPV 46%, NPV 75%, aOR 1.99, 95% CI 1.09-3.64) accurately predicted significant expansion. PPV increased with higher HEP scores, but at the cost of lower sensitivity. The diagnostic characteristics of the spot sign (n = 82, Sensitivity 49%, Specificity 81%, PPV 55%, NPV 76%, aOR 2.95, 95% CI 1.61-5.42) were similar to HEP scores ≥ 4. CONCLUSION: The HEP score is predictive of significant expansion (≥ 6 mL or ≥ 33%) and is comparable to the spot sign in diagnostic accuracy. Non-contrast prediction tools may have a potential role in the recruitment of patients in future intracerebral hemorrhage trials.

A Multicenter Phase IV Study to Investigate the Immunogenicity of Recombinant Human Follicle-Stimulating Hormone and Its Impact on Clinical Outcomes in Females Undergoing Controlled Ovarian Stimulation.

CONTEXT: Therapeutic proteins can cause immune responses, which may have clinical implications. AIMS: The aim of the study was to assess the immunogenicity of recombinant human follicle-stimulating hormone (r-hFSH), when used for controlled ovarian stimulation (COS). SETTINGS AND DESIGN: Prospective, multicenter study conducted at reproductive medicine clinics in India and Vietnam. MATERIALS AND METHODS: A total of 285 women, aged 20-40 years, undergoing 354 COS cycles for either intrauterine insemination (IUI) or in vitro fertilization (IVF) were studied. The primary outcome measure was the incidence of development of anti-drug antibodies (ADA) and their neutralization potential. Other outcome measures were follicle development, dose and duration of r-hFSH, positive serum pregnancy test, clinical pregnancy, cycle cancellation, and adverse events (AEs). STATISTICAL ANALYSIS USED: A sample size of 250 was planned. Descriptive statistics are presented. RESULTS: Four patients tested positive for ADA after r-hFSH administration at different time points; all of them tested negative, subsequently. None were found to have neutralization potential. The mean dose and duration of r-hFSH were 816 IU and 8.1 days in IUI and 2183 IU and 9.5 days in IVF, respectively. The serum and clinical pregnancy rates were 12.4% and 11.6% in IUI and 32.7% and 29.9% in IVF cycles, respectively. Seven AEs were reported, including two cases of ovarian hyperstimulation syndrome; two AEs were judged to be serious. CONCLUSIONS: The tested r-hFSH has very low immunogenic potential and did not lead to the development of neutralizing antibodies. The overall efficacy and safety of the drug were in-line with existing literature data, and no specific clinical impact of immunogenicity could be identified.