Is controlled ovarian stimulation and insemination an effective treatment in older women with male partners with decreased total motile sperm counts?

OBJECTIVE: To assess the effect of the total motile sperm counts (TMSC) on the success of controlled ovarian stimulation (COH) and intra-uterine insemination (IUI) in women 38-42 years of age. STUDY DESIGN: A database of all women aged 38-42 years who underwent IUI with stimulation at a University Reproductive Centre between 2009 and 2018 inclusive was developed. Including stimulation with clomiphene citrate, letrozole or gonadotropins and divided into TMSC 5.00-10.0 mil and < 5.00 mil. Statistics were compared with multivariate logistic regression, t tests or Chi-squared tests. RESULTS: A total of 397 cycles of IUI in 397 patients were included, of which, 190 cycles with TMSC 5.00-10.0 and 207 cycles with TMSC < 5.00. There were no statistical differences in the baseline characteristics between the two groups including: age (P = 0.2), gravidity (P = 0.7), parity (P = 0.6), basal FSH (P = 0.2), basal E2 (P = 0.4), antral follicular count (P = 0.5) and the number of mature follicles stimulated (P = 0.2). As expected, TMSC was 7.6 ± 1.5 mil in the first group and 2.4 ± 1.6 mil in the second group (P < 0.0001). The clinical pregnancy rate per cycle in the 5.01-10.00 TMSC group was 9.5 vs. 3.4% when TMSC < 5.00 (P = 0.01). When evaluating only women 40-42 years of age (99 women in the 5.00-10.00 TMSC group and 95 in the group of TMSC < 5.00); the pregnancy rates were not statistically different between the two groups (7 vs. 7.3%, P = 1), nor was the clinical pregnancy rate (5 vs. 6.3%, P = 0.7). CONCLUSIONS: Women 38-39 years of age have poorer outcomes at COH/IUI when TMSC < 5 million than if it is 5-10 million. Once a woman is 40 years of age, this effect is lost. With TMSC 5-10 million, women 38-39 years of age have respectable outcomes at COH/IUI. Clinical pregnancy rates are very low in women 40 years of age with TMSC ≤ 10 million or 38-39 years old with TMSC < 5 million and other treatments should be offered.

How to dose follitropin delta for the first insemination cycle according to the ESHRE and ASRM guidelines; a retrospective cohort study.

BACKGROUND: Follitropin Delta (FD) is indicated exclusively for in-vitro fertilization however, being a gonadotropin it could be used for other purposes. A dosing algorithm exists for FD and IVF but is needed for intrauterine insemination (IUI) cycles. The objective of this study is to determine dosing for FD for the first controlled ovarian hyperstimulation (COH) cycle according to current stimulation guidelines. RESULTS: A retrospective study of 157 subjects from a single university fertility center from January 2017 to March 2020, was performed. All patients stimulated with FD for IUI were included. The number of failed, normal, or overstimulation cycles was determined based on stimulating not more than 2 mature follicles. We then stratified the group based on the AFC, AMH, and body weight. Of 157 subjects, 49% stimulated correctly, 5.6% failed and 45.4% overstimulated. An analysis of the COH IUI cycles based on stratification and over or lack of stimulation per published guidelines found that women with a bodyweight < 80 kg or AMH ≥ 1.5 ng/ml or AFC ≥ 10 initially stimulate with FD 2.0 to 3.0mcg daily. For women with an AFC of 6-9 stimulate with Follitropin Delta 3.0mcg daily. For women with an AFC < 6 or serum AMH < 1.5 ng/ml stimulate with FD 3.0-4.0mcg daily. For women with body weight > 80 kg stimulate initially with daily with 4.0-6.0mcg FD. CONCLUSIONS: Follitropin Delta can be used safely for controlled ovarian stimulation and insemination at doses easily dispensed by the current methods of delivery, within the current published guidelines for follicle development.

The feasibility of fully automated pacemaker advise in treating atrial tachyarrhythmias.

BACKGROUND: Modern pacemakers continuously store significant cardiac-related events. Interpreting these data and reprogramming the pacemaker can be time-consuming and demands expert knowledge. A software-based expert system, the therapy advisor (TA), was developed, which analyzes stored data and provides reprogramming recommendations. This study addresses whether pacemaker experts consider the messages that are automatically generated appropriate in the management of atrial tachyarrhythmias/atrial fibrillation (AT/AF). METHODS: This observational, international, multicenter study follows 150 patients with suspected or documented atrial arrhythmias who received a dual-chamber pacemaker (model Vitatron T-70, Medtronic Inc., Minneapolis, MN, USA) incorporating the TA. The TA summarizes technical and clinical data stored in the pacemaker into key messages and may suggest programming changes. Twenty-five cardiologists examined their patients per normal practice during two follow-up visits. They reported the therapy changes they deemed necessary without initially reviewing the TA messages. Next, they rated their satisfaction with and the clinical relevance of the TA messages and recorded the final therapy changes. RESULTS: The TA generated (mostly AT/AF-related) main observations in 49% and programming advice in 33% of the patients. The experts rated 95% of the TA messages as satisfactory and deemed therapy changes necessary in roughly half the patients. Pacemaker changes in AT/AF therapy or general settings were prompted primarily by the diagnostic information stored in the device. Medication changes were mostly led by the symptoms reported by the patient. CONCLUSION: This study demonstrates that experienced cardiologists agree with 95% of the observations and programming suggestions that the TA automatically generates.

Opportunistic screening for atrial fibrillation with a single lead device in geriatric patients.

OBJECTIVE: To determine the diagnostic yield of repeated screening for atrial fibrillation (AF) among geriatric patients. METHODS: A pragmatic prospective cohort study into applying opportunistic screening for AF with a handheld single lead ECG device (SLD) in a geriatric cohort. Consecutive patients of 65 years old and older visiting the geriatric outpatient clinic were eligible for inclusion. A 12 lead ECG was performed, followed by measurements with the SLD during every visit to the geriatric outpatient clinic. A frailty index was based on the accumulation of deficits model. RESULTS: 478 patients were eligible. Patients were excluded if they did not give informed consent (17 patients), had a pacemaker or implantable cardioverter defibrillator (20 patients), or had incomplete medical files (two patients). After exclusion, 439 patients participated in this study. The mean age was 78 years (range 65 to 100 years), 54% were female. AF was known in 89 patients (20%), first detected on the baseline ECG in four patients (1%) and first detected with the SLD in 20 patients (5%) during follow up visits. Sensitivity of the SLD was 90.0%, specificity 99.0%, negative predictive value 99.7%, and positive predictive value 73.5%. Most patients (82%) with AF were frail and 53% were severely frail. CONCLUSION: Repeated screening in geriatric patients has a five times higher diagnostic yield than usual care. It was easily combined with usual care. Because of the positive predictive value of 73.5%, it remains necessary to confirm AF with a 12 lead ECG or 24-h Holter monitoring.

Human oocytes harboring damaged DNA can complete meiosis I.

OBJECTIVE: To determine whether human oocytes possess a checkpoint to prevent completion of meiosis I when DNA is damaged. DESIGN: DNA damage is considered a major threat to the establishment of healthy eggs and embryos. Recent studies found that mouse oocytes with damaged DNA can resume meiosis and undergo germinal vesicle breakdown (GVBD), but then arrest in metaphase of meiosis I in a process involving spindle assembly checkpoint (SAC) signaling. Such a mechanism could help prevent the generation of metaphase II (MII) eggs with damaged DNA. Here, we compared the impact of DNA-damaging agents with nondamaged control samples in mouse and human oocytes. SETTING: University-affiliated clinic and research center. PATIENT(S): Patients undergoing ICSI cycles donated GV-stage oocytes after informed consent; 149 human oocytes were collected over 2 years (from 50 patients aged 27-44 years). INTERVENTIONS(S): Mice and human oocytes were treated with DNA-damaging drugs. MAIN OUTCOME MEASURE(S): Oocytes were monitored to evaluate GVBD and polar body extrusion (PBE), in addition to DNA damage assessment with the use of γH2AX antibodies and confocal microscopy. RESULT(S): Whereas DNA damage in mouse oocytes delays or prevents oocyte maturation, most human oocytes harboring experimentally induced DNA damage progress through meiosis I and subsequently form an MII egg, revealing the absence of a DNA damage-induced SAC response. Analysis of the resulting MII eggs revealed damaged DNA and chaotic spindle apparatus, despite the oocyte appearing morphologically normal. CONCLUSION(S): Our data indicate that experimentally induced DNA damage does not prevent PBE in human oocytes and can persist in morphologically normal looking MII eggs.

New insights into the initiation of atrial fibrillation: a detailed intraindividual and interindividual analysis of the spontaneous onset of atrial fibrillation using new diagnostic pacemaker features.

BACKGROUND: This study investigated onset scenarios of atrial fibrillation (AF), the first phase of the Atrial Fibrillation Therapy (AFT) trial, to determine potential arrhythmogenic triggers as targets for atrial pacing algorithms that have been proposed for prevention of AF. METHODS AND RESULTS: Ninety-eight patients (58 men; age 65+/-11 years) with recurrent, symptomatic, drug-refractory AF and a conventional pacemaker indication in 31 of 98 received a dual-chamber pacemaker. Using novel diagnostic pacemaker features AF onset scenarios were prospectively evaluated in 612 AF episodes during a 2-month monitoring period, with atrial pacing limited to 40 bpm. The most common onset scenario was premature atrial complexes (PACs) before AF (48% onsets per patient), followed by bradycardia (33%), sudden onset (17%), and tachycardia (0%). Combinations of onset scenarios were frequent (median 2 different scenarios per patient). A main study finding was the significance of repetitive AF, with 33% of onsets per patient being initiated within 5 minutes of a previous AF episode. Sudden onsets were more frequent among patients with than without repetitive AF (24% versus 0% onsets per patient, P=0.011), whereas the proportion of PACs before AF was not statistically different (50% versus 37%, P=0.52); however, patients with repetitive AF had more PACs per hour (72 versus 29, P=0.023) and a higher number of AF episodes per day (17 versus 0, P=0.001) and were more likely to have at least 1 PAC-related onset (90% versus 53%, P<0.0001). CONCLUSIONS: Novel diagnostic pacemaker features allowed a detailed individual analysis of rate and rhythm changes before AF and thus uncovered a substantial intraindividual and interindividual variability of AF onset scenarios.

Malfunction of the automatic slope adjustment of the QT sensor in patients with normal QT intervals.

DDDR pacemakers with QT driven sensor algorithms may be susceptible to inappropriate pacemaker tachycardia when implanted into patients who have a relatively extended cardiac repolarization. The inability to detect and measure the QT interval at near maximum sensor rate, results in an inappropriate adjustment of the automatic QT slope. Triggering pacemaker induced tachycardia.