Collecting semen samples at home for fertility assessment: time for a new standard?

BACKGROUND: In fertility clinics the standard approach to semen collection involves a private room close to the laboratory to avoid fluctuations in temperature and to control the time between collection and processing. There are still no firm conclusions whether collecting semen at home has any influence on sperm quality and reproductive competence. The purpose of this study was to assess whether the site of semen collection affects semen parameters. METHODS: This retrospective cohort study performed at a tertiary level public fertility center included 8634 semen samples from 5880 men undergoing fertility assessment from 2015 to 2021. The impact of sample collection site was evaluated using a generalized linear mixed model. A subgroup analysis comparing clinic to home collection within the same patient was performed on 1260 samples from 428 men by paired t-test or Wilcoxon Signed Rank Test. RESULTS: Samples collected at home (N.=3240) had significantly higher semen volume, sperm concentration and total sperm count respect to samples collected at clinic (N.=5530) (median (range): 2.9 (0.0-13.9) mL versus 2.9 (0.0-11.5) mL, P=0.016; 24.0 (0.0-252.0) million/mL versus 18.0 (0.0-390.0), P<0.0001; 64.6 (0.0-946.0) million versus 49.3 (0.0-1045.0), P<0.0001, respectively). There was no difference in abstinence period and sperm motility. Paired comparisons of semen characteristics in 428 patients with home-collected (N.=583) and clinic-collected (N.=677) samples confirmed a no negative effect on volume and total sperm count. CONCLUSIONS: Our data provide evidence for a not disadvantage with collection at home.

Hyaluronic acid-sperm selection significantly improves the clinical outcome of couples with previous ICSI cycles failure.

BACKGROUND: Beneficial effects of hyaluronic acid (HA)-based selection of spermatozoa for intracytoplasmic sperm injection (ICSI) are still controversial, and further studies are needed to categorize patients that might benefit from such a method. OBJECTIVE: We investigated whether HA sperm selection improved ICSI outcome of couples with previous ICSI cycle failure. MATERIALS AND METHODS: In this retrospective study, we prospectively collected data of (i) Group 1: 96 couples who performed one failed ICSI cycle ("1st procedure," n = 96) followed by another ICSI cycle ("2nd procedure," n = 101); ii) Group 2: 87 couples who performed one failed ICSI cycle (n = 87) followed by an HA-ICSI cycle (n = 104). Differences between procedures and groups were measured by paired and independent statistical tests, respectively. A generalized linear mixed model analyzed the effect of procedure on the outcomes and the interaction between procedures and groups. RESULTS: Injection of HA-bound sperm significantly improved cleavage rate with respect to standard ICSI (p = 0.026). No evolutive pregnancies were obtained in the 1st ICSI attempts. The 2nd ICSI cycles resulted in successfully seven pregnancies. In HA-ICSI cycles, the better quality of embryos with respect to ICSI (p = 0.034) increased the choice of day 5 embryo transfer (p = 0.030), which resulted in successfully 28 pregnancies. No differences were observed in clinical outcomes of the two ICSI procedures in Group 1, while pregnancy and implantation rates were significantly higher in HA-ICSI with respect to ICSI cycles (p = 0.001, p < 0.0001, respectively). No negative perinatal outcomes were recorded. DISCUSSION: In couples where previous 1st ICSI failed, selection of HA-bound spermatozoa significantly improved clinical outcomes with respect to further standard ICSI. CONCLUSION: This study identified couples with previous ICSI cycles failure as a category of infertile patients that really may benefit from HA sperm selection before ICSI.

Fifteen Year Regional Center Experience in Sperm Banking for Cancer Patients: Use and Reproductive Outcomes in Survivors.

Cancer treatments frequently impair the reproductive ability of patients by damaging spermatogenesis. International guidelines recommend semen cryopreservation to preserve the fertility of oncological adult males and pubertal boys. However, due to the low usage rate of banked samples, not a lot of data on assisted reproductive treatments (ART) success rates in this population and follow-up data for children born are available in the literature. The aims of this study were to report our 15 years of experience, the clinical outcomes of ART as well as neonatal characteristics of babies born. We retrospectively reviewed 682 oncological patients who were referred to our center from 2004 to 2019 for fertility preservation. Over the years, only 26 patients (4%) returned to use their sperm by ART. They were survivors of leukemia and lymphomas (52%), testicular cancer (20%), and other malignant diseases (28%). These couples performed 45 cycles: 34 intracytoplasmic sperm injection (ICSI) plus 11 frozen embryo transfers. A total of 13 children were born, with 35% of the cumulative live-birth delivery rate per couple. No stillbirths or malformations were recorded. These successful findings demonstrated that pregnancy could be safely achieved using frozen-thawed sperm of cancer survivors who cryopreserved before gonadotoxic therapies.

Failure modes and effects analysis for testicular sperm extraction management process.

Failure modes and effects analysis (FMEA) is a proactive risk evaluation to identify and reduce potential failures that may occur during a procedure within a quality management programme. One of the procedures performed in assisted reproduction technology centres is testicular sperm extraction (TESE) as treatment of azoospermic patients. To examine the risks associated with the 'TESE management' process, we applied the FMEA method, before and after implementation of corrective measures defined in a standard operative procedure (SOP). A multidisciplinary team was formed. Possible causes of failures and their potential effects were identified, and risk priority number (RPN) for each failure was calculated. The FMEA team identified 4 process activities, 19 process steps and 19 potential failure modes. The re-evaluation after the corrective measures disclosed a reduction in the number of phases with high/moderate risk (pre-SOP: n = 13; post-SOP: n = 3). Improvements in the traceability system removed 11 out of 13 (85%) steps with a low risk of occurrence. In our experience, FMEA is efficient in helping multidisciplinary groups to strengthen knowledge and awareness on routine processes, identifying critical steps and planning practical improvements for a better compliance with criteria of traceability and conformity of biological samples and patients.

A successful healthy childbirth and an ongoing evolutive pregnancy in a case of partial globozoospermia by hyaluronic acid sperm selection.

We here report a successful healthy childbirth and an ongoing evolutive pregnancy in a case of partial globozoospermia after selection of mature spermatozoa bound to hyaluronic acid (HA). The couple underwent two in vitro fertilisation (IVF) cycles. In the first attempt, 14 MII oocytes were retrieved. Randomly, seven oocytes were injected by conventional PVP-ICSI and seven by HA-ICSI. Fertilised oocytes were 2/7 and 4/7 after PVP-ICSI and HA-ICSI respectively. Transfer of two grade A embryos from HA-ICSI lead to birth of a healthy baby. The surplus embryo of the HA-ICSI group was vitrified at blastocyst stage. The two embryos from PVP-ICSI arrested their development. Two years after the childbirth, the vitrified blastocyst was transferred into the uterus, but implant failed. In the second cycle, 14 MII oocytes were retrieved and they were injected by HA-ICSI. Fertilised oocytes were 10 out of 14 injected oocytes. On day 5, two blastocysts were transferred into uterus and a single evolutive pregnancy is ongoing. On day 6, one blastocyst was vitrified. The remaining surplus embryos arrested their development. A healthy childbirth and an ongoing evolutive pregnancy in two consecutive ICSI attempts of the same couple suggest that HA sperm selection might assist in cases with partial globozoospermia.

Stroop interference task and single-photon emission tomography in anorexia: a preliminary report.

OBJECTIVE: The aim of this preliminary study was to investigate the physiologic substrate of executive function in anorexia nervosa (AN) by assessing the relation between brain perfusion and Stroop interference task (SIT). METHOD: The classical SIT test and brain single-photon emission tomography (SPET) were evaluated in 16 AN females (mean age = 23.69 +/- 8.68 years; mean body mass index [BMI] = 16.19 +/- 1.53 kg/m2). The relation between the two examinations was searched by statistical parametric mapping (SPM 99) with a height threshold of p = .001. RESULTS: An abnormally low or a borderline SIT value was found in 25% of patients. A significant correlation between the SIT score and brain perfusion was found in the superior frontal gyrus of both hemispheres (Brodmann's area [BA] 6 in both hemispheres and BA 8 in the right hemisphere). No correlation was found in the anterior cingulate gyrus. CONCLUSION: BA 6 and BA 8 and the anterior cingulate are believed to be the basis of both error detection and immediate correction. Activity of BA 6 and BA 8 reflects this executive task in AN patients as well, whereas the lack of correlation in the anterior cingulate may suggest its blunted activity in AN patients, similarly to what is shown in other conditions characterized by impaired executive function, such as patients with depression, patients with schizophrenia, and abstinent drug abusers. However, these findings should still be quoted as preliminary, given some limitations of the study design, such as the lack of a control group, and the unfeasibility of controlling some relevant confounding variables, such as psychiatric comorbidity, medication, and the time interval between examinations, mainly deriving from the relatively few patients studied.

Resting SPECT-neuropsychology correlation in very mild Alzheimer's disease.

OBJECTIVE: To investigate the relationships between brain function and some of the most frequently impaired cognitive domains in the first stages of Alzheimer's disease (AD), we searched for correlation between the scores on 3 neuropsychological tests and brain perfusion, assessed by single photon emission computed tomography (SPECT) in patients with very mild AD. METHODS: Twenty-nine consecutive outpatients (mean age 78.2+/-5.5) affected by probable AD in the very mild phase (i.e. with a score > or =20 on the mini-mental state examination, MMSE) underwent brain SPECT with (99m)Tc-ethylcisteinate dimer. For correlative purposes, word list learning (by the selective reminding test, SRT), constructional praxis test (CPT) and visual search test (VST) were chosen a priori out of an extended battery employed to diagnose AD at first patient evaluation. Voxel-based correlation analysis was achieved by statistical parametric mapping (SPM99) with a height threshold of P=0.005. Age, years of education and the MMSE score were inserted in the correlative analysis as confounding variables. RESULTS: The SRT score showed correlation with brain perfusion in 3 clusters of the left hemisphere, including the post-central gyrus, the parietal precuneus, the inferior parietal lobule and the middle temporal gyrus, and in one cluster in the right hemisphere including the middle temporal gyrus and the middle occipital gyrus. The CPT score was significantly correlated with brain perfusion in the parietal precuneus and the posterior cingulate gyrus in the left hemisphere, whereas the VST score gave a significant correlation with brain perfusion in a left cluster including the parietal precuneus and the superior temporal gyrus. CONCLUSIONS: Cognitive impairment in very mild AD is reflected by brain dysfunction in posterior associative areas, with peculiar topographical differences proper of each domain. The parietal precuneus was a common site of correlation of all 3 neuropsychological tests. This region, together with the posterior cingulate and the superficial posterior temporal-parietal cortex, is thought to be affected by disconnection from the mesial temporal lobe, besides being directly affected by increased oxidative stress and by atrophy as well. The impairment of these areas is thought to contribute to cognitive decline in verbal memory, constructional praxis and visual sustained attention which are indeed among the earliest signs of cognitive impairment in AD. SIGNIFICANCE: Assessing the relationships between neuropsychology and brain functional imaging is a key approach to clarify the pathophysiology of cognitive failure in AD; the specificity of these findings in AD remains to be proven through comparison with correlation achieved in matched controls.

Quantitative EEG and perfusional single photon emission computed tomography correlation during long-term donepezil therapy in Alzheimer's disease.

OBJECTIVE: There is an increasing interest in the effects of the acetylcholinesterase inhibitors (AChEIs) in Alzheimer's disease (AD), as investigated by means of objective, neurophysiological tools. In an open-label study, we evaluated the neurophysiological effects of chronic administration of donepezil to AD patients, by means of a correlative approach between quantitative EEG (qEEG) and perfusional brain single photon emission computed tomography (SPECT). METHODS: Sixteen patients (mean age: 74.8+/-7.9 years) with mild to moderate AD (MMSE score >13, mean: 20.7+/-4.6) underwent qEEG and SPECT examinations at the time of diagnosis (t0) and after approximately 1 year of donepezil therapy (t1). The brain SPECT (99mTc-hexamethylpropyleneamine oxime) was performed by means of a high-resolution SPECT camera; the qEEG was recorded from 19 scalp electrodes by average reference and digitized at 512 Hz. The mean frequency (MF) value of the mean power spectrum (fast Fourier transform) from 4 brain regions (one frontal and one temporal-parietal in each hemisphere) was chosen for statistical analysis. Changes in MMSE score and qEEG-MF values between t0 and t1 were assessed by analysis of variance. SPECT differences between t0 and t1, as well as the relationships between SPECT and qEEG changes, were assessed by statistical parametric mapping (SPM 99; height threshold: P=0.001 at cluster level). RESULTS: Between t0 and t1, the MMSE score significantly (P<0.05) decreased (from 20.7+/-4.64 to 19.1+/-5.09; 95% confidence interval: 1.14) and qEEG was unchanged. There was no regional perfusion decrease; a small area of relative perfusion increase was observed, including the right occipital cuneus and the left lingual gyrus. A positive correlation was found between the right frontal MF and brain perfusion in the left superior parietal lobule. A post hoc SPM analysis (height threshold: P=0.01) showed a positive correlation between brain perfusion and each of the 4 qEEG MF values in the left parietal lobe, including the precuneus, the superior parietal lobule, and the post-central gyrus. CONCLUSIONS: The posterior parietal region, which is involved in memory and attention, is often affected by hypoperfusion in AD, as a likely consequence of disconnection from the atrophic mesial temporal cortex. Metabolic activation induced by AChEIs may especially influence this disconnected but still not grossly impaired area, which could be one of the pathophysiological substrates of the cognitive effects of AChEIs. The modest topographical sensitivity of qEEG, reflecting the rather diffuse changes in AD, is further confirmed.

Quantitative EEG changes in Alzheimer patients during long-term donepezil therapy.

Twenty patients affected with probable mild-to-moderate Alzheimer's disease (AD; NINCDS-ADRDA criteria; 14 women and 6 men, mean age 75.2 +/- 7.1 years) who regularly received an oral acetylcholinesterase inhibitor (AChEI; donepezil 5 mg/day; Dz group) were compared with a control group of 11 AD patients (6 women and 5 men, mean age 73.5 +/- 6.0 years) diagnosed and followed up in the pre-AChEIs era (C group). At basal evaluation (t(0)), the 2 groups were comparable for age, education, and severity of disease (Global Deterioration Scale). All patients underwent quantitative EEG (qEEG, average reference, 10-20 International System), and were reexamined about 1 year later (t(1); i.e., after 12.3 +/- 3.6 months the Dz group, and after 13.7 +/- 3.9 months the C group). Log-transformed values of two qEEG bands, i.e. 2-6 and 6.5-12 Hz, were averaged between adjacent channels (frontal F3 and F7, F4 and F8; parietotemporal P3 and T7, P4 and T8) to obtain a qEEG ratio (6.5-12/2-6 Hz.) from one frontal and one temporoparietal region in each hemisphere. Neuropsychological impairment was summarized by the Mini-Mental Status Examination (MMSE). At t(0), both the MMSE score and the qEEG ratio values were somewhat higher in the C than in the Dz group, although nonsignificantly. Between t(0) and t(1), the MMSE score decreased significantly (p < 0.01) more in the C group (-4.36 +/- 2.25) than in the Dz group (-1.45 +/- 2.16), as did the qEEG ratio in the right frontal region (p < 0.01), whereas in the left frontal region the significance level was not reached (p = 0.02). Between t(0) and t(1), the qEEG ratio difference in both frontal regions and in the right temporoparietal region significantly correlated with the MMSE difference (p < 0.01), but neither with time between examinations nor with the difference on the Visual Search Test score. Long-term treatment with Dz led to a lesser deterioration of qEEG, paralleling a milder neuropsychological decline. The effect was significant in frontal regions, possibly because they are relatively spared during the mild-to-moderate phases of the disease.

Effects of long-term Donepezil therapy on rCBF of Alzheimer's patients.

BACKGROUND: The recent introduction of acetylcholinesterase inhibitors (AChEIs) therapy for Alzheimer's Disease (AD) has led to the need to assess the brain's response to the therapy on an objective, neurophysiological basis. Brain perfusion single photon emission computed tomography (SPECT) was used in an open-label study to evaluate the effect of chronic Donepezil administration to a group of patients affected by mild to moderate AD, compared to a group of AD patients not receiving AChEIs and kept under observation for a similar period. METHODS: Twenty-five consecutive patients with probable AD (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria) (19 women, 6 men; mean age: 74.2+/-7.2; mean Mini-Mental State Examination score, MMSE: 19.8+/-3.5) underwent (t0) brain SPECT with 99mTc-hexamethylpropylene-amine-oxime by a brain-dedicated, high-resolution camera and were re-evaluated (t1) after 11+/-2.6 months of chronic Donepezil administration (5mg/day) (treated group). Thirteen AD patients (9 women, 4 men, mean age: 71.4+/-5.7, MMSE score: 20.6+/-3.5) were not treated with AChEIs and served as controls (untreated group). They were subjected to the same evaluation after 13+/-1.4 months as the treated group. Statistical parametric mapping (SPM) was employed to analyse SPECT findings. RESULTS: The MMSE score declined significantly (P<0.01) from t0 to t1 both in untreated (from 20.6+/-3.5 to 17.8+/-4.4) and in treated (from 19.8+/-3.5 to 17.8+/-4.1) group. At t(0), the untreated group showed higher regional cerebral blood flow (rCBF) than the treated group in a frontal and a frontal-parietal region of the left hemisphere. Between t0 and t1, significant rCBF reduction was observed in the temporal lobe and occipital-temporal cortex of the left hemisphere in the untreated group, whereas no significant change was observed in the treated group. The rCBF of the two groups did not significantly differ at t1. By covariate SPM analysis between t0 and t1 in treated patients, MMSE score changes correlated significantly with rCBF changes in a large left frontal-temporal region. CONCLUSIONS: Brain perfusion is preserved in AD patients undergoing chronic Donepezil therapy while it is reduced in untreated patients. SPECT is a promising tool with which to assess the impact of AChEI therapy on brain functioning of AD patients.