Intracytoplasmic sperm injection versus conventional in vitro fertilisation in couples with males presenting with normal total sperm count and motility.

BACKGROUND: Starting over 40 years ago, in vitro fertilisation (IVF) has become the cornerstone for fertility treatment. Since then, in 1992, Palermo and colleagues successfully applied the technique intracytoplasmic sperm injection (ICSI) to benefit couples where conventional in vitro fertilisation (c-IVF) and sub-zonal insemination (SUZI) proved unsuccessful. After this case report, ICSI has become the treatment of choice for couples with severe male factor subfertility. Over time, ICSI has been used in the treatment of couples with mild male and even unexplained infertility. This review is an update of the review, first published in 1999, comparing ICSI with c-IVF for couples with males presenting with normal total sperm count and motility. OBJECTIVES: To evaluate the effectiveness and safety of ICSI relative to c-IVF in couples with males presenting with normal total sperm count and motility. SEARCH METHODS: We searched the following databases and trial registers: Cochrane Central Register of Controlled Trials (CENTRAL), Embase (excerpta Medica Database), MEDLINE (Medical Literature Analysis and Retrieval System Online) and PsycINFO (Psychological literature database) for articles between January 2010 and 22 February 2023. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared ICSI with c-IVF in couples with males presenting with normal total sperm count and motility. DATA COLLECTION AND ANALYSIS: We used standard methodical procedures recommended by Cochrane. The primary review outcomes were live birth and adverse events. Secondary outcomes included clinical pregnancy, viable intrauterine pregnancy and miscarriage. MAIN RESULTS: The original review published in 2003 included one RCT. In this 2023 update, we identified an additional two RCTs totalling a cohort of 1539 couples, comparing ICSI with c-IVF techniques. Two studies reported on live birth. Using the GRADE method, we assessed the certainty of evidence and reported evidence as low-certainty for live birth. We are uncertain of the effect of ICSI versus c-IVF for live birth rates (risk ratio (RR) 1.11, 95% confidence interval (CI 0.94 to 1.30, I2 = 0%, 2 studies, n = 1124, low-certainty evidence). The evidence suggests that if the chance of live birth following c-IVF is assumed to be 32%, the chance of live birth with ICSI would be between 30% and 41%. For adverse events; multiple pregnancy, ectopic pregnancy, pre-eclampsia and prematurity, there was probably little or no difference between the two techniques. No study reported the primary outcome stillbirth. For secondary outcomes, we are uncertain of the effect of ICSI versus c-IVF for clinical pregnancy rates (RR 1.00, 95% CI 0.88 to 1.13, I2 = 45%, 3 studies, n = 1539, low-certainty evidence). Comparison of viable intrauterine pregnancy rates showed probably little or no difference between ICSI and c-IVF (RR 1.00, 95% CI 0.86 to 1.16, I2=75%, 2 studies, n = 1479 couples, moderate-certainty evidence). The high heterogeneity may have been caused by one older study conducted when protocols were less rigorous. The evidence suggests that if the chance of viable intrauterine pregnancy following c-IVF is assumed to be 33%, the chance of viable intrauterine pregnancy with ICSI would be between 28% and 38%. Miscarriage rates also showed probably little or no difference between the two techniques. AUTHORS' CONCLUSIONS: The current available studies that compare ICSI and c-IVF in couples with males presenting with normal total sperm count and motility, show neither method was superior to the other, in achieving live birth, adverse events (multiple pregnancy, ectopic pregnancy, pre-eclampsia and prematurity), also alongside secondary outcomes, clinical pregnancy, viable intrauterine pregnancy or miscarriage.

The impact of COVID-19 mitigation measures on fertility patients and clinics around the world.

RESEARCH QUESTION: What is the impact of the response to COVID-19 on the management of fertility treatments and clinical practice around the world? DESIGN: Fertility clinic associates around the world were approached. They completed an online survey containing 33 questions focused on the country's response to the COVID-19 pandemic. Known fertility clinic associates that were contacted comprised scientific directors, medical directors and laboratory managers. RESULTS: There were 43 individual country responses from Asia (13), Africa (3), Europe (17), North America (3), Oceania (2) and South America (5). In nine countries, clinics followed their government body recommendations, in 22 countries there was a combination of recommendations, in 3 countries changes were made by clinic initiative, and 9 countries did not specify. In 34 countries IVF/intracytoplasmic sperm injection (ICSI) and frozen embryo transfer (FET) treatments had an average delay of 56 days (IVF/ICSI) (minimum 0, maximum 160) and 57 days (FET) (minimum 0, maximum 166 days). During the shutdown, the number of freeze-all cycles increased in 22 countries. Only 23 countries reported patients having to undergo a SARS-CoV-2 test, and 20 countries did not report any COVID-19 testing in their clinic. Additional support counselling was offered in 28 countries, partner restrictions at clinics were reported in 41 countries and time between patients' appointments was increased in 39 countries. CONCLUSIONS: The implications of COVID-19 mitigation measures proved the need for government societies to introduce a set protocol that includes requirements such as increased patient counselling and additional guidelines for prioritizing couples who need care most urgently.

User-centered design of multi-gene sequencing panel reports for clinicians.

The objective of this study was to develop a high-fidelity prototype for delivering multi-gene sequencing panel (GS) reports to clinicians that simulates the user experience of a final application. The delivery and use of GS reports can occur within complex and high-paced healthcare environments. We employ a user-centered software design approach in a focus group setting in order to facilitate gathering rich contextual information from a diverse group of stakeholders potentially impacted by the delivery of GS reports relevant to two precision medicine programs at the University of Maryland Medical Center. Responses from focus group sessions were transcribed, coded and analyzed by two team members. Notification mechanisms and information resources preferred by participants from our first phase of focus groups were incorporated into scenarios and the design of a software prototype for delivering GS reports. The goal of our second phase of focus group, to gain input on the prototype software design, was accomplished through conducting task walkthroughs with GS reporting scenarios. Preferences for notification, content and consultation from genetics specialists appeared to depend upon familiarity with scenarios for ordering and delivering GS reports. Despite familiarity with some aspects of the scenarios we proposed, many of our participants agreed that they would likely seek consultation from a genetics specialist after viewing the test reports. In addition, participants offered design and content recommendations. Findings illustrated a need to support customized notification approaches, user-specific information, and access to genetics specialists with GS reports. These design principles can be incorporated into software applications that deliver GS reports. Our user-centered approach to conduct this assessment and the specific input we received from clinicians may also be relevant to others working on similar projects.

The dead salmon strikes again: Reports of unconscious processing in the hippocampus may reflect Type-I error.

Steinkrauss and Slotnick (2024) reviewed neuroimaging studies linking the hippocampus with implicit memory. They conclude that there is no convincing evidence that the hippocampus is associated with implicit memory because prior studies are confounded by explicit memory (among other factors). Here, we ask a different yet equally important question: do reports of unconscious hippocampal activity reflect a Type-I error (i.e. a false positive)? We find that 39% of studies linking the hippocampus with implicit memory (7 of 18) do not report correcting for multiple comparisons. These results indicate that many unconscious hippocampal effects may reflect a Type-I error.

The rate of undetectable genetic causes by Cell-free DNA test in congenital heart defects.

OBJECTIVE: The study aimed to estimate the rate of genetic causes that were undetectable by Cell-free DNA (cfDNA) test in prenatally diagnosed congenital heart defect (CHD) cases based on an assumption that cfDNA would accurately detect common aneuploidies including trisomy 21/18/13/45X, and del22q11.2. METHODS: This study included prenatally diagnosed CHD cases with diagnostic genetic results. The possibility of false-positive/negative results from cfDNA testing was discarded. Thus, cfDNA results would be positive in common aneuploidies or del22q11.2 and negative in normal diagnostic genetic testing results or other genetic conditions. The rate of genetic causes that were undetectable by cfDNA test was estimated for all cases as well as for CHD subgroups. RESULTS: Of 302 cases, 98 (34.8%) had a type of genetic abnormalities, with 67 having common aneuploidies or del22q11.2 and 31 having other genetic conditions. The rate of genetic causes that were undetectable by cfDNA test in CHD cases was 13.2% among those with assumingly negative cfDNA screen results and 10.3% among the entire study population. These rates were similar between CHD subgroups (p > .05). The rate of genetic causes that were undetectable by cfDNA test was higher in the non-isolated cases than in the isolated ones among those with assumingly negative-screen results (20.5% and 9.9%, respectively, p = .025). CONCLUSION: In prenatally diagnosed CDH cases, a significant number of chromosomal abnormalities are still identified after diagnostic testing even if cfDNA screen is negative, and thus it is important to extensively counsel patients with negative cfDNA screen carrying a CHD-affected fetus.

Using Workflow Modeling to Identify Areas to Improve Genetic Test Processes in the University of Maryland Translational Pharmacogenomics Project.

Delivering genetic test results to clinicians is a complex process. It involves many actors and multiple steps, requiring all of these to work together in order to create an optimal course of treatment for the patient. We used information gained from focus groups in order to illustrate the current process of delivering genetic test results to clinicians. We propose a business process model and notation (BPMN) representation of this process for a Translational Pharmacogenomics Project being implemented at the University of Maryland Medical Center, so that personalized medicine program implementers can identify areas to improve genetic testing processes. We found that the current process could be improved to reduce input errors, better inform and notify clinicians about the implications of certain genetic tests, and make results more easily understood. We demonstrate our use of BPMN to improve this important clinical process for CYP2C19 genetic testing in patients undergoing invasive treatment of coronary heart disease.