The bibliometric analysis of studies on intracytoplasmic sperm injection from 2002 to 2021.

Background: Infertility is estimated to occur in 1 out of every 4-7 couples. Intracytoplasmic sperm injection (ICSI), a type of assisted reproduction introduced in 1992, has been used across the world for almost all indications of infertility, yielding high pregnancy rates. There is a growing concern worldwide about ICSI since semen quality has declined in recent years, accompanied with the potential risks of this technology. This study aims to analyze the current status and hotspots of ICSI via a bibliometric analysis. Methods: We retrieved publications on ICSI from the Web of Science Core Collection database from 2002 to 2021. CiteSpace was used to summarize knowledge mapping of subject categories, keywords, and co-citation relationships with the strongest citation bursts. VOSviewer was used to explore co-citation and co-occurrence relationships for countries, organizations, references, authors, and keywords. Results: A total of 8271 publications were analyzed between 2002 and 2021. The major findings are as follows: the USA, China, Italy, Japan, and Belgium are the top five prolific countries. The Free University of Brussels, University of Copenhagen, University of Valencia, Ghent University, and the University of California San Francisco are the top five contributing organizations. Fertility and Sterility and Human Reproduction are the most productive and cited journals. The hotspot topics are risks of ICSI, oocyte preservation, live birth rate, infertile men, and embryo quality in the past two decades. Conclusion: This study presents a research overview of ICSI from different perspectives. These findings will contribute to a better understanding of the current status of ICSI research and provide hotspots and trends for future studies.

Safety of COVID-19 vaccination in women undergoing IVF/ICSI treatment - Clinical study and systematic review.

Background: It was suggested that vaccination in general might affect reproductive health. Safety of COVID-19 vaccination in women undergoing assisted reproductive techniques (ART) treatment is not well established. Methods: We performed a retrospective study including 536 women undergoing fresh embryo transfer after IVF/ICSI treatment in a huge IVF center in southern China to investigate the effect of COVID-19 vaccination on oocyte maturation, fertilization rate, blastulation rate, implantation rate, clinical pregnancy rate and miscarriage rate. In addition, we performed a systematic review of existing studies on the safety of COVID-19 vaccination in women undergoing ART treatment. Results: In our study, 268 women received inactivated or recombinant COVID-19 vaccination and 268 controls were enrolled based on propensity score matching. We observed a decreased fertilization rate and signs for impaired oocyte maturation in vaccinated women. Besides our study, there were 15 studies analyzing the safety of COVID-19 vaccination in women undergoing ART treatment. For the mRNA vaccines, no adverse signals were reported concerning oocyte maturation, fertilization rate, blastulation rate, implantation rate, clinical pregnancy rate and miscarriage rate. In women being vaccinated with an inactivated vaccine, implantation rate, clinical pregnancy rate and miscarriage rate were not affected, whereas oocyte maturation and fertilization rate were impaired. Conclusions: Vaccination against COVID-19 in women undergoing ART treatment seems to be safe especially for women getting mRNA vaccines. The effects on oocyte maturation and fertilization rate of inactivated and recombinant COVID-19 vaccinations might be a safety signal and need further investigation and independent confirmation.

Necrozoospermia: The tree that hides the forest.

BACKGROUND: Necrozoospermia is a condition found in 0.2%-0.4% of male infertility cases. The causes of necrozoospermia are multiple: they can be related to testicular and/or post-testicular damage. Additionally, these causes most often involve the production of reactive oxygen species (ROS) and/or sperm DNA fragmentation (SDF) which can reduce the chances of spontaneous pregnancy or affect the outcome of assisted reproductive technologies. OBJECTIVE: To focus on potential etiologies of necrozoospermia, its diagnosis and its therapeutic management especially before the employment of ICSI. METHODS: Authors searched PubMed/Medline, Web of Science, Cochrane Library, Google and Institutional websites for medical subheading terms and free text words referred to "necrozoospermia", "sperm vitality", "sperm viability", SDF and "ICSI". RESULTS: We identified 12 main etiologies of necrozoospermia responsible for either a decrease of sperm vitality, a mild, a moderate or a severe necrozoospermia. In case of a confirmed decreased vitality, a thorough check-up should be conducted and if available, etiological treatment should be proposed. Therapeutic management could also include repeated ejaculations, drug treatments, the use of ICSI with ejaculated or surgically extracted spermatozoa in case of a non-treatable necrozoospermia. DISCUSSION AND CONCLUSION: The potential causes of necrozoospermia should be investigated because many of them could be corrected, thus avoiding the use of ICSI. Moreover, if ICSI procedure remains necessary, the therapeutic management of necrozoospermia could also improve the chances of success by reducing oxidative stress and/or SDF.

Investigating the impact of SARS-CoV-2 infection on basic semen parameters and in vitro fertilization/intracytoplasmic sperm injection outcomes: a retrospective cohort study.

BACKGROUND: This study aimed to evaluate the influences of SARS-CoV-2 infection on semen parameters and investigate the impact of the infection on in vitro fertilization (IVF) outcomes. METHODS: This retrospective study enrolled couples undergoing IVF cycles between May 2020 and February 2021 at Tongji Hospital, Wuhan. Baseline characteristics were matched using propensity score matching. Participants were categorized into an unexposed group (SARS-COV-2 negative) and exposed group (SARS-COV-2 positive) based on a history of SARS-CoV-2 infection, and the populations were 148 and 50 after matching, respectively. IVF data were compared between the matched cohorts. Moreover, semen parameters were compared before and after infection among the infected males. The main measures were semen parameters and IVF outcomes, including laboratory and clinical outcomes. RESULTS: Generally, the concentration and motility of sperm did not significantly differ before and after infection. Infected males seemed to have fewer sperm with normal morphology, while all values were above the limits. Notably, the blastocyst formation rate and available blastocyst rate in the exposed group were lower than those in the control group, despite similar mature oocytes rates, normal fertilization rates, cleavage rates, and high-quality embryo rates. Moreover, no significant differences were exhibited between the matched cohorts regarding the implantation rate, biochemical pregnancy rate, clinical pregnancy rate, or early miscarriage rate. CONCLUSIONS: The results of this retrospective cohort study suggested that the semen quality and the chance of pregnancy in terms of IVF outcomes were comparable between the males with a history of SARS-CoV-2 infection and controls, although a decreased blastocyst formation rate and available blastocyst rate was observed in the exposed group, which needs to be reinforced by a multicenter long-term investigation with a larger sample size.

Immediate versus postponed frozen embryo transfer after IVF/ICSI: a systematic review and meta-analysis.

BACKGROUND: In Europe, the number of frozen embryo transfer (FET) cycles is steadily increasing, now accounting for more than 190 000 cycles per year. It is standard clinical practice to postpone FET for at least one menstrual cycle following a failed fresh transfer or after a freeze-all cycle. The purpose of this practice is to minimise the possible residual negative effect of ovarian stimulation on the resumption of a normal ovulatory cycle and receptivity of the endometrium. Although elective deferral of FET may unnecessarily delay time to pregnancy, immediate FET may be inefficient in a clinical setting, following an increased risk of irregular ovulatory cycles and the presence of functional cysts, increasing the risk of cycle cancellation. OBJECTIVE AND RATIONALE: This review explores the impact of timing of FET in the first cycle (immediate FET) versus the second or subsequent cycle (postponed FET) following a failed fresh transfer or a freeze-all cycle on live birth rate (LBR). Secondary endpoints were implantation, pregnancy and clinical pregnancy rates (CPR) as well as miscarriage rate (MR). SEARCH METHODS: We searched PubMed (MEDLINE) and EMBASE databases for MeSH and Emtree terms, as well as text words related to timing of FET, up to March 2020, in English language. There were no limitations regarding year of publication or duration of follow-up. Inclusion criteria were subfertile women aged 18-46 years with any indication for treatment with IVF/ICSI. Studies on oocyte donation were excluded. All original studies were included, except for case reports, study protocols and abstracts only. Covidence, a Cochrane-tool, was used for sorting and screening of literature. Risk of bias was assessed using the Robins-I tool and the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation framework. OUTCOMES: Out of 4124 search results, 15 studies were included in the review. Studies reporting adjusted odds ratios (aOR) for LBR, CPR and MR were included in meta-analyses. All studies (n = 15) were retrospective cohort studies involving a total of 6,304 immediate FET cycles and 13,851 postponed FET cycles including 8,019 matched controls. Twelve studies of very low to moderate quality reported no difference in LBR with immediate versus postponed FET. Two studies of moderate quality reported a statistically significant increase in LBR with immediate FET and one small study of very low quality reported better LBR with postponed FET. Trends in rates of secondary outcomes followed trends in LBR regarding timing of FET. The meta-analyses showed a significant advantage of immediate FET (n =2,076) compared to postponed FET (n =3,833), with a pooled aOR of 1.20 (95% CI 1.01-1.44) for LBR and a pooled aOR of 1.22 (95% CI 1.07-1.39) for CPR. WIDER IMPLICATIONS: The results of this review indicate a slightly higher LBR and CPR in immediate versus postponed FET. Thus, the standard clinical practice of postponing FET for at least one menstrual cycle following a failed fresh transfer or a freeze-all cycle may not be best clinical practice. However, as only retrospective cohort studies were assessed, the presence of selection bias is apparent, and the quality of evidence thus seems low. Randomised controlled trials including data on cancellation rates and reasons for cancellation are highly needed to provide high-grade evidence regarding clinical practice and patient counselling.

Failure to Detect Viral RNA in Follicular Fluid Aspirates from a SARS-CoV-2-Positive Woman.

Although there is no known difference between the clinical manifestations of SARS-CoV-2 in pregnant and non-pregnant women based on the studies published until now, in vitro fertilization (IVF) treatments were suspended during the pandemic due to uncertainties with the suggestions of associated societies. However, we do not have enough data on the exact effects of SARS-CoV-2 on fertility and pregnancy and whether there are damaging effects on IVF outcome. There is no available evidence about the transmission of SARS-CoV-2 by either sexual way or through intrauterine insemination (IUI) or IVF. Up until now, there is no report to document the presence or absence of viral RNA in follicular fluid of SARS-CoV-2-positive women. In this paper, we present a case of oocyte retrieval from a SARS-CoV-2-positive woman and the search for viral RNA by polymerase chain reaction (PCR) in the follicular fluid aspirates.

Absence of SARS-CoV-2 (COVID-19 virus) within the IVF laboratory using strict patient screening and safety criteria.

RESEARCH QUESTION: Is there a risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral exposure and potential cross-contamination from follicular fluid, culture media and vitrification solution within the IVF laboratory using strict patient screening and safety measures? DESIGN: This was a prospective clinical study. All women undergoing transvaginal oocyte retrieval were required to have a negative SARS-CoV-2 RNA test 3-5 days prior to the procedure. Male partners were not tested. All cases used intracytoplasmic sperm injection (ICSI). The first tube of follicular fluid aspirated during oocyte retrieval, drops of media following removal of the embryos on day 5, and vitrification solution after blastocyst cryopreservation were analysed for SARS-CoV-2 RNA. RESULTS: In total, medium from 61 patients, vitrification solution from 200 patients and follicular fluid from 300 patients was analysed. All samples were negative for SARS-CoV-2 viral RNA. CONCLUSIONS: With stringent safety protocols in place, including testing of women and symptom-based screening of men, the presence of SARS-CoV-2 RNA was not detected in follicular fluid, medium or vitrification solution. This work demonstrates the possibility of implementing a rapid laboratory screening assay for SARS-CoV-2 and has implications for safe laboratory operations, including cryostorage recommendations.

The effect of semen collection location and time to processing on sperm parameters and early IVF/ICSI outcomes.

PURPOSE: We aimed to assess whether home collection and increased time to semen processing are associated with altered sperm parameters, fertilization rates (FR), day 5 usable quality blastocyst development rates (D5-UQBR), or pregnancy rates (PR) in patients undergoing IVF/ICSI. METHODS: This was a retrospective cohort study of patients undergoing IVF/ICSI before the coronavirus disease 2019 (COVID-19) pandemic ("clinic" collection, n = 119) and after COVID-19 ("home" collection, n = 125) at an academic fertility practice. Home collection occurred within 2 h of semen processing. Patient sperm parameters, FR (#2PN/MII), D5-UQBR (# transferable and freezable quality blastocysts/# 2PN), and PR in fresh transfer cycles were compared between clinic and home groups with t-tests. The association between time to processing on outcomes was assessed with regression modeling, controlling for potential confounders. RESULTS: Mean male age was 37.9 years in the clinic group and 37.2 years in the home group (p = 0.380). On average, men were abstinent for 3.0 days (SD 1.7) in the clinic group and 4.1 days (SD 5.4) in the home group (p = 0.028). Mean time to semen processing was 35.7 min (SD 9.4) in the clinic group and 82.6 min (SD 33.8) in the home group (p < 0.001). There was no association between collection location and increased time to processing on sperm motility, total motile count, FR, D5-UQBR, or PR. CONCLUSIONS: Our data suggest that increased time to processing up to 2 h with home semen collection does not negatively impact sperm parameters or early IVF/ICSI outcomes.

High-security closed devices are efficient and safe to protect human oocytes from potential risk of viral contamination during vitrification and storage especially in the COVID-19 pandemic.

PURPOSE: The main purpose and research question of the study are to compare the efficacy of high-security closed versus open devices for human oocytes' vitrification. METHODS: A prospective randomized study was conducted. A total of 737 patients attending the Infertility and IVF Unit at S.Orsola University Hospital (Italy) between October 2015 and April 2020 were randomly assigned to two groups. A total of 368 patients were assigned to group 1 (High-Security Vitrification™ - HSV) and 369 to group 2 (Cryotop® open system). Oocyte survival, fertilization, cleavage, pregnancy, implantation, and miscarriage rate were compared between the two groups. RESULTS: No statistically significant differences were observed on survival rate (70.3% vs. 73.3%), fertilization rate (70.8% vs. 74.9%), cleavage rate (90.6% vs. 90.3%), pregnancy/transfer ratio (32.0% vs. 31.8%), implantation rate (19.7% vs. 19.9%), nor miscarriage rates (22.1% vs. 21.5%) between the two groups. Women's mean age in group 1 (36.18 ± 3.92) and group 2 (35.88 ± 3.88) was not significantly different (P = .297). A total of 4029 oocytes were vitrified (1980 and 2049 in groups 1 and 2 respectively). A total of 2564 were warmed (1469 and 1095 in groups 1 and 2 respectively). A total of 1386 morphologically eligible oocytes were inseminated by intracytoplasmic sperm injection (792 and 594 respectively, P = .304). CONCLUSIONS: The present study shows that the replacement of the open vitrification system by a closed one has no impact on in vitro and in vivo survival, development, pregnancy and implantation rate. Furthermore, to ensure safety, especially during the current COVID-19 pandemic, the use of the closed device eliminates the potential samples' contamination during vitrification and storage.

COVID-19 and assisted reproductive technology services: repercussions for patients and proposal for individualized clinical management.

The prolonged lockdown of health services providing high-complexity fertility treatments -as currently recommended by many reproductive medicine entities- is detrimental for society as a whole, and infertility patients in particular. Globally, approximately 0.3% of all infants born every year are conceived using assisted reproductive technology (ART) treatments. By contrast, the total number of COVID-19 deaths reported so far represents approximately 1.0% of the total deaths expected to occur worldwide over the first three months of the current year. It seems, therefore, that the number of infants expected to be conceived and born -but who will not be so due to the lockdown of infertility services- might be as significant as the total number of deaths attributed to the COVID-19 pandemic. We herein propose remedies that include a prognostic-stratification of more vulnerable infertility cases in order to plan a progressive restart of worldwide fertility treatments. At a time when preventing complications and limiting burdens for national health systems represent relevant issues, our viewpoint might help competent authorities and health care providers to identify patients who should be prioritized for the continuation of fertility care in a safe environment.