Effect of histidine and L-Tyrosine supplementation in maturation medium on in-vitro developmental outcomes of buffalo oocytes.

The present study was designed to investigate the effects of amino acid (histidine and L-Tyrosine) on in vitro maturation (IVM), in vitro fertilization (IVF), cleavage (CR) rates, and in vitro embryonic cultivation (IVC; Morula and Blastocyst stage) in buffaloes. Within two hours of buffalo slaughter, the ovaries were collected and transported to the laboratory. Follicles with a diameter of 2 to 8 mm were aspirated to recover the cumulus oocyte complexes (COCs). Histidine (0.5, 1, and 3 mg/ml) or L-Tyrosine (1, 5, and 10 mg/ml) were added to the synthetic oviductal fluid (SOF) and Ferticult media. The IVM, IVF, CR, and IVC (Morula and Blastocyst) rates were evaluated. The results showed that SOF maturation media containing histidine at 0.5 mg/ml significantly (P ≤ 0.01) improved the oocyte maturation when compared to control and other concentrations. The addition of histidine to FertiCult media at 0.5, 1, and 3 mg/ml did not improve the IVM, IVF, CR, or IVC percentages. However, the embryos in the control group were unable to grow into a morula or blastocyst in the SOF or Ferticult, while addition of L-Tyrosine to the SOF or Ferticult at various concentrations improved IVC (morula and blastocyst rates). There was a significant (P ≤ 0.01) increase in IVM when histidine was added to SOF medium at a concentration of 0.5 mg/ml compared with L-Tyrosine. Also, there were significant (P ≤ 0.01) increases in IVC when L-Tyrosine was added to SOF medium at concentrations of 1 and 10 mg/ml compared with histidine. In conclusion, the supplementation of the SOF and FertiCult with the amino acids histidine and L-Tyrosine improve the maturation rate of oocytes and development of in vitro-produced buffalo embryos.

Electroporation Delivery of Cas9 sgRNA Ribonucleoprotein-Mediated Genome Editing in Sheep IVF Zygotes.

The utilization of electroporation for delivering CRISPR/Cas9 system components has enabled efficient gene editing in mammalian zygotes, facilitating the development of genome-edited animals. In this study, our research focused on targeting the ACTG1 and MSTN genes in sheep, revealing a threshold phenomenon in electroporation with a voltage tolerance in sheep in vitro fertilization (IVF) zygotes. Various poring voltages near 40 V and pulse durations were examined for electroporating sheep zygotes. The study concluded that stronger electric fields required shorter pulse durations to achieve the optimal conditions for high gene mutation rates and reasonable blastocyst development. This investigation also assessed the quality of Cas9/sgRNA ribonucleoprotein complexes (Cas9 RNPs) and their influence on genome editing efficiency in sheep early embryos. It was highlighted that pre-complexation of Cas9 proteins with single-guide RNA (sgRNA) before electroporation was essential for achieving a high mutation rate. The use of suitable electroporation parameters for sheep IVF zygotes led to significantly high mutation rates and heterozygote ratios. By delivering Cas9 RNPs and single-stranded oligodeoxynucleotides (ssODNs) to zygotes through electroporation, targeting the MSTN (Myostatin) gene, a knock-in efficiency of 26% was achieved. The successful generation of MSTN-modified lambs was demonstrated by delivering Cas9 RNPs into IVF zygotes via electroporation.

Effect of Waiting Period on Initial Adverse Vaginal Microbiome Composition in IVF-ICSI Patients.

Background/Objectives: In this observational prospective cohort study, conducted at the Fertility Centre of the University Hospital, Duesseldorf Germany, the spontaneous reversal capacity and the effect of waiting time on an adverse vaginal microbiome profile in subfertile patients were investigated. Methods: Vaginal swabs of 76 patients were obtained before starting a fertility treatment using a commercially available test to perform a microbiome analysis. Patients with a favorable microbiome profile ("medium" or "high profile") according to the manufacturer's algorithm proceeded with the fertility treatment. Patients with an unfavorable microbiome profile ("low profile") postponed their fertility treatment and were sampled up to four times in each successive cycle or until a shift to a more favorable profile was detected. Results: Initially, 54/76 subjects had a high or medium profile and 23/76 had a low profile. Within 3 months, 75% of patients with an initial low profile shifted to a more favorable profile (7/23 dropouts). The presence of Lactobacillus crispatus in the initial sample was associated with a higher likelihood of a spontaneous shift to a more favorable profile. Conclusions: The vaginal microbiome is subject to strong fluctuations. Even an unfavorable microbiome profile can develop into a favorable microbiome profile within a few months without treatment.

Adenomyosis: An Update Concerning Diagnosis, Treatment, and Fertility.

This review article aims to summarize current tools used in the diagnosis of adenomyosis with relative pharmacological and surgical treatment and to clarify the relative association between adenomyosis and infertility, considering the importance of an accurate diagnosis of this heterogeneous disease. Among different reported concepts, direction invagination of gland cells from the basalis endometrium deep into the myometrium is the most widely accepted opinion on the development of adenomyosis. Adenomyosis has been increasingly identified in young women with pain, AUB, infertility, or no symptoms by using imaging techniques such as transvaginal ultrasound and magnetic resonance. Furthermore, adenomyosis often coexists with other gynecological conditions, such as endometriosis and uterine fibroids, increasing the heterogeneity of available data. However, there is no agreement on the definition and classification of adenomyotic lesions from both the histopathology and the imaging points of view, and diagnosis remains difficult and unclear. A standard, universally accepted classification system needs to be implemented to improve our understanding and inform precise diagnosis of the type of adenomyosis. This could be the key to designing RCT studies and evaluating the impact of adenomyosis on quality of life in terms of menstrual symptoms, fertility, and pregnancy outcome, given the high risk of miscarriage and obstetric complications.

The effect of intratesticular autologous platelet-rich plasma injection on sperm retrieval rates and in vitro fertilization outcomes in couples with non-obstructive azoospermia.

AIM: To assess the efficacy of intratesticular injection of autologous platelet-rich plasma (PRP) in men with non-obstructive azoospermia (NOA) and a history of failed microdissection-testicular sperm extraction (mTESE) procedures. METHODS: A prospective case series of a cohort study was conducted involving couples diagnosed with NOA. Patients with at least one failed mTESE procedure were included. Intratesticular PRP injection was performed using a standardized protocol. Follow-up assessments included sperm analysis, hormonal evaluation, and in vitro fertilization (IVF) outcomes. RESULTS: Data from 177 men with NOA were analyzed, with 135 patients meeting eligibility criteria. PRP treatment resulted in positive sperm retrieval rates of 27.5% in patients with one prior failed mTESE procedure and 16.4% in patients with two or more failed attempts. IVF outcomes showed fertilization rates of 86.4% and 100.0% in respective groups, with pregnancy rates of 36.8% and 22.2% per embryo transfer. Histopathological examination post-mTESE revealed varied patterns, including Sertoli cell-only syndrome and maturation arrest. CONCLUSIONS: Intratesticular PRP injection shows promise as a potential therapeutic approach for NOA patients with prior failed mTESE procedures, demonstrating improved sperm retrieval rates and favorable IVF outcomes. Further randomized controlled trials are warranted to validate these findings and refine the technique's efficacy in male infertility management to answer the question of whether PRP could significantly improve the second attempt retrieval rate.

Assisted reproductive technologies in Africa: The African Network and Registry for ART, 2020.

RESEARCH QUESTION: What were the utilization, effectiveness and safety of assisted reproductive technology (ART) in Africa during 2020? DESIGN: Cross-sectional, cycle-based and retrospective summary data were collected from voluntarily participating ART centres. RESULTS: During 2020, 37,063 ART procedures were reported by 67 centres in 15 countries. Autologous fresh transfers were predominant at 65.0%, whereas autologous frozen embryo transfers (FET) represented 26.2% and oocyte donation cycles remained less than 10%. Women undergoing autologous fresh embryo transfer had a mean age of 34.9 years and received a mean number of 2.4 embryos per transfer. The clinical pregnancy rate (CPR) per embryo transfer was 37.3% after fresh embryo transfer and 37.8% after frozen embryo transfer. The cumulative CPR per aspiration was 41.9% in autologous cycles. Most ART procedures resulted in a multiple delivery rate above 20%. After autologous ART, multiples were predominantly born preterm (twin and triplet deliveries 59.5% versus singleton 21.9% born before 37 weeks), with a substantially increased perinatal mortality compared with ART singletons (59.0‰ versus 22.2‰). Cycle-based data documented that elective single embryo transfer (eSET) provides the optimal balance of effectiveness (eSET CPR per embryo transfer 36.7%) and safety. CONCLUSION: This fourth report of the African Network and Registry for ART provides real-world evidence of ART utilization, practices and outcomes in Africa, which is relevant to many stakeholders. It critically informs and represents regional ART development based on national, regional and global cooperation.

Informed consent and coercion in recruitment advertisements for oocyte donors.

BACKGROUND: As the use of donor eggs for in vitro treatment has increased, both medically affiliated and private donor egg agencies have turned to online advertisements to recruit donors. The American Society for Reproductive Medicine provides recommendations encouraging ethical recruitment of donors, however there is no formal regulation for the informed consent process for egg donor recruitment and compensation. Underrepresentation of risks and targeted financial incentives may pose a risk to the informed consent process. METHODS: Data from online advertisements for egg donors active between January 1 - August 31, 2020, were collected to analyze content related to risks, Covid-19 precautions, donor payment, and desired donor characteristics. Advertisements for egg donors on Google, Craigslist, and social media were analyzed. Primary outcomes included the mention of the risks of egg donation, including the risk of Covid-19 exposure, in donor egg advertisements. Secondary outcomes included language targeting specific donor characteristics and financial compensation. RESULTS: 103 advertisements were included. 35.9% (37/103) of advertisements mentioned some risk of the egg donation process, and 18.5% (19/103) mentioned risks or precautions related to Covid-19 exposure. Of advertisements for private donor egg agencies, 40.7% (24/59) mentioned any risk, compared to 29.6% (13/44) of medically affiliated egg donation programs; the difference was not statistically significant (p-value = 0.24). Agencies targeting students and donors of a specific race were more likely to offer payments over $10,000 for an egg donation cycle. Among advertisements offering over $20,000 for donor compensation, 72.7% (8/11) recruited women under the age of 21. CONCLUSION: Egg donor recruitment advertisements, for both medically affiliated programs and private agencies, were unlikely to mention risks including the risk of exposure to Covid-19. Non-medically affiliated private donor egg agencies were more likely to violate multiple American Society for Reproductive Medicine ethics guidelines, including offering higher than average compensation, and recruiting donors from young and vulnerable populations.

Enhancing outcomes in IVF laboratories: navigating the human element through leadership and emotional intelligence.

PURPOSE: We analyze the psychological and interpersonal aspects of in vitro fertilization (IVF) laboratory operations, highlighting how human factors such as leadership style, emotional intelligence (EI), and team dynamics influence the effectiveness of IVF treatments. We also examine the role of personality dynamics in team functioning and the adverse effects of toxic behaviors on laboratory performance and morale. METHODS: The manuscript comprehensively reviews contemporary literature about leadership styles, EI, and team dynamics. It also includes a detailed analysis of the ramifications of their operations within IVF laboratories. The primary emphasis resides in determining how these human factors contribute to the overall efficacy of IVF treatments and following patient outcomes. RESULTS: The findings suggest that staff well-being is not just a concern, but a critical factor in enhancing successful IVF outcomes. Leadership styles that promote emotional intelligence and healthy team dynamics significantly improve laboratory performance. On the other hand, a toxic workplace negatively impacts staff well-being and patient outcomes. The study highlights the need for management development and EI training as vital components of successful IVF laboratory operations, reassuring the audience that these measures can lead to improved outcomes. CONCLUSION: This manuscript presents the case for an equitable operational framework that recognizes the value of soft skills and technical expertise in IVF laboratories. It underscores the significance of emphasizing the human element in reproductive medicine, proposing that by prioritizing empathy and delineating the contributions of the human factor, the field can achieve its maximum potential and enhance outcomes for staff members and patients. The pivotal role of future research in empirically substantiating the influence of these human factors in realizing successful IVF laboratories cannot be overstated, and we urge the academic community to participate actively in this crucial area of research.

GnRH agonist-only trigger, compared to dual trigger, reduces oocyte retrieval rate in high responders without affecting cumulative live birth rate.

Introduction: This study compared, in high responders undergoing IVF treatment, GnRH agonist-only trigger and dual trigger on oocyte retrieval rate and cumulative live birth rate (LBR). The aim was to determine if the GnRH agonist-only triggers had provided outcomes comparable to dual trigger, while minimizing the risk of ovarian hyperstimulation syndrome (OHSS). Materials and methods: A retrospective, matched case-control study was conducted at Taichung Veterans General Hospital, Taiwan, including women who underwent IVF/ICSI between January 1, 2014, and December 31, 2022. Inclusion criteria were: GnRH antagonist protocol and estrogen level >3,000 pg/ml on trigger day. Exclusion criteria were: immune/metabolic diseases, donated oocytes, and mixed stimulation cycles. Propensity score matching was applied to balance age, AMH level, and oocyte number between the GnRH agonist-only and dual trigger groups. Outcomes were analyzed for patients who had complete treatment cycles, focusing on oocyte retrieval rate and cumulative LBR. Results: We analyzed 116 cycles in the agonist-only group, and 232 cycles in the dual trigger group. No inter-group difference was found in their age, BMI, and AMH levels. The dual trigger group had a higher oocyte retrieval rate (93% vs. 80%; p <0.05), while fertilization rates, blastocyst formation rates, and cumulative LBR were comparable. Notably, no OHSS cases had been reported in the GnRH agonist-only group, compared with 7 cases in the dual trigger group. Conclusion: GnRH agonist-only triggers resulted in a lower oocyte retrieval rate compared to dual triggers but did not significantly affect cumulative LBR in high responders. This approach effectively reduces OHSS risk without compromising pregnancy outcomes, making it a preferable option in freeze-all strategies, despite a longer oocyte pick-up duration and a medium cost. GnRH agonist-only trigger, however, may not be suitable for fresh embryo transfers or patients with low serum LH levels on trigger day.

Maternal Characteristics in Natural and Medically Assisted Reproduction Dizygotic Twin Pregnancies.

Previous studies have shown that mothers of naturally conceived dizygotic (DZ) twins tend to be taller, older, and smoke more than mothers of naturally conceived monozygotic (MZ) twin and mothers of singletons. Here, we investigate whether mothers of naturally conceived DZ twins differ from mothers who conceived their DZ twins after medically assisted reproduction (MAR) in eight maternal traits related to fertility based on observational survey data. We include data from 33,648 mothers from the Netherlands Twin Register (NTR) and 1660 mothers of twins from the Norwegian Mother, Father and Child Cohort Study (MoBA). We contrast mothers of naturally conceived DZ twins with mothers of MAR DZ twins. Next, we further segment the MAR group into mothers who underwent hormonal induction of ovulation but not in vitro fertilization (IVF) and those who IVF twins, comparing them both to each other and against the mothers of naturally conceived DZ twins. Mothers of naturally conceived DZ twins smoke more often, differ in body composition, have a higher maternal age and have more offspring before the twins than mothers of MZ twins. Compared to MAR DZ twin mothers, mothers of naturally conceived DZ twins have fewer miscarriages, lower maternal age and increased height, more offspring and are more often smokers. BMI before the twin pregnancy is similar in both natural and MAR DZ twin mothers. Mothers who received hormonal induction of ovulation (OI) have a lower maternal age, fewer miscarriages, and a higher number of offspring before their twin pregnancy than twin mothers who received IVF and/or intracytoplasmic sperm injection (ICSI) treatments. Our study shows that twin mothers are a heterogenous group and the differences between twin mothers should be taken into account in epidemiological and genetic research that includes twins.

Livebirth rates are influenced by an interaction between male and female partners' age: analysis of 59 951 fresh IVF/ICSI cycles with and without male infertility.

STUDY QUESTION: Does advanced male partner's age impact live birth rates (LBRs) in IVF treatment when female partner's age is factored in? SUMMARY ANSWER: In fresh IVF cycles LBRs decline with male partner's age ≥40 years when the female partner is aged 35-39 years, irrespective of the presence or absence of male factor; but not when the female partner is <35 years or ≥40 years of age; this decline is not observed in ICSI cycles. WHAT IS KNOWN ALREADY: Advanced paternal age is associated with declining sperm parameters, impaired embryo development, compromised pregnancy outcomes, and abnormalities in the offspring in IVF/ICSI cycles. However, data on the interaction between maternal and paternal age on IVF outcomes are very limited and inconsistent. No significant effect of male partner's age on pregnancy outcomes has been noted in donor oocyte cycles. STUDY DESIGN, SIZE, DURATION: Retrospective analysis of all eligible autologous IVF/ICSI cycles with oocyte retrieval and intended fresh embryo transfer (ET) from the UK's national anonymized registry, published online by the Human Fertilisation and Embryology Authority (HFEA). There were 59 951 cycles that qualified the inclusion criteria in the study period: 1 January 2017 to 31 December 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: Couples underwent IVF (n = 27 226) or ICSI (n = 32 725) treatment with partner's sperm followed by fresh ET due to unexplained (n = 31 846), tubal (n = 6605), or male infertility (n = 22 905). Treatment cycles with endometriosis (n = 5563), ovulatory disorders (n = 9970), female partner aged >44 years (n = 636), and PGT (n = 280) were excluded. Women were stratified by age in the following groups: <35, 35-39, 40-42, and 43-44 years; male partner's age as <35 (reference group), 35-37, 38-39, 40-42, 43-44, 45-50, 51-55, 55-60, and >55 years as presented by the HFEA. Some age-groups were merged in the analysis to increase the population size. Chi-square test was used to compare binominal data; and multiple logistic regression to find any association between male and female age-groups on live birth adjusting for other confounders that had a significant effect on this outcome. MAIN RESULTS AND THE ROLE OF CHANCE: LBRs per oocyte retrieval as well as per ET were no different across the male partners' age-groups when the female partners were aged <35 years or in 40- to 44-year age-group, whether male-factor infertility was included or excluded and whether it was IVF or ICSI cycle. However, when IVF was the method of insemination in the female partner's age-group of 35-39 years, LBRs per oocyte retrieval dropped significantly from 27.0% in the male age-group of <35 years (reference group) to 22.9% (P = 0.002), 22.0% (P = 0.006), and 18.8% (P = 0.004) in 40-44, 45-50, and >50 years age-group, respectively in population that included male-factor infertility. Likewise, LBR per retrieval declined from 27.6% in 35 years age-group to 23.5% (P = 0.002) and 22.2% (P = 002) in 40-44 years and older groups, respectively in cycles without male infertility. However, there was no impact of male age on LBR in any female partner's age-group when ICSI was performed in either the presence or the absence of male infertility. A similar decline in the LBR per retrieval and per ET was observed in female age-group of 35-39 years in the analyses with IVF and ICSI cycles combined. The inference remained unchanged when only the first treatment cycle was included (per patient analysis) or when single blastocyst transfer cycles were analysed, eliminating the impact of the number and stage of embryo transferred. After adjusting for confounders including male age, female age, number of previous treatment cycles, previous live birth, insemination method (IVF or ICSI), number of embryos transferred, and day (stage) of ET, male partner's age remained significantly associated with LBR in the female age-group of 35-39 years, but not when women were in <35 years or 40- to 44-year age-group, in population including as well as excluding male infertility. Miscarriage rates per single ET trended to rise (non-significantly) in IVF as well as ICSI cycle only when men were over 55 years and female partners aged <40 years, particularly when male infertility was excluded. LIMITATIONS, REASONS FOR CAUTION: Information on ovarian reserve and stimulation protocols was not available. This probably would have had little impact, given the large size of the population studied. The ages of female and male partners were given in groups necessitating taking them as ordinal variable in the regression analysis. Cumulative LBRs could not be determined as the information on subsequent frozen-thawed ET cycles could not be traced and the severity or cause of abnormal semen parameters were not present in the HFEA database. Some age-groups with small number of patients were merged to obtain a reliable result. WIDER IMPLICATIONS OF THE FINDINGS: This is the largest clinical data to support the laboratory evidence of the ability of oocytes from young women to reverse the age-related deterioration of sperm quality. As the ageing oocytes lose this reparatory mechanism, the ageing sperm exert a detrimental effect on the LBR. The message of this study is important in counselling of patients and planning out treatment. Further research on interaction between male and female age will increase our understanding of this matter and help to establish whether ICSI procedure is more appropriate for older male partners even when there is no apparent semen abnormality. STUDY FUNDING/COMPETING INTEREST(S): No funding was required. There is no competing interest. TRIAL REGISTRATION NUMBER: N/A (retrospective analysis).

Automated endometrial identification and volume calculation in normal uteri using a novel smart ERA technique.

To evaluate the repeatability of a novel automated technique called Smart ERA (Smart Endometrial Receptivity Analysis) for the automated segmentation and volume calculation of the endometrium in patients with normal uteri,, and to compare the agreement of endometrial volume measurements between Smart ERA, the semi-automated Virtual Organ Computer-aided Analysis (VOCAL) technique and manual segmentation. This retrospective study evaluated endometrial volume measurement in infertile patients who underwent frozen-thawed embryo transfer (FET). Transvaginal three-dimensional ultrasound scans were performed using a Resona R9 ultrasound machine. Data was collected from patients between 2021 and 2022. Patients with normal uteri and optimal ultrasound images were included. Endometrial volumes were measured using Smart ERA, VOCAL at 15° rotation, and manual segmentation. Intra-observer repeatability and agreement between techniques were assessed using the intraclass correlation coefficient (ICC) and Bland-Altman analysis. A total of 407 female patients were evaluated (mean age 33.2 ± 4.7 years). The repeatability of Smart ERA showed an ICC of 0.983 (95% CI 0.984-0.991). The agreement between Smart ERA and the manual method, Smart ERA and VOCAL, and VOCAL and the manual method, as assessed by ICC, were 0.986 (95% CI 0.977-0.990), 0.943 (95% CI 0.934-0.963), and 0.951 (95% CI 0.918-0.969), respectively. The Smart ERA technique required approximately 3 s for endometrial volume calculation, while VOCAL took around 5 min and the manual segmentation method took approximately 50 min. The Smart-ERA software, which employs a novel three-dimensional segmentation algorithm, demonstrated excellent intra-observer repeatability and high agreement with both VOCAL and manual segmentation for endometrial volume measurement in women with normal uteri. However, these findings should be interpreted with caution, as the algorithm's performance may not be generalizable to populations with different uterine characteristic. Additionally, Smart ERA required significantly less time compared to VOCAL and manual segmentation.

How can the failure mode and effect analysis improve the working processes in the ART center?

OBJECTIVE(S): Assisted reproductive technology (ART) Centers and laboratories perform complex tasks with patients and their gametes/embryos daily. The degree of problems/non-conformances in such surroundings must be minimized at zero point. This study aimed to establish the proper risk management system with well-defined process steps to prevent and eliminate problems/non-conformances. STUDY DESIGN: Failure mode and effect analysis (FMEA) was introduced in the ART Center and the IVF laboratory. ART Center working processes were grouped into the categories of Clinical procedures, Forms, Identification, Personnel, Patients, and Facility. Working processes in the IVF laboratory were grouped into the categories of Consumables, Media, Equipment, Personnel, Working space, and Procedures. The traceability and safety of the working processes were evaluated before and after corrective measures regarding risk priority number (RPN). The severity (S), occurrence (O), and detection (D) index of problems/non-conformance were scaled from 1 to 5. The RPN was calculated by multiplying the SOD index, and the cut-off value for RPN was ≥12. RESULTS: The increased RPN was found in the following working processes of the ART Center: Embryo transfer and pregnancy (RPN = 18) in the category of Clinical procedures; Informed consents and agreements (RPN = 16) in the category Forms; Continuous education of the knowledge and skills (RPN = 12) in Personnel category; Space conditions (RPN = 24) and Equipment (RPN = 12) in the category Facility. In the IVF laboratory, increased RPN was found in the following working processes: Production of the plasticware (RPN = 12), Transport (RPN = 12) and Storage (RPN = 12) in the category Consumables; Media production (RPN = 16) in category Media; Alarm notification system for the critical equipment (RPN = 12) in category Equipment; Personnel number and qualifications (RPN = 12), Standard operative procedures (SOP) (RPN = 12) and Continuous education of the knowledge and skills (RPN = 12) in category Personnel; Working conditions (RPN = 18) and Security (RPN = 20) in Working space; Patient identification (RPN = 20), Biological samples identification (RPN = 20), Records (RPN = 12), ART procedure (RPN = 30), Embryo transfer (RPN = 30) and Cryopreservation and thawing of biological samples (RPN = 30) in category Procedures. According to the RPN score, corrective measures were implemented. Most RPN scores were reduced after the implementation of the electronic witnessing system in patient/sample tracing steps. Phases Patient identification and Biological sample identification showed a double reduction of RPN scores, from 20 to 10. Also, for critical steps in ART procedures, Embryo transfer, Cryopreservation, and thawing of biological samples, the RPN score was reduced from 30 to 10. Proper education of personnel was another corrective measure that significantly contributed to a reduction of RPN scores in most of the categories. CONCLUSION(S): The FMEA analysis is useful in recognizing the critical steps of an ART Center. The RPN scores for patient traceability were successfully reduced using the electronic witnessing system. Nonetheless, the study has certain limitations, as FMEA is highly dependent on the specific healthcare organization, adherence to national guidelines, and the subjective nature of SOD and RPN evaluations.

Neutral effect of Zishen Yutai Pill on frozen-thawed embryo transfer: a propensity score matching study.

Objective: To investigate whether using Zishen Yutai Pills (ZYP) following embryo transfer would affect the live birth rate in frozen-thawed embryo transfer (FET) cycles. Methods: A retrospective analysis was performed on 15044 FET cycles in the Reproductive Medicine Center of The Affiliated Chenggong Hospital of Xiamen University from January 2013 to December 2020. Patients who used Zishen Yutai Pills were defined as Zishen Yutai Pills Group (ZYP, n=2735), while patients who did not use them were defined as Non- Zishen Yutai Pills Group (Non-ZYP, n=12309). The propensity score matching method was used to control for potential confounders between the two groups, and logistic regression analysis was also used to assess whether using ZYP would affect the live birth rate. Results: After propensity score matching, basic characteristics were similar between the two groups. Using ZYP did not increase the pregnancy rate (51.5% vs. 52.7%, P=0.372), and live birth rate (43.0% vs. 44.7%, P=0.354). This was also confirmed by the logistic regression analysis results (OR=0.95, 95%CI=0.85-1.06). In the subgroup analysis of the endometrial preparation protocols, however, it was found that the use of ZYP in patients with natural cycles increased the live birth rate (47.4% vs. 41.5%, P=0.004). A significant interaction between endometrial preparation and ZYP was found (OR=1.38, 95%CI=1.07-1.79) in the multivariate model. Conclusion: The use of ZYP may not improve the live birth rate of unselected patients in FET cycles. However, a future study is needed on the effect of ZYP in natural cycles for endometrial preparation.

The effects of growth hormone supplementation in poor ovarian responders undergoing In vitro fertilization or Intracytoplasmic sperm injection: A systematic review and meta-analysis of randomized controlled trials.

To evaluate the effect of growth hormone (GH) supplementation on outcomes of in vitro fertilization (IVF) or Intracytoplasmic sperm injection (ICSI) for women with poor ovarian response. Relevant randomized controlled trials (RCTs) were obtained through search in several databases including PubMed, Scopus, Clinicaltrials.gov, Google Scholar, and Cochrane Library. Outcome measures included live birth rate, clinical pregnancy rate, cycle cancelation rate, number of retrieved oocytes, number of transferred embryos, total dose of gonadotropin, duration of gonadotropin treatment, and peak estradiol level. Additionally, a meta-regression analysis was carried out to determine any potential linear relationships between these outcomes and IVF success. After analyzing 18 RCTs comprising of 1870 patients, the study found that GH supplementation improved the number of retrieved oocytes [standardized mean difference (SMD), 0.65; 95% confidence interval (CI), 0.29-1.00] and transferred embryos group (SMD, 0.80, 95% CI, 0.39, 1.21) as well as peak E2 level (SMD, 1.20; 95% CI, 0.59, 1.81). While reduced the total dose and duration of gonadotropin treatment (SMD, -0.82, 95% CI, -1.25, -0.39, and SMD, -0.63, 95% CI, -1.04, -0.22, respectively). The meta-regression analysis found no linear relationship between clinical pregnancy, live birth rate, or cycle cancelation rate and the outcomes measured (p>0.1). Based on the available evidence, GH supplementation appears to improve the outcomes of IVF or ICSI in women with poor response. However, there is a need for further RCTs with larger sample sizes to determine the cost-effectiveness of adding GH to conventional protocols of IVF/ICSI for treating infertility in women with poor ovarian response.

Risk assessment of patients with underlying health conditions who present for IVF treatment.

The increasing number of women with underlying health conditions seeking in vitro fertilization (IVF) necessitates a comprehensive risk assessment framework tailored to their needs. This review aims to provide a practical framework for IVF specialists to systematically assess and manage the risks associated with medically complex patients. The GRASP mnemonic (Genetics, Retrieval, Anaesthetics, Stimulation, Pregnancy) is introduced to facilitate a thorough risk assessment process. The review emphasizes the importance of obtaining detailed medical histories, corroborating information from other healthcare providers, and involving maternal medicine specialists in pre-pregnancy counselling. Furthermore, it highlights the ethical considerations of informed consent, advocating for fertility specialists to take a central role in coordinating care and ensuring patient understanding of risks. Continuous health evaluation throughout the IVF process and clear communication of risks are crucial for improving patient outcomes.

Maturational competence of equine oocytes is associated with alterations in their "cumulome".

Assisted reproductive technologies are an emerging field in equine reproduction, with species dependent peculiarities, such as the low success rate of conventional in vitro fertilisation. Here, the "cumulome" was related to the developmental capacity of its corresponding oocyte. Cumulus oocyte complexes (COCs) collected from slaughterhouse ovaries were individually matured, fertilised by intracytoplasmic sperm injection (ICSI), and cultured. After maturation, the cumulus was collected for proteomics analysis using label-free mass spectrometry (MS) based protein profiling by nano-HPLC MS/MS and metabolomics analysis by UPLC-nanoESI MS. Overall, a total of 1671 proteins and 612 metabolites were included in the quantifiable "cumulome". According to the development of the corresponding oocytes, three groups were compared with each other: not matured (NM; n = 18), cleaved (CV; n = 15) and blastocyst (BL; n = 19) groups. CV and BL were also analysed together as the matured group (M; n = 34). The dataset revealed a closer connection within the two M groups and a more distinct separation from the NM group. Over-representation analysis detected enrichments related to energy metabolism as well as vesicular transport in the M group. Functional enrichment analysis found only the KEGG pathway of oxidative phosphorylation as significantly enriched in NM group. A compound attributed to ATP was observed with significantly higher concentrations in the BL group compared with the NM group. Finally, in the NM group, proteins related to degradation of glycosaminoglycans were lower and components of cumulus extracellular matrix were higher compared to the other groups. In summary, the study revealed novel pathways associated with the maturational and developmental competence of oocytes.

LGBTQ+ Family Building: Progress but Lots More to Do.

Great strides have been made in society and in Reproductive Endocrinology and Infertility (REI) in support of LGBTQ+ family building. While many of the concepts used in heterosexual reproduction can be applied to the LGBTQ+ community, there are specific differences that must be understood to provide the highest level of care to this community.

Telomeric RNAs, TERRA, as a Potential Biomarker for Spermatozoa Quality.

Characterization of long non-coding telomeric repeat-containing RNAs in sperm of normozoospermic and oligoasthenozoospermic men as new biomarker of idiopathic male infertility. We conducted an observational prospective study with two groups of men with normal or orligoasthenozoospermic spermiogram, aged 40 and above. Fertility parameters were analyzed in men undergoing intracytoplasmic sperm injection with donor oocytes, to avoid the female factor. Telomeric RNAs and telomere length were measured by quantitative fluorescent in situ hybridization. Data from seminal parameters and in-vitro fertilization were assessed according to IVIRMA protocols. Patients with oligoasthenozoospermia, who had worse seminal parameters, also obtained embryos with lower inner-cell-mass quality (p = 0.04), despite using donor oocytes. While mean levels of telomeric RNAs were similar for both groups, the percentage of spermatozoa with more than 3 foci was higher in oligoasthenozoospermic men (p = 0.02). Regarding telomere length, oligoasthenozoospermic men had shorter mean, a higher accumulation of short telomeres (15th percentile; p = 0.03) and a lower percentage of very-long telomeres (85th percentile; p = 0.01). Finally, a positive correlation was found between telomeric-RNAs intensity and total progressive motility in the spermatozoa of normozoospermic patients (r = 0.5; p = 0.03). Telomeric parameters were altered in the spermatozoa of the oligoasthenozoospermic group, which also showed lower quality embryos. Interestingly, in the normozoospermic group, a correlation was found between progressive motility and telomeric RNA levels, suggesting that they could be a good biomarker of sperm quality. Further studies are required to confirm these results and translate them into the clinical practice.Trial registration number: 1711-MAD-109-CB, 07/07/2021.

Programing the onset of ovarian stimulation: From early follicular phase start to oral contraceptive (OC) pill, to luteal phase E2, Duo-Stim and random start OS protocols.

Ovarian stimulation has been the single most efficient measure ever taken in ART for improving outcome by harvesting multiple oocytes and ultimately, embryos. Today, ovarian stimulation protocols consist in administrating exogenous gonadotropins in order to override the natural mechanisms which controls the ovulatory quota to one in humans. For practicality issues, there has been numerous attempts to control, or 'program', when ovarian stimulation are initiated in order to improve functionality and in turn efficacy for ART programs. The different options for controlling the onset of ovarian stimulation currently available are discussed here, as well as the novel possibility of using progestins for blocking premature ovulation.