Effects of Metabolic Syndrome on Pregnancy Outcomes in Women Without Polycystic Ovary Syndrome.

Context: Metabolic syndrome (MetS) is a cluster of metabolic risk factors that predict cardiovascular disease. Previous studies suggested that MetS impaired clinical outcomes in women with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF). Objective: To evaluate the effects of MetS on IVF/intracytoplasmic sperm injection (ICSI) outcomes in women without PCOS. Methods: This retrospective study collected 8539 eligible women without PCOS who came for their first cycle of IVF/ICSI to the Institute of Women, Children and Reproductive Health, Shandong University, from 2017 to 2020, including 1147 subjects in the MetS group and 7392 in the control group. The primary outcome was live birth. Secondary outcomes included other pregnancy outcomes and the risk of maternal and neonatal complications. Results: Women in the MetS group had a lower live birth rate (50.6% vs 54.9%, adjusted odds ratio [aOR] 0.87, 95% CI 0.75-1.00, P = .045) and higher risks of late miscarriage (5.8% vs 3.3%, aOR 1.52, 95% CI 1.02-2.27, P = .041), gestational diabetes mellitus (13.7% vs 7.0%, aOR 1.84, 95% CI 1.30-2.60, P = .001), hypertensive disorder of pregnancy (7.8% vs 3.5%, aOR 1.79, 95% CI 1.14-2.83, P = .012), and preterm birth (9.0% vs 4.4%, aOR 2.03, 95% CI 1.33-3.08, P = .001). Singleton newborns in the MetS group were at higher risk of large for gestational age (33.3% vs 20.5%, aOR 1.66, 95% CI (1.31-2.13), P < .001) but at lower risk of small for gestational age (2.7% vs 6.2%, aOR 0.48, 95% CI 0.25-0.90, P = .023). Conclusion: MetS was associated with adverse IVF/ICSI outcomes in women without PCOS.

Relationship between fresh single embryo morphology scores and serum HCG values at 14 days and 14-18-day doubling values.

RESEARCH QUESTION: What is the effect of embryo morphology score on 14-day ß-HCG levels and 14-18-day ß-HCG doubling values, and do they have differences in day-3 embryo or day-5 blastocyst transfers? DESIGN: Retrospective analysis of 4434 fresh cycles of single embryo transfers (SET) with ß-HCG ≥15 mIU/ml on day 14 after transfer via IVF and ICSI. The correlation between embryo morphology score and 14-day ß-HCG was examined. Doubling of 14-18 day ß-HCG was analysed in 2628 cycles to determine correlations with embryo morphology score. RESULTS: In day-3 SET, number of embryonic cells was positively correlated with 14-day post-transfer ß-HCG values (R = 0.076; P = 0.013). No significant correlation was observed between the grade of the transferred embryos and the 14-18-day serum ß-HCG doubling values. In day-5 single blastocyst transfers, the degree of blastocyst expansion, trophoblast cell and inner cell mass (ICM) grades demonstrated a significant positive correlation with 14-day post-transfer ß-HCG (P < 0.001, P = 0.014, P = 0.003). Degree of blastocyst expansion was significantly correlated with 14-18-day ß-HCG doubling values (R = -0.051, P = 0.027). Grades of the ICM and trophoblast cells showed no significant correlation with 14-18-day ß-HCG doubling values. CONCLUSION: In fresh SET, embryo morphology score influences 14-day ß-HCG values in day-3 embryos and day-5 blastocyst transfers. Embryo morphology score in day-3 SET does not affect 14-18-day ß-HCG doubling values. Degree of blastocyst expansion significantly affects 14-18-day ß-HCG doubling values in day-5 blastocyst transfers.

Use of Zebrafish (Danio rerio) for Biosafety Evaluation of Strontium Nanostructured Hydroxyapatite.

Despite the numerous studies on biocompatibility with nano-biomaterials, the biological effects of strontium-substituted HA nanoparticles (nSrHA) need to be better understood. So, we conducted an embryotoxicity test using zebrafish (Danio rerio) according to the OECD 236 guideline, a model that represents a viable alternative that bridges the gap between in vitro and mammalian models. Zebrafish embryos were exposed for 120 h to microspheres containing nSrHA nanoparticles with low and high crystallinity, synthesized at temperatures of 5°C (nSrHA5) and 90°C (nSrHA90). We evaluated lethality, developmental parameters, and reactive oxygen species (ROS) production. The larval behavior was assessed at 168 hpf to determine if the biomaterials affected motor responses and anxiety-like behavior. The results showed that the survival rate decreased significantly for the nSrHA5 group (low crystalline particles), and an increase in ROS was also observed in this group. However, none of the biomaterials caused morphological changes indicative of toxicity during larval development. Additionally, the behavioral tests did not reveal any alterations in all experimental groups, indicating the absence of neurotoxic effects from exposure to the tested biomaterials. These findings provide valuable insights into the biosafety of modified HA-based nanostructured biomaterials, making them a promising strategy for bone tissue repair. As the use of hydroxyapatite-based biomaterials continues to grow, it is crucial to ensure rigorous control over the quality, reliability, and traceability of these materials.

Mouse embryo CoCoPUTs: novel murine transcriptomic-weighted usage website featuring multiple strains, tissues, and stages.

Mouse (Mus musculus) models have been heavily utilized in developmental biology research to understand mammalian embryonic development, as mice share many genetic, physiological, and developmental characteristics with humans. New explorations into the integration of temporal (stage-specific) and transcriptional (tissue-specific) data have expanded our knowledge of mouse embryo tissue-specific gene functions. To better understand the substantial impact of synonymous mutational variations in the cell-state-specific transcriptome on a tissue's codon and codon pair usage landscape, we have established a novel resource-Mouse Embryo Codon and Codon Pair Usage Tables (Mouse Embryo CoCoPUTs). This webpage not only offers codon and codon pair usage, but also GC, dinucleotide, and junction dinucleotide usage, encompassing four strains, 15 murine embryonic tissue groups, 18 Theiler stages, and 26 embryonic days. Here, we leverage Mouse Embryo CoCoPUTs and employ the use of heatmaps to depict usage changes over time and a comparison to human usage for each strain and embryonic time point, highlighting unique differences and similarities. The usage similarities found between mouse and human central nervous system data highlight the translation for projects leveraging mouse models. Data for this analysis can be directly retrieved from Mouse Embryo CoCoPUTs. This cutting-edge resource plays a crucial role in deciphering the complex interplay between usage patterns and embryonic development, offering valuable insights into variation across diverse tissues, strains, and stages. Its applications extend across multiple domains, with notable advantages for biotherapeutic development, where optimizing codon usage can enhance protein expression; one can compare strains, tissues, and mouse embryonic stages in one query. Additionally, Mouse Embryo CoCoPUTs holds great potential in the field of tissue-specific genetic engineering, providing insights for tailoring gene expression to specific tissues for targeted interventions. Furthermore, this resource may enhance our understanding of the nuanced connections between usage biases and tissue-specific gene function, contributing to the development of more accurate predictive models for genetic disorders.

Progesterone-modified natural cycle preparation for frozen embryo transfer.

RESEARCH QUESTION: Is there any difference in clinical outcomes between the progesterone-modified natural cycle (P4mNC) and hormone replacement therapy (HRT) endometrial preparation protocols after single euploid blastocyst frozen embryo transfer (FET) cycles? DESIGN: A retrospective cohort study was performed at a single, private, high-volume fertility centre. Patients who underwent single euploid blastocyst FET between January 2017 and December 2019 were included. A total of 1933 FET cycles were reviewed, and 723 FET cycles from 548 patients met the inclusion criteria. Two groups were compared according to endometrial preparation: 327 P4mNC-FET and 396 HRT-FET cycles. The primary outcome was the live birth rate. The secondary outcomes included the clinical pregnancy rate and the miscarriage rate. RESULTS: There were no differences in the clinical pregnancy rate (50.2% versus 47.0%, P = 0.688), miscarriage rate (9.8% versus 14.5%, P = 0.115) and live birth rate (45.0% versus 39.6%, P = 0.331) between the P4mNC-FET and HRT-FET groups after covariate adjustments. CONCLUSIONS: There were no differences in the clinical outcomes between the P4mNC-FET and HRT-FET cycles. These results indicate that P4mNC-FET cycles produce clinical outcomes comparable to those of more traditional HRT-FET while allowing greater flexibility in the timing of embryo transfer.

Dichorionic triamniotic triplets after two blastocysts transfer underwent multifetal pregnancy reduction: two case reports and literature review.

BACKGROUND: The increase in the rate of multiple pregnancies in clinical practice is associated with assisted reproductive technology (ART). Given the high risk of dichorionic triamniotic (DCTA) triplet pregnancies, reducing DCTA triplet pregnancies to twin or singleton pregnancies is often beneficial. CASE PRESENTATION: This article reports on two cases of DCTA triplet pregnancies resulting from two blastocyst transfers. Given the high risk of complications such as twin-to-twin transfusion syndrome (TTTS) in monochorionic diamniotic (MCDA) twin pregnancies, patients have a strong desire to preserve the dichorionic diamniotic (DCDA) twins. Multifetal pregnancy reduction (MFPR) was performed in both cases to continue the pregnancy with DCDA twins by reducing one of the MCDA twins. Both of the pregnant women in this report eventually gave birth to healthy twins at 37 weeks. CONCLUSIONS: For infertile couples with multiple pregnancies but with a strong desire to remain the DCDA twins, our report suggests that reducing DCTA triplets to DCDA twin pregnancies may be an option based on clinical operability and assessment of surgical difficulty.

Live birth after transmyometrial embryo transfer in a patient with radical trachelectomy.

OBJECTIVE: To report the successful utilization of transmyometrial embryo transfer (TMET) in a patient with a history of radical trachelectomy. DESIGN: Video article. SETTING: Academic fertility center. SUBJECT(S): A 39-year-old, para 1, woman with a history of radical trachelectomy and abdominal cerclage presented with secondary infertility. Her prior pregnancy was conceived naturally. Her first in vitro fertilization (IVF) cycle yielded only one day-7 euploid blastocyst. All attempts at performing mock embryo transfers, cervical dilatation and hysteroscopy were unsuccessful due to absence of clinically identifiable cervical tissue. The euploid embryo was transferred into a gestational carrier; however, this resulted in a biochemical pregnancy. She underwent a second IVF cycle that yielded one day-5 euploid blastocyst. Given her history, TMET was planned. The patient included in this video gave consent for publication of the video and posting of the video online including social media, the journal website, scientific literature websites (such as PubMed, ScienceDirect, Scopus, etc.) and other applicable sites. INTERVENTION: TMET using the Towako® catheter. MAIN OUTCOME MEASURES: Implantation, clinical pregnancy and live birth. RESULTS: Following institutional and Health Canada approval of the Towako® catheter, a transvaginal-ultrasound guided TMET was performed under sedation with intravenous midazolam and fentanyl. The day-5 euploid blastocyst from the second IVF cycle was transferred and the patient's ß-human chorionic gonadotropin (ß-hCG) levels 9 and 11 days after TMET were 86 IU/L and 262 IU/L, respectively. A single intrauterine pregnancy with cardiac activity of 119 beats/min was noted at a gestational age of 7 weeks and 2 days. The patient delivered a live singleton at 35 weeks and 2 days weighing 2182 grams. CONCLUSION: TMET is a useful clinical technique for transferring embryos in patients with acquired or congenital cervical issues in whom trans-cervical embryo transfer is either very difficult or impossible.

ZEB1 Promotes Epithelial-Mesenchymal Transition of Endometrial Epithelial Cells and Plays a Critical Role in Embryo Implantation in Mice.

Zinc finger E-box binding homeobox 1 (ZEB1) promotes epithelial-mesenchymal transition (EMT) in carcinogenesis, but its role in embryo implantation has not yet been well studied. In the present study we evaluated the hypothesis that ZEB1-induced EMT is essential for embryo implantation in vivo. Endometrial epithelium from female Kunming mice (non-pregnant, and pregnant from day 2.5 to 6.5) were collected for assessment of mRNA/protein expression of ZEB1, and EMT markers E-cadherin and vimentin, by employment of real-time quantitative reverse transcription PCR, Western blot, and immunohistochemical staining. To test if knockdown of ZEB1 affects embryo implantation in vivo, mice received intrauterine injection of shZEB1 before the number of embryos implanted was counted. The results showed that, ZEB1 was highly expressed at both mRNA and protein levels in the mouse endometrium on day 4.5 of pregnancy, paralleled with down-regulated E-cadherin and up-regulated vimentin expression (P < 0.05). Intrauterine injection of shZEB1 markedly suppressed embryo implantation in mice (P < 0.01). Conclusively, the present work demonstrated that ZEB1 is essential for embryo implantation under in vivo condition, and is possibly due to its effect on modulation of endometrial receptivity through EMT.

Embryo recovery(rescue) studies in different Vitis species.

BACKROUND: In recent years, with the increasing demand for seedless grape varieties that have lower production costs, are disease resistant/tolerant and require less chemical pesticides, the embryo recovery technique has begun to be used more in table grape breeding studies. However, the desired high success rate has not yet been achieved in these studies. Although there are different reasons for this, especially the grape varieties selected for cross-breeding and the timing of transferring the embryos to medium are among the most important reasons. In this study, focusing on these two important factors, the embryos obtained from different hybridization combinations were transferred to agar medium at different weeks for 4 years and the most successful combination and time were determined. In addition, seedless and large berry grape varieties and some seeded varieties that are resistant/tolerant to fungal diseases were selected as parents because they can provide resistance to disease infections in vitro and thus increase the success rate. RESULTS: The results obtained from the study showed that the selected variety and combination significantly affected the success rate in embryo rescue. Especially in combinations with the 'Yalova Seedless' variety as the female parent, more successful results were obtained compared to combinations of other varieties. When 'Yalova Seedless' variety was pollinated with pollen of 'Red Globe', 'Muscat Bailey A' and 'Exalta' varieties, more seedlings were obtained with the help of embryo rescue. The results obtained over four years showed that the best sampling time after pollination was the eighth week and then the seventh week. CONCLUSIONS: According to the results obtained, it has been shown that the selected varieties and the sampling time significantly affect the success rate in embryo rescue studies. Therefore, higher success rates can be achieved in comprehensive breeding studies in which they will be included as pollinators, especially in different seeded varieties that are resistant to diseases and have larger berry size.

Proteomic analysis and in vivo visualization of extracellular vesicles from mouse oviducts during pre-implantation embryo development.

Pre-implantation embryonic development occurs in the oviduct during the first few days of pregnancy. The presence of oviductal extracellular vesicles (oEVs, also called oviductosomes) is crucial for pre-implantation embryonic development in vivo as oEVs often contain molecular transmitters such as proteins. Therefore, evaluating oEV cargo during early pregnancy could provide insights into factors required for proper early embryonic development that are missing in the current in vitro embryo culture setting. In this study, we isolated oEVs from the oviductal fluid at estrus and different stages of early embryonic development. The 2306-3066 proteins in oEVs identified at the different time points revealed 58-60 common EV markers identified in exosome databases. Oviductal extracellular vesicle proteins from pregnant samples significantly differed from those in non-pregnant samples. In addition, superovulation changes the protein contents in oEVs compared to natural ovulation at estrus. Importantly, we have identified that embryo-protectant proteins such as high-mobility protein group B1 and serine (or cysteine) peptidase inhibitor were only enriched in the presence of embryos. We also visualized the physical interaction of EVs and the zona pellucida of 4- to 8-cell stage embryos using transmission electron microscopy as well as in vivo live imaging of epithelial cell-derived GFP-tagged CD9 mouse model. All protein data in this study are readily available to the scientific community in a searchable format at https://genes.winuthayanon.com/winuthayanon/oviduct_ev_proteins/. In conclusion, we identified oEVs proteins that could be tested to determine whether they can improve embryonic developmental outcomes in vivo and in vitro setting.

The effect of flunixin meglumine on the premature regression of corpus luteum, recovery rate, and embryo production in superovulated Dorper ewes.

This study evaluated the use of flunixin meglumine to prevent the occurrence of premature corpus luteum (CL) regression in superovulated ewes, improving embryo recovery and viability. Ewes (n=23) submitted to conventional superovulatory protocol and laparoscopic artificial insemination were treated with 2.2 mg/kg/day of flunixin meglumine (FLU, n=12) or 1.5 mL saline solution (CONT, n=11) on Days 2, 3, and 4 (Day 0 = 48 h after device removal). Serum progesterone (P4) concentrations were measured (Day 1-6). Ultrasound (US, Days 3 and 6) and laparoscopic evaluation (Day 6) were performed to identify luteinized structures. In the US, laparoscopy, and P4 assessments, the percentage of ewes with premature CL regression differed (P<0.05) between CONT (54.5; 63.6; and 54.5 %) and FLU (0.0; 0.0; and 0.0 %), respectively. The US exams revealed the effect (P<0.05) of treatment on the number of regressing CL between CONT (1.4 ± 0.6) and FLU (0.0 ± 0.0). Greater (P<0.05) number of normal CLs (10.5 ± 1.8 vs. 4.4 ± 1.5), ova/embryos (9.1 ± 2.1 vs. 3.7 ± 1.3), viable embryos (5.1 ± 1.1 vs. 2.6 ± 1.2), and recovery rate (79.5 ± 9.6 vs. 41.3 ± 15.0 %) were observed in FLU compared to CONT, respectively. The embryo viability rate did not differ (P>0.05) between FLU (60.7 ± 10.5 %) and CONT (45.5 ± 16.1 %). In conclusion, the flunixin meglumine protocol was able to prevent the occurrence of premature CL regression in superovulated ewes, increasing the recovery rate and embryo production.

The thyroid hormone system disrupting potential of resorcinol in fish.

Environmental pollutants capable of interfering with the thyroid hormone (TH) system increasingly raise concern for both human and environmental health. Recently, resorcinol has received attention as a compound of concern due to its endocrine disrupting properties. It is a known inhibitor of thyroperoxidase (TPO), an enzyme required in TH synthesis, and therapeutic use of resorcinol exposure has led to hypothyroidism in humans. There is limited evidence concerning ecotoxicologically relevant effects of resorcinol in fish. A set of adverse outcome pathways (AOPs) has recently been developed linking thyroid hormone system disruption (THSD) to impaired swim bladder inflation and eye development in fish. In the present study, these AOPs were used to provide the background for testing potential THSD effects of resorcinol in zebrafish eleutheroembryos. We exposed zebrafish eleutheroembryos to resorcinol and assessed TH levels, swim bladder inflation and eye morphology. As a TPO inhibitor, resorcinol is expected to affect TH levels and eye morphology but not swim bladder inflation during embryonic development. Indeed, thyroxine (T4) levels were significantly decreased following resorcinol exposure. In contrast to our hypothesis, swim bladder inflation was impaired at 5 days post fertilization (dpf) and no effects on eye morphology were detected. Therefore, in vitro assays were performed to identify potential additional thyroid hormone system disruption-related mechanisms through which resorcinol may act. Two new mechanisms were identified: TH receptor (TR) antagonism and transthyretin (TTR) binding inhibition. Both of these mechanisms can plausibly be linked to impaired swim bladder inflation and could, therefore, explain the observed effect. Overall, our study contributes to the knowledge of the THSD potential of resorcinol both in vivo in the zebrafish model as well as in vitro.

The impact of intracytoplasmic sperm injection versus conventional in vitro fertilization on the reproductive outcomes of couples with non-male factor infertility and frozen-thawed embryo transfer cycles.

This study was aimed to investigate the impact of intracytoplasmic sperm injection (ICSI) on reproductive outcomes in couples with non-male factor infertility and frozen-thawed embryo transfer (FET) treatment. This retrospective cohort study involved a total of 10,143 cycles from 6206 couples who underwent FET at the Third Affiliated Hospital of Zhengzhou University between January 2016 and September 2022. Patients were categorized into two groups based on the insemination methods of transferred embryos. Clinical and neonatal outcomes were compared between ICSI and conventional in vitro fertilization (cIVF) groups. The results showed that ICSI was not associated with improved clinical outcomes compared to cIVF. However, ICSI was associated with lower birthweight when twins were born. In conclusion, although subgroup analysis showed that ICSI was associated with slightly improved live birth rate for infertile couples with non-male factor infertility compared to cIVF, the regression analysis showed that ICSI did not demonstrate any improvement of the reproductive outcomes. The infertile women with twin pregnancies should be further informed of the lower birthweight and lower birth length when their oocytes were inseminated with ICSI. The findings of this study provide valuable insights for clinicians when discussing the benefits and risks of ICSI in patients with non-male factor infertility.

Integrated ultrasensitive metabolomics and single-cell transcriptomics identify crucial regulators of sheep oocyte maturation and early embryo development in vitro.

INTRODUCTION: Developmental competence of oocytes matured in vitro is limited due to a lack of complete understanding of metabolism and metabolic gene expression during oocyte maturation and embryo development. Conventional metabolic analysis requires a large number of samples and is not efficiently applicable in oocytes and early embryos, thereby posing challenges in identifying key metabolites and regulating their in vitro culture system. OBJECTIVES: To enhance the developmental competence of sheep oocytes, this study aimed to identify and supplement essential metabolites that were deficient in the culture systems. METHODS: The metabolic characteristics of oocytes and embryos were determined using ultrasensitive metabolomics analysis on trace samples and single-cell RNA-seq. By conducting integrated analyses of metabolites in cells (oocytes and embryos) and their developmental microenvironment (follicular fluid, oviductal fluid, and in vitro culture systems), we identified key missing metabolites in the in vitro culture systems. In order to assess the impact of these key missing metabolites on oocyte development competence, we performed in vitro culture experiments. Furthermore, omics analyses were employed to elucidate the underlying mechanisms. RESULTS: Our findings demonstrated that betaine, carnitine and creatine were the key missing metabolites in vitro culture systems and supplementation of betaine and L-carnitine significantly improved the blastocyst formation rate (67.48% and 48.61%). Through in vitro culture experiments and omics analyses, we have discovered that L-carnitine had the potential to promote fatty acid oxidation, reduce lipid content and lipid peroxidation level, and regulate spindle morphological grade through fatty acid degradation pathway. Additionally, betaine may participate in methylation modification and osmotic pressure regulation, thereby potentially improving oocyte maturation and early embryo development in sheep. CONCLUSION: Together, these analyses identified key metabolites that promote ovine oocyte maturation and early embryo development, while also providing a new viewpoint to improve clinical applications such as oocyte maturation or embryo culture.

Comparing the outcomes of in-vitro fertilization in patients receiving vaginal, subcutaneous, and intramuscular progesterone for luteal phase support: a three-armed randomized controlled trial.

BACKGROUND: The optimal approach to luteal-phase support in infertility treatment remains a subject of debate. This study was conducted to investigate the clinical outcomes, side effects, and patient satisfaction associated with vaginal, subcutaneous, and intramuscular progesterone administration in infertile women undergoing Frozen Embryo Transfer (FET). METHODS: This three-armed randomized clinical trial assigned infertile patients eligible for FET to three progesterone treatment groups: vaginal suppositories (400 mg twice daily; n = 100), subcutaneous injections (25 mg daily; n = 102), and intramuscular injections (50 mg daily; n = 108). The primary outcomes were chemical and clinical pregnancy rates per embryo transfer cycle, with chemical pregnancy defined as beta-human chorionic gonadotropin levels > 50 IU/mL two weeks post-transfer and clinical pregnancy confirmed by ultrasound four weeks later. Exploratory outcomes included progesterone-related adverse effects and participant satisfaction, assessed via a Likert-scale survey 12 weeks post-transfer. Statistical analyses included Chi-square tests for categorical data, one-way analysis of variances, and Kruskal-Wallis tests for continuous data. RESULTS: The intramuscular progesterone group had significantly higher chemical pregnancy rates compared to the vaginal and subcutaneous groups (41.7% vs. 26.0% and 27.5%, respectively; p = 0.026). Although the clinical pregnancy rate was also higher in the intramuscular group (32.4%) compared to the vaginal (23.0%) and subcutaneous groups (21.6%), this difference was not statistically significant (p = 0.148). Additionally, patient satisfaction was greater with vaginal and subcutaneous applications than with intramuscular injections (p < 0.001), likely due to a significantly higher incidence of side effects, such as pain and edema at the injection site, in the intramuscular group (p < 0.001). CONCLUSIONS: We found that intramuscular progesterone resulted in higher chemical pregnancy rates than vaginal or subcutaneous routes, but this did not translate into higher clinical pregnancy rates. Despite its effectiveness, intramuscular administration was associated with more adverse effects and lower patient satisfaction. Future research should explore optimizing progesterone regimens to balance efficacy and patient comfort. TRIAL REGISTRATION: The trial protocol was registered on December 6, 2020, in the Iranian Registry of Clinical Trials (IRCT), a primary registry in the World Health Organization (WHO) Registry Network, under the registration number IRCT20141217020351N12.

Fertility preserving techniques in neuro-oncology patients: A systematic review.

Background: Advancements in cancer treatments have enhanced survival rates and quality of life for patients with central nervous system (CNS) tumors. There is growing recognition of the significance of fertility preservation methods. Currently, techniques, including oocyte cryopreservation and sperm cryopreservation are established. Nevertheless, oncologists may exhibit reluctance when referring patients to reproductive specialists. This review aimed to assess the best evidence for fertility preservation techniques used in patients with CNS cancers and evaluate outcomes relating to their success and complications. Methods: Two reviewers performed a search of Pubmed, Embase, Medline, Cochrane, and Google Scholar. Papers were included if they reported at least 1 fertility preservation technique in a neuro-oncology patient. Non-English studies, editorials, animal studies, and guidelines were excluded. Meta-analysis was performed using the random effects model. Results: Sixteen studies containing data from 237 participants (78.8% female) were included in the systematic review and meta-analysis, of whom 110 (46.4%) underwent fertility preservation techniques. All patients (100%) successfully underwent fertility preservation with 1 participant (2.9%) returning to rewarm their oocytes, embryos or sperm. On average, 17.8 oocytes were retrieved with 78%, ultimately being cryopreserved. Five (6.0%) patients successfully conceived 9 healthy-term children after utilizing their cryopreserved sperm, embryos, or oocytes. Moreover, 6 patients successfully conceived naturally or using intrauterine insemination, resulting in 7 healthy-term children. Conclusions: Fertility preservation techniques could offer a safe and effective way for neuro-oncology patients to deliver healthy-term babies following treatment. However, further studies concerning risks, long-term pregnancy outcomes, and cost-effectiveness are needed.

Let's not abandon programmed frozen embryo transfers yet: a countercurrent perspective.

The countercurrent opinion given in this paper is that the optimal management of frozen embryo transfers (FET) is not a one-size-fits-all matter, but rather one that should be decided after considering all the various parameters and options. This choice should notably encompass patients' individual characteristics - including variable risks of obstetric complications - and weigh out the respective advantages of each FET option in each case. While there may be real advantages for natural-cycle FET in many cases, these need to be balanced against both practical and clinical issues. Contrary to several prevailing, sometimes loudly expressed suggestions, there is not a one single effective approach when it comes to choosing a mode of scheduling FET.

Gene biomarkers for the assessment of thyroid-disrupting activity in zebrafish embryos.

Active ingredients of pesticides or biocides and industrial chemicals can negatively affect environmental organisms, potentially endangering populations and ecosystems. European legislation mandates that chemical manufacturers provide data for the environmental risk assessment of substances to obtain registration. Endocrine disruptors, substances that interfere with the hormone system, are not granted marketing authorization due to their adverse effects. Current methods for identifying disruptors targeting the thyroid hormone system are costly and require many amphibians. Consequently, alternative methods compliant with the 3R principle (replacement, reduction, refinement) are essential to prioritize risk assessment using reliable biomarkers at non-protected life stages. Our study focused on detecting robust biomarkers for thyroid-disrupting mechanisms of action (MoA) by analyzing molecular signatures in zebrafish embryos induced by deiodinase inhibitor iopanoic acid and thyroid peroxidase inhibitor methimazole. We exposed freshly fertilized zebrafish eggs to these compounds, measuring lethality, hatching rate, swim bladder size and transcriptomic responses. Both compounds significantly reduced swim bladder size, aligning with prior findings. Transcriptome analysis revealed specific molecular fingerprints consistent with the MoA under investigation. This analysis confirmed regulation directions seen in other studies involving thyroid disruptors and allowed us to identify genes like tg, scl2a11b, guca1d, cthrc1a, si:ch211-226h7.5, soul5, nnt2, cox6a2 and mep1a as biomarker genes for thyroid disrupting MoA in zebrafish embryos as per OECD test guideline 236. Future screening methods based on our findings will enable precise identification of thyroid-related activity in chemicals, promoting the development of environmentally safer substances. Additionally, these biomarkers could potentially be incorporated into legally mandated chronic toxicity tests in fish, potentially replacing amphibian tests for thyroid disruption screening in the future.

Exposure levels and maternal transfer of emerging organophosphate flame retardants (OPFRs) in pregnant women: Comparison with traditional OPFRs.

Prenatal exposure to organophosphorus flame retardants (OPFRs) has been linked with adverse effects on reproductive health, and new OPFRs are continually emerging. In this study, emerging OPFRs, such as bis(2-ethylhexyl) phenyl phosphate (BEHPP), triamyl phosphate (TAP), tris(4-tert-butylphenyl) phosphate (T4tBPPP), oxydi-2,1-ethanediyl phosphoric acid tetrakis(2 chloro-1-methylethyl) ester (RDT905), cresyl diphenyl phosphate (CDP), and 2-isopropylphenyl diphenyl phosphate (2IPPDPP), were detected in 84 %, 100 %, 100 %, 52 %, 40 %, and 40 % of 25 decidua samples with average concentrations of 2.36, 6.21, 1.5, 2.6, 1.07, and 0.09 ng/g of dry weight (dw), respectively. Six of the aforementioned emerging OPFRs (BEHPP, T4tBPPP, RDT905, 2IPPDPP, CDP, and TAP) were simultaneously detected in paired chorionic villus samples, and their average concentrations were 11.3, 1.77, 3.64, 0.11, 0.58, and 3.34 ng/g, which were significantly higher than and positively correlated with those in decidua samples. The geometric mean concentration ratios between chorionic villus and decidua samples for BEHPP, T4tBPPP, RDT905, 2IPPDPP, CDP, and TAP were 4.02, 1.61, 1.73, 1.48, 0.82, and 0.69, respectively, consistent with transthyretin binding-dependent behavior. Prenatal exposure to such emerging OPFRs, especially for BEHPP with relatively high concentration and maternal transfer, is of high concern from the view of women's reproductive health.

Clinical pregnancy rates after blastocyst culture at a stable temperature of 36.6°C versus 37.1°C: a prospective randomized controlled trial.

STUDY QUESTION: Is there a difference in clinical pregnancy rates (CPRs) in good prognosis patients after single embryo transfer (SET) on Day 5, in case of stable culture at 36.6°C or 37.1°C? SUMMARY ANSWER: CPR (with heartbeat at 7 weeks) after blastocyst transfer do not differ after culturing at 36.6°C or 37.1°C. WHAT IS KNOWN ALREADY: Since the beginning of IVF, embryo culture has been performed at 37.0°C; however, the optimal culture temperature remains unknown. Changes in incubator types have led to significant improvements in temperature control. Stable temperature control, i.e. with temperature differences of max. 0.1°C between chambers, is possible in some incubators. A previous prospective pilot study showed that embryo development on Day 5/6 was not affected when embryos were cultured at a stable temperature of 36.6°C or 37.1°C, but culture at 37.1°C resulted in an increased CPR when compared to culture at 36.6°C (74.2% vs 46.4%). STUDY DESIGN, SIZE, DURATION: A prospective randomized controlled trial was performed in a tertiary fertility centre between February 2017 and November 26, 2022. A sample size of 89/89 patients with fresh single embryo transfer (SET) was required to achieve 80% power to detect a difference of 0.22 between group proportions (0.43-0.65) at a significance level of 0.05 using a two-sided z-test with continuity correction. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients were recruited on the day of oocyte retrieval based on inclusion criteria with final randomization after denudation once six mature oocytes were present. The primary endpoint was CPR (heartbeat at 7 weeks); secondary endpoints were fertilization rate, blastocyst development, biochemical pregnancy rate, live birth rate (LBR), and cumulative live birth rate (CLBR). MAIN RESULTS AND THE ROLE OF CHANCE: A total of 304 patients were eligible for the study; of these 268 signed the consent, 234 (intention-to-treat) were randomized and 181 (per-protocol) received a SET on Day 5: 90 received culture at 36.6°C and 91 at 37.1°C. Patients were on average 32.4 ± 3.5 versus 32.5 ± 4.2 years old, respectively. No differences were observed in embryological outcomes per cycle between culture at 36.6°C versus 37.1°C: 12.0 ± 3.8 vs 12.1 ± 3.8 COCs retrieved (P = 0.88), 10.0 ± 3.1 versus 9.9 ± 2.9 mature oocytes inseminated (P = 0.68), with a maturation rate of 84.2% (901/1083) versus 83.5% (898/1104) (P = 0.87); and 8.0 ± 3.1 versus 7.9 ± 2.7 normally fertilized oocytes with a fertilization rate of 79.7% (720/901) vs 80.5% (718/898) (P = 0.96), respectively. On average 1.5 ± 1.7 versus 1.4 ± 1.9 (P = 0.25) and 1.1 ± 1.1 versus 0.9 ± 1.0 (P = 0.45) supernumerary blastocysts were vitrified on Day 5 and Day 6, respectively. The utilization rate per fertilized oocyte was 46.1% vs 41.5% (P = 0.14). A SET was performed for 181 patients, leading to a biochemical pregnancy rate of 72.2% (65/90) versus 62.7% (57/91) (P = 0.17), respectively. The CPR per fresh transfer cycle was 51.1% (46/90) versus 48.4% (44/91) [OR (95% CI) 1.11 (0.59-2.08), P = 0.710]. To date, a CLBR of 73.3% (66/90) versus 67.0% (61/91) (P = 0.354) has been observed, respectively. In each group, seven patients without live birth have remaining blastocysts frozen. The CPR for the intention-to-treat groups were 38.3% vs 38.6% [OR (95% CI) 0.98 (0.56-1.73), P = 0.967], respectively, for culture at 36.6°C versus 37.1°C. LIMITATIONS, REASONS FOR CAUTION: Only selected patients with expected good prognosis were eligible for the study. WIDER IMPLICATIONS OF THE FINDINGS: Embryos tend to tolerate small changes in temperature deviations during culture to the blastocyst stage, as demonstrated by their similar implantation potential at two slightly different temperatures. STUDY FUNDING/COMPETING INTEREST(S): There is no funding or conflicts of interest to declare. TRIAL REGISTRATION NUMBER: NCT03548532. TRIAL REGISTRATION DATE: 23 October 2017. DATE OF FIRST PATIENT'S ENROLMENT: 10 November 2017.