Embryo Cryopreservation Research Articles

Risk of placenta previa in assisted reproductive technology: A Nordic population study with sibling analyses.

A higher risk of placenta previa after assisted reproductive technology (ART) is well established. The underlying mechanisms are poorly understood, but may relate to embryo culture duration, cryopreservation, and cause of infertility. Within-mother analyses, where each woman is her own control (i.e., sibling design), help disentangle treatment contributions from maternal confounders that are stable between pregnancies. We aimed to investigate the risk of placenta previa in pregnancies achieved after ART according to embryo culture duration, cryopreservation, and infertility factors while accounting for stable maternal factors using within-mother analyses. We used linked nationwide registry data from Denmark (1994 to 2014), Finland (1990 to 2014), Norway (1988 to 2015), and Sweden (1988 to 2015). All women who gave their first birth during the study period at age 20 years or older were eligible and contributed up to 4 deliveries (singleton or multifetal) occurring between 22 and 44 weeks of gestation, excluding deliveries where maternal age exceeded 45 years. We used multilevel logistic regression to compare risk of placenta previa after ART (n = 139,694 deliveries) versus natural conception (n = 5,614,512 deliveries), both at the population level and within mothers, adjusting for year of delivery, maternal age, parity, and country. We categorized ART according to culture duration, embryo cryopreservation, and infertility factors. Population level risk of placenta previa was higher for ART versus natural conception (odds ratio [OR], 4.16; 95% confidence interval [CI], 3.96-4.37). Controlling for stable maternal factors, the association attenuated, but risk remained higher for ART versus natural conception (OR within mothers, 2.64; 95% CI, 2.31-3.02). Compared to naturally conceived, a larger difference in risk was seen for pregnancies from fresh embryos than for pregnancies from frozen embryos. Further categorization by culture duration showed the largest risk difference after fresh blastocyst transfer, and the smallest after frozen cleavage stage embryo transfer, which persisted in sensitivity analyses (including restriction to singletons). When stratified according to infertility factors at the population level, women with endometriosis conceiving by ART had the highest risk of placenta previa (OR, 9.35; 95% CI, 8.50-10.29), whereas women with polycystic ovary syndrome (PCOS) conceiving by ART had the lowest risk (OR, 1.52; 95% CI, 1.12-2.09), compared to natural conception. Within mothers, we found a higher risk of placenta previa after ART compared to natural conception for women with endometriosis (OR, 2.08; 95% CI, 1.50-2.90), but not for women with PCOS (OR, 0.88; 95% CI, 0.41-1.89 [unadjusted due to sparse data]). However, within-mother analyses are restricted to multiparous women with deliveries after different conception methods. Therefore, findings from these analyses might not generalize to all women undergoing ART. The risk of placenta previa in pregnancies conceived by ART differed by embryo culture duration, cryopreservation, and underlying infertility. The highest risk was seen after fresh embryo transfer and especially fresh blastocyst transfer. Women with endometriosis had a higher risk than women with other infertility factors, and within mothers, their risk was higher after ART than after natural conception. Identifying the responsible mechanisms might provide opportunities for prevention.

Factors Affecting the Success of Ovum Pick-Up, In Vitro Production and Cryopreservation of Embryos in Cattle

Increasing global demand for animal proteins warrants improved productivity by genetic selection of superior cattle and faster dissemination of genetics. Availability of more progeny for genomic selection should maximize chances of identifying animals with desirable traits and increase selection pressure. OPU and IVP of embryos using these oocytes will substantially increase calves produced compared to conventional embryo transfer (ET). The OPU-IVP technology not only supports genetic improvement but also contributes to reducing environmental impacts of livestock production systems by improving efficiency and optimizing resources, aligning with the Sustainable Development Goals of the United Nations. However, there are several factors influencing the success of OPU-IVP. This review is focused on these factors and the impacts of in vitro culture conditions on the lipid content of embryos and potential role of L-carnitine, a lipolytic agent, on developmental competence of IVP embryos. The documented effects of L-carnitine and current knowledge regarding regulation of the Hippo signaling pathway suggest that supplementation of embryo culture media with L-carnitine will increase post-thaw survival of IVP embryos and their subsequent developmental competence by regulating lipid metabolism, production of reactive oxygen species, and Hippo signaling. Therefore, this review highlights current advancements in the field of OPU-IVP and potential areas for refining culture conditions to yield developmentally competent embryos that survive cryopreservation procedures.

Embryo Cryopreservation: What do couples think about it?

To investigate the perspectives of infertile couples regarding embryo cryopreservation throughout assisted reproduction treatment. The convenience sample included infertile couples undergoing assisted reproduction treatment. They responded to a questionnaire specifically designed to gauge views and opinions on cryopreservation of surplus embryos. Statistical analysis was conducted using SPSS, employing the Mann-Whitney U and Fisher's exact tests (p<0.05). The study included 187 couples, with average ages of 35 years for women and 38 years for men. A total of 182 couples (97.3%) agreed with the practice of freezing surplus embryos and, the desire to increase the odds of pregnancy within the same ovarian stimulation cycle was the main motivation (89%). Almost 40% of participants said they might consider embryo donation to other couples for assisted reproductive treatment. However, less than 20% of volunteers (15.38% of women and 12.08% of men) expressed the desire to donate for research purposes. Women with higher levels of education were significantly (p<0.05) more likely to support the donation of surplus embryos for research. Gender, religion, and education did not influence (p>0.05) the respondents' perspectives regarding the beginning of life and posthumous conception. Embryo cryopreservation provides infertile couples with hope however, the fate of surplus embryos remains controversial. A careful approach with appropriate regulation is necessary to ensure safe and ethical practices.

Controlled ovarian hyperstimulation with or without letrozole for fertility preservation in breast cancer patients: study protocol for a randomised controlled trial

IntroductionMultimodal anticancer therapies greatly damage the fertility of breast cancer patients, which raises urgent demand for fertility preservation. The standard options for fertility preservation are oocyte and embryo cryopreservation; both...

Gynecological complications and treatment strategies in patients after hematopoietic stem cell transplantation.

In women after hematopoietic stem cell transplantation (HSCT), complications associated with the original disease and therapies used both before and after transplantation often occur, which significantly affects their quality of life. The most common gynaecological complications include secondary cancers, premature ovarian insufficiency (POI), infertility and chronic graft-versus-host disease (cGVHD). Cervical cancer is the most common secondary genital cancer in patients after HSCT. Regular screening and vaccination against HPV (Human Papillomavirus) can significantly reduce the risk for its occurrence. The specific complication after allogeneic hematopoietic stem cell transplantation is graft-versus-host disease (GVHD), the genital form of which can lead to labial and vaginal adhesions, significantly reducing the women's quality of life. The basis of treatment is local steroid therapy and immunosuppression. A consequence of chemotherapy and radiation therapy may be damage to the gonads leading to premature ovarian insufficiency and the onset of menopause symptoms. The basis of treatment is systemic hormone therapy used until middle age when natural menopause is reached. Women after HSCT who are of reproductive age also suffer from infertility. An important role of the doctor is to educate patients about the risk for infertility and to suggest appropriate methods of preserving fertility before starting treatment. The recommended procedure for fertility preservation is cryopreservation of embryos or oocytes. The freezing and retransplantation of ovarian tissue is becoming an increasingly popular method of fertility protection. Preventive examinations and early detection and treatment of gynaecological complications significantly improve the comfort of life and health of women after HSCT.

Legal Analysis and Practical Proposals for Application of the Law on Inheritance by Contract

Introduction. For our country, the modern era is characterised by the rapid development and sophistication of the social relationships, especially in the field of economics and private property preservation as the basis for enhancing market relations. Over the past few years, new institutions and norms have been formed within the civil law of the Russian Federation, which officially stipulated the relationships already existing among the subjects. The most atypical innovation for the Russian legislation was integration of the new rules of inheritance based on the contractual relationships (Article 1140.1) into the Civil Code of the Russian Federation in 2019. Unfortunately, this institution has not become widely used in practice, probably due to the rather incorrect regulation of the rights and obligations of the parties to this legal relationship and their unequal position in obtaining the final result. Significant difficulties arise when using this norm in the context of inheritance of the agricultural lands, residential premises, joint property, etc. The study of the institution of inheritance by contract is highly relevant due to the fact that this norm has a potential to become a fairly strong basis for the formation of equal relationships of the parties in terms of the redistribution of property, but, taking into account the imperfection of legal regulation, it requires the detailed elaboration for its implementation into the objective reality. The aim of the research is to conduct a comprehensive analysis of this institution and develop the practical proposals for improving the legislation on inheritance contracts.Materials and Methods. The following methods have been used in the research: the general scientific method of theoretical research, comparative analysis, formal-logical approach to the analysis of the legislation regulating the application of the contractual relationships in the frame of property inheritance. A review of the data on law enforcement and judicial practice in the research area has been provided.Results. The paper identifies the problems of efficient application of the norms of inheritance by contract to the certain types of property, suggests the ways to improve the legislative norms that determine the legal status of counterparties, as well as the content of their powers. A number of proposals for adjusting the acting norms of inheritance by contract have been formulated. In particular, the authors propose to add a separate chapter referring to the inheritance by contract to the Civil Code of the Russian Federation and include in it the norms, which ensure the possibility of preserving property that is the subject of the contract until the moment of contract coming into effect and which regulate the rules of inheriting the residential premises and agricultural lands in accordance with the same procedure. Within the research, it has been also proposed to legislatively stipulate the legal status of nasciturus and children conceived after the death of the testator by means of medical technologies (IVF, embryo cryopreservation, surrogacy, etc.), and the procedure of inheriting property by the spouses upon conclusion of the inheritance contract.Discussion and Conclusion. The conducted research allowed the authors to identify the existing inaccuracies in the legislative regulation of the inheritance by contract and to determine further directions for studying and adjusting the theoretical and practical aspects of this institution. With respect to the foreign country examples of rule-making in the studied subject area, the trends in the formation of such rules of inheritance by contract were determined that would allow this rarely used practice an opportunity to become an acting procedure that contributes to strengthening the legal order in the frame of legal relationships on inheritance.

Ultra-Fast Warming Procedure of Vitrified Blastocysts Results in Maintained Embryology and Clinical Outcomes.

Vitrification has revolutionized embryo cryopreservation, but represents a significant workload in the IVF lab. We evaluated here an ultrafast blastocyst warming procedure in order to improve workflow while maintaining clinical outcome. We first evaluated the expression of main markers of lineage specification in a subset of blastocysts donated to research warmed with ultrafast protocol. We then performed a prospective pseudo-randomized pilot study comparing blastocyst survival, reexpansion and live birth rates between standard (3 steps, 15min), and ultrafast warming protocol (1 step, 2min). Finally, survival, reexpansion and live birth rates (LBR) obtained with ultrafast warming protocol were prospectively collected during 3months and compared with previous indicators. Immunofluorescence experiments showed that staining and spatial organization of cell fate markers were conserved with ultrafast protocol. Survival, reexpansion and LBR were strictly comparable between standard (n = 47 cycles) and ultrafast (n = 39 cycles) groups in the pilot study (100 vs 100%, 80 vs 76% and 29.8 vs 30.7% in standard and simplified groups respectively). Survival, expansion and LBR obtained with the ultrafast warming protocol over the next 3-month period (321 cycles, 336 embryos) were comparable with those obtained with the standard protocol throughout the 6months (547 FBT cycles, 578 embryos) preceding shifting protocol (97.6 and 29.6% vs 97.8 and 28.3% respectively, p > 0.05 for both). In conclusion, using an ultrafast blastocyst warming procedure results in similar embryology and clinical outcomes compared with standard protocol, but significantly shortens the technical procedure, ultimately improving the overall lab's workflow.

Effect of hydroxypropyl cellulose on vitrification of sheep embryos.

Vitrification is a conventional and mature method for embryo cryo-preservation, but ice crystals formed during the vitrification process can damage embryos. HPC has the property of forming a high-viscosity gel under low-temperature conditions, so it can be added to vitrification solutions to investigate whether it improves the negative impact of vitrification on embryos. The results showed that the addition of HPC (50μg/ml) to the vitrification solution significantly increased the post-warming survival rate of sheep morula embryos. Compared to the vitrification group, the addition of HPC significantly reduced the level of ROS (reactive oxygen species, ROS) and increased the level of GSH (glutathione, GSH) in embryos after warming, mitigating the damage to mitochondria caused by vitrification. It also had clear positive effects on the developmental potential of vitrified-warmed sheep embryos. Overall, the addition of 50μg/ml HPC to the vitrification solution can significantly improve the quality of sheep morula embryos after vitrification and warming.

Ultrastructural Characteristics of Bovine Embryos Produced In Vitro And Vitrified Using the Cryotop Method

BACKGROUND: Despite advancements in bovine embryos cryopreservation techniques, challenges remain, warranting further investigation into their impact on embryo morphology and viability so that outcomes can be improved. OBJECTIVE: To analyze, through transmission electron microscopy (TEM), in vitro-produced bovine embryos vitrified using the Cryotop method. MATERIALS AND METHODS: Groups of embryos were transferred to a stabilization solution (SS) containing 7.5% EG, 7.5% DMSO in maintenance medium (TCM-199 supplemented with 20% FBS) for 2 min, and then transferred to a vitrification solution (VS) containing 15% EG, 15% DMSO, and 0.5 M sucrose in maintenance medium. Warming was performed in five stages with decreasing concentrations of sucrose. After warming, the blastocysts were cultured for 24 h for subsequent survival analysis and ultrastructural evaluation. In vitro-produced bovine embryos that did not undergo the vitrification process were used as a fresh control. RESULTS: Blastocoel reestablishment was observed in 52.3% (66/126) of vitrified embryos 24 h after warming, demonstrating the method's effectiveness in postcryopreservation survival. Ultrastructural analysis of embryos from the fresh control group showed flattened trophoectodermal cells with prominent nuclei, well-preserved mitochondria, and Golgi complexes were also evident. Microvilli were observed in some regions near the zona pellucida. Embryos vitrified using the Cryotop method exhibited lesions consistent with the cryopreservation process, such as intracellular disorganization, mitochondrial injuries, and dispersion of microvilli. CONCLUSIONS: Ultrastructural evaluation of in vitro-produced bovine embryos vitrified using the Cryotop method is an effective tool for increased understanding of the injuries caused to embryonic cells during the cryopreservation process.

On The Legal Status of Cryopreserved Embryos

Cryopreserved embryo transfer, as one of the assisted reproductive technologies (ART), while safeguarding the right to reproduce, raises numerous complex legal issues. Historical disputes over cryopreserved embryos have primarily centered on determining right holders and have generally positioned cryopreserved embryos as objects. But the latest judicial precedents recognize that children born through cryopreserved embryo transfer have the right to claim child support for torts committed by their fathers during the cryopreserved embryo stage, thus confirming the stance that cryopreserved embryos are subjects. This revolutionary shift has transitioned the debate over the legal status of cryopreserved embryos in China from theory to practice. Theoretically, there are three divergent views on the legal status of cryopreserved embryos: the object theory, the subject theory, and the intermediary theory. Judicial practice follows the theoretical disputes, with various precedents leading to starkly different conclusions regarding the legal status of cryopreserved embryos, resulting in a state of disorder in judicial rulings. The main reason for this phenomenon is the multifaceted nature of cryopreserved embryos, which are related to, inter alia, life, personality, ethics, and morality. There has not been a unified consensus in legislation yet, and the embarrassing situation of legislative deficiencies can only be temporarily alleviated through judicial judgments. It is necessary to build a tiered system on the legal status of cryopreserved embryos. In terms of the legal status of a cryopreserved embryo implanted into a womb, the cryopreserved embryo should be confirmed to have the capacity as a subject of law in accordance with Article 16 of the Civil Code on the protection of fetuses’ interests. Before implantation, a retroactive rule may be applied, thereby recognizing that a cryopreserved embryo still in a cryopreserved state also has the capacity as a subject of law. While in terms of the legal status of a cryopreserved embryo hasn’t yet implanted into a womb, the presumption rule shall apply: the embryo shall be presumed to be a subject or object according to whether there is a possibility of implantation. 作为辅助生殖技术之一的冷冻胚胎移植在保障生育权的同时，也产生很多难解的法律问题。此前对于冷冻胚胎的争议主要集中于谁才是权利人，即坚持冷冻胚胎为客体的立场，但最新判例认为，利用冷冻胚胎移植出生的孩子，对其处于冷冻胚胎阶段针对其父亲的侵权行为具有抚养费请求权，即确认冷冻胚胎为主体的立场。这一颠覆性的立场变化，使得中国对于冷冻胚胎法律地位的争议从理论走向实践。理论上，对冷冻胚胎的法律地位存在客体说、主体说和中间体说三种观点，且分歧巨大。司法实践也在步理论争议的后尘，各种判例对冷冻胚胎法律地位的认定结果迥异，这使得冷冻胚胎法律地位的司法裁判呈现无序的状态。导致这种现象的主要原因在于，冷冻胚胎关涉到生命、人格、伦理、道德等，立法也未形成统一的共识，只能暂时通过司法裁判的方式缓解立法缺失的尴尬处境。应分层构建冷冻胚胎的不同法律地位，对植入母体内的冷冻胚胎的法律地位，应参照适用《民法典》第16条关于胎儿利益保护的规定赋予其主体资格，在其被植入母体前，可以采用溯及规则，溯及既往的认为处于冷冻阶段的冷冻胚胎也具有主体地位。对植入母体前的冷冻胚胎的法律地位，应采取推定规则，根据是否具有植入的可能性，推定其为主体还是客体。

Sex differences in childhood cancer risk following ART conception: a registry-based study.

Does the risk of childhood cancer following ARTs vary by sex? In this registry-based study, some childhood cancers showed positive sex- and age-specific associations in children conceived using certain ART modalities, which were not evident in overall combined analyses. The relationship between ART and risk of childhood cancer has shown diverse outcomes in prior research. Studies examining whether there are sex differences in childhood cancer risk after ART conception are lacking. This registry-based cohort study included all children born in Norway between 1984 and 2022 (n = 2255025), followed until 31 December 2023. Children were identified via the Medical Birth Registry of Norway, and information was extracted on whether they were conceived via ART (defined as IVF/ICSI). Of the 2255025 children included in the study, 53694 were ART-conceived. Birth records were linked to the Cancer Registry of Norway. Childhood cancer was defined as a cancer diagnosis according to the International Classification of Childhood Cancer Third Edition (ICCC-3) before the age of 18years. Cox regression models were used to estimate the age- and sex-specific risk of cancer for ART-conceived children compared to children not conceived via ART. Among all children, 0.25% had a cancer diagnosis before the age of 18years. The cumulative incidence of cancer was higher in children conceived by ART (IVF/ICSI) than in those not conceived via ART (21.5 vs 17.5 per 100000 person-years, P = 0.04), and especially higher in boys conceived with ICSI or after cryopreserved embryo transfer. When combining all age groups, both sexes and all cancer types, there was little evidence of increased cancer risk with ART (adjusted hazard ratio (aHR) 1.13, 95% CI 0.94-1.36). However, differences were found when stratifying by age and sex. From age 5-9years, ART-conceived children had a higher overall risk of cancer (aHR 1.53, 95% CI 1.06-2.20), with a slightly higher estimate in boys (aHR 1.73, 95% CI 1.09-2.74), than in girls (aHR 1.28, 95% CI 0.70-2.33). The risk was not higher up to age 5years, or after age 10years. In combined analyses, there was no overall increased risk after ICSI. When stratifying by sex, a higher risk was seen after ICSI for boys (aHR 1.69, 95% CI 1.18-2.42), but not for girls (aHR 0.65, 95% CI 0.37-1.16). The combined risk after cryopreservation (aHR 1.42, 95% CI 0.95-2.13) was driven by a higher risk in boys (aHR 1.79, 95% CI 1.09-2.94), while no evidence of an association was found in girls (aHR 1.01, 95% CI 0.50-2.03). No increased risk was seen with IVF or after fresh transfer for either boys or girls. Childhood cancer is a rare outcome, and some analyses of cancer subtypes were likely underpowered. Results from this large registry-based study suggest that addressing age- and sex-specific differences in the risk of childhood cancer following ART conception reveals increased risks for certain groups. Our findings require further study with consideration of possible underlying sex-specific mechanisms related to ART and different childhood cancers. This work was funded by: the Research Council of Norway through its Centres of Excellence Funding Scheme (project number 262700); the Norwegian Cancer Association (project number 244291); and the Norwegian Institute of Public Health. The funding agencies had no role in the conceptualization, design, data collection, analysis, decision to publish, or preparation of the manuscript. The authors declare no conflict of interests. N/A.

Fertility potential in patients with ovarian cancer

Malignant neoplasms of the reproductive system are the most common form of oncological morbidity in women, accounting for over 30% of all cancer cases. Most antineoplastic agents act by inducing DNA damage in highly proliferating cancer cells, resulting in oocyte death. Ovarian toxicity is the most common side effect of cancer treatment in young women. Both chemotherapy and radiotherapy have been shown to be toxic to the ovaries, increasing the risk of premature ovarian failure, early menopause, endocrine disorders, and infertility. Patients who have undergone cancer treatment have severe follicular atresia, even if they have a regular menstrual cycle. Currently, the most effective methods of preserving fertility in cancer patients include cryopreservation of oocytes and embryos after ovarian hyperstimulation. Other fertility preservation methods include ovarian tissue cryopreservation, follicle or embryo maturation in vitro, ovarian transposition, ovarian suppression, and adjuvant therapy. Despite promising fertility prospects, iatrogenic infertility is one of the most undesirable adverse effects of cancer therapy for young women. Timely referral to a gynecologist prior to chemotherapy or radiation therapy is key to successful fertility preservation. Women should be aware of the available opportunities of assisted reproductive technologies, along with potential risks and failures with regard to their age, stage of disease, and treatment method. At this stage, it is necessary to develop well-defined and effective algorithms for oncologists, obstetrician-gynecologists, fertility specialists, and embryologists.

Public fertility preservation programme for cancer patients in Hong Kong.

Fertility preservation (FP) offers cancer patients the opportunity to have biological children after completing treatment. This study was performed to review the experience and changes in service demand since the implementation of a public FP programme for cancer patients in Hong Kong. This retrospective study included men and women who attended an assisted reproduction unit for public FP services before cancer treatment from August 2020 to February 2023. Their medical records were reviewed and the results were compared with findings from our previous study to evaluate trends in service demand. During the study period, there were 48 consultations for female FP, compared with 72 women who presented for FP from 2010 to 2020 prior to establishment of the public FP programme. The median time from referral to consultation was 3 days (interquartile range [IQR]=2-5). Eighteen women (37.5%) underwent 19 cycles of ovarian stimulation for oocyte or embryo cryopreservation. Thirty women (62.5%) received gonadotropin-releasing hormone agonists during cancer treatment. There were 58 consultations for male FP during the study period, compared with 265 men who presented for sperm cryopreservation from 2005 to 2020. The median time from referral to consultation was 4 days (IQR=2-7). Fifty-five men (94.8%) attempted sperm cryopreservation, and 49 (84.5%) successfully preserved sperm. Since the establishment of a public FP programme for cancer patients, there has been an increase in the demand for FP services at our centre. Regular review of FP services is warranted to assess changes in demand and identify areas for improvement.

The costs per live birth after uterus transplantation: results of the Swedish live donor trial.

What is the cost per live birth after live donor uterus transplantation in a Swedish clinical trial setting? The total cost per child, from a health care perspective, was calculated to be €124894 and if only surgically successful transplants are considered, the total cost per live birth was €107120. Uterus transplantation has proved to be a feasible treatment for uterine factor infertility by accomplished live births, both after live donor and deceased donor transplantation procedures. Our previous study, the only existing cost analysis of uterus transplantation, found that the initial (up to 2 months after surgeries) societal costs of preoperative interventions, live donor uterus transplantation surgeries, and postoperative care were between €50000 and €100000 (mean €74000) in Year 2020 values per uterus transplantation. That study also included costs of sick leave for both donors and recipients. This real-data health economic cost study is based on a prospective cohort study, which included nine live donor uterus transplantation procedures. Study duration included the time from the first pre-transplantation investigation until postoperative controls after graft removal. Recipients, live donors, and neonates of nine uterus transplantation procedures participated. The recipients and donors underwent pre-transplantation investigations with imaging, laboratory tests, and psychological/medical screening. In vitro fertilization with embryo cryopreservation was performed in advance of transplantation. Donor hysterectomy and transplantation were by laparotomy and the recipient received immunosuppression. Pregnancy attempts by ET started 1 year after transplantation and delivery was by caesarean section. Hysterectomy was performed either after birth of one or two children, after graft failure, or after multiple pregnancy failures. Nine transplantation procedures resulted in seven surgically successful (adequate blood flow and regular menstruations) grafts and six women delivered a total of nine children. The total cost of preoperative investigations, live donor uterus transplantation, postoperative care, immunosuppression, IVF, follow-up, pregnancy care, delivery, and graft removal after completed childbirth(s) or failure to achieve live birth was calculated, based on inclusion of cost for six women, giving birth to a total of nine children, and three women, with no childbirth. Cost for live donors was also included in the analysis. The total cost per child was calculated to be €124894. However, if only surgical successful transplants (seven out of nine transplants) are considered, the cost per live birth was €107120. The cost for preoperative preparations with IVF, surgeries, and postoperative follow-up during the initial 2 months was around 53% of total costs. Smaller sub-costs were those for monitoring, ETs with additional IVF (14%), immunosuppression and other drugs from Month 3 until hysterectomy (13%), and pregnancy care with delivery and neonatal care (13%). Limitations are the restricted sample size, the experimental phase of the procedure and that the results only reflect the cost in one country (Sweden). The results provide the first information concerning the cost per child of the uterus transplantation intervention. In the future, the cost per child will most likely decrease due to predicted increase in the rate of surgical success, decreased surgical durations, decreased graft duration to achieve live birth(s), and increased rate of transplantations giving not only one, but two or three singletons. Funding was received from the Jane and Dan Olsson Foundation for Science, the Knut and Alice Wallenberg Foundation, the Swedish Research Council, and an ALF grant from the Swedish state under an agreement between the government and the county councils. There are no conflicts of interest for any of the authors. NCT01844362.

The legal regime of a human embryo created in vitro

The article is dedicated to the study of the legal regime of a human embryo created in vitro, considering national and international legal approaches, as well as ethical and bioethical aspects. The aim of the work is to develop a comprehensive approach to regulating the legal status of embryos in Ukrainian law, which meets the modern challenges ofbiomedical technologies and international standards. The subject of the study is the legal norms concerning the use, storage, and destruction of embryos created in vitro, as well as the ethical limitations influencing their legal status.A comparative legal method was applied in the study, allowing the analysis of the approaches of different legal systems (including European continental, Anglo-Saxon, and international) to the definition of the legal status of an embryo. The methodology also includes the analysis of bioethical norms related to law enforcement in the field of reproductive technologies. The scientific novelty of the research lies in the formation of new proposals for improving Ukraine's national legislation and ensuring a balance between legal and ethical requirements. The relevance of the topic is due to the rapid development of biomedical technologies and the increasing need for their proper legal regulation.The main results of the study are the formulation of recommendations for improving national legislation in the field of legal regulation of embryos created in vitro. In particular, it is proposed to define clear time limits for embryo storage, the conditions for their use in scientific research, and the establishment of a balance between patients' rights and ethical restrictions. Additionally, recommendations for protecting the rights of participants in the reproductive technology process, including medical and research institutions, were developed.The practical significance of the work lies in the possibility of using the results to improve law enforcement in the field of reproductive technologies and to protect the rights of participants in the reproductive process. The proposed recommendations can be implemented in national legislation to increase its effectiveness and ensure compliance with modern international standards.

Clinical utilization and outcomes over eight consecutive years following oocyte cryopreservation.

To compare embryologic and clinical outcomes following oocyte cryopreservation (OC) and immediate fertilization for embryo cryopreservation (EC) in non-infertile patients. Retrospective cohort study SUBJECTS: Patients treated at a single fertility center from 2016 to 2023. OC MAIN OUTCOME MEASURES: Blastocyst development was compared between women undergoing OC and non-infertile women undergoing immediate fertilization for EC between 18 and 42years of age. ICSI, PGT-A, and eSET were used in all cycles. Outcomes from 3697 thawed MII oocytes obtained from 239 OC patients were compared to 28,959 fresh MII oocytes obtained from 2031 patients undergoing immediate fertilization for EC. Average thaw MII survival rate was 92% and high across age groups. Post-thaw oocytes demonstrate lower fertilization rate compared to fresh oocytes (85% v 90%, p < 0.05). As oocyte age increased, the mean number of MII used per blastocyst increased to a greater extent among thawed compared to fresh oocytes (2.9 v 2.2 MII age 18-34, 3.3 v 2.5 MII age 34-37, 3.9 v 2.9 MII age 38-40, 7.5 v 3.9 MII age 41-42, p < 0.05). Among patients achieving transfer of a euploid blastocyst, clinical pregnancy rate and live birth rate per transfer were similar using thawed and fresh oocytes (p = 0.82 and p = 0.79, respectively). Blastocyst conversion is lower from thawed oocytes compared to fresh oocytes. Differences in blastocyst development between thawed and frozen oocytes increase with advancing oocyte age, suggesting that older oocytes may be less efficient in their conversion to blastocysts after vitrification and warming.

Embryo Cryopreservation Strategy May Improve Live Birth for Women Underwent In Vitro Maturation After Early Oocyte Retrieval: A Retrospective Cohort Study.

There is limited clinical research investigating the optimal transplantation strategy in early oocyte retrieval cycles. We aimed to assess whether the maturation of oocytes from early oocyte retrieval influenced pregnancy outcomes, and to find the optimal embryo transfer strategy (fresh or frozen-thawed embryo transfers) for patients who had early oocyte retrieval and underwent in vitro maturation (IVM). A retrospective cohort study was conducted in a university-based reproductive medical center. A total of 234 women who underwent single embryo transfer after early oocyte retrieval were included. The primary outcome was live birth rate. The live birth rate (12.5% vs. 27.5%, p = 0.005, adjusted p = 0.010) was significantly lower in IVM cycles compared with no IVM cycles. There was a significant decrease in live birth (3.6% vs. 19.0%, p = 0.008, adjusted p = 0.011) and a markedly elevated early pregnancy loss rate (62.5% vs. 11.1%, p = 0.014, adjusted p = 0.012) for IVM fresh cycles compared with no IVM fresh cycles. However, these findings were not repeated in subgroup analysis when frozen-thaw embryos were transferred. These results indicate that patients who underwent early oocyte retrieval and then IVM-intracytoplasmic sperm injection should be recommended the embryo cryopreservation strategy. Resynchronization of the embryo and the endometrium in frozen-thaw embryo transfer cycles may optimize live birth and decrease early pregnancy loss in IVM-intracytoplasmic sperm injection cycles after early oocyte retrieval.

Breast cancer Treatment and Fertility Preservation: A Narrative Review of Impacts, Strategies and Ethical Considerations.

At present, breast cancer represents the most common malignancy diagnosed in women worldwide. Due to the trend toward delayed childbearing, many women of reproductive age are being diagnosed with breast cancer and treated with chemotherapy or hormone therapy which can adversely affect their fertility. This literature review discusses the effects of breast cancer treatment on fertility and options for fertility preservation. Treatments used in the management of breast cancer often result in a diminished ovarian reserve, premature ovarian insufficiency, and treatment-related amenorrhea. Chemotherapy may cause direct damage to oocytes and deplete ovarian reserve, while hormone therapies such as tamoxifen can cause amenorrhea and delay childbearing. Targeted therapies and radiotherapy may also pose risks to reproductive health. Fertility preservation is a concern for patients, and many of them may refuse or prematurely discontinue treatment to preserve their fertility. It is relevant to incorporate considerations of fertility at the time of treatment planning for breast cancers and to provide information to appropriate patients regarding their options. Current techniques available for fertility preservation include ovarian suppression, oocyte and embryo cryopreservation, and ovarian tissue cryopreservation. In spite of these techniques being in existence, there are plenty of barriers that deter the patients from availing them, including lack of awareness, financial constraints, and the need for timely treatment. This review implicates that these challenges require multidisciplinary approaches and a patient-centered approach. Further research is warranted toward the improvement of fertility preservation techniques, individual variability in protocols, and newer advances in reproductive medicine to further optimize quality of life in survivors of breast cancer.

Assessment of the cyst wall and surface microbiota in dormant embryos of the Antarctic calanoid copepod, Boeckella poppei.

Embryos of zooplankton from inland waters and estuaries can remain viable for years in an extreme state of metabolic suppression. How these embryos resist microbial attack with limited metabolic capacity for immune defence or repair is unknown. As a first step in evaluating resistance to microbial attack in dormant zooplankton, surface colonization of the Antarctic freshwater copepod, Boeckella poppei, was evaluated. Scanning electron micrographs demonstrate the outer two layers of a five-layered cyst wall in B. poppei fragment and create a complex environment for microbial colonization. By contrast, the third layer remains undamaged during years of embryo storage in native sediment. The absence of damage to the third layer indicates that it is resistant to degradation by microbial enzymes. Scanning electron microscopy and microbiome analysis using the 16S ribosomal subunit gene and internal transcribed spacer (ITS) region demonstrate the presence of a diverse microbial community on the embryo surface. Coverage of the embryos with microbial life varies from a sparse population with individual microbes to complete coverage by a thick biofilm. Extracellular polymeric substance binds debris and provides a structural element for the microbial community. Frequent observation of bacterial fission indicates that the biofilm is viable in stored sediments.

The Success Rate of Cryopreservation and Thawing of Embryos at Day 3 and Day 5 Following Intracytoplasmic Sperm Injection (ICSI)

Cryopreservation, the technique of freezing and thawing embryos, is essential in in vitro fertilization (IVF) treatments to ensure the long-term preservation of embryos for future use. This innovative study evaluates the effectiveness of these procedures conducted at a private hospital in Tangerang, Indonesia, over a period of seven years (2016-2023), involving 18,000 couples. The design research was conducted retrospectively. The study examined embryos that underwent cryopreservation and subsequent thawing, with data collected on the rates of cell division observed on Day 3 and the rates of blastocyst formation on Day 5 after thawing. The study investigated the rates of cellular division on Day 3 and the development of blastocysts on Day 5 following the thawing process. The findings demonstrated a remarkable cleavage rate of 95.24% and a blastocyst rate of 97.22%. The remarkable results underscore the efficacy of the advanced freezing and thawing techniques employed. This discovery is highly significant since there is an urgent requirement to improve the success rates of in vitro fertilization (IVF) for couples facing infertility. It offers a fresh sense of hope and increased opportunities for establishing successful pregnancies with the improvement of cryopreservation techniques.