Development Of Assisted Reproductive Technologies Research Articles

Research Progress on Luteinizing Hormone and Polycystic Ovary Syndrome

Polycystic ovary syndrome is a common endocrine disease in women of childbearing age, with an incidence of about 6% to 10%, which is the main cause of anovulatory infertility. With the development of assisted reproductive technology, up to 60% of patients with polycystic ovary syndrome need to be pregnant successfully through in vitro fertilization and embryo transfer. Ovarian controlled ovulation induction is an important process in assisted reproductive therapy. Luteinizing hormone plays an important role in the development and maturation of follicles in the ovary, and high levels of luteinizing hormone have a negative effect on pregnancy outcome. at present, it is still controversial that the appropriate level of luteinizing hormone will improve the pregnancy outcome, and the mechanism of how luteinizing hormone affects the pregnancy outcome is still unclear. This article will mainly review the above two aspects in order to provide reference for clinical research in the future.

Current Issues of Cryopreservation and Storage of Human Reproductive Biomaterial

With the development of assisted reproductive technologies (ART), contracts covering cryopreservation and the storage of germ cells, as well reproductive organ tissues and embryos are beginning to find wide practical application. Parties to such contracts are faced with questions not currently set out in the current legislation of the Russian Federation. This aim of this article is to identify legal models capable of resolving the most pressing issues arising from these contracts. It is proposed that the following types of biomaterial be reviewed as a continuation of the human body: reproductive biomaterial extracted from the human body in the aims of subsequent reintroduction, and capable of fulfilling that biological function for which it is designated; as well as material aimed at restoration or improvement of organ function. Any intervention upon such biomaterial should be qualified as intervention upon human health. Thus any medical organization found to be in violation of its obligation to preserve health must compensate for any damage caused to a patient’s reproductive health - as set out in the rules of chapter 59 of the Civil Code of the Russian Federation. The author suggests the notion of “abandoned biomaterial” be incorporated in Russian legislation. “Abandoned biomaterial” presupposes the termination of the rights of a person to this biomaterial and enables the medical organization, while ensuring its preservation, to utilize such biomaterial or to use it for research purposes. This would ensure the protection of human rights and legitimate the interests of the contracting party in the event of any violation of the terms of the contract by the client. The author also proposes legal models for the resolution of conflicts related to the plurality of contractual parties, as well as to postmortem human reproduction.

Impact of Graphene Oxide Nanoparticles on In Vitro Development of a Mouse Preimplantation Embryo andInteraction With the Zona Pellucida.

The development of assisted reproductive technologies increases the likelihood of nanoparticles' (NPs) direct contact with gametes and embryos in in vitro conditions. Analyzing the influence of nanomaterials on the early mammalian embryo becomes increasingly relevant. This work is devoted to the effect of graphene oxide (GO) NPs on the in vitro development of mammalian embryos. Mouse 2-cell embryos were preincubated with GO NPs. The interaction of GO with the Zona Pellucida (ZP) of the embryo was investigated using fluorescence lifetime imaging with two-photon excitation (2p-FLIM). During embryo development, the NPs penetration into ZP (blastocyst stage) and perivitelline space (blastocyst hatching stage) was observed. Despite this, GO did not affect the embryo's ability to develop till late and hatching blastocysts. The mechanism of the NPs getting into the perivitelline space and the consequences of NP-embryo direct contact are discussed. The 2p-FLIM efficiency for studying NP interaction with mammalian embryos is evaluated.

Main stream and scientific innovations in the field of obstetric services in the Ural Federal District

The article provides analytical data on the results of the obstetrics and childhood service of the Ural Federal District in 2023, analyzes the key indicators of the service over the past five years and provides directions for optimizing the work of the service. In the sphere of implementation of national projects “Healthcare” and “Demography”, applied scientific research and development of the “Ural Research Institute of Maternity and Child Care” of the Russian Ministry of Health makes a significant contribution to the development of medicine by improving methods of prediction, diagnosis, treatment and prevention of perinatal pathology, development of assisted reproductive technologies, which will improve the work of obstetrics and childhood services.

Hotspots and frontiers in luteal phase defect research: An in-depth global trend bibliometric and visualization analysis over a 52-year period

Luteal phase defect (LPD) is a common female reproductive endocrine defect，which is associated not only with certain diseases but also with the menstrual cycle and fertility in women. With the development of assisted reproductive technology (ART) in recent years, the incidence of luteal phase defect is high among patients using assisted reproductive technology. The aim of this study was to evaluate worldwide research on luteal phase defects using bibliometric analysis. A total of 631 documents related to the study of luteal phase defect were identified over the last 52 years. The current status and trend of globalization can be comprehended by analyzing the annual number of publications, institutions, authors, countries and regions of corresponding authors, journals, influential luteal phase defect publications (which were highly cited), highly cited references in luteal phase defect publications (cocitation analysis) and keywords. The study results provide a comprehensive overview of the development of scientific literature and are of great significance for the future development of the field，especially infertility and early pregnancy loss.

Chromosomal abnormalities detected by chromosomal microarray analysis and pregnancy outcomes of 4211 fetuses with high-risk prenatal indications

With the gradual liberalization of the three-child policy and the development of assisted reproductive technology in China, the number of women with high-risk pregnancies is gradually increasing. In this study, 4211 fetuses who underwent chromosomal microarray analysis (CMA) with high-risk prenatal indications were analysed. The results showed that the overall prenatal detection rate of CMA was 11.4% (480/4211), with detection rates of 5.82% (245/4211) for abnormal chromosome numbers and 5.58% (235/4211) for copy number variants. Additionally, the detection rates of clinically significant copy number variants were 3.78% (159/4211) and 1.8% (76/4211) for variants of uncertain significance. The detection rates of fetal chromosomal abnormalities were 6.42% (30/467) for pregnant women with advanced maternal age (AMA), 6.01% (50/832) for high-risk maternal serum screening (MSS) results, 39.09% (224/573) with abnormal non-invasive prenatal testing (NIPT) results, 9.21% (127/1379) with abnormal ultrasound results, and 5.1% (49/960) for other indications. Follow-up results were available for 4211 patients, including 3677 (3677/4211, 87.32%) whose infants were normal after birth, 462 (462/4211, 10.97%) who terminated their pregnancy, 51 (51/4211, 1.21%) whose infants were abnormal after birth, and 21 (21/4211, 0.50%) who refused follow-up. The results of this study demonstrate significant variation in the diagnostic rate of chromosomal microarray analysis across different indications, providing valuable guidance for clinicians to assess the applicability of CMA technology in prenatal diagnosis.

Prenatal post-implantation development of collared peccaries (Pecari tajacu Linnaeus, 1758).

Given the importance of information on intrauterine development in diagnosing anomalies in the gestational development of the species for the development of assisted reproduction technologies as well as understanding the autonomy and responsiveness of the newborn, the aim of the present study was to describe the external morphology of collared peccary conceptuses. For this study, two conceptuses were used per gestational age of 25-120 days post-copulation (dpc) and neonates with 145 dpc, totalling 22 animals. Females were euthanised, and embryos/foetuses were examined, measured, and photographed. During the first third of the gestational period (25-50 dpc, n = 8), a marked body curvature, brain vesicles, somites, internal organs, placid lens, auricular protrusion and limb buds are noted. In the second third of the gestational period (51-100 dpc, n = 10), foetuses lose their body curvature, displaying greater anatomical definition, including skeletal, external ears, nostrils, eyelids and tactile hair formation and cranial suture closure. In addition, dorsal scent gland and genital tubercle differentiation were visualized at 50 days post-copulation. In the third of the gestational period (101-145 dpc, n = 4), the organs become completely formed, alongside skin darkening, eyelid opening, dental eruption, dorsal odorous gland development, sexual organ externalization, and fanero attachment development. These data allowed for the construction of a prenatal growth curve, providing comparative anatomy information for ungulates and further contributing towards rational reproductive management and reproductive biotechnologies for this species.

Potential impact on using aspirin as the primary prevention of adverse pregnancy outcomes in twins conceived using ART

With the development of assisted reproductive technology, the number of twin pregnancies is increasing year by year. Given the increased risk of pregnancy complications associated with twin pregnancies, and the fact that these babies are rare and difficult to obtain through assisted reproductive technology, clinicians urgently require finding effective and safe drugs to improve pregnancy outcomes. Low-dose aspirin can not only promote placental blood supply, but also effectively anti-inflammatory. Whether Low-dose aspirin can effectively reduce the risk of pregnancy complications in this special group needs to be clarified. We therefore retrospectively analyzed 665 twin pregnancies from assisted reproduction technology, grouped according to aspirin use, and followed pregnancy outcomes to assess bleeding risk. Low-dose aspirin was found to be effective in preventing preeclampsia without a significant risk of bleeding. However, aspirin does not prevent specific complication in twin pregnancies and seems to have a better preventive effect only when the mother is under 30, which should alarm clinicians should not blindly using aspirin in this particular group.

The Role of Male Consent in Assisted Reproductive Technology Procedures: an Examination of Japanese Court Cases.

The online version contains supplementary material available at 10.1007/s41649-023-00274-1.

Sperm proteome and sperm parameters of captive Amazon squirrel monkeys (Saimiri collinsi Osgood, 1916) during the non-fatted and fatted condition

The aims of this work were (1) to characterize the proteome profile of Saimiri collinsi (Amazon squirrel monkey) sperm, and (2) to evaluate if there are meaningful differences in sperm quality and sperm protein landscape during the non-fatted and fatted conditions of the animals. Semen of adult males (n=4) was collected by electroejaculation and diluted in ACP-118® extender. Sperm concentration, motility, vigor, plasma membrane integrity and functionality, and sperm morphology were evaluated. Sperm proteome was characterized by mass spectrometry. The non-fatted and fatted conditions were defined according to the fattening index. There were increases in seminal volume, pH, and sperm motility of S. collinisi during the fatted in comparison with the non-fatted condition (p < 0.05). Animals in the fatted condition had greater body mass (909 ± 23.98 g) in comparison with the non-fatted condition (818.8 ± 5.97 g, p = 0.0001). There were 1161 proteins identified in the sperm of the monkeys. Thirty-seven proteins were upregulated (p < 0.05) in non-fatted condition (such as coiled-coil domain-containing protein 105, protein kinase C alpha type isoform X1, pyruvate dehydrogenase protein X component – mitochondrial and heat shock 70 kDa protein 1-like) and they were involved in cellular and metabolic processes, catalytic activity and binding. Twenty-eight sperm proteins proteins were upregulated (p < 0.05) in fatted condition (such as Cytochrome b-c1 complex subunit 2, mitochondrial; calcium-binding mitochondrial carrier protein SCaMC-1-like; heat shock 70 kDa protein 13, and izumo sperm-egg fusion protein 1), participating in cellular processes, metabolic processes, and localization, binding, catalytic activity, ATP-dependent activity, and transport activity. Functional annotations of sperm proteins upregulated in non-fatted condition were described as hydrogen ion transport, chaperone, cilium, flagellum, and cell projection. In in fatted conditions, such annotations were described as fertilization, spermatogenesis and transport, chaperone, and motor protein. The present study brings an unprecedent contribution to our understanding about the reproductive biology of adult Saimiri collinsi. It also provides support for conservation and development of assisted reproductive technologies for Neotropical primates.

Definition of the Beginning of Life and Its Legal Significance

The article analyzes the positions of scientists, as well as the current legislation regarding the definition of the beginning of human life in the context of child conception and ensuring the right of human embryo for life. The problem has not only theoretical, but also important practical significance, as the grounds and limits of legal regulation of a number of relations depend on it. The definition of the beginning of life allows for optimal legal regulation, including the provision of legal guarantees to preserve the life of the human embryo. States independently decide on the establishment of prohibition on artificial termination of pregnancy or the time limits after which such a termination is prohibited. Attention is drawn to the development of assisted reproductive technologies, the emergence of the possibility to use cryopreserved embryos, which can be stored for a long time. There is a lack of development of this aspect in science and a small and heterogeneous judicial practice. According to the author, the use of cryopreserved embryos in resolving issues of inheritance of property, as well as after divorce, should be based on a contractual basis. Due to the fact that the legislation allows artificial termination of pregnancy up to a certain period, as well as on medical grounds, the best way to determine the legal capacity of the embryo (foetus) as conditional. Proposals are being made to improve the norms of civil law, including a proposal to call to inheritance for children born as a result of the use of the biomaterial of the testator for in vitro fertilization within six months after testator’s death and born alive after the opening of the inheritance.

Визначення особливостей перебігу вагітності та пологів, стану плода і новонародженого у вагітних після застосування допоміжних репродуктивних технологій (дані ретроспективного аналізу)

The rapid growth in the number of infertile couples leads to the development of assisted reproductive technologies (ART). Among the most common forms of infertility are tubo-peritoneal, endocrine, and caused by the male factor, and prevention of pregnancy complications caused by ART treatment cycles becomes one of the main tasks of practicing clinicians. Purpose - to determine the features of the course of pregnancy and childbirth; to assess the condition of the fetus and newborn in pregnant women after the application of ART to improve the perinatal outcomes of pregnancy and childbirth. Materials and methods. A retrospective clinical and statistical analysis of 334 histories of pregnancy and childbirth of women, as well as medical records of newborns from women, was conducted over the past five years, which formed the ART group - 221 history of pregnancy and childbirth, and the group of spontaneous pregnancy - 113 history of pregnancy and childbirth. Results. The structure of the subjects was statistically significant dominated by pregnant women over the age of 35 years and pregnant women in late reproductive age. The main characteristics of women after the ART application were a statistically significant predominance of somatic and gynecological pathology. The structure of pregnancy complications in women after ART application was dominated by threatening late spontaneous miscarriages, isthmic-cervical insufficiency and vaginitis, and in the structure of labor complications - anomalies of labor activity and premature rupture of fetal membranes. Among newborns from women in the ART group, perinatal mortality was 18.0%. Conclusions. The revealed features of somatic and gynecological anamnesis, as well as aspects of the course of pregnancy and childbirth and the condition of newborns in women after ART application are the basis for an in-depth examination of this category of pregnant women in order to improve approaches to predicting, diagnosing and optimizing preventive measures, as well as to improve the perinatal consequences of pregnancy and childbirth. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. No conflict of interests was declared by the authors.

Gamete Collection, Artificial Fertilization and Captive-Rearing of Eggs in a Terrestrial-Breeding Anuran with Parental Care: Alytes obstetricans.

The genus Alytes consists of six primitive terrestrial-breeding species (five of them endangered or present in restricted distributions) with unique male parental care. Alytes obstetricans was used as a model for the development of assisted reproductive technologies for gamete collection, artificial fertilization and captive-rearing of embryos. Sperm collection was achieved with human chorionic gonadotropin (hCG), but only 17 to 50% of males responded to the hormone. In addition, an effect of captivity on sperm quality was observed. A combination of gonadotropin-releasing hormone agonist (GnRHa) and hCG was tested for induction of ovulation, and 100% of females responded to the treatment. Recently collected sperm was used in artificial fertilization, and 10% of eggs showed complete embryo development. To design a method for captive-rearing of embryos, natural clutches (n = 13) were removed from males and divided into two sub-clutches. One was kept with all eggs together and in the other, the egg string was cut and eggs were split individually. All sub-clutches with eggs kept separated presented embryo survival (ranging from 27 to 61%) that hatched normally, while only one sub-clutch with embryos maintained together had some embryo survival (36%). These results may contribute to the management of this and related species.

An expanded view of infertility: The challenge of the changing profiling of major birth defects in China.

Over the past two decades, China has experienced a significant decline in birth rates, accompanied by a decrease in fertility and changes in major congenital defects. The development of assisted reproductive technology (ART) has brought hope to individuals facing infertility. However, some issues related to reproductive health and congenital defects have arisen. The reasons for the changing profiling of birth defects and the relationship between the decline in fertility and ART need to be further investigated. Lifestyle factors such as nutritional supplementation need to be altered to protect reproductive capacity. Birth defects, such as congenital heart defects and hypospadias, may serve as a signal for understanding the decline in fertility. To improve fertility, the factors contributing to it need to be identified, vital genetic and medical technologies need to be introduced, and environmental interventions, such as nutritional changes, need to be implemented.

Fact-finding survey on assisted reproductive technology in Japan.

In anticipation of the future development of assisted reproductive technology (ART) and to smoothly introduce new technology, it is necessary to understand the current staffing status of the medical system and the current state of treatment, as well as the status of in vitro fertilization add-ons, where the need for insurance coverage is currently a matter of debate. ART facilities in Japan were surveyed (437 valid responses, response rate: 71%). Current staffing status of the medical system, implementation rates of ART, add-on treatments, and medical supplies were investigated. Despite the abundance of embryologists, nurses, and obstetricians and gynecologists in facilities, the majority of facilities lacked counselors, anesthesiologists, and other essential medical professionals. Conventional ovarian stimulation was widely adopted (median 120 [interquartile range 60-300] cycles), followed by mild ovarian simulation (60 [30-200]). Additionally, freeze-thaw embryo transfer cycles (300 [120-750]) were performed more frequently than fresh embryo transfer cycles (30 [30-60]). Among the add-ons, assisted hatching (85.1%), chronic endometritis examination (77.2%) and treatment (76.9%), artificial oocyte activation (67.3%), endometrial receptivity analysis (64.2%), and endometrial microbiome analysis (58.9%) were relatively widely employed. The implementation of frozen-thawed embryo transfer cycles, freeze-all strategies, and add-on treatments have become popular and widely accepted despite the lack of robust evidence regarding their safety and efficacy.

Problems of subjects and legal personality in family law

In family legislation, unlike civil legislation, the subjects of legal relations are not directly named. In addition to the disparity of norms concerning subjects of family legal relations, the mobility of the composition of such persons, due to the evolution of society and law, is a problem. A comparative analysis of the norms of law and doctrinal positions is carried out, as a result of which various classifications of subjects of family legal relations are identified, the inclusion of organizations and public legal entities, the family as a quasi-legal entity, is justified. As a result of the introduction of the institution of the foster family, new special subjects of family legal relations appeared — foster children and foster parents. In connection with the development of assisted reproductive technologies, the issue of qualification of potential parents, sperm donor and surrogate mother as subjects of family legal relations has been raised. There is a problem of legal qualification of the embryo. The problems associated with the legal personality of participants in family legal relations are revealed: the mixing of marital and family legal personality, the absence of separate norms on family legal capacity and legal capacity, etc. It is proved that the scope of family legal personality varies depending on age, a number of other legal facts, including other sectoral nature; it is associated with the goal-setting of the exercise of rights and performance of duties.

SCM is potential resource for non-invasive preimplantation genetic testing based on human embryos single-cell sequencing

The ongoing development of assisted reproductive technologies has provided hope to individuals struggling with infertility, promising the potential for a healthy pregnancy. One significant innovation in field of pre-implantation genetic screening (PGS) requires the biopsy of embryos or oocytes, which has potential implications for the health and development of the resultant offspring. Therefore, a non-invasive approach to preimplantation genetic screening is highly sought after. The clinical application of non-invasive preimplantation genetic testing (ni-PGT) is currently limited, with its sensitivity and specificity requiring further investigation. In this study, we used 218 human embryos for single-cell whole genome amplification (WGA), along with ni-PGT of blastocoele fluid (BF) and spent culture medium (SCM). Whole blastocyst (WB), trophectoderm biopsy (TB), and inner cell mass (ICM) from embryo biopsies were used as controls to track genomic signal alterations. Our results showed that the overall genome similarity between SCM and ICM was higher than that of BF. Apart from the Y chromosome, both SCM and ICM demonstrated numerous variant sites across other chromosomes.Further categorization of gene variants in these two sample types revealed that missense variants were the most prevalent, single nucleotide polymorphisms were more common than insertions or deletions, and C > T was the dominant single nucleotide variants in both ICM and SCM. Lastly, we found that the mutant genes in SCM and ICM had different biological functions and pathways. This study indicates that SCM provides a more effective source of embryonic DNA for preimplantation genetic screening, offering a novel reference point for genetic screening research.

Клінічна характеристика вагітних з алогенним плодом

The development of assisted reproductive technologies (ART) today allows many women to overcome biological barriers to motherhood. However, the use of such relatively new areas as oocyte donation and surrogacy, which result in the formation of an allogeneic fetus, is associated not only with legal but also with medical problems. Purpose - to analyze the clinical characteristics of pregnant women with an allogeneic fetus and pregnant women who were involved in ART programs with their own oocytes. Materials and methods. 120 pregnant women were examined, who were divided into the following groups: the Group I - 40 pregnant women who were involved in ART programs using foreign oocytes with the formation of an allogeneic fetus and whose management is planned to be carried out according to an improved algorithm; the Group II - 40 pregnant women who were involved in ART programs using foreign oocytes with the formation of an allogeneic fetus and whose management is planned to be carried out according to the generally accepted algorithm; the Group III - 40 pregnant women who underwent ART using the woman's own oocytes. The features of reproductive and somatic history, as well as social and demographic factors of the patient’s lives, were established. Results. Among pregnant women with an allogeneic fetus, a significantly higher proportion of women with pelvic inflammatory disease, bacterial vaginosis, cervical pathology, as well as patients with a history of surgical termination of pregnancy at the woman’s request were recorded. At the same time, the rates of registration of late menarche, endometriosis, polycystic ovary syndrome, early spontaneous abortions, as well as the following extragenital pathology: chronic arterial hypertension, diseases of the urinary system, and diabetes mellitus were significantly lower in patients of the Groups I and of the Groups II. The following social and demographic features of patients with an allogeneic fetus were noted: a smaller proportion of women with higher education, as well as those who live in their own home and are in a registered marriage compared to the control group. Conclusions. Registration of higher levels of a number of gynecological complications in pregnant women with an allogeneic fetus, as well as unfavorable social and demographic factors, requires the development of an improved management algorithm for such women, taking into account these features, which can help to reduce the rates of various obstetric and perinatal complications. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the author.

Recent Status of Pregnancies at an Advanced Maternal Age at a Japanese Perinatal Center.

Objective We compared the recent obstetric outcomes of women aged 40 and over as advanced maternal age (AMA) to those with AMA more than 10 years ago. Methods This was a retrospective study of primiparous singleton pregnancies who delivered at ≥22 weeks of gestation managed at Japanese Red Cross Katsushika Maternity Hospital between 2003-2007 and 2013-2017. Results The percentage of primiparous women aged with AMA who delivered at ≥22 weeks of gestation increased from 1.5 to 4.8% (p<0.01) due to the increase in the pregnancy conceived by in vitro fertilization (IVF). In the pregnancies with AMA, the percentage of cesarean delivery decreased from 51.7 to 41.0% (p=0.01), while the prevalence of postpartum hemorrhage increased from 7.5 to 14.9% (p=0.01). The latter was associated with an increased rate of in vitro fertilization (IVF) use. Conclusions The percentage of AMA pregnancies significantly increased with the development of assisted reproductive technology, and the prevalence of postpartum hemorrhage also increased in AMA pregnancies.

Estrogen upregulates DNA2 expression through the PI3K-AKT pathway in endometrial carcinoma.

Endometrial cancer is the most common gynecological malignancy, affecting up to 3% of women at some point during their lifetime (Morice et al., 2016; Li and Wang, 2021). Based on the pathogenesis and biological behavioral characteristics, endometrial cancer can be divided into estrogen-dependent (I) and non-estrogen-dependent (II) types (Ulrich, 2011). Type I accounts for approximately 80% of cases, of which the majority are endometrioid carcinomas, and the remaining are mucinous adenocarcinomas (Setiawan et al., 2013). It is generally recognized that long-term stimulation by high estrogen levels with the lack of progesterone antagonism is the most important risk factor; meanwhile, there is no definite conclusion on the specific pathogenesis. The incidence of endometrial cancer has been on the rise during the past two decades (Constantine et al., 2019; Gao et al., 2022; Luo et al., 2022). Moreover, the development of assisted reproductive technology and antiprogestin therapy following breast cancer surgery has elevated the risk of developing type I endometrial cancer to a certain extent (Vassard et al., 2019). Therefore, investigating the influence of estrogen in type I endometrial cancer may provide novel concepts for risk assessment and adjuvant therapy, and at the same time, provide a basis for research on new drugs to treat endometrial cancer.