Advances In Assisted Reproductive Technology Research Articles

Subcutaneous G-CSF administration improves IVF outcomes in patients with recurrent implantation failure presenting a KIR/HLA-C mismatch

Research questionDespite advances in assisted reproductive technologies, many blastocysts are lost unexpectedly during implantation. Alterations in maternal immune tolerance towards fetal antigens may contribute to adverse IVF outcomes. The purpose of this study is to evaluate whether administering Granulocyte Colony-Stimulating Factor (G-CSF) to couples with a Human Leukocyte Antigen/Killer-Cell Immunoglobulin-Like Receptor (HLA/KIR) mismatch could positively modulate the implantation process in patients with recurrent implantation failure (RIF). A KIR/HLA-C mismatch occurs when the interaction between KIRs and HLA-C causes an inhibition of NK cells, which may result in reduced G-CSF secretion leading to impaired placentation and increased risk of miscarriage, pre-eclampsia and fetal growth restriction. DesignA retrospective monocentric cohort study conducted at the IVI Clinic in Rome, including women with a history of at least two failed blastocyst transfers. Couples underwent KIR and HLA-C testing. Couples with a KIR/HLA-C mismatch received G-CSF subcutaneously up to week nine of gestation. The mismatch included cases with inhibitory KIR genotypes and HLA-C2C2 females with HLA-C1C1, or C1C2 males or HLA-C1C2 females with male HLA-C2C2. The reproductive outcomes were assessed, and the logistic regression models controlled for potential confounders affecting IVF outcomes. Results79 patients with RIF and a KIR/HLA-C mismatch were included in the study. 30 patients were administered G-CSF, and 49 received no treatment. In the univariate analysis, no statistically significant differences were reported in the reproductive outcomes after IVF between the women treated with G-CSF and the control group. However, the logistic regression analysis that controlled for confounding factors showed that patients treated with subcutaneous G-CSF had statistically significant higher ongoing-pregnancy (aOR=3.808) and live-birth (aOR=4.998) rates, and a lower miscarriage rate (aOR=0.057). No statistically significant differences were found in other reproductive outcomes. ConclusionThe use of subcutaneous G-CSF in patients with a KIR/HLA-C mismatch undergoing IVF may reduce miscarriage and improve live-birth rates. G-CSF may modulate NK-mediated immune mechanisms and improve trophoblast invasion and development. Randomized trials are warranted to validate these findings and enhance the chances of successful pregnancies in couples with an immunological mismatch.

Men and Female Infertility: Multidisciplinary Review

Abstract—Infertility is one of society's physical, social, and psychological difficulties. "Failure to obtain a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse," according to the definition. Ovulation induction has remained a watershed moment in the lives of women. Infertility is a prevalent problem that is sometimes misunderstood. Male infertility has affected an increasingly large population over the past few decades, affecting over 186 million people globally. The advent of assisted reproductive technologies (ARTs) and artificial intelligence (AI) has changed the landscape of diagnosis and treatment of male infertility. Because of its effects on families, its importance to study in related fields such as fertility trends and reproductive health, and its implications for practitioners who work with individuals and couples facing infertility. Infertility is an important topic for family scientists. Inability or difficulty in conceiving is a physically and psychologically draining experience for a woman. Polycystic Ovary Syndrome (PCOS) has been determined as one of the serious health problems in women that affects the fertility of women and leads to significant health conditions. Therefore, early diagnosis of polycystic ovary syndrome can be effective in the treatment process Keywords—infertility; hormones; clinical data,PCOS,adolescene ,harmone,

Plasticity in moth mating behavior and ejaculate proteomic diversity induced by male competition

In male competition, large and costly ejaculates are advantageous. Prior research on male accessory gland secretions in Plutella xylostella left open questions about how males modulate their mating behaviors and ejaculate composition allocation in response to varying levels of competition. The current study aimed to delve deeper into these unexplored facets. A totally of 928 ejaculate proteins were identified across males exposed to different competition conditions. Notably, males courting under non–, low-, and high-competition scenarios exhibited 867, 635, and 858 ejaculate proteins, respectively. Approximately 10% of these ejaculate proteins displayed variations that aligned with changes in competition intensity. Subsequent analyses focused on the proteins transferred to females, revealing that 44% of ejaculate proteins were transferred, with 37 proteins exhibiting differential expression. Functional analyses uncovered their crucial roles in sperm maturation, motility, and capacitation. Our findings reveal adaptive adjustments in ejaculate protein abundance and transmission in P. xylostella as a response to varying competition levels. Moreover, fluorescent sperm labeling indicated higher sperm transfer during low competition correlated with shorter sperm length. Furthermore, evidence suggests that males shorten their courtship duration and extend their mating duration when faced with competition. These results illustrate how competition drives ejaculate investment and behavioral plasticity, offering valuable insights for advancements in assisted reproductive technologies and pest management strategies.

P-148 Humid versus dry culture: impact on euploidy, live birth sex ratio and clinical outcomes

Abstract Study question Does humidity have an impact on top-quality blastocyst rate, ploidy, live birth sex ratio and clinical outcomes? Summary answer Humid culture conditions in time-lapse incubators may enhance clinical outcomes, particularly in autologous cycles, without biasing euploidy or newborn sex. What is known already Recent advances in assisted reproductive technology have focused on improving embryo culture conditions and incubators are becoming more sophisticated. Although culture conditions such as oxygen and temperature are well-studied, the optimal humidity level remains uncertain. Dry atmospheres favour higher evaporation of culture media compared to humid conditions, increasing its osmolality. This appears to be detrimental to several animal model embryos: developmental arrest, changes in gene expression and epigenetic alterations in the embryos. Previous studies have shown than incubator humidification improves clinical outcomes and embryonic development. However, other studies showed no significant improvements. Study design, size, duration A single center retrospective study was performed. Data included a total of 793 cycles of IVF/ICSI between January 2019 and May 2023. Participants/materials, setting, methods 793 cycles of IVF/ICSI from 734 patients were studied. Study population was categorized in autologous (n = 544) and egg-donation (n = 249) cycles. A total of 5909 embryos were included in the study. Patients were randomly distributed in two distinct cohorts at the moment of their treatment: dry condition (DC) and humid condition (HC). Blastocyst quality (BR), biochemical pregnancy (BPR), implantation rate (IR), live birth rate (LBR) were studied. Ploidy rate and LB sex ratio was also studied. Main results and the role of chance In egg donation cycles, no differences were observed between HC and DC groups in the rates of top-quality blastocysts (61.5 HC vs 64.4% DC), BPR, (71.1% HC vs 71.2% DC), IR (53.8% HC vs. 59.2% DC) or LBR (51.9% HC vs. 44.8% DC). However, autologous cycles showed an improvement when humid conditions were used. BR and IR were higher in humid conditions (BR: 58.8% HC vs. 55,6% DC, p-value 0.03; IR:57.1% HC vs. 39.7% DC, p-value 0.011)). Humid and dry culture conditions yielded similar rates of BPR (65.0% HC vs 53.0% DC, p-value: 0.11) and live birth rate (44.3% HC vs 34.5% DC, p-value: 0.16). Although there is a tendency towards a 20% of benefit in presence of humidity in both rates, no significance was reached. No differences were found in euploidy between dry and humid groups. When stratifying patients by age, all age groups met the ploidy expected rates in both culture conditions. Humid culture conditions enhance clinical outcomes, particularly in autologous cycles. Donated oocytes may take advantage of their better quality to compensate the detrimental effect of dry ambients. Our study, moreover, demonstrates that humidity does not introduce any bias towards chromosomal alterations or newborn sex. Limitations, reasons for caution This is a retrospective study and should be further confirmed with a prospective randomized study. Sample size should be increased, especially for ploidy Specific humidity values could also be tested. Wider implications of the findings Humid culture conditions may highly improve ART outcomes for particular groups of patients. If tested with stratified groups by age, a specific age group might be especially benefited of humidity, without any bias in sex ratios when best embryo is transferred in fresh cycles. Trial registration number not applicable

P-448 Placental histopathology in frozen embryo transfer HRT induced IVF pregnancies and non-IVF pregnancies and its correlation with maternal and fetal outcomes: a prospective case-control study

Abstract Study question Is Placental histopathology altered in Frozen Embryo transfer, HRT induced IVF pregnancies when compared to non-IVF pregnancies; if yes,any implications on maternal and fetal outcome? Summary answer Pathological placental lesions and adverse maternal outcomes were found to be significantly higher in IVF pregnancies compared to non-IVF pregnancies. What is known already Studies on placental histopathology in IVF pregnancies suggest that there may be differences compared to naturally conceived pregnancies. Some research indicates an increased risk of certain placental abnormalities such as changes in vascularization and structure (Uroka Belak, et al., 2023). Additionally, alterations in gene expressions and epigenetic modifications in placenta have been observed in IVF pregnancies. However, it is essential to note that findings can vary, and more research is needed to fully understand the implications and potential long-term effects. Study design, size, duration Prospective, single centre, comparative clinical study, including 100 pregnancies between November, 2022 and November, 2023; 50 FET HRT induced IVF pregnancies, 50 non-IVF pregnancies. Participants/materials, setting, methods Patients aged 32-45 years, >34 weeks gestation, with no associated maternal and obstetrical complications were recruited after proper screening and informed consent. Among 100 pregnancies, we compared placental HPE using the Amsterdam Placental Workshop Group Consensus and feto-maternal outcomes between FET HRT induced IVF pregnancies and non-IVF pregnancies. We used Chi-square test to compare groups(p < 0.05). Main results and the role of chance Out of 100 participants, 50 were frozen embryo transfer, HRT induced IVF pregnancies and 50 were non-IVF pregnancies. Out of 50 IVF pregnancies; 27(54%) had pathological placental lesions, of which 17(63%) were noted to have adverse maternal outcomes and 6(22.2%) had adverse fetal outcomes. Out of 50 non-IVF pregnancies, 4(8%) had pathological placental lesions; of which 1(25%) were noted to have adverse maternal outcomes and 1(25%) had adverse fetal outcomes. On comparing these 2 groups, our result was found to be statistically significant(p < 0.05). Limitations, reasons for caution This study has some limitations owing to it being a single centered comparative trial, possibility of observer bias in histopathological examination and that the study is restricted to HRT induced IVF pregnancies. Wider implications of the findings This study reveals valuable insights into potential differences in placental and fetal development. Understanding these variances could influence clinical practices, patient counseling, and contribute to advancements in assisted reproductive technologies. Additionally, insights into long-term health outcomes for both mothers and babies may emerge, guiding future research and healthcare strategies. Trial registration number Not applicable

The Effect of Progesterone Elevation on the Day of Trigger Administration: A Review of the Literature

Since the advent of assisted reproductive technology, different variables have been shown to affect pregnancy outcomes. One of the most prevalent studied events is the premature rise in serum progesterone concentrations on the day of trigger administration during cycles of ovarian stimulation. This phenomenon, classically known as premature luteinization, has been observed significantly for decades and has been linked to adverse pregnancy outcomes and lower live birth rates. Ultimately, a quest to find a precise serum progesterone concentration cut-off value that can be effectively used to predict pregnancy outcomes prior to trigger administration is still underway. The purpose of the current research was to study the available literature on the relationship between serum progesterone on the day of trigger administration in controlled ovarian stimulation cycles used for IVF in an attempt to identify a cut-off serum progesterone concentration that can be used to effectively predict future pregnancy outcomes in fresh transfers. This study is a review of the literature and is based on information and data gathered from 36 published articles. The majority of the literature shows that a serum progesterone concentration cut-off of 1.5 ng/ml (4.77 nmol/L) can be used prior to trigger administration to effectively predict pregnancy outcomes. Premature progesterone elevation on the day or prior to the trigger administration is associated with adverse pregnancy outcomes in IVF cycles. Other factors such as follicle number, serum concentration of other hormones, and ovarian response to ovarian stimulation should also be considered to predict the success of IVF protocols.

Rethinking 'family': A call for conceptual amelioration.

The modern concept of 'family' in the United States recognizes many types of social groups as families, a conceptual shift which was largely helped along by advancements in assisted reproductive technologies enabling those formerly unable to biologically reproduce to have children, as well as by social movements aimed at garnering recognition for these emergent nonbiologically related social groups spearheaded by LGBTQ+ and adoption activists. That these social groups are now recognized as types of families is unquestionably an improvement to the concept, though there are still defects in the concept that preclude these nonnuclear families from achieving the same social-ontological status as nuclear families. Drawing from the nascent philosophical field of conceptual engineering, I analyze our current conception of 'family' and argue that it is tacitly exclusionary of nonnuclear families, which can be attributed to a combination of widespread genetic essentialism and linguistic practices that unduly cast the nuclear family as a more desirable type of family by emphasizing genetic relatedness as a valuable quality. I then offer proposals to ameliorate these defects, such as educational interventions to reduce genetic essentialism and the introduction of new terminology that does not connote one type of family as being superior to another. In doing so, my hope is to reveal and begin to resolve an overlooked defect in the concept of 'family' in order to bolster the movement to view all families as equal.

USP22 is required for human endometrial stromal cell proliferation and decidualization by deubiquitinating FoxM1

Despite significant advances in assisted reproductive technology (ART), recurrent implantation failure (RIF) still occurs in some patients. Poor endometrial receptivity and abnormal human endometrial stromal cell (HESC) proliferation and decidualization have been identified as the major causes. Ubiquitin-specific protease 22 (USP22) has been reported to participate in the decidualization of endometrial stromal cells in mice. However, the role of USP22 in HESC function and RIF development remains unknown. In this study, clinical endometrial tissue samples were gathered to investigate the involvement of USP22 in RIF, and HESCs were utilized to examine the molecular mechanisms of USP22 and Forkhead box M1 (FoxM1). The findings indicated a high expression of USP22 in the secretory phase of the endometrium. Knockdown of USP22 led to a notable reduction in the proliferation and decidualization of HESCs, along with a decrease in FoxM1 expression, while overexpression of USP22 yielded opposite results. Furthermore, USP22 was found to deubiquitinate FoxM1 in HESCs. Moreover, both USP22 and FoxM1 were downregulated in the endometria of patients with RIF. In conclusion, these results suggest that USP22 may have a significant impact on HESCs proliferation and decidualization through its interaction with FoxM1, potentially contributing to the underlying mechanisms of RIF pathogenesis.

Recent advances in assisted reproductive technologies of feline reproduction

Many wildcat species are threatened with extinction, rare or vulnerable due to habitat destruction and poaching. In addition, Ankara and Van domestic cat species originating from Türkiye are in danger of extinction and are under protection. Thus, the requirement for assisted reproductive techniques in b oth domestic and nondomestic cat species has been increasing in recent years. Assisted Reproductive Technologies (ART) such as in vitro maturation, in vitro fertilization, embryo transfer, and cloning in domestic cats (Felis catus) provide a useful and suitable model for the conservation of endangered cat species. Domestic cats can be recipients for embryo transfer and recipient cytoplasm for nuclear transfer from various small wildcat species. Thanks to ART, it is possible to ensure the continuation of the generation by producing in vitro embryos or by making intra or inter-species clones from wild cats that have lost their reproductive functions or even died recently. Many inherited genetic disorders have been identified in cats that are similar to humans. Due to their genetic closeness, they have recently begun to be used as animal models in some therapeutic studies on humans, especially on kidney and nervous system diseases. In the early years, in vitro study results were less successful than in farm animals but in recent years ART’s such as in vitro embryo production, embryo transfer, cloning, and transgenesis have made significant progress in domestic of domestic and wild cats. This review includes the assisted reproductive technologies applied in recent years and the results obtained in domestic cat and felines.

Surrogacy: An important pathway to parenthood. A call for international standardization

This comprehensive review examines the multifaceted landscape of surrogacy, a revolutionary treatment for infertility. The study examines historical origins, shifting trends, medical considerations, psychological implications, legal complexities, international variations, and ethical dilemmas surrounding surrogacy. With the advent of assisted reproductive technology, gestational surrogacy allows intended parents a genetic connection to their child. Medical facets encompass indications for gestational surrogacy, drawing attention to maternal health risks and infertility factors. Evidence indicates that medical outcomes are comparable to conventional pregnancies, suggesting a viable reproductive solution for intended parents. Due to the complex nature of surrogacy psychological and emotional vulnerability is inevitable; yet studies underscore positive psychological well-being and satisfaction among gestational carriers (GCs), intended parents (IPs) and children. Surrogacy also has many religious dimensions, as each religion has its own perspective on the distinctive process of creating life and its outcomes, such as, the determination of the child's mother according to their beliefs. Legal considerations emerge as a fundamental aspect, with differing regulations globally. The review emphasizes the significance of comprehensive agreements to safeguard the rights and responsibilities of surrogates and IPs. The unique surrogacy laws in Israel serve as a noteworthy example, reflecting a progressive approach that provides a promising template to establish crucial international guidelines on surrogacy. The absence of international consensus necessitates attention from the global community to address key concerns, including the well-being of GCs, legal recognition for IPs, and the child's best interests, with the goal of establishing a universal standard of care in the field.

The Role of Artificial Intelligence in Male Infertility: Evaluation and Treatment: A Narrative Review

Male infertility has affected an increasingly large population over the past few decades, affecting over 186 million people globally. The advent of assisted reproductive technologies (ARTs) and artificial intelligence (AI) has changed the landscape of diagnosis and treatment of male infertility. Through an extensive literature review encompassing the PubMed, Google Scholar, and Scopus databases, various AI techniques such as machine learning (ML), artificial neural networks (ANNs), deep learning (DL), and natural language processing (NLP) were examined in the context of evaluating seminal quality, predicting fertility potential, and improving semen analysis. Research indicates that AI models can accurately estimate the quality of semen, diagnose problems with sperm, and provide guidance on reproductive health decisions. In addition, developments in smartphone-based semen analyzers and computer-assisted semen analysis (CASA) are indicative of initiatives to improve the price, portability, and accuracy of results. Future directions point to possible uses for AI in ultrasonography assessment, microsurgical testicular sperm extraction (microTESE), and home-based semen analysis. Overall, AI holds significant promise in revolutionizing the diagnosis and treatment of male infertility, offering standardized, objective, and efficient approaches to addressing this global health challenge.

Navigating conflicts of reproductive rights: Unbundling parenthood and balancing competing interests.

Advances in assisted reproductive technologies can give rise to several ethical challenges. One of these challenges occurs when the reproductive desires of two individuals become incompatible and conflict. To address such conflicts, it is important to unbundle different aspects of (non)parenthood and to recognize the corresponding reproductive rights. This article starts on the premise that the six reproductive rights-the right (not) to be a gestational, genetic, and social parent-are negative rights that do not entail a right to assistance. Since terminating or continuing a pregnancy is a form of assistance, the right (not) to be a gestational parent should enjoy primacy in conflicts. However, while refusing assistance may hinder the reproductive project of another person, "prior assistance" does not entitle someone to violate a reproductive right. Therefore, our analysis provides reasons to argue that someone has a right to unilaterally use cryopreserved embryos or continue the development of an entity in an extracorporeal gestative environment (i.e., ectogestation). Although this could lead to a violation of the right not to be a genetic parent, it does not necessarily entail a violation of the right not to be a social parent.

Yoga and Lifestyle Changes: A Path to Improved Fertility - A Narrative Review.

Infertility, a widespread medical condition affecting numerous couples globally, persists as a challenge despite advances in assisted reproductive technologies (ARTs), often burdened by financial, physical, and emotional strains. Complementary and alternative approaches, notably yoga, have garnered attention for potentially enhancing fertility outcomes. Studies reveal yoga's influence on factors contributing to infertility, including reduced oxidative stress (OS) and oxidative DNA damage (ODD). OS, linked to mutagenic base formation, higher malondialdehyde levels, abnormal methylation, and altered gene expression, can impair sperm genome integrity. Yoga's efficacy is evident in lowering OS, positively affecting signal transmission, gene expression, and physiological systems. Furthermore, yoga has a positive impact on addressing the dysregulation of apoptosis, resulting in improved processes such as spermatogenesis, sperm maturation, and motility, while also reducing DNA fragmentation. OS correlates with genome-wide hypomethylation, telomere shortening, and mitochondrial dysfunction, contributing to genome instability. Yoga and meditation significantly reduce OS and ODD, ensuring proper reactive oxygen levels and preserving physiological systems. The review explores potential mechanisms underlying yoga's positive impact on infertility, including enhanced blood flow, reduced inflammation, relaxation response, and modulation of the hypothalamic-pituitary-adrenal axis. Furthermore, a comprehensive review of the literature reveals substantial evidence supporting the positive effects of yoga on infertility factors. These include oxidative stress (OS), oxidative DNA damage (ODD), epigenetic changes, hormonal balance, ovarian function, menstrual irregularities, and stress reduction. In summary, yoga emerges as a promising adjunctive therapy for infertility, demonstrating the potential to mitigate key factors influencing reproductive success. Although preliminary evidence indicates the positive effects of yoga on infertility, further clinical research is imperative to define specific benefits, molecular mechanisms associated, optimal protocols, and long-term effects in infertility treatment plans.

Development and evaluation of a decision-making aid for couples hesitant about transitioning from infertility treatment to advanced assisted reproductive technology: a usability and feasibility study

ObjectivesThe aims of this study were (1) to develop a decision-making aid for couples hesitant about transitioning from infertility treatment to advanced assisted reproductive technology, (2) to examine the adequacy of this aid, and (3) to evaluate its usability. After the first version of the decision-making aid was created, the first version was supervised and finally a prototype of the decision-making aid was completed. We conducted a feasibility study from February to March 2022. We used a quantitative cross-sectional descriptive design involving 22 medical professionals and infertility survivors recruited.ResultsTwenty-two participants (3 reproductive medical specialists, 11 nurses who specialize in reproductive medicine, and 8 infertility survivors) were included in the final analysis (91.7% valid response rate). Of these participants, 81.8% answered Agree regarding “Easy-to-read degree of charts”, 17 (77.3%) answered It is just the right amount regarding “Appropriateness of information volume”, 81.8% answered Agree regarding “Ease of understanding content”, and 90.9% answered Good regarding “Overall performance”. From the opinions received, we extracted 4 categories: “Useful for decision making,” “Suitable for providing information,” “Useful in clinical practice,” and “Needs improvement.” Certain degrees of surface validity and content validity were confirmed for the trial version of the decision-making aid.

The neonatal southern white rhinoceros ovary contains oogonia in germ cell nests

The northern white rhinoceros is functionally extinct with only two females left. Establishing methods to culture ovarian tissues, follicles, and oocytes to generate eggs will support conservation efforts using in vitro embryo production. To the best of our knowledge, this is the first description of the structure and molecular signature of any rhinoceros, more specifically, we describe the neonatal and adult southern white rhinoceros (Ceratotherium simum simum) ovary; the closest relation of the northern white rhinoceros. Interestingly, all ovaries contain follicles despite advanced age. Analysis of the neonate reveals a population of cells molecularly characterised as mitotically active, pluripotent with germ cell properties. These results indicate that unusually, the neonatal ovary still contains oogonia in germ cell nests at birth, providing an opportunity for fertility preservation. Therefore, utilising ovaries from stillborn and adult rhinoceros can provide cells for advanced assisted reproductive technologies and investigating the neonatal ovaries of other endangered species is crucial for conservation.

MYC–MAX heterodimerization is essential for the induction of major zygotic genome activation and subsequent preimplantation development

In mouse preimplantation development, zygotic genome activation (ZGA), which synthesizes new transcripts in the embryo, begins in the S phase at the one-cell stage, with major ZGA occurring especially at the late two-cell stage. Myc is a transcription factor expressed in parallel with ZGA, but its direct association with major ZGA has not been clarified. In this study, we found that developmental arrest occurs at the two-cell stage when mouse embryos were treated with antisense oligonucleotides targeting Myc or MYC-specific inhibitors from the one-cell stage. To identify when MYC inhibition affects development, we applied time-limited inhibitor treatment and found that inhibition of MYC at the one-cell, four-cell, and morula stages had no effect on preimplantation development, whereas inhibitor treatment at the two-cell stage arrested development at the two-cell stage. Furthermore, transcriptome analysis revealed that when MYC function was inhibited, genes expressed in the major ZGA phase were suppressed. These results suggest that MYC is essential for the induction of major ZGA and subsequent preimplantation development. Revealing the function of MYC in preimplantation development is expected to contribute to advances in assisted reproductive technology.

Comparative reproduction of the female horse, elephant and rhinoceros: implications for advancing Assisted Reproductive Technologies (ART).

Recent loss of rhinoceros subspecies has renewed interest in using more advanced assisted reproductive technologies (ART) in rhinoceroses and elephants. Currently, only semen collection, semen preservation and artificial insemination (AI) have been used repeatedly with success in these species. Although ovum pick-up (OPU) and intra-cytoplasmic sperm injection (ICSI) have been reported in rhinoceroses, the techniques are not yet optimised. In contrast, multiple ART applications are routinely used in the horse. Since elephant and rhinoceroses share some reproductive features with equids, we postulate that procedures such as OPU, ICSI, in vitro fertilisation (IVF) and embryo transfer (ET), which are well established in the horse, may represent a basis to develop protocols for endangered pachyderms. In this review, we summarize current knowledge on reproductive physiology relevant to ART. We discuss the current state of ART in all three families and the requirements for the successful implementation of OPU, ICSI, IVF and ET in these species.

Recurrent Implantation Failure: Reality or a Statistical Mirage?: Consensus Statement From the July 1, 2022 Lugano Workshop on Recurrent Implantation Failure

ABSTRACT Despite advancements in assisted reproductive technologies over the past few decades, a 35% failure rate is still observed for unexplained reasons when transferring euploid embryos to an anatomically normal uterus. Recurrent implantation failure (RIF) is defined based on cumulative ART cycles failing; however, there is an absence in consensus on the diagnostic criteria, which leads to the risk of overdiagnosing and overtreating the condition. This consensus statement by the Lugano RIF Workshop aimed to merge variation in the clinical concept and management of RIF, focusing primarily on euploid blastocyst transfers in hormone replacement-primed cycles. The workshop comprised a panel of 27 international experts selected on the basis of overall research activities and publications on the subject. A literature search as conducted for all relevant titles and abstracts published between January 2015 and May 2022 for review. Consensus conclusions were based on the literature search and expert opinions. Consideration of an RIF diagnosis was determined to focus on failure to achieve sustained implantation (defined as a gestational sac identified on ultrasound). Historically, RIF was defined as the failed transfer of >10 embryos; however, today, a common number used is 3, which is also similar to the rate of failure based on a 95% confidence interval. Based on large clinical data sets, approximately 2%–5% of patients pursuing ART treatment may have RIF, and the decline in future implantation rate with each cycle fits more to an exponential delay curve than a linear decrease. The diagnosis of RIF should not be considered based on a single cohort of embryos, but rather on the number of euploid blastocyst transferred adjusted to patient’s age. In the absence of abnormal uterine bleeding and normal uterine size, further evaluation of asymptomatic adenomyosis is not warranted. Testing for biomarkers of endometrial receptivity and the endometrial microbiome have not been validated using RCTs and should not be used. The role of chronic inflammation in RIF remains unclear, but evidence suggests chronic endometritis does not directly play a role in ART outcome as assessed by sustained implantation rate after euploid embryo transfer. Substantial evidence exists that is low progesterone on the day of embryo transfer results in worse ART outcomes, and that IM progesterone may be superior to vaginal progesterone. There are no effective treatments for RIF currently, and immunomodulatory treatments that may be offered including glucocorticoids, IVIG, and GCSF have a lack of comprehensive data. This consensus document finds that RIF is likely present in fewer than 5% of patients undergoing ART and has been overdiagnosed and overtreated without sufficient critical evaluation of the presumed condition. It also highlights areas where future research is needed, both in the pathophysiologic cause of RIF and hypothetical treatment modalities.

Minor changes in the incidence of primary and secondary involuntary childlessness across birth cohorts 1916 to 1975, but major differences in treatment success.

There have been tremendous advances in assisted reproductive technologies (ARTs) over the past 50 years. The present study assessed infertility outcomes among women of reproductive age during this period. The seventh survey of the Tromsø Study (Tromsø7, 2015-16) recruited Tromsø residents aged 40-98 years. The questionnaire collected information on sociodemographics and infertility, as well as data from a wide range of validated health questionnaires. Primary involuntary childlessness was defined as reporting one or more of the following: the clinical definition of infertility (i.e., infertility period of >1 year), infertility examination, use of ART, and/or the birth of a child conceived during ART. Women with secondary involuntary childlessness were those who reported infertility experience and had least one naturally conceived child. Parous women without infertility experience were classified as fertile, and nulliparous women without infertility experience as voluntarily childless. The main exposure was birth cohort (1916-35, aged 80-98 years; 1936-45, aged 70-79 years; 1946-55, aged 60-69 years; 1956-65, aged 50-59 years; 1966-75, aged 40-49 years). The incidence of primary involuntary childlessness was significantly higher in the 1956-75 cohort (6.0%; 95% CI: 5.4-6.6) than the 1916-55 cohort (3.7%; 95% CI: 3.2-4.3). The incidence of secondary involuntary childlessness was higher than that of primary involuntary childlessness across all birth cohorts and was highest for the 1966-75 cohort (10%), with no differences observed across the other birth cohorts (6-7%). An increasing proportion of women from the oldest to the youngest birth cohorts reported infertility examination and ART. ART success increased substantially with time, reaching 58% for primary and 46% for secondary infertility in the 1966-75 cohort. Voluntarily childless women comprised 5-6% of the 1916-55 cohort and 9-10% of the 1956-75 cohort. There were minor differences in the incidence of primary and secondary involuntary childlessness across the 1916-75 cohorts. Advances in ART over the past 50 years comprised 2.0% and 3.3% of population growth in the 1956-65 and 1966-75 cohorts, respectively: a remarkable achievement.

P-698 Genetics and reproductive health outcomes: An Asian perspective

Abstract Study question Does genetics play a role in the reproductive outcomes in women undergoing assisted reproductive technology (ART)? Summary answer We describe a trend towards poorer reproductive outcomes associated with Asian women and ART. Subsequently, we posit a potential biological mechanism. What is known already In the last four decades, advances in assisted reproductive technology (ART) have afforded the possibility of conceiving a child to individuals who encounter fertility complications. However, a closer examination of the clinical outcomes of ART shows a stark contrast in Asian women compared to Caucasians, with the majority of studies reporting lower reproductive success among Asian women. In this study, a systematic review was performed to elucidate the genes associated with ART clinical outcomes, with a focus on Asian ethnicities. Concomitantly, we highlight the need for personalized medicine to bridge the gaps in female reproductive health. Study design, size, duration We performed a Pubmed and Embase database search, from inception to December 2022, to identify all studies which investigated the differential reproductive outcomes in Asian women compared to their Caucasian counterparts, genetic mutations contributing to fertility in Asian women and personalized medicine. Following the PRISMA workflow, the preliminary search yielded a total of 2,145 papers to be reviewed. Participants/materials, setting, methods Following the inclusion/exclusion criteria screening, 128 studies were analyzed (ART outcomes in Asians, n=75; Genetics on women’s reproductive health, n=38; Personalized medicine in Asians, n=15). As each research paper identified one or more genes/SNPs involved in female fertility and reproductive health, we took a step further and performed a pathway analysis of gene-sets using STRING in Cytoscape v3.4.0. Network analysis and biological process associations were performed using GSEA and MSigDB. Significant gene-sets were annotated if FDR<0.05. Main results and the role of chance We observed that age at menarche(AAM) was found to be correlated with the timing of the first pregnancy, with Hawaiians having the lowest age(22.2yrs) and Japanese women having the highest age(25.0yrs). LIN28 mutations were highly associated with AAM and prevalent in both Chinese and American populations. FMR1 was most associated with ovarian reserve, with BMP15, ESR1, INHA, PRIM, TMEM150B to a lesser extent. Finally, FSHR polymorphisms were found to affect IVF outcomes most significantly. Network analysis highlighted a close association between 5 genes; FMR1, FSHR, ESR1, BMP15 and INHA, through biological functions of ovarian follicle development, menstrual cycle and hyperpituitarism. Network analysis revealed 4 major biological pathways (ovarian follicle development, oocyte maturation, ovulation, steroidogenesis), as well as key proteins which are involved in female fertility and reproductive health outcomes. PI3K/Akt are critical regulators of ovarian function through primordial follicle maturation and granulosa cell proliferation. MAPK signaling is involved with gonadotrophin-releasing hormone which controls FSH and LH secretion while Gq/11 signaling is activated through LH receptor. Therefore, PI3K/Akt, MAPK and Gq/11 protein signaling pathway appear to be key components to a broad range of reproductive outcomes and represent potential pathways to target in future studies investigating ovarian, follicular and steroidogenesis dysfunction. Limitations, reasons for caution A large majority of the papers reviewed relied on the self-reporting of ethnicities, which can vary considerably in accordance to how an individual defines his or her own ethnicity. Hence, we could not exclude the possibility of reporting bias in the studies. Wider implications of the findings Leveraging these findings,we propose the development of a biomarker panel which would enhance patient stratification,moving towards personalized medicine to address every woman’s unique reproductive potential.With several countries reporting low fertility rates due to shifts in socio-economic and life priorities, this has strong implications for those who wish to delay childbearing. Trial registration number Not applicable