Reproduction & fertility最新文献

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Abstract: In vitro semen purification techniques have been developed that seek to mimic the in vivo selection process in order to generate the highest possible chance of oocyte fertilization following artificial insemination. Numerous methods have been developed to isolate functional spermatozoa for artificial insemination, yet only one method, single-layer centrifugation using commercial preparations like EquiPure, has been widely employed. In this study, we have introduced a novel approach for isolating spermatozoa and compared their quality to those isolated using EquiPure. The AI port system (Memphasys, Ltd. in Sydney, Australia) features a disposable cartridge with an inoculation chamber for depositing extended semen and a harvest chamber for extracting isolated spermatozoa. These chambers are separated by a 5 µm polyethylene terephthalate (PETE) membrane, allowing highly motile spermatozoa to migrate from the inoculation chamber to the harvest chamber over a 20-minute period. This migration effectively leaves behind seminal plasma and other cell types, such as leukocytes. Comparative analyses between spermatozoa isolated with the AI port and EquiPure demonstrated that, across all measured sperm parameters, including yield, vitality, motility, morphology, DNA fragmentation, and mitochondrial superoxide generation, the AI port-isolated cells exhibited comparable or superior performance, particularly in terms of DNA fragmentation. In summary, the AI port system demonstrates the potential to efficiently isolate high-quality spermatozoa, possibly offering a cost-effective and user-friendly alternative that may enhance the success rates of artificial insemination in breeding programs.

Lay summary: This study aimed to create a new method for refining stallion semen to increase the likelihood of a successful pregnancy through artificial insemination. While there are existing techniques for isolating high-quality sperm, the most common involves a complicated process using a centrifuge, which spins the semen to separate it. This research introduces a new approach called the AI port system that uses a disposable cartridge with two separate chambers for putting in semen and getting out isolated sperm. A membrane between the chambers acts like a filter, letting highly motile sperm swim across, leaving behind unwanted substances like bacteria and blood cells. Compared to the centrifugation method, the AI port system effectively produces sperm with comparable or better quality in various aspects, including vitality, movement, shape, DNA integrity, and energy production. In summary, the AI port system is an easy-to-use alternative with the potential to improve the success of artificial insemination in horse breeding programs.

Abstract: Maternal gut microbiome impairment has garnered attention for its potential role in influencing neurodevelopmental outcomes in offspring, especially in situations that increase brain vulnerability such as perinatal asphyxia (PA). Maternal microbiome and fetal brain interplay emerge as a critical link between maternal health and offspring neurodevelopment. This study aims to generate a model to assess the impact of maternal dysbiosis triggered by gestational antibiotic administration and PA on offspring neurodevelopment. Wistar rats were subjected to antibiotics in drinking water from the 11th gestational day until birth. On the 6th postnatal day, pups were subjected to PA/normoxia, resulting in four experimental groups: control-normoxia, antibiotics-normoxia, control-asphyxia, and antibiotics-asphyxia. Early-life behavioral tests were conducted between postnatal days 7 and 9. The initial antimicrobial cocktail (ampicillin, vancomycin, neomycin, clindamycin, amphotericin-B) led to an increased number of miscarriages, poor weight gain during pregnancy, reduced offspring weight, and changes in the maternal gut microbiome compared to control. Offspring presented impaired neurodevelopmental reflexes in both PA and antibiotic groups and increased hippocampal neuroinflammation. Due to these detrimental effects, a more pregnancy-safe antibiotic cocktail was used for a second experiment (ampicillin, vancomycin, neomycin, meropenem). This resulted in no miscarriages or pregnancy-weight loss but was still linked to gut microbiome disruption. PA impaired neurodevelopmental reflexes and increased neuroinflammation, effects amplified by antibiotic administration. These preliminary findings reveal the cumulative potential of maternal dysbiosis and PA on neurodevelopment impairment, emphasizing caution in gestational antimicrobial use. Further investigations should include offspring long-term follow-up and maternal behavior and integrate probiotics to counteract antibiotic effects.

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Lay summary: This study investigates the impact of maternal gut microbiome disruptions caused by gestational antibiotic treatment and low oxygen exposure shortly after birth on the development of the rats' babies. We found that both antibiotic exposure and reduced oxygen levels led to changes in early behavior and increased inflammation of the nervous tissue in the baby rats. Although using a different, potentially safer antibiotic combination reduced pregnancy complications, it still changed the bacteria in the mother's gut and worsened early behavior. These findings show that antibiotics during pregnancy can affect the developing brain of baby rats and careful consideration should be used before prescribing them. Future research will explore longer-term effects and potential medicines.

Objective: To investigate whether infertile women with a history of levonorgestrel intrauterine device (LNG IUD) use have impaired pre-transfer endometrial thickness and pregnancy rates after embryo transfer.

Methods: Retrospective cohort study at a single academic medical center of infertile women ages 18-44 with a history of LNG IUD use undergoing their first embryo transfer cycle between January 2019 and January 2021 compared to controls with a history of no prior birth control use (NONE) or only prior oral contraceptive use (OCP). The primary outcome is endometrial thickness prior to embryo transfer. Secondary outcomes include embryo transfer results.

Results: We analyzed data from a total of 616 patients (197 NONE, 357 OCP, 62 LNG IUD). Women with a history of LNG IUD use had thinner endometrial stripes than women with a history of no prior birth control use (LNG IUD 8.93mm, NONE 10.32mm [aRR 0.88, 95% CI 0.80-0.97]), but not when compared to women with a history of OCP use (OCP 9.61mm [aRR 0.92, 95% CI 0.84-1.01]). Women with a history of LNG IUD use had slightly higher implantation rates than those with no birth control use history (LNG IUD 43.37%, NONE 24.17% [RR 1.79, 95% CI 1.21-2.45]), though not when compared to prior OCP users (OCP 38.72% [RR 1.12, 95% CI 0.86-1.47]). The remainder of the embryo transfer outcomes were similar between the three groups.

Conclusions: Prior LNG IUD users have reduced endometrial thickness at the time of embryo transfer but do not have worse pregnancy outcomes.

Despite the centrality of the role embryologists in in-vitro fertilization, there is relatively little literature on the nature of their work. In this article, we draw on results from a large ethnographic study on the emerging IVF industry in South Africa and reproductive travel in Sub-Saharan Africa (SSA), where IVF clinics and embryologists are scarce. Drawing on qualitative interviews with 12 embryologists, who work(ed) in SSA, we illustrate how their care practices are produced through the interaction of people and things. We emphasize the importance of context in shaping their practices, including: the shortage of embryologists; the need to set up 'first' clinics in their respective countries; the paucity of trained counsellors in clinics; and the mobility of IVF staff. The embryologists we interviewed performed multiple tasks on top of their laboratory work, including entrepreneurial tasks; advocacy; training; the development of regulations; mentoring and patient counselling. They enacted care in several ways, towards gametes and embryos, patients, clinics, and the profession. These multiple tasks and care practices make for dynamic and fulfilling careers of the interviewed embryologists, but also stretch their capacities. They also raise questions about their contribution to the scarcity of embryological work in SSA. If access to IVF is to be achieved in the SSA region, more embryologists need to be trained and retained.

Abstract: Seminal fluid extracellular vesicles (SFEVs) have previously been shown to interact with spermatozoa and influence their fertilisation capacity. Here, we sought to extend these studies by exploring the functional consequences of SFEV interactions with human spermatozoa. SFEVs were isolated from the seminal fluid of normozoospermic donors prior to assessing the kinetics of sperm-SFEV binding in vitro, as well as the effects of these interactions on sperm capacitation, acrosomal exocytosis, and motility profile. Biotin-labelled SFEV proteins were transferred primarily to the flagellum of spermatozoa within minutes of co-incubation, although additional foci of SFEV biotinylated proteins also labelled the mid-piece and head domain. Functional analyses of high-quality spermatozoa collected following liquefaction revealed that SFEVs did not influence sperm motility during incubation at pH 5, yet SFEVs induced subtle increases in total and progressive motility in sperm incubated with SFEVs at pH 7. Additional investigation of sperm motility kinematic parameters revealed that SFEVs significantly decreased beat cross frequency and increased distance straight line, linearity, straightness, straight line velocity, and wobble. SFEVs did not influence sperm capacitation status or the ability of sperm to undergo acrosomal exocytosis. Functional assessment of both high- and low-quality spermatozoa collected prior to liquefaction showed limited SFEV influence, with these vesicles inducing only subtle decreases in beat cross frequency in spermatozoa of both groups. These findings raise the prospect that, aside from subtle effects on sperm motility, the encapsulated SFEV cargo may be destined for physiological targets other than the male germline, notably the female reproductive tract.

Lay summary: A male's influence over the biological processes of pregnancy extends beyond the provision of sperm. Molecular signals present in the ejaculate can influence the likelihood of pregnancy and healthy pregnancy progression, but the identity and function of these signals remain unclear. In this study, we wanted to understand if nano-sized particles present in the male ejaculate, called seminal fluid extracellular vesicles, can assist sperm in traversing the female reproductive tract to access the egg. To explore this, we isolated seminal fluid extracellular vesicles from human semen and incubated them with sperm. Our data showed that seminal fluid extracellular vesicles act to transfer molecular information to sperm, but this resulted in only subtle changes to the movement of sperm.

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Choline is a known developmental programming agent of the bovine preimplantation embryo. Culture of the embryo with 1.8 mmol/L choline, a concentration much higher than in blood, alters development to cause increased weaning weight and other changes during the postnatal period. It was hypothesized here that choline exerts similar effects on the developmental program of the embryo when added at concentrations similar to those in peripheral blood (i.e., 4 mol/L). Oocytes were collected via ovum pick up and embryos were produced in vitro. Embryos were cultured until day 7 after fertilization in medium with 4 mol/L choline chloride, or, as a vehicle control, with an additional 4 mol/L sodium chloride. Blastocysts were transferred into recipients and pregnancy was diagnosed at approximately 28 d of gestation. Subsequent calves (n=37 for vehicle and n=35 for choline) were weighed at birth and at weaning. Addition of choline to culture medium did not affect the proportion of embryos that became blastocysts or the proportion of transferred blastocysts that produced a pregnancy. Birth weight was unaffected by treatment but calves derived from choline-treated embryos were heavier at time of weaning and gained more per day from birth until weaning than calves derived from embryos treated with vehicle. Results demonstrate that choline can act on the preimplantation embryo at a physiologically-relevant concentration to alter postnatal phenotype. Observations are further evidence for the importance of the first days of embryonic development for the phenotype of the resulting calf.

Historically, infertility has been stigmatized in the Indian society, primarily due to societal norms that equate marriage with procreation. In twentieth century, India focused primarily on over-fertility in its family planning programs, with little attention given to the complexities of infertility. The introduction of Assisted Reproductive Technology (ART) in the late 1970s made a global revolution, including in India, offering hope to infertile couples. Despite a significant rise in ART clinics offering a wide range of treatment options in the recent years, challenges remain, particularly regarding the affordability. In India, ART is typically dominated by the private sector as government support remains limited. Efforts to standardize ART practices, including the establishment of the National ART & Surrogacy Registry and ART act aim to regulate, improve outcomes and curb unethical practice. Despite these advancements, the high cost of treatment cycles and lack of insurance coverage limit many couples' ability to undergo fertility treatment. Addressing these issues requires a multifaceted approach, including policy reform, increased public awareness, and the development of affordable treatment options to ensure broader access to reproductive care across India.

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Abstract: This study aimed to evaluate the effectiveness of a clinical decision support tool, Opt-IVF, in achieving the following outcomes: reducing the total cumulative dosage of Gonadotropins (Gns) used during controlled ovarian stimulation cycles and reducing the repeated ultrasonograms (USG) for monitoring follicular growth without compromising the number of good quality blastocysts obtained. The study design employed a multi-center randomized trial. The study enrolled 115 women aged 25-45 years undergoing IVF. Among the participants, 55 were randomly assigned to the intervention group (Opt-IVF), and 60 were randomly assigned to the control group. The intervention involved using a clinical decision support tool, Opt-IVF, to guide Gn dosing and trigger dates. The participants in the intervention group required significantly lower cumulative Gn dosage. The intervention group had higher numbers of oocytes retrieved and M2 retrieved than the control group. The number of good-quality blastocysts, the good-quality blastocyst rate, the ovarian sensitivity index (OSI), and the pregnancy rate in the intervention group were significantly higher than in the control group. The utilization of the clinical decision support tool led to several positive outcomes, including eliminating the need for ultrasound exams after day 5, reducing the dosage of Gn required, and yielding significantly higher numbers of high-quality blastocysts and higher pregnancy rates. Thus, Opt-IVF can successfully provide a personalized, optimized, and simplified approach to superovulation. Opt-IVF consistently outperformed the clinical teams in most of the outcomes. Clinical trials registration: ClinicalTrials.gov (ID - NCT05811065). Date of Registration: 15 March 2023. Date of enrollment of the first subject: 20 March 2023.

Lay summary: The high cost of IVF is a result of costly drugs, fixed prices for infrastructure, extensive testing required, and labor costs for physicians and other healthcare personnel. Superovulation, which involves the drug-induced release of multiple eggs needed for IVF, accounts for a significant share of these costs. Current approaches to superovulation involve almost daily monitoring of follicle development using ultrasound and/or blood tests. The daily dosage of stimulatory hormones is then prescribed by physicians based on empirical data and clinical experience. However, the dose is not optimized for each patient, and overstimulation complications can occur. The cost of testing and drugs makes this stage very expensive. To overcome the shortcomings of this system, we have developed a decision support tool (Opt-IVF) that can provide a personalized model-optimized dosage profile for each patient. The clinical results show that Opt-IVF optimizes and personalizes dosage, reduces testing, and provides better outcomes for patients.