Reproduction & fertility最新文献

Abstract: Embryo implantation is vital for successful conception but remains to be fully understood. Trophoblast invasion is key for implantation, with anchorage and depth of placentation determined by its extent. There is a dearth of synchronous information regarding IVF, implantation site, and trophoblastic thickness (TT). Our aim was to determine whether pregnancy implantation site and TT, had an impact on outcomes of IVF pregnancies. This prospective observational study was undertaken at a tertiary referral UK fertility unit over 14 months, collecting data on implantation site and TT from three-dimensional (3D) images of the uterus following early pregnancy scan. Of the 300 women recruited, 277 (92%) had live births, 20 (7%) miscarried, 2 (0.7%) had stillbirths, and 1 (0.3%) had a termination. Significantly more pregnancies that resulted in miscarriage (7/20, 35%) were located in the lower uterine cavity when compared to ongoing pregnancies (15/277, 5%) (P < 0.01). TT was significantly higher in ongoing pregnancies when compared with those who miscarried (7.2 mm vs 5.5 mm; P < 0.01). Implantation in the lower half of the uterine cavity and decreased TT are significantly associated with an increased rate of miscarriage. Identification of those at risk should prompt increased monitoring with the aim of supporting these pregnancies.

Lay summary: Implantation of an embryo in the womb is vital for a successful pregnancy. We wanted to find out whether findings on an ultrasound scan in early pregnancy had an impact on outcomes of IVF pregnancies. Three hundred women were recruited to the study, 277 (92%) had live births and unfortunately 20 (7%) had a miscarriage, 2 (0.7%) had stillbirths, and 1 (0.3%) had a termination. Many more of the pregnancies that miscarried implanted in the lower part of the womb. The thickness of the infiltration of the pregnancy into the womb was significantly higher in the ongoing pregnancies. We concluded that implantation in the lower half of the womb and reduced infiltration of the pregnancy seen on scan are associated with an increased rate of miscarriage. We propose that when we identify those at risk, we should increase monitoring, with the aim of supporting these pregnancies.

Abstract: Sex steroids are converted to bioactive metabolites and vice versa by endometrial steroid-metabolising enzymes. Studies indicate that alterations in this metabolism might affect endometrial receptivity. This pilot study determined whether the endometrial formation and inactivation of 17β-oestradiol differed between the supposedly embryo-receptive endometrium and non-receptive endometrium of women undergoing IVF/intracytoplasmic sperm injection (ICSI). Endometrial biopsies were obtained from IVF/ICSI patients 5-8 days after ovulation in a natural cycle, prior to their second IVF/ICSI cycle with fresh embryo transfer (ET). Endometrial biopsies from patients who achieved clinical pregnancy after fresh ET (n = 15) were compared with endometrial biopsies from patients that did not conceive after fresh ET (n = 15). Formation of 17β-oestradiol (oxidative 17β-hydroxysteroid dehydrogenases (HSDs)), oestrone (reductive HSD17Bs) and inhibition of HSD17B1 activity were determined by high-performance liquid chromatography. The endometrial transcriptome was profiled using RNA sequencing followed by principal component analysis and differentially expressed gene analysis. The false discovery rate-adjusted P < 0.05 and log fold change >0.5 were selected as the screening threshold. Formation and inactivation of 17β-oestradiol resulted similar between groups. Inhibition of HSD17B1 activity was significantly higher in the non-pregnant group when only primary infertile women (n = 12) were considered (27.1%, n = 5 vs 16.2%, n = 7, P = 0.04). Gene expression analysis confirmed the presence of HSD17B1 (encoding HSD17B1), HSD17B2 (encoding HSD17B2) and 33 of 46 analysed steroid metabolising enzymes in the endometrium. In the primary infertile subgroup (n = 10) 12 DEGs were found including LINC02349 which has been linked to implantation. However, the exact relationship between steroid-metabolising enzyme activity, expression and implantation outcome requires further investigation in larger, well-defined patient groups.

Lay summary: Sex hormones are produced and broken down by enzymes that can be found in the endometrium (the inner lining of the womb). This enzyme activity might influence the chances of becoming pregnant. We compared (i) enzyme activity in the endometrium of 15 women who did and 15 women who did not become pregnant in their second in vitro fertilisation attempt, (ii) how enzyme activity can be blocked by an inhibitor, and (iii) differences in gene expression (the process by which instructions in our DNA are converted into a product). Enzyme activity was similar between groups. We found that in women who have never been pregnant in the past, inhibition of enzyme activity was higher and found differences in a gene that has been linked to the implantation of the embryo, but future studies should be performed in larger, well-defined patient groups to confirm these findings.

We aim to investigate the correlation of the position of the transferred air bubble with the clinical pregnancy rate (PR) in frozen-thawed embryo transfer(FET) cycles. A prospective clinical study was carried out at Reproductive medicine center of West China Second University Hospital between June 2020 and May 2021. 1159 women underwent FET were included in this study. Transabdominal ultrasonographic guidance was used during the transfer procedure. The distance from the air bubble to endometrial cavity fundus（DAF）was measured in the freeze-frame ultrasound immediately after ET. In group DAF ≤3mm, 3-15mm and ≥15mm, the clinical PR in women transferred with cleavage embryos were 33.3% (7/21), 55.0% (153/280), and 31.3% (5/16), respectively, the difference was statistically significant (P＜0.05). Among women transferred with blastocysts, the clinical PR was 63.0% (34/54), 68.5% (485/708) and 55.0% (44/80), respectively, the difference was statistically significant (P＜0.05). In multivariate logistic regression model for clinical PR, the clinical PR was associated with age, embryo quality, number of embryo transferred, and endometrial thickness. DAF was an independent risk factor influencing clinical PR in blastocysts FET cycles rather than in cleavage embryos FET cycles.In conclusion, our results suggested that DAF was associated with the clinical PR and DAF between 3mm and 15mm is the optimal position in blastocysts FET cycles.

Many parts of the animal and human body host groups of bacteria, viruses, and fungi that together are known as the microbiome. Microbiomes do not cause disease but are important for the healthy working of many systems in the body, including for reproduction and fertility. While the microbiome that lives in a reproductive tract play the most direct role, microbiomes from other areas of the body may also affect reproductive health. However, not much is known about how these groups of microorganisms regulate fertility as well as the health of parents and offspring and help animals to cope with environmental changes. Furthermore, compared to the large amount of research in laboratory species and humans, there is less information about domestic or wild animal species. This special series of Reproduction and Fertility on microbiomes is aimed at filling this gap with articles from experts highlighting important evidence in reproductive microbiomes, current research gaps, and new directions.

Approximately 50% of human pregnancies humans fail, most before or during implantation. One factor contributing to pregnancy loss is abnormal glucose metabolism in the endometrium. Glucose contributes to preimplantation embryo development, uterine receptivity, and attachment of the embryo. Across multiple species, the epithelium stores glucose as the macromolecule glycogen at estrus. This reserve is mobilized during the preimplantation period. Glucose from circulation or glycogenolysis can be secreted into the uterine lumen for use by the embryo or metabolized via glycolysis, producing ATP for the cell. The resulting pyruvate could be converted to lactate, another important nutrient for the embryo. Fructose is an important nutrient for early embryos, and the epithelium and placenta can convert glucose to fructose via the polyol pathway. The epithelium also uses glucose to glycosylate proteins, which regulates embryo attachment. In some species, decidualization of the stroma is critical to successful implantation. Formation of the decidua requires increased glucose metabolism via the pentose phosphate pathway and glycolysis. After decidualization, the cells switch to aerobic glycolysis to produce ATP. Paradoxically, the decidua also stores large amounts of glucose as glycogen. Too little glucose or an inability to take up glucose impairs embryo development and decidualization. Conversely, too much glucose inhibits these same processes. This likely contributes to the reduced pregnancy rates associated with conditions like obesity and diabetes. Collectively, precise control of glucose metabolism is important for several endometrial processes required to establish a successful pregnancy. The factors regulating these metabolic processes remain poorly understood.

The field of fertility preservation (FP) for oncology patients has evolved significantly in recent years, offering new possibilities for individuals with life-threatening illnesses. We commend Jones et al. for their comprehensive ethical review of offering FP to patients with poor prognoses, acknowledging the potential benefits that it may bring. "Poor prognosis" in this context implies a high likelihood of death due to cancer progression. We highlight the importance of considering posthumous reproduction, involving the use of cryopreserved gametes or embryos to conceive a child after one or both partners have passed away, a topic briefly mentioned by Jones et al. Posthumous reproduction raises complex ethical, logistical, and legal questions. Distinctions between cryopreserved sperm and oocytes are discussed, with each scenario presenting unique challenges. The article also examines the complexities faced by same-sex couples in posthumous reproduction, addressing issues related to donor selection, legal parentage, and rights. Legal and regulatory aspects play a crucial role, including obtaining clear and legally valid consent, defining parental rights, navigating surrogacy laws, and addressing inheritance and estate planning. Ethical dilemmas require healthcare professionals to ensure informed decision-making, consider psychological impacts, and offer information on alternative family-building options.

The refinement of embryo culture media is essential in improving embryo viability and in vitro production efficiency. Our previous work demonstrated that the nutrients (carbohydrates, amino acids, and vitamins) in traditional culture media far exceed the need for an embryo and producing developmentally competent embryos in a reduced nutrient environment is feasible. Here, we aim to evaluate the impact of exogenous lipid and L-carnitine supplementation on bovine blastocyst development and refine our RN condition further. Zygotes were cultured in the control medium (100% nutrients) and reduced nutrient media containing 6.25% of the standard nutrient concentrations supplemented with L-carnitine and lipid free or lipid rich BSA. Increased blastocyst development was observed in the reduced nutrient lipid rich medium compared to the other two groups. However, in both reduced nutrient conditions, blastocyst cell numbers were lower than those obtained in the control condition. We then examined the expression level of 18 transcripts correlated with lipid metabolism, glucose metabolism, redox balance, and embryo quality, along with mitochondrial DNA copy numbers, ATP productions, and lipid profile. The results indicated lipid metabolism, embryo quality, and redox enzyme related genes were upregulated while glucose related gene was downregulated in embryos derived from reduced nutrient lipid rich condition Finally, we identified that the lipid rich BSA has enriched linoleic, stearic, oleic, palmitic, and alpha-linoleic fatty acids, a lipid profile that may contribute to the increased lipid metabolism and improved blastocyst development of the bovine embryos under the reduced nutrient condition.

Previous quantitative research has shown that cannabis use, mostly illicit, is used for symptom management amongst those with endometriosis living in Australia or New Zealand, but the drivers and barriers for use of legal, medicinal cannabis in this population are currently unclear. This study sought to investigate, via online focus-groups, the perceptions, barriers, drivers, and experiences associated with cannabis use, whether legal or illicit, amongst 37 Australians and New Zealanders, aged 18-55, with a medical diagnosis of endometriosis. Previous cannabis usage was not required to participate. Discussion topics included strategies employed to manage symptoms, exploration of current medications, previous use of cannabis for pain management, and interest in using medicinal cannabis as a management strategy. Participants with moderate to severe symptoms of medically diagnosed endometriosis reported inadequacies with their current medical and self-management strategies and were inclined to try medicinal cannabis, both as part of their medical management and as part of a clinical trial. Barriers to medicinal cannabis adoption identified in this cohort included high costs of legal cannabis products, lack of clarity and fairness in current roadside drug testing laws and workplace drug testing policies, concern over the impact of stigma affecting familial, social and workplace life domains, and subsequent judgement and the lack of education/engagement from their medical providers regarding cannabis use. Given the interest in medicinal cannabis and the reported lack of effective symptom management, clinical trials are urgently required to determine the potential role that medicinal cannabis may play in reducing the symptoms of endometriosis.

In the context of a cancer diagnosis, fertility preservation interventions are used to mitigate the potential impact of gonadotoxic cancer treatment upon fertility. They provide patients with cancer the option to freeze their reproductive material to have their own biological child following treatment. The evidence suggests some clinicians are less likely to have fertility preservation discussions with patients who have an aggressive or metastatic cancer which has a poor prognosis. Although this is contrary to current policy recommendations, there is a lack of guidance relating to offering fertility preservation in the context of a poor prognosis to support clinicians. Controversy surrounds posthumous reproduction, and whether the wishes of the cancer patient, when living and deceased should take precedence over others' wellbeing. We consider the question of whether cancer patients with a poor prognosis should be offered FP from an ethics perspective. We structure the paper around key arguments to which multiple ethical principles might pertain, first establishing a central argument in favour of offering fertility preservation based on respect for autonomy, before exploring counterarguments. We conclude by proposing that a defeasible assumption should be adopted in favour of offering fertility preservation to all cancer patients who might benefit from it. It is important to recognise that patients could benefit from fertility preservation in many ways, and these are not limited to having a parenting experience. The burden of proof rests on the clinician in collaboration with their multi-disciplinary team, to show that there are good grounds for withholding the offer.