Reproduction & fertility最新文献

Abstract: Poly- and per-fluoroalkyl substances (PFAS) are synthetic environmentally persistent chemicals. Despite the phaseout of specific PFAS, their inherent stability has resulted in ubiquitous and enduring environmental contamination. PFAS bioaccumulation has been reported globally with omnipresence in most populations wherein they have been associated with a range of negative health effects, including strong associations with increased instances of testicular cancer and reductions in overall semen quality. To elucidate the biological basis of such effects, we employed an acute in vitro exposure model in which the spermatozoa of adult male mice were exposed to a cocktail of PFAS chemicals at environmentally relevant concentrations. We hypothesized that direct PFAS treatment of spermatozoa would induce reactive oxygen species generation and compromise the functional profile and DNA integrity of exposed cells. Despite this, post-exposure functional testing revealed that short-term PFAS exposure (3 h) did not elicit a cytotoxic effect, nor did it overtly influence the functional profile, capacitation rate, or the in vitro fertilization ability of spermatozoa. PFAS treatment of spermatozoa did, however, result in a significant delay in the developmental progression of the day 4 pre-implantation embryos produced in vitro. This developmental delay could not be attributed to a loss of sperm DNA integrity, DNA damage, or elevated levels of intracellular reactive oxygen species. When considered together, the results presented here raise the intriguing prospect that spermatozoa exposed to a short-term PFAS exposure period potentially harbor an alternate stress signal that is delivered to the embryo upon fertilization.

Lay summary: PFAS are synthetic chemicals widely used in non-stick cookware, food packaging, and firefighting foam. Such extensive use has led to concerning levels of environmental contamination and reports of associations with a spectrum of negative health outcomes, including testicular cancer and reduced semen quality. To investigate the effects of PFAS on male reproduction, we incubated mouse sperm in a cocktail of nine PFAS at environmentally relevant concentrations before checking for a range of functional outcomes. This treatment strategy was not toxic to the sperm; it did not kill them or reduce their motility, nor did it affect their fertilization capacity. However, we did observe developmental delays among pre-implantation embryos created using PFAS-treated sperm. Such findings raise the intriguing prospect that PFAS-exposed sperm harbor a form of stress signal that they deliver to the embryo upon fertilization.

In the registrational trials, follitropin delta was compared with a fixed dose of 150 UI of follitropin alpha/beta, finding higher chances to reach a target response of 8-14 oocytes compared to controls. For this reason, follitropin delta is marketed as particularly useful in expected hyper-responder patients. The main outcome of this study is to report if comparable results are reached in a real-life scenario with follitropin alpha/beta personalized doses, based on patients' characteristics. This is a retrospective study performed in two public fertility centres. All first cycles from January 2020 to June 2022 with either follitropin delta (cases) or alpha/beta (controls) in patients with antiMüllerian hormone >2.5 ng/ml were compared by an inverse probability weighting approach based on propensity score. The follitropin total dose was higher in controls (1179.06 ± 344.93 vs. 1668.67 ± 555.22 IU, p<0.001). The target response of 8-14 oocytes was reached by 40.2% of cases and 40.7% of controls (odds ratio (OR) 0.99, 95% confidence interval (CI) 0.65-1.53, p=0.98). Fewer than 8 oocytes were collected in 24.1% of cases and 22% of controls (OR 1.10, 95% CI 0.71-1.69, p=0.67); more than 14 oocytes in 35.7% of cases and 37.3% of controls (OR 0.83, 95% CI 0.54-1.28, p=0.40). Our experience did not find worse results in term of proportion of patients who reached the target response with an algorithm-chosen dose of follitropin delta compared to a personalised starting dose of follitropin alpha/beta, with follitropin delta having the advantage of objectivity. Larger numbers are needed to confirm these results.

Lay summary: The decreasing rate of successful pregnancies, both naturally and through assisted conception, has led to innovations in the way eggs, sperm, and embryos are stored. Despite these advances, the use of assisted reproductive techniques to preserve endangered or rare species remains unexplored. Since the location where samples are collected and facilities are often far apart, we aim to address part of this challenge by comparing different methods to store and handle ovarian tissue before freezing. This may pave the way for further research in preserving endangered species, despite the challenges posed by the distance between sample collection sites and suitable facilities.

Nigeria has the largest population in Africa, a high fertility rate, and unmet needs for family planning. Family planning is a key strategy for sustainable development. Good knowledge of factors that determine contraceptive uptake is imperative for policy formulation. A nationally representative secondary dataset of 33,924 women aged 15-49 years who participated in the 2018 Nigeria Demographic and Health Survey was analyzed. Multivariate logistic regression was used to examine the association between various factors and the current use of modern contraceptives. The respondents' average age was 35.9 +/- 7.9 years. Overall, contraceptive prevalence was 16.6% for traditional methods and 12.2% for modern methods. Factors associated with an increase in modern contraception use were age 40-44 (aOR = 1.07, 95% CI: 0.75-1.53); being a working-class woman (aOR = 1.15, 95% CI: 0.99-1.33); living in an urban area (aOR = 1.14, 95% CI: 0.97-1.33); living in the South-West (aOR = 1.36, 95% CI: 1.03-1.79); increasing wealth (aOR = 0.78, 95% CI: 0.66-0.93);and health insurance (aOR = 1.22, 95% CI: 0.89-1. 68. Couple dynamics influencing modern contraceptive use were joint decision (aOR = 2.16, 95% CI: 1.81-2.59), self-decision on healthcare (aOR = 1.34, 95% CI: 1.06-1.70), and earning more than a partner (aOR = 1.14, 95% CI: 0.78-1.66). There are significant variations in contraceptive uptake attributable to socio-economic and political inequalities, requiring a holistic approach to mitigate barriers and improve contraceptive uptake.

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.