Highly anabolic diets and excessive body fat accumulation have been shown to negatively impact sperm biology in humans and murine biomedical models. Current research indicates that obesity is associated with decreased semen quality and represents a major contributor to male subfertility in humans. Male overnutrition is commonly observed in the beef cattle industry and the use of high energy diets during bull development has been shown to negatively impact semen quality. Most research efforts in bovine reproductive physiology have focused on understanding and optimizing female fertility. This emphasis is even more evident in research investigating the relationship between nutritional interventions and reproductive performance, which has limited the development of nutritional strategies that optimize fertility in bulls. Increasing our understanding of the genetic and environmental factors that influence bull fertility will contribute to future increases in cattle reproductive and productive efficiency. Moreover, exploring the impact of overnutrition in bulls may offer valuable insight and help address diet-induced male subfertility in humans. Herein, we summarize the currently available literature evaluating the impact of highly anabolic diets on male fertility, with an emphasis in the bovine species. Literature summarized in the present review evaluates the impact of overnutrition on sperm biology, early embryonic development, and explores its potential to impact postnatal performance of the offspring.
Abstract: Dyspareunia, or pain during sex, is a common and often debilitating symptom in individuals with endometriosis and/or interstitial cystitis/bladder pain syndrome (IC/BPS). Despite its significant impact on quality of life, it is frequently overlooked in research. This review evaluates how dyspareunia has been addressed in preclinical investigations of these conditions. A systematic search was conducted using Embase from 1998 to 2021, identifying original in vivo preclinical studies using female rodents to model (i) endometriosis and (ii) IC/BPS. The search aimed to identify studies that assessed dyspareunia. Study quality and risk of bias were evaluated using a modified CAMARADES checklist. Our analysis found 1,286 studies modelling endometriosis and 674 modelling IC/BPS, but only 18 and 1, respectively, measured dyspareunia. The most common method involved vaginal distention in rats, assessed by either behavioural escape responses or visceromotor reflexes of abdominal muscles. Despite the high prevalence of dyspareunia in these conditions, it is rarely measured in preclinical studies. We identify a significant gap in the literature and offer succinct recommendations for future translational research to address this important symptom.
Lay summary: Dyspareunia describes pain occurring before, during or after sexual intercourse. This poorly understood symptom is particularly common in people suffering from two chronic pain-related conditions: endometriosis and IC/BPS, severely impacting their quality of life. Therefore, effective treatments addressing painful sex in people with these conditions are needed. To see the benefits of medical research at the patient's bedside, it is important to build from basic science research to preclinical animal studies then to human studies. Our study aims to assess the work that has been done so far at the 'preclinical' stage. Developments have been made in the methodology used to investigate this symptom in animals, and a summary of all the key findings may help build a platform to design future studies. Given the urgent need to develop new therapeutic strategies, attention given to painful sex by scientific medical researchers and physicians needs to improve.
Abstract: Chemotherapeutic agents result in the loss of growing follicles, which can manifest as amenorrhoea. Alkylating chemotherapy (AC) is known to be more gonadotoxic than non-alkylating chemotherapy (NAC). Anti-Müllerian hormone (AMH), an indirect marker of ovarian reserve, and age have been investigated as predictors of ovarian function after chemotherapy; however, little is known about the time to return of menses. This study aimed to assess how patient age and baseline serum AMH levels at cancer diagnosis affect the time to return of menses post-chemotherapy. This retrospective cohort study examined oncology patients (n = 67) who underwent chemotherapy and were treated through the Reproductive Services Unit of two institutions in Melbourne, Australia. Primary outcomes included the correlation between age and baseline AMH with time to return of menses after chemotherapy. Secondary outcomes include the change in AMH levels at 6- and 12-months post-completion of chemotherapy. Pairwise correlation of the pre-chemotherapy AMH level and time to return of menses demonstrated statistical significance (Spearman's coefficient, ρ = -0.40) for patients who underwent AC. This analysis in breast cancer patients who underwent AC displayed a negative correlation but was not statistically significant. No association was found between age and time to return of menses for all cancer (NAC or AC) or breast cancer patients who underwent AC. Higher AMH levels prior to AC were associated with an earlier return of menses after chemotherapy. Age at the commencement of chemotherapy was not associated with return of menses. Further prospective research is required to assess post-chemotherapy recovery of AMH.
Lay summary: Chemotherapy, used to treat cancer, is known to damage women's ovaries, with certain types having a more toxic effect than others. This may result in a temporary loss of periods while undergoing chemotherapy. AMH is a hormone produced by the ovaries and gives an indication of their level of function. This study looks at whether an individual's AMH or age when beginning chemotherapy can predict the time before the resumption of periods after completing chemotherapy. This study found that for cancer patients who underwent the chemotherapy type known to be more toxic to ovaries, the higher their AMH level was before beginning chemotherapy, the more rapidly their periods would return after completing chemotherapy. Age was not found to accurately predict how rapidly periods would return after completing chemotherapy. This information can be used to inform patients before treatment of the chances of periods returning and, consequentially, pregnancy after the completion of their chemotherapy.
Abstract: Blood lymphocyte reference ranges in non-pregnant females are established, but changes in pregnancy are less well understood. The early identification of immunological markers that could suggest an increased risk of early pregnancy loss may allow for timely intervention to improve outcomes. A lymphocytic immunophenotype provides a broad assessment of important immune parameters and potential indicators, which may be of relevance to pregnancy outcome. Comparison of immunophenotype results on the day of a positive hCG after embryo transfer between successful and failed pregnancies allows for this assessment. Baseline non-pregnant lymphocyte percentage and cell/µL profiles were established with a comprehensive panel on 93 age-matched male factor controls. Sixty-five in-vitro fertilisation (IVF) patients had an immunophenotype assessment on the day of a positive hCG, followed by further hCG tests and ultrasound monitoring as required to ultimately evaluate success (live birth) or failure (miscarriage). Thirty-one pregnancies were viable, leading to a live birth, while 34 ended in miscarriage. Total CD56, pNK, NKT, CD4 and CD8 levels were equivalent between all groups. Regardless of the outcome, B lymphocytes increased in pregnancy compared to controls. Of interest, in the later miscarriage cohort, pNK-specific CD69 was reduced (1.6 vs 5.4%, P = 0.02), while CD57+ cells were increased (45.4 vs 38.9%, P = 0.025). Corresponding changes were observed in cell/µL concentrations. Low level CD69 activation and elevated CD56dim and CD57+ NK cells were identified as markers that could potentially identify a pregnancy at risk of miscarriage, with further study needed to explore whether these changes represent cause or effect.
Lay summary: Unexplained infertility remains a difficult issue for patients and physicians alike, but despite recent diagnostic strides and innovative methods, there are no clear solutions on the horizon. Pregnancies can still occur in these challenging populations, either spontaneously or by interventions such as IVF. The early identification of various immune markers by blood sampling that may correlate with the subsequent outcome could be beneficial in identifying pregnancies at increased risk of miscarriage and perhaps allowing for timely and effective interventions.
Abstract: The inability of animals to get pregnant, pregnancy loss and weak or stillborn offspring are significant economic burdens to livestock producers worldwide. Progesterone, the hormone of pregnancy, has a crucial role in the establishment of pregnancy, and it has been suggested that progesterone supplementation may be a promising strategy to improve pregnancy outcomes and conceptus development. This review article describes the existing literature on progesterone supplementation in sheep and pigs in relation to pregnancy outcomes and conceptus development.
Lay summary: Pregnancy loss and weak offspring are significant problems both in humans and in agriculturally relevant species. Progesterone (the hormone of pregnancy) is important for establishing pregnancy and regulating fetal and placental growth, and it is speculated that progesterone supplementation could be a promising method to improve pregnancy outcomes and both fetal and placental growth. This review article describes the existing literature on progesterone supplementation in sheep and pigs in relation to pregnancy outcomes and fetal and placental development.
Abstract: Chronic pelvic pain (CPP) is a debilitating condition that reduces quality of life (QoL). In the United Kingdom, there is currently no standardised treatment pathway for women suffering from CPP. Therefore, it is essential to understand individuals' concerns regarding CPP, their treatment experiences and what they seek from treatment. To do this, we conducted a two-month social media survey focused on the UK population to explore treatment experiences and identify the factors that people consider important to managing their condition. Of 1,279 respondents, women who completed ≥50% of the questions were included (n = 864; 68%). Results suggest that many women are living with moderate-intensity CPP and experience symptoms for 6 years (average) before receiving a diagnosis. Initially, most women see general practitioners and gynaecologists (90%), with varied care beyond these providers. Using an adapted STarT Back tool, 85% of respondents were classified as medium-high risk of poor outcomes based on physical, psychosocial, and psychological risk. Thematic analysis identified that people desire treatment validation/understanding, self-management, and support to manage pain and QoL. Notably, only 26% of respondents report satisfaction with their healthcare experience, suggesting that current treatment approaches do not address these themes. In conclusion, results suggest that treatment should focus on quality-of-life improvement to enhance CPP treatment outcomes and satisfaction. Findings endorse the need for improved and standardised treatment approaches that address patients' needs.
Lay summary: CPP is persistent pain in the lower abdomen or pelvis for at least 6 months. It is common and affects approximately 1 in 6 women in the UK. To improve treatment, it is important to understand people's treatment experiences and treatment needs. We conducted a social media survey to understand how people with CPP experience treatment and what they would like from treatment. The survey was posted online for two months (May and June 2023) and received 897 responses. Responses suggested that people experience long waits before receiving help for their pain and that treatment journeys vary greatly. Overall, people reported low treatment satisfaction. People felt that effective treatment should improve pain and QoL. Themes of understanding their pain, knowing how to manage their pain and understanding treatments were identified as important. Clinicians should consider QoL and pain education as part of treatment.
Abstract: Despite the centrality of the role of embryologists in in vitro fertilization (IVF), 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 11 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, 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.
Lay summary: Embryologists play a central role in IVF. Yet, there is limited knowledge about the nature of their work. We examine the work of embryologists in SSA, where IVF clinics and embryologists are scarce. Based on qualitative interviews conducted with 12 embryologists, we illustrate the multiple tasks they perform on top of their laboratory work: entrepreneurial tasks, advocacy, training, development of regulations, mentoring and patient counselling. Context is important in shaping these practices. This includes the shortage of embryologists in the SSA region, the need to set up 'first' clinics in their respective countries, the lack of trained counsellors in clinics and the mobility of IVF staff. These multiple tasks, while professionally fulfilling, raise questions about their contribution to the scarcity of embryological work in SSA, which contributes to the limited access to IVF in this region.
N/A - research letter.
Methods to quantify germ cell number in human immature testicular tissues are essential to evaluate the impact of chemotherapy exposures and for optimising cryopreservation protocols used in fertility preservation for prepubertal boys. Established quantification methods rely on the presence of round tubules within the tissue. However, round tubular cross sections are limited in human prepubertal testicular tissues, especially when using in vitro culture. We aimed to assess whether an alternative method of germ cell quantification would provide similar results to recently established methods, without the requirement for round tubules. Human testicular samples included fetal tissue (exposed in vitro to cisplatin, carboplatin, or control) or prepubertal tissue (fresh, cryopreserved, fresh in vitro cultured or cryopreserved in vitro cultured). Immunofluorescence assessed AP2γ (gonocytes) and MAGE-A4 ((pre)spermatogonia) expression. Germ cells were quantified by tubular germ cell density (Method 1) and compared to methods that require round tubules including: spermatogonial number per round tubular cross-section (S/T) (Method 2), fertility index (FI) (Method 3), and round tubular germ cell density (Method 4). Correlation analysis between methods was performed. Method 1 is strongly and significantly correlated with Method 2 (r=0.838, p<0.0001; r=0.833, p<0.0001), 3 (r=0.752, p<0.001; r=0.802, p<0.0001), and 4 (r=0.863, p<0.0001; r=0.914, p<0.0001) for fetal and prepubertal tissues, respectively. Given that Method 1 assess tubules irrespective of shape, it may increase the total number of germ cells available for quantification, validating its use for quantification of human testicular tissue samples where the amount of tissue or presence of round tubules is limited.