Top 10 priorities for future infertility research: an international consensus development study

Developing a core outcome set for future infertility research: an international consensus development study

To determine the future priorities for ectopic pregnancy research. Potential research questions were collated from an initial international survey, a systematic review of clinical practice guidelines, and Cochrane systematic reviews. A rationalized list of confirmed research uncertainties was prioritized in an interim international survey. Prioritized research uncertainties were discussed during a consensus development meeting. Using a formal consensus development method, the modified nominal group technique, diverse stakeholders identified the top 10 research priorities for future ectopic pregnancy research. Healthcare professionals, people with lived experience of ectopic pregnancy, and others were brought together in an open and transparent process using formal consensus methods advocated by the James Lind Alliance. Not applicable. Top 10 research priorities for ectopic pregnancy. The initial survey was completed by 855 participants from 35 countries, and 1,220 potential research questions were submitted. Three clinical practice guidelines and 43 Cochrane systematic reviews identified a further 24 potential research questions. A rationalized list of 49 confirmed research uncertainties was entered into an interim prioritization survey completed by 413 respondents from 20 countries. The top 10 research priorities were identified during a consensus development meeting involving 37 participants from 10 countries. These research priorities are diverse and seek answers to questions regarding prevention, treatment, and the longer-term impact of ectopic pregnancy. We anticipate that the identified research priorities, developed to specifically highlight the most pressing clinical needs as perceived by healthcare professionals, people with lived experience of ectopic pregnancy, and others, will help research funding organizations and researchers to develop their future research agenda.

The authorship Dhruva et al. study indicates no named pain specialist participated in the study. Two of the authors are cardiologists and the remaining 5 authors are employees of Optum (UnitedHealth Group). The UnitedHealth Group includes the largest for-profit health insurance company in the US and concerns have been raised about their attempts to enter the health care delivery space and discourage expensive treatment options in cardiology and now pain medicine.15 The study by Dhruva et al. has been praised by the absence of conflicts of interest from the medical device industry.2 However, a study absent of conflicts of interest from the medical device industry does not necessarily mean that the study represents an independent evaluation. As studies with conflicts of interest from the medical device industry may be considered as presenting some bias in producing favorable results to medical devices, we consider that a study with employees of a health insurance company writing a negative article about an expensive intervention should be interpreted with at least the same caution. In conclusion, the findings from Dhruva et al. need to be interpreted with great caution and in the context of the lack of representativeness of their population considered for SCS, limitation of surrogate outcome measures reported, potential conflict of healthcare insurance company involvement, and the absence of a balanced presentation of the evidence in this field. Sam Eldabe reports consultancy fees from Medtronic, Mainstay Medical, Boston Scientific, and Abbott. He has received department research funding from the National Institute of Health Research, Medtronic and Nevro. Christopher Gilligan reports payment to his institution (for part of his salary) and stock-options received from Mainstay, personal fees from Mainstay, Saluda Medical, Persica, Eli Lilly, Iliad, research funded by Sollis, expert witness testimony fees, and serving as Editor in Chief of Pain Practice. Rod S Taylor reports consultancy fees from Medtronic, Nevro and Saluda Medical. Kiran V Patel is a consultant and speaker for Abbott. Rui V Duarte is an employee of Saluda Medical. He has previously received consultancy fees from Boston Scientific, Mainstay Medical, Medtronic and Saluda Medical. The data that support the findings of this study are available from the corresponding author upon reasonable request.

Sodium-glucose co-transporter 2 inhibitors in heart failure with preserved ejection fraction: reasons for optimism.

The value proposition of investigator-initiated clinical trials conducted by networks.

Study question Q1: What are the lifestyle habits of couples undergoing treatment for different fertility problems? Q2: Do the individual lifestyles of female and male partners differ? Summary answer Lifestyle differences exist in couples treated for unexplained infertility. While men show statistically higher emotional well-being, and women demonstrate statistically greater proficiency in technology use. What is known already Fertility is influenced by modifiable lifestyle factors affecting reproductive hormones and endocrine pathways. Key factors include age, diet, stress, physical activity, obesity, environmental exposures, and etc. While men and women with fertility problems may have distinct lifestyles, infertility remains a shared experience requiring a holistic assessment. Existing research has examined lifestyle differences by gender, but few studies assess couples together. Since infertility treatment outcomes affect both partners, a couple-based lifestyle assessment is essential. Addressing lifestyle factors in couples with different fertility problems may drive meaningful behaviour change, enhance reproductive outcomes, and underscore the need for fertility-specific interventions. Study design, size, duration This descriptive, cross-sectional study was conducted in three fertility treatment centers in Turkey (March 2023–March 2024). The sample size was 171 couples using a 95% confidence interval in G-Power, with 176 couples (352 individuals) included. Data were collected face-to-face at various infertility treatment stages. Healthy lifestyle behaviors were assessed individually and also as a couple in a private clinical setting. After explaining the study’s purpose, consenting participants completed questionnaires. Participants/materials, setting, methods Data were collected using the Personal Information Form and the Healthy Lifestyle Behaviors Scale in Improving Fertility (HLBSI). The HLBSI is a 46-item, 5-point Likert scale (range: 46–230) with seven sub-dimensions: emotional well-being, physical activity, sleep, nutrition, technology, hygiene, and spirituality. The scale’s Cronbach’s alpha was 0.87. The mean HLBSI scores of men and women were used for couple assessments, with an average response time of seven minutes. Main results and the role of chance Although the mean total score of the couples on the Healthy Lifestyle Behaviors Scale-II (HLBS-II) (156.95 ± 10.10) was above the scale’s midpoint, it remained considerably low relative to the maximum possible score of 230. Analyzing the sub-dimensions of the scale, technology use, sleep quality, and physical activity were identified as the areas with the lowest scores among couples. Notably, couples with unexplained infertility exhibited significantly lower scores in the technology sub-dimension, indicating higher levels of technology use. Additionally, spirituality scores were significantly lower among couples experiencing infertility due to male factor (p < 0.05). When analyzed separately by gender, the total HLBS-II scores of men and women were found to be similar. However, a significant difference was observed in the technology sub-dimension, with men reporting higher technology use than women (Z=-4.03, p = 0.00). Furthermore, subgroup analyses revealed that women with unexplained infertility had significantly lower scores in the emotional well-being sub-dimension, while men diagnosed with male factor infertility had significantly lower scores in the technology sub-dimension (p < 0.05). These findings suggest that lifestyle behaviors, particularly in relation to technology use and emotional well-being, may be influenced by both gender and the underlying cause of infertility. Limitations, reasons for caution As most of the study sample comprised young couples with bachelor’s degrees, the findings may not be fully generalizable to the broader fertility treatment population. Lifestyle awareness may vary with age and education level. Furthermore, completing questionnaires simultaneously may have introduced response bias due to mutual influence between partners. Wider implications of the findings Although couples undergoing fertility treatment exhibit similar lifestyle habits, these behaviors are negatively influenced throughout the treatment process. Additionally, further research is needed to expand the limited literature on the impact of infertility treatment on couples’ lifestyle behaviors, emphasizing the importance of targeted, fertility-specific lifestyle modifications to optimize treatment outcomes. Trial registration number No

Is temporary ovarian suspension following laparoscopic surgery for severe pelvic endometriosis an effective method for reducing the prevalence of postoperative ovarian adhesions? Temporary ovarian suspension for 36-48 h following laparoscopic treatment of severe endometriosis does not result in a significant reduction of postoperative ovarian adhesions. Pelvic adhesions often develop following laparoscopic surgery for severe pelvic endometriosis. Adhesions can cause chronic pelvic pain and fertility problems compromising the success of treatment. Small observational studies suggested that temporary postoperative ovarian suspension to the abdominal wall may significantly reduce the prevalence of postoperative ovarian adhesions. This was a prospective within group comparison double-blind RCT. We recruited premenopausal women with severe pelvic endometriosis who required extensive laparoscopic surgery with preservation of the uterus and ovaries. Severity of the disease and eligibility for inclusion were determined at surgery. A total of 55 women were randomized to unilateral ovarian suspension for 36-48 h, 52 of which were included in the final analysis. Both ovaries were routinely suspended to the anterior abdominal wall during surgery. At the end of the operation, each woman was randomized to having only one ovary suspended postoperatively. The suture suspending the contralateral ovary was cut and a new transabdominal suture was inserted to act as a placebo. Both sutures were removed 36-48 h after surgery prior to discharge. Three months after surgery, all women attended for a detailed transvaginal ultrasound scan to assess ovarian mobility. Both the women and the ultrasound operators were blinded as to the side of postoperative ovarian suspension. The primary outcome was the prevalence of ovarian adhesions as described on ultrasound examination. Secondary outcomes were the severity of adhesions and the presence and intensity of postoperative pain. All 55 participants had severe pelvic endometriosis confirmed at laparoscopy. As each participant had only one of their ovaries suspended at the end of surgery, they acted as their own control. The median interval between ovarian suspension and postoperative scan was 99 days (interquartile range 68-114). There was no significant difference (P = 0.23) in the prevalence of postoperative ovarian adhesions between the suspended (20/52) and unsuspended (27/52) side (38.5 versus 51.9%) [odds ratio 0.56 (95% confidence interval 0.22-1.35)]. Ovaries were suspended postoperatively for 36-48 h. Longer suspension could result in lower prevalence of postoperative adhesions. The value of temporary ovarian suspension in women having surgery for mild-to-moderate endometriosis should be investigated further. The potential benefits of other adhesion prevention strategies, such as surgical barrier agents, in women undergoing surgical treatment for severe pelvic endometriosis should also be explored. E.S. received honoraria from Ethicon for provision of training to healthcare professionals and consultancy fees from Bayer. W.H. was supported by the research fund provided by the Gynaecology Ultrasound Centre, London UK. A.C. is on the advisory board for surgical innovations for which he receives an annual honorarium. A.C. also received support for courses and education from Storz and Johnson and Johnson and support for clinical nursing from Covidien and Lotus. The other authors declared no competing interests. Current Controlled Trials ISRCTN24242218.

THE AGE AND BY WHOM A DONOR-CONCEIVED PERSON RECEIVES INFORMATION SIGNIFICANTLY EFFECTS THEIR EXPERIENCE

This current study investigated a link between stress and coping with some male infertility problems via psychoneuroimmunological theories. The study was carried out on 77 males who came to a fertility clinic for sperm diagnosis. Appraisal and coping with stress reaction to negative life events and to infertility were related to non-sperm cells within the seminal plasma. Those men who had felt strained from external events and from problems of infertility, and had used emotional escape coping strategies, were more prone to have an immunosuppressed reaction, indicated by bacteria within their plasma. Those using task focused control strategies were more prone to have an immunostimulatory reaction, indicated by white blood cells, including in some cases, sperm destroying phagocytes suggesting a possible auto-immunity reaction. When the analyses were done separately on patients with known male fertility problems in comparison with those with unexplained infertility, the two opposing psychoneuroimmun...

STUDY QUESTIONDo sense of meaning and acceptance mediate the relationships between gratitude and infertility-related stress among women undergoing IVF?SUMMARY ANSWERAmong women undergoing IVF, the negative relationships between gratitude and infertility-related stress are explained by a general sense of meaningfulness and acceptance of life.WHAT IS KNOWN ALREADYInfertility experts increasingly call for a re-balancing of the deficit-based view of psychosocial adjustment in IVF, which has been heavily dominated by studies of risk factors and psychological distress. Attention has been given to strength-based perspectives that emphasize character strengths and personal growth. Gratitude has been found to be a potent protective factor in coping with life stressors; however, its salutary effects and protective processes for infertile women undergoing IVF are yet to be explored.STUDY DESIGN, SIZE, DURATIONThis study utilized baseline data of a randomized controlled trial for mind–body interventions with 357 Hong Kong Chinese women. Data collection was conducted between January 2015 and December 2017.PARTICIPANTS/MATERIALS, SETTINGS, METHODSEligible women were approached by a research assistant immediately after their first medical consultation at an ART centre of a major university-affiliated hospital. Participants were asked to complete a battery of questionnaires, including the Gratitude Questionnaire-6, the Fertility Problem Inventory, and the Holistic Well-Being Scale. Mediation analyses were conducted with bootstrapped samples.MAIN RESULTS AND THE ROLE OF CHANCEOf the 494 women who were approached, 357 (72.3%) provided informed consent and participated in the study. Results show that gratitude was negatively associated with all infertility-related stress domains (rs = −0.19 to −0.36), and these relationships are mediated by acceptance and loss of sense of meaning. Further, the link between gratitude and relationship concerns is mediated by loss of sense of meaning in women with a definable cause of infertility (95% CI = [−0.31, −0.08]), but by acceptance among those with unexplained infertility (95% CI = [−0.33, −0.01]).LIMITATIONS, REASONS FOR CAUTIONThe cross-sectional nature of the study precluded inferences of causality. Self-selection and self-report biases could be present. Our findings may not be readily generalizable to women who do not intend to undergo psychosocial intervention for their infertility or ART.WIDER IMPLICATIONS OF THE FINDINGSOur findings support the salutary effects of gratitude in coping with IVF and highlight the role of unexplained infertility in the coping process. These findings offer preliminary support to the use of psychosocial interventions in promoting gratitude, acceptance, and meaning reconstruction for reducing infertility-related stress in women undergoing IVF.STUDY FUNDING/COMPETING INTEREST(S)This study was funded by the Hong Kong University Grant Council—General Research Fund (HKU27400414). All authors declare no competing interests.TRIAL REGISTRATION NUMBERHKUCTR-1984.

Anthocyanins comprise polyphenols having recognized antioxidant capacity, whichare involved in several biological processes such as the protection or reduction of heart disease, arthritis, diabetes, and cancer and also play an important role in infertility as well as impotency. Such qualities, including stability and bioavailability, are determined by their chemical composition. The current study provides a brief overview of anthocyanin's chemical components, bioavailability, as well as anti-inflammatory properties. If a couple has already been attempting to conceive for more than a year without success, then they may be regarded ashaving fertility problems. Worldwide, 20% of all couples are unable to have offspring. Subfertility canaffect either female, male, or even both partners. Nevertheless, for some couples, the source of infertility cannot be determined, which is known as unexplained infertility. Antioxidants are expected to reduce the harm resulting from oxidative stress, which is known to be implicated in the pathogenesis of infertility. Antioxidants are commonly available and reasonably priced. However, there is currently insufficient high-quality research to establish whether consuming antioxidants would benefit or damage infertile women.

Multiple long-term conditions (MLTC), also known as multimorbidity, has been identified as a priority research topic globally. Research priorities from the perspectives of patients and research funders have been described. Although most care for MLTC is delivered in primary care, the priorities of academic primary care have not been identified. To identify and prioritise the academic primary care research agenda for MLTC. This was a three-phase study with primary care MLTC researchers from the UK and other high-income countries. The study consisted of: an open-ended survey question, a face-to-face workshop to elaborate questions with researchers from the UK and Ireland, and a two-round Delphi consensus survey with international multimorbidity researchers. Twenty-five primary care researchers responded to the initial open-ended survey and generated 84 potential research questions. In the subsequent workshop discussion (n = 18 participants), this list was reduced to 31 questions. The longlist of 31 research questions was included in round 1 of the Delphi; 27 of the 50 (54%) round 1 invitees and 24 of the 27 (89%) round 2 invitees took part in the Delphi. Ten questions reached final consensus. These questions focused broadly on addressing the complexity of the patient group with development of new models of care for multimorbidity, and methods and data development. These high-priority research questions offer funders and researchers a basis on which to build future grant calls and research plans. Addressing complexity in this research is needed to inform improvements in systems of care and for disease prevention.

At least 30-40% of stallions in commercial breeding programs are moderately fertile and 8-12% are subfertile (0.5-3% with severe subfertility). From the total reported cases of the subfertility, in 2-20% of the stallions the cause is unknown or was not established. The objective of this work is to present the concept of subfertile stallion based on the current state of knowledge and advanced molecular diagnostic technologies. Low pregnancy rates have been reported in stallions with normal semen quality after conventional evaluation. Acrosome reaction (AR) is necessary for natural fertilization and impaired acrosome reaction (IAR) leads to subfertility or infertility in horses, however, AR test is not included in routine semen analysis. Genome-wide association study identified FKBP6 as a strong candidate gene responsible for this failure. The gene encodes for FK506 binding protein 6 (FKBP6) which is involved in sperm development and functions. We could conclude that the evaluation of the acrosomal status is essential in cases of stallions with good motility, concentration, morphology and viability but unexplained (idiopathic) subfertility or infertility. It is important to highlight the recent increase in reports of fertility problems in stallions related to disorders of genetic origin.

Study question Are the novel mutations of TSPY1 gene associated with idiopathic male infertility in men? Summary answer Sporadic TSPY1 gene mutation is one of the major causes of idiopathic male infertility among men. What is known already As per the published research, there are several studies including AZF micro-deletion, sex chromosome copy number variation but surprisingly studies on Y chromosome genes are not that much available. Due to the genetic cross-talks of different regulatory mechanisms involved in the spermatogenesis process, male infertility still remains idiopathic. Contradictory outcome of the analyses intrigues the association of the variations of TSPY1 gene with male infertility. Previous analyses did not reveal implication of TSPY1 gene as etiologic factor of male infertility. Study design, size, duration This was a population-based case-control study that includes 184 cases of spermatogenic failure and 197 age-matched fertile men as controls and the study was conducted between March, 2018 and February, 2021 to infer whether the genetic mutations are significantly associated with spermatogenic failure. Participants/materials, setting, methods The samples were collected from the Institute of Reproductive Medicine (IRM) and Genome-the fertility centre. All the selected individuals agreed to participate in the study and provided blood samples. We isolated DNA from the blood samples, designed specific primers and went for PCR. We performed Sanger’s dideoxy sequencing of TSPY1 gene reading frame followed by in silico analyses of detected variations to interpret their intuitive effects on transcript and protein level of TSPY1 gene. Main results and the role of chance We found one novel deletion namely MN734578 (NC_000024.10:g.9468830del) and one novel insertion MN719944 (NC_000024.10:g.9468815_9468816insA). Both these mutations exhibited strong association with male infertility. MN734578 showed compelling confederacy with male infertility increasing the risk factor against the odd 19.023 (P value 0.0027). Here the mutation was found in 8 out of 184 case individuals. MN719944 was found to be extremely correlated with male infertility increasing the risk factor by 14.547 folds (P value 0.0117). This mutation is found in 6 out of 184 case individuals. Both the mutations were not not found in the control individuals. In silico analyses using different software SIFT, PROVEAN, REGULATIONSPOTTER, HSF and SpliceAid suggest prospective disruption in splice sites and alteration in different isoforms of TSPY1 transcripts and amino acid sequence in TSPY1 protein. We calculated Odds ratios with respective 95% confidence interval (CI) by performing Fisher’s exact test. After Bonferroni's correction, a two-tailed P-value of less than 0.02 was considered statistically significant. Limitations, reasons for caution The origin of the novel mutations is unknown and the outcome does not provide mechanistic details how do de novo mutations imperil the process of spermatogenesis. Wider implications of the findings The study provides evidence in favour of implication of TSPY1 gene in male fertility. The outcome sheds light to get insight into the issue of unexplained male infertility in Bengali will help to manage fertility problem in men. Trial registration number Not applicable

AimsTo undertake a Priority Setting Partnership (PSP) to establish priorities for future research in diabetes and pregnancy, according to women with experience of pregnancy, and planning pregnancy, with any type of diabetes, their support networks and healthcare professionals.MethodsThe PSP used established James Lind Alliance (JLA) methodology working with women and their support networks and healthcare professionals UK‐wide. Unanswered questions about the time before, during or after pregnancy with any type of diabetes were identified using an online survey and broad‐level literature search. A second survey identified a shortlist of questions for final prioritisation at an online consensus development workshop.ResultsThere were 466 responses (32% healthcare professionals) to the initial survey, with 1161 questions, which were aggregated into 60 unanswered questions. There were 614 responses (20% healthcare professionals) to the second survey and 18 questions shortlisted for ranking at the workshop. The top 10 questions were: diabetes technology, the best test for diabetes during pregnancy, diet and lifestyle interventions for diabetes management during pregnancy, emotional and well‐being needs of women with diabetes pre‐ to post‐pregnancy, safe full‐term birth, post‐natal care and support needs of women, diagnosis and management late in pregnancy, prevention of other types of diabetes in women with gestational diabetes, women's labour and birth experiences and choices and improving planning pregnancy.ConclusionsThese research priorities provide guidance for research funders and researchers to target research in diabetes and pregnancy that will achieve greatest value and impact.