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Controlling the principal African malaria vector, the mosquito Anopheles gambiae, is considered essential to curtail malaria transmission. However, existing vector control technologies rely on insecticides, which are becoming increasingly ineffective. Sterile insect technique (SIT) is a powerful suppression approach that has successfully eradicated a number of insect pests, yet the A. gambiae toolkit lacks the requisite technologies for its implementation. SIT relies on iterative mass releases of nonbiting, nondriving, sterile males which seek out and mate with monandrous wild females. Once mated, females are permanently sterilized due to mating-induced refractoriness, which results in population suppression of the subsequent generation. However, sterilization by traditional methods renders males unfit, making the creation of precise genetic sterilization methods imperative. Here, we introduce a vector control technology termed precision-guided sterile insect technique (pgSIT), in A. gambiae for inducible, programmed male sterilization and female elimination for wide-scale use in SIT campaigns. Using a binary CRISPR strategy, we cross separate engineered Cas9 and gRNA strains to disrupt male-fertility and female-essential genes, yielding >99.5% male sterility and >99.9% female lethality in hybrid progeny. We demonstrate that these genetically sterilized males have good longevity, are able to induce sustained population suppression in cage trials, and are predicted to eliminate wild A. gambiae populations using mathematical models, making them ideal candidates for release. This work provides a valuable addition to the malaria genetic biocontrol toolkit, enabling scalable SIT-like confinable, species-specific, and safe suppression in the species.

In vitro gametogenesis (IVG), the reconstitution of germ cell development in vitro, is an emerging stem cell-based technology with profound implications for reproductive science. Despite researchers' long-term goals for future clinical applications, little is currently known about the views of IVG held by the stakeholders potentially most affected by its introduction in humans. We conducted focus groups and interviews with 80 individuals with lived experience of infertility and/or LGBTQ+ family formation in the US, two intersecting groups of potential IVG users. Respondents expressed hope that IVG would lead to higher reproductive success than current assisted reproductive technology (ART), alleviate suffering associated with ART use, and promote greater social inclusion, while expressing concerns predominantly framed in terms of equity and safety. These findings underscore the importance of sustained engagement with stakeholders with relevant experience to anticipate the implications of IVG for research and clinical translation.

PURPOSE: This study characterizes attitudes and decision-making around the desire for future children in young women newly diagnosed with early-stage breast cancer and assesses how clinical factors and perceived risk may impact these attitudes. METHODS: This is a prospective study in women

IntroductionFemale reproductive function depends on a choreographed sequence of hormonal secretion and action, where specific stresses such as inflammation exert profound disruptions. Specifically, acute LPS-induced inflammation inhibits gonadotropin production and secretion from the pituitary, thereby impacting the downstream production of sex hormones. These outcomes have only been observed in acute inflammatory stress and little is known about the mechanisms by which chronic inflammation affects reproduction. In this study we seek to understand the chronic effects of LPS on pituitary function and consequent luteinizing and follicle stimulating hormone secretion.MethodsA chronic inflammatory state was induced in female mice by twice weekly injections with LPS over 6 weeks. Serum gonadotropins were measured and bulk RNAseq was performed on the pituitaries from these mice, along with basic measurements of reproductive biology.ResultsSurprisingly, serum luteinizing and follicle stimulating hormone was not inhibited and instead we found it was increased with repeated LPS treatments.DiscussionAnalysis of bulk RNA-sequencing of murine pituitary revealed paracrine activation of TGFβ pathways as a potential mechanism regulating FSH secretion in response to chronic LPS. These results provide a framework with which to begin dissecting the impacts of chronic inflammation on reproductive physiology.

Objective: While infertility affects about 15% of women during their reproductive years, its long-term impact on stroke mortality after this period remains unclear. This study aims to investigate the association between infertility and stroke mortality in women using data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial. Methods: We analyzed data from 75,778 female participants aged 55-74 years with a median follow-up of 16.84 years. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for stroke mortality, adjusting for potential confounders. Results: Among participants, 14.53% reported infertility. During follow-up, 1,159 women died from stroke. Compared to women without infertility, those with infertility had a higher risk of stroke mortality (HR 1.21, 95% CI 1.04-1.41, p = 0.016). This association remained statistically significant after adjusting for age, race, education level, marital status, smoking status, body mass index, history of hypertension, history of heart attack, history of diabetes mellitus, birth control pill use, hormone replacement therapy, endometriosis, first menstrual period and pregnancy history (HR 1.20, 95% CI 1.02-1.42, p = 0.029). Sensitivity and subgroup analyses yielded consistent results. Conclusion: The findings of this study indicate that infertility is associated with an increased risk of stroke mortality in women. Further research is needed to confirm these findings and elucidate the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a common metabolic disorder of the reproductive system in women of adolescent and childbearing age. In addition to ovulatory dysfunction, menstrual dysfunction and infertility, most patients suffer from endocrine abnormalities such as insulin resistance (IR), hyperandrogenemia (HA) and abdominal obesity. Ferroptosis, a highly iron-dependent programmed cell death mediated by the lipid peroxidation and the imbalance in the oxidative -antioxidant system is a hot research topic in reproductive medicine. The relevance of ferroptosis in PCOS has received much attention in recent years, and recent studies suggest that ferroptosis may be involved in the regulation of PCOS -associated metabolic disorders and affect reproductive function in women with PCOS by disrupting oocyte quality and uteroplacental function. To further enrich and improve the system of diagnosis, prevention, and prognosis assessment of PCOS, we summarize the mechanisms related to ferroptosis, systematically discusses the correlation between ferroptosis and the pathophysiology of PCOS, and its research progress in the treatment of PCOS. [ABSTRACT FROM AUTHOR]

Problem: Predicting the impact of systemic inflammation on oocyte and embryonic development in unexplained infertile women using the new immunological indexes. Method of Study: This retrospective cohort study was conducted using the records of the In Vitro Fertilization Department of Ankara Gülhane Training and Research Hospital. After reviewing the records of patients who had undergone in vitro fertilization (IVF) for unexplained infertility (UI) and excluding all known factors that could cause systemic immune inflammation, the systemic immune response index (SIRI), and pan‐immune score were calculated from the pre‐treatment hemogram parameters between the embryo arrest (EA) group and the embryo transfer group. It was investigated whether there was a statistical difference between the two groups and whether an SIRI value affecting embryo quality was found. A receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cut‐off values for inflammatory markers to predict EA. Results: The 108 EA group (embryos that were arrested during their development and could not be transferred) and the 140 embryo transfer group showed statistically significant differences in the parameters of systemic inflammatory index (SII), SIRI, pan‐immune inflammation value (PIV), and neutrophil/lymphocyte ratio (NLR) (p < 0.05). These inflammatory parameters, which were examined before ovulation induction, also correlated positively with the required total dose of gonadotropin and negatively with the ovarian sensitivity index (OSI). SII, SIRI, PIV, and NLR have specific cut‐off values with ROC analysis and determine the effect of the inflammatory status of the environment in which the oocyte develops on EA (p < 0.005). Conclusion: In women with UI, high levels of systemic immune inflammation have a negative impact on oocyte and embryo development, and treatments to suppress inflammation may improve IVF success. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to identify factors influencing oncofertility and to explore the oncofertility experiences of patients with gynecological cancer using quantitative and qualitative methods, respectively. Methods: An explanatory sequential mixed-methods study was conducted. The quantitative study involved 222 patients with gynecological cancer recruited from online cafes and hospitals. Data were analyzed using IBM SPSS Statistics 28. For qualitative research, eight patients with gynecological cancer were interviewed. Data were analyzed using theme analysis method. Results: Oncofertility performance was quantitatively assessed in 40 patients (18.0%). Factors that significantly affected oncofertility were fertility preservation awareness (odds ratio [OR] = 14.97, 95% confidence interval [CI]: 4.22???53.08), number of children planned before cancer diagnosis (OR = 6.08, 95% CI: 1.89~19.62; OR = 5.04, 95% CI: 1.56~16.29), monthly income (OR = 3.29, 95% CI: 1.23~8.86), social support (OR = 1.08, 95% CI: 1.01~1.17), and anxiety (OR = 0.79, 95% CI: 0.66~0.95). Qualitative results showed three theme clusters and eight themes: (1) themes for determinant factors affecting oncofertility selection: 'desire to have children' and 'special meaning of the uterus and ovaries;' (2) themes for obstructive factors affecting oncofertility selection: 'fertility preservation fall behind priorities,' 'confusion caused by inaccurate information,' and 'my choice was not supported;' (3) themes for support factors affecting oncofertility selection: 'provide accurate and reasonable information about oncofertility,' 'addressing the healthcare gap,' and 'need financial support for oncofertility.' Conclusion: Financial support, sufficient information, social support, and anxiety-relief interventions are required for oncofertility in patients with gynecological cancer. [ABSTRACT FROM AUTHOR]

Endometriosis is a common estrogen-dependent disorder wherein uterine lining tissue (endometrium) is found mainly in the pelvis where it causes inflammation, chronic pelvic pain, pain with intercourse and menses, and infertility. Recent evidence also supports a systemic inflammatory component that underlies associated co-morbidities, e.g., migraines and cardiovascular and autoimmune diseases. Genetics and environment contribute significantly to disease risk, and with the explosion of omics technologies, underlying mechanisms of symptoms are increasingly being elucidated, although novel and effective therapeutics for pain and infertility have lagged behind these advances. Moreover, there are stark disparities in diagnosis, access to care, and treatment among persons of color and transgender/nonbinary identity, socioeconomically disadvantaged populations, and adolescents, and a disturbing low awareness among health care providers, policymakers, and the lay public about endometriosis, which, if left undiagnosed and under-treated can lead to significant fibrosis, infertility, depression, and markedly diminished quality of life. This review summarizes endometriosis epidemiology, compelling evidence for its pathogenesis, mechanisms underlying its pathophysiology in the age of precision medicine, recent biomarker discovery, novel therapeutic approaches, and issues around reproductive justice for marginalized populations with this disorder spanning the past 100 years. As we enter the next revolution in health care and biomedical research, with rich molecular and clinical datasets, single-cell omics, and population-level data, endometriosis is well positioned to benefit from data-driven research leveraging computational and artificial intelligence approaches integrating data and predicting disease risk, diagnosis, response to medical and surgical therapies, and prognosis for recurrence.

Certain chemotherapy agents, radiation, and surgery can all negatively impact future fertility. Consults regarding treatment-related risk for infertility and gonadal late effects of these agents should occur at the time of diagnosis as well as during survivorship. Counseling on fertility risk has traditionally varied significantly across providers and institutions. We aim to provide a guide to standardize the assignment of gonadotoxic risk, which can be used in counseling patients both at the time of diagnosis and in survivorship. Gonadotoxic therapies were abstracted from 26 frontline Childrens Oncology Group (COG) phase III protocols for leukemia/lymphoma, in use from 2000-2022. A stratification system based on gonadotoxic therapies, sex, and pubertal status was used to assign treatments into minimal, significant, and high level of increased risk for gonadal dysfunction/infertility. Risk levels were assigned to protocols and different treatment arms to aid oncologists and survivor care providers in counseling patients regarding treatment-related gonadotoxicity. Males were most commonly at high risk, with at least one high-risk arm in 14/26 protocols (54%), followed by pubertal females (23% of protocols) and prepubertal females (15% of protocols). All patients who received direct gonadal radiation or hematopoietic stem cell transplant (HSCT) were considered at high risk. Partnering with patients and their oncology/survivorship team is imperative for effective fertility counseling both prior to and post treatment, and this comprehensive guide can be used as a tool to standardize and improve reproductive health counseling in patients undergoing COG-based leukemia/lymphoma care.

Background and purpose: Infertility has been raised as a reproductive health problem all over the world. Based on the other studies the prevalence of infertility in different regions of the world is different, and its prevalence in Iran is higher than the global average. There are various methods for treating infertility, one of the most important of which is the IVF microinjection method, which is considered one of the last treatment methods for infertile couples. Because various factors play a role in the success of this treatment, many of which may not be known yet, so this study was conducted to investigate the paraclinical and demographic factors affecting infertility treatment by IVF microinjection method in the infertility treatment center of Imam Khomeini Hospital in Sari. Materials and methods: The data of this cross-sectional study were extracted using information from the files of infertile women who are being treated at the Infertility Treatment Center of Imam Khomeini Hospital in Sari. Information was collected on cases that were Iranian couples, married women whose diagnosis of infertility was definite, and the problem of infertility was related to the woman. Paraclinical and demographic factors affecting the success of infertility treatment by IVF microinjection method were investigated using a logistic regression model. First, using a univariate model, important variables were identified, and a multivariate model was fitted. SPSS21 software was used for data analysis. Results: 64 people (19.9%) were successfully treated using the IVF microinjection method. Women who were successfully treated had a lower average age at the time of diagnosis of infertility than women who were not treated successfully (P= 0.015). Also, the treatment success rate in women who had a history of psychiatric diseases is higher than in women who did not have (P= 0.005). Also, less than one year after the diagnosis of infertility, an increase in the age of the woman at the time of diagnosis of infertility, reduces the chances of successful IVF microinjection treatment. The success rate of treatment for women who were treated for less than one year was 17/5% (13/3% - 22.4%), and for women who were treated for more than one year was 31.5% (20/3% - 44.6%). Conclusion: The overall success rate of microinjection IVF treatment in this study was lower than in similar studies, although, in women who had been treated for less than one year, this rate was lower than in women who had been treated for more than one year. So, continuing infertility treatment by IVF microinjection method for a longer period after the start of treatment increases the chance of treatment success. A woman's age when infertility is diagnosed is one of the most important factors in the treatment of infertility, and the younger the infertility is diagnosed and the sooner treatments are started, the higher the chance of success in treatment and fertility. Therefore, early referral to a specialist can affect the success of the treatment. The success of treatment was higher in women with a history of psychiatric diseases than other women, which could be due to their insistence on treatment.

Background and purpose: Infertility has been raised as a reproductive health problem all over the world. Based on the other studies the prevalence of infertility in different regions of the world is different, and its prevalence in Iran is higher than the global average. There are various methods for treating infertility, one of the most important of which is the IVF microinjection method, which is considered one of the last treatment methods for infertile couples. Because various factors play a role in the success of this treatment, many of which may not be known yet, so this study was conducted to investigate the paraclinical and demographic factors affecting infertility treatment by IVF microinjection method in the infertility treatment center of Imam Khomeini Hospital in Sari. Materials and methods: The data of this cross-sectional study were extracted using information from the files of infertile women who are being treated at the Infertility Treatment Center of Imam Khomeini Hospital in Sari. Information was collected on cases that were Iranian couples, married women whose diagnosis of infertility was definite, and the problem of infertility was related to the woman. Paraclinical and demographic factors affecting the success of infertility treatment by IVF microinjection method were investigated using a logistic regression model. First, using a univariate model, important variables were identified, and a multivariate model was fitted. SPSS21 software was used for data analysis. Results: 64 people (19.9%) were successfully treated using the IVF microinjection method. Women who were successfully treated had a lower average age at the time of diagnosis of infertility than women who were not treated successfully (P= 0.015). Also, the treatment success rate in women who had a history of psychiatric diseases is higher than in women who did not have (P= 0.005). Also, less than one year after the diagnosis of infertility, an increase in the age of the woman at the time of diagnosis of infertility, reduces the chances of successful IVF microinjection treatment. The success rate of treatment for women who were treated for less than one year was 17/5% (13/3% - 22.4%), and for women who were treated for more than one year was 31.5% (20/3% - 44.6%). Conclusion: The overall success rate of microinjection IVF treatment in this study was lower than in similar studies, although, in women who had been treated for less than one year, this rate was lower than in women who had been treated for more than one year. So, continuing infertility treatment by IVF microinjection method for a longer period after the start of treatment increases the chance of treatment success. A woman's age when infertility is diagnosed is one of the most important factors in the treatment of infertility, and the younger the infertility is diagnosed and the sooner treatments are started, the higher the chance of success in treatment and fertility. Therefore, early referral to a specialist can affect the success of the treatment. The success of treatment was higher in women with a history of psychiatric diseases than other women, which could be due to their insistence on treatment. [ABSTRACT FROM AUTHOR]

The study encompassing research papers documented in the last two decades pertaining to the possible influence of bisphenol A (BPA) on the fertility of females are appraised with emphasis on the influence of BPA in reproductive organs (uterus and ovaries) and pregnancy outcomes including discussion on the reproductive process (implantation, estrous cycle, hormone secretion); outcomes reveal a connection amongst BPA and female infertility. Ovary, uterus, and its shape as well as function can alter a person's ability to become pregnant by influencing the hypothalamus-pituitary axis in the ovarian model. Additionally, implantation and the estrous cycle may be affected by BPA. However, more research is warranted to comprehend the underlying action mechanisms and to promptly identify any imminent reproductive harm. [ABSTRACT FROM AUTHOR]

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The microbiota is in symbiosis with the human body as a holobiont. Infertility conditions affect the female reproductive tract (FRT) and its resident microbiota. However, a disturbance in homeostasis could influence the FRT and other distal body sites, such as the gastrointestinal tract (GIT). We included 21 patients with endometriosis and other infertility-associated diseases with clinical profiles and biological samples from the FRT (endometrium, endometrial fluid, and vagina), and GIT samples (oral and feces). We performed a 16S rRNA analysis of site-specific microbial communities and estimated diversity metrics. The study found body site-specific microbial patterns in the FRT–GIT. In both study groups, Lactobacillus was the most shared Amplicon Sequence Variant (ASV), a precise identifier of microbial sequences, between endometrial and vagina samples. However, shared Gardnerella and Enterobacteriaceae ASVs were linked to other conditions but not endometriosis. Remarkably, Haemophilus was a specific GIT-shared taxon in endometriosis cases. In conclusion, infertility influences distinctly the FRT and GIT microbiomes, with endometriosis showing unique microbial characteristics. We proposed the concept of 'female holobiont' as a community that comprises the host and microbes that must maintain overall homeostasis across all body sites to ensure a woman's health. Insights into these microbial patterns not only advance our understanding of the pathophysiology of infertility but also open new avenues for developing microbe-based therapeutic interventions aimed at restoring microbial balance, thereby enhancing fertility prospects. [ABSTRACT FROM AUTHOR]

Reproductive longevity is associated with health outcomes. Early menopause, loss of ovarian function, and male infertility are linked to shorter lifespan and increased adverse health outcomes. Here we examined the extragonadal effects of whole animal loss of spermatogenesis and oogenesis specific basic helix-loop-helix 1 (Sohlh1) gene in mice, a well-described mouse model of female and male infertility. Sohlh1 encodes a transcription factor that is primarily expressed in the male and female germline and regulates germline differentiation. The Sohlh1 knockout mouse model, just like human individuals with SOHLH1 loss of function, presents with hypergonadotropic hypogonadism and loss of ovarian function in females and impaired spermatogenesis in males, with a seemingly gonad restricted phenotype in both sexes. However, extragonadal phenotyping revealed that Sohlh1 deficiency leads to abnormal immune profiles in the blood and ovarian tissues of female animals, sex-specific alterations of metabolites, and behavior and cognition changes. Altogether, these results show that Sohlh1 deficiency impacts overall health in both male and female mice.

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention.

Endometriosis is an incurable, under-diagnosed, systemic inflammatory disease affecting millions world-wide. Common symptoms include life-impacting pain, gastrointestinal/urinary symptoms, excessive fatigue, and infertility. Global public health policies are urgently needed to promote awareness, implement multidisciplinary care, and fund research for aetiology, biomarker discovery, and effective therapies for symptoms associated with endometriosis.

Endometriosis is a leading cause of pain and infertility affecting millions of women globally. Herein, we characterize variation in DNA methylation (DNAm) and its association with menstrual cycle phase, endometriosis, and genetic variants through analysis of genotype data and methylation in endometrial samples from 984 deeply-phenotyped participants. We estimate that 15.4% of the variation in endometriosis is captured by DNAm and identify significant differences in DNAm profiles associated with stage III/IV endometriosis, endometriosis sub-phenotypes and menstrual cycle phase, including opening of the window for embryo implantation. Menstrual cycle phase was a major source of DNAm variation suggesting cellular and hormonally-driven changes across the cycle can regulate genes and pathways responsible for endometrial physiology and function. DNAm quantitative trait locus (mQTL) analysis identified 118,185 independent cis-mQTLs including 51 associated with risk of endometriosis, highlighting candidate genes contributing to disease risk. Our work provides functional evidence for epigenetic targets contributing to endometriosis risk and pathogenesis. Data generated serve as a valuable resource for understanding tissue-specific effects of methylation on endometrial biology in health and disease.

Long COVID disproportionately affects premenopausal women, but relatively few studies have examined Long COVID's impact on female reproductive health. We conduct a review of the literature documenting the female reproductive health impacts of Long COVID which may include disruptions to the menstrual cycle, gonadal function, ovarian sufficiency, menopause, and fertility, as well as symptom exacerbation around menstruation. Given limited research, we also review the reproductive health impacts of overlapping and associated illnesses including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), postural orthostatic tachycardia syndrome (POTS), connective tissue disorders like Ehlers-Danlos syndrome (EDS), and endometriosis, as these illnesses may help to elucidate reproductive health conditions in Long COVID. These associated illnesses, whose patients are 70%-80% women, have increased rates of dysmenorrhea, amenorrhea, oligomenorrhea, dyspareunia, endometriosis, infertility, vulvodynia, intermenstrual bleeding, ovarian cysts, uterine fibroids and bleeding, pelvic congestion syndrome, gynecological surgeries, and adverse pregnancy complications such as preeclampsia, maternal mortality, and premature birth. Additionally, in Long COVID and associated illnesses, symptoms can be impacted by the menstrual cycle, pregnancy, and menopause. We propose priorities for future research and reproductive healthcare in Long COVID based on a review of the literature. These include screening Long COVID patients for comorbid and associated conditions; studying the impacts of the menstrual cycle, pregnancy, and menopause on symptoms and illness progression; uncovering the role of sex differences and sex hormones in Long COVID and associated illnesses; and addressing historical research and healthcare inequities that have contributed to detrimental knowledge gaps for this patient population.

As a common endocrinopathy of reproductive-aged women, polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, oligo-anovulation and polycystic ovarian morphology. It is linked with insulin resistance through preferential abdominal fat accumulation that is worsened by obesity. Over the past two millennia, menstrual irregularity, male-type habitus and sub-infertility have been described in women and confirm that these clinical features of PCOS were common in antiquity. Recent findings in normal-weight hyperandrogenic PCOS women show that exaggerated lipid accumulation by subcutaneous (SC) abdominal stem cells during development to adipocytes in vitro occurs in combination with reduced insulin sensitivity and preferential accumulation of highly-lipolytic intra-abdominal fat in vivo. This PCOS phenotype may be an evolutionary metabolic adaptation to balance energy storage with glucose availability and fatty acid oxidation for optimal energy use during reproduction. This review integrates fundamental endocrine-metabolic changes in healthy, normal-weight PCOS women with similar PCOS-like traits present in animal models in which tissue differentiation is completed during fetal life as in humans to support the evolutionary concept that PCOS has common ancestral and developmental origins.

Millions of women worldwide are infertile due to gynecological disorders, including premature ovarian insufficiency, polycystic ovary syndrome, Asherman syndrome, endometrial atrophy, and fallopian tube obstruction. These conditions frequently lead to infertility and have a substantial impact on the quality of life of the affected couples, primarily because of their psychological implications and high financial costs. Recently, using platelets to stimulate cell proliferation and tissue differentiation has emerged as a promising approach in regenerative medicine. Platelet-rich plasma (PRP) shows considerable potential for promoting endometrial hypertrophy and follicle development, making it a promising therapeutic option for tissue repair or replacement. This review provides an overview of the recent advancements and underlying mechanisms of PRP therapy for various female reproductive diseases and presents new therapeutic options for addressing female infertility. [ABSTRACT FROM AUTHOR]

Introduction. Chromosomal polymorphisms are chromosomal variations in constitutive heterochromatin. For a long time, constitutive heterochromatin has been considered a minor chromosomal rearrangement, composed of highly repetitive DNA sequences that have no coding potential and do not correlate with abnormal phenotypes. However, an increasing number of studies show a higher incidence of chromosomal polymorphism in infertile couples. The aim. To study chromosomal polymorphisms associated with couple infertility and to provide a comparative description of chromosomal polymorphisms associated with female and male infertility in the population of the Republic of Moldova. Materials and Methods. An observational-analytical study was conducted from 2012 to 2022, analyzing 59 karyotypes with chromosomal polymorphisms, of which 23 were female and 36 were male. In 11 couples, chromosomal polymorphisms were present in both partners. The inclusion criteria for the study were the presence of one of the following conditions: failure to conceive after unprotected sexual intercourse for more than one year, recurrent abortions, established sterility as a diagnosis. Results. Results revealed that 25 polymorphic variants were identified in 23 female karyotypes, and 42 polymorphisms were diagnosed in 36 male karyotypes, totaling 67 chromosomal polymorphisms analyzed in the evaluation of 59 karyotypes with chromosomal polymorphisms. The most frequently identified variants associated with infertility in the population of the Republic of Moldova were Yqh+ (23.8%), 1qh+ (11.9%), 9qh+ (8.9%), and 15ph+ (8.9%). In women from the Republic of Moldova, the most commonly detected chromosomal polymorphisms are: 15ph+ (16%), followed by 9qh+ (12%), 1qh+ (12%), 14st (12%), and 13st+ (8%). Polymorphisms 15psts+, 15st+, 16qh+, 17ps+, 14ps+, 21ph+, 21ps+, 21st+, 22ps+, and 14pss+ account for 4%. Men more frequently exhibit chromosomal polymorphisms Yqh+ - 38.0%, 1qh+ - 12.1%, 21ps+, 14ps+, 9qh+, Yqh-7.3%, 15ph+, 15psts+, 13ps+ - 4.8%, 22sts+, 16qh+ - 2.4%. Conclusion. Chromosomal polymorphisms are an important component to consider in the evaluation of couples with infertility. The chromosomal polymorphisms 1qh+ and 9qh+ are commonly found in karyotypes associated with infertility not only in literature data but also in infertile couples from the population of the Republic of Moldova. [ABSTRACT FROM AUTHOR]

Background: The Life's Simple 7 (LS7) metric is a comprehensive measure of cardiovascular health (CVH) that encompasses seven distinct risk factors and behaviors associated with cardiovascular disease (CVD). Some studies have shown an association between infertility and CVD. The present study aimed to explore the potential association between the LS7 factors and infertility. Methods: A cross-sectional study was conducted on a sample of 3537 women aged 18-44 years from the National Health and Nutrition Examination Survey (NHANES) spanning the years 2013-2018. The LS7 metrics encompassed various factors including physical activity, smoking habits, bodymass index, blood pressure levels, dietary patterns, blood glucose levels, and total cholesterol levels. We computed a 14-point LS7 score based on participants' baseline data, classifying themas "inadequate" (3-6), "average" (7-10), or "ideal" (11-14). Infertility is defined as an affirmative answer to either of two questions on the NHANES questionnaire: "Have you tried to conceive for at least one year without success?" and "Have you sought medical help for your inability to conceive?" Logistic regression was utilized to estimate odds ratios (O.R.s) and 95% confidence intervals (C.I.s). Results: In total, 17.66% of participants were classified as individuals who reported experiencing infertility. In the continuous analysis, each one-unit increase in LS7 score was associated with a significantly decreased odds of infertility (OR=0.88 [0.77-0.89]). Analyzing the categorical representation of LS7 score, compared to individuals with poor scores, those with ideal scores exhibited a substantial 58% reduction in the odds of infertility (OR=0.42 [0.26-0.69]). Additionally, the observed interaction suggested that the influence of age on the relationship between LS7 and infertility is not consistent across different age groups (P for interaction < 0.001). Among individuals aged 35 or younger, each unit increase in LS7 score was associated with a substantial 18% (OR=0.82 [0.76-0.89]) decrease in the odds of infertility. However, in the older age group (>35), the association was attenuated and non-significant. Conclusions: Our research suggests a significant inverse association between LS7 scores and infertility. Age demonstrated a varying impact on this relationship, with a more pronounced impact observed among individuals aged 35 or younger. [ABSTRACT FROM AUTHOR]

Background: Hemoglobin A1c (HbA1c) is commonly known as a plasma glucose monitoring indicator. However, the relationship between HbA1c and fertility has not been clarified in previous literature. This study aims to investigate the association between HbA1c and the incidence of infertility. Methods: Data from the U.S. National Health and Nutrition Examination Survey (NHANES) 2013 - 2018 was utilized. The final study contained 3,319 women aged 18 to 45 years. Multivariable logistic regression models were performed to analyze the correlation of HbA1c on female infertility with adjustment for relevant covariates including demographic characteristics, lifestyle, clinical laboratory biomarkers, and comorbidities. Results: We found a significant linear correlation between HbA1c and infertility even in the fully-adjusted model (OR: 1.27, 95% CI: 1.07 - 1.5). Subgroup analysis stratified by age showed a significant linear association with HbA1c and infertility in the younger group (age < 35 years). Whereas, results showed a lack of significant association in the older group (age > 35 years). Conclusions: Data from a population-based sample in US women aged 18 to 45 years suggest that elevated HbA1c level correlated with increasing risk of infertility, even HbA1c is within the normal range. Further well-designed randomized controlled trials are needed to determine whether strategies to reduce HbA1c levels are effective in decreasing the incidence of female infertility. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The objective of this clinical practice guideline is to provide updated and new evidence-based recommendations for the comprehensive care of persons with diabetes mellitus to clinicians, diabetes-care teams, other health care professionals and stakeholders, and individuals with diabetes and their caregivers. METHODS: The American Association of Clinical Endocrinology selected a task force of medical experts and staff who updated and assessed clinical questions and recommendations from the prior 2015 version of this guideline and conducted literature searches for relevant scientific papers published from January 1, 2015, through May 15, 2022. Selected studies from results of literature searches composed the evidence base to update 2015 recommendations as well as to develop new recommendations based on review of clinical evidence, current practice, expertise, and consensus, according to established American Association of Clinical Endocrinology protocol for guideline development. RESULTS: This guideline includes 170 updated and new evidence-based clinical practice recommendations for the comprehensive care of persons with diabetes. Recommendations are divided into four sections: (1) screening, diagnosis, glycemic targets, and glycemic monitoring; (2) comorbidities and complications, including obesity and management with lifestyle, nutrition, and bariatric surgery, hypertension, dyslipidemia, retinopathy, neuropathy, diabetic kidney disease, and cardiovascular disease; (3) management of prediabetes, type 2 diabetes with antihyperglycemic pharmacotherapy and glycemic targets, type 1 diabetes with insulin therapy, hypoglycemia, hospitalized persons, and women with diabetes in pregnancy; (4) education and new topics regarding diabetes and infertility, nutritional supplements, secondary diabetes, social determinants of health, and virtual care, as well as updated recommendations on cancer risk, nonpharmacologic components of pediatric care plans, depression, education and team approach, occupational risk, role of sleep medicine, and vaccinations in persons with diabetes. CONCLUSIONS: This updated clinical practice guideline provides evidence-based recommendations to assist with person-centered, team-based clinical decision-making to improve the care of persons with diabetes mellitus.

Human induced pluripotent stem cells (hiPSCs) enable reproductive diseases to be studied when the reproductive health of the participant is known. In this study, monozygotic (MZ) monoamniotic (MA) twins discordant for primary ovarian insufficiency (POI) consent to research to address the hypothesis that discordant POI is due to a shared primordial germ cell (PGC) progenitor pool. If this is the case, reprogramming the twin's skin cells to hiPSCs is expected to restore equivalent germ cell competency to the twins hiPSCs. Following reprogramming, the infertile MA twin's cells are capable of generating human PGC-like cells (hPGCLCs) and amniotic sac-like structures equivalent to her fertile twin sister. Using these hiPSCs together with genome sequencing, our data suggest that POI in the infertile twin is not due to a genetic barrier to amnion or germ cell formation and support the hypothesis that during gestation, amniotic PGCs are likely disproportionately allocated to the fertile twin with embryo splitting.

Polycystic ovary syndrome (PCOS) occurs in approximately 10% of all reproductive-age women, with over 50% of these patients having imaging-confirmed nonalcoholic fatty liver disease (NAFLD). Whether PCOS increases the risk for more clinically relevant disease, such as nonalcoholic steatohepatitis (NASH), is unclear. Such findings are relevant to prognosticating risk of progressive liver disease in the growing population of young adults with NAFLD. Using weighted discharge data from the United States National Inpatient Sample from 2016 to 2018, we evaluated the association of PCOS with the presence of NASH among reproductive-age women with NAFLD. The association of PCOS with NASH was assessed by logistic regression, adjusting for demographic and comprehensive metabolic comorbidities. Other causes of hepatic steatosis and chronic liver diseases were excluded. Our analysis included 189,440 reproductive-age women with NAFLD, 9415 of whom had PCOS. Of those with PCOS, 1390 (15%) had a distinct code for NASH. Women with PCOS were younger (median age, 33 vs. 40 years; p

BackgroundGonadotoxic treatment-related infertility has a significant impact on quality of life in childhood cancer survivors. Genome-wide association analyses to delineate the risk of infertility in childhood cancer survivors have not been previously reported.MethodsLeveraging genotype data from a large survivor cohort, the Childhood Cancer Survivor Study (CCSS), we investigated the role of SNPs on future pregnancy or siring a pregnancy in survivors without pelvic, testicular, or brain radiation who had ever been married. We calculated sex-stratified hazard ratios, using Cox proportional hazards modeling, adjusting for birth cohort (before 1965 vs. 1965 or later) and doses of relevant chemotherapies; replication was attempted in the independent St. Jude Lifetime Cohort study (SJLIFE).ResultsIn the CCSS cohort, nine SNPs were found to be suggestive (P < 10-7) or statistically significantly (P < 5 × 10-8) associated with pregnancy, however, none of the SNPs were replicated in SJLIFE. Cohorts differed based on the overall pregnancy rate, frequency of sterilizing procedures, and birth cohort.ConclusionsWe were not able to replicate our findings of SNPs associated with pregnancy in childhood cancer survivors.ImpactFuture attempts at replication should be considered in cohorts treated in a comparable era. In addition, understanding the role of genetics in fertility in childhood cancer survivors may be better approached using more advanced sequencing techniques.

In rodents, eating at atypical circadian times, such as during the biological rest phase when feeding is normally minimal, reduces fertility. Prior findings suggest this fertility impairment is due, at least in part, to reduced mating success. However, the physiological and behavioral mechanisms underlying this reproductive suppression are not known. In the present study, we tested the hypothesis that mistimed feeding-induced infertility is due to a disruption in the normal circadian timing of mating behavior and/or the generation of pre-ovulatory luteinizing hormone (LH) surges (estrogen positive feedback). In the first experiment, male+female mouse pairs, acclimated to be food restricted to either the light (mistimed feeding) or dark (control feeding) phase, were scored for mounting frequency and ejaculations over 96 h. Male mounting behavior and ejaculations were distributed much more widely across the day in light-fed mice than in dark-fed controls and fewer light-fed males ejaculated. In the second experiment, the timing of the LH surge, a well characterized circadian event driven by estradiol (E2) and the SCN, was analyzed from serial blood samples taken from ovariectomized and E2-primed female mice that were light-, dark-, or ad-lib-fed. LH concentrations peaked 2 h after lights-off in both dark-fed and ad-lib control females, as expected, but not in light-fed females. Instead, the normally clustered LH surges were distributed widely with high inter-mouse variability in the light-fed group. These data indicate that mistimed feeding disrupts the temporal control of the neural processes underlying both ovulation and mating behavior, contributing to infertility.

The tumor necrosis factor (TNF)-related apoptosis-inducing ligand receptor (TRAIL-R) suppresses inflammation and could therefore affect the course of Chlamydia infections and their long-term sequelae. Wild-type (WT) and TRAIL-R-/- C57BL/6 mice were inoculated vaginally with Chlamydia muridarum; the course of the infection was followed with vaginal cultures and the presence of hydrosalpinx determined. To evaluate the role of TRAIL-R following a secondary infection, the mice were vaginally reinfected. WT and TRAIL-R-/- male mice were also infected and reinfected in the respiratory tract, and the course of the diseases and the infections were followed. Following the primary and secondary vaginal infection, no significant differences in vaginal shedding or hydrosalpinx formation were observed between the WT and TRAIL-R-/- mice. The WT and TRAIL-R-/- mice mounted antibody responses in serum and vaginal washes that were not significantly different. After the primary and secondary intranasal infections of the male mice, changes in body weight were determined, and no significant differences were observed between the WT and TRAIL-R-/- mice. Ten days after the primary and the secondary infections, the weight of the lungs and number of C. muridarum inclusion forming units (IFU) were determined. The lungs of the WT mice weighed less compared with the TRAIL-R-/- mice following a primary infection but not after a secondary infection. No differences in the number of C. muridarum IFU in the lungs were observed between the two groups of mice. In conclusion, despite playing a role in inflammation cell-signaling pathways in vitro, TRAIL-R does not appear to play a major role in the susceptibility, clinical outcomes, or long-term sequelae of C. muridarum infections in vivo. IMPORTANCE TNF-related apoptosis-inducing ligand receptor (TRAIL-R) is involved in suppressing inflammatory responses. Bacterial pathogens such as Chlamydia spp. elicit inflammatory responses in humans following genital, ocular, and respiratory infections. The inflammatory responses are important to control the spread of Chlamydia. However, in certain instances, these inflammatory responses can produce long-term sequelae, including fibrosis. Fibrosis, or scarring, in the genital tract, eye, and respiratory system results in functional deficiencies, including infertility, blindness, and chronic obstructive lung disease, respectively. The goal of this study was to determine if mice deficient in TRAIL-R infected in the genital and respiratory tracts with Chlamydia spp. suffer more or less severe infections, infertility, or lung diseases than wild-type mice. Our results show no differences between the immune responses, infection severity, and long-term sequelae between TRAIL-R knockout and wild-type animals following a genital or a respiratory infection with Chlamydia.

Purpose of reviewAdenomyosis has recently been associated with infertility. Relief of bleeding and pain has been demonstrated with medical and surgical therapy. Less is known about reproductive outcomes after treatment.Recent findingsImaging findings during infertility evaluation can be suggestive of adenomyosis without pathologic evaluation. Among women with infertility undergoing assisted reproductive technologies (ART), adenomyosis is associated with lower live birth rates and clinical pregnancy rates. Treatment with gonadotropin releasing hormone (GnRH) modulators prior to frozen embryo transfer may increase the live birth rate and clinical pregnancy rate among women with adenomyosis. Pregnancy has been documented following image-guided adenomyosis ablation; however, the reproductive impact is not well established. Pregnancy following excisional procedures appears to be well tolerated, although may carry a higher risk of uterine rupture compared with pregnancy following myomectomy. It is not clear if ablative therapy or resection increases pregnancy rates.SummaryAdenomyosis is associated with lower embryo implantation rates and ongoing pregnancy rates. Adenomyotic changes in the uterus can be seen by ultrasound and MRI. GnRH modulators may be useful for women with adenomyosis undergoing ART. Additional prospective data is warranted to determine the optimal medical or surgical therapy for women with adenomyosis desiring conception.Video abstract Supplementary digital content, http://links.lww.com/COOG/A78.

BACKGROUND: Infertility is not only a reproductive health problem; it’s also emotionally painful. Currently, treatments for infertility are receiving more attention, but emotional support is equally important. The aim of this study was to assess the effect of meditation, exercises, dietary, and life-style modifications on depression, anxiety, stress, and self-esteem among infertile women. MATERIAL AND METHODS: This randomized controlled trial was carried out on randomly assigned 60 infertile women (30 experimental and 30 control groups) with the above-mentioned distress at the Infertility Clinic of a tertiary-level hospital in India during the period from 01.07.2020 to 30.6.2021. Infertile women were enrolled using a systematic random sampling technique. The pretest was done with the Depression, Anxiety and Stress Scale (DASS) and the Rosenberg self-esteem scale. Interventions were operated on an experimental group for five subsequent visits for 60 minutes and the control group received routine care. A post-test was done on sixth visit. RESULTS: The pretest mean score of infertile women was 16.13 ± 4.95 for depression, 18.93 ± 4.26 for anxiety, 29.27 ± 4.59 for stress and 10.47 ± 3.49 for self-esteem, respectively. The post-test mean score was 9.07 ± 3.14 for depression, 10.73 ± 3.17 for anxiety, 18.4 ± 3.77 for stress, and 17.5 ± 1.96 for self-esteem. The study results showed the post-test mean score was significantly different in the experimental and control groups at P < 0.001. CONCLUSION: These complementary therapies could potentially lessen the emotional distress experienced by infertile women and boost pregnancy rates. So, infertility management should be comprehensive instead of only using medical treatment to get a better outcome.

Study questionIs sperm epigenetic aging (SEA) associated with probability of pregnancy among couples in the general population?Summary answerWe observed a 17% lower cumulative probability at 12 months for couples with male partners in the older compared to the younger SEA categories.What is known alreadyThe strong relation between chronological age and DNA methylation profiles has enabled the estimation of biological age as epigenetic 'clock' metrics in most somatic tissue. Such clocks in male germ cells are less developed and lack clinical relevance in terms of their utility to predict reproductive outcomes.Study design, size, durationThis was a population-based prospective cohort study of couples discontinuing contraception to become pregnant recruited from 16 US counties from 2005 to 2009 and followed for up to 12 months.Participants/materials, setting, methodsSperm DNA methylation from 379 semen samples was assessed via a beadchip array. A state-of-the-art ensemble machine learning algorithm was employed to predict age from the sperm DNA methylation data. SEA was estimated from clocks derived from individual CpGs (SEACpG) and differentially methylated regions (SEADMR). Probability of pregnancy within 1 year was compared by SEA, and discrete-time proportional hazards models were used to evaluate the relations with time-to-pregnancy (TTP) with adjustment for covariates.Main results and the role of chanceOur SEACpG clock had the highest predictive performance with correlation between chronological and predicted age (r = 0.91). In adjusted discrete Cox models, SEACpG was negatively associated with TTP (fecundability odds ratios (FORs)=0.83; 95% CI: 0.76, 0.90; P = 1.2×10-5), indicating a longer TTP with advanced SEACpG. For subsequent birth outcomes, advanced SEACpG was associated with shorter gestational age (n = 192; -2.13 days; 95% CI: -3.67, -0.59; P = 0.007). Current smokers also displayed advanced SEACpG (P

Glutathione (GSH) is a tripeptide thiol antioxidant that has been shown to be important to overall reproductive health. Glutamate cysteine ligase, the rate-limiting enzyme in GSH synthesis consists of a catalytic and a modifier (GCLM) subunit. We previously showed that oxidative stress in the ovary and oocytes of Gclm-/- mice is associated with accelerated age-related decline in ovarian follicles and decreased female fertility due to preimplantation embryonic mortality. Mammalian preimplantation development is a highly regulated and energy-intensive process that primarily relies on coordination between lipid droplets (LDs) and mitochondria to maintain cellular homeostasis. In this study, we hypothesized that GSH deficiency in oocytes increases oxidative stress, leading to increased mitochondrial dysfunction and decreased LD consumption, thereby decreasing oocyte developmental competence. We observed that Gclm-/- oocytes have increased oxidative stress, primarily in the form of mitochondrial superoxide and decreased subcortical mitochondrial clusters. Further, Gclm-/- oocytes have decreased mitochondrial membrane potential (ΔΨm) compared with Gclm+/+. We surmise this is likely due to the decreased availability of LDs, as we observed a significant decrease in LD content in Gclm-/- oocytes compared with Gclm+/+. The decreased oocyte LD content is likely related to an altered serum lipidome, with Gclm-/- serum having relatively lower unsaturated fatty acids and triglycerides than that of Gclm+/+ and Gclm+/- females. Altogether these data support that decreased LDs and increased oxidative stress are primary drivers of decreased oocyte developmental competence in GSH-deficient oocytes.

Oxytocin has been used to treat neurodevelopmental conditions in adolescent patients but possible effects on reproductive development have not been well investigated. The effects of daily intra-nasal oxytocin treatment (12-18 months of age) on puberty and fertility were studied in colony-housed, male and female titi monkeys (Plecturocebus cupreus). Body weight, urinary conjugated pregnanes and estrogens (defining cyclicity) in females, and androgens and sperm in urine of in males, were measured from 1 to 3 years of age to detect puberty. Serum testosterone was also measured in males at 13, 23 and 33 months of age and hemi-castration at 3 years of age enabled assessment of testicular morphometry and oxytocin receptor expression. An oxytocin treatment*time interaction suggested a minor, transient suppression in weight gain after treatment ended. Note that females weighed 10% less across all ages. Oxytocin-treated females exhibited early, spurious ovulations but neither regular cyclicity (≈30 months) nor pregnancies were affected by treatment. Oxytocin did not affect the pubertal increase in urinary androgen or the first appearance of sperm, which occurred as early as 15 months of age. Treatment did delay the puberty-associated rise in serum testosterone in males. All males were pubertal by 22 months and all females by 32 months of age. Although no major male or female fertility outcome was observed, oxytocin demonstrated some physiological effects through a delay of testosterone secretion in males, induction of precocious ovulation in females, and a suppression of general weight gain for the months following treatment.

Study questionWhat biological processes are linked to the signaling of the energy sensor 5'-AMP-activated protein kinase (AMPK) in mouse and human granulosa cells (GCs)?Summary answerThe lack of α1AMPK in GCs impacted cell cycle, adhesion, lipid metabolism and induced a hyperandrogenic response.What is known alreadyAMPK is expressed in the ovarian follicle, and its activation by pharmacological medications, such as metformin, inhibits the production of steroids. Polycystic ovary syndrome (PCOS) is responsible for infertility in approximately 5-20% of women of childbearing age and possible treatments include reducing body weight, improving lifestyle and the administration of a combination of drugs to improve insulin resistance, such as metformin.Study design, size, durationAMPK signaling was evaluated by analyzing differential gene expression in immortalized human granulosa cells (KGNs) with and without silencing α1AMPK using CRISPR/Cas9. In vivo studies included the use of a α1AMPK knock-out mouse model to evaluate the role of α1AMPK in folliculogenesis and fertility. Expression of α1AMPK was evaluated in primary human granulosa-luteal cells retrieved from women undergoing IVF with and without a lean PCOS phenotype (i.e. BMI: 18-25 kg/m2).Participants/materials, setting, methodsα1AMPK was disrupted in KGN cells and a transgenic mouse model. Cell viability, proliferation and metabolism were evaluated. Androgen production was evaluated by analyzing protein levels of relevant enzymes in the steroid pathway by western blots, and steroid levels obtained from in vitro and in vivo models by mass spectrometry. Differential gene expression in human GC was obtained by RNA sequencing. Analysis of in vivo murine folliculogenesis was performed by histology and immunochemistry, including evaluation of the anti-Müllerian hormone (AMH) marker. The α1AMPK gene expression was evaluated by quantitative RT-PCR in primary GCs obtained from women with the lean PCOS phenotype (n = 8) and without PCOS (n = 9).Main results and the role of chanceSilencing of α1AMPK in KGN increased cell proliferation (P

ObjectiveTo investigate the association of infertility with atherosclerotic cardiovascular disease (ASCVD) among postmenopausal participants in the Women's Health Initiative (WHI). We hypothesized that nulliparity and pregnancy loss may reveal more extreme phenotypes of infertility, enabling further understanding of the association of infertility with ASCVD.DesignProspective cohort study.SettingForty clinical centers in the United States.Patient(s)A total of 158,787 postmenopausal participants in the Women's Health Initiative cohort.Intervention(s)Infertility, parity, and pregnancy loss.Main outcome measure(s)The primary outcome was risk of ASCVD among women with and without a history of infertility, stratified by history of live birth and pregnancy loss. Cox proportional-hazards models were adjusted for demographics and risk factors for ASCVD.Result(s)Among 158,787 women, 25,933 (16.3%) reported a history of infertility; 20,427 (80%) had at least 1 live birth; and 9,062 (35%) had at least 1 pregnancy loss. There was a moderate overall association between infertility and ASCVD (adjusted hazard ratio, 1.02; 95% confidence interval [CI], 0.99-1.06) over 19 years of follow-up. Among nulliparous women, infertility was associated with a 13% higher risk of ASCVD (95% CI, 1.04-1.23). Among nulliparous women who had a pregnancy loss, infertility was associated with a 36% higher risk of ASCVD (95% CI, 1.09-1.71).Conclusion(s)Women with a history of infertility overall had a moderately higher risk of ASCVD compared with women without a history of infertility. Atherosclerotic cardiovascular disease risk was much higher among nulliparous infertile women and among nulliparous infertile women who also had a pregnancy loss, suggesting that in these more extreme phenotypes, infertility may be associated with ASCVD risk.

Objective: To analyze the characteristics of intrauterine microbiota in infertile women with poor endometrial receptivity (PER) and identify its biomarkers. Methods: A total of 63 infertile women who visited our gynecology department from July 2021 to May 2022 were selected. According to ultrasound evaluation of endometrial receptivity, 40 cases were assigned to the PER group, while 23 cases with good endometrial receptivity were assigned to the control group. Endometrial tissue samples were collected from two groups of patients for 16S rRNA sequencing, to compare the characteristics and differences of intrauterine microbiota between the two groups. Results: There was no significant difference in the α diversity of intrauterine microbiota between the two groups(P＞0.05). However, the individual difference of intrauterine microbiota in PER group was significantly higher than that in control group (P＜0.05). The relative abundance of the dominant phylum Proteobacteria in the intrauterine of the PER group was significantly higher than that in the control group (50.52% vs. 19.35%). The dominant genus in both groups was Lactobacillus, but the relative abundance of Lactobacillus in the intrauterine of the PER group was significantly lower than that of the control group (21.76% vs. 45.96%), while the relative abundance of Ralstonia was significantly higher than that in the control group (18.01% vs. 0.48%). The relative abundance of Ralstonia_unclassified in the intrauterine microbiota of the PER group was significantly higher than that in the control group (18.01% vs. 0.48%), while the relative abundance of Lactobacillus_crispatus was significantly lower than that in the control group (3.82% vs. 23.78%). The Biomakers at the phylum, family, and genus levels of the intrauterine microbiota in the PER group are Proteobacteria; Burkholderiaceae, Vibrionaceae, etc; Ralstonia, Vibrio, etc. Conclusions: Infertility women with PER may have dysbiosis of the intrauterine microbiota, with a decrease in the relative abundance of Lactobacillus and an increase in the relative abundance of characteristic pathogenic bacteria such as Burkholderia and Ralstonia possibly related to PER. [ABSTRACT FROM AUTHOR]

Background: Infertility affects around 10-15% of couples worldwide and is both a social and medical problem. Parental consanguinity is considered to reduce fertility reserve. Consanguineous marriages, especially first cousin marriages, are very common in Oman according to the Oman National Health Survey data. Objective: This study aimed to determine whether women born to consanguineous parents have reduced ovarian reserve. Materials and Methods: This cohort study was conducted on 414 women aged ≤ 39, treated for infertility at Sultan Qaboos University hospital and Royal hospital, Muscat, Oman from January 2019-December 2020. Each participant was interviewed and a complete history, including parental consanguinity and physical examination, were recorded. On day 2 of the menstrual cycle, serum concentration of the following was performed: follicle-stimulating hormone (FSH), luteinizing hormone, estradiol, prolactin, thyroid stimulating hormone, and anti-Müllerian hormone (AMH). AMH was done, if necessary, on other days of the cycle. Antral follicle count (AFC) was done on day 2 and 3 of the menstrual cycle. Results: Of the 414 women, parental consanguinity was present in 40.2% of couples. In women with low AFC, parental consanguinity was present in 15.3% compared to 13.0% in the non-consanguineous group. About 15% of women with low AMH had consanguineous parents, compared to 20.2% from the non-consanguineous group. High levels of FSH were present in 6.5% and 4.2% of the consanguineous and nonconsanguineous groups, respectively. No significant difference was observed in AFC with reference to body mass index. Conclusion: The results from this study showed no statistically significant difference in low ovarian reserves (AFC, AMH, and FSH) in women whose parents had a consanguineous marriage. [ABSTRACT FROM AUTHOR]

Fertility preservation is a growing field in reproductive medicine that may raise ethical questions. Preservation of fertility must be discussed with the patient if gonadotoxic treatment is required, whether in the case of benign or malignant pathology, or in the management of transgender identity. As a result, surgery or chemotherapy that has fewer adverse impacts on fertility should be proposed if this does not alter the prognosis of the disease. If the risk of infertility persists, then fertility cryopreservation should be proposed for children and adults of reproductive age. Sperm, oocytes, and gonadal tissue can be cryopreserved for many years. FIGO wishes to emphasize the importance of fertility preservation in the medical and surgical management of patients, and the importance of a specialized, multidisciplinary approach. Synopsis: Fertility preservation is a major concern of 21st century reproductive medicine, and FIGO wishes to support its development worldwide. [ABSTRACT FROM AUTHOR]

Objective To investigate the effects of different fertilization methods on embryo quality and clinical outcome in advanced age infertility patients with fewer oocytes retrieved. Methods Clinical data of 706 advanced age infertility patients with fewer oocytes retrieved who underwent in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) in our center were retrospectively analyzed. The patients were divided into IVF group (559 cases) and ICSI group (147 cases) according to the fertilization method. The general information, fertilization, embryo quality and clinical outcome were compared between two groups. Results There were no significant differences in female age, body mass index (BMI), anti-mullerian hormone (AMH) and baseline FSH (bFSH) between the two groups (P >0. 05). There were no significant differences in the number of oocytes retrieved, the total fertilization failure rate, normal fertilization rate, 2PN cleavage rate, Transplantable embryo rate, high-quality embryo rate and cycle cancellation rate between the two groups (P >0. 05) . The Mil egg rate in IVF group was significantly higher than that in ICSI group (P <0. 05) . There were no significant differences in the number of embryo transfers, clinical pregnancy rate, implantation rate, early abortion rate, multiple pregnancy rate, ectopic pregnancy rate, live birth rate, birth weight and male female ratio between the two groups (P>0.05). Conclusions ICSI cannot improve the embryo quality and clinical outcome for the advanced age infertility patients with fewer oocytes retrieved. IVF remains the preferred fertilization method. [ABSTRACT FROM AUTHOR]

BackgroundThere is growing recognition that reproductive factors are associated with increased risk of future cardiovascular disease. Infertility has been less well studied, although emerging data support its association with increased risk of cardiovascular disease. Whether infertility is associated with future risk of heart failure (HF) is not known.ObjectivesThis study sought to examine the development of HF and HF subtypes in women with and without history of infertility.MethodsWe followed postmenopausal women from the Women's Health Initiative prospectively for the development of HF. Infertility was self-reported at study baseline. Multivariable cause-specific Cox models were used to evaluate the association of infertility with incident overall HF and HF subtypes (heart failure with preserved ejection fraction [HFpEF]: left ventricular ejection fraction of ≥50% vs heart failure with reduced ejection fraction [HFrEF]: left ventricular ejection fraction of

BackgroundFemale adolescent and young adult (AYA) cancer survivors face higher infertility and pregnancy risks than peers with no cancer history. Preconception health behaviors such as physical activity (PA), tobacco smoking, and alcohol intake influence reproductive outcomes. In general populations, pregnancy intention is positively associated with healthy preconception behaviors, but it has not been studied among AYA survivors. The authors hypothesized that higher pregnancy intention would be associated with healthier behaviors, especially among AYA survivors with perceived infertility risk.MethodsA cross-sectional analysis was conducted with data collected between 2013 and 2017 from 1071 female AYA survivors aged 18 to 39 years who had completed their primary cancer treatment and enrolled in an ovarian function study. Self-reported intention dimensions were measured as a pregnancy intention score (PIS) and trying now to become pregnant. Multivariable linear (PA), binary (smoking), and ordinal (alcohol use) logistic regressions were used to estimate associations between intentions and preconception behaviors, with adjustments made for demographic and cancer characteristics. Effect modification by perceived infertility risk was assessed.ResultsThe mean PIS was 1.1 (SD, 0.77) on a 0 to 2 scale (2 = high intention), and 8.9% were attempting pregnancy now. A higher PIS was associated with increased PA (β, 0.08; 95% CI, 0.11-1.04), whereas ambivalence in pregnancy intention was associated with lower alcohol consumption (odds ratio, 0.72; 95% CI, 0.55-0.95). Pregnancy intentions were not associated with smoking. Perceived infertility risk strengthened the relationship between PIS and PA (P < .05).ConclusionsPregnancy intentions were associated with some healthier preconception behaviors in AYA survivors. Medical professionals caring for AYA survivors may consider pregnancy intention screening to guide conversations on preconception health.

The ovarian reserve defines the female reproductive lifespan, which in humans spans decades due to robust maintenance of meiotic arrest in oocytes residing in primordial follicles. Epigenetic reprogramming, including DNA demethylation, accompanies meiotic entry, but the chromatin changes that underpin the generation and preservation of ovarian reserves are poorly defined. We report that the Polycomb Repressive Complex 1 (PRC1) establishes repressive chromatin states in perinatal mouse oocytes that directly suppress the gene expression program of meiotic prophase-I and thereby enable the transition to dictyate arrest. PRC1 dysfuction causes depletion of the ovarian reserve and leads to premature ovarian failure. Our study demonstrates a fundamental role for PRC1-mediated gene silencing in female reproductive lifespan, and reveals a critical window of epigenetic programming required to establish ovarian reserve.

The uterine lining (endometrium) exhibits a pro-inflammatory phenotype in women with endometriosis, resulting in pain, infertility, and poor pregnancy outcomes. The full complement of cell types contributing to this phenotype has yet to be identified, as most studies have focused on bulk tissue or select cell populations. Herein, through integrating whole-tissue deconvolution and single-cell RNAseq, we comprehensively characterized immune and nonimmune cell types in the endometrium of women with or without disease and their dynamic changes across the menstrual cycle. We designed metrics to evaluate specificity of deconvolution signatures that resulted in single-cell identification of 13 novel signatures for immune cell subtypes in healthy endometrium. Guided by statistical metrics, we identified contributions of endometrial epithelial, endothelial, plasmacytoid dendritic cells, classical dendritic cells, monocytes, macrophages, and granulocytes to the endometrial pro-inflammatory phenotype, underscoring roles for nonimmune as well as immune cells to the dysfunctionality of this tissue.

The microbiota is in symbiosis with the human body as a holobiont. Infertility conditions affect the female reproductive tract (FRT) and its resident microbiota. However, a disturbance in homeostasis could influence the FRT and other distal body sites, such as the gastrointestinal tract (GIT). We included 21 patients with endometriosis and other infertility-associated diseases with clinical profiles and biological samples from the FRT (endometrium, endometrial fluid, and vagina), and GIT samples (oral and feces). We performed a 16S rRNA analysis of site-specific microbial communities and estimated diversity metrics. The study found body site-specific microbial patterns in the FRT–GIT. In both study groups, Lactobacillus was the most shared Amplicon Sequence Variant (ASV), a precise identifier of microbial sequences, between endometrial and vagina samples. However, shared Gardnerella and Enterobacteriaceae ASVs were linked to other conditions but not endometriosis. Remarkably, Haemophilus was a specific GIT-shared taxon in endometriosis cases. In conclusion, infertility influences distinctly the FRT and GIT microbiomes, with endometriosis showing unique microbial characteristics. We proposed the concept of ‘female holobiont’ as a community that comprises the host and microbes that must maintain overall homeostasis across all body sites to ensure a woman’s health. Insights into these microbial patterns not only advance our understanding of the pathophysiology of infertility but also open new avenues for developing microbe-based therapeutic interventions aimed at restoring microbial balance, thereby enhancing fertility prospects.

The November 2018 Camp Fire, a devastating wildfire in Northern California, occurred during the peak of breeding season for field monkeys at the California National Primate Research Center (CNPRC). Effects of environmental stressors, such as wildfires, on birth outcomes in primates, and in humans, are poorly understood. Additionally, wildfires are of growing concern due to their increasing frequency and severity. The objective was to examine the impact of wildfire smoke on fertility, timing of birth, and pregnancy loss for field monkeys. A unique case-control study to investigate birth outcomes in rhesus macaques (Macaca mulatta) was conducted at the CNPRC. All females in the study were maintained in outdoor fields during a period of elevated ambient wildfire smoke from November 8-22, 2018. In addition to ambient air quality evaluations, the effects on fertility, timing to birth, and pregnancy loss were documented. Archival records of approximately 5,000 conceptions from the previous nine years served as control data. During the Camp Fire, ambient fine particulate (PM 2.5) levels exceeded the 24 -h National Ambient Air Quality Standard (35 μg/m 3) of the United States Environmental Protection Agency, reaching levels as high as 185 μg/m 3. A statistically significant association was observed between birth loss and the 2018-2019 CNPRC breeding season. As this wildfire event occurred during various stages of early pregnancy, an association can be inferred between early gestational exposure and increased risk of pregnancy loss.

PurposeTo determine whether concomitant tamoxifen 20 mg with gonadotropins (tamoxifen-gonadotropin) versus letrozole 5 mg with gonadotropins (letrozole-gonadotropin) affects mature oocyte yield.MethodsOpen-label, single-institution, randomized trial. Inclusion criteria included the following: females, ages 18-44 years old, with new diagnosis of non-metastatic breast cancer, who were undergoing fertility preservation with either oocyte or embryo cryopreservation. Those with estrogen-receptor-positive (ER+) breast cancer were randomized to tamoxifen-gonadotropin or letrozole-gonadotropin. Another group with estrogen-receptor-negative (ER-) breast cancer was recruited, as a prospectively collected comparison arm who took neither letrozole nor tamoxifen (gonadotropin only). The primary outcome was the number of mature oocytes obtained from the cycle. The randomized groups were powered to detect a difference of three or more mature oocytes.ResultsForty-five patients were randomized to tamoxifen-gonadotropin and fifty-one to letrozole-gonadotropin. Thirty-eight patients completed gonadotropin only. Age, antral follicle count, and body mass index were similar between the randomized groups. Our primary outcome of mature oocyte yield was similar between the tamoxifen-gonadotropin and letrozole-gonadotropin groups (12±8.6 vs. 11.6±7.5, p=0.81, 95%CI of difference =-2.9 to 3.7). In a pre-specified secondary comparison, mature oocyte yield was also similar with tamoxifen-gonadotropin or letrozole-gonadotropin versus gonadotropin only (12±8.6 vs. 11.6±7.5 vs. 12.4±7.2). There were no serious adverse events in any of the groups.ConclusionsTamoxifen-gonadotropin and letrozole-gonadotropin produced a similar number of mature oocytes. Women who received either tamoxifen-gonadotropin or letrozole-gonadotropin had a similar number of oocytes to the gonadotropin-only group.Trial registrationNCT03011684 (retrospectively registered 1/5/2017, after 9% enrolled).