Seminars in reproductive medicine最新文献

Nearly all (97%) the studies in the recent literature addressing the relationship between environmental hazards and male fertility use at least one of three common study design strategies: recruiting men presenting to fertility centers (53%), evaluating only one environmental exposure at a time (87%), and using conventional semen quality parameters as the only study outcome (45%). While each of these study design features is logical, defensible, and has generated an enormous amount of information regarding the impact of the environment on male reproductive function, they may also be barriers to furthering our understanding. In this article, we examine in which ways each of these study design features limits progress on male fertility research and propose strategies to go beyond them. Rather than abandoning these strategies, we propose that they should be a starting point instead of the default strategy for the future of male fertility research to more fully understand how men's environmental exposures impact human fertility and human reproduction more generally.

Polycystic ovary syndrome (PCOS) is the most common heterogeneous endocrine disorder in women of reproductive age, affecting around 5 to 10% of women and up to 21% depending on the applied diagnostic criteria and study population. People with PCOS may experience oligomenorrhea, androgen excess, and polycystic ovary morphology. The etiology of the disease is not completely understood, with genetics, epigenetics, endocrine, metabolic, lifestyle, and environmental factors contributing to its development and severity. Environmental exposures are an important, burgeoning field in menstrual research, as they potentially link to menstrual cycle disruption and the risk of reproductive disorders such as PCOS. This review examines the recent research investigating environmental exposures-air pollution, micro- and nanoplastics, heavy metals, and endocrine-disrupting chemicals-and PCOS in human and animal models, concluding with potential mechanisms, limitations, and considerations for future work. Overall, research on environmental exposures and PCOS is limited and yields heterogeneous results across studies. Specifically, exposures such as air pollutants, micro- and nanoplastics, persistent organic pollutants, and parabens have noticeably limited research. Future research can help fill the gap in understanding how environmental exposures, particularly across gestational, childhood, and reproductive adult life stages, may impact PCOS.

Female reproductive aging often affects women's emotional, physical, and physiological well-being. Ovarian aging is characterized by fluctuations in reproductive hormones and determines the age at which menopause occurs. Understanding potentially modifiable factors that influence this process is essential for addressing health disparities, improving quality of life, and informing relevant public health strategies. This review synthesizes in vivo, in vitro, and epidemiological findings about the effects of endocrine-disrupting chemicals (EDCs), specifically heavy metals and perfluoroalkyl and polyfluoroalkyl substances (PFAS) on female reproductive aging. Most in vivo and in vitro studies have demonstrated that heavy metals alter ovarian morphology, folliculogenesis, and steroidogenesis. Evidence regarding the effects of PFAS is limited and inconsistent. Epidemiological studies have consistently shown that heavy metals are associated with a higher risk of diminished ovarian reserve (indicated by decreased anti-Müllerian hormone) and earlier menopause, with limited findings regarding reproductive hormone changes. PFAS exposure has been associated with decreased estradiol and earlier menopause but not significantly with ovarian reserve. Gaps in the literature require more comprehensive epidemiological research on the effects of EDCs on female reproductive aging, including ovarian reserve, age at menopause, and vasomotor symptoms, to inform future interventions to reduce hazardous exposures and improve women's health.

Per- and polyfluoroalkyl substances (PFASs) are persistent environmental contaminants found in human tissues and persist in the environment, posing significant risks to reproductive health. This review examines the impact of PFAS exposure on male reproductive health, with a focus on sperm epigenetics. PFASs disrupt endocrine function by altering key reproductive hormones and impairing sperm motility, quality, and viability. Epidemiologic and animal studies highlight inconsistent yet concerning associations between PFAS exposure and semen parameters, as well as altered gene expression and DNA methylation patterns. Moreover, PFAS exposure during critical windows of development has been linked to differential impacts on male versus female pubertal development, cognitive outcomes, and reproductive physiology, emphasizing the complexity of PFAS interactions. This comprehensive analysis highlights the need for continued research into the mechanisms by which PFASs influence reproductive health and development with potential implications for sperm epigenetics. The review emphasizes the importance of understanding the epigenetic mechanisms behind these disruptions, particularly DNA methylation and its role in heritable changes. Investigating the epigenetic modifications driven by PFAS exposure is crucial for elucidating the mechanisms by which these chemicals influence reproductive health. Future research should focus on understanding these epigenetic changes in both immediate fertility outcomes and transgenerational health risks.

Environmental pollutants, including endocrine-disrupting chemicals (EDCs), air pollution, and climate change, are increasingly recognized for their potential impact on pregnancy outcomes. EDCs, found in pesticides, industrial chemicals, and personal care products, are associated with preterm birth and fetal growth restriction, primarily through hormonal interference. Air pollution, notably PM_2.5, NO₂, and O₃, has been linked to increased rates of preterm birth, low birth weight, and stillbirth. Climate factors, such as extreme heat, elevate risks of pregnancy loss and preterm birth, with significant impacts on vulnerable populations across diverse socioeconomic and geographic regions. These exposures contribute to adverse pregnancy outcomes through mechanisms involving oxidative stress, inflammation, and endocrine disruption. The interplay among these environmental factors underscores the need for integrated, longitudinal studies to understand their combined effects on pregnancy outcomes better. Future research should focus on region-specific impacts, cumulative exposure, and policy-driven interventions to mitigate these environmental risks, especially in vulnerable populations disproportionately affected by these hazards. This scoping review synthesizes recent findings from 2019 to 2024 to highlight these associations and identify research gaps.

Antiphospholipid syndrome (APS) is a disease characterized by the presence of antiphospholipid (aPL) antibodies, thrombosis, and obstetric complications. While patients with APS can have successful pregnancies, many important considerations exist. APS can also cooccur with other systemic autoimmune diseases which can affect pregnancy, particularly systemic lupus erythematosus. This article reviews specific considerations for pregnancy and reproductive health in patients with APS. Similar to other autoimmune diseases, stable or quiescent disease and planning with a rheumatologist and obstetrician prior to conception are vital components of a successful pregnancy. Pregnancy management for patients with aPL antibodies or diagnosis of APS with aspirin and/or anticoagulation depending on disease profile is discussed, as well as the effects of physiologic changes during pregnancy in maternal and fetal outcomes for this population. Given the reproductive span lasts beyond conception through delivery, we include discussions on safe contraception options, the use of assistive reproductive technology, pregnancy termination, menopause, and male fertility. While APS is a relatively rare condition, the effects this disease can have on maternal and fetal outcomes even with available therapies demonstrates the need for more high-quality, evidence-based research.

Hashimoto thyroiditis and Graves' disease are autoimmune thyroid disorders that are common in women of reproductive age and have a complex relationship with female fertility and health of the maternal-fetal dyad. Both hyperthyroidism and hypothyroidism, whether subclinical or overt in severity, directly or indirectly affect nearly every level of the hypothalamic-pituitary-ovary axis, uterine and ovarian function, as well as fetal development from implantation through delivery. Autoimmunity itself also appears to negatively impact both spontaneous and assisted fertility, as well as miscarriage risk, although the mechanism remains unclear, and the presence and magnitude of risk is variable in published literature. While treatment of overt hyperthyroidism and hypothyroidism is unequivocally recommended by professional societies, the impact of treatment on fertility outcomes, and the role of treatment in subclinical thyroid disease is more controversial. Unfortunately, levothyroxine has not been shown to abrogate the risk of subfertility and miscarriage observed in euthyroid thyroid autoantibody positive women.

Many individuals with systemic lupus erythematosus (SLE) face significant challenges manifesting their family planning goals due to numerous factors, including disease-related complications, treatment-induced effects, immunological factors, self-imposed limitations, and the socioeconomic impacts of having a chronic disease. Instances of unexplained infertility are also prevalent. Encouragingly, advancements in treatment modalities, risk factor management, specialized training within the medical community, and enhanced patient/provider education have contributed to an increase in successful pregnancies among SLE patients, fostering a safer, more promising reproductive landscape. However, despite advances, individuals with SLE continue to struggle with the complexities of family building. This review explores infertility and pregnancy outcomes in SLE, fertility preservation, the role of assisted reproductive technology, and considerations for tailoring these approaches to SLE patients.

Celiac disease is a systemic autoimmune disorder triggered by dietary gluten ingestion. The classic clinical presentation is characterized by diarrhea with malabsorption and weight loss; however, the spectrum of possible initial symptoms is broad. Affected individuals may be asymptomatic or may suffer from extraintestinal manifestations that can include metabolic bone disorders, thyroid dysfunction, neurologic manifestations, amenorrhea, or impaired fertility. Several studies have demonstrated an association between celiac disease and infertility and worsened pregnancy outcomes. Numerous possible mechanisms through which celiac disease could be associated with women's fertility have been proposed in the literature.