Stacey A Missmer

Harvard University - Schools of Medicine and Public Health · Obstetrics, Gynecology, & Reproductive Biology / Epidemiology

Objective To build consensus on most important symptoms and related consequences for use in questionnaires to characterise individuals with suspected and confirmed endometriosis in the general population. Design A questionnaire of 107 symptoms and related consequences of endometriosis was collaboratively developed by patients, medical doctors and...

Objective To prospectively assess the effect of endometriosis and uterine fibroids on the long term risk of premature mortality (younger than 70 years). Design Prospective cohort study Setting The Nurses’ Health Study II, United States (1989-2019). Participants 110 091 women aged 25-42 years in 1989 without a history of hysterectomy before endom...

Endometriosis is a complex and heterogeneous condition affecting 10% of reproductive-age women, and yet, it often goes undiagnosed for several years. Limited observed heritability (7%) of large genetic association studies may be attributable to underlying heterogeneity of disease mechanisms. Therefore, we conducted this study to investigate genetic...

Objective To quantify the variation, triggers and impact on quality of life of symptom flares in women with chronic pelvic pain (CPP). Design Cross‐sectional questionnaire within the Translational Research in Pelvic Pain clinical cohort study. Setting Women with CPP, with subgroups of women with endometriosis (EAP), interstitial cystitis/bladder...

The evidence for a greater prevalence of immunological diseases among endometriosis patients has varied in robustness and been subject to selection bias. We investigated the phenotypic and genetic association between endometriosis and 31 immunological diseases in the UK Biobank (8,223 endometriosis, 64,620 immunological disease cases). In cross-sec...

Introduction Prior studies have investigated the diagnostic potential of microRNA (miRNA) expression profiles for endometriosis. However, the vast majority of previous studies have only included adult women. Therefore, we sought to investigate differential expression of miRNAs among adolescents and young adults with endometriosis. Methods The Wome...

Chronic pelvic pain is heterogeneous with potentially clinically informative subgroups. We aimed to identify subgroups of pelvic pain based on symptom patterns and investigate their associations with inflammatory and chronic pain-related comorbidities. Latent class analysis (LCA) identified subgroups of participants (n = 1255) from the Adolescence...

Background: While the majority of reproductive-aged females will experience pelvic pain during their lives, biological mechanisms underlying pelvic pain are not well understood. We investigated associations between pelvic pain symptoms and oxidative stress among people with and without surgically-confirmed endometriosis. Methods: Using an enzyme-li...

Introduction Over four million women in the US alone have been diagnosed with endometriosis. For those living with this disease, surgery and hormonal treatment reduce associated pelvic pain in some, while others continue to experience life impacting pain. Therefore, identification of accessible and cost-effective methods of pain reduction to compli...

Background Peritoneal fluid is a medium for endometriosis-associated biomarker discovery from which the local peritoneal environment and pathophysiologic pathways are often inferred. Therefore, we evaluated the associations between peritoneal fluid color and volume at time of endometriosis-related laparoscopic surgery with patient characteristics,...

Background There are limited data on endometriosis from the Eastern Mediterranean region. This study for the first time estimates the prevalence and impact of endometriosis on women in Northern Cyprus, an under-represented region in Europe. Methods Cyprus Women’s Health Research Initiative, a cross-sectional study recruited 7646 women aged 18–55 i...

Introduction: Endometriosis is a chronic inflammatory disease that affects ~10% of women. A significant fraction of patients experience limited or no efficacy with current therapies. Tissue adjacent to endometriosis lesions often exhibits increased neurite and vascular density, suggesting that disease pathology involves neurotrophic activity and an...

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 f...

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 participant...

Abdominal pain is a common symptom of several debilitating conditions (eg, inflammatory bowel disease, irritable bowel syndrome, and endometriosis) and affects individuals throughout their lifespan. Quantitative sensory testing (QST) reference values exist for many body sites but not the abdomen. Using a QST battery adapted from the German Research...

Chronic pelvic pain (CPP), despite its high prevalence, is still relatively poorly understood mechanistically. This study, as part of the Translational Research in Pelvic Pain (TRiPP) project, has used a full quantitative sensory testing (QST) paradigm to profile n = 85 women with and without CPP (endometriosis or bladder pain specifically). We use...

Introduction Chronic pelvic pain (CPP) is a common condition affecting up to 26.6% of women, with many suffering for several years before diagnosis and/or treatment. Its clinical presentation is varied and there are frequently comorbid conditions both within and outside the pelvis. We aim to explore whether specific subgroups of women with CPP repo...

Study question: What are the similarities and differences in the systemic proteomic profiles by endometriosis-associated pain subtypes among adolescents and young adults with endometriosis? Summary answer: Endometriosis-associated pain subtypes exhibited distinct plasma proteomic profiles. What is known already: Endometriosis patients, especia...

Background: Hysterectomy, oophorectomy, and tubal ligation are common surgical procedures. The literature regarding cardiovascular disease (CVD) risk after these surgeries has focused on oophorectomy with limited research on hysterectomy or tubal ligation. Materials and Methods: Participants in the Nurses' Health Study II (n = 116,429) were followe...

Purpose Research on infertility and risk of breast cancer has been conflicting, potentially because many well-established breast cancer risk factors, such as pregnancy history, are strongly correlated with infertility. Methods We followed participants in the Nurses’ Health Study II from 1989 to 2015 (n = 103,080) for the development of invasive br...

Identifying genetic determinants of reproductive success may highlight mechanisms underlying fertility and identify alleles under present-day selection. Using data in 785,604 individuals of European ancestry, we identified 43 genomic loci associated with either number of children ever born (NEB) or childlessness. These loci span diverse aspects of...

Background: Women are at greater risk than men of developing chronic inflammatory conditions and of developing 'long COVID.' However, few gynecologic health risk factors for long COVID have been identified. Endometriosis is a common gynecological disorder associated with chronic inflammation, immune dysregulation, and comorbid presentation with au...

Background Certain symptoms associated with infertility are associated with cardiovascular disease, including menstrual cycle irregularity, early menopause, and obesity; however, few studies have investigated the association between infertility and cardiovascular disease risk. Methods and Results Participants in the NHSII (Nurses' Health Study II)...

Objective: To investigate the association between infertility and incidence of invasive cancer. Design: Prospective cohort study (1989-2015). Subjects: 103,080 women aged 25-42 years in the Nurses' Health Study II who were cancer free at baseline (1989). Exposure: Infertility status (failure to conceive after one year of trying) and causes o...

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in women, affecting approximately 6% to 15% of reproductive-aged women. Polycystic ovarian syndrome is associated with obesity, metabolic syndrome, impaired glucose tolerance, insulin resistance, adverse pregnancy outcomes, and infertility. Previous meta-analyses and reviews h...

Background: Physicians' preferences for attributes of medical treatments for endometriosis-associated pain have not previously been quantified. Methods: US obstetrician-gynecologists completed an online discrete-choice experiment survey. In a series of questions, physicians chose a medical treatment for a hypothetical patient with endometriosis...

Importance: Surplus cryopreserved embryos pose a challenge for in vitro fertilization patients and clinics; with Roe v. Wade overturned, some states may deem the discarding of surplus embryos illegal, radically changing in vitro fertilization practice. An evidence-based tool would help limit surplus embryo creation. Objective: To develop a predi...

Few studies have assessed endogenous steroid hormone levels and subsequent endometriosis diagnosis. We prospectively evaluated premenopausal plasma sex hormone levels and the risk of laparoscopically-confirmed endometriosis in a nested case-control study within the Nurses’ Health Study II. Between blood collection (1996-1999) and 2009, we ascertain...

Objective: To examine the association between consumption of fruits and vegetables and pesticide residue intake from consumption of fruits and vegetables and risk of ultrasound- or hysterectomy-confirmed fibroids. Only a few studies have evaluated the association of fruit and vegetable intake with uterine fibroids, with inconsistent results. No st...

Endometriosis is a leading cause of pain and infertility affecting millions of women globally. Identifying biologic and genetic effects on DNA methylation (DNAm) in endometrium increases understanding of mechanisms that influence gene regulation predisposing to endometriosis and offers an opportunity for novel therapeutic target discovery. Herein,...

Endometriosis affects approximately 190 million women and people assigned female at birth worldwide. It is a chronic, inflammatory, gynecologic disease marked by the presence of endometrial-like tissue outside the uterus, which in many patients is associated with debilitating painful symptoms. Patients with endometriosis are also at greater risk of...

Objective To investigate barriers in accessing care for infertility in Mexico, as little is known about this issue for low and middle-income countries, which comprise 80% of the world’s population. Design Cross-sectional analysis Setting Mexican Teachers’ Cohort Patients 115,315 female public-school teachers from 12 states in Mexico Interventio...

Importance Menstrual cycle characteristics may be associated with an increased risk of cardiovascular disease (CVD). However, existing studies are limited, and few have explored the mediating role of established CVD risk factors. Objective To explore the associations of menstrual cycle characteristics across the reproductive lifespan with the risk...

Background Breastfeeding has been associated with a reduced maternal long-term risk of chronic diseases, but its association with mortality is poorly known. Methods We included 166,708 female United States (US) nurses from the Nurses’ Health Study (1986-2016) and the Nurses’ Health Study II (1989-2019) who experienced at least one pregnancy lastin...

Study question: Do subgroups of women with chronic pelvic pain (CPP) report different clinical symptoms and differing impact of pain on their quality of life? Summary answer: Clinical profiles of women with CPP show variability of clinical symptoms both within and between subgroups. However, there is an obvious negative impact of pain on the patien...

Study question: Do women with polycystic ovary syndrome (PCOS) have a greater risk of adverse pregnancy complications (gestational diabetes, preeclampsia, cesarean section, placental abnormalities) and neonatal outcomes (preterm birth, small for gestational age, prolonged delivery hospitalization) compared to women without a PCOS diagnosis and doe...

Background Prior research suggests that women with endometriosis are at greater risk of coronary heart disease. Therefore, our objective was to prospectively investigate the association between laparoscopically confirmed endometriosis and risk of incident stroke during 28 years of follow-up. Methods Participants in the NHSII cohort study (Nurses’...

Numerous studies have demonstrated that assisted reproductive technology (ART: defined here as including only in vitro fertilization and related technologies) is associated with increased adverse pregnancy, neonatal, and childhood developmental outcomes, even in singletons. The comparison group for many had often been a fertile population that conc...

Background Despite anecdotal reports, the impacts of SARS-CoV-2 infection or COVID-19 vaccination on menstrual health have not been systemically investigated. Objective To examine the associations of SARS-CoV-2 infection and COVID-19 vaccination with menstrual cycle characteristics. Study Design We prospectively followed 3,858 pre-menopausal wome...

Study question: What are the systemic molecular profiles of endometriosis diagnosed in adolescents and young adults? Summary answer: Significant enrichment and increased activation of proteins related to angiogenesis and cell migration pathways were observed in endometriosis cases compared to controls (P-value < 2.4 × 10-8). What is known alrea...

Endometriosis affects reproductive-aged females and varies considerably in terms of symptom presentation, morphologic features, and treatment response. Most studies investigating symptom recurrence after an endometriosis-related surgery have been conducted among adults. The Endometriosis pain QUality aftEr Surgical Treatment (EndoQUEST) Study was e...

While non-malignant, endometriosis shares similar features with cancer. Several epidemiologic studies were conducted in an attempt to quantify cancer risk in endometriosis patients. The results from a meta-analysis of studies on the associations between endometriosis and cancer published up to 2019 are presented and discussed. The chapter also cons...

Objectives Chronic pelvic pain is common, poorly understood, and many women suffer for years without proper diagnosis and effective treatment. The Translational Research in Pelvic Pain (TRiPP) project takes a phenotyping approach, with a particular focus on endometriosis-associated pain (EAP) and bladder pain syndrome (IC/BPS), to improve our funda...

Background The etiology of endometriosis is not well understood. Limited evidence suggests that dietary factors influence risk, but prospective data related to carbohydrate, fiber, and gluten consumption are scarce. Despite this, recommendations concerning fiber, gluten intake and endometriosis are pervasive in the lay literature. Objective To inv...

Background Sexual minority (lesbian, bisexual, mostly heterosexual) young women face many sexual and reproductive health disparities, but there is scant information on their experiences of chronic pelvic pain, including an absence of information on prevalence, treatment, and outcomes. Aim The purpose of this study was to describe the characteristi...

Background Hypertensive disorders of pregnancy (HDP), including gestational hypertension and preeclampsia, are associated with an increased risk of CVD. Objectives The purpose of this study was to evaluate associations between HDP and long-term CVD and identify the proportion of the association mediated by established CVD risk factors. Methods Pa...

Objective To examine the association between intake of fruits and vegetables with high versus low pesticide residue burden and diagnosis of laparoscopically-confirmed endometriosis. The etiology of endometriosis is not well understood, but dietary factors may influence risk. Pesticides may act as endocrine disruptors and intake of pesticide contami...

Objectives: To examine women's perceptions of endometriosis-associated disease burden and its impact on life decisions and goal attainment. Design: An anonymous online survey was distributed in October 2018 through the social media network MyEndometriosisTeam.com. Participants: Women aged 19 years and older living in several English-speaking c...

Background: In the field of endometriosis, several classification, staging and reporting systems have been developed and published, but there are no data on the uptake of these systems in clinical practice. Objectives: The objective of the current study was to examine whether clinicians routinely use the existing endometriosis classification sys...

Objective In the field of endometriosis, several classification, staging and reporting systems have been developed, but do clinicians routinely use these classification systems, which system do they use and what are the clinicians’ motivations? Data sources A cross-sectional study was performed to gather data on the current use of endometriosis cl...

Study question: Which classification system for endometriosis do clinicians use most frequently, and why? Summary answer: Even with a high uptake of the three existing endometriosis classification systems, most clinicians managing endometriosis would like a new simple surgical descriptive system for endometriosis. What is known already: In the...

Objective To identify metabolites in presurgical blood associated with risk of persistent postsurgical pelvic pain 1 year after endometriosis surgery in adolescent and young adult patients. Design Prospective observational study within the Women’s Health Study: From Adolescence to Adulthood, a US-based longitudinal cohort of adolescents and women...

Background Investigating the burden of access to infertility treatment has primarily been conducted in high-income countries, with little known for low- and middle-income countries, which comprise 80% of the world’s population. The objective of this study was to investigate access to infertility care in Mexico. Methods This was a cross-sectional a...

Purpose To investigate assisted reproductive technology (ART) outcomes among adolescent and young-adult female cancer survivors. Methods The Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) data were linked to the Massachusetts Cancer Registry for 90,928 ART cycles in Massachusetts to women ≥ 18 years old fr...

Background Endometriosis and uterine fibroids are common gynecologic conditions associated with greater risk of infertility. Prior research has suggested that these conditions are associated with adverse pregnancy outcomes, potentially due to increased utilization of fertility treatments. Objective Therefore, our objective was to investigate wheth...

Objective To determine if women with endometriosis experience lower urinary tract symptoms (LUTSs) more often than those without. Design Cross-sectional analysis at enrollment in a longitudinal cohort. Setting Enrollment at 2 academic hospitals and from the local community. Patient(s) This analysis included 1,161 women with (n = 520) and without...

Importance: Early natural menopause (ENM) has been associated with reduced reproductive span, cardiovascular disease risk, and early mortality. The potential adverse implications of endometrioma surgery for ovarian reserve are known, yet the association of endometriosis with menopausal timing remains understudied. Objective: To investigate the a...

Objective To investigate hospitalizations up to 8 years after live birth among women who used assisted reproductive technology (ART) or who were subfertile compared with women who conceived naturally. Design Retrospective cohort. Setting Deliveries among privately insured women aged ≥18 years between 2004 and 2017 from Massachusetts state vital r...

Endometriosis, psoriasis and psoriatic arthritis (PsA) are chronic inflammatory disorders that have etiologies that remain poorly understood but may be correlated, as endometriosis has been associated with other inflammatory disorders. We investigated the bi-directional associations between laparoscopically-confirmed endometriosis, and physician-di...

Endometriosis, affecting 5-10% of reproductive-age women, is a common contributor to dysmenorrhea and chronic pelvic pain. Diagnosis requires laparoscopic tissue biopsy, but careful pelvic examination, and/or imaging with either ultrasound or MRI, may identify patients who should receive empiric first-line therapy. The presence of dyschezia, partic...

STUDY QUESTION Are menstrual cycle characteristics throughout the reproductive lifespan associated with cancer risk? SUMMARY ANSWER Irregular and long menstrual cycles throughout the reproductive lifespan were associated with increased risk of total invasive cancer, especially obesity-related cancers. WHAT IS KNOWN ALREADY Long and irregular mens...

Objective To investigate whether there is an association between season, temperature, and day length at oocyte retrieval and/or embryo transfer (ET) and clinical outcomes in frozen ET cycles. Design Retrospective cohort study. Setting Large academically affiliated research hospital. Patient(s) A total of 3,004 frozen ET cycles from 1,937 differe...

Background Infertility has been associated with common chronic non-communicable diseases. However, the association of infertility with long-term mortality is unclear. Methods We followed 101,777 women aged 25–42 years at enrollment between 1989 and 2017. Biennial questionnaires updated participants’ infertility status and underlying reasons for in...

Aims The aim of this study was to explore the association of pregnancy loss (PL) with the incidence of cardiovascular disease (CVD) and examine the extent to which this relation is mediated by subsequent metabolic disorders. Methods and results We followed 95 465 ever-gravid women participating in the Nurses’ Health Study II between 1993 and 2017....

STUDY QUESTION Can a set of terms and definitions be prepared on endometriosis that would be the basis for standardization in disease description, classification and research? SUMMARY ANSWER The current paper outlines a list of 49 terms and definitions in the field of endometriosis. WHAT IS KNOWN ALREADY Different classification systems have been...

STUDY QUESTION Which endometriosis classification, staging and reporting systems have been published and validated for use in clinical practice? SUMMARY ANSWER Of the 22 endometriosis classification, staging and reporting systems identified in this historical overview, only a few have been evaluated, in 46 studies, for the purpose for which they w...