ABSTRACT
Previous studies reported that exposures to per- and polyfluoroalkyl substances (PFAS), largely in higher exposed populations, were associated with elevated risk of polycystic ovary syndrome (PCOS). However, studies evaluating PCOS risk in populations with lower background exposures to PFAS are limited. This study aimed to examine the associations between serum PFAS concentrations and PCOS risk among women attending a U.S. academic fertility clinic during 2005-2019. A total of 502 females who sought fertility evaluation and assisted reproduction treatments were included. Nine PFAS were quantified in non-fasting serum samples collected at study entry. Diagnosis of PCOS was based on the Rotterdam criteria. We used logistic regression to examine the odds ratio (OR) of PCOS in relation to individual PFAS concentrations (continuous and by tertiles) and quantile g-computation (QGC) and Bayesian Kernel Machine Regression (BKMR) to examine the joint associations of PFAS mixture with PCOS. Most participants were White and had a graduate degree or higher. Per doubling of serum perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) concentrations were associated with higher odds of PCOS [OR (95%CI): 1.70 (1.06, 2.81) and 1.45 (1.02, 2.08) for PFOS and PFHxS respectively]. There was a dose-response relationship of PFOS with PCOS risk (p of trend by PFOS tertiles = 0.07). Both QGC and BKMR identified PFOS as the most important contributor among the mixture to PCOS risk. No clear joint effects were found for other PFAS or PFAS mixtures on PCOS risk. Our findings are consistent with existing evidence in populations with higher background PFAS concentrations and highlight the adverse effects of PFAS exposure on reproductive health. Findings can inform public health measures and clinical care to protect populations vulnerable to PCOS, in part, due to environmental exposures.
ABSTRACT
Previous studies have examined the predictors of PFAS concentrations among pregnant women and children. However, no study has explored the predictors of preconception PFAS concentrations among couples in the United States. This study included 572 females and 279 males (249 couples) who attended a U.S. fertility clinic between 2005 and 2019. Questionnaire information on demographics, reproductive history, and lifestyles and serum samples quantified for PFAS concentrations were collected at study enrollment. We examined the PFAS distribution and correlation within couples. We used Ridge regressions to predict the serum concentration of each PFAS in females and males using data of (1) socio-demographic and reproductive history, (2) diet, (3) behavioral factors, and (4) all factors included in (1) to (3) after accounting for temporal exposure trends. We used general linear models for univariate association of each factor with the PFAS concentration. We found moderate to high correlations for PFAS concentrations within couples. Among all examined factors, diet explained more of the variation in PFAS concentrations (1-48%), while behavioral factors explained the least (0-4%). Individuals reporting White race, with a higher body mass index, and nulliparous women had higher PFAS concentrations than others. Fish and shellfish consumption was positively associated with PFAS concentrations among both females and males, while intake of beans (females), peas (male), kale (females), and tortilla (both) was inversely associated with PFAS concentrations. Our findings provide important data for identifying sources of couples' PFAS exposure and informing interventions to reduce PFAS exposure in the preconception period.
Subject(s)
Alkanesulfonic Acids , Environmental Pollutants , Fluorocarbons , Child , Animals , Humans , Male , Female , Pregnancy , United States , Fertility Clinics , Diet , Linear ModelsABSTRACT
Per- and polyfluoroalkyl substances (PFAS) exposure was associated with changes in thyroid function in pregnant mothers and the general population. Limited such evidence exists in other susceptible populations such as females with fertility problems. This cross-sectional study included 287 females seeking medically assisted reproduction at a fertility clinic in Massachusetts, United States, between 2005 and 2019. Six long-alkyl chain PFAS, thyroid hormones, and autoimmune antibodies were quantified in baseline serum samples. We used generalized linear models and quantile g-computation to evaluate associations of individual PFAS and their total mixture with thyroid biomarkers. Most females were White individuals (82.7%), had graduate degrees (57.8%), and nearly half had unexplained subfertility (45.9%). Serum concentrations of all examined PFAS and their mixture were significantly associated with 2.6%-5.6% lower total triiodothyronine (TT3) concentrations. Serum concentrations of perfluorononanoate (PFNA), perfluorodecanoate (PFDA), and perfluoroundecanoate (PFUnDA), and of the total mixture were associated with higher ratios of free thyroxine (FT4) to free triiodothyronine (FT3). No associations were found for PFAS and TSH or autoimmune antibodies. Our findings support the thyroid-disrupting effect of long alkyl-chain PFAS among a vulnerable population of subfertile females.
Subject(s)
Alkanesulfonic Acids , Environmental Pollutants , Fluorocarbons , Pregnancy , Humans , Female , Thyroid Gland , Triiodothyronine , Cross-Sectional Studies , Fertility Clinics , Thyroid Hormones , BiomarkersABSTRACT
Prenatal per and polyfluoroalkyl substances (PFAS) exposure is associated with adverse birth outcomes. There is an absence of evidence on the relationship between maternal and paternal preconception PFAS exposure and birth outcomes. This study included 312 mothers and 145 fathers with a singleton live birth from a preconception cohort of subfertile couples seeking fertility treatment at a U.S. clinic. PFAS were quantified in serum samples collected before conception. Gestational age (GA) and birthweight (BW) were abstracted from delivery records. We also assessed low birthweight (BW < 2500 g) and preterm birth (GA < 37 completed weeks). We utilized multivariable linear regression, logistic regression, and quantile-based g computation to examine maternal or paternal serum concentrations of individual PFAS and mixture with birth outcomes. Maternal serum concentrations of perfluorooctanesulfonate (PFOS), perfluorohexanesulfonate (PFHxS), and the total PFAS mixture were inversely associated with birthweight. Maternal PFOS concentration was associated with a higher risk of low birthweight. Conversely, paternal PFOS and PFHxS concentrations were imprecisely associated with higher birthweight. No associations were found for gestational age or preterm birth. The findings have important implications for preconception care. Future research with larger sample sizes would assist in validating these findings.
Subject(s)
Alkanesulfonic Acids , Environmental Pollutants , Fluorocarbons , Premature Birth , Male , Pregnancy , Female , Humans , Infant, Newborn , Birth Weight , Premature Birth/epidemiology , FathersSubject(s)
Laparoscopy , Pregnancy, Abdominal , Pregnancy , Female , Humans , Pregnancy, Abdominal/surgery , Omentum/surgerySubject(s)
Gynecology , Infertility, Female , Specialization , Female , Humans , Infertility, Female/therapyABSTRACT
For years, reproductive surgery was the mainstay of reproductive care. With the evolution and ultimate success of in vitro fertilization (IVF), reproductive surgery became an adjuvant therapy, indicated mainly for severe symptoms or to enhance success rates with assisted reproductive technologies. As success rates for IVF have plateaued, and emerging data rekindles the enormous benefits of surgically correcting reproductive pathologies, there is renewed interest among reproductive surgeons in reviving research and surgical expertise in this area. In addition, new instrumentation and surgical techniques to preserve fertility have gained traction and will solidify the need to have skilled reproductive endocrinology and infertility surgeons in our practice.
Subject(s)
Infertility, Female , Laparoscopy , Female , Humans , Infertility, Female/surgery , Infertility, Female/diagnosis , Laparoscopy/methods , Fertility , Reproductive Techniques, Assisted , Fertilization in Vitro/methodsABSTRACT
Objective: To describe a case of a personal and family history of early uterine leiomyomatosis that revealed a pathogenic variant in the FH gene encoding fumarate hydratase. After the patient's diagnosis, a first-degree relative was detected with early-stage renal cell carcinoma. The patient decided to undergo preimplantation genetic testing to reduce the risk to her future children. Design: A case report of autosomal dominant hereditary leiomyomatosis and renal cell cancer syndrome where the patient underwent 2 cycles of in vitro fertilization with preimplantation genetic testing for monogenic disease/aneuploidy (PGT-MA) that resulted in 3 unaffected, euploid embryos. Setting: Large academic single-center hospital. Patients: A 35-year-old nulligravida woman with a personal history of an early-onset uterine leiomyomatosis and a family history of renal cell carcinoma and uterine leiomyomas, who is heterozygous for a pathogenic variant in FH and diagnosed with hereditary leiomyomatosis and renal cell cancer syndrome. Informed consent was obtained. Interventions: Two laparoscopic myomectomies were performed, and tissue was sent for histopathology and immunostaining. Hereditary leiomyomatosis and renal cell cancer syndrome was confirmed by germline testing, and 2 cycles of PGT-MA were performed. Main Outcome Measures: Through PGT-MA, the patient was able to mitigate the risk of passing a known familial variant to her future children. Results: After 2 cycles of in vitro fertilization with PGT-MA, 3 unaffected embryos were available for transfer. An unaffected, euploid embryo was transferred for pregnancy, and the patient is currently pregnant in her second trimester. Conclusions: Pathogenic variants in FH should be suspected in patients with early-onset uterine leiomyomas and a family history of cutaneous and/or uterine leiomyomas. Familial variant testing is crucial in identifying relatives at risk to start early screening.
ABSTRACT
Providing medical care at the highest levels across various reproductive endocrinology and infertility settings necessitates seamless partnership among multiple people with diverse skill sets. In this introductory article for this month's Views and Reviews, the concept of teaming is presented, including the key concepts of collaboration, assembling the right team members, establishing goals, inspiring and empowering others, and encouraging new approaches to optimize outcomes. Following this introduction, thought leaders from diverse reproductive endocrinology and infertility spaces, including clinical, ambulatory surgery, laboratory, and research settings, present their experiences using teaming models to adapt team members' thinking, elevate the quality of scientific productivity, and achieve excellence in both patient care and laboratory and clinical outcomes.
Subject(s)
Endocrinology/organization & administration , Patient Care Team/organization & administration , Reproductive Medicine/organization & administration , Ambulatory Surgical Procedures , Biomedical Research/organization & administration , Efficiency, Organizational , Female , Humans , Infertility/diagnosis , Infertility/therapy , Interdisciplinary Communication , Laboratories, Clinical/organization & administration , Male , Patient Safety/standards , Pregnancy , Quality Assurance, Health Care/organization & administrationABSTRACT
Healthcare teams must be deliberately cultivated to reach their full potential. Shifting focus from individual performance to a team's collective competence allows for targeted and evidence-based interventions that support teamwork and improve patient outcomes. We reviewed essential concepts drawn from team science and explored the practical applications of teaming. Reproductive endocrinology and infertility healthcare providers play a pivotal role by teaching, modeling, and fostering teaming attitudes and behaviors. Through teaming, we can maximize our teams' ability to learn, innovate, compete with other teams, and thrive in today's healthcare environment.
Subject(s)
Health Personnel/education , Inventions , Patient Care Team/organization & administration , Reproductive Medicine , Clinical Competence , Endocrinology/education , Endocrinology/organization & administration , Female , Health Personnel/organization & administration , Health Personnel/standards , Humans , Inventions/trends , Learning , Male , Pregnancy , Reproductive Medicine/education , Reproductive Medicine/organization & administration , Reproductive Medicine/trends , Therapies, Investigational/trendsABSTRACT
The purpose of this video is to illustrate the evolution of minimally invasive surgery from the perspectives of several pioneering surgeons in the field of reproductive surgery who, among others, were present during its nascence and exponential growth. Interviews were conducted with five reproductive surgeons who had foundational roles in the innovation of operative laparoscopy and hysteroscopy. Surgeons interviewed include Drs. Victor Gomel, Togas Tulandi, Stephen Corson, Jacques Donnez, and Camran Nezhat. The interviews were conducted using standardized questions and recorded, edited, and grouped both thematically and in sequence to develop an illustration of their perspectives. A diverse array of reproductive surgeons has been instrumental in establishing minimally invasive surgery as a safe and effective means of diagnosing and treating patients with infertility. The transition from laparotomy to laparoscopy consistently has had distinct challenges for each but ultimately led to significant advances in surgical management and improvement in outcomes for patients with infertility and chronic pelvic pain. Through structured interviews from some of our surgical pioneers, they not only recognize their predecessors and contemporaries but also teach us valuable lessons about our history, sparking innovation, and newer surgical applications of reproductive surgery in reproductive endocrinology and infertility practice.
Subject(s)
Endocrinology , Hysteroscopy , Laparoscopy , Reproductive Medicine , Female , HumansABSTRACT
OBJECTIVE: To compare the effect of preoperative intravenous (IV) acetaminophen versus oral (PO) acetaminophen or placebo on postoperative pain scores and the time to discharge in women undergoing oocyte retrieval. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Single academic fertility center. PATIENT(S): Women aged 18-43 years undergoing oocyte retrieval. INTERVENTION(S): Randomization to preoperative 1,000 mg IV acetaminophen and PO placebo (group A), IV placebo and 1,000 mg PO acetaminophen (group B), or IV and PO placebo (group C) MAIN OUTCOME MEASURE(S): Difference in patient-reported postoperative visual analog scale pain scores from baseline and the time to discharge. RESULT(S): Of the 159 women who completed the study, there were no differences in the mean postoperative pain score differences or the time to discharge. Although not statistically significant, the mean postoperative opioid dose requirement in group A was lower than that in groups B and C (0.24 vs. 0.59 vs. 0.58 mg IV morphine equivalents, respectively) due to fewer women in group A requiring rescue pain medication (8% vs. 19% vs. 15%, respectively). Group A also reported less constipation when compared with groups B and C (19% vs. 33% vs. 40%, respectively). The rates of postoperative nausea were similar, and there were no differences in embryology or early pregnancy outcomes between the study groups. CONCLUSION(S): Preoperative IV acetaminophen for women undergoing oocyte retrieval did not reduce postoperative pain scores or shorten the time to discharge when compared with PO acetaminophen or placebo and, thus, cannot currently be recommended routinely in this patient population. CLINICAL TRIAL REGISTRATION NUMBER: NCT03073980.
Subject(s)
Acetaminophen/administration & dosage , Oocyte Retrieval/methods , Pain Management/methods , Administration, Intravenous , Adolescent , Adult , Double-Blind Method , Female , Humans , Massachusetts/epidemiology , Oocyte Retrieval/adverse effects , Pain Measurement , Pain, Postoperative/drug therapy , Pain, Postoperative/epidemiology , Pain, Postoperative/etiology , Perioperative Period , Placebos , Young AdultABSTRACT
There are many proposed classification systems for müllerian anomalies. The American Fertility Society (AFS) Classification from 1988 has been the most recognized and utilized. The advantages of this iconic classification include its simplicity, recognizability, and correlation with clinical pregnancy outcomes. However, the AFS classification has been criticized for its focus primarily on uterine anomalies, with exclusion of those of the vagina and cervix, its lack of clear diagnostic criteria, and its inability to classify complex aberrations. Despite this classification and others, the wide range of müllerian anomalies is still largely unknown and confusing to many providers. Consequently, müllerian anomalies may go undiagnosed for extended periods, receive inappropriate or inadequate surgical interventions, and result in persistent issues such as pain or loss of reproductive function. The American Society for Reproductive Medicine Task Force on Müllerian Anomalies Classification was formed and charged with designing a new classification. The Task Force set goals for a new classification and chose to base it on the iconic AFS classification from 1988 because of its simplicity and recognizability, while expanding and updating it to include all categories of anomalies. In addition, this was recognized as an opportunity to raise awareness of this area of medicine, educate providers and learners, and promote patient advocacy. Presented here is the new American Society for Reproductive Medicine Müllerian Anomalies Classification 2021.
Subject(s)
Decision Support Techniques , Magnetic Resonance Imaging , Mullerian Ducts/diagnostic imaging , Terminology as Topic , Ultrasonography , Urogenital Abnormalities/diagnostic imaging , Uterus/abnormalities , Vagina/diagnostic imaging , Cervix Uteri/abnormalities , Cervix Uteri/diagnostic imaging , Female , Humans , Male , Mullerian Ducts/abnormalities , Predictive Value of Tests , Urogenital Abnormalities/classification , Uterus/diagnostic imaging , Vagina/abnormalitiesABSTRACT
In machine learning for image-based medical diagnostics, supervised convolutional neural networks are typically trained with large and expertly annotated datasets obtained using high-resolution imaging systems. Moreover, the network's performance can degrade substantially when applied to a dataset with a different distribution. Here, we show that adversarial learning can be used to develop high-performing networks trained on unannotated medical images of varying image quality. Specifically, we used low-quality images acquired using inexpensive portable optical systems to train networks for the evaluation of human embryos, the quantification of human sperm morphology and the diagnosis of malarial infections in the blood, and show that the networks performed well across different data distributions. We also show that adversarial learning can be used with unlabelled data from unseen domain-shifted datasets to adapt pretrained supervised networks to new distributions, even when data from the original distribution are not available. Adaptive adversarial networks may expand the use of validated neural-network models for the evaluation of data collected from multiple imaging systems of varying quality without compromising the knowledge stored in the network.