Food, nutrition, and fertility: from soil to fork.

Food and nutrition-related factors, including foods and nutrients consumed, dietary patterns, use of dietary supplements, adiposity, and exposure to food-related environmental contaminants, have the potential to impact semen quality and male and female fertility; obstetric, fetal, and birth outcomes; and the health of future generations, but gaps in evidence remain. On 9 November 2022, Tufts University's Friedman School of Nutrition Science and Policy and the school's Food and Nutrition Innovation Institute hosted a 1-d meeting to explore the evidence and evidence gaps regarding the relationships between food, nutrition, and fertility. Topics addressed included male fertility, female fertility and gestation, and intergenerational effects. This meeting report summarizes the presentations and deliberations from the meeting. Regarding male fertility, a positive association exists with a healthy dietary pattern, with high-quality evidence for semen quality and lower quality evidence for clinical outcomes. Folic acid and zinc supplementation have been found to not impact male fertility. In females, body weight status and other nutrition-related factors are linked to nearly half of all ovulation disorders, a leading cause of female infertility. Females with obesity have worse fertility treatment, pregnancy-related, and birth outcomes. Environmental contaminants found in food, water, or its packaging, including lead, perfluorinated alkyl substances, phthalates, and phenols, adversely impact female reproductive outcomes. Epigenetic research has found that maternal and paternal dietary-related factors can impact outcomes for future generations. Priority evidence gaps identified by meeting participants relate to the effects of nutrition and dietary patterns on fertility, gaps in communication regarding fertility optimization through changes in nutritional and environmental exposures, and interventions impacting germ cell mechanisms through dietary effects. Participants developed research proposals to address the priority evidence gaps. The workshop findings serve as a foundation for future prioritization of scientific research to address evidence gaps related to food, nutrition, and fertility.

Living Your Best Life: Lifestyle Medicine for All Women.

In an era of ever-increasing healthcare expenditures, yet simultaneously worsening outcomes, many of our patients choose between traditional medical care or often unproven alternative therapies. While the recognition of lifestyle change in addressing cardiovascular and metabolic disease grows, there is less understanding of the impact of lifestyle change on issues facing women every day. Millions of women around the globe struggle with infertility, cancer, sexual dysfunction, and dermatologic needs. Yet, research on the benefits of lifestyle change on these conditions is scarce, and gaps exist both in our understanding of evidence-based approaches to address these issues, as well as adequate provider education when evidence exists. The Women's Health Member Interest Group convened medical experts in these areas that affect women's lives to provide insights and meaningful education applicable not only for our patients, but also in our own lives.

Dietary Approaches to Women's Sexual and Reproductive Health.

Over the course of the reproductive life span, it is common for women to experience one or more of the most common gynecologic conditions, including sexual dysfunction, polycystic ovary syndrome, fibroids, endometriosis, and infertility. Although current management guidelines often turn to the established pharmaceutical approaches for each of these diagnoses, the scientific literature also supports an evidence-based approach rooted in the paradigm of food as medicine. Achieving healthy dietary patterns is a core goal of lifestyle medicine, and a plant-forward approach akin to the Mediterranean diet holds great promise for improving many chronic gynecologic diseases. Furthermore, creating an optimal preconception environment from a nutritional standpoint may facilitate epigenetic signaling, thus improving the health of future generations. This state-of-the-art review explores the literature connecting diet with sexual and reproductive health in premenopausal women.

A cross-sectional survey of fertility knowledge in obstetrics and gynecology residents.

BACKGROUND: To evaluate fertility knowledge among current Obstetrics and Gynecology (OB-GYN) residents using a recently published validated instrument, the Fertility and Infertility Treatment Knowledge Score (FIT-KS). METHODS: OB-GYN residents in the United States were recruited through an email to all residency coordinators nationwide. They were asked to voluntarily respond to a short questionnaire including demographic information and the FIT-KS instrument, through an online survey platform. Of approximately 5000 OB-GYN residents in the country, 177 responded. RESULTS: The sample was 91% female, with 69% between the ages of 26 and 30. Participants evenly represented all 4 years of training. Mean FIT-KS score was 21.2 (73% correct; range 17-26). No statistically significant differences were noted across the level of training. Several knowledge gaps were noted. Residents could define the common assisted reproductive technologies; however overestimated their success rates per cycle. CONCLUSIONS: Substantial gaps exist in fertility knowledge among OB-GYN residents, with understanding of male fertility and success rates of Assisted Reproductive Technologies (ART) being particularly limited. Knowledge of fertility does not change throughout residency training, demonstrating consistent gaps in fertility knowledge. Knowledge during post graduate year (PGY)-1 year is consistent with mean scores found in prior research in Internal Medicine residents (65%), as well as a cohort of female medical students and obstetrics and gynecology residents and fellows (64.9%) (Fertil Steril 108:711-7, 2017; Fertil Steril 110:e239, 2018).

Fertility Counseling for Adolescents.

Fertility awareness, or general knowledge about one's fertility, is low in adolescents and in adult women as well. Misconceptions about reproduction contribute to high rates of unplanned pregnancy in the United States, as well as delayed childbearing and infertility. Alhough primary care providers caring for adolescents have historically focused on contraception and reduction of sexually transmitted infections during their sexual and reproductive health conversations with adolescents and young adult women, fertility awareness counseling would help these women optimize their future fertility and make informed reproductive choices throughout their life. This is particularly true for adolescents with chronic medical conditions, certain gynecologic conditions, or a history of therapies that could potentially affect fertility, for whom preemptive conversations about fertility are needed, but often overlooked. [Pediatr Ann. 2019;48(2):e86-e91.].

The effect of female body mass index on in vitro fertilization cycle outcomes: a multi-center analysis.

PURPOSE: The aim of this study is to examine the impact of female body mass index (BMI) on IVF cycle outcomes. METHODS: This is a retrospective cohort study including 51,198 women who initiated their first autologous IVF cycle in 13 fertility centers in the USA between 2009 and 2015. The effect of underweight, overweight, and obese BMI on four different IVF cycle outcomes (cycle cancellation, oocyte and embryo counts, and ongoing clinical pregnancy [OCP]) was evaluated in logistic or Poisson regression analyses with confounders adjusted. RESULTS: Women with an overweight or obese BMI experienced worse outcomes than those with a normal BMI. These differences included (1) greater odds of cycle cancellation (aOR [95%CI] 1.17 [1.08, 1.26] for overweight, 1.28 [1.15, 1.41] for class-I obesity, and 1.50 [1.33, 1.68] for class-II/III obesity, P < .001 for all); (2) fewer oocytes retrieved (aIRR [95%CI] 0.98 [0.98,0.99] for class-I obesity, 0.93 [0.92,0.94] for class-II/III obesity, P < .001 for both); (3) fewer usable embryos (aIRR [95%CI] 0.98 [0.97,0.99] for overweight, 0.97 [0.96,0.99] for class-I obesity, 0.95 [0.93,0.97] for class-II/III obesity, P < .01 for all); and (4) lower odds of OCP (aOR [95%CI] 0.89 [0.83,0.95] for class-I obesity, 0.86 [0.79,0.93] for class-II/III obesity, P < .001 for both). In a subgroup analysis based on primary infertility diagnosis, these trends persisted in those with male or uterine factor and were especially pronounced in women with ovulatory dysfunction or PCOS. CONCLUSIONS: A BMI above the normal range was an independent negative prognostic factor for multiple outcomes, including cycle cancellation, oocyte and embryo counts, and OCP. These negative outcomes were most profound in women with class-II/III obesity, ovulatory dysfunction, or PCOS.

Low fertility awareness in United States reproductive-aged women and medical trainees: creation and validation of the Fertility & Infertility Treatment Knowledge Score (FIT-KS).

OBJECTIVE: To create, validate, and use a fertility awareness survey based on current U.S. DESIGN: Cross-sectional study. SETTING: Not applicable. PATIENT(S): Phase 1 included U.S. women ages 18-45; phase 2 included female medical students and obstetrics and gynecology trainees at two urban academic programs. INTERVENTION(S): Survey including demographics, the Fertility & Infertility Treatment Knowledge Score (FIT-KS) instrument, and General Nutrition Knowledge Questionnaire. MAIN OUTCOME MEASURE(S): Knowledge of natural fertility and infertility treatments. RESULT(S): The FIT-KS was validated through detailed item and validity analyses. In phase 1, 127 women participated; their median age was 31 years, and 43.7% had children. Their mean FIT-KS score was 16.2 ± 3.5 (55.9% correct). In phase 2, 118 medical trainees participated; their median age was 25 years, and 12.4% had children. Their mean FIT-KS score was 18.8 ± 2.1 (64.9% correct), with year of training correlating to a higher score (r=0.40). Participant awareness regarding lifestyle factors varied, but it was particularly low regarding the effects of lubricants. The majority underestimated the spontaneous miscarriage rate and overestimated the fecundability of 40-year-old women. There was general overestimation of success rates for assisted reproductive technologies, particularly among medical trainees. CONCLUSION(S): The FIT-KS is validated to current U.S. data for use in both general and medical populations as a quick assessment of fertility knowledge. The knowledge gaps demonstrated in this study correlate with national trends in delayed childbearing and time to initiate treatment. For medical trainees, these results raise concerns about the quality of fertility counseling they may be able to offer patients. Greater educational outreach must be undertaken to enhance fertility awareness.

Elevated Prevalence of Polycystic Ovary Syndrome and Cardiometabolic Disease in South Asian Infertility Patients.

South Asians (SA) develop cardiometabolic disease at elevated rates. We investigate whether reproductive-aged SA women are at higher risk for a precursor condition, polycystic ovary syndrome (PCOS), as compared to Caucasian controls. 52 SA and 52 Caucasian infertility patients from a single institution were included in a cross-sectional analysis. Outcomes were compared using Student's t, Mann-Whitney U, Pearson's Chi-squared and Fisher's exact tests. SA women were younger, with six-fold greater odds of PCOS. SA women were not obese, with similar body mass indices to controls. However, when screened, they demonstrated abundant metabolic disease, including insulin resistance, diabetes and dyslipidemia, and endometrial disease, including hyperplasia and polyps. The SA population was younger with more PCOS and high rates of metabolic and endometrial pathology. These findings, in the context of ethnicity-specific elevations in cardiometabolic risk, highlight the need for comprehensive screening and counseling in this patient population.

Fertility Awareness Counseling for Adolescent Girls; Guiding Conception: The Right Time, Right Weight, and Right Way.

STUDY OBJECTIVE: To provide a detailed summary of fertility awareness counseling pearls for healthy teens and those with fertility-relevant comorbidities, and to assist providers in offering such counseling to adolescents and young adult women. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: Comprehensive literature review of English-language studies relating to fertility in pediatric and adolescent female patients (ages 13-21 years), and evidence-based dialogue guide. RESULTS: The literature indicates that although adolescents are interested in discussing sexuality and reproduction, this is commonly overlooked during the standard office medical visit. As a result, adolescents often turn to less reliable sources and hold a variety of reproductive misconceptions and a sense of lack of control over future fertility. We found no studies that examined the routine provision of fertility awareness counseling with healthy adolescents. There are a multitude of specific gynecologic and medical conditions that have ramifications for fertility. We detail these comprehensively, and provide a dialogue guide to assist with fertility awareness counseling for the female adolescent, containing specific information and indications for referral. CONCLUSION: Providers caring for adolescent girls have the opportunity to enhance fertility awareness as part of a larger reproductive health conversation that adolescents desire, and from which they might benefit. Identifying potential future fertility issues, understanding age-related fertility decline, and aiding in health optimization before future conception might empower the adolescent to make informed reproductive decisions. We provide an algorithm to use with adolescents to discuss the "right time, right weight, right way" to pursue childbearing.

Thin endometrium after radiation therapy as an unresolved treatment challenge: a case report.

Receptive endometrium is essential for successful implantation and ongoing pregnancy. Significant health issues and associated therapies, especially oncologic therapies, have potential to negatively impact future fertility in young women. Irradiation and chemotherapeutic alkylating agents are known to cause ovarian failure in most females; however, less well is characterized the impact of irradiation on uterine development and integrity. With an increasing number of cancer survivors, women are seeking infertility treatment after such therapies. Here, we present a young woman who developed ovarian failure after the treatment of acute myeloid leukemia with bone marrow transplant and preceding irradiation and chemotherapy and who was diagnosed with thin endometrial lining while seeking infertility therapy.

Menopausal implications of polycystic ovarian syndrome.

Polycystic ovary syndrome (PCOS) is a common endocrinopathy affecting up to 8 to 10% of reproductive-aged women. Although the medical and metabolic consequences of PCOS are well-described in young reproductive-aged women, its impact on female reproductive senescence and the menopausal transition is poorly understood. This review summarizes current knowledge regarding the effect of PCOS is menopausal and perimenopausal women. We also highlight areas that are ripe for clinical research.

Rescue karyotyping: a case series of array-based comparative genomic hybridization evaluation of archival conceptual tissue.

BACKGROUND: Determination of fetal aneuploidy is central to evaluation of recurrent pregnancy loss (RPL). However, obtaining this information at the time of a miscarriage is not always possible or may not have been ordered. Here we report on "rescue karyotyping", wherein DNA extracted from archived paraffin-embedded pregnancy loss tissue from a prior dilation and curettage (D&C) is evaluated by array-based comparative genomic hybridization (aCGH). METHODS: A retrospective case series was conducted at an academic medical center. Patients included had unexplained RPL and a prior pregnancy loss for which karyotype information would be clinically informative but was unavailable. After extracting DNA from slides of archived tissue, aCGH with a reduced stringency approach was performed, allowing for analysis of partially degraded DNA. Statistics were computed using STATA v12.1 (College Station, TX). RESULTS: Rescue karyotyping was attempted on 20 specimens from 17 women. DNA was successfully extracted in 16 samples (80.0%), enabling analysis at either high or low resolution. The longest interval from tissue collection to DNA extraction was 4.2 years. There was no significant difference in specimen sufficiency for analysis in the collection-to-extraction interval (p=0.14) or gestational age at pregnancy loss (p=0.32). Eight specimens showed copy number variants: 3 trisomies, 2 partial chromosomal deletions, 1 mosaic abnormality and 2 unclassified variants. CONCLUSIONS: Rescue karyotyping using aCGH on DNA extracted from paraffin-embedded tissue provides the opportunity to obtain critical fetal cytogenetic information from a prior loss, even if it occurred years earlier. Given the ubiquitous archiving of paraffin embedded tissue obtained during a D&C and the ease of obtaining results despite long loss-to-testing intervals or early gestational age at time of fetal demise, this may provide a useful technique in the evaluation of couples with recurrent pregnancy loss.

Reproductive and oncologic outcomes after progestin therapy for endometrial complex atypical hyperplasia or carcinoma.

OBJECTIVES: This study evaluated fertility and oncological outcomes in women with complex atypical hyperplasia (CAH) or nonmyoinvasive grade 1 endometrioid endometrial carcinoma (EM) who desired fertility-sparing therapy. STUDY DESIGN: The retrospective cohort study included women younger than 45 years with CAH or EM who desired fertility-sparing treatment at our institution. Only patients for whom both oncological treatment and pregnancy outcomes were available were included. Statistical analyses were performed using a Fisher exact test, Pearson χ(2) test, and Spearman rank correlation test, as appropriate. RESULTS: Seventy-five patients were identified, and 23 (13 CAH, 10 EM) met the inclusion criteria. All 23 patients had at least 1 prior pregnancy. Treatment was split between oral progesterone only (38.5% CAH, 40% EM), levonorgestrel intrauterine device only (30.8% CAH, 20% EM), and both (30.8% CAH, 40% EM). After a median follow-up of 13 months (range, 3-74 months), 9 patients (46.2% CAH, 30% EM, P = .39) had persistent/progressive disease. Eight patients (30.8% CAH, 40% EM, P = .69) ultimately had a hysterectomy, and 3 of these (13.0%) were found to have persistent/progressive disease. Median time from diagnosis to hysterectomy was 13 months (range, 4-56 months). Fourteen of the 23 patients utilized assisted reproductive techniques (60.9%); 12 underwent IVF and 2 chose a gestation carrier. Seven clinical intrauterine pregnancies (30.4%) resulting in 6 live births (26.1%) were found in the entire cohort. CONCLUSION: Fertility-sparing treatment for CAH and grade 1 endometrial cancer is feasible with progestin therapy and leads to clinically meaningful rates of pregnancy in young women who desire fertility.

Pelvic Salmonella infection masquerading as gynecologic malignancy.

BACKGROUND: Salmonella species tubo-ovarian abscess is a rare clinical occurrence. Salmonella organisms are gastrointestinal pathogens that are not thought to create disease with sufficient spread or severity to result in intraperitoneal extension. CASE: A 32-year-old nulligravid woman presented with abdominal pain, fever, and bloody diarrhea. On imaging, she was found to have complex pelvic masses highly suspicious for neoplasm. Surgical exploration revealed tubo-ovarian abscesses and peritonitis. The ovarian tissue culture revealed a Salmonella infection. The final pathology showed bilateral ovarian abscesses and an endometriotic cyst in the right ovary. After a 6-week course of antibiotics, tissue cultures were negative for Salmonella infection, and the patient has remained asymptomatic with normal menstrual cycles. CONCLUSION: Preoperative evaluation of a pelvic mass in a reproductive-aged woman continues to be challenging, with a broad differential diagnosis. Although obstetrician-gynecologists rely on radiographic imaging for diagnosis, the results can be misleading.

Physician knowledge of and adherence to the revised breast cancer screening guidelines by the United States Preventive Services Task Force.

OBJECTIVE: We sought to assess knowledge and adherence to the revised US Preventive Services Task Force breast cancer screening guidelines among gynecologic care providers. STUDY DESIGN: This was a cross-sectional descriptive study based on a survey conducted among gynecologic care providers. RESULTS: Forty providers completed the survey (80%). In response to the statement "The current recommended age to initiate breast cancer screening is … .," 48.7% of providers responded in accordance with revised guidelines. For the statement "Women between the age of 50 and 74 years old are recommended to have screening mammography," 46.2% of respondents answered in accordance. In response to the statement "The United States Preventative Services Task Force recommends teaching breast self-examination," 71.8% of providers responded in accordance. A total of 37 respondents (92.5%) stated that they were aware of the revised guidelines, but 17 (42.4%) stated that they were applicable to their patient population. CONCLUSION: Knowledge of the revised guidelines appeared to be relatively low in our provider sample.

Practice variation among Michigan neurologists in the use of intravenous heparin.

BACKGROUND/OBJECTIVE: The indications for intravenous (IV) heparin use in acute ischemic stroke are uncertain. We sought to determine the current practice patterns of neurologists in Michigan with regard to IV heparin use, in view of the fact that several major multi-center trials evaluating heparin and related compounds have been completed in the last decade. METHODS: A survey was conducted of 180 active, practicing neurologists in Michigan. Five clinical scenarios were included and factors influencing heparin use were also determined. RESULTS: The vast majority of neurologists in Michigan would use IV heparin for patients with atrial fibrillation-related stroke (91% of those with a defined opinion). Heparin use was also popular for stroke-in-evolution (77%). There was a lesser degree of heparin use for patients with more than one transient ischemic attack (49%) or for patients with stroke and normal cardiac rhythm. Medicolegal factors at least sometimes influenced the selection of heparin as a therapy for 41% of physicians. CONCLUSIONS: Despite recent clinical trial data on heparin and related compounds which for the most part has been negative, IV heparin use remains popular for certain clinical scenarios, especially acute stroke with atrial fibrillation. Further studies are necessary to determine whether negative clinical trials have the same impact on neurologist behavior as positive studies.