Climate change and human health: a primer on what women's health physicians can do on behalf of their patients and communities.

PURPOSE OF REVIEW: To describe the current state of knowledge on the impact on climate change on women's health and to highlight opportunities for healthcare providers to serve as advocates and subject matter experts. RECENT FINDINGS: Healthcare providers are a uniquely respected voice in society but have not used this advantage to advocate for their communities and participate in mitigation, adaptation, and resiliency efforts on behalf of their patients and communities. SUMMARY: Healthcare providers feel that climate change is real, is human caused, and is currently or will shortly negatively impact their patients. They feel unprepared to serve as leaders and advocates due to time limitations and a knowledge gap. Resources in the current climate movement can help close this gap.

Concordance of hemoglobin A1c and reproductive hormone levels in menstrual and venous blood.

Objective: To explore whether menstrual blood collected via a modified menstrual pad is a surrogate for venous blood drawn in analyzing hemoglobin A1c (HbA1c) and fertility-associated hormones. Design: Cross-sectional study. Setting: Clinical testing laboratory. Patients: This study included 152 female participants who have regular menses, aged 19-50 years old. Interventions: Participants collected menstrual effluent using a menstrual pad modified with a removable dried blood spot (DBS) strip. Peripheral blood samples were collected via venipuncture within 60 hours of menstrual pad use. Main Outcome Measures: Menstrual pad and venous blood drawn samples were analyzed for levels of HbA1c, thyroid stimulating hormone (TSH), follicle-stimulating hormone (FSH), anti-müllerian hormone (AMH), and luteinizing hormone (LH). Correlation between menstrual pad and venipuncture samples was performed using Deming linear regression, and r coefficients were measured using Pearson correlation. Results: The interassay variability of menstrual pad DBS sample measurements was <6%. Menstrual HbA1c values were stabilized in the DBS strips through 53 days, and menstrual hormone levels remained stable through 15 days. Menstrual HbA1c levels were highly correlated with venipuncture samples (r = 0.96). The levels of TSH (r = 0.94), AMH (r = 0.94), FSH (r = 0.91), and LH (r = 0.91) also showed a high correlation between menstrual strip and venipuncture samples. Conclusions: The levels of HbA1c, TSH, AMH, FSH, and LH measurements in menstrual effluent showed a high correlation to venous blood samples, supporting the use of menstrual effluent as a surrogate sample for hormone testing.

Utility of Repeat Uterine Cavity Evaluation in the Infertility Workup.

Background: Uterine cavity abnormalities contribute to infertility. The purpose of this study was to evaluate the incidence, recurrence rates, and risk factors for uterine cavity abnormalities in women undergoing infertility workup and treatment, focusing on the utility of routinely repeated imaging. Methods: Retrospective cohort study at single academic medical center of 833 infertile women who had uterine cavity evaluations performed at least 9 months apart. Results: Of 833 eligible patients, 664 (79.7%) had normal initial imaging and 169 (20.3%) had abnormal initial imaging. Among the former, 10% had abnormal uterine cavity on repeat saline infusion sonohysterography (SIS); among the latter, 32% had abnormal repeat SIS [Chi-square p < 0.0001, risk ratio 2.30 (95% confidence interval 1.85-2.86)]. On average, 23.1 ± 13.6 months passed between studies. Regardless of initial imaging findings, women with abnormal repeat SIS were older than those with normal repeat SIS, with no difference in time elapsed between studies. There were no associations between repeat imaging outcomes and body mass index, uterine instrumentation, number of treatment cycles, or maximum peak estradiol levels in a single cycle between studies. There was no difference in live birth rate among cycles started within 1 year after repeat SIS across groups. Conclusions: Uterine cavity abnormalities were found in 10% of patients on repeat imaging despite initially normal testing. No risk factors for cavity abnormality on repeat imaging were identified besides age and prior abnormality. It would be prudent to continue performing routine repeat uterine cavity evaluation for women undergoing fertility treatment, particularly if corrective measures had been taken in the past.

Meeting the demand for fertility services: the present and future of reproductive endocrinology and infertility in the United States.

The field of reproductive endocrinology and infertility (REI) is at a crossroads; there is a mismatch between demand for reproductive endocrinology, infertility and assisted reproductive technology (ART) services, and availability of care. This document's focus is to provide data justifying the critical need for increased provision of fertility services in the United States now and into the future, offer approaches to rectify the developing physician shortage problem, and suggest a framework for the discussion on how to meet that increase in demand. The Society of REI recommend the following: 1. Our field should aggressively explore and implement courses of action to increase the number of qualified, highly trained REI physicians trained annually. We recommend efforts to increase the number of REI fellowships and the size complement of existing fellowships be prioritized where possible. These courses of action include: a. Increase the number of REI fellowship training programs. b. Increase the number of fellows trained at current REI fellowship programs. c. The pros and cons of a 2-year focused clinical fellowship track for fellows interested primarily in ART practice were extensively explored. We do not recommend shortening the REI fellowship to 2 years at this time, because efforts should be focused on increasing the number of fellowship training slots (1a and b). 2. It is recommended that the field aggressively implements courses of action to increase the number of and appropriate usage of non-REI providers to increase clinical efficiency under appropriate board-certified REI physician supervision. 3. Automating processes through technologic improvements can free providers at all levels to practice at the top of their license.

Reproductive endocrinologist and infertility specialists' knowledge, skills, behaviors, and attitudes regarding the care for transgender and gender-diverse individuals.

Objective: To investigate associations between reproductive endocrinology and infertility (REI) providers' prior training and current knowledge, skills, attitudes, and behaviors regarding fertility preservation and family building for transgender and gender-diverse (T/GD) patients. Design: The survey was distributed to members of the Society for Reproductive Endocrinology and Infertility, the REI-physician-focused professional body within the American Society for Reproductive Medicine, with additional participants recruited through snowball sampling. Results: Participants (n = 206) reported on training in T/GD care; 51% endorsed prior training. Most participants (93%) believed T/GD individuals were as fit for parenthood as cisgender individuals. Prior training was associated with an increased likelihood of offering T/GD health resources and more frequent consultations with specialist colleagues.Common barriers to providing care indicated by respondents included cost, delays in gender-affirming care, and lack of knowledge of the potential impact of hormonal interventions. Common facilitators included education and training, prior experience, and affordability of services. Conclusions: Most REI providers believed T/GD individuals are fit for parenthood and agreed that prior training facilitates care for T/GD patients. The lack of provider knowledge emerged as a barrier to care. Although training helped facilitate some components of care, systemic barriers such as the cost and variability of patient population characteristics/experiences are important considerations when serving T/GD individuals.

The no-man's land of nontubal ectopic and cesarean section scar pregnancies.

Nontubal ectopic pregnancy (NTEP) and cesarean section scar pregnancy (CCSP) are a relatively uncommon but potentially very dangerous conception event. If diagnosed early, they can be treated very effectively. Cesarean section scar ectopic is unique in that expectant management may allow them to persist longer, but with overwhelmingly catastrophic consequences. Reproductive endocrinologists are uniquely positioned to diagnose and treat NTEP/CCSP early, thereby avoiding long-term catastrophic consequences.

Oocyte and embryo cryopreservation in assisted reproductive technology: past achievements and current challenges.

Cryopreservation has revolutionized the treatment of infertility and fertility preservation. This review summarizes the milestones that paved the way to the current routinary clinical implementation of this game-changing practice in assisted reproductive technology. Still, evidence to support "the best practice" in cryopreservation is controversial and several protocol adaptations exist that were described and compared here, such as cumulus-intact vs. cumulus-free oocyte cryopreservation, artificial collapse, assisted hatching, closed vs. open carriers, and others. A last matter of concern is whether cryostorage duration may impact oocyte/embryo competence, but the current body of evidence in this regard is reassuring. From social and clinical perspectives, oocyte and embryo cryopreservation has evolved from an afterthought when assisted reproduction was intended for immediate pregnancy with supernumerary embryos of secondary interest to its current purpose, which primarily is to preserve fertility long-term and more comprehensively allow for family planning. However, the initial consenting process, which still is geared to short-term fertility care, may no longer be relevant when the individuals that initially preserved the tissues have completed their reproductive journey. A more encompassing counseling model is required to address changing patient values over time.

Cost-effectiveness of IVF with PGT-M/A to prevent transmission of spinal muscular atrophy in offspring of carrier couples.

PURPOSE: To evaluate the cost-effectiveness of in-vitro fertilization with preimplantation genetic testing for aneuploidy and monogenic disorders (IVF with PGT-M/A) to prevent transmission of spinal muscular atrophy to offspring of carrier couples. METHODS: A decision-analytic model was created to compare the cost-effectiveness of IVF with PGT-M/A to unassisted conception with prenatal diagnostic testing and termination (if applicable). IVF with PGT-M/A costs were determined using a separate Markov state-transition model. IVF outcomes data was derived from 76 carriers of monogenic disorders who underwent IVF with PGT-M/A at a single academic REI center. Other probabilities, costs, and utilities were derived from the literature. Costs were modeled from healthcare perspective. Utilities were modeled from the parental perspective as quality-adjusted life-years (QALYs). RESULTS: The incremental cost-effectiveness ratio for IVF with PGT-M/A compared to unassisted conception is $22,050 per quality-adjusted life-year. The average cost of IVF with PGT-M/A is $41,002 (SD: $8,355). At willingness-to-pay thresholds of $50,000 and $100,000, IVF with PGT-M/A is cost-effective 93.3% and 99.5% of the time, respectively. CONCLUSIONS: Compared to unassisted conception, IVF with PGT-M/A is cost-effective for preventing the transmission of spinal muscular atrophy to the offspring of carrier couples. These findings support insurance coverage of IVF with PGT-M/A for carriers of spinal muscular atrophy.

Assessment of patients' perceptions towards embryo disposition after donation of embryos to a research biobank.

PURPOSE: To explore perceptions towards embryo disposition among patients donating excess embryos to a research biobank. METHODS: Cross-sectional study of survey responses collected as part of enrollment in a research biobank. Patients are asked questions regarding the difficulty of their disposition decision, their alternative disposition choice if donation to research was not available, quality of the counseling they received, and if additional counseling throughout their treatment would have been beneficial. Survey responses use 5-point Likert scales, with "1" being lowest/least and "5" being highest/most. RESULTS: A total of 157 men and 163 women enrolled in the biobank. Median scores for difficulty of disposition decision were 3 for females and 2 for males, and for quality of counseling, the median scores were 4 for females and 3 for males. Seventy percent of patients would have chosen to discard their excess embryos had donation to research not been an option. Statistical analyses showed no significant difference in responses based on variations in race, religion, sexual orientation, and infertility diagnoses. Concordance of responses within heterosexual couples was tested and found to be poor to moderate. CONCLUSIONS: Assessing patients' perceptions towards embryo disposition after donation of their excess embryos to a research biobank affords a unique perspective. The difficulty of the disposition decision, the tendency to discard embryos in the absence of a means for donation to research, and the poor agreement between heterosexual partners highlight the importance of donation to research as an accessible disposition option and the need for a personalized approach to counseling and consenting for embryo disposition.

Implementation of a comprehensive fertility biobanking initiative.

OBJECTIVE: To present the framework of Stanford Fertility and Reproductive Health's comprehensive reproductive biobanking initiatives and the results of the first year of recruitment. DESIGN: Technical description article. SETTING: Academic fertility center. PATIENT(S): Fertility patients >18 years of age. INTERVENTION(S): Enroll the patients interested in research in biobanking protocols. MAIN OUTCOME MEASURE(S): Patient recruitment and sample inventory from September 2020 to September 2021. RESULT(S): A total of 253 patients have enrolled in the Stanford Fertility and Reproductive Health biobanking initiatives since September 2020. The current inventory consists of 1,176 samples, including serums, plasmas, buffy coats, endometria, maternal deciduae, miscarriage chorionic villi, and human embryos (zygote, cleavage, and blastocyst stages). CONCLUSION(S): This biobanking initiative addresses a critical, unmet need in reproductive health research to make it possible for patients to donate excess embryos and gametes and preserves, for future research, valuable somatic and reproductive tissues that would otherwise be discarded. We present the framework of this biobanking initiative in order to support future efforts of establishing similar biorepositories.

The third degree: climate change and reproductive health.

Climate change is a public health emergency, yet the medical community has been inconsistent in its understanding and engagement of the crisis. Reproductive endocrinology and infertility and reproductive biology will be impacted broadly by the changing climate. This Views and Reviews hopes to enlist reproductive endocrinology and infertility specialists to first understand the issues and then take action to support mitigation and accommodation efforts.

Is living in a region with high groundwater arsenic contamination associated with adverse reproductive health outcomes? An analysis using nationally representative data from India.

BACKGROUND: Exposure to groundwater arsenic via drinking water is common in certain geographies, such as parts of India, and causes a range of negative health effects, potentially including adverse reproductive health outcomes. METHODS: We conducted an ecological analysis of self-reported rates of stillbirth, recurrent pregnancy loss, and infertility in relation to groundwater arsenic levels in India. We used a gridded, modeled dataset of the probability of groundwater arsenic exceeding 10 µg/L (World Health Organization drinking water limit) to calculate mean probabilities at the district level (n = 599 districts). A spatial integration approach was used to merge these estimates with the third India District-Level Health Survey (DLHS-3) conducted in 2007-08 (n = 643,944 women of reproductive age). Maps of district level arsenic levels and rates of each of the three outcomes were created to visualize the patterns across India. To adjust for significant spatial autocorrelation, spatial error models were fit. FINDINGS: District-level analysis showed that the average level of stillbirth was 4.3%, recurrent pregnancy loss was 3.3%, and infertility was 8.1%. The average district-level probability of groundwater arsenic levels exceeding 10 µg/L was 42%. After adjustment for sociodemographic factors, and accounting for spatial dependence, at the district level, for each percentage point increase in predicted arsenic levels exceeding 10 µg/L increased, the rates of stillbirths was 4.5% higher (95% confidence interval (CI) 2.4-6.6, p < 0.0001), the rates of RPL are 4.2% higher (95% CI 2.5-5.9, p < 0.0001), and the rates of infertility are 4.4% higher (95% CI 1.2-7.7, p=<0.0001).). CONCLUSIONS: While arsenic exposure has been implicated with a range of adverse health outcomes, this is one of the first population-level studies to document an association between arsenic and three adverse reproductive pregnancy outcomes. The high levels of spatial correlation suggest that further and targeted efforts to mitigate arsenic in groundwater are needed.