Haem homeostasis is regulated by the conserved and concerted functions of HRG-1 proteins.

Haems are metalloporphyrins that serve as prosthetic groups for various biological processes including respiration, gas sensing, xenobiotic detoxification, cell differentiation, circadian clock control, metabolic reprogramming and microRNA processing. With a few exceptions, haem is synthesized by a multistep biosynthetic pathway comprising defined intermediates that are highly conserved throughout evolution. Despite our extensive knowledge of haem biosynthesis and degradation, the cellular pathways and molecules that mediate intracellular haem trafficking are unknown. The experimental setback in identifying haem trafficking pathways has been the inability to dissociate the highly regulated cellular synthesis and degradation of haem from intracellular trafficking events. Caenorhabditis elegans and related helminths are natural haem auxotrophs that acquire environmental haem for incorporation into haemoproteins, which have vertebrate orthologues. Here we show, by exploiting this auxotrophy to identify HRG-1 proteins in C. elegans, that these proteins are essential for haem homeostasis and normal development in worms and vertebrates. Depletion of hrg-1, or its paralogue hrg-4, in worms results in the disruption of organismal haem sensing and an abnormal response to haem analogues. HRG-1 and HRG-4 are previously unknown transmembrane proteins, which reside in distinct intracellular compartments. Transient knockdown of hrg-1 in zebrafish leads to hydrocephalus, yolk tube malformations and, most strikingly, profound defects in erythropoiesis-phenotypes that are fully rescued by worm HRG-1. Human and worm proteins localize together, and bind and transport haem, thus establishing an evolutionarily conserved function for HRG-1. These findings reveal conserved pathways for cellular haem trafficking in animals that define the model for eukaryotic haem transport. Thus, uncovering the mechanisms of haem transport in C. elegans may provide insights into human disorders of haem metabolism and reveal new drug targets for developing anthelminthics to combat worm infestations.

Hormonal contraception as treatment for heavy menstrual bleeding: a systematic review.

A systematic review to compare the effectiveness of contraceptives to treat heavy menstrual bleeding (HMB). PubMed was searched for studies using hormonal contraceptive methods to treat HMB. Two reviewers screened 734 citations and extracted eligible trials based on rigid inclusion and exclusion criteria. Fourteen articles met inclusion criteria. The evidence was good to poor quality and suggested that all contraceptives tested were effective in the treatment of HMB, but the levonorgestrel intrauterine system was the most effective method. Hormonal contraceptives effectively treat HMB. The levonorgestel intrauterine system is the superior method.

Implementation of telemedicine preoperative visits for abortion procedures through 18 weeks gestation at a Northern California hospital-based center.

OBJECTIVE: Describe the implementation of a preoperative telemedicine program at a Northern California hospital-based center for abortion procedures requiring cervical preparation. STUDY DESIGN: We implemented a pilot program using telemedicine for preoperative visits for patients needing cervical preparation prior to an abortion procedure from 12 to 18 weeks. We required ultrasonography for gestational age documentation in addition to placental localization in patients with a prior cesarean delivery. We prescribed misoprostol for cervical preparation for patients undergoing the telemedicine preoperative visit; in-person preoperative visits typically involve placement of osmotic dilators. Secondarily, we surveyed patients who had telemedicine and in-person preoperative visits to compare their preoperative experiences. RESULTS: Implementation required 8 months of multidisciplinary meetings. From March 2018 through March 2019, we received 200 abortion referrals at 12 to 18 weeks gestation. Of these 200 patients, 119 did not meet telemedicine eligibility criteria, most commonly due to inability to obtain required ultrasonography (n = 89 [75%]). Of the remaining 81 patients, 43 scheduled telemedicine visits of which 41 initiated and 38 (88%) completed the visits. Twenty-one (55%) telemedicine encounters had no or minor technical difficulties. Thirty-one of 34 (91%) telemedicine and 91 of 108 (84%) in-person visit patients expressed high satisfaction with their preoperative appointment (p = 0.4); none reported dissatisfaction. Patients chose the telemedicine visit primarily for convenience and transportation concerns. CONCLUSION: A multidisciplinary team is essential for the successful implementation of a preoperative telemedicine program for procedural abortion care. Patients reported high satisfaction and reduced logistical burdens with the telemedicine option. IMPLICATIONS: Telemedicine preoperative visits for abortion procedures at 12 to 18 weeks gestation may improve access to abortion care, reduce patient burdens, and provide an alternative encounter option which may improve the patient experience.

Mifepristone prior to osmotic dilators for dilation and evacuation cervical preparation: A randomized, double-blind, placebo-controlled pilot study.

OBJECTIVES: To evaluate mifepristone impact on osmotic dilator placement and procedural outcomes when given 18 to 24 hours before dilator placement for dilation and evacuation (D&E) at 18 weeks 0 days to 23 weeks 6 days gestation. STUDY DESIGN: We performed a randomized, double-blind, placebo-controlled trial from April 2019 through February 2021, enrolling participants undergoing osmotic dilator (Dilapan) placement for a planned, next-day D&E. Participants took mifepristone 200 mg or placebo orally 18 to 24 hours before dilator placement. We used a gestational age-based protocol for minimum number of dilators. Our primary outcome was the proportion of participants for whom 2 or more additional dilators could be placed compared to the minimum gestational age-based standard. We secondarily evaluated cervical dilation after dilator removal in the operating room, subjective procedure ease, and complication rates (cervical laceration, uterine perforation, blood transfusion, infection, hospitalization, or extramural delivery). RESULTS: Of the planned 66 participants, we enrolled 44 (stopped due to coronavirus disease 2019-related obstacles), and 41 (19 mifepristone; 22 placebo) completed the study. We placed 2 or more additional dilators compared to standard in 7 (36.8%) and 3 (13.6%) participants after mifepristone and placebo, respectively (p = 0.14). We measured greater median initial cervical dilation in the mifepristone (3.2 cm[2.6-3.6]) compared to placebo (2.6 cm[2.2-3.0]) group, p = 0.03. Surgeon's perception of procedure being "easy" (8/19[42.1] vs 9/22[40.9], respectively, p = 1.00) and complication rate (3/19[15.8%] vs 3/22[13.6], respectively, p = 1.00) did not differ. CONCLUSION: Our underpowered study did not demonstrate a difference in cervical dilator placement, but mifepristone 18 to 24 hours prior to dilators increases cervical dilation without increasing complications. IMPLICATIONS: Mifepristone 18 to 24 hours prior to cervical dilator placement may be a useful adjunct to cervical dilators based on increased cervical dilation at time of procedure; however, logistical barriers, such as an additional visit, may preclude routine adoption without definite clinical benefit.

Twelve-month prescribing of contraceptive pill, patch, and ring before and after a standardized electronic medical record order change.

OBJECTIVE: To evaluate the proportion of 12-month contraceptive pill, patch, and ring prescriptions before and after an institution-wide change of default electronic medical record facility orders to dispensing 12-month supply. STUDY DESIGN: This retrospective pre-post study compares outpatient contraception prescriptions from August 10, 2019 through April 9, 2020 obtained from our institutional electronic medical record prescription database. On December 10, 2019, we facilitated a change in the default orders for dispensing self-administered hormonal contraceptives from one-month to 12-months. We evaluated the primary outcome of 12-month supply prescriptions during the four months before and after the change. We also compared 12-month supply prescriptions for pills, patch, and ring by prescriber specialty and location. RESULTS: The dataset included 4897 distinct evaluable prescriptions for the pill, patch, or ring, with an overall increase in 12-month prescriptions from 260/2437 (10.7%) to 669/2460 (27.2%) after the order change (p < 0.001). Twelve-month pill prescriptions increased from 238/2250 (10.6%) to 607/2250 (27.0%) (p < 0.001), patch prescriptions from 6/40 (15.0%) to 21/44 (47.7%) (p = 0.002), and ring prescriptions from 16/147 (10.9%) to 41/165 (24.8%) (p = 0.001). Twelve-month prescriptions increased after the order change among all provider types at the medical center campus (194/594 [32.7%] to 329/623 [52.8%], p < 0.001). At community clinics, non-obstetrics/gynecology providers increased 12-month prescriptions after the order change (58/1616 [3.6%] to 327/1612 [20.3%], p < 0.001), but obstetrics/gynecology providers did not (8/227 [3.5%] to 13/225 [5.8%], p = 0.27). CONCLUSION: Providers more frequently prescribed a 12-month supply of contraceptive pills, patches, and rings after a change in the default dispensing quantity in electronic medical record orders. IMPLICATIONS: Institution-wide changes to the electronic medical record default facility order settings can increase 12-month supply contraceptive prescriptions. As a 12-month prescription order represents only one step of many in obtaining a 12-month contraception supply, additional research is required to elucidate and remove other potential barriers.

US referral center experience removing nonpalpable and difficult contraceptive implants with in-office ultrasonography: A case series.

OBJECTIVES: To assess referral center outcomes with removal of difficult or nonpalpable contraceptive implants using high-frequency point-of-care ultrasonography. STUDY DESIGN: We present a case series examining patients referred to our specialty center from January 2019 through September 2020 for difficult or nonpalpable implant removal. RESULTS: Of the 54 referrals, 6 had palpable implants and 48 required ultrasonography. We localized 46 (96%) implants in-office, including 13 located subfascially; 2 Implanon implants could not be localized. We successfully completed 50 (96%) of 52 attempted in-office removals, including 12 (92%) subfascial implants. CONCLUSION: High-frequency point-of-care ultrasonography can effectively localize nonpalpable contraceptive implants leading to successful in-office removal. IMPLICATIONS: Specialists can use high-frequency point-of-care ultrasonography to localize nonpalpable implants without formal radiology scans and skilled technologists, optimizing patient time and convenience. However, the probe is expensive, and providers may need to consider this cost in the context of reimbursement for these highly specialized procedures.

Progestin-only pill use over 6 months postpartum.

OBJECTIVES: To determine progestin-only pill (POP) use at 3 and 6 months postpartum among women who chose POPs at the postpartum visit. STUDY DESIGN: Secondary data analysis of a prospective observational study with telephone interviews at 3 and 6 months postpartum to assess contraceptive use. RESULTS: Of 440 women who attended the postpartum visit, 92 (20.9%) chose POPs. Current POP use was 44/84 (52.4%) at 3 months, 33/76 (43.4%) at 6 months, and 32/76 (42.1%) at both 3- and 6-month follow-up assessments. CONCLUSION: About half of women who plan POP use at the postpartum visit are not using this method at 3 months after delivery. IMPLICATIONS: About half of women with a prescription for progestin-only pills will be not using this method at 3 months postpartum; further understanding of continued sexual activity and breastfeeding may clarify pregnancy risk for those not reporting modern contraception use during the postpartum period.

Referral Center Experience With Nonpalpable Contraceptive Implant Removals.

OBJECTIVE: To describe our experience with office removal of nonpalpable contraceptive implants at our referral center. METHODS: We performed a retrospective cohort study by reviewing the charts of patients referred to our family planning specialty center for nonpalpable or complex contraceptive implant removal from January 2015 through December 2018. We localized nonpalpable implants using high-frequency ultrasonography and skin mapping in radiology, followed by attempted removal in the office using local anesthesia and a modified vasectomy clamp. We abstracted information on demographics, implant location, and outcomes. RESULTS: Of 61 referrals, 55 patients attended their scheduled appointments. Seven patients had palpable implants; six elected removal. The other 48 patients had ultrasound localization, which identified 47 (98%) of the implants; the remaining patient had successful localization with computed tomography imaging. Nonpalpable implants were suprafascial (n=22), subfascial (n=25) and intrafascial (n=1); four of these patients opted to delay removal. Of 50 attempted office removals, all palpable (n=6), all nonpalpable suprafascial (n=21 [100%, 95% CI 83-100%]), and 19 out of 23 (83%, 95% CI 67-98%) subfascial implants were successful. Three of the four patients with failed subfascial implant office removal had successful operating room removal with a collaborative orthopedic surgeon; the other patient sought removal elsewhere. Transient postprocedure neuropathic complaints were noted in 7 out of 23 (30%, 95% CI 12-49%) subfascial and 1 out of 21 (5%, 95% CI 0-13%) suprafascial removals (P=.048). Nonpalpable implants were more likely to be subfascial in nonobese patients (24/34, 71%) as compared with obese (1/13, 8%) patients (P<.001). Seven (28%) of the 25 subfascially located implants had been inserted during a removal-reinsertion procedure through the same incision. CONCLUSION: Most nonpalpable contraceptive implants can be removed in the office by an experienced subspecialty health care provider after ultrasound localization. Some patients may experience transient postprocedure neuropathic pain. Nonpalpable implants in thinner women are more likely to be in a subfascial location.

Home or office etonogestrel implant insertion after pregnancy: a randomized trial.

OBJECTIVES: To evaluate whether home visits for contraceptive implant insertion result in an increase in postpartum uptake compared to clinic insertion and to assess the feasibility of home insertions. STUDY DESIGN: We randomized women within 10 weeks of a birth or dilation and curettage (D&C) for abortion or miscarriage to home or standard office insertion. The primary outcome was successful insertion of the implant. To achieve 80% power to detect a 40% difference in visit attendance, 20 women were assigned to each group. The secondary outcome was attendance of the 4-week postpartum visit. RESULTS: From June 2013 through February 2014, we screened 45 women and 40 were randomly assigned to home and office insertion visits. We enrolled 37 postpartum women and 3 women post-D&C. Because of the significant under enrollment of the latter, we chose to report results of only the postpartum women. The results were similar whether we included or excluded post-abortion women. A majority of women desired a home visit for their implant insertion appointment at time of enrollment. Postpartum appointment attendance rates were similar between home and office visits at 53% and 50% (p=1.00), respectively. Home visits resulted in a trend toward increased implant uptake [12/19 (63%) vs 6/18 (33%), p=.10]. CONCLUSION: Home insertion of the contraceptive implant may be a feasible option. Future studies that examine the feasibility and uptake in both postpartum and post-D&C women are warranted. IMPLICATIONS: Women reported preference for home insertion visits in this pilot study. We also showed that a greater proportion of women received the etonogestrel implant at a home visit compared to the current standard of care, which may warrant larger studies that would have sufficient power to evaluate smaller differences.