 about sickle cell disease (SCD). As noted, life expectancy of patients with SCD now approximates 50 years of age, compared to 10 years of age in the 1970s. This major improvement in outcomes didn't spontaneously happen via genetic mutation or evolution.

It should be known in wider circles that such an improvement in patient outcomes and life expectancy of patients with SCD is primarily due to the yeoman, trailblazing work of 

, a Black female pediatrician who practiced in New York City. I was happy and honored to have had her as my pediatrician when I was  a little girl. I used to love to go to her office, smell the rubbing alcohol waft through the air and know that "she helped people feel better." She was instrumental in my becoming a physician.

 was the third Black female to graduate Yale School of Medicine (1952). She later became Chief of Pediatrics at Knickerbocker Hospital (which previously refused to admit or treat Black patients). She served in that capacity at other hospitals, including Mount Sinai St. Luke's Hospital in NYC, where in 1958, she became the first Black attending physician.

Wethers opened SCD programs at every hospital in which she practiced and was recognized among her peers and by legislative bodies. Her efforts led to New York being the first state to mandate testing for all children.

, Wethers was "renowned for research and advocacy that helped lead to mandatory testing of all newborns for sickle cell anemia."

Because SCD can be found not only in Blacks, in 1987 Dr. Wethers chaired a panel of the 

; "it recommended routine screening of all babies, regardless of race or ethnicity." As a result of Wethers' work, since 2006, 

I wish to recognize the exemplar work of my former pediatrician, Dr. Doris Wethers.

Founder & Medical Director, Atlanta Women's Health Care

Articles

Life expectancy of patients with SCD now approximates 50 years of age, compared to 10 years of age in the 1970s. This major improvement in outcomes didn't spontaneously happen.

Readers React: SCD and the work  of Dr. Doris Wethers

Magnetic resonance imaging (MRI) uses magnetic fields to provide detailed anatomic images that reflect distribution and magnetic properties of tissues (specifically of hydrogen nuclei in water and fat) to aid in diagnosis of many pathologic conditions. Gadolinium-based intravenous contrast agents (GBCA) provide additional information based on signal intensity changes after GBCA administration. GBCA are used in approximately 45% of MRI exams in the United States. In the 30 years since the first GBCA was introduced into clinical practice, almost a half billion enhanced MRI studies have been performed worldwide. In the field of gynecology, MRI is widely used to enhance detection of early breast cancers in women at elevated risk, or to better delineate complex pelvic anatomy in the setting of prior pelvic surgery, severe endometriosis, distorting fibroids, cervical, uterine cancer or ovarian cancer.

A recent concern with use of GBCA surfaced in 2014, when the link between permanent high T1 signal in the dentate nucleus and globus pallidus of the brain and repeated prior GBCA exposure was identified.

 Post-mortem analysis of these deep brain structures confirmed that gadolinium deposition in the brain of patients who had GBCA-enhanced MRI of any part of the body. Specifically, higher signal intensities were seen in patients who had undergone at least six contrast-enhanced MRI examinations compared to patients who had undergone only non-contrast MRI. Case reports in children noted the same pattern of gadolinium deposition as that seen in adult patients following GBCA.

Industry-sponsored studies in rats serially exposed to GBCA found progressively higher signal intensity on imaging, which correlated with post-mortem gadolinium concentrations in the brain.

 Notably, at the time of this writing, no human or animal data have shown any association between GBCA exposure and neurologic toxicity or neurological symptoms related to gadolinium deposition in the dentate nucleus of globus pallidus.

Ob/gyns need to be aware of the current data about gadolinium-based contrast and the potential implications of its use when they order MRI for their patients.


	In response to the reports of gadolinium deposition in the brain of GBCA-exposed individuals, the US Food and Drug Administration (

) required a new class warning and other safety measures for all GBCA for MRI in December 2017. Updates to GBCA labeling in May 2018 stated that GBCA was safe and should be used when medically necessary, and directed MRI centers to make educational information available to every outpatient the first time they receive GBCA.

 includes risk of gadolinium retention associated with the two types of GBCA (linear and macrocyclic) and indicates that linear GBCA appears to result in higher retention for longer periods of time than macrocyclic GBCA. Providers are encouraged to consider patient characteristics that may result in increased risk of gadolinium retention, and to minimize closely spaced or multiple GBCA MRI. 

Gulani and colleagues, on behalf of the International Society for Magnetic Resonance in Medicine (

) summarized the evidence and offered guidelines to clinicians in 

 They highlighted incomplete understanding of the clinical implications and mechanisms that drive gadolinium deposition, and discordant data comparing different types of gadolinium. The authors advised health care professionals to use caution when administering GBCA and to carefully document 

a specific GBCA is given to a patient. They did not endorse macrocyclic over linear GBCA, and suggested that patient and clinical factors in addition to pharmacokinetics of the available agents should guide selection of the best GBCA. The American College of Radiology independently endorsed the same recommendation.

 Finally, the ISMRM Summary urged ongoing research to elucidate clinical implications of gadolinium deposition. The Pharmacovigilance 

Risk Assessment Committee of the European Medicines Agency

 has proposed a ban on all linear agents. Radiologists from the 

 have recommended that use of macrocyclic rather than linear agents be considered, if possible.

Implications for MRI utilization in gynecology


	MRI imaging of the pelvis is indicated to further characterize masses seen on computed tomography (CT) or ultrasound. An MRI without contrast offers sensitivity comparable to CT with contrast and superior specificity in diagnosis of adnexal malignancy following an indeterminate ultrasound.

 MRI provides better assessment of soft tissue structures and improved localization of pelvic masses, which is useful to discriminate between ovarian and uterine pathology. T2-weighted imaging is helpful in determining whether the lesion is a unilocular cyst, mixed solid and cystic, or homogeneously solid. T1-weighted imaging without and with fat saturation allows for detection of adnexal lesions containing macroscopic fat. Fat-saturated T1-weighted imaging is useful for identifying ovarian endometriomas, extraovarian endometriosis, and other lesions with blood degradation products, such as hemorrhagic cysts.

 Adding contrast may allow better discrimination between benign and malignant pathology due to the kinetics of contrast enhancement and washout, although its use may vary by institutional MRI protocol. 

The incremental additional clinical information that is gained with use of GBCA in MRI evaluation of variant pelvic anatomy and suspected benign pathology is small. Adding GBCA has been shown to improve evaluation of myometrial invasion from endometrial carcinoma

 and identification of the correct primary tumor when there are multiple sites of biopsy-proven uterine adenocarcinoma.

 Contrast may also be useful in identifying vulvar cancers and occult inguinal metastases

 and it has shown to be useful in identifying neoplastic nodules within complex adnexal lesions and distinguishing endometriosis from pelvic inflammatory disease.

Breast cancer screening in high-risk women


	Intensive breast cancer surveillance is advised for women at the highest risk of breast cancer. Women with inherited genetic susceptibility due to 

 and other less well-known germline mutations (CHEK2, ATM, PALB2), family history, prior chest radiation (cumulative dose > 10 Gy before age 30), or calculated lifetime risk of breast cancer exceeding 20% or more are advised to start breast cancer screening between ages 25 and 30.

 While mammography remains the gold standard for breast cancer screening in the general population, it has been less successful in detection of early, curable cancers in higher-than-average-risk patients. Prospective studies of annual mammography in 

-positive women showed an interval cancer rate of 35% to 50% and the majority of invasive cancers were > 1 cm and 20% to 56% of them had lymph node involvement.

 Some factors cited to explain the poorer detection of 

-associated breast cancer may relate to the confounding effect of breast density, which is more common in younger women. Mammography relies upon abnormal tissue density, tissue distortion, and calcifications to identify breast cancers. 

-associated breast cancers tend to be less mammographically detectable than sporadic breast cancers, which has been attributed to their distinctive histologic growth patterns, such as pushing borders, the relative absence of associated ductal carcinoma in situ, and high cellularity.

In observational studies, adding contrast-enhanced MRI to annual mammography in BRCA mutation carriers significantly improved detection of early, treatable breast cancers with a combined sensitivity of 94% compared to 39% with mammography alone.

 MRI provides a functional assessment of breast tissue. Contrast- enhanced MRI can detect microvascular changes and peritumoral inflammation as the contrast accumulates rapidly, and is then washed out rapidly, in more vascular tumors compared to benign breast tissue. Consequently, annual contrast-based MRI has been incorporated into breast cancer surveillance guidelines for women at the highest risk of breast cancer.

There has been no change to the recommendation of annual breast MRI by the 

 due to the increased benefit of early detection of cancer in these high-risk patients.

 In view of the concerns raised over GBCA, macrocyclic agents are advised, and alternatives to conventional MRI imaging are being investigated. These include investigations of lower-dose gadolinium scans

 or alternative MRI contrast agents such as Feraheme (ferumoxytol an ultrasmall, superparamagnetic iron oxide nanoparticle), which is currently used for vascular imaging.

Some high-volume centers enriched with populations of BRCA mutation carriers have amended the recommended surveillance for women at high risk of breast cancer. Breast ultrasound may be alternated with annual MRI, in addition to annual mammography. Ongoing study of novel strategies to improve the mammogram, such as use of iodinated contrast and breast tomosynthesis, which creates a 3-D image of the breast by stacking multiple 2D mammographic renderings, are underway in women with BRCA mutations. Such advances may allow reduction in cumulative exposure to GBCA in these high-risk women.

Weighing risks and benefits in women at high risk


	While it’s discomforting to consider progressive accumulation of gadolinium in the body over time, the clinical consequences and level of risk associated with GBCA are, as yet, unknown. On the contrary, the consequences of missing an aggressive breast cancer are all too well known. In the absence of an effective non-gadolinium alternative to GBCA, until we have more definitive data on the true risk of gadolinium deposition, we forego surveillance of women at high risk of breast cancer with contrast-enhanced MRI at our peril. Best practice suggests that providers consider the necessity of contrast based upon clinical circumstances, and that macrocyclic rather than linear agents be used when necessary.

 Judicious use of gadolinium, coupled with vigilance in identifying women who might be pregnant, can minimize inadvertent fetal exposure to gadolinium, which is estimated to occur in 1 in 860 pregnancies in the United States.

The authors report no potential conflicts of interest with regard to this article.

Kanda T, Osawa High signal intensity in dentate nucleus on unenhanced T1 weighted MRI images: association with linear versus macrocyclic gadolinium chelate administration. 

Roberts DR, Holden KR. Progressive in of T1 signal intensity in the dentate and nucleus and globus pallidus on unenhanced T1-weighted MR images in the pediatric brain exposed to multiple doses of gadolinium contrast. 

Robert P, Lehericy S, Grand S, et al. T1 weighted images hypersignal in the deep cerebellar nuclei after repeated administrations of gadolinium-based contrast agents in healthy rats: difference between linear and macrocyclic agents. 

Terashima KH, Reich DS. Gadolinium deposition: practical guidelines in the face of uncertainty. 

FDA Safety Communication 5/16/2018 Update https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-warns-gadolinium-based-contrast-agents-gbcas-are-retained-body

Gulani V, Calamante FG, Shellock FG, et al. Gadolinium deposition in the brain: summary of evidence and recommendations 

American College of Radiology. Committee on Drugs and Contrast Media. ACR Manual on Contrast Media, Version 10.3. Available at https://www.acr.org/-/media/ACR/Files/Clinical-Resources/Contrast_Media.pdf Accessed April 10, 2018.

European Medicines Agency. PRAC concludes assessment of gadolinium agents used in body scans and recommends regulatory actions, including suspension of for some marketing authorizations. March 2017 Available at 

http://www.ema.europa.eu/docs/en_GB/documnent_library/Press_release/2017/03

Kinkel K, Lu Y, Mehdizade A, et al. Indeterminate ovarian mass at US: incremental value of second imaging test for characterization–meta-analysis and Bayesian analysis. 

Masch WR, Daye D and Lee SI. MRI imaging for incidental adnexal mass characterization. 

Ha HK, Lim YT, Kim HS, et al. Diagnosis of pelvic endometriosis: fat-suppressed T1-weighted vs conventional MR images. AJR 

Bazot M, Bharwani N, Huchon C, Kinkel K, et al. European society of urogenital radiology (ESUR) guidelines: MR imaging of pelvic endometriosis. 

Nougaret S, Horta M, Sala E, Lakhman Y, et al. Endometrial Cancer MRI staging: Updated Guidelines of the European Society of Urogenital Radiology. 

Vargas HA, Akin O, Zheng J, Moskowitz C, et al. The value of MR imaging when the site of uterine cancer origin is uncertain. 

Kataoka MY, Sala E, Baldwin P, et al. The accuracy of magnetic resonance imaging in staging of vulvar cancer: a retrospective multi-centre study. 

Suzuki S, Yasumoto M, Matsumoto R, Andoh A. MR findings of ruptured endometrial cyst: comparison with tubo-ovarian abscess. 

Tanaka YO, Okada S, Yagi T, et al. MRI of endometriotic cysts in association with ovarian carcinoma. 

Warner E, Plewes DB, Hill KA, et al. Surveillance of BRCA1 and BRCA2 mutation carriers with magnetic resonance imaging, ultrasound, mammography, and clinical breast examination. 

Monticciolo DL, Newell MS, Moy L, Niell B, Monsees B, Sickles EA. Breast cancer screening in women at higher-than-average risk: recommendations from the ACR. 

Brekelmans CTM, Saynaeve C, Bartels CC, et al. Effectiveness of breast cancer surveillance in BRCA1/2 gene mutation carriers and women with high familial risk. 

Warner E. Screening BRCA1 and BRCA2 mutation carriers for breast cancer. 

Lee JM, McMahon PM, Kong CY, et al. Cost-effectiveness of breast MR imaging and screen-film mammography for screening BRCA1 gene mutation carriers. 

Warner E Messersmith H, Causer P, et al. Systematic review: Using MRI to screen women at high risk of breast cancer. 

Daly MB. PIlarski R, Berry MP, Buys SS et al. Genetic/familial high risk assessment: breast and ovarian cancers. Version 2.2019. Available at 

https:///www.nccn.org/professionals/physician

Rowley H. To be alarmed or not to be alarmed over gadolinium contrast revelations: That is the question. European Congress in Radiology 2017 Annual Meeting. Available at 

BIRI Registry for Development and Validation of Novel MR Imaging Techniques, Cedars-Sinai Medical Center PI Dr Debaio Li (correspondence)

Shahrouki P, Moriarty JM, Khan SN, et al. High resolution, 3-dimensional Ferumoxytol-enhanced cardiovascular magnetic resonance venography in central venous occlusion. 

Bird S, Gelperin K, Sahin L et al. First-trimester exposure to gadolinium-based contrast agents: a utilization study of 4.6 million U.S. pregnancies. 

Concerns have been raised about the safety of GBCA. Experts review the latest data to support counseling of patients who may have repeated exposure.

Gadolinium-based contrast in breast MRI: What ob/gyns need to know

Uterine leiomyomas (fibroids) are benign smooth muscle neoplasms that affect up to 70% of women over their lifetime.

 They are the most common primary indication for hysterectomy and account for over $34 billion in health care costs annually in the United States.

 Common symptoms of fibroids include heavy or prolonged menstrual bleeding, pelvic pain, pressure-related symptoms, and bladder and bowel disturbance.

For the woman who wants to manage symptoms while maintaining her uterus or improve her fertility outcome, myomectomy has been considered the gold standard.

 However there are substantial risks to myomectomy with overall reported complications in surgeon-reported series of 3% to 16% and 25% in analysis of an insurance claims database.

 Common complications include hemorrhage and transfusion (5% risk), and damage to other organs requiring a subsequent procedure (25%).

 Also for women desiring future pregnancy, many myomectomy procedures commit women to a cesarean delivery in future pregnancies, further increasing surgical morbidity. 

In addition to complications, surgery can be expensive and require a significant recovery period with estimates from the literature of 15 to 30 days, and shorter recoveries in women who undergo endoscopic procedures.

 Moreover, because of the high rate of new fibroid formation, many women undergo multiple surgeries. Rates of reintervention with a second uterine-sparing procedure are 22% and with a hysterectomy are 16.7% with 5-year follow-up based on claims data.

 With our increasing knowledge of fibroid biological development and technological innovation, we now have multiple alternatives to traditional surgery, including medical and less invasive procedural management that will be considered here. The 

Agency for Healthcare Research and Quality

 recently produced a comprehensive evidence report on fibroid therapies which comprehensively assesses this topic.


	Combined estrogen/progestin and progestin-only oral contraceptives (OCs) have historically been seen as first-line therapy for fibroids due to their safety profile, low cost and reliable contraception. The levonorgestrel intrauterine system (LNG-IUS) is also being increasingly used for heavy or prolonged menstrual bleeding (AUB-L utilizing FIGO nomenclature); it also provides reliable contraception that does not require daily use. 

Surprisingly, high-quality data to support OCs or LNG-IUS for treatment of symptomatic fibroids are limited, as many studies do not have a proper comparison group.

 Observational data have demonstrated support for OCs. However, one randomized trial of 58 women demonstrated significantly decreased AUB-L in those treated with LNG-IUS when compared to OCs (mean menstrual blood loss decreased by 77.5% by extraction of blood from sanitary products and 34.5% by menstrual pictogram.

) Overall, we are still in need of better evidence demonstrating the superiority of contraceptive steroids.


	Although classically estradiol (E2) has been thought of as the key hormonal influence of fibroid pathophysiology, both scientific investigation and clinical use of progesterone receptor modulators (PRMs) for fibroid treatment now suggest that progesterone is the major hormonal influence.

In contrast to contraceptive steroids, PRMs have been studied in multiple randomized controlled trials (RCTs) and have shown moderate evidence for symptomatic relief, including reduction in fibroid size and decreased AUB-L and pain.

 Mifepristone and ulipristal acetate have been studied most commonly and there are 14 RCTs with more than 1200 participants demonstrating an improvement in quality of life.

 Thus, PRMs are widely used as first-line therapy outside the United States but are not approved by the US Food and Drug Administration (FDA).

While original reports focused safety concerns on endometrial changes following continuous use of PRMs, rare but serious liver injury has recently become the focus of safety with ulipristal acetate treatment as currently used in intermittent courses separated by shedding of the endometrium.

 had been issued by the European Medicines Agency (

) based on serious events involving the liver, in some cases requiring liver transplantation, occurring in approximately 1:100,000 women. This guidance requires screening women for liver dysfunction with both history and liver function tests before, during, and after treatment. Finally, the guidelines recommend restricting ulipristal acetate to one treatment course in women who are eligible for surgery.  

Gonadotropin-releasing hormone (GnRH) agonists/antagonists


	GnRH agonists exert their effect by having a higher potency and longer half-life than endogenous GnRH, which when used in a recurring manner leads to prolonged binding to its receptor.

 This initially leads to an increase in FSH and LH secretion from the anterior pituitary and subsequently a flare in estrogen production followed by suppression. GnRH agonists have shown a reduction in fibroid volume and improvement in AUB-L along with an improvement in quality of life.

 Concerns with long-term treatment with GnRH analogues stem from evidence showing a decrease in bone mass after 4 to 6 months of therapy along with significant hypoestrogenic side effects that include vasomotor symptoms, atrophic vaginitis, and insomnia, which occurs due to the hypothalamic-pituitary-ovarian axis blockade.

 The GnRH agonist leuprolide acetate is FDA-approved for short-term use in treatment of uterine fibroids in conjunction with iron for preoperative treatment. Add-back therapy with different modalities (raloxifene, conjugated estrogens, estriol) can be useful in preserving bone density but there is limited evidence that this leads to improvement in hypoestrogenic symptoms.

 In addition, after discontinuation of therapy, fibroid growth will typically resume, leading to a return in original size or beyond.

In contrast to GnRH agonists, GnRH antagonists exert their effect by competing for the GnRH receptor and thus have a more rapid onset without the initial flare. GnRH antagonists for fibroids demonstrated a significant reduction in tumor volume but require daily treatment.

 A new generation of oral GnRH antagonists used either alone or with hormonal add-back therapy is in clinical trials for treatment of uterine fibroids. A recent noninferiority trial demonstrated more rapid onset of amenorrhea with an oral GnRH antagonist (relugolix) and similar reductions in AUB-L and uterine volume when compared to leuprolide acetate.

 An RCT evaluating add-back therapy with a second oral GnRH antagonist (elagolix) demonstrated a continued reduction in AUB-L and add-back therapy reduced negative effects on bone mineral density.


	Uterine artery embolization (UAE) utilizes a single small incision in the groin and radiographic guidance of catheters and embolic agents to the uterine arteries bilaterally.  Thus multiple fibroids can be targeted simultaneously. UAE requires sedation and typically is performed as an overnight admission or same-day procedure. 

Multiple RCTs have demonstrated the efficacy of UAE in women with fibroids. The quality of evidence has been high for a significant volume reduction that continued for 5 years and improvements in AUB-L along with moderate evidence for an improvement in quality of life.

 When compared to hysterectomy and myomectomy, risk of transfusion with UAE was drastically reduced (OR 0.07, 95% CI, 0.01-0.52). Women undergoing UAE also recovered more rapidly and had fewer major complications, but more minor complications requiring no or nominal therapy, including overnight admission for observation, were noted when UAE was compared to hysterectomy but not when compared to myomectomy.

 In the RCT between UAE and hysterectomy, postembolization and vaginal discharge were the most frequent minor complication following UAE and infection and hemorrhage the most common following hysterectomy; the median length of stay was 1 day for UAE and 5 days for hysterectomy possibly affecting readmission for observation.

Concerns regarding UAE are associated with a higher rate of subsequent surgical intervention with estimates of 7% for myomectomy and hysterectomy versus 15% to 32% for UAE.

However, studies have not reported whether failures of UAE are due to concomitant diseases such as adenomyosis, which is also treated with hysterectomy but not uterine-sparing approaches. In a study based on insurance claims, the chance of a complication requiring a subsequent procedure was substantially higher following myomectomy compared to UAE in a propensity-matched group (24.6 vs. 18.1%, HR 1.38 (95% CI, 1.25-1.52).

Another concern of UAE is the potential impact on ovarian reserve, fertility, and pregnancy complications. A systematic review that compared obstetric outcomes in women following UAE to age-matched women with fibroids who did not undergo myomectomy reported an increased risk of miscarriage (OR 2.8, 95% CI, 2.0-3.8), cesarean delivery (OR 2.1, 95% CI, 1.4-2.9), and postpartum hemorrhage (OR 6.4, 95% CI, 3.5-11.7), but no difference in other obstetric outcomes.

 Studies have demonstrated there is no significant difference in ovarian failure rates at long-term follow-up and there is very-low-level evidence that there is a decrease in fertility following UAE compared to myomectomy.

 Finally, there are numerous reports of successful pregnancy following UAE and some national guidance recommending UAE for fertility preservation.


	High-intensity focused ultrasound ablation (HIFU) is a noninvasive method that uses ultrasound energy to create coagulative necrosis in a well-defined area through the anterior abdominal wall. HIFU can be performed under magnetic resonance imaging (MRI) or ultrasound guidance; however, only the device that uses MRI guidance is approved in the United States. Both procedures are performed on an outpatient basis with sedation and no incisions.

Overall, HIFU has been shown to be effective for decreasing fibroid size/volume.

 Recent investigation has shown that other important patient outcomes are also improved. A large cohort study compared 1353 women undergoing ultrasound-guided HIFU to hysterectomy (N=472) or myomectomy (N=586).

 Quality of life improved more quickly after HIFU compared to surgical intervention and HIFU had only 0.2% major adverse outcomes compared to 12.6% in the surgical cases (

 < 0.001). Despite multiple differences in patient demographics between the treatment groups, with the patients undergoing HIFU being younger, better educated, and wealthier compared to the surgery groups, the authors concluded there is less morbidity when patients undergo HIFU compared to surgery.

 A case control study analyzing approximately 10,000 women who underwent HIFU demonstrated successful rates of ablation with a mean volume ablation rate of 83.1% ± 15.6% (range, 25%-100%) for patients with fibroids.

 The authors found that with conscious sedation and analgesia there were minimal side effects and very few severe complications.

 Case series have documented successful pregnancy outcomes following MRgFUS.

The Fibroid Interventions: Reducing Symptoms Today and Tomorrow (

) study analyzed patients randomized into UAE or MRgFUS groups and a parallel group declining randomization.

 Both groups had improved fibroid symptoms and quality of life for up to 2 years but improvement was significantly better for women who underwent UAE and risk of needing another fibroid procedure was higher (HR 2.81, 95% CI, 1.01-7.79, 

Introduced in 1999, laparoscopic, intra-abdominal-guided radiofrequency ablation (RFA) is another surgical modality developed to be less invasive. Benefits of this procedure include ease of use as it does not require laparoscopic suturing and there is no dissemination of tissue in the abdomen, which can occur with laparoscopic hysterectomy/myomectomy. A RCT by Bruker et al. demonstrated a shorter hospital stay and decreased blood loss when comparing RFA to laparoscopic myomectomy.

 While this is an attractive option we have limited evidence about long-term outcomes for RFA and it still requires a laparoscopy. A transcervical, intrauterine sonography-guided RFA device has been studied and is approved for use outside the United States but is not FDA-approved.


	In the not too recent past, surgical intervention represented the only strategy for symptomatic and/or large fibroids. With our growing appreciation of high fibroid incidence and burden, we are continuing to develop less-invasive strategies to improve symptoms and patient quality of life. Overall, there is good evidence that demonstrates that GnRH agonists and PRMs result in reduction of fibroid volume and improvement in quality of life for women with fibroids. UAE has also been shown to reduce uterine and fibroid volume with improvement in quality of life with more data needed to verify the procedure’s safety in patients planning to conceive in the future. While OCs have been first-line therapy in the past, there is a paucity of data supporting their benefit and, therefore, other strategies should be explored. Lastly, HIFU has been shown to reduce fibroid volume but more rigorous studies are needed to determine long-term outcomes and assess fertility following treatment.

Stewart EA, Cookson CL, Gandolfo RA, Schulze-Rath R. Epidemiology of uterine fibroids: a systematic review. 

Merrill RM. Hysterectomy surveillance in the United States, 1997 through 2005. 

Cardozo ER, Clark AD, Banks NK, Henne NB, Stegmann BJ, Segars JH. The estimated annual cost of uterine leiomyomata in the United States. 

Ezzati M, Norian JM, Segars JH. Management of uterine fibroids in the patient pursuing assisted reproductive technologies. 

Hartmann KE, Fonnesbeck C, Surawicz T, et al. Management of uterine fibroids. Agency for Healthcare Research and Quality Evidence-Based Report. Rockville (MD). Available at: 

www.effectivehealthcare.ahrq.gov/reports/final.cfm

Borah BJ, Yao X, Laughlin-Tommaso SK, Heien HC, Stewart EA. Comparative effectiveness of uterine leiomyoma procedures using a large insurance claims database’ 

Sangkomkamhang US, Lumbiganon P, Laopaiboon M, Mol BW. Progestogens or progestogen-releasing intrauterine systems for uterine fibroids. 

Ishikawa HK, Ishi V, Serna A, Kakazu R, Bulun SE, Kurita T. Progesterone is essential for maintenance and growth of uterine leiomyoma, 

Murji A., Whitaker L, Chow TL, Sobel ML. Selective progesterone receptor modulators (SPRMs) for uterine fibroids, 

Tristan M, Orozco LJ, Steed A, Ramirez-Morera A, Stone P. Mifepristone for uterine fibroids. 

Moroni RM, Martins WP, Ferriani RA, et al. Add-back therapy with GnRH analogues for uterine fibroids. 

Perry CM, Brogden RN. Goserelin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in benign gynaecological disorders. 

Sinai Talaulikar V, Belli AM, Manyonda I. GnRH agonists: do they have a place in the modern management of fibroid disease? 

Osuga Y, Enya K, Kudou K, Tanimoto M, Hoshiai H. Oral gonadotropin-releasing hormone antagonist relugolix compared with leuprorelin injections for uterine leiomyomas: a randomized controlled trial. 

Carr BR, Stewart EA, Archer DF, et al. Elagolix alone or with add-back therapy in women with heavy menstrual bleeding and uterine leiomyomas: a randomized controlled trial. 

Gupta JK, Sinha A, Lumsden MA, Hickey M. ‘Uterine artery embolization for symptomatic uterine fibroids. 

Edwards RD, Moss JG, Lumsden MA, Wu O, Murray LS, Twaddle S, et al. Uterine artery embolization versus surgery for symptomatic uterine fibroids. 

Homer H, Saridogan E. ‘Uterine artery embolization for fibroids is associated with an increased risk of miscarriage. 

Shalina RI, Krasnova AS, Simukhina MA, Kubataeva AK. Uterine artery embolisation (UAE). Pregnancy, delivery and perinatal outcomes. 

Chen J, Li Y, Wang Z, et al. Evaluation of high-intensity focused ultrasound ablation for uterine fibroids: an IDEAL prospective exploration stud., 

Chen J, Chen W, Zhang L, et al. Safety of ultrasound-guided ultrasound ablation for uterine fibroids and adenomyosis: A review of 9988 cases. 

Zou J, Chen L, Wu C, Hu C, Xiong Y. Pregnancy outcomes in patients with uterine fibroids treated with ultrasound-guided high-intensity focused ultrasound. 

Rabinovici J, David M, Fukunishi K, et al. Pregnancy outcome after magnetic resonance-guided focused ultrasound surgery (MRgFUS) for conservative treatment of uterine fibroids. 

Laughlin-Tommaso S, Barnard EP, AbdElmagied AM, et al. FIRSTT study: randomized controlled trial of uterine artery embolization vs focused ultrasound surgery. 

Brucker SY, Hahn M, Kraemer D, Taran FA, Isaacson KB, Kramer B. ‘Laparoscopic radiofrequency volumetric thermal ablation of fibroids versus laparoscopic myomectomy’, 

Brolmann H M. Bongers JG, Garza-Leal J, et al The FAST-EU trial: 12-month clinical outcomes of women after intrauterine sonography-guided transcervical radiofrequency ablation of uterine fibroids. 

Experts provide an update on current and emerging drugs and procedures as an alternative to myomectomy for uterine leiomyomas.

Alternatives to traditional surgery for fibroids

A 56-year-old G2P2 presents with longstanding vulvar pain, difficulty swallowing, and pain and bleeding with intercourse. On vulvar examination, you see loss of the labia minora, fusion of the prepuce over the clitoris, and erosions around the introitus (

Click here for diagnosis, next step in evaluation, and discussion


	Based on this patient’s history and clinical examination, the most likely diagnosis is lichen planus (LP), a chronic inflammatory condition that can involve the skin, mucosa, scalp and nails.

 Vulvar LP is a subtype that involves the genital skin with or without involvement of the vagina. Women with vulvar LP may present with one of three subtypes-classic, papulosquamous, or erosive-and often present with complaints of itching, pain with intercourse, vaginal discharge, or bleeding. Some patients may be asymptomatic. The patient in this case represents the erosive subtype of vulvovaginal LP, which is the most common of the three. 


	LP is uncommon, often presenting in the 5

 decades of life, although it can be seen in younger and older women. The prevalence of LP is not well defined, given limited and often under-reporting of this condition. Current rates for LP in the literature are estimated to be between 0.01% and 3%,

 although prevalence data specific to vulvar lichen planus are unknown. One study of 37 women with cutaneous LP demonstrated a prevalence of 51% for vulvar involvement.


	While the exact etiology is not known, LP is defined as a chronic inflammatory condition that can involve the skin, scalp, mucosal surfaces, or nails. It is classified as an autoimmune condition with demonstrated cell-mediated autoimmunity.

 The proposed mechanism includes T-cell-mediated keratinocyte damage of the basal cell layer of the dermis.

 LP also is associated with other autoimmune diseases including thyroid disease, alopecia, and vitiligo.

 Patients with LP should be screened for other autoimmune diseases when clinically indicated. A significant association between hepatitis C and LP has also been reported in the international literature, although the relevance of this in North America is not clear.


	The clinical features vary based on subtype of vulvar LP. The classic or papular subtype most often presents with pruritus, but can be asymptomatic. On clinical examination you will see flat, papular lesions with a characteristic white, lacy pattern (Wickham’s striae). It is often seen in patients with cutaneous LP of other sites and can sometimes resolve spontaneously. Classic or papular LP does not typically cause scarring. The least common subtype is hypertrophic. Patients will typically complain of pruritus and the appearance is characterized by purple/red brown well-demarcated flat-topped shiny papules on keratinized skin.

 It is most common in the perineal and perianal area and does not involve the vagina.

 Biopsy is often required, as the plaque-like appearance can mimic other diagnoses. The most common vulvar subtype is erosive, which is seen in Figure 1. Patients will often complain of pain, including dyspareunia, or difficulties with urination. On examination you will see white, lacy papules or red erosions which may involve the vestibule (Figure 1) and vagina (Figure 2).

Erosions can lead to scarring, particularly in the vagina. Architectural changes with loss of tissue can also occur, as seen in Figure 1. Erosive LP can also involve other mucosal surfaces including urethral, oral (Figure 3) and esophageal mucosa. Vulvovaginal-gingival (VVG) syndrome is a specific erosive subtype involving each listed mucosal surface. Sites of involvement may not be concurrent, so history of prior site involvement or symptoms in those sites should be solicited.


	Clinical examination is crucial for diagnosis but biopsy may be helpful as well. When performing a biopsy, you should target areas of white reticular borders or erosion.

 If you are taking a biopsy in the area of an erosion, it is important to biopsy on the border of the erosion, including some normal skin.

 Tissue should be sent for H&E staining and also for immunofluorescence as often findings can be non-specific on histopathology.

 Of note, the specimen used for immunofluorescence should be sent fresh. In our clinic, we typically use Zeus Tissue Fixative. 

On H&E staining you will often see the following:

Thickening of the epidermis in a saw-toothed pattern

Band-like mononuclear infiltrate in the upper epidermis which hugs the dermal-epidermal junction and creates some areas of vacuolar degeneration of the basal cell layer (Figure 4)

Individual dyskeratotic keratinocytes within the epidermis 

On immunofluorescence, you will see irregular deposition of fibrinogen, IgM, cytoid bodies and occasionally granular IgG or IgA on staining of the basement membrane.

In 2013, diagnostic criteria for erosive lichen planus were created by electronic-Delphi consensus pooling of members of the International Society for the Study of Vulvovaginal Disease (ISSVD).

 Nine characteristics were identified with three of nine necessary to confirm the diagnosis (Table 1).


	The goals of treatment are to address symptoms and prevent disease progression.

 Typically papular or classic vulvar LP will respond to local treatments such as topical corticosteroids (e.g. triamcinolone 0.1% ointment or clobetasol 0.05% ointment).

What is your diagnosis when vulvar examination shows loss of the labia minora?

Vol 64 No 9

Readers React: SCD and the work of Dr. Doris Wethers

Gadolinium-based contrast in breast MRI: What ob/gyns need to know

Alternatives to traditional surgery for fibroids

Vulvar pain, difficulty swallowing, and bleeding with intercourse

Has gestational hypertension been banished?

Immediate postpartum LARC for women at high risk for medical complications

Substance use in the breastfeeding woman

When seven surgeries equal one lawsuit

Vaginal gel shows promise for recurrent BV

Urologic chronic pelvic pain syndrome and female sexual function

Age at menopause and type 2 diabetes

Does drug treatment work for obstetric cholestasis?

Diagnosing rectosigmoid endometriosis