Uterine Sparing Surgery for Severe Adenomyosis

MDEDGE.COM/OBGYN | VOL 31, NO 2 | FEBRUARY 2019 Offer most women labor induction by 41 weeks Robert L. Barbieri, MD

Uterine aspiration: From OR to of ce

New data on vaginal estrogen and chronic disease JoAnn V. Pinkerton, MD A member of the Network Uterine sparing surgery for severe adenomyosis

Camran Nezhat, MD, and colleagues

Oral vs transdermal estrogen: Is one route safer? Andrew M. Kaunitz, MD

Limb loss postcystectomy: $109M verdict

Update on fertility p. 18

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t e r o g o g r e d ns An

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EDITOR IN CHIEF Robert L. Barbieri, MD Chief, Department of Obstetrics and Gynecology Brigham and Women’s Hospital Kate Macy Ladd Professor of Obstetrics, Gynecology, and Reproductive Biology Harvard Medical School Boston, Massachusetts

BOARD OF EDITORS

Arnold P. Advincula, MD David G. Mutch, MD Vice Chair and Levine Family Professor of Women’s Health, Ira C. and Judith Gall Professor of Obstetrics and Gynecology, and Department of Obstetrics & Gynecology, Columbia University Vice Chair, Department of Obstetrics and Gynecology, Washington Medical Center; Chief of Gynecologic Specialty Surgery, University School of Medicine, St. Louis, Missouri Sloane Hospital for Women, New York-Presbyterian Hospital/ Columbia University, New York, New York Errol R. Norwitz, MD, PhD, MBA, Section Editor Chief Scienti c O cer, Tufts Medical Center; Louis E. Phaneuf Linda D. Bradley, MD Professor and Chairman, Department of Obstetrics & Gynecology, Professor of Surgery and Vice Chairman, Obstetrics, Gynecology, Tufts University School of Medicine, Boston, Massachusetts and Women’s Health Institute, and Vice Chair for Diversity and Inclusion for the Women’s Health Institute; and Director, Center for Menstrual Disorders, Fibroids, & Hysteroscopic Services, Cleveland JoAnn V. Pinkerton, MD, NCMP Clinic, Cleveland, Ohio Professor, Department of Obstetrics and Gynecology, and Director, Midlife Health, University of Virginia Health System, Amy L. Garcia, MD Charlottesville, Virginia; Executive Director, e North American Menopause Society, Pepper Pike, Ohio Medical Director, Garcia Sloan Centers; Center for Women’s Surgery; and Clinical Assistant Professor, Department of Obstetrics and Gynecology, John T. Repke, MD University of New Mexico, Albuquerque, New Mexico Professor Emeritus, Obstetrics and Gynecology, Penn State University College of Medicine, Hershey, Pennsylvania Steven R. Goldstein, MD, NCMP, CCD Professor, Department of Obstetrics and Gynecology, Joseph S. San lippo, MD, MBA New York University School of Medicine; Director, Gynecologic Professor, Department of Obstetrics, Gynecology, and Ultrasound, and Co-Director, Bone Densitometry, Reproductive Sciences, University of Pittsburgh; New York University Medical Center, New York, New York Academic Division Director, Reproductive Endocrinology and Infertility, Magee-Womens Hospital, Cheryl B. Iglesia, MD Pittsburgh, Pennsylvania Director, Section of Female Pelvic Medicine and Reconstructive Surgery, MedStar Health; James A. Simon, MD, CCD, IF, NCMP Professor, Departments of ObGyn and Urology, Clinical Professor, Department of Obstetrics and Gynecology, Georgetown University School of Medicine, Washington, DC George Washington University; Medical Director, IntimMedicine™ Specialists, Washington, DC Andrew M. Kaunitz, MD, NCMP, Section Editor University of Florida Term Professor and Associate Chairman, Department of Obstetrics and Gynecology, University of Florida College of Medicine-Jacksonville; Medical Director and Director of Menopause and Gynecologic Ultrasound Services, UF Women’s Health Specialists at Emerson, Jacksonville, Florida

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25 Commentary Intimate partner violence, guns, and the ObGyn KATHERINE KONIARES, MD, AND MEGAN L. EVANS, MD, MPH

38 Break This Practice Habit Uterine aspiration: From OR to of ce LAUREN THAXTON, MD, MBA, AND BRI TRISTAN, MD

52 Examining the Evidence Is vaginal estrogen used for GSM associated with a higher risk of CVD or cancer? JOANN V. PINKERTON, MD, NCMP

10 EDITORIAL How do you feel about expectantly managing a well-dated pregnancy past 41 weeks’ gestation? 28 ROBERT L. BARBIERI, MD A patient with severe 45 MEDICAL VERDICTS Woman loses hands and feet after cystectomy: adenomyosis requests $109M award

uterine-sparing surgery 48 PRODUCT UPDATE Combined laparoscopy and minilaparotomy is the Bijuva, Liletta extended use, endometrial ablation authors’ preferred technique. It can relieve many technology, new fertility app symptoms of adenomyosis with a low complication rate, and preserve, even improve, fertility 49 OBG MARKETPLACE CAMRAN NEZHAT, MD; MICHELLE A. WOOD, DO; The of cial job board of OBG MANAGEMENT MEGAN KENNEDY BURNS, MD, MA; AND AZADEH NEZHAT, MD

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Table 2: Bleeding Patterns Using the Non-Radiopaque Etonogestrel Implant (IMPLANON) During the First 2 Years of Use* Bleeding Patterns De¤nitions %† BRIEF SUMMARY (For full Prescribing Information, see package insert.) Infrequent Less than three bleeding and/or spotting episodes in 33.6 Women should be informed that this product does not protect against HIV infection (the virus 90 days (excluding amenorrhea) that causes AIDS) or other sexually transmitted diseases. Amenorrhea No bleeding and/or spotting in 90 days 22.2 INDICATION AND USAGE NEXPLANON is indicated for use by women to prevent pregnancy. Prolonged Any bleeding and/or spotting episode lasting more than 17.7 DOSAGE AND ADMINISTRATION 14 days in 90 days The efcacy of NEXPLANON does not depend on daily, weekly or monthly administration. All healthcare Frequent More than 5 bleeding and/or spotting episodes in 90 days 6.7 providers should receive instruction and training prior to performing insertion and/or removal of NEXPLANON. A single NEXPLANON implant is inserted subdermally in the upper arm. To reduce the risk of neural * Based on 3315 recording periods of 90 days duration in 780 women, excluding the rst 90 days or vascular injury, the implant should be inserted at the inner side of the non-dominant upper arm after implant insertion about 8-10 cm (3-4 inches) above the medial epicondyle of the humerus. The implant should be † % = Percentage of 90-day intervals with this pattern inserted subdermally just under the skin, avoiding the sulcus (groove) between the biceps and triceps In case of undiagnosed, persistent, or recurrent abnormal vaginal bleeding, appropriate measures muscles and the large blood vessels and nerves that lie there in the neurovascular bundle deeper should be conducted to rule out malignancy. in the subcutaneous tissues. An implant inserted more deeply than subdermally (deep insertion) 3. Ectopic Pregnancies may not be palpable and the localization and/or removal can be difcult or impossible [see Dosage and Administration and Warnings and Precautions]. NEXPLANON must be inserted by the expiration As with all progestin-only contraceptive products, be alert to the possibility of an ectopic date stated on the packaging. NEXPLANON is a long-acting (up to 3 years), reversible, hormonal pregnancy among women using NEXPLANON who become pregnant or complain of contraceptive method. The implant must be removed by the end of the third year and may be replaced lower abdominal pain. Although ectopic pregnancies are uncommon among women using by a new implant at the time of removal, if continued contraceptive protection is desired. NEXPLANON, a pregnancy that occurs in a woman using NEXPLANON may be more likely to be ectopic than a pregnancy occurring in a woman using no contraception. CONTRAINDICATIONS 4. Thrombotic and Other Vascular Events NEXPLANON should not be used in women who have • Known or suspected pregnancy The use of combination hormonal contraceptives (progestin plus estrogen) increases the • Current or past history of thrombosis or thromboembolic disorders risk of vascular events, including arterial events (strokes and myocardial infarctions) or deep • Liver tumors, benign or malignant, or active liver disease venous thrombotic events (venous thromboembolism, deep venous thrombosis, retinal vein • Undiagnosed abnormal genital bleeding thrombosis, and pulmonary embolism). NEXPLANON is a progestin-only contraceptive. It is • Known or suspected breast cancer, personal history of breast cancer, or other progestin-sensitive unknown whether this increased risk is applicable to etonogestrel alone. It is recommended, cancer, now or in the past however, that women with risk factors known to increase the risk of venous and arterial • Allergic reaction to any of the components of NEXPLANON [see Adverse Reactions] thromboembolism be carefully assessed. There have been postmarketing reports of serious arterial and venous thromboembolic events, including cases of pulmonary emboli (some WARNINGS AND PRECAUTIONS fatal), deep vein thrombosis, myocardial infarction, and strokes, in women using etonogestrel The following information is based on experience with the etonogestrel implants (IMPLANON ® implants. NEXPLANON should be removed in the event of a thrombosis. [etonogestrel implant] and/or NEXPLANON), other progestin-only contraceptives, or experience with combination (estrogen plus progestin) oral contraceptives. Due to the risk of thromboembolism associated with pregnancy and immediately following 1. Complications of Insertion and Removal delivery, NEXPLANON should not be used prior to 21 days postpartum. Women with a history of NEXPLANON should be inserted subdermally so that it is palpable after insertion, and this should be thromboembolic disorders should be made aware of the possibility of a recurrence. Evaluate for conrmed by palpation immediately after insertion. Failure to insert NEXPLANON properly may go retinal vein thrombosis immediately if there is unexplained loss of vision, proptosis, diplopia, unnoticed unless it is palpated immediately after insertion. Undetected failure to insert the implant papilledema, or retinal vascular lesions. Consider removal of the NEXPLANON implant in case may lead to an unintended pregnancy. Complications related to insertion and removal procedures, of long-term immobilization due to surgery or illness. such as pain, paresthesias, bleeding, hematoma, scarring or infection, may occur. 5. Ovarian Cysts If NEXPLANON is inserted deeply (intramuscular or in the fascia), neural or vascular injury If follicular development occurs, atresia of the follicle is sometimes delayed, and the follicle may occur. To reduce the risk of neural or vascular injury, NEXPLANON should be inserted at may continue to grow beyond the size it would attain in a normal cycle. Generally, these the inner side of the non-dominant upper arm about 8-10 cm (3-4 inches) above the medial enlarged follicles disappear spontaneously. On rare occasion, surgery may be required. epicondyle of the humerus. NEXPLANON should be inserted subdermally just under the skin 6. Carcinoma of the Breast and Reproductive Organs avoiding the sulcus (groove) between the biceps and triceps muscles and the large blood vessels and nerves that lie there in the neurovascular bundle deeper in the subcutaneous tissues. Deep Women who currently have or have had breast cancer should not use hormonal contraception insertions of NEXPLANON have been associated with paraesthesia (due to neural injury), because breast cancer may be hormonally sensitive [see Contraindications]. Some studies migration of the implant (due to intramuscular or fascial insertion), and intravascular insertion. suggest that the use of combination hormonal contraceptives might increase the incidence of If infection develops at the insertion site, start suitable treatment. If the infection persists, the breast cancer; however, other studies have not conrmed such ndings. Some studies suggest implant should be removed. Incomplete insertions or infections may lead to expulsion. that the use of combination hormonal contraceptives is associated with an increase in the risk Implant removal may be difcult or impossible if the implant is not inserted correctly, is of cervical cancer or intraepithelial neoplasia. However, there is controversy about the extent to inserted too deeply, not palpable, encased in brous tissue, or has migrated. which these ndings are due to differences in sexual behavior and other factors. Women with a There have been reports of migration of the implant within the arm from the insertion site, family history of breast cancer or who develop breast nodules should be carefully monitored. which may be related to deep insertion. There also have been postmarketing reports of 7. Liver Disease implants located within the vessels of the arm and the pulmonary artery, which may be related Disturbances of liver function may necessitate the discontinuation of hormonal contraceptive use to deep insertions or intravascular insertion. In cases where the implant has migrated to the until markers of liver function return to normal. Remove NEXPLANON if jaundice develops. Hepatic pulmonary artery, endovascular or surgical procedures may be needed for removal. adenomas are associated with combination hormonal contraceptives use. An estimate of the If at any time the implant cannot be palpated, it should be localized and removal is recommended. attributable risk is 3.3 cases per 100,000 for combination hormonal contraceptives users. It is not Exploratory surgery without knowledge of the exact location of the implant is strongly known whether a similar risk exists with progestin-only methods like NEXPLANON. The progestin discouraged. Removal of deeply inserted implants should be conducted with caution in order in NEXPLANON may be poorly metabolized in women with liver impairment. Use of NEXPLANON in to prevent injury to deeper neural or vascular structures in the arm and be performed by women with active liver disease or liver cancer is contraindicated [see Contraindications]. healthcare providers familiar with the anatomy of the arm. If the implant is located in the 8. Weight Gain chest, healthcare providers familiar with the anatomy of the chest should be consulted. Failure In clinical studies, mean weight gain in U.S. non-radiopaque etonogestrel implant (IMPLANON) to remove the implant may result in continued effects of etonogestrel, such as compromised users was 2.8 pounds after one year and 3.7 pounds after two years. How much of the weight gain fertility, ectopic pregnancy, or persistence or occurrence of a drug-related adverse event. was related to the non-radiopaque etonogestrel implant is unknown. In studies, 2.3% of the users 2. Changes in Menstrual Bleeding Patterns reported weight gain as the reason for having the non-radiopaque etonogestrel implant removed. After starting NEXPLANON, women are likely to have a change from their normal menstrual 9. Elevated Blood Pressure bleeding pattern. These may include changes in bleeding frequency (absent, less, more frequent or continuous), intensity (reduced or increased) or duration. In clinical trials of the Women with a history of hypertension-related diseases or renal disease should be discouraged non-radiopaque etonogestrel implant (IMPLANON), bleeding patterns ranged from amenorrhea from using hormonal contraception. For women with well-controlled hypertension, use of (1 in 5 women) to frequent and/or prolonged bleeding (1 in 5 women). The bleeding pattern NEXPLANON can be considered. Women with hypertension using NEXPLANON should be experienced during the rst three months of NEXPLANON use is broadly predictive of the future closely monitored. If sustained hypertension develops during the use of NEXPLANON, or if bleeding pattern for many women. Women should be counseled regarding the bleeding pattern a signicant increase in blood pressure does not respond adequately to antihypertensive changes they may experience so that they know what to expect. Abnormal bleeding should be therapy, NEXPLANON should be removed. evaluated as needed to exclude pathologic conditions or pregnancy. 10. Gallbladder Disease In clinical studies of the non-radiopaque etonogestrel implant, reports of changes in bleeding Studies suggest a small increased relative risk of developing gallbladder disease among pattern were the most common reason for stopping treatment (11.1%). Irregular bleeding (10.8%) combination hormonal contraceptive users. It is not known whether a similar risk exists with was the single most common reason women stopped treatment, while amenorrhea (0.3%) was progestin-only methods like NEXPLANON. cited less frequently. In these studies, women had an average of 17.7 days of bleeding or spotting 11. Carbohydrate and Lipid Metabolic Effects every 90 days (based on 3,315 intervals of 90 days recorded by 780 patients). The percentages of patients having 0, 1-7, 8-21, or >21 days of spotting or bleeding over a 90-day interval while Use of NEXPLANON may induce mild insulin resistance and small changes in glucose using the non-radiopaque etonogestrel implant are shown in Table 1. concentrations of unknown clinical signicance. Carefully monitor prediabetic and diabetic women using NEXPLANON. Women who are being treated for hyperlipidemia should be Table 1: Percentages of Patients With 0, 1-7, 8-21, or >21 Days of Spotting or Bleeding Over followed closely if they elect to use NEXPLANON. Some progestins may elevate LDL levels and a 90-Day Interval While Using the Non-Radiopaque Etonogestrel Implant (IMPLANON) may render the control of hyperlipidemia more difcult. Total Days of Percentage of Patients 12. Depressed Mood Spotting or Bleeding Treatment Days Treatment Days Treatment Days Women with a history of depressed mood should be carefully observed. Consideration should 91-180 271-360 631-720 be given to removing NEXPLANON in patients who become signicantly depressed. (N = 745) (N = 657) (N = 547) 13. Return to Ovulation 0 Days 19% 24% 17% In clinical trials with the non-radiopaque etonogestrel implant (IMPLANON), the etonogestrel 1-7 Days 15% 13% 12% levels in blood decreased below sensitivity of the assay by one week after removal of the 8-21 Days 30% 30% 37% implant. In addition, pregnancies were observed to occur as early as 7 to 14 days after removal. >21 Days 35% 33% 35% Therefore, a woman should re-start contraception immediately after removal of the implant if Bleeding patterns observed with use of the non-radiopaque etonogestrel implant for up to 2 years, and continued contraceptive protection is desired. the proportion of 90-day intervals with these bleeding patterns, are summarized in Table 2. 14. Fluid Retention Substances increasing the plasma concentrations of HCs: Co-administration of certain HCs and Hormonal contraceptives may cause some degree of uid retention. They should be prescribed strong or moderate CYP3A4 inhibitors such as itraconazole, voriconazole, uconazole, grapefruit with caution, and only with careful monitoring, in patients with conditions which might be juice, or ketoconazole may increase the serum concentrations of progestins, including etonogestrel. aggravated by uid retention. It is unknown if NEXPLANON causes uid retention. Human Immunodeciency Virus (HIV)/Hepatitis C Virus (HCV) protease inhibitors and non- 15. Contact Lenses nucleoside reverse transcriptase inhibitors: Signi cant changes (increase or decrease) in the Contact lens wearers who develop visual changes or changes in lens tolerance should be plasma concentrations of progestin have been noted in cases of co-administration with HIV protease assessed by an ophthalmologist. inhibitors (decrease [e.g., nel navir, ritonavir, darunavir/ritonavir, (fos)amprenavir/ritonavir, lopinavir/ 16. In Situ Broken or Bent Implant ritonavir, and tipranavir/ritonavir] or increase [e.g., indinavir and atazanavir/ritonavir])/HCV protease There have been reports of broken or bent implants while in the patient’s arm. Based on in inhibitors (decrease [e.g., boceprevir and telaprevir]) or with non-nucleoside reverse transcriptase vitro data, when an implant is broken or bent, the release rate of etonogestrel may be slightly inhibitors (decrease [e.g., nevirapine, efavirenz] or increase [e.g., etravirene]). These changes may be increased. When an implant is removed, it is important to remove it in its entirety [see Dosage clinically relevant in some cases. Consult the prescribing information of anti-viral and anti-retroviral and Administration]. concomitant medications to identify potential interactions. 17. Monitoring Effects of Hormonal Contraceptives on Other Drugs A woman who is using NEXPLANON should have a yearly visit with her healthcare provider for Hormonal contraceptives may affect the metabolism of other drugs. Consequently, plasma a blood pressure check and for other indicated health care. concentrations may either increase (for example, cyclosporine) or decrease (for example, lamotrigine). 18. Drug-Laboratory Test Interactions Consult the labeling of all concurrently-used drugs to obtain further information about interactions Sex hormone-binding globulin concentrations may be decreased for the rst six months after with hormonal contraceptives or the potential for enzyme alterations. NEXPLANON insertion followed by gradual recovery. Thyroxine concentrations may initially be USE IN SPECIFIC POPULATIONS slightly decreased followed by gradual recovery to baseline. 1. Pregnancy ADVERSE REACTIONS Risk Summary In clinical trials involving 942 women who were evaluated for safety, change in menstrual bleeding NEXPLANON is contraindicated during pregnancy because there is no need for pregnancy patterns (irregular menses) was the most common adverse reaction causing discontinuation of use prevention in a woman who is already pregnant [see Contraindications]. Epidemiologic studies of the non-radiopaque etonogestrel implant (IMPLANON® [etonogestrel implant]) (11.1% of women). and meta-analyses have not shown an increased risk of genital or non-genital birth defects Adverse reactions that resulted in a rate of discontinuation of ≥1% are shown in Table 3. (including cardiac anomalies and limb-reduction defects) following maternal exposure to Table 3: Adverse Reactions Leading to Discontinuation of Treatment in 1% or More low dose CHCs prior to conception or during early pregnancy. No adverse development of Subjects in Clinical Trials of the Non-Radiopaque Etonogestrel Implant (IMPLANON) outcomes were observed in pregnant rats and rabbits with the administration of etonogestrel during organogenesis at doses of 315 or 781 times the anticipated human dose (60 μg/day). Adverse Reactions All Studies N = 942 NEXPLANON should be removed if maintaining a pregnancy. 2. Nursing Mothers Bleeding Irregularities* 11.1% Lactation Emotional Lability† 2.3% Risk Summary Small amounts of contraceptive steroids and/or metabolites, including etonogestrel are present Weight Increase 2.3% in human milk. No signi cant adverse effects have been observed in the production or quality Headache 1.6% of breast milk, or on the physical and psychomotor development of breastfed infants. Hormonal contraceptives, including etonogestrel, can reduce milk production in breastfeeding mothers. Acne 1.3% This is less likely to occur once breastfeeding is well-established; however, it can occur at Depression‡ 1.0% any time in some women. When possible, advise the nursing mother about both hormonal and non-hormonal contraceptive options, as steroids may not be the initial choice for these patients. * Includes “frequent”, “heavy”, “prolonged”, “spotting”, and other patterns of bleeding irregularity. The developmental and health bene ts of breastfeeding should be considered along with the † Among US subjects (N=330), 6.1% experienced emotional lability that led to discontinuation. mother’s clinical need for NEXPLANON and any potential adverse effects on the breastfed child ‡ Among US subjects (N=330), 2.4% experienced depression that led to discontinuation. from NEXPLANON or from the underlying maternal condition. Other adverse reactions that were reported by at least 5% of subjects in the non-radiopaque 3. Pediatric Use etonogestrel implant clinical trials are listed in Table 4. Safety and ef cacy of NEXPLANON have been established in women of reproductive age. Table 4: Common Adverse Reactions Reported by ≥5% of Subjects in Clinical Trials Safety and ef cacy of NEXPLANON are expected to be the same for postpubertal adolescents. With the Non-Radiopaque Etonogestrel Implant (IMPLANON) However, no clinical studies have been conducted in women less than 18 years of age. Use of this product before menarche is not indicated. All Studies Adverse Reactions 4. Geriatric Use N = 942 This product has not been studied in women over 65 years of age and is not indicated in this population. Headache 24.9% 5. Hepatic Impairment Vaginitis 14.5% No studies were conducted to evaluate the effect of hepatic disease on the disposition of NEXPLANON. The use of NEXPLANON in women with active liver disease is contraindicated Weight increase 13.7% [see Contraindications]. Acne 13.5% 6. Overweight Women Breast pain 12.8% The effectiveness of the etonogestrel implant in women who weighed more than 130% Abdominal pain 10.9% of their ideal body weight has not been de ned because such women were not studied in clinical trials. Serum concentrations of etonogestrel are inversely related to body weight and Pharyngitis 10.5% decrease with time after implant insertion. It is therefore possible that NEXPLANON may be Leukorrhea 9.6% less effective in overweight women, especially in the presence of other factors that decrease In uenza-like symptoms 7.6% serum etonogestrel concentrations such as concomitant use of hepatic enzyme inducers. Dizziness 7.2% OVERDOSAGE Overdosage may result if more than one implant is inserted. In case of suspected overdose, the Dysmenorrhea 7.2% implant should be removed. Back pain 6.8% NONCLINICAL TOXICOLOGY Emotional lability 6.5% In a 24-month carcinogenicity study in rats with subdermal implants releasing 10 and 20 mcg Nausea 6.4% etonogestrel per day (equal to approximately 1.8-3.6 times the systemic steady state exposure in women using NEXPLANON), no drug-related carcinogenic potential was observed. Etonogestrel was Pain 5.6% not genotoxic in the in vitro Ames/Salmonella reverse mutation assay, the chromosomal aberration Nervousness 5.6% assay in Chinese hamster ovary cells or in the in vivo mouse micronucleus test. Fertility in rats Depression 5.5% returned after withdrawal from treatment. PATIENT COUNSELING INFORMATION Hypersensitivity 5.4% See FDA-Approved Patient Labeling. • Counsel women about the insertion and removal procedure of the NEXPLANON implant. Provide the Insertion site pain 5.2% woman with a copy of the Patient Labeling and ensure that she understands the information in the Patient Labeling before insertion and removal. A USER CARD and consent form are included in the In a clinical trial of NEXPLANON, in which investigators were asked to examine the implant site after packaging. Have the woman complete a consent form and retain it in your records. The USER CARD insertion, implant site reactions were reported in 8.6% of women. Erythema was the most frequent should be lled out and given to the woman after insertion of the NEXPLANON implant so that she implant site complication, reported during and/or shortly after insertion, occurring in 3.3% of subjects. will have a record of the location of the implant in the upper arm and when it should be removed. Additionally, hematoma (3.0%), bruising (2.0%), pain (1.0%), and swelling (0.7%) were reported. • Counsel women to contact their healthcare provider immediately if, at any time, they are unable to Effects of Other Drugs on Hormonal Contraceptives palpate the implant. Substances decreasing the plasma concentrations of hormonal contraceptives (HCs) and • Counsel women that NEXPLANON does not protect against HIV or other STDs. potentially diminishing the efcacy of HCs: Drugs or herbal products that induce certain enzymes, • Counsel women that the use of NEXPLANON may be associated with changes in their normal including cytochrome P450 3A4 (CYP3A4), may decrease the plasma concentrations of HCs and menstrual bleeding patterns so that they know what to expect. potentially diminish the effectiveness of HCs or ncrease breakthrough bleeding. Manufactured for: Merck Sharp & Dohme Corp., a subsidiary of Some drugs or herbal products that may decrease the effectiveness of HCs include efavirenz, phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, topiramate, MERCK & CO., INC., Whitehouse Station, NJ 08889, USA. rifabutin, ru namide, aprepitant, and products containing St. John’s wort. Interactions between HCs For more detailed information, please read the Prescribing Information. and other drugs may lead to breakthrough bleeding and/or contraceptive failure. Counsel women to use an alternative non-hormonal method of contraception or a back-up method when enzyme inducers are USPI-MK8415-IPTX-1705r019 Revised: 05/17 used with HCs, and to continue back-up non-hormonal contraception for 28 days after discontinuing the enzyme inducer to ensure contraceptive reliability. Copyright © 201Merck Sharp & Dohme B.V., a subsidiary of Merck & Co., Inc. All rights reserved. 80./ EDITORIAL

How do you feel about expectantly managing a well-dated pregnancy past 41 weeks’ gestation? Most women with a well-dated pregnancy should be offered the option of induction of labor before or at 41 weeks’ gestation

Robert L. Barbieri, MD Editor in Chief, OBG MANAGEMENT Chair, Obstetrics and Gynecology Brigham and Women’s Hospital, Boston, Massachusetts Kate Macy Ladd Professor of Obstetrics, Gynecology and Reproductive Biology Harvard Medical School, Boston

ost people know that a greater rate of fetal and newborn ical trial, 3,407 women with low-risk preterm birth is a major morbidity and mortality.1 pregnancy were randomly assigned M contributor to perinatal e fetal and newborn benets of to induction of labor at 41 weeks’ morbidity and mortality. Conse- delivery, rather than expectant man- gestation or expectant management, quently, strict guidelines have been agement, at term include: a decrease awaiting the onset of labor with serial enforced to prevent non–medi- in stillbirth and perinatal death rates, antenatal monitoring (nonstress tests cally indicated scheduled deliveries a decrease in admissions to the neo- and assessment of amniotic uid vol- before 39 weeks’ gestation. Fewer natal intensive care unit (NICU), a ume).4 e CD rate was lower among people recognize that late-term birth decrease in meconium-stained amni- the women randomized to induc- is also an important and avoidable otic uid and meconium aspiration tion of labor at 41 weeks’ (21.2% vs contributor to perinatal morbidity. syndrome, a decrease in low Apgar 24.5% in the expectant management To improve pregnancy outcomes, scores, and a decrease in problems group, P = .03). e rate of meco- we may need enhanced guidelines related to uteroplacental insu- nium-stained uid was lower in the about minimizing expectant man- ciency, including oligohydramnios.2 induction of labor group (25.0% vs agement of pregnancy beyond 41 In a comprehensive meta-analysis, 28.7%, P = .009). e rate of CD due weeks’ gestation. induction of labor at or beyond term to fetal distress also was lower in the reduced the risk of perinatal death or induction of labor group (5.7% vs For the fetus, what is the stillbirth by 67%, the risk of a 5-minute 8.3%, P = .003). e risks of maternal optimal duration of a healthy Apgar score below 7 by 30%, and the postpartum hemorrhage, sepsis, and pregnancy? risk of NICU admission by 12%.2 e endometritis did not dier between When pregnancy progresses past number of women that would need the groups. ere were 2 stillbirths the date of the connement, the risk to be induced to prevent 1 perinatal in the expectant management group of fetal or newborn injury or death death was estimated to be 426.2 (2/1,706) and none in the induction increases, especially after 41 weeks’ of labor group (0/1,701). ere were gestation. Analysis of this risk, day by Maternal benets of avoiding no neonatal deaths in this study.4 day, suggests that after 40 weeks’ and late-term pregnancy Obstetric management, includ- 3 days’ gestation there is no medical e maternal benets of avoiding accurate dating of pregnancy and benet to the fetus to remain in utero ing continuing a pregnancy past 41 membrane sweeping at term, can because, compared with induced weeks’ gestation include a reduc- help to reduce the risk that a preg- delivery, expectant management tion in labor dystocia and the risk of nancy will progress beyond 41 weeks’ of the pregnancy is associated with cesarean delivery (CD).2,3 In one clin- gestation.5

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10 OBG Management | February 2019 | Vol. 31 No.21 mdedge.com/obgyn

Editorial 0219.indd 10 2/4/19 3:08 PM Enhancing patient outcomes, managing costs, and optimizing delivery of care.

The value of care: VAGINITIS TESTING

LabCorp’s NuSwab® portfolio combines cost-eective, clinically relevant, research-driven testing with the convenience of a single-swab collection and is a targeted approach to testing for bacterial vaginosis, yeast (Candida), and four common STDs.

Amplied molecular target testing (NuSwab) has been shown to exceed non-amplied testing by: • Identifying an additional 20-25% of symptomatic patients with suspected vulvovaginitis (VV). Which in turn helps:

• Lower odds of preterm labor or delivery for symptomatic pregnant patients by 15%

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• Lower odds of all-cause hospitalization by 22%

Value beyond testing.

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1. Ackerman SJ, Wahl PM, Knight T, Cartwright, CP. Healthcare Resource Utilization and Costs of Amplied Versus Non-amplied Molecular Probe Testing for Vaginitis/Vaginosis: A U. S. Commercial Payer Perspective. LabCorp.

CONTINUED FROM PAGE 10

Routinely use ultrasound to accurately establish gestational age First trimester ultrasound should be oered to all pregnant women because it is a more accurate assessment of gestational age and will result in fewer pregnancies that are thought to be at or beyond 41 weeks’ gestation.5 In a meta-analysis of 8 studies, including 25,516 women, early ultrasonography reduced the rate of intervention for postterm pregnancy by 42% (31/1,000 to 18/1,000 pregnant women).6

Membrane sweeping (or stripping) Membrane sweeping, which causes the release of prostaglandins, has been reported to reduce the risk of late-term and postterm induction of study of women planning a trial of one nger in the cervix and rotate labor. 7,8 In the most recent Cochrane labor after CD, membrane sweeping the nger in a circle to separate the review on the topic, sweeping mem- did not impact the duration of preg- amnion from the cervix. branes reduced the rate of induction nancy, onset of spontaneous labor, or 4. After the procedure. Provide the of labor at 41 weeks by 41% and at 42 the CD rate.12 woman with a sanitary pad and weeks by 72%.7 To avoid one induc- Steps from an expert. A skillfull mid- recommend acetaminophen and tion of labor for late-term or postterm wife practicing in the United King- a warm bath if she has discomfort pregnancy, sweeping of membranes dom provides the following guidance or painful contractions. Advise her would need to be performed on 8 on how to perform membrane to come to the maternity unit in the women. In a recent meta-analysis, sweeping.13 following situations: severe pain, membrane sweeping reduced the 1. Prepare the patient. Explain the signicant bleeding, or spontane- rate of induction of labor for postma- procedure, have the patient empty ous rupture of the membranes. turity by 48%.9 her bladder, and encourage relaxed Membrane sweeping can be Membrane sweeping is asso- breathing if the vaginal examina- performed as frequently as every ciated with pain and an increased tion causes pain. 3 days. Formal cervical ripening and rate of vaginal bleeding.10 It does not 2. Abdominal exam. Assess uterine induction of labor may need to be increase the rate of maternal or neo- size, fetal lie and presentation, and planned if membrane sweeping does natal infection, however. It also does fetal heart tones. not result in the initiation of regular not reduce the CD rate. In the United 3. Vaginal exam. Ascertain cervical contractions. Kingdom, the National Institute for dilation, eacement, and position. Health and Clinical Excellence rec- If the cervix is closed a sweep may Collaborative decision making ommends that all clinicians have a not be possible. In this case, mas- All clinicians recognize the primacy discussion of membrane sweeping saging the vaginal fornices may of patient autonomy.14 Competent with their patients at 38 weeks’ ges- help to release prostaglandins and patients have the right to select the tation and oer membrane strip- stimulate uterine contractions. If course of care that they believe is ping at 40 weeks to increase the rate the cervix is closed but soft, mas- optimal. When a patient decides of timely spontaneous labor and to sage of the cervix may permit the to continue her pregnancy past avoid the risks of prolonged preg- insertion of a nger. If the cervix 41 weeks, it is helpful to endorse nancy.11 Of note, in one randomized is favorable for sweeping, insert respect for the decision and inquire

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Editorial 0219.indd 12 2/4/19 3:08 PM about the patient’s reasons for con- some interference in a pregnancy action to prevent one airplane crash tinuing the pregnancy. Understand- with the need to act to prevent for every 400 ights, you would likely ing the patient’s concerns may begin adverse pregnancy outcomes. e move heaven and earth to try to pre- a conversation that will result in the challenge is daunting. A comprehen- vent that disaster. Unless the patient patient accepting a plan for induc- sive meta-analysis of the bene t of strongly prefers expectant manage- tion near 41 weeks’ gestation. If the induction of labor at or beyond term, ment, well-managed induction of patient insists on expectant man- estimated that 426 inductions would labor at or before 41 weeks’ gestation agement well beyond 41 weeks, the need to be initiated to prevent one is likely to reduce the rate of adverse medical record should contain a perinatal death.2 From one perspec- pregnancy events and, hence, summary of the clinician recommen- tive it is meddlesome to intervene on is warranted. dation to induce labor at or before more than 400 women to prevent one 41 weeks’ gestation and the patient’s perinatal death. However, substan- preference for expectant manage- tial data indicate that expectant man- ment and her understanding of the agement of a well-dated pregnancy decision’s risks. at 41 weeks’ gestation will result in [email protected] Obstetricians and midwives adverse outcomes that likely could constantly face the challenge of bal- be prevented by induction of labor. If Dr. Barbieri reports no nancial rela- ancing the desire to avoid meddle- you ran an airline and could take an tionships relevant to this article.

References 1. Divon MY, Ferber A, Sanderson M, et al. A func- weeks. J Obstet Gynaecol Can. 2017;39:e164-e174. controlled trial. BJOG. 2006;113:402-408. tional de nition of prolonged pregnancy based 6. Whitworth M, Bricker L, Mullan C. Ultrasound 11. National Collaborating Centre for Women’s and on daily fetal and neonatal mortality rates. Ultra- for fetal assessment in early pregnancy. Cochrane Children’s Health. NICE Guideline 70. Induc- sound Obstet Gynecol. 2004;23:423-426. Database Syst Rev. 2015;7:CD007058. tion of labour; July 2008. https://www.nice.org 2. Middleton P, Shepherd E, Crowther CA. Induc- 7. Boulvain M, Stan C, Irion O. Membrane sweeping .uk/guidance/cg70/evidence/cg70-induction- tion of labour for improving birth outcomes for for induction of labour. Cochrane Database Syst of-labour-full-guideline2. Accessed January 23, women at or beyond term. Cochrane Database Rev. 2005;1:CD000451. 2019. Syst Rev. 2018;5:CD004945. 8. Berghella V, Rogers RA, Lescale K. Stripping of 12. Hamdan M, Sidhu K, Sabir N, et al. Serial mem- 3. Caughey AB, Sundaram V, Kaimal AJ, et al. Sys- membranes as a safe method to reduce prolonged brane sweeping at term in planned vaginal birth tematic review: elective induction of labor versus pregnancies. Obstet Gynecol. 1996;87:927-931. after cesarean: a randomized controlled trial. expectant management of pregnancy. Ann Intern 9. Avdiyovski H, Haith-Cooper M, Scally A. Mem- Obstet Gynecol. 2009;114:745-751. Med. 2009;151:252-263. brane sweeping at term to promote spontane- 13. Gibbon K. How to perform a stretch and sweep. 4. Hannah ME, Hannah WJ, Hellmann J, et al; ous labour and reduce the likelihood of a formal Midwives Magazine. 2012. https://www.rcm Canadian Multicenter Post-term Pregnancy Trial induction of labour for postmaturity: a system- .org.uk/news-views-and-analysis/analysis/how- Group. Induction of labor as compared with serial atic review and meta-analysis. J Obstet Gynaecol. to%E2%80%A6-perform-a-stretch-and-sweep. antenatal monitoring in post-term pregnancy. N 2018:1-9. Accessed January 23, 2019. Engl J Med. 1992;326:1587-1592. 10. de Miranda E, van der Bom JG, Bonsel G, et al. 14. Ryan KJ. Erosion of the rights of pregnant women: 5. Delaney M, Roggensack A. No. 214-Guidelines Membrane sweeping and prevention of post-term in the interest of fetal well-being. Womens Health for the management of pregnancy at 41+0 to 42+0 pregnancy in low-risk pregnancies: a randomised Issues. 1990;1:21-24.

Coming soon…

Update on cancer Is oral or IV iron therapy more Jason Wright, MD bene cial for postpartum anemia? Julianna Schantz-Dunn, MD What is your approach to the persistent occiput posterior (OP) malposition? Update on genetic testing Robert L. Barbieri, MD Mary Norton, MD

Your 15-year-old patient requests Beyond enhanced recovery contraception: e dilemmas of after surgery adolescent consent and treatment Sean C. Dowdy, MD Joseph San lippo, MD, and Steven R. Smith, JD

mdedge.com/obgyn Vol. 31 No. 2 | February 2019 | OBG Management 13

Editorial 0219.indd 13 2/4/19 3:08 PM Examining the EVIDENCE

Does the type of menopausal HT used increase the risk of venous thromboembolism?

Yes, according to a case-control study that analyzed data from 2 large UK databases in which 80,396 women aged 40 to 79 with a primary diagnosis of venous thromboembolism (VTE) between 1998 and 2017 were matched to 391,494 controls. Use of oral conjugated equine estrogen (CEE) or estradiol was associated with an elevated risk of VTE (odds ratio [OR], 1.49 and 1.27, respectively), while transdermal preparations were safest (OR, 0.96) when risk of VTE was assessed.

FAST TRACK EXPERT COMMENTARY aimed at determining the association UK researchers Andrew M. Kaunitz, MD, is University of Florida between the risk of VTE and the use of dier- Term Professor and Associate Chairman, Department identied 2 of Obstetrics and Gynecology, University of Florida ent types of HT. 80,396 women College of Medicine–Jacksonville; Medical Director with VTE and Director of Menopause and Gynecologic Ultra- Details of the study matched to sound Services, UF Women’s Health Specialists at Vinogradova and colleagues used 2 UK pri- 391,494 controls Emerson, Jacksonville. Dr. Kaunitz serves on the OBG MANAGEMENT Board of Editors. mary care research databases, QResearch and to assess the Clinical Practice Research Datalink, to iden- association Vinogradova Y, Coupland C, Hippisley-Cox J. Use of hor- tify cases of incident VTE in general practice between VTE mone replacement therapy and risk of venous thrombo- records, hospital admissions, and mortality and different embolism: nested case-control studies using the QResearch records. ey identied 80,396 women (aged types of HT and CPRD databases. BMJ. 2019;364:k4810. 40 to 79 years) diagnosed with VTE between 1998 and 2017 and 391,494 control women matched by age and general practice. e he Women’s Health Initiative trials, mean age of the case and control women was in which menopausal women were approximately 64 years; the great majority of Trandomly assigned to treatment with women were white. Analyses were adjusted oral CEE or placebo, found that statistically for smoking, body mass index (BMI), family the largest risk associated with menopausal history of VTE, and comorbidities associated hormone therapy (HT) was increased VTE.1 with VTE. Recently, investigators in the United King- Types of HT used. e investigators found dom (UK) published results of their research that 5,795 (7.2%) women with VTE and

The author reports receiving grant or research sup- 21,670 (5.5%) controls were exposed to HT port from Allergan, Bayer, and Mithra and that he is a in the 90 days before the index date (the rst consultant to AMAG, Merck, and Pzer. date of VTE diagnosis for cases became the

CONTINUED ON PAGE 16

14 OBG Management | February 2019 | Vol. 31 No. 2 mdedge.com/obgyn

Evidence Kaunitz 0219.indd 14 2/4/19 3:02 PM In-officetubal patency diagnostic test

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CONTINUED FROM PAGE 14

index date for matched controls). In those WHAT THIS EVIDENCE exposed to HT: MEANS FOR PRACTICE • 4,915 (85%) cases and 16,938 (78%) controls used oral preparations (including 102 Although randomized trials have not [1.8%] cases and 312 [1.4%] controls who compared VTE risk with oral versus also had transdermal preparations) transdermal estrogen, prior observational • 880 (14%) cases and 4,731 (19%) controls studies have consistently suggested used transdermal HT only. that transdermal estrogen does not Association of VTE with HT. Risk of VTE elevate VTE risk; this is consistent with was increased with all oral HT formulations, the results from this large UK study. In including combined (estrogen plus proges- my practice, congruent with the authors’ suggestions, I recommend transdermal togen) and estrogen-only preparations. Use rather than oral estrogen for patients of oral CEE (odds ratio [OR], 1.49) and estra- (notably, those who are obese) who at diol (OR, 1.27) were both associated with an baseline have risk factors for VTE. For P elevated risk of VTE ( <.05 for both com- menopausal women for whom use of parisons). In contrast, use of transdermal oral estrogen is indicated, I recommend estradiol (the great majority of which was estradiol rather than CEE, since estra- administered by patch) was not associated diol is less expensive and, based on this with an elevated risk of VTE (OR, 0.96). study’s results, may be safer than CEE. Direct comparison of oral estradiol and ANDREW M. KAUNITZ, MD CEE found that the lower VTE risk with oral estradiol achieved statistical signicance (P = .005). Direct comparison of oral and based on HT prescriptions and not actual FAST transdermal estrogen revealed an OR of 1.7 use; data on some factors were not avail- TRACK for the oral route of administration (P<.001) able, such as indications for HT, age at menopause, and education level; and for Elevated risk of VTE Study strengths and weaknesses a small proportion of women, some data was associated is study used data from the 2 largest pri- (smoking status, alcohol consumption, with use of oral mary care databases in the United King- BMI) were missing and had to be imputed CEE (OR, 1.49) dom. Analyses were adjusted for numerous for analysis. and oral estradiol confounding factors, including acute and (OR, 1.27) but not chronic conditions, lifestyle factors, and References 1. Manson JE, Chlebowski RT, Stefanick ML, et al. Menopausal with transdermal social deprivation. Additional sensitivity hormone therapy and health outcomes during the estradiol (OR, 0.96) analyses were conducted and yielded results intervention and extended poststopping phases of the Women’s Health Initiative randomized trials. JAMA. similar to those of the main analysis. 2013;310:1353-1368. Several limitations could have resulted 2. Vinogradova Y, Coupland C, Hippisley-Cox J. Use of hormone replacement therapy and risk of venous thromboembolism: in some residual confounding bias. For nested case-control studies using the QResearch and CPRD example, drug exposure information was databases. BMJ. 2019;364:k4810.

Dr. JoAnn V. Pinkerton’s Examining the Evidence: DON’T MISS... Is vaginal estrogen used for GSM associated with a higher risk of CVD or cancer? page 52

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Evidence Kaunitz 0219.indd 16 2/4/19 3:02 PM iron sucrose]. The mean age of study patients was 43 years (range, 18 to Table 3 shows the baseline and the change in hemoglobin from baseline to 94); 94% were female; 42% were Caucasian, 32% were African American, highest value between baseline and Day 56 or time of intervention. 24% were Hispanic, and 2% were other races. The primary etiologies of iron Table 3. Mean Change in Hemoglobin From Baseline to the Highest deficiency anemia were heavy uterine bleeding (47%) and gastrointestinal Value Between Baseline and Day 56 or Time of Intervention (Modified disorders (17%). Intent-to-Treat Population) Table 2 shows the baseline and the change in hemoglobin from baseline to Hemoglobin (g/dL) Injectafer Venofer highest value between baseline and Day 35 or time of intervention. Mean (SD) (N=1249) (N=1244) Table 2. Mean Change in Hemoglobin From Baseline to the Highest Value Baseline 10.3 (0.8) 10.3 (0.8) Between Day 35 or Time of Intervention (Modified Intent-to-Treat Population) Highest Value 11.4 (1.2) 11.3 (1.1) Hemoglobin (g/dL) Cohort 1 Cohort 2 Change (from baseline to highest value) 1.1 (1.0) 0.9 (0.92) Mean (SD) Injectafer Oral Iron Injectafer IV SCa (N=244) (N=251) (N=245) (N=237) Treatment Difference (95% CI) 0.21 (0.13, 0.28) Baseline 10.6 (1.0) 10.6 (1.0) 9.1 (1.6 ) 9.0 (1.5) Increases from baseline in mean ferritin (734.7 ± 337.8 ng/mL), and transferrin saturation (30 ± 17%) were observed prior to Day 56 in Highest Value 12.2 (1.1) 11.4 (1.2) 12.0 (1.2) 11.2 (1.3) Injectafer-treated patients. Change (from 17 PATIENT COUNSELING INFORMATION baseline to 1.6 (1.2) 0.8 (0.8) 2.9 (1.6) 2.2 (1.3) • Question patients regarding any prior history of reactions to parenteral highest value) iron products. p-value 0.001 0.001 • Advise patients of the risks associated with Injectafer. SD=standard deviation; a: Intravenous iron per standard of care • Advise patients to report any signs and symptoms of hypersensitivity that may develop during and following Injectafer administration, such as Increases from baseline in mean ferritin (264.2 ± 224.2 ng/mL in Cohort 1 rash, itching, dizziness, lightheadedness, swelling and breathing and 218.2 ± 211.4 ng/mL in Cohort 2), and transferrin saturation problems [ see Warnings and Precautions (5) ]. (13 ± 16% in Cohort 1 and 20 ± 15% in Cohort 2) were observed at Day 35 in Injectafer-treated patients. Injectafer is manufactured under license from Vifor (International) Inc, Switzerland. 14.2 Trial 2: Iron Deficiency Anemia in Patients with Non-Dialysis Dependent Chronic Kidney Disease AMERICAN Trial 2: REPAIR-IDA, Randomized Evaluation of efficacy and safety of Ferric REGENT, INC. carboxymaltose in Patients with iron deficiency Anemia and Impaired Renal SHIRLEY, NY 11967 function, (NCT00981045) was a randomized, open-label, controlled clinical IN0650 study in patients with non-dialysis dependent chronic kidney disease. RQ1052-B Revised: 04/2018 Inclusion criteria included hemoglobin (Hb) ≤ 11.5 g/dL, ferritin ≤ 100 ng/mL or ferritin ≤ 300 ng/mL when transferrin saturation (TSAT) ≤ 30%. Study patients were randomized to either Injectafer or Venofer. The mean age of study patients was 67 years (range, 19 to 101); 64% were female; 54% were Caucasian, 26% were African American, 18% Hispanics, and 2% were other races. LAST CHANCE! 13.25 AMA PRA Category 1 Credits™ | 13.25 Pharmacy Contact Hours 13.25 Nursing Contact Hours | 13.25 AAFP Prescribed Credits

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G. David Adamson, MD Max Ezzati, MD Dr. Adamson is Founder and CEO of Dr. Ezzati is a Board-certi ed reproductive Advanced Reproductive Care, Inc (ARC endocrinology and infertility (REI) specialist Fertility); Clinical Professor, ACF, at Stanford and the Medical Director of Department of University School of Medicine; and Associate Reproductive Endocrinology and Infertility Clinical Professor at the University of at Palo Alto Medical Foundation Fertility California, San Francisco. He is also Director Physicians of Northern California. of Equal3 Fertility, APC in Cupertino, California.

Dr. Adamson reports being a consultant to Abbott, AbbVie, Ferring, Guerbet, Hernest, and Merck, and that he has equity in ARC Fertility. Dr. Ezzati reports no nancial relationships relevant to this article.

Progress is being made in recognizing infertility as a disease (thus meriting insurance coverage) and in improving embryo selection techniques for IVF treatment, but more work is needed. Plus, the SART’s redesigned report includes a new feature for calculating a personalized prognosis that can aid in treatment decision making. Two fertility experts boil down

IN THIS these complex issues. ARTICLE

Infertility rofessional societies, global organiza- Next, we detail several notable new fea- as a disease tions, and advocacy groups are con- tures available in the annual report of the So- tinually working toward the goal of ciety for Assisted Reproductive Technology This page P having the costs of infertility care covered by (SART), an online interactive document that insurance carriers. Paramount to that e ort can be used to assist clinicians and patients Redesigned is obtaining recognition of infertility as a bur- in treatment decisions. SART report densome disease. In this Update, we sum- We also tackle the complexities of page 20 marize national and international initiatives embryo selection for in vitro fertilization and societal trends that are helping to move (IVF) and describe a potentially promising Improved us closer to that goal, and we encourage aneuploidy screening test, and explore its embryo selection ObGyns to lead advocacy e orts. limitations. page 23 Advances in recognizing infertility as a disease that merits insurance coverage

rticle 16 of the United Nations Dec- out any limitation due to race, nationality or laration of Human Rights states that religion, have the right to marry and to found

A “Men and women of full age, with- a family. ey are entitled to equal rights as PHOTO: SHUTTERSTOCK

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Update 0219.indd 18 2/4/19 3:06 PM TABLE 1 How infertility is dened by the international glossary on infertility and fertility care2 Denition Infertility is a disease characterized by the failure to establish a clinical pregnancy after 12 months of regular, unprotected sexual intercourse or due to an impairment of a person’s capacity to reproduce either as an individual or with his/her partner. Fertility interventions may be initiated in less than 1 year based on medical, sexual and reproductive history, age, physical ndings, and diagnostic testing. Infertility is a disease, which generates disability as an impairment of function. Supporters of infertility as a disease • American Medical Association • American Society for Reproductive Medicine • European Society of Human Reproduction and Embryology • International Federation of Fertility Societies • International Federation of Gynecology and Obstetrics • March of Dimes • World Health Organization • Multiple other global and regional professional societies

to marriage, during marriage and at its dis- ever, regarding global or national policy that solution.”1 While few people value anything recognizes the importance of infertility as a more than their family, the inability to have medical and public health problem. FAST one because of infertility has long been in the In 2009, the glossary published by the TRACK shadows. Infertility is surrounded by myth, WHO with the International Committee for The ASRM for poorly understood by the public, rarely dis- Monitoring Assisted Reproductive Technol- many years cussed in polite company, badly managed by ogy (ICMART) dened infertility as a dis- has recognized physicians, and rarely covered by insurance. ease.4 is recognition is important because e current inadequacy of infertility insur- it aids policy making, insurance coverage, infertility as a ance coverage denies the basic human right and/or other payments for services. disease, but to found a family and perpetuates gender e WHO also has begun the pro- only in 2017 did inequalities. cess of developing new infertility guide- AMA delegates Major reproductive medicine organiza- lines. Recently, the WHO held a summit on support the tions globally have endorsed the denition of safety and access to fertility care, which was WHO’s designation infertility as a disease that “generates disability attended by many representatives of nation- of infertility as an impairment of function” (TABLE 1).2 Fortu- state governments and international experts. as a disease nately, medical, societal, and judicial changes It is hoped that a document from those pro- have resulted in progress for the 6.1 million ceedings will reinforce the public health women (and equivalent number of men) importance of infertility and support the aected by infertility in the United States.3 need to promote equality in access to safe fertility care. WHO initiatives matter because they apply to nation-states. Professional group advocacy In the United States, the American Soci- efforts, and judicial rulings ety for Reproductive Medicine (ASRM) for e World Health Organization (WHO) has many years has recognized infertility as a dis- addressed infertility over the past several ease. Only in 2017, however, did delegates at decades, with the organization’s standards the American Medical Association’s annual on semen analysis being the most recognized meeting vote to support the WHO’s designa- outcome. Progress has been limited, how- tion of infertility as a disease. CONTINUED ON PAGE 20

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Update 0219.indd 19 2/4/19 3:06 PM UPDATE fertility CONTINUED FROM PAGE 19

employees’ reproductive needs and provid- WHAT THIS EVIDENCE MEANS FOR PRACTICE ing improved bene ts for reproductive care. The time is now for ObGyns and other women’s health care providers to advocate for insurance coverage of infertility care. When our patients have inadequate coverage, we should encourage them to take ObGyns must continue action by contacting their insurance company and their employers to lead advocacy to explain the reasons and argue for better coverage. Also, contact Not all has been progress. Personhood bills RESOLVE for additional information. in several states threaten basic reproductive rights of women and men. e ASRM and RESOLVE (the National Infertility Asso- Judicial views. In 1998, the US Supreme ciation) have taken leading roles in opposing Court held that infertility is a disability under these legislative initiatives and supporting the Americans with Disabilities Act (ADA). reproductive rights.5 e Court subsequently held, however, that a Advocacy e orts through events and person is not considered disabled under the trends have resulted in gradually improving act if the disability can be overcome by miti- the recognition of the burden of infertility, gating or corrective measures. In 2000, a lower inadequate insurance coverage, and con- court held that, while infertility is a disability, tinuing gender inequalities in reproduction. an employer’s health plan that excludes treat- Today, patients, professionals, and national ment for it is not discriminatory under the and international organizations are coalesc- ADA if it applies to all employees. ing around demands for recognition, access Societal recognition. Interestingly, improved to care, and gender and diversity equality. technology for oocyte cryopreservation has While much remains to be done, progress FAST resulted in greater recognition of reproduc- is being made in society, government, the TRACK tive issues and the disparity in reproductive workplace, and the health care system. health societal norms and rights between ObGyns and other women’s health ObGyns and men and women. care providers can help continue the prog- other women’s Media stories and gender issues in ress toward equality in reproductive rights, health care employment, especially in such high-pro le including access to infertility care, by dis- providers can industries as technology and nance, have cussing insurance inequities with patients, help continue highlighted long-standing inequities, many informing insurance companies that infer- the progress of which concern reproductive issues. ese tility is a disease, and encouraging patients toward equality issues have been further disseminated by to challenge inadequate and unequal insur- in reproductive the #metoo movement. Some employers are ance coverage of needed reproductive rights, including beginning to respond by recognizing their health care. access to infertility care Latest SART report o ers new features to aid in treatment decision making

nowledge of the prognosis and its var- Summary Report (CSR), which includes valu- ious treatment options is an impor- able new features for patients and physicians K tant aspect of infertility treatment. considering assisted reproductive technol- e SART recently updated its annual Clinic ogy (ART) treatment.6

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Update 0219.indd 20 2/4/19 3:06 PM SART compiles complex data Notable changes and reports outcomes A major change in the CSR is that there is a e SART has been reporting IVF outcomes preliminary report for a given year and then and other ART outcomes since 1988. e soci- a nal report the following year. is helps ety’s annual report is widely read by consum- to more accurately report cycles that have ers, patients, physicians, and policy makers, been “delayed” because of egg retrieval and and it has many important uses. However, embryo freezing performed in the reported the report is complicated and dicult to year but then transferred in the following interpret for many reasons. For example, reporting year. treatments are complex and varied (espe- Cycle counting. A cycle is counted when a cially with application of new cryopreserva- woman has started medications for an ART tion technology), and there are variations procedure or, in a “natural” cycle when no among clinics with respect to patient selec- medications are used, the rst day of men- tion, protocols used, philosophy of practice, ses of the ART cycle. If several cycles are per- and numerous other variables. formed to bank eggs or embryos, each will be Because of this, the SART states, “ e counted in the denominator when calculat- SART Clinic Summary Report (CSR) allows ing the pregnancy rate. is more accurately patients to view national and individual reects the patient treatment burden and clinic IVF success rates. e data presented costs. A cycle cancelled before egg retrieval is in this report should not be used for compar- still counted as a cycle. ing clinics. Clinics may have dierences in Dening success. Success is characterized patient selection and treatment approaches as delivery of a child, since this is the out- which may articially inate or lower preg- come patients desire. Singleton deliveries nancy rates relative to another clinic. Please are emphasized, since twin and higher-order FAST discuss this with your doctor.”6 multiple pregnancies have a higher risk of TRACK Nevertheless, the CSR is extremely use- prematurity, morbidity, mortality, and cost. Success is ful because it reports outcomes, which can e percentages of triplet, twin, and single- characterized as lead to more informed patients and physi- ton births contributing to the live birth rate delivery of a child, cians and thus better access to safe and eec- are provided for each cycle group, as is pre- since this is tive use of ART. e SART has redesigned the maturity (TABLE 2, page 22).6 CSR to make it more useful. e end point of a treatment cycle can the outcome vary. e new CSR captures the success rate patients desire following one or more egg retrievals and the Redesigned CSR focuses on rst embryo transfer (primary outcome), the outcomes important to patients success of subsequent cycles using frozen eggs In recent years, new technologies have or embryos not transferred in the rst embryo increased dramatically the use of embryo transfer, and the combined contribution of the cryopreservation, genetic testing, and single primary and subsequent cycles to the cumu- embryo transfer (SET). e new CSR format lative live birth rate for a patient both in the is more patient focused and identies more preliminary report and the nal report for directly the treatment burden: ovarian stimu- any given year. e live birth rate per patient lation, egg retrieval, intracytoplasmic sperm also is reported and includes the outcomes injection, preimplantation genetic testing for patients who are new to an infertility cen- (PGT), cryopreservation, frozen embryo ter and starting their rst cycle for retrieval of transfer, and multiple cycles. It also focuses their own eggs during the reporting year. on the important patient outcomes, includ- Outcomes and prognostic factors. Out- ing live birth of a healthy child, multiple comes are reported by multiple factors, pregnancy, number of cycles, and chances of including patient age and source of the eggs. success per patient over time (including both ese are important prognostic factors; sepa- fresh and frozen embryo transfers). rating the data allows you to obtain a better

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Update 0219.indd 21 2/4/19 3:06 PM UPDATE fertility

TABLE 2 SART 2016 preliminary assisted reproductive technology outcomes6 Preliminary cumulative outcome per egg retrieval cycle, using patient’s own eggs Age of woman <35 35–37 38–40 41–42 >42 Number of cycle starts 44,899 24,645 23,842 12,427 9,797 Singletons 39.4% 28.9% 18.8% 10.1% 3.1% Twins 8.1% 5.7% 3.0% 1.1% 0.2% Triplets or more 0.2% 0.2% 0.1% 0.0% 0% Live births 47.6% (47.2–48.1) 34.8% (34.2–35.4) 21.8% (21.3–22.4) 11.2% (10.6–11.7) 3.3% (3.0–3.7) (condence range)

Abbreviation: SART, Society for Assisted Reproductive Technology.

FIGURE Filter report included in the can help patients and physicians choose the 6 SART National Summary Report best treatment based on prognosis. Personalized prognosis. An important new feature is the SART Patient Predictor (https:// www.sartcorsonline.com/predictor/patient), a model that permits an individual patient to obtain a more personalized prognosis. While the SART predictor uses only basic patient information, such as age, body mass index, and diagnosis, its estimate is based on the entire US sample of reported ART experience and therefore can help patients in decision making. Furthermore, the predictor calculates percentages for the outcome of one transfer of 2 embryos, and 2 transfers of a single embryo, to demonstrate the advantages of SET that result in a higher live birth rate but a signicantly lower multiple pregnancy rate.

The lter report, available from the “Filter” tab on the SART National Summary Report website menu Summing up bar, contains various factors that can be included e SART’s new CSR is extremely useful to or excluded for calculating outcomes. patients and to any physician who cares for infertility patients. It can help users both idea of both national and individual clinic understand the expected results from dierent experience by these factors. ART treatments and enable better physician- e CSR also contains lters for infertility patient communication and decision making. diagnosis, stimulation type, and other treatment details (FIGURE).6 e lter is a useful WHAT THIS EVIDENCE feature because multiple types of treatment MEANS FOR PRACTICE can be included or excluded. e outcome of The updated annual SART Clinic Summary dierent treatment interventions can then be Report is an exceptionally valuable and estimated based on outcomes from the entire easy-to-use online tool for you and your sample of US patients with similar character- infertility patients. istics and interventions. is powerful tool

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Update 0219.indd 22 2/4/19 3:06 PM Embryo selection techniques re ned with use of newer technologies

ince the introduction of IVF in 1978, nal age: 40% to 50% of blastocysts in the nal cumulative live birth rates women younger than age 35 and about 90% S per cycle initiated for oocyte retrieval of blastocysts in women older than age 42.8 after all resulting embryos have been e premise with PGT-A is to identify these trasferred continue to rise, currently stand- aneuploid embryos and increase the chances ing at 54% for women younger than age 35 of success per embryo transfer by transfer- in the United States.7 A number of achieve- ring euploid embryos. ments have contributed to this remarkable at concept was initially applied to success, namely, improvements in IVF labo- cleavage-stage embryos through the use of ratory and embryo culture systems, advances uorescence in situ hybridization (FISH) in cryopreservation technology, availability technology to interrogate a maximum of 5 to of highly e ective gonadotropins and gonad- 9 chromosomes in a single cell (single blasto- otropin–releasing hormone analogues, mere); however, although initial results from improved ultrasound technology, and the observational studies were encouraging, sub- introduction of soft catheters for atraumatic sequent randomized controlled studies unex- embryo transfers. pectedly showed a reduction in pregnancy rates.9 is was attributed to several factors, FAST including biopsy-related damage to the cleav- TRACK Treatment now focuses on age-stage embryo, inability of FISH technol- Chromosomal improved embryo selection ogy to assess aneuploidies of more than 5 to 9 abnormalities Now that excellent success rates have been chromosomes, mosaicism, and technical limi- of the embryo attained, the focus of optimizing e orts in tations associated with single-cell analysis. fertility treatment has shifted to improv- (aneuploidies) are ing safety by reducing the rates of multiple the most common pregnancy through elective single embryo Second-generation PGT-A cause of treatment transfer (eSET), reducing the rates of miscar- testing has promise, and failure following riage, and shortening the time to live birth. limitations embryo transfer Methods to improve embryo selection lie at e newer PGT-A tests the embryos at the in IVF the forefront of these initiatives. ese vary blastocyst stage by using biopsy samples from and include extended culture to blastocyst the trophectoderm (which will form the future stage, standard morphologic evaluation as placenta); this is expected to spare the inner well as morphokinetic assessment of embry- cell mass ([ICM] which will give rise to the onic development via time-lapse imaging, embryo proper) from biopsy-related injury. and more recently the reintroduction of pre- On the genetics side, newer technolo- implantation genetic testing for aneuploidy gies, such as array comparative genomic (PGT-A), formerly known as preimplantation hybridization, single nucleotide polymor- genetic screening (PGS). phism arrays, quantitative polymerase chain Chromosomal abnormalities of the reaction, and next-generation sequenc- embryo, or embryo aneuploidies, are the ing, o er the opportunity to assess all 24 most common cause of treatment failure fol- chromosomes in a single biopsy specimen. lowing embryo transfer in IVF. e propor- Although a detailed discussion of these test- tion of embryos a ected with aneuploidies ing platforms is beyond the scope of this

PHOTO: SHUTTERSTOCK signi cantly increases with advancing mater- Update, certain points are worth mentioning. CONTINUED ON PAGE 24

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Update 0219.indd 23 2/4/19 3:06 PM UPDATE fertility CONTINUED FROM PAGE 23

All these technologies require some form of limitation, as the biopsied trophectoderm genetic material ampli cation (most com- cells may not accurately represent the chro- monly whole genome ampli cation or mul- mosomal makeup of the ICM. Also, an tiplex polymerase chain reaction) to increase embryo may be able to undergo self-cor- the relatively scant amount of DNA obtained rection during subsequent stages of devel- from a sample of 4 to 6 cells. ese ampli - opment, and therefore even a documented cation techniques have limitations that can trophectoderm abnormality at the blasto- subsequently impact the validity of the test cyst stage may not necessarily preclude that results. embryo from developing into a healthy baby. Furthermore, there is no consistency Standardization is needed. Despite wide- in depth of coverage for various parts of the spread promotion of PGT-A, well-designed genome, and subchromosomal (segmental) randomized clinical trials (RCTs) have not copy number variations below 3 to 5 Mb may yet consistently shown its bene ts in improv- not be detected. e threshold used in bio- ing pregnancy rates or reducing miscarriage informatics algorithms employed to interpret rates. Although the initial small RCTs in a the raw data is subject to several biases and selected group of good prognosis patients is not consistent among laboratories. As a suggested a bene cial eect in ongoing result, the same sample assessed in dierent pregnancy rates per transfer, the largest laboratories can potentially yield dierent multicenter RCT to date did not show any results. improvement in pregnancy rates or reduc- In addition to these technical limitation in miscarriage rates.10 In that study, a tions, mosaicism can pose another biologic post hoc subgroup analysis suggested a possible bene cial eect in women aged 35 to 40. However, those results must be validated and WHAT THIS EVIDENCE MEANS FOR PRACTICE reproduced with randomization at the start of stimulation, with the primary outcome Standardization of clinical and laboratory protocols and additional being the live birth rate per initiated cycle, studies to assess the effects of PGT-A on live birth rates per initi- instead of per transfer, before PGT-A can be ated cycles are recommended before this new technology is widely adopted universally in clinical practice. adopted in routine clinical practice. In our practice, we routinely With all the above considerations, the offer and perform extended culture to blastocyst stage and stan- ASRM has appropriately concluded that “the dard morphologic assessment. After a thorough counseling on the current status of PGT-A, about 15% to 20% of our patients opt to value of preimplantation genetic testing for undergo PGT-A. aneuploidy (PGT-A) as a screening test for IVF patients has yet to be determined.”11

References 1. United Nations website. General Assembly resolution 217A: Declaration of report. 2016 Preliminary national data. https://www.sartcorsonline.com human rights. December 10, 1948. http://www.un.org/en/universal-declara /rptCSR_PublicMultYear.aspx?reportingYear=2016 . Accessed January 12, 2019. tion-human-rights/. Accessed January 11, 2019. 7. Society for Assisted Reproductive Technology website. National summary 2. Zegers-Hochschild F, Adamson GD, Dyer S, et al. e international glossary on report 2015. https://www.sartcorsonline,com/rptCSR_PublicMultYear.aspx infertility and fertility care, 2017. Fertil Steril. 2017;108:393-406. ?reportingYear=2015. Accessed January 12, 2019. 3. US Department of Health and Human Services O¤ce on Women’s Health web- 8. Harton GL, Munne S, Surrey M, et al; PGD Practitioners Group. Diminished eect site. Infertility. https://www.womenshealth.gov/a-z-topics/infertility. Accessed of maternal age on implantation after preimplantation genetic diagnosis with January 24, 2019. array comparative genomic hybridization. Fertil Steril. 2013;100:1695-1703. 4. Zegers-Hochschild F, Adamson GD, de Mouzon J, et al; International Commit- 9. Mastenbroek S, Twisk M, van Echten-Arends, et al. In vitro fertilization with tee for Monitoring Assisted Reproductive Technology, World Health Organiza- preimplantation genetic screening. N Engl J Med. 2007;357:9-17 tion. International Committee for Monitoring Assisted Reproductive Technol- 10. Munne S, Kaplan B, Frattarelli JL, et al. Global multicenter randomized con- ogy (ICMART) and the World Health Organization (WHO) revised glossary of trolled trial comparing single embryo transfer with embryo selected by pre- ART terminology, 2009. Fertil Steril. 2009;92:1520-1524. implantation genetic screening using next-generation sequencing versus 5. RESOLVE: e National Infertility Association website. Opposing person- morphologic assessment [abstract O-43]. Fertil Steril. 2017;108(suppl):e19. hood: RESOLVE ghts to keep fertility medical treatments legal in the US. 11. Practice Committees of the American Society for Reproductive Medicine and https://resolve.org/get-involved/advocate-for-access/our-issues/opposing the Society for Assisted Reproductive Technology. e use of preimplanta- -personhood/. Accessed January 11, 2019. tion genetic testing for aneuploidy (PGT-A): a committee opinion. Fertil Steril. 6. Society for Assisted Reproductive Technology website. National summary 2018;109:429-436.

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Update 0219.indd 24 2/4/19 3:06 PM COMMENTARY

Intimate partner violence, guns, and the ObGyn Gun violence affects us all, let’s not “stay in our lane”

Katherine Koniares, MD Megan L. Evans, MD, MPH Resident, Department of Obstetrics and Gynecology, Assistant Professor, Tufts University School of Tufts Medical Center, Boston, Massachusetts Medicine; Associate Program Director, Department of Obstetrics and Gynecology, Tufts Medical Center

n the afternoon of Novem- Intimate partner violence is patients for IPV. Part of the sacred ber 19, 2018, Dr. Tamara “our lane” patient–physician relationship is O O’Neal was shot and killed e shooting at Mercy Hospital being present for our patients when by her ex-ancé outside Mercy Hos- occurred amongst a backdrop of con- they need us most. e American pital and Medical Center in Chicago, troversy between the National Rie College of Obstetricians and Gyne- Illinois. After killing Dr. O’Neal, the Association (NRA) and the medical cologists (ACOG) recommends that gunman ran into the hospital where community. On November 7, 2018, ObGyns screen patients for IPV at he exchanged gunre with police, the NRA tweeted that doctors should regular intervals and recognizes that killing a pharmacy resident and a “stay in their lane” with regard to it may take several conversations police ocer, before he was killed by gun control after a position paper before a patient discloses her his- ocers.1 from the American College of Phy- tory of IPV.6 Additionally, given the is horric encounter between sicians on reducing rearm deaths increased risk of gun injuries and a woman and her former partner and injuries was published in the death, it behooves us to also screen begs for a conversation about inti- Annals of Internal Medicine.3 Doctors for gun safety in the home. mate partner violence (IPV). A data from every eld and from all over the brief of e National Intimate Partner country responded through social Ask patients about IPV, and Sexual Violence Survey was pub- media by stating that treating bullet and ask again lished in November 2018. Accord- wounds and caring for those aected e shooting at Mercy Hospital was ing to this report, 30.6% of women by gun violence was “their lane.”4 a stark reminder that IPV can aect experienced physical violence by an It is time for us as a community any of us. With nearly one-third of intimate partner in 2015, with 21.4% to recognize that gun violence aects women and more than one-quarter of women experiencing severe physi- us all. e majority of mass shooters of men experiencing IPV in their life- cal violence. In addition, 31.0% of have a history of IPV and often target time, action must be taken. e rst men experienced physical violence their current or prior partner during step is to routinely screen patients by an intimate partner in 2015; 14.9% the shooting.5 At this intersection of for IPV, oering support and com- of men experienced severe physical IPV and gun control, the physician munity resources (see “Screening for violence.2 has a unique role. We not only treat intimate partner violence” on page those aected by gun violence and 26). e second step is to work to The authors report no nancial relationships rel- advocate for better gun control but decrease the access perpetrators of evant to this article. we also have a duty to screen our IPV have to weapons with which to

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Commentary Evans 0219.indd 25 2/4/19 3:00 PM COMMENTARY

Screening for intimate partner violence

There are numerous veried screening tools available to assess for intimate partner violence (IPV) for both pregnant and nonpregnant patients. Many recommended tools are accessible on the Centers for Disease Control and Prevention (CDC) website: https://www.cdc.gov/violenceprevention/pdf/ipv/ipvandsvscreening.pdf. In our ofce, the tool most commonly used is a 3-part question assessing domestic violence and IPV. It is important to recognize IPV can affect everyone—all races and religions regardless of socioeconomic background, sexual orientation, and pregnancy status. All patients deserve screening for IPV, and it should never be assumed a patient is not at risk. During an annual gynecology visit for return and new patients or a new obstetric intake visit, we use the following script obtained from ACOG’s Committee Opinion 518 on IPV1: Because violence is so common in many women’s lives and because there is help available for women being abused, I now ask every patient about domestic violence: 1. Within the past year (or since you have become pregnant) have you been hit, slapped, kicked, or otherwise physically hurt by someone? 2. Are you in a relationship with a person who threatens or physically hurts you? 3. Has anyone forced you to have sexual activities that made you feel uncomfortable? If a patient screens positive, we assess their immediate safety. If a social worker is readily available, we arrange an urgent meeting with the patient. If ofces do not have immediate access to this service, online information can be provided to patients, including the National Resource Center on Domestic Violence (https://nnedv.org/) and a toll-free number to the National Domestic Violence Hotline: 1-800-799-7233. Additionally, we ask patients about any history of verbal, physical, or sexual violence with prior partners, family members, acquaintances, coworkers, etc. Although the patient might not be at immediate risk, prior experiences with abuse can cause fear and anxiety around gynecologic and obstetric exams. Acknowledging this history can help the clinician adjust his or her physical exam and support the patient during, what may be, a triggering experience. As an additional resource, Dr. Katherine Hicks-Courant, a resident at Tufts Medical Center, in Boston, Massachusetts, created a tool kit for providers working with pregnant patients with a history of sexual assault. It can be accessed without login online under the Junior Fellow Initiative Toolkit section at http://www.acog.org.

Reference 1. American College of Obstetricians and Gynecologists. Committee Opinion No. 518: intimate partner violence. Obstet Gynecol. 2012;119:412-417.

enact violence—through legislation, who are in violent relationships are 5 #BreakeCycle, and be on the look- community engagement, and using times more likely to die if their part- out for important legislation to enact our physician voices. ner has access to a rearm.5 real change. States that have passed legisla- To sign the open letter from tion that prohibits persons with active #BreakTheCycle American Healthcare Professionals restraining orders or a history of IPV e 116th Congress convened in to the NRA regarding their recent or domestic violence from possess- January. We have an opportunity comments and our medical expe- ing rearms have seen a decrease in to make real gun legislation reform riences with gun violence, visit IPV rearm homicide rates.7 ese and work to keep our communities https://affirmresearch.org/this-is- policies can make a profound impact and our patients at risk for IPV safer. our-lane-petition. Currently, there on the safety of our patients. Women Tweet your representatives with are more than 41,000 signatures.

References 1. Buckley M, Gorner J, Greene M. Chicago hospital College of Physicians. Reducing rearm injuries Gynecologists. ACOG Committee Opinion No. shooting: Young cop, doctor, pharmacy resident and deaths in the United States: a position paper 518: intimate partner violence. Obstet Gynecol. and gunman die in Mercy Hospital attack. Chi- from the American College of Physicians. Ann 2012;119(2 pt 1):412-417. https://www.acog cago Tribune. Nov. 20, 2018. Intern Med. 2018;169:704-707. .org/Clinical-Guidance-and-Publications/Com- 2. Smith SG, Zhang X, Basile KC, et al. e National 4. Papenfuss M. NRA Tweets Warning to Anti-Gun mittee-Opinions/Committee-on-Health-Care- Intimate Partner and Sexual Violence Survey Doctors: ‘Stay In Your Lane’. e Hungton Post. for-Underserved-Women/Intimate-Partner- (NISVS): 2015 data brief – updated release. November 8, 2018. Violence. Atlanta, GA: National Center for Injury Prevention 5. Everytown for Gun Safety website. Mass Shoot- 7. Zeoli AM, McCourt A, Buggs S, et al. Analysis of and Control, Centers for Disease Control and Pre- ings in the United States: 2009–2016. Available the strength of legal rearms restrictions for per- vention; November 2018. at https://everytownresearch.org/reports/mass- petrators of domestic violence and their associa- 3. Butkus R, Doherty R, Bornstein SS; for the Health shootings-analysis/. Accessed January 17, 2019. tions with intimate partner homicide. Am J Epide- and Public Policy Committee of the American 6. e American College of Obstetricians and miol. 2018;187:2365-2371.

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Commentary Evans 0219.indd 26 2/4/19 3:00 PM Ongoing gynecologic cancer resources for your practice

Did you read these recent news and clinical articles?

iiObesity-related cancers increasing iiThe HPV vaccine is now in younger adults recommended for adults aged 27–45: Counseling implications iiWhen NOT to perform a Pap test iiBMI changes in adolescence linked iiNationwide implementation of to later cancer risk MIS reduced complications and increased survival in early-stage iiMaternal health bene ts endometrial cancer of breastfeeding

iiSoy didn’t up all-cause mortality in iiDoes low-dose aspirin decrease a breast cancer survivors woman’s risk of ovarian cancer?

iiShould we abandon minimally iiWhen is it appropriate to remove invasive surgery for cervical cancer? ovaries in hysterectomy?

iiStudy shows evidence of herd iiAddressing your patient’s sexual immunity with HPV vaccine function after cancer

Bookmark the GYNECOLOGIC CANCER page at mdedge.com/obgyn

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Cancer AD 0219.indd 27 2/4/19 2:58 PM Focal adenomyosis treated by wedge resection of the diseased myometrium, with subsequent closure of the remaining myometrial defect using a barbed V-Loc delayed absorbable suture in layers. ILLUSTRATION: KIMBERLY MARTENS FOR OBG MANAGEMENT MARTENS KIMBERLY ILLUSTRATION:

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Nezhat 0219.indd 28 2/6/19 3:45 PM HOW DO YOU PROCEED? A patient with severe adenomyosis requests uterine-sparing surgery

Combined laparoscopy and, when necessary, minilaparotomy is the authors’ preferred technique. It can relieve many symptoms of adenomyosis with a low complication rate, and preserve, even improve, fertility

Camran Nezhat, MD; Michelle A. Wood, DO; Megan Kennedy Burns, MD, MA; and Azadeh Nezhat, MD

CASE denomyosis is characterized by endo- A 28-year-old patient presents for evaluation metrial-like glands and stroma deep and management of her chronic pelvic pain, A within the myometrium of the uterus dysmenorrhea, and menorrhagia. She previ- and generally is classified as diffuse or focal. ously tried ibuprofen with no pain relief. She This common, benign gynecologic condition also tried oral and long-acting reversible con- is known to cause enlargement of the uterus IN THIS traceptives but continued to be symptomatic. secondary to stimulation of ectopic endome- ARTICLE She underwent pelvic sonography, which dem- trial-like cells.1-3 Although the true incidence onstrated a large globular uterus with myo- of adenomyosis is unknown because of the Best imaging metrial thickening and myometrial cysts with difficulty of making the diagnosis, preva- options increased hypervascularity. Subsequent mag- lence has been variously reported at 6% to page 30 netic resonance imaging indicated a thickened 70% among reproductive-aged women.4,5 junctional zone. Feeling she had exhausted In this review, we rst examine the clini- Surgical medical manegement options with no signi - cal presentation and diagnosis of adeno- cant improvement, she desired surgical treat- myosis. We then discuss clinical indications management ment, but wanted to retain her future fertility. for, and surgical techniques of, adenomyo- page 33 As a newlywed, she and her husband were mectomy, including our preferred uterine- planning on building a family so she desired to sparing approach for focal disease or when Wedge resection retain her uterus for potential future pregnancy. the patient wants to preserve fertility: laparo- page 36 How would you address this patient’s dis- scopic resection without robotic assistance, ruptive symptoms, while af rming her long-term aided by minilaparotomy when indicated. plans by choosing the proper intervention?

Treatment evolved Dr. C. Nezhat is Director of the Camran Nezhat Institute, Palo Alto, California, and Founder in a century and a half of Worldwide Endometriosis March. Adenomyosis was rst described more than Dr. Wood is Fellow, Camran Nezhat Institute. 150 years ago; historically, hysterectomy was Dr. Burns is Fellow, Camran Nezhat Institute. the mainstay of treatment.2,6 Conservative Dr. A. Nezhat is Co-Director, Center for Special Minimally Invasive and Robotic Surgery, Palo Alto, California. surgical treatment for adenomyosis has been reported since the early 1950s.6-8 Surgical The authors report no nancial relationships relevant to this treatment initially became more widespread article. following the introduction of wedge resection,

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which allowed for partial excision of adenomy- histologic analysis was performed on speci- otic nodules.9 mens following hysterectomy but, more More recent developments in diagnostic recently, has utilized specimens obtained technologies and capabilities have allowed from hysteroscopic and laparoscopic myo- for the emergence of additional uterine- metrial biopsies.19 Importantly, although sparing and minimally invasive surgical treat- hysteroscopic and laparoscopic biopsies are ment options for adenomyosis.3,10 Although taken under direct visualization, there are the use of laparoscopic approaches is lim- no pathognomonic signs for adenomyosis; a ited because a high level of technical skill is diagnosis can therefore be missed if adeno- required to undertake these procedures, such myosis is not present at biopsied sites.1 e approaches are becoming increasingly impor- sensitivity of random biopsy at laparoscopy tant as more and more patients seek fertility has been found to be as low as 2% to as high conservation.11-13 as 56%.20

Imaging How does Imaging can be helpful in clinical decision adenomyosis present? making and to guide the dierential diagno- Adenomyosis symptoms commonly consist sis. Transvaginal ultrasonography (TVUS) is of abnormal uterine bleeding and dysmenor- often the rst mode of imaging used for the rhea, aecting approximately 40% to 60% and investigation of abnormal uterine bleeding or 15% to 30% of patients with the condition, re- pelvic pain. Diagnosis by TVUS is dicult be- spectively.14 ese symptoms are considered cause the modality is operator dependent and nonspecic because they are also associated standard diagnostic criteria are lacking.5 FAST with other uterine abnormalities.15 Although e most commonly reported ultrasono- TRACK menorrhagia is not associated with extent of graphic features of adenomyosis are21,22: disease, dysmenorrhea is associated with both • a globally enlarged uterus Stimulation the number and depth of adenomyotic foci.14 • asymmetry of ectopic Other symptoms reported with adenomy- • myometrial thickening with heterogeneity endometrial cells osis include chronic pelvic pain, dyspareunia, • poorly dened foci of hyperechoic regions, causes uniform as well as infertility. Note, however, that a large surrounded by hypoechoic areas that cor- hyperplasia and percentage of patients are asymptomatic.16,17 respond to smooth-muscle hyperplasia hypertrophy of On physical examination, patients com- • myometrial cysts. the myometrium, monly exhibit a diusely enlarged, globular Doppler ultrasound examination in pa- resulting in an uterus. is nding is secondary to uniform tients with adenomyosis reveals increased enlarged uterus hyperplasia and hypertrophy of the myo- ow to the myometrium without evidence of that often presents metrium, caused by stimulation of ectopic large blood vessels. on physical exam endometrial cells.2 A subset of patients ex- 3-dimensional (3-D) ultrasonography. perience signicant uterine tenderness.18 Integration of 3-D ultrasonography has al- Other common ndings associated with ad- lowed for identication of the thicker junc- enomyosis include uterine abnormalities, tional zone that suggests adenomyosis. In a such as leiomyomata, endometriosis, and systematic review of the accuracy of TVUS, endometrial polyps. investigators reported a pooled sensitivity and specicity for 2-dimensional ultrasonography of 83.8% and 63.9%, respectively, Two-pronged route to diagnosis and a pooled sensitivity and specicity for and a differential 3-dimensional ultrasonography of 88.9% and Histology 56.0%, respectively.22 Adenomyosis is denitively diagnosed based Magnetic resonance imaging (MRI) is on histologic ndings of endometrial-like also used in the evaluation of adenomyosis. tissue within the myometrium. Historically, Although MRI is considered a more accurate

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FIGURE 1 MRI suggests adenomyosis

Left: Asymmetrical thickening of the myometrium. Right: Hyperintense foci within the uterine body.

diagnostic modality because it is not operator fect include combined or progestin-only oral dependent, expense often prohibits its use in contraceptive pills, gonadotropin-releasing the work-up of abnormal uterine bleeding hormone (GnRH) agonists, levonorgestrel- and chronic pelvic pain.2,23 releasing intrauterine devices, danazol, and FAST e most commonly reported MRI nd- aromatase inhibitors. TRACK ings in adenomyosis include a globular or Use of a GnRH agonist, such as leupro- asymmetric uterus, heterogeneity of myo- lide, is limited to a short course (<6 months) Off-label medical metrial signal intensity, and thickening of the because menopausal-like symptoms, such as management junctional zone24 (FIGURE 1). In a systematic hot ashes, vaginal atrophy, and loss of bone- options include: review, researchers reported a pooled sen- mineral density, can develop.16 Symptoms of oral contraceptive sitivity and specicity of 77% and 89%, re- adenomyosis often return upon cessation of pills (combined spectively, for the diagnosis of adenomyosis hormonal treatment.1 or progestin only), using MRI.25 Novel therapies are under investiga- GnRH agonists, tion, including GnRH antagonists, selective LNG-IUDs, progesterone-receptor modulators, and anti- danazol, and Approaches to treatment platelet therapy.27 aromatase Medical management Although there are few data showing inhibitors No medical therapies or guidelines specic the eectiveness of medical therapy on ad- to the treatment of adenomyosis exist.9 Of- enomyosis-specic outcomes, medications ten, nonsteroidal anti-inammatory drugs are particularly useful in patients who are (NSAIDs) are employed to combat cramping poor surgical candidates or who may prefer and pain associated with increased prosta- not to undergo surgery. Furthermore, medi- glandin levels.26 A systematic review found cal therapy has considerable use in conjunc- that NSAIDs are signicantly better at treat- tion with surgical intervention; a prospective ing dysmenorrhea than placebo alone.26 observational study showed that women Moreover, adenomyosis is an estrogen- who underwent GnRH agonist treatment dependent disease; consequently, many following surgery had signicantly greater medical treatments are targeted at suppress- improvement of their dysmenorrhea and ing the hypothalamic–pituitary–ovarian axis menorrhagia, compared with those who un- and inducing endometrial atrophy. Medica- derwent surgery only.28 In addition, preop- tions commonly used (o-label) for this ef- erative administration of a GnRH agonist or

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Nezhat 0219.indd 32 2/4/19 3:04 PM danazol several months prior to surgery has been shown to reduce uterine vascularity Key practice points in managing adenomyosis and, thus, blood loss at surgery.29,30 • Adenomyosis is common and benign, but remains underdiagnosed Surgery because of a nonspecic clinical presentation and lack of e objective of surgical management is standardized diagnostic criteria. to ameliorate symptoms in a conservative • Adenomyosis can cause signicant associated morbidity: manner, by excision or cytoreduction of ade- dysmenorrhea, heavy menstrual bleeding, chronic pelvic pain, and nomyotic lesions, while preserving, even im- infertility. proving, fertility.3,11,31 e choice of procedure • High clinical suspicion warrants evaluation by imaging. depends, ultimately, on the location and ex- • Medical management is largely aimed at ameliorating symptoms. • A patient who does not respond to medical treatment or does not tent of disease, the patient’s desire for uterine desire pregnancy has a variety of surgical options; the extent of preservation and fertility, and surgical skill.3 disease and the patient’s wish for uterine preservation guide the Historically, hysterectomy was used to selection of surgical technique. treat adenomyosis; for patients declining fer- • Hysterectomy is the denitive treatment but, in patients who want tility preservation, hysterectomy remains the to avoid radical resection, techniques developed for laparotomy are denitive treatment. Since the early 1950s, available, to allow conservative resection using laparoscopy. several techniques for laparotomic reduction • Ideally, surgery is performed using a combined laparoscopy and have been developed. Surgeries that achieve minilaparotomy approach, after appropriate imaging. partial reduction include: Wedge resection of the uterine wall en- tails removal of the seromuscular layer at which total resection is achieved by remov- the identied location of adenomyotic tis- ing diseased myometrium until healthy, soft sue, with subsequent repair of the remaining tissue—with normal texture, color, and vas- FAST muscular and serosal layers surrounding the cularity—is reached.2 Repair with this tech- TRACK wound.3,32 Because adenomyotic tissue can nique reduces the risk of uterine rupture by After appropriate remain on either side of the incision in wedge reconstructing the uterine wall using a mus- imaging, resection, clinical improvement in symptoms cle ap prepared by metroplasty.7 In a study ideal surgical of dysmenorrhea and menorrhagia are mod- of 64 women who underwent triple-ap re- est, and recurrence is possible.7 section, a clinical pregnancy rate of 74% and management Modi ed reduction surgery. Modica- a live birth rate of 52% were reported.7 includes a tions of reduction surgery include slicing Minimally invasive approaches. Although combined adenomyotic tissue using microsurgery and several techniques have been developed for laparoscopy and partial excision.33 focal excision of adenomyosis by laparot- minilaparotomy Transverse-H incision of the uterine wall omy,7 the trend has been toward minimally approach involves a transverse incision on the uterine invasive surgery, which reduces estimated fundus, separating serosa and myometrium, blood loss, decreases length of stay, and re- followed by removal of diseased tissue us- duces adhesion formation—all without a sta- ing an electrosurgical scalpel or scissors. tistically signicant dierence in long-term Tensionless suturing is used to close the clinical outcomes, compared to other tech- myometrial layers in 1 or 2 layers to estab- niques.35-39 Furthermore, enhanced visualiza- lish hemostasis and close the defect; serosal tion of pelvic organs provided by laparoscopy aps are closed with subserosal interrupted is vital in the case of adenomyosis.3,31 sutures.34 Data show that, following surgery How our group approaches surgical with this technique, 21.4% to 38.7% of pa- management. A challenge in laparoscopic tients who attempt conception achieve clini- surgery of adenomyosis is extraction of an cal pregnancy.7 extensive amount of diseased tissue. In 1994, Complete, conservative resection in our group described the use of simultane- cases of diuse and focal adenomyosis is ous operative laparoscopy and minilapa- possible using the triple-ap method, in rotomy technique as an eective and safe

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Pathophysiology of adenomyosis

How adenomyosis originates is not fully understood. Several theories have been proposed, however (including, more prominently, the rst 2 below): Invasion theory. The endometrial basalis layer invaginates and invades the myometrium1,2 (FIGURE); the etiology of invagination remains unknown. Reaction theory. Myometrial weakness or dysfunction, brought on by trauma from previous uterine surgery or pregnancy, could predispose uterine musculature to deep invasion.3 Metaplasia theory. Adenomyosis is a result of metaplasia of pluripotent Müllerian rests. Müllerian remnant theory. Related to the Müllerian metaplasia theory, adenomyosis is formed de novo from 1) adult stem cells located in the endometrial basalis that is involved in the cyclic regeneration of the endometrium4-6 or 2) adult stem cells displaced from bone marrow.7,8 Once adenomyosis is established, it is thought to progress by epithelial–mesenchymal transition,2 a process by which epithelial cells become highly motile mesenchymal cells that are capable of migration and invasion, due to loss of cell–cell adhesion properties.9

FIGURE Competing theories of adenomyosis pathogenesis

Increased intrauterine pressure mechanical stretch Endometrial cells

FAST Reaction theory (Tissue and injury repair) Myometrial TRACK dysfunction Stroma cells The invasion Invasion theory

theory, which Stroma asserts that the invagination

endometrial basalis Stroma cell layer invades the metaplasia

myometrium, Myobroblastic is only one of metaplasia several proposed Myometrial cells mechanisms of adenomyosis Metaplasia theory Müllerian remnant theory development

References 1. Struble J, Reid S, Bedaiwy MA. Adenomyosis: a clinical review of a challenging gynecologic condition. J Minim Invasive Gynecol. 2016; 23:164-185. 2. García-Solares J, Donnez J, Donnez O, et al. Pathogenesis of uterine adenomyosis: invagination or metaplasia? Fertil Steril. 2018;109:371-379. 3. Ferenczy A. Pathophysiology of adenomyosis. Hum Reprod Update. 1998;4:312-322. 4. Gargett CE. Uterine stem cells: what is the evidence? Hum Reprod Update. 2007;13:87-101. 5. Chan RW, Schwab KE, Gargett CE. Clonogenicity of human endometrial epithelial and stromal cells. Biol Reprod. 2004;70:1738-1750. 6. Schwab KE, Chan RWS, Gargett CE. Putative stem cell activity of human endometrial epithelial and stromal cells during the menstrual cycle. Fertil Steril. 2005;84(Suppl 2):1124-1130. 7. Sasson IE, Taylor HS. Stem cells and the pathogenesis of endometriosis. Ann N Y Acad Sci. 2008;1127:106-115. 8. Du H, Taylor HS. Stem cells and female reproduction. Reprod Sci. 2009;16:126-139. 9. Acloque H, Adams MS, Fishwick K, et al. Epithelial-mesenchymal transitions: the importance of changing cell state in development and disease. J Clin Invest. 2009;119:1438-1449.

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Nezhat 0219.indd 34 2/4/19 3:04 PM 19 DRUGS, PREGNANCY, & LACTATION 11 Gerald G. Briggs discusses antimigraine INTERPREGNANCY INTERVALS agents. 2 Shorter ones may increase adverse EDITORIAL ADVISORY BOARD outcomes. We welcome Dr. Mark P. Trolice to the ■ 22 YOGA Intervention offers modest benefit for stress incontinence. ■ DECEMBER 2018 ■ board. Vol. 53 No. 12 MDedge.com/ObGynNews 16 EMERGENCY CONTRACEPTION Teens deem it more discreet than nonemergent contraceptives.

The Leading Independent Newspaper for the Obstetrician/Gynecologist—Since 1966 16 NEWS Trump administration erodes ACA contraception mandate.

Cervical cancer survival higher with open surgery in LACC trial

BY SHARON WORCESTER FROM THE NEW ENGLAND JOURNAL OF MEDICINE

ervical cancer was more likely to recur and overall survival was lower among patients STAY TUNED who underwent minimally invasive vs. open C abdominal radical hysterectomy, based on findings from the randomized, controlled phase 3 Laparoscopic Approach to Cervical Cancer Dr. Susan Mann (LACC) trial of more than 600 women. for meeting coverage from the The alarming findings, which led to early study termination, also were supported by results from a second population-based study. Both studies

Courtesy Dr. Susan Mann Susan Dr. Courtesy were published concurrently in the Oct. 31 issue of the New England Journal of Medicine. MATERNAL MORTALITY Gynecologic oncologists who commented on Pelvic Anatomy and Gynecologic the results of these studies suggest that surgeons should discuss these results with patients, but it does not necessarily mean that use of minimally invasive laparoscopic hysterectomy for cervical Hospitals could reduce the risk with cancer should never be used again. (See View on the News on page 5 and Gynecologic Oncology Surgery Symposium Consult on page 8.) four achievable steps The authors, including Kimberlee McKay, MD, The disease-free survival at 4.5 years among president of the American College of Obstetri- BY KARI OAKES 319 patients who underwent minimally invasive cians and Gynecologists (ACOG), also call for FROM THE NEW ENGLAND JOURNAL OF MEDICINE surgery in the LACC trial was 86.0% vs. 96.5% collaboration with family physicians to increase in 312 patients who underwent open surgery, Pe- access to obstetric care in rural areas. dro T. Ramirez, MD, of the University of Texas our quickly achievable actions that can be The president of the American Academy of undertaken by every hospital providing ob- MD Anderson Cancer Center, Houston, and his ` Family Physicians (AAFP), John S. Cullen, MD, in stetric care could make a big difference in the colleagues reported (N Engl J Med.See SURVIVAL 2018 Octon page 31. 5 a separate statement, welcomed the opportunity high maternal mortality rate in the United ` F for collaboration in addressingSee MATERNAL the MORTALITY maternal on page 3 States, according to a new perspective from leading obstetricians published in the New England Journal of Medicine. VTE risk DON’T MISS Venous thromboembolism risk appearsDr. to Antonio be high Castaneda throughout the disease offers some course of uterine serous carcinoma. perspective on the study by Gressel et al. our exclusive columns See page 10. > Drugs, Pregnancy, & Lactation > Gynecologic Oncology Consult > Master Class

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FIGURE 2 Wedge resection of focal adenomyosis

Uterus Fallopian tube

Fundus of uterus

Endometrium 2.

3. Myometrium

The authors’ preferred uterine-sparing surgical approach to focal adenomyosis, or when a patient wants to preserve fertility. FAST TRACK alternative to laparotomy in the treatment might have required less time to perform.3 Our preferred of myomectomy6; the surgical principles of We therefore advocate laparoscopic approach to that approach are applied to adenomyomec- wedge resection without robotic assistance, provide symptom tomy. e technique involves treatment of aided by minilaparotomy when necessary for relief and to pelvic pathology with laparoscopy, removal safe removal of larger adenomyomas, as the preserve fertility of tissue through the minilaparotomy inci- preferred uterine-sparing surgical approach is laparoscopic sion, and repair of the uterine wall defect for focal adenomyosis or when the patient wedge resection in layers. wants to preserve fertility (FIGURE 2). We without robotic In 57 women who underwent this proce- think that this technique allows focal adeno- assistance (with dure, the mean operative time was 127 min- myosis to be treated by wedge resection of minilaparotomy utes; average estimated blood loss was 267 the diseased myometrium, with subsequent for larger mL.40 Overall, laparoscopy with minilaparot- closure of the remaining myometrial defect adenomyomas) omy was found to be a less technically dicult using a barbed V-Loc (Medtronic, Minneap- technique for laparoscopic myomectomy; al- olis, Minnesota) delayed absorbable suture lowed better closure of the uterine defect; and in layers (FIGURE 3). Minilaparotomy can be

FIGURE 3 Surgical wedge resection and closure

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Nezhat 0219.indd 36 2/4/19 3:04 PM utilized when indicated to aid removal of the of her symptoms of dysmenorrhea, menorrha- resected myometrial specimen. gia, and pelvic pain. She retained good uterine In our extensive experience, we have found integrity. Three years later, she and her husband that this technique provides signicant relief of became parents when she delivered their rst symptoms and improvements in fertility out- child by cesarean delivery at full term. After she comes while minimizing surgical morbidity. completed childbearing, she ultimately opted for minimally invasive hysterectomy. CASE Resolved The patient underwent successful wedge e authors would like to acknowledge resection of her adenomyosis by laparoscopy. Mailinh Vu, MD, Fellow at Camran Nezhat She experienced nearly complete resolution Institute, for reviewing and editing this article.

References 1. Garcia L, Isaacson K. Adenomyosis: review of the literature. 555-556. J Minim Invasive Gynecol. 2011;18:428-437. 20. Brosens JJ, Barker FG. ¨e role of myometrial needle biopsies 2. Nezhat C, Nezhat F, Nezhat C, eds. Nezhat’s Video-Assisted in the diagnosis of adenomyosis. Fertil Steril. 1995;63:1347- and Robotic-Assisted Laparoscopy and Hysteroscopy. 4th ed. 1349. Cambridge, UK: Cambridge University Press; 2013. 21. Van den Bosch T, Van Schoubroeck D. Ultrasound diagnosis 3. Osada H. Uterine adenomyosis and adenomyoma: the of endometriosis and adenomyosis: state of the art. Best Pract surgical approach. Fertil Steril. 2018;109:406-417. Res Clin Obstet Gynaecol. 2018;51:16-24. 4. Azziz R. Adenomyosis: current perspectives. Obstet Gynecol 22. Andres MP, Borrelli GM, Ribeiro J, et al. Transvaginal Clin North Am. 1989;16:221-235. ultrasound for the diagnosis of adenomyosis: systematic 5. Struble J, Reid S, Bedaiwy MA. Adenomyosis: A clinical review review and meta-analysis. J Minim Invasive Gynecol. of a challenging gynecologic condition. J Minim Invasive 2018;25:257-264. Gynecol. 2016;23:164-185. 23. Bazot M, Cortez A, Darai E, et al. Ultrasonography compared 6. Rokitansky C. Ueber Uterusdrsen-Neubildung in Uterus- und with magnetic resonance imaging for the diagnosis of Ovarial-Sarcomen. Gesellschaft der Ärzte in Wien. 1860;1 adenomyosis: correlation with histopathology. Hum Reprod. 6:1-4. 2001;16:2427-2433. 7. Osada H. Uterine adenomyosis and adenomyoma: the 24. Bragheto AM, Caserta N, Bahamondes L, et al. Eectiveness surgical approach. Fertil Steril. 2018;109:406-417. of the levonorgestrel-releasing intrauterine system in the 8. Van Praagh I. Conservative surgical treatment for treatment of adenomyosis diagnosed and monitored by adenomyosis uteri in young women: local excision and magnetic resonance imaging. Contraception. 2007;76:195- metroplasty. Can Med Assoc J. 1965;93:1174-1175. 199. 9. Donnez J, Donnez O, Dolmans MM. Introduction: Uterine 25. Champaneria R, Abedin P, Daniels J, et al. Ultrasound adenomyosis, another enigmatic disease of our time. Fertil scan and magnetic resonance imaging for the diagnosis of Steril. 2018;109:369-370. adenomyosis: systematic review comparing test accuracy. 10. Nishida M, Takano K, Arai Y, et al. Conservative surgical Acta Obstet Gynecol Scand. 2010; 89:1374-1384. management for diuse uterine adenomyosis. Fertil Steril. 26. Marjoribanks J, Proctor M, Farquhar C, et al. Nonsteroidal 2010;94:715-719. anti-inªammatory drugs for dysmenorrhoea. Cochrane 11. Abbott JA. Adenomyosis and abnormal uterine bleeding Database Syst Rev. 2010;(1):CD001751. (AUB-A)—Pathogenesis, diagnosis, and management. Best 27. Vannuccini S, Luisi S, Tosti C, et al. Role of medical therapy Pract Res Clin Obstet Gynaecol. 2017;40:68-81. in the management of uterine adenomyosis. Fertil Steril. 12. Matalliotakis IM, Katsikis IK, Panidis DK. Adenomyosis: 2018;109:398-405. what is the impact on fertility? Curr Opin Obstet Gynecol. 28. Wang PH, Liu WM, Fuh JL, et al. Comparison of surgery 2005;17:261-264. alone and combined surgical-medical treatment in the 13. Devlieger R, D’Hooghe T, Timmerman D. Uterine management of symptomatic uterine adenomyoma. Fertil adenomyosis in the infertility clinic. Hum Reprod Update. Steril. 2009;92:876-885. 2003;9:139-147. 29. Wood C, Maher P, Woods R. Laparoscopic surgical techniques 14. Levgur M, Abadi MA, Tucker A. Adenomyosis: symptoms, for endometriosis and adenomyosis. Diagn er Endosc. histology, and pregnancy terminations. Obstet Gynecol. 2000;6:153-168. 2000;95:688-691. 30. Wang CJ, Yuen LT, Chang SD, et al. Use of laparoscopic 15. Weiss G, Maseelall P, Schott LL, et al. Adenomyosis a variant, cytoreductive surgery to treat infertile women with localized not a disease? Evidence from hysterectomized menopausal adenomyosis. Fertil Steril. 2006;86:462.e5-e8. women in the Study of Women’s Health Across the Nation 31. Nezhat C, Hajhosseini B, King LP. Robotic-assisted (SWAN). Fertil Steril. 2009;91:201-206. laparoscopic treatment of bowel, bladder, and ureteral 16. Huang F, Kung FT, Chang SY, et al. Eects of short-course endometriosis. JSLS. 2011;15:387-392. buserelin therapy on adenomyosis. A report of two cases. 32. Sun A, Luo M, Wang W, et al. Characteristics and e«cacy J Reprod Med. 1999;44:741-744. of modied adenomyomectomy in the treatment of uterine 17. Benson RC, Sneeden VD. Adenomyosis: a reappraisal of adenomyoma. Chin Med J. 2011;124:1322-1326. symptomatology. Am J Obstet Gynecol. 1958;76:1044-1061. 33. Fedele L, Bianchi S, Zanotti F, et al. Surgery: Fertility after 18. Shrestha A, Sedai LB. Understanding clinical features conservative surgery for adenomyomas. Hum Reprod. of adenomyosis: a case control study. Nepal Med Coll J. 1993;8:1708-1710. 2012;14:176-179. 34. Fujishita A, Masuzaki H, Khan KN, et al. Modied reduction 19. Fernández C, Ricci P, Fernández E. Adenomyosis visualized surgery for adenomyosis. A preliminary report of the during hysteroscopy. J Minim Invasive Gynecol. 2007;14: transverse H incision technique. Gynecol Obstet Invest. CONTINUED ON PAGE 49

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Nezhat 0219.indd 37 2/4/19 3:04 PM BREAK THIS PRACTICE HABIT Uterine aspiration: From OR to of ce

Compared with uterine aspiration in the OR, an of ce-based procedure is as safe, less expensive, and more patient centered—all reasons to make it the standard for surgical management of early pregnancy failure

Lauren Thaxton, MD, MBA, and Bri Tristan, MD

CASE Patient with early pregnancy failure advent of manual vacuum aspiration (MVA) opts for surgical management using a 60-mL handheld syringe aspirator, A 36-year-old woman (G3P2) at 9 weeks from office-based treatment of pregnancy failure her last menstrual period presents for an initial has become more widely available. obstetric examination. On transvaginal ultra- In this article we make the case for why, sound, her ObGyn notes an embryo measuring in appropriate clinical situations, o ce- 9 weeks without cardiac activity. The ObGyn based uterine aspiration, compared with informs her of the early pregnancy failure diag- uterine aspiration in the OR, should be the IN THIS nosis and offers bereavement support, and then standard for surgical management of early ARTICLE reviews the available options: expectant man- pregnancy failure, for these reasons: agement with follow-up in 2 weeks, medical 1. equivalent safety pro le Safety, costs of management with mifepristone and misopro- 2. reduced costs, and of ce MVA stol, and surgical management with a dilation 3. patient-centered characteristics. and curettage (D&C). The patient is interested page 40 in expedited treatment and thus selects D&C, and the staff books the next available operat- Of ce-based procedures Patient-centered ing room (OR) slot for her the subsequent week. 1are safe procedure Over the weekend, the patient calls to report Suction curettage is one of the most common page 42 heavy bleeding and passage of clots, and the surgical procedures for a woman to undergo ObGyn’s practice partner takes her to the OR Necessary for a D&C for incomplete abortion. equipment Instant Poll page 44 arly pregnancy failure occurs in about 1 in 5 pregnancies. Treatment options E include expectant, medical, or surgical Do you agree that the standard location for uterine aspiration management. Surgical management is clas- should be in the office? sically offered in the OR via D&C. With the Yes, in appropriate clinical situations Dr. Thaxton is Assistant Professor, Department of Women’s Health, University of Texas at Austin. No Dr. Tristan is Assistant Professor and Residency Program Director, Department of Women’s Tell us at [email protected] Health, University of Texas at Austin. Please include your name and city and state. The authors report no nancial relationships relevant to this article.

CONTINUED ON PAGE 40

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during her lifetime, and it has an excellent than 50 days’ gestational age, estimated blood safety pro le. Authors of a recent systematic loss and severe pain occurred less commonly review found that major surgical compli- during procedures performed using MVA.5 cations, including transfusion and uterine perforation requiring repair, occurred in less than 0.1% of all uterine aspiration proce- Ofce-based procedures dures.1 Importantly, this complication rate 2 are less expensive did not dier by inpatient or outpatient site ere has been a trend in recent decades of procedure. to obtain cost savings by moving appropri- Anesthesia-related complications at the ately selected gynecologic procedures from time of aspiration also are extremely rare, the operative suite to the outpatient setting. and they are less likely to occur in the oce Because of MVA’s minimal up-front and on- setting than in surgical centers or hospital- going costs, oce-based suction aspiration based clinics (<0.2% and <0.5%, respec- is one of the most cost-eective procedures tively).1 is may be a result of the types of performed in the outpatient setting. anesthesia oered at varying locations, given Dalton and colleagues, for example, dem- that local analgesia or moderate sedation is onstrated that in women diagnosed with early likely used in oce-based procedures while pregnancy failure, suction curettage is 50% deep sedation or general anesthesia may be less expensive when performed in the oce as employed at other practice locations. compared to in the operating suite.6 Likewise, Studies speci cally designed to deter- in a cohort of patients who presented to the mine the safety of suction aspiration by prac- emergency department with an incomplete tice location have yielded similar results. abortion, Blumenthal and colleagues showed FAST Researchers who conducted a systematic a 41% procedural cost reduction by oering TRACK review comparing the safety of procedures D&C in the outpatient setting instead of the done at ambulatory surgical centers with OR.7 Waiting times and mean procedure times Major surgical oce-based procedures found no dierence also were reduced by nearly half. complications in safety between procedures performed in Recent studies have broadened cost occurred in less these 2 settings.2 ese ndings were con- analyses beyond the comparison of inpatient than 0.1% of all rmed by results from a large retrospective versus outpatient procedures. A multicenter uterine aspiration cohort study that reviewed more than 50,000 trial of women with rst-trimester pregnancy procedures, and aspiration procedures performed in ambula- failure compared the costs of medication the rate did not tory surgical centers versus private oces.3 In management with those of surgical proce- differ by inpatient that study, only 0.32% of women had any ma- dures; as expected, the cost of D&C in the or outpatient site jor adverse event, and there were no statisti- OR was signi cantly more expensive than of procedure cally signi cant dierences in complication medication management.8 However, MVA in rates between settings.3 the oce was less expensive than medication Complication rates based on procedure management, due largely to the increased type are similar for MVA and electric suction cost of managing medication failures. aspiration. Early studies revealed no dier- In addition, a recent, well-designed ence in the need for reaspiration or other decision model study demonstrated that complications for MVA compared with elec- oering women with early pregnancy fail- tric suction.4 is was later con rmed by a ure a greater array of management options systematic review that found no signi cant decreases costs.9 e study compared the dierences in safety by type of suction over- costs when women were oered the most all, and a possible trend toward fewer uterine common options, expectant management perforations with MVA.5 When procedures or uterine evacuation in the OR, versus the were assessed by gestational age, additional costs when additional options were also of- trends toward the safety of MVA emerged. fered. When options were expanded to in- For example, in procedures performed at less clude medication management and MVA

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CONTINUED FROM PAGE 40

in the oce, costs decreased by nearly 20% below for performing oce-based uterine overall.9 aspiration. Clinicians should review their clinic’s protocols prior to implementing such a plan. Ofce-based procedures Review the patient history and preg- 3 are more patient centered nancy dating. Patients with serious medical e benets of surgical management of an conditions, such as history of postabortion early pregnancy failure include very high hemorrhage or a bleeding disorder, may success rates (98%) and convenient timing. not be appropriate candidates for an oce- Among women who elect surgical manage- based procedure. We perform bedside ultra- ment, a desire to expedite the process in a sonography to conrm pregnancy dating and predictable fashion is a common factor in diagnosis of pregnancy failure. their decision.10,11 It is unsurprising then that Review consent for the procedure and 68% of patients will select an oce-based sedation. Risks of oce-based uterine as- procedure if they do not perceive that the cli- piration are the same as those for D&C: nician has a setting preference.6 bleeding, uterine perforation, and failure to When surgical management is per- fully evacuate the uterus. Benets include formed in the OR, scheduling delays are rapid, safe evacuation of the pregnancy. Al- common. Such delays can be clinically im- ternative treatments include expectant or portant: Women progressing to a miscar- medical management. riage while awaiting surgical treatment may For pain management, we start by dis- be at risk for urgent, unplanned interval cussing expectations with the patient. Pro- procedures for incomplete abortion, and viding general anesthesia in the outpatient FAST they may be dissatised with the inability setting is not safe; many women are satised, TRACK to access the desired management. While however, with local anesthesia with or with- women are highly satised after treatment out sedation. Very high for early pregnancy failure in general,6 OR Local anesthesia may be given using a success rates treatment can cause dissatisfaction because paracervical block with 2 mL of 1% lidocaine and convenient patients miss more work days or need assis- at the tenaculum site followed by 18 mL di- timing are tance at home.12 In a cross-sectional study, vided between the 4 and 8 o’clock positions. 2 bene ts patients who elected oce-based aspiration In our practice, we are trained providers of of surgical reported less delay to treatment (less than 2 conscious sedation, so additionally we oer management of hours) compared with women who elected IV fentanyl 100 μg and IV midazolam 2 mg an early OR procedures (more than 12 hours), and given prior to the procedure. pregnancy failure shorter time to procedure initiation was a Provide antibiotic prophylaxis. e Amer- satiser.13 ican College of Obstetricians and Gynecolo- Women also note fear of the hospital gists and the Society for Family Planning setting and general anesthesia, and they recommend doxycycline 200 mg orally as tend to see hospital-based services as more a preoperative prophylaxis for oce-based invasive.11 Clinicians can oer anesthesia in uterine aspiration.14,15 Metronidazole is an the outpatient setting with nonsteroidal anti- acceptable alternative for patients who have inammatory medications and a paracervi- medication allergies. cal block, oral sedation with an anxiolytic, or Prepare the surgical eld. To complete in some cases intravenous (IV) sedation with this procedure, you will need the following conscious sedation. equipment: • one MVA kit that includes an aspirator, curettes, and dilators (FIGURE, page 44) Our process for ofce-based • 20 mL 1% lidocaine, divided into two 10- uterine aspiration mL syringes with a 22-gauge 3.5-inch spi- We follow the step-by-step process outlined nal needle

CONTINUED ON PAGE 44

42 OBG Management | February 2019 | Vol. 31 No. 2 mdedge.com/obgyn

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FIGURE Manual vacuum description of how to perform the MVA evacuation kit contains procedure using the Ipas MVA Plus As- pirator device is available online at syringe aspirator, curettes, http://provideaccess.org/wp-content and dilators /uploads/2012/09/4Performing-MVA-Us ing-the-Ipas-MVA-Plus.pdf.

A good option for many women A D&C in the OR remains an appropriate option for patients who are clinically unstable due to heavy vaginal bleeding. With highly sensitive home urine pregnancy tests, preg- Used with permission of HPSRx Enterprises, Inc. nancies often are diagnosed before clinically apparent miscarriage. In fact, many such patients are diagnosed with pregnancy fail- • speculum ure in the oce, as was our patient in the • cervical antiseptic prep case scenario. For such women, oce-based • single-tooth tenaculum management of early pregnancy failure is • ring forceps. preferred because it is safe, cost-eective, Perform the MVA procedure. A full and patient centered.

References FAST 1. White K, Carroll E, Grossman D. Complications from rst- 8. Rausch M, Lorch S, Chung K, et al. A cost-eectiveness TRACK trimester aspiration abortion: a systematic review of the analysis of surgical versus medical management of early literature. Contraception. 2015;92:422-438. pregnancy loss. Fertil Steril. 2012;97:355-360. 2. Berglas NF, Battistelli MF, Nicholson WK, et al. e eect of 9. Dalton VK, Liang A, Hutton DW, et al. Beyond usual care: the A D&C in the facility characteristics on patient safety, patient experience, economic consequences of expanding treatment options in OR remains an and service availability for procedures in non-hospital- early pregnancy loss. Am J Obstet Gynecol. 2015;212:177.e1-6. aliated outpatient settings: a systematic review. PloS One. 10. Schreiber CA, Chavez V, Whittaker PG, et al. Treatment appropriate option 2018;13:e0190975. decisions at the time of miscarriage diagnosis. Obstet Gynecol. for patients who 3. Roberts SC, Upadhyay UD, Liu G, et al. Association of facility 2016;128:1347-1356. type with procedural-related morbidities and adverse events 11. Smith LF, Frost J, Levitas R, et al. Women’s experiences of are clinically among patients undergoing induced abortions. JAMA. three early miscarriage management options: a qualitative unstable due to 2018;319:2497-2506. study. Br J Gen Pract. 2006;56:198-205. 4. Goldberg AB, Dean G, Kang MS, et al. Manual versus 12. Edwards S, Tureck R, Fredrick M, et al. Patient acceptability of heavy vaginal electric vacuum aspiration for early rst-trimester abortion: manual versus electric vacuum aspiration for early pregnancy bleeding a controlled study of complication rates. Obstet Gynecol. loss. J Womens Health (Larchmt). 2007;16:1429-1436. 2004;103:101-107. 13. Dodge LE, Ho¨er LG, Hacker MR, et al. Patient satisfaction and 5. Wen J, Cai QY, Deng F, et al. Manual versus electric vacuum wait times following outpatient manual vacuum aspiration aspiration for rst-trimester abortion: a systematic review. compared to electric vacuum aspiration in the operating room: BJOG. 2008;115:5-13. a cross-sectional study. Contracept Reprod Med. 2017;2:18. 6. Dalton VK, Harris L, Weisman CS, et al. Patient preferences, 14. American College of Obstetricians and Gynecologists. satisfaction, and resource use in oce evacuation of early ACOG practice bulletin no. 195: Prevention of infection after pregnancy failure. Obstet Gynecol. 2006;108:103-110. gynecologic procedures. Obstet Gynecol. 2018;131:e172-e189. 7. Blumenthal PD, Remsburg RE. A time and cost analysis of the 15. Achilles SL, Reeves MF; Society of Family Planning. management of incomplete abortion with manual vacuum Prevention of infection after induced abortion. Contraception. aspiration. Int J Gynaecol Obstet. 1994;45:261-267. 2011;837:295–309.

The “Break This Practice Habit” series is spearheaded by Dr. Lauren Demosthenes, who makes overarching high value cost decisions in her role as Medical Director of High Value Care and Innovation, Department of ObGyn at Greenville Health System in Greenville, South Carolina. Watch for quarterly case presentations of low value, low evidence practices that should be questioned in current day, followed by reasons why that practice should be abandoned. If you would like to contribute to this series, please submit your query to Dr. Demosthenes at [email protected].

44 OBG Management | February 2019 | Vol. 31 No. 2 mdedge.com/obgyn

Tristan 0219.indd 44 2/4/19 3:01 PM Verdicts 0219.indd 45

PHOTO: SHUTTERSTOCK mdedge.com/obgmanagement nal pain, can walk a short distance, and uses a wheel- a uses and distance, short a walk can pain, nal abdomi- constant hands.hasprostheticCurrently, she her use to and feet prosthetic with walk to learned she colostomy a was performed. developed, stula a When body. her of outside intestines her hold to created was sac skin a wall, abdominal an had longer no she Because grene. gan- to due ankles the above feet both and above wrists the hands both of amputation as well as bacteria the control to Janu- surgeries additional of required end She ary. the until operation exploratory the of abdominal muscles andwall. including bacteria, the by aected areas and intestine injured the resected He fasciitis. necrotizing of development the to leading intestine small her in ration sepa- a found he surgery, During vasopressors. of use the cancelled and surgery exploratory ordered diately imme surgeon trauma e consult. surgery trauma administeredthey vasopressors. tomography (CT) scan but she had to be stabilized before computed transport; abdominal an have she that but soon went into organ failure. ICU physicians suggested (ICU), unit care intensive the to transferred was She suspected. was shock septic measured,and be not A large amount discharge ofbloody drained. the while patient was attempting to opened stand up from the commode. incision umbilical 5-cm the gery, sur- after hours Twenty-seven stabilized. be not could BP her and incoherent became she day, next e low. remained BP her but uids, given was She declined. (BP) pressure blood patient’s the surgery, After geon. formed by a minimally invasive gynecologic (MIG) sur- She went to a Maryland hospital for rehab,where for hospital Maryland a to went She time the from unconscious remained patient e a for called surgeon the day, next the 4:30 At At 11:00 that day, her BP was so low that it could ein vra cs per- cyst ovarian benign a underwent of excision laparoscopic woman old On November 1, a 45-year- $109M award cystectomy: feet after hands and Woman loses

- She can nolonger work andisondisability. tasks. everyday for assistance 24/7 requires chair.She to gangrene andthesubsequent amputations. to the 4 extremities. In this case, use of vasopressors led sors, which increase BP by cutting o blood circulation vasopres- of doses extensive required have not would She spreading. from prevented been have would teria bac the and discovered, been have would the diagnosis earlier, occurred surgery exploratory or scan CT the later.Had hours 12 until consult surgical a for call not did procedureand the repeatedly delayed surgeon the but scan, CT a for transported be to enough stable to ourish. fasciitis necrotizing the allowed that environment an patient’screated thatADEPT concluded ObGynexpert e adhesions. of formation the prevent to solution a enterotomy, an as injury not atear. the to referred trauma surgeon e fasciitis. necrotizing and sepsis causing cavity, abdominal the enter to bacteria allowed surgery. is during injury the nd not did but intestine, the cystectomy, he almost completely transected her small During surgeon. MIG the employed that system PATIENT’SCLAIM: VERDICT: DEFENSE: DEFENDANTS’ o a T cn eas i wud o hv son the shown have source ofthepatient’s not condition. would it because scan CT a for call not did surgeon the that claimed also defense e own. its on occurred had that tear a was injury main the that and intestine the nicked only had surgeon the that opined defense the for witness gations.expert e a separate claims bill. $100,000 of the award through the Florida but legislature in all of recovery seek must patient the statute, nity versity health system. Under Florida’s sovereign uni- immu- the against returned was verdict Florida million and awards.and in litigation and are meant to illustrate nationwide variation in jury verdicts less, these cases represent of clinicalthe types situations that typically result times incomplete. Moreover, the cases may or may not have merit. Neverthe- information available to the editors about the cases presented here is some- e (www.verdictslaska.com). Laska of Lewis editor, the editors of permission the with by selected were 46, M¤¥¤¦§§¥¨ page from on those and case, is e ICU physicians concluded that the patient was ADEPT, used surgeon the procedure, the During Vol. 31 No.2|February2019 After 2 trials ended with hung juries, a $109 a juries, hung with ended trials 2 After Medical NOTABLE JUDGMENTSANDSETTLEMENTS Medical Malpractice Verdicts, Settlements, & , Experts e patiente universitythe sued health e defendants denied all alle- all denied defendants e VERDICTS OBGManagement CONTINUED ONPAGE 46 OBG OBG 45 - 2/4/19 3:02PM Medical VERDICTS

CONTINUED FROM PAGE 45

PATIENT’S CLAIM: Her kidney loss was to release the shoulder dystocia. Child has hypoxic a direct result of the ObGyn’s initial VERDICT: A $1.2 million Virginia set- brain injury: surgical procedure. He had placed tlement was reached. $7.75M settlement several clips near the ureter and did not verify their position or protect At 41 weeks’ gestation, a mother the ureter. He also failed to address Ureter injured during presented to the emergency depart- her reported symptoms in a timely hysterectomy ment (ED) for delivery after an unre- manner. markable pregnancy. During the last PHYSICIAN’S DEFENSE: e damage When a patient was found to have 90 minutes of labor, fetal heart-rate to the ureter is a known risk of hys- multiple, symptomatic broids and (FHR) monitoring showed nonreas- terectomy and oophorectomy. e an enlarged uterus, her gynecolo- suring ndings. After a vaginal deliv- obstruction developed over time, gist suggested a total laparoscopic ery, the infant was found to have a not as an immediate result of the hysterectomy. During the proce- hypoxic brain injury. surgery. dure, when he inspected the pelvis PARENTS’ CLAIM: Even though non- VERDICT: A Kentucky defense verdict and found multiple broids in and reassuring FHR monitoring ndings was returned. around the uterus, the gynecolo- occurred, the physicians did not gist converted to a supracervical oer cesarean delivery (CD). e hysterectomy. Surgery was dicult pediatrician and ED physician were History of shoulder because of a large myoma on the negligent in failing to provide proper dystocia, Erb’s palsy: right broad ligament. neonatal resuscitation and in recog- $1.2M settlement e patient tolerated surgery nizing a problem with the infants’ well and was released home the next intubation. e delay in delivery and An obese mother was admitted to day. At follow-up one week later, she poor resuscitation procedure caused the hospital at 39 weeks’ gestation had no signs or symptoms of ureter the child’s injury. with signs of labor. She requested injury. Later that same evening, she DEFENDANTS’ DEFENSE: All allega- a CD and was advised that she had experienced sharp ank pain and tions were denied. ere was no progressed too far for that to be an nausea. When she called the gyne- deviation from the standard of care. option, and that vaginal delivery cologist, he sent her to the emer- VERDICT: A $7.75 million Massachu- would be safe. During the second gency department. A computed setts settlement was reached. stage of labor, shoulder dystocia was tomography scan showed extravasa- encountered. e ObGyn made sev- tion of the right ureter. She under- eral attempts to deliver using down- went months of stent placements Kidney failed ward traction, but was unsuccessful. and replacements, nephrostomies, after hysterectomy A second ObGyn swept the shoulder and ultimately ureteral reimplanta- with an internal maneuver of his tion surgery. A 46-year-old woman underwent hand and delivered the baby. e PATIENT’S CLAIM: e gynecologist a hysterectomy performed by her child has a severe brachial plexus caused a thermal injury to her right ObGyn. Surgery went well but the injury at multiple spinal levels result- ureter during the hysterectomy by patient continued to report symp- ing in Erb’s palsy. misusing an electrocautery device. toms. A year later, she underwent PARENT’S CLAIM: A CD should have ere was a delay in timely diagnosis an oophorectomy. Two years later, been performed. e rst ObGyn postsurgery. the patient reported blood in her failed to provide a CD and repeat- PHYSICIAN’S DEFENSE: e gynecolo- urine and underwent a computed edly applied excessive downward gist contended that he employed tomography scan, which revealed traction, causing the infant’s injury. proper surgical technique, and that an obstructed left ureter that had PHYSICIAN’S DEFENSE: Shoulder he reacted properly when the patient caused injury to the left kidney. dystocia is unpredictable and an reported the pain. Seven months later, the kidney was unpreventable obstetric emergency. VERDICT: A Virginia defense verdict removed. e ObGyn used proper maneuvers was returned.

46 OBG Management | February 2019 | Vol. 31 No. 2 mdedge.com/obgmanagement

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48 OBG Management | February 2019 | Vol. 31 No. 2 mdedge.com/obgyn

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A patient with severe adenomyosis requests uterine-sparing surgery

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2004;57:132-138. tubal pregnancy: a randomized trial versus laparotomy. Fertil Steril. 1991;55:911-915. 35. Operative Laparoscopy Study Group. Postoperative adhesion development after 38. Kwack JY, Kwon YS. Laparoscopic surgery for focal adenomyosis. JSLS. 2017;21. operative laparoscopy: evaluation at early second-look procedures. Fertil Steril. pii:e2017.00014. 1991;55:700-704. 39. Podratz K. Degrees of Freedom: Advances in Gynecological and Obstetrical Surgery. 36. Luciano AA, Maier DB, Koch EI, et al. A comparative study of postoperative Remembering Milestones and Achievements in Surgery: Inspiring Quality for a Hundred adhesions following laser surgery by laparoscopy versus laparotomy in the rabbit Years 1913–2012. Chicago, IL: American College of Surgeons; 2012. model. Obstet Gynecol. 1989;74:220-224. 40. Nezhat C, Nezhat F, Bess O, et al. Laparoscopically assisted myomectomy: a report of 37. Lundor P, Hahlin M, Källfelt B, et al. Adhesion formation after laparoscopic surgery in a new technique in 57 cases. Int J Fertil Menopausal Stud. 1994;39:39-44.

medjobnetwork.com Vol. 31 No. 2 | February 2019 | OBG Management 49

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50 OBG Management | February 2019 | Vol. 31 No. 2 medjobnetwork.com

OBG_0119_Classifieds.indd 50 2/4/19 2:56 PM Examining the EVIDENCE

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health outcomes. Investigators used medical WHAT THIS EVIDENCE MEANS FOR PRACTICE records to con rm health outcomes. After adjusting for covariates, no signi - Despite the boxed warning on vaginal estrogen, the ndings from cant dierences in risks were found for CVD, this study support the safety of vaginal estrogen use for effective cancer, and hip fracture between users and relief of GSM in women with and without a uterus. nonusers of vaginal estrogen, regardless of JOANN V. PINKERTON, MD, NCMP hysterectomy status.

Key ndings therapies during the NHS included vaginal After adjusting for multiple variables (includ- estrogen tablets, creams, and an estradiol ing age, race, physical activity, age at meno- ring, with higher doses available during ear- pause, hysterectomy, aspirin use, parental lier parts of the study than the lower doses history of cancer, etc), health outcomes for commonly prescribed in current day. CVDs, all cancers, and hip fracture were: • myocardial infarction: hazard ratio (HR), Overall 0.73 (95% con dence interval [CI], 0.47– e ndings from this long-term follow-up 1.13) of the NHS provide support for the safety • stroke: HR, 0.85 (95% CI, 0.56–1.29) of vaginal estrogen for treatment of GSM. • pulmonary embolism/deep vein throm- No statistically signi cant increased health bosis: HR, 1.06 (95% CI, 0.58–1.93) risks were found for users of vaginal estro- • hip fracture: HR, 0.91 (95% CI, 0.60–1.38) gen, similar to earlier reported ndings from • all cancers: HR, 1.05 (95% CI, 0.89–1.25). the large Women’s Health Initiative.2 Low- Health outcomes for speci c inva- dose vaginal estrogen is recommended for sive cancers (risk for endometrial cancer treatment of GSM by e North American FAST included only women with an intact uterus) Menopause Society, the American College TRACK were: of Obstetricians and Gynecologists, and the • invasive breast cancer: HR, 1.07 (95% CI, Endocrine Society. Low-dose 0.78–1.47) Absorption of low-dose vaginal estro- vaginal estrogen • ovarian cancer: HR, 1.17 (95% CI, gen preparations appears minimal, and they is effective and 0.52–2.65) are eective and generally safe for the treat- generally safe for • endometrial cancer: HR, 1.62 (95% CI, ment of GSM for women at any age. Proges- treating GSM in 0.88–2.97) terone is not recommended with low-dose women of any age • colorectal cancer: HR, 0.77 (95% CI, vaginal estrogen therapies, based primar- 0.45–1.34). ily on randomized clinical trial safety data of 12 months.3 Postmenopausal bleeding, Study strengths and weaknesses however, needs to be thoroughly evaluated. A causal relationship cannot be proven as For women with breast cancer, include the the study was observational. However, a oncologist in decision making about the use strength included the 18 years of follow-up. of low-dose vaginal estrogen. Women used vaginal estrogen for an average of 3 years, which provided longer-term safety data than available 12-month clinical trial References 1. Gandhi J, Chen A, Dagur G, et al. Genitourinary syndrome data. Data were collected through self-report of menopause: an overview of clinical manifestations, on questionnaires every 2 years, which is a pathophysiology, etiology, evaluation, and management. Am J Obstet Gynecol. 2016;251:704-711. drawback; however, participants were reg- 2. Crandall CJ, Hovey KM, Andrews CA, et al. Breast cancer, istered nurses, who have been shown to endometrial cancer, and cardiovascular events in participants who used vaginal estrogen in the Women’s Health Initiative provide reliable health-related information. Observational Study. Menopause. 2018;25:11-20. Comparisons between therapies were not 3. e NAMS 2017 Hormone erapy Position Statement Advisory Panel. e 2017 hormone therapy position possible as data were not collected about statement of e North American Menopause Society. type or dosage of vaginal estrogen. Available Menopause. 2017;24:728-753.

mdedge.com/obgyn Vol. 31 No. 2 | February 2019 | OBG Management 51

Evidence Pinkerton 0219.indd 51 2/4/19 3:07 PM Examining the EVIDENCE

Is vaginal estrogen used for GSM associated with a higher risk of CVD or cancer?

No. Vaginal estrogen use (average duration of use, 37.5 months) for genitourinary symptoms of menopause (GSM) was not associated with a higher risk of cardiovascular disease (CVD) or cancer in nonusers of systemic hormone therapy in the Nurses’ Health Study. During 18 years of follow-up for the almost 900 postmenopausal users of vaginal estrogen, compared with about 53,000 nonusers, the risks of CVD, cancers, and hip fractures were not different between groups. Presence or absence of a uterus did not change the study results.

FAST EXPERT COMMENTARY Despite lack of any observational or clin- TRACK JoAnn V. Pinkerton, MD, NCMP is Professor ical trial evidence for chronic health disease of Obstetrics and Gynecology, University of Virginia Health System, and Executive Director, The North risks related to low-dose vaginal estrogen use, The package American Menopause Society. Dr. Pinkerton serves on there remains an US Food and Drug Admin- label for low- the OBG MANAGEMENT Board of Editors. istration boxed warning on the package label dose vaginal for low-dose vaginal estrogen related to risks estrogen warns of Bhupathiraju SN, Grodstein F, Stampfer MJ, et al. Vaginal of heart disease, stroke, venous thromboem- chronic disease estrogen use and chronic disease risk in the Nurses’ Health bolism, pdementia, and breast cancer. e risks with use Study. Menopause. December 17, 2018. doi: 10.1097/ objective of the investigation by Bhupathiraju despite lack of GME.0000000000001284. and colleagues was to evaluate associations observational data between vaginal estrogen use and health out- or trial evidence comes, including CVD (myocardial infarc- to support the SM, a chronic and often progressive tion, stroke, and pulmonary embolism/deep warning condition, occurs in almost 50% of vein thrombosis), cancer (total invasive, Gpostmenopausal women and has breast, endometrial, ovarian, and colorectal), been shown to impair sexual function and and hip fracture. quality of life.1 Symptoms include vaginal dryness, vulvar or vaginal itching, dyspa- Details of the study reunia, urinary urgency or frequency, and e prospective analysis included 896 post- increased urinary tract infections. Although menopausal current users of vaginal estro- lubricants or vaginal moisturizers may be gen in the Nurses’ Health Study (NHS; sucient to treat GSM, targeted hormonal 1982 –2012), compared with 52,901 nonusers. therapy may be needed to improve the Eighteen years of follow-up was evaluated. symptoms and resolve the underlying cause, Users of systemic hormone therapy were due to vaginal hormone loss. excluded from the analysis. For the NHS, self- The author reports no nancial relationships relevant reported data were collected every 2 years on to this article. questionnaires for vaginal estrogen use and

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52 OBG Management | February 2019 | Vol. 31 No. 2 mdedge.com/obgyn

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