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    220 Cae Ectopic Pregnancy TUBAL PREGNANCY. 220 TUBAL PREGNANCY DIAGNOSIS m MEDICAL MANAGEMENT ns SURGICAL MANAGEMENT 28 INTERSTITIAL PREGNANCY. a ‘CESAREAN SCAR PREGNANCY ne CERVICAL PREGNANCY 20 ABDOMINAL PREGNANCY 20 OVARIAN PREGNANCY a HETEROTOPIC PREGNANCY a REFERENCES. m Following fertilization and fallopian tube transit, the blasto- ‘st normally implants in the endometrial lining of the wter ine cavity. Implantation elsewhere ix considered ectopic. In the United States, numbers fom an insurance database and from Medicaid claims showed ectopic pregnancy rates of 1.54 percent and 1.38 percent, respectively, in 2013 (Tao, 2017) Ectopic implantation accounts for 3 percent of all pregnaney- related deaths (Creanga, 2017). Fortunately, beta-human chorionic gonadotropin (B-hCG) assays and. wansvaginal sonography (IVS) aid earlier diagnosis, maternal survival, and fertility conservation. TUBAL PREGNANCY Classification OF ectopic pregnancies, neatly pala (70 percent) is the most frequent site (Vig. 12-1). The rate for 'sthmie implantation is 12 percent; fimbial, 11 percent: and ines, 2 percent (Bouycr, 2002), Nontubal ectopic preg- fancies compose the remaining 5 percent and implant in the TEER REEMA Oo ee eee rein eee wih normal uterine implantation and che other implanted ectopi- cally. This is termed a heterotopic pregnancy (p. 231). For all ectopic pregnancy sites, management is influenced by pregnancy viability, gestational age, maternal health, desires for FIGURE 12-1. Ampulary tubal pregnancy (arow) seen duting laparoscopy. (Reproduced with permission from Dr isa Chao) the index pregnancy and for Fare frit, physician sil, and aihble escuces, Renee ‘pike etopie pregnancy we get an6-D imamunogiobalin In fsetsimester pregnancies,» single intramuscular 50- oF 120g dose i appropriate. Lice gestions are given 300 jig (American Collegeof Obstetricians and Gynecologists, 20195). 1m Risks ‘Abnormal fallopian tube anatomy underlies most eases of tubal cctopic pregnancy. Surgeries for a prior tubal pregnancy, for feriliy estoraion, oF for sterilization confer the highest risk ‘After one prior ectopic pregnancy, the chance of another near, 10 percent (de Bennetot, 2012). Previous tubal infection, which can distort normal tubal anatomy, is another risk. Specifically, ine episode of salpingitis ean be followed by a subsequent ecto- pic pregnancy in up to 9 percent of women (Westrom, 1992) Pericubal adhesions that form ftom silpingts, appendicitis, of endometriosis also raise chances. Inferiity and the use of assisted reproductive technologies (ART) to overcome it are inked to increased ectopic pregnancy rates (Li, 2015; Perkins, 2015). Newer techniques aim to lower this rate with ART (Londra, 2015; Zhang, 2017). Smoking is another known association, although the underlying mecha- nism is unclear (Hyland, 2015) ast, wihrany formjof contra: ception, the absolute number of ectopic pregnancies declines because pregnancy is effectively prevented. However, some methods more efficiently prevent intracavity implantation and ‘with cher failure, ectopic implantation i favored. These meth- ods are tubal sterilization, intrauterine devices (IUDs), and progestin-only contraceptives, 1 Pathogenesis and Potential Outcomes With tubal pregnancy, because the fallopian tube lacks a sub- ‘mucosal layer, the fertilized ovum promptly burrows through the epithelium. The zygote comes to lie near or within the mus- cilatis, which is invaded by rapidly proliferating trophoblast. Potential outcomes from this include tubal rupture, tubal abor- tion, or pregnancy failure with resolution. With rupeure, che invading and expanding conceptus can ‘car the fallopian tube. Tubal ectopic pregnancies usually rup- ture spontancously but may occasionally burst fllowing coitus or bimanual examination. Hemorthage usualy persists and can become life threatening. ‘Tubal abortion describes the pregnancy's passage out the fal- lopian cube's distalend. Subsequently, hemorshage may cease, and symptoms eventually disappear. However, bleeding instead can progress to induce symptoms as long as products remain, in the tube. Blood slowly issues from the tubal fimbria into the peritoneal cavity and pools in the rectouterine eul-de-sac. If the fimbriated extremity is occluded, the fallopian tube may gradually distend with blood to form a hematosalpinx. Rarely, an aborted fetus will secondarily implant on a peritoneal surfice and become an abdominal pregnancy (p. 231). Last, spontaneous failure reflects ectopic pregnancy death and subsequene reabsorption, These are now more regularly identi- fed by current sensitive 3-hCG assays and surveillance. Ectopic Pregnancy Distinctions berween aeueeetopi pregnancy, just described, and chronic ectopie pregnancy also can be drawn. Acute ectopic pregnancies are more common, produce a high serum -hCG level, and grow rapidly, leading to a timely diagnosis. These carry a greater risk of rupture (Barnhart, 2003e). With ehronie cetopie pregnancy, abnormal trophoblasts die early, and thus serum B-hCG levels are negative or are low and static. Chronic cctopie pregnancies typically rupeure late, if at all, bue come ‘monly form a persistent complex pelvie mass. "This sonographic finding, rather than patient symptoms, often isthe reason that prompts diagnostic surgery (Tempfer, 2019) I Clinical Manifestations Sources of abdominal pain during pregnancy are extensive. Uterine conditions include miscarriage, infection, degenerating or enlarging leiomyomas, of round-ligament pain. Adnexal pain ‘may reflect ectopic pregnancy oF ovarian masses that are hem- lorthagic, ruptured, oF torsed. Appendicitis, renal stone, cyst tis, and gastroenteritis are some nongynecological reasons for lower abdominal pain in early pregnancy. Thus, an initial urine B-ACG assay, urinalysis, and measure of hemoglobin or hema- tocrit are routine. A complete blood count (CBC) to assess the white blood cell count may be preferred if serious infection isa possible diagnosis. A positive urine pregnancy test result should prompt a serum 3-hCG assay for those with pain or bleeding. Before rupture, symptoms and signs of ectopic pregnancy are often subtle of absent. ‘The classic triad is amenorrhea that is followed by pain and vaginal bleeding. Wich tubal rupture, lower abdominal and pelvic pain is usually severe and fre- quently described as sharp, stabbing, or tearing. Some degree of vaginal sporting or bleeding is reported by most women with tubal pregnancy. Although profuse vaginal bleeding suggests an incomplete abortion, such bleeding occasionally is seen with tubal gestations. Moreover, tubal pregnancy can lead to signifi- cant intraabdominal hemorthage. Neck or shoulder pany espe= cially on inspiration, develops in women with diaphragmatic irritation from a sizable hemoperitoneum., Vertigo and syncope ‘may reflect hemorshage-rclated hypovolemia ‘OF physical findings, abdominal palpation elicits tenderness. Bimanual pelvic examination may reveal a mass and tenderness, but chis examination should be limited and gentle to avoid iat- rogenic ruprure. The uterus itself can be slightly enlarged due ro hormonal stimulation, Responses to moderate bleeding include rho change in vital signs, a slight rise in blood pressure, of a vvasovagal response with bradycardia and hypotension. Blood ppressute will fall and pulse will rise only if bleeding continues and hypovolemia becomes significant. (Of laboratory findings, hemoglobin or hematocrit readings ‘may at first show only a slight reduction, even after substantive hemorrhage. Thus, after acute hemorthage, a tending decline in hemoglobin or hematocrit levels over several hours isa more valuable index of blood loss than is the initial level. In approxi- imately half of women with a euptured ectopic pregnancy, vary- ing degrees of leukocytosis may reach 30,000/pL. Decidua is endometrium that is hormonally prepared for pregnancy. The degree to which the endometrium is converted with ectopic pregnancy varies. Thus, in addition to bleeding, 221 fame re) De) 222 First- and Second-Trimester Pregnancy Loss S NOILDaS FIGURE 12-2 This 7-cm decidua cast was passed by a patient ‘witha tubal ectopic pregnancy. The cast mitrrs the shape ofthe tendometial cavity, and each arrow marks the portion of decidua that lined the cornua, ‘EGET eco cel ree TO (DSgenETemtre ouEied esoenetrcaTCaeT EL ETS (Fig. 12-2). Importantly, decidual sloughing may also occur with miscartiage. Thus, tissue is care. fully examined by the provider and chen submitted to evaluate for histological evidence of a conceptus. If no clear gestational sac isseen by inspection ot ifno vill are identified histologically, the possibility of ectopic pregnancy must stil be considered. ‘TUBAL PREGNANCY DIAGNOSIS For ectopic pregnancy, physical findings, serum B-CG level, measurement, TVS, and at times diagnostic surgery are tools for diagnosis. Women with evidence of tubal rupture undergo prompt surgery, For all other hemodynamically stable women, swithous a clearly identified pregnancy, diagnostic strategies use these tools to identify ectopic pregnancy. Serategies involve trade-offs, Those that maximize ectopic pregnancy detection may terminate a normal intrauterine preg- nancy (IUP). Conversely, those that reduce the potential inter- ruption of a normal [UP can delay ectopic pregnancy diagnosis, Patient desires forthe index pregnancy are sought and influence these trade-off, § Beta-Human Chorionic Gonadotropin Rapid and accurate detrinittion of pregnancy ia fandamenal step. hCG is a glycoprotein produced by placental trophoblast Curren pg nancy test ar immanoasays hat eck the beta subunit of KCC. ‘Lower limits of detection are 20 to 25 miU/mL for wine and (Greene, 2015). Diffrentasays an have ress tha vary by 5 10 peront. Thos, rial wales a more reliable when performed by the same laboratory (Desai, 2014). IVS finding. With values above discriminatory eheshold tas. Some institutions ser their discriminatory threshold at >1500 mlU/ mL, whereas others use 2000 mIU/mL. Connolly and associ- ates (2013) suggested an even higher threshold. They noted that I Transvaginal Sonography Pregnancy of Unknown Location fayolk sac, embryo, or fetus is found within the uterus or within the adnexa, a diagnosis is made. However: ifno evidenee of an ‘cps tc Se oR AE ATOOTR (Searae RUE oe EU Ua reece Oa ee TUTE recent est ERR CS EO DC EES ‘Without clear evidence for ectopie pregnancy, serial B-hCG level assessment is reasonable, and a second level is obtained 48 hhours after the frst. This practice averts unnecessary methotrex- ate therapy and avoids harming an early, normal IUP. With earlypmormal IUPs, Barnhart and coworkers (2004b) reported 353: Seeber and colleagues (2006) found an even more conservative minimal 235-pereent rise in normal IUPs. With ULs fl before thet cation is identified. With fing PULs, Bues and coworkers (2013) found aes of desine that ranged SING [STORE AREAS sad OS eS ZIpeTCe RE Gam and 5000 malin Despite these benchmarks thi of 7 (Sika, S006), Overall, whereas fly. Imporantly, despite» declining G-RCG level a resolving ectopic pregnaney may rupture Rapa at low values key sflets partial disruption ofthe vascular connection bxeween trophoblast and. maternal yes Hers, although BshCG is produced it isunable to ener ceuion ad be detected Ta geen ecsing is eppeally more Requent if symproms or Q-4CG level trends reflec a higher ectapie pregnaney tk (American College of Obstetricians and Gynecologists, 20196). TVS also may be tepeted. This wil esas to reach a iagnods is bolaneed ana che uprre rdf he pregraney is indeed ecto sion and/euretage (D&O) ivanopdion (Barshar, 2021). I gre a ster diognoss but may interrupt a normal TUP. are ctctoge a sonnd TVS exatsination may be indicted and inay diplay new informative Endings ‘A nated, ectopic pragnances an suptre even atlow B-hOG levels. Thus, serum B-hCG values are usually followed until they lie bow the negativereul threshold fr the given aay. Endometrial Findings In a woman in whom ectopic pregnancy is suspected, TVS is performed to look for Findings indicative of an IP or ectopic FIGURE 12-3 Transvaginal sonography of a pseu within the endometrial cavity ts central location is characteris of these anechote fui collections. The endornetium is marked by calipers and distal to ths fad, the endometial thickness has a telaminar patter. This pattern is common with ectopic pregnanc (Reproduced with permission from Jason Mehr, ARDMS d pregnancy. During endometrial cavity evaluation, an intrauter: estational sac is usually visible between 4¥4 and 5 weeks, “The yolk sac appears between 5 and 6 weeks, and a fetal pole with cardiac activity is first detected at 515 to 6 weeks (Fig. 14-1 p. 248). With transabdominal sonography, these structures are visualized slightly later. In contrast, with ectopic pregnancy, a trilaminar endome- trial pattern is characteristic ( ). les specificity is 94 percent, but with a sensitivity of only 38\percent (Hammoud, 200 in women with a PUL at presentation that no normal IUPs had an endometial stripe thickness <8 mm, Anechoic fluid collections, which might normally suggest an early intrauterine gestational sac, may also be seen with ectopic pregnancy. These include pseudogestational sac and ddecidual cyst. Fist, a pseudosae is a fluid collection between the endometrial layers and conforms to the cavity shape (see Fig, 12-3). Ifa pseudosac is noted, the risk of ectopic pr nancy is inereased (Hill, 1990). Second, a decidual eyst is iden: tified as an anechoic area lying within the endometrium but remote from the canal and often at the enclomettial-myometral border. This may represent early decidual breakdown that pre- cedes cast formation (Ackerman, 1993b). These two findings contrast with the intradecidual sign seen with IUPs, With this sign, the early gestational sac is an, anechoic sac eccentrically located within one of the endome- trial stipe layers (Dashefiky, 1988). The American College of Obstetricians and Gynecologists (2020) advises caution in diagnosing an IUD if a definite yolk sac or embryo is not In addition, Moschos and Twickler (2008) determined Adnexal Findings “The sonographic diagnosis of ectopic pregnancy rests on see ing an adnexal mass separate from the ovary ( Die an extrauterine yolk sic, embryo, or fetus is identified, ectopic pic Pregnancy 223 ZL WaldVHD FIGURE 12-4 Various transvaginal sonographic findings with ubal pregnancies. For sonographic ca be seen in the adnexa separate fom the ovary and rem as-(A) a yolk sac (shown here) and/or fetal pole with out cardac activity within an extrauteine sac, (B) an e ith a hyperechoic ring, or (€) an inhome topic pty adnexal mass In this last imag oppler shows a classic "ing Of fie which reflects increased vasculaity typical of ectopic preg nancies, LT OV = lft vary; SAG LT AD = sagital et adnexal UT = uterus 224 First- and Second-Trimester Pregnancy Loss. S NOILDaS pregnancy is clearly confirmed. In other cases, a hyperechoic halo or tubal ring surrounding an anechoic gestational sac is seen. Alternatively, hemorrhage within the ectopic pregnancy ‘can form a solid, complex adnexal mass. Overall, 60 percent ‘of ectopic pregnancies are a complex mass) 2O)percene are a hyperechoic ring; and 13 percent have an obvious gestational sac with a yolk sac or embryo (Condous, 2005). Importantly, not all adnexal masses represent an ectopic pregnancy. In this, ‘case, integration of sonographic findings with other clinical information is necessary. Placental blood ow within the periphery of the complex adnexal mass—the ring of fire—can be seen with application (of color Doppler. A corpus luteum cyst often displays a similar vascular pattern, and differentiation can be challenging. Hemoperitoneum In affected women, blood in the peritoneal cavity is most often TVS ( ). A small amount of perito- real fuid is physiologically normal. Howevery with hemo= peritoneum, anechoic or hypoechoic Auid initially: collects injtheldependentretrouterinejeulalesae; Ic then additionally surrounds the uterus as blood fills the pelvis. With significant intraabdominal hemorthage, blood will track up the pericolic {gutters to fill Morison pouch near the liver. Eree fluid in this pouch typically is not seen until accumulated volumes reach 400 t0 600 ml. (Branney, 1995; Rodgerson, 2001). Diagnosti- cally, peritoneal fluid in conjunction with an adnexal mass and 4 postive pregnancy test resule are highly predictive of ectopic pregnancy (Nyberg, 1991). Ascites from cancer is a notable Ifsonography is unavailable, cildocentesis is simple tech- nique and was used commonly in the past. The cervieis pulled ‘outward and upward toward the symphysis with a tenaculum, and a long, 18-gauge needle is inserted through the posterior ‘vaginal fornix into the retrouterine cul-de-sac. f present, Buid ‘can be aspirated, However, no fluid is interpreted only as unsatisfactory entry into the cul-de-sac. Bloody fluid or fluid identified using FIGURE 12-5 Hermopertoncurn, A. This cukde-sac (*.Large accumulations will a fluid is seen in Morison pouch (arowhead).C ‘extend into the antes nsvaginal sagittal view of the pelvis shows anechoic fluid intaly po evi; F= fundus; K = kidneys L = Iner. with old clot fragments suggests hemoperitoneum. IF the blood sample clos, it may reflect an adjacent blood vessel puncture or brisk bleeding from ectopic pregnancy rupture I Serum Progesterone Although not our practice, this hormone is used’ by some’ to aid ectopic pregnancy diagnosis when serum -hCG levels and TTVS findings are inconclusive (Stovall, 1992). A single value is sufficient, From studies, a serum progesterone level <6 ng/ml. (<20 nmol/L) hasa pooled specificity of 98 percent to predict a rnonviable pregnancy in women with a PUL (Verhaegen, 2012) A value >: ig/ml. suggests a live IUP and excludes ectopic pregnancy with 97-percene sensitivity (Carson, 1993). With ‘most ectopic pregnancies, progesterone levels range between 10 and 25 ng/mL and thus have limited diagnostic utility (Ameri- 2019¢). Serum progesterone levels can be used to butressa clinical impression, but again they cannor reliably identify location (Guha, 2014). can College of Obstetricians and Gynecologist 1 Endometrial Sampling jeveral endometsal changes accompany ectopic pregnancy, and, all lack coexistent chorionie vill, Decidual reaction is found in 42 percent of samples, secretory endometrium in 22 percent, and proliferative endometrium in 12 percent (Lopez, 1994). Some recommend that lack of chorionic vill be confirmed by D & E (2011) found that the presumptive diagnosis of ectopic pregnancy is inaccurate in 27 percent of cases without histological exclusion fore methotrexate treatment is given, Chuing and associates of a spontaneous pregnancy loss. Nevertheless, the risks of D & (Care weighed aguinst che limited maternal risks of methotrexate Endometrial biopsy with a Pipelle catheter or endometrial aspiration was studied as an alternative to surgical curettage and found inferior (Barnhart, 2003b; Insogna, 2017). Instead, frozen section of curettage fragments to identify products of conception is accurate in 95 percent of cases (Li, 2014), ng in the retrouterine ram, anechs n fiom Ot. Devin Iede-sac (9B. In this right upper quadrant duced with pe Laparoscopy Direct visualization of the fallopian tubes and pelvis by laparos- copy olfers a reliable diagnosis in most cases of suspected ccto- pic pregnancy. This aso permits a ready transition to definitive operative therapy, which is discussed subsequently. MEDICAL MANAGEMENT 1 Regimen Options For most ectopic pregnancies, medical therapy is preferred, if feasible, to avoid surgical risks. Disqualifying criteria are a rup- tured fallopian tube and drug contraindications. Other consid zations include reasonably close access to emergency care and 4 commitment to surveillance laboratory testing. Medical therapy traditionally involves the antimetabolite methotrexate (MIX). This drug is a folic acid antagonist. Ic tightly binds to dihydrofolate reductase, blocking the reduc- tion of dihydrofolate to tetrahydrofolate, which is the active form of folic acid. As a result, de novo purine and pyrimidine production is halted, which then arrests DNA, RNA, and ps fein synthesis. ‘Thus, MIX is highly effective against rapidly proliferating trophoblast. However, gastrointestinal mucosa, bone marrow, and respiratory epithelium also can be harmed, To help select suitable candidates, laboratory tests are obtained, First, MUX is renally cleared, and significant renal dysfunction, reflected by an elevated serum creatinine level, precludes its use. Second, MIX can be hepato- and myelo- toxic, and CBC and liver Function tests (LETs) help establish ‘baseline, Last, blood type and Rh status are determined. All except blood typing are considered surveillance laboratory tests and are repeated prior to additional MTX doses. With administration, women are counseled co aiid several aggravating agents unil treatment is completed. These are: (1) Ectopic Pregnancy 225 folic acid-containing supplements, which can competitively reduce MTX binding to dibydrofolate reductase; (2) nonste- roidal antiinflammatory drugs, which reduce renal blood low and delay drug excretion; (3) alcohol, which can predispose to concurrent hepatic enzyme elevation: (4) sunlight, which can provoke MX-related dermatitis; and (5) sexual activity, which ‘can rupee the ectopic pregnancy (American College of Obste- tticians and Gynecologists, 2019). MIX is a potent teratogen, and MTX embryopathy is nota- ble for craniofacial and skeletal abnormalities and feta-growth restriction (Nurmohamed, 2011). MTX ‘mill and may accumulate in neonatal tissues and interfere with neonatal cellular metabolism (American Academy of Pediat- Fics, 2001; Briggs, 2017). Based on all these findings, a list of. contraindications and pretherapy laboratory testing is found in Table 12-1 For ease and efficacy, intramuscular MIX administration is used most often for ectopic pregnancy treatment, and single- dose and multidose MIX protocols are available. With single- dose therapy, the dose is 50 mg/m? body surface area (BSA). and BSA can be derived using various Internet-based BSA cal- culators. At our institution, patients are observed for 30 min- tutes following MTX injection to exclude an adverse reaction. With the multidose regimen, leucovorin is added to blunt MIX toxicity. Leucovorin is foinic acid and has folic acid activity. ‘Thus, it allows some purine and pyrimidine synthesis to butfer side effets. ‘Comparing these two protocols, trade-off are recognized, Single-dose therapy offers simplicity, less expense, and less intensive postherapy monitoring. However, some but not all studies report a higher success rate for the multidose regimen (Barnhart, 2003a; Lipscomb, 2005; Tabatabail, 2012). Overall, cctopic tubal pregnancy resolution rates approximate 90 percent with MIX use, At our institution, we use single-dose MTX. ZL WaldVHD is excreted into breast ‘TABLE 12-1. Medical Treatment Protocols for Ectopic Pregnancy gle Dosing (One dose; repeat if necessary Medication Dosage Methotrexate 50 mg/m® BSA (day 1) Leucovorin NA Serum B-hCG level (baseline), 4, and 7 Indication for additional Days dose 15% from day 4 to day 7 Less than 1596 decline during weekly surveillance Surveillance IF serum B-hCG level does not decline by On Up to four doses of bath drugs until serum B-ACG declines by 15% ma/kg, days 1,3,5,and7 0.1 mg/kg days 2,4, 6, and 8 Days 1 (baseline), 3 §,and 7 IFserum B-hCG level decines <15%, give additional dose; repeat serum -hCG in 48 hours and compare with previous value: maximum four doses (Once 1596 decline achieved, then weekly serum B-hCG levels until undetectable MIX sensitivity Tubal rupture Breastfeeding Intrauterine pregnancy Peptic ulcer disease Active pulmonary disease Immunodeficiency Hepatic, renal, or hematologic dysfunction BSA = body surface area; B-hG = B-human chorionic gonadotropin; MTX = methotrexate; NA = not applicable. From American College of Obstetricians and Gynecologists, 2019c; American Society for Reproductive Medicine, 2013, 226. First- and Second-Trimester Pregnancy Loss S NOILDaS lt Patient Selection “The best candidate for medical therapy is the woman who is asymptomatic, motivated, and complians. With medical therapy, some clasie predictors of success include a low initial serum -bCG level, small ectopie pregnancy sie, and absent feral cardiac actviey. OF these, inital serum (-hCG level i the best prognostic indicator with single-dose MTX. Reported fil ure cates are 1.5 percent ifthe inital serum B-hOG concentra tion is <1000 mIU/mL: 5.6 percent at 1000 to 2000 mlU/mL: 3.8 percent at 2000 to 5000 mlU/mL; and 14.3 pereen for levels beeween 5000 and 10,000 mlUmL. (Menon, 2007). Many carly als also used large size as an exclusioneite: tion. Lipscomb and colleagues (1998) reported a 93-percent success rate with single-dose MIX when the ectopic mass was $35 em. This compared with succes rates berween 87 and 90 percent when the mass was >3.5 em, These author alo found cctopic pregnancies measuring <4 em and lacking. cardiac activity to be suitable candidates. Failure rates rise if cardiac activity is seen, with an 87-percent succes rate in sch cases ll Side Effects “These regimens are associated with minimal laboratory changes and symproms, but rarely toxicity may be severe. Kooi and Kock (1992) reviewed 16 studies and reported that adverse cffets were resolved by 3 t0 4 days after MTX was discontin- ued. The most frequent were liver involvement —12 percent stomatitis—6 percent; and gastroenteritis percent. One woman had bone marrow depression, Moze commonly, 65 t0 75 percent of women given MIX will have increasing pain beginning several days after therapy. Thought to reflec separa- tion of the ectopic pregnancy from the tubal wal, chs pain generally is mild and relieved by analgesics. Ina series of 258 ‘women treated with MTX by Lipscomb and colleagues (1999), 20 percent had pain that merited evaluation ina clinic or emer- gency department to exclude tubal rupture. Long term, MIX treatment does not diminish ovarian reserve (Ohannessian, 2014). However, after suecessful MIX therapy, pregnancy is ideally delayed for at least 3. months because this drug may persist in human tissues for months after a single dose (Hackmon, 2011). Although data are very limited, conception before this waiting period appears reas suring. In one study, 45 women who conceived <6 months after MTX had similar pregnancy outcomes compared with 80 ‘women who conceived >6 months after MTX (Svirsky, 2009). i Surveillance [As shown in Table 12-1, monitoring single-dose therapy calls for serum G-hCG determinations at days 4 and 7 following inital MIX injection om day 1. Aftcr single-dose MTX, mean serum BshCG levels may rise or fll during the Best 4 days and then should gradually decline. Ifthe level fils to drop by 215 percent benween days 4 and 7, a second MIX doses ree- ‘ommended. ‘his is necessary in 20 percent of women treated with single-dose cherapy (Cohen, 2014). In such eases, a CBC, ctcatnine level, and LFTs ate rechecked, If these surveillance rests are normal, a second equivalent dose is administered. The date of this second injection will become the new day 1, and the protocol i restarted ‘Multidose therapy provides MIX (1 mg/kg) treatment with leeovorin (0.1 mgfk) therapy on alternating days. Afr this fst pair of injections, a serum [B+hCG concentration is obtained. Values between days | and 3 are anticipated to drop by B15 percent IF not and if surveillance tests are normal an additional MTX/leucovorin pai is given: A serum -hCG level i repeated 2 days later. Up to four doses may be given if required Stovall, 1991) ‘With either dosing regimen, once a decline 215 percent is achieved, weekly serum [-hCG level testing then begins until talus are undetectable. Lipscomb and collegues (1998) used single-dose MTX to successfully reat 287 womcn and reported thatthe average time to resolution—defined asa serum [-hCG level <15 mlUfml—was 34 days. he longest ime was 109 days SURGICAL MANAGEMENT 1 Options Before surgery, ature fertility desires are diseussed. In women desiring sterilization, the unaffected tube can be ligated of removed. This is done concurrently with salpingectomy for the cectopic-containing tube. Laparoscopy is the preferred surgical approach for ectopic pregnancy unless a woman is hemodynamically unstable. This is supported frst by comparable subsequent uterine pregnancy rates and tubal pateney rates in those undergoing salpingos- tomy completed either by laparoscopy or by laparotomy (Haje- sus, 2007). Second, laparoscopy has lower infection, adhesion, and thromboembolism risks and faster recovery times than laparotomy. Morcover, as experience has accrued, cases previ- ously managed by laparotomy—for example, those with hemo- peritoneum —can safely be managed laparascopically by those with suitable expertise. However, the lowered venous return and cardiae ousput associated with pneumoperitoneum must be factored into the selection of minimally invasive surgery for a hypovolemic woman, Two procedures—salpingostomy or salpingectomy—are options. In the past, some favored salpingostomy 0 pre~ serve future fertility. However, two randomized trials com- pared laparoscopic outcomes between the two procedures in women with a normal contralateral fallopian tube, The Eu pean Surgery in Ectopic Pregnancy (ESEP) study random- ied 231 women to salpingectomy and 215 to salpingostomy. After surgery, the subsequent cumulative rates of ongoing pregnancy by natural conception did not differ significantly between groups—56 versus G1 percent, respectively (Mol, 2014). Again, in the DEMETER trial, the subsequent 2-year rate for achieving an IUP did not differ between groups—64 versus 70 percent, respectively (Fernandez, 2013). However, for women with an abnormal-appearing contralateral tube, sal- pingostomy of the ectopic-containing tube may be preferred if feasible to help preserve fertility OF the two procedures, salpingectomy may be used for both rupeured and unruptured ectopic pregnancies. With one laparoscopic technique, che affected fallopian tube i lifted and held with atraumatic grasping forceps. One of several suitable bipolar grasping devices is placed across che fallopian tube at the uterotubal junction, Once desiccated, the tube is cut from, its uterine attachment. ‘The bipolar device is then advanced across the mesosalpinx to free the entire tube. Salpingostomy is typically used to remove a small unrup- tured pregnancy. A 10- to 15-mm linear incision is made on the antimesenteric border of the fallopian tube and over the pregnancy. ‘The products usually will extrude from the inci- sion, hese can be carefully extracted or can be Bushed out tusing high-pressure irrigation that more thoroughly removes the trophoblastic tissue. Small bleeding sites are controlled with ncedlepoint electrosurgical coagulation, and the incision is lft tunsutured to heal by secondary intention (Tulandi, 1991), With either procedure and after specimen removal, the pelvis and abdomen are irrigated and suctioned free of blood and tis- sue debris to remove all trophoblastic tissue. i Persistent Trophoblast ‘After trophoblast removal during surgery, B+hCG levels usually fall quickly: Persistent trophoblast is rare following, salpingee- tomy but complicates 5 co 15 percent of salpingostomy cases (Pouly, 1986; Scifer, 1993). Incomplete trophoblast removal can be identified by stable or rising (-hCG levels (Hajenius, 1995). Monitoring approaches are not codified. Weekly mea- sures are reasonable following salpingostomy (Mol, 2008) Following uncomplicated salpingectomy, we do not repeat B-hCG levels in women without pain oF symptoms of hemo- peritoneum: With stable or increasing B-hCG levels, additional surgi- cal or medical therapy is necessary. In ¢hose without evidence for tubal rupture, standard therapy for persistent trophoblast is single-dose MTX, 50 mg/m! x BSA. Tubal rupture and bleed- ing require a second surgery. I Medical versus Surgical Therapy Of options, multidose MTX treatment and laparoscopic salpin- gostomy have been compared in one randomized tral of 100 Patients, The authors found no diferences for rates of tubal preservation, primary treatment success, and subsequent feri- ity (Dias Pereira, 1999; Hajenis, 1997). For single-dose MTX, its efcacy compared with laparo- scopic slpingostomy shows conflicting results. In one random- ized til, single-dose MTX was less successful in pregnancy resolution, whereas in che other, single-dose MTX was equally effective (Sarai, 1998: Soweter, 2001). Krag Moeller and associ- ates (2009) reported during a median surveillance period of 8.6 years that ectopi-resolution success rates and cumulative spon- tancous IUP rates were not significanly diferent between those ‘managed by lparoscopicsalpingostomy and those treated with single-dose MTX. Salpingectomy effectively removes the entire conceptus and yields high resolution rates, I thus outperforms MTX in this regard. Yet, when future ferility and ectopic pregnancy recurrence rates ate analyzed, both salpingectomy and MTX Ectopic Pregnancy therapy show comparable results (de Bennetot, 2012; lan, 2017). In another study, surgery, MTX, oF expectant manage- ‘ment all yelled stastially similar subsequent spontaneous IUD rates (Demizdag, 2017) In sum, medical oF surgical management offer similar out= comes in women who ate hemodynamically stable, have serum [B+hCG concentrations <5000 mIUfml. and have a smal preg- nancy with no cardiac activity. Despite lower success rates with sedical therapy for women with larger tubal size, higher serum -HCG levels, and fetal cardiac activity, medical management can be offered to the motivated woman who understands the risks of emergency surgery in the event of treatment falure 1 Expectant Management In select asymptomatic women, observation of a very early tubal pregnancy that is asociated with stable or filing serum B-NCG levels is reasonable. A commitment to surveillance visits and relative proximity to emergency care are other safeguards Inmportancy, this dilfers fom expectant management of a PUL, daring is evaluation. Predictive factors for success inclide a love initial scrum B= CG concentration, a significant drop in levels over 48 hours and a sonographic inhomogeneous mass rather than a tubal halo oF other gestational stuctares. For example, initial val tues <175 mlUiml. predict spontancous esolution in 88 v0 96 percent of attempts (Elson, 2004; Kirk, 2011). Initial values *<1000 mlL/mL have success rates ranging from 71 t0 92 per- eene(Jurkovie, 2017; Mavelos, 201 ‘With expectant management, subsequent rates of tubal patency and intrauterine pregnancy are comparable with surgery (Helmy, 2007). That suid, compared with che estab- lished safety of medical or surgical therapy, the prolonged surveillance and risks of tubal rupture support the practice of expectant therapy only in appropriately selected and coun- seled womca, INTERSTITIAL PREGNANCY BH Diagnosis [An interstitial pregnancy is one that implants within the tubal segment that lies within the muscular uterine wall (Pig. 12-0) Incorrectly, they may be called cornual pregnancies; but this term deseribes a conception that develops in the nudimen- tary horn of a uterus with a miillerian anomaly. Risk factors are similar to others discussed for tubal ectopic pregnancy, although previous ipsilateral salpingectomy is a specific one for interstitial pregnancy (Lau. 1999). Undiagnosed interstitial pregnancies usally rupture following 8 to 16 weeks of amenor- thea, which is later than for more distal eubal pregnancies. The ‘myometrium covering the interstitial fillopian tube segment permits greater distention before rupture, Because of the prox- imity of these pregnancies to the uterine and ovarian arteries, hemorrhage can be severe and associated with mortality rates as hhigh as 2.5 percent (Tulandi, 2004). In many cases, these pregnancies are identified early, bu diag- nosis can stil he challenging, ‘These pregnancies sonographically 227 fame re) De) 228. First- and Second-Trimester Pregnancy Loss PNET FIGURE 12-6 Intesttal ectopic pregnancy. A. This parasagittal view using transvaginal sonography shows an empty uterine cavity anda mass that is cephalad and lateral to the uterine fundus (calipers). Intraoperative photograph during laparotomy and before corral resec: tion ofthe same ectopic pregnancy. In this frontal view, the bulging right-sided interstitial ectopic pregnancy is lateral tothe round ligament insertion and medial to the isthmic portion ofthe fallopian t ‘can appear similar to an eccentrcally implanted IUD, especially in a uterus with a millerian anomaly. C differentiation include: an empry uterus, a gestational sic seen separate from the endometrium and >1 cm away from the most lateral edge of the uterine cavity, and a thin, 9 weeks, BsACG levels > 10,000 mIU/mL; erown-rump length 310 mm, and fetal cardiac activity. For this reason, fet tidal KCL can be injected into the fetus or gestational sac (erma, 2009). Notably, during. posttherapy_ surveillance sonographic resolution lags far behind serum B-4CG level regression (Song, 2009) Although conservative management is feasible for many women with cervical pregnancies, suction evacuation oF hys- terectomy may be selected. Morcover, hysterectomy may be required with bleeding uncontrolled by conservative methods (Fowles, 2021). During hysterectomy, because ofthe else prox. dnnity of the ureters tothe ballooned cereis, urinary trace injury Ie suction evacuation of che cervix is planned, intraoperative bleeding may be lesened by preoperative UAE, by intracervi- cal vasopressin injection, or by a cerclage placed at the internal cervical os to compress feeding vessels (Chen, 2015; Fylstra, 2014; Wang, 2011). Cervical branches of the uterine artery can effectively be ligated with vaginal placement of hemostatic cervical sutures on the lateral aspects of the cervix at 3 and o'clock (Bianchi, 2011) Asan adjunct to medical or surgical therapy, UAE has been described either as a response to bleeding or as a preprocedural prevention (Hirakawa, 2009; Zakaria, 2011). Also, in the event of hemorshage, a 26F Foley catheter with a 30-ml. balloon can, be placed intracervcally and inflated to effect hemostasis by vessel tamponade and to monitor bloody drainage. The balloon remains inflated for 24 to 48 hours and is gradually decom- pressed over a few days (Ushakov, 1997). ABDOMINAL PREGNANCY 1 Diagnosis These rare ectopic pregnancies are defined as an implantac tion in the peritoneal cavity exclusive of tubal, ovarian, oF inralgimentous implantations. Most ate thought to follow carly tubal rupture oF tubsl abortion with reimplantation. ally, symptoms may be absent or vague. Laboratory text are ypically uninformative, although maternal serum alphacetoprotein levels can be elevated. With later gestations, abnormal fetal postions may be palpated, oF the cervix is dis placed (Zeck, 2007). Sonographically, clus ae a fetus oF pla- centa seen eccentrically positioned within the pelvis or separate feom the uterus; lack of myometrium between the feeus and the maternal anterior abdominal wall oF bladder; oF bowel loops surrounding the gestational sc (Alibone, 1981; Chukus, 2015). Oligohydrampios is common but nonspecific. Often needed, MR imaging can aid diagnosis and provide placental information @ Management Abdominal pregraney treatment depends on the gestational age a diagnosis Seevens (1993) reported fetal malformations and: deforma: ions in 20 percent. Thus, we believe chat eermination gener silyrt:indteaed roe the cians is maciey Ceresinky; before d Despite this, some describe waiting until fetal viability with close surveillance (Harirah, 2016) Principal surgical objectives are delivery of the fetus and. carefl assessment of placental implantation without provak- iL =: SEER cele ete Dor eo (Sema oer Neomteetioea TeoneeoeaL ay EOY sas SSeS oes cegacnssciiess eee Hee ea See sects spoie eee So eteecates Spee eee a Soe Seis See sia fo eee Sapa aes oe a eee Hee i benefit most (Ansong, 2019). Ectopic Pregnancy 231 OVARIAN PREGNANCY Ectopic implantation of the fertilized egg in the ovary is rare and is diagnosed ‘are met, These were ‘Gformlinicalneseccy ‘outlined by Spicgelberg (1878): (1) dhe ipsilareral tube is intact (Ed peer eer yl2 ectopic TC seg eee eee Sa URLS PRAT (denomrcarecniscological omni teyparenalepae, RISC (Sageresimlerro cee orrabel preraace ARCO failure ae prominent (Zhu, 2014). Presenting complaints and findings mirror those for tubal ectopic pregnancy. Although the covary can accommodate the expanding pregnancy more easly than the fallopian tube, rupture at an early stage is the usual consequence (Meleer, 2016) tex (Comstock, 2005). In one review of 49 cases, the diagnosis was not be made until surgery, and many cases were presumed t0 bea tubal ectopic pregnancy (Choi, 2011). Moreover, at surgery, an early, unrecognized ovarian pregnancy may instead be consid- cred and managed as a hemorshagie corpus luteum, Evidence-based management accrues mainly from case reports (Hassan, 2012). Classically, (Elvell, 2015; Melcer, 2015). With HETEROTOPIC PREGNANCY “his pring of an TUP and an ectopically loested pregnancy is rare, and the most common dyad isan IUP and an ampule HEMGIRAMBNERRINER The netarl ncccner of ese bere pregacies approximates 1 case pet 30,00 pregnancies (Reece 1983). However, with ART, ther incidence ts higher and is 9 cases in 10,000 pregnancies (Perkins, 2015) Initial clinic syiproms usually reflect those fom the ectopic. Because an TUPsscen sonogeaphicly and the ectopic preganey may not be visualized, ates of rupture are higher in heteroopic pre nancy (Dendas, 2017) tn patients vshing to preserve the TUP, management ini tally it dceaed by bled, In those with hemorehage, teat ment of the ectopic pregnancy is surgea. Depending onthe coop location, section or suction aspiration i the mor common method (Wu, 2018). Of note, adjunctive UAE and wasopressin and thei effects on uterine blood flow are les desble for the ongoing IUP. With a rare comorbid ovarian ectopic pregnancy, ery excision ofthe corpus luteum merits progesterone supplementation (Chap 66 1170) Tn those without siguicane bleeing, media steps to dis rupt the ecopie preancy yicllyinvelvegestatonalsac infection of KCL oof hyperosmolar glucose. Ths may be fl Towed by later aspiration evacuation ofthe epic gestation Because of toxicity to the 1UD, MTX is avoided fame re) De) 232 First- and Second-Trimester Pregnancy Loss S NOILDaS With ongoing pregnancy, adverse neonatal outcome rates are not appreciably elevated (Clayton, 2007). However, inital sono- ‘graphic surveillance of fetal growth scems reasonable, Route of tukimate delivery is influenced mainly by myometrial integrity following ectopic treatment (Dendas, 2017; OuYang, 2014) REFERENCES Ackerman TE, Lew CS, Datelky SM, cal Interline sonographic inginintersil(coemul} ectopic pregnancy. Radiology 1891183, 19933 Ackerman TE, Levi CS, Lyons EA, ee ak Deidl ee endovagil sono ‘tzapic ign of copie pregnancy. Radiology 189(3)727 1993 Allbone GW, Fagan C Porer SC. 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