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Obstentrics_Williams. Pymar HC, Creinin MD, Schwartz JL: Mifepristone followed on the same day by vaginal misoprostol for early abortion. Contraception 64:87,r2001 Raghavan S, Comendant R, Digol I, et al: Two-pill regimens of misoprostol after mifepristone medical abortion through 63 days' gestational age: a randomized controlled trial of sublingual and oral misoprostol. Contraception 79(2):84, 2009 Ramzy AM, Sattar M, Amin Y, et al: Uterine myomata and outcome of assisted reproduction. Hum Reprod 13: 198, 1998 Rauch ER, Schattman GL, Christos PJ, et al: Embryonic heart rate as a predictor of irst-trimester pregnancy loss in infertility patients after in vitro fertilization. Fertil Steril 91 (6):2451, 2009 Rathat G, Do Trinh P, Mercier G, et al: Synechia ater uterine compression sutures. Fertil Sterilr95(1):405, 201r1 Ray BK, Vallejo Me, Creinin MD, et al: Amniotic fluid embolism with second trimester pregnancy termination: a case report. Can J Anaesth 51 (2): 139, 2004


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Obstentrics_Williams. after previable iatrogenic rupture of the membranes: a two-center review. Prenat Diagn 33(4):391,r2013 Roberts D, \ ause S, Martin W, et al: Amnioinfusion in very early preterm prelabor rupture of membranes (AMIPROM): pregnancy, neonatal and maternal outcomes in a randomized controlled pilot study. Ultrasound Obstet GynecoIr43(5):490, 2014 Ruano R, Dumez Y, Cabrol 0, et al: Second-and third-trimester therapeutic terminations of pregnancy in cases with complete placenta previa-does feticide decrease postdelivery maternal hemorrhage? Fetal Diagn Ther 19(6):475,r2004 Rust OA, Atlas RO, Reed J, et al: Revisiting the short cervix detected by transvaginal ultrasound in the second trimester: why cerclage may not help. Am J Obstet Gyneco1r185:1098, 2001


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Obstentrics_Williams. Siedhof M, Cremer ML: Pregnancy outcomes after laminaria placement and second-trimester removal. Obstet Gynecol 114(2 Pt 2):456,e2009 Silver M, Branch DW, Goldenberg R, et al: Nomenclature for pregnancy outcomes. Obstet GynecoIe118(6):1402, 2011 Simpson]L: Causes offetal wastage. Clin Obstet GynecoIe50(1):10, 2007 Sloan EP, Kirsh S, et al: Viewing the fetus following termination of pregnancy for fetal anomaly.e] Obstet Gynecol Neonatal Nurs 37(4):395, 2008 Society for Assisted Reproductive Technology: Preimplantation genetic testing: a Practice Committee opinion. Fertil Steril 90(5 Suppi):S136, 2008 Society for Maternal-Fetal Medicine: Cervical cerclage for the woman with prior adverse pregnancy outcome. Reairmed 2015. Available at: https://ww.smfm.org/ p u blications/ 9 8-cervical-cerclage-fo r-the-woman -wi thprior-adverse-pregnancy-outcome. Accessed May 12, 201


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Obstentrics_Williams. Stephenson MD: Frequency offactors associated with habitual abortion in 197 couples. Fertil Steril 66(1):24, 1996 Stephenson MD, Awartani A, Robinson P: Cytogenetic analysis of miscarriages from couples with recurrent miscarriage: a case-control study. Hum Reprod 17(2):446, 2002 Stephenson MD, Kutteh WH, Purkiss S, et al: Intravenous immunoglobulin and idiopathic secondary recurrent miscarriage: a multicentered randomized placebo-controlled trial. Hum Reprod 25(9):2203,e2010 Stockheim D, Machtinger R, Wiser A, et al: A randomized prospective study of misoprostol or mifepristone followed by misoprostol when needed for the treatment of women with early pregnancy failure. Fertil Steril 86:956, 2006 Stoddard A, Eisenberg DL: Controversies in family planning: timing of ovulation after abortion and the conundrum of postabortion intrauterine device insertion. Contraception 84(2):119, 2011


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Obstentrics_Williams. Stoddard A, Eisenberg DL: Controversies in family planning: timing of ovulation after abortion and the conundrum of postabortion intrauterine device insertion. Contraception 84(2):119, 2011 Stoval N, Sibai B, Habli M: Is there a role for cerclage in twin gestation with short cervical length (CL)? Single center experience. Abstract No. 143, Am ] Obstet Gynecole208(1 Suppl):S73, 2013 Stubbleield PG, Altman M, Goldstein SP: Randomized trial of one versus two days of laminaria treatment prior to late midtrimester abortion by uterine evacuation: a pilot study. Am] Obstet GynecoI143(4):481, 1982 Sugibayashi S, Aeby T, Kim D, et al: Amniotic luid arborization in the diagnosis of previable preterm premature rupture of membranes. ] Reprod Med 57(3-4):136,e2012 Sullivan E, Silver M, LaCoursiere DY, et al: Recurrent fetal aneuploidy and recurrent miscarriage. Obstet Gynecol 104:784,e2004


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Obstentrics_Williams. Sullivan E, Silver M, LaCoursiere DY, et al: Recurrent fetal aneuploidy and recurrent miscarriage. Obstet Gynecol 104:784,e2004 Sundtoft I, Langhof-Roos ], Sandager P, et al: Cervical collagen is reduced in non-pregnant women with a history of cervical insuiciency and a short cevix. Acta Obstet Gynecol Scand 96(8):984, 2017 Sunkara SK, Khairy M, EI-Toukhy T, et al: he efect of intramural ibroids without uterine cavity involvement on the outcome of IVF treatment: a systematic review and meta-analysis. Hum Reprod 25(2):418, 2010 Tang OS, Gemzell-Danielsson K, Ho PC: Misoprostol: pharmacokinetic proiles, efects on the uterus and side-efects. Inte] Gynaecol Obstet 99 Suppl 2:S 160, 2007 Templeton A, Grimes D: A request for abortion. N Engl] Med 365(23):2198, 2011 Terkildsen MFC, Parilla BV, Kumar P, et al: Factors associated with success of emergent second-trimester cerclage. Obstet Gynecol 101 :565, 2003


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Obstentrics_Williams. Terkildsen MFC, Parilla BV, Kumar P, et al: Factors associated with success of emergent second-trimester cerclage. Obstet Gynecol 101 :565, 2003 Thangaratinam S, Tan A, Knox E, et al: Association between thyroid autoantibodies and miscarriage and preterm birth: meta-analysis of evidence. BM] 342:d2616,e2011 homason ]L, Sampson MB, Beckman CR, et al: he incompetent cevix: a 1982 update.e] Reprod Med 27:187, 1982 Timor-Tritsch IE, Farine D, Rosen MG: A close look at early embryonic development with the high-frequency transvaginal transducer. Am J Obstet GynecoIe159(3):676, 1988 To MS, Alirevic Z, Heath VCF, et al: Cervical cerclage for prevention of preterm delivery in women with short cervix: randomised controlled trial. Lancet 363:1849,e2004 Trinder ], Brocklehurst P, Porter R, et al: Management of miscarriage: expectant, medical, or surgical? Results of randomized controlled trial (miscarriage treatment (MIST) trial). BM] 332(7552):1235, 2006


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Obstentrics_Williams. Tulandi T, lghanaim N, Hakeem G, et al: Pre and post-conceptional abdominal cerclage by laparoscopy or laparotomy. ] Minim Invasive Gynecol 21(6):987,e2014 Tuuli MG, Norman SM, Odibo AO, et al: Perinatal outcomes in women with subchorionic hematoma: a systematic review and meta-analysis. Obstet GynecoIe117(5):1205,e2011 Tzeng CR, Hwang ]L, Au HK, et al: Sonographic patterns of the endometrium in assessment of medical abortion outcomes. Contraception 88(1):153,e2013 Upadhyay UD, Desai S, Zlidar V, et al: Incidence of emergency department visits and complications after abortion. Obstet Gynecol 125(1): 175, 2015 Vincienne M, Anselem 0, Cordier AG, et al: Comparison of the induction-todelivery interval in terminations of pregnancy with or without Dilapan-S. Fetal Diagn her March 29, 201 [Epub ahead of print] Virk], Zhang], Olsen]: Medical abortion and the risk of subsequent adverse pregnancy outcomes. N Engle] Med 357:648, 2007


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Obstentrics_Williams. H, Piaggio G, Wojdyla D, et al: Two mifepristone doses and two intervals of misoprostol administration for termination of early pregnancy: a randomized factorial controlled equivalence trial. B]OG 116(3):381, 2009


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Obstentrics_Williams. Waters TP, Mercer BM: he management of preterm premature rupture of the membranes near the limit of fetal viability. Am 1 Obstet Gynecol 201(3):230,r2009 Webber K, Grivell M: Cervical ripening before irst trimester surgical evacuation for non-viable pregnancy. Cochrane Database Syst Rev 11 :CD009954, 2015 Weiss lL, Malone FD, Vidaver 1, et al: hreatened abortion: a risk factor for poor pregnancy outcome, a population-based screening study. Am 1 Obstet Gynecol 190(3):745,r2004 Weng X, Odouki R, Li DK: Maternal cafeine consumption during pregnancy and the risk of miscarriage: a prospective cohort study. Am 1 Obstet Gynecol 198:279.e1,r2008 White K, Carroll E, Grossman D: Complications from irst-trimester aspiration abortion: a systematic review of the literature. Contraception 92(5):422, 2015 White KO, Nucatola DL, Westhof C: Intra-fetal compared with intraamniotic digoxin before dilation and evacuation: a randomized controlled trial. Obstet GynecoIr128(5):1071, 2016


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Obstentrics_Williams. White KO, Nucatola DL, Westhof C: Intra-fetal compared with intraamniotic digoxin before dilation and evacuation: a randomized controlled trial. Obstet GynecoIr128(5):1071, 2016 Whittle L, Singh SS, Allen L, et al: Laparoscopic cervico-isthmic cerclage: surgical technique and obstetric outcomes. Am 1 Obstet Gynecol 201:364. e1, 2009 Wijesiriwardana A, Bhattachatya S, Shetty A, et al: Obstetric outcome in women with threatened miscarriage in the irst trimester. Obstet Gynecol 107:557,r2006 Wilcox AF, Weinberg CR, O'Connor IF, et al: Incidence of early loss of pregnancy. N Engl 1 Med 319:189, 1988 WinikofB, Dzuba IG, Creinin MD, et al: Two distinct oral routes of misoprostol in mifepristone medical abortion: a randomized controlled trial. Obstet GynecoIr112(6):1303,2008 Winn HN, Chen M, Amon E, et al: Neonatal pulmonaty hypoplasia and perinatal mortality in patients with mid trimester rupture of amniotic membranes-a critical analysis. Am 1 Obstet GynecoIr182:1638, 2000


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Obstentrics_Williams. Witter FR: Negative sonographic indings followed by rapid cervical dilatation due to cervical incompetence. Obstet Gynecol 64: 136, 1984 Wong LF, Schliep KC, Silver RM, et al: The efect of a very short interpregnancy interval and pregnancy outcomes following a previous pregnancy loss. Am 1 Obstet Gynecol 212(3):375.e1, 2015 World Health Organization: Safe Abortion: Technical and Policy Guidance for Health Systems, 2nd ed. Geneva, WHO, 2012 Wyatt PR, Owolabi T, Meier C, et al: Age-speciic risk of fetal loss observed in a second trimester serum screening population.r·Am 1 Obstet Gynecol 192:240,r2005 York S, Lichtenberg ES: Characteristics of presumptive idiopathic disseminated intravascular coagulation during second-trimester induced abortion. Contraception 85(5):489, 2012 Yu D, Wong YM, Cheong Y, et al: Asherman syndrome-one century later. Fertil Steril 89(4):759, 2008


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Obstentrics_Williams. Yu D, Wong YM, Cheong Y, et al: Asherman syndrome-one century later. Fertil Steril 89(4):759, 2008 Zane S, Creanga A, Berg Cl, et al: Abortion-related mortality in the United States: 1998-2010. Obstet GynecoIr126(2):258, 2015 Zaveri V, Aghajafari F, Amankwah K, et al: Abdominal versus vaginal cerclage after a failed transvaginal cerclage: a systematic review. Am 1 Obstet Gynecol 187:868,r2002 Zeisler H, laura A, Bancher-Todesca D, et al: Prophylactic cerclage in pregnancy. Efect in women with a history of conization. 1 Reprod Med 42(7):390, 1997 Zhang 1, Gilles 1M, Barnhart K, et al: A comparison of medical management with misoprostol and surgical management for early pregnancy failure. N Engll Med 353:761,r2005 TUBAL PREGNANCY. .e..e.....e..e....e...e....e....e..e.371 CLINICAL MANIFESTATIONS ........e.......e.e..e..e.372 MUL TIMODALITY DIAGNOSIS .e...........e... ...373 MEDICAL MANAGEMENT ........e..e..e....e...e..... 377


Obstentrics_Williams

Obstentrics_Williams. CLINICAL MANIFESTATIONS ........e.......e.e..e..e.372 MUL TIMODALITY DIAGNOSIS .e...........e... ...373 MEDICAL MANAGEMENT ........e..e..e....e...e..... 377 SURGICAL MANAGEMENT ..e...e....e.e....e....e..e... 378 INTERSTITIAL PREGNANCY .e.e..e.....e..e....e. ...e.380 CESAREAN SCAR PREGNANCYe. . . . . . . ............. 381 CERVICAL PREGNANCY. . . . . . . . . . . . . ............. 382 ABDOMINAL PREGNANCY . . . . . . . . . . ............. 383 OVARIAN PREGNANCYe. . . . . . . . . . . . . ............. 384 As soon as an unruptured extra-uterine pregnancy is positivey diagnosed, its immediate removal by laparotomy is urgenty indicate, since rupture may occur at any time and the patient die rom haemorrhage bore operative aid can be obtaine. -J. Whitridge Williams (1903)


Obstentrics_Williams

Obstentrics_Williams. -J. Whitridge Williams (1903) Following fertilization and fallopian tube transit, the blastocyst normally implants in the endometrial lining of the uterine cavity. Implantation elsewhere is considered ectopic and accounts for 0.5 to 1.5 percent of all irst-trimester pregnancies in the United States (Hoover, 2011; Stulberg, 2014). his small proportion disparately accounts for 3 percent of all pregnancyrelated deaths (Creanga, 2017). Fortunately, urine and serum beta-human chorionic gonadotropin (�-hCG) assays and transvaginal sonography allow earlier diagnosis. As a result, both maternal survival rates and conservation of reproductive capacity are improved.


Obstentrics_Williams

Obstentrics_Williams. Nearly 95 percent of ectopic pregnancies are implanted in the various segments of the fallopian tube. hese segments are shown in Chapter 2 (Fig. 2-14, p. 29). he ampulla (70 percent) is the most frequent site, followed by isthmic (12 percent), imbrial (1i1 percent), and interstitial tubal pregnancies (2 percent) (Bouyer, 2002). The remaining 5 percent of nontubal ectopic pregnancies implant in the ovary, peritoneal cavity, cervix, or prior cesarean scar. Occasionally, a multifetal pregnancy contains one conceptus with normal uterine implantation that coexists with one implanted ectopically. he natural incidence of these heterotopic pregnancies approximates 1 per 30,000 pregnancies (Reece, 1983). However, with assisted reproductive technologies (ART), their incidence is 9 in 10,000 pregnancies (Perkins, 2015). Rarely, twin tubal pregnancy with both embryos in the same tube or with one in each tube has been reported (Eze, 2012; Goswami, 2015).


Obstentrics_Williams

Obstentrics_Williams. Regardless of location, D-negative women with an ectopic pregnancy who are not sensitized to D-antigen are given IgG anti-D immunoglobulin (American College of Obstetricians and Gynecologists, 2017). In irst-trimester pregnancies, a 50-�g or 300-�g dose is appropriate, whereas a standard 300-�g dose is used for later gestations (Chap. 15, p. 305).


Obstentrics_Williams

Obstentrics_Williams. Abnormal fallopian tube anatomy underlies many cases of tubal ectopic pregnancy. Surgeries for a prior tubal pregnancy, for fertility restoration, or for sterilization confer the highest risk. After one previous ectopic pregnancy, the chance of another is increased ivefold (Bhattacharya, 2012). Prior sexually transmitted disease or other tubal infection, which can distort normal tubal anatomy, is another factor. Speciically, one episode of salpingitis can be followed by a subsequent ectopic pregnancy in up to 9 percent of women (Westrom, 1992). Peritubal adhesions subsequent to salpingitis, appendicitis, or endometriosis can also increase chances. Sapingitis isthmica nodosa, which is a condition in which epithelium-lined diverticula extend into a hypertrophied muscularis layer, is another (Bolaji, 2015). Finally, congenital fallopian tube anomalies, especially those secondary to in utero diethylstilbestrol exposure, can predispose (Hoover, 2011).


Obstentrics_Williams

Obstentrics_Williams. Infertility, as well as the use of ART to overcome it, is linked to substantively increased risks for ectopic pregnancy (Clayton, 2006). With ART, the ectopic pregnancy rate in the United States between 2001 and 2011 was 1.6 percent (Perkins, 2015). And "atypical" implantations-cornual, abdominal, cervical, ovarian, and heterotopic pregnancy-are more frequent. Smoking is another known association, although the underlying mechanism is unclear (Hyland, 2015). Last, with any form of contraception, the absolute number of ectopic pregnancies is decreased because pregnancy occurs less often. However, with some contraceptive method failures, the relative number of ectopic pregnancies is increased. Examples include tubal sterilization, copper and progestin-releasing intrauterine devices (IUDs), and progestin-only contraceptives (Chap. 38, p. 680).


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Obstentrics_Williams. With tubal pregnany, because the fallopian tube lacks a submucosalilayer, the fertilized ovum promptly burrows through the epithelium. he zygote comes to lie near or within the muscularis, which is invaded by rapidly proliferating trophoblast. The embryo or fetus in an ectopic pregnancy is oten absent or stunted. Outcomes of ectopic pregnancy include tubal rupture, tubal abortion, or pregnancy failure with resolution. With rupture, the invading expanding conceptus and associated hemorrhage can tear rents in the fallopian tube (Fig. 19-1). Tubal ectopic pregnancies usually burst spontaneously but may occasionally rupture following coitus or bimanual examination.


Obstentrics_Williams

Obstentrics_Williams. FIGURE 19-1 Ruptured ampullary early tubal pregnancy. (Used with permission from Dr. Togas Tulandi.) lternatively, the pregnancy may pass out the distal fallopian tube. Tubal abortion frequency depends in part on the initial implantation site, and distal implantations are favored. Subsequently, hemorrhage may cease and symptoms eventually disappear. But bleeding can persist as long as products remain in the tube. Blood slowly trickles from the tubal fimbria into the peritoneal cavity and typically pools in the rectouterine cul-de-sac. If the fimbriated extremity is occluded, the fallopian tube may gradually become distended by blood, forming a hematosalpinx. Uncommonly, an aborted fetus will implant on a peritoneal surface and become an abdominal pregnancy, which is discussed on page 383. Last, an unknown number of ectopic pregnancies spontaneously fail and are reabsorbed. This may be documented now more regularly with the advent of sensitive 3-hCG assays.


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Obstentrics_Williams. Last, an unknown number of ectopic pregnancies spontaneously fail and are reabsorbed. This may be documented now more regularly with the advent of sensitive 3-hCG assays. Distinctions beween "acute" ectopic pregnancy just described and "chronic" ectopic pregnancy can be drawn. The more common acute ectopic pregnancies are those with a high serum 3hCG level and rapid growth, leading to a timely diagnosis. hese carry a higher risk of tubal rupture (Barnhart, 2003c). With chronic ectopic pregnancy, abnormal trophoblast dies early, and thus negative or low, static serum 3-hCG levels are found (Brennan, 2000). Chronic ectopic pregnancies typically rupture late, if at all, but commonly form a complex pelvic mass, which oten is the reason prompting diagnostic surgery (Cole, 1982; Ugur, 1996).


Obstentrics_Williams

Obstentrics_Williams. Earlier patient presentation and more precise diagnostic technology typically allow identiication before rupture. In these cases, symptoms and signs of ectopic pregnancy are often subtle or even absent. The woman does not suspect tubal pregnancy and assumes that she has a normal early pregnancy or is having a miscarriage.


Obstentrics_Williams

Obstentrics_Williams. With later diagnosis, the classic triad is delayed menstruation, pain, and vaginal bleeding or spotting. With tubal rupture, lower abdominal and pelvic pain is usually severe and frequently described as sharp, stabbing, or tearing. Abdominal palpation elicits tenderness. Bimanual pelvic examination, especially cervical motion, causes exquisite pain. The posterior vaginal fornix may bulge from blood in the rectouterine cul-de-sac, or a tender, boggy mass may be felt beside the uterus. The uterus can also be slightly enlarged due to hormonal stimulation. Symptoms of diaphragmatic irritation, characterized by neck or shoulder pain, especially on inspiration, develop in perhaps half of women with sizable hemoperitoneum.


Obstentrics_Williams

Obstentrics_Williams. Some degree of vaginal spotting or bleeding is reported by 60 to 80 percent of 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 signiicant intraabdominal hemorrhage. Responses to moderate bleeding include no change in vital signs, a slight rise in blood pressure, or a vasovagal response with bradycardia and hypotension. Blood pressure will fall and pulse will rise only if bleeding continues and hypovolemia FIGURE 19-2 This decidual cast was passed by a patient with a tubal ectopic pregnancy. The cast mirrors the shape of the endometrial cavity, and each arrow marks the portion of decidua that lined the cornua. becomes significant. Vasomotor disturbances develop, ranging from vertigo to syncope.


Obstentrics_Williams

Obstentrics_Williams. becomes significant. Vasomotor disturbances develop, ranging from vertigo to syncope. Even after substantive hemorrhage, hemoglobin or hematocrit readings may at irst show only a slight reduction. Hence, after an acute hemorrhage, a trending decline in hemoglobin or hematocrit levels over several hours is a more valuable index of blood loss than is the initial level. In approximately half of women with a ruptured ectopic pregnancy, varying degrees of leukocytosis up to 30,000/�L may be documented.


Obstentrics_Williams

Obstentrics_Williams. Decidua is endometrium that is hormonally prepared for pregnancy, and the degree to which the endometrium is converted with ectopic pregnancy is variable. Thus, in addition to bleeding, women with ectopic tubal pregnancy may pass a decidual cast. his is the entire sloughed endometrium that takes the form of the endometrial cavity (Fig. 19-2). Importantly, decidual sloughing may also occur with uterine abortion. hus, tissue is carefully evaluated visually by the provider and then histologically for evidence of a conceptus. If no clear gestational sac is seen or if no villi are identified histologically within the cast, then the possibility of ectopic pregnancy must still be considered.


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Obstentrics_Williams. he diferential diagnosis for abdominal pain coexistent with pregnancy is extensive. Pain may derive from uterine conditions such as miscarriage, infection, degenerating or enlarging leiomyomas, or round-ligament pain. Adnexal disease may include ectopic pregnancy; hemorrhagic, ruptured, or torsed ovarian masses; salpingitis; or tuboovarian abscess. Last, appendicitis, cystitis, renal stone, and gastroenteritis are more common nongynecological sources of lower abdominal pain in early pregnancy.


Obstentrics_Williams

Obstentrics_Williams. Several algorithms have been proposed to identiY ectopic pregnancy. Most include these key components: physical indings, transvaginal sonography (TVS), serum 3-hCG level measurement-both the initial and the subsequent pattern of rise or decline, and diagnostic surgery, which includes dilation and curettage (D&C), laparoscopy, and occasionally, laparotomy (Fig. 19-3). Algorithm use applies only to hemodynamically stable women, and those with presumed rupture undergo prompt surgical therapy. For a suspected unruptured ectopic pregnancy, all diagnostic strategies involve trade-ofs. Strategies that maximize detection of ectopic pregnancy may result in termination of a normal intrauterine pregnancy (IUP). Conversely, those that reduce the potential for normal pregnancy interruption will delay ectopic pregnancy diagnosis. Patient desires for the index pregnancy are also discussed and may inluence these trade-ofs.


Obstentrics_Williams

Obstentrics_Williams. apid and accurate determination of pregnancy is essential to iden tiY an ectopic pregnancy. Current pregnancy tests use enzyme linked immunosorbent ssays (ELISAs) for the beta subunit of hCG. With these assays, lower limits of detection are 20 to 25 mIU/mL for urine and :;5 mIU/mL for serum (Greene, 2015). With bleeding or pain and a positive pregnancy test result, an initial TVS is typically performed to identiY gestation loca tion. If a yolk sac, embryo, or fetus is identiied within the uterus or the adnexa, then a diagnosis can be made. In many cases, however, TVS is nondiagnostic, and tubal pregnancy is still a possibility. In these cases in which neither intrauterine nor extrauterine pregnancy is identiied, the term pregnancy of unknown location (PUL) is used until additional clinical infor mation allows determination of pregnancy location.


Obstentrics_Williams

Obstentrics_Williams. Levels above the Discriminatory Zone. Several investigators ure to visualize a uterine pregnancy indicates that the pregnancy either is not alive or is ectopic (Barnhart, 1994). Some institu tions set their discriminatory threshold at ::1500 mIU/mL, whereas others use ::2000 mIU/mL. Connolly and associates (2013) suggested an even higher threshold. hey noted that with live uterine pregnancies, a gestational sac was seen 99 percent of the time with a discriminatory level of >3510 mIU/mL.


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Obstentrics_Williams. If the initial 3-hCG level exceeds the set discriminatory level and no evidence for an IUP is seen with TVS, then ectopic pregnancy is a concern. The diagnosis is narrowed in most cases to a failing IUP, a recent complete abortion, or an ectopic pregnancy. Early multifetal gestation also remains a possibility. Without clear evidence for ectopic pregnancy, serial 3-hCG level assessment is reasonable, and a level is checked 48 hours later. This averts unnecessary methotrexate administration and avoids harming an early normal multifetal pregnancy. With greater concern for an ectopic gestation, D&C is another option to distinguish an ectopic from a failing IUP. Importantly, patient factors greatly influence these decisions.


Obstentrics_Williams

Obstentrics_Williams. Levels below the Discriminatoy Zone. If the initial 3-hCG level is below the set discriminatory value, pregnancy location is often not technically discernible with TVS. With these PULs, serial 3-hCG level assays are done to identiY patterns that indicate either a growing or failing IUP. Levels that rise or fall outside these expected parameters increase the concern for ectopic pregnancy. hus, appropriately selected women with a possible ectopic pregnancy, but whose initial 3-hCG level is below the discriminatory threshold, are seen 2 days later for further evaluation. Trends in levels aid diagnosis. IUP t Prenatal care FIGURE 19-3 One suggested algorithm for evaluation of a woman with a suspected ectopic pregnancy. aExpectant management, D&C, or medical regimens are suitable options. bMay consider repeat 3-hCG level if normal IUP suspected. 3-hCG = beta human chorionic gonadotropin; D&C = dilatation and curettage; IUP = intrauterine pregnancy; VS


Obstentrics_Williams

Obstentrics_Williams. Nondiagnostic t D&Cb Chorionic villi Absent t Treat ectopic pregnancy Present = transvaginal sonography. With early normal progressing IUPs, Barnhart and coworkers (2004b) reported a 53-percent 48-hour minimum rise with a 24-hour minimum rise of 24 percent. Seeber and associates (2006) found an even more conservative minimal 35-percent 48-hour rise in normal IUPs. With multifetal gestation, this same anticipated rate of rise is expected (Chung, 2006). Despite these guidelines, Silva and colleagues (2006) caution that a third of women with an ectopic pregnancy will have a 53-percent rise at 48 hours. They further reported that no single pattern characterizes ectopic pregnancy and that approximately half of ectopic pregnancies will show decreasing �-hCG levels, whereas the other half will have increasing levels. Also, despite a declining �-hCG level, a resolving ectopic pregnancy may rupture.


Obstentrics_Williams

Obstentrics_Williams. With a failing IUP, patterned rates of �-hCG level decline can also be anticipated. Following spontaneous abortion, rates decline by 21 to 35 percent at 48 hours and 68 to 84 percent at 7 days. Of note, these ranges relect that �-hCG percentages drop faster if the initial �-hCG level is higher (Barnhart, 2004a). With resolving PULs, Butts and coworkers (2013) found greater rates of decline that ranged from 35 to 50 percent at 48 hours and 66 to 87 percent at 7 days for starting hCG values between 250 and 5000 mIU/mL. In pregnancies without these expected rises or falls in �-hCG levels, distinction between a nonliving IUP and an ectopic pregnancy may be aided by additional �-hCG levels (Zee, 2014). Again delay is balanced against the risk from rupture. D&C is an option and provides a quicker diagnosis balanced against normal pregnancy interruption. Before curettage, a second TVS examination may be indicated and may display new informative indings.


Obstentrics_Williams

Obstentrics_Williams. A single serum progesterone measurement may clariy the diagnosis in a few cases (Stovall, 1989, 1992). A value exceeding 25 ng/mL excludes ectopic pregnany with 92-percent sensitivity (Lipscomb, 1999a; Pisarska, 1998). Conversely, values <5 ng/mL are found in only 0.3 percent of normal progressing IUPs (Mol, 1998; Verhaegen, 2012). hus, values <5 ng/mL suggest either a nonliving IUP or an ectopic pregnancy. Because in most ectopic pregnancies, progesterone levels range between 10 and 25 ng/mL, the clinical utility of this practice is limited. One caveat is that pregnancy achieved with assisted reproductive technology may be associated with higher than usual progesterone levels (Perkins, 2000).


Obstentrics_Williams

Obstentrics_Williams. Endometrial Findings. In a woman in whom ectopic pregnancy is suspected, TVS is performed to look for findings indicative of uterine or ectopic pregnancy. During endometrial cavity evaluation, an intrauterine gestational sac is usually visible between 4Y2 and 5 weeks. The yolk sac appears between 5 and 6 weeks, and a fetal pole with cardiac activity is irst detected at 5Y2 to 6 weeks (Fig. 9-3, p. 159). With transabdominal sonography, these structures are visualized slightly later. In contrast, with ectopic pregnancy, a trilaminar endometrial pattern can be diagnostic (Fig. 19-4). Its speciicity is 94 percent, but with a sensitivity of only 38 percent (Hammoud, 2005). In addition, Moschos and Twickler (2008b) determined sac within the endometrial cavity. Its cavity-conforming shape and central location are characteristic of these anechoic fluid col lections. Distal to this fluid, the endometrial stripe has a trilaminar pattern, which is a common finding with ectopic pregnancy.


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Obstentrics_Williams. (Reproduced with permission from Gala RB: Ectopic pregnancy. In Hoffman BL, Schorge JO, Bradshaw KD, et al: Williams Gynecology, 3rd ed. New York, McGraw-Hili Education; 2016. Photo contributor: Dr. Elysia Moschos.) in women with a pregnancy of unknown location at presenta tion that no normal IUPs had a stripe thickness <8 mm.


Obstentrics_Williams

Obstentrics_Williams. Dr. Elysia Moschos.) in women with a pregnancy of unknown location at presenta tion that no normal IUPs had a stripe thickness <8 mm. Anechoic luid collections, which might normally suggest an early intrauterine gestational sac, may also be seen with ectopic pregnancy. These include pseudogestational sac and decidual cyst. First, a pseudosac is a fluid collection between the endometrial layers and conforms to the cavity shape (see Fig. 19-4). If a pseudosac is noted, the risk of ectopic pregnancy is increased (Hill, 1990; Nyberg, 1987). Second, a decidual cyst is identiied as an anechoic area lying within the endometrium but remote from the canal and often at the endometrial-myometrial border. Ackerman and colleagues (1993 b) suggested that this finding represents early decidual breakdown and precedes decidual cast formation.


Obstentrics_Williams

Obstentrics_Williams. hese two indings contrast with the intradecidual sign seen with uterine pregnancies. With this, an early gestational sac is seen as an anechoic sac eccentrically located within one of the endometrial stripe layers (Dashefsky, 1988). The American College of Obstetricians and Gynecologists (2016) advises caution in diagnosing an IUP in the absence of a deinite yolk sac or embryo.


Obstentrics_Williams

Obstentrics_Williams. Adnexal Findings. he sonographic diagnosis of ectopic pregnancy rests on visualization of an adnexal mass separate from the ovary (Fig. 19-5). If fallopian tubes and ovaries are visualized and an extrauterine yolk sac, embryo, or fetus is identified, then an ectopic pregnancy is conirmed. In other cases, a hyperechoic halo or tubal ring surrounding an anechoic sac is seen (Nadim, 2017). Alternatively, an inhomogeneous adnexal mass is usually caused by hemorrhage within the ectopic sac. Overall, approximately 60 percent of ectopic pregnancies are seen as an inhomogeneous mass adjacent to the ovary; 20 percent appear as a hyperechoic ring; and 13 percent have an obvious gestational sac with a fetal pole (Condous, 2005). Importantly, not all adnexal masses represent an ectopic pregnancy, and integration of sonographic findings with other clinical information is necessary. adnexal mass. In this last image, color Doppler shows a classic "ring


Obstentrics_Williams

Obstentrics_Williams. adnexal mass. In this last image, color Doppler shows a classic "ring FIGURE 19-5 Various transvaginal sonographic findings with ectopic tubal pregnancies. For sonographic diagnosis, an ectopic mass should be seen in the adnexa separate from the ovary and may be seen as: (A) a yolk sac (shown here) and/or fetal pole with or without cardiac activity within an extrauterine sac, (B) an empty extrauterine sac with a hyperechoic ring, or (C) an inhomogeneous of fire," which reflects increased vascularity typical of ectopic pregnancies. LT OV = left ovary; SAG LT AD = sagittal left adnexa; UT = uterus. Placental blood low within the periphery of the complex adnexal mass-the ring ofire-can be seen with transvaginal color Doppler imaging. Although this can aid diagnosis, this finding can also be seen with a corpus luteum cyst, and differentiation can be challenging.


Obstentrics_Williams

Obstentrics_Williams. Hemoperitoneum. In afected women, blood in the peritoneal cavity is most often identified using sonography, but assessment can also be made by culdocentesis (Fig. 19-6). Sonographically, anechoic or hypoechoic luid initially collects in the dependent retrouterine cul-de-sac, and then additionally surrounds the uterus as it fills the pelvis. As much as 50 mL of blood can be seen in the cul-de-sac using TVS, and transabdominal imaging then is used to assess the hemoperitoneum extent. Importantly, however, a small amount of peritoneal luid is physiologically normal. With signiicant intraabdominal hemorrhage, blood will track up the pericolic gutters to fill Morison pouch near the liver. Free luid in this pouch typically is not seen until accumulated volumes reach 400 to 700 mL (Branney, 1995; Rodgerson, 2001; Rose, 2004). Diagnostically, peritoneal fluid in conjunction with an adnexal mass is highly predictive of ectopic pregnancy (Nyberg, 1991). Ascites from ovarian or other cancer is a


Obstentrics_Williams

Obstentrics_Williams. Rodgerson, 2001; Rose, 2004). Diagnostically, peritoneal fluid in conjunction with an adnexal mass is highly predictive of ectopic pregnancy (Nyberg, 1991). Ascites from ovarian or other cancer is a notable mimic.


Obstentrics_Williams

Obstentrics_Williams. Culdocentesis is a simple technique used commonly in the past. The cervix is pulled ourward and upward toward the symphysis with a tenaculum, and a long 18-gauge needle is inserted through the posterior vaginal fornix into the retrouterine culde-sac. If present, fluid can be aspirated. However, a failure to do so is interpreted only as unsatisfactory entry into the culde-sac. Fluid containing fragments of old clots or bloody fluid that does not clot suggests hemoperitoneum. In contrast, if the blood sample clots, it may have been obtained from an adjacent blood vessel or from a briskly bleeding ectopic pregnancy. Several studies have challenged its usefulness, and culdocentesis has been largely replaced by TVS (Glezerman, 1992; Vermesh, 1990).


Obstentrics_Williams

Obstentrics_Williams. Several endometrial changes accompany ectopic pregnancy, and all lack coexistent trophoblast. 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 the absence of trophoblastic tissue be confirmed by D&C before methotrexate treatment is given (Chung, 201i1; Shaunik, 201l). Investigators found that the presumptive diagnosis of ectopic pregnancy is inaccurate in nearly 40 percent of cases without histological exclusion of a spontaneous pregnancy loss. Nevertheless, the risks of D&C are weighed against the limited maternal risks of methotrexate. Endometrial biopsy with a Pipelle catheter was studied as an alternative to D&C and found inferior (Barnhart, 2003b; Ries, 2000). By comparison, frozen section of curettage fragments to identiY products of conception is accurate in more than 90 percent of cases (Barak, 2005; Li, 2014b).


Obstentrics_Williams

Obstentrics_Williams. Direct visualization of the fallopian tubes and pelvis by laparoscopy ofers a reliable diagnosis in most cases of suspected FIGURE 19-6 Techniques to identiy hemoperitoneum. A.Transvaginal sonography of an anechoic fluid collection (arrow) in the retrouterine cul-de-sac. B. Culdocentesis: with a 16-to 18-gauge spinal needle attached to a syringe, the cul-de-sac is entered through the posterior vaginal fornix as upward traction is applied to the cervix with a tenaculum. (B, Reproduced with permission from Gala RB: Ectopic pregnancy. In Hofman BL, Schorge JO, Bradshaw KD, et al: Williams Gynecology, 3rd ed. New York, McGraw-Hili Education, 2016.) ectopic pregnancy. This also permits a ready transition to definitive operative therapy, which is discussed on page 378.


Obstentrics_Williams

Obstentrics_Williams. Medical therapy traditionally involves the antimetabolite methotrexate (MTX). This drug is a folic acid antagonist. It tightly binds to dihydrofolate reductase, blocking the reduction of dihydrofolate to tetrahydrofolate, which is the active form of folic acid. As a result, de novo purine and pyrimidine synthesis is halted, which leads to arrested DNA, RNA, and protein synthesis. Thus, MTX is highly efective against rapidly proliferating tissue such as trophoblast. Overall, ectopic tubal pregnancy resolution rates approximate 90 percent with its use. The drawbacks, however, are that bone marrow, gastrointestinal mucosa, and respiratory epithelium can also be harmed. It is directly toxic to hepatocytes and is renally excreted. MTX is also a potent teratogen, and MTX embryopathy is notable for craniofacial and skeletal abnormalities and fetal-growth restriction (N urmohamed, 201i1). In addition, MTX is excreted into breast milk and may accumulate in neonatal tissues and interfere with


Obstentrics_Williams

Obstentrics_Williams. for craniofacial and skeletal abnormalities and fetal-growth restriction (N urmohamed, 201i1). In addition, MTX is excreted into breast milk and may accumulate in neonatal tissues and interfere with neonatal cellular metabolism (American Academy of Pediatrics, 2001; Briggs, 2015). Based on all these findings, a list of contraindications and pre therapy laboratory testing is found in Table


Obstentrics_Williams

Obstentrics_Williams. TABLE 19-1. Medical Treatment Protocols for Ectopic Pregnancy Sensitivity to MTX Tubal rupture Breastfeeding One dose; repeat if necessary Days 1 (baseline), 4, and 7 If seru m �-hCG level does not decline by 15% from day 4 to day 7 Less than 15% decline during Up to four doses of both drugs until serum �-hCG declines by 15% 1 mg/kg, days 1,s3,5, and 7 0.1 mg/kg days 2, 4, 6, and 8 Days 1 (baseline), 3, 5, and 7 If serum �-hCG level declines < 15%, give additional dose; repeat serum �-hCG in 48 hours and compare with previous value; maximum four doses Once 15% decline achieved, then weekly serum �-hCG levels until undetectable Intrauterine pregnancy Immunodeficiency Peptic ulcer disease Hepatic, renal, or hematologic dysfunction Active pulmonary disease BSA = body surface area; �-hCG =�-human chorionic gonadotropin; MTX = methotrexate; NA = not applicable. Data from American Society for Reproductive Medicine, 2013.


Obstentrics_Williams

Obstentrics_Williams. BSA = body surface area; �-hCG =�-human chorionic gonadotropin; MTX = methotrexate; NA = not applicable. Data from American Society for Reproductive Medicine, 2013. Of precautions, MTX is bound primarily to albumin, and its displacement by other medications such as phenytoin, tetracyclines, salicylates, and sulfonamides can increase MTX serum drug levels. Moreover, renal clearance of MTX may be impaired by nonsteroidal antiinlammatory drugs including aspirin, probenecid, or penicillins (Stika, 2012). Last, vitamins containing folic acid may lower MTX eicacy.


Obstentrics_Williams

Obstentrics_Williams. For ease and eicacy, intramuscular MTX administration is used most often for ectopic pregnancy medical resolution, and single-dose and multidose MTX protocols are available (see Table 19-1). As noted, MTX can lead to bone marrow depression. his toxicity can be blunted by early administration of leucovorin, which is olinic acid and has activity equivalent to folic acid. Thus, leucovorin, which is given within the multidose protocol, allows for some purine and pyrimidine synthesis to bufer side efects. In comparing these two protocols, trade-ofs are recognized. For example, single-dose therapy ofers simplicity, less expense, and less intensive posttherapy monitoring and does not require leucovorin rescue. However, some but not all studies report a higher success rate for the multidose regimen (Alleyassin, 2006; Barnhart, 2003a; Lipscomb, 2005). At our institution, we use single-dose MTX.


Obstentrics_Williams

Obstentrics_Williams. The best candidate for medical therapy is the woman who is asymptomatic, motivated, and compliant. With medical therapy, some classic predictors of success include a low initial serum 3-hCG level, small ectopic pregnancy size, and absent fetal cardiac activity. Of these, initial serum 3-hCG level is the single best prognostic indicator of successful treatment with single-dose MTX. Speciically, reported failure rates are 1.5 percent if the initial serum 3-hCG concentration is < 1000 mID/mL; 5.6 percent at 1000 to 2000 mID/mL; 3.8 percent at 2000 to 5000 mID/mL; and 14.3 percent when levels range between 5000 and 10,000 mID/mL (Menon, 2007). Interestingly, the initial serum 3-hCG value is not a valid indicator of the number of doses needed for successful resolution (NowakMarkwitz, 2009).


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Obstentrics_Williams. Many early trials also used "large size" as an exclusion criterion, although these data are less precise. Lipscomb and colleagues (1998) reported a 93-percent success rate with single-dose MTX when the ectopic mass was <3.5 cm. This compared with success rates between 87 and 90 percent when the mass wasi> 3.5 cm. Last, failure rates rise if cardiac activity is seen, with an 87 -percent success rate in such cases.


Obstentrics_Williams

Obstentrics_Williams. hese regimens are associated with minimal laboratory changes and symptoms, although occasional toxicity may be severe. Kooi and Kock (1992) reviewed 16 studies and reported that adverse efects resolved by 3 to 4 days ater MTX was discontinued. he most common were liver involvement-12 percent; stomatitis6 percent; and gastroenteritis-1 percent. One woman had bone marrow depression. Fortunately, MTX treatment does not diminish ovarian reserve (Boots, 2016; Dyar, 2013). Moreover, conceptions within the irst 6 months after MTX treatment for this indication are not associated with elevated rates of miscarriage or fetal malformations and growth restriction (Svirsy, 2009).


Obstentrics_Williams

Obstentrics_Williams. Importantly, 65 to 75 percent of women initially given MTX will have increasing pain beginning several days ater therapy. Thought to relect separation of the ectopic pregnancy from the tubal wall, this "separation pain" generally is mild and relieved by analgesics. In a series of 258 MTX-treated women by Lipscomb and colleagues (1999b), 20 percent had pain that merited evaluation in a clinic or emergency room. Dltimately, 10 of these 53 underwent surgical exploration. Said another way, 20 percent of women given single-dose MTX will have significant pain, and about 20 percent of these will require laparoscopy.


Obstentrics_Williams

Obstentrics_Williams. As shown in Table 19-1, monitoring single-dose therapy calls for serum 3-hCG determinations at days 4 and 7 following initial injection on day 1. After single-dose MTX, mean serum 3-hCG levels may rise or fall during the first 4 days and then gradually decline. If the level fails to drop more than 15 percent between days 4 and 7, then a second dose of MTX is required. This is necessary in 15 to 20 percent of women treated with single-dose therapy (Cohen, 2014a; Kirk, 2007). With multi dose MTX, levels are measured at 48-hour intervals until they fall more than 15 percent. D p to four doses may be given to one patient if required (Stovall, 1991).


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Obstentrics_Williams. With multi dose MTX, levels are measured at 48-hour intervals until they fall more than 15 percent. D p to four doses may be given to one patient if required (Stovall, 1991). Once appropriately dropping levels are achieved in either regimen, serum 3-hCG determinations are then measured weekly until undetectable. Outpatient monitoring is preferred, but if patient safety or compliance is questioned, the woman is hospitalized during initial surveillance. Lipscomb and colleagues (1998) used single-dose MTX to successfully treat 287 women and reported that the average time to resolutiondeined as a serum 3-hCG level < 15 mID/mL, was 34 days. Importantly, the longest time was 109 days. Failure is judged when the 3-hCG level plateaus or rises or the tube ruptures. Importantly, tubal rupture can occur even with declining 3-hCG levels. Lipscomb and associates (1998) described a 14-day mean time to rupture, but one woman had tubal rupture 32 days after single-dose MTX.


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Obstentrics_Williams. From one metaanalysis, the overall success rate for treatment with MX is 89 percent. The success for the multidose regiment is 92.7 percent, whereas that for single-dose is 88.1 percent (Barnhart, 2003a). Despite this diference, the single dose is more frequently used because of its simplicity and convenience.


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Obstentrics_Williams. Studies have compared laparotomy with laparoscopic surgery for ectopic pregnancy (Lundorf, 1991; Murphy, 1992; Vermesh, 1989). Overall, tubal patency and number of subsequent uterine pregnancies do not difer between these routes. hus, laparoscopy is the preferred surgical treatment for ectopic pregnancy unless a woman is hemodynamically unstable. As experience has accrued, cases previously managed by laparotomy-for example, ruptured tubal pregnancies with hemoperitoneum-can safely be managed laparoscopically by those with suitable expertise (Cohen, 2013; Sagiv, 2001). hat said, the lowered venous return and cardiac output associated with the pneumoperitoneum of laparoscopy must be factored into the decision to select mini mally invasive surgery for hypovolemic women. Before surgery, future fertility desires are discussed. In women desiring permanent sterilization, the unafected tube can be ligated or removed concurrently with salpingectomy for the afected fallopian tube.


Obstentrics_Williams

Obstentrics_Williams. Two procedures-salpingostomy or salpingectomy-are options. Two multicenter, randomized controlled trials have compared laparoscopic outcomes between the two procedures in women with a normal contralateral fallopian tube. he European Surgery in Ectopic Pregnancy (ESEP) study randomized 23i1 women to salpingectomy and 215 to salpingostomy. After surgery, subsequent rates of ongoing pregnancy by natural conception did not difer significantly between groups-56 versus 61 percent, respectively (Mol, 2014). Again, in the DEMETER trial, the subsequent 2-year rate for achieving a uterine pregnancy did not difer between groups-64 versus 70 percent, respectively (Fernandez, 2013). In women with an abnormalappearing contralateral tube, salpingostomy is a conservative option for fertility preservation.


Obstentrics_Williams

Obstentrics_Williams. his procedure is typically used to remove a small unruptured pregnancy. A 10-to 15-mm linear incision is made on the anti mesenteric border of the fallopian tube over the pregnancy. The products usually will extrude from the incision. These can be carefully removed or flushed out using high-pressure irrigation that more thoroughly removes the trophoblastic tissue (Al-Sunaidi, 2007). Small bleeding sites are controlled with needlepoint electrocoagulation, and the incision is left unsutured to heal by secondary intention. Serum 3-hCG levels are used to monitor response to both medical and surgical therapy. After linear salpingostomy, serum 3-hCG levels decline rapidly over days and then more gradually, with a mean resolution time of approximately 20 days.


Obstentrics_Williams

Obstentrics_Williams. Seldom performed today, salpingotomy is essentially the same procedure except that the incision is closed with delayedabsorbable suture. According to T ulandi and Guralnick (1991), prognosis does not difer with or without suturing, and laparoscopic suturing adds surgical time.


Obstentrics_Williams

Obstentrics_Williams. Tubal resection may be used for both ruptured and unruptured ectopic pregnancies. To minimize the rare recurrence of pregnancy in the tubal stump, complete excision of the fallopian tube is advised. With one laparoscopic technique, the afected fallopian tube is lifted and held with atraumatic grasping forceps (Thompson, 2016). One of several suitable bipolar grasping devices is placed across the fallopian tube at the uterotubal junction. Once desiccated, the tube is cut. The bipolar device is then advanced across the most proximal portion of mesosalpinx. Similarly, current is applied, and the desiccated tissue cut. This process moves serially from the proximal mesosalpinx to its distal extent under the tubal ampulla. Alternatively, an endoscopic suture loop can be used to encircle and ligate the knuckle of involved fallopian tube and its underlying vascular supply within the mesosalpinx. Two consecutive suture loops are placed, and the tube distal to these ligatures is then cut free


Obstentrics_Williams

Obstentrics_Williams. the knuckle of involved fallopian tube and its underlying vascular supply within the mesosalpinx. Two consecutive suture loops are placed, and the tube distal to these ligatures is then cut free with scissors. Salpingectomy during laparotomy is shown in Chapter 39 (p. 704).


Obstentrics_Williams

Obstentrics_Williams. Most tubal ectopic pregnancies are small and pliant. Accord ingly, they can be held firmly by grasping forceps and drawn up into one of the accessory site cannulas. Larger tubal ectopic pregnancies may be placed in an endoscopic sac to prevent frag mentation as they are removed through the laparoscopic port site. Importantly, to remove all trophoblastic tissue, the pelvis and abdomen should be irrigated and suctioned free of blood and tissue debris. Slow and systematic movement of the patient from Trendelenburg to reverse Trendelenburg positioning dur ing irrigation can also assist in dislodging stray tissue and luid. hese should be suctioned and removed from the peritoneal cavity.


Obstentrics_Williams

Obstentrics_Williams. hese should be suctioned and removed from the peritoneal cavity. After surgery, 3-hCG levels usually fall quickly and approxi mate 10 percent of preoperative values by day 12 (Hajenius, 1995; Vermesh, 1988). Persistent trophoblast is rare following salpingectomy, but complicates 5 to 15 percent of salpingos tomies (Kayatas, 2014; Pouly, 1986; Seifer, 1993). Rates are lower for laparotomy versus laparoscopic procedures (Hajenius, 1995). Other risk factors are debatable but may include greater serum 3-hCG levels and smaller ectopic size (Rabischong, 2010; Seifer, 1997). Bleeding caused by retained trophoblast is the most serious complication.


Obstentrics_Williams

Obstentrics_Williams. Incomplete removal of trophoblast can be identiied by stable or rising 3-hCG levels. v1onitoring approaches are not codified. One scheme measures serum 3-hCG levels on postoperative day 1, and values dropping < 50 percent of the preoperative value relect risk for persistent trophoblast (Spandorfer, 1997). Another measures weekly levels (Mol, 2008). With stable or increasing 3-hCG levels, additional surgical or medical therapy is necessary. Without evidence for tubal rupture, standard therapy for this is single-dose MTX, 50 mg/m2 X body surface area (BSA). Rupture and bleeding require surgical intervention.


Obstentrics_Williams

Obstentrics_Williams. Several randomized trials have compared methotrexate treatment with laparoscopic surgery. One multicenter trial compared a multidose MTX protocol with laparoscopic salpingostomy and found no diferences for tubal preservation and primary treatment success (Hajenius, 1997). In this same study group, however, health-related quality-of-life factors such as pain, posttherapy depression, and decreased perception of health were significantly impaired after systemic MX compared with laparoscopic salpingostomy (Nieuwkerk, 1998). In their randomized controlled trial, Fernandez and coworkers (2013) compared multidose medical therapy against salpingostomy and found that medical and conservative surgery provided similar 2-year rates of attaining a uterine pregnancy.


Obstentrics_Williams

Obstentrics_Williams. Evidence is conlicting when single-dose MTX is compared with surgical intervention. In two separate studies, single-dose MTX was overall less successful in resolving pregnancy than laparoscopic salpingostomy, although tubal patency and subsequent uterine pregnancy rates were similar between both groups (Fernandez, 1998; Sowter, 2001). Women treated with MTX had significantly better physical functioning immediately following therapy, but there were no diferences in psychological functioning. Krag NIoeller and associates (2009) reported the results from their randomized trial that had a median surveillance period of 8.6 years during which future pregnancy rates were evaluated. Ectopic-resolution success rates were not significantly diferent between those managed surgically and those treated with MTX. Moreover, cumulative spontaneous uterine pregnancy rates were not diferent between the MTX group (73 percent) and the surgical group (62 percent).


Obstentrics_Williams

Obstentrics_Williams. Based on these studies, we conclude that women who are hemodynamically stable and in whom there is a small tubal diameter, no fetal cardiac activity, and serum �-hCG concentrations <5000 mIU/mL have similar outcomes with medicalior surgical management. Despite lower success rates with medical therapy for women with larger tubal size, higher serum �-hCG levels, and fetal cardiac activity, medical management can be ofered to the motivated woman who understands the risks. In select cases, it is reasonable to observe very early tubal pregnancies that are associated with stable or falling serum �-hCG levels. Mavrelos and coworkers (2013) noted that almost one third of 333 tubal ectopic pregnancies measuring <3 cm and with �-hCG levels < 1500 mIU/mL resolved without intervention. Cohen and associates (20 14b) similarly followed 674 women with declining �-hCG levels to successul resolution. hese findings have been supported by smaller randomized trials Qurkovic, 2017; van Mello, 2013).


Obstentrics_Williams

Obstentrics_Williams. With expectant management, subsequent rates of tubal patency and intrauterine pregnancy are comparable with surgical or medical management. That said, compared with the established safety of medical and surgical therapy, the prolonged surveillance and risks of tubal rupture support the practice of expectant therapy only in appropriately selected and counseled women.


Obstentrics_Williams

Obstentrics_Williams. An interstitial pregnancy is one that implants within the proximal tubal segment that lies within the muscular uterine wall (Fig. 19-7). Incorrectly, they may be called cornual pregnancies, but this term describes a conception that develops in the rudimentary horn of a uterus with a miillerian anomaly (Moawad, 2010). Risk factors are similar to others discussed for tubal ectopic pregnancy, although previous ipsilateral salpingectomy is a specific risk factor for interstitial pregnancy (Lau, 1999). Undiagnosed interstitial pregnancies usually rupture following 8 to 16 weeks of amenorrhea, which is later than for more distal pregnancies. his is due to greater distensibility of the myometrium covering the interstitial fallopian tube segment. Because of the proximity of these pregnancies to the uterine and ovarian arteries, hemorrhage can be severe and associated with mortality rates as high as 2.5 percent (Tulandi, 2004).


Obstentrics_Williams

Obstentrics_Williams. With transvaginal sonography and serum �-hCG assays, interstitial pregnancy can now be diagnosed early in many cases, but diagnosis can be challenging. hese pregnancies sonographically can appear similar to an eccentrically implanted uterine pregnancy, especially in a uterus with a miillerian anomaly. Criteria that may aid diferentiation include: an empty uterus, a gestational sac seen separate from the endometrium and > 1 cm away from the most lateral edge of the uterine cavity, and a thin, < 5-mm myometrial mantle surrounding the sac (Timor-Tritsch, 1992). Moreover, an echo genic line, known as the "interstitial line sign," extending from the gestational sac to the endometrial cavity most likely represents the interstitial portion of the fallopian tube and is highly sensitive and specific (Ackerman, 1993a). In unclear cases, three-dimensional (3-D) sonography, magnetic resonance (MR) imaging, or diagnostic laparoscopy can help clariy anatomy (Parker, 2012; Tanaka, 2014).


Obstentrics_Williams

Obstentrics_Williams. and specific (Ackerman, 1993a). In unclear cases, three-dimensional (3-D) sonography, magnetic resonance (MR) imaging, or diagnostic laparoscopy can help clariy anatomy (Parker, 2012; Tanaka, 2014). Laparoscopically, an enlarged protuberance is found lying outside the round ligament and coexistent with a normal distal fallopian tube and ovary.