Obstentrics_Williams

Obstentrics_Williams. FIGURE 19-7 Interstitial ectopic pregnancy. A.This parasagittal view using transvaginal sonography shows an empty uterine cavity and a mass that is cephalad and lateral to the uterine fundus (calipers). B. Intraoperative photograph during laparotomy and before cornual resection of the same ectopic pregnancy. In this frontal view, the bulging right-sided interstitial ectopic pregnancy is lateral to the round ligament insertion and medial to the isthmic portion of the fallopian tube. (Used with permission from Drs. David Rogers and Elaine Duryea.)


Obstentrics_Williams

Obstentrics_Williams. Surgical management with either cornual resection or cornuostomy may be performed via laparotomy or laparoscopy, depending on patient hemodynamic stability and surgeon expertise (Hofman, 2016; Zuo, 2012). With either approach, intraoperative intramyometrial vasopressin injection may limit surgical blood loss, and 3-hCG levels should be monitored postoperatively to exclude remnant trophoblast. Cornual resection removes the gestational sac and surrounding cornual myometrium by means of a wedge excision (Fig. 19-8). Alternatively, cornuostomy involves incision of the cornua and suction or instrument extraction of the pregnancy. Both instances require myometrial closure.


Obstentrics_Williams

Obstentrics_Williams. With early diagnosis, medical management may be considered. But because of the low incidence, consensus regarding methotrexate regimens is lacking. In their small series, J ermy and associates (2004) reported a 94-percent success with systemic MTX using a dose of 50 mg/m2 X BSA. Others have described direct MTX injection into the gestational sac (Framarino-dei-Malatesta, 2014). Importantly, because these women typically have higher initial serum 3-hCG levels, longer surveillance is usually needed. The risk of uterine rupture with subsequent pregnancies following either medical or surgical management is unclear. hus, careful observation of these women during pregnancy, along with strong consideration of elective cesarean delivery, is warranted.


Obstentrics_Williams

Obstentrics_Williams. FIGURE 19-8 During cornual resection, the pregnancy, surrounding myometrium, and ipsilateral fallopian tube are excised en bloc. The incision is angled inward as it is deepened. This creates a wedge shape into the myometrium, which is then closed in layers with delayed-absorbable suture. The serosa is closed with subcuticular style suturing. (Reproduced with permission from Hofman BL, Corton MM: Surgeries for benign gynecologic conditions. In Hofman BL, Schorge JO, Bradshaw KD, et al: Williams Gynecology, 3rd ed. New York, McGraw-Hili Education, 2016.)


Obstentrics_Williams

Obstentrics_Williams. Distinct from interstitial pregnancy, the term angular pregnany describes implantation within the endometrial cavity but at one cornu and medial to the uterotubal junction and round ligament. An angular pregnancy displaces the round ligament upward and outward, whereas an interstitial tubal pregnancy does not shift it (Arleo, 2014). This distinction is important because angular pregnancies can sometimes be carried to term but with increased risk of abnormal placentation and its consequences Qansen, 1981).


Obstentrics_Williams

Obstentrics_Williams. This term describes implantation within the myometrium of a prior cesarean delivery scar. Its incidence approximates 1 in 2000 normal pregnancies and has increased along with the cesarean delivery rate (Ash, 2007; Rotas, 2006). he pathogen esis of cesarean scar pregnancy (CSP) has been likened to that rhage (Timor-Tritsch, 2014a,b). It is unknown if the incidence increases with multiple cesarean deliveries or if it is afected by either one-or two-layer uterine incision closure during cesarean.


Obstentrics_Williams

Obstentrics_Williams. Women with CSP usually present early, and pain and bleed ing are common. Still, up to 40 percent of women are asymp tomatic, and the diagnosis is made during routine sonographic examination (Rotas, 2006). Sonographically, diferentiating be diicult (Moschos, 2008a; Timor-Tritsch, 2016). According to Godin (1997), four sonographic criteria should be satisied for the diagnosis and are described in Figure 19-9. Although TVS is the typical first-line imaging tool, MR imaging is useful when sonography is inconclusive (Huang, 2014; Osborn, 2012).


Obstentrics_Williams

Obstentrics_Williams. Treatment standards are lacking, and several options are available. Expected management is an option, and live birth rates were 57 percent in one review (Maheux-Lacroix, 2017). However, hemorrhage, placenta accreta, and uterine rupture are risks. Thus, hysterectomy is an acceptable initial choice in those desiring sterilization. It is sometimes necessary with heavy uncontrolled bleeding. Fertility-preserving options include systemic or locally injected methotrexate, either alone or combined with conservative surgery (Birch Petersen, 2016; Cheung, 2015). Surgical procedures include visually guided suction curettage, hysteroscopic removal, or isthmic excision done abdominally or vaginally. hese are completed solely or with adjunctive MTX Qurkovic, 2016; Li, 2014a; Wang, 2014; Yang, 2009). Often uterine artery embolization (UE) is used preoperatively to minimize hemorrhage risk (Zhang, 2012; Zhuang, 2009). Foley balloon catheter placement can be another option for procedure-associated


Obstentrics_Williams

Obstentrics_Williams. Often uterine artery embolization (UE) is used preoperatively to minimize hemorrhage risk (Zhang, 2012; Zhuang, 2009). Foley balloon catheter placement can be another option for procedure-associated bleeding (TimorTritsch,i2015a).


Obstentrics_Williams

Obstentrics_Williams. Following conservative treatment, subsequent pregnancies have good outcomes, but placenta accreta and recurrent CSP are risks (Gao, 2016; Wang, 2015). Uterine arteriovenous malformations are a potential long-term complication (TimorTritsch,i2015b).


Obstentrics_Williams

Obstentrics_Williams. FIGURE 19-9 Cesarean scar pregnancy. A. Transvaginal sonogram of a uterus with a cesarean scar pregnancy (CSP) in a sagittal plane. An empty uterine cavity is identified by a bright hyperechoic endometrial stripe (long, white arrow). An empty cervical canal is similarly identified (short, white arrow). Last, an intrauterine mass is seen in the anterior part of the uterine isthmus (red arrows). Myometrium between the bladder and gestational sac is absent or thinned (1 to 3 mm). Photo contributor: Dr. Elysia Moschos.) B. Hysterectomy specimen containing a cesarean scar pregnancy. C. This same hysterectomy specimen is transversely sectioned at the level of the uterine isthmus and through the gestational sac. The uterine body lies to the left, and the cervix is on the right. A metal probe is placed through the endocervical canal to show the eccentric development of this gestation. Only a thin layer of myometrium overlies this pregnancy, which pushes anteriorly through the uterine wall.


Obstentrics_Williams

Obstentrics_Williams. placed through the endocervical canal to show the eccentric development of this gestation. Only a thin layer of myometrium overlies this pregnancy, which pushes anteriorly through the uterine wall. (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 contributors: Drs. Sunil Balgobin, Manisha Sharma, and Rebecca Stone.) his rare ectopic pregnancy is defined by cervical glands noted histologically opposite the placental attachment site and by all or part of the placenta found below the entrance of the uterine vessels or below the peritoneal relection on the anterior uterus. In a typical case, the endocervix is eroded by trophoblast, and the pregnancy develops in the fibrous cervical wall. Predisposing risks include ART and prior uterine curettage (Ginsburg, 1994; Jeng, 2007).


Obstentrics_Williams

Obstentrics_Williams. Painless vaginal bleeding is reported by 90 percent of women with a cervical pregnancy-a third of these have massive hemorrhage (Ushakov, 1997). As pregnancy progresses, a distended, thin-walled cervix with a partially dilated external os may be evident. Above the cervical mass, a slightly enlarged uterine fundus can be felt. Identification of cervical pregnancy is based on speculum examination, palpation, and TVS. Sonographic indings typical of cervical pregnancy are shown and described in Figure 19-10. MR imaging and 3-D sonography have also been used to confirm the diagnosis Q ung, 2001; Sherer, 2008).


Obstentrics_Williams

Obstentrics_Williams. Cervical pregnancy may be treated medically or surgically. Conservative management strives to minimize hemorrhage, resolve the pregnancy, and preserve fertility. In many centers, including ours, methotrexate has become the first-line therapy in stable women, and administration follows protocols listed in Table 19-1 (Verma, 2011; Zakaria, 2011). he drug has also been injected directly into the gestational sac, alone or with systemic doses Qeng, 2007; 1urji, 2015). Others describe MTX infusion combined with uterine artery embolization"chemoembolization" (Xiaolin, 2010). FIGURE 19-10 Cervical pregnancy. Transvaginal sonographic findings may include: (1) an hourglass uterine shape and ballooned cervical canal; (2) gestational tissue at the level of the cervix (black arrow); (3) absent intrauterine gestational tissue (white arrows); and (4) a portion of the endocervical canal seen interposed between the gestation and the endometrial canal. (Used with permission from Dr. Elysia Moschos.)


Obstentrics_Williams

Obstentrics_Williams. With MTX regimens, resolution and uterine preservation are achieved for gestations < 12 weeks in 91 percent of cases (Kung, 1997). In selecting appropriate candidates, Hung and colleagues (1i996) noted higher risks of systemic MTX treat ment failute in those with a gestational age >9 weeks, �-hCG levels > 10,000 mIU/mL, crown-rump length > 10 mm, and fetal cardiac activity. For this reason, many induce fetal death with intracardiac or intrathoracic injection of potas sium chloride. With a single-dose intramuscular protocol, an MTX dose between 50 and 75 mg/m2 X BSA is typical. To resolve fetal cardiac activity, a sonographically guided fetal intracardiac injection of 2 mL (2 mEq/mL) potassium chlo ride solution can be given (Verma, 2009). Song and associ ates (2009) described management of 50 cases and observed regression.


Obstentrics_Williams

Obstentrics_Williams. As an adjunct to medical or surgical therapy, uterine artery embolization has been described either as a response to bleeding or as a preprocedural preventive tool (Hirakawa, 2009; Zakaria, 2011). Also, in the event of hemorrhage, a 26F Foley catheter with a 30-mL balloon can be placed intracervically and inlated to efect hemostasis by vessel tamponade and to monitor uterine drainage. The balloon remains inlated for 24 to 48 hours and is gradually decompressed over a few days (Ushakov, 1997). Although conservative management is feasible for many women with cervical pregnancies, suction curettage or hysterectomy may be selected. Moreover, hysterectomy may be required with bleeding uncontrolled by conservative methods. Because of the close proximity of the ureters to the ballooned cervix, urinary tract injury rates are a concern during hysterectomy.


Obstentrics_Williams

Obstentrics_Williams. If cervical curettage is planned, intraoperative bleeding may be lessened by preoperative UAE, by intracervical vasopressin injection, or by a cerclage placed at the internal cervical os to compress feeding vessels (Chen, 2015; Fylstra, 2014; Wang, 2011). Also, cervical branches of the uterine artery can efectively be ligated with vaginal placement of hemostatic cervical sutures on the lateral aspects of the cervix at 3 and 9 o'clock (Bianchi, 2011). Following curettage, a Foley balloon can be placed to tamponade bleeding and is managed as described earlier. Suction curettage may be especially favored in rare cases of a heterotopic pregnancy composed of a cervical and a desired uterine pregnancy (Tsakos, 2015).


Obstentrics_Williams

Obstentrics_Williams. hese rare ectopic pregnancies are defined as an implantation in the peritoneal cavity exclusive of tubal, ovarian, or intraligamentous implantations. Although a zygote can traverse the tube and implant primarily in the peritoneal cavity, most abdominal pregnancies are thought to follow early tubal rupture or abortion with reimplantation. In cases of advanced extrauterine pregnancy, it is not unusual for the placenta to be still at least partially attached to the uterus or adnexa.


Obstentrics_Williams

Obstentrics_Williams. Diagnosis may be diicult. First, symptoms may be absent or vague. Laboratory tests are typically uninformative, although maternal serum alpha-fetoprotein levels can be elevated. Clinically, abnormal fetal positions may be palpated, or the cervix is displaced (Zeck, 2007). Sonographically, the diagnosis is often missed (Costa, 1991). Oligohydramnios is common but nonspecific. Other clues include a fetus seen separate from the uterus or eccentrically positioned within the pelvis; lack of myometrium beween the fetus and the maternal anterior abdominal wall or bladder; extrauterine placental tissue; or bowel loops surrounding the gestational sac (Allibone, 1981; Chukus, 2015). If additional anatomical information is needed, MR imaging can help confirm the diagnosis and provide maximal information concerning placental implantation (Bertrand, 2009; Mittal, 2012).


Obstentrics_Williams

Obstentrics_Williams. Treatment of an abdominal pregnancy depends on the ges tational age at diagnosis. Conservative management carries a maternal risk for sudden and dangerous hemorrhage. Moreover, in 20 percent. Thus, we believe that termination generally is indicated when the diagnosis is made. Certainly, before 24 weeks, conservative treatment rarely is justified. Despite this, some have described waiting until fetal viability with close sur veillance (Kim, 2013; Marcellin, 2014).


Obstentrics_Williams

Obstentrics_Williams. Once placental implantation has been assessed, several options to control intraoperative hemorrhage mimic those used for placenta accrete syndrome (Chap. 41, p. 792). he principal surgical objectives involve delivery of the fetus and careful assessment of placental implantation without provoking hemorrhage. Unnecessary exploration is avoided because the anatomy is commonly distorted and surrounding areas are extremely vascular. Importantly, placental removal may precipitate torrential hemorrhage because the normal hemostatic mechanism of myometrial contraction to constrict hypertrophied blood vessels is lacking. If it is obvious that the placenta can be safely removed or if there is already hemorrhage from its implantation site, then removal begins immediately. When possible, blood vessels supplying the placenta should be ligated irst.


Obstentrics_Williams

Obstentrics_Williams. Some advocate leaving the placenta in place as the lesser of two evils. It decreases the chance of immediate life-threatening hemorrhage, but at the expense of long-term sequelae. If let in the abdominal cavity, the placenta commonly becomes infected, with subsequent formation of abscesses, adhesions, intestinal or ureteral obstruction, and wound dehiscence (Bergstrom, 1998; Martin, 1988). In many of these cases, surgical removal becomes inevitable. If the placenta is let, its involution may be monitored using sonography and serum �-hCG levels (France, 1980; Martin, 1990). Color Doppler sonography can be used to assess changes in blood low. In some cases, and usually depending on its size, placental function rapidly declines, and the placenta is resorbed. But placental resorption may take years (Roberts, 2005; Valenzano, 2003).


Obstentrics_Williams

Obstentrics_Williams. If the placenta is left in place, postoperative methotrexate use is controversial. It has been recommended to hasten involution but has been reported to cause accelerated placental destruction with accumulation of necrotic tissue and infection with abscess formation (Rahman, 1982). It is diicult to envision a supporting role for the use of an antimetabolite for a senescent organ (Worley, 2008).


Obstentrics_Williams

Obstentrics_Williams. Ectopic implantation of the fertilized egg in the ovary is rare and is diagnosed if four clinical criteria are met. hese were outlined by Spiegelberg (1878): (1) the ipsilateral tube is intact and distinct from the ovary; (2) the ectopic pregnancy occupies the ovary; (3) the ectopic pregnancy is connected by the uteroovarian ligament to the uterus; and (4) ovarian tissue can be demonstrated histologically amid the placental tissue. Risk factors are similar to those for tubal pregnancies, but ART or IUD failure seems to be disproportionately associated (Zhu, 2014). Presenting complaints and findings mirror those for tubal ectopic pregnancy. Although the ovary can accommodate the expanding pregnancy more easily than the fallopian tube, rupture at an early stage is the usual consequence (Melcer, 2016).


Obstentrics_Williams

Obstentrics_Williams. Transvaginal sonography use has resulted in a more frequent diagnosis of unruptured ovarian pregnancies. Sonographically, an internal anechoic area is surrounded by a wide echogenic ring, which in turn is surrounded by ovarian cortex (Comstock, 2005). In their review of 49 cases, Choi and associates (2011) noted that the diagnosis may not be made until surgery, as many cases are presumed tubal ectopic pregnancy. Moreover, at surgery, an early ovarian pregnancy may be considered to be a hemorrhagic corpus luteum. Evidence-based management accrues mainly from case reports (Hassan, 2012; Scutiero, 2012). Classically, management for ovarian pregnancies has been surgical. Small lesions can be managed by ovarian wedge resection or cystectomy, whereas larger lesions require oophorectomy (Elwell, 2015; Melcer, 2015). With conservative surgery, 3-hCG levels should be monitored to exclude remnant trophoblast.


Obstentrics_Williams

Obstentrics_Williams. Pregnancy implanted toward the mesosalpinx may rupture into a space formed between the broad ligament leaves and become an intraligamentous or broad ligament pregnancy. Rents in prior cesarean sca's serve as another conduit (Rudra, 2013). hese are rare, and information accrues from case reports. Clinical indings and management mirror those for abdominal pregnancy. Although laparotomy is required in most instances, a few case reports describe laparoscopic excision of early small pregnancies (Apantaku, 2006; Cormio, 2006).


Obstentrics_Williams

Obstentrics_Williams. Ectopic placental implantations in less expected sites have been described in case reports and include the omentum, liver, and retroperitoneum, among others (Brouard, 2015; Liang, 2014; Watrowski, 2015). Also, intramural uterine implantations at sites other than a cesarean scar have been noted in women with prior uterine surgeries, ART, or adenomyosis (Memtsa, 2013; Wu, 2013). Although laparotomy is preferred by many for these ectopic sites, laparoscopic excision by those with suitable skills is gaining acceptance. Ackerman TE, Levi CS, Dashefsky SM, et al: Interstitial line: sonographic finding in interstitial (cornual) ectopic pregnancy. Radiology 189(1):83, 1993a Ackerman TE, Levi CS, Lyons A, et al: Decidual cyst: endovaginal sono graphic sign of ectopic pregnancy. Radiology 189(3):727, 1993b


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Obstentrics_Williams. Alleyassin A, Khademi A, Aghahosseini M, et al: Comparison of success rates in the medical management of ectopic pregnancy with single-dose and multiple-dose administration of methotrexate: a prospective, randomized clinical trial. Fertil Steril 85(6): 1661, 2006 Allibone GW, Fagan CJ, Porter SC: The sonographic features of intra-abdominal pregnancy. J Clin Ultrasound 9(7):383, 1981 Al-Sunaidi M, Tulandi T: Surgical treatment of ectopic pregnancy. Semin Reprod Med 25(2): 117, 2007 American Academy of Pediatrics Committee on Drugs: Transfer of drugs and other chemicals into human milk. Pediatrics 108(3):776,o2001 American College of Obstetricians and Gynecologists: Prevention ofRh D alloimmunization. Practice Bulletin No. 181, August 201 American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine: Ultrasoound in pregnancy. Practice Bulletin No. 175, December 2016


Obstentrics_Williams

Obstentrics_Williams. American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine: Ultrasoound in pregnancy. Practice Bulletin No. 175, December 2016 American Society for Reproductive Medicine: Medical treatment of ectopic pregnancy: a committee opinion. Fertil Sterilo100(3):638, 2013 Apantaku 0, Rana P, Inglis T: Broad ligament ectopic pregnancy following invitro fertilization in a patient with previous bilateral salpingectomy. J Obstet Gynaecol 26(5):474, 2006 Arleo EK, DeFilippis EM: Cornual, interstitial, and angular pregnancies: clariying the terms and a review of the literature. Clin Imaging 38(6):763, 2014


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Obstentrics_Williams. Ash A, Smith A, Maxwell D: Caesarean scar pregnancy. BJOG 114:253,2007 Barak S, Oettinger M, Perri A, et al: Frozen section examination of endometrial curettings in the diagnosis of ectopic pregnancy. Acta Obstet Gynecol Scand 84(1):43, 2005 Barnhart K, Mennuti MT, Benjamin I, et al: Prompt diagnosis of ectopic pregnancy in an emergency department setting. Obstet GynecoIo84:o1010, 1994 Barnhart KT, Gosman G, Ashby R, et al: The medical management of ectopic pregnancy: a meta-analysis comparing "single dose" and "multidose" regimens. Obstet Gynecol 101:778, 2003a Barnhart KT, Gracia CR, Reindl B, et al: Usefulness of Pipelle endometrial biopsy in the diagnosis of women at risk for ectopic pregnancy. Am J Obstet Gynecol 188:906, 2003b Barnhart KT, Rinaudo P, Hummel A, et al: Acute and chronic presentation of ectopic pregnancy may be two clinical entities. Fertil Steril 80: 1345, 2003c


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Obstentrics_Williams. Barnhart KT, Sammel MD, Chung K, et al: Decline of serum hCG and spontaneous complete abortion: defining the normal curve. Obstet Gynecol 104:975,o2004a Barnhart KT, Sammel MD, Rinaudo PF, et al: Symptomatic patients with an early viable intrauterine pregnancy: hCG cuves redeined. Obstet Gynecol 104:50,o2004b


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Obstentrics_Williams. Bergstrom R, Mueller G, Yankowitz J: A case illustrating the continued dilemmas in treating abdominal pregnancy and a potential explanation for the high rate of postsurgical febrile morbidity. Gynecol Obstet Invest 46:268, 1998 Bertrand G, Le Ray C, Simard-Emond L, et al: Imaging in the management of abdominal pregnancy: a case report and review of the literature. J Obstet Gynaecol Can 31(1):57, 2009 Bhattacharya S, McLernon DJ, Lee AJ, et al: Reproductive outcomes following ectopic pregnancy: register-based retrospective cohort study. PLoS Med 9(6):el001243,o2012 Bianchi P, Salvatori MM, Torcia F, et al: Cervical pregnancy. Fertil Steril 95(6):2123.e3,o2011 Birch Petersen K, Hofmann E, Rifbjerg Larsen C, et al: Cesarean scar pregnancy: a systematic review of treatment studies. Fertil Steril 105(4):958, 20o16 Bolaji II, Oktaba M, Mohee K, et al: n odyssey through salpingitis isthmica nodosa. Eur J Obstet Gynecol Reprod BioI 184:73, 2015 Boots CE, Hill MJ, Feinberg EC, et al:


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Obstentrics_Williams. Steril 105(4):958, 20o16 Bolaji II, Oktaba M, Mohee K, et al: n odyssey through salpingitis isthmica nodosa. Eur J Obstet Gynecol Reprod BioI 184:73, 2015 Boots CE, Hill MJ, Feinberg EC, et al: Methotrexate does not afect ovarian reserve or subsequent assisted reproductive technology outcomes. J Assist Reprod Genet 33(5):647,o2016 Bouyer J, Coste J, Fernandez H, et al: Sites of ectopic pregnancy: a 10 year population-based study of 1800 cases. Hum Reprod 17(12):3224,o2002 Branney SW, Wolfe E, Moore EE, et al: Quantitative sensitivity of ultrasound in detecting free intraperitoneal fluid. J Trauma 40(6):1052, 1995 Brennan DF, Kwatra S, Kelly M, et al: Chronic ectopic pregnancy-two cases of acute rupture despite negative beta hCG. J Emerg Med 19(3):249,2000 Briggs GG, Freeman RK (eds): Drugs in Pregnancy and Lactation. Philadelphia, Wolters Kiuwer, 2015


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Obstentrics_Williams. Brouard KJ, Howard BR, Dyer A: Hepatic pregnancy suspected at term and successful delivery of a live neonate with placental attachment to the right lobe of the liver. Obstet GynecoIo126(1):207, 2015 Butts SF, Guo W, Cary MS, et al: Predicting the decline in human chorionic gonadotropin in a resolving pregnancy of unknown location. Obstet Gynecol 122(2 Pt 1):33, 2013 Chen H, Yang S, Fu J, et al: Outcomes of bilateral uterine artery chemoembolization in combination with surgical evacuation or systemic methotrexate for cervical pregnancy. J Minim Invasive GynecoIo22(6):1029, 2015 Cheung Y: Local methotrexate injection as the first-line treatment for cesarean scar pregnancy: review of the literature. J Minim Invasive Gynecol 22(5):753,o2015 Choi HJ, 1m KS, Jung HJ, et al: Clinical analysis of ovarian pregnancy: a report of 49 cases. Eur J Obstet Gynecol Reprod Bioi 158(1):87,2011


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Obstentrics_Williams. Choi HJ, 1m KS, Jung HJ, et al: Clinical analysis of ovarian pregnancy: a report of 49 cases. Eur J Obstet Gynecol Reprod Bioi 158(1):87,2011 Chukus A, Tirada N, Restrepo R, et al: Uncommon implantation sites of ectopic pregnancy: thinking beyond the complex adnexal mass. Radiographies 35(3):946,o2015 Chung K, Chandavarkar U, Opper N, et al: Reevaluating the role of dilation and curettage in the diagnosis of pregnancy of unknown location. Fertil Steril 96(3):659, 2011 Chung K, Sammel MD, Coutifaris C, et al: Defining the rise of serum HCG in viable pregnancies achieved through use ofIVF. Hum Reprod 21(3):823, 2006 Clayton HB, Schieve A, Peterson HB, et al: Ectopic pregnancy risk with assisted reproductive technology procedures. Obstet Gynecol 107(3):595, 2006 Cohen A, Almog B, Satel A, et al: Laparoscopy versus laparotomy in the management of ectopic pregnancy with massive hemoperitoneum. Int J Gynaecol Obstet 123(2):139, 2013


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Obstentrics_Williams. Cohen A, Almog B, Satel A, et al: Laparoscopy versus laparotomy in the management of ectopic pregnancy with massive hemoperitoneum. Int J Gynaecol Obstet 123(2):139, 2013 Cohen A, Bibi G, lmog B, et al: Second-dose methotrexate in ectopic pregnancies: the role of beta human chorionic gonadotropin. Fertil Steril 102(6):1646,o2014a Cohen A, Zakar L, Gil Y, et al: Methotrexate success rates in progressing ectopic pregnancies: a reappraisal. m J Obstet GynecoI211(2):128.e1, 2014b Cole T, Corlett RC Jr: Chronic ectopic pregnancy. Obstet Gynecol 59(1):63, Comstock C, Huston K, Lee W: he ultra-sonographic appearance of ovarian ectopic pregnancies. Obstet Gynecol 105:42, 2005 Condous G, Okaro E, Khalid A, et al: he accuracy of transvaginal ultrasonography for the diagnosis of ectopic pregnancy prior to surgery. Hum Reprod 20(5): 1404, 2005


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Obstentrics_Williams. Condous G, Okaro E, Khalid A, et al: he accuracy of transvaginal ultrasonography for the diagnosis of ectopic pregnancy prior to surgery. Hum Reprod 20(5): 1404, 2005 Connolly A, Ryan DH, Stuebe AM, et al: Reevaluation of discriminatory and threshold levels for serum 3-hCG in early pregnancy. Obstet Gynecol 121(1):65,o2013 Cormio G, Ceci 0, Loverro G, et al: Spontaneous left broad ligament pregnancy after ipsilateral salpingo-oophorectomy. J Minim Invasive Gynecol 13(2):84,o2006


Obstentrics_Williams

Obstentrics_Williams. Costa SO, Presley J, Bastert G: Advanced abdominal pregnancy. Obstet Gynecol Surv 46:515, 1991 Creanga A, Syverson C, Seed K et al: Pregnancy-related mortaliry in the United States, 2011-2013. Obstet GynecoIo130(2):366, 2017 Dashefsky SM, Lyons EA, Levi CS, et al: Suspected ectopic pregnancy: endovaginal and transvesical US. Radiology 169: 181, 1988 Elwell E, Sailors JL, Denson PK, et al: Unruptured second-trimester ovarian pregnancy. J Obstet Gynaecol Res 41(9):1483,o2015 Eze IN, Obuna JA, Ejikeme BN: Bilateral tubal ectopic pregnancies: a report of rwo cases. Ann Afr Med 11 (2): 112, 2012 Fernandez H, Capmas P, Lucot JP, et al: Fertiliry after ectopic pregnancy: the DEMETER randomized trial. Hum Reprod 28(5):1247,o2013 Fernandez H, Yves Vincent SCA, Pauthier S, et al: Randomized trial of conservative laparoscopic treatment and methotrexate administration in ectopic pregnancy and subsequent fertiliry. Hum Reprod 13:3239, 1998


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Obstentrics_Williams. Framarino-dei-Malatesta M, Piccioni MG, Derme M, et al: Transabdominal ultrasound-guided injection of methotrexate in the treatment of ectopic interstitial pregnancies. J Clin Ultrasound 42(9):522,o2014 France JT, Jackson P: Maternal plasma and urinary hormone levels during and after a successful abdominal pregnancy. BJOG 87:356, 1980 Fylstra DL: Cervical pregnancy: 13 cases treated with suction curettage and balloon tamponade. m J Obstet GynecoIo210(6):581.e1, 2014 Gala RB: Ectopic pregnancy. In Hofman BL, Schorge JO, Bradshaw KO, et al: Williams Gynecology, 3rd ed. New York, McGraw-Hill Education, 2016 Gao L, Huang Z, Zhang X, et al: Reproductive outcomes following cesarean scar pregnancy-a case series and review of the literature. Eur J Obstet Gynecol Reprod Bioi 200: 1 02, 2016 Ginsburg ES, Frates MC, Rein MS, et al: Early diagnosis and treatment of cervical pregnancy in an in vitro fertilization program. Fertil Steril 61 :966, 1994


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Obstentrics_Williams. Ginsburg ES, Frates MC, Rein MS, et al: Early diagnosis and treatment of cervical pregnancy in an in vitro fertilization program. Fertil Steril 61 :966, 1994 Glezerman M, Press F, Carpman M: Culdocentesis is an obsolete diagnostic tool in suspected ectopic pregnancy. Arch Gynecol Obstet 252:5, 1992 Godin PA, Bassil S, Donnez J: An ectopic pregnancy developing in a previous caesarian section scar. Fertil Sterilo67:398, 1997 Goswami 0, Agrawal N, Arora V: Twin tubal pregnancy: a large unruptured ectopic pregnancy. J Obstet Gynaecol Res 41(1o1):o182,o20o15 Greene ON, Grenache OG, Education Committee of the Academy of Clinical Laboratory Physicians and Scientist: Pathology consultation on human chorionic gonadotropin testing for pregnancy assessment. m J Clin Pathol 144(6):830,o2015 Hajenius PJ, Engelsbel S, Mol BW, et al: Randomized trial of systemic methotrexate versus laparoscopicosalpingostomy in tubal pregnancy. Lancet 350:774,o1997


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Obstentrics_Williams. Hajenius PJ, Engelsbel S, Mol BW, et al: Randomized trial of systemic methotrexate versus laparoscopicosalpingostomy in tubal pregnancy. Lancet 350:774,o1997 Hajenius PJ, Mol BWJ, Ankum WM, et al: Clearance curves of serum human chorionic gonadotropin for the diagnosis of persistent trophoblast. Hum Reprod 10:683, 1995 Hammoud AO, Hammoud I, Bujold E, et al: The role of sonographic endometrial patterns and endometrial thickness in the diferential diagnosis of ectopic pregnancy. m J Obstet GynecoIo192:1o370, 2005 Hassan S, Arora R, Bhatia K: Primary ovarian pregnancy: case report and review of literature. BMJ Case Rep Nov 21, 20o12 Hill LM, Kislak S, Martin JG: Transvaginal sonographic detection of the pseudogestational sac associated with ectopic pregnancy. Obstet Gynecol 75(6):986, 1990


Obstentrics_Williams

Obstentrics_Williams. Hill LM, Kislak S, Martin JG: Transvaginal sonographic detection of the pseudogestational sac associated with ectopic pregnancy. Obstet Gynecol 75(6):986, 1990 Hirakawa M, Tajima T, Yoshimitsu K, et al: Uterine artery embolization along with the administration of methotrexate for cervical ectopic pregnancy: technical and clinical outcomes. AJRAmJ RoentgenoIo192(6):1601, 2009 Hofman BL, Corton MM: Surgeries for benign gynecologic conditions. In Hofman BL, Schorge JO, Bradshaw KD, et al (eds): Williams Gynecology, 3rd ed. New York, McGraw-Hill Education, 20o16 Hoover RN, Hyer M, Pfeifer M, et al: Adverse health outcomes in women exposed in utero to diethylstilbestrol. N Engl J Med 365 (14): 1304, 2011 Huang Q, Zhang M, Zhai RY: he use of contrast-enhanced magnetic resonance imaging to diagnose cesarean scar pregnancies. Int J Gynaecol Obstet 127(2):144,o2014 Hung TH, Jeng CJ, Yang yc, et al: Treatment of cervical pregnancy with methotrexate. Int J Gynaecol Obstet 53:243, 1996


Obstentrics_Williams

Obstentrics_Williams. Hung TH, Jeng CJ, Yang yc, et al: Treatment of cervical pregnancy with methotrexate. Int J Gynaecol Obstet 53:243, 1996 Hyland A, Piazza KM, Hovey KM, et al: Associations of lifetime active and passive smoking with spontaneous abortion, stillbirth and tubal ectopic pregnancy: a cross-sectional analysis of historical data from the Women's Health Initiative. Tob Control 24(4):328, 2015 Jansen RP, Elliott PM: Angular intrauterine pregnancy. Obstet Gynecol 58(2):167,o1981 Jeng ], Ko ML, Shen J: Transvaginal ultrasound-guided treatment of cervical pregnancy. Obstet Gynecol 109: 1 076, 2007 Jermy K, homas J, 000 A, et al: The conservative management of interstitial pregnancy. BJOG 111:1283,o2004 J ung SE, Byun JY, Lee JM, et al: Characteristic MR findings of cervical pregnancy. J Magn Reson Imaging 13(6):918, 2001


Obstentrics_Williams

Obstentrics_Williams. J ung SE, Byun JY, Lee JM, et al: Characteristic MR findings of cervical pregnancy. J Magn Reson Imaging 13(6):918, 2001 Jurkovic 0, Knez J, Appiah A, et al: Surgical treatment of Cesarean scar ectopic pregnancy: eicacy and safery of ultrasound-guided suction curettage. Ultrasound Obstet GynecoIo47(4):51, 2016 Kayatas S, Demirci 0, Kumru P, et al: Predictive factors for failure of salpingostomy in ectopic pregnancy. J Obstet Gynaecol Res 40(2):453, 2014 Kim MJ, Bae JY, Seong WJ, et al: Sonographic diagnosis of a viable abdominal pregnancy with planned delivery after fetal lung maturation. J Clin Ultrasound 41(9):563, 2013 Kirk E, Condous G, Van Calster B, et al: A validation of the most commonly used protocol to predict the success of single-dose methotrexate in the treatment of ectopic pregnancy. Hum Reprod 22(3):858, 2007 Kooi S, Kock HC: A review of the literature on nonsurgical treatment in tubal pregnancy. Obstet Gynecol Surv 47:739, 1992


Obstentrics_Williams

Obstentrics_Williams. Kooi S, Kock HC: A review of the literature on nonsurgical treatment in tubal pregnancy. Obstet Gynecol Surv 47:739, 1992 Krag Moeller LB, Moeller C, homsen SG, et al: Success and spontaneous pregnancy rates following systemic methotrexate versus laparoscopic surgery for tubal pregnancies: a randomized trial. Acta Obstet Gynecol Scand 88(12):1331,o2009 Kung FT, Chang SY, Tsai yc, et al: Subsequent reproduction and obstetric outcome after methotrexate treatment of cevical pregnancy: a review of original literature and international collaborative follow-up. Hum Reprod 12:591, 1997 Lau S, Tulandi T: Conservative medical and surgical management of interstitial ectopic pregnancy. Fertil Steril 72:207, 1999 Li JB, Kong LZ, Fan L, et al: Transvaginal surgical management of cesarean scar pregnancy: analysis of 49 cases from one tertiary care center. Eur J Obstet Gynecol Reprod Bioi 182: 102, 2014a


Obstentrics_Williams

Obstentrics_Williams. Li JB, Kong LZ, Fan L, et al: Transvaginal surgical management of cesarean scar pregnancy: analysis of 49 cases from one tertiary care center. Eur J Obstet Gynecol Reprod Bioi 182: 102, 2014a Li Y, Yang Y, He QZ, et al: Frozen section of uterine curetting in excluding the possibiliry of ectopic pregnancy-a clinicopathologic study of 715 cases. Clin Exp Obstet GynecoIo41(4):419, 2014b Liang C, Li X, Zhao B, et al: Demonstration of the route of embryo migration in retroperitoneal ectopic pregnancy using contrast-enhanced computed tomography. J Obstet Gynaecol Res 40(3):849,o2014 Lipscomb GH, Bran 0, McCord ML, et al: Analysis of three hundred fifteen ectopic pregnancies treated with single-dose methotrexate. Am J Obstet Gynecol 178:o1o354, 1998 Lipscomb GH, Givens VM, Meyer NL, et al: Comparison of multidose and single-dose methotrexate protocols for the treatment of ectopic pregnancy. m J Obstet GynecoIo192:1844, 2005


Obstentrics_Williams

Obstentrics_Williams. Lipscomb GH, Givens VM, Meyer NL, et al: Comparison of multidose and single-dose methotrexate protocols for the treatment of ectopic pregnancy. m J Obstet GynecoIo192:1844, 2005 Lipscomb GH, McCord ML, Stovall TG, et al: Predictors of success of methotrexate treatment in women with tubal ectopic pregnancies. N Engl J Med 341:1974, 1999a Lipscomb GH, Puckett KJ, Bran 0, et al: Management of separation pain after single-dose methotrexate therapy for ectopic pregnancy. Obstet Gynecol 93:590, 1999b Lopez HB, Micheelsen U, Berendtsen H, et al: Ectopic pregnancy and its associated endometrial changes. Gynecol Obstet Invest 38(2):104, 1994 LundorfP, Thorburn J, Hahlin M, et al: Laparoscopic surgery in ectopic pregnancy. A randomized trial versus laparotomy. Acta Obstet Gynecol Scand 70(4-5):343, 1991


Obstentrics_Williams

Obstentrics_Williams. LundorfP, Thorburn J, Hahlin M, et al: Laparoscopic surgery in ectopic pregnancy. A randomized trial versus laparotomy. Acta Obstet Gynecol Scand 70(4-5):343, 1991 Maheux-Lacroix S, Li F, Bujold E, et al: Cesarean scar pregnancies: a systematic review of treatment options. J Minim Invasive Gynecol 24(6):915, 2017 Marcellin L, Menard S, Lamau MC, et al: Conservative management of an advanced abdominal pregnancy at 22 weeks. AJP Rep 4(1):55, 2014 Martin IN Jr, McCaul JF IV: Emergent management of abdominal pregnancy. Clin Obstet Gynecol 33:438, 1990 Martin IN Jr, Sessums JK, Martin RW, et al: Abdominal pregnancy: current concepts of management. Obstet Gynecol 71:549, 1988 Mavrelos 0, Nicks H, Jamil A, et al: Eicacy and safety of a clinical protocol for expectant management of selected women diagnosed with a tubal ectopic pregnancy. Ultrasound Obstet Gynecol 42(1): 1 02, 2013


Obstentrics_Williams

Obstentrics_Williams. Melcer Y, Maymon R, Vaknin Z, et al: Primary ovarian ectopic pregnancy: still a medical challenge. J Reprod Med 61(1-2):58,o2016 Melcer Y, Smorgick N, Vaknin Z, et al: Primary ovarian pregnancy: 43 years experience in a single institute and still a medical challenge. Isr Med Assoc J 17(11):687,2015


Obstentrics_Williams

Obstentrics_Williams. Memtsa M, Jami! A, Sebire N, et al: Rarity revisited: diagnosis and management of intramural ectopic pregnancy. Ultrasound Obstet Gynecol 42(3):359,o2013 Menon S, Colins J, Barnhart KT: Establishing a human chorionic gonadotropin cutof to guide methotrexate treatment of ectopic pregnancy: a systematic review. Ferti! Steri! 87(3):481, 2007 Mittal SK, Singh N, VermaoAK, et al: Fetal MRI in the pre-operative diagnosis and assessment of secondary abdominal pregnancy: a rare sequela of a previous caesarean section. Diagn Interv RadioIo18(5):496, 2012 Moawad NS, Mahajan ST, Moniz MH, et al: Current diagnosis and treatment of interstitial pregnancy. AmJ Obstet GynecoIo202(1):15, 2010 Mol BWJ, Lijmer JG, Ankum WM, et al: he accuracy of single serum progesterone measurement in the diagnosis of ectopic pregnancy: a meta-analysis. Hum Reprod 13:3220, 1998 Mol F, Strandell A, Jurkovic 0, et al: The ESEP study: salpingostomy versus salpingectomy for tubal ectopic pregnancy; the impact on future


Obstentrics_Williams

Obstentrics_Williams. pregnancy: a meta-analysis. Hum Reprod 13:3220, 1998 Mol F, Strandell A, Jurkovic 0, et al: The ESEP study: salpingostomy versus salpingectomy for tubal ectopic pregnancy; the impact on future ferti!ity: a randomized controlled trial. BMC Womens Health 8:11, 2008 Mol F, van Mello NM, Strandell A, et al: Salpingotomy versus salpingectomy in women with tubal pregnancy (ESEP study): an open-label, multicentre, randomized controlled trial. Lancet 383(9927): 1483, 2014 Moschos E, Sreenarasimhaiah S, Twickler OM: First-trimester diagnosis of cesarean scar ectopic pregnancy. J Clin Ultrasound 36(8):504, 2008a Moschos E, Twickler OM: Endometrial thickness predicts intrauterine pregnancy in patients with pregnancy of unknown location. Ultrasound Obstet Gynecol 32(7):929, 2008b Murji A, Garbedian K, Thomas J, et al: Conservative management of cervical ectopic pregnancy. J Obstet Gynaecol Can 37(11):1016, 2015 Murphy A, Nager CW, Wujek JJ, et al: Operative laparoscopy versus laparotomy for the


Obstentrics_Williams

Obstentrics_Williams. K, Thomas J, et al: Conservative management of cervical ectopic pregnancy. J Obstet Gynaecol Can 37(11):1016, 2015 Murphy A, Nager CW, Wujek JJ, et al: Operative laparoscopy versus laparotomy for the management of ectopic pregnancy: a prospective trial. Ferti! Steril 57(6):1180, 1992 Nadim B, Infante F, Lu e, et al: he morphological ultrasound types known as 'blob' and 'bagel' signs should be reclassiied from probable to deinite ectopic pregnancy. Ultrasound Obstet Gynecol February 13, 2017 [Epub ahead of print] Nieuwkerk PT, Hajenius PJ, Ankum WM, et al: Systemic methotrexate therapy versus laparoscopic salpingostomy in patients with tubal pregnancy. Part 1. Impact on patients' health-related quality oflife. Fertil Steril 70:511, 1998


Obstentrics_Williams

Obstentrics_Williams. Nowak-Markwitz E, Michalak M, Olejnik M, et al: Cutof value of human chorionic gonadotropin in relation to the number of methotrexate cycles in the successful treatment of ectopic pregnancy. Fertil Steril 92(4): 1203, 2009 Nurmohamed L, Moretti ME, Schechter T, et al: Outcome following highdose methotrexate in pregnancies misdiagnosed as ectopic. Am J Obstet GynecoI205(6):533.e1,o2011 Nyberg DA, Hughes MP, Mack A, et al: Extrauterine findings of ectopic pregnancy of transvaginal US: importance of echogenic fluid. Radiology 178:823, 1991 Nyberg DA, Mack A, Laing Fe, et al: Distinguishing normal from abnormal gestational sac growth in early pregnancy. J Ultrasound Med 6(1):23, 1987 Osborn DA, Williams TR, Craig BM: Cesarean scar pregnancy: sonographic and magnetic resonance imaging indings, complications, and treatment. J Ultrasound Med 31(9):1449, 2012 Parker A 3rd, Yano M, Tai A W, et al: MR imaging indings of ectopic pregnancy: a pictorial review. Radiographics 32(5):1445,o2012


Obstentrics_Williams

Obstentrics_Williams. Parker A 3rd, Yano M, Tai A W, et al: MR imaging indings of ectopic pregnancy: a pictorial review. Radiographics 32(5):1445,o2012 Perkins M, Boulet SL, Kissin OM, et al: Risk of ectopic pregnancy associated with assisted reproductive technology in the United States, 2001-2011. Obstet Gynecol 125(1):7,o2015 Perkins SL, Al-Ramahi M, Claman P: Comparison of serum progesterone as an indicator of pregnancy nonviability in spontaneously pregnant emergency room and infertility clinic patient populations. Fertil Steri! 73:499, 2000 Pisarska MD, Carson SA, Buster JE: Ectopic pregnancy. Lancet 351: 1115, 1998 Pouly JL, Mahnes H, Mage G, et al: Conservative laparoscopic treatment of 321 ectopic pregnancies. Ferti! Steril 46: 1 093, 1986


Obstentrics_Williams

Obstentrics_Williams. Rabischong B, Larrain 0, Pouly JL, et al: Predicting success of laparoscopic salpingostomy for ectopic pregnancy. Obstet Gynecol 116(3):701,2010 Rahman MS, Al-Suleiman SA, Rahman J, et al: Advanced abdominal preg nancy-observations in 10 cases. Obstet Gynecol 59:366, 1982 Reece A, Petrie RH, Sirmans MF, et al: Combined intrauterine and extra uterine gestations: a review. Am J Obstet Gynecol 146(3):32, 1983 Ries A, Singson P, Bidus M, et al: Use of the endometrial Pipelle in the diagnosis of early abnormal gestations. Fertil Steril 74(3):593, 2000 Roberts RV, Dickinson JE, Leung Y, et al: Advanced abdominal pregnancy: still an occurrence in modern medicine. Aust N Z J Obstet Gynaecol 45(6):518,o2005 Rodgerson JD, Heegaard WG, Plummer 0, et al: Emergency department right upper quadrant ultrasound is associated with a reduced time to diagnosis and treatment of ruptured ectopic pregnancies. Acad Emerg Med 8(4):331, 2001


Obstentrics_Williams

Obstentrics_Williams. Rose JS: Ultrasound in abdominal trauma. Emerg Med Clin North Am 22(3):581,o2004 Roras A, Haberman S, Levgur M: Cesarean scar ectopic pregnancies. Obstet Gynecolo107:1373,o2006 Rudra S, Gupta S, Taneja BK, et al: Full term broad ligament pregnancy through a Cesarean scar. Obstet Gynecol Sci 56(6):404, 2013 Sagiv R, Debby A, Sadan 0, et al: Laparoscopic surgery for extrauterine pregnancy in hemodynamically unstable patients. J Am Assoc Gynecol Laparosc 8(4):529,o2001 Scutiero G, Di Gioia P, Spada A, et al: Primary ovarian pregnancy and its management. JSLS 16(3):492,o2012 Seeber BE, Sammel MD, Guo W, et al: Application of redeined human chorionic gonadotropin curves for the diagnosis of women at risk for ectopic pregnancy. Ferti! Steril 86(2):454, 2006 Seifer DB: Persistent ectopic pregnancy: an argument for heightened vigilance and patient compliance. Ferti! Steril 68 :402, 1997


Obstentrics_Williams

Obstentrics_Williams. Seifer DB: Persistent ectopic pregnancy: an argument for heightened vigilance and patient compliance. Ferti! Steril 68 :402, 1997 Seifer DB, Gutmann IN, Grant WD, et al: Comparison of persistent ectopic pregnancy after laparoscopic salpingostomy versus salpingostomy at laparotomy for ectopic pregnancy. Obstet Gynecol 81 (3):378, 1993 Shaunik A, Kulp J, Appleby DH, et al: Utility of dilation and curettage in the diagnosis of pregnancy of unknown location. Am J Obstet Gynecol 204(2):130.e131,2011 Sherer OM, Gorelick e, Dalloul M, et al: hree-dimensional sonographic indings of a cervical pregnancy. J Ultrasound Med 27(1): 155,o2008 Silva C, Sammel MD, Zhou L, et al: Human chorionic gonadotropin proile for women with ectopic pregnancy. Obstet Gynecol 107:605,o2006 Song MJ, Moon MH, Kim JA, et al: Serial transvaginal sonographic indings of cervical ectopic pregnancy treated with high-dose methotrexate. J Ultrasound Med 28:55, 2009


Obstentrics_Williams

Obstentrics_Williams. Song MJ, Moon MH, Kim JA, et al: Serial transvaginal sonographic indings of cervical ectopic pregnancy treated with high-dose methotrexate. J Ultrasound Med 28:55, 2009 Sowter MC, Farquhar CM, Petrie KJ, et al: A randomized trial comparing single dose systemic methotrexate and laparoscopic surgery for the treatment ofunruptured tubal pregnancy. BJOG 108(2):192,o2001 Spandorfer SO, Sawin SW, Benjamin I, et al: Postoperative day 1 serum human chorionic gonadotropin level as a predictor of persistent ectopic pregnancy after conservative surgical management. Ferti! Steril 68:430, 1997 Spiegelberg 0: Zur Casuistic der Ovarialschwangerschaft. Arch Gynaekol 13:73, 1878 Stevens CA: Malformations and deformations in abdominal pregnancy. Am J MedoGeneto47:1189,o1993 Stika CS: Methotrexate: the pharmacology behind medical treatment for ectopic pregnancy. Clin Obstet Gynecol 55(2):433, 2012


Obstentrics_Williams

Obstentrics_Williams. Stika CS: Methotrexate: the pharmacology behind medical treatment for ectopic pregnancy. Clin Obstet Gynecol 55(2):433, 2012 Stovall TG, Ling FW, Carson SA, et al: Serum progesterone and uterine curettage in diferential diagnosis of ectopic pregnancy. Ferti! Steri!o57:456, 1992 Stovall TG, Ling FW, Cope BJ, et al: Preventing ruptured ectopic pregnancy with a single serum progesterone. Am J Obstet Gynecol 160: 1425, 1989 Stovall TG, Ling FW, Gray A, et al: Methotrexate treatment of unruptured ectopic pregnancy: a report of 100 cases. Obstet Gynecol 77(5):749, 1991 Stulberg DB, Cain LR, Dahlquist I, et al: Ecropic pregnancy rates and racial disparities in the Medicaid population, 2004-2008. Ferti! Steril 102(6):1671, 2014 Svirsky R, Rozovski U, Vaknin Z, et al: The safety of conception occurring shortly after methotrexate treatment of an ectopic pregnancy. Reprod Toxicol 27(1):85, 2009


Obstentrics_Williams

Obstentrics_Williams. Svirsky R, Rozovski U, Vaknin Z, et al: The safety of conception occurring shortly after methotrexate treatment of an ectopic pregnancy. Reprod Toxicol 27(1):85, 2009 Tanaka Y, Mimura K, Kanagawa T, et al: hree-dimensional sonography in the diferential diagnosis of interstitial, angular, and intrauterine pregnancies in a septate uterus. J Ultrasound Med 33(11):2031, 2014 hompson M, Kho K: Minimally invasive surgery. In Hofman BL, Schorge JO, Bradshaw KD, et al (eds): Williams Gynecology, 3rd ed. New York, McGraw-Hill Education, 2016 Timor-Tritsch IE, Cali G, Monteagudo A, et al: Foley balloon catheter to prevent or manage bleeding during treatment for cervical and cesarean scar pregnancy. Ultrasound Obstet Gynecol 46(1): 118, 2015a Timor-Tritsch IE, Khatib N, Monteagudo A, et al: Cesarean scar pregnancies: experience of 60 cases. J Ultrasound Med 34(4):601, 2015b


Obstentrics_Williams

Obstentrics_Williams. Timor-Tritsch IE, Khatib N, Monteagudo A, et al: Cesarean scar pregnancies: experience of 60 cases. J Ultrasound Med 34(4):601, 2015b Timor-Tritsch IE, Monteagudo A, Cali G, et al: Cesarean scar pregnancy and early placenta accreta share common histology. Ultrasound Obstet Gynecol 43(4):383,o2014a Timor-Tritsch IE, Monteagudo A, Cali G, et al: Cesarean scar pregnancy is a precursor of morbidly adherent placenta. Ultrasound Obstet Gynecol 44(3):346,o2014b Timor-Tritsch IE, Monteagudo A, Cali G, et al: Easy sonographic diferential diagnosis between intrauterine pregnancy and cesarean delivery scar pregnancy in the early irst trimester. Am J Obstet GynecoI215(2):225.e1, 2016 Timor-Tritsch IE, Monteagudo A, Matera C, et al: Sonographic evolution of cornual pregnancies treated without surgery. Obstet Gynecol 79(6):1044, 1992


Obstentrics_Williams

Obstentrics_Williams. Timor-Tritsch IE, Monteagudo A, Matera C, et al: Sonographic evolution of cornual pregnancies treated without surgery. Obstet Gynecol 79(6):1044, 1992 Tsakos E, Tsagias N, Dafopoulos K: Suggested method for the management of heterotopic cervical pregnancy leading to term delivery of the intrauterine pregnancy: case report and literature review. J Minim Invasive Gynecol 22(5):896,o2015 Tulandi T, A1-Jaroudi 0: Interstitial pregnancy: results generated from the Society of Reproductive Surgeons. Obstet Gynecol 103:47, 2004 Tulandi T, Guralnick M: Treatment of tubal ectopic pregnancy by salpingotomy with or without tubal suturing and salpingectomy. Ferti! Steri! 55:53, 1991 Ugur M, Turan C, Vicdan K, et al: Chronic ectopic pregnancy: a clinical analysis of 62 cases. Aust N Z J Obstet Gynaecol 36(2): 186, 1996 Ushakov FB, Elchalal U, Aceman PJ, et al: Cervical pregnancy: past and future. Obstet Gynecol Surv 52:45, 1997


Obstentrics_Williams

Obstentrics_Williams. Ushakov FB, Elchalal U, Aceman PJ, et al: Cervical pregnancy: past and future. Obstet Gynecol Surv 52:45, 1997 Uyar I, Yucel OU, Gezer C, et al: Efect of single-dose methotrexate on ovarian reserve in women with ectopic pregnancy. Fertil Sterilo100(5):1310, 2013 Valenzano M, Nicoletti L, Odicino F, et al: Five-year follow-up of placental involution after abdominal pregnancy. J Clin Ultrasound 31 (1):39, 2003 van Mello NM, Mol F, Verhoeve HR, et al: Methotrexate or expectant management in women with an ectopic pregnancy or pregnancy of unknown location and low serum hCG concentrations? A randomized comparison. Hum Reprod 28(1):60,o2013 Verhaegen J, Gallos 10, van Mello NM, et al: Accuracy of single progesterone test to predict early pregnancy outcome in women with pain or bleeding: meta-analysis of cohort studies. B\1] 345:e6077, 2012 Verma U, English 0, Brookfield K: Conservative management of nontubal ectopic pregnancies. Fertil Steril 96(6): 1391,o2011


Obstentrics_Williams

Obstentrics_Williams. Verma U, English 0, Brookfield K: Conservative management of nontubal ectopic pregnancies. Fertil Steril 96(6): 1391,o2011 Verma U, Goharkhay N: Conservative management of cervical ectopic pregnancy. Fertil Steril 91(3):671, 2009 Vermesh M, Graczykowski JW, Sauer MV: Reevaluation of the role of culdocentesis in the management of ectopic pregnancy. Am J Obstet Gynecol 162:41o1, 1990 Vermesh M, Silva PO, Rosen GF, et al: Management of unruptured ectopic gestation by linear salpingostomy: a prospective, randomized clinical trial of laparoscopy versus laparotomy. Obstet Gynecol 73(3 Pt 1):400, 1989 Vermesh M, Silva PO, Sauer MV, et al: Persistent tubal ectopic gestation: patterns of circulating beta-human chorionic gonadotropin and progesterone and management options. Fertil Steri! 50:584, 1988 Wang G, Liu X, Bi F, et al: Evaluation of the eicacy of laparoscopic resection for the management of exogenous cesarean scar pregnancy. Ferri! Steril 101(5):1501,o2014


Obstentrics_Williams

Obstentrics_Williams. Wang G, Liu X, Bi F, et al: Evaluation of the eicacy of laparoscopic resection for the management of exogenous cesarean scar pregnancy. Ferri! Steril 101(5):1501,o2014 Wang Q, Peng HL, He L, et al: Reproductive outcomes after previous cesarean scar pregnancy: Follow up of 189 women. Taiwan J Obstet Gynecol 54(5):551,o2015 Wang Y, Xu B, Dai S, et al: An eicient conservative treatment modality for cervical pregnancy: angiographic uterine artery embolization followed by immediate curettage. Am J Obstet Gynecol 204(1):31.e1, 2011 Watrowski R, Lange A, Mackel J: Primary omental pregnancy with secondary implantation into posterior cul-de-sac: laparoscopic treatment using hemostatic matrix. J Minim Invasive Gynecol 22(3):501, 2015 Westrom L, Joesoef R, Reynolds G, et al: Pelvic inflammatory disease and fertility: a cohort study of 1,844 women with Iaparoscopically veriied disease and 657 control women with normalolaparoscopic results. Sex Transm Dis 19(4):185,o1992


Obstentrics_Williams

Obstentrics_Williams. Worley KC, Hnat MD, Cunningham FG: Advanced extrauterine pregnancy: diagnostic and therapeutic challenges. Am J Obstet Gynecol 198:297e1, 2008 WU PJ, Han CM, Wang C], et al: Early detection and minimally invasive management of intramural pregnancy. J Minim Invasive GynecoI20(1): 123, 2013 Xiaolin Z, Ling L, Chengxin Y, et al: Transcatheter intraarterial methotrexate infusion combined with selective uterine artery embolization as a treatment option for cervical pregnancy. J Vase Interv RadioI21(6):836, 2010 Yang Q, Piao S, Wang G, et al: Hysteroscopic surgery of ectopic pregnancy in the cesarean section scar. J Minim Invasive Gynecol 16(4):432,o2009 Zakaria MA, Abdallah ME, Shavell VI, et al: Conservative management of cervical ectopic pregnancy: utility of uterine artery embolization. Ferti! Steril 95(3):872,o201o1 Zeck W, Kelters I, Winter R, et al: Lessons learned from four advanced abdominal pregnancies at an East African Health Center. J Perin at Med 35(4):278, 2007


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Obstentrics_Williams. Zeck W, Kelters I, Winter R, et al: Lessons learned from four advanced abdominal pregnancies at an East African Health Center. J Perin at Med 35(4):278, 2007 Zee J, Sammel MD, Chung K, et al: Ectopic pregnancy prediction in women with a pregnancy of unknown location: data beyond 48 h are necessary. Hum Reprod 29(3):441, 2014 Zhang B, Jiang ZB, Huang MS, et l: Uterine artery embolization combined with methotrexate in the treatment of cesarean scar pregnancy: results of a case series and review of the literature. J Vase Interv RadioI23(12): 1582,2012 Zhu Q, Li C, Zhao WH, et al: Risk factors and clinical features of ovarian pregnancy: a case-control study. BMJ Open 4(12):e006447, 2014 Zhuang Y, Huang L: Uterine artery embolization compared with methotrexate for the management of pregnancy implanted within a cesarean scar. Am J Obstet GynecoIo201(2):152.e1, 2009


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Obstentrics_Williams. Zhuang Y, Huang L: Uterine artery embolization compared with methotrexate for the management of pregnancy implanted within a cesarean scar. Am J Obstet GynecoIo201(2):152.e1, 2009 Zuo X, Shen A, Chen M: Successful management of unruptured interstitial pregnancy in 17 consecutive cases by using laparoscopic surgery. Aust N Z J Obstet Gynaecol 52(4):387,o2012 HYDATIDIFORM MOLE-MOLAR PREGNANCY . . . 388 PATHOGENESIS ..e....e....e. .. .. ...e...e...e.... 389 DIAGNOSIS......e.... ..e....e....e............ 391 ......e....e...e....e...e.. .. ...e.. 392 GESTATIONAL TROPHOBLASTIC NEOPLASIA ..e... .. 393 DIAGNOSIS, STAGING, AND PROGNOSTIC SCORING ... 393 HISTOLOGICAL CLASSIFICATION ..........e....e...e.394 TREATMENTe. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 395


Obstentrics_Williams

Obstentrics_Williams. DIAGNOSIS, STAGING, AND PROGNOSTIC SCORING ... 393 HISTOLOGICAL CLASSIFICATION ..........e....e...e.394 TREATMENTe. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 395 SUBSEQUENT PREGNANCY ....................... 396 . .. the terminal extremities of the chorionic vili are converted into transparent vesicles with clear, viscid contents. These vay in size from minute bodies a ew milimetres in diameter to cystic structures the size of hazel-nuts, and hang in clusters from the vilous stems, to which they are connected by thin pedicles, giving to the external suace of the chorion a grape-like appearance. -J. Whitridge Williams (1903)


Obstentrics_Williams

Obstentrics_Williams. -J. Whitridge Williams (1903) Gestational trophoblastic disease (GTD) is the term used to encompass a group of tumors typiied by abnormal trophoblast proliferation. Trophoblast produces human chorionic gonadotropin (hCG), thus the measurement of this peptide hormone in serum is essential for GTD diagnosis, management, and surveillance. GTD histologically is divided into hydatidiorm moles, which are characterized by the presence of villi, and into nonmolar trophoblastic malignant neoplasms, which lack villi. Hydatidiform moles are excessively edematous immature placentas (Benirschke, 2012). These include the benign complete hydatidorm mole and partial hydatidiorm mole and the malignant invasive mole. Invasive mole is deemed malignant due to its marked penetration into and destruction of the myometrium and its ability to metastasize.


Obstentrics_Williams

Obstentrics_Williams. Nonmolar trophoblastic neoplasms include choriocarcinoma, placental site trophoblastic tumor, and epithelioid trophoblastic tumor. hese three are diferentiated by the type of trophoblast they contain. The malignant forms of gestational trophoblastic disease are termed gestational trophoblastic neoplasia (GTN). hese include invasive mole, choriocarcinoma, placental site trophoblastic tumor, and epithelioid trophoblastic tumor. Other terms applied to GTN are malignant gestational trophoblastic disease and persistent gestational trophoblastic disease. hese malignancies develop weeks or years following any type of pregnancy, but frequently follow a hydatidiform mole.


Obstentrics_Williams

Obstentrics_Williams. Each of the GTN malignancy types is histologically distinct and varies in its propensity to invade and metastasize. However, histological confirmation is typically not available. Instead, measurement of serum hCG levels combined with clinical indingsrather than a histological specimen-is used to diagnose and treat this malignancy. Accordingly, GTN is often identified and efectively treated as a group. In the past, these metastatic tumors had a prohibitively high mortality rate. However, with chemotherapy, most tumors currently are highly curable. Early-stage GTN is typically cured with single-agent chemotherapy, whereas laterstage disease usually responds to combination chemotherapy (Ngan,i2015). The classic histological findings of molar pregnancy include trophoblast proliferation and villi with stromal edema (Fig. 20-1).


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Obstentrics_Williams. The classic histological findings of molar pregnancy include trophoblast proliferation and villi with stromal edema (Fig. 20-1). FIGURE 20-1 Complete hydatidiform mole. A. Gross specimen with characteristic vesicles of variable size. (Used with permission from Dr. Brian Levenson.) B. Low-magnification photomicrograph shows generalized edema and cistern formation (black asterisks) within avascular villi. Haphazard trophoblastic hyperplasia is marked by a yellow asterisk on the right. (Used with permission from Dr. Erika Fong.) The degree of histological changes, karyotypic diferences, and the absence or presence of embryonic elements are used to clas siy them as either complete orpartial moles. hese two also vary and postevacuation GTN. Of the two, GTN more frequently follows complete hydatidiform mole.


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Obstentrics_Williams. A complete mole has abnormal chorionic villi that grossly appear as a mass of clear vesicles. These vary in size and often hang in clusters from thin pedicles. In contrast, a partial molar pregnancy has focal and less advanced hydatidiform changes and contains some fetal tissue. Both forms of moles usually fill the uterine cavity, but they rarely may be tubal or other forms of ectopic pregnancy (Hassadia, 2012; Sebire, 2005). An ethnic predisposition is seen with hydatidiform mole, which has increased prevalence in Asians, Hispanics, and American Indians (Drake, 2006; Lee, 2011; Smith, 2006). he incidence in the United States and Europe has been relatively constant at 1 to 2 per 1000 deliveries (Eysbollts, 2016; Lee, 2011).


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Obstentrics_Williams. The strongest risk factors are age and a prior hydatidiform mole. Women at both extremes of reproductive age are most vulnerable. Speciically, adolescents and women aged 36 to 40 years have a twofold risk, but those older than 40 have an almost tenfold risk (ltman, 2008; Sebire, 2002a). With a prior complete mole, the risk of another mole is 0.9 percent, and with a previous partial mole, the rate is 0.3 percent. Mter two prior complete moles, approximately 20 percent of women have a third mole (Eagles, 2015). Molar pregnancies typically arise from chromosomally abnormal fertilizations Figure 20-2. Complete moles most often have a diploid chromosomal composition (Table


Obstentrics_Williams

Obstentrics_Williams. Molar pregnancies typically arise from chromosomally abnormal fertilizations Figure 20-2. Complete moles most often have a diploid chromosomal composition (Table These usually are 46,X and result from androgenesis, meaning both sets of chromosomes are paternal in origin. The chromosomes of the ovum are either absent or inactivated. The ovum is fertilized by a haploid sperm, which then duplicates its own chromosomes after meiosis. Less commonly, the chromosomal pattern may be 46,Y or 46,X and due to fertilization by two sperm, that is, dispermic ertilization or dispermy (Lawler, 1991; Lipata, 2010). 23,Y FIGURE 20-2 Typical pathogenesis of complete and partial moles. A. A 46,XX complete mole may be formed if a 23,x-bearing haploid sperm penetrates a 23,X-containing haploid egg whose genes have been "inactivated." Paternal chromosomes then duplicate to create a 46,XX diploid complement solely of paternal origin.


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Obstentrics_Williams. B. A partial mole may be formed if two sperm-either 23,X-or 23,Y-bearing-both fertilize (dispermy) a 23,X-containing haploid egg whose genes have not been inactivated. The resulting fertilized egg is triploid with two chromosome sets being donated by the father. This paternal contribution is termed diandry .. aTypical karyotypes. bThese include anemia, hyperthyroidism, hyperemesis gravidarum, preeclampsia, and infection. GTN = gestational trophoblastic neoplasia; hCG = human chorionic gonadotropin.


Obstentrics_Williams

Obstentrics_Williams. aTypical karyotypes. bThese include anemia, hyperthyroidism, hyperemesis gravidarum, preeclampsia, and infection. GTN = gestational trophoblastic neoplasia; hCG = human chorionic gonadotropin. Partial moles usually have a triploid karyotype-69 ,XX, 69,Y-or much less commonly, 69,YY. These are each composed of two paternal haploid sets of chromosomes contributed by dispermy and one maternal haploid set (see Fig. 20-2B). Less frequently, a similar haploid egg may be fertilized by an unreduced diploid 46,Y sperm. These triploid zygotes result in some embryonic development, however, it ultimately is a lethal fetal condition a oergensen, 2014; Lakovschek, 2011). Fetuses that reach advanced ages have severe growth restriction, multiple congenital anomalies, or both.


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Obstentrics_Williams. Rarely, in some twin pregnancies, one chromosomally normal fetus is paired with a complete diploid molar pregnancy. Importantly, these cases must be distinguished from a single partial molar pregnancy with its associated abnormal fetus. Amniocentesis and fetal karyotyping aid confirmation. Several unique pregnancy problems complicate such twin pregnancies. And, many women may choose to terminate the gestation, if diagnosed early. In those with continuing pregnancy, survival of the normal fetus varies and depends on associated comorbidity from the molar component. The most worrisome are preeclampsia or hemorrhage, which frequently necessitate preterm delivery. Wee and Jauniaux (2005) reviewed outcomes in 174 women, of whom 82 chose termination. Of the remaining 92 pregnancies, 42 percent either miscarried or had a perinatal death; approximately 60 percent delivered preterm; and only 40 percent delivered at term.


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Obstentrics_Williams. Another concern for those continuing their pregnancy is the risk for developing subsequent GTN. However, most data indicate no significant diference between women who continue or terminate their pregnancy (Massardier, 2009; Sebire, 2002b). Postdelivery surveillance is conducted as for any molar pregnancy (p. 393). The presentation of women with a molar pregnancy has changed remarkably over the past several decades because prenatal care is sought much earlier and because sonography is virtually universal. Typically, 1 to 2 months of amenorrhea precede the diagnosis. For example, in 194 women with a complete mole, evacuation was completed at a median gestational age of 9 weeks and at 12 weeks for 172 patients with a partial mole (Sun, 2015b). As a result, most molar pregnancies are detected before complications ensue (Kerkmeijer, 2009; Mangili, 2008).


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Obstentrics_Williams. As gestation advances, symptoms tend to be more pronounced with complete compared with partial moles (Niemann, 2007). Untreated molar pregnancies will almost always cause uterine bleeding that varies from spotting to profuse hemorrhage. Bleeding may presage spontaneous molar abortion, but more often, it follows an intermittent course for weeks to months. In more advanced moles with considerable concealed uterine hemorrhage, moderate iron-deiciency anemia develops. Nausea and vomiting may be signiicant. Of physical findings, many women have uterine growth that is more rapid than expected, and the enlarged uterus is comparatively softer. Fetal heart motion is absent with complete moles. he ovaries can be fuller and cystic from multiple theca-lutein cysts (Fig. 20-3). These are more common with a complete mole and likely result from ovarian overstimulation by excessive hCG levels. Because theca-lutein cysts regress following pregnancy evacuation, expectant management is preferred.


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Obstentrics_Williams. with a complete mole and likely result from ovarian overstimulation by excessive hCG levels. Because theca-lutein cysts regress following pregnancy evacuation, expectant management is preferred. Occasionally a larger cyst may undergo torsion, infarction, and hemorrhage. However,


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Obstentrics_Williams. FIGURE 20-3 Sonographic image of an ovary with theca-lutein cysts in a woman with a hydatidiform mole. oophorectomy is not performed unless extensive infarction persists after untwisting. The thyrotropin-like efects of hCG frequently cause serum free thyroxine (T4) levels to be elevated and thyroid-stimulating hormone (TSH) levels to be decreased. Despite this, clinically apparent thyrotoxicosis is unusual and in our experience can be mimicked by bleeding and sepsis from infected products. Moreover, the serum free T4ilevels rapidly normalize after uterine evacuation. Despite this, cases of presumed "thyroid storm" have been reported (Koinas, 2015).


Obstentrics_Williams

Obstentrics_Williams. Severe preeclampsia and eclampsia are relatively common with advanced molar pregnancies. However, these are seldom seen today because of early diagnosis and evacuation. An exception is the case of a normal fetus coexisting with a complete mole, described earlier. In continuing twin gestations, severe preeclampsia frequently mandates preterm delivery. prompts pregnancy testing and sonography. Some women will present with spontaneous passage of molar tissue.


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Obstentrics_Williams. prompts pregnancy testing and sonography. Some women will present with spontaneous passage of molar tissue. With a complete molar pregnancy, serum �-hCG levels are commonly elevated above those expected for gestational age. With more advanced moles, values in the millions are not unusual. Importantly, these high values can lead to erroneous false-negative urine pregnancy test results. Termed a "hook efect," excessive �-hCG hormone levels oversaturate the assay's targeting antibody and create a falsely low reading (Cormano, 2016). In these cases, serum �-hCG determinations with or without sample dilution will clariy the conundrum. With a partial mole, �-hCG levels may also be significantly elevated, but more commonly concentrations fall into ranges expected for gestational age.


Obstentrics_Williams

Obstentrics_Williams. Although this is the mainstay of trophoblastic disease diagnosis, not all cases are confirmed initially. Sonographically, a com plete mole appears as an echogenic uterine mass with numerous anechoic cystic spaces but without a fetus or amnionic sac. The appearance is often described as a "snowstorm" (Fig. 20-4). A partial mole has features that include a thickened, multicystic placenta along with a fetus or at least fetal tissue. However, in early pregnancy, these sonographic characteristics are seen in fewer than half of hydatidiform moles. In the largest series of more than 1000 patients with molar pregnancy, the reported sensitivity and speciicity of sonography were 44 and 74 percent, respectively (Fowler, 2006). he most common mimics are incomplete or missed abortion. Occasionally, molar pregnancy may be confused for a multifetal pregnancy or a uterine leiomyoma with cystic degeneration.


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Obstentrics_Williams. FIGURE 20-4 Sonograms of hydatidiform moles. A. Sagittal view of a uterus with a complete hydatidiform mole. The characteristic "snowstorm" appearance is due to an echogenic uterine mass, marked by calipers, that has numerous anechoic cystic spaces. Notably, a fetus and amnionic sac are absent. B. In this image of a partial hydatidiform mole, the fetus is seen above a multicystic placenta. (Used with permission from Dr. Elysia Moschos.) Surveillance for subsequent neoplasia following molar pregnancy is crucial. Thus, moles must be distinguished from other types of pregnancy failure that have hydropic placental degeneration, which can mimic molar villous changes. Some distinguishing histological characteristics are shown in Table 20-1.


Obstentrics_Williams

Obstentrics_Williams. In pregnancies before 10 weeks, classic molar changes may not be apparent because villi may not be enlarged and molar stroma may not yet be edematous and avascular. Histopathologic evaluation can be enhanced by immunohistochemical staining for pS7 expression and by molecular genotyping (Banet, 2014). pS7IP2 is a nuclear protein whose gene is paternally imprinted and maternally expressed. his means that the gene product is produced only in tissues containing a maternal allele. Because complete moles contain only paternal genes, the pS7IP2 protein is absent in complete moles, and tissues do not pick up this stain (Merchant, 200S). In contrast, this nuclear protein is strongly expressed in normal placentas, in spontaneous pregnancy losses with hydropic degeneration, and in partial hydatidiform moles (Castrillon, 2001). Accordingly, immunostaining for pS7IP2 is an efective means to isolate complete mole from the diagnostic list. For distinction of a partial mole from a non molar hydropic


Obstentrics_Williams

Obstentrics_Williams. moles (Castrillon, 2001). Accordingly, immunostaining for pS7IP2 is an efective means to isolate complete mole from the diagnostic list. For distinction of a partial mole from a non molar hydropic abortus, both of which express pS7, molecular genotyping can be used. Molecular genotyping determines the parental source of alleles. Thereby, it can distinguish among a diploid diandric genome (complete mole), a triploid diandric-monogynic genome (partial mole), or biparental diploidy (nonmolar abortus).


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Obstentrics_Williams. Maternal deaths from molar pregnancies are rare because of early diagnosis, timely evacuation, and vigilant postevacuation surveillance for GTN. Preoperative evaluation attempts to identiy known potential complications such as preeclampsia, hyperthyroidism, anemia, electrolyte depletions from hyperemesis, and metastatic disease (Table 20-2) (Lurain, 2010). Most recommend chest radiography, whereas computed tomography (CT) and magnetic resonance (MR) imaging are not routinely done unless a chest radiograph shows lung lesions or unless other extrauterine disease is suspected.


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Obstentrics_Williams. Regardless of uterine size, molar evacuation by suction curettage is usually the preferred treatment. Preoperative cervical dilatation with an osmotic dilator is recommended if the cervix is minimally dilated. Intraoperative bleeding can be greater with molar pregnancy than with a comparably sized uterus containing nonmolar products. hus with large moles, adequate anesthesia, suicient intravenous access, and blood-banking support is imperative. he cervix is mechanically dilated to preferably allow insertion of a larger suction curette. Depending on uterine size, a 10-to 14-mm diameter is typical. As evacuation is begun, oxytocin is infused to limit bleeding. Intraoperative sonography is often recommended to help ensure complete uterine cavity emptying. When the myometrium has contracted, a thorough but gentle curettage with a sharp large-loop TABLE 20-2. Some Considerations for Management of Hydatidiform Mole


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Obstentrics_Williams. TABLE 20-2. Some Considerations for Management of Hydatidiform Mole Hemogram; serum 3-hCG, creatinine, electrolyte, and hepatic aminotransferase levels TSH, free T4 levels Oxytocin (Pitocin): 20 units in 1000 mL Ringer lactate for continuous infusion One or more other uterotonic agents may be added as needed: Methylergonovine (Methergine): 0.2 mg = 1 mL = 1 ampule 1M every 2 hr prn Carboprost tromethamine (PGF20) (Hemabate)k 250 .Lg = 1 mL = 1 ampule 1M every 15-90 min prn Misoprostol (PGE1) (Cytotec): 200 mg tablets for rectal administration, 800-1000 mg once Karman cannula-size 10 or 14 mm Consider sonography machine Serum hCG levels: within 48 hours of evacuation, weekly until undetectable, then monthly for 6 months alntrauterine devices are not suitable during surveillance. hCG = human chorionic gonadotropin; 1M = intramuscular; PG = prostaglandin; T4 = thyroxine; TSH = thyroid-stimulating hormone.


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Obstentrics_Williams. hCG = human chorionic gonadotropin; 1M = intramuscular; PG = prostaglandin; T4 = thyroxine; TSH = thyroid-stimulating hormone. Sims curette is performed. If bleeding continues despite uterine evacuation and oxytocin infusion, other uterotonic agents are given (see Table 20-2). In rare cases, pelvic arterial emboliza tion or hysterectomy may be necessary (Tse, 2007). Profuse management are discussed in Chapter 41 (p. 755).


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Obstentrics_Williams. Some volume of trophoblast is deported into the pelvic venous system during molar evacuation (Hankins, 1987). With large moles, the amount of tissue may be suicient to produce clinically apparent respiratory insuiciency, pulmonary edema, or even embolism. In our earlier experiences with substantial moles, these and their chest radiographic manifestations clear rapidly without specific treatment. However, fatalities have been described (Delmis, 2000). Because of deportation, there is concern that trophoblastic tissue will thrive within the lung parenchyma to cause persistent disease or even overt malignancy. Fortunately, no evidence suggests that this is a major problem.


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Obstentrics_Williams. Following curettage, anti-D immunoglobulin (Rhogam) is given to Rh D-negative women because fetal tissues with a partial mole may include red cells with D-antigen (Chap. 15, p. 305). Those with suspected complete mole are similarly treated because a deinitive diagnosis of complete versus partial mole may not be conirmed until histologicl evaluation of the evacuated products. Following evacuation, the long-term prognosis for women with a hydatidiform mole is not improved with prophylactic chemotherapy. Moreover, chemotherapy toxicity-including death-may be significant, and thus it is not recommended routinely (Gueye, 2014; Wang, 2017).


Obstentrics_Williams

Obstentrics_Williams. Methods other than suction curettage can be considered for select cases. Hysterectomy with ovarian preservation may be preferable for women with complete moles who have inished childbearing. Of women aged 40 to 49 years, 30 to 50 percent will subsequently develop GTN, and hysterectomy markedly reduces this likelihood (Bandy, 1984; Elias, 2010, 2012). Theca-lutein cysts seen at the time of hysterectomy do not require removal, and they spontaneously regress following molar termination. Labor induction or hysterotomy is seldom used for molar evacuation in the United States. Both will likely increase blood loss and theoretically may increase the incidence of persistent trophoblastic disease (American College of Obstetricians and Gynecologists, 2016; Tidy, 2000).


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Obstentrics_Williams. Close biochemical surveillance for persistent gestational neoplasia follows each hydatidiform mole evacuation. This monitoring is by serial measurement of serum 3-hCG to detect persistent or renewed trophoblastic proliferation. s a glycoprotein, hCG shows structural heterogeneity and exists in diferent isoforms. Thus for surveillance, an hCG assay that can detect all forms of hCG should be used (Harvey, 2010; Ngan, 2015). hese are different from those used for routine pregnancy testing (de Medeiros, 2009). he initial 3-hCG level is obtained within 48 hours ater evacuation. This serves as the baseline, which is compared with 3-hCG quantiication done thereater every 1 to 2 weeks until levels progressively decline to become undetectable.


Obstentrics_Williams

Obstentrics_Williams. he median time for such resolution is 7 weeks for partial moles and 9 weeks for complete moles. Once 3-hCG is undetectable, this is confirmed with monthly determinations for another 6 months (Lurain, 2010; Sebire, 2007). Concur rently, reliable contraception is imperative to avoid confusion caused by rising 3-hCG levels from a new pregnancy. Most recommend combination hormonal contraception, injectable depot medroxyprogesterone acetate, or progestin implant (Dantas, 2017). he latter two are particularly useful if poor patient compliance is anticipated. Intrauterine devices are not used until 3-hCG levels are undetectable because of the risk of uterine perforation if there is an invasive mole. lthough not recommended, if a woman conceives during surveillance, live birth rates and risk for congenital anomalies appear to mirror the general population (Tuncer, 1999a,b). Mter these 6 months, monitoring is discontinued and pregnancy allowed.


Obstentrics_Williams

Obstentrics_Williams. Importantly, during 3-hCG level surveillance, either increasing or persistently plateaued levels mandate evaluation for trophoblastic neoplasia. If the woman has not become pregnant, then these levels signiY increasing trophoblastic proliferation that is most likely malignant. Several factors predispose a patient to trophoblastic neoplasia following molar evacuation. Most important, complete moles have a 15 to 20 percent incidence of malignant sequelae, compared with 1 to 5 percent following partial moles. Surprisingly, with much earlier recognition and evacuation of molar pregnancies, the risk for neoplasia has not been lowered (Schorge, 2000; Sun, 2015a). Other risk factors are older maternal age, 3-hCG levelsi> 100,000 mIU/mL, uterine size that is large for gestational age, theca-lutein cysts >6 cm, and slow decline in 3-hCG levels (Berkowitz, 2009; Kang, 2012; Wolfberg, 2005).


Obstentrics_Williams

Obstentrics_Williams. This group includes invasive mole, choriocarcinoma, placental site trophoblastic tumor, and epithelioid trophoblastic tumor. These tumors almost always develop with or after some form of recognized pregnancy. Half follow hydatidiform mole, a fourth follow miscarriage or tubal pregnancy, and another fourth develop after a preterm or term pregnancy (Goldstein, 2012). Although these four tumor types are histologically distinct, they are usually diagnosed solely by persistently elevated serum 3-hCG levels because tissue is infrequently available for study. Criteria to diagnose postmolar GTN are shown in Table 20-3.


Obstentrics_Williams

Obstentrics_Williams. hese placental tumors are characterized clinically by their aggressive invasion into the myometrium and propensity to metastasize. he most common inding with GTN is irregular bleeding associated with uterine subinvolution. The bleeding may be continuous or intermittent, with sudden and sometimes massive hemorrhage. Myometrial perforation from trophoblastic growth may cause intraperitoneal hemorrhage. In some women, lower genital tract metastases are evident, whereas in others only distant metastases are found with no trace of uterine tumor. • Diagnosis, Staging, and Prognostic Scoring Consideration for the possibility of GTN is the most important factor in its recognition. Unusually persistent bleeding ater any type of pregnancy should prompt measurement of serum 3-hCG TABLE 20-3. Criteria for Diagnosis of Gestational Trophoblastic Neoplasia 1. Plateau of serum �-hCG level (± 10 percent) for four measurements during a period of 3 weeks or longer-days 1, 7, 14,s21 2.


Obstentrics_Williams

Obstentrics_Williams. Plateau of serum �-hCG level (± 10 percent) for four measurements during a period of 3 weeks or longer-days 1, 7, 14,s21 2. Rise of serum �-hCG levels> 10 percent during three weekly consecutive measurements or longer, during a period of 2 weeks or more-days '1, 7, 14 3. 4. levels and consideration for diagnostic curettage if levels are elevated. Uterine size is assessed along with careful examination for lower genital tract metastases, which usually appear as bluish vascular masses (Cagayan, 2010). Tissue diagnosis is unnecessary, thus biopsy is not required and may cause significant bleeding.


Obstentrics_Williams

Obstentrics_Williams. Once the diagnosis is veriied, in addition to a baseline serum J-hCG level and hemogram, a search for local disease and metastases includes tests of liver and renal function, transvaginal sonography, chest CT scan or radiograph, and brain and abdominopelvic CT scan or MR imaging. Less commonly, positron-emission tomographic (PET) scanning and cerebrospinal luid J-hCG level determination are used to identiy metastases (Lurain, 2011). GTN is staged clinically using the system of the International Federation of Gynecology and Obstetrics (FIGO) (2009). his includes a modiication of the World Health Organization (WHO) (1983) prognostic index score, with which scores of 0 to 4 are given for each of the categories shown in Table 20-4. Women with WHO scores of 0 to 6 are considered to have low-risk disease, whereas those with a score :::7 are considered in the high-risk group.


Obstentrics_Williams

Obstentrics_Williams. Again, it is stressed that the diagnosis of trophoblastic neoplasias is usually made by persistently elevated serum J-hCG levels without conirmation by tissue study. Clinical staging is assigned without regard to histological indings, even if available. Still, there are distinct histological types, described next. These are the most common trophoblastic neoplasms that follow hydatidiform moles, and almost all invasive moles arise from partial or complete moles. Previously known as chorioadenoma destruens, invasive mole is characterized by extensive tissue invasion by trophoblast and whole villi. There is penetration deep into the myometrium, sometimes with involvement of the peritoneum, adjacent parametrium, or vaginal vault. Although locally aggressive, invasive moles are less prone to metastasize. his is the most common type of trophoblastic neoplasm to follow a term pregnancy or a miscarriage, and only a third of


Obstentrics_Williams

Obstentrics_Williams. his is the most common type of trophoblastic neoplasm to follow a term pregnancy or a miscarriage, and only a third of TABLE 20-4. International Federation of Gynecology and Obstetrics (FIGO) Staging and Diagnostic Scoring System for Gestational Trophoblastic Neoplasia Age (years) <40 :::40 Antecedent pregnancy Mole Abortion Term <103 largest tumor size (including uterus) <3 cm 3-4 cm :::5 cm Site of metastases Spleen, kidney GI Liver, brain Number of metastases Previous failed chemotherapy drugs :::2 aAdapted by FIGO. blow risk = WHO score of 0 to 6; high risk = WHO score ofs:::7. J-hCG = beta human chorionic gonadotropin; GI = gastrointestinal; GTN = gestational trophoblastic neoplasia. Adapted with permission from FIGO Committee on Gynecologic Oncology: Current FIGO staging for cancer of the vagina, fallopian tube, ovary, and gestational trophoblastic neoplasia, Int J Gynaecol Obstet 2009 Apr;l 05(1 )j3-4. 4-6 7-12 >12 103 to 104 104 to 105 :::105


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Obstentrics_Williams. FIGURE 20-5 Metastatic choriocarcinoma. A. Chest radiograph demonstrates widespread metastatic lesions. B. Autopsy specimen with multiple hemorrhagic hepatic metastases. (Used with permission from Dr. Michael Conner.) cases follow a molar gestation (Soper, 2006). Choriocarcinoma is composed of cells reminiscent of early cytotrophoblast and syncytiotrophoblast, however, it contains no villi. his rapidly growing tumor invades both myometrium and blood vessels to create hemorrhage and necrosis. Myometrial tumor may spread outward and become visible on the uterine surface as dark, irregular nodules. Metastases often develop early and are generally blood-borne (Fig. 20-5). The most common sites are the lungs and vagina, but tumor may travel to the vulva, kidneys, liver, brain, ovaries, and bowel. Bleeding can complicated these metastases (Fatema, 2016; Wei, 2016; Zhang, 2017). Choriocarcinomas are commonly accompanied by ovarian theca-lutein cysts.


Obstentrics_Williams

Obstentrics_Williams. This rare tumor arises from intermediate trophoblasts at the placental site. hese tumors have associated serum �-hCG levels that may be only modestly elevated. However, they produce variant forms of hCG, and identiication of a high proportion of free �-hCG is considered diagnostic. Treatment of placental site trophoblastic tumor by hysterectomy is preferred because these locally invasive tumors are usually resistant to chemotherapy (Baergen, 2006). For higher-risk stage I and for later stages, adjuvant multidrug chemotherapy is also given (Schmid, 2009). This rare tumor develops from chorionic-type intermediate trophoblast. he uterus is the main site of involvement, and bleeding and low hCG levels are typical findings (Scott, 2012). Primary treatment is hysterectomy because this tumor is relatively resistant to chemotherapy. Metastatic disease is common, and combination chemotherapy is employed (Davis, 2015) .


Obstentrics_Williams

Obstentrics_Williams. Women with GTN are best managed by oncologists, and some (Kohorn, 2014). The prognosis is excellent with rare excep tions, and patients are routinely cured even in the presence of widespread disease. Chemotherapy alone is usually the primary treatment. Although controversial, some also consider a sec ond uterine evacuation to be an adjuvant therapeutic option in some GTN cases to avoid or minimize chemotherapy (Pezeshki, 2004; van Trommel, 2005). In other cases, suction curettage may infrequently be needed to resolve bleeding or remove a sub stantial amount of retained molar tissue. In speciic cases, hys terectomy may be primary or adjuvant treatment (Clark, 2010).


Obstentrics_Williams

Obstentrics_Williams. Single-agent chemotherapy protocols are usually suicient for nonmetastatic or low-risk metastatic neoplasia (Lawrie, 2016). In their review of 108 women with low-risk disease, Abrao and colleagues (2008) reported that monotherapy protocols with either methotrexate or actinomycin D were equally efective compared with a regimen containing both. In general, methotrexate is less toxic than actinomycin D (Chan, 2006; Secki, 2010). Regimens are repeated until serum �-hCG levels are undetectable. Combination chemotherapy is given for high-risk disease, and reported cure rates approximate 90 percent (Lurain, 2010). Several regimens have been used with success. One is EMA-CO, which includes �toposide, methotrexate, gctinomycin D, �yclophosphamide, and


Obstentrics_Williams

Obstentrics_Williams. Oncovin (vincristine). In selected cases, adjuvant surgical and radiotherapy may also be employed (Hanna, 2010). Frequent causes of death include hemorrhage from metastatic sites, respiratory failure, sepsis, and multiorgan failure due to widespread chemoresistant disease (Lybol, 2012; Neubauer, 2015). With either low-or high-risk disease, once serum �-hCG levels are undetectable, serosurveillance is continued for 1 year. During this time, efective contraception is crucial to avoid any teratogenic efects of chemotherapy to the fetus and to mitigate conusion from rising �-hCG levels caused by superimposed pregnany (Secki, 2010; Williams, 2014). For those who conceive despite this within the surveillance year following treatment, pregnancy may continue since most will have a favorable outcome (Tse, 2012; Woolas, 1998). Importantly, this group is advised of the low but important risk of delayed diagnosis if tumor recurs during the pregnancy (Blagden, 2002; Tuncer, 1999b).


Obstentrics_Williams

Obstentrics_Williams. A small number of women during surveillance, despite no evidence of metastases, will be found to have very low �-hCG levels that plateau. This phenomenon is called quiescent hCG and presumably is caused by dormant trophoblast. Close observation without therapy is recommended, but 20 percent will eventually have recurrent active and progressive trophoblastic neoplasia (Ngu, 2014). Women with prior hydatidiform mole generally do not have impaired fertility, and their pregnancy outcomes are usually normal Qoneborg, 2014; Matsui, 2011; Sebire, 2003). One concern is the 2-percent risk for developing trophoblastic disease in a subsequent pregnancy, which was described earlier. Sonographic evaluation is recommended in early pregnancy, and subsequently if indicated.


Obstentrics_Williams

Obstentrics_Williams. Women who have successfully completed GTN chemotherapy are advised to delay pregnancy for 12 months. Fertility and pregnancy outcomes are typically normal, and congenital anomaly rates are not increased (Berkowitz, 2000; Tse, 2012). One exception is an unexplained higher stillbirth rate of 1.5 percent compared with a background rate of 0.8 percent (Vargas, 2014). After hydatidiform mole or GTN treatment, in subsequent pregnancy, the placenta or products of conception are sent for pathological evaluation at delivery. A serum 3-hCG level is measured 6 weeks postpartum (Lurain, 2010). Abrao A, de Andrade ]M, Tiezzi DG, et al: Treatment for low-risk gestational trophoblastic disease: comparison of single-agent methotrexate, dactinomycin and combination regimens. Gynecol Oncol 108:149,o2008 Altman AD, Bently B, Murray S, et al: Maternal age-related rate of gestational trophoblastic disease. Obstet Gynecol 11o2:244, 2008


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Obstentrics_Williams. Altman AD, Bently B, Murray S, et al: Maternal age-related rate of gestational trophoblastic disease. Obstet Gynecol 11o2:244, 2008 American College of Obstetricians and Gynecologists: Diagnosis and treatment of gestational trophoblastic disease. Practice Bulletin No. 53, June 2004, Reairmed 2016 Baergen N, Rutgers ]L, Young RH, et al: Placental site trophoblastic tumor: a study of 55 cases and review of the literature emphasizing factors of prognostic significance. Gynecol Oncol 100:511, 2006 Bandy LC, Clarke-Pearson DL, Hammond CB: Malignant potential of gestational trophoblastic disease at the extreme ages of reproductive life. Obstet Gynecol 64(3):395, 1984 Banet N, DeScipio C, Murphy M, et al: Characteristics of hydatidiform moles: analysis of a prospective series with p57 immunohistochemistry and molecular genotyping. Mod PathoIo27(2):238, 2014


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Obstentrics_Williams. Banet N, DeScipio C, Murphy M, et al: Characteristics of hydatidiform moles: analysis of a prospective series with p57 immunohistochemistry and molecular genotyping. Mod PathoIo27(2):238, 2014 Benirschke K, Burton G], Baergen N (eds): Molar pregnancies. In Pathology of the Human Placenta, 6th ed. New York, Springer, 2012, p 687 Berkowitz RS, Goldstein DP: Current management of gestational trophoblastic diseases. Gynecol Oncol 112(3):654, 2009 Berkowitz RS, Tuncer ZS, Bernstein MR: Management of gestational trophoblastic diseases: subsequent pregnancy experience. Semin Oncol 27(6):678, 2000 Blagden SP, Foskett A, Fisher A, et al: he efect of early pregnancy following chemotherapy on disease relapse and foetal outcome in women treated for gestational trophoblastic tumours. Bro] Cancer 86(1):26,o2002 Cagayan MS: Vaginal metastases complicating gestational trophoblastic neoplasia.o] Reprod Med 55(5-6):229, 2010


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Obstentrics_Williams. Cagayan MS: Vaginal metastases complicating gestational trophoblastic neoplasia.o] Reprod Med 55(5-6):229, 2010 Castrillon DH, Sun 0, Weremowicz S, et al: Discrimination of complete hydatidiform mole from its mimics by immunohistochemistry of the paternally imprinted gene product p57KIP2. Am] Surg PathoI25(10):1225, 2001 Chan KK, Huang Y, Tam F, et al: Single-dose methotrexate regimen in the treatment of low-risk gestational trophoblastic neoplasia. Am ] Obstet GynecoIo195:1282,o2006 Clark RM, Nevadunsky NS, Ghosh S, et al: The evolving role of hysterectomy in gestational trophoblastic neoplasia at the New England Trophoblastic Disease Center.o] Reprod Med 55(5-6):194, 2010 Cormano ], Mackay G, Holschneider C: Gestational trophoblastic disease diagnosis delayed by the hook efect. Obstet GynecoIo126(4):811, 2015


Obstentrics_Williams

Obstentrics_Williams. Cormano ], Mackay G, Holschneider C: Gestational trophoblastic disease diagnosis delayed by the hook efect. Obstet GynecoIo126(4):811, 2015 Dantas PRS, Maesd. I, Filho ]R, et al: Does hormonal contraception during molar pregnancy follow-up influence the risk and clinical aggressiveness of gestational trophoblastic neoplasia after controlling for risk factors? Gynecol Oncol September 16, 2017 [Epub ahead of print] Davis MR, Howitt BE, Quade B], et al: Epithelioid trophoblastic tumor: a single institution case series at the New England Trophoblastic Disease Center. Gynecol Oncol 137(3):456,o20o15 Delmis ], Pfeifer 0, Ivanisecvic M, et al: Sudden death from trophoblastic embolism in pregnancy. Euro] Obstet Gynecol Reprod Bioi 92:225, 2000 de Medeiros SF, Norman RJ: Human chorionic gonadotrophin protein core and sugar branches heterogeneity: basic and clinical insights. Hum Reprod Update 15(1):69,o2009


Obstentrics_Williams

Obstentrics_Williams. Drake D, Rao GG, McIntire DO, et al: Gestational trophoblastic disease among Hispanic women: a 21-year hospital-based study. Gynecol Oncol 103:81,o2006 Eagles N, Sebire N], Short 0, et al: Risk of recurrent molar pregnancies following complete and partial hydatidiform moles. Hum Reprod 30(9):2055, 20o15 Elias M, Goldstein DP, Berkowitz RS: Complete hydatidiform mole in women older than age 50.] Reprod Med 55(5-6):208, 2010 Elias KM, Shoni M, Bernstein M, et al: Complete hydatidiform mole in women aged 40 to 49 years.o] Reprod Med 57(5-6):254, 2012 Eysbouts K, Bulten ], Ottevanger PB, et al: Trends in incidence for gestational trophoblastic disease over the last 20 years in a population-based study. Gynecol Oncol 140(1):70,o2016 Fatema N, Arora NV, l Abri FM, et al: Pancreatic and hepatic metastasis of an undiagnosed choriocarcinoma: an exceptional cause ofhaemoperitoneum in young women-report of a rare case. Case Rep Oncol 9(3):633,o2016


Obstentrics_Williams

Obstentrics_Williams. FIGO Committee on Gynecologic Oncology: Current FIGO staging for cancer of the vagina, fallopian tube, ovary, and gestational trophoblastic neoplasia. Int] Gynaecol Obstet 105:3,2009 Fowler 0], Lindsay I, Seck! M], et al: Routine pre-evacuation ultrasound diagnosis of hydatidiform mole: experience of more than 1000 cases from a regional referral center. Ultrasound Obstet Gynecol 27(1):56, 2006 Goldstein DP, Berkowitz RS: Current management of gestational trophoblastic neoplasia. Hematol Oncol Clin North Am 26(1):111,o2012 Gueye M, Kane-Gueye SM, Ndiaye-Gueye MD, et al: Gestational trophoblastic neoplasia after achieving a nondetectable serum human chorionic gonadotrophin level. B]OG 121(11):1415,o2014 Hankins GO, Wendel GO, Snyder R, et al: Trophoblastic embolization during molar evacuation: central hemodynamic observations. Obstet Gynecol 63:368, 1987


Obstentrics_Williams

Obstentrics_Williams. Hankins GO, Wendel GO, Snyder R, et al: Trophoblastic embolization during molar evacuation: central hemodynamic observations. Obstet Gynecol 63:368, 1987 Hanna RK, Soper ]T: The role of surgery and radiation therapy in the management of gestational trophoblastic disease. Oncologist 15(6):593,o2010 Harvey A, Mitchell HD, Stenman UH, et al: Diferences in total human chorionic gonadotropin immunoassay analytical specificiry and ability to measure human chorionic gonadotropin in gestational trophoblastic disease and germ cell tumors.o] Reprod Med 55(7-8):28, 2010