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Case Report Management of Bilateral Ectopic Pregnancies after Ovulation Induction Using Unilateral Salpingectomy and Methotrexate for the Remaining Ectopic with Subsequent Intrauterine Pregnancy Quinton Katler , Lindsey Pflugner, and Anjali Martinez Department of Obstetrics and Gynecology, e George Washington University Hospital, Washington, DC, USA Correspondence should be addressed to Quinton Katler; [email protected] Received 25 March 2018; Accepted 12 June 2018; Published 5 July 2018 Academic Editor: Akihisa Fujimoto Copyright © 2018 Quinton Katler et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Bilateral ectopic pregnancy is a rare phenomenon which is found with increased frequency when using assisted reproductive technology (ART). is diagnosis is most oſten made incidentally and intraoperatively, as ultrasound and serial -hCG trends have shown poor efficacy for accurate diagnosis. Management of bilateral ectopic pregnancies is most commonly reported using bilateral surgical removal of the ectopic pregnancy (salpingostomy and/or salpingectomy). We present a case of an ART patient with incidentally found bilateral tubal ectopic pregnancies, where multiple management strategies including medical and surgical techniques were used concurrently which resulted in a subsequent spontaneous intrauterine pregnancy. While the standard of care is difficult to establish, we recommend individualizing management decisions based on the patient’s reproductive goals and overall risk profile. 1. Introduction Unilateral ectopic pregnancy is a well-known and common diagnosis in the general population [1]. Conversely, bilateral ectopic pregnancy is a much rarer phenomenon, occurring in approximately 1 per 200,000 live births [2]. While bilateral ectopic pregnancies have been documented in the literature since the 1900s, the invention of assisted reproductive tech- nologies (ART) has led to an increase in reported cases of bi- lateral ectopic pregnancies [3, 4]. Given the relative frequency of bilateral ectopic preg- nancies in the ART population, the importance of choosing an appropriate management strategy is further underscored given the known morbidity and potential mortality of rup- tured ectopics within the context of the patient’s reproductive goals. ere are established criteria for management of unilateral ectopic pregnancies, which include pharmacologic, surgical, and expectant management under specific circum- stances. However, there are no well-defined studies or data to suggest standard of care in the case of bilateral tubal ectopic pregnancies, particularly in the setting of one ruptured and one nonruptured ectopic pregnancy. Upon review of the existing literature, there are no reports of medical and surgical management being used simultaneously for the management of bilateral ectopic pregnancies, nor are there reports of a subsequent spontaneous intrauterine pregnancy following this treatment approach. Here we present a case of an ART patient with incidentally found bilateral tubal ectopic pregnancies, where two different management strategies were used concurrently with a successful outcome. 2. Case Report A 32-year-old G2P0020 healthy Caucasian female initially presented to our institution for outpatient evaluation and management of secondary infertility. Her obstetric history was notable for two first-trimester miscarriages that were both managed expectantly. e couple’s infertility evalua- tion revealed normal ovarian reserve testing and semen- analysis parameters with an unremarkable hysterosalpin- gogram (HSG) study, and they were diagnosed with unex- plained infertility. e patient underwent ovulation induc- tion with clomiphene citrate and HCG trigger with timed intrauterine insemination (IUI) using her partner’s sperm. In Hindawi Case Reports in Obstetrics and Gynecology Volume 2018, Article ID 7539713, 4 pages https://doi.org/10.1155/2018/7539713

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  • Case ReportManagement of Bilateral Ectopic Pregnancies after OvulationInduction Using Unilateral Salpingectomy and Methotrexate forthe Remaining Ectopic with Subsequent Intrauterine Pregnancy

    Quinton Katler , Lindsey Pflugner, and Anjali Martinez

    Department of Obstetrics and Gynecology, The George Washington University Hospital, Washington, DC, USA

    Correspondence should be addressed to Quinton Katler; [email protected]

    Received 25 March 2018; Accepted 12 June 2018; Published 5 July 2018

    Academic Editor: Akihisa Fujimoto

    Copyright © 2018 QuintonKatler et al.This is an open access article distributed under the Creative Commons Attribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

    Bilateral ectopic pregnancy is a rare phenomenon which is found with increased frequency when using assisted reproductivetechnology (ART). This diagnosis is most often made incidentally and intraoperatively, as ultrasound and serial 𝛽-hCG trendshave shown poor efficacy for accurate diagnosis. Management of bilateral ectopic pregnancies is most commonly reported usingbilateral surgical removal of the ectopic pregnancy (salpingostomy and/or salpingectomy). We present a case of an ART patientwith incidentally found bilateral tubal ectopic pregnancies, where multiple management strategies including medical and surgicaltechniques were used concurrently which resulted in a subsequent spontaneous intrauterine pregnancy.While the standard of careis difficult to establish, we recommend individualizing management decisions based on the patient’s reproductive goals and overallrisk profile.

    1. Introduction

    Unilateral ectopic pregnancy is a well-known and commondiagnosis in the general population [1]. Conversely, bilateralectopic pregnancy is a much rarer phenomenon, occurringin approximately 1 per 200,000 live births [2]. While bilateralectopic pregnancies have been documented in the literaturesince the 1900s, the invention of assisted reproductive tech-nologies (ART) has led to an increase in reported cases of bi-lateral ectopic pregnancies [3, 4].

    Given the relative frequency of bilateral ectopic preg-nancies in the ART population, the importance of choosingan appropriate management strategy is further underscoredgiven the known morbidity and potential mortality of rup-tured ectopics within the context of the patient’s reproductivegoals. There are established criteria for management ofunilateral ectopic pregnancies, which include pharmacologic,surgical, and expectant management under specific circum-stances. However, there are no well-defined studies or data tosuggest standard of care in the case of bilateral tubal ectopicpregnancies, particularly in the setting of one ruptured andone nonruptured ectopic pregnancy. Upon review of the

    existing literature, there are no reports ofmedical and surgicalmanagement being used simultaneously for the managementof bilateral ectopic pregnancies, nor are there reports of asubsequent spontaneous intrauterine pregnancy followingthis treatment approach. Here we present a case of anART patient with incidentally found bilateral tubal ectopicpregnancies, where two differentmanagement strategies wereused concurrently with a successful outcome.

    2. Case Report

    A 32-year-old G2P0020 healthy Caucasian female initiallypresented to our institution for outpatient evaluation andmanagement of secondary infertility. Her obstetric historywas notable for two first-trimester miscarriages that wereboth managed expectantly. The couple’s infertility evalua-tion revealed normal ovarian reserve testing and semen-analysis parameters with an unremarkable hysterosalpin-gogram (HSG) study, and they were diagnosed with unex-plained infertility. The patient underwent ovulation induc-tion with clomiphene citrate and HCG trigger with timedintrauterine insemination (IUI) using her partner’s sperm. In

    HindawiCase Reports in Obstetrics and GynecologyVolume 2018, Article ID 7539713, 4 pageshttps://doi.org/10.1155/2018/7539713

    http://orcid.org/0000-0002-2389-9181https://doi.org/10.1155/2018/7539713

  • 2 Case Reports in Obstetrics and Gynecology

    Figure 1: TVUS image of right adnexa with corpus luteal cyst versusectopic gestation.

    Figure 2: TVUS image of left adnexa with embryonic structuresconsistent with an ectopic pregnancy.

    the weeks following IUI, the 𝛽-hCG level rose appropriatelyfrom 641 to 971 in 48 hours. One week later, the 𝛽-hCGlevel rose to 3,448 and TVUS revealed a small, irregularlyshaped gestational sac in the uterus without a clear yolk sacor evidence of a fetal pole.The right adnexa appeared to havetwo corpus luteal cysts. Of note, no free fluid was identified inthe cul-de-sac and the patient was asymptomatic at that clinicvisit. The plan was for a repeat 𝛽-hCG level and TVUS in 48hours.

    The patient subsequently presented to the emergencyroom the following morning with diffuse lower abdominalpain and vaginal bleeding. TVUS identified what appearedto be a corpus luteal cyst in the right ovary (Figure 1) and alikely ectopic pregnancy in the left adnexa (Figure 2) with asmall amount of complex free fluid within the cul-de-sac. Herabdominal exam was significant for involuntary guarding ofthe lower quadrants bilaterally with diffuse tenderness. Afterdiscussion with the patient regarding our concern for rup-tured ectopic pregnancy, the patient was amenable with theplan of proceeding with a laparoscopic unilateral salpingec-tomy.

    Figure 3: Left tubal ectopic pregnancy (active bleeding, treatedwithsalpingectomy).

    Figure 4: Right tubal ectopic pregnancy (treated with MTX).

    A diagnostic laparoscopy was performed which revealedmoderate hemoperitoneumupon abdominal entry. On pelvicsurvey, the left fallopian tubewas noted to have a dilated distalportion, approximately 2cm in diameter with active bleeding,consistent with a ruptured left ectopic versus tubal abortion(Figure 3). Notably, the mid-portion of the right fallopiantube appeared dilated at the junction between the isthmusand the ampulla, about 3cm in diameter, without evidenceof rupture or bleeding, which was concerning a concurrentsecond ectopic pregnancy (Figure 4).

    The surgeons were then faced with a difficult decisionregarding management of the unruptured contralateral tube.The patient’s husband (and power of attorney) subsequentlybecame involved with all decisions regarding the patient’splan of care. A left salpingectomy was essential given theabnormal left fallopian tube with active bleeding. Optionsfor management of the contralateral tube were presented:right salpingectomy, right salpingostomy with Methotrexate(MTX) administration, or MTX administration alone with-out surgical intervention on the right fallopian tube. Afterthorough risk-benefit consideration, as well as intraoperativeconsultationwith the patient’s Reproductive Endocrinologist,the decision was made to retain the right fallopian tube and

  • Case Reports in Obstetrics and Gynecology 3

    proceed conservatively with MTX administration (single-dose regimen of 50mg/m2) due to the patient’s likely desireto preserve her fallopian tube.

    The patient had an uneventful recovery and her day 4and day 7 𝛽-hCG values confirmed an appropriate declinein 𝛽-hCG levels after MTX injection. The 𝛽-hCG levelhad dropped to a nonpregnant level by approximately threeweeks following MTX administration. Histology of the leftfallopian tube included the presence of chorionic villi, whichconfirmed the diagnosis of a left ectopic pregnancy. RepeatTVUS one-month following the surgery was normal withoutevidence of right tubal dilatation. Approximately 14 weeksafter surgery, the patient had a repeat TVUS which revealeda single viable intrauterine pregnancy, which was conceivedspontaneously.

    3. Discussion

    The general incidence of single ectopic pregnancies variesby study but according to the Center for Disease Controland Prevention accounts for about 2% of pregnancies [5].Despite improvements in early detection and managementmodalities, ruptured ectopic pregnancies still account for asignificant percentage of pregnancy-related mortality. Evolv-ing data suggests that conception from ART is an indepen-dent risk factor for the development of an ectopic gestation.In literature review, studies describe a higher incidence ofectopic pregnancies after various methods of ART, ranginganywhere from 2.2 to 4.5% of ART cycles compared to spon-taneous conception [6, 7]. In selected groups of patients withtubal infertility, the incidence of ectopic pregnancies afterIVF may be as high as 11% [8]. A recent retrospective cohortstudy published by the Zhengzhou Reproductive MedicalCenter analyzed the incidence of ectopic pregnancies intheir IVF and IUI cycles over the preceding six years [9].The overall ectopic rate was 3% in both subgroups, suggestingan increased ectopic risk when comparing ART with sponta-neous conception. Bilateral, or heterochronic, ectopics are therarest form of ectopic pregnancy. We have witnessed a 3-foldincrease in diagnosed bilateral ectopic pregnancies over thepast several decades, in part due to the increasing use of ARTtechnology [10].

    Whenmanaging bilateral ectopic pregnancies, importantissues arise with regard to detection and treatment. Primarily,trending the 𝛽-hCG values in bilateral ectopic pregnancieshas not been shown to be an effective diagnostic practice [11].Additionally, in most published case reports on this topic,early ultrasound use typically fails to make a diagnosis ofbilateral tubal involvement. In a review of 16 case reports onbilateral ectopic pregnancies after ovulation induction, bothectopic pregnancies were identified by ultrasound imagingin only 6 of the cases prior to surgical intervention [12].Accordingly, in a review by de los Rios et al. only 2 of 42bilateral ectopic pregnancies were accurately diagnosed byultrasound [13]. Commonly, ultrasound imaging identifiesone ectopic pregnancy, which precipitates further investiga-tion and subsequent management. Our case highlights thisdiscrepancy between ultrasound results and intraoperativefindings. Ultrasound may not be necessary to make the

    diagnosis, and patients with significant risk factors should becounseled on the possibility of bilateral ectopic pregnancies,and decisions regarding the management algorithm shouldideally be decided before surgery ensues. As a majority ofbilateral ectopic pregnancies are diagnosed intraoperatively,inspection of both fallopian tubes should be standard of carein any ectopic casewhere the patient has risk factors formulti-ple gestations.

    Previous studies have suggested that the same options forunilateral ectopic pregnancies be applied for bilateral ectopicpregnancies, including MTX administration or laparoscopy(with either salpingostomy or salpingectomy). However, dueto the rare nature of bilateral ectopic pregnancies, there are nopublished guidelines to help advise management decisions.Also, data is sparse with regard to fertility outcomes andrecurrent ectopic pregnancy rate after management of theconcurrent ectopic pregnancy.With regard toMTX adminis-tration for bilateral ectopic pregnancies, a previously publish-ed report described treatment failure using single-dose MTXtherapy, as the patient subsequently required surgery [14]. Todate, there are no published reports that describe effectiveMTX dosage or regimen for bilateral ectopic pregnancies.

    Bilateral ectopic pregnancies pose a unique dilemma inthat both tubes are likely damaged, increasing the risk offuture ectopic recurrence. As such, most cases of bilateralectopic pregnancies are treated with bilateral salpingectomy.For instance, 12 of the 16 cases described byZhu et al. involvedbilateral salpingectomy [12]. In our case, the power of attor-ney was counseled about potential reproductive options. Itwas discussed that both fallopian tubes would likely haveunderlying damage regardless of the chosen treatment op-tion. Discussion continued where bilateral salpingectomieswould guarantee the need for IVF while a retained damagedtube would increase the rate of recurrent ectopic pregnancy.The only option that would maintain the possibility of spon-taneous intrauterine pregnancy would be to retain the non-ruptured tube and to treat medically or with salpingostomy.However, with this approach, if ART was used the Reproduc-tive Endocrinologist would likely recommend IVF in order todecrease the risk of a repeat ectopic pregnancy. This complexand rare situation emphasizes the importance of thoroughevaluation of treatment options while utilizing a patient-centric approach.

    When deciding between salpingostomy and salpingec-tomy, it is important to consider the potential impact onfuture fertility and subsequent ectopic pregnancy risk. RCTscomparing the two techniques in unilateral ectopics have notfound significantly different rates for subsequent intrauterinepregnancies or repeat ectopic pregnancies. However, cohortstudies have shown higher pregnancy rates for salpingos-tomy, including both intrauterine and ectopic rates [15].Surgical management by bilateral salpingectomy should berecommended for usual indication: the patient is exhibitinghemodynamic instability or tubal bleeding. Salpingostomy orMTX administration may be considered for the remainingtube if IVF is not an option; however the patient should becounseled on the recurrence risk and the possible need forfuture surgery.

    In the absence of established guidelines for the manage-ment of bilateral ectopic pregnancies, successful outcomes

  • 4 Case Reports in Obstetrics and Gynecology

    are required in order to help establish protocols for clinicalcare.Our case presents a unique approach to themanagementof the contralateral ectopic using medical therapy alonewithout salpingostomy while already undergoing a surgicalprocedure, which helped to preserve the remaining tube andallow for spontaneous pregnancy. Complete treatment wasconfirmed by a downtrend in the patient’s 𝛽-hCG level to anonpregnant level. Additionally, patients having a unilateralsalpingectomy with Methotrexate for the remaining ectopicmay consider performing a HSG remote from surgery inorder to determine residual tubal patency. One limitation ofour study is that tissue was not extracted from the secondfallopian tube; thus histologic confirmation of the secondectopic pregnancy is not available.

    In conclusion, we present a case of bilateral ectopic preg-nancy which was successfully managed with unilateral salp-ingectomy and medical management with Methotrexate forthe contralateral ectopic. As the use of ART technique maybecome increasingly more common, wemay continue to wit-ness a rising incidence of bilateral ectopic pregnancies. Asscarce data is published on this topic, it is essential to investi-gate innovative diagnostic and treatment modalities in orderto promote improved clinical care within this context.

    Ethical Approval

    According to guidelines set forth byThe George WashingtonUniversity Office of Human Research, IRB approval was notrequired for this study.

    Conflicts of Interest

    Theauthors have no potential conflicts of interest to disclose.

    References

    [1] F. Cunningham, K. Leveno, S. Bloom et al., Ectopic Pregnancy.Williams Obstetrics, McGraw-Hill, New York, NY, USA, 24thedition, 2013.

    [2] S. Hoffmann, H. Abele, and C. Bachmann, “Spontaneous Bi-lateral Tubal Ectopic Pregnancy: Incidental Finding duringLaparoscopy - Brief Report and Review of Literature,” Geburt-shilfe und Frauenheilkunde, vol. 76, no. 4, pp. 413–416, 2016.

    [3] M. C. Edelstein andM. A.Morgan, “Bilateral simultaneous tub-al pregnancy,”Obstetrical & Gynecological Survey, vol. 44, no. 4,pp. 250–252, 1989.

    [4] N. Sugawara, R. Sato,M. Kato et al., “Bilateral tubal pregnanciesafter a single-embryo transfer,” Reproductive Medicine and Bio-logy, vol. 16, no. 4, pp. 396–400, 2017.

    [5] Centers for Disease Control and Prevention (CDC), “CurrentTrends in Ectopic pregnancy—United States, 1990-1992,” Mor-bidity and Mortality Weekly Report, vol. 44, pp. 46–48, 1995.

    [6] S. F. Marcus and P. R. Brinsden, “Analysis of the incidence andrisk factors associatedwith ectopic pregnancy following in-vitrofertilization and embryo transfer,”Human Reproduction, vol. 10,no. 1, pp. 199–203, 1995.

    [7] A. Strandell, J. Thorburn, and L. Hamberger, “Risk factors forectopic pregnancy in assisted reproduction,” Fertility and Steril-ity, vol. 71, no. 2, pp. 282–286, 1999.

    [8] J. B.Dubuisson, F. X. Aubriot, L.Mathieu,H. Foulot, L.Mandel-brot, and J. B. De Joliniere, “Risk factors for ectopic pregnancyin 556 pregnancies after in vitro fertilization: Implications forpreventive management,” Fertility and Sterility, vol. 56, no. 4,pp. 686–690, 1991.

    [9] Z. Bu, Y. Xiong, K. Wang, and Y. Sun, “Risk factors for ectopicpregnancy in assisted reproductive technology: a 6-year, single-center study,” Fertility and Sterility, vol. 106, no. 1, pp. 90–94,2016.

    [10] I. Stabile and J. G.Grudzinskas, “Ectopic Pregnancy,”Obstetrical& Gynecological Survey, vol. 45, no. 6, pp. 335–347, 1990.

    [11] S. K. Jena, S. Singh,M. Nayak, L. Das, and S. Senapati, “Bilateralsimultaneous tubal ectopic pregnancy: a case report, review ofliterature and a proposed management algorithm,” Journal ofClinical andDiagnostic Research, vol. 10, no. 3, pp. QD01–QD03,2016.

    [12] B. Zhu,G.-F. Xu, Y.-F. Liu et al., “Heterochronic bilateral ectopicpregnancy after ovulation induction,” Journal of Zhejiang Uni-versity Science B, vol. 15, no. 8, pp. 750–755, 2014.

    [13] J. F. de los Rı́os, J. D. Castañeda, and A. Miryam, “Bilateral ec-topic pregnancy,” Journal of Minimally Invasive Gynecology, vol.14, no. 4, pp. 419–427, 2007.

    [14] I.Marcovici andB. Scoccia, “Spontaneous bilateral tubal ectopicpregnancy and failed methotrexate therapy: A case report,”American Journal of Obstetrics & Gynecology, vol. 177, no. 6, pp.1545-1546, 1997.

    [15] X. Cheng, X. Tian, Z. Yan et al., “Comparison of the fertility out-come of salpingotomy and salpingectomy in women with tubalpregnancy: a systematic review and meta-analysis,” PLoS ONE,vol. 11, no. 3, p. e0152343, 2016.

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