IsabelGuerridoMartinezObstetricsandGynecologyClerkshipNuriaLunaRamrezEvidenceBasedMedicineWrittenPresentationNicoleP.RebolloRodriguezOctober23,2015RaymondRiveraVergaraUterineMyomasHISTORYChiefComplaint:Llevo14mesessangrandoHistory of Present Illness: Patient is a 59 year old G6 P1051 woman who is an inmate that was brought to the OBER at Hospital Universitario de Adultos (UDH) after she was found to have profuse bleeding and anemia secondary to blood loss. Patient refers that 1 year ago, she was on medical evaluation at Centro Correccional de Mujeres in Bayamn due to a 2 month history of vaginal bleeding and was diagnosed with abortive uterine myomas, with treatment recommendations of undergoing total abdominal hysterectomy. On April 2015, patient was admitted to UDH for surgical evaluation but refers that medical clearance was not granted due to absent evidence of pulmonary function tests. Patient refers that since April she continued to experience profuse vaginal bleeding and a vaginal discharge described as acid pink water of foul odor. She complained that medical evaluation at prison has been neglectful for the past months until 5 days ago, when she was brought 5 days ago to OBER for evaluation and was found to have prolapsed myomas into vaginal canal. Patient was admitted to UDH and is currentlyawaitinghysterectomythathasbeenscheduledtotakeplacein3days. PastMedical History:Hypertension treated with Vasotec, Lasix and Trental (unknown dosages). COPD was diagnosed 14 years ago and currently receiving treatment with Spiriva, Ventolin and Proventil (unknown dosages). Patient diagnosed 20 years ago with Diabetes Mellitus Type 2, currently insulindependent. Diabetic neuropathy was diagnosed 10 years ago, receiving treatment with Neurontin which patient refers has not been effective. Osteoarthritis diagnosed 6yearsago,notcurrentlybeingtreated.ReviewofSystems:General:persistentfatigue,norecentweightlossHEENT:noheadaches,noblurryvisionLungs:shortnessofbreath,persistentcoughandphlegmBreasts:norecentchangesinbreastconsistency,nogalactorrhea. Cardiovascular:nopalpitations,nochestpainGastrointestinal:refersconstipationatprison,currentlywithnormalbowelmovementsUrinary:highurinevolumes,needstostraininordertovoid,nobloodinurine

Musculoskeletal:jointpain,unabletoambulatewithoutassistanceNeurological:abnormalsensationsinrightleg,lossofsensationinplantarsurfacesbilaterallyPHYSICALEXAMINATION

VitalSigns:BP:130/82HR:82bpmRR:22Temp:36.6CGeneral: awake, alert and oriented to person, place and time; patient appears older thanchronologicalagebuthasadequatehygiene.Handcuffedtobed.

Chest:dyspnea,tachypnea,diffusebilateralcracklesBreasts:pendulous,nopalpablemassesAbdomen:enlarged,mobileuterusapproximately21weeksinsize,positivebowel soundsPelvic:cervixisanteriorlydisplaced,withuterinemyomasprolapsedintovaginalcanalDIAGNOSIS,DIFFERENTIALDIAGNOSES,ANDDIAGNOSTICMODALITIES

Diagnosis in this patient is abnormal uterine bleeding due to uterine leiomyomas. In this patient, risk factors for development of uterine myomas (early menarche, multiparity, AfricanAmerican race, use of hormonal contraception, obesity) are inconsistent with her medical history but physical examination sonographic findings suggest this diagnosis. Nonetheless, a definitive diagnosis is obtainable only after pathologic examination of the uterus removedontotalabdominalhysterectomy.

Differential diagnoses in a postmenopausal patient with abnormal uterine bleeding include adenomyosis, leiomyosarcoma, endometrial carcinoma, and ovarian or tuboovarian masses. In the case of adenomyosis, physical examination would have shown a diffuse uterine enlargement, generally not exceeding the size of a 12 week uterus. Formation of adenomyomas would have been differentiated from leiomyomas solely on the basis of pathological examination. On the other hand, presence of leiomyosarcomas would have been distinguished from myomas by pathological examination as well, as clinical presentation is indistinguishable from that of myomas. Endometrial carcinoma is another diagnostic possibility due to postmenopausal bleeding, but less likely given the clinical presence of prolapsed uterine masses. Lastly, ovarian or tuboovarian masses are also considered in the differential diagnoses, but sonographic evaluation and midline location of palpable masses in the patient favor a uterineetiology.

Main diagnostic tests employed in this patient were ultrasound examination, both pelvic and transvaginal sonograms. And, as stated above, definitive diagnosis was determined histologically.

CLINICALMANAGEMENT

Treatment needs to be individualized depending on presentation age, parity and others. In this case, the patient had already reached the end of her reproductive age, and had had multiple pregnancies of which only one was successfully carried to term. The patient had been initially treated with Provera, which proved to be of little efficacy. However, with her clinical presentation of uterine bleeding compromising her hemodynamic stability, and the symptoms of pelvic bulkiness and pressure sensation along with the prolapsed myoma into the vaginal canal, hysterectomy is the only definitive treatment. Other pharmacologic treatments that could have been attempted in this patient were combined oral contraceptives, GnRH agonists and levonorgestrel intrauterine devices. GnRH agonists are the most effective for decreasing uterine fibroid volume, but can only be used as a short term treatment after which normal fibroidgrowthresumes.

When scientific literature was researched, the following alternative treatments for uterineleiomyomaswerefound:

1.Noninvasiveprocedure:Magneticresonanceimagingguidedfocusedultrasound surgery(MRgFUS)2.Uterinearteryembolization3.Myomectomyopenabdominal,laparoscopic,hysteroscopicorroboticassisted.

In this patient, management was drastic and focused on eliminating with certainty the

source of myomas. Medical consequences of a total abdominal hysterectomy in a patient who has already entered menopause are not as significant as they would have been to a patient still in the midst of her reproductive years and who desired to maintain fertility. This is why we wanted to further investigate which could be the most effective management options had our patient been premenopausal. Five research articles were reviewed in order to identify other treatment options, the clinical significance of myomas in terms of effects on fertility and how treatmentcorrelateswithpregnancyoutcomes.CLINICALQUESTIONGiven that hysterectomy is the only treatment for complete eradication of symptomatic uterine myomas, what other alternative treatments would be effective for women diagnosed with uterinemyomaswhowishtomaintainfertility?DISCUSSIONOFEVIDENCE

The objective of the scientific article Do submucous myoma characteristics affect fertility and menstrual outcomes in patients who underwent hysteroscopic myomectomy? was

to determine the longterm effects of uterine myomas on fertility and menorraghia. According to this article, submucous myomas are associated to heavy menstrual bleeding along with infertility in premenopausal patients. This study was pertinent to clinical question in order to learn of the management of uterine myomas and how it could improve fertility in patients. A total of 98 women who were referred to hysteroscopy for symptomatic submucosal fibroids, 51 of these with symptoms of menorrhagia and 47 of these with infertility were enrolled in this retrospective cohort study. Limitations in this study include a small sample size, 47 of these being pertinent to our clinical question. Also, being a retrospective cohort study is a limitations considering little control over data recollected. Exclusion criteria included patients with multiple myomas, infertility with other causes, persistent anovulation or patients that received invitro fertilization. This article concludes that 60% of patients (28/47) experienced thirty pregnancies and found no significant effect of myoma size, type or location on pregnancy rates. This study is considered a level II2 which is an observational study without controls. This level of study is difficult to generalize to the population and could have possible confounding variablesthataffectthefinaldata.

Do submucous myoma characteristics affect fertility and menstrual outcomes in patients who underwenthysteroscopicmyomectomyAhmed Namazov M.D., Resul Karakus M.D., Ezgi Gencer M.D., Hamdullah Sozen M.D., Levent AcarM.D.IranJReprodMedVol.13.No.6.pp:367372,June2015The aim of this study was to determine the long term effects of submucosal myoma resection on menorrhagia and infertility; also to detect whether the type, size, and location of myoma affectthesurgicalsuccessandoutcomes.Database of hysteroscopic myomectomies in Zeynap Kamil Training and Research Hospital. Data recollected included: demographics, pregnancy rates before surgery, indications for surgery, duration of infertility, menstrual bleeding pattern, causes of infertility, complications related to procedures.ResultsandConclusionsrelatedtothePICOquestion:There was no statistical difference according to the myoma size. 28 of 47 infertile women spontaneously experienced thirty pregnancies, with an overall 2310 months postoperatively period (60%). The mean myoma size in patients who became pregnant was 30.38 mm, in

patients who did not conceive was 29.95 mm and no statistical difference was found (p=0.961, MannWhitneyUtest)Pregnancy rates according to myoma location and type were: lower segment 50%, fundus 57%, and corpus 80%; type 0) 75%, type 1) 62%, type 2) %50. Those variations were not statistically significant(ChiSquaretest).These results suggest that pregnancy rates, bleeding after hysteroscopic myomectomy are not significantly influenced by myoma location, type and size. This data is consistent with most of the literature already present. Because there are many mechanisms by which myomas may affect fertility, this paper also suggests that regardless of the size, their effects on fertility are more or less the same, even with myomas smaller than 2 cm. This implies that there is no need to stratify study subjects based on location or size of myoma in fertility outcomes. We consider the information and research provided reliable because they excluded patients with previously diagnosed infertility causes such as patients with multiple myomas, persistent anovulation or bilateral tubal occlusion and those patients who received intravaginal fertilization in order eliminate other possible bias and strengthen conclusions. However, sample size was small and even though it was a retrospective cohort study, there is the need of a metaanalysis examinationwithsimilarinvestigationsinordertoestablishasolidconclusion.Menorrhagia and pregnancy rates after hysteroscopic myomectomy were not significantly affected by variations in myoma size, type or location. According to our study the myoma characteristics do not affect improvement rates after hysteroscopy myomectomy in patients with unexplained infertility or excessive uterine bleeding. Large prospective randomized trials could be designed, to assess the relationship between submucous myoma characteristics and postoperative outcomes. But we think that in symptomatic patients (menorrhagia and infertility) with submucous myoma, an expectant management will not be ethical. So randomizedcontrolledtrialswillbedifficulttodesign.Fertility and Pregnancy Outcome after Myoma Enucleation by Minilaparotomy under MicrosurgicalConditionsinPronouncedUterusMyomatosus

This research article asses the fertility capability and pregnancy outcome after operative removal of myomas by minilaparotomy in a special patient collective. This explores a possible management for myomas to see if it has beneficial effects in the fertility of the patients. This research was designed as a retrospective cohort study. They used SPSS 18 and calculated results with the Wald test. The relationship between symptoms and complaints were determined by the logistic regression method. The results for this paper was that an average of 5.0 myomas were removed in the patients. The average of the maximum size was 6.6 cm and the biggest size was 19 cm. 82.5% of the myomas that were selected were intramural. Postoperative pregnancy rate was 60.3% for which 28.4% were vaginal deliveries and 71.6% were C/S. Also, the preoperative miscarriage rate of 75.6% was reduced to 22.5%. Some of the strengths of this paper was that throughout the discussion of the paper they compare constantly their results with previously published data and both have similar results. Also, they incorporated myomas that were intramural that are known to cause sterility, infertility or serious complications of pregnancy. Some of the limitations of this research was that many women of the study were overweight or with advanced maternal age that are factors that are known to cause infertility. Since this is a retrospective study, it could have possible confounding factors affecting the final data. Also, retrospective studies are not generalizable to the general population.Therefore,thisstudyisconsideredLevelII2asevidence.PregnancyOutcomesFollowingRobotAssistedMyomectomyThis study assesses the pregnancy outcomes in women with symptomatic leiomyomata uteri who underwent robotassisted laparoscopic myomectomy (RALM). This aim is important to our study because it explores a possible management for myomas to see if that management has beneficial effects in the fertility of the patients. Also, RALM treatment may offer a minimally invasive alternative for uterine preservation for women with uterine fibroids. Some of the strengths, is that throughout the discussion of the paper they compare constantly their results with previously published data and both have similar results. Also, it utilized a large group of people from three different institutions. Some of the limitations are that Dr. Pitter, one of the authors, is on the speaker bureau for Intuitive Surgical. Also, since this was a retrospective study it did not include all women who attempted conception after surgery. Also, the majority of the women, around 57.4%, were overweight or obese which are risk factors known to affect fertility. Since this is a retrospective study and used a population from three different institutions it is considered a level II2 of evidence. Of note, this paper utilizes different populations from different institutions. Therefore, this has a higher level of evidence than the otherselectedpapers.Pregnancy and Natural Delivery Following Magnetic Resonance ImagingGuided FocusedUltrasoundSurgeryofUterineMyomas.

This scientific article describes a 31 years old Korean patient who became pregnant and gave birth following a series of two consecutive Magnetic Resonance ImagingGuided Focused Ultrasound Surgery (MRgFUS) treatments, treating two distinct uterine myomas. This study its consider a type III based on case report study design. The researchers established that MRgFUS for uterus myomatosus could be a potential beneficial treatment for women with myomas who are seeking to retain their reproductive capabilities, with reduced complications compared to conventional treatments. Most of the classical treatments for myomas involve invasive surgical procedures that lead to scar and adhesion formation. MRgFUS is a procedure that is noninvasive, thus avoiding scar formation in the uterus. The operator uses the integrated system to deliver accurate energy pulses to a location identified on anatomical MRI images. The heat generated during the course of these sonication is monitored using images acquired in realtime. At the end of the treatment, the results areevaluatedbythenonperfusedregionsonT1weightedcontrastenhancedimages.Their study design was a case report study in CHA Bundang Medical Center, CHA University,Seongnam,Korea.Four months post treatment, the patient spontaneously conceived, and she continued her pregnancy to term. After 39 weeks of normal pregnancy, a baby girl was born, weighing 3,190 gram, through a vaginal delivery. No complications were recorded during the labor or postpartum periods. This case report proposed that by noninvasively ablating the inner portions of the treated myomas, they would both shrink in size and would become more flexible. The combination of these phenomena may have contributed to reduction of the submucous component of these myomas and reduced the possibility of uterinecavity distortion contributing to such a positive fertility outcomes. Some limitations of this case report are the lack of knowledge of prior infertility issues and the limitation to evaluate its applications of this fertility outcomes to the general population. Therefore it is necessary to find similar case reports to further strengthentheirscientificsignificance.Theeffectivenessofcombinedabdominalmyomectomyanduterinearteryembolization.

In this journal article, investigators establish comparisons between the effectiveness of abdominal myomectomy (AM) versus a combination of uterine artery embolization (UAE) and AM in the treatment of uterine myomas larger than 4 cm. Their study design was a retrospective cohort that allowed the review of charts from patients who had undergone AM within 1 week after UAE. Sample size was limited to 20 study subjects, which is known to represent a limitation to the study. Outcomes were defined as a decrease in uterine volume

and myoma diameter, days spent on hospital stay, blood loss volume, amount of myoma removed as well as pregnancy rates amongst the study subjects. Comparisons were made using reports from previously published cohort studies that evaluated these treatments separately. This reports study design is subject to a decreased level of evidence given the inevitable disparities between the collected data in the present study and the other retrospective data with which the information is being compared to. Of consequence, confounding of results is more likely than if comparisons were established within the same study group and researchers. Nonetheless, the present study is considered to be a level II2 in quality of evidence, due to inclusion of a cohort study from more than one research group or center. Conclusions of the present study include decreased rates of blood transfusion and shorter hospital stays in patients undergoing UAEAM versus patients undergoing AM alone. Thirty percent of the women in the study were able to conceive after being subjected to the procedures and postoperative complications were significantly less than those reported in other studies evaluating UAE and AM alone. Of note, the results presented here provide supporting evidence toourproposedstudyquestionthatisofacceptablequality.CONCLUSIONSTATEMENTSToconclude,aninterventionmustbedoneinordertoimprovefertilityinpatientswithuterinemyomas.Watchfulwaitingisnotanoptionwhenfertilityisaffectedbyageofthewomen.Thereisnoconsensusinspecificmanagementofuterinemyomas.Notreatmenthasbeenprovenmoreeffectivethanothers.Therefore,selectingtheprocedureofchoicemainlydependsintheresourcesavailableineachhospitalsettingandpatientsdesire.Ideally,inpatientswhowishtomaintainfertility,aminimallyinvasiveprocedurecouldbedoneinordertomaintainuterinepreservation.Forexample,myomectomyincombinationwithuterinearteryembolizationisafeasibleandcosteffectiveoptionforpatientswithamyomatousuterusthatareofreproductiveageanddesireacosteffectivetreatment. BONUSIdeally, a randomized clinical trial would be the best way to assess the best treatment for uterine myomas in patients who wish to maintain fertility. It would be able to assess the relationship between uterine myomas and fertility postsurgery and provide information on whether the study could be generalizable to the population. However, in contrast to pharmaceutical clinical trials, a randomized clinical trial would be difficult to apply to surgical interventions due to its dependence on multiple factors. For example, blinding and influence of case providers can present difficulties for randomized trials. Surgical procedures involve

various components such as preoperative care, anesthetic procedures, the main surgical intervention and postoperative care which involve several care providers that directly affect the outcomes of the patient. Therefore, the success of the intervention majorly depends on the skill, training and dedication of those that intervene. For this reason, variations in techniques andskillcouldbeconfoundingvariableswiththetreatmenteffects. A prospective cohort study that follows patient fertility outcomes after undergoing myomectomy, uterine artery embolization, MRgFUS, robot assisted myomectomy or minilaparotomy myomectomy would be a better study design to assess the most effective treatment in enhancing pregnancy rates in previously diagnosed infertile patients with uterine myomas. This would represent an improvement from the retrospective cohort studies that we have reviewed because we would have more control over the data collected, over sample size and other possible long term outcomes such as myoma recurrence and time to recovery after surgery. Ideally, we would want a sample size from the Puerto Rican population of more than 500 patients from different gynecologic clinics and hospitals. Information would be included in a database that could be constantly updated on follow up appointments. Assisted reproductive technologies would not be used in our study as it could affect our final results and pregnancy rates. Inclusion criteria would be to have inability to conceive in 1 year without other known causesofinfertility,patientsfrom2035yearsofagewithnoknownhistoryofsystemicillness.REFERENCESTheeffectivenessofcombinedabdominalmyomectomyanduterinearteryembolization.McLucas,B.andVoorheesIII,W.D.InternationalJournalofGynecologyandObstetrics130(2015)241243. (SangWook Yoon, 2010) Pregnancy and Natural Delivery Following Magnetic Resonance ImagingGuided Focused Ultrasound Surgery of Uterine Myomas. Yonsei MedJ51(3):451453.