© science source / biophoto associates 1 be consideredwhendecidingwhattypeofmanagementisrequired. pregnancyvaginalbleeding mustA number ofpotentialcausesearly early stagesofpregnancy Vaginal bleeding in the and Bonnie Kimberly D. Walker; Kathy Dexter, MLS, MHA, MPA, PA-C; uterine cavity. implants outside the the embryo ( embryo the pregnancy, ectopic an In the clinical the clinical ad CME feature CE A. Dadig, E shown visor • ) d .D., PA-C april 2013 • T n n n urn to page 27 for additional information on this month’s CME month’s this on information additional for 27 page to urn

• • • • additiona comp Learning objecti ex t here t Tex here t Tex here t Tex here t Tex www.ClinicalA dvisor.com l P posttest: the ete l CME www.ClinicalA dvisor.com / CE v

es : P : ages xx age xx age U defined as bleeding at at as bleeding defined common cause of fetal demise and subsequent subsequent and demise fetal of cause common bleeding in the first half of her pregnancy. pregnancy. her of half first the in bleeding to effectively assess and manage a patientand mortality, the withastute practitionervaginal should be able demise prior to the week. demise 20th fetal intrauterine experience to on go will women ( pregnancy early in bleeding vaginal of diagnoses patient requires an understanding the ofof the management differential and assessment Appropriate Causes disease and/or lesions of cervix/vagina. the lesions and/or disease and fewer 1% (EP), than by are caused trophoblastic of7%which areattributable toectopic pregnancy demise, fetal indicate bleeds to of pregnancy 50% early viable intrauterine pregnancies (IUP). A total of 30% Table 1 Table While chromosomal abnormalities are the mostchromosomalthe abnormalitiesare While ). Fifty percent of early pregnancy bleeds— pregnancy of percent early Fifty ). or spotting. Even more sobering,pregnancy half will experienceof vaginal thosebleeding p to of womenof 25% all in stages the early • the clinical the clinical ad < / CE 20 weeks’ gestation—occur in courses.

1 visor • To reduce morbidity morbidity To reduce April 2013 2

1 CME CE early pregnancy bleeding The patient will present with vaginal bleeding and mild-to-moderate subrapubic or midline lower abdominal pain that may radiate to the lower back. spontaneous abortion, other causes include infection, reproductive Ask whether the patient has experienced any trauma. Are tract abnormalities, toxin exposure and endocrine/autoim- nausea, vomiting, syncope, fever or cramping associated mune disease.2,3 Spontaneous abortions can be divided into with the bleeding? Carefully review the woman’s obstetric four types: (1) complete (all products of conception (POC) history, exposure to sexually transmitted infections (STIs), have passed out of the uterus); (2) incomplete (some POC and potential bleeding disorders. have passed through a dilated cervix); (3) inevitable (bleeding In EP, there is no set constellation of findings that confirm is present with a dilated cervix with or without POC); and or exclude the diagnosis. In fact, clinicians cannot reliably (4) septic (an incomplete spontaneous abortion accompanied exclude the diagnosis of EP on the basis of history and physical by infection).1 exam findings alone. However, a patient who describes the A threatened abortion is defined as any vaginal bleeding that abdominal pain as “sharp” and denies recent passage of tissue occurs in early pregnancy with an embryo/fetus present in is more likely to have an EP than the patient without these the uterus, detectable cardiac activity, and a closed cervical findings. A study found that the frequency of EP in women os. In a missed abortion, the embryo/fetus is larger than 5 mm, presenting with a positive -human chorionic gonadotropin without heart tones, and the POC are retained.1 (hCG), moderate-to-severe abdominal pain, and no history of An EP is a conceptus that implants outside of the uterus.1 tissue passage was 25%.8 Approximately 75% of women with EP is the most common cause of pregnancy-associated death confirmed EP will report a history of amenorrhea.5 Factors in early pregnancy,4 constituting 6% of all maternal deaths that increase a woman’s risk for EP include an intrauterine annually.1 It is estimated that the diagnosis of EP missed at device currently in place, a history of previous EP, in utero initial presentation 12% of the time.2 Gestational trophoblastic exposure to diethylstilbestrol, genital infection, prior tubal disease (also known as molar pregnancy or hydatidiform mole) surgery, in vitro fertilization, infertility, and smoking.1 is a potentially malignant condition in which the placenta The clinician should suspect an anembryonic pregnancy develops without an embryo.5 In an anembryonic pregnancy if the woman reports that her pregnancy symptoms have (also known as a blighted ovum), the gestational sac is larger regressed. A transvaginal ultrasound (TVUS) should be than 18 mm in size but does not contain embryonic or performed to confirm the presence of the fetal heartbeat.1 fetal tissue. A subchorionic hemorrhage (blood between the Trophoblastic disease will present with hyperemesis, irregular chorion and uterine wall) may produce early pregnancy and/or heavy bleeding, and vaginal pain in the first half of bleeding but does not necessarily result in the termination the pregnancy. 2,5 of the pregnancy.1 Physical examination History and presentation The physical examination of a woman with early pregnancy Understanding the factors that put a woman at a higher bleeding will be focused on the abdominal/pelvic area. If risk for spontaneous abortion is important when taking the the woman presents with fever in the presence of adnexal/ patient’s history. These factors include endocrine disorders; peritoneal symptoms and such signs as rebound tenderness, genetic aneuploidy (abnormal number of chromosomes); rigidity and/or guarding, consider a diagnosis of septic such immunologic disorders as systemic lupus erythemato- abortion. Hypotension, absent or diminished bowel sounds, sus, such infections as gonorrhea, chlamydia, syphilis, and abdominal distension, and shoulder pain on the ipsilateral herpes; chemical exposure; radiation exposure; and uterine side could signify a ruptured EP.1 The pelvic and abdominal abnormalities.1 Usually, the patient will present with vaginal examination will often yield inconclusive findings, making bleeding and mild-to-moderate subrapubic or midline lower ultrasound and quantitative -hCG the diagnostic tests abdominal pain that may radiate to the lower back.6 The of choice. The physical exam is particularly important if clinician should ask about prior confirmation of pregnancy, there is no access to ultrasound or -hCG or if the results last known menstrual period, when the bleeding began, of either are inconclusive. Physical findings that indicate a quantity and character of bleeding, and current medica- viable IUP include minimal cervical and abdominal ten- tions (ovulation agents put a woman at risk for a heterotopic derness, benign adnexa, a closed os, and absence of POC. pregnancy, which is an IUP and an EP simultaneously).7 Because these findings may also be present in a nonviable

2 the clinical advisor • april 2013 • www.ClinicalAdvisor.comwww.ClinicalAdvisor.com • the clinical advisor • april 2013 2 CME CE early pregnancy bleeding Identification of an embryo/fetus with cardiac activity located outside of the uterus is conclusive evidence of an ectopic pregnancy. pregnancy, the diagnosis of a normal pregnancy should be 1,500-2,000 mIU/mL.1,3 This range is referred to as the dis- made primarily through ultrasonography.2 criminatory zone. If -hCG levels are too low, serial -hCG The size and position of the uterus should be assessed for levels may be taken every 48 hours (doubling time) until the size-date discrepancy.1,3 Molar pregnancies will present with a discriminatory zone is reached. At that point, the TVUS uterus larger than gestational dates would suggest; in women would prove effective in assessing for IUP.3 Findings of a with an excluded IUP, a uterus size smaller than what would normally progressing IUP include a normal gestational sac be expected at 8 weeks’ gestation may point to EP.2,8 The consisting of a central blastocyst surrounded by a double ring bimanual exam may reveal masses and cervical motion tender- of echogenic chorionic villi and decidua. Visualization of this ness, leading the clinician to consider EP, but these findings structure and absence of a pseudogestational sac rules out an are not definitive.1,8 The classic EP triad of pain, vaginal bleed- EP. Cardiac activity is noted when the crown-rump length ing, and adnexal mass is nonspecific and is interestingly more is >5 mm (around 10 to 11 weeks’ gestation).1 The presence often associated with a diagnosis of miscarriage. Literature of a detectable heart beat decreases the risk of pregnancy loss states that the pelvic-exam findings in diagnosing an EP are by 10%,3 and the absence of the above findings allows the unreliable in isolation.2 clinician to identify failure of the pregnancy.1 The speculum exam may identify such nonobstetric causes All women presenting with signs and symptoms suggestive of bleeding as polyps, STI, cancer, or trauma.1 Any tissue in of EP should have an ultrasound, regardless of specific find- the os indicates a dilated cervix. If the os is dilated, inevi- ings in the history and physical examination, as the specificity table, incomplete, and/or septic spontaneous abortions are of the TVUS in detecting IUP is around 98% with greater in the differential. If the os is closed, threatened, complete, than 90% sensitivity.8,11 When an IUP is verified, the EP is embryonic demise, and/or septic abortion are included.6 The ruled out, but care must be taken not to miss a heterotopic speculum exam also allows the practitioner to quantify the pregnancy.11 An adnexal mass or free fluid in the pelvis is an amount of blood present and remove any POC. Many women EP until proven otherwise. Identification of an embryo/fetus who eventually miscarry have inconclusive physical exam with cardiac activity located outside of the uterus is conclusive findings. For example, a dilated os is found in only 24% of evidence of an EP. If an intrauterine embryo/fetus without women who go on to miscarry, and the finding of POC on cardiac activity is identified and there is tissue and/or cervical speculum exam is only present in 13% of women who go on os dilation, fetal demise has most likely taken place. Pathologic to miscarry.2 To summarize, the findings needed to diagnose examination of tissue from the cervical os in a suspected inevi- spontaneous abortion or EP are not obtained by the physical table spontaneous abortion should show chorionic villi. Lack exam, but by ultrasound and -hCG levels.2,8 of fetal heartbeat by 10 to 11 weeks’ gestation in the absence fetal tissue within the gestational sac signifies an anembry- Diagnostic workup onic pregnancy. Gestational trophoblastic disease presents The diagnostic workup of a women presenting with early with classic “snowstorm” appearance of material within the pregnancy bleeding includes a complete blood count, WBC uterine space. Subchorionic hemorrhage may be present in count with differential to rule out infection, urinalysis to a normally progressing pregnancy, but once hemorrhage is rule out urinary tract infection, gonorrhea/chlamydia swab, identified, verification of heartbeat is necessary.1 Rh-type, qualitative -hCG, transvaginal ultrasound, A serum progesterone level >25 ng/mL suggests a viable quantitative -hCG, and serum progesterone levels.1,3,9 IUP.5 High serum progesterone levels will rule out an EP, Currently, the TVUS and the quantitative -hCG are con- but its predictive value depends on the serum -hCG levels.8 sidered first-line for diagnosis in early pregnancy bleeding.2 Serum progesterone levels are less helpful when -hCG levels Data show that 91% of EPs are diagnosed with TVUS,10 are <2,000 IU/L and within the first four weeks of gestation. which is preferred over transabdominal ultrasound because A -hCG level >2,000 IU/L and a serum progesterone level of increased sensitivity.1 >22 ng/mL together confer greater than 30% specificity for Confirmation of a viable IUP is achieved by visualization ruling out an EP. The best role for serum progesterone is of the yolk sac by TVUS five to six weeks after the start of in identifying women at low risk for EP when paired with the last menstrual period, or when -hCG levels are between -hCG levels.4

3 the clinical advisor • april 2013 • www.ClinicalAdvisor.comwww.ClinicalAdvisor.com • the clinical advisor • april 2013 3 CME CE early pregnancy bleeding Ectopic pregnancy is an emergent diagnosis that must be rapidly ruled out in all women presenting with abdominal pain and early pregnancy bleeding.

Increasing -hCG serum levels are the first definitive marker 48 hours later) of <0.87 reliably predicts that the pregnancy of pregnancy, and levels begin to increase approximately eight which will resolve spontaneously with no intervention.10 If days after conception.1 A -hCG level <5 mIU/mL is negative history, physical exam, and diagnostic test findings point to a for pregnancy, and a level >25 mIU/mL is positive.12 -hCG pregnancy loss of a previously confirmed pregnancy, expect- levels should predictably increase 80% to 100% every 48 hours ant management should entail a repeat TVUS one week after until the eighth or 10th week of a healthy pregnancy, at which initial presentation to confirm complete passage of tissue.1,3 An time it peaks, usually around 100,000 U/mL.1,6 If levels are 80% drop in -hCG levels one week after complete evacuation too low, a failing IUP or an EP should be suspected, and if of tissue also confirms termination. However, if the IUP was levels are too high, the possibility of gestational trophoblastic never confirmed, continue to follow serial -hCG levels to disease should be investigated. An increase <53% deems the nonpregnant values to rule out EP. High fever, heavy bleeding, pregnancy nonviable.1 pelvic pain, and general malaise may indicate retained tissue or endometritis.3 Infection may be found more commonly with Management medical management,13 but expectant management is more The management of early pregnancy bleeding includes likely to result in poorer outcome with embryonic demise and expectant (watchful waiting), medical, and surgical anembryonic pregnancy than in spontaneous abortion.1 approaches.1 No interventional methods have been proven Dilation and curettage (D&C) is the treatment of choice after to prevent SA.3 There is evidence to support the admin- a SA or in embryonic demise or anembryonic pregnancy, but istration of RhoGam (50 µg of anti-D immune globulin) some evidence indicates that watchful waiting or treatment to Rh-negative patients at <12 weeks’ gestation presenting with the prostaglandin analogue misoprostol (Cytotec) may be with any bleeding.3 The hemodynamically unstable patient safer, equally effective, and psychologically gentler.1,3 However, presenting to the emergency department should be given the FDA has not approved misoprostol for the management of IV fluids and oxygen and admitted to the hospital.6 miscarriage, and clinical discretion must be used.1 Misoprostol EP is an emergent diagnosis that must be rapidly ruled out will typically result in cramping and bleeding within two to in all women presenting with abdominal pain and early preg- six hours of initiation. Nonsteroidal anti-inflammatory and nancy bleeding.11 Early detection of EP allows for conservative, narcotic/acetaminophen pretreatment is helpful in managing nonsurgical treatment and conservation of the fallopian tubes.2 discomfort, fever, and chills. Regardless of the treatment used, Expectant management is recommended in patients diag- a follow-up appointment is necessary for these women.3 nosed with an EP and declining -hCG values <1,000 mIU/ Additional research has found that uterine aspiration may mL.1 Medical management with methotrexate (Abitrexate, be more effective and a viable alternative to D&C in women Folex, Mexate) is the best option for a stable patient with an with anembryonic gestation and embryonic demise. Uterine unruptured EP measuring <3.5 cm, no detectable heart beat aspiration was found to be as safe as D&C, quicker to perform, on ultrasound, and a -hCG <15,000 mIU/mL. A patient more cost-effective, and amenable to use in the primary-care with an unruptured EP and -hCG levels >15,000 mIU/mL setting, but should only be used urgently if the woman is expe- requies immediate hospitalization, stabilization and surgical riencing brisk bleeding, prolonged bleeding with a subsequent intervention.1,5 The management of a ruptured EP entails drop in hemoglobin, or is showing signs of infection.3 hospitalization, stabilization, and open surgery.1 If fetal cardiac activity is identified, as seen in a threatened Stable patients presenting with threatened, inevitable, com- abortion, the best management involves serial TVUS in place plete, or missed abortions and minimal bleeding may only of -hCG levels.1 Identification of a septic abortion is an urgent require observation and IV fluids5 and may be discharged home diagnosis, and treatment requires antibiotic administration, with an obstetrics follow-up and instructions to abstain from obstetrics/gynecology consultation, and evacuation of the intercourse, observe bed rest, and return if bleeding worsens.6 uterine cavity.1,6 In the setting of incomplete abortion, watchful waiting is 90% Surgery and careful follow-up is the only method of man- effective.3 In a pregnancy of unknown location – defined as agement for the molar pregnancy (hydatidiform mole). A a pregnancy too early to be visualized, a positive pregnancy urine -hCG four to six weeks after the pregnancy loss will test, and no POC – a -hCG ratio (levels measured at 0 and confirm that there is no persistent disease.1

4 the clinical advisor • april 2013 • www.ClinicalAdvisor.comwww.ClinicalAdvisor.com • the clinical advisor • april 2013 4 CME CE early pregnancy bleeding Any method of contraception is acceptable immediately after a failed pregnancy, and there is no ideal interpregnancy interval.

Ultimately, all management options for early pregnancy loss 5. LP Roppolo LP, D Davis, and SP Kelly, eds. Emergency Medicine are safe, effective, and will not affect future fertility, so the Handbook: Critical Concepts for Clinical Practice, 1st ed., Philadelphia, Pa.: specific management choice should rest with the patient.3 Mosby, Inc.;2006:905-909. 6. Copland B. Vaginal bleeding in the first trimester.I n: Mick NW, Peters Follow-up JR, Egan D, et al. Emergency Follow-up with a woman who has experienced a failed Medicine, 2nd ed., Philadelphia, Pa.: Lippincott Williams & Wilkins; pregnancy should include addressing issues of contraception, 2005:140-142. future fertility/pregnancy, and the emotional impact of 7. Hessert MJ, Juliano M. Fetal loss in symptomatic first-trimester preg- pregnancy loss. Any method of contraception is acceptable nancy with documented yolk sac intrauterine pregnancy. Am J Emerg Med. immediately after a failed pregnancy, and there is no ideal 2012;30:399-404. interpregnancy interval.1 A woman’s menstrual cycle should 8. Dart RG, Kaplan B, Varaklis K. Predictive value of history and physical resume four to six weeks after the resolution of the loss.9 examination in patients with suspected ectopic pregnancy. Ann Emerg Given the numerous causes of early pregnancy vaginal Med. 1999;33:283-290. bleeding, the practitioner must employ sound clinical and 9. PubMed Health. Miscarriage. Available at www.ncbi.nlm.nih.gov/ diagnostic skills in the assessment, workup, and management of pubmedhealth/PMH0002458/. the patient. The importance of taking an appropriate history, 10. Condous G, Kirk E, Van Calster B, et al. Failing pregnancies of unknown to include asking about character, distribution, and severity location: a prospective evaluation of the human chorionic gonadotrophin of pain, cannot be overstated. A thorough physical exam, ratio. BJOG. 2006;113:521-527. appreciating cervical-motion tenderness, a dilated cervical 11. McRae A, Murray H, Edmonds M. Diagnostic accuracy and clinical os, or abdominal rigidity, will aid in arriving at the correct utility of emergency department targeted ultrasonography in the evalua- diagnosis. The appropriate use of a TVUS and the quantitative tion of first-trimester pelvic pain and bleeding: a systematic review.CJEM . -hCG is also essential. Finally, the practitioner must take into 2009;11:355-364. Available at www.cjem-online.ca/v11/n4/p355. consideration all clinical findings to reach a correct diagnosis 12. American Pregnancy Association. Human chorionic gonadotropin and work with the patient to mutually decide on expectant, (hCG); the pregnancy hormone. Available at americanpregnancy.org/dur- medical, or surgical management, leading to a reduction in ingpregnancy/hcglevels.html. morbidity and mortality. n 13. Shelley JM, Healy D, Grover S. A randomised trial of surgical, medical and expectant management of first trimester spontaneous miscarriage. Ms. Walker is a physician assistant in the emergency department Aust N Z J Obstet Gynaecol. 2005;45:122-127. at Gwinnett Medical Center’s campuses in Duluth, Ga., and Lawrenceville, Ga. Ms. Dexter is associate professor and clinical director All electronic documents accessed March 15, 2013. of the physician assistant department at Georgia Regents University in Augusta, Ga., where Dr. Dadig is associate professor and chair.

References 1. Deutchman M, Tubay AT, Turok D. First trimester bleeding. Am Fam Physician. 2009;79:985-994. Available at www.aafp.org/afp/2009/0601/p985.html. 2. Isoardi K. Review article: the use of pelvic examination within the emer- gency department in the assessment of early pregnancy bleeding. Emerg Med Australas. 2009;21:440-448. 3. Prine LW, MacNaughton H. Office management of early pregnancy loss. Am Fam Physician. 2011;84:75-82. Available at www.aafp.org/ afp/2011/0701/p75.html. 4. Buckley RG, King KJ, Disney JD, et al. Serum progesterone testing to predict ectopic pregnancy in symptomatic first-trimester patients.Ann Emerg Med. 2000;36:95-100.

5 the clinical advisor • april 2013 • www.ClinicalAdvisor.comwww.ClinicalAdvisor.com • the clinical advisor • april 2013 5 CME CE early pregnancy bleeding

Table 1. Differential diagnosis of early pregnancy vaginal bleeding Differential Definition Additional history Physical Diagnostic Management diagnosis examination tests Spontaneous Pregnancy loss Endocrine disorders, Transvaginal ultrasould (TVUS): -hCG ratio <0.87 ­reliably predicts abortion at <20 weeks’ genetic aneuploidy, embryonic/fetal tissue without that the pregnancy will resolve sponta- (subtypes gestation immunologic disorders, heart tones neously without intervention below) infection, chemical/radi- -human chorionic gonadotropin ation exposure, uterine (-hCG): doubling rate <80% abnormalities to 100% every 48 hours (failing intrauterine pregnancy [IUP]); deemed ­nonviable if <53% Complete All products of Endocrine disorders, Closed os Expectant: observation, IV fluids; spontaneous conception (POC) genetic aneuploidy, discharge home with obstetic (OB) abortion evacuated from immunologic disorders, follow-up and ­instructions to include uterus infection, chemical/ no intercourse, bed rest, and return if radiation exposure, bleeding worsens; repeat TVUS one uterine abnormalities week after initial presentation Medical: misoprostol (Cytotec) with ­follow-up appointment Surgical: dilation and curettage (D&C) Incomplete Some POC Endocrine disorders, Open os Expectant (90% effective): observation, IV ­spontaneous passed through genetic aneuploidy, with or fluids, discharge home with OB follow-up abortion dilated cervix immunologic disorders, without POC and instructions to include no intercourse, infection, chemical/ bed rest, and return if bleeding worsens; radiation exposure, repeat TVUS one week after initial uterine abnormalities presentation Medical: misoprostol with follow-up ­appointment Surgical: D&C Inevitable Bleeding and a Endocrine disorders, Open os Pathologic Expectant: observation, IV fluids, discharge spontaneous dilated cervix with genetic aneuploidy, with or examination of POC: chorionic home with OB follow-up and instructions abortion or without POC immunologic disorders, without POC villi observed to include no intercourse, bed rest, and infection, chemical/radi- return if bleeding worsens; repeat TVUS ation exposure, uterine one week after initial presentation abnormalities Medical: misoprostol with follow-up appointment Surgical: D&C Septic Incomplete Peritoneal Peritoneal/ Urgent antibiotic administration, uterine spontaneous spontaneous symptoms, fever adnexal signs, evacuation, and OB/GYN consult abortion abortion plus fever with infection or without dilated cervix and POC Threatened Confirmed IUP, Closed os TVUS: confirmed Expectant: observation, IV fluids, dis- abortion bleeding, cardiac heart tones charge home with OB follow-up and in- activity, and closed structions to include no intercourse, bed os at <20 weeks’ rest, and return if bleeding worsens, serial gestation TVUS in place of serial -hCG levels

6 the clinical advisor • april 2013 • www.ClinicalAdvisor.comwww.ClinicalAdvisor.com • the clinical advisor • april 2013 6 CME CE early pregnancy bleeding

Missed Embryo/fetus Closed os TVUS: intrauterine embry- Expectant: observation, IV fluids, discharge abortion >5 mm, no heart onic/fetal tissue without heart home with OB follow-up and instructions tones, retained tones; -hCG <53% increase to include no intercourse, bed rest, and POC return if bleeding worsens, repeat TVUS oneweek after initial presentation Medical: misoprostol with follow-up ­appointment Surgical: D&C or ­uterine aspiration Ectopic A conceptus Severe, sharp, unilat- Ruptured EP: TVUS: adnexal mass, free Ruptured EP: IV fluids, monitor, oxygen, pregnancy (EP) outside the uterus eral, or bilateral adn- hypoten- fluid in pelvis, ­cardiac activity admission, open surgery exal pain; no passage sion, absent/ detected outside of uterus, Expectant: declining -hCG values of POC; amenorrhea; diminished pseudogestational sac <1,000 mIU/mL, follow serial -hCG intrauterine device in bowel sounds, Progesterone: rule out EP with levels to nonpregnant values place; history of EP; abdominal -hCG values >2,000 IU/L Medical: methotrexate (Abitrexate, in utero exposure to distension, and progesterone >22 ng/mL diethylstilbestrol; genital hemodynami- Folex, Mexate) if unruptured EP <3.5 infection; tubal surgery; cally unstable, -hCG: doubling rate <80% cm, stable vitals, no heartbeat, and in vitro fertilization; ipsilateral to 100% every 48 hours -hCG <15,000 mIU/ml infertility; smoking shoulder pain Surgical: immediate hospitalization and Unruptured stabilization if unruptured EP with EP: uterus <8 -hCG >15,000 mIU/ml weeks’ gesta- tional size, cer- vical motion tenderness, adnexal mass Gestational Placental Hyperemesis, irregular Uterus larger TVUS: classic snowstorm Surgery and close follow-up, urine trophoblastic development and/or heavy bleeding, than gesta- appearance within uterine -hCG four to six weeks after preg- disease without embryo vaginal pain at <20 tional dates cavity nancy loss weeks’ gestation would suggest Anembryonic Gestational sac Regression of TVUS: lack of heart tones by Medical: misoprostol with follow-up pregnancy >18 mm but pregnancy symptoms 10 to 11 weeks’ gestation and appointment no embryonic/ no tissue within Surgical: D&C or fetal tissue gestational sac uterine aspiration Subchorionic Blood between TVUS: blood between cho- Expectant management hemorrhage chorion and rion and uterine wall, cardiac uterine wall activity confirmed Benign bleed 50% of all early Minimal cervi- TVUS: yolk sac by 5 to 6 Expectant management of viable IUP pregnancy bleeds cal/abdominal weeks’ gestation, central tenderness, blastocyst with chorionic villi benign adnexa, and decidua, cardiac activity by closed os, ab- 10 to 11 weeks’ gestation with sence of POC, crown-rump length >5 mm nonobstetric Progesterone: >25 ng/mL causes (e.g., polyps, sexu- -hCG: 80% to 100% increase ally transmit- every 48 hours until 8 to 10 ted infection, weeks’ gestation vaginal trauma, cancer)

7 the clinical advisor • april 2013 • www.ClinicalAdvisor.comwww.ClinicalAdvisor.com • the clinical advisor • april 2013 7