O predictors o treatment ailure, extrauterine yolk sac as a predictor o methotrexate ailure has con icting evidence (Lipscomb, 2009). Moreover, all except blood typing are repeated prior to additional doses (Lipscomb, 2007). With administration, women are counseled to avoid the ollowing until treatment is completed: olic acid-containing supplements, which can competitively reduce methotrexate binding to dihydro olate reductase; nonsteroidal antiin ammatory drugs, which reduce renal blood ow and delay drug excretion; alcohol, which can predispose to concurrent hepatic enzyme elevation; sunlight, which can provoke methotrexate-related dermatitis; and coitus, which can rupture the ectopic pregnancy (American College o Obstetricians and Gynecologists, 2014). Importantly, methotrexate is a teratogen and is a Food and Drug Administration pregnancy category X. As such, it can lead to a pro ound embryopathy that includes intrauterine growth retardation and cardiac, cranio acial, and skeletal abnormalities (Nurmohamed, 2011). The most common side e ects o methotrexate include stomatitis, conjunctivitis, and transient liver dys unction, although myelosuppression, mucositis, pulmonary damage, and anaphylactoid reactions have been reported with only one dose o 50 to 100 mg (Isaacs, 1996; Straka, 2004). Side e ects are seen in as many as a third o women treated, however, they are usually sel -limited. In some cases, leucovorin (olinic acid) is given ollowing treatment to blunt or reverse methotrexate side e ects. Ectopic Pregnancy the single-dose and multidose methotrexate protocols shown in able 7-3 are associated with overall resolution rates or ectopic pregnancy that approximate 90 percent. Although the study was underpowered to detect a small di erence in success rates, they did observe that 89 percent in the single-dose group and 93 percent in the multidose group were success ully treated. When analyzed rom the standpoint o treatment ailure, single-dose therapy had a 50-percent higher ailure rate compared with multidose therapy (6/54 versus 4/54). Lipscomb and colleagues (2005) reviewed their institutional experience with methotrexate therapy in 643 consecutively treated patients. Barnhart and coworkers (2003a) per ormed a metaanalysis o 26 studies that included 1327 women treated with methotrexate or ectopic pregnancy. It was less expensive, was easily accepted because o less intensive posttherapy monitoring, and did not require leucovorin rescue (Alexander, 1996). The major limitation was that multidose treatment had a ve old greater chance o success than singledose therapy. Failures included women with tubal rupture, massive intraabdominal hemorrhage, and need or urgent surgery and blood trans usions. A decline o less than 15 percent is seen in approximately 20 percent o treated women. Approximate time to resolution or all women averages 36 days, but in some, treatment requires as long as 109 days (Lipscomb, 1998). During the rst ew days ollowing methotrexate administration, up to hal o women experience abdominal pain that can be controlled with mild analgesics. This separation pain presumably results rom tubal distention caused by tubal abortion or hematoma ormation or both (Stovall, 1993). In some cases, inpatient observation with serial hematocrit determinations and gentle abdominal examinations help assess the need or surgical intervention. The most common regimen is seen in able 7-3 and consists o up to our doses o parenteral methotrexate, ollowed by adjunctive doses o leucovorin 24 hours later. A hybrid "two dose" protocol strives to balance the ef cacy and convenience o the two most commonly used protocols (Barnhart, 2007). The regimen administers 50 mg/m2 o methotrexate on days 0 and 4 without leucovorin rescue. Although the protocol is still considered experimental, no sa ety concerns were noted in the 101 patients treated, and the success rate approached 87 percent. A recent comparison o the single dose and "two dose" methotrexate protocols ound equivalent success rates (87 and 90 percent, respectively) with a trend toward increased needs or repeated doses in the single-dose cohort (Gungorduk, 2011). Korhonen and coworkers (1996) randomly assigned women with candidate tubal pregnancies to be managed expectantly or to receive low-dose oral methotrexate, 2. Logically, the addition o mi epristone, 600 mg orally, to single-dose methotrexate might improve unruptured ectopic pregnancy resolution. However, in a randomized trial o 212 cases, success rates did not di er i mi epristone was added (Rozenberg, 2003). Direct injection o methotrexate with sonographic or laparoscopic guidance into an ectopic pregnancy aims to minimize systemic side e ects o methotrexate. However, ewer drug-related side e ects were seen with local injection (Fernandez, 1995). T us, i the contralateral allopian tube appears normal, then salpingectomy is a reasonable treatment option that avoids the 5 to 8 percent complication rate caused by persistent or recurrent ectopic pregnancy in the same tube (Rulin, 1995). For laparoscopic salpingectomy, many techniques have been described, and a surgical description is ound in Section 44-3 (p. Lim and associates (2007) compared electrosurgical coagulation o the tube and mesosalpinx during laparoscopic salpingectomy with laparoscopic suture-loop (Endoloop) ligation. Endoloop use was associated with signi cantly shorter operating times (48 versus 61 minutes) and lower postoperative pain scores. For laparoscopic salpingostomy, a woman who is hemodynamically stable and strongly desires to preserve ertility is an appropriate candidate. All ree and tubal placental tissue should be meticulously removed, as retained trophoblast in the tube can lead to later invasion and bleeding. E S Surveillance Posttherapy monitoring assesses treatment success and screens or signs o persistent ectopic pregnancy. In the absence o symptoms, bimanual examinations are de erred to avoid the theoretical risk o manual tubal rupture. Brown and colleagues (1991) described persistent masses to be resolving hematomas rather than persistent trophoblastic tissue. For this reason, posttherapy sonography is reserved or suspected complications such as tubal rupture. Most recommend contraception or 3 to 6 months a ter success ul medical therapy with methotrexate, as this drug may persist in human tissues or up to 8 months a ter a single dose (Warkany, 1978). In sum, investigators ound no signi cant di erences in overall tubal patency determined at second-look laparoscopy. Each method was ollowed by a similar number o subsequent intrauterine pregnancies. Fewer repeat ectopic pregnancies were noted in women treated laparoscopically, although this di erence was not signi cant. Laparoscopy o ered shorter operative times, less blood loss, ewer analgesic requirements, and shorter hospital stays. Laparoscopic surgery was signi cantly less success ul in resolving the tubal pregnancy, but this was balanced by the just-mentioned bene ts o minimally invasive surgery. With improvements in laparoscopic equipment and with accrued experience, cases previously managed by laparotomy, such as ruptured tubal or intact interstitial pregnancies, can now be considered or laparoscopy in those with commensurate skills (Sagiv, 2001). Among experienced surgeons, shorter operating times and expedited hemorrhage control are both advantages o laparoscopic intervention or ruptured ectopic pregnancies (Cohen, 2013). A metaanalysis using data rom two trials concluded that compared with laparotomic salpingostomy, laparoscopic salpingostomy leads to one case o persistent trophoblastic disease or every 12 women undergoing the laparoscopic approach (Mol, 2008). One multicenter trial compared a multidose methotrexate protocol with laparoscopic salpingostomy and ound no di erences or tubal preservation and primary treatment success (Hajenius, 1997). However, in this same study group, health-related quality o li e actors such as pain, posttherapy depression, and decreased perception o health were signi cantly impaired a ter systemic methotrexate compared with laparoscopic salpingostomy (Nieuwkerk, 1998). Evidence is con icting when single-dose methotrexate is compared with surgical intervention. In two separate studies, single-dose methotrexate was overall less success ul in resolving pregnancy than laparoscopic salpingostomy, although tubal patency and subsequent uterine pregnancy rates were similar between both groups (Fernandez, 1998; Sowter, 2001). Krag Moeller and associates (2009) reported during a median surveillance period o 8. Moreover, cumulative spontaneous intrauterine pregnancy rates were not di erent between the methotrexate group (73 percent) and the surgical group (62 percent). Intuitively, it is dif cult to accurately predict which woman will have an uncomplicated course with such management. Interestingly, in this study, there was no di erence in ipsilateral tubal patency or 1-year ertility rates with either success or ailure o expectant management. An argument could be made that the minimal side e ects o methotrexate make it pre erable to a potentially prolonged surveillance and associated patient anxiety. These were outlined by Spiegelberg (1878) and include: (1) the ipsilateral tube is intact and distinct rom 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 in the placental tissue. A more recent increased incidence in ovarian pregnancy likely is arti actual due to improved imaging. Nearly a third o women with an ovarian pregnancy present with hemodynamic instability because o rupture. T us, abdominal pain ollowing conservative management prompts immediate suspicion or persistent trophoblast proli eration. Following salpingostomy, persistent ectopic pregnancy is more likely with very early pregnancies. Speci cally, surgical management is more dif cult because pregnancies smaller than 2 cm are harder to visualize and completely remove. The optimal monitoring schedule to identi y persistent ectopic pregnancy a ter surgical therapy has not been determined. Spandor er and associates (1997) estimated the risk o persistent ectopic pregnancy based on Interstitial pregnancies implant in the proximal tubal segment that lies within the muscular uterine wall. Swelling lateral to the insertion o the round ligament is the characteristic anatomic nding. Incorrectly, these are sometimes called cornual pregnancies, but this term describes conceptions that develop in the horns o uteri with müllerian anomalies (Lau, 1999; Moawad, 2010). In the past, interstitial pregnancies usually ruptured ollowing 8 to 16 weeks o amenorrhea. Risk actors are similar to others discussed, although prior ipsilateral salpingectomy is a speci c risk actor or interstitial pregnancy (Lau, 1999). Because o the proximity o these pregnancies to the uterine and ovarian arteries, hemorrhage with rupture can be severe and is associated with mortality rates as high as 2. Distinct rom interstitial pregnancy, the term angular pregnancy describes intrauterine implantation in one o the lateral angles o the uterus and medial to the uterotubal junction and round ligament. Transvaginal sonogram, parasagittal view shows an empty uterine cavity (white arrows) and a mass lateral to the uterine fundus (red arrow). Improved imaging modalities, such as 3-dimensional sonography, may help di erentiate eccentrically located gestational sacs rom an interstitial pregnancy (Singh, 2015; anaka, 2014). For interstitial pregnancies, surgical management involves cornual resection by either laparotomy or laparoscopy (Section 43-9, p. As discussed or suspected tubal pregnancy, interstitial pregnancy can now o ten be diagnosed early enough to consider conservative medical therapy (Bernstein, 2001). Given its low incidence, no consensus regarding prediction o success using methotrexate has been established. Deruelle and coworkers (2005) advocate adjuvant postmethotrexate uterine artery embolization to help avert hemorrhage and hasten ectopic pregnancy resolution. O other therapies, uterine artery methotrexate in usion and embolization combined with systemic methotrexate has shown promising results (Hiersch, 2014; Krissi, 2014). Hysteroscopic resection or transcervical suction curettage o interstitial pregnancies has been described (Sanz, 2002; Zhang, 2004). Following either medical or conservative surgical management, the risk o uterine rupture with subsequent pregnancies is unclear. T us, care ul observation o these women during pregnancy, along with strong consideration o elective cesarean delivery, is warranted. A risk actor unique to cervical pregnancy is a history o dilatation and curettage in a prior pregnancy and is seen in nearly 70 percent o cases (Hung, 1996; Pisarska, 1999). For most hemodynamically stable women with a rsttrimester cervical pregnancy, nonsurgical management with systemic methotrexate can be o ered and administered as in able 7-3. Jeng and colleagues (2007) also described 38 cases success ully treated with methotrexate injection into the gestational sac. Resolution and uterine preservation is achieved with methotrexate regimens or gestations < 12 weeks in 91 percent o cases (Kung, 1997). For this reason, many induce etal death with intracardiac or intrathoracic injection o potassium chloride (Jeng, 2007; Verma, 2009). Uterine artery embolization, either be ore or a ter methotrexate administration, may be an additional adjunct to limit bleeding complications (Cipullo, 2008; Hirakawa, 2009). Although conservative management is easible or many women with cervical pregnancies, surgical intervention may also be selected. Moreover, in those with advanced gestations or with bleeding uncontrolled by conservative methods, hysterectomy is typically required. Importantly, patients should understand the increased risk o urinary tract injury with hysterectomy due to the close proximity o the ureters to the ballooned cervix. Prior to either procedure, uterine artery embolization may be considered to limit intra- and postoperative bleeding (Nakao, 2008; rambert, 2005). Sonographic findings with cervical pregnancy 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. Hysterectomy specimen containing a cervical ectopic pregnancy from a different case. Following curettage, in the event o hemorrhage, a 26F Foley catheter with a 30-mL balloon can be placed intracervically and in ated to e ect hemostasis and to monitor uterine drainage (Ushakov, 1997). First, an empty uterine cavity is identified by a bright hyperechoic endometrial stripe (white arrow). Last, an intrauterine mass is seen in the anterior part of the uterine isthmus (red arrows).

Additional information:

• Metformin and pioglitazone

The American College o Obstetricians and Gynecologists (2014c) outlines legislative, institutional, and social barriers to abortion training and supports the use o "opt-out" programs. In these, abortion training is integrated as a standard part o the residency schedule, but residents with religious or moral objections can decline to participate. Ryan Residency raining Program was established in 1999 to improve residency training in abortion and amily planning. Disappointingly, a recent survey o United States residency programs determined that no abortion training was available in 16 percent o programs and that 30 percent continue to use the "opt-in" approach (urk, 2014). Other programs teach residents technical aspects through management o early incomplete and missed abortions and through pregnancy interruption or etal death, severe etal anomalies, and li e-threatening medical or surgical disorders (Steinauer, 2005). Freedman and coworkers (2010) rightly emphasize that abortion training should include discussion o the social, moral, and ethical aspects o the procedure. By 2010, these were located in 22 departments o obstetrics and gynecology at academic centers nationwide. With outpatient abortion, capabilities or cardiopulmonary resuscitation and or immediate trans er to a hospital must be available. First-trimester abortion can be per ormed either medically or surgically by several methods that are listed in Table 6-10. Distinctive eatures o each technique were reviewed by the American College o Obstetricians and Gynecologists (2009). Results with either surgical or medical methods are comparable with those or spontaneous miscarriage as previously shown in able 6-4. Both have a high success rate-95 percent with medical and 99 percent with surgical techniques. With medical therapy, surgery is usually avoided as is the need or sedation (Table 6-11). Medical terminations have lower average costs and may allow or more privacy during the termination. However, medical abortion may extend or days up to a ew weeks, bleeding is usually heavier and less predictable, and incomplete abortion is more common with medical versus surgical abortion (Niinimäki, 2009; Robson, 2009). Likely or these reasons, only 10 percent o abortions in the United States are managed using medical methods (empleton, 2011). It also emphasizes the need to provide standard-o care counseling and timely re erral i providers have individual belie s that preclude pregnancy termination. From a mail survey o 1800 obstetrician-gynecologists, 97 percent had encountered women seeking an abortion, but only 14 percent per ormed them (Stulberg, 2011). In any event, any Medical a All procedures are aided by pretreatment using hygroscopic cervical dilators. Comparison of Medical versus Surgical Abortion Factor Invasive Pain V aginal bleeding Incomplete abortion Failure rate Severe hemorrhage Infection rate Anesthesia Time involved Medical Usually no More Prolonged, unpredictable More common 2­5% 0. Marginal bene ts ascribed to misoprostol included easier cervical dilatation and a lower composite complication rate. Another e ective cervical-ripening agent is the progesterone antagonist mi epristone (Mi eprex). Other options include ormulations o prostaglandins E2 and F2, which have unpleasant side e ects and are usually reserved as second-line drugs or cervical ripening (Kapp, 2010). The pregnancy is then evacuated by suctioning out the contents-suction curettage, by mechanically scraping out the contents-sharp curettage, or both. According to one review, the use o suction curettage is superior i available (unçalp, 2010). In addition to intravenously or orally administered sedatives, success has been reported with paracervical lidocaine blockade, with or without other analgesics (Renner, 2012). Perioperative antibiotic prophylaxis is also recommended as described on page 143. Data from American College of Obstetricians and Gynecologists, 2015; Templeton, 2011. Surgical Abortion Surgical pregnancy termination includes a transvaginal approach through an appropriately dilated cervix. Rarely, pregnancies are evacuated transabdominally by either hysterotomy or hysterectomy. O transvaginal procedures, electric vacuum aspiration is the most commonly used orm and is illustrated in Chapter 43 (p. Alternatively, manual vacuum aspiration is done with a similar cannula that attaches to a handheld syringe or its vacuum source. Menstrual Aspiration Aspiration o the endometrial cavity within 1 to 3 weeks a ter a missed menstrual period has been re erred to as menstrual extraction, menstrual induction, instant period, traumatic abortion, and mini-abortion. The procedure is done using a exible 5- or 6-mm Karman cannula and attached syringe. The primary drawbacks are that the small pregnancy may be missed or an ectopic pregnancy can be unrecognized. Despite the possibility o missing the products, Paul and coworkers (2002) reported a 98-percent success rate with more than 1000 such procedures. Cervical Preparation For transvaginal evacuation, preoperative cervical ripening so tens and slowly dilates the cervix to minimize trauma rom mechanical dilatation. This preparation is typically associated with less pain, a technically easier procedure, and shorter operating times (Kapp, 2010). O methods, hygroscopic dilators draw water rom cervical tissues and expand to gradually dilate the cervix. One type is derived rom various species o Laminaria algae that are harvested rom the ocean oor (Chap. Schneider and associates (1991) described 21 cases in which women who had a hygroscopic dilator placed changed their minds. O 17 women who chose to continue their pregnancy, 14 carried to term, two delivered preterm, and one miscarried 2 weeks later. None su ered in ection-related morbidity, including three untreated women with cervical cultures positive or Chlamydia trachomatis. In spite o this generally reassuring report, it seems prudent to presume irrevocability with regard to dilator placement and abortion. In the metaanalysis by Kapp (2010), ef cacy o these medications was ound to be similar to that o hygroscopic dilators. The most common is misoprostol (Cytotec), which is used o -label, and patients are counseled accordingly (ang, 2013). The dose Manual Vacuum Aspiration this procedure is similar to menstrual aspiration but is used or early pregnancy ailures or elective termination up to 12 weeks. Some recommend that pregnancy terminations done in the of ce with this method be limited to 10 weeks because blood loss rises sharply between 10 and 12 weeks (Masch, 2005; West all, 1998). A ter this time, some recommend that osmotic dilators be placed the day prior to or misoprostol given 2 to 4 hours be ore the procedure. A vacuum is created in the syringe attached to the cannula, which is inserted transcervically into the uterus. A ter this time, available data-albeit less robust-support surgical abortion as pre erable. Bleeding and cramping with medical termination can be signi cantly worse than menstrual cramps, thus adequate analgesia, usually including a narcotic, is provided. Currently, only three medications or early medical abortion have been widely studied. These are used either alone or in combination and include: (1) the antiprogestin mi epristone, (2) the antimetabolite methotrexate, and (3) the prostaglandin misoprostol. Mi epristone and methotrexate increase uterine contractility by reversing progesteroneinduced inhibition, whereas misoprostol directly stimulates the myometrium. Clark and associates (2006) have reported that mi epristone causes cervical collagen degradation, possibly rom increased expression o matrix metalloproteinase. Methotrexate and misoprostol are both teratogens, thus there must be a commitment to completing the abortion once these drugs are given. With these three agents, several dosing schemes are e ective, and some are shown in Table 6-12. For these regimens, misoprostol is either given alone or given with methotrexate or mi epristone. As discussed on page 144 and previously shown in able 6-4, any o several regimens used or "early pregnancy loss" are also likely to be success ul or elective pregnancy interruption (American College o Obstetricians and Gynecologists, 2014e). Similar results were reported rom 10 large urban Planned Parenthood clinics (Fjerstad, 2009). In this later study, buccal misoprostol- 1 N Administration With the mi epristone regimens, mi epristone treatment is ollowed by misoprostol given at that same time or up to 72 hours later. Some pre er that misoprostol be administered on site, a ter which the woman typically remains or 4 hours. Symptoms are common within 3 hours and included lower abdominal pain, vomiting, diarrhea, ever, and chills/shivering. In the rst ew hours a ter misoprostol is given, i the pregnancy appears to have been expelled, an examination is done to con rm expulsion. I the pregnancy has not been expelled, a pelvic examination is per ormed, and the patient is discharged and appointed to return in 1 to 2 weeks. At this time, i clinical or sonographic evaluation ails to con rm completed abortion, a suction procedure usually is recommended. With the methotrexate regimens, misoprostol is given 3 to 7 days later, and women are seen again at least 24 hours a ter misoprostol administration. They are next seen approximately 7 days a ter methotrexate is given, and sonographic examination is per ormed. Regimens for Medical Termination of Early Pregnancy Mifepristone/Misoprostol a Mifepristone, 100­600 mg orally followed by: b Misoprostol, 200­600 µg orally or 400­800 µg vaginally, buccally, or sublingually given immediately or up to 72 hours Met otrexate/Misoprostol c Methotrexate, 50 mg/m 2 intramuscularly or orally followed by: d Misoprostol, 800 µg vaginally in 3­7 days. Repeat if needed 1 week after methotrexate initially given Misoprostol Alone e 800 µg vaginally or sublingually, repeated for up to three doses a Doses of 200 versus 600 mg are similarly effective. Oral route may be less effective; possibly more side effects, namely, nausea and diarrhea. Data from Borgatta, 2001; Coyaji, 2007; Creinin, 2001, 2007; Fekih, 2010; Guest, 2007; Hamoda, 2005; Honkanen, 2004; Jain, 2002; K ulier, 2011; Pymar, 2001; Raghavan, 2009; Schaff, 2000; Shannon, 2006; von Hertzen, 2003, 2007, 2009, 2010; Winikoff, 2008. I abortion has not occurred by the second visit, it is usually completed by suction curettage. With regimens using solely misoprostol, an initial 800-µg dose is repeated every 3 to 24 hr or up to three doses. Importantly, misoprostol-only regimens are associated with signi cantly higher continuing pregnancy rates (Grossman, 2004). The American College o Obstetricians and Gynecologists (2014e) recommends that a woman be instructed to contact her provider during these regimens i bleeding soaks two or more pads per hour or at least 2 hours. Unnecessary surgical intervention in women undergoing medical abortion can be avoided by the proper interpretation o ollow-up sonographic results. Speci cally, i no gestational sac is seen and there is no heavy bleeding, then intervention is unnecessary. This is true even when, as is common, the uterus contains sonographically evident debris. Another study reported that a multilayered sonographic pattern indicated a success ul abortion (zeng, 2013). Assessment o the clinical course along with bimanual pelvic examination is generally adequate. Increasing evidence suggest that misoprostol is a sa e and e ective method to ully evacuate the uterus in the case o retained products ollowing spontaneous or surgical abortion (American College o Obstetricians and Gynecologists, 2009). O long-term sequelae, abortion-related deaths are likely underreported (Horon, 2005). Legally induced abortion, perormed by trained gynecologists, especially when per ormed during the rst 2 months o pregnancy, has a mortality rate o less than 1 per 100,000 procedures (Grimes, 2006; Pazol, 2014). Moreover, pregnancy-associated mortality is 14- old greater than abortion-related mortality-8 versus 0. Some data suggest that certain adverse pregnancy outcomes are more common in women who have had an induced abortion (Maconochie, 2007). Multiple sharp curettage procedures may raise the subsequent risk o placenta previa, whereas vacuum aspiration procedures likely do not (Johnson, 2003). Other studies suggest that subsequent pregnancy outcomes are similar regardless o whether a prior induced abortion was completed medically or surgically (Virk, 2007). The rates o in ertility or ectopic pregnancy do not appear to be signi cantly increased by prior abortion. There may be exceptions i there are postabortal in ections, especially those caused by chlamydial species. It may be reasonable to compare women undergoing a pregnancy termination with those having a rst-trimester miscarriage, in whom the 5-year live-birth rate was approximately 80 percent ollowing pregnancy loss (Smith, 2009). In one case-control study, there was no evidence or excessive mental health disorders (Munk-Olsen, 2011). A review by the American College o Obstetricians and Gynecologists (2013a) concluded that there is no causal relationship between prior induced abortion and breast cancer risk. These include: in situ intrauterine device; severe anemia, coagulopathy, or anticoagulant use; and signi cant medical conditions such as active liver disease, cardiovascular disease, or uncontrolled seizure disorders. Because misoprostol diminishes glucocorticoid activity, women with disorders requiring glucocorticoid therapy are usually excluded (American College o Obstetricians and Gynecologists, 2009). In women with renal insuf ciency, the methotrexate dose is modi ed and given with caution, or pre erably, another regimen is chosen (Kelly, 2006). These hormonal events agree with histological changes observed in endometrial biopsies (Boyd, 1972). Accordingly, e ective contraception should be initiated soon a ter abortion unless another pregnancy is desired immediately. An intrauterine device can be inserted a ter the procedure is completed (Bednarek, 2011; Shimoni, 2011). Alternatively, any o the hormonal contraceptive methods discussed in Chapter 5 can be initiated at this time (Madden, 2009; Reeves, 2007). As might be predicted, complication rates increase with progressing gestation in both spontaneous and induced abortions.

Hog Apple (Podophyllum). Fulvicin.

• Are there safety concerns?
• Dosing considerations for Podophyllum.
• Raised areas on the tongue and mouth in people with immune system diseases (hairy leukoplakia), liver problems, cancer, and other conditions.
• What is Podophyllum?
• Treating human papilloma virus (genital and anal warts).
• How does Podophyllum work?

Source: http://www.rxlist.com/script/main/art.asp?articlekey=96783

Although abdominal incision in ection may develop alone or with pelvic in ection ollowing abdominal hysterectomy, it develops uncommonly a ter other gynecologic procedures. Unlike pelvic in ection, the incidence o this in ection is not altered by antimicrobial prophylaxis. I this is suspected early and therapy is initiated, the complete syndrome may not develop. Serologies or Rocky Mountain spotted ever, measles, and leptospirosis must be negative. While awaiting culture results or selection o speci c antistaphylococcal antibiotics, empiric therapy covers both methicillin-susceptible and methicillin-resistant S aureus. Vancomycin (15 to 20 mg/kg/dose) can be given every 8 to 12 hours, not exceeding 2 g per dose. These patients may develop signi cant edema and are best managed in an intensive care unit. This syndrome may also ollow gynecologic surgical procedures such as D & C, hysterectomy, urethral suspension, and tubal ligation. Necrotizing Fasciitis Although described in the 1870s, it was not named until 1952, by a Parkland Hospital surgeon (Wilson, 1952). Risk actors or this postoperative incision in ection are age older than 50 years, arteriosclerotic heart disease, diabetes mellitus, obesity, debilitating disease, smoking, and previous radiation therapy, all o which are associated with decreased tissue per usion. In our clinical service, vulvar in ection in obese diabetic women is a prominent risk. Only approximately 20 percent o cases ollow surgery, the majority developing a ter minor injuries or insect bites. Bacteria recovered rom women with this in ection are similar to those recovered rom any postoperative gynecologic in ection site, namely predominantly E coli, E aecalis, Bacteroides spp, Peptostreptococcus spp, S aureus, and groups A and B hemolytic streptococci. Although this postoperative super cial incisional in ection begins like any other postoperative in ection with pain and erythema, its hallmark is subcutaneous and super cial ascial necrosis, mani ested by excessive tissue edema in adjacent areas. Crepitus or induration and edema beyond the region o visible erythema may be present. The skin will slip over underlying tissue, and i incised, due to the lack o vascularity, there will be no bleeding but instead usually a thin gray transudate. In obvious cases, no imaging is needed, and patients are prepared or surgical debridement. In less-clear cases, radiographs or C scans, i these can be quickly obtained, may add in ormation by revealing gas in a ected tissues produced by clostridial species such as Clostridium per ringens. Although broad-spectrum antibiotic administration is required, the cornerstone o treatment is prompt recognition and immediate surgical removal o necrotic tissue to a level at which viable bleeding tissue is reached. Although this is potentially dis guring, postponing surgery while waiting or antimicrobial activity only increases the volume o tissue death. The required intraoperative resection was extensive (Used with permission from Dr. Early atality rates or patients with this in ection approximated 20 percent in the systematic review o 1463 patients by Goh and associates (2014). Wounds are le t open and treated as wound in ections as described earlier with local hydrotherapy or a wound vacuum device. These newer drugs are expensive and may have restricted ormulary use to only in ectious disease specialists. In early stages, surrounding cellulitis may be the most prominent nding and only a small or no abscess is identi ed. When present, smaller abscesses may be treated with incision and drainage, abscess packing i indicated, and oral antibiotics to treat surrounding cellulitis. This provides adequate pain control or abscess drainage and or abscess cavity exploration to disrupt loculated areas o pus, as described in Section 43-21 (p. Drainage can typically be completed in an outpatient setting and is described in Section 43-18 (p. The most common bacteria isolated rom these abscesses include anaerobic Bacteroides and Peptostreptococcus spp and aerobic E coli, S aureus, and E aecalis (Bhide, 2010; Kessous, 2013). Accordingly, polymicrobial coverage is selected, and suitable single-agent oral outpatient therapy includes, among others, trimethoprim-sul amethoxazole, amoxicillin-clavulanate, second-generation cephalosporins, or uoroquinolones, such as cipro oxacin. Common isolates include Staphylococcus, group B Streptococcus, Enterococcus species, E coli, and P mirabilis. Gynecologic Infection American College o Obstetricians and Gynecologists: Vaginitis. Sex ransm Dis 30(4):310, 2003 Association o Public Health Laboratories: Laboratory diagnostic testing or Chlamydia trachomatis and Neisseria gonorrhoeae. Genitourin Med 66:24, 1990 Bornstein J, Lakovsky Y, Lavi I, et al: the classic approach to diagnosis o vulvovaginitis: a critical analysis. Am J Obstet Gynecol 176:1270, 1997 Centers or Disease Control and Prevention: Expedited partner therapy in the management o sexually transmitted diseases. Accessed April 14, 2015 Centers or Disease Control and Prevention: Seroprevalence o herpes simplex virus type 2 among persons aged 14­49 years-United States, 2005­2008. Microbes In ect 10(6):620, 2008 Daley G, Russell D, abrizi S, et al: Mycoplasma genitalium: a review. Actinomyces Infection Actinomyces israelii is a gram-positive, slow-growing, anaerobic bacterium ound to be part o the indigenous genital ora o healthy women (Persson, 1984). Pelvic in ection and abscess are rare, even in those identi ed to harbor the bacteria. Importantly, i signs or symptoms o in ection develop in women who harbor Actinomyces, the device is removed and antimicrobial therapy instituted. Early ndings include ever, weight loss, abdominal pain, and abnormal vaginal bleeding or discharge. Actinomyces is sensitive to antimicrobials with gram-positive coverage, notably the penicillins. Sex ransm Dis 32:185, 2005 American College o Obstetricians and Gynecologists: Antibiotic prophylaxis or gynecologic procedures. Am J Obstet Gynecol 155:954, 1986 Hae ner H: Current evaluation and management o vulvovaginitis. Am J Obstet Gynecol 166:100, 1992 Leitich H, Kiss H: Asymptomatic bacterial vaginosis and intermediate ora as risk actors or adverse pregnancy outcome. J Clin Microbiol 49(5):1990, 2011 Lippes J: Pelvic actinomycosis: a review and preliminary look at prevalence. Arch Intern Med 169(13):1233, 2009 Mayo Clinic: Symposium on Antimicrobial Agents. Obstet Gynecol 73:622, 1989 Persson E, Holmberg K: A longitudinal study o Actinomyces israelii in the emale genital tract. Acta Obstet Gynecol Scand 63:207, 1984 Romosan G, Bjartling C, Skoog L, et al: Ultrasound or diagnosing acute salpingitis: a prospective observational diagnostic study. Ann Intern Med 107:204, 1987 Schachter J, Stephens R: In ections caused by Chlamydia trachomatis. Ultrasound Obstet Gynecol 12(1):56, 1998 orrone E, Weinstock H: Prevalence o Chlamydia trachomatis genital in ection amongpersonsaged 14­39 years-United States, 2007­2012. Accessed November 26, 2014 Van der Pol B: Trichomonas vaginalis in ection: the most prevalent nonviral sexually transmitted in ection receives the least public health attention. Recent perspectives in the diagnosis and evidencebased treatment o Mycoplasma genitalium. Contraception 75:S48, 2007 Westrom L: E ect o acute pelvic in ammatory disease on ertility. They may relate protracted histories o assorted diagnoses and treatments by numerous providers and may voice rustration and doubt that relie is possible. Patients are not promised a cure but rather that every e ort will be made to alleviate their symptoms. This can require multiple visits, tissue sampling, treatment attempts, and even a multidisciplinary plan. A patient-provider partnership approach to management enhances compliance and care satis action. During counseling, the suspected diagnosis, current treatment plan, and recommended vulvar skin care are outlined. Printed materials that explain common conditions, medication use, and skin care are help ul. Patients are o ten relieved to learn that their complaints and conditions are not unique. Diagnosis History the lower reproductive tract, comprising the vulva, vagina, and cervix, exhibits a wide spectrum o benign and neoplastic diseases. Disorder characteristics o ten overlap, and thus di erentiating normal variants, benign disease, and potentially serious lesions can be challenging. Lower reproductive tract in ection is a requent cause and discussed in Chapter 3, whereas congenital anomalies and preinvasive neoplasia are in requent and described in Chapters 18 (p. The benign lesions highlighted in this chapter are common, and mastery o their identi cation and treatment is essential. Scheduling adequate time or the initial evaluation is a wise investment, as detailed in ormation is essential. Symptom characterization includes descriptions o abnormal sensations, duration, precise location, and associated vaginal pruritus or discharge. Patients o ten re er to vulvar pruritus as vaginal, and symptom location should be clari ed. A thorough medical history addresses systemic illnesses, medications, and known allergies. Obstetric, sexual, and psychosocial histories and any potentially provocative events around the time o symptom onset o ten suggest etiologies. Patients may have been previously diagnosed with psoriasis, eczema, or dermatitis at other body sites. Patients may identi y oods that provoke or intensi y symptoms, and in such cases, a ood diary may be help ul. Excessive washing and use o wash cloths can result in skin drying and mechanical trauma. Washing o ten becomes more aggressive with pruritus as patients assume their hygiene is lacking. Any o these practices can create an escalating itch-scratch cycle or exacerbate the symptoms o other preexisting dermatoses. Last, patients requently use nonprescription remedies or relie o vulvovaginal itching or perceived odor. These products commonly contain multiple known contact allergens, and their use is discouraged (Table 4-1). Accordingly, pathology can develop in this area, although requency estimates are di cult because o patient underreporting and clinician misdiagnosis. Lesions may result rom allergen or irritant exposure, in ection, trauma, or neoplasia. As a result, symptoms may be acute or chronic and include pain, pruritus, dyspareunia, bleeding, and discharge. E ective therapies are available or most disorders, yet embarrassment and ear may prove signi cant roadblocks to care or many women. Common Vulvar Irritants and Allergens General Categories Antiseptics Body fluids Colored or scented toilet paper Condoms Contraceptive creams, jellies, foams Dyes Emollients Laundry detergents, fabric softeners, dryer sheets Rubber products Sanitary baby or adult bathroom wipes Sanitary pads or tampons Soaps, bubble bath and salts, shampoos Topical anesthetics Topical antibacterials Topical corticosteroids Topical antifungal creams Examples of Specific Agents Povidone iodine, hexachlorophene Semen, feces, urine, saliva Latex, lubricant, spermicide, thiuram Nonoxynol-9, lubricants 4-Phenylene diamine Lanolin, jojoba oil, glycerin Latex, thiuram 87 Benzocaine, lidocaine Neomycin, bacitracin, polymyxin, framycetin, tea tree oil Clobetasol propionate Ethylene diamine, sodium metabisulfite Data from American College of Obstetricians and Gynecologists, 2010; Crone, 2000; Fisher, 1973; Marren, 1992. Physical Examination Examination o the vulva and surrounding skin is completed using adequate lighting, optimal patient positioning, and a magni ying lens or colposcope. Both ocal and generalized skin changes are care ully noted, as neoplasia may arise within a eld o generalized dermatosis. A medical record diagram noting vulvar ndings and symptoms aids treatment assessment over time. Vaginal complaints or vulvar conditions without obvious etiology typically prompt vaginal examination. Care ul inspection may reveal generalized inf ammation or atrophy, abnormal discharge, or ocal mucosal lesions such as ulcers. In these cases, saline preparation o secretions or microscopic evaluation ("wet prep"), vaginal pH testing, and aerobic culture to detect yeast overgrowth are collected. A general skin examination, including the oral mucosa and axillae, may suggest the cause o some vulvar conditions. A ocused neurologic examination to evaluate lower extremity sensation and strength as well as perineal sensation and tone may help evaluate vulvar dysesthesias. Vulvar Biopsy Vulvar skin changes are requently nonspeci c and typically require biopsy or accurate diagnosis. Biopsy is strongly considered i the cause o symptoms is not obvious; i initial empiric treatment ails; i the cause o symptoms is not obvious; or i ocal, exophytic, or hyper-/hypopigmented lesions are present. During biopsy, ulcerative lesions are sampled at their edges, and hyper- or hypopigmented areas at their thickest region (Mirowski, 2004). Conditions with variable histologic appearance may require multiple biopsies or correct disorder classi cation. First, the biopsy site is cleaned with an antimicrobial agent and in ltrated with a 1- or 2-percent lidocaine solution. The open, circular blade is designed to remove a shallow disc o tissue when gently pressed against the skin and rotated. Keyes punches are available in various diameters, ranging rom 2 to 6 mm, and size selection is based on lesion dimensions and on whether sampling or excision is the goal. Vulvar skin and lesion thicknesses are variable, and over-rotation o or undue pressure on the Keyes punch is avoided. Rotation and pressure should stop when decreased resistance is elt, signaling the dermis has been reached.

Usage: p.c.

These antibiotics are designed or polymicrobial bacterial in ections, primarily those with resistant aerobic gram-negative bacteria not susceptible to other -lactam agents. They should be reserved to preserve ef cacy by preventing the development o resistance. It has a spectrum o activity similar to that o aminoglycosides, that is, gram-negative aerobic species. Like other -lactam antibiotics, these compounds inhibit bacterial cell wall synthesis by binding to penicillin-binding proteins or causing cell lysis. Aztreonam has af nity only or the binding proteins o the gram-negative bacteria and lacks af nity or either grampositive bacteria or anaerobic organisms. For the gynecologist, aztreonam provides coverage or gram-negative aerobic bacteria, which is usually provided by aminoglycosides, or patients with signi cantly impaired renal unction or aminoglycoside allergy. Moreover, it is one o the mainstays o combination antimicrobial therapy given to women with serious postoperative or community-acquired pelvic in ections, including pelvic abscess. Since it is active only against obligate anaerobes, metronidazole must be combined with agents e ective against gram-positive and gram-negative aerobic bacterial species, such as ampicillin and gentamicin. Up to 12 percent o patients taking oral metronidazole may have nausea, and an unpleasant metallic taste has also been described. Patients should abstain rom alcohol use to avoid a disul ram-like e ect and emesis. Peripheral neuropathy and convulsive seizures have been reported, are probably doserelated, and are rare. Clindamycin this antibiotic is a workhorse in the treatment o serious gynecologic in ections. Clindamycin is primarily active against aerobic gram-positive bacteria and most anaerobic bacteria, with little activity against aerobic gram-negative bacteria. It may be delivered by one o three routes: orally, intravenously, or vaginally (ovules or 2-percent cream). The principal application o clindamycin or the gynecologist has been its combination with gentamicin and administration to women with serious community-acquired or postoperative so t-tissue in ections or pelvic abscess. Moreover, in women with early stages o hidradenitis suppurativa, some patients improve with long-term topical or oral clindamycin. Because there are parenteral and oral orms o this antibiotic, patients can transition rom the more expensive parenteral therapy to oral therapy early. Fluoroquinolones Also known simply as quinolones, these antibiotics have become rst-line agents or treating various in ections because o their excellent bioavailability with oral administration, tissue penetration, broad-spectrum antibacterial activity, long hal -lives, and good sa ety pro le. As with cephalosporins, uoroquinolones are separated into generations by their development, antibacterial activity, and pharmacokinetic properties. Quinolones are contraindicated in children, adolescents, and pregnant and breast eeding women because they may a ect Gynecologic Infection cartilage development. These agents are widely used by gynecologists to treat acute lower urinary tract in ections and some sexually transmitted diseases. However, overuse has limited their use ulness in certain in ections due to bacterial resistance (Centers or Disease Control and Prevention, 2007). I a less expensive, sa er, and equally e ective alternative agent is available to treat a given in ection, it should be used to preserve uoroquinolone ef cacy. Most young sexually active women in the United States who have genital ulcers will have herpes simplex in ection or syphilis, but some will have chancroid, lymphogranuloma venereum, or granuloma inguinale. Sexual contacts require examination and treatment, and both require reevaluation ollowing treatment. The virus enters sensory nerve endings and undergoes retrograde axonal transport to the dorsal root ganglion, where the virus develops li elong latency. Spontaneous reactivation by various events results in anterograde transport o viral particles/protein to the sur ace. It is postulated that immune mechanisms control latency and reactivation (Cunningham, 2006). In ected patients can shed in ectious virus while asymptomatic, and most in ections are transmitted sexually by patients who are unaware o their in ection. Tetracyclines These bacteriostatic antimicrobials are commonly used orally and inhibit bacterial protein synthesis. Doxycycline, tetracycline, and minocycline are active against many gram-positive and gram-negative bacteria, although their activity is greater against gram-positive species. Susceptible organisms also include several anaerobes, Chlamydia and Mycoplasma species, and some spirochetes. Speci cally, or these in ections, minocycline and doxycycline are superior to tetracycline. As such, they provide antiinammatory as well as antimicrobial activity or in ammatory conditions such as acne vulgaris and hidradenitis suppurativa. In teeth and growing bones, tetracyclines readily bind calcium, causing de ormity, growth inhibition, or discoloration. Accordingly, tetracyclines are not prescribed or pregnant or nursing women or or children younger than 8 years. Vaginal ora also may be altered with resultant Candida species overgrowth and symptomatic vulvovaginitis. Symptoms Patient symptoms at initial presentation will depend primarily on whether or not a patient during the current episode has antibody rom previous exposure. I a patient has no antibody, the attack rate in an exposed person approaches 70 percent. Up to 90 percent o those who are symptomatic with their initial in ection will have another episode within a year. The virus in ects viable epidermal cells, the response to which is erythema and papule ormation. The three stages o lesions are: (1) vesicle with or without pustule ormation, which lasts approximately a week; (2) ulceration; and (3) crusting. In contrast, erosion describes partial loss o the epidermis without dermal penetration. Alternatively or additionally, herpetic lesions can involve the vagina, cervix, bladder, anus, and rectum. Commonly, a woman has other signs o viremia such as a low-grade ever, headache, malaise, and myalgias. Viral load undoubtedly contributes to the number, size, and distribution o lesions. Normal host de ense mechanisms inhibit viral growth, and healing starts within 1 to 2 days. Immune-de cient patients are at increased susceptibility but display diminished response and delayed healing. Heralding paresthesias are requently described as pruritus or tingling in the area prior to lesion ormation. Clinical mani estations or women with recurrences are more limited, with only 1 week or less o symptoms. IgM testing can lead to ambiguous results as the IgM assays are not type-speci c and also may be positive during a recurrent outbreak. It can also add management in ormation or couples thought but not con rmed to be discordant or in ection (American College o Obstetricians and Gynecologists, 2014b). Analgesia with nonsteroidal antiin ammatory drugs or a mild narcotic such as acetaminophen with codeine may be prescribed. Patient education is mandatory, and speci c topics include the natural history o the disease, its sexual transmission, methods to reduce transmission, and obstetric consequences. A comprehensive discussion o obstetric management is ound in Williams Obstetrics, Diagnosis the gold standard or the diagnosis o genital herpes is tissue culture. Importantly, a negative culture result does not mean that there is no herpetic in ection. The herpes simplex virus is surrounded by envelope glycoproteins, and o these, glycoprotein G is the antigen o interest or antibody screening. For all women, acquisition o this in ection may have signi cant psychological impact, and several websites provide patient in ormation and support. Women with genital herpes should re rain rom sexual activity with unin ected partners when prodrome symptoms or lesions are present. Latex condom use potentially reduces the risk or herpetic transmission (Martin, 2009; Wald, 2005). Currently available antiviral therapy includes acyclovir (Zovirax), amciclovir (Famvir), and valacyclovir (Valtrex). Although these agents may hasten healing and decrease symptoms, therapy does not eradicate latent virus or a ect uture rate o recurrent in ections. Oral Agents for Genital Herpes Simplex Infection First clinical episode Acyclovir 400 mg three times daily for 7­10 days or Acyclovir 200 mg five times daily for 7­10 days or Famciclovir (Famvir) 250 mg three times daily for 7­10 days or V alacyclovir (V altrex) 1 g twice daily for 7­10 days Episodic therapy for recurrent disease Acyclovir 400 mg three times daily for 5 days or Acyclovir 800 mg twice daily for 5 days or Acyclovir 800 mg three times daily for 2 days or Famciclovir 125 mg twice daily for 5 days or Famciclovir 1 g twice daily for 1 day or Famciclovir 500 mg once, then 250 mg twice daily for 2 days or V alacyclovir 500 mg twice daily for 3 days or V alacyclovir 1 g once daily for 5 days Suppressive therapy Acyclovir 400 mg twice daily or Famciclovir 250 mg twice daily or V alacyclovir 0. Patients may be given a prescription ahead o time so that medication is available to begin therapy with prodromal symptoms. I episodes recur at requent intervals, a woman may elect daily suppressive therapy, which reduces recurrences by 70 to 80 percent. Suppressive therapy may eliminate recurrences and decreases sexual transmission o virus by approximately 50 percent (Corey, 2004). Women at highest risk are those rom lower socioeconomic groups, adolescents, those with early onset o sexual activity, and those with a large number o li etime sexual partners. In 2011, more than 49,000 cases (all stages) o syphilis were reported by state health departments in the United States (Centers or Disease Control and Prevention, 2012). The natural history o syphilis in untreated patients can be divided into our stages. With primary syphilis, the hallmark lesion is the chancre, in which spirochetes are abundant. Classically, it is an isolated nontender ulcer with raised rounded borders and an unin ected base. Chancres are o ten ound on the cervix, vagina, or vulva but may also orm in the mouth or around the anus. This lesion can develop 10 days to 12 weeks a ter exposure, with a mean incubation period o 3 weeks. With secondary syphilis, bacteremia develops 6 weeks to 6 months a ter a chancre appears. Its hallmark is a maculopapular rash that may involve the entire body and includes the palms, soles, and mucous membranes. With secondary syphilis, disseminated papulosquamous eruptions may be seen on the palms, soles, or trunk. Soft, flat, moist, pink-tan papules and nodules on the perineum and perianal area are typical. Because syphilis is a systemic in ection, other mani estations may include ever and malaise. During the rst year ollowing secondary syphilis without treatment, termed early latent syphilis, secondary signs and symptoms may recur. Late latent syphilis is de ned as a period greater than 1 year a ter the initial in ection. Tertiary syphilis is the phase o untreated syphilis that may appear up to 20 years a ter latency. However, cardiovascular and neurosyphilis are hal as common in emales as in males. A our old titer decrease is required by 6 months a ter therapy or primary or secondary syphilis or within 12 to 24 months or those with latent syphilis or women with initially high titers (> 1:32)(Larsen, 1998). However, some women may have a persistent low titer, and these patients are described as sero ast. Moreover, women with a reactive treponemal-speci c test will more than likely have a positive test or the remainder o their lives, but up to 25 percent may revert to a negative result a ter several years. Treatment Penicillin is the rst-line therapeutic agent or this in ection, and benzathine penicillin is primarily chosen. Treatment of Syphilis Primary, secondary, early latent (< 1 year) syphilis Recommended regimen: Benzathine penicillin G, 2. Early syphilis is diagnosed primarily by dark- eld examination or direct uorescent antibody testing o lesion exudate. A positive test result in a woman who has not been treated previously or syphilis or a ourold titer (two dilutions) increase in a woman previously treated or syphilis should prompt con rmation with treponemalspeci c tests. For all patients, an acute, sel limited ebrile response, termed a Jarisch-Herxheimer reaction, may develop within the rst 24 hours a ter treatment o early disease and is associated with headache and myalgia. As with other S Ds, all patients treated or syphilis and their sexual contacts are screened or other S Ds. Patients with evidence o neurologic or cardiac involvement are treated by an in ectious disease specialist. A ter initial treatment, women are seen at 6-month intervals or clinical evaluation and serologic retesting. I this does not occur, a patient either has ailed treatment or was rein ected and should be reevaluated and retreated. It is caused by a nonmotile, non-spore- orming, acultative, gram-negative bacillus, Haemophilus ducreyi. Incubation usually spans 3 to 10 days, and host access probably requires a break in the skin or mucous membrane. In ection presents initially with an erythematous papule that becomes pustular and ulcerates within 48 hours. Edges o these pain ul ulcers are usually irregular with erythematous nonindurated margins. The ulcer bases are usually red and granular and, in contrast to a syphilitic chancre, are typically so t. Lesions are requently covered with purulent material and may become secondarily in ected. The most common locations in women include the ourchette, vestibule, clitoris, and labia. Concurrently, approximately hal o patients will develop unilateral or bilateral tender inguinal lymphadenopathy.