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Dr seyed Mehdi Ahmadi OB & GynecologistIsfahan Fertility & Infertility Centre ( IFIC )

Iran 17th Oct 20122Vulvovaginal CandidiasisClassification of Vulvovaginal CandidiasisUncomplicatedSporadic or infrequent in occurrence

Mild to moderate symptoms

Likely to be Candida albicans

Immunocompetent women

ComplicatedRecurrent symptoms

Severe symptoms

Non-albicans Candida

Immunocompromised, e.g., diabetic women

TreatmentThe treatment of VVC is summarized as follows: 1. Topically applied azole drugs are the most commonly available treatment for VVC and are more effective than nystatin. Treatment with azoles results in relief of symptoms and negative cultures in 80% to 90% of patients who have completed therapy. Symptoms usually resolve in 2 to 3 days. Short-course regimens up to 3 days are recommended. Although the shorter period of therapy implies a shortened duration of treatment, the short -course formulations have higher concentrations of the antifungal agent, causing an inhibitory concentration in the vagina that persists for several days.

2. The oral antifungal agent, fluconazole, used in a single 150-mg dose, is recommended for the treatment of VVC. It appears to have equal efficacy when compared with topical azoles in the treatment of mild to moderate VVC. Patients should be advised that their symptoms will persist for 2 to 3 days so they will not expect additional treatment.3. Women with complicated VVC . benefit from an additional 150-mg dose fluconazole given 72 hours after the first dose. Patients with complications can be treated with a more prolonged topical regimen lasting 10 to 14 days. Adjunctive.Vulvovaginal Candidiasis-Topical Treatment RegimensButoconazole2% cream, 5 g intravaginally for 3 days a.bClotrimazole1% cream, 5 g intravaginally for 7-14 days a.b2% cream 5 g intravaginally for 3 days

Miconazole 2% cream, 5 g intravaginally for 7 days a.b200-mg vaginal suppository for 3 days a100-mg vaginal suppository for 7 days a.b4% cream 5 g intravaginally for 3 days1,200 mg vaginal suppository, one suppository for one dayNystatin100,000-Uvaginal tablet, one tablet for 14 daysTioconazole6.5% ointment, 5 g intravaginally, single doseaTerconazole0.4% cream, 5 g intravaginally for 7 daysa0,8% cream, 5 g intravaginally for 3 daysa80-mg suppository for 3 daysaa : Oil-based, may weaken latex condoms.b : Available as over-the-counter preparation.Treatment with a weak topical steroid, such as 1% hydrocortisone cream, may be helpful in relieving some of the external irrigative symptoms.

Recurrent Vulvovaginal CandidiasisThe treatment of patients with RVVC consists of inducing a remission of chronic symptomswith fluconazole (150 mg every 3 days for three doses). Patients should be maintained on a suppressive dose of this agent (fluconazole, 150 mg weekly) for 6 months. On this regimen, 90% of women with RVVC will remain in remission. After suppressive therapy, approximatelyhalf will remain asymptomatic. Recurrence will occur in the other half and should prompt reinstitution of suppressive therapy.

Bacterial VaginosisTreatment: Ideally, treatment of BV should inhibit anaerobes but not vaginal lactobacilli. The following treatments are effective:

1. Metronidazole, an antibiotic with excellent activity against anaerobes but poor activity against lactobacilli, is the drug of choice for the treatment of BV.A dose of 500 mg administered orally twice a day for 7 days should be used. Patients should be advised to avoid using alcohol during treatment with oral metronidazole and for 24 hours thereafter. 2. Metronidazole gel, 0.75%, one applicator (5 g) intravaginally once daily for 5 days, may also be prescribed.

The overall cure rates range from 75% to 84% with the aforementioned regimens. Clindamycin in the following regimens is effective in treating BV:1. Clindamycin ovules, 100 mg, intravaginally once at bedtime for 3 days2. Clindamycin bioadhesive cream, 2%, 100 mg intravaginally in a single dose3. Clindamycin cream, 2%, one applicator full (5 g) intravaginally at bedtime for 7 days4. Clindamycin, 300 mg, orally twice daily for 7 daysMany clinicians prefer intravaginal treatment to avoid systemic side effects such as mild to moderate gastrointestinal upset and unpleasant taste.

Treatment of the male sexual partner does not improve therapeutic response and therefore is not recommended.

Trichomonas VaginitisTreatmentThe treatment of trichomonal vaginitis can be summarized as follows:1. Metronidazole is the drug of choice for treatment of vaginal trichomoniasis. Both a single-dose (2 g orally) and a multidose (500 mg twice daily for 7 days) regimen are highly effective and have cure rates of about 95%.2. The sexual partner should be treated.3. Metronidazole gel, although effective for the treatment of BV, should not be used for the treatment of vaginal trichomoniasis.4. Women who do not respond to initial therapy should be treated again with metronidazole, 500 mg, twice daily for 7 days. If repeated treatment is not effective, the patient should be treated with a single 2-g dose of metronidazole once daily for 5 days or tinidazole, 2 g, in a single dose for 5 days.5. Patients who do not respond to repeated treatment with metronidazole or tinidazole and for whom the possibility of reinfection is excluded should be referred for expert consultation. In these uncommon refractory cases, an important part of management is to obtain cultures of the parasite to determine its susceptibility to metronidazole and tinidazole.

Inflammatory VaginitisInitial therapy is the use of 2% clindamycin cream, one applicator full (5 g) intravaginally once daily for 7 days. Relapse occurs in about 30% of patients. who should be retreated with intravaginal 2% clindamycin cream for 2 weeks. When relapse occurs in postmenopausal patients. supplementary hormonal therapy should be consideredCervicitisTreatment:Treatment of cervicitis consists of an antibiotic regimen recommended for the treatment of uncomplicated lower genital tract infection with both chlamydia and gonorrhea. Fluoroquinolone resistance is common in Neisseria gonorrhoeae isolates, and, therefore, these agents are no longer recommended for the treatment of women with gonococcal cervicitis.It is imperative that all sexual partners be treated with a similar antibiotic regimen. Cervicitis is commonly associated with BV, which, if not treated concurrently, leads to significant persistence of the symptoms and signs of cervicitis.Treatment Regimens for Gonococcal and Chlamydial InfectionsNeisseria gonorrhoeae endocervicitisCeftriaxone, 250 mg 1Min a single dose, or, if not an optionCefexime, 400 mg in a single doseChlamydia trachomatis endocervicitisAzithromycin, 1 g orally (single dose), orDoxycycline, 100 mg orally twice daily for 7 daysPelvic InflammatoryDiseaseClinical Criteria for the Diagnosis of Pelvic Inflammatory Disease:Symptoms:None necessarySigns:Pelvic organ tendernessleukorrhea and/or mucopurulent endocervicitis

Additional criteria to increase the specificity or the diagnosis:Endometrial biopsy showing endometritisElevated C-reactive protein or erythrocyte sedimentation rateTemperature higher than 38C (1OOAOF)leukocytosisPositive test for gonorrhea or chlamydiaElaborate criteria:Ultrasound documenting tubo-ovarian abscesslaparoscopy visually confirming salpingitisGuidelines for Treatment of Pelvic Inflammatory DiseaseOutpatient TreatmentCefoxitin, 2 g intramuscularly, plus probenecid, 1 g orally concurrently, orCeftriaxone, 250 mg intramuscularly, or Equivalent cephalosporinPlus:Doxycycline, 100 mg orally 2 times daily for 14 days, orAzithromycin, 500 mg initially and then 250 mg daily for a total of 7 days

Inpatient Treatment:Regimen A:Cefoxitin, 2 g intravenously every 6 hours, orCefotetan, 2 g intravenously every 12 hoursPlus:Doxycycline, 100 mg orally or intravenously every 12 hoursRegimen B:Clindamycin, 900 mg intravenously every 8 hoursPlus:Ceftriaxone, 1-2 g intravenously every 12 hours, orGentamicin, loading dose intravenously or intramuscularly (2 mg/kg of body weight)followed by a maintenance dose (1.5 mg/kg) every 8 hours

Genital Ulcer DiseaseTreatment:Chancroid:Recommended regimens for the treatment of chancroid include azithromycin, 1 g orally in a single dose; ceftriaxone, 250 mg intramuscularly in a single dose; ciprofloxacin, 500 mg orally twice a day for 3 days; or erythromycin base, 500 mg orally four times daily for 7 days. Patients should be reexamined 3 to 7 days after initiation of therapy to ensure the gradual resolution of the genital ulcer, which can be expected to heal within 2 weeks unless it is unusually large.Herpes:A first episode of genital herpes should be treated with acyclovir, 400 mg orally three times a day; or famciclovir, 250 mg orally three times a day; or valacyclovir, 1.0 orally twice a day for 7 to 10 days or until clinical resolution is attained. Although these agents provide partial control of the symptoms and signs of clinical herpes, it neither eradicates latent virus nor affects subsequent risk, frequency, or severity of recurrences after the drug is discontinued. Daily suppressive therapy (acyclovir, 400 mg orally twice daily; or famciclovir, 250 mg twice daily; or valacyclovir, 1.0g orally once a day) reduces the frequency of HSV recurrences by at least 75% among patients with six or more recurrences of HSV per year. Suppressive treatment partially, but not totally, decreases symptomatic and asymptomatic viral shedding and the potential for transmission.SyphilisParenteral administration of penicillin G is the preferred treatment of all stages of syphilis.Benzathine penicillin G, 2.4 million units intramuscularly in a single dose, is the recommended treatment for adults with primary, secondary, or early latent syphilis. The Jarisch-Herxheimer reaction-an acute febrile response accompanied by headache, myalgia, and other symptoms may occur within the first 24 hours after any therapy for syphilis; patients should be advised of this possible adverse reaction.Genital WartsHuman Papillomavirus (HPV)

Papillomavirus TreatmentPrimary goal for treatment of visible warts is the removal of symptomatic wartsTherapy may reduce but probably does not eradicate infectivity Difficult to determine if treatment reduces transmissionNo laboratory marker of infectivityVariable results utilizing viral DNA

HPV Treatment OptionsChemical agentsCryotherapyElectrosurgerySurgical excisionLaser surgeryImiquimod (Aldara)Defer treatmentNatural therapies

PapillomavirusSurgical removal

Patient-appliedPodofilox (Condylox) 0.5% solution or gelApply 2x/day for 3 days, followed by 4 days of no therapy. Repeat as needed, up to 4xorImiquimod (Aldara) 5% creamApply 1x/day @ bedtime 3x/week for up to 16 weeks

Provider-administeredCryotherapy (liquid nitrogen) *repeat every 1-2 weeksorPodophyllin resin 10-25% *thoroughly wash off in 1-4 hrsorTrichloroacetic or Bichloroacetic acid 80-90% *can be repeated weekly

PapillomavirusVaginal wartsCryotherapy or TCA/BCA 80-90%Urethral meatal wartsCryotherapy or podophyllin 10-25%Anal wartsCryotherapy or TCA/BCA 80-90%PapillomavirusTherapy choice needs to be guided by preference of patient, experience of provider, and patient resources (time and/or money)No evidence exists to indicate that any one regimen is superiorAn acceptable alternative may be to do nothing but watch and wait; possible regression/uncertain transmission

HumanImmunodeficiency VirusDecisions regarding the initiation of antiretroviral therapy should be guided by monitoring the laboratory parameters of HIV RNA (viral load) and CD4+ T-cell count, and the clinical condition of the patient. The primary goals of antiretroviral therapy are maximal and durable suppression of viral load, restoration or preservation of immunologic function, improvement of quality of life, reduction of mV-related morbidity and mortality, and prevention of mv transmission. Antiretroviral therapy should be initiated in all women with a history of an AIDS-defining illness or with a CD4 count less than 350 cells per mm3.Antiretroviral treatment should be started regardless of CD4 count in women with the following conditions: pregnancy, HIV-associated nephropathy, and hepatitis B coinfection when treatment of hepatitis B is indicated. Patients must be willing to accept therapy to avoid the emergence of resistance caused by poor compliance. Dual nucleoside regimens used in addition to a protease inhibitor or non nucleoside reverse transcriptase inhibitor provide a better durable clinical benefit than monotherapy.Patients with less than 200 CD4+ T cells per ,L should receive prophylaxis against opportunistic infections, such as trimethoprim/sulfamethoxazole or aerosol pentamidine for the prevention of PCP pneumonia. Those with less than 50 CD4+ T cells per uL should receive azithromycin prophylaxis for mycobacterial infections.Aberrations of Pubertal DevelopmentI.Delayed or interrupted pubertyA. Anatomic abnormalities of the genital outflow tract1. Mullerian dysgenesis (Rokitansky-Kuster-Hauser syndrome)2. Distal genital tract obstruction a. Imperforate hymen b. Transverse vaginal septum

B. Hypergonadotropic (follicle-stimulating hormone >30 mlUlmL) hypogonadism(gonadal "failure")1. Gonadal dysgenesis with stigmata of Turner syndrome2. Pure gonadal dysgenesis a. 46,XX b. 46,XY3. Early gonadal "failure" with apparent normal ovarian development

C. Hypogonadotropic (luteinizing hormone and follicle stimulating hormone < 10 mlU/mL) hypogonadism1. Constitutional delay2. Isolated gonadotropin deficiency a. Associated with midline defects (Kallmann syndrome) b. Independent of associated disorders c. Prader-Labhart-Willi syndrome d. Laurence-Moon-Bardet-Biedl syndrome e. Many other rare syndromes3. Associated with multiple hormone deficiencies4. Neoplasms of the hypothalamic-pituitary area a. Craniopharyngiomas b. Pituitary adenomas c. Other5. Infiltrative processes (Langerhans cell-typehistiocytosis)6. After irradiation of the central nervous system7. Severe chronic illnesses with malnutrition8. Anorexia nervosa and related disorders9. Severe hypothalamic amenorrhea (rare)10. Antidopaminergic and gonadotropin-releasing hormone-inhibiting drugs (especially psychotropic agents, opiates)11. Primary hypothyroidism12. Cushing syndrome13. Use of chemotherapeutic (especially alkylating) agents

II. Asynchronous pubertal development A. Complete androgen insensitivity syndrome (testicular feminization) B. Incomplete androgen insensitivity syndromeIII. Precocious puberty A. Central (true) precocious puberty1. Constitutional (idiopathic) precocious puberty2. Hypothalamic neoplasms (most commonly hamartomas)3. Congenital malformations4. Infiltrative processes (Langerhans cell-type histiocytosis)5. After irradiation6. Trauma7. Infection B. Precocious puberty of peripheral origin (precocious pseudopuberty)1. Autonomous gonadal hypersecretion a. Cysts b. McCune-Albright syndrome2. Congenital adrenal hyperplasia a. 21-Hydroxylase (P450c21) deficiency b. 11,-Hydroxylase (P450cll) deficiency c. 3-Hydroxysteroid dehydrogenase deficiency3. Iatrogenic ingestion/absorption of estrogens or androgens4. Hypothyroidism5. Gonadotropin-secreting neoplasms

a. Human chorionic gonadotropin secreting i. Ectopic germinomas (pinealomas) ii. Choriocarcinomas iii. Teratomas iv. Hepatoblastomas b. Luteinizing hormone-secreting (pituitary adenomas)6. Gonadal neoplasms a. Estrogen-secreting i. Granulosa-theca cell tumors ii. Sex-cord tumors b. Androgen-secreting i. Sertoli-Leydig cell tumors (arrhenoblastomas) ii. Teratomas7. Adrenal neoplasms a. Adenomas b. CarcinomasIV. Heterosexual pubertyA. Polycystic ovarian syndromeB. Nonclassic forms of congenital adrenal hyperplasiaC. Idiopathic hirsutismD. Mixed gonadal dysgenesisE. Rare forms of male pseudohermaphroditism (Reifenstein syndrome, Sa-reductasedeficiency)F. Cushing syndrome (rare)G. Androgen-secreting neoplasms (rare)

Differential Diagnosis of Acute Pelvic Pain43Acute Pain1. Complication of pregnancy a. Ectopic pregnancy b. Abortion, threatened or incomplete2. Acute infection a. Endometritis b. Pelvic inflammatory disease (acute PID) or salpingo-oophoritis c. Tubo-ovarian abscess3. Adnexal disorders a. Hemorrhagic functional ovarian cyst b. Torsion of adnexa C. Rupture of functional, neoplastic, or inflammatory ovarian cyst

Recurrent Pelvic Pain1. Mittelschmerz (midcycle pain)2. Primary dysmenorrhea3. Secondary dysmenorrheaGastrointestinal1. Gastroenteritis2. Appendicitis3. Bowel obstruction4. Diverticulitis5. Inflammatory bowel disease6. Irritable bowel syndrome

Genitourinary1. Cystitis2. Pyelonephritis3. Ureteral lithiasisMusculoskeletal1. Abdominal wall hematoma2. HerniaOther1. Acute porphyria2. Pelvic thrombophlebitis3. Aortic aneurysm4. Abdominal angina

Leaking or Rupture of anOvarian CystManagement:Orthostatic, significant anemia, hematocrit of the culdocentesis fluid of greater than 16%, or a large amount of free peritoneal fluid on ultrasound suggests significant hemoperitoneum and usually requires surgical management by laparoscopy or laparotomy. Patients who are not orthostatic or febrile, who are not pregnant or anemic, and who have only a small amount of fluid in the cul-de-sac can often be observed in the hospital, without surgical intervention, or even discharged home from the emergency room after observation.

Adnexal TorsionAdnexal torsion must be treated surgically. The adnexa may be untwisted and a cystectomy Performed if appropriate. Even if it appears that necrosis occurred, there is evidence that it remains functional and sparing the adnexa can preserve its hormonal and reproductive function. Treatment can be accomplished by laparoscopy or laparotomy, depending on the size of the mass.

Tubo-Ovarian AbscessTubo-ovarian abscesses should always be treated as an inpatient, and conservative medical therapy with broad spectrum antibiotics can be attempted . In one study, this yielded a treatment success rate of 75% . If the patient is persistently febrile or not improving clinically, CT or ultrasound-guided drainage of the abscesses should be undertaken. CT-guided percutaneous drainage can be achieved trans abdominally or Trans vaginally. Drainage along with intravenous antibiotics is considered first-line therapy. If fertility is not desired, bilateral salpingo-oophorectomy and hysterectomy will provide definitive therapy.A ruptured tubo-ovarian abscess rapidly leads to diffuse peritonitis, evidenced by tachycardia and rebound tenderness in all four quadrants of the abdomen. With endotoxic shock, hypotension and oliguria ensue, and the result can be fatal. Exploratory laparotomy with resection of infected tissue is mandatory

Uterine LeiomyomasDiagnosis and Management:With degeneration there is usually leukocytosis. Ultrasound can distinguish adnexal from uterine etiology of an eccentric mass. If diagnosis is still uncertain, a pelvic MRI is more accurate. The fibroid can be excised laparoscopically; however, surgery is not mandatory.A submucous leiomyoma with pain and hemorrhage should be excised transcervically withhysteroscopic guidance.

Differential Diagnosis of Chronic Pelvic PainGynecologicNoncyclic AdhesionsEndometriosisSalpingo-oophoritisOvarian remnant or retained ovary syndromePelvic congestionOvarian neoplasm benign or malignantPelvic relaxation Cyclic:Primary dysmenorrheaMittelschmerzSecondary dysmenorrheaEndometriosisUterine or vaginal anomalies with obstruction of menstrual outflowIntrauterine synechiae (Asherman syndrome)Endometrial polyps intrauterine device(IUD)Uterine leiomyomataAdenomyosisPelvic congestion syndromeAtypical cyclic:EndometriosisAdenomyosisOvarian remnant syndromeChronic functional cyst formationGastrointestinalIrritable bowel syndromeUlcerative colitisGranulomatous colitis (Crohn's disease)CarcinomaInfectionRecurrent partial bowel obstructionDiverticulitisHerniaAbdominal anginaRecurrent appendiceal colicGenitourinaryRecurrent or relapsing cystourethritis Urethral syndrome Interstitial cystitis/bladder pain syndromeUreteral diverticuli or polyps Carcinoma of the bladder Ureteral obstruction Pelvic kidney NeurologicNerve entrapment syndrome, neuroma, or other neuropathiesTrigger pointsMusculoskeletalMyofascial pain and trigger points

Low-back pain syndromeCongenital anomaliesScoliosis and kyphosisSpondylolysisSpondylolisthesisSpinal injuriesInflammationTumorsOsteoporosisDegenerative changesCoccydyniaMyofascial syndromeSystemicFibromyalgiaAcute intermittent porphyriaAbdominal migraineConnective tissue disease including systemic lupus erythematosusLymphomaNeurofibromatosis

Secondary Dysmenorrhea AdenomyosisManagementThe management of adenomyosis depends on the patient's age and desire for future fertility. Relief of secondary dysmenorrhea caused by adenomyosis can be ensured after hysterectomy, but less invasive approaches can be tried initially. NSAIDs, hormonal contraceptives, and menstrual suppression using oral, intrauterine, or injected progestins or gonadotropin-releasing hormone agonists are all useful. Treatment follows the same protocol as treatment for endometriosis. Uterine artery embolization can be effective.EndometriosisManagement of Secondary Dysmenorrhea Due to Endometriosis:

PharmacologicMedications can be used to reduce the cyclic hormonal stimulation of these lesions and eventually decidualize or atrophy the lesions. No studies directly compared medical versus surgical management of endometriosis. However, given the excellent response rate, relatively low cost, and fair tolerability with hormonal therapy, an expert consensus panel recommended that women with suspected endometriosis who are not actively trying to conceive and who do not have an adnexal mass start with first-line medical management before laparoscopy. . First-line treatment consists of a trial of NSAIDs with or without combined estrogen-progestin formulations.Both cyclic and continuous combined oral contraceptives (OCs) can be used with equal efficacy.Most studies used OCs containing low-dose estrogen and more androgenic progestins; however, newer generation progestins are also effective. For women who continue to have dysmenorrhea after using hormonal contraceptives in a cyclical fashion, continuous OCs regimen can be tried, without a hormonal break or with menstruation every 3 months.

Second-line medical therapy involves high-dose progestins or gonadotropin-releasing hormone (GnRH) analogues. This can be initiated for refractory symptoms or for patients with contraindication to estrogen. Progestins alone are associated with few metabolic concerns and are safe and inexpensive alternatives to surgical intervention. Progestins or progestins plus estrogen effectively manage pain symptoms in approximately three-quarters of the women with endometriosis. High-dose medroxyprogesterone acetate and norethindrone acetate are equally effective to the GnRH analogues. Progestins should be given at a dose to achieve amenorrhea, then the dose can be tapered to control symptoms.A randomized controlled trial comparing levonorgestrel intrauterine system (LNG-IUS) with depot GnRH for the treatment of endometriosis-related chronic pain found that both were effective treatments. Androgenic hormones such as danazol are thought to inhibit the luteinizing hormone surge and steroidogenesis and may have anti-inflammatory effects. These medications increase free testosterone, resulting in possible side effects such as deepening of voice, weight gain, acne, and hirsutism. Vaginal danazol in lower doses may be effective.GnRH agonist and add-back treatment can be used as pharmacologic treatments for endometriosis. A randomized-controlled trial of GnRH agonist therapy for 6 months in cases of confirmed endometriosis showed decreased size of endometriotic lesions and pain symptoms. Side effects are related to the hypo estrogenic state and include vasomotor symptoms, mood swings, vaginal dryness, decreased libido, myalgias, and, eventually, bone loss. These side effects can be reduced with supplemental calcium and hormonal add-back therapy with norethindrone acetate 2 to 5 mg daily with or without low-dose estrogen (0.625 mg of conjugated estrogen or I mg of 17 ,B-estradiol). Given the side effects, GnRH agonists usually are not used for more than 8 to 12 months, but with add-back hormones and/or bisphosphonate, GnRH therapy can be considered for use for more than I year. Recurrence of symptoms after discontinuation of GnRH agonist ranges from 36% to 70% 5 years after completion of treatment.Aromatase p-450 and prostaglandin E2 (PgE2) pathways arc thought to be involved in the genesis of endometriotic implants. Aromatase plays an important role in estrogen biosynthesis by catalyzing the conversion of androstenedione and testosterone to estrone and estradiol. Although aromatase activity is not detectable in normal endometrium, it is found in eutopic endometrium and endometriotic lesions. Thus, aromatase inhibitors (AIs) are now being used as adjunctive therapy with medical therapies in refractory cases.

A 2008 review of eight studies evaluated Als for management of endometriosis and found that AIs combined with progestins or OCs or GnRH analogues decreased mean pain scores and lesion size and improved quality oflife. In the only randomized controlled trial (97 women) evaluated in this meta-analysis, aromatase inhibitor (anastrozole) in combination with GnRH agonist significantly improved pain (P