Selected Disorders of the Female Reproductive System

Hormonal effect Drug Bilateral Hypoestrogenic NA oophorectomy (often with hysterectomy) Laser or electro- NA NA fulguration ablation of endometrial implants GnRH agonist Hypoestrogenic Nafarelin (Synarel) Leuprorel in (Lupron) Androgenic agonist Hyperandrogenic Danazol (Danocrine) High progesterone Hyperprogestational Medroxyprogesterone (relative low acetate (Amen, estrogen) Curretab, Cyrin, Provera) Continuous oral Combined Birth control pills contraceptives estrogenic and (many types) (pseudopregnancy) progestational NA = not available; SC = subcutaneous. endometriosis becomes a chronic affliction that requires ongoing education, treatment, and compassion. If the pa­ tient requests, the physician should meet with other members of the family to offer information and address questions or concerns. Patients and families may benefit from contacting the Endometriosis Association to obtain educational materials and information regarding support groups that deal with the impact of this chronic condi­ tion. 32 Women with documented endometriosis who de­ sire pregnancy should be counseled regarding its relation to infertility so these desires and the timing of childbear­ ing can be discussed. Effectively managing patients with endometriosis challenges the family physician to remain an informed patient advocate, as comprehensive care fre­ quently involves referral and familiarity with long-term treatment modalities not routinely used by family physi­ cians. 33 Evaluation of the Infertile Couple Infertility is generally diagnosed when pregnancy has not occurred in a couple trying to conceive after 1 year of unprotected intercourse. It is estimated that nearly 15% of couples in the United States are infertile. 34 The infertility risk doubles for women age 35 to 44 compared to women Route of administration Typical daily dose Problems Laparotomy NA Permanent sterility, bone loss, meno- pausal symptoms Laparoscopy NA Surgical risks; ? benefit or for severe disease, laparotomy recurrence Nasal 0.4-0.8 mg Bone loss, hot flashes, SC 0.5-1.0 mg decreased libido, vaginal discharge Oral 400-800 mg Androgenic side effects, weight gain, acne, oily skin, deep voice Oral 30-60 mg Mood changes, bloating, break- through bleeding Oral e.g., 0.035 mg Oral contraceptive eth i nylestrad ioll side effects: mood 1 mg norethindrone changes, weight (1-4 per day) gain, bloating age 30 to 34; consequently, about one-third of women older than 35 who desire pregnancy experience infertil­ ity.35 Couples are seeking professional help for infertility on a increasing basis, and family physicians are in an ideal position to begin this evaluation. Their familiarity with partner's family, medical, and physical histories allow the assessment to begin with both partners, which contrib­ utes to the cost-effectiveness of the family physician's infertility evaluation. The major goals when evaluating the infertile couple include (1) identifying and correcting causes of infertility, (2) providing accurate information for the couple, (3) providing emotional support during and after the evaluation process, and (4) providing counseling regarding alternatives should pregnancy be unlikely or impossible. 36 This discussion presents the initial workup of the infertile couple, which is sufficient to allow diagno­ sis in approximately 60% of couples seeking helpP There are various estimates regarding the causes for infertility. Table 108.4 summarizes the experience for in­ fertile couples in the United States. 36-38 Initial Fertility Workup A timely and cost-effective approach to evaluating the infertile couple requires initial evaluation of both the male 108. Selected Disorders of the Female Reproductive System 945 Table 10B.4. Male and Female Infertility Factors Male factors (40% of couples) Disorders of spermatogenesis Obstruction of efferent ducts Disorders of sperm motility Sexual dysfunction Female factors (45% of couples) Pelvic origin (30-50% of female causes) Tubal disorders Uterine disorders Endometriosis Ovulatory origin (40% of female causes) Endocrine (adrenal, thyroid, pituitary) disorder Ovarian: luteal phase defects Cervical origin (10% of female causes) Mucous problems Infectious problems Combined factors (15-30% of couples) Unidentifiable factors (15% of couples) and female factors for infertility. Table 108.5 summarizes an organized approach to the fertility workup.36-39 Both partners are scheduled for extended examination times. Ample time is afforded to explain the need and methods for the various initial tests and data collection including (1) semen analysis, (2) documentation of ovulation, (3) postcoital test, and (4) evaluation of tubal patency. The exact sequence in which a physician evaluates a couples' infertility varies based on historical and physical findings ascertained during the initial visit. A semen sample is analyzed within 2 hours of ejacula­ tion after 48 hours of ejaculatory abstinence. Evaluation should be by persons experienced with fertility semen analysis. If an abnormality is found on this initial assess­ ment, two additional semen analyses are performed 2 weeks apart. If the abnormality persists, urologic consul­ tation is appropriate. Assessing ovulation can be accomplished by one or more methods: (1) basal body temperature (BBT) assess­ ment; (2) timed serum progesterone levels; (3) urinary LH screening; and (4) endometrial biopsy. The method of re­ cording BBT data is explained during the initial visit. Serum progesterone levels are measured 7 days after esti­ mated ovulation. Values consistent with ovulation vary with each laboratory, but generally values of more than 15 ng/ml are consistent with normal ovulatory function and levels under 5 ng/ml imply anovulation. Endometrial biopsy, in addition to histologically detect­ ing ovulation, provides timing of the progestational effect with the day of the cycle and can provide information regarding ovulation and luteal phase defects. Endome­ trial sampling is easily accomplished using small aspira­ tion catheters (Pipelle, Z-sampler) at as close to 7 days Table 10B.S. Evaluation Plan for the Infertile Couple Initial visit (extended visit time for both partners) Complete medical, family, drug and sexual history Laboratory studies Sexually transmitted disease cultures (especially Chlamydia, Ureaplasma urealyticum, Neisseria gonorrhoeae) Assess need for HIV screening Consider CBC, FBS, VORL, urinalysis Men: semen analysis Women Papanicolaou screening KOH and wet mount Focused stud ies Thyroid history?-thyroid function tests Galactorrhea?-prolactin levels Abnormal pelvic examination?-ultrasonography, laparoscopy History PI D?-hysterosal pi ngography Endometriosis I ikely?-Iaparoscopy History sexual dysfunction?-education, counseling Ovulatory monitoring (BBT, urinary LH) Education Alcohol, drugs, hot tubs, sexual practices/frequency, douching, lubricants Arrange for postcoital sample analysis with next visit Second visit (midcycle/ovulatory as predicted by BBT and/or urinary LH testing) Review laboratory studies, semen analysis, ovulatory monitoring data to date Analyze postcoital sample Consider and discuss need for endometrial biopsy Arrange for hysterosalpingography during follicular phase (days 7-9). If laparoscopy deemed necessary, HSP often accomplished during laparoscopy Third visit (midluteal phase of cycle, 7-9 days postovulation) Review studies to date Perform endometrial sampling Consider progesterone and prolactin levels if not already done Consider HSP or laparotomy; referral often appropriate at this time CBC = complete blood counts; FBS = fasting blood sugar; LH = luteinizing hormone; HSP = hysterosalpingography; BBT = basal body temperature; HIV = human immunodeficiency virus; PIO = pelvic inflammatory disease. after presumed ovulation as possible (roughly, day 22 of a 28-day cycle). Postcoital testing requires evaluation of the sperm-mucus interaction. The couple is instructed to have intercourse fol­ lowing 48 hours of abstinence. Pelvic examination is per­ formed and aspirated cervical mucous is examined within 2 to 8 hours of intercourse. Intercourse should occur within 946 Gary R. Newkirk and Patricia Ann McGuire 24 to 48 hours of presumed ovulation as determined by

outlined above. The postcoital mucus is exam­ ined by experienced individuals for quantity, clarity, pH, spinnbarkeit (ability of cervical mucus to stretch), and the number, forms, and motility of sperm. Generally, finding 5 to 10 sperm with linear motility per high power field in clear, acellular mucus with more than 8 cm spinnbarkeit excludes cervical factors as a major cause for infertility. During a subsequent office visit, results of the initial laboratory studies, cultures, and semen analysis are dis­ cussed. The postcoital sample can be obtained and an appointment for the endometrial biopsy, luteal progester­ one and prolactin levels scheduled. The results of these studies are carefully reviewed during the third visit, at which time a decision is made to pursue hysterosal­ pingography, laparoscopy, hysteroscopy, or laparotomy. The frequency of these visits also facilitates emotional support and encouragement for the couple. RESOLVE (5 Water Street, Arlington, MA 02174), a national nonprofit infertility organization, has chapters throughout the United States and is an excellent resource for support and coun­ seling groupS.39 Hysterosalpingography Hysterosalpingography (HSP) is a safe, high yield proce­ dure when performed during the early proliferative phase of the cycle. During HSP a special catheter is passed through the vagina into the endocervical canal through which contrast medium is injected and fluoroscopically followed through the endometrial and fallopian tube lumen. An undiagnosed pelvic mass or PID contraindi­ cates this procedure, as does an iodine or radiocontrast dye allergy. HSP can be performed during laparoscopic surgery as well. The appearance of uterine defects on HSP implicate a uterine cause for infertility, which include post-DES uterine abnormalities (T-shaped, hypoplastic cavity), intrauterine synechiae (Asherman syndrome), submucous or large intramural myomas, congenital anom­ alies, and leiomyomas. Further evaluation of pelvic factors for infertility re­ quire laparoscopy. Laparoscopy is indicated if HSP is contraindicated or abnormal and is also performed if his­ torical (e.g., PID, endometriosis) or physical (e.g., adhe­ sions, tube/ovarian abnormality) findings implicate a pelvic cause. Women with endometriosis are twice as likely to be infertile as women without this condition. Endometriosis is confirmed and staged by laparoscopy. Treatment for endometriosis was discussed earlier in this chapter. Finally, laparoscopy is indicated if no other sig­ nificant cause for infertility is identified. Ovulatory disorders for infertility include adrenal and thyroid disorders. Fasting blood glucose, thyroid func­ tion, FSH, LH, and prolactin levels assist the evaluation of endocrinologic factors for infertility. Drug-related infertil­ ity must also be considered, as a number of medications contribute to disruption of thyroid, adrenal, or ovarian functioning in both men and women (e.g., antihyperten- sive drugs, major tranquilizers, steroids). Therapy for ovula­ tory factors is directed toward the underlying disorder, including thyroid replacement for hypothyroidism, bromo­ criptine for hyperprolactinemia (with pituitary macro­ adenoma ruled out), or clomiphene to induce ovulation. Evidence supports a possible link between the risk of ovar­ ian cancer in women receiving ovulatory stimulants. 40 Cervical factors for infertility are assessed initially by the postcoital test. The finding of leukocytes suggests cer­ vicitis; and cultures for gonorrhea, Ureaplasma urealyti­ cum, and Chlamydia are useful for directing treatment. Finding nonmotile or nonprogressively motile sperm with a "shaking" pattern suggests sperm antibodies. Miscalcula­ tion of ovulation timing is suggested by poor quality cervical mucus, which is abnormally thick, cloudy, and demonstrates poor spinnbarkeit. A repeat postcoital test is necessary if ovulatory timing is in question. Despite comprehensive evaluation 5% to 10% of cou­ ples have no identifiable cause for their infertility. Often referral to infertility centers for consideration of assisted reproductive technologies (ART) is necessary (e.g., in vitro fertilization, GIFT) and appropriate. Attitudes re­ garding adoption and assisted reproductive technologies should be explored. Often individual or joint guilt regarding infertility can be underestimated. Family physicians are in an ideal po­ sition to utilize established trust and comfort with their patients to explore potential past history and guilt issues that might relate to infertility. Emotional support remains a part of every visit. Toxic Shock Syndrome In 1978 an acute, febrile, exanthematous illness associated with multisystem organ failure became known as the toxic shock syndrome (TSS).41 There are currently no definitive tests or specific serologic markers for diagnosing TSS. The diagnosis requires the presence of the six clinical criteria, outlined in Table 108.6.42,43 TSS should be suspected in all patients who present with flu-like symptoms, rash, and otherwise unexplained hypotension. Early reports indicate that more than 90% of the re­ ported TSS cases involved menstruating females. 44 Be­ cause of the high correlation of TSS with menstruation and tampon use, the perception of TSS as strictly a "tam­ pon disease" persists. More recent data reveal that only half of the reported cases were female, and many of these cases were not associated with menstruation. 45 Most cases of tampon-related TSS occurred during the teenage years; 97% of reported patients were white, and 42% were ado­ lescents.46 Physicians must recognize that TSS can occur in nonmenstruating women, men, and children of all ages. Nonmenstrual cases of TSS occur in males and fe­ males equally with various sites and types of infection, including surgical wounds, burns, abscesses, sinus in­ fections, bronchopneumonia, tracheitis, empyema, septic abortion, intravenous drug injections, pilonidal abscess, 108. Selected Disorders of the Female Reproductive System 947 Table 708.6. Toxic Shock Syndrome, Criteria for Diagnosis Confirmed diagnosis requires that all six criteria be met. 1. Acute fever 2. Scarlatin iform rash 3. Desquamation of palms and soles 1-2 weeks after illness onset 4. Hypotension 5. Clinical or laboratory evidence of involvement of at least three organ systems: hematologic, gastro­ intestinal, neurologic, cardiovascular, hepatic, renal, muscular 6. Other causes excluded (e.g., sepsis, measles, drug or toxic ingestion) Source: Data from Todd and Fishaut 41 and Tofte and Williams. 42 insect bites, diaphragm use, and even ear piercing. Inter­ estingly, menstruation-related TSS affects Caucasians al­ most exclusively, whereas non-menstruation-related forms affect the races proportionate to the racial! sexual mix of the population. 47 Pathogenesis The expression of TSS depends on the interaction of sev­ eral bacterial and host factors that are incompletely understood. In the original studies, patients with TSS usually had a source of staphylococcal infection. More recent reports have characterized a streptococcal toxic shock-like syndrome caused by toxins elaborated by group A streptococci. 48,49 Both have in common the pres­ ence of bacteria-related toxins that appear to initiate the serious multiorgan syndrome characteristic of these dis­ orders. Toxic shock syndrome toxin-1 (TSST-1) has been identified as one of the significant staphylococcal media­ tors of pathogenicity in TSS,50 although TSS can occur in the absence of TSST-1. Endotoxin from co-infecting gram­ negative or streptococcal bacteria has also been implicated in TSS.51 Staphylococcal toxins may interact synergistically with these endotoxins. TSST-1 enhances the release of a wide variety of endogenous mediators produced by the host, which partly explains the multiorgan dysfunction characteristic of this syndrome. Finally, the correlation of TSS with vaginal materials such as tampons, barrier sponges, or the diaphragm strongly implies an as yet uncharacterized relation between foreign materials and the induction and maintenance of this condition. TSS ap­ parently results from multiple, cumulative effects of pri­ mary and secondary mediators initiated by the continued growth of certain bacteria. Clinical Presentation Toxic shock syndrome presents with a broad spectrum of clinical findings ranging from relatively mild symptom­ atology to a rapidly fatal illness. 42 Mortality is about 3%. Patients may progress from onset of symptoms to overt multisystem failure within 48 hours. Hypotension and poor tissue perfusion, with nonhydrostatic leakage of fluid from the intravascular to the interstitial space, ac­ counts for a portion of the multisystem organ failure (renal, hepatic, central nervous system, hematologic). Fatal com­ plications include refractory shock, renal failure, arrhyth­ mias, intravascular coagulopathy, and respiratory distress syndrome. The initial fever, rash, and malaise of TSS may mimic a common viral syndrome early in the disease process. These symptoms typically progress rapidly to include high fever (104 OF), pharyngitis, conjunctivitis, di­ arrhea, vomiting, myalgia, and scarlet fever-like rash. Within a matter of hours orthostatic dizziness, fainting, or overt hypotension may occur; these first symptoms clear­ ly set this syndrome apart from benign infectious pro­ cesses. The rash of TSS is usually a prominent finding and typically appears as a diffuse scarlatiniform exanthem beginning on the trunk and spreading to the arms and legs with flexural accentuation. Some clinicians have de­ scribed this rash as having a "sunburn" appearance that blanches with pressure. "Strawberry tongue," as seen with scarlet fever, is a common finding. Erythema of the mucous membranes and intense conjunctival hyperemia without purulence are characteristic. Generalized non­ pitting edema accompanies the rash in many cases. Des­ quamation of the hands and feet is commonly seen within 10 to 21 days after presentation. Reversible patchy alope­ cia and shedding of fingernails has been described as well. 52 Toxic shock syndrome is rare in children, but when it does appear the clinical features of the illness do not differ appreciably from those described in adults. There does seem to be a higher likelihood of respiratory in­ volvement in children. 50 The differential diagnosis of TSS in children includes Kawasaki disease, staphylococcal scalded skin syndrome, scarlet fever, Rocky Mountain spotted fever, leptospirosis, erythema multiforme, Stevens­ Johnson syndrome, and measles. Common laboratory findings of TSS reflect widespread organ involvement: sterile pyuria; normocytic anemia; leukocytosis with left shift; prolongation of the prothrom­ bin and partial thromboplastin times; an increase in serum bilirubin, creatinine, and creatine kinase; hyponatremia; hypokalemia; and metabolic acidosis. 53 Management Hospitalization is necessary for all patients with pre­ sumed TSS, as the illness may progress from mild to life-threatening within a matter of hours. Supportive measures tailored to the patient's symptoms are the main­ stay of therapy.54 A search is made for the potential source of the staphylococcal or streptococcal toxin, and cultures of any suspected source are obtained. Removal of vaginal tampons, pads, sponges, or diaphragms is paramount. Recent surgical wounds are explored even if they appear not to be inflamed or infected. All presumed sources of toxin must be thoroughly drained and irrigated. 948 Gary R. Newkirk and Patricia Ann McGuire Prospective management includes administration of large volumes of colloid and crystalloid fluids with glu­ cose (10-20 ml/kg) over the first hour to reestablish vas­ cular volume. Patients may require 5 to 10 liters of fluid during the first 24 hours to maintain tissue perfusion and urinary output. Swan-Ganz catheterization is required for severe cases. After specimens for culture are obtained, antistaphylococcal antibiotics (e.g., methicillin, oxacillin, nafcillin, first generation cephalosporin, or vancomycin) are given intravenously until oral fluids can be tolerated. Antibiotics are continued for at least 10 days. Steroid ther­ apy (e.g., methylprednisolone 10-30 mg/kg/day) maybe given to patients with severe unresponsive shock. Intra­ venous immune globulin may be also given to patients who are not improving, although the effectiveness of this therapy has not been proved. Signs of adult respiratory distress syndrome (ARDS) often develop on the second or third day of treatment with severe TSS. Intubation with continuous positive air­ way pressure may be required; generally, fluids are not restricted. Acute renal failure may require dialysis. Recurrences of TSS are common but generally milder. Female patients who experience TSS are advised to avoid the use of vaginal devices (tampons, sponges, diaphragms). Prophylactic antistaphylococcal oral antibiotics at the time of menses have been recommended for patients experi­ encing TSS associated with menses. Oral contraceptives have been shown to decrease the risk of TSS recurrence. 44 These approaches have not yet been conclusively sup­ ported by rigorous studies.

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