Functional cysts These are enlarged or persistent follicular or corpus lu- teum cysts. They are so common that they may be considered normal if they are small (<5cm). They may cause pain by rupture, failing to rupture at ovu- lation, or bleeding. If <5cm they usually resol ve over 2 \200\2233 cycles. Serous cystadenomas These develop papillary growths that may be so pro- li \201 c that the cyst appears solid. They are commonest in women aged 30 \200 \22340 years. About 30% are bilateral and about 30% are malignant. Mucinous cystadenomas Th e commonest large ovarian tumors; these may become enormous. They are \201 lled with muci nous material and rupture may rarely cause pseudomyxoma peritonei (p280). They may be multi locu- lar. They are commonest in the 30 \200\22350 age group. About 5% will be malig- nant. Remove the appendix at operation in those with suspected mucinous cystadenoma and send for histology. (Interestingly men can get pseudo- myxoma from intestinal or appendicular neopl asms; most women with pseu- domyxoma peritonei do not have overt rupture of ovarian tumors and 90% have concurrent intestinal or appendicular tumors and it is now thought that the ov arian tumors may be secondary to GI tumors.) Fibromas These are small, solid, benign, \201 brous tissue tumors. They are as- sociated with Meigs \200\231 syndrome: pleural eff u sion, often right sided + benign ovarian \201 broma (or thecoma, cystadenoma, granulosa c ell tumor) + ascites. Teratomas These arise from primitive germ cells. A benign mature tera to- ma (dermoid cyst) may contain well-diff erentiated tissue, eg hair, teeth. 20% are bila teral. They are most common in young women. Poorly diff erentiated malignant teratomas are rare. Other germ cell tumors (all malignant and all rare) Non-gestational cho- riocarcinoma s (secrete HCG); ectodermal sinus tumors (yolk sac tumors \200\224 secrete \200 -fetoprote in); dysgerminomas. Sex-cord tumors (rare; usually of low-grade malignancy) These arise fro m cortical mesenchyme. Granulosa-cell and theca-cell tumors produce oes- trogen and may pre sent with precocious puberty, menstrual problems, or postmenopausal bleeding. Arrhenoblasto mas secrete androgens. y g o o c e a n y G l Symptoms suggestive of ovarian cancer \200 100 \200 \200\230Bloating \200\231, abdomina l distension \200 Early satiety \200 Loss of appetite \200 Unexplained weight loss \200 Change of bowel habit \200 Fatigue \200 Onset of \200\230irritable bowel \200 \231 symptoms age >50 years \200 Urinary frequency or urgency \200 Abdominal or pelvic pain Examine: if pelvic mass or ascites refer under 2-week rule to gynecology. Check CA-125 (cancer antigen 125), (and \200 -fetoprotein ( \200 FP), \200 -human chori- onic gonadot rophin ( \200 HCG) if <40yrs to identify women who may not have ovarian epithelial cancer). See above. Ovarian epithelial cancers are ad- enocarcinomas. If CA-125 is >35 IU/mL arrang e urgent abdominal and pelvic ultrasound. If ultrasound suggests ovarian cancer refer under 2-week rule to gynecology. If ultrasound has suggested cancer arrange staging CT of abdome n ( chest) in secondary care. Ovarian tumors in pregnancy These are found in 1/1000 pregnancies. It is easier to disting uish them (lying as they do in the rectovaginal pouch) with an anteverted uterus than with a gravid retroverted uterus. Suspicion of presence of a tumor can be con- \201 rmed by ul trasound. Torsion of ovarian cysts is more common in pregnancy and the puerperium than at o ther times. Cyst rupture and hemorrhage into cysts may also occur, but not more commonly th an at other times. Torsion may present with abdominal pain, nausea, vomiting, shock, local tenderness (usually at 8 \200\22316 weeks). 2 \200\2235% of tumors are malignant. Suspect m alignancy with ruptures (then biopsy other ovary). 25% of malignant tumors will be dysgerm inomas. 282 Tumors can become necrotic due to pressure on them in labor. Tumors lying in the pelvis can obstruct labor so cesarean section will be needed unless they are cysts which can be aspir ated under ultrasound control before labor. Asymptomatic simple cysts <5cm across can be left until after delivery if watched by ultras ound. Those 5 \200\22310cm may be aspirated under ultrasound control (and the aspirate exam ined cytologically). Other tumors (those that are complex multilocular or with solid portio ns on ultrasound) should be removed at about 16 weeks \200\231 gestation (by which time the pregnancy is not dependent on the corpus luteum and miscarriage is less likely) to exclude car- cinoma and prevent complications developing. If the diagnosis is made late in pregnan cy and the tumor is not obstructing the pelvis, it is usual to let labor progress normally, and to remove the tumor in the early puerperium because of the risk of torsion then. y g o o c e a n y G l Postmenopausal ovarian tumors The aim is to identify those with high risk of cancer for tre atment at special cancer centers. 21% of postmenopausal women have cysts on screening ul- t rasound. Ultrasound is 89% sensitive and 73% speci \201 c for detecting cancer. CA-125 (p2 83) estimations 81% and 75% respectively. A CA-125 >30u/mL is +ve in 80% of malignancies (b ut in only 50% stage I). Risk of malignancy (RMI) can be calculated with the formula below. RMI <25 has a cancer risk <3%, risk is 75% if RMI > 250 (manage these high-risk women at a cancer center). RMI=U \211\210 M \211\210 CA-125 (M=3; CA-125 is the number for U/mL; U is 1 if ultrasound score=1, and 3 if ultrasound score 2 \200\2235.) To calculate ultrasound score add 1 for each of the following ultrasound features: multilocular cyst; solid area i n cyst; bilateral lesions; evidence of metastases; ascites present. \200\225111 Unilocular cysts <5cm with a normal CA-125 can be managed conservatively (ultrasound every 4 months for 1 year). Low-risk cysts may be removed at bilateral laparoscopic oophorectomy (if suitable for laparoscopic treatment). Postmenopausal cysts should not be aspirated. Hig h-risk cysts need optimal surgical staging ie total abdominal hysterectomy + bilateral salp ingo-oopho- rectomy + infracolic omentectomy at a cancer center with cytology of ascites an d washings, + biopsy of suspicious (eg peritoneal) areas/adhesions (random biopsy if none s uspicious), + retroperitoneal lymph node assessment, (biopsy palpably abnormal para-aortic or pelvic wall nodes or random samples if none palpable). 283 Ovarian carcinoma This is rare, but more women die from it (it is the 5th commonest cause o f cancer-related death in UK women) than from carcinoma of the cervix and uterine body comb ined because in 80% it causes few symptoms until it has metastasized, often to the pelvis with omental and peritoneal seedlings ( lymphatic spread via the para-aortic nodes). Over all 5-yr survival <35%. Incidence 1 in 2500 women >55yrs; 1 in 3800 if >25yrs. If 2 close r elatives aff ected lifetime ovarian cancer risk is 40% (liaise with a gynecologist; see bel ow). 10% of aff ected North American women carry mutations in BRCA1 or BRCA2 genes. Carrier risk of developing carcinoma is 40% for women with BRCA1 mutation, 25% if BRCA2. It is com moner in those with many ovulations (late menopause, nullipara) and, possibly, after subfer tility treatment (p294). Combined oral contraceptive Pill use (p300), breastfeeding, hyster ectomy and tubal ligation reduce risk. Current HRT use increases risk.1 Presentation Sympto ms are often vague. See page 281. Screening & prevention There is really no good screening test. Transvaginal ultrasound with tumor blood \202 ow measurement can diff erentiate bet ween benign and malignant neoplasms at an early stage but does not seem to re- duce mortali ty in high-risk women. 112 Plasma levels of cancer-associated anti- gen (CA-125) lack suffi cient sensitivity or speci \201 city for population screening. y g o o c e a n y G l Consider prophylactic oophorectomy when older women have hysterec- tomy. It is used for tho se with BRCA1 & 2 mutations. The combined oral con- traceptive Pill reduces the risk (up to 40%). Tubal ligation also reduces risk in those with BRCA1 mutation. 113 Diagnosis Histolo gy. Ascites, ultrasound/CT, and CA-125 \200\200 suggestive. Staging at laparotomy Stage I: Disease limited to 1 or both ovaries. Stage Ic if ruptured capsule, tumor on ovarian surface, or ascites/peritoneal washings +ve. Stage II: Growth extends beyo nd the ovaries but con \201 ned to the pelvis. Stage III: Growth involving ovary and perit oneal implants outside pelvis (eg super \201 cial liver), or +ve retroperitoneal or inguin al nodes. Stage IV: Those with distant metastases (including liver parenchyma). 80% present with stag e III or IV disease. 5-yr survival: Stage I, 67%; Stage II, 42%; Stage III and IV, 14.4%. T reatment Best carried out in specialist centers; 114 this depends on tumor type. Adenocarci nomas (89%, also called ovarian epithelial carcinomas) are treated with surgery and chemoth erapy, which aims for cure. Surgery re- moves as much tumor as possible: the less left, the more eff ective is chemo- therapy and the better the prognosis. In a young woman with earl y disease, the uterus and other ovary may be left for fertility. Ensure optimal surgical st aging (OPPOSITE). NICE says low-risk stage 1a or b disease may not need chemotherapy. \200 110 Chemotherapy for 6 months post-op is usual. Carboplatin with paclitaxel (from Paci \201 c yew trees) produces higher response rates and longer survival both when used for ini tial treatment and for treatment of recurrences com- pared to use of carboplatin alone. Rad iotherapy may be tried. Further treatment may involve \200\230second look \200\231 laparotomy, with secondary cyto reduction if appropriate, further chemotherapy, or radiotherapy. Colloidal gold may control ascites. Advanced or relapsed ovarian cancer: see NICE. Options include paclitaxel, pegylated liposo mal doxorubicin, and topotecan. Palliative care involves relief of symptoms, which are gene rally due to extensive peritoneal disease. 1 NNT=1 extra cancer/2000 users, 1 extra death per 3300 users.48 Vaginal discharge Discharge may be physiological (eg pregnancy; sexual arousal; puberty; Pi ll). Most discharges are smelly, itchy, and due to infection. Foul discharge may be due to a foreign body (eg forgotten tampons, or beads in children). Note the details of the discha rge. Has she a sexually transmitted disease (STD)? See OHCM p404. If so, refer to a genitou rinary clinic. Do a speculum examination and take swabs: urine and endocervical samples for chlamydia (BOX); cervical swabs for gonorrhea (OHCM p416). \200\207Discharges rarely rese mble their classi- cal descriptions. Thrush (Candida) The 2nd commonest cause of discharge (1st is bacterial vaginosis), 95% is due to C. albicans, 5% C. glabrata (harder to treat). Vulva and vagina may be red, \201 ssured, and sore, especially if allergic component; dis charge is non-off ensive, classically white curds. Her partner may be a car- rier who is as ymptomatic. Pregnancy, contraceptive and other steroids, im- munode \201 ciencies, antibio tics, and diabetes are risk factors \200\224check glucose. Candida elsewhere (eg mouth, nat al cleft) in both partners may cause rein- fection. Thrush is not necessarily sexually tran smitted. Diagnosis: Microscopy (shows mycelia or spores) and culture. Treatment: Topical tr eatment (eg clotrimazole 500mg pessary + cream for the vulva) gives similar cure rates to o ral \202 uconazole 150mg PO as a single dose. C. glabrata may require topi- cal nystatin or 7 \200\22314-day course of an imidazole. Use topical regimen alone if pregnant or breast feeding. Very recurrent infection may be treated by weekly maintenance doses of treatment ( unlicensed). Trichomoniasis Trichomonas vaginalis (TV; \201 g 1; sexu- ally transmitted) produces vaginitis and a bubbly, thin, \201 sh- smelling discharge. Exclude gonorrhea (of ten coexists). Motile \202 agellates are seen on wet \201 lms ( \211\210400), or cultur ed. \201\227: (treat partner too) metronidazole 2g PO stat or 400mg/ 12h PO for 5 days (eg if pregnant); if allergic or recalcitrant disease, vaginal acidi \201 cation with boric a cid can help. 115 Bacterial vaginosis Prevalence 10% mostly asympto- matic. Any discharge has \201 shy odor, from cadaverine & pu- trescine. Vaginal pH is >4.5. The vagina is not in \202 amed and pruritus is uncommon. Mixed with 10% potassium hydroxide on a slide, a wh iff of ammonia may be detected. Stippled vaginal epithelial \200\230clue cells \200\231 ma y be seen on wet microscopy ( \201 g 2, top). There is altered bacterial \202 ora \200 \224overgrowth, eg of Gardnerella vaginalis, Mycoplasma hominis, peptostrep- tococci, Mobil uncus and anaerobes, eg Bacteroides spe- cies \200\224with too few lactobacillae. There is \200\200 risk of preterm labor, intra-amniotic infection in pregnancy, susceptibility to H IV, 116 and post-termination sepsis. \201 : By culture. \201\227: Met- ronidazole 2g PO o nce, gel PV, or clindamycin 2% vaginal cream, 1 applicatorful/night PV 7 times. If recurren t, treating the partner may help. If pregnant, use metronidazole 400mg/12h PO for 5 days. B alance activ vaginal acidic gel can be a useful (more natural) alternative. Discharge in children may re \202 ect infection from fecal \202 ora, associated with alkalinity from lack of vaginal estrogen (prepubertal atrophic vagini- tis). Staphs and streps may cause pu s. Threadworms cause pruritus. Always consider sexual abuse. Gentle rectal examination may exclude a foreign body. Tests: Vulval vaginal swab (hard to know if result is normal \202 ora). MSU: is there glycosuria? For prolonged or bloody discharge, examine under anaes - thesia (pediatric laryngoscopes can serve as specula) ultrasound or x-rays. Management : Discuss hygiene. If an antibiotic is needed, erythromycin is a good choice. An estrogen c ream may be tried ( \211 1cm strip). 284 \200 y g o o c e a n y G l Fig 1. TV. Prof S Upton; Kansas Univ. Fig 2. Clue cells . Oxford Textbook of Medicine, OUP 285 Testing for chlamydia Special swabs/kits exist for chlamydia transportation to the lab and conventional enzyme immunoassay assay \200\224but may be unreliable (sensitivity 79%). 117 An example is the IDEIA chlamydia specimen collection kit with a Dacron tip supplied b y some labs. First-void (early morning) urine may be the single best diagnostic speci- men (for M. genitalium and C. trachomatis) detection by PCR. An additional endocervical specime n may also be needed. 118 In one study, sensitivities for LCR (ligase chain reaction), PCR (polymerase chain reaction), gene probe, and EIA (enzyme immuno-assay) on urine were 96%, 8 6%, 92%, and 38%, respec- tively, while on cervical swabs the corresponding sensitivities o f PCR, gene probe, and EIA were 89%, 84%, and 65%. DNA ampli \201 cation methods may work best for urine and swabs in low-prevalence populations. 119 One-stop test-and-treat: In an eff ort to decrease the number of chlamydial infections in the UK, the NHS is assessing ove r-the-counter availability of azithromycin for those visiting pharmacies (and their partner s) \200\224whose urine tests +ve for chlamydia. y g o o c e a n y G l Pelvic infection Pelvic infection aff ects the Fallopian tubes (salpingitis) and may involv e ovaries and parametria. 90% are sexually acquired, mostly chlamydia: 60% of these are asy mptomatic ( \200 / \200 =1 : 1) but subfertility or ectopic pregnancy may be the result, wh ich is why screening has been proposed \200\224eg by a urine ligase chain reaction DNA: see BOX. Other causes, eg the gonococcus, are rarer (14% \200\224if found, retest after treatm ent). Organisms cultured from infected tubes are commonly diff erent from those cultured fr om ectocervix, and are usually multiple. 10% follow childbirth or instrumentation (insertio n of IUCD, ToP) and may be streptococcal. Infection can spread from the intestinal tract du ring appendicitis (Gram \200\223ve and anaerobic organisms) or be blood-borne (tuberculosi s). Salpingitis Patients with acute salpingitis may be most unwell, with pain, fever, spasm of lower abdominal muscles (she may be most comfortable lying on her back with legs \202 exed) and cervicitis with profuse, purulent, or bloody vaginal discharge. Heavy menstrual loss suggests endometritis. Nausea and vomiting suggest peritonitis. Look for suprapubic te nderness or peritonism, cervical excitation, and tenderness in the fornices. It is usually bilateral, but may be worse on one side. Subacute infection can easily be missed, and lapa- roscopy may be needed to make either diagnosis. Management \200\207Prompt treatment and c ontact-tracing minimizes compli- cations. Take endocervical and urethral swabs if practicab le. Remember to check for chlamydia. Admit for blood cultures and IV antibiotics if very un - well (eg ceftriaxone 2g/24h slow IV with doxycycline 100mg/12h PO) initially, then doxycy cline 100mg/12h PO and metronidazole 400mg/12h PO until 14 days treated. Seek advice from m icrobiologist if gonorrhea isolated. If less unwell give o \202 oxacin 400mg/12h PO and me tronidazole 400mg/12h PO for 14 days. If infection is severe remove intrauterine contracept ive device (not needed if mild). \200\225120 Trace contacts (from within last 6 months and ensure they seek treat- ment \200\224seek help of the genito-urinary clinic). Advise avoid ance of intercourse until patient and partner treatments complete. Complications If respons e to antibiotics is slow, consider laparoscopy. She may have an abscess (draining via the p osterior fornix prevents perforation, peritonitis, and septicaemia \200\224but laparotomy m ay be needed). Inadequate or delayed treatment leads to chronic infection and long-term tub al blockage (8% are subfertile after 1 episode, 19.5% after 2, 40% after 3). Advise that ba rrier contraception protects against infection. Ectopic pregnancy rate is increased 10-fold in those who do conceive. Chronic salpingitis Unresolved, unrecognized, or inadequately tr eated infec- tion may become chronic. In \202 ammation leads to \201 brosis, so adhesion s devel- op between pelvic organs. The tubes may be distended with pus (pyosalpinx) or \202 uid (hydrosalpinx). 286 \200 y g o o c e a n y G l Pelvic pain, menorrhagia, secondary dysmenorrhoea, discharge, and deep dyspareunia are some of the symptoms. She may be depressed. Look for tubal masses, tenderness, and \201 xed r etroverted uterus. Laparoscopy diff erentiates infection from endometriosis. Treatment is unsatisfactory. Consider long-term broad-spectrum antibiotics (eg tetracycline 250mg/6h PO 1h before food for 3 months), short-wave dia- thermy and analgesia for pain, a nd counseling. The only cures are the meno- pause or surgical removal of infected tissue. 287 Screening tests to prevent chlamydial pelvic infection Opportunistic screening in family pl anning and ToP contexts, and routine GP appointments for all sexually active women aged up to 25yrs has been sug- gested. This might miss up to 20% of infections (increasing the age limit to 30 might miss just 7%). It is not clear how this screening is to be woven into rou tine appointments (which are already overfull), and whether patients will \201 nd screeni ng acceptable. What is clear is that chlamydia is common in the young, with rates of 8.1% p revalence in under 20s reported as hav- ing infection from general practice settings, and 1 7.3% from genitourinary settings. 121 In Scotland prevalence was found to be 12.1% in under 20s at an- tenatal clinics, and 12.7% at abortion clinics, and cost-eff ectiveness studies suggest screening younger women attending these clinics and all attending colposcopy clini cs as being the most cost eff ective. 122 Postal general popula- tion screening is not eff ective. 123 Infection is increasing annually, with 42,668 cases reported by UK GU clinics i n 1997, and 113,585 cases in 2006, a 166% in- crease. y g o o c e a n y G l In the UK, some pharmacies off er free chlamydia tests funded by the NHS eg for those aged 16 \200\22324yrs (eg in London), and if +ve to their partners, whatever the age ( over-th e-counter \200\224 if +ve, p285). There is also a national screening program that operates in colleges, prisons, and the armed forces. Treatment of uncomplicated genital chlamydial infection is with azithromy- cin 1g PO as a s ingle dose. Note: 80% of infections are asymptomatic. Unsched- uled bleeding may be the onl y symptom. Endometriosis Foci of endometrial glandular tissue, looking like the head of a burnt match, occur beyond the uterine cavity, eg on an ovary (chocolate cyst), in the recto- vaginal po uch, uterosacral ligaments, on the pelvic peritoneum, and rarely in the umbilicus ( \201 g 1), lower abdominal scars, and distant organs, eg lungs. If foci are found in uterine wall muscle, the term adenomyosis is used. Preva- lence: 10% of all women; 35 \200\22350% of t hose with subfertility. Cause Possibly cell rests, or retrograde menstruation (Sampson \200 \231s theory, ex- plaining its association with age \200\224typically 40 \200\22344yrs, lon g duration of IUCD and tampon use, its negative association with pregnancy and the Pill, an d its pelvic distribution, but not its appearance elsewhere). There are genetic com- ponent s, autoantibody associations, and environmental factors. Endometri- otic foci are under hor monal in \202 uence with waning in pregnancy and (usually but not always 124) at the menop ause \200\224and bleeding during menstruation. Free blood irritates, provoking \201 brosi s, adhesions and subfertility. Presentation Asymptomatic (even in extensive disease) \200 \224or pelvic pain (classically cyclical, at the time of periods). It may be constant, eg i f adhe- sions. Secondary dysmenorrhoea and deep dyspareunia are common. Thigh pain and pain on defecation may occur. \200\207Always think of endometriosis as an alternative to diagn osing irritable bowel syndrome. Periods are often heavy and frequent, especially with adeno myosis. Patients may present with subfertility. Extra-pelvic endometriosis causes pain or b leeding at the time of menstruation at the site of the pathology, eg haematuria or haemotho rax. Diagnosis Per vaginam: \201 xed retroverted uterus or uterosacral ligament nodules a nd general tenderness suggest endometriosis. An enlarged, boggy, tender uterus is typical o f adenomyosis. Laparoscopy reveals cysts, adhesions, peritoneal deposits, and diff erentiat es it from chronic infection. Have low threshold for investigation of adolescents in whom i t tends to be missed. Treatment See p241. If asymptomatic, don \200\231t treat. Join an end ometriosis society,1 as treatment can be long and diffi cult: \200\207mutual support helps . If analgesia/NSAIDs fail, consider the options below. Stress is a key exacerbating factor ; address this too (p386). 125 Don \200\231t forget other pain management meth- ods.2 Hormo nal therapy aims to suppress ovulation for 6 \200\22312 months during which some (non-GI) l esions atrophy. Don \200\231t use if pregnant or lactating. The com- bined Pill helps some (low-dose monophasic, continuously). If insuffi cient, or contraindicated, or has bad side eff ects, consider progestogens \200\224oral (eg continuous norethisterone), injected (p304 ), or intrauterine (eg Mirena , p298 \200\224eg if adenomyosis), danazol, or gonadorelin a nalogs (eg leuprorelin). The latter are not recommended for adolescents as they \200\201 b one density (up to 13% loss). Side eff ects are those of premature menopause. Estrogen add- back is recommended with their use to protect bones. 126 Surgery/laparoscopy Excision, ful guration (destruction by electric current) or laser ablation of peritoneal endometrial impl ants, endometrioma and rectovaginal nodule removals reduce pain. Alternative: total hystere ctomy + bilateral salpingo-oophorectomy, depending on lesion site and wishes for fer- tilit y. Surgery may be best if symptoms seriously impinge on a patient \200\231s life, but relap se is common, and repeat surgery is often needed. Complications Obstruction (GI; ureteric; fallopian). It is associated with ovar- ian endometrioid and clear cell cancers, Hodgkin \200\231s lymphoma and melanomas. Prognosis Endometriosis is chronic or relapsing, being pr ogressive in 50%. Surgery minimally helps fertility, but is recommended by NICE. 288 \200 y g o o c e a n y G l 1 In the UK, 50 Artillery Road, London, tel. 0207 222 2776 endo.org.uk. 2 \200\207Encourag e optimism; discourage passive-dependency.4 Biofeedback may \200\201endometriosis pain.127 289 y g o o c e a n y G Fig 1. Endometriotic nodule in the umbilicus seen at menstruation. l Prolapse A prolapse occurs when weakness of the supporting structures allows the pelvic org ans to sag within the vagina. The weakness may be congenital, but it usually results from s tretching during childbirth. Poor perineal repair re- duces support (p92). Weakness is exac erbated by menopausal atrophy and by coughing and straining. They may cause distressing inc ontinence and be a nuisance but are not a danger to health \200\224except for third-degree uterine prolapse with cystocele when ureteric obstruction can occur. 290 \200 Types of prolapse are named by the structures sagging. Several types may coexist in the same patient. Cystocele The upper front wall of the vagina, and the bladder attached to it, bulge. Residual urine within the cystocele may cause frequency and dysuria. Urethrocele If the lower anterior vaginal wall bulges, this will displace the urethra and impair the sphincter mechanisms (p306), so leading to stress in- continence. Does she leak when she laughs? Rectocele The middle posterior wall, which is attached to rectum, may bulg e through weak levator ani. It is often symptomless, but she may have to reduce herniation prior to defecation by putting a \201 nger in the vagina, or pressing on the perineum. En terocele Bulges of the upper posterior vaginal wall may contain loops of intestine from the pouch of Douglas. Uterine prolapse With \201 rst-degree prolapse the cervix stays in the vagina. In second-degree prolapse it protrudes from the introitus when standing or straini ng. With third-degree prolapse (procidentia) the uterine fundus lies out- side the vagina. The vagina becomes keratinized and the cervix may ulcerate. Symptoms: \200\230Dragging \200\231 or \200\230something coming down \200\231 is worse by day. Cystitis, frequency, s tress incontinence, and diffi culty in defecation may occur depend- ing on the type of prol apse. Examine vaginal walls in left lateral position with a Sims \200\231 speculum; ask the patient to bear down to demonstrate the prolapse. Do urodynamic studies (p307) to exclude detrusor overactivity and assess voiding. Prevention: Lower parity; better obstetric practi ces, pelvic \202 oor exercises. Treatment: Mild disease may improve with reduction in int ra-abdominal pressure, so encourage her to lose weight, stop smoking, and stop straining. I mprove muscle tone with exercises or physiotherapy, and, if postmenopau- sal, topical oestr ogens, eg estriol cream 0.1% as often as required (try twice weekly). Estradiol vaginal tab lets used weekly provide a less messy vaginal alternative. y g o o c e a n y G l Severe symptomatic prolapse is best treated surgically. Incontinence needs to have the caus e treated (so arrange urodynamic studies to plan the best type of surgery). Repair operatio ns (p308) excise redundant tissue and strengthen supports, but reduce vaginal width. Is she sexually active? If so, surgery must compromise between reducing prolapse and maintaining width. Marked uterine prolapse is best treated by hysterectomy. Post-hysterectomy vault pro lapse may be treated by sacrocolpopexy (eg with mesh). \200 128 Trans- vaginal mesh repair for cystocoele may give fewer symptoms of recurrent prolapse at 1yr but higher rates of st ress incontinence and serious operative complications (4%). 129 Ring pessaries may be tried as a temporary measure or for the very frail. Select size by di ameter of vagina at level of the fornices; it will only stay in if the vagina narrows neare r the introitus. Insert into the posterior fornix and tuck above the pubic bone (easier if the ring has been softened in hot water \201 rst). Problems: discomfort, infection, ulcer ation (change 6 \200\22312-monthly). For those in whom they keep falling out, try a shelf p essary. This page intentionally left blank Subfertility: causes and tests \200\207This can be devastating to both partners and its in vestigation a great strain. Sympathetic management is crucial. 84% of young couples having regular intercourse conceive within a year (92% by 2 years). Off er investiga- tion after 1 yr of trying (earlier if \200 aged \211 35 years, amenorrhoea, oligomen- orrhoea, or pas t pelvic in \202 ammatory disease, undescended testes or cancer treatments which may aff e ct fertility). Arrange counseling throughout. Fertil- ity decreases with age: girls are bor n with 300,000 potential eggs; by 30yrs, only 12% are left (by 40yrs, just 3%). In the 10% of subfertile couples consider: \200 Is she producing ova? (Anovulation causes 21%.) \200 Is he producing enough, healthy sperm? (Male factors cause 24%.) \200 Are ova and s perm meeting? (Tubal cause 14%, hostile mucus 3%, sexual dys- 292 function 6%.) Aim for intercourse 3 times/week throughout the cycle. Is the embryo implanting? Endometriosis is a cause in 6% (laparoscopic surgery helps). The cause is \200\230unexplained \200\231 in 27% of couples: here, 60 \200\22370% achieve con ception within 3yrs. Initial management It takes 2 to be infertile ( \200 causes \211\210 67%); see both part- ners; advise to stop smoking and lose weight if BMI >29. She should t ake 0.4mg folic acid/day from now on. Reducing stress and boosting wellbeing helps.1 Ask he r about: Menstrual history; previous pregnancies (any miscarriages?); contraception; histor y of pelvic infections or abdominal surgery; drugs. Ask him about: Puberty; previous father hood; previous surgery (hernias; or- chidopexy; bladder neck surgery); illnesses (venereal, adult mumps); drugs; al- cohol; job (is he home at ovulation time?) and erectile problems (seen in 4%).130 Ask both about: Mood; feelings about subfertility; technique; frequency/ti m- ing of intercourse (non-consummation is rare); parenthood; previous tests. Examination C heck the woman \200\231s general health and sexual development and examine the abdomen and pelvis. If the sperm count is abnormal, examine the man for endocrine and penile abnormalit ies, varicoceles; con \201 rm there are 2 normal testes. What is his BMI? Obese men produc e 60% less seminal \202 uid than men with a BMI \211 25, and have 40% higher levels of a bnormal sperm.131 Tests for ovulation If cycles are regular ovulation is likely. Basal body tem- perature rises midcycle (but charting is diffi cult and may raise anxieties). Blood t ests Check rubella status; immunize if non-immune. If you suspect anovulation check: \200 Serum mid-luteal progesterone ie 7 days before expected period (>30nmol/L is indicative of ovulation) \200 Day 5 FSH (>10U/L indicates a poor response to ovarian stimulation; it m ay indicate primary ovarian fail- ure \200\224but FSH is pulsatile in release and one may g et a high reading depending on the stage of the cycle) \200 Day 5 LH (for polycystic ovar y syndrome) \200 TFT if symptomatic \200 Blood prolactin if anovulation or galactorrhoe a (if high may be due to prolactinoma; MRI of brain and pituitary gland). Semen analysis fo r: \200 Volume >2mL (mean 2.75mL now, formerly 3.4mL in the 1940s) \200 Sperm count/mor phology \200 Infection. Normal count >20 million sperm/mL, >50% motile within 1h of ejacu late production (liquefaction also within 1h), and >30% normal form; WBC < 1 million/mL; me an sperm count=66 million/mL (113 million/mL in the 1940s; this average is falling \200\224 which may be due to an environmental in \202 uence \200\224or more frequent ejaculations). Examine 2 specimens (ideally 3 months apart so spermatozoa cycle completed but soon if spe rm severely de \201 cient) as variation may be considerable. Transportation sam- ple fresh to lab (masturbated into a wide topped container). Avoid tempera- tures <15 C or >38 C. Reduced counts require specialist referral. y g o o c e a n y G l 1 Each point on the 5-point wellbeing index score accounts for a 7% increase in sperm conce ntration132 293 Subfertility options: abbreviations, problems, and ethics Donor insemination (In some countries, children have no rights to information about their f ather: this can lead to problems \200\224eg most children want their fathers to be proud of them, and with DI this is im- possible.) The great questions such as where do I come from? become more opaque than ever. UK law does allow tracing of fathers. Fetal egg child (off s pring from an egg taken from an aborted fetus). Gamete intrafallopian transfer. Intracytopl asmic sperm injection (directly into an egg). Sperm may be taken surgically from the testis or epidydimis. Such patients, with no exposure to their partner \200\231s sperm, are at in creased risk of pre-eclamp- sia (p48): this supports a model of pre-eclampsia postulating a bsence of partner-speci \201 c immune tolerance as a causative factor.133 Intra-cytoplasmi c morphologically-selected sperm injection.134 Preg- nancy rate for IMSI is 39% (vs 26% fo r ICSI).135 Intrauterine insemination with superovulation: a USA favorite. In 20%, this cau ses twins (in 10%, higher order pregnancies when pregnancy is achieved; a possibly unaccept able disadvantage). In vitro fertilization: see p69 and p294. In vitro maturation: immature eggs are collected from the ovaries, matured in the lab before sperm injection (ISCI). Avo ids expensive ovulation-inducing drugs and risk of ovarian hyperstimulation, it may be espe cially suitable for women with polycystic ovaries. Microepididymal sperm aspiration from te stis, post-vasectomy DI FEC GIFT ICSI y g o o c e a n y G l IMSI IUI IVF IVM MESA OT/NT(P) Ooplasmic transfer/nuclear transfer procedure: the baby has 2 moth- ers: one (too old to conceive normally) gives a nucleus; the other gives fresher cytoplasm (+mitochondrial DNA) for the ovum. This is an 15 babies were born using example of human ge rmline modi \201 cation. this technique in the USA (2 had Turner \200\231s syndrome). Perc utaneous epididymal sperm aspiration (like MESA, but uses a needle inserted into the epidid ymis, so scrotal exploration is not needed). Pregnancy by human cloning (illegal in many co untries partly because of concern about premature ageing). Peritoneal oocyte sperm transfer . Pregnancy by ovary transplant has been reported (autologous trans- plant, 1 between ident ical twin sisters, another between sisters). PESA PHC POST POT \201\201Various national embryology authorities exist and pronounce on the ethics of fertility options, and their edicts can appear to be set in stone (although being mutual ly contradictory with those from other countries). One problem with this approach is that f ertility options are constantly changing, as are society \200\231s views on what is accepta ble. It is not clear whether these views should lead, or simply be taken into account (an o paque phrase) or be trumped by appeal to some higher authority (God, or the conscience of a quango). The above methods allow embryos to be sexed and screened for genetic diseases wit h implantation only for those with the desired characteristics, eg off ering a perfect matc h for stem-cell trans-plantation to an older sibling, with Fanconi \200\231s anemia. Contro versies surrounding creating an individual expressly for the pur- poses of another might se em to be new, but mythology has, since before the dawn of time,1 acclimatized us to this ac tivity \200\224which is why it is gaining acceptance. 1 According to Paradise Lost, the First Operator, in a controversial act of vivisection, \200\230opened my left side, and took from thence a rib, with cordial spirits warm, and lif e-blood streaming fresh: wide was the wound, but suddenly with \202 esh \201 lled up an d healed: the rib he formed and fashioned with his hands; under his forming hands a creatur e grew, manlike, but diff erent sex, so lovely fair, that what seemed fair in all the world , seemed now mean, or in her summed up. \200\231 Thus was Eve made, not for herself, but si mply to delight Adam and keep him company.136 Operators beware! This sort of activity canno t now be done in your garden but only in clinics licensed by the Human Embryology Authority . Subfertility: tests and treatment Tests of tubal patency (Screen for chlamydia \201 rst). Unless damaged tubes are expected do hysterosalpingogram (or hystero- salpingo-contrast ul trasonography) \201 rst. 1 A hysterosalpingogram (contrast x-ray) demonstrates uterine an atomy and tubal \200\230 \201 ll and spill \200\231. Unpleasant; it may require premedica tion. False posi- tives may occur with tubal spasm. Give antibiotics, eg cefradine 500mg/6h PO with metronidazole 1g/12h PR for 24h before and eg 400mg/12h PO for 5 days after proced ure to prevent pelvic infection. 294 2 Laparoscopy with dye. Pelvic organs are visualized and methylene blue dye injected throug h the cervix: if tubes are blocked proximally they do not \201 ll with dye; with distal b lock there is no \200\230spill \200\231 into the peritoneal cavity. Treatment of subfertility Treatment is directed at the cause. \200 Azoospermia is unrespo nsive to simple treatment. A low sperm count may be improved by avoiding tobacco and alcoho l. Avoiding tight pants does not change testis T or semen parameters. Will they consider donor insemina- tion (AID=arti \201 cial insemination by donor)? If so check \200 ovulat ing; if tubal damage suspected, investigate. Give 3 cycles of intrauterine insemination (IU I) post ovulation; if unsuccessful do tubal investigations, then further 3 cycles. If still unsuccessful off er other treatment. y g o o c e a n y G l Problems of sperm deposition (eg erectile dysfunction) can be circumvent- ed by arti \201 cial insemination using the partner \200\231s sperm. Hyperprolactinaemia (OHCM p228) Remove the cause if one is found (eg pituitary microadenoma , drugs); if not, give bromocriptine 2mg/24h PO, in- creasing slowly until blood prolactin is normal. (Side eff ect: nausea.) Anovulation WHO classi \201 cation: \200 Class 1 is hypothalamic pituitary failure (this responds to pulsed gonadotrophin releasing hormone or gonadotro- phins with luteinizing ho rmone activity): \200 Class 2 is hypothalamic pituitary dysfunction (usually polycystic o vary syndrome, p252). Stimulate follicle development using clomifene 50 \200\223100mg/24h P O on days 2 \200\2236 inclusive. SE: \202 ushes (10%), visual disturbance (1.5%), abdomin al pain (5.5%, p311); warn about risk of multiple pregnancy excess risk of ovarian cance r (p280). Monitor response to clomifene with luteal phase progesterone (+ultrasound in at l east 1st cycle). If still no ovulation, try gonadotrophins. After 6 months ovulating off er clomifene assisted IUI (p293) if not pregnant. \200 Class 3 is ovar- ian failure (treatm ent is IVF, see below using donated ova).