Women with a uterus should also receive cyclical progestogens to reduce incidence of endome trial carcinoma, \200\224or use tibolone 2.5mg/day PO, a prepa- ration which aims not to ca use bleeds \200\224or continuous combined estrogen/ progestogen combinations, eg Kliofem , estradiol (=oestradiol) 2mg and norethisterone 1mg. For both these, start if >1yr after th e last period, or, if changing from cyclical HRT, wait until after 54yrs of age; bleeding i s common, in the 1st 4 months of use \200\224reassure; if after 8 months, do endometrial bi opsy. Kliofem may be useful if cyclical HRT causes \200\230premenstrual \200\231 symptom s. There may be advantages in using \200\230lipid-friendly \200\231 progestogen, dydrogest erone (no androgenic, mineralocorticoid, or oestrogenic action), eg Femoston 2/10 but see p303 for possible SE (DVT). Raloxifene, a selective estrogen receptor mod- ulator (SERM) p rotects bones while reducing breast 45 and endometrial cancer risk. It is ineff ective for \202 ushes. For thromboembolism, see OPPOSITE. HRT contraindications: \200 Estrogen-dep endent cancer \200 Past pulmonary em- bolus \200 Undiagnosed PV bleeding \200 LFT \200 \200 \200 Pregnancy \200 Breastfeeding \200 Phlebitis. Avoid or monitor closely in Du bin \200\223Johnson/Rotor syndromes (OHCM p712). If past spontaneous DVT/PE: is there throm bophilia (OHCM p368)? Side-effects: Weight \200\200; \200\230premenstrual \200\231 syndrom e; cholestasis; vomiting. Alternative therapies \200\22546 eg black cohosh (can cause hepa totoxicity ) \200\224p515. Annual check-up: Breasts; BP (stop if BP >160/100 pending invest igation and treatment). Weight; any abnormal bleeding? Creams, pessaries, and rings are useful for vaginal symptoms, eg Ovestin , ie estriol 0.1% , 1 applicator-full PV daily for 3 weeks, then twice weekly. They are absorbed but, if used intermittently, progestogens are probably unnecessary. If creams are unacceptable, conside r an estrogen-containing vaginal ring (eg Estring ), replaced every 3 months, for up to 2y rs. Vagifem is an estra- diol (=oestradiol) 25 g or 10 g vaginal tablet used daily for 2 weeks, and then twice weekly, with reassessment every 3 months. Transdermal patches are l ess \200\230medical \200\231 but are expensive and women with a uterus still need progesto gen, eg as tablets or Evorel conti patches. Estradiol (=oestradiol) patches supply 25 \200\223100 g/24h for 3 \200\2234 days. SE: dermatitis. Oestradiol gel 2 measures are appl ied daily to arms, shoulders, or inner thighs. Women with a uterus using gel also require p rogestogens for 12 days per cycle. HRT and cancer The Women \200\231s Health Initiative 48 con \201 rmed \200\200breast cancer risk (and showed excess stroke and heart attack risk, and 2-fold increase in dementia 49 in users): the Million Women Study 50 showed that there is greater risk when combined estrogen/progesterone preparations are used (relative risk=R R 2) compared to estrogen alone (RR 1.3) or tibolone (RR 1.45). Risk in- creases with lengt h of use. Ovarian cancer is increased in current users after 5 years \200\231 use (estrogen component RR 1.2). 51 Endometrial cancer risk is \200\200 with unopposed estrogen use, \200\211 with cyclical progesterone added, and possibly \200\201 with continuous combined added progesterone. 52 Lung cancer mortality (but not incidence) is increased, (so stop, if lung cancer develops). 53 Hence our policy on HRT is: \200 To discuss the risk of breast cancer with each patient considering HRT. \200 To document this discussion in the patien t \200\231s notes. \200 Encourage breast awareness and to report breast change. Formal br east examination by nurses may give false reassurance (advice of the UK \200\231s Chief Med ical Offi cer). Mammographic screening may be less eff ective in current users. 54 It is di ffi cult if aged 40 \200\22350yrs (breast density \200\200). \200 To use for symptomatic treatment (warn symptoms often return on stop- ping therapy however long it has been used f or) at the lowest dose needed to control symptoms, for the shortest time possible. 257 y g o o c e a n y G l To be wary about HRT in those with a family history of breast cancer. \200 To consider st opping HRT before 5 completed years of therapy. HRT is no longer licensed for osteoporosis prevention: consider raloxifene (which \200\201risk of breast cancer; it is related to tam oxifen), 55 or bisphosphonates. HRT and venous thromboembolism (VTE) Overall HRT doubles ri sk (which \200\200 with age). Consider other predisposing factors, such as prolonged immob ility, surgery, obesity, severe varicose veins (others see p16). On starting explain risk a nd advise to seek urgent help if symptoms develop. Stop HRT if VTE de- velops. Before start ing, elicit personal and family history of venous thrombo- embolism (VTE), discuss thrombop hilia screen if history. Thrombophilia \200\200 risk ( \211\2108 if Factor V Leiden or pro thrombin 20210A mutation). If thrombophilic seek expert advice. Transdermal use has less ri sk, and oral HRT is contraindicated if past history of VTE. SERM therapy (OPPOSITE) carries same VTE risk as HRT. NICE \200 56 says stop 4 weeks pre-elective surgery; RCOG \200\225 57 says consider cases individually and use thromboprophylactic measures for surgery. Termination of pregnancy (TOP) \200\207Under British law, no one has to have an abortion, and no one has to do one. Worldwide, >20% of pregnancies are terminated and in the UK \205 \223 of women have had a TOP by age 45. Incidence: >200,000 TOP/yr in Great Britain (GB). L egal (GB) constraints The Abortion Act 1967 (amended 2002) and Human Fertilization and Embr yology Act 1990 allow termination if: A There is risk to mother \200\231s life if pregnancy continues. B Termination is necessary to prevent permanent grave injury to physical/ 258 \200 mental health of the woman. C Continuance risks injury to the physical or mental health of the woman greater than if terminated (and fetus not >24 weeks). D Continuance risks injury to physical/mental health of existing children of the woman greater than if terminated (and fetus not >24 weeks). E There is substantial risk that if the child were born he/she would suff er such physical or mental abnormalities as to be seriously handicapped. At present, two doctors must sign c erti \201 cate HSA1. If <16yrs try to get pa- tient \200\231s consent to involve her paren ts or other adult.1 97% are for ground C; 1% for D. <1% of TOPs are done after 20 weeks, us ually after amniocentesis, or when very young or menopausal mothers have concealed, or not recognized, pregnancy. TOPs after 24 weeks may only be carried out in NHS hospitals. Before TOP \200\207She has to live with the decision for the rest of her life. \200 Identify t hose needing support eg counseling. Not needed if sure of decision. \200 Is she de \201 nitely pregnant (eg reliable urine test)? Give information on and choice of methods. If ult rasound needed (eg dates unsure) ask if she wishes to see images. Off er cytology screening if not up to date. If she chooses TOP: \200 Screen for chlamydia: ( other STIs if rele vant). \200 Give antibiotic prophylaxis to reduce post-op infection rate (10% without) eg metronidazole 1g PR/800mg PO at TOP and azithromycin 1g PO same day. y g o o c e a n y G l Discuss contraception (IUCD or sterilization at operation need plans). \200 If RhD \200 \223ve she needs anti-D (all gestations, whatever method see p9). Bloods for Hb, ABO + RhD group and antibodies; HIV, hepatitis B & C, and hemoglobin opathies, if relevant. Assess venous thromboembolism risk. Methods Medical abortion uses an antigestagen, eg mifep ristone to disim- plant the fetus followed by a prostaglandin eg misoprostol to complete ab or- tion. It is highly eff ective from \211 6 weeks (98% eff ective at \211 7 weeks, 95% for weeks 7 \200\2239) and is also used for second trimester abortions. Misoprostol can be used orally or vaginally. For early abortions arrange follow-up (and scan) 2 weeks after pr ocedure unless complete abortion con \201 rmed on day of abor- tion. 5% will need surgical evacuation. Give NSAID pain relief during abortion; narcotic analgesia may also be needed, especially if gestation >13 weeks. Surgical abortion (vacuum aspiration and dilatation). C onsider need for pre- operative cervical priming (eg gestation >10 weeks, women <18 years o f age) in all women eg with misoprostol 400 g PV 3h or sublingual 2 \200\2233h pre-op. Os- motic dilators provide superior dilatation from 14 weeks, but misoprostol can be used up t o 18 weeks. Off er NSAID pain relief during abortion (paracetamol is ineff ective). Bleedin g and pain is less than with medical abortion. Vacuum aspiration Used from 7 to 16 weeks. L ocal anesthesia is safer than GA. If <7 weeks check for gestational sac in aspirate, follow -up with \200 HCG if not seen. If 14 \200\22316 weeks use wide-bore cannula. Access to US is desirable. Dilatation & evacuation Surgical forceps may be used at 13+0 \200\22324+0wks after cervical priming. Experienced operators are required. Real-time ultrasound reduces ut erine perforation rates and is recommended. 1 If the girl is a ward of court, the court has to approve abortion. 58 259 Regimens for terminating intrauterine pregnancies \200\22559 Early medical terminations \211 63 days \200\231 gestation At \211 49 days \200\231 gestation use mifepristone 200mg PO + misoprostol 400 g oral- ly 24 \200\22348h later. At \211 63 days \200\231 gestatio n mifepristone 200mg PO + misoprostol 800 g (4 \211\210200 g tablets) PV/buccal or sublin gual 24 \200\22348h later. For women at 50 \200\22363 days \200\231 gestation, if no aborti on 4h after misoprostol give a further 400 g PO/PV (route depending on preference and amou nt of bleeding). Medical terminations 9 \200\22313 weeks \200\231 gestation Mifepristone 20 0mg PO + misoprostol 800 g vaginally 36 \200\22348h later. A maxi- mum of 4 further doses of misoprostol 400 g may then be given 3-hourly PV/ PO. Medical terminations 13 \200\22324 weeks \200\231 gestation Mifepristone 200mg PO followed 36 \200\22348h later by misoprosto l 800 g PV: then misoprostol 400 g PV/PO every 3h to a maximum of 4 further doses. If abo r- tion does not occur mifepristone can be repeated 3h after the last dose of misoprostol a nd 12h later misoprostol recommenced. If there is clinical evi- dence that abortion is inco mplete, surgical evacuation of the uterus will be needed. Feticide In terminations later th an 21 weeks + 6 days (eg for abnormality) it is es- sential that the fetus is born dead (un less it is a lethal fetal abnormality). This may be achieved by use of 3mL intracardiac 15% potassium chloride ( anesthetic and/or muscle relaxant instillation beforehand to abolis h fetal movement). Con \201 rm asystole with ultrasound. (Intra-amniotic digoxin is a less eff ective alternative requiring less expertise.) If born after 24 weeks the dead fetus is a stillbirth and needs registering (p83). If there are signs of life then a death certi \201 cate is required. \200\22560 Complications of termination (terminology of risk)1 \200 Failure to abort (<1 : 100 medical TOP failure rate is higher than surgical ). \200 Infection post-abortion ( 2 : 100); see screening and antibiotics OPPOSITE. \200 Hemorr hage (<1 : 1000), (4 : 1000 if at \211 20 weeks). \200 Uterine perforation (1 \200\2234 : 1000), surgical terminations only \200 Uterine rupture (mid-trimester medical TOP): < 4 : 1000 \200 Cervical trauma (1 : 100). Risk less if early abortion: if experienced opera tor. \200 Small risk of premature labor in future pregnancies (if surgical abortion). Aft er termination Has she had anti-D (p9)? (250iu if <20 weeks; 500iu +Klei- hauer if later.) Is contraception arranged? (Can start Pill same day. Advise that long acting methods are mo re eff ective.) Give letter with suffi cient in- formation for practitioners elsewhere to m anage complications. Give writ- ten and verbal information on symptoms to be expected, thos e requiring emergency care, and of symptoms of ongoing pregnancy. Give 24h telephone helpli ne number. Off er follow-up. Refer women requiring emotional support/ at mental health risk . Women having medical terminations not con \201 rmed as successful at time of procedure n eed follow-up to ensure no ongoing preg- nancy (rate 0.5 \200\2231%). Misoprostol risks ter atogenicity. Decision to arrange uterine surgical evacuation is made on clinical signs and symptoms. Worldwide it is estimated there are 210 million pregnancies at any one time, and 1 in 5 are terminated. Over three-quarters of women live in developing countries, where 97% of the estimated 20 million unsafe terminations are carried out. 68,000 women die annually after unsafe termination. Accessible contraception reduces need for termination. Legalizat ion of termination re- duces the number of unsafe terminations and subsequent maternal deat h. y g o o c e a n y G l 1 The language of risk: 1 : 1 \200\2231 : 10 is very common; 1 : 10 \200\2231 : 100 is comm on; 1 : 100 \200\2231 : 1000 uncommon; 1 : 1000 \200\2231 : 10,000 is rare; < 1 : 10,000 is very rare (modi \201 ed from Calman et al). \200\22561 Miscarriage (spontaneous abortion) Miscarriage is the loss of a pregnancy before 24 weeks \200\231 gestation. 20 \200\22340% of pregnancies miscarry, mostly in the \201 rst trimes ter. Most present with bleed- ing PV. Diagnosis may not be straightforward (consider ectopi cs p262): have a low threshold for doing an ultrasound scan. Pregnancy tests remain +ve for several days after fetal death. Heavy/persistent bleeding >2 weeks needs ERPC (p308). Mana gement of early pregnancy bleeding Consider the following. \200 \200\207Is she shocked? There may be blood loss, or products of conception in the cervical canal (remove them with sponge forceps). 260 \200 Has pain and bleeding been worse than a period? Have products of concep- tion been seen? (Clots may be mistaken for products.) Is the os open? The external os of a multigravida usually admits a \201 ngertip. \200 I s uterine size appropriate for dates? \200 Is she bleeding from a cervical lesion and not from within the uterus? \200 What is her blood group? If RhD \200\223ve does she need a nti-D (p9)? If symptoms are mild and the cervical os is closed it is a threatened miscar- r iage. Rest is advised but probably does not help. 75% will settle. Threatened miscarriage ( especially second trimester) is associated with risk of subse- quent preterm rupture of mem branes and preterm delivery \200\224so book mother at a hospital with good neonatal facilit ies. y g o o c e a n y G l If symptoms are severe and the os is open it is an inevitable miscarriage or, if most of th e products have already been passed, an incomplete miscarriage. If bleeding is profuse, con sider ergometrine 0.5mg IM. If there is unacceptable pain or bleeding, or much retained tis sue on ultrasound, arrange evacuation of retained products of conception (ERPC). Expectant management is used when the volume of retained products is small eg <15mm across on transva ginal scan; when 15 \200\22350mm, medical management eg with vaginal misoprostol may be off ered (warn bleeding may last up to 3 weeks). Missed miscarriage: The fetus dies but is ret ained. There has usually been bleeding and the uterus is small for dates. Con \201 rm with ultrasound. Mifepris- tone and misoprostol may be used to induce uterine evacuation if the uterus is small but 50% will require surgical evacuation if uterine products are >5cm2 in the transverse plane, >6cm2 in the sagittal plane. Surgical evacuation is re- quired for la rger uteruses, if scar (previous caesar), by senior staff . Mid-trimester miscarriage This is usually due to mechanical causes, eg cer- vical incompetence (rapid, painless delivery o f a live fetus), uterine abnormali- ties, or chronic maternal disease (eg DM, SLE). An inco mpetent cervix can be strengthened by a cervical cerclage suture \200\22562 at 14 weeks o f pregnancy (eg if 3+ premature deliveries/mid-trimester losses, or previous loss/preterm d eliv- ery and ultrasound proven cervical shortening). It is removed prior to labor. After a miscarriage \200\207Miscarriage may be a bereavement. Give the parents space to grieve, t o ask why it happened and if it will recur. Off er follow-up. \200\22563 Fetal products sh ould be incinerated but if the mother requests alternative disposal (to bury herself) respe ct her wishes. Give in opaque container. \200\22564 Most early pregnancy losses are due to aneuploidy and abnormal fetal de- velopment; 10% to maternal illness, eg pyrexia. 2nd trimester loss may be due to infection, eg CMV (p34). Bac terial vaginosis has been implicated. Most sub- sequent pregnancies are normal although at increased risk. Recurrent miscarriage See OPPOSITE. Miscarriage with infection Presents as acute salpingitis (p286) and is treat- ed similarly. Start broad-spectrum antibiotics 1h pr ior to uterine curettage, eg co-amoxiclav (ampoules are 1.2g; 1g is amoxicillin and 200mg i s clavulanic acid; give 1.2g/6h IV) + metronidazole (eg 1g by suppository/8h). 261 Recurrent spontaneous miscarriage (RSM) This is loss of 3 or more consecutive pregnancies b efore 24 weeks \200\231 gesta- tion. It aff ects 1% of women. Prognosis for future successf ul pregnancy is aff ected by the previous number of miscarriages, and maternal age. (Rates of miscarriage are greatest when maternal age is \211 35 years, and paternal age \211 40 years.) Possible causes Endocrine: Polycystic ovaries are thought to be associated via ins ulin resist- ance. Metformin has been shown in small uncontrolled trials to reduce RSM. The role of progesterone in RSM is still being studied. Infection: Bacterial vaginosis (p284) is associated with 2nd trimester loss. Screening (and treatment) was previously recommended for those with pre- vious mid-trimester miscarriage or pre-term birth (bene \201 t unprov en). Parental chromosome abnormality: 2 \200\2235% of those with RSM. It is usually a balan ced reciprocal or Robertsonian translocation (p152). Refer to a clinical geneticist. Geneti c counseling off ers prognosis for future pregnancy, famil- ial chromosome studies, and app ropriate advice for subsequent pregnancy. Pre-implantation genetic diagnosis (p13 \200\224i nvolving in vitro fertilization) has lower rates of achieving healthy pregnancy outcome com pared to natural conception (30% vs 50%). Uterine abnormality: It is uncertain how much abn ormality is associated with RSM or if hysteroscopic correction of abnormality contributes t o suc- cessful pregnancy outcome, though septum division may help. 65 It is known that open uterine surgery increases chance of uterine rupture in pregnancy. Antiphospholipid antibod ies: (lupus anticoagulant, phospholipid and anti- cardiolipin antibodies) These are present in 15% of women with RSM. Most women with antibodies miscarry in the \201 rst trimester. If they are present, giving aspirin eg 75mg/24h PO from the day of positive pregnancy test + low molecular weight heparin, eg enoxaparin 40mg/24h sc) 66 as soon as the fetal heart i s seen (eg at 5 weeks on vaginal ultrasound) until 34 weeks \200\231 gestation helps. 67 Ge t expert advice. Resulting pregnancies are at high risk of repeated miscarriage, pre-eclamp sia, fetal growth restriction, and pre-term birth so need special surveillance. Live birth rate is 80%. Thrombophilia: In those with inherited thrombophilia heparin helps those who suff er from 2nd trimester losses but evidence is less certain for 1st tri- mester losses. Alloimmune causes: The theory is that these women share human leucocyte alleles (HLA) with their partners and do not mount the satisfactory protec- tive response to the fetus. Immuno therapy has not been found to increase live birth rate, is potentially dangerous and should not be off ered. Recommendation \200\22568 \200 Off er referral to specialist recurrent miscarriage clinic. \200 Test all women for antiphospholipid antibodies: positive if 2 t ests +ve, y g o o c e a n y G l taken 12 weeks apart. Women with 2nd trimester losses test for thrombophilia. \200 All women with recurrent 1st trimester losses, (or more than 1, 2nd trimester loss) should have pelvic ultrasound to as sess uterus; further tests eg 3-D ultrasound/laparoscopy/hysteroscopy if anatomy abnormal. Karyotype fetal products (3rd and subsequent fetal losses). If an unbal- anced chromosome a bnormality is identi \201 ed in the products of conception then karyotype the peripheral b lood of both parents. Ectopic pregnancy The fertilized ovum implants outside the uterine cavity. The UK incidence is 11 . 1 : 1000 pregnancies and rising; worldwide rates are higher. 7% of mater- nal dea ths are due to ectopics (1 . 8 deaths/1000 ectopic pregnancies). Predisposing factors Anyth ing slowing the ovum \200\231s passage to the uterus increases risk: damage to the tubes (s alpingitis; previous surgery); previous ectopic; endometriosis; IUCD; the PoP (p302), GIFT (p293). Pregnancy after tubal ligation is 9 times more likely to be ectopic. Site 97% are t ubal, mostly in ampulla; 25% in the narrow inextensible isthmus (presents early; risk of ru pture \200\200). 3% implant on ovary, cervix, or peritoneum. Natural history The trophoblas t invades the tubal wall, weakening it and producing hemorrhage which dislodges the embryo. If the tube does not rupture, the blood and embryo are shed or converted into a tubal mole and absorbed. Rupture can be sudden and catastrophic, or gradual, giving increas- ing pain and blood loss. Peritoneal pregnancies may survive into the third tri- mester, and may pre sent with failure to induce labor. Clinical presentation \200\207Always think of an ectopi c in a sexually active wom- an with abdominal pain; bleeding; fainting; or diarrhea and vom iting. 262 \200 y g o o c e a n y G There is generally 8 weeks \200\231 amenorrhoea but an ectopic may present be- fore a peri od is missed. An early sign is often dark blood loss ( \200\230prune juice \200\231, as the decidua is lost from the uterus) or fresh. In 10 \200\22320% there is no bleeding. Tubal c olic causes abdominal pain which may precede vaginal bleeding. The ectopic may rupture the tube with sudden severe pain, peritonism, and shock. More often there is gradually increasi ng vaginal bleeding, and bleeding into the peritoneum producing shoulder-tip pain (diaphrag matic irritation) and pain on defecation and urination (due to pelvic blood). 10% report no pain. The patient may be faint, with a tender abdomen (95%), enlarged uterus (30%), cervic al excitation (50%), adnexal mass (63%). Presentation may just be as di- arrhoea and vomiti ng, or nausea and dizziness. Classical features may be ab- sent. Examine gently, to reduce risk of rupture; preferably with an IVI in situ. Management \200\207Remember to give anti- D prophylaxis (p9), if needed. Early diagnosis is vital. Dipstix testing for \200 HCG (hum an chorionic gonadotrophin) is sensitive to values of 25IU/L. Quantitate \200 HCG (blood); do ultrasound. If \200 HCG >6000IU/L and an intrauterine gestational sac is not seen, ect opic pregnancy is very likely, as is the case if \200 HCG 1000 \200\2231500IU/L and no sac is seen on trans- vaginal ultrasound. Normally \200 HCG doubles over 48h. The higher the index of suspicion, the quicker the diagnosis. Unless urgent laparotomy needed, consider ty pe of treatment required in the light of the woman \200\231s future pregnancy wishes. Immed iate laparotomy: \200 Shock from a ruptured ectopic can be fatal. Im- mediate laparotomy i s necessary as only clamping the bleeding artery will relieve it. If you suspect an ectopic , put up an IVI; if already shocked put up 2 (14 or 16G). Give crystalloid as fast as possi ble, then blood (group O Rhesus \200\223ve if desperate, but usually better to wait for gr oup compatible). Inform your consultant. Take immediately to theater. Laparoscopy vs laparo tomy: Laparoscopy is preferred to laparotomy as re- covery time is reduced and it is less c ostly. Rates of subsequent intrauterine pregnancy are similar but persisting trophoblast is more of a problem (12% vs 1 . 2%). Single-shot methotrexate use reduces this risk. Persist ent trophoblast can cause later rupture and will need further treatment (surgical or methot rex- ate). See OPPOSITE. Repeat ectopic is slightly less common after laparoscopy. Salpingo tomy vs salpingectomy: If the contralateral tube is healthy, RCOG guidelines say there is n o clear evidence that salpingotomy should be used rather than salpingectomy. Subsequent int rauterine pregnancy rates are high- er after salpingotomy but so are rates of persisting tr ophoblast (8% vs 4%) l and subsequent ectopic pregnancy (18% vs 8%). Salpingotomy should be pri- mary treatment if the other tube is not healthy to preserve chance of future intrauterine pregnancy (49%), b ut warn of risk of future ectopic pregnancy. \200\225 69 Methotrexate: Methotrexate (eg 50m g/m2 IM or intratubal injection into the gestation sac) is sometimes used for small early e ctopics (eg <3.5cm in great- est diameter; \200 HCG level <3000IU/L, minimal symptoms. Vis ualization of a fetal heart is a contraindication to treatment). \211 15% will require mor e than 1 dose, and 10% surgical intervention (rupture rate 7% despite methotrexate treat- m ent). 75% of women will get some abdominal pain with treatment and ad- mission for observat ion and ultrasound may be required to distinguish rupture from the pain of separation with tubal abortion). Variable systemic dose re- gimes have similar success to salpingotomy. 70 Advise avoidance of intercourse during treatment and use of eff ective contraception for th e next 3 months (+ 12 weeks folate to restore levels once \200 HCG <5IU/L before attemptin g pregnan- cy). Multiple ovarian cysts, life-threatening neutropenia, pneumonitis, and late pelvic collections of blood have been reported with methotrexate treatment. Follow-up requ ires good compliance for repeat visits for serial \200 HCG until lev- els very low (usuall y <20IU/L). Fertility rates are no better with methotrexate or expectant management than wi th surgery. 71 Expectant management: Some tubal pregnancies end themselves without any prob lem so conservative treatment may be an option in those without acute symptoms and with fal ling \200 HCG levels that are <1000IU/L initially. 88% successfully resolve if initial \200 HCG <1000IU/L. There should be no evidence of blood, and <100mL \202 uid in the pouc h of Douglas. Follow-up twice weekly. Ide- ally \200 HCG drops by 50% and the adnexal mass is seen to be reducing in size by day 7. Follow-up until \200 HCG <20IU/L (as tubal ruptu re has been known to occur at low levels of \200 HCG). Expectant management may also be us ed for women with pregnancy of unknown origin (ie no ultrasound evidence of uterine or ec- topic pregnancy). It may be used if initial \200 HCG 1000 \200\2231500IU/L. Actively inter - vene if symptoms develop, or \200 HCG levels plateau or rise at 48 \200\22372h (23 \200 \22329%). Management of persistent trophoblast: This occurs in 8.2% having laparo- scopic s alpingotomy; 4% after open salpingectomy. Diagnosis is by \201 nding that \200 HCG does not drop according to the expected curve. Surveillance re- gimes vary: eg suspect if not fa llen to <65% of pre-op value by 48h post-op, or to <10% by 10 days post-op. Treatment is wi th methotrexate IM as above. Measures to reduce risk of missing ectopic pregnancies \200 Always send uterine curettings at ERPC (p308) for histology. \200 If histology does not c on \201 rm uterine failed pregnancy, recall the patient. 263 y g o o c e a n y G l (Ensure rapid return of histology results.) When ultrasound reports suggest an incomplete miscarriage but the fetus has not been seen \200\224think: could this be an ectopic? Gestational trophoblastic disease (GTD) \200\22572 This comprises premalignant hydatidifor m mole, and the malignant conditions of choriocarcinoma and the rare (0.23%) placental site trophoblastic tumor. Complete moles are diploid and androgenic, 75 \200\22380% following d uplication of a single sperm after fertilization of an empty ovum , 20 \200\22325% after d ispermic fertilization of an empty ovum so no maternal nuclear DNA although mito- chondri al DNA is maternal. Partial moles usually follow dispermic fertilization of an ovum and are triploid (2 sets paternal haploid genes, 1 haploid maternal set) but 10% are tetraploid or mosaic conceptions. Partial moles usually have evidence of fetal parts or red cells. They are 3 \211\210commoner, grow slower (so present later), and are less often malignant (1% v s 15%). Hydatidiform moles (see \201 g 1) Tumors consist of proliferating chorionic villi which have swollen and degenerated. Derived from chorion, it makes lots of human chorionic gonadotrophin (HCG), giving rise to exaggerated pregnancy symptoms and strongly +ve pregna ncy tests. Incidence: 1.54 : 1000 births (UK). It is commoner at extremes of child-bearing age, after a previous mole, and in Asians. A woman who has had a past mole is at \200\200r isk for future pregnancies; 0.8 \200\2232.9% after one mole, and 15 \200\22328% after 2 mol es. <1% have familial recurrent moles (recessive) with <1 : 50 chance of normal pregnancy. 73 Signs: Most present with early pregnancy failure, eg failed miscarriage or signs on ultr asound. Bleeding may be heavy; aborted molar tissue may look like frog- spawn. Ultrasound m ay show \200\230snowstorm eff ect \200\231 in a \200\230large-for-dates \200\231 uterus. Severe morning sickness or 1st trimester pre-eclampsia are rarer presentations. If accompan ying twin pregnancy, proceed, if wished, (40% viable baby outcome without \200\200 persist ing neoplasia or adverse treatment results). 264 \200 y g o o c e a n y G l Fig 1. Hydatidiform mole Courtesy of Prof. J. Carter. Abdominal pain may be due to huge theca-lutein cysts in both ovaries. These may rupture or tort. They take 4 months to resolve after molar evacu- ation. HCG resembles TSH, and may c ause hyperthyroidism. \200\207Tell the anaesthe- tist as thyrotoxic storm can occur at eva cuation. Treatment: Molar tissue is removed from the soft, easily perforated uterus by gent le suction. Give anti-D if rhesus \200\223ve (p 9). Pregnancy should be avoided for a year while HCG levels are monitored. Register the woman at specialist center (below) for HCG mo nitor- ing. Levels should return to normal within 6 months. If levels drop rapidly to norma l, oral contraceptives may be used after 6 months. If they do not, either the mole was inva sive (myometrium penetrated) or has given rise to chorio- carcinoma (10%). Invasive moles m ay metastasize, eg to lung, vagina, brain, liver, and skin. Both conditions respond to chem otherapy. See BOX p265. Choriocarcinoma \200\207Investigate all persistent post-pregnancy PV bleeding to exclude choriocarcinoma. This highly malignant tumor occurs in 1 : 40,000 de liveries. The chief contexts are following a benign mole (50%), miscarriage (20%), or a nor mal pregnancy (10%). Presentation: May be years after pregnancy, with general malaise (due to \200\230malignancy \200\231 and \200\200HCG) or uterine bleeding; signs and symptoms f rom metastases (may be very haemorrhagic, eg haematoperitoneum); nodules on CXR. Pulmonary artery obstruction via tu- mour emboli may cause pulmonary artery hypertension (haemoptysis ; dysp- noea). Treatment: Choriocarcinoma in the UK is treated at 3 specialist centers; it is extremely responsive to combination chemotherapy based on methotrex- ate. Outlook is goo d if non-metastatic and fertility is usually retained. Placental site trophoblastic tumor T hese grow slower, present later, pro- duce less HCG. Post chemotherapy residual disease is excised (eg womb and nodes). 265 Indications for chemotherapy 74 \200 Plateauing or rising post evacuation HCG (taken days 1, 7, 14, 21) \200 HCG \211 20,000 IU/L 4 weeks post evacuation \200 \200\200 HCG 6 months post evacuation, even if levels dropping \200 Heavy vaginal bleeding, or gastroin testinal or intraperitoneal bleeding \200 Evidence of brain, liver, or gastrointestinal m etastases, or lung opacities >2cm (smaller lesions may regress spontaneously) Histology of choriocarcinoma y g o o c e a n y G l The vulva Pruritus vulvae Vaginal itch is distressing and embarrassing. Causes: There may b e a disorder causing general pruritus (p586) or skin disease (eg psoria- sis, lichen planus ). The cause may be local: infection and vaginal discharge (eg candida); infestation (eg sc abies, pubic lice, threadworms); or vulval dystro- phy (lichen sclerosis, leukoplakia, carc inoma). Symptoms may be psychogenic in origin. Psychosexual sequelae may ensue. Obesity and incontinence exacer- bate symptoms. Postmenopausal atrophy does not cause itch. 266 \200 The history may suggest the cause. Ask about autoimmune disorders and atopy. Examine genera l health and look for wider spread skin conditions. Ex- amine the vulva and genital tract, under magni \201 cation if possible, and take a cervical smear, if due. Consider taking va ginal and vulval swabs and tests for diabetes and thyroid disease. If vulval dermatitis che ck serum ferritin and dermatology patch tests. Biopsy if diagnosis in doubt, if there is no response to treatment, or vulval intraepithelial neoplasia or carcinoma are suspected. \200\207Scratching and self-medication may have changed the appearance. Treatment is often unsatisfactory.1 Treat the cause if possible. Avoid senstitiz- ers (patch testing may revea l sensitizing agents eg 26 \200\22380% in vulval dermati- tis studies). Reassurance can be very important. Vulval care advice (OPPOSITE), may help. A short course of topical steroids , eg betamethasone valerate cream 0.1% may help. Avoid any topical preparation which may se nsitize the skin, so give antipruritics orally if needed, eg promethazine 25mg/12 \200\2232 4h. Lichen sclerosis Thought to be an autoimmune disorder (40% develop other autoimmune dis orders), elastic tissue turns to collagen (usually after middle age \200\224or, occasionall y, before puberty). The \200\230bruised \200\231 red, purpuric signs may appear, to the un knowing, to suggest abuse \200\224particularly if there are bullae, erosions, and ulceratio ns. The vulva gradually becomes white, \202 at, and shiny. There may be an hourglass shap e around the vulva and anus. It is intensely itchy. It may be pre-malignant and long-term s urveillance is desirable if un- responsive to treatment. Treatment: Clobetasol proprionate cream daily for 28 days, then alternate days for 14 doses, then twice weekly for 8 doses, t hen as needed; 75 vulval ablation may be needed to relieve itch. The 4 \200\22310% who are steroid unresponsive may respond to topical tacrolimus (off license, use in specialist clin ic only, for <2 years). In children, 50% resolve by menarche. Leukoplakia (White vulval pat ches due to skin thickening and hypertrophy). It is itchy. It should be biopsied as it may be a pre-malignant lesion. Treat- ment: Topical corticosteroids (problems: mucosal thinning , absorption); pso- ralens with ultraviolet phototherapy; methotrexate; ciclosporin. Lichen planus Of unknown cause, this is more likely to present with pain than pruritus. In mouth & genital area it can be erosive, appearing with a well de- marcated glazed appearance arou nd the introitus. It can aff ect all ages. Lichen simplexThis presents with chronic intract able itching, especially at night, in those with sensitive skin or eczema. There is non-spe ci \201 c in \202 amma- tion of vulva, ( mons pubis and inner thighs). Stress, sensitiz ing chemicals an low body iron stores can exacerbate symptoms. Treatment is with vulval car e (OPPOSITE), using steroids to break the itch/scratch cycle, if needed. Antihista- mines o r antipruritics (above) can help. Vulvovaginitis Think of \201 xed drug reactions (NSAIDs , statins); stop for 2 weeks. Desquamative in \202 ammatory vaginitis, of unknown cause, c haracter- ized by shiny erythematous patches petechiae. It responds to 2 \200\2234 weeks of intravaginal clindamycin cream with hydrocortisone to the vulva. 76 y g o o c e a n y G l 1 As chronic vulval itch and chronic vulval pain are often recalcitrant (often ignored, or inappropriately diagnosed as candida) \200\224and because of its eff ects on mood and sexua lity, a patients \200\231 group (with profes- sional input) has been set up in the UK (www. vul-pain.dircon.co.uk). 267 Vulval intraepithelial neoplasia Vulval malignancy has a pre-invasive phase, vulval intra-epithelial neoplasia (VIN, \201 g 1, note white areas with surround- ing in \202 ammation). It may be itchy. Cause: often HPV, p269 (esp. HPV16); there may not be visible warts but 5% acetic acid stains aff ected areas white. If VIN is found on bi- opsy, examine cervix, anal canal if within 1.5cm, \200 \22577 natal cleft skin and breasts (>10% have coexistent neoplasia elsewhere, most commonl y cervical). Treating VIN Wide local excision is gold standard treatment of choice. \200 \22578 Women should have access to reconstructive surgery afterwards, if needed. Histology reveals 12 \200\22317% unrec- ognized invasion in wide excision samples. There is higher re sponse rates in women undergoing excision than in those under- going medical treatment. Rec urrences are fewer if excision margins clear. Medical treatments have used 5% imiqui- mod c ream with regression of grade 2 \200\2233 disease in 77%. 79 Cidofovir use is being studied . Laser therapy is useful for areas where surgery is contrain- dicated (eg in glans and cli toral hood). Laser treatment failures are 40%. Therapeutic use of human papilloma virus va ccine, photodynamic therapy, interferon use, and cavitron ultrasonic surgical aspiration te chniques have been tried but none are currently recommended treatments. \200\22578 Recurre nce is common so follow-up regularly. y g o o c e a n y G l Fig 1. Vulval intra-epithelial neopla- sia (VIN). Vulval care for those with vulval disorders \200\22578 \200 Use soap substitute with wat er for washing (less drying than water alone). \200 Shower, bath (with emollient), or cle an vulva once daily only. \200 Wash vulva with hand (not sponge/ \202 annel); dab dry or blow dry with hair- dryer on cool setting held well away from the skin. Wear loose \201 tting silk or cotton white or light colored underwear (blue/ black dyes can be irritant). Sleep without underwear. Avoid tight jeans/cycling trousers but wear loose trousers, dresses or skirts. At home wear ing skirts without underwear may be more comfort- able. Avoid soap, bubble bath, shower gels, biological washing powders, fabric conditioners, vulv al creams or douches, antiseptics, regular sanitary towel or panty liner wear, baby wipe us e, colored toilet paper, nail varnish. \200 Regular emollient use (throughout day) can so othe and reduce \202 are ups. \200 For irritated skin, dabbings of aqueous cream kept i n the fridge can soothe.