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). Tubal problems: Surgery may sometimes help. Proximal blocks may re- spond to tubal catheter ization or hysteroscopic cannulation. Endometriosis: p288. If amenorrhoeic with intrauterin e adhesions, use hysteroscopic adhe- siolysis. In vitro fertilization Screen couple for HIV, hepatitis B & C. Women with hy- drosalpinges should have salpingectomy prior to IVF to \200\200chance of live birth. Psychological stab ility is required in the UK. Some non-UK clinics have given IVF to women >65yrs old.1 4 mil lion IVF babies have been born worldwide, 200,000/ yr.137 Chance of live birth per treatmen t cycle is age dependent: 20% if \200 aged \211 35; 15% if 36 \200\22338; 10% if 39; 6% if \211 40. In vitro fertilization (IVF) is used for tu- bal (and other) problems. Ovaries are stimulated (see hyperstimulation p311), ova collected (by transvaginal aspiration unde r transvaginal ultrasound guid- ance), fertilized, and 2 embryos returned under ultrasound guidance to the uterus as an outpatient procedure. Single fresh ovary transfer with 2nd fro zen embryo later, if needed, gives as good results. 138 For problems of off spring see (p69 ). The possibility of adoption should not be forgotten. Those who remain child- less may va lue counseling or a self-help group. 1 70-year-old Omkari Panwar is the world s oldest IVF mother. The oldest mother for natural conception is recorded as being 59.139 295 Male subfertility Spermatogenesis takes place in the seminiferous tubules. Undiff erentiate d diploid germ cells (spermatogonia) multiply and are then transformed into haploid spermat ozoa, a process taking 74 days. FSH and LH are both important for initiation of spermatogen esis at puberty. LH stimulates Leydig cells to pro- duce testosterone. Testosterone and FSH stimulate Sertoli cells to produce es- sential substances for metabolic support of germ ce lls and spermatogenesis. Spermatozoa A spermatozoon has a dense oval head (containing the h aploid chromosome complement) capped by an acrosome granule (contains enzymes essential for fertilization), and is propelled by the motile tail. Seminal \202 uid forms 90% of ejacu late volume and is alkaline to buff er vaginal acidity. Only 200 sperm from any ejaculate reach the middle \205\223 of the Fallopian tube, the site of fertilization. Sperm counts a re highest in spring and lowest in summer. 140 Male subfertility Male factors are the cause of subfertility in 24% of infer- tile couples. In reality, most are subfertile. Only a sm all number of men have an identi \201 able treatable cause. Causes include (% cited in one study): \200 Idiopathic oligo/azoospermia (16%): testes are usually small and FSH \200 \200. \200 Asthenozoospermia/teratozoospermia (17%): in asthenozoospermia sperm motility is reduced due to structural problems with the tails. Teratozoosperm- ia indicates an exces s of abnormal forms. y g o o c e a n y G l Varicocele (17%): this is controversial for varicocele is found in 15% of males, most of whom have normal fertility. Genital tract infection (4%): gonococci, chlamydia, & Gram \200\223ve enterococci cause ad nexal infection ( painful ejaculation, urethral discharge, haema- tospermia, dysuria, ten der epididymes, tender boggy prostate). Con \201 rm by semen culture, urethral swab or \201 nding >106 peroxidase +ve polymorphs/mL semen. Treatment has not been shown to restore fertility. Sperm autoimmunity (1.6%): Risk factors for antibodies: vasectomy, testis injury, genital t ract obstruction, family history of autoimmunity. Most are on sperm membranes or in seminal \202 uid, but may occur in the woman. Congenital (cryptorchidism, chromosome disorders \200\2242%): Klinefelter \200\231s account for 50% chromosome disorders. For optimal fertility undescended testes should be \201 xe d in the scrotum before 2yrs of age. Obstructive azoospermia (1.8%): azoospermia, normal sized testes with normal or high FSH su ggests this. It may follow infection, vasectomy, or be congenital (as in cystic \201 bros is). It may be amenable to surgery, eg epidid- ymo-vasostomy to bypass epididymal obstructi on. \200 Systemic \200\224eg iatrogenic, or from drugs, eg cannabis (1.3%). 141 \200 Co ital disorders (1%). \200 Gonadotrophin de \201 ciency (0.6%): this is the only cause of testicular failure consistently treatable by hormone replacement. Examination Look at body form and secondary sexual characteristics. Any gynaecomastia? Norm al testicular volume is 15 \200\22335mL (compare with Prader orchidometer). Rectal examinat ion may reveal prostatitis. Tests Semen analysis (p292). Plasma FSH distinguishes primary f rom second- ary testicular failure. Testosterone and LH levels are indicated if you suspect androgen de \201 ciency. Agglutination tests to detect antibodies. Treatment ICSI=intracy toplasmic sperm injection (direct into egg), the main tool for most male infertility. The s ource of sperm is the epididymis or testis in men with obstructive azoospermia; even if the problem is non-obstructive, sperm can be retrieved in 50%. Check the man \200\231s chromo somes, and for cystic \201 brosis carrier status before ICSI if azoospermic, oligospermic (not if post- vasectomy). If they have Y chromosome AFZc deletions, so would off spring so ns. \200\225142 Contraception \200\207Any method, even coitus interruptus, is better than none. Without co n- traception about 85 of every 100 premenopausal sexually active women will become pregnan t each year. Properly used, contraception reduces this rate (see OPPOSITE). When dealing wi th under-16s use Fraser Guidelines (BOX 4). Barrier methods \200\207The main reason for fa ilure is not using them. Condoms reduce transmission of most STDs but not those aff ecting the perineum. Caps give some protection against gonorrhea and chlamydia but not syphilis or herpes. Some spermicides inactivate HIV in vitro but HIV not nonoxyl-9 impreg- nated sheat hs (see below). 143 When failure is anticipated (eg \200\230split sheath \200\231), rememb er post-coital emergency contraception (p299). Stop contraception at 55yrs (95.9% menopausa l) unless regular menstruation. \200 Sheaths (condoms) Eff ective when properly used, unr oll onto the erect pe- nis with the teat or end (if teatless) pinched to expel air. This pr events burst- ing at ejaculation. Method failure rate 5%, typical user failure rate 15%/yr. \200 Caps come in several forms. Diaphragms stretch from pubic bone to poste- rior forni x. Check after insertion that the cervix is covered. Cervical caps \201 t over the cervix (so need a prominent cervix). Insert <2h before intercourse (keep in place >6h after sex). Use with a spermicide.* Problems: UTIs, rubber sensitivity. They need professional \201 tting. 92 \200\22399% eff ective if perfect use.** \200 Cervical sponges Simple to use: s permicide* impregnated: unavailable UK. \200 The female condom (eg Femidom ) Prescriptio n and \201 tting are not needed. It has not proved popular. One reason for failure is tha t the penis goes along- side it, rather than in it; another, that it gets pushed up in the vagina or may fall out. They can be noisy. Uses lubricant, not spermicide. 95% eff ective. \200 \200 Spermicide* Unreliable unless used with a barrier. Nonoxinol-9, the only sperm icide available in UK is not recommended for those with or at high risk of HIV1 as it irrit ates vaginal epithelium and \200\200 chance of HIV transmission. Fertility awareness ( \200\230natural \200\231) methods involve physiological monitoring to \201 nd fertile tim es (6 days prior to ovulation; the life of a sperm) to 2 days after- wards (the life of the ovum). Cervical mucus becomes clear and sticky at the beginning of the fertile time and dr y at ovulation (but is altered by semen and vaginal infections). Basal body temperature \200\200 0.3 C after ovulation (aff ected by fevers, drugs, recent food, or drink). Addit ional observations (mittelschmerz, p310 cervix changes) improve accuracy. Success is com mon if: \200 Regular cy- cles \200 Dedication \200 Self-control. UK teachers are avai lable (tel. 01222 754628). Lactational amenorrhoea See p95. High-technology natural methods Devices eg Persona use urine test sticks to measure oestrone-3-glucuronide (E3G \200\224 peaks 24h pre-ovulation) and luteinizing hormone (LH \200\224ovulation occurs within 36h of LH surge and sperm penetration of cervical mucus drops after surge). Microtechnology build s a database of the woman \200\231s natural variability over time, to give her a green ligh t (almost infertile), a red light (fertile \200\224typically days 6 \200\22310) or an orang e light (test early-morning urine for E3G and LH). Usually, only 8 urine tests are needed p er cycle. She purchases sticks and monitor. A button is pressed the morn- ing her period st arts: she checks the monitor lights before passing urine each morning, in case a test is ne eded. Reliability: 93 \200\22395% (manufacturer \200\231s data, in motivated patients; it m ay be less in practice; results should be regarded as only preliminary; explain uncertainty ). CI: Cycle <23 or >35 days or variation >10 days; breastfeeding; if already on hormones o r tetracycline (minocycline is OK); menopausal; liver or kidney disease; polycystic ovaries , or if pregnancy is de \201 nitely undesired. 296 \200 y g o o c e a n y G l 1 RCOG 2007 FFPRHC Guidance Female Barrier Methods. \200\225144 This paper gives great deta il of all caps, diaphragms etc available. ** but typical use failure rate (TUFR; user+metho d failure) = 16% in 1st year use of diaphragm, (TUFR) for cervical caps: 9% nullips, 20% pa rous \200 . \200 (TUFR) 21%. \201\201Our future depends on contraception145 Unless we meet the huge unmet demand for co ntraception (especially in Asia) preventable starvation is inevitable. 146 A world populati on ( 7 bil- lion) growing at current rates (100 \211\210 106/yr) is unsustainable, now the era of cheap food is over. 297 The ideal contraceptive \200\224and the realities An ideal contraceptive is: 100% effec- ti ve, with only desirable side eff ects (eg protection from sexually transmitted disease), an d it must be readily revers- ible, and be useable unsupervised by professionals. Find the b est compro- mise for each person depending on age, health, and beliefs. Methods available: \200 \200\230Natural methods \200\231 . r e t h g i f Failure rates % in 1st year with typical (T) and perfect (P) use147 \200 No method m o d e e r f 85 (T) 85 (P) 16 \200\22332 y g o o c e a n y G e l b a v Cervical cap 9 \200\22320 i e c n o c l Natural methods 25 1 \200\2239 y n a Female condom 21 5 intercourse near time of ovulation): acceptable to Catholic Church; also, the simplest are free, requiring no \200\230pollution of the body \200\231 with drugs: see OPPOSITE. (no n a h t m o d e e r f Withdrawal 27 4 Diaphragm +spermicide \200 Male condom 16 6 e r o m e l p o e p 15 2 Barrier methods (low health risk but need high user motivation & some protection from HIV). See page OP- POSITE. 0.3 Pills (CoC+PoP) \200 Copper coil (for T-safe Cu380A) 8 0.8 0.6 e r o m n e v Hormonal (complex health interac- tions, but highly eff ective, p300 \200\2233). Depo Provera \200 Tubal ligation 0.3 3 0.5 0.5 IUCD/IUS (convenient and eff ective \200\224if i g s a h not contraindicated \200\224p298). Vasectomy 0.15 0.1 0.1 0.1 Sterilization (very eff ective but eff ec- l l i Levonorgestrel IUS (Mirena ) P tively \200\230irreversible \200\231, p305). e h T \200\234Is she pregnant already? \200\235 This is a frequent question in family planning a nd other clinics. If a preg- nancy test is not available, women who could be pregnant alrea dy will often be denied the contraception they need. Here, consider using this check list t o see if the patient may be pregnant. If she answers Yes to any of these ques- tions, and s he is free from signs or symptoms of pregnancy, then pregnancy is very unlikely (negative p redictive value >99%). \200 Have you given birth in the past 4 weeks? \200 Are you <6 m onths postpartum and fully breastfeeding, and free from menstrual bleeding since you had your child? Did your last menstrual period start within the last 7 days? \200 Have you been using a r eliable contraceptive consistently and correctly? \200 Have you not had sex since your la st period? 148 Fraser guidelines (Gillick competence) Those <16yrs may be prescribed contraception without parental consent if: \200 They understand the doctor \200\231s advice. \200 The young person cannot be persuaded to inform their parents that they are seeking contraceptive advice. They are likely to begin or continue intercourse with or without contracep- tive treatment. Unless the young person receives contraceptive treatment their physical or mental health is likely to suff er. The young person \200\231s best interests require that the doctor gives advice and/ or treatment without parental consent. The intrauterine contraceptive device (IUCD) IUCDs (coils) are plastic shapes 3cm long wit h copper winding, and a plastic thread for a tail. They inhibit implantation and may impair sperm migration. Most need changing every 5 \200\22310 years. The larger, non-copper-beari ng \200\230inert \200\231 types (eg Lippes loop ) caused more complications but did not n eed changing (still sometimes found in situ). Use those with \211 300mm2 copper eg T-Safe copper T380A (the most eff ective), 149 for which pregnancy rate is 2.2 per 100 woman-yea rs. The frameless device may be as eff ective. Most of those who choose the IUCD (5%) are o lder, parous women in stable relationships, in whom the problem rate is low. They can be us ed for emergency contraception (p299). Problems with IUCDS 1 They may be expelled (5%) by a uterus which is nullip- arous or distorted (eg by \201 broids). 2 They are associated wi th pelvic infection and subfertility following sexually transmitted disease, or sometimes i ntro- duced at insertion. 3 They tend to produce heavy, painful periods. Contraindi- cation s: Pregnancy; current pelvic infection/STD (including TB); trophoblastic disease; cancer of ovary, endometrium or cervix; distorted uterine cavity. Insertion Screen for STD prior to insertion or use prophylactic antibiotics. Skilled insertion minimizes complications. Each device has its own technique, so read the instructions carefully and practice beforehand. A n IUCD can be inserted any time (and as postcoital contraception), as long as she \200\231s not pregnant. Insert within 48h of, or >4 weeks after birth. Determine the position of the uterus. Then insert a uterine sound to assess the cavity length. Then insert the IUCD, pla cing it in the fundus. This may cause cramps. Uterine perforation rate is <1 : 1000. Once t he coil is in place, cut threads to leave 3cm visible in the vagina. Teach her to feel the threads: ask her to check after each period. Misoprostol 400 g sublingually 1h before inse rtion dilates the cervix aiding insertion. 150 \200\207Insertion of IUCDs may provoke \200\230cervical shock \200\231 (from increased vagal tone). Have IV atropine (and anti-epi leptics if patient epileptic) and resuscitation equipment to hand. Follow-up Most expulsion s are in the \201 rst 3 months. Follow-up after 1st pe- riod. Threads may be easier to fe el than to see. Expulsion rate <1 : 20 in 5 years. Lost threads The IUCD may have been expe lled, so advise extra contraception and exclude pregnancy. Seek coil on ultrasound; if miss ing arrange X-ray to exclude extra-uterine coils (surgical retrieval advised). Infection Tr eat with the device in place, but if removed do not replace for 3 months. With symptomatic Actinomyces, remove coil, cut off threads and send for culture. If positive, seek expert ad vice on treatment. Pregnancy >90% are intrauterine. Remove coil, if you can as soon as preg - nancy is diagnosed to reduce risk of miscarriage (20% if removed early, 50% if left), and to prevent miscarriage with infection. Exclude ectopic. Removal Alternative contraception should be started (if desired) prior to re- moval, or a fertilized ovum may be in the tubes . At the menopause, remove after 2 years \200\231 amenorrhoea if age <50yrs (1 years \200 \231 amenorrhoea if age >50yrs). IUCDS carrying hormones (IUS, intrauterine systems) \200 \224eg Mirena (carries levonorgestrel). Local eff ect (reversible endometrial atrophy) ma kes implan- tation less likely, and periods lighter; perhaps 20% may experience reversible amenorrhoea (reliability equals sterilization, see p305). It lasts 5 years. (If to protect endometrium with HRT (p256), change at 4 years). There may be less risk of ectopic pregnan cy. Risk of some sexually transmitted infections is reduced. Warn about spotting heavy b leeding (NB: bleeding may become scanty or absent after a few cycles). Pregnancy rate <1 : 1000 over 5 years. It may bene \201 t women with endometriosis, adenomyosis, \201 broids , or endometri- al hyperplasia. Avoid if breast cancer. Minimally aff ected by enzyme induc ers. 298 \200 y g o o c e a n y G l Emergency contraception151 This is for use after isolated episodes of unprotected intercour se (UPSI), eg \200\230the split sheath \200\231 and should not be used regularly. Tablets cover that UPSI only. Although usually given after UPSI advance issue does not increase use and it may be sensible to \200\230be prepared \200\231. ( \200\230Carrying an umbrella in the British climate is considered sensible, not a wish for rain. \200\231) 152 However, ad vance issue has not been shown to reduce pregnancy rates. 153 Management History of LMP; no rmal cycle; number of hours since unpro- tected intercourse. Any CI to later Pill use (p300 )? Check BP. Explain that teratogenicity has not been demonstrated. Discuss future contrace ption. Give supply of oral contraceptives if day 1 start at next period is planned; if star ted immediately advise extra precautions as below. Off er infection screen and to cover HIV . Off er follow-up at 3 \200\2236 weeks if coil inserted; or if pregnancy or STI tests desi red, or if she has contraceptive concerns. Emergency IUCD More eff ective than tablet contr aception (prevents 99% of expected pregnancies); a copper IUCD can be inserted within 120h of un- protected sex. If exposure was >5 days previously it can be inserted up to 5 days af ter likely ovulation, so is useful in women who present later. Screen for infection. Insert under antibiotic cover, eg azithromycin 1g PO if screening results unavailable, or risk of IE. It is thought to inhibit fertilization by toxic eff ects and to inhibit implantation. If for long-term use, coils with 380mm2 Cu have the lowest failure rates so should be used. Unaff ected by enzyme induc- ers (p300), it is the method of choice for those taking them (but see below). Ulipristal acetate Initiate within 120h of unprotected sex. Failure rate i s \211 1.6% in non-inferiority (with levonorgestrel) trials. Effi cacy is not reduced by o besity (levonorgestrel may be). It is thought to inhibit or delay ovulation. If vomiting \211 3h of taking the tablet, advise another (30mg). A progesterone receptor moderator, it is unsuitable for use if on, or within 28 days of taking, an enzyme inducer (p300), if on a ntacids or drugs raising gastric pH, for those with severe asthma uncontrolled by oral cort icosteroids. Use with caution if liver dysfunction, hereditary galactose intolerance, Lapp lactase de \201 ciency, glucose-galactose malabsorption. Avoid breastfeeding for 36h after use. Use only once per menstrual cycle. Periods average 2 days delay (7 days in \211 20%) . Advise extra contraceptive precautions for 14 days for combined pills, 16 days for Qlaira , 9 days for progesterone only pills , if started or continued. Starting oral contracepti ve immediately after ulipristal acetate is off license. Should pregnancy occur, though no h arm known, register via manufacturer. Levonorgestrel Initiate within 72h of unprotected sex . Failure rates are \211 2.6%. Suitable for those with focal migraine and past thromboembo lism, there are no medical contraindications to its use. Levonorgestrel 1.5mg (1 Levonelle 1500 tablet or Levonelle One Step over-the-counter) preferably within 12h and no later than 72h after unprotected sex. If on, or within 28 days of, taking an enzyme inducer (p300 ), or with post-sexual exposure HIV prophylaxis, the dose is 3mg. If vomiting occurs within 2h of taking the dose, take another immediately. The earlier taken after UPSI, the fewer t he pregnan- cies which occur. It is believed to inhibit ovulation. It can be used more than once in 1 cycle; and can be used (but may be less eff ective) in same cycle after uliprist al acetate. 299 \200 y g o o c e a n y G l Warn that eff ective contraception should be used until the next period; and that she shoul d return if she suff ers any lower abdominal pain or the next period is abnormal. Advise pr egnancy test if period >7 days late or unusu- ally light, or after 21 days if \200\230quic k start \200\231 contraception started. If immediate ( \200\230quick start \200\231) oral c ontraception started, or continuing extra contraceptive precautions are needed for 7 days f or combined pills (avoid immediate co- cyprindiol start), 9 days for Qlaira , 2 days for p rogesterone only pills. Hormonal contraception (the Pill), ring, patch Combined hormonal contraception (CHC) as vag inal ring, transdermal patch (p304) or pills (CoC) contain estrogen (eg ethinylestradiol) w ith a progesto- gen, either in \201 xed ratio or varying through the month (phased). Low- dose Pills ( \211 30 g estrogen) are the norm. The combined Pill is taken daily for 3wks f ollowed by a week \200\231s break. This inhibits ovulation, giving a withdrawal bleed in th e Pill-free week. When prescribing CHCs, attend to the following areas. History Why is Pill wanted? Does she know the risks? Explain risks. Alterna- tives considered? Contraindicatio ns? Ask about smoking (below) and drugs. Any anxieties, eg weight gain? (does not cause). O ff er help to stop smoking. If 1st degree relative with thromboembolism <45yrs, do thrombop hilia screen. Weigh: check BP: calculate BMI annually. At age 50 advise alternative method. Contraindications (ukmec4)1,154 Diabetes with neuropathy, retinopathy, ne- phropathy, vasc ulopathy; BP \211 160/95; smoking \211 15/day if age \211 35; migraine with aura or (BOX p301); past stroke or venous or arterial thrombosis; thrombophilia (p33); heart disease wi th pulmonary hypertension or embolus risk; ischaemic heart disease; transient ischaemic att acks; liver adenoma, hepatoma, decom- pensated cirrhosis, active hepatitis, Dubin \200\223J ohnson or Rotor synd.; porphyria; SLE with unknown/+ve antiphospholipid antibodies; past ha emolytic uraemic syndrome; pregnancy related pruritus, cholestatic jaundice, pemphigoid ges ta- tionis, chorea; hydatidiform mole (see p264); breast cancer in last 5yrs; breast- feedi ng (esp. 1st 6 weeks); immobility (eg in bed; leg in plaster cast). Cautions (BNF) Hyperpro lactinaemia (get expert help), BRCA gene carrier. \200 Venous risk factors: Caution if an y of these: ( \200\207avoid if \211 2 risks): 1st degree FH of thromboembolism age <45y;2 BMI \211 30kg/m2; varicose veins ( \200\207avoid during sclerotherapy or past thrombosis); immobility (eg wheelchair). \200 Arterial risk factors: Caution if any of the following ( \200\207avoid if \211 2 risk fac- tors): smoker (or in last year); age \211 35yrs; BP > 140/90 ( \200\207stop if \211 160/95); mi- graine without aura; BMI \211 30kg/m2; diabete s mellitus; 1st-degree relative with arterial disease <45yrs old ( \200\207avoid if she has dyslipidaemia too). Drugs interfering with Pills (use condoms too) Liver enzyme inducers, eg some anticonvulsants,3 aprepitant, bosentan, efavirenz, moda \201 nil, nel \201 navir, nevirapine, ritonavir, St John \200\231s wort, rifampicin and rifabutin \200\201 effi cac y by \200\201 circulating hormones (see Nexplanon p304). If short term, use extra precau - tions (p302) while used and for 28 days after (can cover with Depo-Provera injection) a nd take only 4-day break. If long term, use 50 \200\22370 g ethinylestradiol, or Norinyl-1 , tricycled (3 packs in row) then 4-day break. 155 Use other contra- ception (IUCD/IUS/de pot) with the potent enzyme inducers rifampicin, rifabu- tin. Beware lamotrigine ( \200\201 \201 t control). Ulipristal: see p299. Antibiotics: p302. Bene \201 ts of the Pill Very eff ective contraception; lighter, less painful periods; less PMS (p254) and benign breast disease, fewer menopausal symptoms, im- proved acne. In long-term users, reduced risk of e ndometrial carcinoma ( \200\201 50%) ovarian tumors (carcinoma \200\20150% if 15-yr use) a nd colorectal cancer. Serious disadvantages Risks of arterial and venous disease are increa sed, eg DVT and myocardial infarction. Use thromboprophylaxis (p16) if taking 4 weeks befor e major or leg surgery. Risk of death from the Pill increases sharply in those >40yrs: 1 : 2500 for nonsmokers; 1 : 500 for smokers. Breast cancer: there is slight increase in curren t users and in the 10 years after stopping. Duration of use is not thought to be a factor. The Pill acts as a co-factor with human papilloma virus to increase risk of invasive cervic al cancer. 156 300 \200 y g o o c e a n y G l 1 ukmec4 category denotes that use poses unacceptable health risk: ukmec3=risk from use out weighs advantage; ukmec2=advantage of use outweighs risk; ukmec1=no restriction to use. ukm ec 2009 154 2 If family history of thromboembolism, avoid Pills with desogestrel or gestode ne (or if prothrombotic coagulation abnormality, eg factor V Leiden or antiphospholipid ant ibodies, incl. lupus anticoagulant). 3 Eg: carbamazepine, esli/ox/carbazepine, phenobarbita l, phenytoin, primidone, ru \201 namide,topiramate. 301 Migraine, ischaemic stroke, and the Pill The problem is ischaemic stroke. The background an nual incidence is 2 per 100,000 women aged 20, and 20 per 100,000 for those aged 40. Migrai ne itself is a risk factor. For those with migraine and CoC use, incidence of ischaemic str oke becomes 8 : 100,000 if aged 20; and 80 : 100,000 in those aged 40. Low- dose CoCs only should be used. Those with migraine with aura are known to be at special risk precluding us e of combined Pills in these women (how- ever, there is no problem with them using progeste rone only or nonhormonal contraception). Other risk factors for ischaemic stroke include sm oking, age >35yrs, \200\200BP, obesity (body mass index >30), diabetes mellitus, dyslipida emia and family history of arterial disease <45yrs. Women known to have mi- graine should b e warned to stop Pills immediately if they develop aura or worsening of migraine. If a woma n has 1st migraine attack on CoC, stop it, ob- serve closely: restart cautiously only if th ere are no sequelae and if migraine attack was without aura and there are no other risk fac tors (above). 157 Diagnosing migraine with aura (formerly called classical/focal migraine) 1 Slow evolution of symptoms (see below) over several minutes. 2 Duration of aura usually 1 0 \200\22330min, resolving within 1h, and typically before y g o o c e a n y G l onset of headache. 3 Visual symptoms (99% of auras), eg: \200 Bilateral homonymous hemianopia. \200 Teichops ia and forti \201 cation spectra, eg a gradually enlarging C scintillating edges. \200 Po sitive (bright) scotomata. with 4 Sensory disturbance (31% of auras). Usually associated with visual symptoms. \200 Usually in one arm spreading from \201 nge rs to face (leg rarely aff ected). 5 Speech disturbance (18% of auras): dysphasia; dysarthria; paraphasia. 6 Motor disturbance s (6% of auras). Both motor and speech disturbances are usually accompanied by visual and/ or sensory disturbances. Migraine without aura: (formerly called simple or common migraine) in- cludes symptoms of blurred vision, photophobia, phonophobia, generalized \202 ashing lights aff ecting the whole visual \201 eld in both eyes, associated with headache. Abso lute contraindications to COC use \200 Migraine with aura. \200 Migraine without aura i n women with >1 risk factor for stroke (above). \200 Severe migraine or migraine lasting >72h (status migrainosus). \200 Migraine treated with ergot derivatives. Hormonal contraception: further details Check BP, BMI and health status after 3 months then annually. Do cervical smear if due (p271). Aim to use lowest-dose Pill to give good cycle control (ie no breakthrough bleeding). \200\207If breakthrough bleeds screen for chlamydia . Progesterone issues Norethisterone and levonorgestrel-containing CoCs may cause breakthro ugh bleeding, acne, headaches, so prompted search for new progesterones, eg gestodene or de sogestrel (Femodene , Marvelon , Mer- cilon , Triadene ), but see problems with \200 \200 thrombosis (p303). 302 \200 Drospirenone (DRSP) is a spironolactone-like progesterone with antiandro- genic/antimineral ocorticoid action (said not to \200\200weight; useful in those with acne or polycystic ova ries); thrombosis risk, see opposite. Levonorgestrel containing pills seem safest (try \201 rst). Thrombotic risk of dienogest (Qlaira ), is currently unkown. Switching from PoP: If to a CHC, start without g ap. Use condoms for 7 days (9 if Qlaira ). If to a progesterone-only Pill (POP), start as the old pack \201 nishes. Switching from CHc: If to a CHC, start immediately with no horm one-free interval. If to a PoP, start immediately the CHC preparation is \201 nished. Sta rt CHcs/PoPs on day 1 of cycle, on day of TOP, \211 21 days postpartum, or \211 2wks afte r fully mobile post major surgery. If starting CoC on day 1 \200\2235, cover is imme- diate , no other precautions (condoms) are needed. If later start (and not preg- nant, p297), use condoms for 1wk. Qlaira: start on day 1 (condoms for 9 days). Stopping the Pill Tell to stop at once if she develops: \200 Sudden severe chest pain \200 Sudden breathlessness ( cough/bloody sputum) \200 Severe calf pain \200 Unexplained leg swelling \200 Seve re stomach pain \200 Unusual severe prolonged headache; sudden visual loss; collapse; dys phasia; hemi-motor/sensory loss; 1st seizure \200 Hepatitis, jaundice, liver enlargement. \200 BP \211 160/95 \200 4 weeks before leg or major surgery (p300) \200 Any CI (p3 00). See cautions on p300; low-risk non-smokers may continue in their 40s. On stopping, 66% menstruate by 6 weeks, 98% by 6 months; women amenorrhoeic post-Pill usually were before. Missed Pills (or severe diarrhea): Consult package inserts; advice varies. In general, if t he start delay is \211 48h, or >48h since last Pill continue Pills but use condoms too for 7 days (+ days of diarrhea); if this includes Pill-free days, start next pack without brea k (omit inactive Pills in \200\230ED \200\231 formulations). If 2 pills of 1st 7 days in p ack forgotten, use emergency contraception if unpro- tected intercourse since end of last p ack. Vomiting <2h post-Pill: take another. Non-enzyme-inducing (p300) broad-spectrum antibi otics need extra precau- tions only if causing diarrhea or vomiting. Postcoital options: p2 99. Progestogen-only Pills (POP=mini-Pill) Low-dose progestogen renders cer- vical mucus ho stile to sperm. Desogestrel 75 g is more eff ective, inhibiting ovulation in 97%. Take at the same time of day ( 3h), ( 12h for desogestrel). PoPs can be used in most women with p roblems CI combined Pills, eg migraine, past thrombosis, immobility, major surgery, \200 \200BP, (also if lactating). Avoid if on enzyme inducers (p300); breast cancer in last 5y; IHD, stroke or migraine with aura develop on \200\224; GTD (p264); cirrhosis (metabolism p roblem); active viral hepatitis; liver tumors. Extra precautions are needed for 48h for lat e Pills, for time of use +28d if enzyme inducers given. Postnatal Start 21 days after birth : eg CoC if not breastfeeding; PoP, Depo- Provera (or Nexplanon ) if breastfeeding. IUCD : \201 t 4 weeks postpartum. At the menopause Stop PoP if >50yrs old with >1 year \200 \231s amenorrhoea (2yrs if <50yrs old) \200\224as a rough guide. A spermicide and sponge ma y then be ad- equate in view of declining fertility. As CoC masks the menopause, aim to sto p at 50yrs, and replace with a nonhormonal method. Flying and high altitude Avoid immobilit y if \202 ight \211 3h. If trekking higher than 4500 meters for \211 1 week consider a lternative. y g o o c e a n y G l 303