Ogrm 26.11
Ogrm 26.11
Gynaecology
and Reproductive
Medicine
Obstetrics, Gynaecology and Reproductive Medicine is a great revision guide for the MRCOG and beyond.
Obstetrics, Gynaecology and Reproductive Medicine is an authoritative and comprehensive resource that provides all obstetricians,
gynaecologists and specialists in reproductive medicine with ready access to up-to-date information on all aspects of obstetrics
and gynaecology. Over a three-year cycle of 36 issues, the emphasis of the journal is on the clear and concise presentation of
information of direct clinical relevance to specialists in the field and candidates studying for MRCOG Part II. Each volume contains
review articles on obstetric and gynaecological topics. The journal is invaluable for specialists in obstetrics and gynaecology,
both in their role as trainers of MRCOG candidates and in keeping up to date across the broad span of the subject area. Over
any three-year period, a subscription will ensure access to up-to-date, understandable information on the full range of obstetrics,
gynaecology and reproductive medicine topics.
Editor-in-Chief
Alec McEwan BA BM BCh MD MRCOG
Consultant in Fetal and Maternal Medicine, Department of Obstetrics and Gynaecology,
Queens Medical Centre, Nottingham, UK
Associate Editors
Sabaratnam Arulkumaran MBBS MD PhD FRCS (Ed) FRCOG
Professor of Obstetrics and Gynaecology,
Department of Obstetrics and Gynaecology,
St. Georges Hospital Medical School, London, UK
Trainee Editor
Catherine Aiken MB/BChir MA PhD MRCP MRCOG
Specialist Registrar (ST5) and Academic Clinical Lecturer in Obstetrics and Gynaecology,
Addenbrookes Hospital, Cambridge, UK
Obstetrics, Gynaecology and Reproductive Medicine has an eminent editorial board, all of whom are recognized experts in their field.
Visit our website at: www.obstetrics-gynaecology-journal.com for previous issues, subscription information and further details.
REVIEW
Vaginal discharge
Alexandra Rice
Mohamed ElWerdany
Essam Hadoura
Tahir Mahmood
Abstract
Vaginal discharge is a common presenting symptom at gynaecology
and sexual health clinics and in general practice. It is usually physiological and is subject to hormonal variations in consistency and quantity. With this in mind, appropriate diagnosis and treatment of
abnormal vaginal discharge can be challenging. Concurrent pregnancy
can also complicate the situation. Some pathological conditions may
contribute to vaginal discharge, including cervicitis, aerobic vaginitis,
atrophic vaginitis and mucoid ectopy. We mainly focus on the three
most prevalent pathological causes namely; bacterial vaginosis, vulvovaginal candidiasis and Trichomonas vaginalis and will also provide a
brief overview of atypical inammatory vaginitis as well. Obtaining a
methodical and detailed history from the patient should give the majority of the information required. Examination and analysis of discharge
with swabs are a useful adjunct to aid diagnosis. Once a diagnosis is
made, appropriate treatment must then be instigated and in some
cases partner notication and treatment may also be required.
Keywords bacterial vaginosis; candidiasis; desquamated inammatory vaginitis (DIV); HIV; pregnancy; trichomonas; vaginal discharge
Who to swab?
Introduction
Some patients can be given treatment without the need for full
investigations. A patient who complains with a first episode of
vaginal discharge with a clear clinical evidence of either vulvovaginal candidiasis (VVC) or bacterial vaginosis (BV), and no
other risk factors, can be given empirical treatment without
further investigations. However, the following risk factors
require further investigations:
High STI risk (past history of STI, multiple sexual partners,
sharing needles and intravenous drug use)
Symptoms suggestive of an alternative cause (e.g. vaginal
bleeding and urinary or bowel symptoms)
Recent gynaecological procedure
BV associated with pregnancy
Indications to obtain a swab:
STI risk/requesting STI screening
Symptoms suggestive of upper genital tract infection
Postpartum, post-miscarriage, TOP or recent instrumentation of the uterus
Recurrent symptoms despite treatment
Abnormal symptoms of unknown cause
Cervicitis found on examination.
317
REVIEW
Physiological discharge
B. Endocervical swab (ECS)
The cervical os should be cleaned with a disposable swab and
discarded. The ECS should then be inserted into the cervical os
and rotated firmly. The swab should then be placed in Amies
transport medium with charcoal. It is mainly used in the investigation of Chlamydia and gonorrhoea. The swab is sent for
NAAT (nucleic acid amplification testing). Some labs are now
analysing these samples for BV and TV.
C. pH testing
A swab from the lateral vaginal wall is placed on a narrow
spectrum litmus paper. BV and TV (T. vaginalis) will have pH
>4.5. There is good evidence that clinical features and measurement of vaginal pH is a sensitive (but not specific) predictor.
If HVS and ECS are also obtained, there is an increased accuracy
of diagnosis. Therefore, a swab should be obtained if features are
not suggestive of BV/VVC.
D. Microscopy
Wet microscopy requires a certain level of expertize and technical skills for proper implementation. A small sample of the
discharge should be placed on two ends of a slide. Normal saline
is put on one end and potassium hydroxide on the other. A cover
slip is placed on the slide and these are visualized under a microscope. This test is of varying sensitivities depending on the
offending organism:
70% sensitivity for TV (TV swabs need to be processed
with wet microscopy within 6 hours).
Saline microscopy will show spores/pseudohyphae in 40
e60% of Candida
30e50% sensitivity for Gonorrhoea
Bacterial vaginosis
Aetiology and transmission
Bacterial vaginosis is the commonest cause of vaginal discharge
in women; during their childbearing period. It has been found in
postmenopausal women and rarely prepubertal. It is more
common in black African and American women (45e55%).
Caucasian women have a prevalence of approximately 5e15%.
Previously, it was considered as a harmless finding, but we now
know it to be associated with many pathological conditions such
as puerperal endometritis, preterm labour, premature rupture of
membranes, PID and UTI.
The condition is associated with a prevalence of the anaerobic
species in preference to the normal Lactobacillus species. Organisms associated with bacterial vaginosis include the Prevotella
species, G. vaginalis, Mobiluncus species, Peptostreptococcus
species and Mycoplasma hominis. Some women experience the
change in the microorganism environment really abruptly, while
others take longer time interval to feel the change.
Bacterial vaginosis is experienced more in patients with
multiple sexual partners, no use of condoms or douching. Most
E. Gram stain
Commonly used for the diagnosis and grading of BV
65e68% detection in symptomatic Candida
F. Culture
Candida grows best on Sabouraud agar (95% growth on
culture). Its growth can be classified as light, medium or
heavy. Culture was considered the gold standard for
detecting T. Vaginalis before NAAT (nucleic acid
318
REVIEW
Pregnancy
In the UK, a BV prevalence of 12% was found in women
attending antenatal care, and 30% in women opting for termination of pregnancy.
Treatment of bacterial vaginosis is recommended for all
symptomatic women. Metronidazole regimen (500 mg) is similar
to non-pregnant population. Using Amstel criteria to define cure,
Yudin MH et al., found that oral metronidazole was as effective
as metronidazole gel for treatment during pregnancy, with a cure
rate of 70%. Metronidazole use during pregnancy is not associated with an increase in congenital malformations. A study by
Ugwumadu A. et al. using gram stain criteria showed an 85%
cure in patients receiving clindamycin. Newer studies have
shown that vaginal clindamycin is safe to administer in pregnancy. Both oral and topical regimens are both as effective and
safe to be prescribed in pregnancy.
Mixed results have been noticed in preterm delivery rate in
patients treated. Harm, no harm and benefit have been found in
several studies. Another study showed a decrease in late
miscarriage and adverse neonatal outcome in the treated group.
However, treatment is recommended for all symptomatic women
with BV as benefits outweigh the risks.
Insufficient data is available for treating asymptomatic pregnant women for which bacterial vaginosis was incidentally
discovered. Therefore, routine screening for bacterial vaginosis
in pregnancy is not recommended.
Metronidazole is secreted in breast milk. Studies have
revealed metronidazole and its metabolites in the plasma of babies, but this level was insignificant a lot lower than the levels
used by the mother to treat the infection. However, some obstetricians recommend deferring breastfeeding for at least 24e48
Treatment
Treatment is recommended for the following group of patients:
Patients with symptoms.
319
REVIEW
Management of partner
Routine screening and treatment is not recommended because
studies have shown that treatment of the male partner does not
affect recurrence or relief for women with bacterial vaginosis.
Follow up
It has been found that symptom recurrence occurs within 3e12
months of any regimen used for treatment. Recurrence rate has
been found at 15e30%. No follow up appointments are recommended if symptoms resolve. Patients are advised to contact
their healthcare professional if symptoms persist or recur.
There is limited data for management of persistent or recurring bacterial vaginosis. Using the same regimen or changing the
regimen are both acceptable management plans to treat such
conditions.
Women with recurrent infection may benefit from using
0.75% Metronidazole gel twice weekly for 4e6 months. A study
by Mcclelland and Richardson has found that administering a
monthly dose of 2 g oral metronidazole together with 150 mg
fluconazole is effective in reducing recurrence, although its
suppression is not long term once treatment is discontinued.
Treatment
General advice given to patients:
Avoid synthetic tight fitting clothes, and avoid washing
underwear in biological washing powder.
Avoid perfumed local products such as toiletries, antiseptics, douches and wipes.
Use soap substitutes (e.g. amole root, soap plant root,
soap root bulb, guaiac leaves, papaya leaves and quillaia
bark) and skin conditioners. These products should not be
used more than once per day to clean the vulval area
externally.
Emollients and skin conditioners may be used several
times per day.
Recommended regimens:
A. Over-the-counter products:
a) Intravaginal creams:
1. Clotrimazole 1% 5 g daily for 7e14 days
2. Clotrimazole 2% 5 g daily for 3 days
3. Miconazole 2% 5 g daily for 7 days
4. Miconazole 4% 5 g daily for 3 days
b) Vaginal suppositories:
1. Miconazole 100 mg daily for 7 days
2. Miconazole 200 mg for 3 days
3. Miconazole 1200 mg one single dose
c) Intravaginal ointment:
1. Tioconazole 6.5%, 5 g single vaginal
application
B. Agents which require a prescription:
a) Intravaginal creams:
1. Butoconazole 2%, 5 g in a single application
2. Terconazole 0.4%, 5 g daily for 7 days
3. Terconazole 0.8%, 5 g daily for 3 days
320
REVIEW
b) Vaginal suppositories:
1. Terconazole 80 mg, daily for 3 days
C. Oral agent:
1. Fluconazole 150 mg, single oral dose
All oral azoles and nystatin give about 80% cure rate. If
itching is a major problem, hydrocortisone containing topical
preparations may be of benefit. Creams, suppositories and ointments in the above preparations may weaken latex condoms and
diaphragms. Condom product information should be reviewed.
T. vaginalis
Prevalence
Trichomoniasis is usually acquired through sexual contact. The
prevalence of the disease among black women is 13%, while its
prevalence among white is estimated at a rate of about 1.8%. It
affects about 11% of women aged more than 40 years. The
flagellate protozoan, T. vaginalis, is responsible for the disease.
Abnormal vaginal discharge, pruritus and dysuria are the main
symptoms. The characteristic feature of the infection is the
strawberry cervix. This appears as a friable, erythematous cervix
with punctate areas of exudate.
Urethral infection is present in 90% of cases. However,
isolating the protozoan from just the urethra is just below 5% of
cases.
Screening for T. vaginalis in asymptomatic women is not
recommended. Screening can be considered in asymptomatic
women who are at high risk for infection. These include patients
with multiple sexual partners, drug abusers and patients with a
history of STIs. However, there is insufficient data regarding
screening asymptomatic women without additional risk factors.
Pregnancy
Vulvovaginal candidiasis is common among pregnant women.
Up to 40% of carriers will have symptoms during pregnancy.
Only topical azole therapy is recommended for symptomatic
pregnant women. Animal studies have found that Oral antifungals triazoles (fluconazole and itraconazole) causes fetal abnormalities and should be avoided during pregnancy.
HIV
Vaginal Candida colonization rates among women with HIV
infection are higher than among seronegative women with
similar demographic and risk behaviour characteristics, and the
colonization rates correlate with increasing severity of immunosuppression. Symptomatic VVC is also more frequent in
women with HIV infection and similarly correlates with severity
of immunodeficiency. In addition, among women with HIV
infection, systemic azole exposure is associated with the isolation of non-albicans Candida species from the vagina.
On the basis of available data, therapy for uncomplicated and
complicated VVC in women with HIV infection should not differ
from that for seronegative women. Long-term prophylactic
therapy with fluconazole at a dose of 200 mg weekly has been
effective in reducing C. albicans colonization and symptomatic
VVC.
Diagnosis
About 70e85% of infected patients are asymptomatic. Increased
local polymorph nuclear leucocytes (PMNL) is the main host
response to infection.
Sites for sampling are either by high vaginal swabs from the
posterior fornix, self-taken vaginal swabs or urine samples.
Methods for detection of T. vaginalis include:
NAAT (nucleic acid amplification testing) is a highly sensitive method for detection of T. Vaginalis. It can detect
three to five times more than wet preparations using direct
microscopy. It is now considered the gold standard for
detection of T. vaginalis. Specimens are usually retrieved
from the vagina, endocervix or urine. This method detects
the protozoal RNA with a high sensitivity of 95.3e100%
and a high specificity of 95.2e100%.
Direct microscopy: this is the method of choice for
screening. A wet preparation has a low sensitivity of 50
e70%. Vaginal discharge mixed with a drop of saline on a
glass slide can be used to detect T. vaginalis motility. T.
vaginalis lose their motility quickly, therefore the wet
preparation should be read within 10 minutes of collection. Microscopy with a magnification of 400 is used to
confirm the morphology and visualize the flagella. Acridine orange when used as a stain for films was found
more sensitive than unstained wet preparations. This
method is more practical due to its lower cost compared
to NAAT.
Culture was considered in the past as the gold standard for
detection of the protozoan. It has a sensitivity of 75e96%
and a specificity of up to 100%. For culture, vaginal
discharge is preferred compared to a urine specimen, as
urine culture is less specific.
Immunomodulation: OSOM Trichomonas Rapid Test and
the Affirm VP III.
Cervical smear Pap tests can incidentally detect T. vaginalis, but their false positive and false negative rates make
them unreliable as a diagnostic tool
Management of partner
Asymptomatic partners do not require testing or treatment; as
vaginal candidiasis is not a sexually transmitted disease. However, few male partners may benefit from topical antifungal
agents if they experience balanitis (pruritus with erythema of the
penile glans).
Follow up
No follow-up is required for a single episode of vaginal candidiasis. However, if symptoms persist or recur within 2 months of
over-the-counter products, a medical evaluation and investigations are essential.
Recurrent vulvo-vaginal candidiasis
This is defined as four or more episodes of candidiasis within a
year. Prevalence within symptomatic women is expected to be
less than 5%. Non-albicans yeast species cause 10e20% of
recurrent disease. A comprehensive history and exclusion of risk
factors is mandatory for management. Treatment options are a
longer duration of use (7e14 days) of vaginal creams and suppositories, or using oral Fluconazole weekly for 6 months as
suppression and maintenance regimen. Most patients are disease
free during treatment and for around 6 months afterwards but
most do relapse within a year.
321
REVIEW
Treatment
Indications for treatment:
Testing positive for T. vaginalis, regardless of symptoms
Treatment of sexual partners
Recommended regimen:
A single dose of 2 g metronidazole orally
OR
A single dose of 2 g tinidazole orally
Alternative regimen
Twice daily 500 mg metronidazole orally for 7 days
The only effective treatment against T. vaginalis are metronidazoles. The cure rate for metronidazole is 84e98%, while
that for tinidazole, a more expensive drug, is 92e100% Metronidazole gel is less effective due to its low absorption rate and is
not recommended for treatment.
Alcohol, sexual intercourse or vaginal douching may hinder
the effectiveness of treatment. Alcohol should not be consumed
during treatment up to 24 hours after completion of a course of
metronidazole, or 72 hours after completion of a tinidazole
course, as it may precipitate a disulfiram-like reaction. Sexual
intercourse should be avoided during and at least for one week
after treatment. Douching is not recommended as it alters the
vaginal flora and increases the risk of infection.
HIV
There is increased transmission of both HIV and TV as a result of
increased shedding of the virus. Patients with HIV should be
given a 7-day course of metronidazole so as to ensure full
treatment of the infection. Retesting after 3 months may be
warranted in some cases.
Management of partner
Infection is readily transmitted between partners by the act of
unprotected sexual intercourse. Condom use is the main method
for prevention against infection. Uncircumcised men carry
greater risk of transmission to their partners than those who are
circumcised.
Treatment of the partner is recommended to prevent reinfection or transmission among partners. Abstaining from sexual
intercourse is imperative until both partners are treated. The
same regimen of treatment is advised for the partner. Treatment
should be commenced regardless of their test results.
Follow up
Peterman found a recurrence rate of 17% after treatment for T.
Vaginalis. A test of cure is recommended after 3 months of
completing the treatment course. Retesting by NAAT can be done
after 2 weeks of treatment. Limited data is available to guide
retesting the male partner.
Pregnancy
Screening in pregnancy for T. vaginalis in asymptomatic women
is not recommended. T. vaginalis is a risk factor for the vertical
transmission of HIV. Therefore, screening and treatment of T.
vaginalis is recommended for HIV positive pregnant women.
These individuals should have a repeat test 3 months after
treatment.
Infection in pregnancy is associated with a two-to-three-fold
increase in rates of preterm delivery and low birth weight. The
recommended treatment in pregnancy is 2 g oral metronidazole
as a single dose. Treatment may prevent genital or respiratory
infection in the new born.
Metronidazole can be prescribed at any gestational age, if
indicated. Although it crosses the placenta, no evidence of teratogenicity has been established.
Metronidazole is secreted in breast milk but only low plasma
levels are found in the breast fed babies of women using this
medication. However, some obstetricians recommend deferring
breastfeeding for at least 24e48 hours after completion of
treatment.
Presentation
Most patients with DIV will have complaints for more than a
year. Most patients are typically symptomatic, although asymptomatic DIV occasionally occurs. Purulent vaginal discharge
ranges from mild to profuse, associated with signs of inflammation, such as focal petechiae (30e70%) or diffuse vaginal
erythema. Up to 27% of patients may have a similar lesion
involving the cervix and biopsy may show dense lymphocytic
infiltrates.
There is a marked increase in inflammatory cells, predominantly polymorphonuclear leukocytes, together with an increase
in immature squamous cells. Vaginal flora is abnormal with the
loss of lactobacillus morphotype and pH is always elevated
above 4.5.
The diagnosis of DIV is by exclusion of other conditions as
listed:
Infectious diseases: T. vaginalis, Group A Streptococcus,
Cervicitis
322
REVIEW
Management
It has now been accepted that a trial of treatment with topical
oestrogens is a useful method to differentiate between DIV and
atrophic vaginitis. Menopausal women should continue to apply
vaginal oestrogens in addition to the anti-inflammatory treatment
for DIV as well. It is reasonable to send a vaginal culture in
search for Group A Streptococcus and if positive, be treated. Both
topical vaginal clindamycin and local vaginal corticosteroids are
useful and sometimes curative as both have anti-inflammatory
effects.
The recommended regimens are as follows:
Clindamycin:
Insert 2% clindamycin (5 g) vaginally once a night for
three weeks, followed by a maintenance therapy twice a
week for two months
Clindamycin 200 mg vaginally each night for three
weeks, followed by a maintenance therapy twice a week
for two months
Corticosteroids:
Vaginal hydrocortisone 200e500 mg once a night for
three weeks, followed by a maintenance therapy twice a
week for two months
Vaginal cortisone acetate suppository 25 mg twice a day
for three weeks, followed by polymorphonuclear leukocytes maintenance therapy three times a week for two
months.
25% of patient will develop a symptomatic yeast infection. It
is recommended to add oral fluconazole to the treatment regimen
in patients prone to develop such an infection.
Women with DIV require long term follow up to assess
improvement and remission. The evaluation includes measurement of inflammatory and parabasal cell numbers, vaginal pH
and the presence of normal healthy lactobacillus.
FURTHER READING
British Association of Sexual Health and HIV Infection. UK national
guideline on the management of vulval conditions 2014.
Guidelines developed by the Clinical Effectiveness Unit (CEU) of the
Faculty of Sexual and Reproductive Health Care (FSRH) in
collaboration with the British Association for Sexual Health and HIV
(BASHH) [FSRH, 2012].
Gutman RE, Peipert JF, Weitzen S, Blume J. Evaluation of clinical
methods for diagnosing bacterial vaginosis. Obstet Gynecol 2005;
105: 551e6.
Larsson P-G. Treatment of bacterial vaginosis. Int J STD AIDS 1992; 3:
239e47.
National Institute for Health and Care Excellence Clinical Knowledge
Summary. Vaginal Discharge. May 2013.
Peterman TA, Tian LH, Metcalf CA, et al. High incidence of new
sexually transmitted infections in the year following a sexually
transmitted infection: a case for rescreening. Ann Intern Med 2006;
145: 564e72.
Reichman O, Sobel J. Desquamated inammatory vaginitis (in) vulvovaginal disease-best practice & research. Clin Obstet Gynaecol
2014; 28: 1042e50. Elsevier, Newyork.
Sherrard J, Donders G, White D, Jensen JS. European (IUSTI/WHO)
guideline on the management of vaginal discharge. 2011, www.
isuti.org.
Yudin MH, Landers DV, Meyn L, et al. Clinical and cervical cytokine
response to treatment with oral or vaginal metronidazole for bacterial vaginosis during pregnancy: a randomized trial. ObstetGynecol 2003; 102: 527e34.
Practice points
C
Conclusion
Management of vaginal discharge could never be accomplished
without a thorough medical history. pH strips are a simple
additional diagnostic test that is underutilized in gynaecological
clinics. Routine testing or screening of all gynaecological patients
323
REVIEW
Contraception in women
with medical conditions
Sarah L Millar
Sharon T Cameron
Abstract
Pregnancy can result in both maternal and fetal morbidity in women
with medical conditions, making the provision of contraception a
crucial part of their care. Obstetricians and gynaecologists will
frequently encounter these women in the outpatient and inpatient settings and will be expected to have knowledge of the safest and most
effective methods of contraception for that individual. The UK medical
eligibility criteria gives guidance regarding the safety of contraceptive
methods in women with medical conditions. This review will explain
the rationale behind this guidance for women with conditions of the
cardiovascular, gastrointestinal, reproductive and immune systems
as well as considering the effectiveness of currently available methods
of contraception.
Introduction
Forty six percent of pregnancies in the UK are unplanned. Unplanned pregnancies can have far reaching consequences for
women and healthcare services. It is estimated that unintended
pregnancy costs the NHS 1 billion pounds annually. Increasing
the uptake of effective contraception is one way of reducing
unplanned pregnancies. It is thought that 11 is saved in
healthcare costs for every 1 spent on contraception in England.
The physiological changes in pregnancy may cause some
medical conditions to deteriorate in pregnancy (Table 1). Also,
some medical conditions or their treatments, may adversely
affect the outcome of pregnancy. Pre pregnancy counselling is
often imperative in women with chronic health conditions and
women may be advised to delay or avoid pregnancy. These
women need reliable and effective contraception.
However, clinicians may be unfamiliar with which methods of
contraception are suitable for such women and may be concerned about the safety of contraception. There are several issues
to consider when faced with a woman of reproductive age who
does wish to become pregnant and has an acute or chronic
medical condition:
pregnancy in women with co-existing medical conditions
can result in maternal and perinatal morbidity and
Cardiovascular system
Sarah L Millar MBCHB MFSRH Specialty Trainee Community Sexual
and Reproductive Health, Chalmers Sexual Health Clinic, Edinburgh,
Scotland, UK. Conicts of interest: none declared.
324
REVIEW
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
Endometrial or ovarian
cancer
Epilepsy
Gestational trophoblastic
neoplasia
HIV-related disease
Hypertension
Sickle cell disease
Stroke
Systemic lupus
erythematosus (SLE)
Systemic sclerosis
Thrombogenic conditions
Tuberculosis
Teratogenic drugs
Table 1
Ovulation inhibition
0.05
0.05
0.15
0.5
0.15
0.5
0.2
0.2
0.8
6
9
0.6
0.2
0.3
IUD
Depo-provera
Combined hormonal
contraception (pills, patch, ring)
Progestogen only pill
Diaphragm
Condom
Male
Female
Ovulation inhibition
(desogestrel pills)
Cervical mucus changes
(traditional pills)
Barrier
0.3
12
Barrier
Barrier
18
21
2
5
Table 2
325
REVIEW
Cu-IUD
LNG-IUS
IMP
DMPA
POP
CHC
1
1
1
1
1
1
2
1
1
1
3
3
1
1
3
3
2
I
2
2
2
I
2
2
1
2
1
2
1
2
1
2
1
2
2
4
2
1
2
2
2
1
4
2
1
I
3
1
C
1
2
I
3
1
C
3
3
C
1
2
I
2
2
C
3
3
C
3
3
4
4
4
1
1
2
2
2
2
2
2
2
2
4
4
Cu-IUD copper intrauterine device, LNG-IUS levonorgestrel intrauterine system, IMP implanon/nexplanon, DMPA depot medroxyprogesterone acetate (IM and
SC), POP progestogen only pill, CHC combined hormonal contraception, VTE venous thromboembolism, I initiation of a method, C continuation of a method.
Reproduced under licence from FSRH. Copyright Faculty of Sexual and Reproductive Healthcare 2006e2016.
Table 3
326
REVIEW
Gastrointestinal system
Inammatory bowel disease
Inflammatory bowel disease (IBD) (Crohns disease and ulcerative colitis) most commonly presents in women of reproductive
age. Women should be advised that there is no good evidence
that contraception causes or exacerbates IBD and the UK MEC
guidance is summarized in Table 4. Women with IBD are
generally advised to avoid pregnancy during acute exacerbations
and whilst taking teratogenic medications. Clinicians may wish
to refer to the UKTIS website for accurate and up to date information on the risks of teratogenicity with medications (www.
uktis.org).
IBD can result in malabsorption if the small bowel is affected
or there has been small bowel resection. In these women the
efficacy of oral contraception is likely to be reduced and non oral
methods (progestogen implant, IUD or IUS) are preferable.
Women with IBD have been shown to have slightly reduced
bone mineral density (BMD) and modestly increased risk of
fracture compared with women without IBD. This is probably
related to lower body mass index (BMI) and corticosteroid use.
Reductions in BMD with DMPA (which resolve on stopping)
have also been observed. If DMPA is considered the most suitable method for the woman then she should be advised on lifestyle factors to maintain bone health (stopping smoking,
exercise, adequate calcium and vitamin D intake) and her suitability for DMPA reviewed every 2 years.
Although women with IBD appear to be at slightly increased
risk of VTE there are no restrictions to the use of CHC in women
with mild disease. However, the risk of VTE may be raised to an
unacceptable level in women with IBD who have additional risk
factors for VTE such as prolonged immobilization after surgery
or severe disease. The risks of using CHC in these situations may
outweigh the benefits.
Contraceptive choice in women with IBD should be individualized and dependent on the severity of her symptoms, the
necessity for effective contraception and the risk of complications
such as VTE and osteoporosis. Ideally women with IBD should
Liver disease
The UK MEC for women with liver disease is shown in Table 5.
Hormonal contraception is metabolized by the liver and can
adversely affect liver function in women with pre-existing liver
disease. However, hormonal contraceptives are unlikely to cause
significant damage in women with mild chronic hepatitis, mild
cirrhosis or in carriers of hepatitis and so their use should not be
restricted.
The liver has oestrogen receptors but not progesterone receptors making it slightly more susceptible to damage from
oestrogen containing contraceptives. This is reflected in the difference in the UK MEC categorization for CHC and progestogen
only methods. The effects of ethinylestradiol are no less if given
via a patch or ring.
Cu-IUD
LNG-IUS
IMP
DMPA
POP
Carrier of hepatitis
Chronic hepatitis
Mild cirrhosis
Severe (decompensated) cirrhosis
Benign focal nodular hyperplasia
Benign hepatocellular adenoma
Malignant hepatocellular carcinoma
1
1
1
1
1
1
1
1
1
1
3
2
3
3
1
1
1
3
2
3
3
1
1
1
3
2
3
3
1
1
1
3
2
3
3
CHC
I
3
1
1
1
4
2
4
4
C
1
Cu-IUD copper intrauterine device, LNG-IUS levonorgestrel intrauterine system, IMP implanon/nexplanon, DMPA depot medroxyprogesterone acetate (IM and
SC), POP progestogen only pill, CHC combined hormonal contraception, VTE venous thromboembolism, I initiation of a method, C continuation of a method.
Reproduced under licence from FSRH. Copyright Faculty of Sexual and Reproductive Healthcare 2006e2016.
Table 4
327
REVIEW
Cu-IUD
1
I
4
3
1
I
4
LNG-IUS
C
2
C
2
2
I
4
3
1
I
4
C
2
C
2
IMP
DMPA
POP
CHC
1
2
2
2
1
1
2
2
2
1
1
2
1
1
1
1
1
2
1
1
Cu-IUD copper intrauterine device, LNG-IUS levonorgestrel intrauterine system, IMP implanon/nexplanon, DMPA depot medroxyprogesterone acetate (IM and
SC), POP progestogen only pill, CHC combined hormonal contraception, I initiation of a method, C continuation of a method.
Reproduced under licence from FSRH. Copyright Faculty of Sexual and Reproductive Healthcare 2006e2016.
Table 5
hydatidiform mole or for 1 year after chemotherapy. Contraception therefore needs to be discussed with women. A recent
large (over 2000 women) historical database review found that
women with complete hydatidiform mole who used hormonal
contraception while their HCG was elevated from complete
hydatidiform mole had no difference in time to remission of
their HCG levels or rates of progression to neoplasia compared
with women who did not use hormonal contraception. There is
also some evidence that using CHC does not adversely affect
the regression of neoplasia in women undergoing chemotherapy. The UK MEC guidance relating to GTD and IUC reflects
the theoretical concern of increased risk of perforation when
molar tissue is still present. The UK MEC guidance is summarized in Table 6.
Gynaecological cancer
The management of gynaecological cancers will usually result in
sterility (i.e. pelvic clearance, chemotherapy). Those who have
fertility sparing treatment, by definition, will not require
contraception. However, contraception is important in the lead
up to treatment. Women generally remain fertile while awaiting
treatment and an unplanned pregnancy may delay or alter her
treatment and cause emotional distress.
The benefits of using the progestogen only implant, POP, DMPA
or CHC generally outweigh the risks in women with gynaecological
cancer (Table 6). Anatomy may be distorted in women who have
had trachelectomy and IUC should generally be avoided unless no
other method is acceptable. There may be an increased risk of
bleeding and infection if IUC is fitted in women who are awaiting
treatment for cervical or endometrial cancer. However, if the
women already have IUC, it does not need to be removed.
Breast cancer
Breast cancer treatments (chemotherapy, anti oestrogens) do not
usually result in permanent, or even temporary, sterility and so
contraception is still relevant. Breast cancer is hormone sensitive
and the use of hormonal contraception (including the LNG-IUS)
should be avoided in women with current or past breast cancer
because of the risk of acceleration or recurrence of disease. The
copper IUD would a good option for women with current or past
breast cancer.
Cu-IUD
LNG-IUS
IMP
DMPA
POP
CHC
Cu-IUD copper intrauterine device, LNG-IUS levonorgestrel intrauterine system, IMP implanon/nexplanon, DMPA depot medroxyprogesterone acetate (IM and
SC), POP progestogen only pill, CHC combined hormonal contraception.
Reproduced under licence from FSRH. Copyright Faculty of Sexual and Reproductive Healthcare 2006e2016.
Table 6
328
REVIEW
Cu-IUD
LNG-IUS
IMP
DMPA
POP
CHC
1
1
1
1
4
3
1
2
4
3
1
2
4
3
1
2
4
3
1
2
4
3
1
3
Cu-IUD copper intrauterine device, LNG-IUS levonorgestrel intrauterine system, IMP implanon/nexplanon, DMPA depot medroxyprogesterone acetate (IM and
SC), POP progestogen only pill, CHC combined hormonal contraception, VTE venous thromboembolism, I initiation of a method, C continuation of a method.
Reproduced under licence from FSRH. Copyright Faculty of Sexual and Reproductive Healthcare 2006e2016.
Table 7
Women are often concerned about using hormonal contraception if they have a family history of breast cancer. From the
limited data that is available, hormonal contraception does not
appear to significantly increase the risk of breast cancer in
women who have a family history of breast cancer (see Table 7).
Benign gynaecological disease
Hormonal contraception is often used in the treatment of menstrual disturbance due to its favourable effects on dysmenorrhoea and heavy menstrual bleeding. However, in conditions
where the uterine cavity is significantly distorted or there is a risk
of introducing infection into the pelvis, insertion of IUC may not
be appropriate.
Neurological diseases
Migraine
Migraine is a common complaint among women of reproductive
age. Ischaemic stroke is more common in women with migraine
with aura compared to those without aura. The risk increases
further (two to four fold) if a woman with migraine with aura
takes CHC. The UK MEC (Table 8), therefore, advises against the
use of CHC in women who have migraine with aura. POC does
not appear to increase the risk of stroke and can therefore be
used in women with migraine with aura.
Epilepsy
It is important that women with epilepsy plan their pregnancy in
order to reduce the risk of teratogenicity from antiepileptic drugs
(AEDs) (in particular sodium valproate) and optimize seizure
control. There are no concerns over safety of contraceptives in
women with epilepsy. However, some AEDs can reduce the efficacy of contraception and some contraceptives alter the efficacy
of AEDs.
Cu-IUD
LNG-IUS
IMP
DMPA
POP
Non-migrainous headache
1
1
2
2
2
2
2
2
I
1
2
2
CHC
C
2
I
1
I
2
4
3
C
2
C
3
Cu-IUD copper intrauterine device, LNG-IUS levonorgestrel intrauterine system, IMP implanon/nexplanon, DMPA depot medroxyprogesterone acetate (IM and
SC), POP progestogen only pill, CHC combined hormonal contraception, VTE venous thromboembolism, I initiation of a method, C continuation of a method.
Reproduced under licence from FSRH. Copyright Faculty of Sexual and Reproductive Healthcare 2006e2016.
Table 8
329
REVIEW
Cu-IUD
LNG-IUS
IMP
DMPA
POP
CHC
Rheumatoid arthritis
SLE with no antiphospholipid antibodies
SLE with positive antiphospholipid antibodies
Positive antiphospholipid antibodies
1
1
1
1
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
4
4
Cu-IUD copper intrauterine device, LNG-IUS levonorgestrel intrauterine system, IMP implanon/nexplanon, DMPA depot medroxyprogesterone acetate (IM and
SC), POP progestogen only pill, CHC combined hormonal contraception, VTE venous thromboembolism, I initiation of a method, C continuation of a method.
Reproduced under licence from FSRH. Copyright Faculty of Sexual and Reproductive Healthcare 2006e2016.
Table 9
Immune system
HIV infection
The UK MEC guidance group concluded there was no robust
evidence that hormonal contraception or the copper IUD increases the risk of HIV acquisition or adversely affects the CD4
counts or viral loads of women with HIV infection. However,
clinicians may wish to avoid IUC insertion in women with a CD4
count <200 due to the possible risk of ascending genital tract
infection.
Some antiretrovirals affect the efficacy of contraceptives. Up
to date information on antiretroviral drug interactions can be
found on the Liverpool HIV Drug Interactions website http://
www.hiv-druginteractions.org.
Obesity
Obesity is a common problem in the UK. Obese women are more
likely to have an unplanned pregnancy than women with a
healthy BMI. Furthermore, obesity in pregnancy is associated
with an increased risk of miscarriage, stillbirth, pre eclampsia,
gestational diabetes, wound infections, congenital anomalies and
thromboembolism.
The risk of thromboembolism is the main concern in obese
women using contraception. Obesity is an independent risk factor for thromboembolism and, as already discussed, VTE rates
are overall higher in CHC users. There is evidence that CHC users
with higher BMIs have an increased risk of VTE compared to
Antiphospholipid antibodies
Antiphospholipid syndrome (APS) is an autoimmune condition
where individuals have raised antiphospholipid antibodies (aPL)
and a history of vascular (venous or arterial) thrombosis and/or
an adverse pregnancy outcome such as recurrent miscarriage,
intrauterine death, pre term delivery due to pre eclampsia or
placental insufficiency. APS can occur alone or in association
with conditions such as systemic lupus erythematosus (SLE) and
rheumatoid arthritis. apL without clinical manifestations are,
however, found in 5% of healthy individuals.
Cu-IUD
LNG-IUS
IMP
DMPA
POP
CHC
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
2
3
1
Cu-IUD copper intrauterine device, LNG-IUS levonorgestrel intrauterine system, IMP implanon/nexplanon, DMPA depot medroxyprogesterone acetate (IM and
SC), POP progestogen only pill, CHC combined hormonal contraception, VTE venous thromboembolism, I initiation of a method, C continuation of a method.
Reproduced under licence from FSRH. Copyright Faculty of Sexual and Reproductive Healthcare 2006e2016.
Table 10
330
REVIEW
CHC users with healthy BMIs and this increased risk is reflected
in the UK MEC guidance (Table 10).
Bariatric surgery includes restrictive procedures (laparoscopic
adjustable gastric banding and vertical sleeve gastrectomy),
malabsorptive procedures (biliopancreatic diversion with/
without duodenal switch), both restrictive and malabsorptive
procedures (roux-en-Y gastric bypass) and other procedures such
as gastric stimulation and intragastric balloon. The main concern
surrounding bariatric surgery and contraception is that of
malabsorption of oral methods and reduced effectiveness either
because of the surgery itself or post operative long term diarrhoea and vomiting. Women who have had bariatric surgery
should consider non oral methods if there are concerns over
absorption.
FURTHER READING
Faculty for Sexual and Reproductive Health. UK medical eligibility
criteria for contraceptive use. Clinical effectiveness unit 2016.
Available at:http://ukmec.pagelizard.com/2016.
Faculty of Sexual and Reproductive Health Statement. Venous
thromboembolism (VTE) and hormonal contraception. Clinical
effectiveness unit November 2014. Available at:http://www.fsrh.
org/documents/fsrhstatementvteandhormonalcontraceptionnovember/.
Faculty of Sexual and Reproductive Healthcare Clinical Guidance.
Contraceptive choices for women with cardiac disease. Clinical
effectiveness unit. 2014, https://www.fsrh.org/documents/ceuguidance-contraceptive-choices-for-women-with-cardiac/.
Faculty of Sexual and Reproductive Healthcare Clinical Guidance.
Drug interactions with hormonal contraception. Clinical effectiveness unit 2011. Available at:https://www.fsrh.org/documents/ceuguidance-drug-interactions-with-hormonal-contraception-jan/.
Faculty of Sexual and Reproductive Healthcare Clinical Guidance.
Emergency contraception. Clinical effectiveness unit 2011 (updated 2012), Available at:https://www.fsrh.org/standards-andguidance/documents/ceu-emergency-contraception-jan-2012/.
Emergency contraception
Emergency contraception (EC) can be offered to all women with
medical conditions. The most effective form of EC is the copper
IUD and should be offered first line. Alternatively, levonorgestrel
(LNG) or ulipristal acetate (UPA) can be used. Women taking
enzyme inducing medications should be given a double dose of
LNG rather than UPA. A Cochrane review found that women
who have more unprotected sex in same cycle after EC have a
three fold increased risk of pregnancy than women who do not
go on to have more unprotected sex. Therefore, when a woman
presents for EC she should be given effective contraception to
start immediately, ideally LARC. The FSRH document on Emergency Contraception gives detailed advice on the practicalities of
prescribing EC and on quick starting contraception.
Conclusion
Women with medical conditions may need to avoid or delay
pregnancy to prevent maternal and fetal morbidity. There are no
331
CASE-BASED LEARNING
Problems in obstetric
anaesthesia
Jonathan Lewis
Nav Bhandal
Abstract
Advances in medical management and technologies have increased
the prospects of women with severe chronic disease achieving pregnancy. Women with complex needs are becoming more commonplace
on labour suite and are posing an increasing challenge to healthcare
professionals. The management of dilated cardiomyopathy, postpartum headache and haemophilia are discussed using three theoretical cases. These cases illustrate the issues for both the anaesthetic
and obstetric teams and highlight the importance of a multidisciplinary
approach where good communication is essential in achieving the
safest possible outcome for such patients.
Introduction
A common theme in all of the triennial reports, most recently
under the guise of Mothers and Babies: Reducing Risk through
Audits and Confidential Enquiries across the UK (MBRRACEUK), is that good quality, timely communication and multidisciplinary collaboration is the cornerstone of safe, effective practice. The reports from MBRRACE-UK, and previously from
CEMACH, have made a number of recommendations including
early consultation with a senior multidisciplinary team, use of
early warning scores in all obstetric units, adherence to obstetric
emergency protocols and early identification and targeted management of high-risk obstetric women including appropriate
escalation of care.
This review presents three hypothetical case scenarios to
illustrate some of the challenges encountered by the obstetric
anaesthetist as part of the multidisciplinary team caring for the
complex obstetric woman. An understanding of these issues
should inform the decision making process, in addition to promoting inter-specialty communication.
332
CASE-BASED LEARNING
to allow time for the woman to adjust to fluid shifts that result
from changing pre-load and after-load.
A well established epidural in labour can be cautiously topped-up for caesarean section in theatre with full monitoring. Use
of invasive arterial monitoring is advisable and central venous
access should be considered.
The patient presented in early labour at 34 weeks. She was
breathless on minimal exertion and had clinical evidence of
worsening heart failure with tachypnoea, bibasal crepitations and
ankle swelling.
Her arrival was communicated to the anaesthetic team who
sited an epidural early in labour. The cardiac physiology technicians were alerted to her presence as interrogation and deactivation of the implantable defibrillator would be needed in the event
of her needing to go to the operating theatre.
333
CASE-BASED LEARNING
Pre-eclampsia
Pre-eclamptic disease affects between 3 and 5% of pregnant
woman and the first 48 hours following delivery of the fetoplacental unit still carries significant risk. Headache related to preeclampsia may be accompanied by vomiting, visual disturbance and focal deficits. Patients may fit and are at risk of intracerebral haemorrhage from systolic hypertension. CT imaging
typically shows cerebral oedema. Management of pre-eclampsia
will be effective in reducing the symptoms.
Cerebral venous thrombosis
In both pregnancy and the immediate postnatal period, women are
in a hypercoagulable state. This combined with other risk factors
such as vomiting and dehydration can lead to an increased risk of
cerebral venous thrombosis. It can be difficult to diagnose as the
headache is often non-specific and may have a gradual onset.
There may be associated focal neurological signs or the woman
may fit. Diagnosis is established via a MR or CT venogram.
Meningitis
Although meningitis is an uncommon cause of postnatal headache the classic signs of meningism, photophobia in the presence
of pyrexia and sepsis should be looked for. Group B streptococcus in colonised women is thought to be the commonest
causative organism. Diagnosis is confirmed by microscopy and
culture of cerebrospinal fluid following a CT brain to exclude
other intra-cerebral pathology.
Reversible cerebral vasoconstriction syndrome
(RCVS)
Reversible cerebral vasoconstriction syndrome is a self limiting
syndrome of uncertain cause that is characterised by dysregulation of cerebral arterial tone. Pregnancy is a recognised precipitant with the symptoms occurring with a week of delivery. Other
known precipitating factors include SSRIs and ergot alkaloids.
Patients with migraine are believed to be more susceptible. The
headaches are described as thunderclap and may be associated
334
CASE-BASED LEARNING
Case 3: haemophilia
A 26-year-old nulliparous woman was referred to the anaesthetic
antenatal clinic by the obstetric team. She was known to have a
diagnosis of haemophilia A which was made following investigations into menorrhagia in adolescence. She had been taking oral tranexamic acid during her periods since diagnosis with
good effect. This was a planned pregnancy after pre-conceptual
counselling with a geneticist and an obstetrician and the lady
had undergone chorionic villus sampling (CVS) at 12 weeks. She
was expecting a female baby that had tested positive as a carrier
for haemophilia A.
The haemophilias are a group of genetic bleeding disorders
characterised by partial or complete deficiency in particular
clotting factors. It is subdivided into haemophilia A, B and C with
deficiencies in clotting factors VIII, IX and XI respectively. Both
haemophilia A and B display X-linked recessive inheritance
whereas haemophilia C is inherited as an autosomal recessive
disorder. 30% of patients, however, have no family history of
haemophilia and are affected as a result of new mutation. Haemophilia A is the commonest form with an incidence of
approximately 1 in 5000 live male births with the other two
forms rarer by an order of magnitude.
Haemophilia A and B, being X-linked recessive disorders,
affect males and rarely homozygous females. Normally females
are heterozygous for the mutation and are therefore only carriers,
and as a result only display a milder form of the disease. Their
offspring have a 50% chance of inheriting the affected X chromosome and therefore, if male, have a 50% chance of having the
disease, and, if female, have a 50% chance of being a carrier
themselves.
There is a wide spectrum of clinical severity which relates to
the level of active clotting factors. Levels are commonly
expressed in IU/dl with the normal range being 50e150 IU/dl of
normal. Patients with severe disease have levels <1 IU/dl,
moderate disease 1e5 IU/dl and mild disease 5e40 IU/dl.
Haemophilia A in pregnancy
Known or suspected carriers of haemophilia A should be offered
pre-conception counselling to discuss the risk of having a child
affected by haemophilia including alternatives to pregnancy.
Baseline factor VIII levels should be taken and the carrier status
of the woman tested if unknown. A discussion about different
methods of antenatal fetal sex determination, to identify males at
higher risk, should also take place. It is now possible to have preimplantation genetic diagnosis (PIGD) performed if also having
in vitro fertilisation (IVF). More commonly, testing is post
335
CASE-BASED LEARNING
The patient delivered a baby girl via caesarean section. Estimated blood loss was 950 ml. The baby was born in good condition with no signs of bruising or bleeding. The patient required
further doses of recombinant factor VIII over the next 5 days in
order to maintain levels >50 IU/dl and was then discharged home
with no further bleeding.
Conclusion
Well planned multidisciplinary team working is the key to success when dealing with high risk, complicated obstetric patients.
They need input into their management from before conception
right through to the postnatal period. Planning for delivery is
important but maintaining flexibility in the face of a changing
clinical picture is also essential.
A
Practice points
FURTHER READING
Klein AM. Postpartum headache. IJOA 2010; 19: 422e30.
Knight M, Tuffnell D, Kenyon S, Shakespeare J, Gray R, Kurinczuk JJ
(Eds.) on behalf of MBRRACE-UK. Saving lives, improving mothers
care e Surveillance of maternal deaths in the UK 2011e13 and
lessons learned to inform maternity care from the UK and Ireland
Condential Enquiries into maternal deaths and morbidity 2009
e13. Oxford: National Perinatal Epidemiology Unit, University of
Oxford, 2015.
Lee CA, Chi C, Pavord SR, et al. The obstetric and gynaecological
management of women with inherited bleeding disorders e review
with guidelines produced by a taskforce of UK Haemophilia Centre
Doctors Organization. Haemophilia 2006; 12: 301e36.
Lewis G, ed. The Condential Enquiry into Maternal Deaths (CEMD)
saving mothers lives: reviewing maternal deaths to make
336
CASE-BASED LEARNING
Induction of ovulation
Alpha Gebeh
Mostafa Metwally
Abstract
Anovulatory infertility is one of the commonest causes of infertility and
can be caused by problems related to the ovary (normogonadotropic
and hypergonadotropic hypogonadism) or the pituitary and hypothalamus (hypogonadotropic hypogonadism). Consequently induction of
ovulation will depend on the cause of infertility. For those with normogonadotropic hypogonadism, ovulation can be induced using antioestrogens such as clomifene citrate and tamoxifen or aromatase
inhibitors such as letrozole. Second line treatments include metformin,
gonadotropins and laparoscopic ovarian drilling. Those with hypogonadotropic hypogonadism will require gonadotropins or GnRH analogues. The following review outlines the different approaches to
ovulation induction with a focus on commonly encountered clinical
scenarios.
Case 1
A 28-year-old woman with anovulatory infertility due to polycystic ovarian syndrome (PCOS) and a body mass index (BMI) of
40 kg/m2 has attended the infertility clinic to discuss options for
management of her infertility. Her partner has a normal semen
analysis and her hysterosalpingogram has demonstrated bilateral
patent tubes. She would like to discuss her options.
Discussion
Induction of ovulation for women with PCOS is the commonest
scenario for ovulation induction encountered in most infertility
clinics. Choice of treatment for this patient will depend on her
BMI. Weight loss is the first line of treatment in overweight and
obese PCOS women while Clomiphene citrate and Aromatase
inhibitors are recommended as the first line in lean PCOS ones.
Introduction
Anovulatory infertility is one of the most commonly encountered
problems in the infertility clinic. Anovulation may be due to
problems affecting the ovary, pituitary or hypothalamus. Causes
of anovulation have been classified by the World Health Organisation into three categories based on gonadotropin profile e
follicle stimulating hormone (FSH), luteinizing hormone (LH)
and also oestradiol (E2). WHO type 1 anovulation (10%) is
characterized by a hypogonadotropic hypo-oestrogenic state and
includes hypothalamic amenorrhoea, hypogonadotropic hypogonadism and hypopituitarism. These can be caused by any
lesion affecting the pituitary or hypothalamus and affecting
gonadotropin production including idiopathic, weight-related
amenorrhoea, Sheehan syndrome, extreme stress and strenuous exercise, Kallmans syndrome, craniopharyngiomas etc.
WHO type 2 (normogonadotropic hypogonadism) is by far the
commonest cause of anovulation accounting for 85% of cases
and is most commonly caused by polycystic ovarian syndrome
(PCOS). Hyperprolactinaemic amenorrhoea is another, though
much less common, WHO Group II ovulation disorder. Clinically,
in addition to amenorrhoea and infertility, women with the
condition may have galactorrhoea. The most common source of
337
CASE-BASED LEARNING
The main side effects of clomifene are related to its antioestrogen effects. Centrally this can lead to symptoms such as
hot flushes and uncommon but serious side effects include visual
symptoms such as blurred vision, diplopia, and photosensitivity.
Furthermore due to potential multifollicular development there is
an 8% chance of multiple pregnancies. Another potentially
serious but uncommon side effect is ovarian hyperstimulation
syndrome.
Adjuvants:
Several adjuvants including growth hormone, ketoconazole
and dexamethasone have been used in addition to clomifene in
an attempt to improve ovulation and pregnancy rates but mostly
their use has not been supported by substantial evidence. However, metformin can be used alone or in combination with clomifene for ovulation induction in PCOS. Metformin is associated
with gastrointestinal side effects include nausea, vomiting and
abdominal upset. Dopamine agonists such as bromocriptine are
useful if there is associated hyper-prolactinaemia.
Bariatric surgery:
As a final option, bariatric surgery can be used for those who
have failed to lose weight by other means. The guidelines of the
National Institute for Health and Clinical Excellence (NICE) states
that surgery is a treatment option for people with morbid obesity
(BMI equal to or greater than 40 kg/m2) or with a BMI equal to or
greater than 35 kg/m2 in the presence of significant co-morbid
conditions that could be improved by weight loss e.g. type 2
diabetes, hypertension. Surgical techniques include restrictive
procedures e.g. laparoscopic gastric banding, sleeve gastrectomy
or malabsorptive procedures e.g. Roux-en-Y gastric bypass. A
recent RCOG scientific opinion paper concludes that bariatric
surgery improves several important markers of fertility including
hyperinsulinaemia and ovulatory function. However, its potential
benefits need to be balanced against the risks of surgery.
Case 2
The same patient had succeeded in dropping her BMI to 33 kg/
m2 and was commenced on a course of clomifene citrate. After 6
months she attended the clinic again as unfortunately clomifene
338
CASE-BASED LEARNING
had been unsuccessful at inducing ovulation despite incrementally increasing the dose to 150 mg/day. She would like to
discuss further options.
Discussion
10e30% of women receiving clomifene will remain anovulatory
and are labelled as clomifene resistant. Options for second line
treatments include the use of insulin sensitising agents such as
metformin, the use of gonadotropins or laparoscopic ovarian
drilling.
Case 3
A 34-year-old patient has been diagnosed with secondary infertility. She has had one previous pregnancy that was delivered at
339
CASE-BASED LEARNING
term by emergency caesarean section due to significant antepartum haemorrhage. After delivery she also suffered from
massive postpartum haemorrhage and needed 15 units of blood
transfusion for resuscitation. She was admitted to intensive care
but eventually fully recovered. She was unable to breast feed due
to lack of milk production and also suffered from secondary
amenorrhoea. Analysis of gonadotropins showed low concentrations of FSH and LH.
Conclusions
Discussion
This represents a case of hypogonadotropic hypogonadism
(WHO type 1) due to massive postpartum haemorrhage resulting
in pituitary ischaemia and hypopituitarism (Sheehan syndrome).
Induction of ovulation in this case can be achieved with the use
of a combination of both FSH and LH since both are needed to
maintain normal follicular development. This combination can
be achieved either by the use of human menopausal gonadotropin (HMG) containing both products or by the use of r-FSH
combined with recombinant LH (r-LH).
The potential advantage of using r-FSH/r-LH is being able to
tailor the dosage to individual patient requirements as well as
more batch-to-batch consistency and a more predictable
response to dosage. Consequently r-LH can be combined with rFSH for ovarian stimulation usually at a dose of 150 IU r-FSH and
75 IU r-LH daily.
FURTHER READING
1 Balen A, Platteau P, Andersen AN, Devroey P, Helmgaard L,
Arce JC. Highly puried FSH is as efcacious as recombinant FSH
for ovulation induction in women with WHO Group II anovulatory
infertility: a randomized controlled non-inferiority trial. Hum Reprod
2007; 22: 1816e23.
2 Metwally M, Amer S, Li TC, Ledger WL. An RCT of metformin
versus orlistat for the management of obese anovulatory women.
Hum Reprod 2009; 24: 966e75.
3 Yasmin E, Davies M, Conway G, Balen A. Ovulation induction in
WHO type 1 anovulation: guidelines for practice. Produced on
behalf of the British Fertility Society Policy and Practice Committee.
Hum Fertil 2013; 16: 228e34.
4 National Institute of Clinical Excellence (NICE), CG156. Fertility
problems: assessment and treatment (London); 2013, https://www.
nice.org.uk/guidance/CG156.
Practice points
C
C
340
ETHICS/EDUCATION
William Stones
Abstract
Provision of respectful care in labour requires awareness of the special
circumstances of childbirth as a natural process. The need for woman
centred humanistic care runs alongside the duty to provide access to
clinical interventions as required, recognising the limitations of risk
assessment. Avoidance of over medicalisation and inappropriate interventions contributes to respectful care, as does leadership to develop
and sustain good working relationships among staff, so that women
experience care provided by staff who are functioning at their best.
Institutionalising respectful care provision alongside evidence based
clinical practice represents the goal of motherebaby friendly birthing
facilities as advocated by FIGO.
341
ETHICS/EDUCATION
example is the persistence of routine episiotomy on the subcontinent and in China despite exhaustive systematic review
evidence against this approach.
FURTHER READING
Abuya T, Ndwiga C, Ritter J, et al. The effect of a multi-component
intervention on disrespect and abuse during childbirth in Kenya.
BMC Pregnancy Childbirth 2015; 15: 224. http://dx.doi.org/10.
1186/s12884-015-0645-6.
And Krejzova
v.
European Court of Human Rights. Case of Dubska
2014. Strasbourg: The Czech Republic. Accessible at: http://
hudoc.echr.coe.int/eng?i001-148632.
FIGO Safe Motherhood and Newborn Health Committee, CM, White
Ribbon Alliance, International Pediatric Association, WHO. Motherbaby friendly birthing facilities. Int J Gynecol Obstet 2015; 128:
95e9.
FIGO. Womens rights, health and empowerment (web materials).
Accessible at http://www.glowm.com/womens_health_rights.
General Medical Council. The duties of a doctor. 2013. General
Medical Council. Accessible at: http://www.gmc-uk.org/guidance/
good_medical_practice/duties_of_a_doctor.asp.
Richmond D, Warwick C. The RCOG/RCM joint statement on undermining and bullying in the workplace. 2015. Royal College of Obstetricians & Gynaecologists. Accessible at: https://www.rcm.org.
uk/sites/default/les/Undermining%20Behaviours%20A4_7%20%
20-for%20website.pdf.
342
SELF-ASSESSMENT
Self-assessment questions
Questions
SBA 1
A GP trainee currently on rotation in gynaecology asks for help
with understanding the UK MEC guidance in contraceptive
care. Which one of the following statements is accurate
regarding the MEC?
a) Reflects the effectiveness of contraception in women with
medical conditions.
b) Category 4 means there are no restrictions to use of the
contraception in women with that medial condition or
characteristic.
c) Relates to the use of the method for contraception and its
use in the management of medical disorders.
d) Category 3 means the theoretical or proven risks usually
outweigh the advantages of using the method.
e) Reflects the safety of contraception in women (except those
with chronic medical conditions).
EMQ 4
From the options below please select the most causative pathology or organism. Options may be used once, multiple time
or not at all.
a. Staphylococcus aureus
b. Vulvovaginal candidiasis
c. Candida glabrata
d. Trichomonas vaginalis
e. Bacterial vaginosis
f. Atrophic vaginitis
g. Gardnerella vaginalis
h. Group A streptococcus
1. A 42-year old woman attends the sexual health clinic
complaining of vaginal discharge. When a diagnosis is
reached she is informed that partner notification will be
required as part of management
2. Cause of recurrent candidiasis
3. A major cause of post-partum sepsis
4. Associated with an increased rate of preterm birth
SBA 2
A 34 year old woman who experienced a VTE following her
last pregnancy attends for contraceptive advice. Which of the
following statements is NOT true?
a) She should not use combined hormonal contraception.
b) She can be advised that the safest and most effective
method of contraception is IM/SC depot medroxyprogesterone acetate (DMPA).
c) She could have an IUD/IUS fitted if she is still taking
warfarin.
d) She can be advised that the advantages of using the progestogen only implant (nexplanon) generally outweigh the
theoretical or proven risks.
e) She should be counseled that 18 out of 100 women using
male condoms only for contraception will experience an
unintended pregnancy by 1 year.
SBA 5
You are the obstetrician serving as clinical director of a busy
hospital maternity unit. A patient has complained to the Chief
Executive about her care during labour and delivery and you
are asked to investigate and respond to the complaint. The
complaint letter refers to cleaning staff entering the labour
room without permission while Ms X was exposed, causing
her embarrassment. She also reports that while she was
pushing during the second stage, the midwife called a doctor
as she was concerned about the fetal heart rate. The doctor
thought it was normal and the two argued about whether
intervention was needed. She felt this behaviour was unprofessional. In the end she delivered normally without complications for her or the baby. Which one of the following options
would NOT form part of an appropriate investigation into this
complaint?
a) Review the case notes to identify any clinical issues
b) Confer with your midwifery management counterpart and
the manager responsible for housekeeping
EMQ 3
From the options below pick the single most appropriate
treatment for each scenario.
a. 2 g oral metronidazole
b. 500 mg PV clotrimazole
c. Nystatin 100,000 units four times per day for 3 weeks
d. No treatment required
e. Amphoteracin 1 mg IV daily for 3 days
f. Metronidazole 400 mg orally twice daily for 5 days
g. 150 mg fluconazole
h. Metronidazole 500 mg IV three times daily
i. Dermovate cream once daily for 4 weeks
343
SELF-ASSESSMENT
EMQ 9
From the options below pick the most appropriate treatment
for each scenario. Options can be used once, multiple times or
not at all.
a) Treat with dopamine agonists and address the underlying
cause
b) Start treatment with clomiphene citrate
c) Start treatment with aromatase inhibitors
d) Advise weight loss
e) Advise bariatric surgery
f) Switch to metformin treatment
g) Advise laparoscopic ovarian drilling
h) Start treatment with gonadotrophins
i) Start treatment with GnRH analogs
1. A 26-year old woman attends the infertility clinic with her
boyfriend of 2 years. They have been trying unsuccessfully
to conceive. On questioning, the patient is amenorrhoeic
and has noted a discharge from both breasts during the last
year.
2. A 30-year old woman attends the infertility clinic with her
partner. She reports oligomenorrhoea, hirsutism and acne.
Her body mass index is 38. They have been trying to
conceive for the last year.
3. A 36-year old woman with diagnosed PCOS has failed to
ovulate during several cycles of clomiphene citrate therapy. She has an extensive past history of bowel resection
for Crohns disease.
SBA 6
Having completed the initial investigation into the complaint
outlined in SBA 5, you respond to the complaint. Which one of
the following steps would NOT be an appropriate part of your
response?
a) Invite the patient and her partner to meet with you and the
midwifery manager.
b) Offer apology on behalf of the hospital.
c) Describe the steps taken to avoid a recurrence such as
feedback to the staff involved.
d) Note any additional concerns that the patient or her partner
might have about the service.
e) Explain that as you were not directly involved in the incident you are not best placed to respond to her concerns.
EMQ 7
From the options below pick the most appropriate treatment
for each scenario. Options can be used once, multiple times or
not at all.
a. 2 g oral metronidazole
b. 500 mg PV clotrimazole
c. Nystatin 100,000 units four times per day for 3 weeks
d. No treatment required
e. Repeat swabs in 10 days time
f. Metronidazole 400 mg orally twice daily for 5 days
g. 150 mg fluconazole
h. Daily application of oestrogen cream for 2 weeks
i. Dermovate cream once daily for 4 weeks
1. A 33-year old presents with increased white discharge with
associated vulval pruritus. This is her first presentation;
she has no other risk factors.
2. A 19-year old presents with lower abdominal pain and
profuse yellow, offensive discharge. On examination there
is generalised redness of the cervix and cervical excitation
is present. Multiple swabs are obtained including one for
wet microscopy; protozoa are seen. She is otherwise systemically well.
3. A 65-year woman who has recently become sexually active
with a new partner complains of vaginal discomfort during
and after intercourse, but no discharge.
SBA 10
A 28-year-old woman attends for an elective Caesarean section
at 39 weeks for a breech baby. She has hypertrophic cardiomyopathy and has an implantable cardioverter defibrillator
(ICD). Which of the following is true regarding her care
intraoperatively?
A) It is important to leave the device active during surgery in
case of dysrhythmias
B) A magnet placed near the device is reliable way of
disabling the defibrillator function
C) Patients require continuous cardiac monitoring postoperatively
D) The device is normally found subcutaneously in the right
pectoral region
E) Defibrillation ICDs cannot act as cardiac pacing devices
SBA 8
A 34-year old woman attends the infertility clinic with her
partner. They have been trying unsuccessfully to conceive for
over 2 years. Her periods have never been regular. Both her
gonadotrophin and oestradiol levels are very low on testing.
Which one of the following is not a possible cause of her
infertility?
a) Sheehans syndrome
b) Idiopathic hypogonadotrophic hypogonadism
c) Polycystic ovarian syndrome
SBA 11
A 38-year-old woman who is known to suffer from haemophilia A attends the antenatal clinic to plan delivery. Which
of one of the following statements is true about her
condition?
A) It is inherited via an X-linked dominant gene
B) Haemophilia A results in lower levels of coagulation factor
VIII
C) Haemophilia A is an absolute contraindication to epidural
analgesia
344
SELF-ASSESSMENT
4. e
Bacterial vaginosis should be treated in pregnancy because
of the association with preterm birth
SBA 5 answer
e
In the initial investigation stages of the complaints process,
there should be no assumptions about where, if anywhere,
fault lies. Disciplinary action might be required at some stage,
but there is insufficient detail here to decide whether this is the
case.
Answers
SBA 1 answer
d
The UK MEC categorization reflects the safety of contraception in women with medical conditions. It does not reflect
the effectiveness of contraception in women with medical
conditions.
SBA 6 answer
e
As the clinical director, you have responsibility to represent
the unit whether or not you were directly involved. The initial
investigation should have involved establishing the facts as
clearly as possible. The other steps outlined are all part of the
routine process of responding to patient concerns and
complaints.
SBA 2 answer
b
Combined hormonal contraception is associated with an
increased risk of VTE and its use presents an unacceptable
health risk to women who have had a previous VTE. The
copper IUD is a UK MEC category 1 for women with previous
VTE and the IUS, progestogen only implant, DMPA and pop
are all category 2. The progestogen only implant would,
therefore, be the safest and most effective method of contraception for women with a history of VTE. Women should be
advised of the high typical failure rate of male condoms (18%)
and should be encouraged to use LARC. The IUD/IUS can be
fitted without interruption to anticoagulants so long as INR is
stable and in the target range.
EMQ 7 answers
1. b
This presentation is likely to be vaginal candidiasis, for
which pessary treatment with clotrimazole is appropriate
2. a
This patient has Trichomonas and should be treated with
metronidazole
3. h
This presentation is likely to reflect vaginal dryness from
lack of oestrogen
EMQ 3 answers
1. d
This discharge is most likely to be physiological
2. a
This is appropriate treatment for symptomatic bacterial
vaginosis
3. d
Strep agalactiae is a normal commensal species in the
vagina
4. f
This is an appropriate regimen for treatment of bacterial
vaginosis during pregnancy
SBA 8 answer
c
Polycystic ovarian syndrome is a WHO type 2 cause of
anovulation, in which normal gonadotrophin levels would be
expected. The other options listed are all causes of hypogonadotrophic hypogonadism.
EMQ 9 answers
1. a
The diagnosis here is hyperprolactinaemic amenorrhoea.
The patient will also need an MRI head looking for evidence of
a pituitary adenoma
2. d
This patient is very likely to have PCOS. The first line of
management should be weight loss, which is successful in
restoring ovulation in many patients.
3. h
This patient should move to a second-line ovulation
induction therapy. Addind metformin to clomiphene might be
a possibility, but not metformin alone. In a patient with
extensive previous surgery and likely adhesions, laparoscopy
should be avoided if possible.
EMQ 4 answers
1. d
Trichomonas is a sexually transmitted disease, where
partner notification is required
2. c
This contrasts to Candida albicans, which is more likely to
cause a single episode of vaginal candidiasis
3. h
Ascending genital tract infection with Group A
streptococcus postpartum is a major cause of maternal sepsis
345
SELF-ASSESSMENT
SBA 10 answer
C
SBA 11 answer
B
Haemophilia A is inherited via an X-linked recessive gene in
about 70% of cases and does lead to lower levels of coagulation
factor VIII. Provided that the levels of factor VIII are >50 iu/dl
both epidural insertion and intramuscular injection are safe. This
can be achieved by infusing recombinant factor VIII. After infusion of factor VIII, where levels have been corrected to normal,
patients are at risk of thrombotic events like other postpartum
women and therefore may require thromboprophylaxis.
346