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VOL. 44 NO. 2
JOURNAL OF PAEDIATRICS,
OBSTETRICS & GYNAECOLOGY
GYNAECOLOGY
Endometriosis
Update
OBSTETRICS
Urogynaecological
Complications in
Pregnancy: An Overview
CME ARTICLE
Fertility Preservation
in Young Female Cancer
Patients
Formulir Berlangganan
H A R G AL
SPESIA !
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Editorial Board
CONFERENCE COVERAGE
Board Director, Paediatrics
Royal College of Obstetricians & Gynaecologists
Professor Pik-To Cheung
Associate Professor, Department of Paediatrics and Adolescent Medicine (RCOG) World Congress 2018, March 21-24,
The University of Hong Kong, Hong Kong
Singapore
Board Director, Obstetrics and Gynaecology
Professor Pak-Chung Ho
Director, Centre of Reproductive Medicine 45
The University of Hong Kong - Shenzhen Hospital, China
• Heavy menstrual bleeding tied
to high prevalence of bleeding
disorders
Professor Biran Affandi Professor Seng-Hock Quak
University of Indonesia, Indonesia National University of Singapore,
Professor Hextan
Singapore 46
Yuen-Sheung Ngan Adjunct Associate Professor
Tan Ah Moy • Isoxsuprine, nifedipine similarly
The University of Hong Kong, Hong Kong
KK Women’s and Children’s Hospital, effective in preventing preterm
Professor Kenneth Kwek Singapore
KK Women’s and Children’s Hospital, birth
Singapore Dr. Catherine Lynn Silao
University of the Philippines Manila,
Professor Kok Hian Tan
KK Women’s and Children’s Hospital,
Philippines 47
Dwiana Ocviyanti, MD, PhD
Singapore
University of Indonesia, Indonesia • Ferric carboxymaltose elevates
Professor Dato’
Dr. Karen Kar-Loen Chan Hb levels in women with iron
Dr. Ravindran Jegasothy
Dean Faculty of Medicine,
The University of Hong Kong, deficiency anaemia
Hong Kong
MAHSA University, Malaysia
Dr. Kwok-Yin Leung
Associate Professor Daisy Chan The University of Hong Kong,
Singapore General Hospital, Singapore Hong Kong
Associate Professor Raymond Dr. Mary Anne Chiong
Hang Wun Li University of the Philippines Manila,
The University of Hong Kong, Hong Kong
Adjunct Associate Professor
Philippines
Dr. Wing-Cheong Leung
JOURNAL WATCH
Kwong Wah Hospital, Hong Kong,
Ng Kee Chong Hong Kong
Division of Medicine & Academic Clinical
Program (Paediatrics), c/o KK Women’s and
Children’s Hospital, Singapore
48
• Fast food tied to infertility in women
• Hypothyroidism after TKIs in women with cancer may
help boost survival
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MIMS JPOG 2018 VOL. 44 NO. 2 iii
REVIEW ARTICLE
PAEDIATRICS
CEO Yasunobu Sakai
Managing Editor Elvira Manzano
Medical Editor Elaine Soliven
Designer Sam Shum
49
Production Tetsuya Hamaki, Agnes Chieng, Raymond Choo
Circulation Christine Chok Chronic Arthritis in Children and Young People
Accounting Manager Minty Kwan
Advertising Coordinator Pannica Goh
Arthritis affects 1 in 1,000 children and
young people (CYP), and is a major
Published by: cause of potential morbidity, with
MIMS (Hong Kong) Limited
27th Floor, OTB Building, 160 Gloucester Road, Wan Chai, Hong Kong significant long-term consequences,
Tel: (852) 2559 5888 | Email: enquiry@mimsjpog.com
joint damage, and disability if left
untreated. Diagnosing juvenile idiopathic
arthritis (JIA) can be challenging, and
relies on clinical assessment. Investigations are helpful to exclude
Enquiries and Correspondence other conditions, but are often normal in JIA at presentation. The
China Philippines
history can be vague, and the child may be too young to verbalize
Yang Xuan Rowena Belgica symptoms, detailed probing for inflammatory symptoms, and
Tel: (86 21) 6157 3888 Tel: (63 2) 886 0333
Email: enquiry.cn@mims.com Email: enquiry.ph@mims.com a comprehensive examination of the child’s joints are therefore
Hong Kong Singapore essential.
Jacqueline Cheung Josephine Cheong, Carrie Ong, Michael Hughes, Ruth Wyllie, Helen Foster
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60
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Indonesia Email: enquiry.vn@mims.com
Fatmawati, Fransiska Simamora, Endometriosis is a common, chronic
Ruth Theresia, Sari Wiyanti
Tel: (62 21) 729 2662 condition that affects women of
Email: enquiry.id@mims.com childbearing age. It can significantly
Malaysia impact a woman’s quality of life, her
Tiffany Collar, Sumitra Pakry,
Sharon Ong, Wong Wen Dee fertility, and ability to work. Awareness
Tel: (60 3) 7623 8000 of the condition is increasing amongst
Email: enquiry.my@mims.com
the general population, with drives to
improve the services available to women. The National Institute
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iv MIMS JPOG 2018 VOL. 44 NO. 2
CONTINUING
MEDICAL EDUCATION
81
Fertility Preservation in Young Female
Cancer Patients 2 SKP
EMPOWERING
HEALTHCARE
COMMUNITIES
CONFERENCE COVERAGE MIMS JPOG 2018 VOL. 44 NO. 2 45
Royal College of Obstetricians & Gynaecologists (RCOG) World Congress 2018, March 21-24,
Singapore – Elaine Soliven reports
Heavy menstrual bleeding Using data from the Queensland PAG lence in this study is consistent with the
tied to high prevalence of Service between July 2007 and 2017, the literature,” O’Brien noted.
bleeding disorders researchers retrospectively analysed 124 Among HMB patients with bleeding
disorder, results showed that VWD was
the most common type of bleeding dis-
order, mainly type 1 VWD at 30 percent
and low VWD at 22 percent, followed by
other inherited platelet disorder at 19
percent, dense body deficiency at 15
percent, thrombocytopenia at 11 per-
cent, and factor deficiency at 3 percent.
Of the 49.5 percent (n=53) patients
diagnosed with iron deficiency and/or
anaemia, a 70 percent higher incidence
of bleeding disorder was noted. Two of
the patients with bleeding disorder had
a blood transfusion due to HMB-related
episodes.
O’Brien recommended that “se-
vere bleeding episodes may benefit
from directed therapies, such as desm-
opressin or clotting factor concentrates,
and these agents may be valuable in
perioperative prophylaxis and treatment
of surgical and obstetric haemorrhage,”
Bleeding disorders, such as Von Wille- adolescents with HMB (average age 14 but highlighted that these should be
brand disease (VWD), platelet function years and 3 months), of whom 62.1 per- prescribed under the supervision of the
disorder (PFD), thrombocytopenia, and cent (n=77) were screened for bleeding treating haematologist depending on
clotting factor deficiencies, are more prev- disorder and 86.3 percent (n=107) un- the condition.
alent among adolescent girls with heavy derwent an iron deficiency and/or anae- “A higher level of awareness of these
menstrual bleeding (HMB), according to mia screening. [RCOG 2018, abstract conditions, especially VWD and PFD, is
a study presented at RCOG 2018. KO6055] needed, and close collaboration between
“It is important to identify bleeding Overall, a 35 percent prevalence gynaecologists and haematologists in a
disorders in the adolescent female pop- of bleeding disorder was observed in specialised tertiary centre should be es-
ulation because the obstetric and gy- patients with HMB, and treated with tablished in the management of these
naecologic morbidity goes beyond trou- hormonal therapies (n=96 percent), patients. Accurate and early recognition
blesome heavy periods … [as] they are tranexamic acid (n=87 percent), iron of bleeding disorders in the adolescent
at increased risk of surgical and obstet- therapy (n=70 percent), and combined is critical for the management of bleeding
ric haemorrhage,” according to study oral contraceptive pill (n=61 percent). complications and optimization of therapy
lead author Dr Brooke O’Brien from the “HMB is a common gynaecologi- for HMB,” she added.
Queensland Paediatric and Adolescent cal complaint among adolescents … A
Dr Brooke O’Brien, et al, Royal College of Obstetricians &
Gynaecology (PAG) Service at the Chil- significant proportion of adolescent girls Gynaecologists (RCOG) World Congress 2018, March 21-24,
Singapore [abstract KO6055].
dren’s Health Queensland Hospital and with HMB referred to a PAG clinic will
Health Service, Brisbane, Australia. have a bleeding disorder, and the preva-
46 MIMS JPOG 2018 VOL. 44 NO. 2 CONFERENCE COVERAGE
Royal College of Obstetricians & Gynaecologists (RCOG) World Congress 2018, March 21-24,
Singapore – Elaine Soliven reports
Isoxsuprine, nifedipine Gynecology at Far Eastern University – delivery within 48 hours from initiation of
similarly effective in Dr Nicanor Reyes Medical Foundation, treatment and before 37 weeks age of
preventing preterm birth Quezon City, Philippines. gestation. The delay in delivery has led
to significant improvements in clinically
important neonatal outcomes such as
the Apgar and Ballard’s score for both
agents,” Garcia-Ramos said.
The researchers found no signif-
icant difference in the Apgar scores
for 1 minute (8.6 vs 8.6; p=0.84)
and 5 minutes (9.7 vs 9.7; p=0.75),
which were usually expected from ne-
onates born at >34 weeks. Ballard’s
score (35.2 vs 35.5 weeks; p=0.32)
and birthweight (2,212.6 vs 2,159.8
grams; p=0.49) were also similar
between the infants whose mothers
were treated with isoxsuprine vs with
nifedipine.
Neonatal morbidities were higher
among infants whose mothers received
nifedipine vs isoxsuprine (14.1 percent
vs 9.8 percent), although the difference
was not statistically significant.
“We noted the associated mor-
Treatment with the tocolytic agents isox- The researchers retrospectively bidities with prematurity such as sep-
suprine or nifedipine was similarly ef- analysed 206 women (mean age 29 sis, neonatal pneumonia, and transient
fective in delaying delivery by 2 weeks years) presenting with preterm labour tachypnoea of the newborn to occur
among women who were admitted for (defined as labour occurring between among the neonates of the cases who
preterm labour, according to a study pre- 28 and 36 weeks of gestation) who were delivered at 33 weeks and below,” said
sented at RCOG 2018. given isoxsuprine (n=142) or nifedipine the researchers.
“The ideal tocolytic agent should (n=64). Majority of the participants were However, a significantly higher in-
be myometrium-specific, easy to admin- admitted to the hospital during their cidence of tachycardia was observed
ister, inexpensive, effective in prevent- 32nd week of pregnancy. [RCOG 2018, in women treated with isoxsuprine vs
ing preterm birth, and improve neona- abstract 5638] nifedipine (10 percent vs 0 percent;
tal outcomes, with few maternal, foetal, Both nifedipine and isoxsuprine ex- p=0.03). “With regards to adverse
and neonatal side effects … The World tended pregnancy by 2 weeks in aver- effects, nifedipine was found to be a
Health Organization also stated that age (range 0–7 weeks), and there was favourable choice ... Thus, we can re-
three-quarters of neonates born pre- no significant difference between the port that nifedipine can be better tol-
maturely could be saved with current, two treatment groups (mean gestation- erated than isoxsuprine,” noted Gar-
cost-effective interventions, even with- al age at delivery, 34.8 vs 34.9 weeks; cia-Ramos.
out intensive care facilities,” said lead p=0.67). “Nifedipine is equally efficacious
author Dr Dhanielle E. Garcia-Ramos “Both nifedipine and isoxsuprine as isoxsuprine in preventing preterm
from the Department of Obstetrics and were comparable in reducing the risk of birth with better maternal tolerabili-
CONFERENCE
JOURNAL WATCH
COVERAGE
PEER REVIEWED MIMS JPOG 2018 VOL. 44 NO. 2 47
Royal College of Obstetricians & Gynaecologists (RCOG) World Congress 2018, March 21-24,
Singapore – Elaine Soliven reports
ty. Therefore, this may result in better rum ferritin levels (147.70 vs 98.03 µg/L; lower incidence and severity of throm-
compliance to tocolytic therapy which p=0.001). bophlebitis was observed in women
can contribute to a successful out- In addition, mean corpuscular hae- treated with ISC.
come,” Garcia-Ramos added, who moglobin values were also higher among “Intravenous FCM is more effec-
suggested that future research should women on FCM compared with ISC at 28 tive and safer … [for] the treatment
include women with comorbidities, and days (33.02 vs 29.32 pg; p=0.001). of IDA in women,” said lead author Dr
those at higher risk of preterm labour More women treated with FCM Garima Chaudhry from the Department
such as those diagnosed with multiple achieved a normal mean corpuscular of Obstetrics and Gynaecology at Lady
gestations and premature rupture of volume (≥80.00 fL) compared with those Hardinge Medical College, West Delhi,
membranes. treated with ISC (100 percent, increase Delhi, India.
from 70.14 to 84.35 fL vs 43.33 percent, “The molecular structure of FCM
Dr Dhanielle E. Garcia-Ramos, et al, Royal College of Obstetri-
cians & Gynaecologists (RCOG) World Congress 2018, March increase from 69.94 fL to 78.91 percent) ensures controlled delivery of iron
21-24, Singapore [abstract 5638].
at 28 days of follow-up. within cells of reticuloendothelial sys-
Ferric carboxymaltose
elevates Hb levels in women
with iron deficiency anaemia
Intravenous infusions of ferric carbox-
ymaltose (FCM) may increase haemo-
globin (Hb) levels in women with iron
deficiency anaemia (IDA), according
to a study presented at RCOG 2018.
Sixty women with IDA (aged >18
years, Hb level 6–8 g/dL, serum ferritin
level <15 ng/mL) were randomized in a
1:1 ratio to receive FCM (two infusions
of 500 mg) or iron sucrose complex
(ISC; five infusions of 200 mg) intra-
venously for 2 weeks. IDA was deter-
mined in patients using microcytic hy-
pochromic peripheral smear or by low
serum ferritin levels, while the Ganzoni
formula was used to calculate iron defi-
cit. Patients were followed up every 7,
14, 21, and 28 days. [RCOG 2018, ab- The increase in aspartate transam- tem and subsequent delivery to the
stract 5808] inase and alanine transaminase levels iron binding proteins ferritin and trans-
At 28 days follow-up, Hb levels was comparable between the FCM and ferrin, with minimal risk of release of
increased by 3.17 g/dL from baseline ISC treatment groups. large amounts of ionic iron in the se-
among patients in the FCM treatment Most women in the ISC treatment rum,” Chaudhry noted.
arm (n=19). group had at least one adverse event.
Dr Garima Chaudhry, et al, Royal College of Obstetricians &
Compared with women given ISC, There was a higher incidence of head- Gynaecologists (RCOG) World Congress 2018, March 21-
24, Singapore [abstract 5808].
those who received FCM had higher Hb ache and dizziness among women
(10.14 vs 8.88 g/dL; p=0.001) and se- treated with FCM and a significantly
48 MIMS JPOG 2018 VOL. 44 NO. 2 JOURNAL WATCH PEER REVIEWED
percent in those with the lowest fruit intake Harvard Medical School, Boston, Mas-
O vs 8 percent in those with the highest con- sachusetts, US.
sumption. The study involved 538 adult patients
Obstetrics Absolute differences between the with advanced non-thyroidal cancer who
lowest and highest categories of intake were treated with TKIs (axitinib, pazopanib,
for fruit and fast food were in the order of regorafenib, sorafenib, sunitinib, or vande-
Fast food tied to infertility
0.6–0.9 months for time to pregnancy and tanib) between 2007 and 2017 and had
in women
4–8 percent for infertility. data available on thyroid function testing.
Women who eat a lot of fast food may The study had a few caveats – first it Their cancers were either renal cell car-
take longer to become pregnant and was not designed to prove how the amount cinoma, gastrointestinal stromal tumour,
be more likely to experience infertility, a of fruit or fast food women consume might hepatocellular carcinoma, neuroendocrine
study has shown. impact their fertility. Second, the research- tumour, sarcoma, or primary central nerv-
In the study of almost 6,000 typical- ers relied on dietary questionnaires com- ous system tumour.
ly overweight women in Australia, New pleted by women during their prenatal Overall, 40 percent of patients de-
Zealand, and the UK, those who ate fast visits. Nonetheless, the study offers new veloped hypothyroidism, 13 percent of
food four or more times a week before they evidence on the role of diet in conception.” which had subclinical hypothyroidism
conceived took a longer time to become (thyroid-stimulating hormone (TSH) level,
Grieger JA, et al. Pre-pregnancy fast food and fruit intake is
pregnant by a month vs those who avoid- associated with time to pregnancy. Hum Reprod 2018;doi. 5–10 mIU/L, or a higher TSH if free thyrox-
org/10.1093/humrep/dey079.
ed fast food. ine levels were normal) and 27 percent had
Overall, 2,204 women (39 percent) overt hypothyroidism (TSH >10 mIU/L,
conceived within 1 month of copulation low free thyroxine, or needing hormone
and 468 (8 percent) failed to conceive af- replacement).
ter a year of trying. Women who rarely or G Patients with overt hypothyroidism
never ate fast food had an 8 percent risk had significantly longer median OS of
of infertility vs 16 percent in those who ate 1,643 days vs patients with subclinical
fast food four times weekly. Gynaecology hypothyroidism (1,005 days) and those
“Fast foods contain high amounts with no thyroid dysfunction (685 days;
of saturated fat, sodium, and sometimes Hypothyroidism after TKIs p<0.0001). The association between overt
sugar,” said lead study author Dr Jessi- in women with cancer may hypothyroidism and OS persisted despite
ca Grieger from the Robinson Research adjustment for age, sex, race, cancer type,
help boost survival
Institute at The University of Adelaide in stage, ECOG performance status (a meas-
Australia. She added that although these Hypothyroidism that occurs following treat- ure of functional status), and checkpoint
dietary components and their relationship ment with tyrosine kinase inhibitors (TKIs) inhibitor therapy (p<0.0001).
to fertility has not been studied extensive- in women with cancer is associated with TKI exposure time did not significantly
ly in human pregnancies, higher amounts significantly improved overall survival (OS) differ between patients who did and did not
of saturated fatty acids were identified in and may have important prognostic value, develop hypothyroidism. Of note, there was
oocytes of women undergoing assisted a retrospective cohort study has shown. also no association between hypothyroid-
reproduction. “Hence, we believe that fast The message from this study is ism risk and the number of TKIs received.
food may be one factor mediating infertility that clinicians should not hesitate to “Again, these data provide additional
through altered ovarian function.” give serial TKIs due to concern for de- evidence to support continuation of TKIs in
When they looked at how often these velopment of thyroid dysfunction, as it is the face of hypothyroidism, which can be
women ate fruits, they found that those readily treatable with hormone replace- easily treated,” concluded Lechner.
who consumed fruits less than once a ment and may correlate with improved Lechner MG, et al. Hypothyroidism during tyrosine kinase
inhibitor therapy is associated with longer survival in pa-
month took half a month longer to con- OS, said study author Dr Melissa Lech- tients with advanced nonthyroidal cancers. Thyroid 2018; doi
org/10.1089/thy.2017.0587.
ceive vs those who ate at least three fruit ner from the Department of Medicine,
servings a day. The risk of infertility was 12 Brigham and Women's Hospital and
PAEDIATRICS PEER REVIEWED MIMS JPOG 2018 VOL. 44 NO. 2 49
Arthritis affects 1 in 1,000 children and young people (CYP), and is a major cause
of potential morbidity, with significant long-term consequences, joint damage,
and disability if left untreated. Diagnosing juvenile idiopathic arthritis (JIA) can be
challenging, and relies on clinical assessment. Investigations are helpful to exclude
other conditions, but are often normal in JIA at presentation. The history can be
vague, and the child may be too young to verbalize symptoms, detailed probing
for inflammatory symptoms, and a comprehensive examination of the child’s
joints are therefore essential. If JIA is suspected, early referral to specialist teams
facilitates prompt treatment and prevention of complications. The emergence
of novel and biologic agents, as well as earlier and more aggressive treatment,
has helped to optimize clinical outcomes and dramatically changed the way that
JIA has been managed over the last 15 years. The approach to management is
multidisciplinary, which includes close liaison with other specialists and primary
healthcare teams, and education and support for the family. Adolescence is a time
of physical, psychological, and emotional change, and the multidisciplinary team is
fundamental in helping adolescents cope with the implications of a chronic disease,
often complex treatment regimens, and transitional care into the adult world.
50 MIMS JPOG 2018 VOL. 44 NO. 2 PAEDIATRICS PEER REVIEWED
stiffness and pain, and parents may notice that Table 2. Differential Diagnosis of Joint Pain in Children
their child is “slow to get going in the morning”
or experiences stiffness after periods of rest,
Life-threatening conditions
such as after long car rides – this is known as
• Malignancy (leukaemia, lymphoma, neuroblastoma, and bone tumour)
“gelling”. Parents may also notice that joints ap-
pear swollen, but this can be subtle and easily • Sepsis (septic arthritis and osteomyelitis)
overlooked. Mechanical joint pain, in contrast, • Non-accidental injury
typically worsens with physical activity, and Joint pain with no joint swelling
swelling is uncommon and often transient. The • Hypermobility syndromes (patients sometimes report transient
presence of “red flags”, such as weight loss, fe- swelling)
ver, night pain, and bone tenderness, suggests • Complex regional pain syndromes (localized or widespread)
infection or malignancy that warrants urgent as- • Orthopaedic syndromes (eg, slipped upper femoral epiphysis and
sessment in secondary care. Perthes disease)
• Metabolic (eg, hypothyroidism and lysosomal storage diseases)
Examination Joint pain with joint swelling
The pGALS musculoskeletal examination (Fig- • JIA
ure 1) is quick and easy to perform with sim-
• Trauma
ple manoeuvres often used in clinical practice,
• Infection
and has been validated in the school-aged child
with excellent sensitivity and specificity.2 Free ° Septic arthritis and osteomyelitis (viral, bacterial [including
Lyme disease], and mycobacterial)
educational resources to demonstrate pGALS
° Reactive arthritis (postenteric and sexually acquired)
are available (see www.pmmonline.org/doctor/
° Infection-related (rheumatic fever and vaccination-related)
approach-to-clinical-assessment/examination),
• Inflammatory bowel disease (Crohn’s disease and ulcerative colitis)
as well as a pGALS app, with language trans-
lations. The pGALS is acceptable in acute pae-
• Autoimmune rheumatic disease (systemic lupus erythematosus,
scleroderma, and dermatomyositis)
diatric settings, an effective way to assess all
• Sarcoidosis
joints, and useful in the context of vague pres-
• Metabolic (eg, osteomalacia [rickets], cystic fibrosis, and
entations such as leg pains or limp. mucopolysaccharidoses)
Abnormalities on pGALS examination can
• Haematological (haemophilia and haemoglobinopathy)
be followed with more detailed joint examina-
• Tumour (benign/malignant)
tion such as the paediatric Regional Examina-
• Developmental/congenital (eg, spondyloepiphyseal dysplasia)
tion of the Musculoskeletal System, which is
based on the “look, feel, move, function, and
measure” approach. Joint swelling caused by
effusion or synovitis is the most reliable physi- drugs. Blood tests and radiographs are initially
cal sign of JIA, but can be subtle in very young often normal in JIA and can provide false re-
children, and difficult to assess in joints such assurance at the time of presentation. If there
as the hip, shoulder, and ankle, especially if is clinical concern of suspected rheumatic
changes are symmetrical. disease, referral to a paediatric rheumatology
team for a specialist assessment should not be
Investigation delayed.
Laboratory tests are not diagnostic in JIA, but Raised acute-phase reactants (erythrocyte
help to exclude other diagnoses and are used sedimentation rate, serum C-reactive protein)
by specialist teams to monitor disease activity and a high serum ferritin concentration can be
and the adverse effects of immunosuppressive present in active systemic-onset JIA. However,
52 MIMS JPOG 2018 VOL. 44 NO. 2 PAEDIATRICS PEER REVIEWED
Questions
• Do you (or does your child) have any pain or stiffness in your (their) joints, muscles or back?
• Do you (or does your child) have any difficulty getting yourself (him/herself) dressed without any help?
Or lifting an object above shoulder level?
• Do you (or does your child) have any problem going up and down steps? Or being able to squat?
Figure Manoeuvres What is being assessed?
Observe the child standing Posture, habitus, skin rashes
(from front, back, and sides) Deformity (leg length inequality, alignment, scoliosis, joint
swelling, muscle wasting, and flat feet)
Observe the child walking, turning, Feet, ankles, subtalar, midtarsal, and small joints of feet and
and returning then toes
“Walk on your tip-toes” then Foot posture (check medial longitudinal arch when on tip
“Walk on your heels” toes)
Feel for effusion at the knee Knee effusion (small effusion may be missed by patellar tap
(patellar tap or cross fluctuation) alone
Passive movement (full flexion and Hip flexion and internal rotation
internal rotation of hip)
“Try and touch your shoulder with Cervical spine lateral flexion
your ear”
Figure 1. The pGALS assessment. This material is reproduced from the pGALS app, which is freely available and developed by Professor
Helen Foster at Newcastle University, UK. Further information about pGALS, including video demonstrations, is available at Paediatric
Musculoskeletal Matters (http://www.pmmonline.org) (see Further Reading). All figures reproduced with permission from Professor Helen
Foster, Newcastle University, UK.
54 MIMS JPOG 2018 VOL. 44 NO. 2 PAEDIATRICS PEER REVIEWED
Table 4. Cytokine Modulators Currently in use for the Treatment of Severe JIA
Generic name Mechanism of action Route of administration Important issues for the child
taking cytokine modulators
(apply to all cytokine modulators)
Etanercept TNF-α soluble receptor that binds to Subcutaneous injection twice a Avoid all live vaccines
circulating TNF and competes with week Promote annual flu vaccine
membrane receptor Promote pneumococcal
immunization (current advice
5-yearly)
Vigilance regarding infections
Infliximab Human–murine chimaera antibody Intravenous infusion (eg, varicella and shingles,
that neutralizes TNF-α Various regimens, initially every 2 opportunistic infections such as
weeks and then every 4–8 weeks listeriosis)
Adalimumab Fully human monoclonal antibody Subcutaneous injection Advice regarding travel abroad
that neutralizes TNF-α fortnightly with medicines and travel
insurance
Anakinra IL-1 receptor antagonist Subcutaneous injection daily Advice that signs of serious
Tocilizumab IL-6 receptor antagonist Intravenous infusion fortnightly infection and sepsis can be
or monthly altered or reduced with systemic
immunosuppression
Abatacept CTLA4-antagonist to block T-cell Monthly infusion
and B-cell interaction and initiation
of the proinflammatory pathway
Abbreviations: IL = interleukin; TNF = tumour necrosis factor
cant proportion of patients develop classical Transition into the adult world
ankylosing spondylitis as adults and are at risk JIA is clinically diverse, and although many
of acute symptomatic anterior uveitis (ie, pain- young people achieve remission (either on or
ful red eye). Joint injections and methotrexate off treatment), at least 30% need continuing
are useful to treat the peripheral arthritis, and treatment into their adult years. The literature
biologics are used for those failing to respond reports significant morbidity in adults with JIA
adequately. from sequelae of previous inflammation, includ-
Polyarticular JIA (20% of cases) presents ing joint damage requiring joint replacement
with symmetrical involvement of small and large or visual impairment from uveitis, cardiovascu-
joints. In adolescent girls, polyarticular JIA often lar disease, and osteoporosis. However, most
follows a course similar to that of adult rheuma- reports relate to clinical outcomes before the
toid arthritis, with positive RF, skin nodules, ero- introduction of methotrexate and biologic ther-
sive arthritis, and an association with HLA-DR4. apies. Furthermore, there is considerable psy-
Early introduction of methotrexate, often given chosocial morbidity, including unemployment,
parenterally, is recommended, and prognosis is despite good educational achievement.
variable. Many patients require biologics, often Improved medical management of JIA has
in combination with methotrexate. markedly changed the prospects for young
Systemic-onset JIA is the least common people with JIA. Many patients transferring to
subtype of JIA (10% of cases) but carries the adult care nowadays can expect to have good
worst prognosis. One-third of children devel- disease control, although they are likely to be
op severe polyarthritis, and the disease carries taking complex treatment regimens including
significant mortality from complications, such as biologics and methotrexate. There is a mark-
carditis, macrophage activation, and sepsis, with edly reduced need for orthopaedic interven-
infection risk being compounded by system- tion, which if needed is invariably deferred un-
ic immunosuppression. Systemic-onset JIA is til maximum growth has been attained. Such
characterized by an acute illness with daily (quo- surgery can be technically challenging (eg,
tidian) fever, maculopapular rash (Figure 3), se- intubation can be difficult with cervical spine
rositis, lymphadenopathy, hepatosplenomegaly, disease, temporomandibular joint disease,
and high acute-phase reactant and serum ferritin and osteoporosis).
concentrations. Systemic features can predate Adolescence is a challenging time of phys-
the arthritis by several weeks, and the differen- ical, psychological, and emotional changes.
tial diagnosis includes infection and malignancy Thus, young people with JIA need support
(eg, leukaemia and neuroblastoma). to cope with the complexities of their chronic
Treatment includes aggressive use of cor- disease at a time when they are planning their
ticosteroids (often given intravenously during future, developing relationships, and taking on
the acute systemic illness), high-dose parenter- responsibility to achieve independence away
al methotrexate, and biologic therapy. Tumour from the family unit. Young people with a chron-
necrosis factor (TNF)-α inhibitors appear to be ic disease cope in different ways, and disen-
less effective in systemic JIA than other types gagement with healthcare teams can have pro-
of JIA, and some of the newer agents, such as found adverse impact on healthcare outcomes.
anakinra (an interleukin [IL] receptor antago- Uncontrolled JIA can delay puberty and the ad-
nist) and tocilizumab (an IL-6 receptor antago- olescent growth spurt. Medications can cause
nist), have better efficacy. A minority of patients adverse effects, which can affect self-esteem
with refractory disease can also be considered and body image, for example, corticosteroids
for autologous haemopoietic stem-cell rescue. can worsen acne and growth retardation. Meth-
PAEDIATRICS PEER REVIEWED MIMS JPOG 2018 VOL. 44 NO. 2 59
Endometriosis Update
Susannah Hogg, MRCOG MBChB BSc(Hons); Sanjay Vyas, MD FRCOG
Table 2. NICE Guidance for Suspecting Endometriosis cosa or cervix on speculum examination. An en-
dometrioma may be detected through palpation
of a tender, adnexal mass. Features consistent
Presenting symptoms of endometriosis with deep endometriosis warrant direct referral to
• Chronic pelvic pain a specialist endometriosis service.
• Period-related pain affecting daily activities
DIAGNOSIS
• Deep pain during or after intercourse
• P
eriod-related/cyclical gastrointestinal symptoms, or painful bowel Still the gold standard?
movements
A diagnostic laparoscopy remains the leading in-
• Period-related/cyclical urinary symptoms or haematuria vestigation to confirm a diagnosis of endometrio-
• Infertility in association with one or more of the above sis. A systematic approach should be favoured,
with inspection of the ovaries, tubes, ovarian
fossae, uterosacral ligaments, Pouch of Doug-
las (POD), uterovesical fold, rectosigmoid, and
for young women having laparoscopic evaluation appendix. Adhesions and pelvic mobility should
in their teens, when the disease may not yet be be noted. The operation report should describe
fully expressed. the size, macroscopic appearance, location, and
It has been reported that more than 50% depth of infiltration for all lesions. Images should
of patients with deep infiltrating endometriosis be available to facilitate optimal record keeping
(DIE) present with associated symptoms of dy- and patient education, especially if referral to a
schezia and dysuria. Up to 20% of women with specialist endometriosis service is anticipated.
endometriosis have concurrent irritable bowel Biopsies can be considered during diagnostic
syndrome, interstitial cystitis, and migraines. The procedures, but negative histology does not ex-
use of a pain diary can be a useful adjunct to un- clude endometriosis. Specialist experience is key
derstanding the impact of symptoms. Given the in ensuring a correct diagnosis of endometriosis
genetic basis of endometriosis, a family history is being made from visual inspection alone, with
should also be explored. Taking a targeted histo- reported sensitivity of 94–97% and specificity of
ry is imperative, and NICE advice that endometri- 77–85%.
osis should be suspected in women presenting There are no clinically useful serum markers
with one or more of the symptoms in Table 2. to diagnose or monitor disease activity in endo-
metriosis. While CA125 can be raised in severe
Knowing the signs disease, it lacks sensitivity and is not routinely
An abdominal and pelvic examination should rou- used. Peritoneal markers have been proposed,
tinely be offered to women where endometriosis but these are subject to cyclical variations and
is a differential. While many cases of mild disease none yet exist with enough specificity to corre-
may be associated with a paucity of findings, there late with endometriosis alone. There is no cur-
are subtle signs associated with deeper disease rent evidence to indicate whether endometriosis
which should be identified. These include uterine is progressive in all cases or can remain stable
motion tenderness, a retroverted uterus, reduced over time.
organ mobility, tender nodules in the posterior for-
nix, or palpable thickening of the uterosacral liga- More than meets the eye
ments. The cervix can also be laterally displaced The appearances of endometriotic implants are
if there is unilateral uterosacral thickening. Occa- highly variable. Superficial disease may be easy
sionally, lesions may be visible in the vaginal mu- to identify with the classical appearances of pow-
GYNAECOLOGY PEER REVIEWED MIMS JPOG 2018 VOL. 44 NO. 2 63
looked. Women should receive, or be signposted anticipated duration of treatment and cost-effec-
towards, up-to-date information on endometrio- tiveness will influence the decision. The options
sis. It may be appropriate to recommend local or include the combined pill, progesterone only
national support groups for those with confirmed pill, Mirena coil, and gonadotropin-releasing
disease, particularly in the context of infertility. For hormone (GnRH) agonist ± add back hormone
those with severe disease, the specialist endome- replacement therapy.
triosis nurse can offer vital support pre- and post- Medical therapy with oral contraceptives
operatively, as well as providing expertise in the and progestins enables satisfactory pain con-
psychosocial impacts of the condition. trol in 60% of women. Norethisterone acetate
The pain management service, which in- and Dienogest are the progestins with greatest
cludes specialist anaesthetists and clinical evidence supporting their use. Norethisterone
psychologists, can be a valuable resource for is partly metabolised to ethinylestradiol, mean-
women experiencing chronic pain that is resist- ing there are fewer side effects from oestrogen
ant to medical or surgical therapies. Pain path- deficiency. Use of the Mirena coil after postoper-
ways and pain perceptions, activated over years ative treatment of endometriosis has been eval-
through chronic pain, can be incredibly complex uated in several randomized controlled trials. At
and will often require alternative modes of treat- 1-year follow-up, most trials found use of a Mire-
ment. Negative pain cognition can impair quality na coil resulted in significant improvements in
of life scores and influence postoperative pain pain scores for pelvic pain and dysmenorrhoea
scores. The commencement of pain modulat- compared with pre-treatment testing or expect-
ing medications, transcutaneous electrical nerve ant management. It had no significant effect on
stimulation (TENS), acupuncture, nerve blocks, dyspareunia pain scores. It has also been shown
and cognitive behavioural therapy (CBT) are that surgical excision, combined with postoper-
all potential treatment options. Women should ative hormones, leads to reduction in symptom
be reassured that referral to pain management recurrence compared with the use of hormones
services is a well-recognised, and beneficial, or surgical excision alone.
component of endometriosis management, not Medical treatment is also thought to reduce
a side step or undermining of their symptoms. stimulation of pain fibres leading to decreased
intra- and perilesion inflammation and production
MEDICAL MANAGEMENT – NOT TO of prostaglandins/cytokines. However, in cases of
BE OVERLOOKED DIE, medical therapy is less effective. It partially
Medical management involves the use of hor- treats the lesion, but not the surrounding fibrosis,
mones to achieve a state of amenorrhoea, there- which contributes to higher pain scores and bow-
by providing pain relief. It can be used successful- el symptoms.
ly as a long-term strategy in young women, those
with superficial disease and low pain scores, as IMAGING
an interim measure between pregnancies or while
awaiting surgery, or as an adjunct to postopera- The role of ultrasound
tive management. Symptom recurrence may Transvaginal ultrasound scan (TVUS) is the prima-
occur when treatments are discontinued, and pa- ry imaging technique for evaluating endometriosis
tients should be advised that this does not repre- due to its availability and cost effectiveness. This
sent an ineffective treatment. may detect the presence of an endometrioma,
No single medical treatment outperforms typically appearing as a unilocular, thick-walled,
another in its ability to improve pain scores. and homogenous cyst with low level echogenic-
Consideration of symptoms, side-effect profiles, ity (“ground glass” appearance). There may be
GYNAECOLOGY PEER REVIEWED MIMS JPOG 2018 VOL. 44 NO. 2 65
fluid levels, septations, and calcifications. Use of reported accuracy of 98% in identifying bladder
power doppler can demonstrate absent flow with- endometriosis. Such endometriotic implants
in the cyst and scant vascularisation of the cyst may be confined to the bladder serosa, but can
wall, differentiating it from other types of ovarian invade detrusor muscle and bladder lumen. MRI
cyst. Endometriomas are often associated with confers similar benefits in identification of recto-
adhesions, and application of pressure with the sigmoid disease and can determine the depth
vaginal probe can cause adnexal tenderness. of bowel wall infiltration, length of affected area,
Bilateral endometriomas may appear as “kissing and distance of the lesion from the anus.
ovaries” as they often adhere to one another in
the midline. SURGICAL MANAGEMENT
While ultrasound lacks adequate resolu-
tion to identify superficial peritoneal implants, Who is suitable?
it can detect extra-ovarian endometriosis. The While medical management can offer excellent
uterosacral ligaments, usually barely detecta- short-term pain relief, the presence of ongoing
ble at ultrasound, may appear as stellate hypo- endometriotic lesions, or DIE, mean that symp-
echoic nodules located near the uterine cervix toms can worsen or recur over time. Laparoscop-
if they contain infiltrating endometriosis. Hae- ic excision of these lesions is the most effective
matosalpinx, identified as low-level echoes in a long-term management. In fact, there is much ev-
dilated fallopian tube, may be an isolated ultra- idence that surgery reduces pain associated with
sound finding in a patient with endometriosis. endometriosis in all stages of the disease. Howev-
TVUS has been shown to be more accurate than er, in cases of superficial peritoneal disease only,
transabdominal ultrasound in detecting endo- it is important to consider hormonal treatments
metriotic bladder nodules and remains the first first line, as potential benefits of excision must be
line of investigation in patients with suspected balanced against surgical risks and adhesions
bowel endometriosis. Transrectal ultrasound formation.
can be utilised, but is not considered superior With advances in laparoscopic equipment
to TVUS. The overall accuracy of ultrasound in and techniques, even the most complex cases
evaluating endometriosis has improved in recent can be carried out safely and effectively. It is
years but the severity, and sites, of endometri- imperative that women are counselled preop-
osis identified remains dependent on levels of eratively about their surgery, with emphasis on
ultrasound expertise. potential complications to urinary tract, bowel,
blood vessels, and other viscera, along with av-
Magnetic resonance imaging erage symptom improvement of 60%. Discus-
Magnetic resonance imaging (MRI) should not sion should also include the potential impact of
be utilised as a primary investigation to diagnose the proposed surgery on future fertility and im-
endometriosis. However, it is a useful adjunct in pact on ovarian reserve. Bowel preparation and
diagnosing endometriomas and helpful in dis- the need for joint procedures with colorectal/uro-
tinguishing them from haemorrhagic cysts and logical teams should be anticipated in advance.
dermoids. Endometriomas typically present as Complication rates in specialised centres are re-
solitary, thick-walled masses with homogenous, ported as 2–4% in the immediate postoperative
hyperintense T1 signal intensity, and low T2 sig- period, with rate of serious complications being
nal intensity, reflecting the haemoconcentration of 7–9%. Estimated symptom recurrence is 8–13%.
the cyst. Surgery is not clinically indicated for all
MRI is also excellent in assessing the ex- women. In teenagers, early surgical excision is
tent of deep infiltrating endometriosis. MRI has not recommended as the disease may not be
66 MIMS JPOG 2018 VOL. 44 NO. 2 GYNAECOLOGY PEER REVIEWED
Uterus
Bowel
Bowel lesions occur in 3–37% of cases, with
the majority affecting the sigmoid, rectum, or Figure 4. Endometriotic bladder nodule
rectosigmoid junction. The main symptom is adherent to uterus.
pelvic pain radiating into the rectum and anus,
rather than bowel dysfunction. Management of define the rectosigmoid junction and ensure that
bowel endometriosis may be radical, involving there is no stenosis at the end of the procedure.
complete resection of endometriotic nodules to An underwater bowel test, using normal saline
prevent recurrence (Figure 3). A conservative in the pelvis and air introduced into the rectum
approach may be favoured, where risk of re- (via bladder syringe or sigmoidoscope) should
currence is balanced against risk of developing be performed to ensure patency. Prophylactic
functional bowel disorders. However, if lesions antibiotics are imperative due to the risk of en-
are multifocal, >3 cm in size, involve >50% of tering the bowel lumen. In the unlikely event that
bowel wall circumference, there is evidence of bowel endometriosis is an unexpected finding,
stenosis or sigmoid involvement, then a radical women should be brought back for a secondary
approach may be indicated. procedure.
Removal of bowel lesions should only oc-
cur at specialist centres. Patients should be ap- Urinary tract
propriately counselled and aware of the risk of Urinary tract endometriosis occurs in 1–2% of
colostomy. Preoperative bowel preparation may women and, of these, 85% occur in the bladder.
be needed. A rectal probe, or rigid sigmoido- The ureter is affected in 10% of cases, with kidney
scope, should be used during the procedure to and urethral lesions occurring in less than 5% of
68 MIMS JPOG 2018 VOL. 44 NO. 2 GYNAECOLOGY PEER REVIEWED
ovarian cortex, account for 30% of benign ovarian Table 3. Surgical Approaches to Endometriomas
cysts requiring surgery. Endometriomas involve
prolonged stretching of the ovarian cortex in
conjunction with the presence of proteolytic en-
Surgical Benefits Risks
approach
zymes and inflammatory molecules that can dif-
Drainage Does not require Higher recurrence rate.
fuse through the cyst wall and damage the pool specialist skill set.
of neighbouring primordial follicles. Morpholog- Less ovarian damage.
ically, the ovarian cortex of endometriomas has Diathermy Does not require Vascular injury/heat
been shown to be fundamentally altered, where- specialist skill set. damage to ovarian cortex.
as the cortex in teratomas and benign cystade- Higher recurrence rate.
nomas is not. Bilateral endometriomas are also Greater decline in ovarian
reserve.
associated with a reduced response to gonado-
trophins during assisted reproduction because Cystectomy Less recurrence. Loss of ovarian tissue.
of the loss of primordial follicles. Greatest improvement Impact on ovarian
in pain scores. reserve.
Improved spontaneous
To operate or not? conception rates.
The presence of endometriomas can present a
challenge to management. The main predicament
is the balance of improving pregnancy rates/pain
scores against the potential for reduced ovarian widely accepted approach to surgical manage-
reserve. Classically, surgical management has ment of large endometriomas. This consists of
been performed for women with pain symptoms, laparoscopic cyst drainage, followed by use of
endometriomas >3 cm, or those undergoing fer- GnRH for 3 months to reduce cyst diameter, and
tility treatment. then laparoscopic CO2 laser vaporisation of the
While surgical treatment has historically been cyst wall. This method is associated with less
thought to improve spontaneous pregnancy rates impact on AMH levels than a single procedure
by restoring pelvic anatomy, there are concerns laparoscopic drainage and cystectomy alone.
that the pre-existing inflammatory effects of the en- Ovarian reserves after cystectomy are thought to
dometrioma on the ovary continue in spite of this. be dependent on surgical skill and therefore me-
Ovarian cystectomy is also associated with inad- ticulous technique, and the use of laparoscopic
vertent, or unavoidable, removal of adjacent ovar- suturing, may prevent unnecessary damage. In
ian parenchyma as cleavage planes can be chal- some cases, no treatment for haemostasis may
lenging to develop due to fibrosis. Laparoscopic be required at all after excision and therefore
excision of endometriomas has been shown to cases should be assessed independently. This
cause follicle loss, leading to low levels of an- supports the need for women with severe endo-
ti-mullerian hormone (AMH), with the potential for metriosis to be managed in specialist endometri-
premature ovarian failure, and can be associated osis centres (Figure 6).
with peri-ovarian adhesion formation. The literature From a fertility perspective, however, there is
also suggests that spontaneous ovulation is not af- currently no evidence to support routine cystecto-
fected by the presence of an endometrioma, inde- my prior to assisted reproductive treatment as it is
pendent of the size, and number of cysts. not shown to improve pregnancy rates, in addition
A Cochrane review reported excisional sur- to a poor response to gonadotrophin stimulation
gery of the cyst capsule is associated with bet- and less codominant follicles developing in affect-
ter outcomes than ablative treatment, see Table ed ovaries. This emphasises the importance of tak-
3. A three-step technique is currently the most ing a targeted history from a patient with endome-
70 MIMS JPOG 2018 VOL. 44 NO. 2 GYNAECOLOGY PEER REVIEWED
osis. Women do therefore not require routine diag- More recently, ultrasound guided high-in-
nostic laparoscopy, unless there are other features tensity focused ultrasound (HIFU) has been
to suggest concomitant disease. reported in the literature as a new noninvasive
technique. This uses extracorporeal low-intensi-
Reaching a diagnosis ty ultrasound to form a high-intensity ultrasound
In view of the uncommon nature of the condi- focus to cause coagulative necrosis and reso-
tion, it can be difficult to diagnose, with incisional lution of the lesion, without peripheral tissue
hernia, haematoma or lipoma being favoured as damage. For lesions that incompletely resolve,
initial differentials. A targeted history and thor- the loss of surrounding blood supply is said to
ough examination have been shown to have high enable gradual shrinkage and resolution of the
reliability for diagnosis. Women will classically lesion over time.
describe the presence of a discrete, non-reduc-
ible mass within or adjacent to a scar, which is CONCLUSION
associated with cyclical tenderness, progressive Endometriosis is an important condition that af-
enlargement, and occasionally leakage of brown fects young, healthy women, and can result in
fluid. This is usually in the absence of dysmen- chronic pain and poor quality of life if suboptimally
orrhoea. Transabdominal ultrasound is the radio- managed. Early diagnosis is key, with individual-
logical investigation of choice, although MRI may ised management options dependent on symp-
be required in more complex cases. Important tom profiles, disease stage, and patient expecta-
features to identify are the size of the lesion and tions. The role of specialist endometriosis centres,
whether it lies above or below the rectus sheath, specialist radiological imaging and advanced
which is pertinent if surgical excision is planned. If laparoscopic surgical techniques, is essential for
the diagnosis remains unclear, fine needle aspira- management of severe disease. The overlap be-
tion can be considered, although theoretically this tween endometriosis and fertility must be consid-
may result in further deposits being introduced. ered when planning management and thorough
risk-benefit analysis should be undertaken for all
Management patients considering surgery, balancing the poten-
A proportion of women may achieve acceptable tial of symptom relief versus surgical risks.
control of symptoms through use of the combined
or progesterone only pill. However, complete sur- CASE SCENARIOS
gical excision offers the opportunity for definitive
diagnosis, resolution of symptoms, and preventive Case 1: Start from the beginning
recurrence. One of the difficulties with excision is A 39-year-old nulliparous woman was referred to
being certain of margins of the lesion. Radiologi- a specialist endometriosis centre to discuss lapa-
cal marking can be performed prior to excision, in roscopic excision of endometriosis. This had been
addition to the use of intra-operative transabdom- diagnosed on history and imaging two years prior
inal ultrasound. If the lesion lies above the rectus in another region. The patient had been counselled
sheath, then the defect can be closed routinely with about the risks and listed for surgery but she de-
an absorbable suture. If it lies below the sheath, or clined on the day due to anxiety. On further ques-
involves excision of a large area of tissue around tioning, the patient had low pain scores and her
the sheath, the insertion of a mesh may be indicat- primary issue was the desire to achieve a pregnan-
ed. This is where preoperative imaging plays an cy. Ultrasound assessment revealed bilateral hae-
important role. Recurrence rates are in the region matosalpinx but no evidence of endometriomas
of 4–7% but often relate to incomplete excision, and a normal looking uterus. She had a thickened
rather than development of new lesions. left uterosacral ligament on per vaginal examina-
72 MIMS JPOG 2018 VOL. 44 NO. 2 GYNAECOLOGY PEER REVIEWED
tion. She had self-referred to the fertility service and Case 3: The importance of
was awaiting an appointment to discuss assisted pre-operative review
reproduction. The patient wanted to proceed with A 35-year-old nulliparous woman who worked as
“anything” that might improve her fertility chanc- an accountant was added to a pooled waiting list
es. After careful discussion, the patient understood for laparoscopic ovarian cystectomy after a gen-
that while there was the potential to offer laparo- eral gynaecology outpatient appointment. She
scopic excision of endometriosis, ± bilateral sal- had a six-month history of left-sided pain and was
pingectomy, based on previous assessment and found to have a unilateral 5 cm endometrioma on
the recent imaging results, the clinical benefit did ultrasound. At her preoperative review on the day
not favour surgery at this stage. The woman went of surgery, the admitting consultant who was an
on to have a successful twin pregnancy, with deliv- endometriosis specialist enquired about her fertil-
ery by caesarean section at 36 weeks, after three ity status. The patient admitted that she had been
cycles of in vitro fertilization (IVF). She subsequent- trying to conceive for 18 months and had her AMH
ly opted for medical management with a Mirena level checked privately a year ago, which was 1.1
coil and has avoided the need for further surgery. ng/mL. She was consented for diagnostic lapa-
roscopy, drainage of the endometrioma and dye
Case 2: Dig a little deeper hydrotubation instead. She had moderate endo-
A 27-year-old woman, para 2, with a BMI of 42 was metriosis but a normal POD and free fill and spill
under the care of gynaecology outpatients with of both tubes. She went on to receive 3 months
chronic pelvic pain. She had undergone three pre- of downregulation with GnRH and was referred to
vious laparoscopies: one diagnostic, one ablation the fertility team. Further investigations revealed
of endometriosis, and one excision of mild endo- female factor infertility only and the decision was
metriosis. She had trialled medical management made to not excise the endometrioma as it would
since then with no benefit. She reported high pain further compromise her ovarian reserve. She went
scores in all domains and was signed off work long on to commence IVF treatment and fell pregnant
term due to pain. She was taking paracetamol, on the second cycle, although suffered a first tri-
nonsteroidal anti-inflammatory drugs (NSAIDs), mester miscarriage. She is currently awaiting em-
and a fentanyl patch in addition to mebeverine. bryo transfer after her third cycle. She remains pain
She had recently been started on sertraline for free.
anxiety, which she attributed to the constant lack of
control over her pain. She requested a hysterecto- FURTHER READING
1. Jayaprakasan K, Becker C, Mittal M, on behalf of the Royal College of
my. She was initially referred for a pelvis MRI which Obstetricians and Gynaecologists. The effect of surgery for endometri-
omas on fertility: Scientific Impact Paper 55. BJOG, 2017; https://doi.
showed no evidence of DIE or adenomyosis. She org/10.1111/1471-0528.14834.
2. Maggiore ULR, Gupta JK, Ferrero S. Treatment of endometrioma for im-
was counselled against hysterectomy and referred proving fertility. Eur J Obstet Gynecol Reprod Biol 2017; 209: 81–5.
3. Stochino-Loi E, Darwish B, Mircea O, et al. Does pre-operative Anti-mul-
to the pain management service. At the end of lerian hormone influence postoperative pregnancy rate in women under-
going surgery for severe endometriosis. Fertil Steril 2017; 107(3): 707–13.
the first session, she disclosed that she had been 4. Van Aken MAW, Oosterman JM, van Rijn CM, et al. Pain cognition versus
sexually abused by her stepfather as a child, her pain intensity in patients with endometriosis: toward personalised treat-
ment. Fertil Steril 2017; 108(4): 679–86.
mother never believed this had happened, and she 5. Zhu X, Chen L, Deng X, Xiao S, Ye M, Xue M. A comparison between high
intensity focused ultrasound and surgical treatment for the management
had ended up living in sheltered housing by the of abdominal wall endometriosis. BJOG 2017; 124(3): 53–8.
age of 17. Her pelvic pain had commenced shortly © 2017 Elsevier Ltd. All rights reserved. Initially published in Obstetrics,
Gynaecology and Reproductive Medicine 2017;28(3):61–69.
after this. After 6 months of CBT and acupuncture,
her pain scores had halved and she required oc- About the authors
Susannah Hogg is an ST7 Registrar in Obstetrics and Gynaecology at
casional paracetamol and NSAIDs only. She had Southmead Hospital, Bristol, UK. Conflicts of interest: none.
returned to work part-time and had commenced a
Sanjay Vyas is a Consultant Gynaecologist at Southmead Hospital, Bristol,
weight loss programme. UK. Conflicts of interest: none.
OBSTETRICS PEER REVIEWED MIMS JPOG 2018 VOL. 44 NO. 2 73
Urogynaecological
Complications in Pregnancy:
An Overview
Samantha Cox, MRCOG; Fiona Reid, MD MRCOG
Box 1. Risk Factors for Developing a UTI in Pregnancy portant that the staff inform women clearly how
to obtain a midstream sample.
• Sexual activity UTI is split into three subgroups: asympto-
matic bacteriuria, acute cystitis, and pyelonephritis.
• Low socioeconomic status
• Increasing age Asymptomatic bacteriuria
• Urinary tract abnormalities (congenital and acquired) Asymptomatic bacteriuria (ASB) is diagnosed
• Diabetes mellitus when there is clinically significant numbers of
bacteria in the urine but the patient is asymp-
• Sickle-cell disease
tomatic and remains clinically well. Significant
bacteriuria is defined as 2 voided urine samples
with greater than x105CFU/mL of a single organ-
This physiological hydronephrosis is present in ism. It affects between 4% and 7% of pregnant
up to 90% of pregnant women. It is seen more women, and of these significant numbers will go
commonly in the right than the left kidney. The on to develop acute cystitis and pyelonephritis.
bladder also undergoes change, with detrusor Therefore, it is a common problem that must be
tone decreasing, resulting in increased capacity identified and treated in order to prevent these
and incomplete emptying. The net effect is of in- potentially serious sequelae. ASB is most com-
creased stasis of urine. This incurs an increased monly seen in early pregnancy, with only small
risk of vesicoureteric reflux and subsequent as- numbers of women developing it in later preg-
cending infection. nancy. In recognition of this, it is a standard
antenatal practice to send a urine sample for
URINARY TRACT INFECTION IN microscopy and culture at the initial booking ap-
PREGNANCY pointment in order to highlight any women with
Urinary tract infection (UTI) is extremely com- ASB.
mon in pregnancy, with an overall incidence of The most common organism found in wom-
up to 8%. It can be asymptomatic and is associ- en with ASB is Escherichia coli (E. coli), which
ated with an increased risk of preterm prelabour is responsible for up to 90% of all cases. The
rupture of membranes, preterm labour, and foe- next most frequently observed pathogens are
tal growth restriction. Increased bladder capac- Proteus mirabilis, Klebsiella pneumoniae, and
ity, incomplete emptying, and stasis of urine in Enterococcus, all of which are gram-negative
combination with dilated ureters all facilitate the bacteria. However, gram-positive pathogens,
migration of bacteria to the upper urinary tract. such as Staphylococcus aureus and Group B
Urine is normally bacteriostatic; in pregnancy Streptococcus can also underlie ASB.
however, the osmolality of urine is decreased The treatment of ASB should ideally be
and it becomes relatively alkali. Therefore, part based on the sensitivities of a urine culture,
of the defence system against bacterial prolifer- with penicillins and cephalosporins being safe
ation is lost. Box 1 shows other risk factors for choices during pregnancy. A recent Cochrane
developing a UTI in pregnancy. review analysed 5 randomized control trials
UTI is diagnosed when there are bacterial comparing different antibiotic regimens from
counts >x105 colony forming units (CFU)/mL classes safe in pregnancy in a total of 1,140
and a single strain of pathogen is identified on women with ASB. It concluded that there was
culture. When urine flows over the perineum it no definite advantage of any of the antibiotics
can be contaminated with bowel commensals, studied. There is still debate as to how long
hence the need for a midstream sample. It is im- antibiotics should be prescribed, although it is
OBSTETRICS PEER REVIEWED MIMS JPOG 2018 VOL. 44 NO. 2 75
generally accepted that a 5–7 day course will to initiate treatment. A 5–7 day course of antibiot-
effectively treat ASB. Once treatment has been ic treatment is the accepted course to fully treat
completed, it is advisable to repeat a urine cul- acute cystitis. A repeat urine culture should also
ture as a test of cure. If there is a recurrence be sent following treatment in order to test that the
or persistent bacteriuria on urinary cultures, it organism has been fully treated.
is an indication for commencing long-term sup-
pressive antimicrobial prophylaxis. Low-dose Pyelonephritis
nitrofurantoin or beta-lactam antimicrobials, Pyelonephritis is the most serious complication
such as penicillin or cephalosporins, are safe of UTI, with significant bacteriuria present in ad-
choices during pregnancy. There is a docu- dition to systemic illness and clinical symptoms
mented risk with nitrofurantoin of haemolysis in such as fever, rigors, abdominal pain, vomiting,
babies affected by glucose-6-phosphate dehy- and headache. Ascending infection in the urinary
drogenase (G6PD) deficiency, and therefore it tract results in inflammation of the kidney and
must be used with caution in the third trimester. renal pelvis, which left untreated can develop
Trimethoprim, a folate antagonist, is also an op- into global kidney infection (pyonephrosis) and
tion for treatment of UTI in the second and third ultimately a perinephric abscess. It is associated
trimester. It is not an option in the first trimester with an increased risk of premature labour, pre-
as it increases the risk of miscarriage. mature rupture of the membranes, and low birth
However, a Cochrane review concluded weight. It also has serious implications for mater-
that there were no significant differences in the nal health, causing complications such as septic
prevention of recurrent UTI when comparing shock and acute respiratory distress syndrome.
long-term suppressive treatment with nitrofuran- Therefore, it is of vital importance that pyelone-
toin and close surveillance of urinary cultures. phritis is diagnosed and treated as quickly as
Therefore, the decision to commence long-term possible. It is most commonly caused by E. coli
antimicrobial prophylaxis must be made on care- (present in 80% of cases).
ful evaluation of individual cases and agreement The diagnosis is clinical, based on clinical
of the patient. history of abdominal and flank pain with urinary
symptoms, examination and results of blood
Acute cystitis tests. Urine culture should be sent, along with
Acute cystitis is defined as having significant blood cultures, if the patient is pyrexial or show-
bacteriuria with a single organism on a urine cul- ing signs of sepsis. Pyelonephritis is mostly
ture associated with clinical symptoms, such as managed in hospital and is currently the second
dysuria, urinary frequency, urgency, haematuria, most common cause for hospitalisation not relat-
and suprapubic pain in the absence of systemic ed to delivery. Outpatient management with oral
illness. It complicates 1% of all pregnancies and is antibiotics can be considered if the patient has
more commonly seen in women with diabetes, on few symptoms and there are no signs of sepsis.
immunosuppressant medications and those who The majority will, however, require admission.
have had previous UTIs. As with ASB, the most Most units in the UK have adopted the use
commonly isolated organism responsible is E. of the “Sepsis Six” developed by Dellinger, et al.
coli, followed by the previously mentioned bacte- The Sepsis Six consists of three diagnostic
ria. Nitrites are commonly found on urine dipstick, and three therapeutic steps – all to be delivered
but this is not diagnostic of acute cystitis, with the within 1 hour of the initial diagnosis of sepsis:
gold standard being urine culture. However, the 1. Titrate oxygen to a saturation target of 94%.
presence of nitrites in combination with clinical 2. Take blood cultures.
history and symptoms may prompt the clinician 3. Administer empiric intravenous antibiotics.
76 MIMS JPOG 2018 VOL. 44 NO. 2 OBSTETRICS PEER REVIEWED
UROLITHIASIS
This is the second most common urological
complication affecting pregnant women, com-
Urolithiasis is the second most common urological complication affecting plicating 1/200 to 1/2,000 pregnancies. This in-
pregnant women. cidence is no different from non-pregnant wom-
en, leading to the conclusion that pregnancy
4. Measure serum lactate and send a full blood does not increase a woman’s risk of develop-
count. ing stone disease. However, a major complica-
5. Start intravenous fluid resuscitation. tion of stone disease in pregnancy is preterm
6. Commence accurate urine output measurement. labour. Therefore, it is an important diagnosis
Paracetamol should be used for its analge- during pregnancy.
sic and antipyretic properties. An ultrasound scan Urinary tract stones are seen more com-
(USS) of the urinary tract should be performed in monly in the ureter during pregnancy and they
order to identify hydronephrosis, urinary stones, are mostly composed of calcium phosphate
or other urinary tract abnormalities that could be or calcium oxalate. Renal plasma flow increas-
underlying the pyelonephritis. Once the episode es dramatically during pregnancy, leading to
of pyelonephritis has been successfully treated, increased filtration of both stone forming sub-
it is essential to monitor for recurrence of bac- stances (eg, calcium, sodium, uric acid, and
teriuria by repeating urinary cultures throughout oxalate) and stone inhibiting substances (eg,
the rest of the pregnancy. The recurrence rate citrate, magnesium, and glycosaminoglycans).
for pyelonephritis in the same pregnancy has This is thought to be the reason why the inci-
been quoted to be as high as 10–18%, therefore dence of renal stones in pregnancy is the same
there is an argument for commencing long-term as in the non-pregnant population.
suppressive antimicrobial prophylaxis for the re- Symptomatic stone disease is seen most
mainder of the pregnancy. commonly in the second and third trimester, with
the most common signs and symptoms being col-
Recurrent urinary tract infection icky flank pain and haematuria. Other symptoms
It is estimated that UTI will reoccur in 4–5% of include fever, nausea and vomiting, and signs of
cases and still incurs the same risk of devel- UTI. The colicky pain is secondary to obstruction
OBSTETRICS PEER REVIEWED MIMS JPOG 2018 VOL. 44 NO. 2 77
Fertility Preservation in
2 SKP
INTRODUCTION
Advancement of diagnosis and treat-
ment of cancer has increased the dis-
ease-free interval and overall survival
rate in young cancer patients.1 However,
anticancer treatment including adjuvant
chemotherapy and radiotherapy may
be highly detrimental to the female en-
docrine and reproductive function. As a
consequence, there is increasing aware-
ness for the need to preserve gonadal
function and fertility especially in young
cancer patients undergoing gonadotoxic
treatments.
EFFECT OF GONADOTOXIC
AGENTS ON FEMALE
FERTILITY
Ovaries are very sensitive to gonado-
toxic treatment. Women have a finite re-
serve of primordial follicles that progres- Objective assessment of the ovarian reserve before and after gonadotoxic treatment is
sively depletes during their reproductive useful to further guide fertility counselling, influence the type of gonadotoxic treatment,
and assess the impact of gonadotoxic therapy on future reproduction.
life. Gonadotoxic agents increase the
rate of loss of these primordial folli-
cles, inducing premature ovarian fail- CHEMOTHERAPY lites like methotrexate are less damaging
ure leading to early menopause and Different chemotherapeutic agents have as it only affects the developing follicles
infertility. The effect of chemotherapy different effects on the follicular devel- and causes transient amenorrhoea with-
or radiotherapy can be transient or per- opment of the ovary. Among all chem- out altering the ovarian reserve. The risk
manent. Its gonadotoxic effect depends otherapeutic agents, alkylating agents of gonadotoxicity of the commonly used
on patient’s age, ovarian reserve, the carry the highest risk of gonadotoxicity. 3
chemotherapy is listed in Table 1.1-4
type of gonadotoxic agent used, and Alkylating agents like cyclophosphamide
the cumulative total dose administered. are non-cell specific agents, it not only RADIOTHERAPY
Combination of gonadotoxic treatment affects the growing follicles but also the Radiation not only damages the ovaries
further increases gonadal toxicity and non-proliferating primordial follicle re- but also the uterus. Radiation is more
impairment.1-2 serve. On the other hand, antimetabo- gonadotoxic when the irradiation is giv-
82 MIMS JPOG 2018 VOL. 44 NO. 2 CONTINUING MEDICAL EDUCATION
Table 1. Risk of Gonadotoxicity of Different Chemotherapeutic Agents patient. Figure 1 shows the algorithm for
an individualized approach to the various
options of fertility preservation. Early re-
Low risk Moderate risk High risk
ferral to a fertility specialist at the time of
Methotrexate Adriamycin Cyclophosphamide diagnosis of cancer is the key to maximiz-
5-Fluorouracil Cisplatin Busulfan ing the success of fertility preservation.1,7-8
Diagnosis of cancer
Alternative options:
Multidisciplinary meeting Gamete donor/Gestational
Counselling and risk assessment of gonadotoxicity carrier/Adoption/Accepting
childlessness
Yes
Yes No
Figure 1. Algorithm showing the individualized approach for fertility preservation in young female cancer patients.
may have coexisting endometrial can- for endometrial cancer. Use of pro- oral progestogens are not a standard
cer. Unilateral salpingo-oophorectomy
1
gestogens has been reported to treat treatment and that there is a high risk of
can be considered in those with bor- very early stage endometrial cancer recurrence and their survival chances
derline epithelial ovarian tumours as in young women as a fertility-sparing may be compromised in order to pre-
oncological outcome has been shown option with successful pregnancies serve fertility.
to be comparable to those when treat- reported. Nonetheless, the patients
ed with traditional radical surgery.1 should be warned about the limitation PELVIC SHIELDING AND
Hysterectomy, bilateral salpin- of this treatment including the high re- OVARIAN TRANSPOSITION
go-oophorectomy together with or currence rate and the 10–29% chance Shielding the pelvis away from radiother-
without lymph node dissection has of coexisting ovarian cancer. 1,9,11
Pa- apy can reduce the gonadotoxic effect.
been the standard surgical treatment tients should be fully informed that When shielding is not possible, patients
84 MIMS JPOG 2018 VOL. 44 NO. 2 CONTINUING MEDICAL EDUCATION
OOCYTE PRESERVATION
In cases where the patient has adequate
time for ovarian stimulation but without a
partner, oocyte preservation can be con-
sidered. In oocyte preservation, ovarian
stimulation is required to harvest ma-
ture eggs with subsequent freezing of
unfertilized eggs. This is the only option
applicable to those who do not have a
With ovarian transposition, preservation of ovarian function has been shown in 90% male partner or would not consider the
of the cases.
use of donor sperm. It is also acceptable
to those who have religious or ethical
undergoing gonadotoxic radiotherapy oocytes for retrieval prior to gonadotoxic objections to embryo cryopreservation.
can have their ovaries transposed out of treatment. Following in vitro fertilization Yet, again it requires ovarian stimulation
the field of irradiation laparoscopically or (IVF), embryos are produced either us- causing possible delay in cancer treat-
via laparotomy.15-18 Ovaries can be trans- ing partner’s sperm or donor’s sperm. ment while exposing the patient to a tem-
posed medially behind the uterus or lat- These embryos are then subsequently porary increase in oestradiol levels. In
erally to the paracolic gutters. The most cryopreserved for future use when the addition, mature oocytes are more sus-
simple and effective method is performing patient is ready for pregnancy. ceptible to cryodamage than embryos
lateral ovarian transposition laparoscopi- Embryo cryopreservation is by far due to the sensitivity of the spindle appa-
cally just before initiating radiotherapy. In the most established method for fertility ratus and higher lipid content of the cells.
this case, the ovaries are transposed to preservation. It is used whenever there Cooling and exposure to cyroprotecting
the paracolic gutters after the division of are surplus embryos generated during agents may also increase the incidence
the utero-ovarian ligament and tubes, ly- IVF programmes. Embryos are much of aneuploidy rate.2 Cryopreservation
ing 3 cm above the upper border of the more resistant to cryodamage than oo- also causes hardening of the zona pel-
radiation field. With ovarian transposition, cytes. It has promising results with high lucida and thus oocyte cryopreservation
preservation of ovarian function has been post-thaw survival rate of 35–90%, im- protocols often involve intracytoplasmic
shown in 90% of the cases. 17
plantation rate of up to 30% and cumula- insemination as a precaution to increase
tive pregnancy rate between 30–40%. 2,9
fertilization rates in assisted reproductive
EMBRYO CRYOPRESERVATION However, this procedure requires programmes.8-14
As shown Figure 1, in those patients with ovarian stimulation for 2–3 weeks and Oocyte preservation is no longer
a partner or those who are willing to use thus causes a possible delay in cancer an experimental process.10 With the use
donor sperm for fertilization, embryo cry- treatment. Hence, it is not suitable for of intracytoplasmic injection and vitrifi-
opreservation is the first choice for fertil- patients who require chemotherapy im- cation, higher rates of post-thaw surviv-
ity preservation if there is adequate time mediately. The patient should be of pu- al, fertilization and pregnancy are seen.
for ovarian stimulation. Embryo cryo- bertal age with a preferably good ovarian A recent report showed that pregnancy
preservation involves ovarian stimulation reserve in order to have sufficient embry- rate per transfer with vitrification is 29%
with gonadotrophins to produce mature os cryopreserved. Ideally, they should compared with slow freezing.2 However,
CONTINUING MEDICAL EDUCATION MIMS JPOG 2018 VOL. 44 NO. 2 85
IN VITRO MATURATION
In those cases where the patient needs
to undergo chemotherapy immediately,
collecting the immature oocytes for cryo-
preservation may be considered. These
immature oocytes can then be matured
in vitro with subsequent cryopreserva-
tion. It can also be fertilized with the part-
ner’s or donor’s sperm for embryo cryo- In those cases where the patient needs to undergo chemotherapy immediately,
collecting the immature oocytes for cryopreservation may be considered.
preservation. When compared to mature
oocytes, immature oocytes are more re-
sistant to cryodamage due to lower cell Tamoxifen is a selective oestrogen zole-FSH protocol (letrozole doses of
volume and the absence of metaphase receptor modulator. Other than its an- 2.5–5 mg daily during day 2–3 of men-
spindle. Additional research is required
2
ti-estrogenic action on breast tissue, ses with gonadotrophins started 2 days
to determine the potential pregnancy it has an antagonist action in central later) can be used for ovulation induc-
rate and the safety of its use. 8-14
nervous system and interferes with tion.2 With this protocol, the oestradiol
the negative feedback of oestrogen levels has been reported to be even
NOVEL STIMULATION in hypothalamic/pituitary axis leading lower than those seen in natural cycles
PROTOCOLS to an increase in gonadotrophin-re- with outcome similar to standard IVF
Typical ovarian stimulation requires leasing hormone (GnRH) secretion protocols.24-25
10–14 days of stimulation with gon- from the hypothalamus. The subse- GnRH antagonist protocols are
adotrophins to achieve multifollicular quent release of FSH from the pituitary usually the stimulation protocol of
development and causes an elevation can stimulate follicular development. choice for cancer patients as the oestro-
of serum oestradiol up to 10–15 times In doses of 40–60 mg daily starting on gen level produced is lower when com-
higher than physiological levels. In or- day 2–3 of the cycle for 5–12 days, it can pared with the agonist or flare protocol.
der to minimize the oestrogen expo- be used together with gonadotrophins Conventional controlled ovarian stimu-
sure during ovarian stimulation, oocyte for ovulation induction and should be lation is usually initiated at the beginning
retrieval can be performed during a considered to be used in hormonally of follicular phase. Due to the urgent
natural IVF cycle. However, natural IVF sensitive cancer patients.20-23 need for starting anti-cancer treatment,
cycles are associated with a lower yield Aromatase inhibitors (eg, letrozole) random start protocols have been pro-
of oocytes, embryos and subsequently significantly suppress plasma oestro- posed to provide the shortest time for
poorer pregnancy rates. Novel IVF stim- gen levels by competitively inhibiting oocyte collection and have been shown
ulation protocols with tamoxifen or aro- activity of the aromatase enzyme. Cen- to be as effective as conventional start
matase inhibitors have been developed trally, it releases the hypothalamic/pi- protocols. 26-28
In case patient comes in
to increase the safety margin of ovarian tuitary axis from oestrogenic negative during the luteal phase, GnRH antago-
stimulation, especially for those patients feedback, increasing secretion of FSH nist can be given to cause rapid fall of
with oestrogen-sensitive tumours. by the pituitary gland. Combined letro- progesterone from the corpus luteum
86 MIMS JPOG 2018 VOL. 44 NO. 2 CONTINUING MEDICAL EDUCATION
tissue. Further research is required to as- ALTERNATIVES preservation service is required. This
sess the optimal site for transplantation, Women, who have a reduced ovarian re- should involve a multidisciplinary
improve methods in detecting residual serve but are able to carry a child, can team consisting of the oncologist, sur-
disease, ascertain the optimal size of consider using donor eggs fertilised by geons, fertility specialist, pathologist,
ovarian grafts, optimize freezing/thawing either partner’s semen or donor sperm. radiologist, nurse and psychologist.
techniques, and promote revasculariza- Alternatively, women with a healthy ovar- The government should consider pro-
tion of the transplanted tissue. 33-36
ian reserve who are unable to success- viding funding for patients seeking fer-
fully carry a pregnancy due to hysterec- tility preservation treatment and sup-
WHOLE OVARY tomy or previous pelvic radiotherapy to port clinicians and scientists involved
CRYOPRESERVATION the uterus may undergo hormonal stimu- in researching in this field. Better ed-
There is increasing research interest in lation and IVF with the resulting embryos ucation and advertisement of fertility
fresh or cryopreserved whole ovary trans- being carried by a gestational surrogate. preservation should also be provided
plantation as a method to increase the As a last option, young cancer patients not only to the patients, but also to
longevity of ovarian transplant as larger with good prognosis may consider clinicians dealing with cancer patients
pool of follicles would be available and adoption. 1,22
so that early referral to a fertility spe-
lower the concerns for ischemic dam- cialist can be made.
age. Researchers have also explored the CONCLUSION
possibility of xenografting human ovarian The need for fertility preservation be- About the authors
Assistant Professors Jacqueline Chung Pui Wah and Grace
follicles to immunodeficient mice to grow fore anticancer treatment is on the Kong Wing Shan, and Professor Li Tin Chiu are specialists in
the Department of Obstetrics and Gynaecology, The Chinese
primordial follicles to mature stages.33,36 rise. Development of a good fertility University of Hong Kong, Hong Kong.
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88 MIMS JPOG 2018 VOL. 44 NO. 2 CME QUESTIONS
1. Chlorambucil and vincristine do not cause significant damage to the patient’s ovarian reserve.
2. Radical trachelectomy should be considered in stage 2A cervical cancer patients with fertility wish.
3. Embryo cryopreservation is the option for fertility preservation in married couples while oocyte
cryopreservation should be considered for patients who are single.
4. Mature oocyte cryopreservation requires ovarian stimulation and causes subsequent delay of starting
anticancer treatment.
5. Mature oocyte cryopreservation is still considered experimental at this stage.
6. Oocyte cryopreservation is currently the only acceptable option for prepubertal patients.
7. Tamoxifen is a suitable option for ovarian stimulation in breast cancer patients.
8. Conventional ovarian stimulation protocols allow patients to receive ovarian stimulation irrespective of the
time of the menstrual cycle.
9. GnRH analogues should be given during chemotherapy to reduce the risk of gonadotoxicity alone.
10. Heterotopic ovarian tissue transplantation allows natural conception.