INDONESIA • 2019

ISSN 2411-0140
VOL. 45 NO. 2

JOURNAL OF PAEDIATRICS,
OBSTETRICS & GYNAECOLOGY

YOUR PARTNER IN PAEDIATRIC, OBSTETRIC & GYNAECOLOGY PRACTICE

OBSTETRICS
Management
of a Woman with a
Previous Spontaneous
Preterm Birth

PAEDIATRICS
Hair Loss in Infancy
and Childhood

CME ARTICLE
Hysteroscopic Surgery
in Gynaecological
Practice
 MIMS JPOG 2019 VOL. 45 NO. 2 i

2019 VOL. 45 NO. 2

Editorial Board
CONFERENCE COVERAGE
Board Director, Paediatrics
Pediatric Academic Societies (PAS) 2019 Meeting,
Professor Pik-To Cheung
Associate Professor, Department of Paediatrics and Adolescent Medicine April 24–May 1, Baltimore, Maryland, US
The University of Hong Kong, Hong Kong

Board Director, Obstetrics and Gynaecology

Professor Pak-Chung Ho
Director, Centre of Reproductive Medicine
The University of Hong Kong - Shenzhen Hospital, China
Professor Biran Affandi
University of Indonesia, Indonesia
Professor Hextan
Yuen-Sheung Ngan
The University of Hong Kong, Hong Kong
Professor Kenneth Kwek
KK Women’s and Children’s Hospital,
Singapore
Professor Kok Hian Tan
KK Women’s and Children’s Hospital,
Singapore
Professor Dato’
Dr. Ravindran Jegasothy
Dean Faculty of Medicine,
MAHSA University, Malaysia
Associate Professor Daisy Chan
Singapore General Hospital, Singapore
Associate Professor Raymond
Hang Wun Li
The University of Hong Kong, Hong Kong
45
• Text message reminder improves HPV vaccination rate
• Increased secondhand smoke exposure linked to
elevated BP in children, adolescents
Professor Seng-Hock Quak
National University of Singapore,
Singapore
Adjunct Associate Professor
Tan Ah Moy JOURNAL WATCH
KK Women’s and Children’s Hospital,
Singapore
Dr. Catherine Lynn Silao
University of the Philippines Manila, 46
Philippines
Dwiana Ocviyanti, MD, PhD • Adult tourniquet arrests bleeds
University of Indonesia, Indonesia in children
Dr. Karen Kar-Loen Chan
The University of Hong Kong,
• Battle of pneumococcal
Hong Kong conjugate vaccines: PCV15 as
Dr. Kwok-Yin Leung good as PCV13?
The University of Hong Kong,
Hong Kong
Dr. Mary Anne Chiong
University of the Philippines Manila,
Philippines

Adjunct Associate Professor Dr. Wing-Cheong Leung 47

Kwong Wah Hospital, Hong Kong,
Ng Kee Chong Hong Kong • New oral contraceptive patch as good as other
Division of Medicine & Academic Clinical
Program (Paediatrics), c/o KK Women’s and contraceptives
Children’s Hospital, Singapore
• Timed vaginal insemination can help women with HIV
to conceive

48
• Infertility tied to increased
cancer risk
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 MIMS JPOG 2019 VOL. 45 NO. 2 iii

2019 VOL. 45 NO. 2

REVIEW ARTICLE
GYNAECOLOGY
CEO Yasunobu Sakai
Managing Editor Elvira Manzano
Medical Editor Elaine Soliven
Designer Sam Shum
49
Production Tetsuya Hamaki, Agnes Chieng
Circulation Christine Chok The Subfertile Couple
Accounting Manager Minty Kwan
Advertising Coordinator Pannica Goh
Difficulty conceiving affects one
in seven couples. Infertility, and
Published by: its treatment, is stressful. Initial
MIMS (Hong Kong) Limited
27th Floor, OTB Building, 160 Gloucester Road, Wan Chai, Hong Kong investigations are generally
Tel: (852) 2559 5888 | Email: enquiry@mimsjpog.com
recommended after 12 months of
failure to conceive, but this should
be individualized. Advice on lifestyle
changes that may have a positive impact on conception and
Enquiries and Correspondence general long-term health of the couple should be offered.
China Philippines
Counselling should be offered to support couples in exploring
Yang Xuan Rowena Belgica their feelings and to help maximize emotional wellbeing.
Tel: (86 21) 6157 3888 Tel: (63 2) 886 0333
Email: enquiry.cn@mims.com Email: enquiry.ph@mims.com David K Gatongi, D Rennie Urquhart, Tahir Mahmood
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57
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Tel: (84 8) 3829 7923 Management of a Woman with a Previous
Indonesia Email: enquiry.vn@mims.com
Fatmawati, Fransiska Simamora, Spontaneous Preterm Birth
Ruth Theresia, Sari Wiyanti
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Brenda Yong, Xavier Wee,
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Email: enquiry.my@mims.com
15 million babies are born preterm
each year, and there is no sign that
the rate of preterm birth is slowing.
PUBLISHER: MIMS Journal of Paediatrics, Obstetrics & Gynaecology (JPOG) is published 4 times a year by MIMS Pte Ltd. CIRCULATION:
JPOG is a controlled circulation for medical practitioners in South East Asia. It is also available on subscription to members of allied A history of a previous spontaneous preterm birth is a significant
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back issues US$8 per copy. EDITORIAL MATTER published herein has been prepared by professional editorial staff. Views expressed are not risk factor for a subsequent spontaneous preterm birth,
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iv MIMS JPOG 2019 VOL. 45 NO. 2

2019 VOL. 45 NO. 2

REVIEW ARTICLE CME Accreditation

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PAEDIATRICS accredited for CME points by the Singapore Medical Council (SMC).

Doctors can submit claims for self-reading, authorship or peer

69 review of articles through the SMC website at www.smc.gov.sg.
Hair Loss in Infancy and Childhood
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Caroline Champagne, Noor Alwash, Minal Patel, Nisha Arujuna,
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CONTINUING
MEDICAL EDUCATION
81
Hysteroscopic Surgery in Gynaecological
Practice
Hysteroscopy is a vital surgical technique for diagnosing and
treating intrauterine pathology. The procedure can be divided
into diagnostic and operative hysteroscopy.
Man Hin Menelik Lee

The Cover:
The Subfertile Couple
©2019 MIMS Pte Ltd

Peggy Tio, Designer

CONFERENCE COVERAGE
Pediatric Academic Societies (PAS) 2019 Meeting, April 24–May 1, Baltimore, Maryland, US – Elaine
Soliven reports
Text message reminder
improves HPV vaccination rate
The use of text messaging as a reminder
for the next human papillomavirus (HPV)
vaccine dose may help increase the rates of
HPV vaccine series completion, according
to a study presented at PAS* 2019 Meeting.
“HPV vaccine is a critical cancer-pro-
tecting vaccine; yet, only half of adoles-
cents have received their needed doses
… Even among those who start the se-
ries, only three-quarters get all the doses
needed for protection,” said study lead
author Associate Professor Melissa Stock-
well from the Department of Pediatrics,
Division of Pediatric Child and Adolescent
Medicine at Columbia University Irving
Medical Center in New York, US.
This AHRQ**-funded study consist-
ed of 956 parents and their adolescents
aged 9–17 years (50 percent female) who
underwent a first HPV vaccine at four af-
filiated community clinics in US between
December 2014 and 2016. Participants
were randomized in a 1:1 ratio to receive
either conventional text message (which
stated the due date for the next HPV vac-
cine dose) or enhanced educational text
message (which included educational
information for the parent’s vaccine deci-
sion-making phase). The study’s primary
outcome was the completion of two or
three doses of HPV vaccine at 12 months.
[PAS 2019, abstract 3335.6]
Participants who were enrolled in ei-
ther text messaging groups showed a sig-
nificantly higher completion rate of HPV
vaccine compared with individuals who
were screened but not eligible to enrol in
the study (74.1 percent vs 45.2 percent;
p<0.0001).
A significantly higher completion rate
of HPV vaccine was also observed in both
text messaging groups than those par-
ticipants who had their first HPV vaccine
within 3 years prior to this study (71.1 per-
cent vs 34.8 percent; p<0.0001). “Finally,
a population-wide effect was seen during
the years of the study 2014–2016, above
historical trends,” Stockwell said.
The completion rates of HPV vaccine
series at 12 months were comparable be-
tween the conventional and educational
text messaging groups (75.7 percent vs
72.4 percent).
“In this study, we found that text mes-
sage vaccine reminders are a powerful,
rapid, and scalable way to help encour-
age families to have adolescents complete
their vaccine series,” Stockwell noted.
*PAS: Pediatric Academic Societies
**AHRQ: Agency for Healthcare Research & Quality
Dr Melissa Stockwell, et al. Pediatric Academic Societies
2019 Meeting, April 24–May 1, Baltimore, Maryland, US
[abstract 3335.6].
Increased secondhand smoke
exposure linked to elevated BP
in children, adolescents
Increased exposure to secondhand tobac-
co smoke (SHS) was significantly associ-
ated with an elevated blood pressure (BP)
in children and adolescents, according to
a study presented at PAS* 2019 Meeting.
“Nearly 24 million children and ad-
olescents are exposed to SHS in the US.
SHS detrimentally affects cardiovascular
function; however, few studies have exam-
ined the effects of SHS on BP in children
and adolescents,” said the researchers.
Researchers gathered data from the
National Health and Nutrition Examination
Survey between 2007 and 2012 and an-
alysed children and adolescents (mean
age 12.6 years, 51 percent boys), of whom
MIMS JPOG 2019 VOL. 45 NO. 2 45
13.7 percent lived in homes with smokers.
SHS biomarkers were used to measure
the level of SHS exposure. BP levels were
measured according to the 2017 guide-
lines. [PAS 2019, abstract 3540.5]
Mean NNAL and serum cotinine
concentrations, two biomarkers of tobac-
co smoke exposure, were 1.60 pg/mL (in-
terquartile range [IQR], 0.4–4.19 pg/mL)
and 0.06 ng/mL (IQR, 0.01–0.16 ng/mL),
respectively.
After adjusting for race/ethnicity,
family poverty to income ratio, waist cir-
cumference, cadmium, lead, first albumin
creatinine ratio, and urinary creatinine, an
increased level of NNAL concentration was
associated with elevated diastolic BP lev-
els in boys and systolic BP levels in girls.
Also, boys who had an increased
level of serum cotinine concentration were
more likely to develop an elevated systolic
BP, but not in girls.
In another study, an increased se-
rum cotinine level was observed among
children who reported SHS exposure at
home compared with those who were not
exposed (median, 3.44 ng/mL, IQR 1.0–
10.83 vs 0.13, 95 percent confidence in-
terval, 0.03–0.67; p<0.01), indicating that
serum cotinine level correlates with SHS
exposure. [PAS 2019, abstract 1820.163]
“Our findings provide the first char-
acterization of the relationship between a
major tobacco-specific metabolite, NNAL,
and diastolic BP and systolic BP percen-
tiles in a nationally representative popula-
tion of US children [and adolescents],” the
researchers noted.
*PAS: Pediatric Academic Societies
**NNAL: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol
Assistant Professor Shelley Liu, et al. Pediatric Academic
Societies 2019 Meeting, April 24–May 1, Baltimore, Mary-
land, US [abstract 3540.5].
46 MIMS JPOG 2019 VOL. 45 NO. 2
P trasound. The tourniquet was applied ac-
Paediatrics
Adult tourniquet arrests
bleeds in children
Adult, military tourniquets may be
safely used in children to arrest bleeds
during emergencies, according to new
research. This confirmed previous an-
ecdotal reports that adult tourniquets
are being relied on in paediatric trau-
ma cases in war-torn zones.
The Combat Application Tourniquet
was effective in controlling blood flow to
the arms and legs of children, as meas-
ured by a Doppler pulse, in 100 percent
of cases involving upper extremities and
93 percent for lower extremities.
Lead author Dr Theodore Harcke
from the Nemours/Alfred I. duPont
Hospital for Children said the military
tourniquet may be an effective tool for
treating haemorrhage in children dur-
ing traumatic situations or emergency
settings. “A severely injured child could
bleed to death before medical help can
arrive. Tourniquets have the potential
to save lives from gunshot injuries.”
Adult tourniquets were tied to the
upper arms and thighs of 60 children
(36 boys and 24 girls) reflective of US
school population, and their pulse
monitored through vascular Doppler ul-
JOURNAL WATCH PEER REVIEWED
cording to the manufacturer's guidelines.
As tourniquets were not designed for
children, the authors’ main concern was
about its safety and efficacy when used in
children with smaller limbs.
To avoid inflicting pain to children,
the protocol allowed not more than three
turns of the tourniquet windlass. How-
ever, three turns did not fully arrest the
pulse of three older and obese children
(BMI >30) in the study. In both the up-
per and lower extremities, the number
of turns required to occlude blood flow
gradually increased with greater arm
and thigh circumferences. More wind-
lass turns typical of actual trauma care
practice better occluded blood flow in
some cases.
The researchers said the greatest im-
pact of the study may be on pre-hospital Researchers compared two lots of
care and paediatricians who should be fa- the 15-valent vaccine (n=350 for lot one
miliar with tourniquet use in children. Fur- and n=347 for lot two) with the 13-va-
ther training may be appropriate for other lent vaccine (n=347) in healthy infants
healthcare providers. at 2, 4, 6, and 12–15 months of age.
The percentage of infants who
Harcke HT, et al. Adult Tourniquet for Use in School-Age Emergen-
cies. Pediatrics 2019;doi:10.1542/peds.2018-3447. achieved WHO-accepted thresholds
for immune response (IgG 0.35 g/mL)
with either lot of V114 was noninferior
to those seen with the PCV13 for the 13
Battle of pneumococcal serotypes present in both vaccines. Of
conjugate vaccines: PCV15 note, more infants vaccinated with ei-
as good as PCV13? ther of the two lots of V114 achieved the
threshold of immune response against
An investigational 15-valent pneumo- serotype 3. “These results are encour-
coccal conjugate vaccine (PCV15) was aging and mark important progress
noninferior to a 13-valent (PCV13) in to helping expand protection against
protecting children 6–12 weeks of age pneumococcal disease in this vulner-
against two other serotypes: 22F and able patient population,” said study
33F, a double-blind, randomized phase investigator Dr David Greenberg from
2 trial has shown. the paediatric infectious disease unit of
The PCV15 previously received a the Soroka University Medical Center in
breakthrough therapy designation from the Beer’Sheva, Israel.
US FDA to prevent invasive pneumococcal More than 98 percent of infants
disease) caused by vaccine serotypes in who received V114 reached the thresh-
children aged 6 weeks to 18 years. old of immune response for serotype
JOURNAL WATCH PEER REVIEWED
22F (98.9 percent for lot one and 98.5
percent for lot two), whereas more than
87 percent of infants reached the thresh-
old for serotype 33F (87.7 percent for lot
one and 90.1 percent for lot two) — both
of which are not included in PCV13.
Adverse events were comparable
between the two vaccines.
Hurtado K, et al. A phase 2, double-blind, randomized, multi-
center trial to evaluate the safety and immunogenicity of 15-va-
lent pneumococcal conjugate vaccine (PCV15) compared to
PCV13 in healthy infants. Presented at the Annual Meeting of
the European Society for Paediatric Infectious Diseases 2019.
G men, timed vaginal insemination led to
Gynaecology
New oral contraceptive patch
as good as other contraceptives
The investigational oral contraceptive
patch AG200-15 had comparable safety
profile with currently approved contra-
ceptives, according to data from three
trials presented at ACOG 2019.
AG200-15, otherwise known as
Twirla, delivers approximately 120 mg
of levonorgestrel and 30 mg of ethinyl
estradiol daily to women users, said
Dr Anita Nelson, professor and chair of
obstetrics and gynecology at Western
University Health Sciences in Pomona,
California, US. Like most birth control
pills, the patch contains oestrogen and
progestin, which are absorbed through
the skin and stops ovulation.
In terms of adverse events (AEs),
the rates of treatment emergent and se-
vere AEs were generally similar across
the three phase 3 trials. “To add to that,
the adverse event profile of AG200-15
appears to be comparable to approved
[oral contraceptives],” Nelson and her
team said.
Of the 3,481 patients included in
the three trials, more than 50 percent
had experienced an AE. At least 26 per-
cent were drug-related, 11 percent led
to study discontinuation, and 5 percent
were considered severe.
Common AEs reported were na-
sopharyngitis, upper respiratory tract
infection, nausea, headache, and uri-
nary tract infections at 5.7 percent, 4.5
percent, 4.3 percent, 3.6 percent, and
3.5 percent, respectively. At least, less
than 2 percent of patients had severe
AEs such as cholelithiasis, deep vein
thrombosis, pulmonary embolism, and
depression.
Nelson AL, et al. “Safety of AG200-15, an investigational
transdermal patch, in three phase 3 studies.” Presented at
American College of Obstetricians and Gynecologists Annual
Clinical and Scientific Meeting.
MIMS JPOG 2019 VOL. 45 NO. 2 47
O
Obstetrics
Timed vaginal insemination
can help women with HIV
to conceive
A new study has shown that timed vag-
inal insemination is feasible and effec-
tive in helping HIV-infected women to
conceive.
Among 23 couples comprising
HIV-positive women and HIV-negative
six live births without a single case of
HIV transmission, said principal author
and Assistant Professor Okeoma Mme-
je who conducted the study while at the
University of California in San Francis-
co, California, US.
“Our study describes a feasible,
safe, and effective method for women
with HIV who want to achieve pregnan-
cy,” she said. “Our findings are applicable
to low-resource environments through-
out the world. This strategy could have
high impact on empowering HIV-affected
women with an affordable and readily
accessible reproductive option that sup-
ports their desire to have children.”
Current guidelines for HIV recom-
mend antiretroviral treatment in HIV-se-
rodiscordant couples to keep HIV at low
levels. However, the effectiveness of an-
tiretroviral therapy may not be routinely
assessed or guaranteed with an unde-
tectable HIV viral load, Mmeje said.
“We know there’s a strong desire
among many HIV-affected couples to have
children but the current strategies to sup-
press the virus may be inadequate,” said
Mmeje, who is also a member of the U-M
Institute for Healthcare Policy and Innova-
tion. “Additional options to support safe
48 MIMS JPOG 2019 VOL. 45 NO. 2
pregnancy should be offered to these cou-
ples and integrated into the HIV prevention
programmes.”
She added that health care providers
should offer fertility evaluation to HIV-se-
rodiscordant couples before attempting
to conceive or after several unsuccessful
attempts.
The study participants included
women aged 18–34 years from eight
HIV care and treatment clinics in West-
ern Kenya. Mmeje’s team used instruc-
tional aids during the procedures, edu-
cation, and counselling sessions. The
couples were observed for 2 months
before the timed vaginal insemination,
tested, and were treated for sexually
transmitted infections.
Timed vaginal insemination was
performed up to six menstrual cycles.
Fertility evaluation was offered to cou-
ples who failed to conceive. Given the
desire for children and inadequate viral
suppression, interventions to support
safe pregnancy should be integrated into
HIV prevention programmes, the authors
concluded.
Mmeje O, et al. Empowering HIV-infected women in low-re-
source settings: A pilot study evaluating a patient-centered HIV
prevention strategy for reproduction in Kisumu, Kenya. PLoS
ONE2019;doi.org/10.1371/journal.pone.0212656.
Infertility tied to increased
cancer risk
Infertile women appeared more likely
to develop certain malignancies than
women without fertility problems, ac-
cording to a retrospective cohort anal-
ysis in the US.
“Although the absolute risks are
small, women diagnosed with infertility
are at a higher relative risk for several
cancers,” said Dr Gayathree Murugap-
pan from the Stanford University School
of Medicine, Stanford, California, US.
“We were surprised to find several
significant risk associations between
infertile women and incidence of both
gynaecologic and non-gynaecologic
malignancies, including leukaemia.”
As the findings are associative,
Murugappan said the results should be
interpreted with caution. She and her
team utilized a health claims database,
which included information on 57 mil-
lion individuals from 2003–2016, for the
analysis.
At least 64,345 infertile women
(mean age, 34 years) and more than 3.1
million non-infertile women (mean age,
32.7 years) who sought routine gynaeco-
logic care during the study period were
included in the analysis. Women with pri-
or cancer diagnosis were excluded.
Development of any cancer and
specific malignancies as determined
by International Classification of Dis-
eases (ICD)-9 and ICD-10 codes were
the primary outcomes. Mean follow-up
was 3.8 years for the infertile group and
3.9 years for the control group, trans-
lating to a total follow-up of 246,485
person-years in the infertile group and
>12.26 million person-years in the
control group. Results were adjusted
for age at index date and year, nulli-
parity, race, smoking, obesity, number
JOURNAL WATCH PEER REVIEWED
of visits per year, and highest level of
education.
At the time of analysis, 1,310 cancers
were diagnosed among infertile women
and 53,116 were diagnosed among those
without fertility problems. Breast cancer
was the most common malignancy in
each group. Overall, infertile women had
an 18 percent higher risk for cancer vs
women without fertility problems.
The absolute risk in both groups
was small (2 percent vs. 1.7 percent; ad-
justed hazard ratio [adjHR], 1.18), which
means that one in 49 infertile women
would develop cancer during the fol-
low-up period vs one in 59 women in the
control group.
In addition, there were higher
risks of certain malignancies in infertile
women, which included uterine cancer
(adjHR, 1.78), ovarian cancer (adjHR,
1.64), liver and gallbladder cancers
(adjHR,1.59), leukaemia (adjHR,1.55),
lung cancer (adjHR,1.38), and thyroid
cancer (adjHR, 1.29).
Murugappan said the short dura-
tion of the follow-up was one of the study
caveats. “Continued follow-up should
be considered after reproductive goals
are achieved. In the future, we hope to
better understand the aetiologies of the
risk associations we uncovered.”
Murugappan G, et al. Risk of cancer in infertile women: analy-
sis of US claims data. Hum Reprod 2019;doi:10.1093/humrep/
dez018.
GYNAECOLOGY PEER REVIEWED MIMS JPOG 2019 VOL. 45 NO. 2 49

The Subfertile Couple

David K Gatongi, MSc MRCOG; D Rennie Urquhart, MD FRCOG; Tahir Mahmood, MD FRCPE FACOG FRCPE FRCOG

Difficulty conceiving affects one in seven couples. Infertility, and its treatment,
is stressful. Initial investigations are generally recommended after 12 months of
failure to conceive, but this should be individualized. Advice on lifestyle changes
that may have a positive impact on conception and general long-term health of
the couple should be offered. Counselling should be offered to support couples
in exploring their feelings and to help maximize emotional wellbeing.

INTRODUCTION AND may have significant psychological im-

EPIDEMIOLOGY
Around one in seven couples may have
difficulty conceiving. A woman’s max-
imum monthly chance of becoming
pregnant after unprotected intercourse is
about 30% per cycle. Traditionally, sub-
fertility is defined as failure to conceive
after regular unprotected sexual inter-
course for 12 months. Failure to conceive
pact, eliciting a variety of moral, cultural,
spiritual, and emotional feelings. This is
true across all population groups. How-
ever, in certain communities, especially
ethnic minorities, the consequences of
infertility can be overwhelming, some-
times leading to rejection and isolation
from the community. This is especially
true for the female partner who is often
50 MIMS JPOG 2019 VOL. 45 NO. 2 GYNAECOLOGY PEER REVIEWED

Table 1. History and Physical Examination for the Subfertile Couple neal factors (10%). Twenty percent of cases are
unexplained.

Female
History
1 Demographics-age, BMI
2 Previous pregnancies
3 Menstrual history
(a) Dysmenorrhoea
(b) Oligomenorrhoea
4 Smoking/alcohol/substance
misuse
5 Medical and surgical history
6 Medication
7 Sexual history
8 Sexually transmitted disease
and type of treatment received
9 Cervical smear history
10 Family history of genetic
problems
Examination
1 BMI
2 Hirsutism, acne
3 Pelvic and abdominal
examination as indicated in
the history
Male
History
1 Demographics-age, BMI
2 Past pregnancies in other
relationships
3 Medical and surgical history
4 Testicular problems (eg,
infection, injury, maldescent,
or surgery)
5 Smoking/alcohol/substance
misuse
6 Family history of subfertility or
genetic problems
7 Medication (including anabolic
steroids)
8 Sexual history, erectile
dysfunction
9 Past history of STI and
treatment given
Examination
1 BMI
2 Abdominal examination looking
for inguinal surgical scars
3 Testicular examination
assessment for varicosities,
testicular masses, tenderness,
and testicular volume
Ovulatory disorders
Disorders of ovulation are classified by WHO into
three groups:
i. Group I (hypothalamic pituitary failure)
Hypothalamic/pituitary disorders charac-
terized by low FSH/LH and oestradiol. This may
occur secondary to stress, endurance exercise,
brain tumours, head injury, or genetic abnormali-
ties. It may also be idiopathic.
ii. Group II (dysfunction of the hypothalamic-pi-
tuitary ovarian axis)
Hypothalamic-pituitary-ovarian dysfunction
characterized by normal FSH/LH and normal or
slightly elevated oestradiol levels. Polycystic ovar-
ian syndrome and weight-related hormonal disor-
ders are the most common causes in this group.
iii. Group III (ovarian failure)
Primary ovarian dysfunction is characterized
by high FSH/LH and low oestradiol. The cause
is most often premature ovarian failure (chromo-
somal, genetic, or infective) immunological, iat-
rogenic (surgery, radiation, or chemotherapy), or
idiopathic.
Tubal pathology
Postinfective tubal disease remains an important
cause of infertility.

viewed as being responsible for the failure to pro-
duce children. Sensitivity, awareness, and under-
standing are important for all staff involved in the
management of the infertile couple.
AETIOLOGY
Subfertility is caused by a variety of factors, both
female and male contributing almost equally.
The most common causes of infertility are ovu-
latory disorders (25%), tubal pathology (15%),
sperm dysfunction (30%), and uterine or perito-
Sperm dysfunction
The quality of the semen is reported to be grad-
ually deteriorating, with multiple underlying con-
tributory factors implicated such as smoking,
obesity, environmental contamination, underly-
ing genetic causes, and advancing age.
Unexplained infertility
This is where investigations demonstrate normal
ovulatory function, tubal patency, and normal
sperm parameters and constitutes one of the
largest groups.
GYNAECOLOGY PEER REVIEWED
HISTORY TAKING AND PHYSICAL
EXAMINATION
Thorough history of both partners is essential.
The extent of any physical examination during
the clinic visit is usually guided by the history
and is directed at identifying potential causes or
comorbidities, as listed in Table 1.
INVESTIGATING INFERTILITY
NICE guidelines recommend initiating investiga-
tion of the infertile couple after 12 months of ac-
tively trying to conceive. However, if there is no ob-
vious reproductive pathology, then investigations
may be delayed for up to 2 years. This is especially
so for young couples as they have good chance
of spontaneous conception. Equally, if there is an
obvious reason for failing to conceive (eg, amenor-
rhoea), then referral and investigation should start
sooner than the recommended 12 months.
Investigations are aimed at finding underly-
ing causes, but also should screen for infections
which may have been causative/contributory or
nevertheless influence management. These in-
vestigations are summarized in Table 2.
Semen analysis, mid-luteal D21 progester-
one and infection screening are commonly done
by the primary care provider. Other investiga-
tions are usually reserved for secondary and ter-
tiary centres depending on availability.
Infection screening
Screening for chlamydia and syphilis should be
offered and rubella immunity should be checked.
HIV and hepatitis screening are not done rou-
tinely at the primary care level, but are usually
required for those couples seeking assisted con-
ception or where there is a specific clinical indi-
cation based on history.
MANAGEMENT OF THE SUBFERTILE
COUPLE
Management of the infertile couple must be indi-
vidualized, based on the results of history taking,
examination, and the results of investigations.
However, there are also general measures appli-
MIMS JPOG 2019 VOL. 45 NO. 2 51
cable to all, including lifestyle changes, support,
and counselling.
Lifestyle changes
There are various modifiable lifestyle changes
that may have a positive impact on conception
and general long-term health of the couple. These
should be addressed as an essential part of sub-
fertility management and counselling. They include
weight reduction, nutrition, exercise, stopping
smoking, and reduction in alcohol consumption as
well as reviewing medication, including the poten-
tial abuse of anabolic steroids. Couples may be too
embarrassed to report unsatisfactory sexual activ-
ity, and healthcare providers often do not capture
this aspect clearly in their history. Coital problems
are responsible for failure to conceive in up to 6% of
couples. Satisfying and regular sexual activity can
be adversely affected by erectile dysfunction, dys-
pareunia, and the demands and stresses of mod-
ern day living, and these should be considered.
Counselling
The negative impact of subfertility on psycholog-
ical and emotional wellbeing is well recognized,
however formal support and/or counselling has
not routinely been provided to couples experi-
encing subfertility or undergoing investigation
and treatment for it. Healthcare staff must ap-
preciate this and help to signpost and refer for
formal counselling, ideally to professionals who
have experience of helping to support couples in
this situation. These services are mainly provid-
ed in tertiary assisted conception facilities where
Human Fertilisation & Embryology Authority reg-
ulations make provision of counselling mandato-
ry. Counselling helps couples better understand
the implications of their treatments, the choices
they make and to better accept the outcomes of
treatment, particularly if unsuccessful.
The British Infertility Counselling Associa-
tion (BICA) is the national association for fertility
counsellors and has very helpful information on
their website for patients and healthcare provid-
ers (https://www.bica.net/browse).
52 MIMS JPOG 2019 VOL. 45 NO. 2 GYNAECOLOGY PEER REVIEWED

Table 2. Investigations for the Subfertile Couple

Target Investigation Comment

Male factor Semen analysis • Use quality assured laboratory
• Timing; <3 hours between production and analysis
• Abstinence of 2–3 days prior to sample production
• Use an appropriate container supplied by the fertility service
• Be aware of potential cultural issues; some prohibit masturbation
• Use WHO (2010) guidance for normal levels (see Table 3)
Tubal factor HSG • Advantages
¡ Outpatient service

¡ Rapid results

¡ Intrauterine adhesions (Asherman syndrome) can be diagnosed

• Risks
¡ Exacerbation of pelvic infection

¨ Chlamydia screening is essential

¨ Prophylactic antibiotic should be used where screening has been missed

¡ Some patients find this procedure painful

HyCoSy • Uterine, ovarian, and adnexal morphology can be investigated

• Tubal patency is assessed
• Outpatient procedure
• Not universally available
Laparoscopy and • Laparoscopy with attendant risks
dye test ¡ Tubal patency assessed, and other pelvic pathology can be diagnosed

¡ Treatment can potentially be carried out at the same time for certain pathologies

Ovulatory factor D21 progesterone • Simple test to carry out for woman with regular monthly cycles
Irregular cycles/ (mid-luteal) • Mid-luteal phase levels >30 nm/L suggest ovulation
anovulation
Ultrasound follicular • Timing may be a problem with irregular cycles
tracking • There may be cycle-to-cycle variations in levels, therefore may need repeating
FSH/LH/oestradiol/ • Requires skill and hospital attendance
prolactin/ • Not usually available in most primary and secondary care settings. If a woman
testosterone levels is having very infrequent menses, these hormone profiles may need to be
d2-5 performed following a progesterone challenge test
Ovarian reserve Antral follicle count • >4 follicles per ovary is considered sufficient (not usually available in primary care)
¡ Not usually recommended in the primary care
Anti-Mullerian
hormone ¡ Follicular phase gonadotrophins d2-4 (as high baseline levels of FSH/LH and
FSH, LH, and low levels of oestradiol provide indirect evidence of lower ovarian reserve)
oestradiol
Endometrial and Pelvic ultrasound • Diagnosis of fibroids
uterine factor Hysteroscopy ¡ Endometrial polyps

¡ Hydrosalpinx

¡ Endometrioma

¡ Ovarian cysts

¡ Uterine anomalies

• Allows assessment of the endometrium for polyps, submucous fibroids, and

uterine anomalies
GYNAECOLOGY PEER REVIEWED
CASE DISCUSSIONS
Three cases are presented to help illustrate the
early steps in the investigation and management
of subfertility.
Case 1
Mr & Mrs S are referred to a hospital infertility
clinic by their GP with a history of failure to con-
ceive for 14 months’ duration. Mrs S is 28 years
old and has never been pregnant. Her partner is
32 years old and he has never had a pregnancy
in any past relationships.
Both have no significant medical or surgical
history, take no medications, and are non-smok-
ers.
Examination of both partners is normal.
Mrs S has regular cycles and her mid-luteal
phase progesterone is 40 nmol/L. Her pelvic ul-
trasound scan shows normal ovaries, and a hys-
terosalpingogram (HSG) confirms patent fallopi-
an tubes. Mrs S is negative for chlamydia and
she is rubella immune.
Mr S has a semen sample analysed with the
following results:
• Volume: 2.5 mL
• Sperm count: 4.5 million/mL
• Normal forms: 4%
• Total motility: 30%
What are the next steps?
When an abnormal semen analysis result
is obtained, the test should be repeated 10–12
weeks later, or sooner if the couple are >35 years
of age. Mr S repeats the test which again shows
semen parameters suggestive of oligospermia.
Abnormal sperm parameters are a common
occurrence during investigations for subfertility,
and in at least half of all cases, there is no un-
derlying cause (idiopathic). However, in the re-
maining cases, causes of oligospermia can be
classified as pretesticular, testicular, or post-tes-
ticular (Table 4).
An abnormal semen result can come as a
great shock and therefore sensitivity and clarity
when explaining the results, and their implica-
tions, is vital. It is important to emphasize that
MIMS JPOG 2019 VOL. 45 NO. 2 53
Table 3. Normal Semen Parameters (WHO 2010)
Normal semen parameters (WHO 2010) Normal ranges
Semen volume (mL) 1.5 (1.4–1.7)
Sperm concentration (million/mL) 15 (12–16)
Total sperm count (million/mL in ejaculate) 39 (33–46)
Progressive motility (%) 32 (31–34)
Total motility (PR + non-PR) 40 (38–42)
Vitality; live spermatozoa (%) 58 (55–63)
Normal sperm morphology (%) 4 (3.0–4.0)
Abbreviation: PR = progressive motility
low sperm count reduces the chance of concep-
tion but does not mean sterility. Therefore, there
remains the possibility of spontaneous concep-
tion in all but the most extreme cases.
This couple should be referred to a tertiary
centre for assisted conception.
Case 2
A 28-year-old woman presents with a history of sec-
ondary infertility of 18 months’ duration. She gives
a history of previous spontaneous conception 5
years ago, resulting in a normal pregnancy and de-
livery. Her BMI is 35 and she has a normal menstru-
al cycle. She has no significant medical or surgical
history. She is a non-smoker and is not currently
taking any medications. Her partner is 35 years old.
They have been in stable relationship for the past 8
years. He is not currently on any medication.
A number of basic investigations are per-
formed, and the results are as follows:
• Rubella immune
• Mid-luteal phase progesterone: 32 nmol/L
• 
Pelvic ultrasound – normal appearance of
both ovaries and uterine cavity
• 
HSG shows bilateral tubal patency with
prompt flow of dye
• Chlamydia screening negative
Her partner’s semen analysis is reported as
follows:
54 MIMS JPOG 2019 VOL. 45 NO. 2 GYNAECOLOGY PEER REVIEWED

Table 4. Causes of Male Factor Infertility of conception in the presence of regular unpro-
tected sexual intercourse, demonstrable tubal
patency, regular ovulation, and normal semen
Type Cause
analysis. Unexplained subfertility is present in
Pretesticular • Kallmann syndrome approximately 30–40% of subfertile couples. In
(Hypothalamic or pituitary
• Pituitary damage by tumour such cases, the chances of becoming pregnant
disorder)
• Hyperprolactinaemia during the subsequent 24 months of actively try-
• Male exogenous steroids ing is high. Fertilization and implantation require
competent gametes, a functional fallopian tube, a
Testicular • Idiopathic
(Spermatogenetic failure) supportive peritoneal milieu, and a receptive en-
• Genetic defects
dometrium. Advanced female age, and to a lesser
• Klinefelter syndrome
extent male age are detrimental to gamete quality
• Noonan syndrome leading to less efficient fertilization and poor-qual-
• Y-microdeletions ity embryos. This also results in an elevated mis-
• Undescended testis carriage risk. Tubal patency is not synonymous
• Testicular disease (orchitis, tumours) with normal tubal function. Mild asymptomatic

Post-testicular • Congenital bilateral absence of vas
(Obstructive or deferens (commonly secondary to
sperm dysfunction) cystic fibrosis)
• Infection and subsequent blockage of
the vas deferens
• Kartagener syndrome
• Vasectomy
• Erectile dysfunction
• Volume: 3.5 mL
• Count: 24.5 million/mL
• Normal forms: 3%
• Total motility: 50%
All parameters are normal apart from a
slightly lower proportion of normal forms, but
within the normal range. However, the good
sperm count, and sperm motility is reassuring.
This sample should be regarded as potentially
fertile.
What are the next steps?
No further investigations are required. The
Investigations carried out are normal, meaning
that this is unexplained secondary subfertility.
The woman should be advised to lose weight
and to take a higher dose of folic acid (5 mg) in
the periconceptual period.
Unexplained infertility is, strictly speaking,
not an actual diagnosis. It describes the failure
tubal infection without blockage can damage ep-
ithelial activity and compromise gamete transfer
and fertilization. Mild endometriosis and perito-
neal adhesions are associated with subfertility,
however these will only have been excluded if a
laparoscopy has been performed during the in-
vestigative workup.
Obesity is associated with reduced fertility in
both men and women. Male obesity is linked to
decreased libido, reduced sperm quality, and in-
creased sperm DNA damage, the latter not being
assessed in a standard semen analysis. In wom-
en, obesity is associated with anovulatory cycles,
a longer time to achieve a pregnancy, and an in-
creased subsequent miscarriage risk.
Weight reduction through diet and exercise
should be advised, with NICE recommending a
target BMI of 30.
Expectant management is appropriate after
addressing the lifestyle issues because the cou-
ple are still young. A period of up to 2 years would
be appropriate as they have a good chance of
spontaneous conception and they would not be
eligible for free assisted conception treatment
through the NHS.
Couples may find this unacceptable. Alter-
natively, various forms of assisted reproductive
technology can be offered. Timed intercourse,
intrauterine insemination (IUI) in the periovulatory
GYNAECOLOGY PEER REVIEWED
phase, ovarian stimulation, with or without IUI, or
even in vitro fertilization (IVF), can be considered.
A Scottish multicentre trial comparing timed
IUI in a spontaneous cycle with expectant man-
agement did not report any significant difference
in pregnancy rates between the study groups. Re-
cently, Farquhar and colleagues conducted a ran-
domized controlled trial to compare ovarian stim-
ulation with IUI against expectant management
for the care of unexplained infertility. The Cumu-
lative Live Birth Rates (intention-to-treat) was sig-
nificantly higher in the IUI group (31% vs 9%, risk
ratio, 3.41, 95% confidence interval, 1.71–6.79).
IVF is an option and the couple should be
counselled with regards its success rates, risk of
multiple pregnancies, complications (including
ovarian hyperstimulation syndrome), and high
failure rate.
Case 3
A 32-year-old nulliparous woman with a BMI of
24 has been trying to conceive for the past 18
months. She has regular periods but they are ex-
tremely painful. She suffers from chronic pelvic
pain and complains of deep dyspareunia. There
is no past history of pelvic infection. Pelvic exam-
ination demonstrates tenderness in both adnex-
ae. Her partner is 36 years old and has a BMI of
32. He is a non-smoker and has had two children
in a previous relationship.
Simple investigations are reported as follows:
• Mid-luteal phase progesterone: 45 nmol/L
• Pelvic ultrasound: Normal
• Chlamydia screening: Negative
His semen analysis results are:
• Volume: 4.5 mL
• Count: 54.5 million/mL
• Normal forms: 4%
• Total motility: 70%
What other investigations should be consid-
ered?
The clinical presentation with dysmenor-
rhoea, chronic pelvic pain, and deep dyspareu-
nia raise the possibility of pelvic pathology. She
should be offered a laparoscopy and dye test in
MIMS JPOG 2019 VOL. 45 NO. 2 55
preference to HSG to assess tubal patency as this
procedure will also to diagnose or rule out pelvic
pathology such as endometriosis and adhesions.
Bilateral tubal patency was demonstrated.
Deep deposits of endometriosis were noted on
both uterosacral ligaments, and superficial de-
posits were also noted on the surface of both ova-
ries. It was possible to ablate all visible deposits
of endometriosis at the time of the laparoscopy
because consent for this had been taken in ad-
vance of the procedure.
Endometriosis is a common condition al-
though the true prevalence in the general popula-
tion is unknown. Many women with endometriosis
are asymptomatic and conceive spontaneously.
Commonly, endometriosis presents with pelvic
pain, dysmenorrhoea, heavy menstrual bleeding,
dyspareunia, and subfertility. Endometriosis is 6–8
times more common in women experiencing sub-
fertility and is found in approximately 7% of patients
undergoing laparoscopic sterilization. Most often,
a diagnosis of endometriosis is made on clinical
grounds. Ultrasound imaging is helpful in identify-
ing endometriomas, and laparoscopy remains the
gold standard for diagnosing endometriosis.
Although endometriosis is more common
in subfertile women, a causal relationship has
not been clearly established. The time to natural
conception in women with minor endometriosis
is longer compared with those with unexplained
subfertility, suggesting that endometriosis may be
a contributing factor.
How does endometriosis contribute to
subfertility?
Multiple mechanisms have been postulated to
explain the role of endometriosis in subfertility.
Inflammation leading to adhesion formation can
lead to tubal dysfunction or blockage as well as
interfere with ovulatory activity.
Impaired immunological activity and inflam-
mation of the pelvic organs may interfere with
peritoneal fluid composition, follicular develop-
ment, ovulation, fertilization, early embryo de-
velopment, and implantation. Interference with
56 MIMS JPOG 2019 VOL. 45 NO. 2
Practice Points
• All subfertile couples should be encouraged to address lifestyle
factors as part of general health measures, and to improve fertility.
• Counselling should be considered to address the emotional and
psychological effects of infertility.
• When and how to investigate the subfertile couple should be
individualized.
• Male and female factors should be investigated.
• Medical treatment of endometriosis does not improve fertility.
follicular development may lead to poor oocyte
quality. Endometriomas have been shown to be
associated with a reduction in the number of pri-
mordial follicles thus reducing ovarian reserve.
Coital frequency is significantly affected by pel-
vic pain and dyspareunia and this reduces the
chances of conception.
Treatment for endometriosis
associated subfertility
Medical treatment of endometriosis does not
improve fertility. Surgical ablation or excision of
mild and minor endometriosis has been shown
to be beneficial. For moderate and severe endo-
metriosis surgery may improve fertility, although
this has not been subject to randomized studies.
Surgery in these cases should be undertaken by
appropriately trained and experienced gynae-
cologists. Laparoscopic surgery is the preferred
approach. The benefits on fertility in such cas-
es may be due to restoration of pelvic anatomy,
and amelioration of pain symptoms leading to
increased coital frequency.
Management of endometrioma identified
in subfertile patients can be challenging. The
RCOG has recently published a scientific impact
paper to offer guidance. Expectant management
is appropriate for young couples where an en-
dometrioma is identified with no suspicion of
malignancy. The decision to operate should be
individualized bearing in mind the potential for
damage to the ovarian cortex. Surgery should be
GYNAECOLOGY PEER REVIEWED
considered for patients with significant pain and
for cysts greater than 3 cm in size.
For moderate or severe cases, or where con-
ception fails following surgical management, IVF
remains the mainstay of management for subfer-
tile women with endometriosis.
CONCLUSION
Failure to conceive is common and has a neg-
ative impact on psychological and emotional
wellbeing. Treatment for infertility is also ex-
tremely stressful. All staff involved in the man-
agement of infertile couple should be sensitive
to this. Formal counselling services should be
available.
Female and male factors contribute al-
most equally in the failure to conceive and both
should be investigated. Expectant management
and lifestyle changes should be advised where
appropriate.
Surgery for minor degrees of endometri-
osis improves conception rates. Patients with
endometriomas greater than 3 cm and signifi-
cant pain symptoms should be considered for
surgery by suitably trained gynaecologists.
FURTHER READING
1. Bereir Mamoun, Coughlan Carol. The subfertile couple Obstetrics. Gy-
naecol Reproductive Med 2016; 26: 210–5.
2. Jayaprakasan K, Becker C, Mittal M, on behalf of the Royal College
of Obstetricians and Gynaecologists. The effect of surgery for endo-
metriomas on fertility. Scientific impact paper No. 55. BJOG 2017; 125:
e19–28.
3. Karavolos S, Stewart J, Evbuomwan I, McEleny K: Assessment of
the infertile male. The Obstetrician and gynaecologist:https://doi.
org/10.1111/j.1744-4667.2012.00145.x.
4. Nandi A, Homburg R. Unexplained subfertility: diagnosis and man-
agement. Obstet Gynaecol 2016; 18: 107–15. https://doi.org/10.1111/
tog.12253.
5. NICE guidelines: Assessment and treatment for people with fertility
problems. https://www.nice.org.uk/guidance/cg156.
6. Practice Committee of the American Society for Reproductive Medi
Medicine. Endometriosis and infertility: a committee opinion. Fertil
Steril 2012 Sep; 98: 591–8. Epub 2012 Jun 15.
7. Sharma R, Biedenharn KR, Fedor JM, Agarwal A. Lifestyle factors and
reproductive health: taking control of your fertility. Reprod Biol Endo-
crinol 2013 Jul 16; 11: 66. https://doi.org/10.1186/1477-7827-11-66.
© 2019 Elsevier Ltd. All rights reserved. Initially published in Obstetrics,
Gynaecology and Reproductive Medicine 2019;29(4):105–110.
About the authors
David K Gatongi is a Consultant Gynaecologist at Victoria Hospital, Kirk-
caldy, Fife, UK. Conflict of interest: none.
D Rennie Urquhart is a Consultant Gynaecologist at Victoria Hospital,
Kirkcaldy, Fife, UK. Conflict of interest: none.
Tahir Mahmood is a Consultant Gynaecologist at Victoria Hospital, Kirk-
caldy, Fife, UK. Conflict of interest: none.
OBSTETRICS PEER REVIEWED MIMS JPOG 2019 VOL. 45 NO. 2 57

Management of a
Woman with a Previous
Spontaneous Preterm Birth
Charlotte Oyston, MB ChB BMedSci (Hons) Dip OMG PhD; Katie Groom, MB BS BSc FRANZCOG PhD CMFM

Preterm birth is an important cause of neonatal morbidity and mortality and has
long-term adverse health consequences. Worldwide, close to 15 million babies
are born preterm each year, and there is no sign that the rate of preterm birth is
slowing. A history of a previous spontaneous preterm birth is a significant risk
factor for a subsequent spontaneous preterm birth, identifying these women pro-
vides an opportunity to optimize care in future pregnancies. Antenatal identifica-
tion of women at the highest risk of preterm birth is challenging, as tests that ac-
curately identify asymptomatic women who go on to deliver preterm are lacking.
Furthermore, the short- and long-term benefits of interventions such as cerclage
and progesterone remain unclear. Research is underway to develop biomarkers
that can accurately predict women who will deliver preterm. However, without
effective strategies that diminish rates of preterm birth and improve perinatal
outcomes, the clinical role of these tests is less well defined.

INTRODUCTION tation. Preterm birth is a leading cause

Preterm birth is defined as birth occur- of perinatal morbidity and mortality.
ring prior to 37 completed weeks of ges- Worldwide, almost 15 million babies are
58 MIMS JPOG 2019 VOL. 45 NO. 2
born preterm, and over 1 million die from com-
plications of prematurity each year. Those that
survive the neonatal period have greater rates
of respiratory disease, visual impairment, deaf-
ness, and neurodevelopmental disability com-
pared with their term peers. Those born preterm
are also more likely to develop noncommunica-
ble diseases such as obesity, type II diabetes,
hypertension, and cardiovascular disease in
adulthood. Despite extensive ongoing research
into causes, predictors and treatments for pre-
term birth, the rate of preterm birth has not fallen,
even increasing in some countries.
Preterm birth may be considered as indi-
cated (iatrogenic) or spontaneous. Indicated
birth accounts for at least one-third of preterm
deliveries and occurs when complications arise
that put mother or foetus at risk unless delivery
is expedited (eg, severe foetal growth restric-
tion, massive antepartum haemorrhage, or se-
vere pre-eclampsia). The remainder of preterm
births are considered spontaneous, including
those preceded by preterm pre-labour rupture of
membranes. Spontaneous preterm labour can
be initiated by a range of pathology, including
infection, uterine stretch, placental ischaemia,
haemorrhage, and other inflammatory causes.
This is likely to explain why, despite considerable
healthcare advances, successful prediction and
prevention of spontaneous preterm birth has re-
mained so elusive, as preterm birth represents
a final common pathway of a heterogeneous
group of conditions, each predictor or interven-
tion is likely to only identify or improve outcomes
for a subset of cases.
There are many risk factors for preterm
birth. However, a prior history of spontaneous
preterm birth is the most significant and con-
sistently identified clinical risk factor, and the
identification of women with a history of preterm
birth gives an opportunity to optimize care for
subsequent pregnancies. This article will review
and discuss risk assessment and management
of singleton pregnancies where there is a history
of a prior preterm birth.
OBSTETRICS PEER REVIEWED
CASE 1
Preconception risk prediction for
women with a previous preterm birth
Mrs PT is a 32-year-old G3P1 who attends
your clinic pre-pregnancy. Her notes docu-
ment an elective early surgical termination in
her first pregnancy, and a previous delivery at
27 weeks, with her baby spending 9 weeks in
the neonatal unit. She is considering becoming
pregnant again and is extremely anxious. She
wants to know the likelihood of this baby being
born preterm.
Risk scoring tools based on clinical histo-
ry alone perform poorly. However, details of the
circumstances leading to the previous preterm
birth may aid prediction and so a full history and
case note review of the previous births is impor-
tant to assess future risk. There may be areas
where there is opportunity to reduce or eliminate
risk factors for recurrent preterm birth as well as
other pregnancy complications.
Number and timing of previous
deliveries
The risk of recurrent spontaneous preterm birth is
dependent on the aetiology of the previous pre-
term birth, the number of previous preterm births,
and the severity of prematurity. The likelihood of
having a preterm birth in a given pregnancy in-
creases with the number of previous preterm
births, with a reducing chance of delivery after 33
weeks of 83, 86 and 68% after 1, 2, or 3 prior pre-
term births. Risk of preterm birth also increases
as the gestational age of previous preterm births
declines, with the greatest risk for those with a
previous delivery at less than 28 weeks’ gestation.
If the previous preterm delivery was an indicated
delivery, the risk of recurrence will be related to
the recurrence risk of the condition leading to the
indicated delivery. A history of previous indicated
preterm birth is also associated with an increased
risk of spontaneous preterm birth in subsequent
pregnancy. Presumably this is due to a shared
aetiology (such as placental ischaemia) between
OBSTETRICS PEER REVIEWED
Cervical conization has the most consistent and strongest association with preterm birth.
pregnancy complications such as pre-eclampsia
and preterm birth. The timing of the last pregnan-
cy should also be reviewed, as risk of early deliv-
ery increases with reducing interpregnancy inter-
val. An analysis of 6,181 women with a previous
preterm birth demonstrated that after adjusting for
confounding factors, those with an interpregnan-
cy interval of less than 6 months had the highest
increase in risk of preterm delivery (44% increase
in risk of recurrent preterm birth), those with an
interval of 6–12 months had a modest increase,
and there was no increase in risk of recurrent pre-
term birth with an interpregnancy interval of 12–18
months compared with the risk of those with an
interval of 18 months or more.
History of cervical surgery or trauma/
uterine instrumentation
Women undergoing excisional treatment for cer-
vical dysplasia have an increased risk of preterm
MIMS JPOG 2019 VOL. 45 NO. 2 59
birth, although the mechanism(s) mediating this
increase in risk are unclear. One hypothesis is
that these procedures reduce the mechanical
support of the cervix which may then increase
susceptibility to cervical insufficiency, or spon-
taneous loss of the cervical mucous plug lead-
ing to ascending infection. Cervical conization
has the most consistent and strongest associ-
ation with preterm birth. Women with a history
of conization are 2–3 times more likely to have
a preterm birth than healthy controls, and those
conceiving within 2–3 months of conization or
large conisation (>1 cm depth) may have the
greatest risk. Meta-analyses also suggest an
increased risk of preterm birth with other exci-
sional therapies – such as large loop excision of
the transformation zone (RR, 1.70 compared to
healthy controls). Although many studies within
the meta-analyses use healthy controls as the
comparison group, an increased risk of preterm
60 MIMS JPOG 2019 VOL. 45 NO. 2
birth with all excisional therapies remains – albeit
attenuated – when women undergoing cervical
treatment are compared to those who had been
diagnosed with precancerous lesions, but not
treated. This suggests that the increase in risk
may be in part due to the underlying pathology
of the precancerous lesion, as well as the cervi-
cal procedure itself.
Cervical dilation and curettage for miscar-
riage or termination of pregnancy also increase
the risk of spontaneous preterm birth in subse-
quent pregnancies. While some large cohort
studies have found no significant difference in
rates, more recent good quality studies have
demonstrated a small but significant increase
in risk of spontaneous preterm birth after these
procedures, with odds ratios (ORs) of up to 1.8
and evidence that the risk of preterm birth in
subsequent pregnancies rises with the number
of procedures performed.
Presence of congenital uterine
anomalies
Congenital uterine anomalies are found more
commonly in women with a history of second tri-
mester loss or preterm birth, with a prevalence of
up to 25% compared with 6% in women from an
unselected population. The risk of preterm birth
varies with the type of uterine anomaly, women
with a uterine didelphys or a septate uterus have
the highest risk with up to 33% of pregnancies
ending in preterm delivery. It has long been
thought that the increased rate of preterm birth
results from a reduced volume and distensibili-
ty of the uterine cavity. However, it is most like-
ly that women with uterine anomalies may also
have a cervical anomaly which contributes to
cervical insufficiency in pregnancy.
Use of assisted reproductive
technologies
Several systematic reviews have shown an in-
crease in risk of preterm delivery in women un-
dergoing IVF treatment compared with those
who conceive naturally, with the risk of preterm
OBSTETRICS PEER REVIEWED
delivery doubling for delivery prior to 37 weeks
and tripling for delivery prior to 33 weeks for
singleton pregnancies. It is unclear whether this
increase in risk results are from the fertility treat-
ment itself, underlying maternal factors associat-
ed with infertility, or iatrogenic bias in the care of
these pregnancies.
Demographic, socioeconomic,
psychosocial, and lifestyle factors
Women who are obese or significantly under-
weight pre-pregnancy are at increased risk of
preterm delivery, as well as other pregnancy
complications. A large meta-analysis of data
from over 1 million individuals found that wom-
en from developed countries with a pre-preg-
nancy body mass index (BMI) of <18.5 kgm-2
are more likely to have a preterm birth – either
spontaneous or indicated – compared with
women with a BMI in the normal range (RR,
1.22). Women with a BMI of ≥35 kgm-2 also ap-
pear to be at increased risk of indicated preterm
birth (OR, 1.5–1.8), which may be partially ex-
plained by an increased prevalence of chronic
disease (such as hypertension or diabetes) in
this population.
Race and ethnicity are important risk factors
for preterm birth. After adjusting for risk factors
such as age, education, and parity, black women
have a two- to three-fold higher risk of preterm
birth compared with non-black women. The ae-
tiology of this association is unclear but is pos-
sibly interlinked with other lifestyle factors and/
or social disparities; rates of preterm birth are
increased amongst socioeconomically deprived
women, women who have high levels of anxiety
or perceived stress or low levels of support, are
at the extremes of maternal age, and those who
smoke, consume alcohol, and use illicit drugs
during pregnancy.
PRECONCEPTION STRATEGIES TO
REDUCE RISK OF PRETERM BIRTH
What advice should be given and what medical
or surgical interventions are available precon-
OBSTETRICS PEER REVIEWED MIMS JPOG 2019 VOL. 45 NO. 2 61

ception that could reduce the risk of preterm

delivery?
There are few preconception interventions
that improve outcomes in preterm birth. Many
risk factors for preterm birth are nonmodifiable,
and those that can be modified only minimally
increase absolute risk and are poorly predictive
of subsequent preterm birth. When assessing the
impact of strategies to prevent preterm birth, it is
important to assess impact on perinatal morbidity
and mortality, as in some instances, preterm birth
may represent a mechanism through which the
foetus escapes an adverse intrauterine environ-
ment; prolonging these pregnancies may be as-
sociated with neonatal harm rather than benefit.

Preconception advice and medical

interventions
Ideally, counselling and assistance regarding
optimal pregnancy spacing, the benefits of main-
taining a healthy weight, and abstinence from
smoking, alcohol, and drugs should be provided
in the preconception period. Smoking cessation
(and limiting passive exposure) is of particular
importance, as this is the largest modifiable risk
factor for preterm birth. At an individual level,
providing behavioural counselling with nicotine
replacement therapy (safer than continuing to
smoke, and associated with increased rates
of cessation) is the most effective strategy for
smoking cessation. Incentive schemes (where
incentives such as cash or vouchers are used
to encourage cessation), also improve cessation
rates. At a population level, clinicians should
support and promote smoke-free environments:
rates of preterm birth reduce by an estimated
10% after introduction of smoke-free legislation.
Medical management of chronic medical
conditions such as diabetes and hypertension
should be optimized; although this may not be
associated with reductions in rate of sponta-
neous preterm birth, optimal control of chronic
conditions may lower the risk of additional preg-
nancy complications, and therefore the rates of
indicated preterm birth, as well as potentially
Cervical dilation and curettage for miscarriage or termination of pregnancy also
increase the risk of spontaneous preterm birth in subsequent pregnancies.
leading to better long-term outcomes for mother
and baby.
Preconception surgical interventions
As uterine anomalies are associated with in-
creased risk of preterm birth, it seems logical
that normalizing uterine anatomy would be as-
sociated with a lowering of preterm delivery. For
women with a septate uterus, there is evidence
from observational studies that pregnancy out-
comes (including preterm birth rates) may be
improved with hysteroscopic resection of the
septum. However, given the paucity of ade-
quately powered randomized studies compar-
ing outcomes of hysteroscopic resection with
no treatment, clear recommendations as to
which women are appropriate candidates for
this procedure cannot be made. Similarly, oth-
er surgeries aimed at normalizing anatomy in
women with different congenital uterine malfor-
mations have been described, but evidence is
limited to case reports and small observational
62 MIMS JPOG 2019 VOL. 45 NO. 2
studies. Where surgery is considered for wom-
en with a uterine anomaly, the benefits and risks
should be carefully considered on a case-by-
case basis.
Cervical cerclage is a procedure where
a nonabsorbable suture is placed around the
cervix to reduce the risk or preterm delivery.
The mechanism of action is thought to be
through increasing mechanical support, or
through reducing the risk of ascending infec-
tion through cervical lengthening or retention
of the mucous plug. Cerclage is typically per-
formed vaginally in the second trimester for at-
risk pregnancies (the indications for cerclage
placement during pregnancy are discussed in
more detail in the section “Antenatal strategies
to reduce the risk of preterm birth” below).
Abdominal placement of a cervical suture via
laparotomy or laparoscopy is sometimes car-
ried out preconception in women with a very
short or scarred cervix (where transvaginal
placement may be difficult), or women with a
history of a failed vaginally-placed cervical su-
ture. Abdominal cerclage is associated with a
higher incidence of serious maternal operative
complications than vaginal cerclage (3.4% vs
0%) and their use should be reserved for those
at highest risk with a previously failed vaginal
cerclage. A systematic review of 13 case se-
ries and one controlled nonrandomized study
of transabdominal cervical cerclage in women
with a history of failed transvaginally-placed
cervical cerclage found a lower risk of perina-
tal death or delivery before 24 weeks in women
who had a transabdominal cerclage compared
with those who had a repeat vaginally-placed
cerclage (6% vs 12.5%). The MAVRIC trial is
the first randomized trial comparing abdominal
with vaginal cerclage. Preliminary data sug-
gests that for women with a previously unsuc-
cessful vaginally-placed cervical cerclage, a
transabdominally-placed cerclage is superior
to repeat vaginally-placed cerclage in reduc-
ing risk of delivery prior to 32 weeks and foetal
death.
OBSTETRICS PEER REVIEWED
CASE 2
Antenatal tests for prediction of
preterm birth
Ms S is a 24-year-old G3P2 with a history of two
previous preterm deliveries at 32 weeks. You
see her in clinic at 12 weeks and she asks if
there are any tests she can have that will detect
whether she will go into labour early.
What tests can be used in pregnancy
to help stratify the risk of preterm delivery in
asymptomatic women?
Accurately identifying women who are
at high risk of delivering preterm provides an
opportunity to optimize the timing and admin-
istration of interventions such as antenatal cor-
ticosteroids, MgSO4, and arrange for transfer to
a centre with tertiary neonatal facilities. A neg-
ative test also provides reassurance for those
who are unlikely to deliver preterm. Tests that
are currently available in clinical practice for the
prediction of spontaneous preterm birth include
sonographic cervical length measurement, and
the vaginal biomarkers, fetal fibronectin (fFN),
placental alpha macroglobulin-1 (PAMG-1), and
cervical phosphorylated insulin-like growth fac-
tor binding protein-1 (phIGFBP-1). Of the bio-
markers tests, only fFN has published data to
support use in asymptomatic women.
Fetal fibronectin
The fFN is a glycoprotein found in the amniotic
fluid, placenta, and between the chorion and de-
cidua. It is described as a “glue” between cho-
rion and decidua and is not normally detectable
in vaginal secretions after fusion of decidua and
foetal membranes. The presence of fFN in vag-
inal secretions after 18 weeks occurs following
disruption of the choriodecidual interface due to
inflammation or mechanical forces and is asso-
ciated with an increased risk of preterm delivery.
A swab taken from the posterior fornix can be
used to detect the presence of fFN in a bedside
test, with results given qualitatively (a positive
corresponding to a concentration of >50 ng/
OBSTETRICS PEER REVIEWED
mL, or negative <50 ng/mL), or quantitatively.
Compared with women with threatened preterm
labour, fFN has a lower sensitivity for the predic-
tion of preterm birth in asymptomatic women
(78–89% compared with 68–76%), although the
specificity appears similar for both asymptomatic
(88–89%), and symptomatic women (86%). Cur-
rently, the greatest utility for fFN is in its negative
predictive value for women symptomatic of pre-
term labour, and the reassurance that imminent
delivery is highly unlikely. It is not clinically useful
as a stand-alone test for prediction of preterm
birth in asymptomatic women with or without
other risk factors for preterm birth. Quantitative
fFN shows an improved prediction of preterm
birth compared with qualitative testing. The risk
of birth before 35 weeks increases with increas-
ing levels of fFN from >20–300 ng/mL. Using a
threshold of 10 ng/mL results in a higher sensi-
tivity for prediction of preterm labour and when
combined with cervical length measurement, is
a more cost-effective approach to identifying the
symptomatic women at greatest risk of preterm
birth (see below).
Phosphorylated insulin-like growth
factor binding protein-1
The phIGFBP-1 is a protein secreted by decidual
cells. Detachment of foetal membranes from the
decidua causes leakage of phIGFBP-1 into vag-
inal secretions. A qualitative bedside test (Actim
PartisTM)is commercially available. As for fFN,
this test is measured from sections obtained on
a vaginal swab. Like fFN, phIGFBP-1 has better
negative predictive value than positive predictive
value for preterm birth in symptomatic women.
Its predictive accuracy in asymptomatic women
is limited, with a recent meta-analysis suggest-
ing a pooled positive likelihood ratio of 14–47%,
and negative likelihood ratio of 76–93% for pre-
term delivery.
Placental alpha microglobulin-1
PAMG-1 is a large glycoprotein synthesized by
decidual cells. PAMG-1 is found in amniotic fluid.
MIMS JPOG 2019 VOL. 45 NO. 2 63
Its detection in the vaginal secretions is nor-
mally low but has been used to detect ruptured
membranes in a bedside test marketed as Amn-
isureTM. More recently, studies have assessed the
role of PAMG-1 in detecting preterm labour inde-
pendently from rupture of membranes in women
with signs or symptoms of preterm labour. The
test appears to perform with high sensitivity and
specificity for symptomatic women. However,
as these studies were of relatively small sample
size, further research is required to confirm the
test’s accuracy, and to clarify its role in the as-
sessment of women who are asymptomatic.
Cervical length measurement
Large prospective studies have consistently
observed an increased risk of preterm birth for
women with a shortened cervix during preg-
nancy, and that the risk of preterm delivery in-
creases with decreasing cervical length. Trans-
vaginal ultrasound is the gold standard method
for visualizing and measuring cervical length,
with high likelihood of obtaining measurements
and low interobserver variability. The alternative
transabdominal approach may be affected by
maternal bladder filling, and is associated with
a lower likelihood of obtaining adequate meas-
urements. Cervical length measurements are
performed over a 5-minute period with an empty
maternal bladder and in the absence of undue
probe pressure. The cervical length is taken as
the shortest measurement that displays the land-
marks of internal, external os, cervical canal. As-
sessment of cervical length in women at high risk
of preterm birth is usually performed between 14
and 24 weeks; risk of spontaneous preterm birth
increases as cervical length decreases and ges-
tational age decreases.
The National Institute of Child Health and
Development (NICHD) Preterm Prediction study
was the first large prospective study to evaluate
cervical length as a predictor for preterm birth
in asymptomatic women. Cervical length was
measured in 3000 women at 22–24+6 weeks.
Compared with women with a cervical length
64 MIMS JPOG 2019 VOL. 45 NO. 2
of more than 40 mm (the 75th centile), women
with a cervical length less than 40, 35, 26, or
13 mm (75th, 50th, 10th, or 1st centile) had a
significantly increased risk of delivery prior to 35
weeks (relative risk, 2.4, 3.8, 9.5, and 14 respec-
tively). It should be noted, however, that less
than half the women with the shortest cervices
(less than 15 mm) delivered prior to 35 weeks.
These findings have since been replicated in
other large prospective studies.
Combined fFN and cervical length
measurements
The combination of transvaginal cervical length
measurement and fFN testing is better at pre-
dicting spontaneous preterm delivery compared
with fFN alone. A subsequent analysis of NICHD
data looked at the effect of cervical length and
fFN at 24 weeks on the risk of preterm delivery in
women with a history of previous preterm birth.
In women with a previous preterm birth, both
cervical length and fFN test results at 24 weeks
modified the risk of preterm delivery. The highest
risk of preterm delivery was in women with a pos-
itive fFN and a cervical length <25 mm (64% risk
of delivery at <35 weeks). The risk was lowest for
women with a negative fFN and a cervical length
of 35 mm or more (7% risk of delivery prior to 35
weeks). Quantitative (q)fFN can also be used in
conjunction with cervical length measurement.
In a study of asymptomatic women with risk fac-
tors for preterm delivery, women with a mid-tri-
mester cervix length <25 mm had a 9.5% risk of
delivery at <34 weeks when qfFN was <10 ng/
mL. The risk of delivery at <34 weeks increased
to 55% for those with levels >200 ng/mL. A risk
prediction tool for both symptomatic and high-
risk asymptomatic women has been developed,
combining qfFN, cervical length, and past ob-
stetric history. This tool has the advantage that
it provides an individualized estimate of preterm
delivery, rather than just a summary estimate of
risk. The algorithm is available to clinicians as a
smart phone app; further information is availa-
ble at www.quipp.org.
OBSTETRICS PEER REVIEWED
ANTENATAL STRATEGIES TO REDUCE
THE RISK OF PRETERM BIRTH
What antenatal strategies are proven to be effec-
tive at reducing the risk of preterm birth in wom-
en with a prior history of preterm birth?
Cervical cerclage
A cervical cerclage is typically performed in the
second trimester for one of three indications: a
history of recurrent preterm losses (history indi-
cated), cervical shortening detectable on ultra-
sound (ultrasound indicated), or in women pre-
senting with signs of cervical dilation or visible
foetal membranes (rescue cerclage). The most
common techniques for cerclage placement
are the Shirodkar and McDonald techniques,
both of which result in a purse-string suture
around the cervix. The Shirodkar technique
describes dissection of the vaginal mucosa
anteriorly and posteriorly to expose the cervix
as close to the level of the internal os as possi-
ble, whereas the McDonald technique does not
conventionally involve dissection. Many studies
of cervical cerclage do not stipulate which tech-
nique has been used and there are no prospec-
tive studies evaluating pregnancy outcomes by
comparison of the two techniques, so choice
of technique is generally governed by sur-
geon preference. There is also little evidence
to guide choice of suture material. Traditional-
ly, a braided filament has been the suture of
choice, due to the perceived superior strength,
and ease of removal compared to monofila-
ment sutures. However, the multifilament braid-
ed suture favours bacterial colonization, and
has been associated with increased infectious
morbidity and poorer tissue healing in non-ob-
stetric settings. There is concern that use of
braided filaments for cerclage may introduce a
route through which preterm birth is stimulated.
The C-STITCH study is a randomized trial that
is currently recruiting, and aims to assess the
effect on pregnancy and neonatal outcomes of
monofilament versus braided suture material in
women undergoing cerclage.
OBSTETRICS PEER REVIEWED
History indicated cerclage
In an international multicentre study, 1292 wom-
en were randomized to cerclage or no cerclage
when there was clinical uncertainty as to whether
or not to perform a cervical cerclage. The cer-
clage group had significantly fewer deliveries
prior to 33 weeks (number needed to treat to
prevent one delivery <33 weeks = 25), howev-
er subgroup analysis showed that only women
with at least three previous pregnancies ending
prior to 37 weeks benefited from cerclage. In this
group, the number of preterm deliveries prior to
33 weeks was halved; however, no differences in
neonatal outcomes were detected. It is possible
that this study underestimated the magnitude of
benefit of cerclage, as it excluded women who
were potentially the most likely to benefit from
cerclage – those that clinicians were not un-
certain as to whether cerclage would provide
benefit.
Ultrasound indicated cerclage in
women with a history of preterm birth
A meta-analysis using individual patient level
data compared cerclage with expectant man-
agement in women with a shortened cervix (<25
mm), and found that cerclage was associated
with a reduction in preterm birth before 35 weeks
in those with singleton pregnancies and a histo-
ry of prior preterm birth or second trimester loss
(RR, 0.63). A further randomized study of wom-
en with a history of preterm birth and a cervical
length of <25 mm showed a reduction in prev-
iable delivery and perinatal mortality, although
there was no reduction in delivery in less than 35
weeks unless cervical length was below 15 mm.
Rescue cerclage
Ideally, women with a previous preterm birth
should be offered elective cervical cerclage or
serial surveillance of cervical length (depending
on prior history), thereby avoiding a presenta-
tion with cervical dilatation. However, in the event
that cervical dilatation occurs, a rescue cerclage
should be considered. A small randomized study,
MIMS JPOG 2019 VOL. 45 NO. 2 65
comparing rescue cerclage with expectant man-
agement (1 week of broad-spectrum antibiotic
therapy and bed rest until 30 weeks) found cer-
clage delayed delivery by an average of 4 weeks,
and had a reduction in delivery prior to 34 weeks,
perinatal morbidity, and a trend towards reduced
perinatal mortality. Similar delays have been seen
in small nonrandomized studies. Cerclage may
be less likely to be effective with significant mem-
brane prolapse (beyond the external os), cervical
dilatation of more than 4 cm, and should never
be performed when there are signs or symptoms
of chorioamnionitis, foetal compromise, death or
foetal anomaly not compatible with life, PPROM,
or ongoing vaginal bleeding.
Cerclage or progesterone?
Cerclage requires a skilled operator and is asso-
ciated with maternal risks relating to anaesthesia
and surgery (cervical laceration, fever, bleeding,
chorioamnionitis, and ruptured membranes).
Therefore, a question of considerable interest is
whether cerclage is better at preventing preterm
birth than other treatments. There is a paucity
of data comparing progesterone to cervical cer-
clage (or pessary). A recently published indirect
meta-analysis (comparing interventions head-
to-head through a common comparison group)
has suggested progesterone is more effective at
preventing preterm delivery (<34, <37 weeks)
than cerclage. The SuPPoRT trial is currently
randomizing women with a cervix <25 mm on
mid trimester ultrasound to cervical cerclage,
progesterone, or pessary to determine the rela-
tive efficacy of these interventions on pregnancy
duration and neonatal outcomes. There is cur-
rently insufficient evidence to support combined
use of multiple (cerclage and progesterone, pro-
gesterone and pessary) vs single interventions.
Progesterone
Progesterone is a key component in the main-
tenance of pregnancy. It has anti-inflammatory
properties and plays a role in the prevention of
cervical ripening and maintenance of myometrial
66 MIMS JPOG 2019 VOL. 45 NO. 2
Progesterone and cervical cerclage are interventions which may reduce the
risk of preterm delivery, in certain groups of high-risk women.
quiescence. There have now been over 40 pub-
lished randomized trials studying the efficacy of
progesterone in reducing preterm birth. The two
main types of progesterone studied are natural
progesterone (rapidly absorbed via vaginal mu-
cosa) and 17 alpha hydroxyprogesterone capro-
nate (which has a longer half-life and is admin-
istered as weekly intramuscular injections). Of
the two, vaginal progesterone is cheaper, and
appears to be more effective.
Meta-analyses of earlier randomized tri-
als suggested a benefit of progesterone in the
prevention of preterm birth in women with a
shortened cervix, or history of a previous pre-
term birth. The use of progesterone for preterm
birth prevention has been endorsed by clinical
guidelines groups, including the National In-
OBSTETRICS PEER REVIEWED
stitute for Health and Care Excellence. More
recently, two large randomized studies (OPPTI-
MUM and PROGRESS) have shown no benefit
of vaginal progesterone in reducing preterm
birth, composite neonatal morbidity and mor-
tality, or childhood cognitive and neurosenso-
ry outcomes at age of 2 years. A subsequent
metanalysis which included data from the
OPPTIMUM study concluded that progesterone
reduced preterm birth, and neonatal morbidity
and mortality when given antenatally to women
with a shortened cervix. However, there remains
debate regarding the specific conditions where
progesterone may reduce risk of preterm birth,
and the optimal formulation, dose, route also
remain unclear. The Evaluating Progestogens
for Prevention of Preterm birth International
Collaborative is an independent meta-analysis
of individual participant data from the totality of
RCTs of progesterone in the prevention of pre-
term birth. Publication is expected in late 2018
and will hopefully clarify whether there are par-
ticular subgroups of pregnant women who may
benefit from progesterone therapy.
Cervical pessary
Cervical pessaries are proposed to prevent pre-
term labour via the alteration of the inclination of
the cervical canal relative to the uterus (resulting
in a more acute uterocervical angle), preventing
direct pressure on the cervix and foetal mem-
branes at the level of the internal os. Pessaries
are a “one-off” treatment, well tolerated with min-
imal side effects and are of relatively low cost,
they are an attractive alternative to cerclage and
progesterone treatments, particularly for wom-
en from countries where resources are limited.
The first randomized controlled trial using Ara-
bin pessaries for the prevention of preterm birth
in women with a shortened cervix detected on
a mid-trimester ultrasound scan demonstrated
reduced rates of preterm delivery and a reduc-
tion in composite neonatal adverse outcomes.
Subsequent randomized studies have shown
conflicting results, with a recent meta-analysis
OBSTETRICS PEER REVIEWED
suggesting that pessary use does not reduce
rates of preterm birth or improve perinatal out-
comes in women with a shortened cervix. In-
terestingly, there appears to be an effect of
clinician-learning curve on the effectiveness of
pessary treatment, with significant differenc-
es in outcomes between those recruited ear-
ly and those recruited later to trials of pessary.
Further randomized trials are underway, as
strong evidence of efficacy is lacking, and ad-
equate training in operation and insertion is
needed to ascertain whether cervical pessaries
can prolong gestation and improve perinatal
outcomes for women at risk of preterm birth.
Preterm birth clinic
Despite a growing body of evidence supporting
the use of cervical cerclage and progesterone for
the prevention of preterm birth, the counselling,
availability and clinical use of these interventions
is inconsistent. In obstetrics (and many other are-
as of medicine), there is a trend toward develop-
ing specialized clinics which focus on prevention
and provide a means for consistent application
of the most up-to-date evidence-based practice.
There is limited evidence that attendance at pre-
term birth prevention clinics reduce the rates of
preterm birth, and such clinics are now an ac-
cepted part of service provision in many centres
and offer other benefits such as an opportunity
for teaching of both clinicians and patients, and
an ideal setting for further research into the aeti-
ology and prevention of preterm birth.
ANTENATAL THERAPIES WITH
INSUFFICIENT EVIDENCE OF
BENEFIT
Screening and treatment of
asymptomatic women for lower
genital tract infection
Although genital tract infection is associated with
preterm birth, there is not consistent evidence
that the screening and treatment of asympto-
matic women improves outcomes. A recent sys-
MIMS JPOG 2019 VOL. 45 NO. 2 67
tematic review found screening women in the
early second trimester and treating for candidia-
sis, bacterial vaginosis (BV), and trichomoniasis
halved the rate of delivery before 37 weeks. In
contrast, studies assessing the effect of screen-
ing and treatment of BV or trichomoniasis inde-
pendently have found that although treatments
are effective at eradicating infection, rates of pre-
term birth were either no different, or increased
compared to untreated women.
Treatment of periodontal disease
Increasing severity of periodontal disease is
associated with increasing likelihood of pre-
term birth. However, randomized controlled
trials have not found a reduction in the rate of
preterm birth when women are treated for this
condition.
Bed rest, relaxation, or stress
reduction
Although many studies have demonstrated an
association between psychological stress and
preterm birth, a limited number of studies have
assessed the effect of relaxation techniques on
preterm birth rates. The studies published use
different relaxation techniques, so are difficult to
compare directly. However, while studies show
evidence of reduced stress and anxiety scores,
they do not show evidence of reduced risk of
preterm birth. Similarly, there is no evidence that
reducing work or reducing sexual activity reduc-
es the likelihood of preterm birth.
Management of women presenting
with preterm labour
The management of women who present with
threatened preterm labour does not differ be-
tween those who have and have not had a previ-
ous preterm birth. In brief, management begins
with a careful history, examination, and inves-
tigations aimed at determining the likelihood
of preterm labour, and excluding the presence
of serious conditions in mother and baby that
require imminent delivery (eg, foetal distress,
68 MIMS JPOG 2019 VOL. 45 NO. 2
Practice Points
• Preterm birth may be considered as either spontaneous or indicated.
• 
For women with a previous indicated preterm birth, risk of
recurrence depends on the specific condition necessitating early
delivery. However, these women are also at slightly higher risk of
spontaneous preterm birth.
• For women with a previous spontaneous preterm birth, risk of early
delivery increases with the number of previous preterm deliveries
and is more likely in those who previously delivered at earlier
gestations. However, most women with a previous preterm delivery
will not deliver preterm in subsequent pregnancies.
• In a general population, risk estimates for preterm delivery can
be improved by transvaginal ultrasound measurement of cervical
length, and fFN testing. However, the role of these investigations in
women with a previous preterm birth is not well defined, and further
research is needed to clarify what optimal cut-offs are whether
available interventions provide significant benefit for those who
“screen positive”.
• Progesterone and cervical cerclage are interventions which may
reduce the risk of preterm delivery, in certain groups of high-risk
women.
placental abruption, or chorioamnionitis). Once
conditions requiring expedited delivery have
been excluded, adjunct tests such as ultrasound
assessment of cervical length (as well as de-
termining foetal presentation and growth), fFN,
phIGFBP-1, and PAMG-1 can be considered.
This allows targeted use of therapies most likely
to improve neonatal outcomes should preterm
delivery ensue: maternal administration of cor-
ticosteroids (if gestational age is <35 weeks);
maternal administration of magnesium sulphate
where delivery is imminent (if gestational age is
<30 weeks); and transfer to a unit able to pro-
vide appropriate neonatal care and the consid-
ered treatment of any precipitating causes of
labour.
SUMMARY AND CONCLUSIONS
A history of a preterm birth is an important risk
factor for spontaneous preterm birth in a subse-
quent pregnancy, although the majority of wom-
en with a previous preterm birth will deliver at
term. Risk factors for spontaneous preterm birth
have been identified, however many of these are
OBSTETRICS PEER REVIEWED
nonmodifiable, and those that can be changed –
such as smoking cessation and weight optimiza-
tion – may result in a modest reduction in risk of
preterm delivery at best. There is evidence that
interventions such as progesterone and cervical
cerclage may be beneficial in certain women at
high risk of preterm birth, however questions still
remain as to how best to screen these women,
the optimal treatment regimen, and whether
these treatments improve perinatal outcomes.
In asymptomatic women, the best biomarkers
for the prediction of preterm delivery are cervi-
cal length measurement, and detection of fFN in
the cervicovaginal secretions. However, without
effective strategies that diminish both the rate of
preterm birth and improve perinatal outcomes,
the role of these tests in the management of
these women is less well defined. These bio-
markers should be used in future research to di-
rect trials of new therapies to those at the highest
risk of preterm birth. Out of this mass of evidence
have arisen a variety of guidelines worldwide for
the prediction and prevention of preterm labour.
An example is the National Institute of Clini-
cal Excellence guideline “Preterm Labour and
Birth”, published in the UK in 2015, but there are
others.
FURTHER READING
1. Abbott DS, Hezelgrave NL, Seed PT, et al. Quantitative fetal fibronec-
tin to predict preterm birth in asymptomatic women at high risk.
Obstet Gynecol 2015; 125: 1168–76. https://doi.org/10.1097/AOG.
0000000000000754.
2. Althuisius SM, Geijn HP. Strategies for prevention – cervical cerclage.
BJOG An Int J Obstet Gynaecol 2005; 112: 51–6. https://doi.org/
10.1111/j.1471-0528.2005.00585.x.
3. Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and
causes of preterm birth. Lancet 2008; 371: 75–84. https://doi.org/
10.1016/S0140-6736(08)60074-4.
4. ‘Preterm labour and birth’ NICE guideline 25. 2015, https://www.nice.
org.uk/guidance/ng25.
5. Shennan AH. Prediction and prevention of preterm birth: a quagmire
of evidence. Ultrasound Obstet Gynecol 2018; 51: 569–70. https://doi.
org/10.1002/uog.19063.
© 2018 Elsevier Ltd. All rights reserved. Initially published in Obstetrics,
Gynaecology and Reproductive Medicine 2018;28(11–12):353–359.
About the authors
Charlotte Oyston is an Advanced Trainee in Obstetrics and Gynaecolo-
gy at Middlemore Hospital, Auckland, New Zealand. Conflicts of interest:
none declared.
Katie Groom is an Associate Professor of Maternal and Perinatal Health
at The Liggins Institute, University of Auckland and a Maternal Fetal Med-
icine Subspecialist in the Department of Obstetrics and Gynaecology at
National Women’s Health, Auckland City Hospital, Auckland, New Zea-
land. Conflicts of interest: none declared.
PAEDIATRICS PEER REVIEWED MIMS JPOG 2019 VOL. 45 NO. 2 69

Hair Loss in Infancy

and Childhood
Caroline Champagne, MBChB MSc MRCP; Noor Alwash, MBBS MRCP; Minal Patel, MBBS MRCP; Nisha Arujuna, (MBBS MRCP); Paul Farrant, MBBS BSc FRCP

Hair problems can cause considerable anxiety to both children and their parents.
This article discusses hair growth and cycling, the common presentations of hair
loss in infancy and childhood and an approach to diagnosis. This information will
help equip the reader to manage common types of hair loss in the paediatric setting.

INTRODUCTION tematic approach to evaluating hair dis-

Hair problems in children are common
and can cause considerable anxiety to
both parents and children. Conditions
such as alopecia areata and trichotillo-
mania can present in adults as well as
in children. However, in children further
consideration must be given to rarer
congenital and hereditary causes of hair
loss which can occasionally present as
part of a multisystem syndrome. A sys-
orders in children is crucial to ensure
that you make the correct diagnosis.
NORMAL HAIR GROWTH
At 9 weeks of gestational age the first
hair follicles start to appear and are
fully established by 22 weeks. Hair fol-
licles are conventionally divided into
two regions: the upper permanent part
made up of the infundibulum and isth-
70 MIMS JPOG 2019 VOL. 45 NO. 2 PAEDIATRICS PEER REVIEWED

mus and the lower cycling (growing and then

regressing) part consisting of the hair bulb and
suprabulbar region (Figure 1).
Hair follicle stem cells reside in the bulge
Infundibulum region of the isthmus. Evidence suggests that
the lower part of the hair follicle is immunolog-
Sebaceous gland ically “privileged” (a site that is not subject to
Isthmus
typical immune surveillance). The hair cycle
Pili muscle is made up of an anagen (growth) phase, fol-
lowed by a catagen (involution) phase and then
a telogen (resting) phase (Figures 2 and 3).
The hair is eventually shed through an active
Outer root sheath process called “exogen”.
Dermal sheath The hair passes through at least two hair
Hair bulb Inner root sheath cycles in utero in a wave-like synchronized
Matrix fashion from the frontal hair line. Lanugo downy
hair is replaced by vellus hair and then vellus
Dermal papilla hair is replaced by thicker terminal hair. Howev-
er, in the occipital area of the scalp, hair cycling
Figure 1. Schematic diagram of basic components of the hair follicle. is delayed until after birth, which can give rise
to a patch of occipital hair loss in the neonatal
period. Hair cycling up to this stage is synchro-
nized, thereafter the hair follicles starts cycling
independently. Throughout childhood, there
Catagen
Anagen (Regression phase) is gradual transition from vellus (soft, short,
90% scalp hair, 2-5 years
(Growing phase) unmedullated, and usually nonpigmented) to
intermediate and then terminal hairs (longer,
Sebaceous gland coarser, medullated, and pigmented).

Hair matrix Epithelial column EVALUATION OF A CHILD WITH

HAIR LOSS
Dermal papilla

History
Exogen It is important to establish whether the hair
(Exit phase) Telogen
10% scalp hairs was normal at birth, when the hair loss began,
(Resting phase) and whether this was a diffuse or patchy loss
or failure to grow. Symptoms such as itch or
Old club hair
burning are often associated with infection or
infestation (both common) or inflammation
(rare). History of teeth and nail development
should be obtained as well as problems with
heat and sweating if an ectodermal dysplasia is
suspected. Other important areas to ask about
Figure 2. Stages of the hair cycle. the history include cutaneous lesions and rash-
es, as well as the general health of the child
PAEDIATRICS PEER REVIEWED MIMS JPOG 2019 VOL. 45 NO. 2 71

and achievement of developmental milestones. Table 1. Potential Hair Pull findings

A family history of hair problems is likely to
be relevant in inherited conditions but is also
Condition Positive hair pull findings
important when considering infective causes
such as tinea capitis. Telogen effluvium Increased telogen hairs extracted from all
areas, hairs are often normal length
Alopecia areata Increased telogen hairs or dystrophic hairs
Clinical examination from affected areas
Clinical examination should include an assess-
Primary scarring Increased anagen hairs extracted
ment of the pattern and extent of hair loss. If a alopecias
patchy alopecia is apparent, it is important to Loose anagen Painless extraction of dysplastic anagen hairs
determine whether there are patent follicular os- syndrome (may lack root sheath and have a hockey stick
tia (openings where hair usually comes out of) appearance)
or whether these are lost, suggesting a scarring Short anagen Increase in telogen hairs; hairs are often short
syndrome
condition. Perifollicular erythema (redness), fol-
licular hyperkeratosis (scale around the base
of hairs), and pustules or swelling are all signs
that suggest an inflammatory process. Abnor-
malities in the skin, nails, and teeth should be
noted as well as any syndromic features.
The hair pull technique can be used to
assess hair shedding in generalized hair loss
as well as disease activity in focal conditions.
An informal hair pull comprises of passing a
hand with splayed fingers through the hair and
pulling up through the hair to see if any hairs
come away. A more formal test involves grasp-
ing a group of hairs (30–60) from a 1 cm x 1
cm area, twisting loosely, then, holding at the
base of the hairs between finger and thumb,
gently applying a tractional force at 90 degrees
from the scalp. For focal conditions, it can be
informative to grasp a few hairs from the patch
of hair loss and pull gently at 90 degrees from
the scalp. The number and type of hairs ex-
tracted may give clues to the underlying diag- Telogen Anagen
nosis (see Table 1). Anagen hairs have a pig-
mented bulb enclosed within its root sheath, Figure 3. Telogen hair with depigmented bulb and anagen hair showing
whereas telogen hairs have a depigment- pigmented bulb enclosed within its root sheath.
ed club-shaped bulb (Figure 3). A modified
hair pull test can be used to assess hair hair shaft disorders. Scanning electron micros-
breakage. copy will provide even more detailed images of
hair shafts, but expertise and availability limits
Microscopy and scalp biopsies its use. Scalp biopsies sent for both horizontal
Light microscopy of hairs trimmed at their base and vertical sectioning may give useful clues
should be used for the investigation of possible to the underlying cause but requires at least
72 MIMS JPOG 2019 VOL. 45 NO. 2
Figure 4. Triangular alopecia.
Figure 5. Triangular alopecia.
two skin biopsies and it should be avoided in
children if possible.
HAIR DISORDERS IN INFANCY
Aplasia cutis congenita
An uncommon condition characterized by are-
as of absent or scarred skin at birth. It reflects
disruption of intrauterine skin development,
and potential causes include vascular compro-
mise, trauma, intrauterine infection, or terato-
PAEDIATRICS PEER REVIEWED
genic medication. It may be incorrectly attribut-
ed to obstetric trauma such as forceps delivery
or foetal scalp electrodes application. It is typ-
ically an isolated abnormality, but can be as-
sociated with developmental anomalies or dis-
orders such as Bart syndrome, Adams-Oliver
syndrome, or Seitles syndrome.
The most common presentation is usually
a solitary erosion, deep ulceration, or scar af-
fecting the scalp. The lesion is usually located
on the vertex of the scalp lateral to the mid-
line and varies in size from 1–10 cm in diame-
ter. Distorted hair growth around the lesion is
known as the hair collar sign, which might be
associated with an underlying neural tube de-
fect. The abnormality in aplasia cutis congenita
is usually limited to the epidermis, dermis, and/
or fat. Most lesions heal spontaneously within a
few months leaving hairless scars which gener-
ally become less noticeable as the child grows.
Temporal triangular alopecia
Temporal triangular alopecia is a relatively com-
mon condition of localized non-scarring hair
loss. The majority of patients present between
2 and 6 years of age with a well circumscribed
triangular, lancet, or oval patch of alopecia in
the frontotemporal region (Figures 4 and 5).
Most lesions are unilateral with the base of the
triangle orientated forwards. On closer exam-
ination, the patches contain fine vellus hairs.
Due to the location and typical lancet shape,
the diagnosis of triangular alopecia is usually
made clinically, with alopecia areata being the
main differential.
Occipital neonatal alopecia
A type of localized non-scarring alopecia devel-
ops in the occipital region during the first few
months of life (Figure 6). It occurs due to altera-
tions in the hair cycle. Unlike hairs at other sites,
the occipital hairs don’t move into the telogen
phase until after birth and therefore shedding
in this area commonly occurs 2–3 months after
birth. Friction between the pillow and the scalp
PAEDIATRICS PEER REVIEWED MIMS JPOG 2019 VOL. 45 NO. 2 73

may contribute to the shedding. This alopecia

will resolve spontaneously. The important dif-
ferential diagnoses to be considered are pres-
sure alopecia and alopecia areata.

Atrichia congenita and atrichia with

papular lesions
Atrichia congenita is a rare condition charac-
terized by total and permanent scalp hair loss.
It may begin at birth or hair can start shedding
in infancy leading to total hair loss. Autosomal
dominant and recessive variants have been de-
scribed. It can be an isolated phenomenon or
associated with other defects such as atrichia
with papular lesions, where children develop Figure 6. Occipital alopecia courtesy of Professor Andrew Messenger, Royal
Hallamshire Hospital.
small papules on the face, neck, and scalp.

Ectodermal dysplasia
These are a group of inherited developmental
syndromes with abnormalities in at least two of
the major ectoderm derived structures. Infants
usually present with abnormalities in hair, nails,
skin, teeth, and eccrine glands. Ectodermal
dysplasia (ED) can be associated with other
abnormalities such as deafness, intellectual
developmental disorder, skeletal abnormalities,
and distinctive facies.
The alopecia can be due to hypotricho-
sis or hair shaft defects with increased fragili-
ty. Eyebrows and eyelashes may be involved.
Nails may be absent (anonychia), thickened or
Figure 7. Short anagen syndrome.
dystrophic, and teeth can have enamel defects
causing hypodontia, adontia, or peg-shaped
incisors. Abnormalities of the eccrine glands nant condition characterized by a hair defect
can result in defective sweating and impaired confined to the scalp, with no other ectodermal
thermoregulation. or systemic abnormalities. Hair may be normal
at birth with gradual progressive thinning of
MY CHILD’S HAIR WON’T GROW scalp hair with age. Marie Unna hypotrichosis
is an autosomal dominant disorder character-
Hypotrichosis ized by sparse or absent hair at birth followed
Hypotrichosis is a common feature of many in- by regrowth of coarse, wiry twisted hair during
herited syndromes with gradual development childhood, and finally, a progressive non-scar-
of sparse hair. It is common for hair to be pres- ring hair loss at puberty, often in a pattern re-
ent at birth or in infancy and then thin with age. sembling androgenetic alopecia. Other body
Hypotrichosis simplex is an autosomal domi- hair is typically absent. Autosomal recessive
74 MIMS JPOG 2019 VOL. 45 NO. 2
Monilethrix Trichorrhexis
invaginata
Pili torti Trichorrhexis
nodosa
Figure 8. Hair shaft abnormalities with increased fragility.
hereditary hypotrichosis is characterized by
sparse woolly hair associated with skin fragility
and palmoplantar keratoderma.
Loose anagen syndrome
Loose anagen is a condition effecting the an-
chorage of growing anagen hairs. Hair can be
easily and painlessly plucked from the scalp.
It classically occurs between 2 and 7 years of
age and is more common in girls with fair skin
and blond hair. Hair is normal at birth but fails
to grow long. A gentle hair pull will painless-
ly remove anagen hairs. Light microscopy of
PAEDIATRICS PEER REVIEWED
extracted hairs will reveal dysplastic anagen
hairs, often resembling a hockey stick. This
condition may resolve spontaneously with age.
Short anagen syndrome
Short anagen syndrome is a hair cycle disorder
where the hair does not grow long or need cut-
ting due to short duration of the anagen phase.
It is usually first noticed by parents around the
age of 2–4 years. The hair shaft is normal with-
out signs of breakage but the anagen phase is
shortened and subsequently, there are overall
more telogen hairs (Figure 7). Short anagen
syndrome tends to improve after puberty.
HAIR SHAFT ABNORMALITIES
Abnormal hair fibre production can produce un-
ruly hair due to hairs being irregularly shaped,
spangled hair where hair twists reflect light at
variable angles and fragile hair. Hair fragility
can lead to localized or diffuse areas of hair
loss occur due to breakage of structurally weak
hair. Hair shaft disorders are divided into those
with or without increased fragility.
Hair shaft abnormalities with increased
fragility
Trichorrhexis nodosa (TN): TN is the com-
monest hair shaft disorder. The cuticular cells
are disrupted causing the cortical cells to fray
forming a fragile node which breaks leaving a
paint-brush like tip (Figure 8). It may be con-
genital or acquired. Congenital TN may be
present at birth or appears later in the first 1–2
years of life. The breakage of hair occurs at the
proximal and distal shaft. Beard, moustache,
eyebrow, eyelashes, axillary, and pubic hairs
can be affected as well. Acquired TN occurs in
structurally normal hair exposed to excessive
trauma (heat, straightening, chemicals, sun-
light, etc). The hair can be dry, dull, or brittle
with whitish nodules at the ends. It affects the
scalp hair only, with distal shaft breakage. Ex-
cessive physical and chemical trauma must be
avoided.
PAEDIATRICS PEER REVIEWED MIMS JPOG 2019 VOL. 45 NO. 2 75

Monilethrix: An autosomal dominant disorder

caused by mutations of the genes encoding
hair keratins. It results in beading (wide and
narrow zones in the hair shaft) with increased
fragility and breakage in the narrow zones
(Figure 8). This leads to a stubble appearance
with dry and brittle hair. Topical minoxidil and
oral retinoids may help and avoidance of be-
haviours causing excessive weathering is im-
portant. There tends to be some improvement
with age.

Pili torti: A rare, congenital, or acquired con-

dition, in which the hair shaft is flattened at ir-
regular intervals and twisted 180⁰ along its axis.
(Figure 8). Not all hairs are affected. It is char-
acterized by fragile, brittle, unruly, and luster-
less hairs, due to uneven light reflection on the
twisted hair surface. In the classic form, hair is
normal at birth and is then gradually replaced by
spangled blond hair. At puberty, the hair darkens
and becomes less fragile. Pili torti can also be a
feature of other syndromes such as Menkes syn-
drome and several ectodermal dysplasias. There
is no specific treatment for this condition, but it
may improve spontaneously after puberty.
Trichorrhexis invaginata: Trichorrhexis invagi-
nata (bamboo hair – Figure 8) is a specific hair
shaft abnormality seen in patients with Nether-
ton’s syndrome and is usually associated with a
Figure 10. Uncombable hair syndrome.
distinctive rash, ichthyosis linearis circumflexa,
and atopy. Netherton’s syndrome is an auto-
somal recessive condition with variable expres-
sion that affects girls more than boys. It results
from mutations in the SPINK5 gene which
encodes the serum protease inhibitor protein
LEKTI. The hair abnormality usually becomes
noticeable in infancy with the development of
short, sparse, brittle, and fragile hair. The eye-
brows and eyelashes are usually sparse or ab-
sent. Light microscopy will show areas where
the distal hair shaft invaginates into the proxi-
mal hair shaft. The hair may improve with age
as the follicles thicken but defects in eyebrow
and body hair tend to persist.

Figure 9. Uncombable hair showing triangular hairs on microscopy and unruly “spun glass” hair.
76 MIMS JPOG 2019 VOL. 45 NO. 2
Figure 11. Woolly hair.
MY CHILD HAS UNRULY HAIR
Hair shaft abnormalities without
increased fragility
Pili annulati: This condition is characterized
by hair shafts that have alternating light and
dark bands caused by air cavities in the cor-
tex. Patches of hair have an attractive spangled
appearance with patients often describing their
hair as stripy.
About 20–80% of the hair can be affected
and is usually visible on clinical examination,
however the diagnosis is confirmed on electron
microscopy.
The condition can be inherited as an auto-
somal dominant or sporadic with patients pre-
senting anytime from infancy to adulthood.
Uncombable hair (Cheveux incoiffables, pili
trianguli et canaliculi, spun glass hair): This
disorder is inherited in either an autosomal reces-
sive or an autosomal dominant pattern, charac-
terized by triangular hairs only affecting the scalp
(Figures 9 and 10).
The abnormality may first present be-
tween 3 months and 12 years of age. While
normal in quantity and length, the hair is un-
PAEDIATRICS PEER REVIEWED
ruly with a disordered appearance and resists
being combed flat, and the hair does not grow
downward but in all directions from the scalp.
The hair is often silvery blond in colour and
typically more than 50% of the scalp hairs are
affected.
On light microscopy, the hairs have a trian-
gular shape in cross section with a longitudinal
groove. The appearance tends to become less
marked and the hair more manageable with
age with affected patients in adolescence often
having completely normal or normal textured
hair.
Woolly hair: This is tightly coiled “Afro” tex-
tured hair covering all or part of the scalp oc-
curring in non-African individuals (Figure 11).
Some patients present with a circumscribed
patch of woolly hair (woolly hair naevus).
Generalized woolly hair can be autosomal
dominant hereditary disorder or an autosomal
recessive trait. The triad of woolly hair, pal-
mar-plantar keratoderma, and cardiomyopathy
may indicate either Naxos or Carvajal disease.
Telogen effluvium: Scalp hair loss due to in-
creased telogen hair shedding can be acute,
occurring after a triggering event with spon-
taneous complete regrowth, or chronic, if the
insult is prolonged or repeated. There is usu-
ally a 2- to 3-month delay between insult and
the start of hair shedding. Common triggers in
children include high fever/infections, physical
and emotional stress, a period of anorexia/
starving, and certain medications. In a third of
cases, no trigger can be identified. Unless the
trigger is repeated, the shedding stops and re-
growth occurs by 3–6 months. A hair pull test
reveals hairs in telogen phase throughout the
scalp.
Hair shedding may be more chronic in
children with thyroid disorders, iron deficiency
anaemia, acrodermatitis enteropathica (zinc
deficiency), malnutrition, malignancy, drugs
and autoimmune disorders such as system-
PAEDIATRICS PEER REVIEWED
Figure 12. Alopecia areata ophiasis pattern.
Figure 13. Patchy alopecia areata.
ic lupus erythematosus and dermatomyositis.
The history may identify a known trigger, but
investigations should include full blood count,
electrolytes, liver function, thyroid function,
ferritin/iron studies, B12, folate, serum zinc lev-
els, vitamin D, and antinuclear antibodies. If a
drug is thought to be the culprit, this should be
stopped for a minimum of 3 months.
MY CHILD HAS DEVELOPED NEW
PATCHES OF HAIR LOSS
Alopecia areata
Alopecia areata (AA) is a non-scarring form of
alopecia that is considered to be a chronic in-
flammatory disorder in which a T-cell autoim-
mune mediated attack on hair follicles and oc-
MIMS JPOG 2019 VOL. 45 NO. 2 77
casionally nails occur. A genetic predisposition
is also suggested as about 20% of people with
AA have a family history of the disease. The in-
flammatory process targets anagen hairs caus-
ing dystrophic anagen hairs and their transition
into the telogen phase. The disorder can occur
at any age.
In patchy alopecia, spontaneous recovery
can occur in up to 80% within 1 year, and about
14–25% progress to total loss of scalp hair (al-
opecia totalis, AT) or loss of entire body hair
(alopecia universalis, AU). Poor prognostic fea-
tures include onset of AA pre-puberty, severe
disease at presentation, ophiasis pattern of al-
opecia (band-like loss over the occipital scalp,
see Figure 12), nail involvement and associat-
ed atopic disease.
78 MIMS JPOG 2019 VOL. 45 NO. 2
The hair abnormality usually becomes noticeable in infancy with the development of short, sparse, brittle, and fragile hair.
The characteristic presentation of AA is
the development of well-circumscribed, totally
bald, smooth patch of alopecia on the scalp
(Figure 13). Other presentations include AT,
AU, ophiasis pattern, and rarely a diffuse var-
iant with widespread thinning. The eyebrows
and eyelashes are lost in many cases and
may be the only sites affected. Regrowth can
be fine and depigmented at first. Often excla-
mation-mark hairs (dystrophic hairs with frac-
tured tips) are present as well as cadaverised
hairs (hairs fractured before passing through
the scalp). A hair pull can reveal telogen or
dystrophic anagen hairs.
The management of AA is dependent on
the extent of the disease and on the psycholog-
ical impact it is having on the child and the fam-
ily. Referral to a paediatric psychologist may
be needed to develop a coping mechanism
and prevent social and educational disruption.
PAEDIATRICS PEER REVIEWED
Leaving AA untreated is a legitimate option, es-
pecially when spontaneous remission is pos-
sible or when effective treatments are unlikely
to be tolerated well. In such situations, a wig,
headscarf, and semi-permanent tattoos can be
helpful.
In limited patchy hair loss, potent topi-
cal steroids with or without occlusion and in-
tralesional steroid injections may induce hair
growth, but can cause skin atrophy. Discomfort
from injections restricts their use in young chil-
dren under 10 years of age.
For more extensive patchy hair loss or AT/
AU, systemic corticosteroids can produce re-
growth but this is often not sustained, and the
risks may outweigh the benefits. Pulsed oral
steroids have been favourable due to fewer
significant systemic side effects.
Contact immunotherapy has been shown
to be effective but is not widely available and
PAEDIATRICS PEER REVIEWED MIMS JPOG 2019 VOL. 45 NO. 2 79

can be difficult and disruptive in young children

as it needs to be repeated frequently (weekly).
Contact dermatitis, eczema, and urticaria are
common following treatment.

Trichotillomania
A behavioural disorder characterized by com-
pulsive hair pulling or plucking. It occurs in two
main forms. In infants and young children, it
represents as a habit, similar to thumb sucking.
It is more common in boys and usually resolves
spontaneously.
In older children and adolescents, it is
seen predominantly in females often with evi-
dence of psychological or behavioural stress.
This form is characterized by the American
Psychiatric Association as an impulse control
disorder where irresistible hair pulling results
in release of tension and distress. Hair is most
commonly plucked from the frontotemporal re-
gions of the scalp and results in patches of hair
loss with irregular borders containing hairs of Figure 14. Tinea capitis.
variable length. The extent of alopecia can vary
but it is unusual for hair to be lost completely. shaft. This does not fluoresce under UV light but
An accurate clinical diagnosis is essential hair shaft damage causes hairs to break off close
but may not always be easy and might require to the scalp surface creating a “black dot” ap-
observation overtime. In young children, it is pearance.
usually self-limiting. Management in adoles- Microsporum canis, another common path-
cents can be more challenging; those with in- ogen, causes an ectothrix pattern with fungal
sight should be referred to a psychologist for spores formed around the hair shaft. This causes
cognitive behavioural therapy, including habit the hair shaft to fluoresce bright green with UV
reversal, and potentially pharmacological ther- light.
apy. A combination of both is more likely to re- The clinical features may vary from a rela-
duce the chance of relapse. tively non-inflammatory patchy alopecia, with or
without scale, to an inflamed boggy lesion with
Tinea capitis pustules and abscess formation, known as a ker-
Tinea capitis is a common dermatophyte infec- ion. Discrete patches are the commonest pres-
tion of the scalp in children (Figure 14). The entation. Many children have associated lym-
causative organisms are the Trichophyton and phadenopathy.
Microsporum species. Currently Trichophyton Scalp scrapings or hair brushings sent for
tonsurans is the commonest pathogen in the microscopy and culture are essential to confirm
UK especially in urban areas but the epidemiol- the diagnosis.
ogy varies worldwide. Oral antifungal agents are needed to en-
The Trichophyton species cause an endo- sure eradication but combined use with topical
thrix infection, with fungal spores within the hair treatment such as ketoconazole shampoo may
80 MIMS JPOG 2019 VOL. 45 NO. 2
Practice Points
• Establish the principle complaint: diffuse or patchy hair loss, hair
shedding, poor growth, or breakage.
• Determine whether there are signs of inflammation or scarring.
• A dermatologist may use the hair pull technique, light microscopy,
and occasionally scalp biopsies to aid the diagnosis of more
complex cases.
• Abnormalities in hair shaft production can produce fragile hair
where breakage may cause either localized or diffuse areas of hair
loss.
• A common cause of hair shedding is acute telogen effluvium, which
occurs 2–3 months after a triggering event.
• 
Alopecia areata characteristically produces well-circumscribed
non-scarred patches of hair loss.
• The features of tinea capitis vary from scaly patches of alopecia to
a boggy swelling or kerion formation and oral antifungal agents are
required after diagnostic hair samples/skin scrapes are taken.
reduce the risk of transmission. Although not li-
censed in children, oral terbinafine is generally
recommended as it is particularly effective for
the Trichophyton species. It is fungicidal and the
duration of treatment (2–4 weeks) is shorter than
griseofulvin, a fungistatic agent. For infection with
Microsporum species, griseofulvin remains the
treatment of choice.
Combs, brushes, hats, etc should be
disinfected or discarded and family members
must also be examined, screened, and treat-
ed accordingly to prevent reinfection. Both
clinical and mycological clearance should be
confirmed once the standard course of treat-
ment is completed.
Scarring alopecia
Scarring or cicatricial alopecia implies perma-
nent hair loss associated with destruction of
hair follicles and scarring of the pilosebaceous
unit. This can result from a disease that affects
the follicles primarily or a secondary external
process.
Examples of secondary causes include
burns, radiodermatitis, morphoea, and infec-
tions such as the favus form of tinea capitis.
PAEDIATRICS PEER REVIEWED
Primary scarring alopecia in children is ex-
tremely rare.
In African-American girls, traction alopecia
can result in a permanent alopecia if traction
from hair styling is excessive and prolonged.
Initially, the hair loss is temporary and behaves
like a non-scarring alopecia.
CONCLUSION
Understanding the basic hair biology im-
proves the clinical assessment of a child with
hair problems and helps to explain why some
congenital disorders do not present until later
in childhood. Approaching a hair disorder in
children according to the principle complaint,
be it patches of hair loss, hair shedding, poor
growth or hair breakage, is more likely to lead
to a diagnosis. An ability to recognize both the
common and rarer hair conditions will ensure
early access to correct management for these
distressing conditions.
FURTHER READING
1. Farrell A, Sinclair R, Dawber R. Disorders of the hair and scalp. Fast
facts. Health Press Limited, 2000.
2. Franklin M, Zagrabbe K, Benavides K. Trichotillomania and its treat-
ment: a review and recommendations. Expert Rev Neurother 2011
Aug; 11: 1165–74.
3. Fuller LC, Barton RC, Mohd Mustapa MF, et al. British Association
of Dermatologists’ guidelines for the management of tinea capitis
2013. Draft update from: Higgins EM, Fuller LC, Smith CH. Guide-
lines for the management of tinea capitis. Br J Dermatol 2000; 143:
53–8.
4. Messenger AG, de Berker DAR, Sinclair RD. Disorders of hair. In:
Burns T, Breathnach S, Cox N, Griffiths C, eds. Rook’s textbook of
dermatology. 8th edn., 4. Wiley- Blackwell, 2010; 66.1–6675.
5. Messenger AG, McKillop J, Farrant P, et al. British Association of
Dermatologists’ guidelines for the management of alopecia areata
2012. Br J Dermatol 2012; 166: 916–26.
6. Sperling L. Alopecias. In: Bolognia JL, Jorizzo JL, Rapini R, et al.,
eds. Dermatology. 2nd edn. Elsevier Limited, 2008; 987–1005.
© 2018 Elsevier Ltd. All rights reserved. Initially published in Paediatrics
and Child Health 2018;29(2):66–73.
About the authors
Caroline Champagne is a Consultant in the Dermatology Department at
The Churchill Hospital, Oxford University Hospitals NHS Trust, Oxford,
UK. Conflicts of interest: none declared.
Noor Alwash is a Clinical fellow in the Dermatology Department at
Brighton General Hospital, Brighton and Sussex University Hospitals,
Brighton, UK. Conflicts of interest: none declared.
Minal Patel is a Clinical fellow in the Dermatology Department at Brigh-
ton General Hospital, Brighton and Sussex University Hospitals, Brigh-
ton, UK. Conflicts of interest: none declared.
Nisha Arujuna is a Registrar in the Dermatology Department at Worthing
Hospital, Worthing, UK. Conflicts of interest: none declared.
Paul Farrant is a Consultant Dermatologist in the Dermatology Depart-
ment at Brighton General Hospital, Brighton and Sussex University Hos-
pitals, Brighton, UK. Conflicts of interest: none declared.
CONTINUING MEDICAL EDUCATION MIMS JPOG 2019 VOL. 45 NO. 2 81

Hysteroscopic Surgery in
Gynaecological Practice
Man Hin Menelik Lee, MBBS, MRCOG, FHKCOG, FHKAM (O&G)

INTRODUCTION
Hysteroscopy is a vital surgical tech-
nique for diagnosing and treating intra-
uterine pathology. The procedure can
be divided into diagnostic and operative
hysteroscopy.

DIAGNOSTIC
HYSTEROSCOPY
Diagnostic hysteroscopy (rigid or flexi-
ble hysteroscopy) is regularly performed
to evaluate the uterine cavity and treat
menstrual disorders and fertility con-
ditions. Detection of polyps, fibroids,
endometrial cancer, and endometrial
hyperplasia remains to be the key for
patients with menorrhagia or abnormal
menstruation. Transvaginal ultrasound
(TVS), with or without the use of saline
infusion sonography (SIS), is commonly Hysteroscopy is a vital surgical technique for diagnosing and treating intrauterine
used in the diagnosis of uterine abnor- pathology.
malities. However, sensitivity and speci-
ficity of TVS, including the use of SIS, is Asherman’s syndrome, intrauter- of a hysteroscope. These procedures
lower than that of a diagnostic hysteros- ine adhesions, endometrial polyps, fi- usually involve a rigid hysteroscope and
copy (Table 1).1 broids, and congenital abnormality of working channels (conventional hyster-
Imaging alone cannot detect the the genital tract may present with amen- oscope or resectoscope) to allow for
presence of endometrial cancer or hyper- orrhoea, irregular bleeding, or failure to continuous flow of distending media.
plasia. In women below age 40, endome- conceive. Diagnostic hysteroscopy can The working channel generally incor-
trial cancer is rare, however its incidence accurately confirm the presence, loca- porates a working element using either
rises steeply beyond ages 45–50+.1 Up tion, and extensiveness of the scarring, a monopolar or bipolar electric energy
to 10% of women with post-menstrual as well as diagnose other congenital through diathermy loop, tip, or roller-
bleeding (PMB) will have endometrial abnormalities. ball. Newer techniques may incorporate
cancer.2
Diagnostic hysteroscopy with tissue morcellation or removal using
endometrial sampling provide the most OPERATIVE HYSTEROSCOPY electric motor cutting blades where tis-
accurate investigation available for such Operative hysteroscopy involves pro- sues are simultaneously cut and aspi-
diagnosis (Table 2). cedures performed under the guidance rated from the uterine cavity.
82 MIMS JPOG 2019 VOL. 45 NO. 2 CONTINUING MEDICAL EDUCATION

Table 1. Sensitivity and Specificity for Detecting Intrauterine
Pathology with Different Investigating Modalities
Type of pathology Investigation
Submucosal TVS
fibroids
SIS
Hysteroscopy
Endometrial polyps TVS
SIS
Hysteroscopy
Abbreviations: TVS = transvaginal ultrasound; SIS = saline infusion sonography
Table 2. Sensitivity and Specificity of Hysteroscopy for Endometrial
Pathology1
Type of pathology Sensitivity
Endometrial cancer 82.6%
Endometrial hyperplasia 75.2%
Hysteroscopic resection
of submucosal fibroid
Resection of submucosal fibroid involves
the use of an operating hysteroscope.
With complete removal, improvement of
menorrhagia can be as high as 94.1%.3
Traditionally, it is performed using a
diathermy loop which passes through the
resectoscope. Monopolar or bipolar energy
can be used, and the procedure is complet-
ed with a progressive slicing of the intra-
cavity portion of the submucous myomas,
a subsequent “cold loop” pushing of the
intramural part (to preserve the pseudocap-
sule), and finally, a slicing resection of it.
The availability of Hysteroscopic
Tissue Removal systems (HTRs) opened
a new era.4 Multiple devices (TRUCLEAR,
MyoSure, BIGATTI shaver), all share sim-
ilar techniques. Under the guidance of a
hysteroscope and after distension of the
uterus, a specially designed morcellator
According to the Manufacture
and User Facility Device Experience
(MAUDE) database,8 adverse events
associated with hysteroscopic morcel-
Sensitivity Specificity
lation is less than 0.1%, which is less
80% 69%
than conventional hysteroscopic sur-
0.82 1.0
gery. Although limited to case reports,
97% 98.9%
major complications (eg, intubation
80% 69%
and admission to intensive care unit,
0.82 0.96
bowel damage, hysterectomy, and
95.4% 96.4%
death) have been reported. 5
Minor
events reported include uterine per-
foration requiring no other treatment,
uncomplicated fluid overload, postop-
erative bleeding, and pelvic infections.
Systematic review by Vitale, et al,4
showed that overall complete fibroid re-
section rates between HTRs and con-
Specificity
ventional procedures were comparable.
99.7%
Although Lee and Matsuzono9 found no
91.5%
significant difference between overall pa-
tient satisfaction and improvement in hae-
moglobin level, Rubino, et al,10 showed
is introduced through the hysteroscope significant improvement in uterine fibroid
to cut and aspirate the morcellated tissue symptoms and health-related quality of
which is then collected for histological life at 12 months when myomectomy was
analysis (Figure 1).
5
performed using HTRs.
Several studies have evaluated
the efficacy and safety of HTRs com- Resection of endometrial polyps
pared with conventional operative Though malignancy is uncommon in
hysteroscopy. polyps, it can occur in 0–12.9% of cases
A randomized controlled trial (RCT) depending on the population studied.11
by van Dongen, et al, reported mean Increasing age during the reproductive
operative times of 11 and 17 minutes period, obesity, tamoxifen use, and pol-
(p=0.008) for HTRs and conventional yp size may increase the prevalence and
hysteroscopic resection, respectively, 6
risk of malignancy and hyperplasia.12
while similar fluid deficit of 409 and 545 Given these factors, polyp removal for
mL (p=0.224) were found. Emmanuel, et diagnosis and treatment of abnormal
al, reported operative times of 16 and 42 uterine bleeding are regularly performed.
minutes respectively, with a mean fluid Polypectomy can be done via
deficit of 660 and 742 mL with no statis- several surgical methods: diagnostic
tical significant.7 Both studies suggested hysteroscopy before and after blind
significant reductions in operative time dilatation and avulsion with polyp for-
associated with HTRs but there was no ceps, cold scissors and grasper under
difference in fluid deficit. hysteroscopic vision, hysteroscopic
CONTINUING MEDICAL EDUCATION MIMS JPOG 2019 VOL. 45 NO. 2 83

resection with loop cautery, hystero-

scopic morcellation, tissue vapourising
technique using bipolar vapourisation
A B
(Versapoint) or laser (diode), and polyp
snares (Cook’s Polyp Snare).
Blind endometrial polypectomy
by polyp forceps, only yielded a com-
plete extraction rate of 41%.12 Malignant
cells at the base of the polyp can be
missed,13 while recurrence rate can be
as high as 15%.14
Resection using cold scissors, dia-
thermy resectoscopes, or HTRs are safe,
simple, and superior to blind techniques.
C D
Despite the longer duration and proba-
bly higher cost of hysteroscopic resec-
tion, uterine perforation risk is lower as
direct vision of polyp resection is allowed
during procedure.15 Not a single recur-
rence of endometrial polyp was reported
when resection was performed under di-
rect vision compared with removal using
grasping forceps.14 Tissue vapourising
Abbreviation: HTRs = Hysteroscopic Tissue Removal systems
device such as Versapoint bipolar va-
pourisation or laser device (eg, diode)
Figure 1. Hysteroscopic resection of fibroid with HTRs. (A) Submucosal fibroid; (B) Resection
is also used under direct vision through using HTRs; (C) Further removal of submucosal fibroid using HTRS; and (D) Complete resection.
a hysteroscope. However, as the device
vapourises tissues upon contact, the en-
tire specimen may not be available for my rollerball or transcervical resection were easier to perform, and more likely
pathological evaluation. of endometrium (TCRE) were common to be performed under local anaesthe-
Hysteroscopy with a polyp snare during the 1990s and led to significant sia and in an outpatient setting.
utilizes a specially designed hook reduction in hysterectomies performed. Among all the second-generation
placed through the hysteroscopic op- In recent years, second-generation techniques, bipolar radiofrequency
erative channel and around the base of techniques have gained worldwide and microwave ablation showed su-
the polyp. A current is applied, and the popularity. High-temperature fluids perior results.17 Bipolar radiofrequen-
endometrial polyp is cut at the base and within a balloon (Thermachoice and cy ablation resulted in a higher rate
removed under vision.15 The results are Cavaterm), microwave (Microsulis), or of amenorrhoea compared with ther-
similar to hysteroscopic resection. bipolar radiofrequency electrical en- mal balloon ablation and reduced the
ergy (NovaSure) are most frequently rate of heavy bleeding compared with
Endometrial ablation used (Figure 2). free-fluid ablation.16 In the same re-
Endometrial ablation is a minimally inva- A meta-analysis of RCTs16 suggest- view, bipolar radiofrequency ablation
sive surgical alternative to hysterectomy ed that second-generation techniques appeared to be more favourable to pa-
for the treatment of menorrhagia. were at least as effective as first-gener- tients than free-fluid thermal ablation at
First-generation techniques using ation techniques but had fewer surgical 12 months.16 Locally, overall satisfac-
conventional hysteroscopy and diather- complications, shorter operative time, tion rate is >90%.18
84 MIMS JPOG 2019 VOL. 45 NO. 2
A samples.
B
Abbreviation: TCRE = transcervical resection of endometrium
Figure 2. Types of endometrial ablations: (A) TCRE using diathermy loop; and (B) NovaSure
bipolar impedance controlled endometrial ablation.
However, limitations were
served for second-generation ablation
techniques. Because of the design of
individual devices, second-generation
endometrial ablations are restricted to
uterus of normal size or equivalent to 12
weeks gestation. Despite potential com-
plications reported with previous cae-
sarean scars and coexisting fibroids,
previous transverse scars and fibroids19
less than 3 cm did not appear to affect
the effectiveness of bipolar radiofre-
quency devices. 20
Pregnancy after en-
dometrial ablation has an estimated risk
of 0.24–5.2% and is associated with high
risk of miscarriage, intrauterine death,
intrauterine growth retardation, mor-
bid adherent placentas, and post-par-
tum hysterectomies. 21-22
The procedure
should be avoided by women who have
CONTINUING MEDICAL EDUCATION
ob- fertility wish, and long-term contracep-
tion is advised prior to the procedure.
Resection of endometrial
adhesions/septum and
management of fertility
The presence of polyps, fibroids, uterine
septum, or intrauterine adhesions may
prevent implantation and cause fertility
problems.
Improving the chance of fertility by
removing pathological lesion remains
controversial. The Cochrane review
suggested that hysteroscopic removal
of polyps before intrauterine insem-
ination improved fertility rates from
28% to 50–76%. Fertility also improved
from 21% to 39% after removal of sub-
mucosal fibroids. However, there are
limited studies to deduce concrete ev-
idence, and all studies included small
Regarding uterine septum and
uterine adhesions, there is insufficient
evidence to conclude that a uterine sep-
tum is associated with infertility, but sev-
eral observational studies indicated that
hysteroscopic incision of uterine septum
is associated with improved pregnancy
rates.24 Removal of intrauterine adhe-
sions has also been shown to increase
clinical pregnancy rates in those with re-
current implantation failure.
For fibroids and polyps, convention-
al resectoscope or HTRs can be used.
However, electrosurgical devices, such
as resectoscopes, are best suited for
removal of uterine septum. Resection of
uterine septum and adhesions was as-
sociated with the highest risk of uterine
perforation at 4.5%.23
Hysteroscopic sterilization
Currently, the Essure device is the only
available FDA-approved method of hys-
teroscopic sterilization. The device con-
sists of a micro-insert, and a delivery
catheter, and is deployed using a contin-
uous-flow hysteroscope with a 5-French
operating channel. The micro-insert has
a stainless steel inner coil, a nickel tita-
nium elastic outer coil, and polyethylene
fibres. When released, the outer coil
expands to 1.5–2.0 mm to anchor the
micro-insert into the fallopian tube. The
polyethylene fibres then induce fibrosis
over a period of 3 months, causing per-
23
manent tubal occlusion.25 At 3 months
post-procedure, a hysterosalpingogram
(US) or pelvic ultrasound (UK and Eu-
rope) should be performed to confirm
positioning of the device. Bilateral place-
ment of the Essure device is possible in
81–99% of cases25 with sterilization that
showed a 99.83% success rate based
CONTINUING MEDICAL EDUCATION
on a 5-year study.26 The total pregnancy
rate was reported to be 1.09/1,000 25
or
0.36-1.2% in other studies conducted in
France and the US. 26
Complications of hysteroscopic
sterilization include pain, discomfort,
and heavy menstrual bleeding in 20% of
women, and spontaneous expulsion in
0.04–3%. 26
Uterine perforation risk was
1–2%, while device migrating risk was
0.04%, subsequently embedding in the
intra-abdominal structures as reported in
the MAUDE database. About 14–18% of
27
women27 reported allergic reaction to the
device, which resulted in urticaria and
erythema and required device removal.
Hysteroscopic resection of
placenta or retained products
of conception
Prevalence of placental remnants after
pregnancy (after miscarriage, vaginal de-
livery, caesarean section, or termination
of pregnancy) can be as high as 19% of
pregnancies. Blind dilatation curettage is
most commonly performed but is an im-
portant risk factor for intrauterine adhesion
formation particularly if repeatedly per-
formed. Hysteroscopic resection, either by
loop resection or HTRs, has been shown
to be an alternative surgical approach to
dilatation and curettage that enables se-
lective removal of the remnant tissue un-
der direct vision. The procedure is likely to
achieve higher rates of complete removal
and lower risk of postoperative adhesions.
An RCT by Hamerlynck, et al, revealed a
94.5% complete resection rate with either
the diathermy hysteroscopic resection or
the HTR technique for placental remnants
up to 3 cm. However, HTR showed a
shorter surgical procedure time. 28
Infrequently, morbidly adherent pla-
centas may be left in situ after delivery.
If conservative management fails, hys-
teroscopic resection of retained placenta
through single or multiple procedures
are options to prevent major complica-
tions and preserve fertility. 29
Caesarean
scar pregnancies can also be managed
hysteroscopically. In cases of caesarean
scar pregnancies or morbidly adherent
placentas, resectoscope with electro-
cauterization may be preferred to avoid
bleeding.30-31
GENERAL COMPLICATIONS
OF HYSTEROSCOPIC SURGERY
Minor complications such as infection
and bleeding are potential risks of hys-
teroscopy. Severe complications includ-
ing uterine perforation can occur in up to
0.76% of cases, with subsequent bow-
32
el and bladder damage in some cases.
With over 70% of uterine perforation cas-
es occurring during the cervical dilata-
tion stage, advancement in hysteroscop-
ic surgeries tends to involve reducing the
diameter of the hysteroscopes.
Consequence of excessive
systemic absorption
Excessive systemic fluid absorption is a
major complication but is much more
prevalent in operative hysteroscopy
(0.1–0.2%). 33
Distension media for UK, when ex-
cessively absorbed, leads to systemic
expansion, cardiac failure, and pulmo-
nary oedema. Hypotonic and electro-
lyte-free solutions carry additional risks
(ie, hypo-osmolality, hyponatraemia),
which might consequently lead to com-
plications such as systemic expansion
and cerebral oedema. As excessive ab-
sorption occurs, osmotic imbalance is
created between extracellular fluid and
cells including those in brain. In healthy
patients, the brain compensates itself
and causes minimal harm. However, un-
MIMS JPOG 2019 VOL. 45 NO. 2 85
der conditions of hyponatraemia, water
moves into the brain cells causing cer-
ebral oedema which then leads to pres-
sure necrosis, brain stem herniation and,
in rare cases, death.33 Those with under-
lying medical conditions, particularly car-
diac or renal diseases, must be treated
with caution. Premenopausal status was
associated with a higher risk of neuro-
logical complication and suppressive
effects of oestrogen on ATPase pump,
which regulates electrolytes through the
blood-brain barrier. It has been suggest-
ed that the use of gonadotrophin-releas-
ing hormone (GnRH) analogue prior to
the procedure may reduce such risks.34
Fluid absorption into the systemic
circulation can occur by several ways:
• Retrograde passage of the fluid
through the fallopian tubes
• Through the endometrium
• Operative disruption of venous si-
nus in the deep endometrium and
myometrium. When these vessels or
sinuses are transected, it provides
access for the media to enter the sys-
temic circulation.33
Factors influencing fluid absorption:
• Intrauterine pressure – the higher the
pressure, the greater the degree of
absorption into the body. Intrauterine
pressure over 75 mm Hg increases
the volume of media passing back
along the fallopian tubes and into the
peritoneal cavity.34
• Mean arterial pressure (MAP) – the
lower the MAP, the lower the intra-
uterine pressure required to cause
passage of fluid into the systemic cir-
culation.34
• Depth of myometrial penetration –
the deeper the damage to the myo-
metrium, the more open the myome-
trial venous sinus, causing increased
absorption.
86 MIMS JPOG 2019 VOL. 45 NO. 2
• Duration of surgery – the longer the
procedure, the more time for fluid to
accumulate within the body.
• Size of uterine cavity – a larger cavi-
ty increases the endometrial surface
area, which may require a longer
procedure time and higher intrauter-
ine pressure, and could increase ab-
sorption risk.
• Distension media – all types of flu-
id media are associated with rapid
systemic absorption. However, it is
more likely with hypotonic and elec-
trolyte-free distension media as they
create an osmotic imbalance be-
tween extracellular and intracellular
fluid via hyponatraemia and hypo-os-
molality, while isotonic media does
not cause hyponatraemia. 34
Distension media
Carbon dioxide
Carbon dioxide (CO2) should be used as
a distending medium for diagnostic hys-
teroscopy only. This is because bleed-
ing obscures view, and CO2 is unable to
clear the bleeding debris.
CO2 is highly soluble in blood and
can enter the circulation system. A mod-
erate amount is quickly absorbed and
has no clinical impact. However, if large
volume of CO2 reaches the systemic cir-
culation, cardiorespiratory collapse can
occur.33
High-viscosity distending
media (eg, 32% dextran 70 in
10% glucose)
They are generally used in cases of bleed-
ing, as they are immiscible with blood.
However, it causes fluid expansion when
excessively absorbed leading to heart
failure and pulmonary oedema. The max-
imum recommended volume of infused
fluid should be between 300 and 500 mL.33
CONTINUING MEDICAL EDUCATION
Low-viscosity distending
media (eg, commonly used –
1.5% glycine, normal saline,
3% sorbitol, and 5% mannitol)
Hypotonic solution such as glycine is
metabolized to ammonia and free water
in the liver, which results in reduced se-
rum osmolality. Excess absorption may
cause electrolyte imbalance, particularly
hyponatraemia. It has been established
that a decrease in serum sodium of 10
mmol/L corresponds to an absorbed vol-
ume of 1,000 mL has traditionally been
used and recommended by the British
Society for Gynaecological Endoscopy
(BSGE) as the threshold at which hys-
teroscopy should not be performed in
women when using these media.34
Normal saline and Ringer’s lactate
are isotonic solutions and are generally
safer to use as distension media. Despite
the low likelihood of hyponatraemia,
excessive absorption can lead to ex-
pansion of extracellular fluid, fluid over-
load, pulmonary oedema, hypertension,
heart failure, and cerebral oedema. The
BSGE/European Society for Gynaeco-
logical Endoscopy (ESGE) recommend-
ed a limit of 2,500 mL in fluid deficit when
using an isotonic solution and that the
procedure be abandoned on reaching
this limit.34
Strategies to reduce risk of
excessive fluid absorption
Intrauterine pressure
Should be kept between 70 and 100 mm
Hg – higher pressure may improve visu-
alization but increase the amount of fluid
absorbed. 34
Distension media
Isotonic electrolyte containing distension
media such as normal saline should be
used with mechanical instrumentation
and bipolar electrosurgery. Hypotonic,
electrolyte-free distension media such as
glycine should only be used with monop-
olar electrosurgical instrument.34
GnRH
Pre-operative administration of GnRH
should be considered in premenopau-
sal women before hysteroscopic resec-
tion of fibroids as it reduces electrolyte
disturbance complications and the inci-
dence of fluid overload.35-36
Choice of operative technique
During resection of submucosal fi-
broids or polyps, bipolar devices
should be considered instead of mo-
nopolar devices and isotonic medium
can be used. Mechanical tissue-remov-
ing device should also be considered
over loop resection as it has been
shown to reduce operative time.
As for endometrial ablation, sec-
ond-generation endometrial ablation
should be considered over TCRE as it has
been shown to reduce operative time.
Monitoring and when to stop
procedure
Strict input and output of fluid, and flu-
id deficit monitoring during delivery of
distension media should be performed.
Operative staff should constantly keep
the surgeon informed. Surgeons should
abandon the procedure when fluid
deficit of 1,000 mL for hypotonic solu-
tion or 2,500 mL for isotonic solution is
reached. A two-step procedure should
be considered if procedure cannot be
completed in the first instance.
OUTPATIENT HYSTEROSCOPY
Traditionally, outpatient hysteroscopy
was limited to diagnostic hysteroscopy.
As technology advances and as most
CONTINUING MEDICAL EDUCATION MIMS JPOG 2019 VOL. 45 NO. 2 87

patients prefer to avoid general anaes-
thetics, diagnostic and operative hys-
teroscopies are now being performed
in outpatient settings.
Hysteroscopes of less than 5 Fr in
diameters are being produced to allow
for the passage of hysteroscopic scis-
sors and graspers during surgery. In ad-
dition, new techniques are being devel-
oped to reduce operative time, allowing
for a more tolerable procedure under
office settings.
Endometrial ablation
Bipolar radiofrequency and balloon ab-
lation have been shown to be feasible
in the outpatient settings with analge-
sia and paracervical block.37-39 Accord-
ing to a study by Marsh, et al,38 more
than 70% of women prefer the proce-
dure as an office procedure with local
anaesthesia.
Hysteroscopic resection of polyps
Hysteroscopic devices with working
channels allowing for the insertion of the
cold scissors and excision of polyps are
widely available. Their diameters can be
as small as 1.9 mm, with a 3.5-mm ex-
pandable operating channel. Small hys-
teroscopic morcellators allow complete
15
resection without dilatation in the outpa-
tient setting. Despite the potential risk
of failure due to technical difficulty (eg,
cervical stenosis) or patient intolerance,
outpatient hysteroscopy and polypecto-
my are acceptable to most women and
considered to be less painful than their
usual menstruation.15
CONCLUSION
Hysteroscopic surgery is a common pro-
cedure but carries some complications
such as excessive fluid overload. Gynae-
cologists should be aware of advanced
techniques that reduce operative time
and patient risks and are potentially use-
ful in post-pregnancy-associated condi-
tions that were not commonly performed
in the past.
About the author
Dr Man Hin Menelik Lee is an Associate Consultant in the
Department of Obstetrics & Gynaecology, Queen Elizabeth
Hospital, Hong Kong SAR. Conflict of interest: None.

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88 MIMS JPOG 2019 VOL. 45 NO. 2 CME QUESTIONS

This continuing medical education service is brought to you by MIMS. Read the article
‘Hysteroscopic Surgery in Gynaecological Practice’ and answer the following questions.
Answers are shown at the bottom of this page. We hope you enjoy learning with MIMS JPOG.

CME ARTICLE

Hysteroscopic Surgery
in Gynaecological Practice
Answer True or False to the questions below.

True False
1. Compared with diagnostic hysteroscopy, ultrasound has a higher sensitivity and
specificity in the diagnosis of endometrial polyps and submucosal fibroids.
2. Operative time using HTRs are quicker than conventional resectoscope in treating
submucosal fibroids.
3. Endometrial polyp resection using blind technique (such as polyp forceps) has a
high complete resection rate.
4. Second-generation endometrial ablation is as effective as first-generation
endometrial ablation in the management of menorrhagia.
5. For a premenopausal woman who’s not planning further pregnancies,
contraception is not needed following an endometrial ablation procedure.
6. Severe complications of hysteroscopic procedure occurs in more than 1% of
procedures.
7. CO2 as distension media should be used for diagnostic hysteroscopy only.
8. Isotonic distension media is more likely to cause hyponatraemia than hypotonic
solutions.
9. GnRH analogue given to premenopausal women reduced the incidence of fluid
overload during operative hysteroscopic surgery.
10. BSGE/ESGE recommended that fluid deficit should be limited to 1,000 mL when
using isotonic fluid (eg, normal saline as distending medium).

10.F 9.T 8.F 7.T 6.F 5.F 4.T 3.F 2.T 1.F
Answers