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CASE-BASED LEARNING
Menstrual dysfunction
Gail Busby
Abstract
Menstrual dysfunction is common, with approximately 9e30% of
reproductive-aged women presenting with menstrual irregularities
requiring medical evaluation. The causes are diverse and with multiple
treatment options are available. Appropriate management relies on
relevant investigation and accurate diagnosis. This article reviews
the most common causes of menstrual dysfunction using case histories for illustration. The conditions covered in this review include
menstrual dysfunction around the time of menarche, ovulatory and
anovulatory dysfunctional uterine bleeding, polycystic ovarian syndrome, uterine broids and dysfunctional bleeding around the perimenopause. Appropriate investigations and current management
strategies are also discussed.
Introduction
The majority of menstrual cycles are between 24 and 32 days and
a normal cycle is considered to be 28 days. The menstrual cycle
varies during the reproductive years, and is most regular between the ages of 20 and 40. The mean blood loss per cycle is
between 37 and 43 ml, and the upper limit for menstrual loss is
taken as 80 ml per menses. Menstrual dysfunction, or disruption
in the flow or timing of this cycle is a very common cause for
presentation to a gynaecologist. The causes are myriad, but
several common causes are reviewed here and treatment options
discussed.
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CASE-BASED LEARNING
COCPs
COCPs contain oestrogen and progestogen in combination.
They work on the hypothalamicepituitary axis to inhibit
ovulation and decrease fertility. They may reduce menstrual
loss by 43%, and also provide reliable contraception in the
compliant patient.
Differential diagnosis
Anovulatory
Adolescence
Diabetes mellitus uncontrolled
Eating disorder
Hyper-/hypothyroidism
Hyperprolactinaemia
Anticonvulsants
Antipsychotics
Perimenopause
Polycystic ovarian syndrome
Bleeding disorders (Haemophilia carriers)
Factor deficiency (FVII, FXI, FV FVIII, FXIII,
FV, FX, Fibrinogen deficiency)
Leukaemia
Platelet disorders (Bernard-Soulier Syndrome,
Dense granule deficiency, Glanzmanns
thrombasthenia, Alpha granule deficiency)
von Willebrands disease
Liver disease, advanced
Structural lesions- fibroids, polyps
Ovulatory
Progestogens
Oral progestogens taken solely in the luteal phase of the menstrual cycle have not been shown to be effective in reducing
heavy menstrual bleeding. Cyclical progestogens taken for 21
days of the cycle (day 5eday 26) have been shown in a small
study to reduce menstrual loss by 83%. The mechanism of action
of oral progestogens in reducing menstrual loss is unclear.
The progesterone only pill (POP) can be used to provide
reliable contraception, but has a varied effect on menstrual flow.
Twenty percent patients will be amenorrhoeic, 40% bleed regularly and 40% have erratic bleeding. This inconsistent effect on
menstruation this is not generally first-line treatment. Indeed,
altered bleeding patterns is the most common reason given by
women for stopping POPs. Injected progestogens such as Depot
Medroxyprogesterone Acetate (DMPA) provide reliable contraception and are injected every 12 weeks. Although this is not
licensed for the treatment of heavy menstrual bleeding, it is
associated with amenorrhoea rates of 12e47% after one year of
use.
The levonorgestrel-releasing intrauterine system (Mirena)
provides an effective treatment option for AUB in the patient who
is also desirous of reliable contraception. This device produces a
dramatic decline in menstrual blood loss (65e98%) within 12
months of use. The device, imbedded with 52 mg of levonorgestrel, releases 20 mg of levonorgestrel per day, causes pseudodecidualization of the endometrium with very little systemic
absorption of progesterone. It is licensed for contraception,
treatment of idiopathic menorrhagia, and as the progestogenic
arm of HRT. Its contraceptive effect lasts for 5 years.
In cases of ovulatory AUB where the patient has no further
reproductive ambitions, surgical options can be entertained such
as endometrial ablation and hysterectomy.
Table 1
Endometrial ablation
Endometrial ablation refers to a host of techniques designed to
destroy the endometrium, and thereby reduce menstrual
bleeding. Initially, rollerball ablation, transcervical resection and
laser ablation were the predominant endometrial destruction
techniques performed under direct hysteroscopic vision. Over the
past decade, a second generation of techniques, which do not
require hysteroscopy have been developed which are safer,
easier to perform, involve shorter hospital stays or are performed
in the outpatient setting under local anaesthesia.
These techniques employ devices which are sited within the
uterine cavity and are activated in order to produce global
destruction of the endometrium. Various methods of destruction are used, including high-temperature fluids within a
balloon (Thermachoice and Cavaterm), Microwave energy
(Microsulis), and Bipolar radiofrequency electrical energy
(Novasure). Less commonly used ablative techniques include
free fluid at high temperature (Hydrothermablator), endometrial laser intrauterine thermotherapy (ELITT) and cryoablation
150
CASE-BASED LEARNING
endometrial instability and erratic bleeding. Prolonged unopposed oestrogenic stimulation of the endometrium can lead to
endometrial hyperplasia or carcinoma.
The most common cause of anovulation is polycystic ovarian
syndrome (PCOS). There are however, numerous other causes,
including thyroid disease, uncontrolled diabetes mellitus and
hyperprolactinaemia. Anticonvulsants and antipsychotics can
also cause anovulation.
A thorough history and examination is required to determine
the most likely cause of anovulation. A detailed clinical history
often reveals any systemic and medical conditions that cause
menstrual dysfunction. The examination should note the presence of galactorrhoea, weight gain, acanthosis nigricans, evidence of hyper- or hypo-thyroidism, hirsutism, virilization or
acne. A speculum and bimanual pelvic examination should be
performed to exclude any anatomical pathology. Should positive findings be elicited in the history or examination, appropriate investigations should be performed (e.g. serum prolactin
levels in the presence of galactorrhoea, thyroid function tests if
there is evidence of thyroid disease and a pelvic ultrasound
scan).
In this patient with irregular periods, weight gain and hirsutism, the most likely diagnosis is PCOS.
PCOS
PCOS affects 7e10% women worldwide, making it the most
common endocrine disorder among reproductive-aged women.
Ascribing a diagnosis of PCOS has many implications
including an increased risk of infertility, dysfunctional uterine
bleeding, endometrial carcinoma, obesity, type 2 diabetes, dyslipidaemia, hypertension and possibly cardiovascular disease.
Therefore, this diagnosis should not be undertaken lightly, and
robust criteria used for diagnosis.
The first clinical definition of PCOS arose from the proceedings of a meeting of experts sponsored by the National
Institute of Child Health and Human Disease of the NIH in 1990.
They concluded that the major criteria for PCOS should include:
(1) Hyperandrogenism and/or hyperandrogenaemia (2) menstrual dysfunction and the (3) exclusion of other known
disorders.
An expert conference held in Rotterdam, The Netherlands in
2003 recommended that PCOS be defined when at least two of
the following three features are present: (1) oligo and/or anovulation, (2) clinical and/or biochemical signs of hyperandrogenism and (3) polycystic ovaries. These criteria also
recognize that other androgen excess or related disorders should
be excluded before assigning a diagnosis of PCOS.
More recently, in 2009, the Androgen excess and polycystic
ovary syndrome society proposed new criteria for the diagnosis
of PCOS: (1) hyperandrogenism: hirsutism and/or hyperandrogenaemia AND (2) Ovarian dysfunction: Oligo-anovulation
and/or polycystic ovaries AND (3) Exclusion of other androgen
excess or related disorders.
Hysterectomy
Hysterectomy is the only surgical technique which guarantees
amenorrhoea. It however can be associated with serious complications such as pelvic haematomas (3.9%), urinary tract
injury (1% for cystotomies and 0.1% for ureteric injuries), and
bowel injuries (0.3%). Compared with all other treatment modalities, hysterectomy is favoured for elimination of bleeding
symptoms and need for additional treatment. Hysterectomy is
also favoured over ablation techniques for pelvic pain beyond the
immediate post-operative period. However, these superior outcomes are achieved with the tradeoff of higher risks of adverse
events, and should therefore be reserved for cases in which more
conservative treatments have been unsuccessful.
151
CASE-BASED LEARNING
Thiazolidinediones
Thiazolidinediones act as insulin sensitizers through their
activation of the nuclear receptor PPAR-g, leading to increased
production of insulin-sensitive adipocytes and increased
glucose uptake in these cells, increased secretion of adiponectin
and decreased secretion of pro-inflammatory cytokines. Recent
data suggest that in women with PCOS, thiazolidinediones
exert additional benefit with respect to hyperandrogenism, IR,
anovulation and inflammatory mediator levels, in both lean
and obese women. The thiazolidenedione, pioglitazone, has
been shown to ameliorate the signs and symptoms of PCOS in a
cohort of women who failed a previous trial of metformin.
There have been, however concerns regarding use of these
drugs, including withdrawal from the market of the vanguard
thiazolidenedione, troglitazone, and further concerns regarding
potential adverse cardiovascular events in Type 2 diabetes
patients taking thiazolidinediones. This reinforces the need for
caution when considering use of this class of drugs. These
drugs should not be considered as first line management of
PCOS.
COCPs
COCPs are among the primary treatment options for PCOS,
particularly for those patients not wishing to become pregnant.
They produce regular menstrual periods, lower the risk of
endometrial hyperplasia and improve acne and hirsutism. COCPs
improve symptoms by increasing the production of SHBG,
resulting in a decrease in circulating free androgens, as well as
their bioavailability. They also suppress the production of FSH
and LH which in turn decreases LH-driven ovarian androgen
production. Progestogens protect the endometrium against hyperplasia induced by unopposed oestrogen stimulation. Some
progestogens, such as drospirenone and cyproterone acetate
have proven anti-androgenic effects and therefore are of added
benefit in PCOS.
Despite their potential benefits in PCOS, COCPs fail to
diminish insulin resistance in PCOS and may actually be associated with long-term metabolic derangements such as glucose
intolerance, abnormal lipid profiles and cardiovascular disease.
Further longitudinal studies in adult women with PCOS receiving
COCPs are needed.
Metformin
Metformin increases insulin sensitivity in the liver by reducing
gluconeogenic enzyme activities, inhibiting hepatic uptake of
lactate and alanine, increasing the conversion of pyruvate to
alanine and inhibiting glucose output. In addition, metformin
increases peripheral glucose uptake, decreases fatty acid oxidation and decreases glucose absorption from the gut. It therefore
has a positive effect on the metabolic derangements in PCOS.
The use of Metformin in PCOS has been shown to increase
menstrual cyclicity (in 50%e60%), improve percentage of
ovulatory cycles, and improve fertility.
Metformin use is associated with gastrointestinal side-effects,
which can be minimized by titration to the desired dose over a
one month period.
In adult women with PCOS, the addition of Metformin to a
COCP decreases IR, as well as androgen levels. However, the
anticipated correction of deranged lipid profiles and abdominal
obesity through metformin use appears to be blunted.
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CASE-BASED LEARNING
Myomectomy
Myomectomy, the surgical excision of uterine fibroids, can be
performed hysteroscopically, laparoscopically or via laparotomy
depending on the number, size and position of fibroids. Submucous fibroids are amenable to hysteroscopic removal,
whereas intramural and subserosal fibroids require an abdominal approach.
Pre-operative treatment with Gonadotrophin-releasing analogues or Ulipristal acetate, a selective progesterone-receptor
modulator, decrease fibroid size and increase haemoglobin
due to causing amenorrhoea in most patients. Due to the risk of
osteoporosis, GnRH analogues should not be used for periods of
longer than six months unless concomitant oestrogen replacement is prescribed. Ulipristal acetate is approved in the European Union for pre-operative treatment of moderate to severe
symptoms of uterine fibroids in adult women of reproductive
age. It is approved for treatment periods of three months
duration or less, as the longer-term tolerability has not been
established.
In two well-conducted trials, PEARL 1 and PEARL 2, Ulipristal
acetate at a dose of 5 mg per day for 13 weeks was shown to
control excessive uterine bleeding in 90% of women with
uterine fibroids. Approximately half of the recipients were amenorrhoeic by day 10. Ulipristal acetate also resulted in a median
reduction in fibroid volume of at least 21% following 13 weeks of
treatment. These results were non-inferior to those of leuprolide
acetate.
Repeated courses of ulipristal acetate
Another trial, PEARL IV evaluated the efficacy and safety of
repeated 12-week courses of daily 5 mg or 10 mg doses of Ulipristal acetate. Amenorrhoea was achieved in 62% and 73%
respectively in the 5- and 10 mg groups. Median times to amenorrhoea was 6 days or fewer and the proportion of patients with
controlled bleeding at the end of both treatment courses were
>80%. The combined fibroid volume of the three largest fibroids
were reduced by 54% and 58% respectively after two courses.
Surgery was performed in only 3 of 230 women taking the 5 mg
does and 5 of 221 women taking the 10 mg dose. Endometrial
biopsies have not shown any increased risk of endometrial atypia
or carcinoma.
Ulipristal acetate may therefore be an alternative option to
surgery in the long-term treatment of uterine fibroids.
Management options
The finding of atypical endometrial hyperplasia conveys a risk of
progression to endometrial carcinoma of 8.2% in 4 years, 12.4%
in 9 years and 27.5% in 19 years. In addition, other studies have
shown the presence of concurrent endometrial carcinoma in
hysterectomy specimens removed for atypical hyperplasia in
43% patients. For this reason, it is recommended that hysterectomy be performed within 3 months of the diagnosis of atypical
endometrial hyperplasia.
In contrast, the finding of endometrial hyperplasia without
atypia has a very low risk of malignant transformation of 1.2% in
4 years, 1.9% in 9 years and 4.6% in 19 years. This abnormality
can be treated with cyclical progestogens with re-biopsy to
confirm regression of the hyperplasia.
In patients who have no further reproductive ambitions, total
hysterectomy with or without bilateral salpingo-oophorectomy
depending on the age group is the treatment of choice for
endometrial hyperplasia with atypia. In patients who wish to
retain their uterus for childbearing, treatment with high dose
progestogens with re-biopsy can be employed after careful
counselling.
Hysterectomy
Patients who have symptomatic uterine fibroids and have
completed their family may opt for hysterectomy, however this is
associated with increased frequency of complications compared
to hysterectomy with a normal-sized uterus.
Conclusion
Abnormal uterine bleeding is the most common cause of anaemia
in the pre-menopausal woman and can have a substantial impact
on womens quality of life. Cases need to be assessed on an
153
CASE-BASED LEARNING
FURTHER READING
Azziz R, Carmina E, Dewailly D, et al. The Androgen Excess and PCOS
Society criteria for the polycystic ovary syndrome: the complete
task force report. Fertil Steril 2009; 91: 456e88.
Croxtall JD. Ulipristal acetate in uterine broids. Drugs 2010; 72:
1075e85.
Daniels JP, Middleton LJ, Champaneria R, et al. Second generation
endometrial ablation techniques for heavy menstrual bleeding:
network meta-analysis. BMJ 2012; 344: e2564.
Donnez J, Hudecek R, Donnez O, et al. Efcacy and safety of repeated
use of ulipristal acetate in uterine broids. Fertil Steril 2015; 103:
519e27.
Geller DH, Pacaud D, Gordon CM, Misra M. State of the art review:
emerging therapies: the use of insulin sensitizers in the treatment of
adolescents with polycystic ovary syndrome (PCOS). Int J Pediatr
Endocrinol 2011; 9.
Lacey Jr JV, Sherman ME, Rush BB, et al. Absolute risk of endometrial
carcinoma during 20 year follow up among women with endometrial hyperplasia. J Clin Oncol 2010; 28: 788e92.
Practice points
C
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REVIEW
Modern management of
broids
Amanda Jefferys
Valentine Akande
Abstract
Uterine broids are present in approximately 20% of women of reproductive age and can be associated with signicant morbidity including
menstrual disturbance, pressure symptoms and in some cases
reduced reproductive potential. Although some women remain asymptomatic any of the above presentations may be an indication for treatment. Many management options exist including conservative,
treatment with medications, radiological interventions and surgery. Interventions can be fertility sparing whereas some are contraceptive,
whilst others can result in permanent infertility. Ultimately optimal
management should be governed by presenting symptoms, size and
location of broids, as well as the desire for fertility and local expertise.
Fibroid management
Fibroid management options can broadly be divided into medical, surgical and more recently radiological options. Each has its
advantages and disadvantages and will appeal to a different
subset of patients. Ultimately decisions regarding whether and
how to treat will depend on symptoms reported, size, number
and position of the fibroids, the willingness of a patient to undergo surgery, plans for future fertility and local expertise. Table
1 summarizes the indications, advantages and disadvantages of
each management option together with symptomatic effects.
menorrhagia;
Medical management
Levonorgestrel releasing intrauterine system (LNGIUS) (for heavy menstrual bleeding only)
The LNG-IUS is also well established in the management of
menorrhagia, so much so that it is now recommended as first line
treatment in the management of menorrhagia. Its effectiveness in
the context of uterine pathology such a fibroids is less clear. One
longitudinal study has reported significant reductions in menstrual blood loss and increased mean Haemoglobin concentration
within three months of insertion of the LNG-IUS, in women with
a uterine size of 12 weeks or less and one or more fibroids greater
then 1.5 cm in diameter. There was also a significant reduction in
fibroid volume within 6 months of insertion. Reductions in
menstrual blood loss were also reported by another smaller
study, with similar inclusion criteria, however at 12 months the
majority of patients with the LNG-IUS still reported symptoms of
menorrhagia, leading the authors to question the effectiveness of
the LNG-IUS in the fibroid setting. We also need to consider the
fact that fibroids are associated with increased rates of discontinuation of the LNG-IUS and difficulties at the time of fitting (e.g.
expulsion), it is also contraceptive and therefore not an option
for women wishing to conceive.
Introduction
Uterine fibroids (myomas, leiomyomas) are common. These
benign tumours of the uterine smooth muscle are thought to be
present in up to 20% of women of reproductive age (and perhaps
up to 60% of women of African descent). Uterine fibroids are
thought to result from increased mitotic divisions within the
myometrium under the influence of oestrogen and progesterone,
however, what initiates fibroid growth is unclear. Symptoms
depend on size and position of the fibroids, but it is thought that
between 20 and 50% of women are symptomatic of their fibroids. Symptoms include bleeding disturbances (often heavy,
prolonged, frequent and unpredictable bleeds) and pressure
symptoms (bladder and bowel symptoms, bloating, chronic
pelvic pain and dyspareunia). Bleeding disturbances are more
pathognomonic of submucosal or intramural fibroids which
protrude into the endometrial cavity, whereas pressure symptoms are dependent on fibroid size and the extent to which these
fibroids encroach on the peritoneal cavity and the structures
within. Importantly over 50% of fibroids are asymptomatic, and
in many symptoms are mild. As such, the majority of patients
may not require treatment.
The role of fibroids in subfertility remains controversial.
Systematic reviews have suggested reduced livebirth rates in
women with both submucosal and intramural fibroids
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REVIEW
Advantages
Disadvantages
Therapeutic effects
Menstrual
symptoms
LNG-IUS
Menorrhagia
GnRH agonists
Menorrhagia
Pressure symptoms
Pre-surgery
SPRMs
Menorrhagia
Pressure symptoms
Pre-surgery
Menorrhagia
Pressure symptoms
Uterine Artery
Embolisation
MRI focused
High intensity
ultrasound
Menorrhagia
Pressure symptoms
Reversible
May be difficult to
fit / expelled if large
fibroids.
Reduce
Hypoestrogenic
intraoperative
side effects limit
blood loss and
duration of use
midline incisions
Fibroid re-growth
shortly after
cessation of
treatment
Oestrogen levels
One month break
maintained
required between
Few side effects
each course
Quick recovery
High rates of minor
Short hospital stay complications post
procedure (pain,
post-embolisation
syndrome)
High rates of
subsequent
intervention
Quick recovery
High rates of
Short hospital stay subsequent
intervention
Not recommended
for pedunculated
fibroids or where
uterine size > 24
weeks
Menorrhagia
Quicker recovery
Pressure symptoms times, shorter
hospital stays.
Reduced mean
blood loss.
Hysteroscopic
myomectomy
Menorrhagia
Shorter operating
times, shorter
hospital stays,
quicker recovery.
Fewer
intraoperative
complications
128
Fibroid size
Fertility
Contraceptive
Insufficient
evidence to confirm
safety
Insufficient
evidence of safety
Insufficiant
evidence of safety
Livebirths reported
in literature.
Livebirths reported
in literature.
REVIEW
Hysterectomy
Menorrhagia
Definitive
Pressure symptoms resolution of
symptoms.
May deal with other
pathologies
Abdominal
approach often
necessary due to
uterine size.
Long recovery time
(especially
abdominal /
vaginal.
Permanent
cessation of
menstrual blood
loss
Permanent fibroid
removal
Permanently
removes option of
future fertility
Table 1
Radiological interventions
More recently interventional radiology has offered a more permanent solution to symptomatic fibroids for women wishing to
avoid surgery. Traditionally this has been with Uterine Artery
Embolisation, however MRI focused high intensity ultrasound
has received increasing attention recently.
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REVIEW
Surgical management
Surgical management often offers a more definitive solution to
uterine fibroids but are more invasive and not without complications. Surgical options for the management of fibroids can
broadly be divided into fertility-sparing and non-fertility-sparing
surgery. Fertility sparing surgery comprises removal of the fibroid(s) from the myometrium which can be approached via
laparotomy, laparoscopy or hysteroscopically. Ultimately the
most definitive option in the management of fibroids is a hysterectomy, however, for some the psychological and fertility
implications of this are too great.
Open myomectomy
First described in 1845 the open myomectomy is achieved via a
laparotomy and enucleation of the fibroid from the myometrium.
This is followed by closure of the myometrium in three layers to
close the dead space. Open myomectomy is preferably undertaken via the low transverse (Pfannensteil) approach, which is
associated with lower postoperative morbidity and quicker recovery times. For large fibroids it may be beneficial to pre-treat
for three months with GnRH agonists or SPRMs (e.g. Ulipristal
acetate) to shrink the fibroid sufficiently for a pfannensteil
approach to be used. Such pretreatment may also provide other
benefits including increasing pre- and post-operative haemoglobin and reducing intra-operative blood loss.
Although myomectomy has traditionally been associated
with excessive blood loss due to the vascular nature of fibroids,
thanks to adjuvant measures to reduce intraoperative blood loss
including mechanical clamps, and more recently intramyometrial vasopressin, intraoperative tranexamic acid, preoperative misoprostol and haemostatic sealing agents, open
myomectomy now offers low rates of conversion to hysterectomy (<1%) and a low rate of blood transfusions (8%),
together with low rates of intraoperative complications (bowel,
bladder, ureteric injury) (2%) even in the case of large fibroids.
Although in many centres the open myomectomy has been
superseded by the laparoscopic approach, in the majority of
centres the considerable technical skill and expertise will not be
available locally, meaning open myomectomy still holds a place
in the modern day management of fibroids. What is more the
open approach is associated with shorter operating times and
lesser cost than the laparoscopic approach. Even those with the
expertise in laparoscopic surgery acknowledge that for large
(>15 cm) or multiple (>5) fibroids open myomectomy offers
the safest approach and for multiple fibroids is more likely to
result in complete fibroid clearance than the laparoscopic
approach.
As with many surgical interventions there are few studies
assessing the effectiveness of myomectomy in the fertility setting.
Studies that have been undertaken have not looked at open
myomectomy independent of other approaches and have not
demonstrated a benefit in those undergoing surgery compared to
controls. However, successful livebirths have been reported
consistently in the literature.
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Laparoscopic myomectomy
Laparoscopic myomectomy is achieved via laparoscopic
enucleation of the fibroid from the myometrium followed by
morcellation and removal of the fibroid with minimal extension
of the laparoscopic port site. The myometrium is then closed in
layers via laparoscopic suturing techniques. Because of the low
intraoperative complication rates (transfusion rates <0.2%,
visceral injury <0.04%), reduced postoperative febrile
morbidity, shorter recovery times and hospital stays and lower
rates of adhesion formation, at least in expert hands, the laparoscopic approach is in many centres replacing the traditional
laparotomy. Obstetric outcomes including time to pregnancy,
pregnancy rates and miscarriage rates are comparable to those
following laparoscopic myomectomy. Concerns have been
raised that rates of uterine rupture may be higher following
laparoscopic myomectomy, because of the difficulties achieving
multi-layer closure under tension. As with open myomectomy
uterine ruptures have been reported following laparoscopic
myomectomy. Risk factors for uterine rupture appear to be
breach of the endometrial cavity and the excessive use of
diathermy. Few studies have assessed the overall risk of uterine
rupture following laparoscopic myomectomy, however the
largest analysis of 145 pregnancies suggested a reassuringly low
rupture rate of 1%.
Although there appear to be many advantages of the laparoscopic approach, studies conducted so far have been undertaken in settings where there is great local expertise in
laparoscopic surgery, these outcomes may not therefore be
generalizable. Intraoperative risks and technical difficulties
with the laparoscopic technique increase with increasing size
and number of fibroids. Recurrence rates have also been reported as being higher (as high as 30%) following laparoscopic
myomectomy, higher than with the open approach, perhaps
because of reduced fibroid clearance, however others have
disputed this.
Most recently, laparoscopic myomectomy has attracted
negative attention due to concerns over possible seeding and
spread of malignancy following morcellation. Such has been the
concern that the FDA has discouraged the use of morcellation in
the treatment of uterine fibroids. In reality the prevalence of
cancer in those undergoing myomectomy is low (<0.2%) and
evidence suggests that there is no increase in sarcoma dissemination with power morcellation. However, knowing that risk of
sarcoma is increased in older women and in those whose fibroids
have grown rapidly, morcellation should perhaps be used with
caution in these groups. Women should be counselled about
these risks pre-operatively to aid decision-making. Techniques
such as undertaking morcellation within the retrieval bag may
further reduce the risk.
Hysterectomy
Hysterectomy offers definitive treatment of fibroid related
symptoms and guarantees no recurrence of disease, but at the
expense of future fertility and therefore can only be considered in
those women who have completed their family. Because of the
effect of the fibroid on uterine size, vaginal hysterectomy, which
carries the lowest risk of complications and fastest recovery time
will often not be possible, meaning an abdominal or laparoscopic
approach is necessary.
Summary
Ultimately the decision as to how to manage fibroids will depend
principally on presenting symptoms and a patients desire for
future fertility. As with the management of any condition it
seems sensible to start with conservative (medical) measures,
however for women with large fibroids and associated pressure
symptoms ultimately a radiological or surgical solution will be
necessary. Which technique is chosen will depend upon local
expertise as well as patient preference following a detailed discussion regarding risks and benefits.
A
Hysteroscopic myomectomy
Hysteroscopic myomectomy, first described in 1976, is the least
invasive option for the surgical removal of fibroids and can be
used to remove submucosal fibroids. Compared to laparoscopic
and open myomectomy the hysteroscopic approach has the
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REVIEW
FURTHER READING
Donnez J, Hudecek R, Donnez O, et al. Efcacy and safety of repeated
use of ulipristal acetate in uterine broids. Fertil Steril 2015; 103:
519e27. e513.
zquez F, et al. Ulipristal acetate versus
Donnez J, Tomaszewski J, Va
leuprolide acetate for uterine broids. New Engl J Med 2012; 366:
421e32.
Donnez J, Vazquez F, Tomaszewski J, et al. Long-term treatment of
uterine broids with ulipristal acetate. Fertil Steril 2014; 101:
1565e73. e1561e1518.
Grigorieva V, Chen-Mok M, Tarasova M, Mikhailov A. Use of a
levonorgestrel-releasing intrauterine system to treat bleeding
related to uterine leiomyomas. Fertil Steril 2003; 79: 1194e8.
Gupta JK, Sinha A, Lumsden MA, Hickey M. Uterine artery embolization for symptomatic uterine broids. Cochrane Database Syst
Rev 2014. Issue. 12. Art. No.: CD005073.
Hehenkamp WJ, Volkers NA, Birnie E, Reekers JA, Ankum WM.
Symptomatic uterine broids: treatment with uterine artery embolization or hysterectomyeresults from the randomized clinical
Embolisation versus Hysterectomy (EMMY) Trial. Radiology 2008;
246: 823e32.
Jun F, Yamin L, Xinli X, et al. Uterine artery embolization versus surgery for symptomatic uterine broids: a randomized controlled trial
and a meta-analysis of the literature. Arch Gynecol Obstet 2012;
285: 1407e13.
Manyonda IT, Bratby M, Horst JS, Banu N, Gorti M, Belli AM.
Uterine artery embolization versus myomectomy: impact on quality
of lifeeresults of the FUME (Fibroids of the Uterus: myomectomy
versus Embolization) Trial. Cardiovasc Intervent Radiol 2012; 35:
530e6.
Wright JD, Tergas AI, Cui R, et al. Use of electric power morcellation
and prevalence of underlying cancer in women who undergo
myomectomy. JAMA Oncol 2015; 1: 69e77.
Practice points
C
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ETHICS/EDUCATION
Tahir Mahmood
Obesity is an independent risk factor for adverse obstetric outcomes and increased maternal and neonatal morbidity and
mortality. This is due to the increased risk of the following obstetric and neonatal problems:
Congenital abnormalities (spina bifida and heart defects)
Pre eclampsia
Gestational diabetes
Deep venous thrombosis
Macrosomia
Intrauterine foetal demise
Induction of labour
Infection related morbidity
Difficult instrumental deliveries
Caesarean section
Postpartum haemorrhage
Omar Thanoon
Abstract
Obesity is now a critical global issue, as more than 2.1 billion people
(nearly 30% of the world population) are either overweight or obese.
It has been reported that , for every increase in body mass index of
5 kg/m2, there was a 30% overall higher mortality with a 40% increase
in vascular mortality, a >50% increase in diabetic, renal and hepatic
mortality. It has been proposed that all obese women should be
encouraged to normalise their weight before embarking on a pregnancy. The most recently published multi-centre study, The Upbeat
has concluded that a behavioural intervention addressing diet and
physical activity in women with obesity during pregnancy is not
adequate to prevent gestational diabetes, or to reduce the incidence
of large for gestational age infants. Therefore not surprisingly, there
is a huge public interest in bariatric surgery for managing morbid
obesity. However question arises whether weight loss by this route
does improve fertility potential of women without any adverse effects
on the pregnancy outcome?
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ETHICS/EDUCATION
Conclusion
Obesity provides an imperfect environment for fertility and
pregnancy. Despite our current understanding of these abnormal
hormonal milieus, there is yet to find a perfect medical or surgical intervention to improve outcomes. The number of women
having bariatric surgery is increasing and these women should
consider the benefits and risks of surgery carefully before having
any surgical procedure.
The current available data does not support the use of bariatric surgery as a treatment method for obese women wanting to
improve their fertility and pregnancy outcome. To date there
seems to be no treatment superior to healthy weight loss through
lifestyle interventions.
A
FURTHER READING
Colquitt JL, Pickett K, Loveman E, Frampton GK. Surgery for weight
loss in adults. Cochrane Database Syst Rev 2014 Aug 8; 8. http://
dx.doi.org/10.1002/14651858.CD003641.pub4. CD003641.
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Mahmood T, Arulkumaran S. Obesity-A ticking time bomb for reproductive health. First edn. Elsevier insight, ISBN 978-0-12-4160453; 2013.
Owers CE, Ackroyd R. In: Metwally M, Li TC, eds. Bariatric surgery (in)
reproductive surgery in assisted conception. London: SpringerVerlag, 2015; 143e50.
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conceive or maintain pregnancy leads to the diagnosis as anovulation and, potentially, miscarriage can be a symptom of thyroid
disease. However, if thyroid dysfunction has not been recognised
prior to conception, establishing the diagnosis during pregnancy
can be problematic as many of the symptoms of thyroid
dysfunction are comparable to those of normal pregnancy. It is
therefore important to have an overview of the physiology of the
thyroid, its impact on reproductive health and how it changes in
pregnancy.
Anja Johansen-Bibby
Joanna Girling
Thyroid physiology
The thyroid gland is controlled from the hypothalamus, which
produces thyrotropin-releasing hormone (TRH). This polypeptide stimulates thyrotroph cells in the anterior pituitary gland
to produce thyroid stimulating hormone (TSH). This glycoprotein hormone, consisting of two alpha and two beta subunits, is
released into the blood to bind to the TSH receptor on the thyroid
gland, stimulating the production of T3 and T4 from thyroglobulin and iodine. T3 and T4 use a negative feedback loop to balance production of TRH and TSH, and this stepwise production
of hormones is modulated by somatostatin, glucocorticoids as
well as excess iodine. In early pregnancy, there is conflict between TSH and the homologous human chorionic gonadotrophin
(HCG) produced by the developing placental tissue, as the alpha
sub-units are identical. HCG can stimulate TSH receptors, (much
less potently than TSH) on the thyroid gland, leading to a decline
in the production of TSH in some women, and in a smaller subset
to a biochemical picture of hyperthyroidism with elevated T4 of
women [see later, gestational thyrotoxicosis].
Normative reference ranges in cohorts of healthy pregnant
women without thyroid disease indicate that the upper limit of
normal for TSH in uncomplicated pregnancy may be higher than
outside pregnancy, and these limits may vary according to the
laboratory technique or the demographics of the population:
ideally local gestation-specific reference ranges should be used.
These changes are of importance when interpreting blood results
of pregnant women, as the reference range throughout pregnancy differs from non-pregnant women (see Table 1). Table 1
also shows a typical reference range in a multiethnic UK
population.
Maternal iodine requirements increase (by as much as 50%)
as iodine is actively transported to the developing fetus and the
maternal thyroid upregulates to absorb more iodine to allow the
total T3 and T4 production to rise. High oestrogen concentrations
extend the half-life of plasma proteins including thyroxine
binding globulin (TBG), such that the concentration increases at
least 1.5 fold by week 8 of pregnancy, and remains at this higher
level until delivery. Thus where women have a good supply of
iodine, total T4 and T3 concentrations are increased, but the
biologically-active free T3 and free T4 stay relatively stable
throughout pregnancy. In areas where women have mild iodine
deficiency, pregnancy-induced goitre can occur, together with
relative hypothyroidism due to the limitation of T4/T3 production; this can impact upon the development of the fetus.
Iodine deficiency is the commonest cause of hypothyroidism
worldwide. The WHO states that iodine deficiency is the single
most important preventable form of brain damage in children,
now referred to as neonatal cretinism. Severe iodine deficiency
also plays a role in increased perinatal mortality. This has led to
Abstract
The number of women with endocrine conditions embarking on pregnancy is growing as more choose to delay conception or require assisted reproduction techniques. It is therefore increasingly important for
clinicians to have an understanding of common endocrine disorders
and how these may impact on pregnancy and fetal development.
Over-investigation and subsequent medicalization and treatment of
sub-clinical endocrine conditions, which have uncertain clinical impact
for the fetus or mother, is a cause for concern and debate surrounding
this practice is ongoing. Vitamin D deciency is increasing in prominence due to the rise in childhood rickets; this startling reemergence has led to more work on the prevalence of vitamin D deciency and identied a higher than expected percentage of women
affected. For this reason, national advice has called for routine vitamin
D supplementation in pregnancy, and diagnosis and treatment of
those most at risk. This review also briey discusses the management
of other rarer endocrine conditions, which can lead to signicant
maternal and fetal morbidity if the diagnosis is delayed or overlooked.
Thyroid disease
The maternal thyroid gland is responsible for both fetal and
maternal production of thyroxine (T4) and tri-iodiothyronine
(T3) until the fetal thyroid starts functioning at the end of the
first trimester. Until then, there is good evidence that inadequate
or excessive maternal T4 can have serious long term effects on
fetal development, which can translate into cognitive neurodevelopmental problems for the child.
As thyroid disorders are common, the incidence being up to
3% of women of child-bearing age, many pregnancies will be
complicated by thyroid dysfunction. The vast majority of these
women will have a formal diagnosis prior to pregnancy, and
should be taking appropriate treatment to ensure they are
euthyroid before embarking on pregnancy. In some, inability to
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Non pregnant
First trimester
Second trimester
Third trimester
FT4 pmol/l
FT3 pmol/l
TSH mu/l
TSH mu/l (Endocrine Ass)
TSH mu/l (European Thyroid Ass)
9e26
2.6e5.7
0.3e4.2
10e16
3e7
0e5.5
0.1e2.5
0.1e2.5
9e15.5
3e5.5
0.5e3.5
0.2e3.0
0.1e3.0
8e14.5
2.5e5.5
0.5e4
0.3e3.0
0.2e3.5
While the literature is useful in identifying antenatal trends in thyroid parameters, the reference ranges cited are to be used as a guide to clinical practice and not an
absolute. Reference ranges may vary depending on the laboratory method used to assay the hormones. FT4 and FT3 (Cotzias C et al. Eur J Obstet Gynecol Reprod Biol.
2008 137(1):61e6).
Table 1
programmes to administer annual boluses of iodine to susceptible women and to national salt, water and flour iodinisation. The
UK population is relatively iodine replete, with dairy and fish
being the main dietary sources, and currently there is no official
UK Government advice to take an iodine supplement prior to or
during pregnancy, although, iodine requirements are 250 micrograms per day for pregnant and lactating women, compared
with 150 micrograms for non-pregnant women.
offspring of women with very high TSH, and others suggest a role
in neurocognitive problems such as attention deficit disorder.
However, there is no convincing evidence of adverse fetal effects
when maternal TSH is within the pregnancy-specific reference
range. Therefore, the ideal for hypothyroid women is to ensure
adequate thyroxine replacement at least 3 months before
conception, to avoid the potential adverse effects of untreated or
under-treated hypothyroidism on the conceptus.
Although rarely seen in the UK, overt symptomatic untreated
hypothyroidism is also associated with an increase in miscarriage, gestational hypertension, preterm delivery, post-partum
haemorrhage together with fetal growth restriction. There has
also been a suggestion that hypothyroidism is associated with
gestational diabetes mellitus, with almost double the number of
women on levothyroxine replacement having this diagnosis
compared with background population.
There are several schools of thought regarding the need for
women with autoimmune hypothyroidism to increase thyroxine
replacement dose during pregnancy. The American Thyroid
Association (ATA) has advocated an empirical increase in levothyroxine at the diagnosis of pregnancy by 25% with the aim
of an upper limit of TSH at 2.5 mU/L. The British Thyroid Association propose an increase of 25e50 micrograms at the
beginning of pregnancy to ensure TSH levels are maintained
within the normal range, and free T4 are in the upper range of
normal. Neither group provide robust evidence to support these
statements. Observational data suggest that women with preconception TSH less than 1.2 mU/L do not require any increase
in thyroxine replacement, but no indication that this is required
for optimal outcome. Others argue that changes in thyroxine
replacement should be guided by pregnancy-specific reference
ranges. There are many reasons for these differing opinions,
and it is important to recall the gestation at which hypothyroidism could have a direct fetal effect, and that the important
end point of neurocognitive function in the offspring is dependent on many different variables; no studies of sufficient size
have prospectively addressed the impact of first trimester
maternal TSH nor shown whether altering thyroxine dose to
achieve a predetermined low TSH is beneficial [or harmful] to
the fetus [or mother]. In addition, there is some evidence that,
at least theoretically, excess circulating T4, as may result from
empirical increases in thyroxine dose, may be associated with
miscarriage.
Hypothyroidism
Overt hypothyroidism [high TSH, low fT4] affects approximately
20,000 pregnant women a year in the UK. Most of these women
have a diagnosis prior to pregnancy, and should aim to conceive
when they are euthyroid taking levothyroxine replacement.
Some women will enter pregnancy on an inadequate dose of
thyroxine, and these women should have their thyroxine dose
adjusted according to pregnancy-specific reference ranges. There
is ongoing discussion about whether thyroxine replacement
should be increased empirically during pregnancy; the evidence
for this appears to depend on the reason underlying the hypothyroid status.
The majority of women have an underlying diagnosis of
Hashimotos thyroiditis, an autoimmune condition where the
thyroid gland is damaged by auto-antibodies to thyroid peroxidase or thyroglobulin. This condition often co-exists with other
auto-immune diseases, particularly Type I diabetes mellitus,
rheumatoid arthritis and systemic lupus erythematosus, which
may be of greater importance to the mother and fetus than the
thyroid dysfunction itself. Other women are hypothyroid
following surgical thyroidectomy for treatment of malignancy,
goitre or thyrotoxicosis, or following radio-active iodine treatment. These women with total thyroidectomy have no ability to
produce thyroxine and are more likely to need an increasing dose
of levothyroxine replacement throughout pregnancy, as they
have no residual thyroid to enable any production; this is
particularly so when complete TSH suppression is required as
part of the management of thyroid cancer.
Fetal brain development relies on maternal supply of
thyroxine and iodine [as TSH and fT3 cannot cross the placenta]
until the fetal thyroid becomes functional, around 12e16 weeks
of gestation. Before this gestation, impairment in neurocognitive
development can occur without adequate thyroxine replacement.
Some studies have demonstrated a reduction in IQ score in the
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Graves disease
This is the most common cause of hyperthyroidism in pregnant
women. Graves disease is an auto-immune condition characterised by suppressed TSH, high T4/T3 and the presence of TSH
receptor stimulating antibodies (TRAb). During pregnancy, disease control is usually achieved by using medication to block
thyroid hormone synthesis, such as propylthiouracil (PTU),
carbimazole (CBZ) and in the US methimazole, combined with
beta-blockers, if required, for symptomatic relief. It can be
particularly active in the first trimester due to the stimulatory
effect of HCG which can often worsen symptoms; this is often
followed by an improvement as the immunomodulating effects of
pregnancy result in a lower titre of TRAb, and medication can
often be discontinued. Total or partial thyroidectomy can be
carried out in pregnancy, usually the second trimester, but is
mainly reserved for women intolerant of or resistant to oral
medication, with goitre compromising the airway or when malignancy is suspected. Radio-active iodine is contraindicated in
pregnancy, as it would render the fetus athyrotic; if required it
should occur at least six months before conception; if considered
in the postnatal period, careful counselling is needed as it will
require a period of separation of mother and baby after administration of the radioactive medicine, and a longer period of
abstinence from breastfeeding.
It is essential for maternal and fetal wellbeing that optimal
control of thyrotoxicosis is maintained, with the lowest effective
dose of medication. Abrupt or inappropriate cessation of therapy is likely to result in a worse outcome than its continuation.
Both PTU and CBZ are associated with mild maternal side effects, and a small chance of agranulocytosis. Carbimazole is
associated with an embryopathy in less than 2% of exposed
infants, which may include feature such as aplasia cutis, choanal atresia, trachea-oesophagael fistula, facial dymorphism and
cognitive development delay, and thus PTU may be preferred in
the first trimester since the link with congenital anomalies
seems weaker. However, PTU can cause hepatotoxicity, and
cases of maternal fulminating hepatotoxicity associated with
PTU in late pregnancy have occurred. Due to these potential
repercussions, some consider that conceiving on PTU and
changing to CBZ from the 2nd trimester onwards is optimal.
Changing medication risks new maternal symptoms, however,
with possible loss of thyroid control and fetal exposure to two
medications. In addition, not all pregnancies are planned, and if
conception (and therefore fetal exposure) has occurred on CBZ,
there may be an argument for continuing this therapy. These
issues should be discussed with the woman, ideally when
medical management of hyperthyroidism is first initiated, and
an individual plan made. Conception should be deferred at least
until biochemical euthyroidism is well established; women who
conceive when control is poor are more likely to have an
adverse pregnancy outcome than those whose condition is well
controlled by antithyroid medication.
The medication dosage should be the lowest possible to
ensure that free T4 level remains at the upper end of the
pregnancy-specific normal range. TSH levels change more
slowly, and may not reflect current thyroid status, so are not
used for medication titration. Women on anti-thyroid medication
should have their thyroid function checked every 6 weeks after a
change of medication, and each trimester if stable. As the
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Hypoparathyroidism
The low calcium status of women with hypoparathyroidism can
have significant effects on pregnancy and fetal development.
Women can develop muscle cramps, paraesthesia and seizures if
untreated, with a reduction in fetal growth occurring due to poor
bone development, and increased likelihood of developing
rickets. These situations, however, are rare in pregnancy, as
most women who have had thyroid surgery, the most common
cause of hypoparathyroidism, have been fully informed of the
need for calcium and vitamin D supplementation. Serum calcium
can be measured through pregnancy to ensure sufficient supplementation and it is rare for this to become a problem in
pregnancy.
Pituitary disorders
The pituitary gland orchestrates many hormonal axes within the
body, the majority of which are activated and functional during
pregnancy. The notable exception is the gonadotrophin axis
(hypothalmic e pituitary- ovarian axis) which is inhibited due to
the high levels of oestrogen and progesterone. Due to the
increased production of mainly prolactin from the anterior pituitary lactotrophs, the pituitary gland increases in size by up to
three fold secondary to hyperplasia as well as hypertrophy. Some
pituitary-like hormones are also produced by the placenta,
namely adrenocorticotrophin (ACTH) and growth hormone
(GH); despite increased pituitary production, the placenta supports pituitary production to ensure the necessary levels of
cortisol are achieved.
Parathyroid dysfunction
Primary hyperparathyroidism
Primary hyperparathyroidism is a common endocrine condition in
adults, however, is uncommonly seen in pregnancy and due to the
changes of pregnancy, rarely causes significant complications.
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Prolactinomas
Prolactinomas are the most common benign pituitary adenomas
in pregnancy, and have usually been diagnosed and treated prior
to conception. Outside of pregnancy, symptoms commonly
include amenorrhoea, anovulation, galactorrhoea and infertility.
Prolactin secretion is under negative feedback control from
dopamine, and hence the dopamine agonists bromocryptine and
more recently cabergoline form the mainstay of management
outside pregnancy. Management during pregnancy depends on
the size of the adenoma; micro adenomas less than 10 mm in size
rarely causing a problem, whereas those which are greater than
10 mm [macroprolactinoma] may require more careful
management.
Acromegaly
Oversecretion of growth hormone from pituitary somatotrophs is
rarely encountered in pregnancy, as most women with acromegaly do not ovulate. 40% also present with hyperprolactinaemia, with or without a macroadenoma. Concerns are
similar to those with prolactinomas regarding growth of the adenoma and pressure on the optic chiasm. Other co-morbidities of
acromegaly, such as high blood pressure, insulin resistance or
diabetes mellitus and cardiac disease can also impact pregnancy
and these must be optimised prior to conception.
Treatment of acromegaly is primarily surgical, however, some
women require medical treatment with a dopamine agonist, somatostatin receptor ligands (such as octreotide) and the new
growth hormone receptor antagonist, pegvisomant. Women
considering pregnancy who have not had surgery should ideally
discuss their management options before conception. There are
some reassuring safety data emerging regarding pegvisomant use
in pregnancy, and it is in FDA category B [no risk identified from
animal studies; no adequate data in humans], however, this is
not recommended unless absolutely necessary, and is usually
discontinued prior to pregnancy or at conception; short acting
octreotide can be used if required.
Women can be reassured that acromegaly appears not to
affect the developing fetus. They should have serial visual fields
testing in pregnancy, and education regarding potential symptoms as well as be considered at high risk of developing gestational diabetes. If symptoms deteriorate an MRI is required to
assess tumour expansion; growth hormone or insulin-like growth
factor-1 levels are not helpful in pregnancy. Medical treatment
may need to be reinstated.
Microprolactinomas
Only 3% of women with a microadenoma will experience
symptomatic enlargement of their adenoma during pregnancy,
mainly consisting of headaches, and visual disturbances secondary to the adenoma encroaching on the optic chiasm. Due to
this low incidence, women usually stop dopamine agonist
medication when they confirm pregnancy. Women need to be
educated to seek advice should they develop symptoms, and
visual fields should be formally tested every trimester, ideally
with a pre-pregnancy baseline. Prolactin levels should not be
measured, as they are elevated during normal pregnancy and
therefore are not useful for management, however, women
should have testing after delivery or after cessation of breastfeeding. Should prolonged periods of breastfeeding be desired, an
MRI should be considered to ensure no significant enlargement
of the prolactinoma. Interestingly, in up to 65% of women with
microprolactinomas, remission occurs after pregnancy; although
the mechanism is unknown, auto-infarction of the tumour has
been proposed.
Cushings syndrome
The classical Cushings disease is caused by a pituitary adenoma
leading to excessive adrenal production of cortisol, however, the
eponym Cushings syndrome is used for any condition leading to
hypercortisolaemia. The condition itself leads to sub fertility and
therefore is rarely encountered in pregnancy, however, when
seen, 40e50% are due to an adrenal adenoma, 15% due to adrenal carcinoma and the remaining from a pituitary adenoma. In
normal pregnancy, ACTH levels significantly increase which
contributes to normal physiological changes of weight gain,
water and salt retention and striae; other symptoms of impaired
glucose tolerance, and high blood pressure can also be attributed
to pregnancy and an alternative diagnosis may not be sought.
Thus diagnosing Cushings syndrome presenting for the first time
in pregnancy can be a significant challenge. High dose dexamethasone suppression test, or loss of circadian variation in
salivary cortisol can be diagnostically helpful, but imaging,
initially ultrasound of the adrenals and then MRI of both the
adrenal and pituitary are required. A multidisciplinary approach
is essential.
A state of excessive hypercortisolaemia has significant
impact on maternal and fetal wellbeing. Pregnancies complicated by this condition have a high chance (70%) of hypertension, together with pre-eclampsia in up to 15%, gestational
diabetes (up to 25%), and a risk of cardiac failure if untreated.
There is increased risk of premature delivery with the subsequent neonatal morbidity, due to the high cortisol levels triggering labour, and resultant hypocortisolaemia in the neonate.
Macroprolactinomas
These are less common than microadenomas, but are more likely
to have a significant impact on management in pregnancy.
Symptomatic enlargement is reported in up to 30% of pregnant
women with macroprolactinoma. The ideal is to have an MRI
prior to commencing pregnancy, to determine the extent of the
adenoma and whether definitive treatment with transphenoidal
surgery or radiotherapy should be pursued prior to pregnancy,
although with careful discussion regarding the potential for hypopituitarism and implications of this as a consequence of
treatment. For those with a large tumour which abuts the optic
chiasm, a dopamine agonist should be continued throughout
pregnancy and if this fails to stop enlargement, surgical treatment
may be needed in the second trimester. For those with a
macroadenoma which is not encroaching the chiasm, discontinuation of dopamine agonist can be considered, however,
formal visual field testing is needed each trimester, and should
any symptoms occur, an MRI performed and cabergoline restarted. Similarly to microprolactinomas, prolactin measurements are unhelpful during pregnancy and not required.
Cabergoline is not licensed in pregnancy, however it has a
good safety profile and minimal adverse side effects. Long term
use (over 1 year) has been associated with heart valve fibrosis
and surveillance with echocardiography is advisable if long term
treatment is being considered.
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There is also a higher risk of fetal growth restriction and intrauterine death. Outside of pregnancy, surgical treatment is the
first line option, and if possible this could take place in the
second trimester, or delivery should be considered if the fetus is
sufficiently mature. In pregnancy there is limited experience of
using metyrapone to block cortisol production, although there
have been reports of an increase in hypertensive related
morbidity.
Hypopituitarism
Most obstetricians have some appreciation of hypopituitarism
secondary to Sheehans syndrome, that is pituitary infarction
secondary to massive postpartum haemorrhage. Other causes of
hypopituitarism include previous pituitary surgery or radiotherapy, infarction of a pituitary adenoma, and auto-immune
lymphocytic hypophysitis. Each case needs assessment
regarding the extent of the hypopituitarism, some will have only
partial disturbance of the pituitary function, whereas other
women will have panhypopituitarism, involving all pituitary
hormones. Over time most women will gradually lose complete
function and will develop panhypopituitarism. The condition is
rare in pregnancy as gonadotrophin axis appears most fragile,
and impairment leads to anovulation, however, there are now
more pregnancies in women conceived using gonadotrophin
replacement. These women are usually given progesterone supplementation to support the corpus luteum, as the low luteinising
hormone levels have been suggested to be one of the causal
factors in the higher miscarriage rates in these women. Those
women who conceive will need careful monitoring of the
replacement hormones throughout pregnancy, which usually
include levothyroxine and glucocorticoid replacement, with hydrocortisone, specifically to avoid an Addisonian crisis (see
below). Some women will also have growth hormone replacement, however, if pregnancy is achieved, the placenta will
overcome this particular maternal deficiency and this can be
discontinued after the first trimester.
Adrenal disease
Pituitary apoplexy
This condition is a set of symptoms and signs which occur with
abrupt haemorrhage or infarction classically into a pituitary adenoma, leading to rapid expansion of the pituitary out of the sella
turcica. The major symptom is severe headache, however, the
situation can deteriorate rapidly with subarachnoid haemorrhage, meningism, visual and neurological deficit, including
cranial nerve palsies and reduced consciousness. This condition
is rare in pregnancy, with only 12 case reports to date. Those
describe patients complaining of sudden onset headache, sometimes with associated nausea and vomiting. Imaging via MRI will
determine the extent of the expansion and whether the optic
chasm has been compromised. Hormone replacement is
mandatory particularly with steroids, otherwise an Addisonian
crisis can develop; the other pituitary controlled hormones,
namely thyroxine, should be checked and adequate dose prescribed. Non-tumourous apoplexy is seen in Sheehans syndrome, when postpartum haemorrhage changes the blood supply
via the single pituitary artery, leading to infarction and necrosis.
Typically, this will present with failure of lactation and persistent
amenorrhea, which should then alert clinicians to the need to
ensure functioning of other pituitary axes.
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If the diagnosis is suspected, further investigations with ultrasound and MRI of the adrenals are recommended. Outside
pregnancy, meta-iodo-benzylguanidine [MIBG] scintiscan is used
to locate tumours, but it is contra-indicated in pregnancy due to
the use of radioactive iodine.
Management is based around blood pressure control and then
surgical removal. Hypertensive crises can be precipitated by labour, delivery and general anaesthetic. Blood pressure control
should be with alpha blockade [usually intravenous phenoxybenzamine] initially and beta blockade [usually propranolol] to
control the tachycardia. There has been a recommendation to
deliver women with phaechromocytoma by elective Caesarean
section [due to the history of maternal deaths during labour and
vaginal delivery, secondary to malignant hypertension], either
combined with removal of the phaeochromocytoa or with the
latter as an interval procedure, potentially laparoscopically.
There have, however, been recent reports of successful vaginal
delivery with regional analgesia and close monitoring. There
have also been reports of successful pregnancy following early
second trimester surgery.
Phaeochromocytoma
This condition is another secondary cause of high blood pressure
which can be overlooked in pregnancy if it is not considered.
Missed diagnoses can potentially be fatal due to the paroxysmal
bursts of extreme blood pressure; maternal mortality is up to
15%. This condition often mimics pre-eclampsia, however, is
associated with much higher fetal mortality. The initial key to
diagnosis is to consider it as a diagnosis, and then to review the
history: typical symptoms include palpitations, excessive
sweating, and labile blood pressure causing postural hypotension, then significant hypertension and the key finding is the
presence of elevated urine catecholamines and their metabolites
specifically vanillylmandelic acid. These findings are caused by
the sporadic release of excessive catecholamines from the
tumour, which may be in the adrenal medulla or elsewhere along
the sympathetic chain.
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management for thyroid dysfunction pre-pregnancy and during
pregnancy for improving maternal and infant health. Cochrane
Database Syst Rev 2015 Sep 21. Issue 9. Art. No.:CD011263.
Stagnaro-Green A, Abalovich M, Alexander E, et al. Guidelines of the
American Thyroid Association for the diagnosis and management
of thyroid disease during pregnancy and postpartum. Thyroid 2011;
21: 1081e125.
Vissenberg R, Fliers E, van der Post JA, van Wely M, Bisschop PH,
Goddijn M. Live-birth rate in euthyroid women with recurrent
miscarriage and thyroid peroxidase antibodies. Gynecol Endocrinol
2015 Oct 2; 1e4.
Yassa L, Marqusee E, Fawcett R, et al. Thyroid hormone early
adjustment in pregnancy (the THERAPY) trial. J Clin Endocrinol
Metab 2010; 95: 3234.
Conclusion
This review summarises the management of common endocrine
conditions, gives an overview of the rarer conditions and covers
important fetal and neonatal issues which need to be considered
during pregnancy.
A knowledge of endocrine conditions is important for the
obstetrician as they are increasingly common, particularly with
the advent of women delaying pregnancy and with increased
assisted reproduction therapy. Ideally, pre-conceptual advice
should be given regarding the pertinent issues, and all healthcare
professionals in primary and secondary care have a role to play
in this. In pregnancy, some women will be managed with minimal change to their routine antenatal care and unnecessary
medicalization can be avoided; others will require a full multidisciplinary approach, with endocrinologists, anaesthetists, paediatricians and surgeons involved, preferably led by an expert in
Obstetric Medicine. A high degree of clinical suspicion is needed
as apparently common symptoms can rarely be due to important
endocrine disorders.
A
Practice points
C
FURTHER READING
Almalki MH, Alzahrani S, Alshahrani F, et al. Managing prolactinomas
during pregnancy. Front Endocrinol (Lausanne) 2015 May 26; 6: 85.
Bhattacharyya R, Mukherjee K, Das A, Biswas MR, Mukherjee A. Antithyroid peroxidase antibody positivity during early pregnancy is
associated with pregnancy complications and maternal morbidity
in later life. J Nat Sci Biol Med 2015 Jul-Dec; 6: 402e5.
Chan S, Boelaert K. Optimal management of hypothyroidism, hypothyroxinaemia and euthyroid TPO antibody positivity preconception and in pregnancy. Clin Endocrinol (Oxf) 2015 Mar; 82: 313e26.
De Groot L, Abalovich M, Alexander EK, et al. Management of thyroid
dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2012; 97:
2543e65.
148
REVIEW
Venous
thromboembolism in
pregnancy
Annabel Lim
Anushika Samarage
Boon H Lim
Abstract
Venous thromboembolism (VTE) is a leading cause of maternal
morbidity and mortality in the developed world. The term includes
deep vein thrombosis (DVT) and pulmonary embolism (PE). Women
are at least ve times more likely to develop VTE during pregnancy
compared to when they are not pregnant. The symptoms of acute
VTE can be non-specic. Strategies should be put in place during
the antenatal period to identify women at increased risk of thromboembolic disease. When an acute event thromboembolic is suspected
in high risk women during pregnancy, therapy may be commenced
empirically whilst investigations are commenced to conrm the
diagnosis.
Introduction
133
REVIEW
Postpartum thromboprophylaxis
All women should have a further risk reassessment of VTE in
labour and the postnatal period. Appropriate arrangements and
education for self-administration of LMWH should be instituted
before discharge.
134
REVIEW
Practice points
C
Table 1
135
REVIEW
Duplex ultrasound
Bilateral compression duplex leg ultrasound should be performed
in all pregnant women suspected to have deep vein thrombosis
(DVT). The higher incidence of isolated iliac vein DVT in pregnancy may lead to increased risk of false negatives. If ultrasound
does not identify DVT, and PE is suspected, further imaging is
required. However, if DVT is diagnosed, then accompanying
chest symptoms may be assumed as the result of PE and further
imaging for PE can be omitted as therapeutic treatment is similar
in both situations.
If ultrasound is negative and there is a low level of clinical
suspicion for DVT, anticoagulant treatment can be ceased. If
ultrasound is negative and a high level of clinical suspicion remains, anticoagulant treatment should be discontinued but the
ultrasound should be repeated on days 3 and 7.
Baseline investigations
Full blood count, coagulation studies, urea, electrolytes and liver
function tests should be performed as baseline blood investigations to check renal and hepatic function before starting
anticoagulant treatment. Thrombophilia screening during acute
VTE is not routinely indicated because coagulation parameters
are altered in pregnancy and testing will not alter immediate
management.
Denitive imaging
Ventilation perfusion (V/Q) scan or computed tomography pulmonary angiogram (CTPA) can be used to provide definitive
diagnosis of PE. If CXR is abnormal, CTPA should be performed.
If CXR is normal, then the choice of scan should be made with
consideration of local availability, sensitivity, maternal and fetal
risks, and discussion with a radiologist. Hospitals should have a
local protocol in place with a diagnostic pathway for suspected
PE in pregnancy. Advantages of CTPA over V/Q scan include
better availability (found in more hospitals, often operated 24
hours a day) and the ability to identify other pathology including
pneumonia (5e7%), pulmonary oedema (2e6%) and rarely
aortic dissection.
CTPA and V/Q scan are associated with similar amounts of
fetal radiation exposure. The exposure is considered low dose
and well below the threshold for teratogenicity, fetal growth restriction and fetal death. The concern associated with this level of
fetal radiation exposure relates to a small increased risk of
childhood cancer (1:280,000 with V/Q scans vs. 1:1,000,000 with
CTPA). The increased risk of fatal childhood cancer to the age of
15 following in utero radiation exposure has been estimated by
the International Commission on Radiological Protection as
0.006% per mGy. Despite the wide variation in estimates of fetal
radiation exposure from CTPA and VQ scans (0.06e0.66 mGy)
the overall risks of radiation to the fetus can be considered low.
When performing a V/Q scan in pregnancy, the ventilation
component can often be omitted, further minimizing the fetal
radiation exposure.
The maternal radiation risk from CTPA is more significant.
CTPA exposes the maternal breast tissue to a relatively high
First-line treatment
Low molecular weight heparin (LMWH) is the treatment of
choice for VTE in both pregnant and non-pregnant populations.
LMWH are safe, easy to administer, and women can be taught to
inject themselves. They do not cross the placenta and can be
used throughout pregnancy.
Warfarin crosses the placenta and is teratogenic in the first
trimester, with a 6% risk of embryopathy if taken between 6 and
12 weeks gestation. Complications such as miscarriage and
stillbirth are more common. Furthermore, the incidence of fetal
intracerebral haemorrhage is increased when warfarin is used in
the third trimester. Warfarin is rarely recommended in pregnancy except in women with prosthetic (mechanical) heart
valves; it is more commonly used in women with metallic mitral
valves who are at the highest risk of thrombotic complications,
but even then should only be continued under specialist maternal
medicine care jointly with a cardiologist.
A Cochrane review of 22 studies of patients with VTE showed
that LMWH treatment was superior to unfractionated heparin (UH)
with lower rates of VTE recurrence or extension, less major haemorrhage during initial treatment, and overall lower mortality.
Knol et al (2012) found that LMWH therapy is associated with an
increased risk of postpartum haemorrhage (30% after vaginal delivery compared to 18% in the control group; 12% after Caesarean
section compared to 4% in the control group) but there was no
136
REVIEW
YES
NO
Perform compression
duplex ultrasound
Compression ultrasound
NO
YES
YES
Continue therapeutic
doses of LMWH
NO
NO
Perform CTPA
YES
Continue therapeutic
doses of LMWH
137
REVIEW
Haemodynamic instability
Patients with massive PE may present with shock, hypoxaemia or
right ventricular dysfunction. In massive life-threatening PE with
cardiovascular compromise, UH is the preferred treatment due to
its rapid effect, reversibility and widespread clinical experience of
its use in this scenario. A multi-disciplinary approach with input
from senior physicians, haematologists, obstetricians and radiologists should be adopted, following local protocol to guide weightbased administration of intravenous UH.
When UH is given, APTT must be measured 4e6 hours after
the loading dose, 6 hours after any dose change, and daily when
in therapeutic range. However, it is noted that in late pregnancy,
increased fibrinogen and factor VIII affect the APTT, which can
lead to the use of higher than necessary doses of heparin and
consequent bleeding problems. Senior haematology advice should
be sought and the anti-Xa level may be used as a measure of
heparin dose. Platelets should also be monitored every 2e3 days
from day 4e14 or until UH is stopped, due to the risk of HIT.
If there is haemodynamic compromise, thrombolysis should
be considered. Randomized trials have provided evidence that
thrombolysis in addition to anticoagulation aids more rapid
dissolution of emboli, helping to restore pulmonary circulation,
but without any beneficial effect on mortality. Case reports of
thrombolysis during pregnancy (most commonly using streptokinase, urokinase and recombinant tissue plasminogen activator) have been published, with complications including fetal
death (1.7%), non-fatal maternal bleeding (2.9%), placental
abruption, and preterm labour. If thrombolysis is contraindicated, thoracotomy and surgical embolectomy can be
considered.
Postnatal treatment
Following delivery, women may choose to convert to warfarin or
remain on LMWH. Women on LMWH or warfarin may continue
to breastfeed as only minimal amounts are found in the
breastmilk.
Postnatally, therapeutic anticoagulant should be continued for
at least 6 weeks, with total therapy duration of at least 3 months.
If continuing anticoagulation with LMWH, the previous antenatal
dose can be continued or changed to the manufacturers recommended dose for non-pregnant patients (1.5 mg/kg enoxaparin daily). If warfarin is selected for continuation of
anticoagulation, it should be started no sooner than day 5 postpartum (longer if there is a risk of PPH), with bridging LMWH in
the interim and daily international normalized ratio (INR)
monitoring during titration to initialize her dose. Both warfarin
and LMWH are suitable for continuation during breast-feeding.
Patients should be ideally followed up at outpatient clinic with
physician or haematology input to assess post-thrombotic venous
damage and plan for thromboprophylaxis in future pregnancies.
Thrombophilia screening should only performed after anticoagulant therapy is ceased and in cases where results would
affect future management plans.
Conclusion
The most recent confidential enquiry into maternal deaths report
from MBRRACE-UK has shown that the pattern of direct maternal
deaths has reverted to that seen prior to 2006e2008, with
thrombosis and thromboembolism as the leading cause of direct
Maintenance treatment
Women receiving therapeutic LMWH for treatment of VTE
should be taught to self-administer injections and can be
managed as outpatients. They should receive therapeutic
138
REVIEW
Practice points
C
FURTHER READING
Cutts BA, Dasgupta D, Hunt BJ. New directions in the diagnosis and
treatment of pulmonary embolism in pregnancy. Am J Obstet
Gynecol 2013 Feb; 208: 102e8.
Leung AN, Bull TM, Jaeschke R, et al. ATS/STR Committee on
Pulmonary Embolism in Pregnancy. An ofcial American
Thoracic Society/Society of Thoracic Radiology clinical
practice guideline: evaluation of suspected pulmonary embolism in pregnancy. Am J Respir Crit Care Med 2011; 184:
1200e8.
139
When a diagnosis of deep vein thrombosis or pulmonary embolism is suspected, there should be no hesitation in commencing
therapeutic doses of low molecular weight heparin whilst waiting
for confirmatory tests
All institutions should have clear guidelines for repeated
assessment of women for VTE risk during pregnancy and postpartum, as well as for the diagnosis and treatment of confirmed
VTE
Appropriate doses of LMWH should be instituted based on the
booking or early pregnancy weight
SELF-ASSESSMENT
Self-assessment questions
Questions
Question 1 (SBA)
A 42 year old woman with pressure symptoms and heavy
menstrual bleeding leading to iron deficiency anaemia is found
to have two large uterine fibroids on ultrasound. You discuss
medical management options first, in detail. Which one of the
following pieces of information is correct regarding selective
progesterone receptor modulators (SPRMs)?
A. Safety prior to pregnancy has been demonstrated
B. They can be used continuously for 6 months
C. The duration of use is limited by hypoestrogenic side
effects
D. Fibroid shrinkage is maintained for at least 3 months
following cessation
E. They are contraindicated in those at risk of thrombosis
Question 4 (SBA)
A 28-year old para 1 was delivered by emergency caesarean
section for obstructed labour 48 hours ago. Her booking BMI
was 35 (booking weight 90 kg) and she was commenced on
prophylactic low molecular weight heparin 40 mg subcutaneously daily immediately after her operation. Although she
remained afebrile, her pulse rate has remained persistently
elevated at 100 per minute. Her haemoglobin level was 10 g/
dL and her white cell count normal. Her ECG showed sinus
tachycardia and chest X-ray was normal. She is keen to
breastfeed. Her oxygen saturation in air is 92% and she is
slightly breathless.
What advice would you give her and how would you
manage her?
A. Order a D-Dimer and get a duplex leg ultrasound scan after
discussing with the medical team on call.
B. Commence enoxaparin 100 mg twice daily and arrange for
a chest X-ray followed by a CTPA or Ventilation/Perfusion
(VQ) scan.
C. Organize a CTPA and advise her that this will increase the
risk of her child getting childhood cancer, so she should
avoid breastfeeding.
D. Commence warfarin and warn her that her baby could be
at risk of developing haemorrhagic complications if she
continues to breastfeed.
E. Investigate with V/Q scan and avoid CTPA because it will
increase her lifetime breast cancer risk by 25%.
Question 2 (SBA)
The same patient, as in question 1, decides that a surgical
management option will suit her better. Which of the
following is true with regards to open myomectomy compared
with laparoscopic management?
A. Longer operating times
B. More complete fibroid clearance
C. Reduced blood loss
D. Reduced rates of fibroid recurrence
E. Shorter recovery times
Question 3 (SBA)
A 36 year old woman presents at 12 weeks gestation for her
antenatal booking visit. She had three previous first trimester
miscarriages prior to this pregnancy. She was fully investigated and was found to be heterozygous for Factor V Leiden
mutation. She smokes 10 cigarettes a day and has no significant past medical or family history. Examination showed her
booking BMI to be 25 kg/m2. Her BP is 120/70 mmHg and no
abnormality is found on examination. What would you advise
her regarding her Factor V Leiden status?
A. She is at significant risk of venous thromboembolism and
should commence on low dose aspirin plus low molecular
weight heparin as soon as possible.
B. She should stop smoking and commence low dose aspirin
immediately. She should undergo duplex ultrasound of her
legs as a screen for deep vein thrombosis.
C. She should be advised to commence on low molecular
weight heparin from 28 weeks gestation and continue with
thromboprophylaxis for 10 days postpartum in the absence
of any additional risk factor after delivery.
Question 5 (SBA)
A 25 year old woman with a BMI of 37 has been trying to
conceive and has been told that reducing her weight might
help. She has normal glucose tolerance and wishes to discuss
weight loss surgery. Which of the following pieces of advice is
incorrect?
A. Surgery is more effective in achieving weight loss than
lifestyle interventions
B. Weight loss surgery would be supported by NICE guidance
in her case
C. Fetal growth restriction is more likely following weight loss
surgery
D. Evidence shows that fertility and miscarriage rates are
favourably affected by weight loss surgery
E. Hypertensive complications of pregnancy are reduced in
women who have undergone weight loss surgery
Question 6 (SBA)
A 28-year old woman attends the antenatal clinic in her first
pregnancy. She is concerned as she has a past history of
158
SELF-ASSESSMENT
D.
E.
F.
G.
H.
Question 7 (SBA)
A 40-year old woman in her third pregnancy is diagnosed with
a prolactinoma at 32 weeks gestation after suffering from
increasing headaches. Which one of the following is true
regarding prolactinomas in pregnancy?
A. Headache, nausea and vomiting can be a sign of enlargement in all trimesters
B. Dopamine agonists are recommended throughout pregnancy for microprolactinomas
C. Visual fields studies should only be performed in women
with known macroprolactinoma who develop symptoms
D. Women are advised not to breastfeed
E. Transphenoidal surgery is mainstay of therapy for
asymptomatic microprolactinoma
Answers
Answer 1
D
Although pregnancies have been reported after treatment
with SPRMs there is insufficient evidence to confirm safety.
Recommendations state that although repeated courses can
be used, there should be a 1 month break between each 12
week course of treatment. Oestrogen levels are maintained in
those taking SPRMs as FSH and LH levels are unaffected by
treatment. Fibroid shrinkage is maintained for at least 3
months following treatment. As SPRMs do not result in
raised oestrogen levels, previous thrombosis is not a
contraindication.
Question 8 (SBA)
A 35-year old woman with a BMI of 32 is referred to the
menstrual dysfunction clinic and, after investigation, receives
a diagnosis of PCOS. She would like to know about the potential health benefits of weight loss. Which one of the
following is not likely to be improved by a 5e10% weight
loss?
A. Anxiety
B. Insulin resistance
C. Cardiovascular risk factors
D. Hypothyroidism
E. Free androgen index
Answer 2
D
Laparoscopic myomectomy is associated with longer
operating times than open myomectomy, however the laparoscopic approach has been associated with reduced operative
blood loss and higher post-operative haemoglobin concentrations. Additionally, duration of hospital stay and recovery
times are reduced with the laparoscopic approach. As more
complete fibroid removal is possible with the open approach,
rates of fibroid recurrence are greater following a laparoscopic
myomectomy.
Question 9 (SBA)
A 51-year old university professor suffers from heavy regular
periods and has opted to have a Mirena IUS fitted in an
attempt to improve these. She has some detailed questions
about how the Mirena will work and how it will treat her
menorrhagia. Which one of the following is not true regarding
the Mirena IUS?
A. She can expect at least a 60% reduction in menstrual blood
loss within a year of use
B. The Mirena IUS is not licensed for this particular indication
C. The contraceptive effect of a Mirena has a duration of 5
years
D. The primary mechanism of action is pseudodecidualization
of the endometrium
E. The Mirena will release 20 mg of levonorgestrel per day
Answer 3
C
There is no evidence that aspirin has any benefit in the
prevention of venous thromboembolism. Heterozygosity for
factor V Leiden, prothrombin gene mutation or antiphospholipid antibodies are considered to be risk factors for
thrombosis in asymptomatic women. In this case, the risk
factors in addition to the womans Factor V Leiden status are
her age of 36 years and her smoking, giving her two additional
risk factors. With three risk factors in total for VTE, thromboprophylaxis should be considered from 28 weeks.
Should another risk factor occur e.g. if she is delivered by
caesarean section, she should be considered for thromboprophylaxis for 6 weeks postpartum.
Question 10 (EMQ)
For each of the cases below (ieiii) choose the most suitable
first line therapy (AeH) for the menstrual dysfunction case
described:
A. Tranexamic acid
B. Oral contraceptive pills
C. Naproxen
159
SELF-ASSESSMENT
Answer 4
C
Whenever there is a suspicion of deep vein thrombosis or
pulmonary embolism, therapeutic doses of LMWH should be
commenced whilst investigative tests are being arranged. DDimer is elevated in pregnancy and is not a useful test to
order. Symptoms of pulmonary embolism can be non-specific
and should be suspected when a woman has unexplained
tachycardia. CTPA will provide definitive diagnosis and can
also reveal the presence of other lung pathology. The correct
dose of enoxaparin is 1.0 mg/kg of the booking weight twice
daily or 1.5 mg/kg daily, as she is post-natal. Estimates of the
increased risk of breast cancer associated with CTPA in
pregnancy vary considerably and are based on modelling or
extrapolated data. The delivery of 10 mGy of radiation to a
womans breast has been estimated to increase her lifetime
risk of developing breast cancer by 13.6% above her background risk and this figure has been cited widely. There is no
contraindication to breastfeeding with either LMWH or
warfarin as minimal amounts of these medications are found
in breast milk.
Answer 7
A
Prolactinomas are the most common benign pituitary adenomas in pregnancy. Management during pregnancy depends on the size of the adenoma; micro adenomas less than
10 mm in size rarely cause a problem, whereas those which
are greater than 10 mm [macroprolactinoma] may require
more careful management.
Answer 8
D
Modest weight loss of 5e14% improves CVD risk factors,
hormonal profile and reproductive function in overweight and
obese women with PCOS. Improvements include reductions in
abdominal fat, blood glucose, blood lipids and IR, improvements in menstrual cyclicity, ovulation and fertility, reductions in testosterone levels and free androgen index and
increases in sex hormone binding globulin. There have also
been demonstrated improvements in self-esteem, depression
and anxiety. Although treatment of hypothyroidism is likely to
result in weight loss, the opposite is not true.
Answer 9
B
The levonorgestrel-releasing intrauterine system (Mirena)
produces a dramatic decline in menstrual blood loss (65
e98%) within 12 months of use. The device, imbedded with
52 mg of levonorgestrel, releases 20 mg of levonorgestrel per
day, causing pseudodecidualization of the endometrium with
very little systemic absorption of progesterone. The Mirena is
licensed for treatment of idiopathic menorrhagia. Its contraceptive effect lasts for 5 years.
Answer 5
B
Good evidence shows that bariatric surgery is more effective at bringing about weight loss than lifestyle interventions.
NICE guidance supports use of bariatric surgery for individuals
with a BMI 40 kg/m2. It only supports weight loss surgery at
lower BMIs if there are other co-morbidities such as type 2
diabetes. There is no randomized controlled evidence to show
that it increases conception rates, or reduces miscarriage risk,
although there are plausible biological explanations for why
this might be the case. Evidence so far does suggest that hypertensive disorders of pregnancy are less frequent in the
treated group, perhaps at the expense of an increased risk of
fetal growth restriction, particularly in the women who have
had malabsorptive procedures.
Answer 10
I. H
This girl needs a reliable method of contraception as well
as a treatment to reduce menstrual blood loss. She should not
be prescribed oestrogens as she suffers from migraines.
II. E
This woman would be suitable for endometrial ablation.
This would avoid the high surgical risks of hysterectomy in
view of her high BMI.
III. G
Resecting this fibroid polyp transcervically should cure
her menstrual dysfunction and retain her future fertility. As
no information is given regarding her future fertility intentions, it should be assumed that this should preserved if
possible.
Answer 6
C
Although rarely seen in the UK, overt symptomatic untreated hypothyroidism is also associated with an increase in
miscarriage, gestational hypertension, preterm delivery, postpartum haemorrhage and fetal growth restriction. There has
also been a suggestion that hypothyroidism is associated with
gestational diabetes mellitus, with almost double the number
of women on levothyroxine replacement having this diagnosis
compared with the background population.
160