What to expect during the course of her care (including expectant management), such as the potential length and extent of pain and/or bleeding, and possible side effects. This information should be tailored to the care she receives.

1. Gynaecology - Early Pregnancy
Complications
Michelle M Fynes
MB BCh BAO (Hons) MD (Research) MRCOG DU DipUS
Subspecialty Accredited Urogynaecologist RCOG (2003) and RANZCOG (2002)
CCST Obstetrics and Gynaecology (2003)
Specialist Complex Peri-partum Childbirth Injury and
Paediatric Adolescent and Forensic Gynaecology

2. Key Points are to understand
• Support and information giving
• Role of early pregnancy assessment units (EPAU)
• Symptoms and signs of ectopic pregnancy and initial assessment
• Using ultrasound for diagnosis
• Human chorionic gonadotrophin measurements in women with pregnancy of unknown location
• Expectant management
• Surgical management
• Performing laparoscopy
• Salpingectomy and salpingotomy
CG154 – NICE Guidance
Ectopic pregnancy and miscarriage: Diagnosis
and initial management in early pregnancy of
ectopic pregnancy and miscarriage
December 2012

3. Support and information giving
Throughout a woman's care, give her and (with agreement)
her partner specific evidence-based information in a variety
of formats. This should include (as appropriate):
When and how seek help if existing symptoms worsen/new symptoms
develop, including a 24-hour contact telephone number.
What to expect during the time she is waiting for an ultrasound scan.
What to expect during the course of her care (including expectant
management), such as the potential length and extent of pain and/or
bleeding, and possible side effects. This information should be tailored to
the care she receives.
Information about post-operative care (for women undergoing surgery).
What to expect during the recovery period – for example, when it is
possible to resume sexual activity and/or try to conceive again, and what
to do if she becomes pregnant again. This information should be tailored
to the care she receives.
Information about the likely impact of her treatment on future fertility.
Where to access support and counselling services, including leaflets, web
addresses and helpline numbers for support organisations.
Ensure that sufficient time is available to discuss these issues with
women during the course of their care and arrange an additional
appointment if more time is needed.

4. Early Pregnancy Assessment Unit - EPAU
First EPAU 20 years ago now almost 150 UK
Considerable variation between centres in access to services and levels of care provided
Little good quality research on effectiveness EPAU in improving physical and emotional health
A National Audit of EPAU required
Outcomes would include time of attendance, length of stay, admission rates, time to
treatment and women's experience.
Evaluation should be structured to allow for comparisons between different models of care.
Comparative outcome data collected would be used to conduct an analysis of the cost
effectiveness of early pregnancy assessment units compared with other models of care.
Regional services organised so EPAU available 7 days a week for women with early
pregnancy complications, where scanning carried out and decisions about management made.
During clinical assessment of women of reproductive age, be aware that:
They may be pregnant, offer a pregnancy test even if symptoms are non-specific
Symptoms and signs ectopic pregnancy can resemble other conditions eg. GI upset, UTI
All healthcare professionals caring for women reproductive age access to pregnancy tests.
Using ultrasound for diagnosis
TVUS available- identify location of pregnancy and whether there is fetal pole and FH .
Scanning interval ideal unclear – 14 days optimal (varies on service provision)
hCG measurements in PUL
Women with PUL could have an ectopic pregnancy until the location is determined.

5. Early pregnancy
problems
• Early pregnancy bleeding
• Miscarriage
• Recurrent miscarriage
• Pregnancy of unknown location (PUL)
• Ectopic pregnancy
• Trophoblastic disease
• Hyperemesis gravidarum
• Ovarian Hyperstimulation Syndrome (OHSS)
• Acute abdomen early pregnancy
• Urinary sepsis
• Vaginal discharge/PID
• Bartholin’s Cyst/Abscess
• The abnormal cervical smear ?
• Female genital mutilation (FGM)

6. Beta hCG
RIA: Variations of lab values of up to 50% can occur among different
laboratories
6–15% between-run precision
Advantages: specific for hCG, sensitive
Disadvantages: requires specialized lab + 3–24 hours for completion
Sensitivity:
qualitative: 25–30 mIU/mL (3 hours test time)
quantitative: 3–4 mIU/mL (24 hours test time)
Rise:
>66% increase β-hCG level by 48 hrs 86% NORMAL pregnancies
<66% increase β-hCG level by 48 hrs 87% ECTOPIC pregnancies
β-hCG levels double every 2–3 days first 60 days of pregnancy
Beta hCG glycoprotein from placental trophoblast cells by
day 8th post conception.
Immunologic Pregnancy Test indirect agglutination test for hCG
in urine; cross-reaction with other hormones or medications
possible. Becomes positive at 5 weeks MA
Advantages: readily available, easily + rapidly performed
Disadvantages: false-positive + false-negative results
Sensitivity:
a. slide: 400–15,000 mIU/mL (2-minute test time)
b. test tube: 1,000–3,000 mIU/mL (2-hour test time)
Radioimmunoassay (RIA) pregnancy test measures beta subunit
serum hCG Sensitivity at 1–2 mIU/mL. Serum β-hCG positive 3
weeks MA 7–10 days after conception.
Standards:
(1) Second International Standard (SIS)
(2) International Reference Preparation (IRP)
(3) Third International Standard (TIS)
1 mIU/mL (SIS) = 2 mIU/mL (IRP) = 2 mIU/mL (TIS)
1 ng/mL = 5–6 mIU/mL (SIS)== 10–12 mIU/mL (IRP or TIS)

7. Anatomy of gestation
Gestational Sac (GS)
Arises from blastocyst, implants into secretory endometrium 6–9
days after ovulation (20–23 days of MA), surrounded by echogenic
trophoblast
GS measures 0.1 mm at time of implantation
Intradecidual sign (earliest sign)
Intrauterine fluid collection corresponds to GS embedded within
decidua (48% sensitive, 66% specific, 45% accurate) at <5 weeks GA
Double decidual sac sign (DDS)
>5 weeks GA 2 concentric hyperechoic rings surround portion of GS:
Outer echogenic ring (decidua parietalis)
Interposed hypoechoic line (apposed endometrial walls)
Inner echogenic ring (decidua capsularis)
DDS present with a mean sac diameter of 10 mm (= 40 days GA)
Double decidual sac sign correlates with presence pregnancy in 98%
• GS surrounded by endometrial thickening >12 mm
• Continuous hyperechoic inner rim >2 mm thick
• Spherical / ovoid shape without angulations
Mean sac diameter grows 1.13 (range 0.71–1.75) mm/day
Choriodecidua
Chorion - trophoblast + fetal mesenchyme with villous stems
protruding into decidua; provides nutrition for developing embryo
a. chorion frondosum- part adjacent to decidua basalis, forms
primordial placenta
b. chorion laeve- smooth portion of chorion with atrophied villi
c. chorionic plate - amnion membrane covers chorionic plate
placenta
β-hCG (IRP) US Landmarks Gestational Age
1,000 mIU/mL gestational sac 32 d (4.5 weeks)
7,200 mIU/mL yolk sac 36 d (5.0 weeks)
10,800 mIU/mL embryo FH 40 d (6.0 weeks)
Decidua
a. decidua basalis- between chorion frondosum/myometrium
b. decidua capsularis- portion protruding uterine cavity
c. decidua parietalis/decidua vera lines uterine cavity elsewhere
3-mm gestational sign (white arrow) within decidua.
Echogenic line (black arrow) uterine cavity.
"double decidual sac" (R) inner echogenic ring GS . Outer ring
basal layer decidua. Yolk sac seen in the GS. The embryo is
not shown.

8. Early pregnancy structures – Gestational Sac (GS) and Yolk Sac (YS)
Secondary Yolk Sac (YS)
Round sonolucent outside amniotic cavity within chorionic sac connected to
umbilicus via a narrow stalk; formed by proliferation of endodermal cells; part
of YS is incorporated into fetal gut; the rest persists as a sac connected to the
fetus by the vitelline duct
Time of formation YS: at around 28 days MA
Mean size YS:
1.0 mm by 4.7 weeks MA;
2.0 mm by 5.6 weeks MA;
3.0 mm by 7.1 weeks MA;
4.0 (2.2–5.3) mm by 10 weeks MA;
YS disappears around 12 weeks MA
It is the first visible structure within gestational sac
Definite visualization YS on TVUS at 5.5 weeks MA
Gestational Sac (GS)
Linear growth:
10 mm by 5th week MA
60 mm by 12th week MA
Fills chorionic cavity by 11th–12th weeks MA
Visualization of Gestational Sac
TVUS earliest seen sac diameter of 2–3 mm
GS versus β-hCG LEVEL :
TAS: 100% with β-hCG levels of >1,800 IU/L
TVUS:
20% with β-hCG levels of <500 IU/L
80% with β-hCG levels of 500–1,000 IU/L
100% with β-hCG levels of >1,000 IU/L
B. GS visualisation versus MA
5.0 ± 1 weeks = 10 mm
5.5 ± 1 weeks = 13 mm
6.0 ± 1 weeks = 17 mm
6.5 ± 1 week = 20 mm
Yolk sac and placenta vascularization 8 wks CRL 15–22mm

9. Embryonic development
Visualisation Embryo versus Gestational Sac (GS)
TAS - 100% visualization GS ≥27 mm
TVUS - 100% visualization GS ≥12 mm
TVUS not necessary if GS >27 mm TAS with no embryo
Failed pregnancy: embryo not seen with mean GS size ≥18 mm
Cardiac Activity of Embryo; FH seen at CRL of 1.5–3 mm (22 days GA/36 days MA)
Amnionic Membrane - Curvilinear echogenic line in chorionic sac; fills chorionic
cavity by 11–12 weeks MA; Fuses with chorionic membrane 16 weeks MA to form
chorionic plate Incomplete fusion with chorion frequent (DDx: subchorionic
haemorrhage, twin abortion, coexistent with limb-body wall complex)
Stages:
1. Pre-embryonic period: 2nd–4th week MA
2. Trilaminar embryonic disk: 5th week MA
3. Embryonic period: 6–10th week MA
4. Physiologic umbilical hernia: 8–12th week MA
5. Fetal period: begins 11th week MA
Embryo:
Mean growth CRL: 0.7 mm/day.
1.5 mm every 2 days; curvilinear growth.
Mean 7mm/ 6.3 weeks MA
Mean 50mm/12.0 weeks MA
First seen TVUS: 5.4 weeks MA (CRL of 1.2 mm)
FH at TVUS FH at TAS FH Rate
46 days GA 55 days GA 5-6 wks GA - 101 bpm
mean sac size 16 mm mean sac size 25 mm 8-9 wks GA - 143 bpm
CRL ≥ 5 mm/ 6.2 wks
Ultrasound Milestones
GS w/o embryo or yolk sac - 5 weeks
GS + yolk sac w/o embryo - 5.5 weeks
Heartbeat ± embryo <5 mm - 6.0 weeks
Accuracy: ± 0.5 week
1 432

10. TVUS – First trimester
TVUS - 3 decidua layers. Amniotic sac and embryo visible
elsewhere in GS. Placenta (P) forms from decidua basalis/chorion
frondosum at implantation site of blastocyst. Decidua capsularis (c)
covers part GS protruding into uterine cavity (u). Decidua vera (v)
lines rest (u). U contains a small amount of blood. The chorion very
thin membrane defined by sharp fluid-tissue interface (arrow) of GS.
TVUS - Empty GS, misshapen
sac measures 31 mm diameter.
Both yolk sac/ embryo should
be seen at this size. GS
keyhole-shape rather than
round. Choriodecidual reaction
thin weakly echogenic
(anembryonic pregnancy)
Dead Embryo–Calcified Yolk Sac. 6.3-week
(cursors) CRL = 5.8 mm no FH.
Yolk sac (arrow) is calcified. Calcification
associated with embryonic demise.
Subchorionic Hemorrhage- clotted blood
(arrow) in the uterine cavity.
TVUS-pseudogestational Sac of EP
(oblong fluid collection arrow),
No defined echogenic rim
(choriodecidual reaction). No DDS.
Small EP was found in right adnexa

11. TVUS (8-12) weeks first trimester
Above -Embryo at 9+4 weeks (crown–rump length
28 mm). Longitudinal section demonstrating the
physiological midgut herniation present as a large
hyperechogenic mass.
Below – 3D image fetus at 12 weeks
Embryo at 8+5 weeks CRL 20 mm. Sagittal
section vascularization and the umbilical cord.
Embryo 9+4 weeks (CRL 28 mm). Sagittal section
relative large head. Cavities of the diencephalon
(Di), mesencephalon (Mes), rhombencephalon (Rh).
Arrow -genital tubercle, not possible to
differentiate male /female yet
Embryo at 10 weeks (CRL 32 mm).
Section through abdomen - umbilical
cord. Arrows show the extent of
physiological midgut herniation
Image of a 12 week fetus

12. Early Pregnancy Bleeding and Miscarriage

13. Early pregnancy bleeding and Miscarriage
WHO – Miscarriage: Expulsion of an embryo <20 weeks or fetus <500grms
Scenario
• Physiological event (I in 4 pregnancies miscarry)
• Pathological ? (haemorrhage, Ectopic, recurrent MC 1% couples )
• Personal
Symptoms
• Physical - pain bleeding
• Psychological symptoms of fear and loss
Sequelae
• Medical investigations
• Clinical follow-up
• Possibility surgery
• Personal loss
• Grief
• Impact on partner and family
Terms miscarriage/abortion
Complete
Incomplete
Inevitable
Infected (septic)
Missed

14. Early Pregnancy Bleeding
• Early pregnancy bleeding is very common (implantation
bleed, ectropion, spotting) not always indicative
miscarriage or pathology
• Pain – attributed ‘round ligament stretch’, CL cyst or
threatened miscarriage or ectopic
• Ectopic pregnancy and miscarriage have an adverse
effect on the quality of life of many women.
• 20% of pregnancies miscarry
• Miscarriages can cause considerable distress.
• Early pregnancy loss accounts for >50,000 UK
admissions per annum
• EP rate 11/1000 pregnancies, maternal mortality
0.2/1000 estimated EP
• 2/3 deaths are associated with substandard care.
• Women who do not access medical help readily (such
as women who are recent migrants, asylum seekers,
refugees, or women who have difficulty reading or
speaking English) are particularly vulnerable.
Referral to EPAU
Pain
• Pregnancy > 6 weeks gestation or uncertain gestation.
Management
Expectant management < 6 weeks gestation who are bleeding
but not in pain. Repeat urine pregnancy test >7–10 days return
EPAU if positive.
Negative pregnancy test means pregnancy has miscarried.
Return EPAU if their symptoms continue or worsen.
Offer TVUS
Role Ultrasound
TVUS Gold standard
TVUS - GS, Fetal pole and FH evaluation
Consider TAS other pathology (eg. Fibroids, ovarian cyst)
TVUS <100% accurate diagnosis MC early gestational ages.
Guidelines TVUS/TAS
Mean GS diameter < 25.0 mm or fetal pole CRL <7.0mm, no FH
Do second scan 7 days (14 days if TAS)
Mean GS> 25.0 mm or CRL>7.0mm TVUS no FH
Get second opinion on viability and/or second scan >7 days
after first before making a diagnosis. TAS 14 days

15. Management of miscarriage
Threatened miscarriage
Vaginal bleeding and confirmed IUP with FH:
Bleeding gets worse, or persists > 14 days, return EPAU
Bleeding stops, start or continue routine ANC
Expectant management (EM)
Use EM 7–14 days as first-line strategy for confirmed diagnosis
miscarriage.
Explore other management options other than EM if -
 Risk haemorrhage (eg. Late T1)
 Previous adverse / traumatic pregnancy experience (eg.
stillbirth, MC or APH)
 > risk from haemorrhage (eg. Coagulopathy, unable to have
blood transfusion)
 Evidence of infection.
Offer repeat TVUS if after a period EM the bleeding and pain:
Have not started
Persisting and/or increasing
Discuss all treatment options ( eg. continued EM or medical)
Medical management – Missed or Incomplete
Indications
Patient choice
Failed EM (eg. Bleeding >14 days)
Therapeutic agent
RU486 (Mifepristone) not used
PV misoprostol missed or incomplete miscarriage.
Oral administration acceptable alternative .
Missed miscarriage, single dose of 800ug misoprostol
Bleeding not started >24 hours contact EPAU
Consider options
Incomplete miscarriage, single dose of 600 micrograms of
misoprostol.
800 micrograms can be used to align protocols for missed and
incomplete MC
Inform all women whether expectant or medical management
what to expect throughout the process,
 Length and extent of bleeding
 Potential side effects of treatment - pain, diarrhoea and
vomiting.
 Offer pain relief and anti-emetics as needed.
 Advise to do urine pregnancy test at 3 weeks
 If (+ve) return for follow-up exclude molar or ectopic
pregnancy
 Experience worsening symptoms, return earlier to EPAU

16. Management Miscarriage
Expectant management
Expectant management 7–14 days as first-line strategy where
diagnosis of miscarriage confirmed.
Explore other options if:
• Increased risk of haemorrhage (eg. late first trimester)
• Previous adverse and/or traumatic experience
associated with pregnancy (eg. stillbirth, MC or APH)
• Adverse risk from effects haemorrhage (eg.
Coagulopathies, unable to have blood transfusion)
• Evidence of infection.
Surgical management
Where clinically appropriate, offer women needing ERPC:
• Manual vacuum aspiration under LA in OPD
• Surgical management in a theatre under GA
Communication breaking bad news
Healthcare professionals providing care should be
aware that early pregnancy complications can cause
significant distress for some women and their
partners. Training in how to communicate
sensitively and breaking bad news.
Non-clinical staff such as receptionists working in
settings where early pregnancy care is provided
should also be given training
Throughout a woman's care, give her and (with
agreement) her partner specific evidence-based
information in a variety of formats.
When and how to seek help if help (24 hour
contact number)
Evidence based information leaflets
Counselling services if required/ pregnancy loss
clinic/websites/support groups
After early pregnancy loss, offer follow-up
appointment healthcare professional of her choice.

17. Anti-D rhesus prophylaxis
• Pregnancy related immuno-prophylaxis anti-D immunoglobulin began UK in 1969.
• Programme astounding success: deaths due to RhD alloimmunisation
• 46/100 000 births (1969) to 1.6/100 000 (1990).
• Give before 72 hours
• Ideally, administer to deltoid muscle.
• Bleeding disorder give anti-D Ig via the subcutaneous or IV
• Administered dose of 250 iu up to 19+6 weeks 500 iu thereafter.
• Check size of FMH (Kleihauer)> 20+0 gestation
Anti-D Ig should be given to -
• All non-sensitised RhD (-ve) spontaneous complete or incomplete MC > 12+0 weeks .
• Anti-D Ig not required spontaneous MC <12+0 weeks
• All anti-D Ig non-sensitised RhD (-ve) surgical evacuation of the uterus ERPC, MTOP, EP.
• Allo-immunisation reported after EP and 25% ruptured tubal EP
But not to those with -
Sole medical management for EP or MC, threatened miscarriage, complete miscarriage or PUL
Rhesus D Prophylaxis, The Use of Anti-D Immunoglobulin for RCOG (Green-top 22) 2011

18. Second Trimester Miscarriage (14-20 weeks)
Fetus formed by 12 weeks (Fetal length)
14 weeks - 12 cms
16 weeks – 16-18 cms
18 weeks - 20 cms
Baby is identifiable and large enough, mother may feel
she wants to spend time holding the fetus after the miscarriage. This is
a very personal choice.
Investigations
Full PM (fetus and placenta)
Karyotype
TORCH
HVS
Perinatal Pathology
Normally cremate fetus
Counselling support
Pastoral care – service (parents wishes)
Follow-up appointment
Risks
Bleeding
Lactation
PTSD/Depression
Support services
Some units have a dedicated
specialist midwife/nurse
trained in bereavement
counselling.
They can liaise with perinatal
pathology, gynaecologist, EPAU
and pastoral services on the
mothers behalf.

19. Pregnancy of unknown location (PUL)

20. Pregnancy of Unknown Location (PUL)
Other markers
• Tri-laminar endometrial stripe pattern, specific (94%) EP but
low sensitivity (38%).
• TVUS colour Doppler no increase detection rates EP vs 2D US
The discriminatory level for each test should be set by each
institution based on the
• hCG assay techniques in use
• quality of ultrasound equipment and operator experience.
Progesterone
• Serum progesterone levels are elevated in early pregnancy
indicating the viability of the corpus luteum, and change little
during the first 8–10 weeks of gestation, but decrease if the
pregnancy fails.
• Serum progesterone 20 nmol/l predicts failing early
pregnancy with a PPV 95%
• Levels 25 nmol/l are likely to indicate ectopic, some ectopics
lower levels but 15% EP resolve spontaneously.
• Levels 60 nmol/l are strongly associated with IUP
Introduction
Pregnancy site not seen in 8–31% EPAU scans.
Sonographer’s experience influences PUL rate.
Initial assessment
Positive pregnancy test
No evidence pregnancy TVUS
Clinical assessment and serum hCG
Serum progesterone useful adjunct in PUL
Discriminatory Zone
Combine both hCG and TVUS using a
discriminatory zone
Level of hCG > at which gestational sac of IUP should be visible
at TVUS with sensitivity approaching 100%.
Value ranges hCG 1000–2400 iu/l
Multiple pregnancies, hCG levels a little higher
requires extra 2-3 days for sacs to be visible.
Consider possibility heterotopic pregnancy
hCG > than discriminatory level but no IUP
PUL steps taken to exclude ectopic.
PPV discriminatory zone alone for ectopic 18.2%.
Diagnosis ectopic based on an extra-uterine sac
and indirect signs complex adnexal mass, echogenic fluid,
Rather than failure to demonstrate IUP
USS signs as described PPV ectopic 93.5–100%

21. Clinical outcomes of PUL
• failing PUL
• intrauterine pregnancy
• ectopic pregnancy
• persisting PUL.
44-69% failing PUL resolve spontaneously
Never seen (intra- or extrauterine) on TVUS
Serum progesterone be 20 nmol/l presentation
Serial serum hCG levels will fall.
30-70% early IUP to small to see TVUS
75% of these are viable on follow-up.
8-42% prevalence early ectopic in a PUL
Population. Lower rates 8–14%, in specialist scan units
2% Persisting PULs serum hCG levels fail to decline, no
evidence of GTD. PUL not identified using TVUS or laparoscopy.
serum hCG low (500 iu/l) and plateau (doubling time >7 days)

22. PUL – Clinical Algorithms
Symptoms/no symptoms
1. Pain
2. Bleeding
3. Nausea
May have
1. Discharge (physiological/infection)
2. Urinary symptoms (pregnancy or
UTI)
History – very important
1. Ectopic
2. PID/STD
3. CS
4. Pelvic surgery (eg. appendicitis)
5. Endometriosis
6. ART (eg. IVF, GIFT, ICSE)
Investigations
1. Urinary pregnancy test (+ve)
2. Serum HCG level (static or serial)
3. TVUS ‘empty uterus’ or sac only
Other tests
1. Serum progesterone

23. Ectopic Pregnancy

24. Ectopic pregnancy
Incidence and risks
• 13 Maternal Deaths UK ectopic pregnancy 1997–99.
• Ectopic incidence 11.1/1000 pregnancies
• Laparoscopic management superior haemodynamically stable
• Collapse – most expedient method employed
• Salpingectomy not salpingotomy (healthy contralateral tube)
• Laparoscopic salpingotomy considered as the primary
treatment tubal pregnancy contralateral tubal disease and
desire for future fertility.
• Outcome study IUP rate salpingotomy 49% versus
salpingectomy 27% where contralateral tubal disease
present.
• Salpingotomy - Increased risk further ectopic, persistent
trophoblast in tube, may still need IVF
1. Ruptured ectopic
2. Risks surgery
3. Cornual ectopic
Ovarian ectopic Heterotopic pregnancy

25. Ectopic pregnancy
Service provision and training
• All NHS trusts should provide an EPAU with direct
access for GP’s and A&E.
Facilities for management suspected ectopic
pregnancy should include:
• Diagnostic and therapeutic algorithms
• Transvaginal ultrasound
• Serum hCG estimations.
Options for managing ectopic pregnancy
1. Laparoscopy
2. Open mini laparotomy
3. Medical (methotrexate)
4. Expectant?
Ideally, EPAU sited in a dedicated area, appropriate staffing,
available daily, at least during working week.
• Clinicians undertaking the surgical management of
ectopic pregnancy must have received appropriate
training.
• Laparoscopic surgery requires appropriate equipment
and trained theatre staff.
• Should be trained open and laparosocpic
• Retrospective studies laparoscopic ectopic management
low rate intraoperative /postoperative complications
surgery can safely be undertaken by appropriately
trained registrars
• Non-sensitised Rh-ve confirmed or suspected ectopic
give anti-D immunoglobulin (250iu).
• Audit clinical data regularly
• Training modules ATSM/Fellowship/Subspeciality
modules
Evidenced based
Clinical Algorithms

27. Medical therapy offered first line
Unruptured pregnancy, no FH
Adnexal mass <35mm
No evidence IUP, no blood POD
No significant pain
Serum hCG <1500iu/l
Surgical therapy
Unable return follow-up after methotrexate
EP significant pain
Adnexal mass > 35 mm
EP with visible FH on US
Serum hCG level of>5000 IU/litre.
Medical or Surgical
Serum hCG 1500-5000 IU/litre
Able to return for follow-up and meet all of the
following criteria:
No significant pain
Unruptured EP
Adnexal mass <35 mm
No FH
No IUP on TVUS
Management options for Ectopic Pregnancy (EP)
Advise those choosing methotrexate risk of
needing further intervention is increased and may
need to be urgently admitted if condition
deteriorates.
Salpingotomy up to 1 in 5 may need further
treatment eg. methotrexate and/or a
salpingectomy.
Salpingotomy, 1 serum hCG 7 days post surgery
If still +ve then 1 serum hCG per week until -ve.
Salpingectomy urine hCG test after 3 weeks.
Return for assessment if test is positive.

28. Medical management Ectopic
Medical therapy offered as first line treatment to suitable
women, units should have treatment and follow-up
protocols for the use of methotrexate.
• Many ectopics follow a relatively chronic course.
• TVUS & hCG permits confident diagnosis ectopic pregnancy
• Previously laparoscopy often used to diagnose ectopic
• IM methotrexate (single dose) calculated by body surface
area (50 mg/m2), usually 75- 90 mg.
• Serum hCG day 4 and 7 and 2nd dose if hCG levels fall by <
15% day 4-7. 14% need > one dose methotrexate
• <10% require surgical intervention.
Clear information (preferably written) re need for further
treatment and adverse effects following treatment should
be able to return for assessment any time during follow-up.
• 75% experience abdominal pain following treatment.
• Occasional conjunctivitis, stomatitis, gastrointestinal upset.
• Differentiating ‘separation pain’ (tubal abortion) from
‘rupture pain’ can be difficult.
• Small % need to be admitted for observation, TVUS and
assessment following methotrexate therapy.
• Avoid sex, maintain ample fluid intake, use reliable
contraception for 3mths possible teratogenic risk.
Suitability for methotrexate therapy
• Unruptured pregnancy, no FH ,adnexal mass <35mm
• No evidence IUP, no blood POD
• No significant pain
• Serum hCG <1500iu/l
OPD therapy with single-dose methotrexate is associated with
saving treatment costs.
• Direct costs < half those associated with laparoscopy.
• Indirect costs less with women/ carers losing work time
• No cost saving serum hCG >1500 iu/l due to need for more
treatment and prolonged follow-up.
Day 0 -Serum hCG, FBC, U&E, LFT’s, G&S
Day 1 - Serum hCG, IM methotrexate 50 mg/m2
Day 4 - Serum hCG
Day 7 - hCG, U&E, LFT’s . 2nd dose methotrexate
if hCG decrease <15% on D4–7. hCG >15% repeat
hCG weekly until <10 iu
Mechanism of action of Methotrexate

29. Ectopic pregnancy
Consent Form Laparoscopy
Intended benefits
• Remove ectopic pregnancy if confirmed by laparoscopy.
• Obesity, significant pathology, previous surgery, pre-existing
medical conditions quoted risks for serious or frequent
complications increased.
Serious risks include
• Damage bowel, bladder, uterus, blood vessels requiring
immediate laparosocpic /open repair
• 15% of bowel injuries may not be diagnosed at laparoscopy
• Failure to gain entry to abdomen cavity requiring laparotomy
• Risk of serious complications from diagnostic laparoscopy is
approximately two in 1000
• 3-8 /100 000 undergoing laparoscopy die as a result of
complications(very rare).
Frequent risks
• Inability identify cause for presenting complaint
• Bruising
• Shoulder-tip pain
• Wound gaping or wound infection
• Persistent trophoblastic tissue, when salpingotomy
performed (4–8 in 100) -8.1–8.3% laparoscopic salpingotomy
and 3.9–4.1% open salpingotomy. Factors that may increase
risk of persistent trophoblast; high pre-op hCG levels (>3000
iu/l), rapid pre-op rise hCG, presence active tubal bleeding.
• Hernia at site of entry.
Any extra procedures which may become necessary during the
procedure
• Laparotomy.
• Salpingectomy.
• Repair of damage to bowel, bladder, uterus or blood vessels.
• Blood transfusion.
• Oophorectomy.

30. Other investigations
Serum tests – Viable intra-uterine pregnancy (VIP), Ectopic Pregnancy (EP), Spontaneous Abortion (SA)
Activin enhances FSH synthesis and secretion regulates menses cycle Also roles in cell proliferation. Conversely inhibin down
regulates FSH synthesis and inhibits FSH secretion. 17OH progesterone secreted by Corpus Luteum early pregnancy to
maintain. Activin A, Inhibin A and 17OH Progesterone serum markers measured as an adjunct to evaluate PUL possible EP.
Box plot - measure hCG IU/l, progesterone ng/ml, activin A ng/ml
in patients with VIP, SA, and EP. Boxes represent quartiles;
whiskers represent upper/lower hinge
(± 1.5 × IQR of lower or upper quartile).
ROC’s analysis of serum hCG, progesterone, and activin A for prediction
EP. Cutoffs chosen based on optimal sensitivity and specificity.
hCG = 0.736 [0.679–0.793]; progesterone = 0.660 [0.597–0.723];
activin A = 0.627 [0.560–0.693]; Multi-marker = 0.752 [0.695–0.810].
MRI 96% accurate for detecting
ectopic pregnancy high sensitivity to
fresh haematoma.

31. Special circumstances
From Left to Right –
Caesarean section scar (heterotopic)
Cornual pregnancy (US and laparoscopy)
Ovarian ectopic
Heterotopic pregnancy
Abdominal pregnancy
1. Ectopic caesarean section scar – Increasing incidence repeat CS. Medical management
methotrexate IM or direct injection under US guidance into sac.
2. Cornual pregnancy – 4/11 (200-2002) ectopic deaths were due to cornual ectopic
rupture. Treatment surgical resection (laparoscopic, open, hysteroscopic) highly vascular
area, may necessitate hysterectomy. Increased risk of uterine rupture in a future
pregnancy. Methotrexate minimises haemorrhage and preserves the uterus for future
pregnancies, treatment suitable in EPAU with clear guidelines on treatment.
3. Ovarian ectopic -0.15-3% of ectopics occur in the ovary (1:3,000-1:7,000 deliveries).
Mature egg not expelled /picked up from. Sperm enters and fertilizes giving intra-
follicular pregnancy. Egg cell fertilized outside ovary could also implant on the ovarian
surface, aided by eg.endometriosis. Rarely go >4 weeks; very rarely pregnancy finds a
sufficient foothold outside ovary to continue as abdominal pregnancy.
4. Heterotopic pregnancy - 0.6-2.5:10,000 pregnancies. Increase incidence with ovulation
induction, IVF and GIFT. Treat ectopic pregnancy laparoscopic. Risk miscarriage.
5. Abdominal pregnancy - 1% of ectopics or about 10 /100,000 pregnancies. Risk factors
similar to ectopic. The maternal mortality 5/1,000 cases (x7 that for ectopics).
Implantation sites include peritoneum outside uterus, POD, Omentum, Bowel.
Placenta may be attached to several organs including tube and ovary. Rare other sites
have been hepatic pregnancy or splenic pregnancy.

32. The Investigation and Treatment of
Couples with Recurrent First-trimester
and Second-trimester Miscarriage
Green-top Guideline No. 17 - April 2011

33. Recurrent Miscarriage (RM) and risk factors
Antiphospholipid syndrome APAS - treatable cause RM.
Association APA – LAC, ACA and anti-B2 glycoprotein-I antibodies
with adverse pregnancy outcome or vascular thrombosis
Adverse pregnancy outcomes include:
3 or > MC consecutive and <10 weeks
1 or > morphologically normal fetal loss >10th week
1 or > preterm births <34th week due to placental disease.
APA - cause pregnancy morbidity by inhibit trophoblastic function and
differentiation, activation complement pathways at materno–fetal
interface with local inflammatory response.
Later pregnancy, thrombosis utero-placental vessels reversed with
heparin.
APA present in 15% of women with RM.
Live birth rate with no pharmacological intervention is only 10%.
Miscarriage
Spontaneous loss before fetus viable <24 weeks
RM 3 or > consecutive pregnancies (1% couples)
1–2% of T2 pregnancies miscarry <24 weeks
Risk factors
Epidemiological factors
Maternal age : 12–19 years, 13%; 35–39
years,25%; 40–44 years,51%; and ≥45 years,93%.
Advanced paternal age (>40)
Risk MC > after successive losses > 40% with 3
consecutive MC worse with increasing age (>35).
Smoking and caffeine increase risk spontaneous
MC dose-dependent.
Alcohol is toxic to the embryo
Working VDU does not increase risk
Anaesthetic gases theatre workers conflicting risk
Obesity > risk sporadic and recurrent MC

34. Recurrent Miscarriage (RM) and risk factors
Genetic factors
Parental chromosomal rearrangements
2–5% of couples RM one carries a balanced
structural chromosomal anomaly: most often balanced reciprocal or
Robertsonian translocation. phenotypically normal, their pregnancies are
at risk of miscarriage or live birth multiple congenital anomalies or
mental disability
Embryonic chromosomal abnormalities
RM chromosomal abnormalities embryo account 30–57%
Risk chromosomal abnormalities embryo increases > maternal age.
Anatomical factors
Congenital uterine malformations
Prevalence and reproductive implications uterine anomalies in general
population unknown
RM uterine anomalies in 1.8% and 37.6% RM.
Higher in T2 MC ?related weak cervix (associated with malformation).
Arcuate uteri tend miscarry T2 and septate uteri T1.
Cervical weakness
Cervical weakness recognised cause T2 MC diagnosis is clinical .
History T2 MC preceded by PSROM or painless cervical dilatation.

35. Recurrent Miscarriage (RM) and risk factors
Endocrine factors
Disorders DM and thyroid disease associated with MC
High HbA1c levels in T1 are risk for MC and fetal anomaly
Well-controlled DM not a risk factor for RM
Nor is treated thyroid dysfunction.
Prevalence DM and thyroid dysfunction in RM similar to general population.
Immune factors
No evidence HLA incompatibility in partners, absence of maternal leucocytotoxic
antibodies or absence of maternal blocking antibodies.
NK cells are not a marker of events at maternal–fetal interface.
These tests should not be routine investigations for couples with RM.
Infective agents
Severe infection with bacteraemia or viraemia can cause MC.
Role in RM not proven. TORCH screening should be abandoned.
BV in T1 risk factor 2nd T MC and preterm delivery not associated T1 MC . Oral
clindamycin for BV significantly reduces T2 MC and preterm birth.
Inherited thrombophilic defects
Inherited/acquired; activated protein C resistance (factor V Leiden mutation),
deficient protein C/S, antithrombin III, hyperhomocysteinaemia, prothrombin
gene mutation cause systemic thrombosis.
May cause RM or late pregnancy complications.
Presumed mechanism is thrombosis uteroplacental circulation.

36. Recommended treatment for couples with RM in the first
and second trimester?
Offer referral to a specialist clinic – psychological support EPAU
Antiphospholipid antibodies (APAS)
RM first-trimester screen before pregnancy for APAS. Mandatory to have 2 positive tests 12
weeks apart for either LAC, ACA of IGG or IGM medium/high titre (> 40 g/l or ml/l)
Consider low-dose aspirin plus heparin to prevent further MC.
These pregnancies remain at high risk of complications during all three trimesters, including
repeated miscarriage, pre-eclampsia, fetal growth restriction and preterm birth; careful antenatal
surveillance.
Neither corticosteroids nor intravenous immunoglobulin therapy improve the live birth rate. May
provoke maternal and fetal morbidity.
Karyotyping
Cytogenetic analysis POC 3rd and subsequent MC.
Parental karyotyping couples with RM where POC report unbalanced structural chromosome
anomaly.
Genetic factors - Abnormal parental karyotype refer clinical geneticist.
Counselling offers prognosis for future risk with an unbalanced chromosome complement/
opportunity familial chromosome studies.
Options in couples with this issue include -natural pregnancy +/-prenatal testing, gamete
donation and adoption.
Pre-implantation genetic screen at IVF with unexplained RM doesn’t improve live birth rates.

37. Recommended investigations and treatment for couples with RM in the first
and second trimester?
Anatomical factors
Congenital uterine malformations
TVUS assess uterine anatomy.
Suspect anomalies further tests - hysteroscopy, laparoscopy or 3D TAS/TVUS.
No evidence effect uterine septum resection to prevent recurrent MC.
Cervical weakness and cervical cerclage
Hazards related cerclage and risk of stimulating uterine contractions .
Indicated history 2nd trimester MC and suspected cervical weakness
Serial USS- History 2nd TMC with cervical factors, TVUS<25mm cervix length <24 weeks offer
cerclage

38. Recurrent Miscarriage - Endocrine Thrombophillic Factors ?
Endocrine factors
Progesterone - necessary successful implantation and maintenance of
pregnancy. No effect progesterone therapy in pregnancy to prevent MC in
women with RM.
hCG - No evidence hCG supplementation in pregnancy prevents MC.
PCOS - No evidence metformin in pregnancy prevents MC in those with
recurrent MC. PCOS risk MC attributed to insulin resistance/ hyperinsulinaemia.
Metformin insulin-sensitising agent. LH hypersecretion, also feature PCOS, risk
factor MC. Suppression LH no effect on pregnancy outcome.
Immunotherapy - Paternal cell immunisation, third-party donor leucocytes,
trophoblast membranes and IV immunoglobulin unexplained recurrent MC does
not improve the live birth rate.
Inherited thrombophilias - Insufficient evidence heparin in pregnancy prevents
recurrent first-trimester MC with inherited thrombophilia.
Heparin therapy pregnancy may improve live birth rate for 2nd trimester MC
associated inherited thrombophilias.
Inherited thrombophilia > risk DVT need prophylaxis eg. enoxaparin

39. Unexplained recurrent miscarriage
1. 40-50% women with RM have unexplained cause
2. Excellent prognosis for future pregnancy outcome without
pharmacological intervention
3. Offer supportive care dedicated EPAU.
4. Supportive care 75% live birth rate (< age and > number MC).
5. Aspirin and or heparin (2xRCT’s) no improved live birth rate.

40. Gestational Trophoblastic Disease

41. Gestational Trophoblastic Disease
Definitions
• GTD group of disorders spanning complete and
• partial molar pregnancies, malignant conditions of
invasive mole, choriocarcinoma and very rare placental
site trophoblastic tumour (PSTT).
• There are reports of neoplastic transformation of
atypical placental site nodules to placental site
trophoblastic tumour.
• GTD, GTN (neoplasia) most commonly defined as
persistent elevation of βhCG.
Objectives
• Describe the presentation, management, treatment and
follow-up GTD
• Advice on future pregnancy outcomes and the use of
contraception.
Transvaginal sonography without (A)
and with (B) color Doppler imaging in a
case of GTD with vascular lakes (arrows)
and deep myometrial invasion.
A
B

42. GTD – Complete (CM) and Partial (PM) Moles
Molar pregnancies
Complete (CM)
• Complete moles are diploid and androgenic with no
fetal tissue.
• 75–80% arise due to duplication single sperm and 20-
25% dispermic fertilisation of an ‘empty’ ovum.
• Partial moles (PM)
• 90% triploid , two sets of paternal and one set
maternal haploid genes.
• Almost all PM’s, due to dispermic fertilisation of an
ovum.
• 10% PM tetraploid or mosaic conceptions.
• PM has evidence of fetal tissue or fetal red blood cells.
• GTD- Hhydatidiform mole, invasive mole,
choriocarcinoma, placental-site trophoblastic tumour is
a rare event
Incidence
• UK incidence 1/714 live births - Ethnic variation UK-
Asian 1/387 vs non-Asian 1/752 live births.
• Incidence after live birth is 1/50 000.
• UK, effective registration and treatment programme –
cure rate (98–100%) and low (5–8%) chemotherapy
rates.
Presentation and Diagnosis
Symptoms
• Irregular bleeding, hyperemesis, excessive
• uterine enlargement and early failed pregnancy.
• Rarer hyperthyroidism, early onset PET, abdominal
distension due to theca lutein cysts.
• Very rarely acute respiratory failure or neurological
symptoms such as seizures; due to metastatic disease.
Investigations
US pre ERPC
HCG levels
Histological examination POC
• Routine US reduced mean gestation Diagnosis -16
(1965–75) to 12 weeks (1988–93).
• Majority histologically proven CM’s associated with US
diagnosis missed miscarriage or anembryonic
pregnancy.3,4 In one study, the accuracy of pre-
evacuation diagnosis of
• CM 56% detection rate at US pre ERPC and histology
• PM US more complex; multiple soft markers -cystic
placental spaces, ratio of transverse:AP dimensions
gestation sac >1.5
• HCG levels > 2 MOM’s for gestational age

43. Management molar pregnancy
What is the best method Medical or surgical of
evacuating a molar CM or PM pregnancy?
• Suction ERPC- CM and PM. Except PM if size fetal parts prohibit.
• Medical (RU486/Misoprostol) may be safe for PM avoid for CM. Urine HCG
at 3 weeks if POC not sent for histology.
• Anti-D prophylaxis for PM but not CM poor vascularisation of the chorionic
villi and absence of the anti-D antigen in CM.
• Oxytocics- may embolise or disseminate trophoblast in venous system.
• Management moles with RU486 and misoprostol Ltd. avoided with CM as >
sensitivity uterus to PG’s.
• Preparation cervix ERPC safe no > risk chemotherapy.
• Excessive vaginal bleeding may occur with CM senior surgeon directly
supervising ERPC. Larger uterine size > risk bleeding and persistent GTD
• Oxytocic infusion before ERPC or before complete not recommended. If
needed weigh need versus risk tumour embolisation.
• CM higher risk chemotherapy treatment persistent GTD, PM risk low 0.5%.

44. Histopathology – Role US, serial HCG, GTD reference centre
Should all POC from miscarriages be
examined histologically?
Miscarriage
• Histological assessment POC from medical/surgical management of
failed pregnancies recommended to exclude GTN (missed
miscarriage, blighted ovum, no fetal parts seen).
• Ploidy status and immunohistochemistry staining for P57 may help
differentiate PM and CM.
STOP
• No if fetal parts seen on prior US.
• Risk GTN after STOP 1/20 000.
• Failure to diagnose GTD at STOP adverse outcomes and higher risk
life threatening complications, surgical
• intervention, hysterectomy and multi-agent chemotherapy.
• RCOG - US prior TOP to exclude non-viable and molar pregnancies.
• No indication routine histology for POC.
Who should be followed up ?
Persisting gynaecological symptoms after
evacuation molar pregnancy, consult GTD
screening centre prior to second ERPC
• Serial hCG and US, may be role second ERPC hCG <5000 Iu/L.
Who should be investigated for persistent GTN
after a non-molar pregnancy?
• Persistent vaginal bleeding after a pregnancy event risk of
GTN.
• Urine pregnancy test performed all with persistent or
irregular bleeding.
• Symptoms from metastatic disease, such as dyspnoea or
abnormal neurology, can occur very rarely.
• Several case series have shown that vaginal bleeding is the
most common presenting symptom of
• GTN diagnosed after miscarriage, therapeutic termination of
pregnancy or postpartum. The prognosis for women with
GTN after non-molar pregnancies may be worse, in part
owing to
• delay in diagnosis or advanced disease, such as liver or CNS
disease, at presentation

45. How is twin pregnancy of a fetus and coexistent molar
pregnancy managed?
Types affected pregnancies
Combined molar and viable pregnancy
Twin pregnancy viable fetus and mole
• Increased risk perinatal morbidity and outcome GTN.
• Prenatal invasive testing fetal karyotype considered if
unclear if CM with coexisting normal twin or a PM
• Also consider testing karyotype abnormal placenta eg.
Suspected mesenchymal hyperplasia.
• Normal pregnancy and co-existing CM outcome is poor,
25% live birth rate. Early fetal loss 40%, PTD 36%
• PET risk varies as high as 5-20%
• > risk maternal death many studies and persistent GTN.
• Successful use of GTD screening and reference centres in
the UK. The risk GTN after such a twin pregnancy and
outcome after chemotherapy is unaffected

46. Which women should be registered
GTD screening centres?
GTD cases - written information about
condition, need for referral and follow-up
to a GTD screening and reference centre
• CM
• PM
• Twin pregnancy with CM/PM
• Limited Macro or Micro molar change suggesting possible partial or
early complete molar change
• Choriocarcinoma
• Placental-site trophoblastic tumour (PSTT)
• Atypical placental site nodules: nuclear atypia trophoblast, areas
necrosis, calcification and > proliferation (Ki67 immuno reactivity within
nodule). % may transform to PSTT.
Registration of GTD cases is a minimum standard of care.
Achieved by postal form or online. http://www.hmole-chorio.org.uk.
Charing X centre established by DoH 1973 has treated > 2500 GTD
UK/overseas. The largest experience of this disease worldwide. Best data,
research and cure rates for GTD, lowest rate chemotherapy required.
Follow-up serial hCG levels - blood or urine by the reference centre. UK
programme - High cure (98–100%) and low (5–8%) chemotherapy rates.

47. Management GTD?
Follow-up after diagnosis and initial treatment
• hCG normal by 56 days of pregnancy event - follow up for 6 months
from date uterine evacuation.
• hCG abnormal 56 days follow-up for 6 months from normal hCG level.
• All notify screening centre end of any future pregnancy, whatever
outcome. Measure hCG for 6-8 weeks to exclude GTD
• When hCG normalised risk GTN is very low.
• GTN can occur after any subsequent pregnancy event, even if normal
pregnancy in between.
Treatment persistent GTD/GTN
• Women with GTN may be treated either with single-agent
or multi-agent chemotherapy for GTN.
• Treatment used is based on the FIGO 2000 scoring system
for GTN following assessment at the treatment centre.
• The need for chemotherapy following a complete mole is 15%
and 0.5 % after a partial mole. The
• development of postpartum GTN requiring chemotherapy
occurs at a rate of 1/50 000 births.
• Women are assessed before chemotherapy using the FIGO
2000 scoring system (Table 1).
• Scores ≤ 6 low risk treated by single-agent IM methotrexate
alternate daily with Folinic acid x 1 week then 6 rest days.
• Scores ≥ 7 high risk treated with IV multi-agent chemo,
includes combination - methotrexate, dactinomycin,
etoposide, cyclophosphamide and vincristine.
• Treatment continued, until hCG level normal and then for a
further 6 weeks.
• Cure rate score ≤ 6 is 100%; score ≥ 7 95%.
• PSTT variant of GTN may be treated with surgery less
sensitive to chemotherapy.

48. GTD – Contraception, Conception Future Risk
Is HRT safe to use after GTD?
• HRT may be used safely hCG levels normal.
Safe contraception after GTD and when can it be
commenced?
• Use barrier methods until hCG levels normal.
• Once normal COCP pill may be used.
• OCP started before diagnosis GTD can remain on OCP
low increase risk of GTN.
• IUD not be used until hCG normal - risk of uterine
perforation.
• Two RCT’s RR 1.19developing GTN on COCP
RCOG- Green-top guideline 38
Future conception and risk ?
• No conception for 1 year after completes treatment GTN.
• Risk molar pregnancy is low (1/80): > 98% pregnancies
following mole will not have further mole
• No> risk of obstetric complications.
• Further molar does occur, 68–80% same histology type.
• Conception <12 months after chemotherapy, > risk
miscarriage (>again with multi-agents)
• Congenital anomaly rate low 1.8%
• Rate stillbirth > normal population 18.6/1000 births
Long-term outcome treated GTN?
Menopause age single-agent advanced by 1 year and 3 years
with multi-agent chemotherapy.
Multi-agent chemo >RR other CA specifically etoposide
• RR 16.6 AML
• RR 4.6 colon cancer,
• RR 3.4 melanoma
• RR 5.79 for breast cancer at >25yrs surviving GTN
Combination chemo <6 months no >RR secondary CA’s

49. Pregnancy with and IUD in place
Faculty of Sexual and Reproductive Healthcare of the
RCOG guidance on IUD 2007.
• Most pregnancies with IUD in situ IUP.
• Ectopic pregnancy (6% these cases) must be
excluded
• Miscarriage frequent complication of pregnancy
with an IUD. 50% -60% IUP if IUD not removed
against background rate of 13%.
• Increased risks of second-trimester MC, preterm
delivery and infection if IUD left in situ
• Removal reduces adverse outcomes with a small
risk of miscarriage
• Threads are visible, or can easily be retrieved from
endocervical canal, remove IUD up to 12 weeks
gestation
• 50% IUD with IUP are malpositioned
• Unsure TVUS.
• Plain film abdomen/pelvis if TVUS (-ve)

50. NVP – Nausea and Vomiting of Pregnancy
and
Hyperemesis Gravidarum

51. Nausea Vomiting of Pregnancy
Incidence
80% of pregnancies experience some degree of NVP
30% of these have severe symptoms
90% resolved by week 16
Of these with NVP symptoms (hours) per pregnancy :
20% have 100–300 hours
10% have 300–700 hours
0.3–1.5% (mean 1%) severe NVP hospital admission rehydration/
correction electrolyte imbalance (Hyperemesis Gravidarum)
In England for 2006/7, total admissions for
ICD-10 021 (Hyperemesis Gravidarum) 25,420
Treatment early stages prevents serious complications,
includes hospital admission
Hyperemesis gravidarum (HG) persistent NVP causes
Weight loss >5% BMI and ketosis.
Severe cases, inadequately or inappropriately treated
Hyperemesis can cause:
1. Wernicke’s encephalopathy
2. Central pontine myelinolysis
3. Maternal death
4. Risk IUGR.
Adverse effects NVP
30% working women need time off NVP
Or cannot carry out household duties or
parenting activities satisfactorily.
15-37 per year TOP for NVP
Terminology
Morning sickness is a misleading
13% have symptoms exclusive mornings
Majority, symptoms occur both/after midday.
More appropriate term, episodic NVP
Hyperemesis Gravidarum. A Neill et al. TOG 2003;5:204–7

52. Nausea Vomiting of Pregnancy
Other issues of recommendation and licence
NHS Clinical Knowledge Summary for NVP states all anti-emetics
(including antihistamines) unlicensed for treatment NVP in UK.
Anti-emetic required in pregnancy, oral promethazine or oral
cyclizine (H1 receptor antagonist antihistamines) may be taken.
Available without prescription in UK, but information leaflet in
the drug packs states: ‘Do not take if you are pregnant unless
they have been recommended by a doctor’.
Lack of approved/licensed drug can be associated with
unwarranted preventable adverse health effects of severe NVP
Many may not receive appropriate treatment because
Misinformation/misconception related to teratogenic risk.
Concerns possible toxicity high dose pyridoxine not resolved
and therefore not recommended by NICE in the UK
(Management of Common Symptoms of Pregnancy. Antenatal
Care Guideline. London: NICE; 2008. Chapter 6)
Cochrane review therapy 2010
Pre-emptive treatment
Previous severe NVP +/- hyperemesis gravidarum
80% experience severe NVP again.
Offer anti-emetic therapy as soon as aware of pregnancy
or no later than onset of NVP symptoms.
Significantly better
Treatment
Lifestyle measures
Oral treatment when max symptoms with severe effect on
QoL (usually 2 weeks after onset NVP)
Medication
UK - H1 receptor antagonist antihistamine + Pyridoxine
Avomine© (promethazine teoclate)
25 mg (up to 100 mg daily) or
Cyclizine 50 mg (up to 150 mg daily) plus,
Pyroxidine 10 mg (up to 40 mg daily).

53. Hyperemesis Gravidarum
Hyponatraemia (plasma sodium <120 mmol/l) - Lethargy, seizures and
respiratory arrest. Both severe hyponatraemia and rapid reversal Central
pontine myelinolysis. Spastic quadraparesis, pseudobulbar palsy, LOC
Other vitamin deficiencies occur -
Cyanocobalamin (B12) and pyridoxine (B6)
causing anaemia and peripheral neuropathy.
Fetal - IUGR
General Management
Rest, small CHO meals when symptoms least
severe and carbonated drinks
Prolonged dehydration or bed rest should
receive thromboprophylaxis (e.g. enoxaparin
40 mg/daily) and TEDS
Admission and rehydration
Symptoms HG
Nausea
Vomiting
Weight loss occur
Ptyalism (inability to swallow saliva) and spitting
Signs
Dehydration
Tachycardia
Postural hypotension
Ketosis
Complications
Mallory–Weiss tears
Loss 10–20% body weight- muscle wasting,
weakness.
Thiamine (vitamin B1) deficiency - Wernicke’s
encephalopathy
Syndrome characterised by diplopia, abnormal
ocular movements, ataxia and confusion. If thiamine
is deficient, IV dextrose/ glucose may
precipitate Wernicke’s encephalopathy.

54. Hyperemesis Gravidarum
Treatment
Cyclizine 50mg TDS PO IM IV
Promethazine 25 mg OD nocte
Prochlorperazine 5mg TDS PO PR 12.5 IM TDS
Metoclopramide 10 mg TDS PO IM SC
Domperidone 10 mg QDS PO 30–60mg QDS PR
Chlorpromazine 10–25mg TDS PO 25 mg TDS IM
Differential diagnosis of Hyperemesis Gravidarum
Infection – UTI
Hepatitis
Drug induced (eg. Iron supplementation)
Antibiotics
Metabolic Thyrotoxicosis
Hyperparathyroidism/hypercalcaemia
Diabetic ketoacidosis
Uraemia
Addison’s disease
Gastrointestinal Appendicitis
Cholecystitis
Small bowel obstruction
Pancreatitis
Management HG – Admission to Hospital
Stop drugs that cause NV (eg. Fe temporarily)
IV fluids
NACL (0.9%,/150 mmol/l Na) or Hartmann’s (131 mmol/l Na).
Add KCL to each bag.
Avoid dextrose saline not enough Na
May cause Wernicke’s encephalopathy
Titrate regimen against daily U&E
Thiamine 25–50 mg TDS/IV infused 30–60
Mins, repeat weekly.
SS-5HT3 receptor antagonist (Ondansetron)
effective in some with HG.
Routine prescribing not recommended.
Histamine receptor blockers (ranitidine)/
PPI omeprazole used with success.
Psychological support
Day-care management of HG
Pyridoxine (vitamin B6) may be useful for severe
nausea, less effective preventing vomiting.
Steroid therapy may give rapid improvement
Hydrocortisone 100mg BD then
40 mg prednisolone OD - 10 mg OD x 20 weeks.

55. Ovarian Hyper-Stimulation Syndrome (OHSS)

56. Ovarian Hyper-Stimulation Syndrome (OHSS)
Risks
1. OHSS is associated with hCG injection at IVF used to
induce final maturation and/or trigger oocyte release.
2. Risk increased > doses of hCG after ovulation and if
the procedure results in pregnancy.[1]
3. Use GnRH agonist instead of hCG inducing oocyte
maturation and/or release results in an elimination
risk OHSS but a decrease delivery live baby rate x6%.
Pathophysiology
A. OHSS characterized by multiple luteinized cysts in the ovaries with enlargement and
secondary complications.
B. Central feature OHSS - vascular hyper permeability shift of fluids into the third space;
C. hCG causes ovary to luteinize with, large amounts oestrogens, progesterone + local
cytokines released.
D. VEGF is a key substance induces vascular hyper permeability (capillaries "leaky“) and shift
of fluids from the intravascular space into the abdominal and pleural cavity.
E. Supraphysiologic levels of VEGF from many follicles under prolonged effect of hCG is key
to OHSS. As fluid ↑in the third space it forms ascites, pleural effusion, intra-vascular
hypovolemia and risk of respiratory, circulatory with arterial thromboembolism (blood is
now thicker), and renal problems. Patients who are pregnant sustain ovarian luteinization
process through production of hCG.
F. ↓OHSS requires interrupting pathological sequence- avoid use hCG (e.g. use GnRH
agonist). ↓pregnancy rates if a fresh non-donor embryo transfer attempted (due to a luteal
phase defect) but GnRH agonist trigger effective oocyte donors and embryo banking
(cryopreservation) cycles.

57. OHSS- Epidemiology and Classification
Symptoms
Mild - abdominal bloating , nausea, diarrhea, slight weight gain.
Moderate - excessive weight gain (>1kg per day), increased girth,
vomiting, diarrhoea, dark urine, less urine, excess thirst, skin
and/or hair dry (+ mild symptoms).
Severe - bloating above waist, dyspnoea, pleural effusion, urine
dark or anuric, calf/chest pain, ascites and abdominal pains (+ mild
and moderate symptoms).
Classification
Mild OHSS - ovaries enlarged (5–12 cm)[3] +/- ascites, abdominal
pain,[3] nausea,[3] and diarrhea.[3]
Severe OHSS - hemoconcentration, thrombosis, oliguria, pleural
effusion, and respiratory distress.
Clinical Criteria
Severe OHSS -USS > ovary size, ascites, hematocrit > 45%, WBC >
15, urine<30ml/hr, creatinine 1.0-1.5 mg/dl, creatinine clearance >
50 ml/min, abnormal LFT’s, anasarca (extreme generalised
oedema)[3]
Critical OHSS – USS very enlarged ovary, tense ascites, hydrothorax,
pericardial effusion, hematocrit > 55%, WBC > 25, oligo-anuria,
creatinine > 1.6 mg/dl, creatinine clearance < 50 ml/min,
thromboembolism, ARDS.[3]
Epidemiology
1. Sporadic OHSS rare ? genetic component.
Clomifene citrate may cause OHSS
2. Most OHSS follows gonadotropin therapy (FSH)
e.g. Pergonal and hCG (induce final oocyte
maturation and/or trigger oocyte release) usually
with IVF.
3. Factors influencing OHSS rate- patient,
management + surveillance.
4. 5% OHSS - moderate to severe risks- young age, >
number ovarian follicles stimulated, very high
serum estradiol, hCG for final oocyte maturation
+/_release, continued hCG for luteal support +
pregnancy resulting in more hCG.
5. Mortality is low, but fatal cases are reported.

58. References
1. Humaidan P, Kol S et al. GnRH agonist for triggering of final oocyte maturation: time for a change of
practice?. Hum. Reprod Update 2011;17 (4): 510–24.
2. Textbook of Assisted Reproductive Techniques, Laboratory and Clinical Perspectives, edited by David K.
Gardner, 2001
3. Youssef MA, van Wely M, Hassan MA, et al. Can dopamine agonists reduce the incidence and severity of
OHSS in IVF/ICSI treatment cycles? A systematic review and meta-analysis. Hum Reprod Update 2010:16
(5): 459–66.
4. Gera, P.; Tatpati, L. Allemand, M. Wentworth, M. Coddington, C. OHSS: steps to maximize success and
minimize effect for assisted reproductive outcome. Fertility and Sterility 2010;94 (1): 173–178.
5. Horwitz, et al. Ovarian Hyperstimulation Syndrome: Treatment and Medication. eMedicine Obstetrics and
Gynecology. 11/2008. http://emedicine.medscape.com/article/1343572-treatment
Complications OHSS
1. Ovarian torsion
2. Ovarian rupture
3. Thrombophlebitis
4. Renal insufficiency
Symptoms generally resolve in 1-2 weeks
More severe and persist longer if pregnancy occurs.
This is due to hCG of pregnancy acting on corpus luteum in the
ovaries in sustaining the pregnancy before the placenta has fully
developed.
Severe OHSS with developing pregnancy the duration does not
exceed the first trimester.
Treatment - Depends on severity OHSS
Mild OHSS – conservative; monitor abdo girth, wgt, discomfort in
OPD (until conception or menstruation). With conception mild
OHSS may ↑
Moderate OHSS- OPD/inpatient (as above)± bed rest, IV fluids,
U&E, FBC, LFT’s and USS monitor size ovarian follicles. Strict I+O
with >1L fluid deficit a cause for concern.
Monitor OHSS resolution by ↓ decrease size follicular cysts
(2 consecutive USS)[6]
Severe OHSS- Aspiration accumulated fluid (ascites or plueral
effusion) from abdominal/pleural cavity. Opioid analgesia for pain.
If OHSS within IVF protocol, postpone transfer of the pre-embryos
as pregnancy can ↑time to recovery or ↑severity OHSS.
OHSS therapy is supportive but may need to be hospitalized for
pain, paracentesis, and/or intravenous hydration.
OHSS - Management
Prevention
1. Reduce OHSS risk by monitoring FSH therapy to use judiciously,
and withhold hCG if ↑risk.
2. Dopamine agonist prophylaxis: meta-analysis concludes
cabergoline ↓ incidence, but not severity OHSS, no ↓ Live Birth
Rate (LBR) [4]
3. OHSS ↓ by coasting during ovarian stimulation for IVF omitting
hCG for final maturation of follicles. ↓ OHSS in high risk cases (
0% vs 20%) [5]
4. But LBR ↓38% with coasting vs. 45% LBR for controls.
5. Also ↓ cumulative LBR 52% vs. 59% [5]. Maybe due to difficulty in
timing oocyte retrieval with full maturation.

59. Urinary sepsis in pregnancy

60. Urinary sepsis in pregnancy
WCC -white blood cells seen under a
microscope from a urine sample.
Pyuria – pus cells in a mid-stream urine sample
Pregnancy
1. Urinary tract infection (UTI) more concerning in pregnancy due
to the increased risk of ascending pyelopnephritis
2. Pregnancy-, high progesterone levels, decrease smooth muscle
tone of ureters and bladder, > risk urine reflux.
3. While pregnant women do not have an increased risk of
asymptomatic bacteriuria.
4. If bacteriuria is present they do have a 25-40% risk of a kidney
infection.
5. Thus if urine testing shows signs of an infection—even in the
absence of symptoms—treatment is recommended.
6. Cephalexin or nitrofurantoin are typically used because they are
generally considered safe in pregnancy.
7. UTI during pregnancy may result in premature birth or pre-
eclampsia and renal dysfunction

61. Common causative organisms:
80–85% E Coli
5-10% Staphylococcus saprophyticus being the
Others causes include:
• Klebsiella
• Proteus
• Pseudomonas
• Enterobacter.
These are uncommon and typically related to abnormalities
urinary system or catheterization.
UTI due to Staphylococcus aureus: typically occur secondary
to blood-borne infections
Diagnosis
Symptoms- dysuria, frequency, urgency, haematuria, loin pain, fever
Urinalysis- (+ve)urinary nitrites, leukocytes or leukocyte esterase.
Microscopy- RCC, WCC, bacteria.
Urine culture – (+ve) > 103 colony-forming units (CFU) per mL of a typical
urinary tract organism.
Antibiotic sensitivity - can also be tested with these cultures, making them
useful in the selection of antibiotic treatment.
Classification
1. Lower urinary tract infection .
2. Ascending upper urinary tract -pyelonephritis.
3. Urine contains significant bacteria but no symptoms- asymptomatic
bacteriuria.
4. UTI is deemed complicated if it involves
• The upper tract
• Diabetic
• Immune compromised
• Pregnancy
MSU Microscopy - multiple rod-
shaped bacteria shown between
white blood cells indicative of UTI
Pathogenesis and treatment

62. Anti-microbial therapy
Antibiotic therapy
Oral antibiotics are the treatment of choice for asymptomatic bacteriuria and
cystitis. Appropriate oral regimens include the following:
• Cephalexin 500 mg 4 times daily
• Ampicillin 500 mg 4 times daily
• Nitrofurantoin 100 mg twice daily
• Sulfisoxazole 1 g 4 times daily
Resistance of E coli to ampicillin and amoxicillin is 20-40%;
These agents are no longer considered optimal for treatment UTIs caused by
this organism. Fosfomycin (phosphonic acid derivative) useful treatment
uncomplicated UTIs caused by susceptible strains of E coli and Enterococcus.
Category B agent in pregnancy (ie, fetal risk is not confirmed by human
studies but shown in some animal studies).
Duration therapy
1-, 3-, and 7-day antibiotic courses have been evaluated
10-14 days treatment recommended to eradicate bacteria.
Studies cephalexin, trimethoprim-sulfamethoxazole, amoxicillin indicate
single dose as effective as a 3- to 7-day course
But cure rate is only 70%. The data are insufficient to justify abandoning the
more traditional long-term regimens.
Treatment success
Depends on eradication bacteria rather than duration of therapy.
MSU should show negative findings 1-2 weeks after therapy.
Non-negative MSU culture result indication for a 10-14 day course different
antibiotic and then suppressive therapy
(eg, nitrofurantoin 50 mg at bedtime) until 6 weeks postpartum.
Complicated UTI
Check renal function
Consider renal ultrasound
1. Risk hydronephrosis
2. Exclude other pathology e.g. calculus
3. Rarely - cystoscopy
E Coli- UTI

63. Urinary sepsis in early pregnancy
UTI common in pregnancy
• May result in significant morbidity for the pregnant woman and fetus.
• All women should be screened for bacteriuria at their first prenatal visit
(5%-10%) women will have asymptomatic bacteruria in the 1st trimester
• Failure to treat bacteriuria during pregnancy may result in 25%
experiencing acute pyelonephritis (1).
• Antibiotics effective in clearing bacteriuria [RR 0.25; 95% CI 0.14-0.48]
and ↓risk [RR: 0.23; 95% CI: 0.13 to 0.41]. (Cochrane review 2007)
• Antibiotics ↓ risk LBW [RR: 0.66 95% CI: 0.49 to 0.89].
• Maternal infection resulting in sepsis may cause up to 30% of ICU
admissions for obstetrics contributes to 2%-3% of maternal mortalities
• Microbiology of sepsis is distinct in pregnancy; endotoxin-producing G(-)
rods e.g. E. coli common aetiologic agent versus G(+) bacteria common
culprits in non-pregnant patients with sepsis.
Complications pregnancy related pyelonephritis-
1. Preterm labour
2. Transient renal failure
3. ARDS
4. Septicemia and shock
5. DIC
Maternal UTI is independently associated with pre-term delivery, pre-
eclampsia, IUGR and CD. Nevertheless, it is not associated with increased
rates of perinatal mortality compared with women without UTI (2).
Those treated for UTI should be followed up closely after treatment up to
1/3 women may experience recurrence.
Reference s–
1. Giltrap et al. UTI during pregnancy.
Obstet Gynecol Clin North Am. 2001 Sep;28(3):581-91
2. Mazor-Dray E, Levy A, Schlaeffer F, Sheiner E. Maternal urinary tract infection:
is it independently associated with adverse pregnancy outcome? J Matern Fetal
Neonatal Med. 2009;22(2):124-8.

64. Vaginal discharge STI’s and Pregnancy
Trichomonas
Treponema Pallidum

65. Normal discharge in pregnancy
Common Changes in Hormones
• Most likely cause of discharge is change in hormones
during menstrual cycle and pregnancy (leucorrhoea).
• When ovulation occurs, vaginal discharge will change.
• Normally, vaginal discharge is thick and sticky when a
woman is not ovulating.
• Ovulation approaches, vaginal discharge changes to a
thin, stretchy film that helps sperm travel to the egg.
• Any change in the vagina's balance of normal bacteria
can affect the smell, colour, or discharge texture.
Causes of vaginal discharge
1. Normal hormone changes during pregnancy
2. Vaginal infection (e.g. Bacterial vaginosis (BV),
candidiasis)
3. STI’s (e.g. gonorrhea or trichomoniasis)
4. Cervical cancer
5. Douches, scented soaps or bubble bath
6. PID (uncommon>12 weeks)
7. Menopause (eg, vaginal atrophy)
8. Vaginitis, irritation in or around the vagina

66. Candidiasis (Thrush)
Candida Albicans
Candida species of fungus, usually Candida Albicans.
Frequently an isolate in vaginal flora but does not usually cause any
symptoms because its growth is kept under control by normal
commensals.
If the immune system is affected or the vaginal flora altered by
antibiotics then candidiasis may occur and cause:
1. itching
2. irritation
3. redness
4. soreness and swelling of the vagina and vulva
5. thick, creamy discharge but no odour
Because of hormonal changes and relative immune suppression
pregnant women often get thrush, especially during the third trimester
of pregnancy but there is no evidence of harm to the fetus.
Treating thrush during pregnancy
1. No treatment.
2. Topical - anti-fungal- cream or pessary e.g. clotrimazole or a similar
drug.
3. Oral – e.g. fluconazole. But advice is to avoid in pregnancy

67. Bacterial Vaginosis (BV)
Incidence
15% pregnant women have BV most are asymptomatic.
BV associated with -
• PPSROM
• PTD
• LBW
Risk complications > earlier in pregnancy the condition
occurs.
1. Detecting and treating BV<20 weeks reduces PTD
2. Treating previous PTD reduces the rate PPSROM and LBW.
3. Treat symptomatic BV but not asymptomatic or
unconfirmed BV in the absence of above.
Screening
No evidence to screen and treat BV asymptomatic pregnancy
Screening with previous PTD may be beneficial
Lower genital tract symptoms, intrapartum or postpartum
fever, than test for BV -
Gram-stain vaginal smear, grades normal, intermediate or BV
• "fishy" odor on wet mount whiff test, add a small
amount of KOH (amines released).
• Loss of acidity litmus paper pH>4.5
• clue cells on wet mount by placing a drop of NACl. They
give a clue to the discharge epithelial cells coated with
bacteria.
These fulfils Amsel’s clinical criteria.
Whether antimicrobial treatment BV in pregnancy causes
more harm than benefit is unclear do not give antibiotics in
the absence of proven infection.

68. Pregnancy and
• STI’s have increased prevalence pregnancy
• STI testing include/repeat HIV test
• <25 yrs chlamydia screen
• Pregnant and STIs EPAU/GUM, treat, screen, partner
tracing, sexual abstinence treatment, safe sex.
• TOP women high prevalence/complication rates STIs
• interaction STIs/pregnancy bidirectional
• Physiological changes may alter natural history
• Treatment options may be ltd and must be effective to
justify any risk to pregnancy/fetus.
Gonorrhoea uncommon UK concentrated in large urban areas.
Median age infected women 20 years.
> rates pharyngeal sepsis pregnancy altered sexual behaviour.
Higher risk disseminated sepsis
40% co-infected with chlamydia.
Increase risk PPSROM, PTD. LBW
Gonorrhoea increases risk postpartum infection
50% babies ophthalmia neonatorum
NAATs used detect >sensitivity, confirmed by supplementary culture
Guide antibiotic treatment (avoid current issue widespread
antimicrobial resistance) with culture/susceptibility testing
Swab pharynx/rectum in women with genital gonorrhoea
Neisseria gonorrhoea
Strawberry spots cervix
Oro-pharyngeal gonorrhoea
Opthalmia Neonatorum

69. Genital herpes
50% a sero +ve HSV-1
25% HSV-2 antibodies at the start of pregnancy
3–4% sero –ve acquire the virus during pregnancy (1 in 60,000)
This small number primary HSV accounts large % neonatal
infections
Primary HSV in pregnancy –
T1 miscarriage
Preterm birth and LBW.
Recurrent HSV is not associated with these
Neonatal HSV
Causes death 31% /chronic disability 83% of survivors.
Transmission risk primary HSV 40–50%
Secondary to maternal viraemia, absent maternal antibodies
and extensive cervical involvement.
HSV 2 virus (recurrent) detected in 15% of asymptomatic HSV-2
Sero +ve pregnant women at delivery; asymptomatic shedding
responsible < 1% neonatal infections due passive
transfer of maternal antibodies.
Primary HSV late pregnancy > risk of transmission.
Women within 6 weeks EDD offered CS
If in established labour, or decline CS avoided invasive procedures
Give IV aciclovir given to mother and neonate.
Primary HSV in T1 or T2 anticipate vaginal delivery.
Recurrent HSV (Statement RCOG )–
CS is not indicated recurrent HSV onset of labour.
Risks transmission small.
Mode delivery discussed with mum .
Invasive procedures avoided.
Aciclovir suppression from 36 weeks (active or prophylactic)
Reduce HSV shedding , lesions at onset labour / need consider CS.
Acyclovir is unlicensed for use in pregnancy but is safe and effective
(400mg BD/TDS).
Latter TDS dose in T3 as altered pharmacokinetics in late pregnancy
HSV 1 and 2

70. Chlamydia Trachomatis
• Complications chlamydia due ascending infection.
• Chlamydia, pre-term birth, PPSROM, LBW, infant
mortality associations usually with primary infection
• 34% primary chlamydia and VD get puerperal
sepsis.
• 50% neonates untreated develop ophthalmia
neonatorum
• 15% neonates chlamydia pneumonitis
Most common non-viral STI causes vulvovaginitis;
10–50% are asymptomatic.
Associated with PTD, LBW, puerperal infection rate unclear
concurrent increase anaerobic bacteria.
Little neonatal morbidity
Test for T. vaginalis by microscopy and/or culture.
NAATs T. vaginalis very sensitive not widely available.
Nitroimidazoles most effective treatment no evidence
teratogenicity with metronidazole pregnancy
90% microbiological cure rate with metronidazole
No protective effect treatment pregnancy outcomes.
Prudent to treat symptomatic women during pregnancy
Test cure recommended if symptoms persist/recur
Trichomoniasis (T Vaginalis)

71. Incidence
Most common viral STI in the UK
Anogenital warts infection low-risk subtypes HPV usually transient; Pregnant
women > rates detectable HPV DNA due to altered immunity, >rate symptoms,
warts can be extensive, rapidly enlarging.
Neonatal Infection
Vertical transmission HPV occurs in 1 in 80 cases
May cause genital and laryngeal warts in infants.
Rare complication vertical transmission low-risk subtypes recurrent respiratory
papillomatosis 4.3/100 000 cases.
<CS compared to VD but given rare operative delivery would not
normally be advised.
Treatment HPV (Warts) in pregnancy
Does not reduce risk vertical transmission, so no treatment is an option.
Treatment may improve symptoms and limit disease extent
Podophyllotoxin contraindicated because toxicity
Imiquimod insufficient safety data to support use
Treatment ltd. liquid nitrogen, trichloroacetic acid, electrocautery, curettage.
CS consider large warts- may obstruct labour, causing extensive cervical disease.
Anogenital warts

72. Pathophysiology
2009-10 UK cases infectious (primary, secondary and early
latent) declined by 14%; Uptake AN syphilis screening 2009 -96%
(0.16% tests +ve). Congenital syphilis low effective antenatal
screening. Treponema pallidum causes syphilis transmitted
across placenta at any stage of pregnancy.
Risk transmission dependent on stage maternal infection and
duration fetal exposure -
Early pregnancy up to 100%
50% PTD and fetal death.
10% late infection will be affected.
Congenital syphilis multi-system infection may result stillbirth,
neonatal death, long-term disability.
Diagnosis
Serology test, enzyme immunoassay, +ve result confirmed with
haemagglutination/particle agglutination suphilis assay.
Non-treponemal test, VDRL test or reactive plasma reagin,
quantitative assay monitor disease activity, treatment response.
Delivery < 30 days completion of treatment, then treat
neonate. Penicillin is the treatment of choice - benzathine
benzylpenicillin G
Syphillis – Treponema pallidum
Up to 45% get Jarisch–Herxheimer reaction
of syphilis treatment pregnancy - Uterine contractions, PTL
FHR decelerations can occur result of maternal fever.
Fetal monitoring for treatment >26 weeks
Management supportive, antipyretics, but oral
corticosteroids not indicated
Monthly serology required monitor treatment response.
Indications further maternal treatment postpartum:
Presented late pregnancy no previous treatment
Adequate treatment response not achieved VDRL reactive
plasma serofast at a titre >1:8
Use of a non-penicillin regimen.
Neonates assessed by neonatologist receiving treatment if
congenital infection.

73. Screening tests, sites, indications and recommended
treatment and follow-up of STIs in pregnancy.
Screening/testing recommendations
Testing
technology
Sites to
sample
First-line treatment Alternative/additional treatment
Indications for test
of cure
Chlamydia
Gonorrhoea
Trichomonas
vaginalis
Bacterial
vaginosis
Inform women <25 years to attend
local National Chlamydia
Screening Programme centre (in
England) Women >25 years: Test
if symptoms of infection or baby
has ophthalmia neonatorum
Test if symptoms of infection or
baby has ophthalmia neonatorum
Test if symptoms of infection
Test if symptoms of infection
NAAT
Culture or NAAT
plus culture if
positive
Culture or NAAT if
available
Gram stain Amsel’s
criteria
Endocervix
or self-
taken
vulvovagin
al swab
Endocervix
plus
pharynx
and rectum
(depending
on sexual
activity)
Posterior
fornix
Lateral
vaginal
wall
Azithromycin 1 g single dose
Ceftriaxone 500 mg
intramuscular single dose
with azithromycin 1 g stat or
spectinomycin 2 g
intramuscular single dose
with azithromycin 1 g stat
Metronidazole 400 mg b.d. 7
days
Metronidazole 400 mg b.d. 7
days Intravaginal treatment
recommended for women
who are breastfeeding
Erythromycin 500 mg b.d. for 14 days or
erythromycin 500 mg q.d.s. for 7 days or
amoxicillin 500 mg t.d.s. for 7 days
Amoxicillin 3 g and probenecid 1 g oral
single dose (if regional prevalence of
penicillin resistance <5%) All should
receive chlamydia treatment
Metronidazole 0.75% gel o.d. vaginally
for 5 days or clindamycin 2% cream o.d.
vaginally for 7 days
All pregnant women 5
weeks following
completion of
treatment (6 weeks
following azithromycin)
In all cases at all
affected sites. Three
weeks following
completion of
treatment
If symptoms
unresolved
If unresolved or
recurrent symptoms

74. Bartholin’s Cysts and Abscess
Bartholin's duct cysts and gland abscesses
Common problems in women of reproductive age.
Located bilaterally at posterior introitus.
Drain through ducts empty into the vestibule at the 4 o'clock and 8 o'clock positions.
Pea-sized glands palpable only if the duct becomes cystic or a gland abscess develops.
Differential diagnosis includes cystic and solid lesions of the vulva
• Epidermal inclusion cyst
• Skene's duct cyst
• Hidradenoma papilliferum
• Lipoma.
Management
1. Preserve the gland and its function if possible.
2. Office-based procedures include insertion of a Word catheter for a duct cyst or gland abscess.
3. Marsupialization of a cyst; marsupialization should not be used to treat a gland abscess.
4. Broad-spectrum antibiotic therapy is warranted only when cellulitis is present.
5. Excisional biopsy is reserved for use in ruling out adenocarcinoma in menopausal or perimenopausal
women with an irregular, nodular Bartholin's gland mass.

75. Other Gynaecology Pathology
Adnexal and Uterine Masses

76. Adnexal masses in pregnancy – 0.4% prevalence at ultrasound

77. Acute abdomen in pregnancy
Rectus sheath hematoma. (A) Axial T1-weighted GRE image
demonstrates a thickened left rectus muscle (arrow) containing
linear increased signal intensity. (B) Fat-saturated T2-weighted FSE
bright signal left rectus muscle (arrow) hematoma
Red degeneration of leiomyoma. Coronal T2-weighted SSFSE
image shows a large exophytic fibroid superior to the gravid
uterus with a central area of high intensity on the T2-weighted
image (arrow), representing hemorrhagic necrosis. The patient's
pain subsided with expectant therapy.
Adnexal torsion. Coronal T2-weighted SSFSE image reveals an enlarged
right ovary (arrow) containing multiple peripherally located follicles.
This pregnant patient at 18 weeks of gestation had acute-onset right
lower quadrant pain, and surgery confirmed the ovarian torsion.
Hemorrhagic cyst. (A) Axial T1-weighted FSE image shows a right
ovarian cystic lesion (arrow) with bright signal. (B) The signal of the
lesion (arrow) is not suppressed on the fat-saturated T2-weighted FSE
image, consistent with a hemorrhagic cyst.

78. Adnexal Mass Emergencies
Isolated tubal torsion. (A) Color Doppler image shows a swirling appearance
of the vascular pedicle (arrows) and a dilated right Fallopian tube
(arrowheads) with findings concerning for tubal torsion. (B) Corresponding
laparoscopic intraoperative image demonstrates the torsed Fallopian tube.
Detorsion of the Fallopian tube with fenestration of the dilated end
(fimbriaplasty) was performed as the tube and ovary appeared viable
Paraovarian cyst with torsion. Midsagittal US scan through the bladder (B)
shows an enlarged, heterogeneous ovary (arrowheads) and an adjacent cyst
(C). No flow could be elicited on color Doppler interrogation. On surgery it
proved to be adnexal torsion related to a paraovarian cyst leading to
ipsilateral salpingo-oophorectomy.

79. Adnexal masses in pregnancy ?
Guideline: The Society of American
Gastrointestinal and Endoscopic
Surgeons (2011):
• Laparoscopy is safe and effective
treatment in gravid patients with
symptomatic ovarian cystic masses.
• Observation for all asymptomatic cystic
lesions if US not concerning for
malignancy and tumor markers normal.
• Observe acceptable cystic lesions <6 cm
Evidence level IV
Risks
• Miscarriage
• Obstetric complications, including LBW,
preterm delivery, use of tocolytics for
preterm labor, low Apgar score, and fetal
anomaly.
• These risks deemed acceptable in case series.
References:
1. Azuar AS. Bouillet-Dejou L et al. Laparoscopy during pregnancy: experience of the French
university hospital of Clermont-Ferrand. Obstetrique & Fertilite. 2009;37(7-8):598-603
2. Bunyavejchevin S, Phupong V. Laparoscopic surgery for presumed benign ovarian tumor
during pregnancy. Cochrane Database of Systematic Reviews 2006, Issue 4. Art. No.:
CD005459. DOI: 10.1002/14651858.CD005459.
3. Ko ML. Lai TH. Chen SC. Laparoscopic management of complicated adnexal masses in the first
trimester of pregnancy. Fertility & Sterility. 2009;092(1):283-7, 2009
4. Koo YJ. Lee JE. Lim KT et al. A 10-year experience of laparoscopic surgery for adnexal masses
during pregnancy. Int J Gynaecol & Obstet. 2011;113(1):36-9.
5. Guidelines for diagnosis , treatment and use of laparoscopy for surgical problems during
pregnancy. Society of American Gastrointestinal and Endoscopic Surgeons (SAGES); 2011

80. Ovarian mass at Caesarean section ?
No studies comparing removal of incidentally found adnexal
masses at caesarean section with later removal . Series by
Hobeika et al 2008 -
• Reviewed histopathology of 43 adnexal masses
incidentally diagnosed and excised during CS –
• Mature cystic teratomas (34.9%)
• Mucinous cystadenomas (16.3%)
• Serous cysts/cystadenomas (14.0%)
• Endometriomas (11.6%)
• Luteomas (7%)
• Paraovarian cysts (4.7%)
• Corpus luteum cyst (2.3%)
• Fibroma (2.3%)
• Inclusion cyst (2.3%)
• Serous-mucinous cyst (2.3%)
• Borderline serous cystadenoma (2.3%).
Lesions rare and mostly benign, but found the case of
borderline tumor alarming.
References:
1. Ahram J. Lakoff K. Miller R. Serous cystadenocarcinoma as incidental finding
during a repeat cesarean section. AmJOG. 1985;153(1):78-9.
2. Ansell J. Bolton L. Spontaneous rupture of an ovarian teratoma discovered
during an emergency Caesarean section. JOG 2006;26(6):574-5.
3. El-Ghobashy A. Ohadike C. Wilkinson N. Lane G. Campbell JD. Recurrent
urachal mucinous adenocarcinoma presenting as bilateral ovarian tumors on
cesarean delivery. Int J of Gynecol Cancer 2009;19(9):1539-41.
4. Engin-Ustun Y. Ustun Y. Dogan K. Meydanh MM. Ovarian carcinoma as an
incidental finding during cesarean section in a preeclamptic woman: case
report. Eur J Gynaecol Oncol 2007;28(5):423-4.
5. Hobeika EM. Usta IM. Ghazeeri GS. Mehio G. Nassar AH. Histopathology of
adnexal masses incidentally diagnosed during cesarean delivery. EJOG and
Reprod Biol 2008;140(1):124-5.

81. Leiomyomata - Fibroids
Impact on fertility and pregnancy
• Torsion
• Red degeneration - pain
• Subfertility
• Miscarriage
• Malpresentation
• Pre-term delivery
• Pressure symptoms/abdominal
distension
• Urinary urge frequency symptoms
• Ureteric obstruction/renal
impairment

82. Recurrent miscarriage
Sub-mucosal fibroids
• Hysteroscopy and Trans-Cervical-
Resection-Fibroid (TCRF)
• Treatment recurrent miscarriage
• Pre-treatment with IVF
May impact on recurrent miscarriage
and suitable for resection

83. Fibroids and pregnancy
Other pregnancy related
complications
1. Miscarriage (2nd trimester)
2. Torsion
3. Mal-presentation
4. Pre-term delivery
5. Obstructed labour
6. Fibroid avulsion and delivery
7. Life-threatening haemorrhage

84. Special circumstances or dilemmas
in early pregnancy

85. The abnormal cervical smear in pregnancy ?
Cervical Screening in the UK and cancer prevention
Based on slide based cytology screening > 50 years
Vaccination for HPV now primary prevention combined with screening.
Age- England >25, Scotland & Wales >20 years (interval 3-5 years - 65yrs)
Population coverage - 81.2% in 2003 (dipped to 78.9% in 2008/09).
Cost - Cervical screening including the cost of treating cervical abnormalities
estimated at £175 million a year in England.
Method - Liquid-based cytology (LBC)
< inadequate smear s reduced by 80%
Faster processing- >costs per slide but overall LBC > cost effectiveness
Role of HPV testing in the NHS Cervical Screening Programme
Identify small % cases of high-grade CIN in the large number with borderline
cytology.
High -ve predictive value of testing HPV for this.
Impact of prophylactic vaccines on screening
HPV vaccines effective against HPV 6, 11, 16, 18 (Gardisil ) & 16, 18 (Cevarix)
>70% cervical cancers HPV 16,18
>90% ano-genital warts HPV 6,11
Impact vaccines > females not infected with the vaccine’s HPV types.
Primarily aimed at 12-13 years
 90% efficacy in prevention of type 16–18-related CIN2+ in such women
 90% efficacy in the prevention of anogenital warts.
Both vaccines exhibit cross-protection against type 31-related CIN2+ (Gardisil)
and against types 33 and 45 (Cervirax).
Vaccines are safe, well tolerated, no evidence of teratogenicity.
Pregnancy and cervical smear tests
• Wait 3/12 post delivery to routinely
screen cervical cytology
• Mild dyskaryosis changes, asymptomatic
and pregnant wait 3/12 post delivery
• Mild dyskaryosis changes, symptomatic,
colposcopy
• Moderate/Severe dyskaryosis –
colposcopy +/- biopsies or LLETZ
• CIS or early invasive? Wait or surgery ?
Management on a case by case basis
Reference - P Sasieni, J Adams and J Cuzick, Benefits of cervical
screening at different ages: evidence from the UK audit of
screening histories, British Journal of Cancer, July 2003

86. Cervical assessment in pregnancy
The key points for management of patients are:
• Repeat smear for most women with a low grade squamous abnormality
• No treatment necessary for women with biopsy proven CIN-1
• Colposcopic assessment for all women with atypical glandular abnormalities
• HPV DNA testing as test of cure following treatment of CIN-2/3 In Pregnancy - eversion endo-
cervix exposed to oestrogen

87. Female genital mutilation-pregnancy issues?
THE LAW -Female Genital Mutilation (FGM) Act 2003
It replaces the 1985 Act. Offence for the 1st time for UK
nationals/residents to carry out FGM abroad, aid, abet, counsel or
procure FGM abroad, even in countries where the practice is legal.
Acute complications FGM
1. Death
2. Severe pain
3. Localised infection, abscess & septicaemia
4. Tetanus
5. Haemorrhage
6. Acute retention of urine
7. Hepatitis and HIV
Late complications and consequences FGM
1. Dyspareunia or apareunia
2. Sexual dysfunction with anorgasmia
3. Chronic pain
4. Keloid scar formation
5. Dysmenorrhoea (including haematocolpos)
6. Incontinence, vodiidng difficulty fistula, urinary
sepsis
7. Vaginal lacerations during sex/rape
8. PTSD
9. Difficulty in gynaecological exam, cervical screening,
evacuation uterus e.g. abortion, vaginal delivery
RCOG Green-top Guideline
No. 53; May 2009
WHO Classification FGM
I. Partial/total removal clitoris and/or the prepuce (clitoridectomy)
II. Partial /total removal clitoris, labia minora, +/- excision labia majora
III. Narrowing vaginal orifice, creation covering seal cutting and
appositioning the labia minora and/or the labia majora +/- excision
clitoris (infibulation)
IV. All other harmful procedures to female genitalia for non-medical
purposes, e.g. pricking, piercing, incising, scraping and cauterising

88. FGM in Pregnancy- De-infundibulation?
• Specialist Midwife and Obstetrician nominated if high
numbers FGM cases
• Identify at booking visit & screen problems
• Assess likely impact on labour and delivery
• > Incidence urinary sepsis with some types (screen
bacteruria)
• Reversal FGM < 20 weeks gestation (LA)
• If > 20 weeks reverse in active labour

89. Any questions?