Early pregnancy Flashcards
Ectopic incidence and locations
~1%
Most common site: ampulla (where fertilisation occurs)
- Tubal = 98%
Other locations - cervix, ovary, abdominal cavity
Risk factors of ectopic pregnancy
25-50% will have risk factors Previous PID Tubal surgery (prev sterilisation) Previous ectopic pregnancy Infertility ART IUCD Smoking Maternal age >40y
HCG for assessment of ectopic
HCG increase <66% in 48h is a/w either ectopic or failing IUP in >85% of cases
Discriminatory zone (ADHB)
- > 6000 IU/L - IUP will be seen on TA USS
- > 2000 IU/L - IUP will be seen on TV USS
- Unreliable for multiple pregnancy
Long-term fertility
Ectopic
In the absence of a history of subfertility or tubal pathology, no difference in the rate of fertility, the risk of future tubal ectopic pregnancy or tubal patency rates between the different management methods
If Hx of subfertility
- Expectant or medical management a/w improved reproductive outcomes compared with radical surgery
MTX has no effect on ovarian reserve
Tubal patency rates (examined by HSG) no different in:
- Ipsilateral tube if managed by MTX or expectant
- Contralateral tube if managed by surgery, MTX or expectant
Recurrence of ectopic
First ectopic with remaining tube normal: 6-12%
First ectopic with remaining tube abnormal: 28-50%
>1 ectopic: 26-40%
USS features of tubal ectopic
Three ultrasound features required to diagnose an ectopic pregnancy
- ‘Empty’ uterus
- Corpus luteum present
- Ectopic mass - usually an adnexal ring or ‘donut’
Visualise adnexal mass that moves separate to the ovary
- Apply doppler as vascular (colour flow more prominent around corpus luteum)
- Ectopic has a thick echogenic rim >6mm (c.f. <2mm with CL)
- Internal structures (yolk sac or fetal pole) are a more definitive sign of ectopic pregnancy
Pseudosac in up to 20%
- Lacks intradecidual and double decidual sign
Free fluid
- Echogenic fluid in 28-56%
USS features of cervical ectopic
- Empty uterus
- Barrel-shaped cervix
- Gestational sac present below the level of the internal cervical os
- Absence of the ‘sliding sign’ - distinguishes from miscarriage in progress
- Blood flow around the gestational sac using colour Doppler
Management of cervical ectopic
Methotrexate
- HCG >10,000, >9+0, CRL >10mm, FH activity a/w decreased chance of successful MTX
- <12+0, absence of FH activity and lower HCG a/w more successful conservative management
Surgical methods are a/w high failure rate
- Reserve for those suffering life-threatening bleeding
Adjunctive methods to control haemorrhage have been described - uterine artery ligation, UAE
Diagnosis of Caesarean scar ectopic
Incidence 1 in 2000
TVS supplemented by TA
1. Empty uterine cavity
2. Gestational sac or solid mass of trophoblast located anteriorly at the level of the internal os embedded at the site of the previous LSCS scar
3. Thin or absent layer of myometrium between the gestational sac and bladder
4. Evidence of prominent trophoblastic / placental circulation of Doppler
5. Empty endocervical canal
Management of CS scar ectopic
Insufficient evidence to recommend one over the other, but current literature supports surgical rather than medical approach as the most effective
Cochrane 2020 - Uncertain if differences in success rates, complications or adverse events between UAE and administration of systemic MTX before suction curettage
Blood loss lower if ERPOC after UAE than after MTX
Interstitial ectopic diagnosis
Ectopic implants in the interstitial part of the fallopian tube (which is 1-2cm in length)
Incidence 1-6.4% of ectopic pregnancies
USS:
- Empty uterine cavity
- sac located laterally in the interstitial (intramural) part of the tube
- bulging cornua with thin myometrial rim
- transverse fundal view, at top of uterus can appear outside of expected cavity
Criteria and outcomes for expectant management of ectopic
Minimal symptoms
No significant FF in the POD
HCG <1500 IU/L
Ectopic pregnancy <30mm on USS with no cardiac activity
Patient able to consent, and understand the need for and be able to f/u
Reported success rates from 57-100% - dependent on initial HCG and rate of decline
- intervention required in up to 30%
Monitoring for expectant management of ectopic pregnancy
Repeat HCG on days 0, 2, 4, and 7
- If HCG drops by >15% from the previous value then repeat weekly until a negative result
- If HCG drops by <15%, stays the same or rises, review
Methotrexate dose and mode of action
50mg/m2 of patient body-surface area IM as a single dose
Typically 75-90mg
Cytotoxic
Folic acid antagonist
Inhibits DNA and RNA synthesis required for normal cell division
Targets cells in the body with a high metabolic rate
Monitoring for MTX for ectopic
Day 0, give MTX, bloods for HCG, FBC, AST, Cr, G&H, Rhesus status
HCG on days 4 and 7. Day 7 repeat AST and FBC
- If decreases by >15% between days 4 and 7, then monitor weekly until HCG <5 iu/l
- If decreases by <15%, consider second dose 1 week after the first (50mg/m2)
Pain can be due to tubal abortion, not rupture. Doesn’t necessarily require OT. Monitor in hospital for 24h if stable
Agrees to avoid pregnancy for 3/12
Criteria for MTX ectopic
Haemodynamically and clinically stable No significant FF in POD Gestational sac <35mm in adnexa (NICE) Normal FBC, LFTs, Cr HCG <5000, but ideally <1500 No FH seen on USS Desire for future fertility (but still an option if don't) Patient able to understand and attend f/u, consented
Contraindications to MTX
Hepatic dysfunction - AST >2x normal Abnormal renal function (elevated Cr) Bone marrow dysfunction, immunodeficiency Active peptic ulcer disease Presence of fetal cardiac activity Any active liver or renal disease
Side effects to MTX
Side effects: GI upset - excessive flatulence, bloating, abdominal pain, gastritis, nausea Conjunctivitis Stomatitis Mouth ulceration Transient mild elevation in LFTs (rare) Rash Photosensitivity
Rare:
- Marrow suppression - leucopenia, thrombocytopenia (rare)
- Pulmonary fibrosis
- Alopecia
Outcomes of MTX
Success rates of single dose: 65-95%
3-27% of women require a second dose
Criteria for salpingotomy over salpingectomy for ectopic
If healthy contralateral tube no significant difference in fertility prospects
Current ectopic pregnancy higher after salpingotomy (15% vs. 10%)
Risk of persistent trophoblast with salpingotomy - 8%
Salpingotomy if contralateral tube abnormal or Hx of subfertility
- Higher rates of subsequent IUP if Hx of fertility-reducing factors (75% vs. 40%)
- If single tube and salpingotomy performed - IUP rate 55%, repeat ectopic 20%
Define Gestational trophoblastic disease (GTD)
Group of disorders including hydatidiform mole, invasive mole, gestational choriocarcinoma, PSTT
Incidence of GTD is 1:200-1000 pregnancies
Incidence of GTD after a live birth 1 / 50,000
More common at extremes of maternal ages
Asian women
Define hydatidiform mole
Originate in villous trophoblast and are characterised by abnormal chorionic villi with trophoblast hyperplasia as a consequence of overexpression of paternal genes
Separated into complete and partial moles based on genetic and histopathological features
Complete mole
Definition
Appearance
Histology
USS features
Derived from paternal duplication (46XX, 75%) or dispermic fertilisation (46XX or 46XY, 25%) of an ‘empty’ ovum (lacking maternal genes)
Mitochondrial DNA is still maternal in origin
characteristic ‘bunch of grapes’ appearance only seen in the second trimester
Histology
- no fetal tissue
- extensive hydropic change to the villi
- excess trophoblast proliferation
- Diploid
- p57 absent
USS features:
- Polypoid mass between 5-7/40
- Thickened cystic appearance of villous tissue and no identifiable sac after 8/40
Partial mole
Definition
Appearance
Histology
USS features
Triploid (90%)
- 2 sets of paternal and 1 maternal haploid set
- Most often occur following dispermic fertilisation
Occasional may also be tetraploid or mosaic
looks like normal POC so Dx can be missed
Histology
- Contains embryonic or fetal material such a fetus or fetal red blood cells
- focal hydropic change to the villi
- Some excess trophoblast proliferation
- p57 immunohistochemistry stain is present
p57 - paternally imprinted, maternally expressed gene. Only present in partial moles as have both maternal and paternal genetic material
USS
- Enlarged placenta
- Cystic changes within the decidual reaction in a/w empty sac or delayed miscarriage
Management of suspected molar pregnancy
Suction evacuation / curettage
- Preferred initial management
- May use US guidance to minimise chance of perforation
- Medical methods a/w higher rates of chemotherapy
- Preparation of the cervix immediately prior to evac is safe
- Oxytocin infusion can be used after if brisk bleeding occurs
- Senior / experienced surgeon present
- Anti D if Rh negative
Hysterectomy not recommend for treatment of molar pregnancy alone
Tumour HCG follow up for molar pregnancy
Partial - Weekly until 3 consecutive normal levels, then stop
Complete - weekly until 3 consecutive normal levels, then monthly for 6 months
Review at 8-10 weeks (provided HCG falling appropriately) to check that menstruation has returned and that adequate contraception is being followed
If tHCG still positive at this point, d/w gynae oncologist
Risk of GTN after end of appropriate follow-up:
- 0% for partial moles
- 0.3% for complete moles
Diagnosis of GTN
- Plateau of hCG lasts for 4 measurements over a period of 3 weeks or longer
- Rise of HCG on 3 consecutive measurements, over a period of 2 weeks or longer
- Histologic diagnosis of choriocarcinoma
Contraception and future pregnancies after GTD
Strongly advised to avoid pregnancy during follow-up as it may mask tumour persistence / recurrence
Oral contraceptives can be taken
IUCDs should be avoided
- Until menstrual pattern and tHCG are normal to reduce perforation risk
Barrier methods preferred during chemotherapy
Don’t conceive until follow up is complete
In all subsequent pregnancies should have an early and mid trimester scan looking for molar tissue
After all future pregnancies (including TOP, miscarriage), should have tHCG at 6-8 weeks
- RCOG - no longer have to do, risk of GTD in subsequent pregnancy is very low (1:4011) in women who have not received chemotherapy for a prior molar pregnancy
Chances of conception does not different from general population
Risk of further molar pregnancy in future pregnancies is 1:70
LBR in subsequent pregnancies ~70%
Staging of GTN
Bloods
- Baseline tHCG
- FBC, U&E, TFTs, coags
- HBsAg
- LFTs - to assess for metastases
- Consider cross-match if heavy bleeding
Radiology:
- CXR
- Pelvic USS (TVS preferred)
If pulmonary metastases or abnormal exam:
- CT abdo and pelvis
- MRI brain
Risk assessment and chemo in GTN
FIGO 2000 criteria
Low risk <6
- Cure rate almost 100%
- IM methotrexate, 2 weekly OP regimen
- Continue until normal HCG + further 3 cycles
- 1 in 4 become resistant to Rx –> EMA-CO or Actinomycin
- consider second erpoc in low risk patients, (FIGO risk score 0-4) - 40% may avoid chemo
High risk >7
- Cure rate is 94%
- MDM guided Rx, likely multi-agent
Consider hysterectomy for GTN in women who have completed their family and GTN confined to the uterus, to reduce the need for chemotherapy
Follow up after chemotherapy for GTN
Re-check sites of original disease (imaging)
tHCG follow up
- Low risk –> monthly for 12 months
- High risk –> month for 2 years
If abnormal, exclude pregnancy, then urgent referral to Med Onc
Contraception advised for >1y after last dose of chemotherapy
- Prevent pregnancy obscuring relapse
- Reduce the incidence of abnormal pregnancies
Risk of relapse - 3.5%
- Median time to relapse is 4/12
Pregnancy after chemotherapy for GTN
Fertility unlikely to be affected
- Further pregnancies in ~80%
Wait >1y after last chemotherapy dose
1 in 70 chance of conceiving further molar pregnancy
If conceive within 12 months of chemotherapy:
- No indication for recommendation of TOP
- Increased risks - spontaneous abortion, stillbirth, repeat mole
- RANZCOG - if receive multi-agent chemotherapy may be at increased risk of early pregnancy complications if conception occurs within 12 months of completion of Rx
Gestational choriocarcinoma
~1 in 50,000 pregnancies
Most commonly follows a complete molar pregnancy (25-50%)
- Within 12 months of a non-molar abortion (25%)
- After a term pregnancy (25-50%)
Difficult pathological Dx as frequent haemorrhage and necrosis
This is a tumour that crosses the placenta, therefore newborn born to a mother newly diagnosed with choriocarcinoma needs to be investigated to exclude disease (urinary HCG)
Placental site trophoblastic tumour
Epithelioid trophoblastic tumour
0.2% of all GTD
Produce less HCG
Confined to the uterus for longer
More chemoresistant than other forms of GTN
Most important prognostic factor: interval to presentation from last known and presumed causative pregnancy
Primary treatment: hysterectomy
Normal HCG rise
Double in 48h
Lower limit of normal 66%
Miscarriage incidence
Occurs in ~20% of pregnancies
- ~30% post-implantation and biochemical pregnancy loss rates
<5% of miscarriages occur after identification of fetal heart activity
Risk factors for miscarriage
Maternal age
- 40-44 = 50%
Paternal age
Number of previous miscarriages
- After 3 consecutive pregnancy losses, risk of further miscarriage is ~40%
Any severe infection that leads to bacteraemia or viraemia can cause sporadic miscarriage
Factors associated with reduced risk of miscarriage:
- Previous live birth
- Nausea
- Vitamin supplementation
- Feeling well enough to fly or have sex
- Eating fresh fruits and vegetables daily
Factors with no evidence of association with miscarriage:
- Caffeine consumption
- Smoking
- Moderate or occasional alcohol consumption
- Education level
- SES
- Working during pregnancy
Expectant management for miscarriage
7-14 days
If resolution of bleeding and pain indicate successful expectant management, take urine HCG 3 weeks later
Infection rate is low at ~3%
From available RCTs, no increased risk of infection or pain
Fewer GI side effects
Patient satisfaction no different
Chances of unplanned intervention, need for blood transfusion, and prolonged bleeding are higher in the expectant group compared to active intervention group
Overall success rates after 14 days - 70-80%
Medical management for miscarriage
Efficacy ranges from 80 to >90%
- Varies with gestational age (higher if <9/40), presence of pv bleeding (onset prior to Rx), duration of f/u
- Mife + miso vs. miso alone - 88% vs. 71%
RPOC requiring surgical evacuation (8-9%) Blood transfusion (2%) Pelvic infection (<1%)
If IUCD in situ, should be removed before administration of mifepristone
Surgical management of miscarriage
Efficacy highest (up to 100%) No substantiated evidence in the literature of any impact on future fertility
Uterine perforation (up to 5 in 1000) Intra-abdominal trauma (0.1%) Blood transfusion (1-2 in 1000) Need for repeat surgical evacuation (up to 5%) Localised pelvic infection (3%)
Cochrane review outcomes for miscarriage
Of cervical prep for 1st trimester ERPOC
- Decreases length of procedure
- No good evidence reduces cervical trauma or perforation - as these are rare events
For 2nd trimester use osmotic dilators rather than miso
Prophylactic antibiotics reduce upper genital tract infection
- No consensus on best regime
Define recurrent pregnancy loss
loss of three or more consecutive pregnancies
Affects 1% of couples
Can be primary or secondary
Causes / risk factors of RPL
AMA (13% in those >40)
Antiphospholipid syndrome
- Antibodies present in up to 20% of women with recurrent miscarriage (c.f. 2%)
Chromosomal abnormalities of the embryo
- ~50% of miscarriages
Parents who are carriers of a balanced translocation - most commonly Robertsonian translocation
- Found in 3-5% of recurrent miscarriage couples
Anatomical factors - uterine malformation, cervical weakness
Overt hypothyroidism
Diabetes
PCOS
Male factors
- Comparing sperm from couples with RPL to those without - lower percentage of normal sperm morphology, concentration and progressive motility
Inhibited thrombophilias
Investigations for RPL
Pelvic USS
Antiphospholipid antibodies
Booking bloods
Thyroid and diabetes screen
Consider thrombophilia screen
Cytogenic analysis should be performed on POC of the third and subsequent consecutive miscarriages
Parental peripheral blood karyotyping of both partners should be performed if POC testing reports an unbalanced structural chromosomal abnormality
83% chance of successful pregnancy if balanced karyotype
Long term risks for patients who have recurrent miscarriage
Increasing evidence that patients with RPL may be a high-risk population for adverse obstetric outcomes
- Retrospective cohort found increased PET, PTB, SGA, abruption and stillbirth <37/40
Women who suffer recurrent miscarriages are an increased risk of future CVD
- Independent of BMI, HTN, WCC
Unexplained RPL management
Excellent prognosis for pregnancy outcome (~75%) without pharmacological intervention if offered supportive care alone in the setting of a dedicated early pregnancy assessment unit
- No evidence for aspirin +/- heparin in these women
Smoking could have a negative impact on chances of LBR, therefore cessation is recommended
Recommend aiming for normal / healthy BMI
Excessive alcohol is a possible risk factor, therefore advise to limit consumption
General advice to consider prophylactic vitamin D supplementation
- Based on significant prevalence of vit D deficiency in women with RPL and possibly a/w complications
Evidence for effectiveness is absent, but considered safe
No evidence for IVF or HCG supplementation
Progesterone in recurrent pregnancy loss
Cochrane 2021
- Progestogens probably make little or no difference to live birth rate for women with threatened or recurrent miscarriage
- However, vaginal micronized progesterone may increase the live birth rate for women with a history of one or more previous miscarriages and early pregnancy bleeding, with likely no difference in adverse events
RANZCOG
- general pop - no change to miscarriage
- threatened misc - may reduce rate, therefore consider
- RPL - doesn’t improve outcomes
- give following IVF
- theoretical possibility of cleft lip
APS and RPL management
low-dose aspirin starting before conception and prophylactic dose LMWH starting at date of positive pregnancy test
Reduces miscarriage rate by 54% compared to aspirin alone
Neither steroids or IVIG improve LBR
LBR only 10% without intervention
Genetic factors and RPL - management
Finding of abnormal parental karyotype --> prompt referral to clinical geneticist, offers the couple a prognosis for the risk of future pregnancies with an unbalanced chromosome complement and the opportunity for familial chromosome studies Higher chance (50-70%) of healthy live birth in future untreated pregnancies following natural conception than is currently achieved after pre-implantation genetic diagnosis / IVF (~30%)
Inherited thrombophilias and RPL
Heparin therapy may improve the LBR of women with second trimester miscarriage a/w inherited thrombophilias
Cochrane - prophylactic clexane a/w no clear difference
Anatomical factors and RPL
Insufficient evidence to assess the effect of uterine septum resection in women with recurrent miscarriage and uterine septum to prevent further miscarriage
Retrospective evidence - improved LBR / reduced miscarriage
TOP incidence
1 in 4 pregnancies will end in abortion
1 in 4 women will have an abortion
In Australia, 4% of abortions performed 14-20/40, only 1% >20/40
GA and options for TOP
Early medical abortion <9/40
Minor surgical procedure under LA - 9-15/40
Surgical abortion under GA - 5-20/40
Early IOL >14/40
IOL >20/40
Long term risks of TOP
Abortion has been blamed for psychological damage, but there is little evidence for this
Factors that may predict negative psychological outcomes:
- Certain personality traits including impulsivity, attachment, low self esteem and dependency
- Late gestation abortion
- Prior psychiatric illness
- Conflict with religious or cultural beliefs
PTB due to cervical damage with recurrent abortions (mixed findings)
RANZCOG recommendations for TOP care
Access should be on the basis of health care need and should not be limited by age, SE disadvantage or geographic isolation
- Non-availability of abortion services has been shown to increase maternal morbidity and mortality
Women should have access to professional counselling
Health practitioners should be aware of the legislation regarding abortion where they practice
Prevention of unintended pregnancy should be a priority
General requirements prior to TOP
All women should be given accurate info and counselling should be available
Clinical assessment including medical Hx and exam
Exclude contraindications
Accurate gestational assessment
USS to confirm gestation and exclude ectopic
Consider screening for STI and/or antibiotic prophylaxis
Blood group and Rh(d) status +/- anti-D
POC treated in accordance with local and legislative protocols
Plan for future contraception
Written consent should be obtained prior to the commencement of treatment
TOP >14/40
Risks of MTOP and STOP
Surgical evacuation Most common risks - Bleeding requiring transfusion <1% - Low grade fever 1-2% Serious risks - Uterine perforation <1% - Injury to bowel or large vessels <1% - Uterine rupture with use of misoprostol <1%
IOL Common risks - Retained placenta requiring OT 10% - Low grade fever 30% - Prolonged procedure 6-20% Rare - Bleeding requiring transfusion 1% - Uterine rupture with use of misoprostol <1%
Contraindications to early medication abortion
Allergy to the drugs involved IUD in situ after failure to remove it Chronic adrenal failure - Mife may have general anti-glucocorticoid actions Severe asthma Chronic renal disease Porphyrias Addison's disease
Medical IOL >14/40
Hospital admission is mandatory Mifepristone - 200mg 24-36h prior to admission - Reduces inpatient time to delivery by up to 50% - 1% chance of outpatient delivery
Misoprostol 400-800mcg PV
then 400mcg q3h until delivery
Complications
- Retained placenta in 10% needing OT
- Transfusion in 1-2%
- Fetus live at birth in 1.5%
- Ruptured uterus - 1% with previous CS
Dilatation and evacuation
for STOP
After 14/40, osmotic dilators superior to medical methods, but misoprostol is acceptable up to 18/40
2 stage procedure
Evacuate fetus with forceps under USS guidance
Empty uterus with suction / curette
Cervical priming mandatory
Failure rates not reported - extremely rare
Major complications 6-15/1000 depending of gestation
Feticide
Ultrasound guided intracardiac injection
KCl + lidnocaine
TOP >22/40
Feticide in multiples
- 7-10% miscarriage risk
DCDA twins - Intracardiac KCl for discordance in fetal anomalies
MC twins
- Complicated due to fetal vascular connections
- Requires cord interruption
Misoprostol
- mode of action
Prostaglandin analogue
Has a direct effect on the uterus and cervix, causing uterine contractions and cervical dilatation, resulting in bleeding
Onset of action = 30 mins
Sublingual - most rapid effect
Mifepristone
- mode of action
Synthetic anti-progesterone
Blocks the effects of progesterone
Sensitises the myometrium to prostaglandin induced contractions –> decidual breakdown and cervical ripening
