Gynaecology landmark Flashcards
Effectiveness of Long-Acting Reversible Contraception (CHOICE project).
Author, journal, year.
Aim
New England Journal of Medicine, 2012.
Winner et al.
To assess the failure rate of common contraceptive methods vs LARCs in women at increased risk of unintended pregnancy
Effectiveness of Long-Acting Reversible Contraception (CHOICE project). Methodology
Large prospective cohort study.
Women (14-45y) selected their contraception (pill, patch, ring, depo, IUD, implant), given for free. Telephone f/u 3/12, 6/12, then every 6/12 after.
Effectiveness of Long-Acting Reversible Contraception (CHOICE project).
Results
7486 women. 156 pregnancies attributed to contraceptive failure.
At 1 yr, short acting failure rate 4.8%, LARC 0.3%, depo 0.1%
* (perfect use).
If <21y and used pill, patch, ring, risk of pregnancy double that of older group. LARC not a/w variable failure rate with age.
Effectiveness of Long-Acting Reversible Contraception (CHOICE project).
Conclusions
LARCs show lower failure rates than shorter acting alternatives, particularly among younger women
Effectiveness of Long-Acting Reversible Contraception (CHOICE project).
Strengths.
Large sample, prospective study, low loss to f/u, objective data gathering (e.g. pharmacy records)
Apart from depo / DMPA assessed typical use efficacy which is more clinically relevant
Effectiveness of Long-Acting Reversible Contraception (CHOICE project). Weaknesses
Not randomised (pt more likely to comply with pill if choose to take it). ? not generalisable to all populations - these women seeking contraception. No data on BMI.
No data on patient satisfaction.
Only counted perfect use for DMPA / depo, and typical use for other methods
Effect of screening on ovarian cancer mortality (PLCO).
Journal, author, year.
Aim
JAMA (Journal of the American Medical Association)
2011
Buys et al.
To evaluate the effect of screening on ovarian cancer mortality
Effect of screening on ovarian cancer mortality (PLCO).
Methodology
RCT. PLCO = prostate, lung, colorectal and ovarian cancer screening trial.
78,216 (excluded those with oophorectomy pre trial).
Randomised to yearly screening (6y with Ca125, 4y with TV USS) vs. usual care, followed up for max 13y.
Effect of screening on ovarian cancer mortality (PLCO).
Results
Mortality from ovarian cancer (primary outcome) not statistically significant between the two groups.
Ovarian Ca incidence not statistically significant b/w 2 groups. 77-78% of cancers high grade (3 or 4) in both groups (no observed stage shift with screening).
3285 false positive results, with 1080 women undergoing surgery - major complication rate of 15%.
Effect of screening on ovarian cancer mortality (PLCO).
Strengths
Randomised
Controlled
Good compliance with assigned groups.
Large sample - boundary for futility had been researched
Effect of screening on ovarian cancer mortality (PLCO).
Weaknesses
Unblinded (invasive tests - TV USS). Self-administered questionnaire - source of bias.
Were the Ca125 and TV USS cut offs appropriate? If changed then high risk of false positives
Effect of screening on ovarian cancer mortality (PLCO).
Conclusions
Simultaneous screening with CA-125 and TV USS compared with usual care did not reduce ovarian cancer mortality.
False positive screening test results associated with complications
Scottish pregnancy intervention (SPIN) study. A multicentre RCT of LMWH and low dose Aspirin in women with recurrent miscarriage.
Journal, year, author.
Aim
Blood, 2010.
Clark et al.
Does enoxaparin, aspirin, and intensive pregnancy surveillance reduce rates of pregnancy loss c.f. intensive pregnancy surveillance alone in women with >/=2 prev consecutive miscarriages.
Scottish pregnancy intervention (SPIN) study. A multicentre RCT of LMWH and Aspirin in women with recurrent miscarriage.
Methodology
Multi-centre RCT
UK and NZ.
Women <7/40 with 2+ prev consecutive misc <24/40 randomised to clexane, aspirin, intense surveillance vs. intense surveillance alone (2/52 USS to 12/40 then 4/52 USS to 28/40).
Scottish pregnancy intervention (SPIN) study. A multicentre RCT of LMWH and Aspirin in women with
recurrent miscarriage.
Results
22% pregnancy loss in pharmacological group, 20% in surveillance alone. No significant difference b/w the groups. No significant safety issues with clexane.
Thrombophilia prevalence similar in general population
Scottish pregnancy intervention (SPIN) study. A multicentre RCT of LMWH and Aspirin in women with
recurrent miscarriage.
Conclusion
LMWH and low dose aspirin for women with 2 or more
consecutive pregnancy losses has no measurable benefit in preventing further loss
compared with intensive fetal surveillance.
Scottish pregnancy intervention (SPIN) study. A multicentre RCT of LMWH and Aspirin in women with
recurrent miscarriage.
Strengths.
Well matched controls, RCT, multicentre.
Central collection and testing blood samples to ensure uniform detection of thrombophilia
Scottish pregnancy intervention (SPIN) study. A multicentre RCT of LMWH and Aspirin in women with
recurrent miscarriage.
Weaknesses
Is intensive surveillance practical and feasible?
Small sample size, unable to examine subgroups.
2 prev miscarriages, rather than 3
Does not test implantation theory as Rx started after pregnancy confirmed
The eVALuate study: Two parallel randomised trials, TLH vs. TAH, TLH vs. TVH.
Journal, year, author, aim
BMJ, 2004
Garry et al.
To compare the effects of lap hyst and abdo hyst in the abdominal trial and lap hyst and vag hyst in the vaginal trial
The eVALuate study: Two parallel randomised trials, TLH vs. TAH, TLH vs. TVH.
Methodology
Two parallel, multicentre, randomised trials. UK and SA. Benign hyst patients. Abdo trial (876): TAH 292 vs. TLH 584 Vag trial (504): TVH 168 vs. TLH 336 F/u at 6/52, 4/12 and 1y
The eVALuate study: Two parallel randomised trials, TLH vs. TAH, TLH vs. TVH.
Results
Abdo trial - TLH a/w higher rate of major complications (11.1% vs. 6.2%), TLH longer operating time, TLH less pain and shorter hospital stay, 6/52 better quality of life
Vag trial - underpowered, TLH took longer and higher rate of detecting unexpected pathology
The eVALuate study: Two parallel randomised trials, TLH vs. TAH, TLH vs. TVH.
Conclusions
Laparoscopic hysterectomy was associated with a significantly higher rate of major complications than abdominal hysterectomy, longer operating time.
TLH less pain, quicker recovery and better short term quality of life.
The eVALuate study: Two parallel randomised trials, TLH vs. TAH, TLH vs. TVH.
Strengths
Randomised
Intention to treat analysis
The eVALuate study: Two parallel randomised trials, TLH vs. TAH, TLH vs. TVH.
Weaknesses
Trial underpowered for vag group. Ended before recruitment target reached.
Conversion to laparotomy major complication.
Surgeons less experienced than are now?
Significant 1y loss to f/u
Aspirin plus heparin or aspirin alone in women with recurrent miscarriage (ALIFE trial)
Journal, year, author, aim
NEJM, 2010
Kaandorp et al
To determine if aspirin and heparin or aspirin alone improve pregnancy rate in woman with unexplained recurrent miscarriage
Aspirin plus heparin or aspirin alone in women with recurrent miscarriage (ALIFE trial)
Methodology
Multi-centre randomized control trial in the Netherlands
364 women, 18-42y, 2+ miscarriages
Aspirin + LMWH vs. aspirin alone vs. placebo
Primary outcome: rate of live birth
Intention to treat analysis
Aspirin plus heparin or aspirin alone in women with recurrent miscarriage (ALIFE trial)
Results
No difference in the live birth rates between three groups – 54.5%, 50.8%, 57%
Those receiving combination therapy delivered 1 week earlier than placebo
Aspirin plus heparin or aspirin alone in women with recurrent miscarriage (ALIFE trial)
Conclusions
No difference in live birth rates for recurrent miscarriage with use of aspirin, LMWH or both.
Aspirin plus heparin or aspirin alone in women with recurrent miscarriage (ALIFE trial)
Strengths
Randomised control trial
Intention to treat analysis
Blinded aspirin
Aspirin plus heparin or aspirin alone in women with recurrent miscarriage (ALIFE trial)
Weaknesses
Broad definition of recurrent miscarriage. 40% of woman had previous live birth ?diluted results of the study.
Small numbers in trial ? underpowered.
LMWH not blinded.
Trial discontinued with 22 still in follow up.
Sponsored by GSK who manufacture LMWH
Breast cancer and HRT in the Million Women Study.
Journal, year, author, aim
The Lancet, 2003, Million Women Study Collaborators.
To investigate the effects of specific types of HRT on incident and fatal breast cancer
Breast cancer and HRT in the Million Women Study.
Methodology
Prospective cohort study. 1,084,110 UK women age 50-64y (1/4). May 1996-March 2001. NHS breast cancer screening centres sent invitation for screening + questionnaire - ever users (current, past), never users, menopausal status.
Cancer registrations and deaths from NHS Central Registers
Breast cancer and HRT in the Million Women Study.
Results
Average age 55.9y. 9364 invasive breast Ca, 637 deaths. Risk of BC higher in ever users than never users. Among ever users, risk increased among current but not past users. Greater risk of BC with E+P HRT. RR in current users increased with increasing total duration of use.
Breast cancer and HRT in the Million Women Study.
Conclusions
Current use of HRT is associated with an increased risk of incident and fatal breast cancer. The effect is substantially greater for oestrogen-progestagen combinations than for other types of HRT.
Breast cancer and HRT in the Million Women Study.
Strengths
Large size of cohort. Prospective collection of exposure information. All study participants had routine mammography soon after completing baseline questionnaires (reporting bias virtually eliminated). Main analysis restricted to post-menopausal women to limit confounding
Breast cancer and HRT in the Million Women Study.
Weaknesses
Small numbers and short follow up for mortality data. Observational. Time order, information and detection bias (women on HRT more likely to participate), confounding. Biological plausibility - BMI known to be a RF, opposite in this study. Majority white 96%
LACE
Journal, year, author, aim
Effect of Total Laparoscopic Hysterectomy vs Total Abdominal Hysterectomy on Disease-Free Survival Among Women with Stage I endometrial cancer. A randomised clinical trial
LACE = Laparoscopic Approach to Cancer of the Endometrium
Janda et al
JAMA, 2017
To investigate whether TLH is equivalent to TAH in women with treatment-naïve endometrial cancer
LACE method
Multinational, randomised equivalence trial
760 women
Randomised to TLH or TAH
Intention to treat analysis
Stage 1 endometrioid adenocarcinoma on histology (any grade) + CT or MRI
Excluded uterine size >10/40
Pelvic LN dissection performed unless
- Morbidly obese
- Grade 1 or grade 2 + stage IA
- Patient medically unfit for LN dissection
LACE
results
Median follow up 4.5y
Disease free survival similar in both groups (~81%)
- favours TLH
No statistically significant difference in:
- Recurrence of endometrial cancer
- Overall survival
Intra-op adverse events similar
Post-op adverse events less frequent in TLH group
Costs lower in TLH group
TLH group - 6% converted to laparotomy
LACE
conclusion
Among women with stage 1 endometrial cancer, the use of TAH c.f. TLH resulted in equivalent disease-free survival at 4.5y and no difference in overall survival. These findings support the use of TLH for women with stage 1 endometrial cancer
LACE
Strengths
Randomised Prospective Large, multicentred Appropriately powered Australia / NZ Credentialing system to ensure surgeons proficient in both surgical techniques
LACE weaknesses
Unable to blind surgeons or patients
- Unlikely to affect disease-free or overall survival - collected by clinical trial staff
LN dissection left to discretion of surgeon
- ? Impact on survival
Surgeons all screened to ensure competent / proficient at both approaches
- Can’t generalise to all surgeons
Ovarian conservation at the time of hysterectomy for benign disease.
journal, year, author, aim
Parker et al
Obstetrics and Gynecology, 2005
Prophylactic oophorectomy is often recommended concurrent with hysterectomy for benign disease. The optimal age for this recommendation in women at average risk for ovarian cancer has not been determined
Ovarian conservation at the time of hysterectomy for benign disease.
method
Retrospective analysis of published data for absolute and relative risk with oophorectomy or conservation
40-80y
4 strategies compared:
• Ovarian conservation +/- estrogen use
• Oophrectomy +/- estrogen use
Ovarian conservation at the time of hysterectomy for benign disease.
results
Ovarian conservation without oestrogen therapy
- Reduced CHD
- Reduced hip fracture
- Reductions outweigh the increase in mortality from ovarian cancer
> 64y - no statistical difference
Ovarian conservation at the time of hysterectomy for benign disease.
conclusions
Ovarian conservation until at least age 65 benefits long-term survival for women at average risk of ovarian cancer undergoing hysterectomy for benign disease
Ovarian conservation at the time of hysterectomy for benign disease.
strengths
Large numbers
Ovarian conservation at the time of hysterectomy for benign disease.
weaknesses
Probability estimates derived from case control studies
- Selection bias - Reporting bias - Chance
Predominantly white Caucasian populations, therefore not necessarily generalisable to all populations
WHI E+P
journal, aim, author, year
Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principle results from the WHI randomised controlled trial
Women’s Health Initiative
JAMA, 2002
To assess the major health benefits and risks of the most commonly used combined hormone preparation in the US
WHI E+P
method
Randomised controlled primary prevention trial
16,600 women
Follow up:
- 6 week phone call
- 6 monthly phone call
- Annual clinic review + mammogram
- ECG at baseline, 3y, 6y
All primary analyses use time-to-event methods and are based on the intention-to-treat principle
Age 50-79 years at initial screening
Intact uterus
Post-menopausal
Combined estrogen and progesterone
Vs. placebo
WHI E+P
results
Mean age 63y
Over 1 year, 10 000 women taking E+P compared with placebo might experience: \+7 CHD events \+8 strokes \+8 PEs \+8 invasive breast cancers
- 6 colorectal cancers
- 5 hip fractures
WHI E+P
conclusion
The results indicate that this regime should not be initiated or continued for primary prevention of CHD
WHI E+P
weaknesses
Average age 63y - higher than those using HRT for symptoms
Only tested 1 drug regimen
High rates of discontinuation in the active treatment arm (42%)
High rate of crossover to active treatment in the placebo arm (10.7%)
Used women who had previous used HRT after “3 month washout period”
Unblinding rate high
WHI E+P
strengths
Large numbers
Randomised
WHI E
journal, aim, author, year
Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: The WHI randomised controlled trial.
The Women’s Health Initiative
JAMA, 2004
To investigate the effects of conjugated equine oestrogen on major disease events in healthy post menopausal women
WHI E
methods
Randomised, double-blind, placebo controlled disease prevention trial
10,700 women randomised
Follow up
- 6 week phone call
- 6 monthly phone and annual clinic visit
- ECGs at baseline 3, 6 and 9 years
- Annual mammograms and breast exams
Age 50-79 years at initial screening
Previous hysterectomy
Oral oestrogen vs. placebo
WHI E
results
Average follow up 6.8y
No difference between two groups for CHD
Incidence of stroke, VTE - in E group
Reduction in fractures in CEE group
Non significant lower rate of invasive breast cancer in E group
WHI E
strengths
Large, randomised
Double blinded
- Low rate of unblinding
WHI E
weaknesses
Higher than expected crossover from placebo to active hormone use
Trial terminated early
At time of study termination, 54% had already stopped taking study medication (similar between groups)
Average age 63 - higher than those using HRT for symptoms
Only one dose and formulation tested
WHI E
conclusion
CEE did not change the risk of CHD, but did increase the risk of stroke and VTE.
Non-statistically significant reduction in risk of breast cancer with CEE.
Provision of no-cost, long-acting contraception and teenage pregnancy
journal, aim, author, year
Secura et al
NEJM, 2014
To determine if promotion and access to no-cost LARCs would reduce unintended teenage pregnancy
Provision of no-cost, long-acting contraception and teenage pregnancy
method
Contraceptive CHOICE Project
Prospective cohort study
St Louis
1404 females 14-19y
Followed for 2 or 3y
Telephone interviews every 6 months
Compared with nationally published data of teenage pregnancy rates in 2010
Provision of no-cost, long-acting contraception and teenage pregnancy
results
72% chose IUD or implant
Teen pregnancy and abortion rates, were approx 4x lower than national average
Implant most common contraceptive choice for 14-17y
IUD most common for 18-19y
Provision of no-cost, long-acting contraception and teenage pregnancy
strengths
Good follow up rates
Findings in keeping with data that LARC is more effective contraception (well established)
Provision of no-cost, long-acting contraception and teenage pregnancy
weaknesses
Information on primary outcomes self reported
Regular survey of teens may have influenced adherence to their contraceptive method
National average in 2010 higher than in 2012 which was when data collection finished
- but still significant reduction
Provision of no-cost, long-acting contraception and teenage pregnancy
conclusions
Teenage girls and women who were provided contraception at no cost and educated about LARC had rates of pregnancy, birth and abortion that were much lower than the national rates for sexually experienced teens
A comparison of medical management with misoprostol and surgical management for early pregnancy failure.
journal, year, author, aim
Zhang et al
NEJM, 2005
To assess the efficacy, safety and acceptability of misoprostol for management of first trimester miscarriage
A comparison of medical management with misoprostol and surgical management for early pregnancy failure.
method
RCT in the US
625 women
3:1
Miso vs. ERPOC
First trimester pregnancy failure
- Missed or incomplete miscarriage
Day 1: 800mcg PV
Day 3: repeat if RPOC on USS
Day 8: offered ERPOC if RPOC
A comparison of medical management with misoprostol and surgical management for early pregnancy failure.
results
Average gestation at pregnancy failure – 7.6 weeks
Success rates at 30 days:
- 84% for medical management
- 97% for surgical management
Misoprostol had a lower rate of success for anembryonic pregnancies
No difference in rate of:
- infection
- bleeding requiring transfusion
similar to acceptability
A comparison of medical management with misoprostol and surgical management for early pregnancy failure.
strengths
RCT
Relatively low rates of loss to follow-up
Well defined primary outcome
A comparison of medical management with misoprostol and surgical management for early pregnancy failure.
weaknesses
Only tested one regime and had a resource intensive follow-up scheme for RPOC (i.e. a mandatory further USS)
May have been underpowered to detect adverse outcomes, particularly with surgical management
A comparison of medical management with misoprostol and surgical management for early pregnancy failure.
conclusion
Treatment of early pregnancy failure with 800mcg pv misoprostol is a safe and acceptable approach, with a success rate of ~84%
Management of miscarriage: expectant, medical, or surgical? Results of randomised controlled trial (miscarriage treatment (MIST) trial)
Aim
BMJ, 2006
Trinder et al
Determine whether a clinically important difference exists in the incidence of gynae infection between surgical management and expectant or medical management of miscarriage
MIST
Method
3 groups
Expectant management
- At home with no intervention
Medical management - pv misoprostol 800mcg - po mifepristone 200mg 24-48h prior
- Admitted to hospital for misoprostol
- Surgical evacuation offered if not successful within 8hr of miso
Surgical evacuation
- ERPOC under GA
MIST
results
No difference in confirmed infection within 14 days
Expectant vs. surgical
- Higher unplanned hospital admissions
- High rate of unplanned surgical curettage
Medical - 398 vs. surgical (403)
- Higher unplanned hospital admissions
- High rate of unplanned surgical curettage
Cessation of bleeding after randomisation was significantly earlier in the surgical group
Incomplete miscarriage
- Expectant management success rates of 75%
- Medical management does not seem to offer greater success
Expectant management
- Used significantly more analgesia
