Gynaecology landmark trials

Question 1

Medical Management cf with Surgical for early pregnancy failure. Zhang NEMJ 2005

Answer 1

RCT
652 women
Randomised to miso day 1 and 3 (800mg vaginally) or ERPOC
If not complete by day 8 miso group got EPROC, and if any women got another EPROC within 30 days this constituted treatment failure
84% success in miso group
97% success in surgical group
No differences in endometritis or haemorrhage
78-83% would recommend the treatment again for the miso group

Question 2

Effect of screening on ovarian cancer mortality RCT PLCO Buys Jama 2011

Answer 2

RCT multi-centre
78216 women 55-74
One group standard care
Other group 4 years of annual TVUSS and 6 years of Ca125, FU 13 years
Outcome - OC, mortality, surgical intervention
Results: No difference in diagnosis or mortality but more surgical intervention on benign disease
Limitations: not a high risk group

Question 3

SPIN Aspirin and Heparin for recurrent miscarriage Smith 2010 Blood

Answer 3

Multi-centre RCT
Participants =/>2 miscarriages <24 weeks and <7 in this pregnancy
Started aspirin 75mg and LMWH 40mg daily vs surveillance. FBC at one week 28 and 36 weeks
Outcome: pregnancy loss at anytime
Result: overall loss 20%, no difference
Limitations: not powered for subgroup of 3+ miscarriages, included women who had a stillbirth after 16 weeks (5 in the intervention group and none in the control group)

Question 4

Aspirin plus heparin or aspirin alone in women with recurrent miscarriage (ALIFE) study Kaandorp NEJM 2010

Answer 4

RCT
364 women, history of unexplained miscarriage attempting to conceive or <6 weeks pregnant
Randomised to 80mg aspirin and LMWH, aspirin alone or placebo
Outcomes: no difference in live birth rates, increased bruising and injection site reactions for LMWH group.
Limitations: 2 or more and some women didn’t ever become pregnant

Question 5

TLH vs TAH on disease free survival for Stage 1 EC LACE Trial Jama 2017

Answer 5

Multi-centre RCT
760 women with stage I endometroid adenocarcinoma (excluded if uterus >10/40)
TLH+BSO and TAH+BSO
Disease free survival at 4.5kg
No difference in disease free survival, improved QoL for TLH
Limitations: No long term FU

Question 6

Million Women study The Lancet 2003
Breast cancer and HRT in the million women study

Answer 6

Multi-centre prospective cohort study
1 million UK women between 50-64 provided information about their HRT, details and cancer incidence
No intervention but about half used HRT
Outcomes: incidence and death from breast cancer
Results: Current users of HRT were more likely than never uses to develop BC and die from it. Past uses not at increased risk. All forms but E+P the most. Increased risk with increasing duration.
10 years = 5/1000 more than oestrogen and 19/1000 E+P
Limitations: Confounding, biases, recent studies suggest risk is neutral if natural progesterone is used

Question 7

WHI E+P Jama 2002

Answer 7

RCT double blinded
50-80yo PM women with uterus (excluded breast Ca etc)
Intervention was CEE + MPA (oral E+P)
Outcomes
CHD 29% increase
Invasive BC: 26% increase
Stroke: 42% increase
VTE: 2x risk
Colorectal cancer: 37% reduction
Endo cancer: no difference
Fracture: 34% reduction
All cause mortality: no difference
Stopped early due to increased risks of breast, stroke, PE, CHD (CHD mostly related to stroke and VTE risk)
Later reinterpretation: Risks not increased if HRT started <10 years of menopause
Limitations: Stopped early, high drop out, average age 62yo

Question 8

WHI E only arm Jama 2004

Answer 8

Double blinded RCT
50-80yo without uterus
Given oral E v placebo
Outcomes
CHD No difference
CRC no difference
Breast ca reduced 23%
Increased stroke 39%
VTE 33%
Fracture -30-40%
But in the lower subgroup 50-59 some of these were improved eg CHD
Average age 63

Question 9

Provision of No-cost Larc and Teen Pregnancy Secura, NEJM 2014

Answer 9

Prospective cohort trial
Teen required and offered free counselling, education and contraception of their choice (pretty much anything)
Then FU’d up at 6month intervals and reviewed if pregnancy/abortion/live birth/still taking the contraception, if the contraception failed
Outcomes: LBR/abortion/pregnancy rate all higher on average US teens and significantly higher in sexually experienced US teens.
Implant the least likely to fail
Interpretation: removing access and cost barriers to teens reduced teen pregnancy rate
Limitations: self reported, required parental consent

Question 10

Ovarian conservation at time of hysterectomy for benign disease Parker O&G 2005

Answer 10

Markov decision analytic model observation study
Set a standard of ‘rules’ from literature.
Imagined groups of people in 5 year age brackets and ‘followed then up’ over time for specific outcomes if had H+BS or H+BSO (E vs nonE)
Outcomes
Mortality - reduced rate of surviving to 80
BC -
Ovarian cancer - reduced but low overall
Osteoporosis - more hip fractures
CHD - increased under 64
Limitations: Used poor data in - got poor data out
Newer study (Update 2022) says age 53 - RANZCOG says 50 in their update