A short course of metformin does not reduce OHSS in a GnRH antagonist cycle for women with PCOS undergoing IVF: a randomised placebo-controlled trial.
Does 'metformin' reduce the incidence of ovarian hyperstimulation syndrome (OHSS) for women with polycystic ovary syndrome (PCOS) undergoing a GnRH antagonist assisted conception treatment cycle?



A short course of metformin does not reduce the incidence of OHSS for women with PCOS undergoing a GnRH antagonist treatment cycle.



Metformin does reduce the incidence of OHSS in a GnRH-agonist treatment cycle.



A randomised placebo-controlled trial (RCT) using metformin or placebo. Randomisation was blinded to both patient and investigator, using a random permuted blocks method with a 50:50 allocation ratio. The study was completed over 5 years (2009-2014) with 153 randomised patients. A sample size calculation based on the incidence of OHSS was completed prospectively suggesting a minimum of 146 recruits was required for the trial with a power of 80% and a type 1 error of 0.05.



All patients met the Rotterdam criteria for PCOS and were treated with a standard GnRH antagonist IVF/ICSI treatment cycle in a tertiary infertility clinic. The study medication was started prior to stimulation and continued to oocyte retrieval. Of the 153 patients, 77 received metformin and 76 placebo.



There was no reduction in the incidence of moderate-severe OHSS (Placebo (PLA) 12.2%, metformin (MET) = 16%, 95% CI -0.08-0.16, P = 0.66). There was no difference in total gonadotrophin dose (PLA = 1200, MET = 1200, 95% CI -118.67-118.67, P = 0.75), oocytes retrieved (PLA = 15, MET = 14, 95% CI -2.37-4.37, P = 0.66) or fertilisation rate (PLA = 60.7%, MET = 53.3%, 95% CI -0.96-14.94, P = 0.07). However, using metformin resulted in a reduced clinical pregnancy rate (CPR) per cycle started (PLA = 48.7%, MET = 28.6%, 95% CI 0.04-0.35, P = 0.02) and live birth rate (PLA = 51.6%, MET = 27.6%, 95% CI 0.05-0.40, P = 0.02). Furthermore, when ethnicity was taken into account there was a significant reduction in pregnancy outcome for the South Asian population irrespective of metformin or placebo use (CPR per cycle started, White Caucasian = 44.4%, South Asian = 19.4%; 95% CI 0.06-0.39, P = 0.01).



This study was only undertaken on an infertility population with PCOS with a limited duration of study medication use.



This is the first adequately powered RCT to assess the impact of metformin on OHSS in a high-risk group (women with PCOS) undergoing a GnRH antagonist cycle. It does not support the empirical prescribing of metformin as an adjunct to a GnRH antagonist treatment cycle.



None.



EudraCT number 2009-010952-81.



21 September 2009.



30 October 2009.
Leeds Centre of Reproductive Medicine, Seacroft Hospital, Leeds LS14 6UH, UK susien1981@gmail.com.
S L
SL
Jacob
Leeds Centre of Reproductive Medicine, Seacroft Hospital, Leeds LS14 6UH, UK.
C
C
Brewer
Regional Fertility Centre, Royal Maternity Hospital, Belfast BT12 6BA, UK.
T
T
Tang
Leeds Centre of Reproductive Medicine, Seacroft Hospital, Leeds LS14 6UH, UK.
H M
HM
Picton
Blood Sciences, Leeds General Infirmary, Leeds LS1 3EX, UK.
J H
JH
Barth
Leeds Centre of Reproductive Medicine, Seacroft Hospital, Leeds LS14 6UH, UK.
A H
AH
Balen
D000328:Adult; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000009:adverse effects / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D006727:Hormone Antagonists / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D007247:Infertility, Female / Q000628:therapy*; D008687:Metformin / Q000627:therapeutic use*; D016471:Ovarian Hyperstimulation Syndrome / Q000139:chemically induced / Q000517:prevention & control*; D010062:Ovulation Induction / Q000379:methods*; D011085:Polycystic Ovary Syndrome / Q000628:therapy*; D011247:Pregnancy; D018873:Pregnancy Rate; D016896:Treatment Outcome
D006727:Hormone Antagonists; D007987:Gonadotropin-Releasing Hormone; D008687:Metformin; C061018:ganirelix; C062876:cetrorelix
GnRH antagonist; IVF; OHSS; PCOS; metformin