Metformin reduces risk of OHSS in patients with PCO during gonadotropin-stimulated IVF cycles – a randomized controlled trial. (Article in-press at Fertility and Sterility Journal)
[box type=”info”]Take Home Message
- Metformin reduced the relative risk of OHSS to 28% (range = 11% – 67%) of that without metformin supplements
- The study had a very low incidence of severe OHSS even with placebo (1.7%)
- Low severe OHSS is likely because 18% of placebo cases were cancelled to prevent severe OHSS versus 5% in the metformin group
- Metformin increased the number of days of stimulation and total gonadotropins used but lowered the estrogen level (a measure of OHSS risk)
- The number of eggs, and the pregnancy rates were the same in both groups
Why is this study important?
OHSS is a potentially serious complication of COH (controlled ovarian hyperstimulation) but it most commonly presents after IVF stimulation because we try to stimulate more for IVF and for ovulation induction. Less than 10% of all IVF patients get OHSS and < 5% get severe OHSS. Yet, it is a very uncomfortable side effect with potentially very serious consequences (think, ICU admission).
Risk factors for OHSS are a high antral follicle count, diagnosis of PCO (because these women have high AFC), high estrogen level with ovarian stimulation (certainly estrogen > 5,000 – 6,000) or high number of eggs retrieved (certainly >30 eggs).
Severe OHSS primarily presents as a large accumulation of fluid in the abdominal cavity. OHSS always resolves by itself but it can take several weeks. Over 90% of severe OHSS patients are pregnant because the HCG hormone from the pregnancy stimulates the ovary, which is its purpose. We can usually treat the fluid accumulation in the office by removing the fluid (paracentesis) every 2-3 days until the OHSS resolves.
Treatment options to prevent OHSS include cancelling the cycle when it appears that the stimulation is going to fast or aggressively, freezing all the embryos without embryo transfer (to prevent the woman from becoming pregnant), or “coasting” the stimulation – withhold stimulation medication until the estrogen levels falls to a reasonable range, then retrieving the eggs.
We want to find ways to lower risk and make IVF more patient-friendly. OHSS may be the most serious complication associated with IVF aside from multiple births. Thus, we welcome any tricks that benefit everyone.
What makes this study worth talking about?
The study uses a technique called “randomized controlled trial, RCT” which is a very difficult study to accomplish because most infertility patients do not want to be randomized to treatments.
RCT means that patients were identified that had similar clinical profiles and then they were randomly assigned to receive the metformin. Randomization reduces the chance the people who were at greatest risk of OHSS got the study drug because that practice would make the drug look more effective. The researchers additionally blinded both the patients and the doctors so that neither of them knew whether the pills were metformin or placebo. Blinding everyone to which patients took the drug and which took placebo prevented the doctors from managing the patients differently.
[ilink url=”http://bit.ly/tYUBCx”]Abstract at Fertility and Sterility[/ilink]
Metformin reduces risk of OHSS in patients with PCO during gonadotropin-stimulated IVF cycles – a RCT
Stefano Palomba, M.D., Department of Gynecology and Obstetrics, University “Magna Graecia” of Catanzaro, Via Tommaso Campanella 182/I, 88100 Catanzaro, Italy.