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Prevention of OHSS in patients with PCOS undergoing IVF

Patients with ovarian hyperstimulation syndrome (OHSS) typically present with ovarian distention, pelvic pressure and fluid build-up in the pelvic area commonly associated with ovarian stimulation or In Vitro Fertilization (IVF). Whereas most cases of OHSS are mild in nature, 1-2% of the time symptoms can be severe, limiting activity, requiring pain management and even hospitalization. Severe OHSS is more common in young patients undergoing IVF treatment and patients with polycystic ovary syndrome (PCOS). The best treatment of OHSS is prevention and identification of high risk patients. Once such patients are identified, individualized protocols and close follow up can prevent severe OHSS in most cases.

Patients with PCOS typically present with ovulation disorder (irregular menstrual cycles) and have high number of antral follicles that can be stimulated even with low dose FSH medications which can result in significant ovarian distention and OHSS. Individualized protocol design is the key to minimize side effects and severe OHSS. In most cases, a “step up” type of protocol can be used in which a low dose of FSH is started and adjusted based on response and estrogen levels.

A number of different approaches have been suggested to prevent severe OHSS such as using lupron trigger (instead of HCG trigger for IVF), taking birth control pills, low dose aspirin, GnRH antagonists (Ganirelix or Cetrotide) post egg retrieval, dopamine agonistic drugs (Bromocriptine or Cabergoline), IV albumin, IVF hydration and more recently metformin especially in patients with PCOS.

In our published study about the use of metformin in Fertility and Sterility in 2007, we reported a significant drop in the number of antral follicles following just one week of metformin use and a significant change in glucose to insulin ratios. We also reported higher Inhibin B and Anti-Mullerian Hormone (AMH) levels in patients with PCOS compared to controls. Please refer to the full article at Following our study, we proposed that the use of metformin can decrease the number of antral follicles and potentially result in better ovarian stimulation and lower incidence of OHSS.

A recent study published in Fertility and Sterility in December 2011 by Palomba and colleagues evaluated the use of metformin in PCOS patients undergoing IVF treatment. In this randomized controlled trial, patients either received metformin or placebo during their IVF cycle to test the development of OHSS. Patients who were treated with metformin during their IVF cycles had a lower incidence of OHSS which was significant.

The conclusion of these studies is promising in reducing the complications related to OHSS in patients undergoing IVF treatment. It may be reasonable to use metformin with the onset of IVF medications to minimize the risk of OHSS in PCOS patients. Other prevention and treatment modalities can also be used to minimize complications related to OHSS such as close surveillance during treatment, paracentesis, and electrolyte and fluid management.

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