Results: Metformin use in IVF patients

The survey was compiled by Dr. Matan Yemini, Director of the Diamond Institute, New Jersey USA.
Over the past 12 years, it has become increasingly recognized that insulin resistance is central to the pathogenesis of the polycystic ovarian syndrome (PCOS). The use of insulin-sensitizing agents, such as Metformin, a biguanide insulin-lowering agent in ovulation induction for IVF, has been widely studied.
The current survey examines variations in attitudes and therapeutic approaches related to Metformin use as part of the IVF treatment protocol. As can be seen, variations exist, and to a large extent reflect lack of solid and evidenced-based data in this field.

Report from 101 centers worldwide performing 50,800 IVF cycles annually, of which 5,260 include Metformin, thus representing 10.4%

The report presented below is based on IVF cycles and not on centers.

It is interesting to note that 75% reported that the data available in the literature is insufficient to reach a decision concerning efficacy of the treatment.

The indications for treatment are not unanimous, as can see below.
Obesity with anovulation was the most common indication reported for treatment.
Only 25% reported that the indication for treatment with Metformin is also glucose intolerance and insulin resistance.

It is noteworthy that the majority who responded to the survey believe that Metformin may improve results in poor-responder patients.

Habitual abortion also serves as an indication for Metformin use.

Those who measure insulin consider high insulin as an indication for Metformin.

Glucose is measured by 66% of the reporting centers before starting Metformin.

Glucose insulin ration is measured by 38%, and the normal values according to the reporting centers vary from 4 to 7. Usually is it accepted that less than 4.5 is suggestive of insulin resistance.

The majority reported that they start Metformin between 1 and 3 months prior to initiating treatment.

Most of the reporting centers use a dose between 1500 and 2000 mg/day.

Perhaps the slow release is not as popular?

The majority do not follow up treatment with any specific blood test.

The majority continue treatment into the pregnancy period. It is interesting that 48% received treatment until the 12th gestational week and 12% continued treatment until delivery.

The majority reported that based on their experience; there is no correlation between the two.

Most of the reported centers believe that treatment with Metformin increases pregnancy rate.

And reduces rate of abortion.

No limit of treatment duration is definitely reported

Comments received and printed (unedited version):

• This worldwide report definitely shows the lack of information in the filed and the need for further investigation of the field.
• I have seen convincing data that frozen embryo transfers of embryos created during a Metformin treated cycle produced a higher pregnancy rate when transferred compared to controls even though the woman was not treated with Metformin in the frozen transfer.
• Have had successful pregnancies in PCO patients with prior failed IVF
• I find metformin most useful in any patient with PCOS.
• There are two main utilities for Metformin: 1) Increasing the proportion of mature oocytes at retrieval and 2) decreasing the risk of OHSS by reducing the number of small follicles at trigger.
• Recommendations on the duration of treatment after pregnancy are lacking.
• The effect of Metformin is not clear on pregnancy rate but for controlling the weight is good specially in PCOD, so , it is possible the effect is indirect through reducing the weight.
• We (in The Netherlands) do not use Metformin unless it has been prescribed by an endocrinologist, for other reasons than the IVF treatment
• Some patients show remarkable improvement in their menstrual cycles with Metformin treatment; it also is effective in preventing mid-trimester abortions in PCOS patients.