Results: PCOS – Definition, Diagnosis and Treatment

Results of 179,300 IVF treatment cycles (262 centers from 68 countries)

The statistics was done based on the number of cycles each unit performed and not on the number of units.
The total number of units responded to survey was 309 of them the computer analysis rejected 47 who were incomplete.

The survey was compiled by Prof. Adam Balen, Leeds Centre for Reproductive Medicine, Seacroft Hospital, Leeds, U.K

This graph describes the number of cycles performed by each unit participating in the survey. The majority of the units performed up to 600 cycles per year (172 Units). There were only two units in this survey performing more than 4000 cycles per year.

Section 1: Definition and diagnosis of "PCOS" patients

Do you think that reaching a clear definition of the ovarian state is important for the treatment?
Yes - 93.5% (167,700 cycles)
No - 6.5% (11,600 cycles)

Do you define a patients with PCOS based on the Rotterdam ESHRE/ASRM Consensus Criteria? (Two of three criteria: Chronic anovulation; Clinical and/or biochemical evidence of hyperandrogenism, and Polycystic ovaries).
Yes – 94.4% (169,200 cycles)
No – 5.6% (10,100 cycles)

Do you measure LH/FSH ratio and androgens to define patients with PCOS?
Yes -  60.4% (108,300 cycles)
No -  39.6% (71,000 cycles)

In your opinion is androgen excess is a prerequisite for the definition of PCOS?
Yes -  31.8%(57,000 cycles)
No -  68.2% (122,300 cycles)

Do you routinely measure anti-Mullerian hormone (AMH)?
Yes -  24.4%(43,700 cycles)
No -  75.6% (135,600 cycles)

Should ultrasound appearance of PCO in the presence of anovulation, with normal prolactin be enough for the definition?
Yes -  66.5% (119,300 cycles)
No -  33.5% (60,000 cycles)

Should a definition of PCOS is important for the treatment?
Yes -  86.9% (155,900 cycles)
No - 13.1% (23,400 cycles)

Do you assess for Impaired Glucose Tolerance (IGT)?
Yes -  73.3% (131,400 cycles)
No -  26.7% (47,900 cycles)

If you assess for IGT is this in: (results presented are from the 73.3% who measured IGT
All patients 38.7%(50,800 cycles)
Obese patients only 61.3% (80,600 cycles)

In the workup for diagnosis would you look for non-classical congenital adrenal hyperplasia?
Yes -  64.0% (114,800 cycles)
No -  36.0% (64,500 cycles)

Do you recommend treatment with Metformin (Glucophage) before starting the IVF treatment (for at least one month)?
Yes - 48.7% (87,400 cycles)
No - 51.3% (91,900 cycles)

Interesting to find is that even in such an extreme case, as presented here, the cancellation rate would be 19.3%. Although there is a meta-analysis advocating the use of albumin to prevent the development of OHSS, only 8.5% would use this treatment. Costing would become the major OHSS preventive method. Use of GnRH agonist to trigger final stage of ovulation was not mentioned here and several physicians would recommend the use of it.

In Summary:

It is interesting to find that for the majority of physicians, pre-treatment definition of the ovarian status is important. For PCOS the "Roterdam ESHRE/ASRM" criteria serve as the definition. This also includes measurement of LH/FSH ratio and androgens, although there is no clear cut which androgen should be measured. Anti Mullerian Hormone (AMH) also can serve for the definition.

In addition to the above, ultrasound in the presence of anovulation and normal prolactin was also described as satisfactory for the definition of patients with PCOS.

Clomiphene Citrate and Metformin still serve as the first line of treatment. For the use of gonadotropin the "Low Dose Step-up" protocols is the dominant one.

To prevent an ill-time LH surge during the IVF stimulation protocol, the preferable drug is GnRH antagonist. The preferable gondotropin for stimulation is the rec-FSH and the usual dose is around half of the regular dose in a none PCOS patient. The majority will not treat a patient with BMI above 35.

Comments received and printed (unedited version):

• • PCOS is still having some hidden aspects which still need to be revealed to have better understanding of this syndrome. I do not think that 2 Gynecologist have the same definition, understanding and treatment for their PCOS patients.
  • Each patient with PCOS is unique and requires a unique treatment as opposed to a standardized treatment
  • We use antagonist protocol and in severe cases we give decapeptyl before aspiration to avoid OHSS. Usually all the embryos are frozen and FET done later. Sometimes fresh ET with HCG support is performed.
  • I give dopamine agonist 0.5mg daily from day of HCG, do the pick-up and freeze all embryos.
  • Many times in this disorder we are treating the symptoms or trying to reach an  outcome (pregnancy) ; thus, I don't always have to have the exact diagnosis.
  • I believe family history is the best assessment of insulin resistance. Not all Multi follicular ovaries are PCOS - some patients just have too many oocytes.
  • For O.I. there was no first option of lifestyle changes. I would advocate significant exercise and reduction of abdominal weight in all but very lean PCOS as first line before CC.
  • I consider very important diagnostic of insulin resistance in PCOS, and think that the stimulation ovarian in PCOS need very careful.
  • For IVF, the polycystic appearing ovary and AMH are predictors of OHSS.
  • Glucophage ER is not as effective as metformin which must be combined with diet and exercise.
  • I normalize androgens prior to IVF & adjust starting dose from AMH.
  • During the last six month period we have been converting to IVM in PCOS at around D5 or D6 when the lead follicle is about 12 mm. This is found to give equally good results in terms of live birth rate
  • HgbA1C is our preferred screen for glucose intolerance (in keeping with recent recommendation by the ADA and others)

On behalf of the IVF-Worldwide team, Prof. Adam Balen and the Advisory Board, we would like to take this opportunity to thank all the centers that participated in the survey by adding to the global knowledge, as this could be of use around the world.