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Individualization of stimulation protocols in IVF -- Part II

Predicting ovarian response

It is now well established in the literature that ovarian response to stimulation will vary from patient-to-patient. Patients can be divided into three groups – poor, high and normal responders. The challenge clinically is to predict which group a patient will fall in so that an individualized treatment plan can be formulated.

Poor responders

After many years of debate, the European Society of Human Reproduction and Embryology (ESHRE) established a standardized definition of poor ovarian response. I have discussed this in detail in a previous blog.

To summarize, according to the criteria established by the ESHRE working group, at least two of the following three features must be present: 1) Advanced maternal age (≥ 40 years) or any other risk factor for poor ovarian response (e.g. previous ovarian surgery, short cycles); 2) a previous poor ovarian response (≤ 3 eggs with a conventional stimulation protocol); 3) an abnormal ovarian reserve test (i.e. antral follicle count (AFC) < 5 – 7 follicles or anti mullerian hormone < 0.5 – 1.1 ng/mL).

Among women < 34 years old, 10 – 20% will be poor responders. In women aged 43 – 44 y, the incidence increases to 50%.

At InVia Fertility Specialists, we will not refuse IVF based on ovarian markers alone. The chance of conception with IVF in patients with severely diminished ovarian reserve is low but not negligible. Young poor responders will do better than their older counterparts with similar ovarian reserve test results.

When poor response is predicted, we will preemptively take steps to maximize ovarian response. These include increasing the dose of medications, pre-treating with androgens (DHEA, Androgel), using a GnRH antagonist protocol etc.

High responders

These are patients who will produce > 15 – 20 eggs with a standard stimulation protocol. High response is expected in about 7% of patients and varies with the woman’s age; being around 15% in women aged < 30 y and declining with advancing age.

High responders are at risk for ovarian hyperstimulation syndrome (OHSS). This is a potentially life threatening condition and we should try our best to minimize it occurrence.

Clinical criteria for predicting high response include young age, long menstrual cycles, evidence of symptoms of polycystic ovarian syndrome (PCOS) and hyper response in a previous cycle.

High AMH levels are associated with high response. There isn’t a consensus cut off level. Also the AMH level varies based on the assay used. Using the new AMH Gen II assay, a level around 3.52 – 3.9 is an acceptable cut-off value for prediction of hyper response.

An elevated AFC is also associated with a high response. Patients with PCO-appearing ovaries (≥ 12 antral follicles per ovary) are at risk for a high response and OHSS. Once again, there isn’t a consensus cut-off AFC number for predicting high response.

When high response is predicted, we will reduce the dosage of medications used, reduce the daily dose (step-down) as required, and take several other precautions to minimize the risk of OHSS. Pregnancy rates in high responders generally are excellent.

Use of GnRH agonists, GnRH antagonists, choice of medications, starting dose of medications and some of the commonly used protocols at InVia will be discussed in my next blog.

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Infertility treatment IVF InVia Fertility Specialists Diminished ovarian reserve

Dr. Vishvanath Karande

Dr. Vishvanath Karande

Dr. Karande is Board Certified in the specialty of Obstetrics and Gynecology as well as the subspecialty of Reproductive Endocrinology and Infertility. He is a Fellow of the American College of Obstetricians and Gynecologists and Member of the American Society for Reproductive Medicine.

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