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High dose stimulation for the poor ovarian responder: is more better?

high dose stimulation for poor ovarian responderThe patient in the in vitro fertilization / IVF process who is a “poor ovarian responder” remains a challenge in clinical practice. The European Society for Human Reproduction and Embryology (ESHRE) working group on Poor Ovarian Response published a consensus definition of “poor ovarian response” after a meeting in Bologna, Italy around 2011. 9 – 24% of patients undergoing the IVF process are poor ovarian responders.

Various stimulation protocols have been devised to improve IVF outcomes in poor ovarian responders. A common strategy is to use an aggressive stimulation protocol that involves the use of high doses of stimulation medications (gonadotropins). These medications are expensive and cost approximately $ 75/- for a vial (75 units) in the U.S. According to a recent survey conducted in 196 centers from 45 countries, 23.7% of patients defined as poor ovarian responders received daily doses from 450 IU to 600 IU of gonadotropins.

An important question therefore is “How much medication should be used to get an optimal response in these patients?” “Does 600 units a day result in better outcomes than 450 units a day?" This very question was addressed by Lefebvre et al. from the University of Montreal, Montreal, Quebec, Canada (Fertil Steril 2015 in press).

About the Study

In a prospective randomized study, they compared the outcome of the IVF process using 450 IU and 600 IU gonadotropin per day in women at risk of poor ovarian response.

Study candidates included 356 women aged less than 41years with basal FSH greater than10 IU/L, anti-mullerian hormone less than 1 ng/mL, antral follicle count less than 8, or a previous IVF cycle with greater than 300 IU/d gonadotropin that resulted in a cancellation, less than 8 follicles, or <5 eggs.

Protocol

Patients underwent an aggressive stimulation protocol (microdose GnRH agonist flare-up protocol) with a fixed daily dose of either 450 IU FSH (n = 176) or 600 IU FSH (n = 180) equally divided between Menopur and Bravelle.

Results and Conclusions

The two groups were similar in terms of age, ovarian reserve, cause of infertility, duration of stimulation, and cycle cancellation rate. There were no significant differences in the number of mature eggs (Metaphase II) retrieved (4 [range 0–6] vs. 4 [range 2–7]), fertilization rate (62.4% vs. 57.0%), biochemical pregnancy rate (20.5% vs. 22.9%), clinical pregnancy rate (16.4% vs. 18.3%), and implantation rate (29.8% vs. 30.4%) between the 450 IU and 600 IU groups, respectively.

The researchers concluded that gonadotropin of 600 IU/d does not improve outcome of IVF cycles compared with 450 IU/d in women at risk of poor ovarian response.

Applying the Research

This is a well-designed study done over a four-year period (October 2009 to September 2013). The study population was indeed composed of “true” poor ovarian responders. This is based on the fact that even with this aggressive stimulation protocol and both groups produced only a handful of mature eggs, most had only one embryo available for a day-3 transfer.

At InVia Fertility Specialists, we will often use 600 IU dose for stimulating poor ovarian responders. On the face of it, this study would appear to suggest we should change our protocol and not use more than 450 units daily. However, the Body Mass Index (BMI) in the 450 unit group was 25.5 kg/m2 (range 22.4 – 28.9) and in the 600 unit group it was 24.2 (range 21.3 – 27.5). In simple words, none of these patients were obese!

Our patient population is a bit different and we accept patients with a BMI up to 35 kg/m2. The proper course of action in most cases would be to alter the dose of gonadotropins to 450 units in patients with a BMI less than 29 kg/m2 and continue to use the higher dose in obese patients.

To see a fertility specialist who has been successfully diagnosing and treating poor ovarian responders for many years, make an appointment at one of InVia's four Chicago area fertility clinics.

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IVF InVia Fertility Specialists

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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