A New Approach for Treating Poor Responder IVF Patients: DuoStim

Despite remarkable advances in IVF treatment protocols, the success rates with poor responder patients remain low (a live birth rate of around 7%).  Poor responders are defined as those that satisfy at least two of the following features:

1. Advanced maternal age (> 40 years); 
2. A previous experience of poor ovarian response (< 3 oocytes (eggs) with a conventional stimulation protocol);
3. Abnormal ovarian reserve tests (i.e., antral follicle count, < 7 or antimullerian hormone, <1.1 ng/mL) (the Bologna criteria).

Vaiarelli et al. (Fertility and Sterility; 2019) recently reported their success rates in poor responder patients with a unique stimulation protocol – DuoStim.

What is DuoStim?

Poor responder patients underwent stimulation with a routinely used protocol (follicular phase stimulation (FPS).  They started oral estrogen tablets (estradiol valerate 4 mg orally daily) on day-21 of a previous menstrual cycle. With a period, they started stimulation with fertility drugs (Gonal-F or Puregon 300 IU/d + Luveris 150 units/d) for 9 – 11 days.  Halfway through the stimulation (when lead follicles measured 13-14 mm in diameter) they added a gonadotropin releasing hormone antagonist (Cetrotide or Ganirelix) to prevent premature ovulation.  Final maturation of oocytes was induced with  a single subcutaneous bolus of buserelin (0.5 mL).  Egg retrieval was then performed 35 hours later in a routine manner.

Five days after the egg retrieval, they stimulated the patients again with the same protocol (luteal phase stimulation (LPS)).  Thus, patients underwent two stimulations and two retrievals in the same menstrual cycle – DuoStim!

All eggs underwent fertilization and subsequent culture for 5 or 6 days (till blastocyst stage) and then underwent a trophectoderm biopsy (testing for chromosomes) and were then frozen.  There were no fresh transfers!

DuoStim Trial Results

The DuoStim protocol was presented to 297 patients from January 2015 to December 2017.  One hundred  (34%) agreed to participate whereas 197 preferred to undergo a conventional second stimulation (66%).  Among the 100 patients choosing to undergo DuoStim, 91 completed both stimulations (5 did not respond to FPS and 4 did not respond to LPS).  There were no complications from the repeated oocyte retrieval in a single menstrual cycle.

More oocytes were obtained after LPS with similar developmental and chromosomal competence as paired FPS-derived ones. The live birth rate increased from 7% after FPS to 15% after DuoStim. Conversely, the live birth rate among the 197 patients that chose a conventional controlled ovarian stimulation strategy was 8%, as only 17 patients who were not pregnant returned for a second stimulation after the first attempt (drop-out rate, 81%).

Conclusions

The authors concluded that the live birth rate for poor responder patients practically doubled with the DuoStim strategy.  This was mainly due to the low drop out rate.  Of the patients that chose to do a second conventional stimulation cycle (instead of DuoStim), only 19% actually returned for a second cycle.  They do not claim that the DuoStim approach is better than doing two conventional stimulation cycles.

At InVia Fertility Specialists, we have been taking care of poor responder patients for many years.  We are currently offering the DuoStim approach to select patients who want to maximize the number of available embryos in a minimum time duration.  Our Board Certified reproductive endocrinologists are available for consultation at our four Chicagoland locations.  Please call 847 884 8884 to schedule an appointment today!