Do poor-responder patients benefit from increasing the daily gonadotropin dose during controlled ovarian hyperstimulation for IVF?

Abstract

We aim to assess the in vitro fertilization-embryo transfer (IVF-ET) outcome in patients receiving an extremely high 450 daily dose (IU) of gonadotropins during controlled ovarian hyperstimulation (COH) for IVF. Moreover, in those who failed to conceive while using 450 daily dose (IU) of gonadotropins, we aim to evaluate whether increasing the daily dose gonadotropins to 600 IU will improve IVF outcome. All consecutive women, admitted to our IVF unit and underwent COH consisting of daily gonadotropin dose of 450 IU were included. Ovarian stimulation characteristics, number of oocytes retrieved, number of embryo transferred and pregnancy rate were assessed. Nine-hundred one consecutive IVF cycles were evaluated. While there was no between-group difference in the duration of COH, patients who conceived were significantly younger, yielded higher number of oocytes retrieved and embryos transferred and had significantly lower cancellations. In a sub-analysis, including only those patients who failed to conceive while using 450 daily dose (IU) of gonadotropins, and who underwent a subsequent IVF cycle attempt with the used of 600 IU daily dose of gonadotropins, no improvements in COH characteristics or cancellation rates were observed with increasing the daily gonadotropin dose to 600 IU. To conclude, in poor responders undergoing COH with an extremely high daily gonadotropin dose (450 IU), the most important factors that predict IVF success are female age and the number of oocytes retrieved. Moreover, patients who failed to conceive on a daily gonadotropin dose of 450 IU will not benefit from increasing the dose to 600 IU and should therefore consider the options of egg donation or adoption.

Assessing ovarian response: antral follicle count versus anti-Müllerian hormone

“…No convincing data that increasing the dose of FSH above a standard level leads to increased egg yields have been published (Haas et al, 2015;Karande and Gleicher, 1999;Land et al, 1996;van Hooff et al, 1993). It is likely the best result that can be achieved in this group of women is avoidance of a submaximal response.…”

Shifting Paradigms in Diminished Ovarian Reserve and Advanced Reproductive Age in Assisted Reproduction: Customization Instead of Conformity

“…In one observational study, women who did not get pregnant with 450 units daily dose of FSH did not show any improvement in outcome when the daily dose of FSH was increased to 600 units. 22 In general, the high dose of gonadotropins required for such protocols is costly and some patients report side effects such as mood swings, bloating, and discomfort with the frequent injections that are required. Because multiple cycles of treatment may be needed to achieve their desired outcome, consideration for a more patient-friendly treatment would be ideal.…”

“…However, this dose increase has not been always been found to be associated with better outcomes. 22 Notably, the quality of the oocytes is just as, if not more important, than the total number of oocytes. Baart et al demonstrated in a randomized controlled trial that women who received milder ovarian stimulation had less oocytes retrieved, but a lower proportion of chromosomally abnormal embryos indicating that exogenous FSH may adversely affect embryo quality.…”

Strategies for Controlled Ovarian Stimulation in the Setting of Ovarian Aging

“…Some retrospective studies compared a poorly responded COS cycle with a subsequent cycle using a higher daily FSH dosage. [49][50][51] The FSH dosage in the index and the subsequent COS cycles were 225 versus 450, 300 versus 450, and 450 versus 600 IU/day, respectively. [49][50][51] Despite being biased by the regression to mean phenomenon introduced by the comparison of a subsequent cycle with an already poorly responded cycle, none of these trials were able to document a benefit of higher daily FSH dosages in any parameter of interest.…”