Applying growth hormone as an adjuvant to correct poor prognosis outcomes in IVF: Study 1 compares melatonin

Abstract

This retrospective study examines the influence of recombinant growth hormone (rGH) and melatonin adjuvants on oocyte numbers, embryo utilization and live births arising from 3637 autologous IVF±ICSI treatment cycles undertaken on 2376 women across ten years (2011-2020) within a pioneer Australian facility. Despite using an FSH-dosing algorithm enabling maximal doses up to 450 IU for women with reduced ovarian reserve, younger women had significantly higher mean numbers of oocytes recovered than older women ranging from 11.1 for women <35 years to 9.4 for women aged 35-39 years reducing to 6.5 for women aged 40-44 years and 4.0 for those aged ≥45 years (p<0.0001). Overall, the embryo utilization rate was 48.5% and live birth productivity rate was 35.4 % across all ages and neither rGH nor melatonin showed any benefit on these rates, in fact, those women with nil adjuvants showed the highest live birth rate per initiated cycle (42.0% overall: p<0.0001, and 55.3% for the youngest group: p<0.001). Embryo utilization was increased marginally by rGH in those women aged 40-44 years who had high ovarian reserve (p<0.05), but this benefit did not translate into any improvement in the live birth rate. Similarly, other factors known to cause a poor prognosis, including low IGF-1 profile, recurrent implantation failure, and low oocyte numbers at OPU, showed no improvement in embryo utilization nor in live births from the adjuvants. The relevance of embryo quality was examined on 1135 women whose residual embryos after a single fresh-embryo transfer failed to develop to a suitable grade for cryopreservation. From 1727 cycles such women often displayed an improved embryo utilization rate with rGH, but not with melatonin. Even so, live birth rates were not improved by either of the adjuvants.

A 10-Year Perspective on the Utility of Three Adjuvants Often Used in IVF: Growth Hormone, Melatonin and DHEA

“…Given the recently defined confounding variables underlying the poor-prognosis outcomes in current day [8,9,14,15], several adjuvants have been introduced into clinical practice with the view of improving ART outcomes for the poor prognosis group. At PIVET we have been exploring three of these, namely, growth hormone since 2010 [16][17][18][19][20], dehydroepiandrosterone (DHEA) since 2014 [21][22][23] and melatonin following an encouraging report in 2014 [24,25]. Growth hormone was introduced soon after the favourable report in 2005 on the use of recombinant manufactured growth hormone (rGH) as an adjuvant for older women undergoing assisted reproduction with ICSI [26], with our PIVET team reporting on its use since 2010 [16].…”

“…With respect to the extreme lowest end (category E in the PIVET Algorithm with AFC < 5 antral follicles and AMH < 5 pmol/L), this aspect is difficult to separate out from the consideration of advanced age, as the algorithm defines a requirement for maximal FSH dosing; hence, oocyte numbers per OPU tend to be optimised, albeit at numbers under 10 ± 2. Two large studies examining three adjuvants have recently been reported from PIVET, the first analysing the influence of rGH ± melatonin [25] and the second from the same period reporting on rGH ± DHEA [23].…”