DHEA Supplementation Confers No Additional Benefit to that of Growth Hormone on Pregnancy and Live Birth Rates in IVF Patients Categorized as Poor Prognosis

Abstract

BackgroundIn vitro fertilization (IVF) patients receive various adjuvant therapies to enhance success rates, but the true benefit is actively debated. Growth hormone (GH) and dehydroepiandrosterone (DHEA) supplementation were assessed in women undergoing fresh IVF transfer cycles and categorized as poor prognosis from five criteria.MethodsData were retrospectively analyzed from 626 women undergoing 626 IVF cycles, where they received no adjuvant, GH alone, or GH–DHEA in combination. A small group received DHEA alone. The utilization of adjuvants was decided between the attending clinician and the patient depending on various factors including cost.ResultsDespite patients being significantly older with lower ovarian reserve, live birth rates were significantly greater with GH alone (18.6%) and with GH-DHEA (13.0%) in comparison to those with no adjuvant (p < 0.003). No significant difference was observed between the GH groups (p = 0.181). Overall, patient age, quality of the transferred embryo, and GH treatment were the only significant independent predictors of live birth chance. Following adjustment for patient age, antral follicle count, and quality of transferred embryo, GH alone and GH–DHEA led to a 7.1-fold and 5.6-fold increase in live birth chance, respectively (p < 0.000).ConclusionThese data indicated that GH adjuvant may support more live births, particularly in younger women, and importantly, the positive effects of GH treatment were still observed even if DHEA was also used in combination. However, supplementation with DHEA did not indicate any potentiating benefit or modify the effects of GH treatment. Due to the retrospective design, and the risk of a selection bias, caution is advised in the interpretation of the data.

Live birth outcomes of vitrified embryos generated under growth hormone stimulation are improved for women categorized as poor-prognosis

“…This may mean that alternative, weaker studies, such as retrospective cohort studies, may be required to advance the field provided they are stringently designed, conducted and analysed. Two recent retrospective studies by our group showed that CP and LB rates were significantly greater with GH (3.42-fold and 6.16-fold higher, respectively) following the transfer of fresh autologous embryos in stimulated cycles [12,13]. Age at embryo transfer (ET) and morphological quality of the transferred embryo were the only other significant independent predictors of the likelihood of CP and LB, but no significant differences were observed in the proportion of high-quality embryos generated in the GH arm, echoing the most recent prospective study [8].…”

“…In our practice, poor-prognosis women can receive GH or other IVF adjuvant (dehydroepiandrosterone [DHEA]) treatment in stimulation cycles if they have one of the following characteristics: age ≥ 40 years, generating ≤ 3 metaphase II oocytes despite high folliclestimulating hormone (FSH) stimulation doses ( ≥ 300 IU), > 50% poorquality embryos, repetitive implantation failure (RIF) in ≥ 3 ETs without achieving pregnancy, and a low ovarian reserve (antral follicle count [AFC] ≤ 8 or anti-Müllerian hormone [AMH] level ≤ 8 pmol/L), designated as AFC groups D and E in our published recombinant FSH dosing algorithms [19,20]. These criteria have been published previously for fresh ET cycles, with group B/C corresponding to 9-19 folli-cles inclusive and group A equating to 20 or more follicles [12,13]. In the current FET study, patients receiving or having a medical history of receiving IVF adjuvants (GH or DHEA) were considered to have a poor prognosis for the above reasons.…”

“…Age at embryo transfer (ET) and morphological quality of the transferred embryo were the only other significant independent predictors of the likelihood of CP and LB, but no significant differences were observed in the proportion of high-quality embryos generated in the GH arm, echoing the most recent prospective study [8]. While these examinations [12,13] were undertaken as retrospective, observational analyses and have significant limitations, they represent one of the largest current GH data-sets published. However, these reports focused on only fresh ET cycles and not subsequent frozen cycles, which are also lacking in the LIGHT study.…”

Effects of Dehydroepiandrosterone (DHEA) Supplementation to Improve Ovarian Response and IVF Outcomes on Women with Poor Ovarian Response

“…Thus, different protocols have been suggested to improve outcomes in those patients, such as: the use of nitric oxide, formed in vivo from L-arginine, which may play a role in follicular maturation and ovulation. Growth hormone is also employed to regulate the effect of FSH, increasing the synthesis of insulin-like growth factor and consequently ovarian function, quality, and embryo implantation [15][16][17].…”

“…These hormones bind to a specific receptor on the cell membrane of the effector organ, activating an intracellular enzyme, the adenylyl cyclase, responsible for converting adenosine triphosphate (ATP) into cyclic adenosine monophosphate (cAMP). The cAMP, in turn, binds to a cytoplasmic protein (guanine nucleotide binding proteins-G protein), and this newly formed complex is responsible for the activation of the enzymes involved in steroidogenesis [17,18].…”