The Evolving Concept of Poor-Prognosis for Women Undertaking IVF and the Notion of Growth Hormone as an Adjuvant; A Single-Center Viewpoint

Abstract

IVF is currently regarded as a successful new technology with the number of IVF children currently well over 8 million worldwide. This has been achieved by an explosive plethora of facilities. However, from its earliest history, IVF has been beset by poor-prognosis on a treatment cycle basis, an aspect which has been a constant feature for the majority of treatments to this stage. The 2019 Australian and New Zealand Assisted Reproduction Database (ANZARD) report shows that IVF clinics have live birth productivity rates (from combined initiated fresh and frozen cycles) ranging from 9.3 to 33.2%. Over the past 40 years there have been a number of innovations which have steadily moved the success rates forward, but progress is held back by an intransigent group of women who can be classified as being poor-prognosis from one or more adverse factors, namely advanced age (>40 years), poor ovarian response (POR) to ovarian stimulation, inability to generate high quality blastocyst-stage embryos, recurrent implantation failure, or recurrent early pregnancy losses. A number of strategies are variously applied including the use of recombinant growth hormone (GH) adjuvant therapy. Our retrospective studies at PIVET over the past decade show a 6.2-fold chance of live birth for fresh cycle embryo transfers following GH injections of 1–1.5 IU daily given for 3–6 weeks in the lead-up to the trigger for ovum pick-up. We have also recently reported the live birth rates from frozen embryo transfers utilizing those blastocyst embryos generated under GH influence and showed the live birth rate was 2.7-fold higher in a carefully matched poor-prognosis group. This experience has been compared to the total 42 GH studies reported since the year 2000, the majority matching those of PIVET with significant increases in both oocyte and embryo utilization rates but only ~50% are followed by elevated live birth rates. We argue that this discrepancy relates to failure in addressing other causes of poor-prognosis along with the wastage of transferring more than a single embryo in the fresh cycle, when ANZARD data indicates a significantly higher chance of live birth from frozen embryo transfers.

Using growth hormone as an adjuvant in IVF: Live birth outcomes from various poor prognosis scenarios

“…At PIVET a number of studies have been reported since 2010 which embrace the concept of poor prognosis in IVF and the potential role of rGH in its management [7]. The studies have been retrospective, undertaken on women who have had 3 or more IVF treatment failures.…”

“…Of the 42 studies published on rGH adjuvant treatment in IVF between 2000 to 2018, almost all of the studies showed improved oocyte and embryo utilization rates, but only half demonstrated any improvement in pregnancy or live birth rates [7]. The most recent reports continue to show better oocyte and embryo quality from rGH [24] and oocytes generated under the influence of rGH have better developmental competence [25,26].…”

“…These 5 studies set the background to determine whether rGH adjuvant could improve the clinical prognosis from ART where poor prognosis factors could be identified [7]. In this study, ART embraces treatments by in-vitro fertilization (IVF) and intra-cytoplasmic sperm injection (ICSI) along with embryo transfers (ETs) from fresh procedures as well as from those cryopreserved embryos arising from the same OPU.…”

Human growth hormone use in poor ovarian response – caution and opportunities

“…Some of the main advocates for human growth hormone have utilised these potentially biased cohort studies to question any resistance to the belief that human growth hormone is effective in these cycles. 8 , 9 It is hard to argue with a clinician who promotes patient experiences where in a number of cycles a pregnancy did not occur, followed by a success with human growth hormone where pregnancy did commence. Selection bias, changing clinical and laboratory techniques and increased clinical attention are alternative explanations.…”

“…Human growth hormone has a long history of being investigated, and promoted, as a biologically active agent on the ovary 5 – 12 and the hypothalamic pituitary axis (possibly through kisspeptin mediation). Its biological effects in natural puberty, growth and metabolism have been extensively described over several decades and long-term use for growth hormone deficiency has been generally shown to be both effective and safe.…”