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.
Highlights
The concept of poor-prognosis for women undertaking in-vitro fertilization (IVF) is embedded in the early history of human IVF and continues to be a stubborn but evolving concept
Extending from this study, we subsequently reported on the outcome of treatments comparing the pregnancy outcomes of those cryopreserved embryos generated under growth hormone (GH) influence with those arising without GH influence [34]
Our concluding viewpoint is that GH is clearly indicated in those women with infertility where this can be shown to be due to adult growth hormone deficiency (AGHD)
Summary
The concept of poor-prognosis for women undertaking in-vitro fertilization (IVF) is embedded in the early history of human IVF and continues to be a stubborn but evolving concept. The productivity rate combining FET cycles is extremely low as the number of women having supernumerary embryos frozen (after fresh ET) is a very low proportion of the total initiated cycles as the majority have 0–4 oocytes recovered These results can be contrasted with the ANZARD report which shows that in 2017, the SET rate in Australia and New Zealand was 89.4% and multiple pregnancies were a low 3.6%, being twins only without a single high-order live birth. Encouraged by the study on women aged >40 years which showed significant improvement of live birth rates by ovarian co-stimulation with GH in IVF [32], a GH adjuvant study was conducted at PIVET and the 5-year project was reported in 2010 [4] It was not an RCT but was designed as a prospective sequential crossover whereby patients identified as poor-prognosis were offered the option of using, or not using, GH in the forthcoming IVF cycle. The data from the 130 women has been analyzed and published [69]
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