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

John L Yovich; Shanthi Srinivasan; Mark Sillender; Shipra Gaur; Philip Rowlands; Peter M Hinchliffe

doi:10.30574/gscbps.2021.15.1.0083

Authors

John L Yovich Department of Pharmacy and Biomedical Sciences Curtin University Perth, Western Australia Australia 6845.
Shanthi Srinivasan PIVET Medical Centre Perth, Western Australia Australia 6007.
Mark Sillender PIVET Medical Centre Perth, Western Australia Australia 6007.
Shipra Gaur PIVET Medical Centre Perth, Western Australia Australia 6007.
Philip Rowlands PIVET Medical Centre Perth, Western Australia Australia 6007.
Peter M Hinchliffe PIVET Medical Centre Perth, Western Australia Australia 6007.

DOI:

https://doi.org/10.30574/gscbps.2021.15.1.0083

Keywords:

Growth Hormone (GH), Insulin growth factor-1 (IGF-1), In vitro fertilization (IVF), Assisted Reproductive Technology (ART), Pregnancy Productivity Rate, Live Birth Productivity Rate, Poor prognosis Fertility Factors

Abstract

Following 5 recent studies at PIVET several female factors were defined which enabled the clear categorization for a poor prognosis in IVF, namely advanced female age ≥42 years, very low antral follicle count (AFC <5), very low serum anti-Mullerian hormone level (AMH<5pmol/L), serum Insulin growth factor-1 (IGF-1 level) in the lowest quartile, repetitive failed IVF cycles (≥3) and the failure of residual embryos to undergo cryopreservation. Following an Assessment Cycle (AC) to define the first 4 factors in IVF-naïve women, women were offered recombinant growth hormone (rGH) as an adjuvant at 1.0 IU daily for 6 weeks in the lead-up to the oocyte pick-up of their first IVF treatment cycle. Of 1173 women who proceeded directly into IVF after completing an AC, 252 women (21.5%) utilized rGH initiating 426 IVF cycles. Very low AFC and AMH levels were defined in 51 of the women who proceeded through 90 IVF treatment cycles utilizing rGH. Clinical outcomes included cancellation rates (reduced among rGH users, p<0.01), oocytes retrieved (no significant benefit from rGH), oocyte utilization (apparent benefit for rGH in older women with several factors), significant improvement in embryo utilization rates for older women with several factors (incremental cycles ≥3; p<0.002) or failure to achieve cryopreserved embryos (p<0.02). However, these benefits failed to translate into an improved pregnancy or live birth productivity rate nor a reduction in miscarriage rates; partly due to the low numbers of women with several poor prognosis factors. Furthermore, a note of caution emerged from this study as younger women who did not receive rGH had significantly better live birth outcomes (p<0.0001 from initiated cycles), regardless of the number of poor prognosis factors identified. Nonetheless, we encourage prospective studies to continue, focusing only on older women ≥40 years with low ovarian reserve and additional poor prognosis factors.

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References

Newman JE, Paul RC, Chambers GM. Assisted reproductive technology in Australia and New Zealand 2018. Sydney: National Perinatal Epidemiology and Statistics Unit, the University of New South Wales, Sydney. 2020; 1-83.

Yovich JL, Zaidi S, Nguyen MDK, Hinchliffe PM. Measuring IGF-1 and IGFBP-3 profiles in women seeking assisted reproduction; relationship to clinical parameters (Study 1). J Pers Med. 2020; 10(3): 122, 1-15.

Yovich JL, Zaidi S, Nguyen MDK, Hinchliffe PM. Measuring IGF-1 and IGFBP-3 profiles in women seeking assisted reproduction; relationship to ovarian reserve parameters (Study 2). GSC Biol & Pharmaceutical Sciences. 2020; 13(02): 035-053.

Yovich JL, Zaidi S, Nguyen MDK, Hinchliffe PM. Measuring IGF-1 and IGFBP-3 profiles in women seeking assisted reproduction; relationship to serum growth hormone levels (Study 3). GSC Biol & Pharmaceutical Sciences. 2020; 13(03): 032-053.

Yovich JL, Zaidi S, Nguyen MDK, Hinchliffe PM. Measuring IGF-1 and IGFBP-3 profiles in women seeking assisted reproduction; response of women categorised as poor prognosis to growth hormone adjuvant therapy (Study 4). GSC Biol & Pharmaceutical Sciences. 2020; 13(03): 064-078.

Yovich JL, Zaidi S, Nguyen MDK, Hinchliffe PM. Measuring IGF-1 and IGFBP-3 profiles in women seeking assisted reproduction; relevance to clinical outcomes from in vitro fertilization (Study 5). GSC Biol & Pharmaceutical Sciences. 2020; 13(03): 079-096.

Yovich JL, Ye Y, Regan SLP, Keane KN. The evolving concept of poor-prognosis for women undertaking IVF and the notion of growth hormone as an adjuvant; a single-center viewpoint. Front Endocrinol. 2019; 10(808): 1-14.

Yovich JL, Craft IL. Founding pioneers of IVF: Independent innovative researchers generating livebirths within 4 years of the first birth. Reprod Biol. 2018; 18: 317-323.

Yovich JL. Founding pioneers of IVF Update: Independent innovative researchers generating livebirths within 4 years of the first birth. Reprod Biol. 2020; 20: 111-113.

Yovich JL. How to Prepare the Egg and Embryo to Maximise IVF Success. In: Monitoring the stimulated IVF cycle. Section II: Stimulation for IVF (Eds: Gabor T Kovacs, Anthony J Rutherford, David K Gardner). Cambridge University Press, Cambridge. 2019; 94-120.

Yovich J, Stanger J, Hinchliffe P. Targeted gonadotrophin stimulation using the PIVET algorithm markedly reduces the risk of OHSS. Reprod Biomed Online. 2012; 24(3): 281-292.

Yovich JL, Alsbjerg B, Conceicao JL, Hinchliffe PM, Keane KN. PIVET rFSH dosing algorithms for individualized controlled ovarian stimulation enables optimized pregnancy productivity rates and avoidance of ovarian hyperstimulation syndrome. Drug Des Devel Ther. 2016; 10: 2561–2573.

Yovich JL, Hinchliffe PM, Lingam S, Srinivasan S, Keane KN. Adjusting the PIVET rFSH dosing algorithm for the biosimilar Bemfola product. J Fertil In vitro IVF Worldw Reprod Med Genet Stem Cell Biol. 2018; 5: 3.

Kuwayama M, Vajta G, Kato O, Leibo SP. Highly efficient vitrification method for cryopreservation of human oocytes. Reprod Biomed Online. 2005; 11: 300-308.

Yovich JL, Conceicao JL, Marjanovich N, Ye Y, Hinchliffe PM, Dhaliwal SS, Keane KN. An ICSI rate of 90% minimizes complete failed fertilization and provides satisfactory implantation rates without elevating fetal abnormalities. Reprod Biol. 2018; 18: 301-311.

Keane K, Cruzat VF, Wagle S, Chaudhary N, Newsholme P, Yovich J. Specific ranges of anti-Mullerian hormone and antral follicle count correlate to provide a prognostic indicator for IVF outcome. Reprod Biol. 2017; 17: 51-59.

Mustafa KB, Keane KN, Walz NL, Mitrovic KI, Hinchliffe PM, Yovich JL. Live Birth Rates are satisfactory following multiple IVF treatment cycles in poor prognosis patients. Reprod Biol. 2017; 17: 34-41.

Yovich JL, Conceicao J, Hinchliffe P, Keane K. Which blastocysts should be considered for genetic screening? Hum Reprod. 2015; 30: 1743-1745.

Yovich JL. Stanger JD, Keane KN. Cumulative live birth rate: An outmoded term. JFIV Reprod Med Genet. 2016; 4: 165.

Hammer Ø, Harper DAT, Ryan PD. PAST: Paleontological Statistics software package for education and data analysis. Palaentologia Electronica. 2001; 4(1): 1-9.

Yovich JL, Regan SL, Zaidi SN, Keane KN. The concept of growth hormone deficiency affecting clinical prognosis in IVF. Front Endocrinol. 2019; 10(650): 1-9.

Norman RJ, Alvino H, Hull LM, Mol BW, Hart RJ, Kelly T-L, et al. Human growth hormone for poor responders: a randomized placebo-controlled trial provides no evidence for improved live birth rate. Reprod Biomed Online. 2019; 38: 908–15.

Tesarik J, Galán-Lázaro M, Conde-López C, Chiara-Rapisarda AM, Mendoza-Tesarik R. The effect of GH administration on oocyte and zygote quality in young women with repeated implantation failure after IVF. Front Endocrinol. 2020; 11; 519-572, 1-7.

Keane KN, Ye Y, Regan SLP, Dhaliwal SS, Yovich JL. Live birth outcomes of vitrified embryos generated under growth hormone stimulation are improved for women categorized as poor-prognosis. Clin Exp Reprod Med. 2019; 46(40): 178-188.

Li J, Chen Q, Wang J, Huang G, Ye H. Does growth hormone supplementation improve oocyte competence and IVF outcomes in patients with poor embryonic development? A randomized controlled trial. BMC Pregnancy and Childbirth. 2020; 20(310): 1-10.

Zhang Y, Zhang C, Shu J, Guo J, Chang H-M, Leung PCK, Sheng J-Z, Huang H. Adjuvant treatment strategies in ovarian stimulation for poor responders undergoing IVF: a systematic review and network meta-analysis. Hum Reprod Update. 2020; 26(2): 247-263.

Yang P, Wu R, Zhang H. The effect of growth hormone supplementation in poor ovarian responders undergoing IVF or ICSI: a meta-analysis of randomized controlled trials. Reprod Biol Endocrinol. 2020; 18(1): 76, 1-10.

Farquhar C. Add-ons for assisted reproductive technology: can we be honest here? Fertil Steril. 2019; 112(6): 971-972.

Annual Capri Workshop Group. IVF, from the past to the future: the inheritance of the Capri Workshop Group. Hum Reprod Open. 2020; 3: 1-9.

Bortoletto P, Spandorfer S. Growth hormone: in search of the holy grail for poor responders (or a felony). Fertil Steril. 2020; 114(1): 63-64.

Yovich JL, Ye Y, Keane KN. Growth hormone adjuvant trial for poor responders undergoing IVF. Eur J Obstet Gynecol. 2019; 236: 249-251.

Devesa J, Caicedo D. The role of growth hormone on ovarian functioning and ovarian angiogenesis. Front Endocrinol. 2019; 10: 1-16.

Ipsa E, Cruzat VF, Kagize JN, Yovich JL, Keane KN. Growth Hormone and Insulin-like growth factor in reproductive tissues. Front Endocrinol. 2019; 777: 1-14.

Weall BM, Al-Samerria S, Conceicao J, Yovich JL, Almahbobi G. A direct action for GH in improvement of oocyte quality in poor-responder patients. Reproduction. 2015; 149: 147-154.

Regan SLP, Knight PG, Yovich JL, Arfuso F, Dharmarajan A. Growth hormone during in vitro fertilization in older women modulates the density of receptors in granulosa cells, with improved pregnancy outcomes. Fertil Steril. 2018; 110: 1298–1310.