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

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

doi:10.30574/gscbps.2021.16.1.0207

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.2021.16.1.0207

Keywords:

In vitro fertilization [IVF], Intracytoplasmic sperm injection [ICSI], Recombinant growth hormone [rGH], Melatonin, Embryo utilization, Live birth productivity rate

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.

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References

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, 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.

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.

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; relationship to clinical parameters (Study 1). J Pers Med. 2020; 10(3): 122, 1-15

Yovich JL, Conceicao JL, Wong J, Marjanovic N, Wicks R, Hinchliffe PM. Fertlization by ICSI generates a higher number of live births than IVF in a pioneer facility applying >90% single blastocyst-stage embryo transfers. GSC Biol & Pharmaceutical Sciences. 2021; 15(01): 087-103.

Mariappen U, Keane KN, Hinchliffe PM, Dhaliwal SS, Yovich JL. Neither male age nor semen parameters influence clinical pregnancy or live birth outcomes from IVF. Reprod Biol. 2018; 18: 324-329.

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, 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.

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.

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.

Keane KN, Hinchliffe PM, Namdar N, Conceicao JL, Newsholme P, Yovich JL. Novel dehydroepiandrosterone troche supplementation improves the serum androgen profile of women undergoing in vitro fertilization. Drug Des Devel Ther. 2015; 9: 5569–78.

Keane KN, Hinchliffe PM, Rowlands PK, Borude G, Srinivasan S, Dhaliwal SS, Yovich JL. DHEA Supplementation confers no additional benefit to that of growth hormone on pregnancy and live birth rates in IVF patients categorized as poor prognosis. Front Endocrinol. 2018; 9(14): 1-11.

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.

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.

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

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.

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.

Your IVF Success Estimator. Find an Australian IVF clinic. Australian & New Zealand Assisted Reproduction Database. University of New South Wales. 2020 [cited 3 March 2021]. Available from https://www.yourivfsuccess.com.au

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), 1-4

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

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

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

Fernando S, Osianlis T, Vollenhoven B, Wallace E, Rombauts L. A pilot double-blind randomised placebo-controlled dose-response trial asssessing the effects of melatonin on infertility treatment (MIART): study protocol. BMJ Open. 2014; 4(8): e0059866, 1-8.

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: Paleontologicalstatistics software package for education and data analysis. Palaentologia Electronica. 2001; 4(1): 1-9.

Yovich JL, Srinivasan S, Sillender M, Gaur S, Rowlands P, Hinchliffe PM. Using growth hormone as an adjuvant in IVF: Live birth outcomes from various poor prognosis scenarios. GSC Biol & Pharmaceutical Sciences. 2021; 15(01): 063-080.

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.

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.

Tesarik J, Yovich JL, Menezo Y. Editorial: Growth hormone in Fertility and infertility: physiology, pathology, diagnosis and treatment. Front Endocrinol. 2021; 12: 621722.

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: 1298–131.