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

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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Single-centre retrospective analysis of growth hormone supplementation in IVF patients classified as poor-prognosis

BMJ Open ◽

10.1136/bmjopen-2017-018107 ◽

2017 ◽

Vol 7 (10) ◽

pp. e018107 ◽

Cited By ~ 25

Author(s):

Kevin N Keane ◽

John L Yovich ◽

Anahita Hamidi ◽

Peter M Hinchliffe ◽

Satvinder S Dhaliwal

Keyword(s):

Growth Hormone ◽

Live Birth ◽

Poor Prognosis ◽

Antral Follicle ◽

Antral Follicle Count ◽

Clinical Pregnancy ◽

In Vitro Fertilisation ◽

Success Rates ◽

Younger Women

BackgroundPatients undergoing in vitro fertilisation (IVF) receive various adjuvant therapies in order to enhance success rates, but the true benefit is actively debated. Growth hormone (GH) supplementation was assessed in poor-prognosis women undergoing fresh IVF transfer cycles.MethodsData were retrospectively analysed from 400 IVF cycles, where 161 women received GH and 239 did not.ResultsClinical pregnancy, live birth rates and corresponding ORs and CIs were significantly greater with GH, despite patients being significantly older with lower ovarian reserve. Patient’s age, quality of transferred embryo and GH were the only significant independent predictors of clinical pregnancy (OR: 0.90, 5.00 and 2.49, p<0.002, respectively) and live birth chance (OR: 0.91, 3.90 and 4.75, p<0.014, respectively). GH increased clinical pregnancy chance by 3.42-fold (95% CI 1.82 to 6.44, p<0.0005) and live birth chance by 6.16-fold (95% CI 2.83 to 13.39, p<0.0005) after adjustment for maternal age, antral follicle count and transferred embryo quality.ConclusionThese data provided further evidence to indicate that GH may support more live births, particularly in younger women. It also appears that embryos generated under GH have a better implantation potential, but whether the biological mechanism is embryo-mediated or endometrium-mediated is unclear.

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

GSC Biological and Pharmaceutical Sciences ◽

10.30574/gscbps.2021.16.1.0207 ◽

2021 ◽

Vol 16 (1) ◽

pp. 219-238

Author(s):

John L Yovich ◽

Shanthi Srinivasan ◽

Mark Sillender ◽

Shipra Gaur ◽

Philip Rowlands ◽

...

Keyword(s):

Growth Hormone ◽

Live Birth ◽

Ovarian Reserve ◽

Poor Prognosis ◽

Birth Rate ◽

Live Birth Rate ◽

Utilization Rate ◽

Fresh Embryo Transfer ◽

Recombinant Growth Hormone ◽

Live Births

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

Clinical and Experimental Reproductive Medicine ◽

10.5653/cerm.2019.00206 ◽

2019 ◽

Vol 46 (4) ◽

pp. 178-188 ◽

Cited By ~ 1

Author(s):

Kevin N Keane ◽

Yun Ye ◽

Peter M Hinchliffe ◽

Sheena LP Regan ◽

Satvinder S Dhaliwal ◽

...

Keyword(s):

Growth Hormone ◽

Birth Outcomes ◽

Live Birth ◽

Poor Prognosis ◽

Hormone Stimulation

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A 10-Year Perspective on the Utility of Three Adjuvants Often Used in IVF: Growth Hormone, Melatonin and DHEA

Reproductive Medicine ◽

10.3390/reprodmed2040016 ◽

2021 ◽

Vol 2 (4) ◽

pp. 155-162

Author(s):

John L. Yovich ◽

Peter M. Hinchliffe

Keyword(s):

Growth Hormone ◽

Poor Prognosis ◽

Poor Quality ◽

Hormone Deficiency ◽

Oocyte Activation ◽

Prognosis Factors ◽

Recombinant Growth Hormone ◽

Female Age ◽

Insulin Growth Factor ◽

Adult Growth

Since 2010, numerous studies reported from PIVET, a pioneer IVF facility established over 40 years ago, have explored the use of three adjuvants designed to improve laboratory and clinical outcomes in cases where a poor prognosis has been demonstrated. The adjuvants reported commenced with recombinant growth hormone (rGH), followed by dehydroepiandrosterone (DHEA) after developing a unique troche to avoid the first-pass effect and, subsequently, melatonin. The studies show that rGH is beneficial in the situation where women have poor-quality embryos in the setting of additional poor prognosis factors, such as advanced female age, a very low ovarian reserve, an insulin growth factor profile in the lowest quartile or recurrent implantation failure. The studies also imply that the adjuvants may actually reduce live birth productivity rates if used on women without poor prognosis factors; hence, further studies, which can now be better designed, should be undertaken to explore the notion of underlying adult growth hormone deficiency in some cases as well as the suggestion that DHEA can provide equivalent benefits in some poor prognosis settings. Melatonin showed no suggestive benefits in any of the studies and can be excluded from consideration in this context. Future studies should compare rGH and DHEA with a focus on those women who have poor embryo quality with additional poor prognosis factors. Such trials should be extended to 12 weeks to cover the entire period of oocyte activation.

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Predicting the chances of live birth for couples undergoing IVF-ICSI: a novel instrument to advise patients and physicians before treatment

F1000Research ◽

10.12688/f1000research.20038.1 ◽

2019 ◽

Vol 8 ◽

pp. 1585

Author(s):

Bruna Estácio da Veiga ◽

Duarte Pedro Tavares ◽

José Luis Metello ◽

Fernando Ferreira ◽

Pedro Ferreira ◽

...

Keyword(s):

Live Birth ◽

Smoking Status ◽

Antral Follicle ◽

Developed Countries ◽

Antral Follicle Count ◽

Male Factor ◽

Discriminatory Ability ◽

Probability Of Success ◽

Variable Probability

Background: In developed countries, the prevalence of infertility ranges from 3.5% to 16.7%. Therefore, the number of in vitro fertilization technique (IVF) and its subtype intracytoplasmic sperm injection (ICSI) treatments has been significantly increasing across Europe. Several factors affect the success rate of in vitro treatments, which can be used to calculate the probability of success for each couple. As these treatments are complicated and expensive with a variable probability of success, the most common question asked by IVF patients is ‘‘What are my chances of conceiving?”. The main aim of this study is to develop a validated model that estimates the chance of a live birth before they start their IVF non-donor cycle. Methods: A logistic regression model was developed based on the retrospective study of 737 IVF cycles. Each couple was characterized by 14 variables (woman’s and man’s age, duration of infertility, cause of infertility, woman’s and man’s body mass index (BMI), anti-Müllerian hormone (AMH), antral follicle count (AFC), woman’s and man’s ethnicity, woman’s and man’s smoking status and woman’s and man’s previous live children) and described with the outcome of the treatment "Live birth" or "No live birth". Results: The model results showed that from the 14 variables acquired before starting the IVF procedures, only male factor, man’s BMI, man's mixed ethnicity and level of AMH were statistically significant. The interactions between infertility duration and woman’s age, infertility duration and man’s BMI, AFC and AMH, AFC and woman’s age, AFC and woman’s BMI and AFC and disovulation were also statistically significant. The area under the receiver operating characteristic (AUROC) curve test for the discriminatory ability of the final prediction model is 0.700 (95% confidence interval (CI) 0.660–0.741). Conclusions: This model might result in a new validated decision support system to help physicians to manage couples’ expectations.

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