Growth Hormone Therapy Beneficial in POR Subgroup

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Growth hormone therapy beneficial in POR subgroup

Clinical Outcomes of Frozen-Thawed Embryos Generated From Growth Hormone Stimulation in Expected Poor Responders

A retrospective cohort study of expected poor responders to IVF treatment was performed to evaluate whether or not growth hormone (GH) therapy, alongside standard treatment, significantly improved clinical outcomes in frozen-thawed IVF cycles.

Expected poor ovarian response (POR) was defined by anti-Mullerian hormone (AMH) < 1.2ng/ml and an antral follicle count (AFC) < 7. Age of participants in both GH and control groups was matched to minimise any bias, while couples with male partners diagnosed with azoospermia or severe oligospermia were excluded, along with any pre-implantation genetic diagnosis (PGD) testing of embryos.

In total, 376 expected POR patients were included in the study, 188 underwent GH therapy and 188 did not (controls). Controlled ovarian stimulation was carried out using a variety of protocols: long and short gonadotrophin-releasing hormone (GnRH) agonist; GnRH antagonist; clomiphene citrate with gonadotrophins and antagonist, all followed by a hCG trigger shot once 2 follicles reached 18µm in size.

In the GH therapy group, treatment started 4 weeks prior to ovarian stimulation, with daily injection of human recombinant GH. Once ovarian stimulation began, GH dosage was doubled, and continued daily until the day of hCG injection.

IVF and ICSI was carried out according to routine procedures. Good quality embryos not originally transferred were frozen either on day 3, or once they reached the blastocyst stage. A dimethyl sulfoxide-ethylene glycol-sucrose system was used during the vitrification and warming process, with only blastocysts showing re-expansion selected for transfer.

The main study outcome was clinical pregnancy rate per transfer cycle, defined by the presence of a gestational sac 4 weeks after embryo transfer. Secondary outcomes included: number of oocytes retrieved, 2 pronuclei zygotes, day 3 available embryos, implantation rate, miscarriage rate and live birth rate, to comprehensively identify any effect of GH therapy.

Initial analysis of patient characteristics confirmed a similar age, BMI, AHM, AFC, type, cause and duration of infertility for both groups. The use of different controlled ovarian stimulation protocols did vary significantly between the 2 groups, however more interestingly, the number of oocytes (7.13 vs 5.89), 2 pronuclei zygotes (4.66 vs 2.76) and day 3 available embryos (3.86 vs 3.26) was significantly higher in the GH group.

Next analysis of frozen-thawed cycles, between the GH group and controls, showed a comparable survival rate for thawed embryos (94.8% vs 93.3%), proportion of day 3 or blastocyst transfers (29.3%/69.2% vs 29.8%/68.1%), endometrial thickness (9.68mm vs 9.80mm) and number of embryos transferred (1.25 vs 1.24).

However following on from embryo transfer, no significant difference was seen in the clinical pregnancy rate (30.3% vs 31.0%), implantation rate (25.3% vs 26.2%), early miscarriage rate (16.1% vs 15.8%) or live birth rate (20.6% vs 20.8%), comparing the GH group to controls. Similarly, when clinical outcomes was further analysed according to age (<35, 35-40, ≥40) or COS protocol, no significant differences emerged as seen in other studies.

Interestingly analysis of clinical outcomes, according to embryo quality, did show that good quality blastocysts (≥4BB) in the GH group had significantly improved clinical pregnancy rates (46.8% vs 32.1%), early miscarriage rates (10.3% vs 20.0%) and live birth rates (35.7% vs 18.9%).

The authors cautioned however that this finding occurred in a small subgroup of the study and should be verified in a large-scale multi-center Randomized Controlled Trial.


SUMMARY: DOES GROWTH HORMONE IMPROVE EGG QUALITY

In this study, growth hormone therapy in poor ovarian response women caused a significant increase in all embryogenesis parameters, including the number of available day 3 embryos (3.86 ±2.62 vs 3.26 ±2.04) compared to controls, indicating that pre-treatment growth hormones can improve egg quality.


Limitations

  1. Retrospective study
  2. Variable protocols


Similar studies

Cai M H, et al. (2019). The Effect of Growth Hormone on the Clinical Outcomes of Poor Ovarian Reserve Patients Undergoing in vitro Fertilization/Intracytoplasmic Sperm Injection Treatment: A Retrospective Study Based on POSEIDON Criteria. https://doi.org/10.3389/fendo.2019.00775

Keane K N, et al. (2019). Live birth outcomes of vitrified embryos generated under growth hormone stimulation are improved for women categorized as poor-prognosis. https://doi.org/10.5653/cerm.2019.00206

Lan K C, et al. (2019). Growth hormone supplementation may improve the pregnancy rate and endometrial receptivity among women aged more than 40 years undergoing in vitro fertilization. https://doi.org/10.1016/j.bj.2019.05.003

Norman R J, et al. (2019). Human growth hormone for poor responders: a randomized placebo-controlled trial provides no evidence for improved live birth rate. https://doi.org/10.1016/j.rbmo.2019.02.003

Dakhly D M R, et al. (2018). The addition of growth hormone adjuvant therapy to the long down regulation protocol in poor responders undergoing in vitro fertilization: Randomized control trial. https://doi.org/10.1016/j.ejogrb.2018.06.035

Regan S L P, et al. (2018). Growth hormone during in vitro fertilization in older women modulates the density of receptors in granulosa cells, with improved pregnancy outcomes. https://doi.org/10.1016/j.fertnstert.2018.08.018

Bassiouny Y A, et al. (2016). Does the addition of growth hormone to the in vitro fertilization/intracytoplasmic sperm injection antagonist protocol improve outcomes in poor responders? A randomized, controlled trial. https://doi.org/10.1016/j.fertnstert.2015.11.026


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