Clinical trial NCT05447208: Effect of GH on the Blastocyst Euploid Rate in AMA Patients
Official title: A Randomized Control Trial to Investigate the Effect of Growth Hormone on the Euploid Rate of Blastocyst in Patients With Advanced Maternal Age
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Preimplantation Genetic Testing
Growth Hormone
Age, Parental
Lead sponsor: ShangHai Ji Ai Genetics & IVF Institute
Sponsor class: OTHER
First posted: 2022-07-07
Enrollment: 400
Sex: FEMALE
Minimum age (years): 38
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This randomized trial aims to compare the euploid rate of blastocysts in AMA patients undergoing PGT-A (preimplantation genetic testing for aneuploidy) with or without growth hormone supplement.

Infertile patients ≥38 years old will be recruited for study after informed consent if they fulfill the inclusion criteria and do not have the exclusion criteria. Eligible women will be randomised into one of the two groups:

Treatment group: Women will receive growth hormone (GH) supplement before and during antagonist protocol for ovarian stimulation.

Control group: Women will receive antagonist protocol for ovarian stimulation. The primary outcome is the euploidy rate of blastocysts.


Eligibility criteria: Inclusion Criteria:

* Age ≥38; intended to undergo PGT-A
* BMI in the normal range (18.50-24.0kg/m2)
* Normal semen analysis for the male partner

Exclusion Criteria:

* Endometriosis grade 3 or higher, untreat hydrosalpinx
* Women with a uterine cavity abnormality, such as a uterine congenital malformation (uterus uni-cornate, bicornate, or duplex); untreated uterine septum, adenomyosis, submucous myoma, or endo-metrial polyp(s)
* Women who are indicated and planned to undergo PGT-SR (Preimplantation genetic testing for structural rearrangement) or PGT-M (Preimplantation genetic testing for monogenic disorder), for example, parental abnormal karyo-type or diagnosed with monogenic disease
* History of endocrine disorder, autoimmune diseases or diagnosed thrombophilia
* History of GH supplementation in the previous IVF treatment or taking other supplementary drugs used during stimulation; patients with absolute or relative contraindications to GH treatment, including active malignancy or history of cancer, diabetic retinopathy, diabetes mellitus, and chronic kidney disease.

Primary outcomes:
measure: euploidy rate
timeFrame: 1 month after oocyte retrieval
Secondary outcomes:
measure: live birth rate
timeFrame: 1 year after embryo transfer
measure: cumulative live birth rate
timeFrame: 1 year after embryo transfer
measure: ongoing pregnancy
timeFrame: 12 weeks' gestation
measure: clinical pregnancy rate
timeFrame: 6 weeks after embryo transfer
measure: number of euploid blastocysts in an OS cycle
timeFrame: 1 month after oocyte retrieval
measure: the probability of obtaining euploid blastocysts in an OS cycle
timeFrame: 1 month after oocyte retrieval
measure: KIDScore of euploid embryos
timeFrame: 6 days after oocyte retrieval
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai JIAI Genetics and IVF Institute
state: Shanghai
Study officials:
affiliation: Shanghai JiAi Genetics & IVF Institute, China
name: XIAOXI SUN, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Demko ZP, Simon AL, McCoy RC, Petrov DA, Rabinowitz M. Effects of maternal age on euploidy rates in a large cohort of embryos analyzed with 24-chromosome single-nucleotide polymorphism-based preimplantation genetic screening. Fertil Steril. 2016 May;105(5):1307-1313. doi: 10.1016/j.fertnstert.2016.01.025. Epub 2016 Feb 8.
citation: 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 Feb;149(2):147-54. doi: 10.1530/REP-14-0494. Epub 2014 Nov 5.
citation: Gong Y, Luo S, Fan P, Jin S, Zhu H, Deng T, Quan Y, Huang W. Growth hormone alleviates oxidative stress and improves oocyte quality in Chinese women with polycystic ovary syndrome: a randomized controlled trial. Sci Rep. 2020 Oct 30;10(1):18769. doi: 10.1038/s41598-020-75107-4.
citation: Liu C, Li S, Li Y, Tian J, Sun X, Song T, Yan G, Ding L, Sun H. Growth hormone ameliorates the age-associated depletion of ovarian reserve and decline of oocyte quality via inhibiting the activation of Fos and Jun signaling. Aging (Albany NY). 2021 Feb 17;13(5):6765-6781. doi: 10.18632/aging.202534. Epub 2021 Feb 17.
citation: Skillern A, Leonard W, Pike J, Mak W. Growth hormone supplementation during ovarian stimulation improves oocyte and embryo outcomes in IVF/PGT-A cycles of women who are not poor responders. J Assist Reprod Genet. 2021 May;38(5):1055-1060. doi: 10.1007/s10815-021-02088-2. Epub 2021 Feb 3.
citation: 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 Dec;110(7):1298-1310. doi: 10.1016/j.fertnstert.2018.08.018.