Abstract

Decline in successful conception decreases more rapidly after 38 years of age owing to follicular depletion and decreased oocyte quality. However, limited information is available regarding the underlying mechanism and the useful treatment. This study aimed to evaluate the effects of growth hormone supplementation on oocyte maturation in vivo in aged and young mice and to determine its effect on mitochondrial function. The influence of three different doses of recombinant human growth hormone (rhGH) (0.4, 0.8 and 1.6 mg/kg/day) for 8 weeks before ovarian stimulation was analyzed. Superovulated oocytes were released from the oviduct of 12-week-old and 40-week-old female C57BL/6J mice 14–16 h after administration of human chorionic gonadotropin. Ovarian follicle and morphological analysis and oocyte maturation parameters were then evaluated. This study is the first, to our knowledge, to report that medium- and high-dose rhGH significantly increases antral follicles in aged mice but anti-Müllerian hormone (AMH) levels. Furthermore, derived oocytes, MII-stage oocyte rate, ATP levels, mitochondrial membrane potential and frequencies of homogeneous mitochondrial distribution increased. In contrast, in both aged and young mice, the mtDNA copy numbers per oocyte were similar before rhGH administration, and upon saline administration, they did not differ significantly. We conclude that medium-dose rhGH supplementation before standard ovarian stimulation regimens improves oocyte quality in aged mice, probably by enhancing mitochondrial functionality.

Highlights

  • The probability of successful conception dramatically declines nonlinearly with maternal age in a nonlinear manner

  • Reproductive efficiency decreases with increasing maternal age

  • Clinical results support a decline in response to ovarian stimulation during in vitro fertilization (IVF), poor oocyte and embryo developmental competence increased incidence of spontaneous pregnancy loss and fetal aneuploidy in older infertility patients

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Summary

Introduction

The probability of successful conception dramatically declines nonlinearly with maternal age in a nonlinear manner. Decline in successful conception decreases more rapidly after 38 years of age (Faddy 2000) owing to the progressive decline in ovarian follicles and decreased oocyte quality (Perheentupa & Huhtaniemi 2009). Adequate patient response to ovarian stimulation determines the number and quality of oocytes available for, and the successful outcome of, in vitro fertilization (IVF). Clinical studies have reported that women over 40 years of age undergoing IVF with donated oocytes have pregnancy rates comparable to those of young patients. The consistent live birth rate, irrespective of maternal age, suggests that decline in oocyte quality majorly contributes to age-related infertility. No treatment method has successfully improved the chances of a live birth in women of advanced maternal age

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