Howles Colin M, Kim Chung-Hoon, Elder Kay
Serono International SA, Department of Product Development, Geneva, Switzerland.
Int Surg. 2006 Sep-Oct;91(5 Suppl):S37-54.
In a spontaneous menstrual cycle, during the follicular phase, only one follicle out of a cohort of 10-20 usually completes maturation and ovulates to release a mature oocyte. The aim of ovarian stimulation in assisted reproductive technology (ART) protocols is to overcome the selection of a dominant follicle and to allow the growth of a cohort of follicles. This strategy leads to an increase in the number of oocytes and hence embryos available for transfer, thereby increasing the chance of transferring up to three viable embryos. However, the chance of pregnancy and also live birth begins to dramatically decline after the age of 35, and successful treatment for these patients continues to be a major challenge in ART programs. Preimplantation genetic screening studies over the last decade have identified a dramatic increase in the rate of aneuploidy as a major contributor to the reduction in embryo viability in older patients. It has also been demonstrated that women of advanced maternal age may have oocytes that are compromised by a significant reduction in the amount of mitochondrial DNA in their cytoplasm. The strategies outlined in this review may provide a means of augmenting follicular recruitment and cytoplasmic integrity by utilizing pharmacogenomics and manipulating endocrinology to improve the prognosis for these women. Recent studies indicate that androgen supplementation may be one area to explore further. The availability of recombinant human leutinizing hormone (rhLH) has made it possible to investigate the role of LH in the endocrinology of follicular recruitment: it appears that a defect in the balance of LH/ follicle-stimulating hormone (FSH) might be involved in the subtle age-related decline in follicular recruitment, and patients of older reproductive age undergoing ART might benefit from the addition of LH and/or hGH. Further studies are required to investigate the physiological mechanisms behind this observation and to assess the possible effect of LH and/or hGH supplementation on the age-related decline in pregnancy rate.
在自然月经周期的卵泡期，通常10 - 20个卵泡组成的卵泡群中只有一个卵泡完成成熟并排卵，释放出成熟卵母细胞。辅助生殖技术（ART）方案中卵巢刺激的目的是克服优势卵泡的选择，使一群卵泡生长。这种策略会增加卵母细胞数量，从而增加可用于移植的胚胎数量，进而提高移植多达三个存活胚胎的机会。然而，35岁以后怀孕及活产的几率开始急剧下降，对这些患者的成功治疗仍然是ART项目中的一项重大挑战。过去十年的植入前基因筛查研究发现，非整倍体率急剧上升是老年患者胚胎活力下降的主要原因。研究还表明，高龄产妇的卵母细胞可能因细胞质中线粒体DNA数量显著减少而受损。本综述中概述的策略可能提供一种方法，即利用药物基因组学和调控内分泌来增强卵泡募集和细胞质完整性，从而改善这些女性的预后。最近的研究表明，补充雄激素可能是一个值得进一步探索的领域。重组人促黄体生成素（rhLH）的出现使研究LH在卵泡募集内分泌学中的作用成为可能：LH/促卵泡生成素（FSH）平衡缺陷似乎与卵泡募集过程中与年龄相关的细微下降有关，接受ART的高龄生殖期患者可能会从添加LH和/或hGH中获益。需要进一步研究来探究这一观察结果背后的生理机制，并评估补充LH和/或hGH对与年龄相关的妊娠率下降可能产生的影响。
