Maximizing Correction of Infertility with Moderate to Marked Diminished Egg Reserve in Natural Cycles by Up-Regulating Follicle Stimulating Hormone Receptors

J. Check, J. Choe
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Abstract

Many infertility specialists advise women with diminished oocyte reserve (DOR) that their remaining oocytes probably are of poor quality similar to women of advanced reproductive age. There have been studies, especially employing in vitro fertilization-embryo transfer (IVF-ET), showing very poor live delivered pregnancy rates despite the transfer of morphologically normal embryos in women even with mild DOR. However, other data suggests that the low pregnancy rates are related to the use of high dosages of follicle stimulating hormone (FSH) drugs which down-regulate some key FSH dependent enzymes, cytokines, or proteins required for proper embryo implantation. Some studies have shown that techniques that favor FSH receptor up-regulation, rather than down-regulation, can provide the chance of live delivery 80% as well in women ≤ 35 with DOR, 70% for women 36-39, and 50% for women 40-42. Though some infertility specialists will encourage women whose only infertility issue is DOR, who reject the initial suggestion to consider donor oocytes, to proceed immediately with IVF-ET to maximize success, pregnancies are quite possible with natural conception. Thus, it seems imprudent to make couples undergo the financial burden of IVF-ET in the absence of a significant tubal or male factor problem. Not only have live deliveries occurred in women with DOR, using the principle described to achieve a mature dominant follicle followed by proper luteal phase support, with serum FSH levels over 100 mIU/mL, but also serum Anti-Mullerian Hormone (AMH) levels that were undetectable. This even applies to women in overt menopause where FSH up-regulation was achieved by negative feedback to the pituitary using ethinyl estradiol inhibiting FSH release, or down-regulation of hypothalamic-pituitary stimulation of FSH production by using gonadotropin releasing hormone agonists or antagonists.
通过上调促卵泡激素受体,最大限度地纠正自然周期中卵子储备中度至显著减少的不孕症
许多不孕症专家建议有卵母细胞储备减少(DOR)的妇女,她们剩余的卵母细胞可能质量较差,类似于育龄妇女。有研究,特别是体外受精-胚胎移植(IVF-ET)的研究表明,即使在轻度DOR的妇女中,尽管移植了形态正常的胚胎,但活产妊娠率非常低。然而,其他数据表明,低妊娠率与使用高剂量的促卵泡激素(FSH)药物有关,这些药物会下调胚胎植入所需的一些关键的促卵泡激素依赖酶、细胞因子或蛋白质。一些研究表明,有利于FSH受体上调而不是下调的技术可以为≤35岁的DOR女性提供80%的活产机会,为36-39岁的女性提供70%的活产机会,为40-42岁的女性提供50%的活产机会。尽管一些不孕症专家会鼓励那些唯一的不孕症是DOR的妇女,她们拒绝考虑供体卵母细胞的最初建议,立即进行IVF-ET以最大限度地提高成功率,但自然受孕怀孕是很有可能的。因此,在没有明显的输卵管或男性因素问题的情况下,让夫妇承受体外受精的经济负担似乎是不明智的。DOR的妇女不仅有活产,使用所描述的原理实现成熟的显性卵泡,然后是适当的黄体期支持,血清FSH水平超过100 mIU/mL,而且血清抗苗勒管激素(AMH)水平也检测不到。这甚至适用于明显绝经的女性,通过使用乙炔雌二醇抑制FSH释放的负反馈到垂体来实现FSH的上调,或者通过使用促性腺激素释放激素激动剂或拮抗剂来下调下丘脑-垂体对FSH产生的刺激。
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