Infertility affects one in six couples, with in vitro fertilization (IVF) offering many the chance of conception. Compared to the solitary oocyte produced during the natural menstrual cycle, the supraphysiological ovarian stimulation needed to produce multiple oocytes during IVF results in a dysfunctional luteal phase that can be insufficient to support implantation and maintain pregnancy. Consequently, hormonal supplementation with luteal phase support, principally exogenous progesterone, is used to optimize pregnancy rates; however, luteal phase support remains largely ‘black-box’ with insufficient clarity regarding the optimal timing, dosing, route and duration of treatment. Herein, we review the evidence on luteal phase support and highlight remaining uncertainties and future research directions. Specifically, we outline the physiological luteal phase, which is regulated by progesterone from the corpus luteum, and evaluate how it is altered by the supraphysiological ovarian stimulation used during IVF. Additionally, we describe the effects of the hormonal triggers used to mature oocytes on the degree of luteal phase support required. We explain the histological transformation of the endometrium during the luteal phase and evaluate markers of endometrial receptivity that attempt to identify the ‘window of implantation’. We also cover progesterone receptor signalling, circulating progesterone levels associated with implantation, and the pharmacokinetics of available progesterone formulations to inform the design of luteal phase support regimens.

六分之一的夫妇患有不孕症，体外受精 (IVF) 为许多人提供了受孕的机会。与自然月经周期中产生的单个卵母细胞相比，体外受精期间产生多个卵母细胞所需的超生理卵巢刺激会导致黄体期功能失调，不足以支持着床和维持妊娠。因此，通过补充黄体期支持的激素（主要是外源性黄体酮）来优化妊娠率；然而，黄体期支持在很大程度上仍然是“黑匣子”，对于治疗的最佳时机、剂量、途径和持续时间不够明确。在此，我们回顾了黄体期支持的证据，并强调了剩余的不确定性和未来的研究方向。具体来说，我们概述了由黄体黄体酮调节的生理黄体期，并评估体外受精过程中使用的超生理卵巢刺激如何改变它。此外，我们描述了用于成熟卵母细胞的激素触发因素对所需黄体期支持程度的影响。我们解释了黄体期子宫内膜的组织学转变，并评估了试图识别“着床窗口”的子宫内膜容受性标志物。我们还介绍孕酮受体信号传导、与植入相关的循环孕酮水平以及可用孕酮制剂的药代动力学，为黄体期支持方案的设计提供信息。