The article discusses the mechanisms of implantation and the factors influencing successful pregnancy. It highlights the importance of the peri-implantation period, where defects can lead to adverse outcomes such as preeclampsia, miscarriage, and preterm birth. The review emphasizes the complex molecular signaling networks that coordinate implantation and decidualization, which are essential for a successful pregnancy. Understanding these mechanisms can help improve natural and in vitro fertilization (IVF) outcomes. Pregnancy is a complex, irreversible process involving implantation, decidualization, placentation, and parturition. The success of each event is crucial for progression to the next stage. However, the molecular dialogue governing these events is not fully understood. The window of implantation is a limited time when the blastocyst is competent for implantation. If this coordination is out of phase, implantation fails or becomes defective. In humans, natural conception per cycle is poor, and 75% of failed pregnancies are due to implantation failure. Successful implantation involves close interactions between the uterus and blastocyst. However, ethical restrictions and lack of mechanistic studies have delayed research on embryo-uterine interactions in humans. Knowledge from transgenic mouse models has helped understand the molecular basis of uterine receptivity, implantation, and decidualization in humans. The concept of uterine receptivity was first proposed by Alexandare Psychoyos. Blastocysts implant only when transferred into receptive uteri. Reciprocal embryo transfer experiments in delayed implanting mouse models showed that blastocyst activation is also critical for implantation. The window of receptivity is transient in humans, and implantation beyond this window results in spontaneous miscarriages. However, many miscarriages result from embryonic abnormalities, including aneuploidy. Successful implantation involves close interactions between the uterus and blastocyst. The uterus is composed of three major tissue compartments: epithelium, stroma, and myometrium. The individual or collective contribution of these cell types to uterine receptivity is poorly understood. The luminal epithelium is perceived as a major mediator of uterine receptivity, transmitting signals to other compartments. Estrogen and P4 coordinate uterine functions via multiple paracrine, juxtacrine, and autocrine factors in a spatiotemporal manner. One major mediator of estrogen action is LIF, a member of the interleukin-6 family of cytokines. LIF is essential for uterine receptivity and implantation, as its deletion imposes implantation failure in mice. LIF binds its receptor LIFR, which partners with co-receptor gp130 to activate the downstream signaling via signal transducer and activator of transcription 3 (Stat3). P4 is considered the 'hormone of pregnancy', and many P4-induced genes in the uterus participate in peri-implantationThe article discusses the mechanisms of implantation and the factors influencing successful pregnancy. It highlights the importance of the peri-implantation period, where defects can lead to adverse outcomes such as preeclampsia, miscarriage, and preterm birth. The review emphasizes the complex molecular signaling networks that coordinate implantation and decidualization, which are essential for a successful pregnancy. Understanding these mechanisms can help improve natural and in vitro fertilization (IVF) outcomes. Pregnancy is a complex, irreversible process involving implantation, decidualization, placentation, and parturition. The success of each event is crucial for progression to the next stage. However, the molecular dialogue governing these events is not fully understood. The window of implantation is a limited time when the blastocyst is competent for implantation. If this coordination is out of phase, implantation fails or becomes defective. In humans, natural conception per cycle is poor, and 75% of failed pregnancies are due to implantation failure. Successful implantation involves close interactions between the uterus and blastocyst. However, ethical restrictions and lack of mechanistic studies have delayed research on embryo-uterine interactions in humans. Knowledge from transgenic mouse models has helped understand the molecular basis of uterine receptivity, implantation, and decidualization in humans. The concept of uterine receptivity was first proposed by Alexandare Psychoyos. Blastocysts implant only when transferred into receptive uteri. Reciprocal embryo transfer experiments in delayed implanting mouse models showed that blastocyst activation is also critical for implantation. The window of receptivity is transient in humans, and implantation beyond this window results in spontaneous miscarriages. However, many miscarriages result from embryonic abnormalities, including aneuploidy. Successful implantation involves close interactions between the uterus and blastocyst. The uterus is composed of three major tissue compartments: epithelium, stroma, and myometrium. The individual or collective contribution of these cell types to uterine receptivity is poorly understood. The luminal epithelium is perceived as a major mediator of uterine receptivity, transmitting signals to other compartments. Estrogen and P4 coordinate uterine functions via multiple paracrine, juxtacrine, and autocrine factors in a spatiotemporal manner. One major mediator of estrogen action is LIF, a member of the interleukin-6 family of cytokines. LIF is essential for uterine receptivity and implantation, as its deletion imposes implantation failure in mice. LIF binds its receptor LIFR, which partners with co-receptor gp130 to activate the downstream signaling via signal transducer and activator of transcription 3 (Stat3). P4 is considered the 'hormone of pregnancy', and many P4-induced genes in the uterus participate in peri-implantation