Abstract

Luteal phase (LP) is the period of time beginning shortly after ovulation and ending either with luteolysis, shortly before menstrual bleeding, or with the establishment of pregnancy. During the LP, the corpus luteum (CL) secretes progesterone and some other hormones that are essential to prepare the uterus for implantation and further development of the embryo, the function known as uterine receptivity. LP deficiency (LPD) can occur when the secretory activity of the CL is deficient, but also in cases of normal CL function, where it is caused by a defective endometrial response to normal levels of progesterone. LPD is particularly frequent in treatments using assisted reproductive technology (ART). Controlled ovarian stimulation usually aims to obtain the highest number possible of good-quality oocytes and requires the use of gonadotropin-releasing hormone (GnRH) analogs, to prevent premature ovulation, as well as an ovulation trigger to achieve timed final oocyte maturation. Altogether, these treatments suppress pituitary secretion of luteinizing hormone (LH), required for the formation and early activity of the CL. In addition to problems of endometrial receptivity for embryos, LPD also leads to dysfunction of the local uterine immune system, with an increased risk of embryo rejection, abnormally high uterine contractility, and restriction of uterine blood flow. There are two alternatives of LPD prevention: a direct administration of exogenous progesterone to restore the physiological progesterone serum concentration independently of the CL function, on the one hand, and treatments aimed to stimulate the CL activity so as to increase endogenous progesterone production, on the other hand. In case of pregnancy, some kind of LP support is often needed until the luteal–placental shift occurs. If LPD is caused by defective response of the endometrium and uterine immune cells to normal concentrations of progesterone, a still poorly defined condition, symptomatic treatments are the only available solution currently available.

Highlights

  • Luteal phase (LP) is the period of time between the transformation of the dominant ovarian follicle into the corpus luteum (CL), shortly after ovulation, and either the establishment of pregnancy or the onset of menstrual bleeding [1]

  • LP deficiency (LPD) can occur in natural ovulatory cycles, causing infertility, though the prevalence of this condition remains to be determined

  • It was speculated that LPD in assisted reproductive technology (ART) cycles is caused by an overreaction of gonadotropin-releasing hormone (GnRH) analogs used to prevent premature ovulation during ovarian stimulation and/or by the inhibitory action of the ovulation trigger (HCG or GnRH agonist) on the forthcoming luteinizing hormone (LH) secretion by the pituitary, responsible for the maintenance of the CL activity required for endometrial receptivity until its role is taken over by embryo-derived human chorionic gonadotropin (HCG)

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Summary

Luteal Phase in Assisted Reproductive Technology

Jan Tesarik*, Cristina Conde-López, Maribel Galán-Lázaro and Raquel Mendoza-Tesarik. Specialty section: This article was submitted to Assisted Reproduction, a section of the journal Frontiers in Reproductive Health. LP deficiency (LPD) can occur when the secretory activity of the CL is deficient, and in cases of normal CL function, where it is caused by a defective endometrial response to normal levels of progesterone. Controlled ovarian stimulation usually aims to obtain the highest number possible of good-quality oocytes and requires the use of gonadotropin-releasing hormone (GnRH) analogs, to prevent premature ovulation, as well as an ovulation trigger to achieve timed final oocyte maturation. These treatments suppress pituitary secretion of luteinizing hormone (LH), required for the formation and early activity of the CL.

INTRODUCTION
PHYSIOLOGICAL BASIS OF CORPUS LUTEUM FORMATION AND MAINTENANCE
ROLE OF CORPUS LUTEUM IN EARLY PREGNANCY
ETIOLOGY OF LUTEAL PHASE DEFICIENCY
Impaired Corpus Luteum Secretory Activity
CONSEQUENCES OF LUTEAL PHASE DEFICIENCY
MANAGEMENT OF LUTEAL PHASE DEFICIENCY IN ASSISTED REPRODUCTIVE TECHNOLOGY
Luteal Phase Deficiency With Low Serum Progesterone Levels
Luteal Phase Deficiency With Normal Serum Progesterone Levels
CONCLUSIONS
Findings
AUTHOR CONTRIBUTIONS

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