Horm Res 1992:37(suppl 1):3—l
Department of Obstetrics and Gynecology. School of Medicine. Teikyo University. Tokyo.Japan
New Aspects of the Physiology and Pathology of the Luteal Phase: An Overview
The luteal phase defect (LPD) is not a unique and inde pendently established clinical entity, but a syndrome char acterized by a multifaceted pathogenesis. Several indica tors and laboratory findings lead to its diagnosis: a short ened luteal phase in basal body temperature, low blood progesterone levels, discrepancies in endometrial histolog ical findings, and so forth. Clinically, the LPD is defined as the impaired function of the corpus lutcum, leading to vari ous signs and symptoms such as a change in the shape of the high phase in the basal body temperature chart, irregular uterine bleeding, or infertility. The way in which the LPD causes infertility has been simply explained as follows: in the LPD. impaired secretion of sex steroids, especially progesterone, results in inade quate development of the endometrium, which thus dis turbs the implantation of the conceptus and induces an early abortion. Because, in many cases, histologic examination has been employed to diagnose the LPD. this concept for the mechanism of infertility in the LPD has been unquestioningly accepted by gynecologists. However, a strict differentiation has not been made between the pri mary failure of the endometrium to respond to hormonal changes, and hormonal defects due to the failure of corpus luteum function. When an impaired endometrium is found, several possi bilities exist as mechanisms underlying infertility in the LPD. (1) A primary failure in the endometrial response to hormonal changes disturbs the implantation of the nor mally developed conceptus. (2) Impaired secretion of hor mones from the corpus luteum due to failure of the luteotropic system, to the primary refractoriness of the corpus
luteum itself, or to an increased activity of the luteolytic system, leading to endometrial inadequacy and early abor tion. (3) An abnormal conception due to an immature ovum is the primary cause of the infertility: follicle develop ment is impaired and/or there is an inadequate or insuffi cient surge of luteinizing hormone, and the LPD is a sec ondary result of the abnormal follicular phase. Figure 1 shows a classification of the LPD based on the complicated considerations discussed above. A variety of possible causes for infertility in the LPD leads, consequently, to multiple choices for its treatment. Treatments should not be based on symptomatology alone, but should be as rationally based as they are for other dis eases. Pathogenesis-oriented treatments are shown in table I. In terms of successful pregnancies, little efficacy has been found with progesterone supplement therapy, but ovulation induction, and bromocriptine administration have resulted in a pregnancy rate > 30% . These results sug gest that the primary cause of infertility in women with the LPD lies not in the luteal phase itself (i.c. the disturbed implantation of a normally developed ovum), but in a less qualified ovum due to impaired follicle development or ovulatory failure, and the LPD is only a result of those in adequacies in the follicular phase. Most gynecologists, when they find an LPD cycle, arc inclined to define the LPD as the cause of infertility, espe cially functional sterility. Once found, does the LPD appear consecutively or sporadically? This question further complicates discussions on the diagnosis and treatment of the LPD.
Hiroyuki Mori. MD Department of Obstetrics anil Gynecology Teikyo University. School of Medicine 2-11-1. Kaga. Itubashi-Ku. Tokyo 173 (Japan)
IW2 Karger AG. Basel 0301-0163/02/0377-0003 $2.75/0
Downloaded by: King's College London 137.73.144.138 - 5/25/2018 2:50:37 PM
H. M ori
— Inadequate proliferation —
Inadequate endometrial response —
Luteal phase defect (LPD) — (Luteal phase inadequacy) (Luteal phase deficiency)
Inadequate response of the secretory endometrium
— Impaired follicle development —
Inadequate corpus luteum function (Luteal insufficiency) (Short luteal phase)
----- Insufficient or inadequate luteinizing hormone surge — Impaired luteotropic system
— Increased luteolysis
—
Primary dysfunction of the corpus luteum
Fig. 1. C lassification of the luteal phase defect (LPD).
Table 1. Pathogenesis-oriented treatment of the luteal phase defect
Pathogenesis
Treatment
Inadequate proliferation
Supplementary estrogen Sequential estrogen-gestagen Supplementary estrogen Supplementary gestagen with/without estrogen Driving of follicle maturation (hMG, clomiphene. bromocriptine) Induction of ovulation (hMG. clomiphene. bromocriptine) Control of LH surge (GnRH analog) Driving of ovulation (hCG) Luteal support (hCG. GnRH pulse, progesterone) Suppression of luteolysis (bromocriptine) Supplementary gestagen with/without estrogen
Inadequate response of the secretory endometrium Impaired follicle development Insufficient or inadequate l.ll surge Impaired luteotropic system Increased luteolysis Primary dysfunction of the corpus luteum
LH = Luteinizing hormone: hMG = human menopausal gonadotropin: GnRH = gonadotropin-releasing hormone: hCG = human chorionic gonadotropin.
4
Mori
infertility, not least because of the difficulties in studying the physiology and pathology of the luteal phase in humans. In this issue, several papers discuss the physiological mechanisms controlling luteal function, new aspects in the diagnosis of the LPD. new clinical points of view on the pathophysiology and treatment of the LPD. and the rela tionship between implantation and luteal function.
New Aspects of the Physiology and Pathology of the Luteal Phase: An Overview
Downloaded by: King's College London 137.73.144.138 - 5/25/2018 2:50:37 PM
Little is known about the physiology of the human luteal phase. Most luteal phenomena are speculations based on results in animal experiments. The luteotropic or lutcolytic mechanisms in humans remain obscure, and. moreover, the most appropriate and precise method to assess luteal function has yet to be established. While clinicians, for sev eral decades, have considered the LPD to be one of the most important causes of infertility, no rational explanation yet exists for the relationship between the LPD and female
Department of Obstetrics and Gynecology. School of Medicine. Teikyo University. Tokyo.Japan
New Aspects of the Physiology and Pathology of the Luteal Phase: An Overview
The luteal phase defect (LPD) is not a unique and inde pendently established clinical entity, but a syndrome char acterized by a multifaceted pathogenesis. Several indica tors and laboratory findings lead to its diagnosis: a short ened luteal phase in basal body temperature, low blood progesterone levels, discrepancies in endometrial histolog ical findings, and so forth. Clinically, the LPD is defined as the impaired function of the corpus lutcum, leading to vari ous signs and symptoms such as a change in the shape of the high phase in the basal body temperature chart, irregular uterine bleeding, or infertility. The way in which the LPD causes infertility has been simply explained as follows: in the LPD. impaired secretion of sex steroids, especially progesterone, results in inade quate development of the endometrium, which thus dis turbs the implantation of the conceptus and induces an early abortion. Because, in many cases, histologic examination has been employed to diagnose the LPD. this concept for the mechanism of infertility in the LPD has been unquestioningly accepted by gynecologists. However, a strict differentiation has not been made between the pri mary failure of the endometrium to respond to hormonal changes, and hormonal defects due to the failure of corpus luteum function. When an impaired endometrium is found, several possi bilities exist as mechanisms underlying infertility in the LPD. (1) A primary failure in the endometrial response to hormonal changes disturbs the implantation of the nor mally developed conceptus. (2) Impaired secretion of hor mones from the corpus luteum due to failure of the luteotropic system, to the primary refractoriness of the corpus
luteum itself, or to an increased activity of the luteolytic system, leading to endometrial inadequacy and early abor tion. (3) An abnormal conception due to an immature ovum is the primary cause of the infertility: follicle develop ment is impaired and/or there is an inadequate or insuffi cient surge of luteinizing hormone, and the LPD is a sec ondary result of the abnormal follicular phase. Figure 1 shows a classification of the LPD based on the complicated considerations discussed above. A variety of possible causes for infertility in the LPD leads, consequently, to multiple choices for its treatment. Treatments should not be based on symptomatology alone, but should be as rationally based as they are for other dis eases. Pathogenesis-oriented treatments are shown in table I. In terms of successful pregnancies, little efficacy has been found with progesterone supplement therapy, but ovulation induction, and bromocriptine administration have resulted in a pregnancy rate > 30% . These results sug gest that the primary cause of infertility in women with the LPD lies not in the luteal phase itself (i.c. the disturbed implantation of a normally developed ovum), but in a less qualified ovum due to impaired follicle development or ovulatory failure, and the LPD is only a result of those in adequacies in the follicular phase. Most gynecologists, when they find an LPD cycle, arc inclined to define the LPD as the cause of infertility, espe cially functional sterility. Once found, does the LPD appear consecutively or sporadically? This question further complicates discussions on the diagnosis and treatment of the LPD.
Hiroyuki Mori. MD Department of Obstetrics anil Gynecology Teikyo University. School of Medicine 2-11-1. Kaga. Itubashi-Ku. Tokyo 173 (Japan)
IW2 Karger AG. Basel 0301-0163/02/0377-0003 $2.75/0
Downloaded by: King's College London 137.73.144.138 - 5/25/2018 2:50:37 PM
H. M ori
— Inadequate proliferation —
Inadequate endometrial response —
Luteal phase defect (LPD) — (Luteal phase inadequacy) (Luteal phase deficiency)
Inadequate response of the secretory endometrium
— Impaired follicle development —
Inadequate corpus luteum function (Luteal insufficiency) (Short luteal phase)
----- Insufficient or inadequate luteinizing hormone surge — Impaired luteotropic system
— Increased luteolysis
—
Primary dysfunction of the corpus luteum
Fig. 1. C lassification of the luteal phase defect (LPD).
Table 1. Pathogenesis-oriented treatment of the luteal phase defect
Pathogenesis
Treatment
Inadequate proliferation
Supplementary estrogen Sequential estrogen-gestagen Supplementary estrogen Supplementary gestagen with/without estrogen Driving of follicle maturation (hMG, clomiphene. bromocriptine) Induction of ovulation (hMG. clomiphene. bromocriptine) Control of LH surge (GnRH analog) Driving of ovulation (hCG) Luteal support (hCG. GnRH pulse, progesterone) Suppression of luteolysis (bromocriptine) Supplementary gestagen with/without estrogen
Inadequate response of the secretory endometrium Impaired follicle development Insufficient or inadequate l.ll surge Impaired luteotropic system Increased luteolysis Primary dysfunction of the corpus luteum
LH = Luteinizing hormone: hMG = human menopausal gonadotropin: GnRH = gonadotropin-releasing hormone: hCG = human chorionic gonadotropin.
4
Mori
infertility, not least because of the difficulties in studying the physiology and pathology of the luteal phase in humans. In this issue, several papers discuss the physiological mechanisms controlling luteal function, new aspects in the diagnosis of the LPD. new clinical points of view on the pathophysiology and treatment of the LPD. and the rela tionship between implantation and luteal function.
New Aspects of the Physiology and Pathology of the Luteal Phase: An Overview
Downloaded by: King's College London 137.73.144.138 - 5/25/2018 2:50:37 PM
Little is known about the physiology of the human luteal phase. Most luteal phenomena are speculations based on results in animal experiments. The luteotropic or lutcolytic mechanisms in humans remain obscure, and. moreover, the most appropriate and precise method to assess luteal function has yet to be established. While clinicians, for sev eral decades, have considered the LPD to be one of the most important causes of infertility, no rational explanation yet exists for the relationship between the LPD and female
