Luteal phase deficiency: an inadequate endometrial response to normal hormone stimulation

J Balasch; J A Vanrell

Reproductive Endocrinology · Luteal Phase

Luteal phase deficiency: an inadequate endometrial response to normal hormone stimulation

Balasch J, Vanrell JA

Published November 1986 International Journal of Fertility, 31(5), 368-371

PMID 2898441

Abstract

Two hundred seventy-four infertile patients and 43 women with two or more previous first-trimester abortions underwent a luteal function evaluation by basal body temperature, plasma progesterone, estradiol and prolactin determination, and endometrial biopsy (repeated in a later cycle when the first was defective). An endometrial luteal phase deficiency was detected in 37 (13.5%) of the infertility cases and in 14 (32.5%) of the patients with recurrent miscarriage. However, the endometrial defect was associated with normal hormonal levels in the great majority of patients (86.3%).

Topics

By this author

Safety and Risks · Long Term Child Outcomes

Assisted reproductive technologies are associated with cardiovascular remodeling in utero that persists postnatally

Valenzuela-Alcaraz B et al., 2013 Circulation

Assisted reproductive technologies (ARTs) have been shown to be associated with general vascular dysfunction in late childhood. However, it is unknown whether cardiac remodeling is also present and if these changes already manifest in prenatal life. Our aim was to assess fetal and infant (6 months of age) cardiovascular function in ART pregnancies. This prospective cohort study included 100 fetuses conceived by ART and 100 control pregnancies. ART fetuses showed signs of cardiovascular remodeling, including a more globular heart with thicker myocardial walls, decreased longitudinal function (tricuspid ring displacement in controls: median, 6.5 mm [interquartile range, 6.1-7.1 mm]; tricuspid ring displacement in 5.5 mm [interquartile range, 5.1-6.1]; P<0.001), impaired relaxation, and dilated atria (atrial area in controls, 1.46 cm(2) [interquartile range, 1.2-1.5 cm(2)]; atrial area in ART, 1.6 cm(2) [interquartile range, 1.3-1.8 cm(2)]; P<0.001). Additionally, ART infants showed persistence of most cardiac changes and a significant increase in blood pressure and aortic intima-media thickness (systolic blood pressure in controls, 74 mm Hg [interquartile range, 67-83 mm Hg]; systolic blood pressure in ART, 83 mm Hg [interquartile range, 75-94 mm Hg]; P<0.001; aortic intima-media thickness in controls, 0.52 mm [interquartile range, 0.45-0.56 mm]; aortic intima-media thickness in ART, 0.64 mm [interquartile range, 0.62-0.67]; P<0.001). We could not demonstrate that our findings were directly caused by ART because of their association with various confounding factors, including intrauterine growth restriction or factors related to the cause of infertility. Children conceived by ART manifest cardiac and vascular remodeling that is present in fetal life and persists in postnatal life, suggesting opportunities for early detection and potential intervention. The underlying mechanisms and the effect of potential confounders such as growth restriction or prematurity remain to be elucidated.

Luteal Phase · Luteal Phase Deficiency

Early follicular phase follicle-stimulating hormone treatment of endometrial luteal phase deficiency

Balasch J et al., 1990 Fertil Steril

Fifteen infertile women with inadequate luteal phase, histologically documented in at least two separate cycles, and normal midluteal plasma levels of progesterone (greater than or equal to 10 ng/mL), estradiol (70 to 300 pg/mL), and prolactin (less than 20 ng/mL) received "pure" follicle-stimulating hormone (pFSH), 150 IU intramuscularly, for 4 days (days 1 to 4 of the cycle). The endometrial defect was corrected in 7 of the 15 (46.7%) patients during the first treated cycle. Hormonal levels were similar in control and treatment cycles. Two of 5 patients with no additional infertility factors except luteal phase deficiency (LPD) became pregnant and carried to term singleton pregnancies. In 5 additional infertile patients with normal luteal function as assessed by endometrial histological study (2 cycles) and hormone measurements (first study cycle), a third biopsy was performed in a consecutive cycle under pFSH administration. In no case was the normal secretory pattern impaired. It is concluded that (1) some forms of LPD may be successfully treated by early follicular pFSH therapy and (2) pFSH does not alter the normal endometrial secretory pattern.

Luteal Phase · Luteal Phase Deficiency

The significance of luteal phase deficiency on fertility: a diagnostic and therapeutic approach

Balasch J et al., 1986 Hum Reprod

Luteal phase deficiency, diagnosed by endometrial biopsy, was found in 1 out of 25 control fertile women and in 46 out of 355 infertile patients, a difference that was not significant. It was also found in 19 [corrected] out of 60 patients with early recurrent abortion which was significantly higher than in controls and in infertile patients. Pregnancy outcome was evaluated in treated and untreated groups of patients diagnosed as having luteal phase deficiency. Our data suggest that treatment improved the results of pregnancy in patients with recurrent abortion, but not in infertile patients.

Endometrial Assessment · Luteal Phase Biopsy

The endometrial biopsy for diagnosis of luteal phase deficiency

Balasch J et al., 1985 Fertil Steril

We studied endometrial luteal phase in specimens from 660 biopsies done in 300 patients from our infertility clinic. A minimum of two (240 women) or three (60 women) endometrial biopsy specimens from separate cycles were taken regardless of the previous histologic findings in all patients. Statistical analysis of results by the McNemar and the Cochran Q tests for the significance of changes leads us to conclude that a minimum of two, and even three, endometrial biopsy specimens are needed for diagnosis of luteal phase deficiency.

Related research

Luteal Phase · Luteal Phase Deficiency

Clinical importance of endometrial histology and progesterone level assessment in luteal-phase defect

Kusuhara K, 1992 Horm Res

In order to clarify the relationship between endometrial histology and progesterone (P4), plasma P4 and estradiol levels in the luteal phase were measured in 126 cases of unexplained infertility. Endometrial biopsies were performed in the midluteal period of menstrual cycles. Forty-three of the 126 cases showed retarded endometrium. Of these 43 cases, 23 exhibited three different types of abnormal P4 secretion. Type A showed low P4 levels throughout the luteal period. Type B showed low P4 levels only in the early luteal period. Type C showed normal P4 levels in the early luteal period followed by a prompt decline. These findings indicated that P4 determination during the early, mid- and late luteal phases is necessary to assess P4 secretion. However, 20 of the 43 cases had normal P4 levels through the entire luteal phase, demonstrating an insufficient response of the endometrium to P4. Consequently, histological examination of the endometrium is required to investigate the luteal phase defect.

Luteal Phase · Luteal Phase Deficiency

The diagnosis of luteal phase deficiency: a critical review

McNeely MJ et al., 1988 Fertil Steril

Luteal phase deficiency is an ovulatory dysfunction problem that is subtle but real. It may be the most common ovulatory problem in women. Luteal phase deficiency has been clearly demonstrated in the research setting (1) in spontaneous cycles, (2) when follicular maturation has been impeded, and (3) when luteotrophic influences have been suppressed. The diagnosis of LPD in the clinical setting remains problematic and controversial primarily because there is no practical diagnostic method that has been validated. This article has reviewed the methods that have been used to diagnose LPD. BBT charts are insensitive; these charts reliably diagnose LPD only when there are persistent short luteal phases. There is disagreement whether ovarian follicular size, as determined by ultrasonography, is decreased in LPD; however, ultrasonographic diagnosis of LPD would require daily scans through ovulation, which makes this approach impractical. Mild hyperprolactinemia is a probable cause of LPD in a minority of patients; a physician should obtain a PRL level in LPD women with the realization that there is considerable sampling variability. Determination of serum gonadotropin levels (LH or FSH or both) is not practical for the clinical diagnosis of LPD. Random serum P levels, whether single or multiple, are not helpful in the diagnosis of LPD in individual patients. The secretory pattern of P results in such wide confidence limits that P samples from individuals cannot be compared to normal in a useful manner. Most of the controversy about the diagnosis of LPD has centered around the use of individual serum P levels. The timed endometrial biopsy relies on the endometrium as a bioassay of P over time. The endometrial biopsy has not been carefully validated in terms of its sensitivity or accuracy for the diagnosis of LPD. However, it remains the best current method for the diagnosis of LPD when the standard guidelines for its use are followed. As opposed to the other tests for LPD, awareness of the usefulness of the biopsy has increased as we have learned more about CL physiology. No current research method for the diagnosis of LPD appears to be a practical method that could be applied in the clinical setting. Specific secretory proteins from the endometrium and methods to measure hormone secretion that circumvent the secretory pattern hold promise for improved methods to diagnose LPD in the future.

Luteal Phase · Luteal Phase Deficiency

Luteal phase deficiency: characterization of reproductive hormones over the menstrual cycle

Soules MR et al., 1989 J Clin Endocrinol Metab

The recurrent deficiency of progesterone (P) secretion by the corpus luteum has been associated with infertility and habitual abortion and given the clinical diagnosis of luteal phase deficiency (LPD). There is evidence that both follicular and luteal phase abnormalities can result in LPD cycles. In this study we have examined reproductive hormone levels and preovulatory follicular size in women with LPD (n = 10). For the purposes of this study, LPD was determined by an endometrial biopsy in the studied cycle that was more than 2 days out of phase. These biopsies were performed in women with infertility or habitual abortion who exhibited an out of phase biopsy in a prior cycle. The control group consisted of 28 normal women. Daily serum levels of the following hormones were determined in each subject: LH and FSH [immuno- and bioactive (LH-immuno and LH-bio)], P, estradiol (E2), and inhibin. The LPD women exhibited significant decreases in integrated luteal phase levels of inhibin [10,615 +/- 898 vs. 13,560 +/- 662 (U/L).days; P less than 0.02] and E2 [5,015 +/- 275 vs. 6,435 +/- 393 (pmol/L).days (1366 vs. 1753 (pg/mL).days); P less than 0.05] in addition to the expected decrease in P [280 +/- 23 vs. 420 +/- 23 (nmol/L).days (88 vs. 132 (ng/mL).days); P less than 0.01]. On days 6-11 after the LH surge (day 0), there was a significant (P less than 0.05) decrease in mean LH-bio levels in LPD compared with those in normal women (146 +/- 26 vs. 212 +/- 24 micrograms/L). The midcycle LH surge was deficient in LPD when both LH-immuno [482 +/- 30 vs. 672 +/- 43 (micrograms/L).days; P less than 0.01] and LH-bio [1711 +/- 179 vs. 2248 +/- 226 (micrograms/L).days; P less than 0.05] levels were compared with normal values. When comparing the follicular phase in LPD with that in normal women, similar follicle size, peak and integrated E2 levels, and mean LH and FSH (immuno and bio) levels were found. The only follicular phase abnormality noted in this study was decreased mean levels of serum inhibin in the early and midfollicular phases (221 +/- 19 vs. 308 +/- 25 U/L; P less than 0.01). In this group of women with LPD, low levels of inhibin in the follicular phase were consistent with the concept of a defect in function of the preovulatory follicle, possibly as a result of previously described defects in gonadotropin secretion in this condition.(ABSTRACT TRUNCATED AT 400 WORDS)

Luteal Phase · Luteal Phase Deficiency

The luteal phase defect

Jones GS, 1976 Fertil Steril

In summary, the luteal phase defect is a deficiency of corpus luteum progesterone steroidogenesis, either in amount or duration, or both. The clinical manifestations include either primary infertility or repeated first trimester abortions. The diagnosis can only be made clinically on the basis of a well-timed endometrial biopsy that is read histologically as 2 or more days out of phase with the next period in at least two cycles.

Reproductive Endocrinology › Luteal Phase › Luteal Phase Deficiency · Diagnostics › Endometrial Assessment › Luteal Phase Biopsy · Menstrual Cycle › Cycle Disorders › Ovulatory Disturbances

PMID 2898441 2898441 Balasch et al. 1986, Balasch 1986

Cite this article

Balasch, J., & Vanrell, J. A. (1986). Luteal phase deficiency: an inadequate endometrial response to normal hormone stimulation. International journal of fertility, 31(5), 368-371.

Keywords

Abortion, Habitual/etiology, Biopsy, Body Temperature, Endometrium/pathology/physiopathology, Estradiol/blood, Female, Humans, Infertility, Female/etiology, Luteal Phase, Pregnancy, Progesterone/blood, Prolactin/blood, Progesterone, Estradiol, Prolactin