The late luteal phase in infertile women: comparison of simultaneous endometrial biopsy and progesterone levels

D C Cumming; Louis H. Honoré; J Z Scott; K P Williams

doi:10.1016/s0015-0282(16)48553-5

Diagnostics · Endometrial Assessment

The late luteal phase in infertile women: comparison of simultaneous endometrial biopsy and progesterone levels

Cumming DC, Honoré LH, Scott JZ, Williams KP

Published May 1985 Fertility and Sterility, 43(5), 715-719

DOI 10.1016/s0015-0282(16)48553-5 PMID 3996616

Read our synopsis

RRM Academy Synopsis

Lining biopsies showed delayed development in 42 of 98 infertile women

A 1985 clinic study of 107 infertile women found about 4 out of 10 datable lining biopsies showed delayed development. The women had regular cycles and no significant tubal or male factor. On the last day before menses, blood progesterone was higher in women with delayed biopsies.

Key Findings

Of 98 biopsies that could be day-dated, 56 were in phase and 42 were out of phase.
Biopsies in the last 4 days of the cycle: 27 of 70 (38.6%) were out of phase. Earlier biopsies: 15 of 28 (53.6%), a significantly higher share (P < 0.05).
On the last day before menses, progesterone was significantly higher in women with out-of-phase biopsies than in women with in-phase biopsies (P < 0.05).
In the late midluteal phase, progesterone was significantly lower in women whose biopsies showed maturational delay than in women with normal development (P < 0.05).
Six women were pregnant at biopsy. Two pregnancies continued, one was ectopic, and three ended in early pregnancy loss.

Interpretation

The study compared one biopsy and one blood sample per woman at a single university clinic. The authors describe their data as suggestive. Participants were referred women aged 20 to 38 years with regular cycles and at least 1 year of infertility. The authors report supportive evidence that biopsies taken more than 4 days before menses are more likely to be out of phase. Outcome data cover only the six women pregnant at biopsy.

RRM Context

Couples with regular cycles and no major tubal or male problem often get the label unexplained infertility. Restorative reproductive medicine treats that label as undiagnosed. It looks for causes after ovulation too. The authors list possible sources of the delay, including hormone signals earlier in the cycle.

Our editorial summary of this paper, not the article's abstract.

Abstract

Endometrial biopsy specimens were obtained from 107 normally menstruating infertile women 2 to 3 days before the anticipated onset of menses and were day-dated according to histologic criteria. A simultaneous blood sample was obtained for measurement of progesterone (P) and beta-subunit of human chorionic gonadotropin. Of 98 biopsies which could be accurately dated, 56 were in-phase (IP) and 42 were out-of-phase (OOP). Mean serum P levels were significantly lower in women with OOP biopsies undertaken more than 4 days before the onset of menses. A sharp decline in serum P levels was observed in women with IP but not OOP biopsies, so that on the final premenstrual day serum P levels were significantly higher than normal in women with OOP biopsies. Pregnancy continued without interruption in two of six patients who underwent biopsy in the cycle of conception. One patient had an ectopic pregnancy; and the three remaining pregnant patients, all with subnormal P values, aborted. The study suggests that there is a high frequency of minor abnormalities in luteal function in normally menstruating, infertile women for whom tubal and male factors were normal. The frequency of subclinical pregnancy (2 of 107) was lower than anticipated from earlier studies.

Topics

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Hormone Testing · Serum Panels

Comparison of serum progesterone and endometrial biopsy for confirmation of ovulation and evaluation of luteal function

Shepard MK et al., 1977 Fertil Steril

An endometrial biopsy and a blood sample for progesterone determination obtained simultaneously in the midluteal phase of the cycles of 55 infertile women were compared for reliability for confirmation of presumptive ovulation and evaluation of luteal function. Progesterone levels of 3 ng/ml or greater were found in 90.5% of the cycles. Secretory endometrium was identified in 81% of the cycles. Thirty-three cycles yielded sufficient information to compare the two methods for evaluation of luteal function. Histology and progesterone levels were consistent with each other and the presumed time of ovulation in only 11 cycles. Histology was inconsistent with the presumed time of ovulation in 20 cycles, while progesterone was inconsistent in only two cycles. Additional samples for progesterone determinations were obtained during the biopsy cycles of 15 patients who presented adequate data for evaluation of luteal function. A single, well-timed progesterone determination appeared adequately to reflect the data obtained from serial samples in the same cycle. These results support the thesis that a single, well-timed serum progesterone determination is superior to a single endometrial biopsy as a screening method for confirmation of presumptive ovulation and for evaluation of luteal function.

Endometrial Assessment · Luteal Phase Biopsy

A prospective controlled study of luteal and endometrial abnormalities in an infertile population

Batista MC et al., 1996 Fertil Steril

To investigate whether luteal and endometrial abnormalities occur more frequently in an infertile population and thus contribute to infertility. Prospective controlled clinical study. Outpatient clinic in an academic research institution. Thirty-three fertile controls and 31 infertile women without ovulatory disorders, tubal disease, or male factors. All women underwent an endometrial biopsy 9 days after the LH surge followed by an IM injection of 5,000 IU hCG. Blood samples were drawn immediately before hCG administration for serum P and placental protein 14 (PP14) measurements, at 6 hours after hCG stimulation for serum P concentrations, and on day 5 after hCG administration for serum PP14 levels. Histologic dating of the endometrium and serum P and PP14 measurements. Abnormal endometrial biopsies occurred more frequently in infertile (43%) than in fertile women (9%). Except for one case, these specimens were not associated with low hCG-stimulated P levels. Serum PP14 measurements varied widely and did not discriminate subjects with abnormal endometrial development. Disruption of endometrial maturation without a concomitant defect of the corpus luteum occurs more frequently in an infertile population and thus may contribute to infertility.

Endometrial Assessment · Luteal Phase Biopsy

Endometrial biopsy in the evaluation of infertility

Wentz AC, 1980 Fertil Steril

One hundred and forty-nine patients presenting with infertility underwent two hundred and ten endometrial biopsies as part of a routine infertility evaluation. The initial biopsy was out of phase in 44 (29.5%), confirmed by subsequent biopsy to yield a total of 28 (19%) patients with luteal phase inadequacy. Of 44 patients taking clomiphene citrate, 13 (29.5%) had out-of-phase biopsies. Although hyperprolactinemia, recurrent miscarriages, extremes of reproductive life, and clomiphene citrate administration have been associated with an increased incidence of the defect, in this series a predisposing cause could not be detected in approximately one-half of the patients. The routinely obtained endometrial biopsy provides a safe, reproducible, and adequate means of providing histologic evidence for normal endometrial development for subsequent implantation.

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.

Diagnostics › Endometrial Assessment › Luteal Phase Biopsy · Reproductive Endocrinology › Luteal Phase › Luteal Phase Deficiency · Menstrual Cycle › Cycle Physiology › Luteal Phase

Louis H. Honoré

L Honoré

PMID 3996616 3996616 DOI 10.1016/s0015-0282(16)48553-5 10.1016/s0015-0282(16)48553-5 Cumming et al. 1985, Cumming 1985

Cite this article

Cumming, D. C., Honoré, L. H., Scott, J. Z., & Williams, K. P. (1985). The late luteal phase in infertile women: comparison of simultaneous endometrial biopsy and progesterone levels. Fertility and sterility, 43(5), 715-719. https://doi.org/10.1016/s0015-0282(16)48553-5

Keywords

Adult, Biopsy, Chorionic Gonadotropin/blood, Endometrium/pathology, Female, Humans, Infertility, Female/pathology/physiopathology, Luteal Phase, Pregnancy, Progesterone/blood, Time Factors, Chorionic Gonadotropin, Progesterone