Endometrial biopsy in the evaluation of infertility

A C Wentz

doi:10.1016/s0015-0282(16)44530-9

Diagnostics · Endometrial Assessment

Endometrial biopsy in the evaluation of infertility

Wentz AC

Published February 1980 Fertility and Sterility, 33(2), 121-124

DOI 10.1016/s0015-0282(16)44530-9 PMID 7353687

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RRM Academy Synopsis

Endometrial biopsy found 29.5% out of phase in 149 infertile patients

A 1980 single-clinic case series of 149 infertility patients found that the first endometrial biopsy was out of phase in 44 patients, 29.5%. The biopsy checks the age of the uterine lining against the next period, to look for luteal phase inadequacy. Among patients not taking clomiphene citrate, 30.5% had an out-of-phase biopsy.

Key Findings

149 patients had 210 endometrial biopsies. The first was in phase for 92 (61.7%), out of phase for 44 (29.5%), and unclassifiable for 13 (8.7%).
Among patients not taking clomiphene citrate, 30.5% had an out-of-phase first biopsy.
Of 31 patients with an out-of-phase first biopsy who had a second one, 6 were in phase, 22 were out of phase, and 3 were sampled in the cycle of conception.
For about one-half of the patients with the defect, the author found no likely cause.
One ampullary ectopic pregnancy was the only unwanted event reported with a biopsy, and the author judged the biopsy unlikely to have caused it. Every attempted biopsy gave enough tissue to read.

Interpretation

This is a case series from one clinic in 1980, with no comparison group. The author describes a patient group with a high share of menstrual and ovulation problems and fewer than usual with tubal or pelvic disease. The rates describe that mix of patients. The author writes that these data cannot show whether finding or treating luteal phase inadequacy changes the chance of pregnancy or delivery. The numbers were too small for statistical analysis.

RRM Context

The author looked for a cause in infertility patients and scheduled each biopsy from cycle history or basal body temperature readings. RRM shares that cycle-informed, evaluation-first approach. About one-half of the patients found to have luteal phase inadequacy had no earlier sign of it.

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

Abstract

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.

Topics

By this author

Safety and Risks · Maternal Complications

Complications of pregnancy in infertile couples: routine treatment versus assisted reproduction

Hill GA et al., 1990 Obstet Gynecol

Ninety pregnancies conceived by infertile couples using assisted reproductive technologies and 86 pregnancies conceived by infertile couples with routine infertility treatment were analyzed to determine the outcome of and the complications experienced during the pregnancies. Pregnancies ending after 24 weeks' gestation were evaluated for the following complications: pregnancy-induced hypertension, diabetes mellitus, preterm labor, premature rupture of membranes, placenta previa, and fetal growth retardation. A matched control group of normal fertile patients admitted to the obstetric service at Vanderbilt University Medical Center was used to compare the incidence of pregnancy complications among the groups. In the group treated by assisted reproduction, 81 pregnancies were singleton and nine were multiple gestations, whereas in the routine group, 84 were singleton and two were multiple gestations. In the group treated by assisted reproduction, 29 of 90 gestations (32%) ended before 24 weeks, compared with 18 of 86 (21%) in the routine group, a nonsignificant difference. Mean birth weight and gestational age were similar among the three groups for singleton gestations. Among multiple gestations, the mean (+/- standard error of the mean [SEM]) birth weights were 2513 +/- 115, 724 +/- 57, and 2282 +/- 132 g in the group treated by assisted reproduction, the group receiving routine methods, and the control group, respectively (P less than .001 when those treated by routine methods were compared with the other two groups). The mean (+/- SEM) gestational ages were 36 +/- 1.2, 26.5 +/- 2.0, and 35.5 +/- 1.2 weeks, respectively (P less than .01 comparing those treated by routine methods and the other two groups).(ABSTRACT TRUNCATED AT 250 WORDS)

Ovarian Hormones · Progesterone

Absorption of oral progesterone is influenced by vehicle and particle size

Hargrove JT et al., 1989 Am J Obstet Gynecol

The oral route of progesterone administration has long been considered impractical because of poor absorption and short biologic half-life. Recent reports suggest that micronization of progesterone enhances absorption and increases serum and tissue levels of progesterone. This study checks serum progesterone levels before and 0.5, 1, 2, 3, 4, and 6 hours after oral administration of 200 mg of progesterone in seven subjects. Progesterone was plain milled, micronized, plain milled in oil, micronized in oil, or micronized in enteric-coated capsules. All patients exhibited a significant increase in serum progesterone levels after oral progesterone administration. Mean peak progesterone levels (30.3 +/- 7.0 ng/ml) (p less than 0.005) were achieved with micronized progesterone in oil at 2.0 +/- 0.3 (p less than 0.05) hours after administration. Four types of oral progesterone had equivalent mean peak elevations and mean times to peak: plain milled, 9.6 +/- 2.5 ng/ml at 4.0 +/- 0.5 hours; micronized 13.2 +/- 2.4 ng/ml at 3.2 +/- 0.4 hours; plain milled in oil, 11.3 +/- 3.0 ng/ml at 4.0 +/- 0.5 hours; and micronized in enteric-coated capsules, 11.2 +/- 3.0 ng/ml at 4.1 +/- 0.7 hours. Contrary to traditional teaching, these data show that significant serum progesterone levels can be achieved by oral administration. Absorption can be significantly improved by the physical characteristics of the progesterone and the vehicle used with oral administration.

Endometrial Assessment · Luteal Phase Biopsy

Diagnosis and management of out-of-phase endometrial biopsies among patients receiving clomiphene citrate for ovulation induction

Keenan JA et al., 1989 Fertil Steril

Eighty-seven patients who underwent a late secretory phase endometrial biopsy while taking clomiphene citrate (CC) for ovulation induction were studied. Of the endometrial biopsies, 21 (24%) showed an endometrium greater than 2 days out of phase (OOP) with respect to the subsequent menstrual cycle. All 87 patients were categorized by age, weight, CC dosage, and underlying disease entity. The patients then were evaluated by these categories in relation to the incidence of an OOP biopsy while taking CC. Patients with a diagnosis of hypothalamic amenorrhea were statistically more likely to have an OOP endometrium. No other subgroup showed an increased or decreased incidence of OOP biopsies. Conception and spontaneous abortion rates were similar among patients with in-phase biopsies and those with out-of-phase biopsies, which subsequently were corrected with further medical therapy. An aggressive approach to the diagnosis and treatment of luteal phase insufficiency in patients who receive CC for ovulation induction is recommended.

Hormonal Agents · Progesterone and Progestins

Sedative and hypnotic effects of oral administration of micronized progesterone may be mediated through its metabolites

Arafat ES et al., 1988 Am J Obstet Gynecol

Progesterone and its metabolites were measured in serum extracts by radioimmunoassay and gas chromatography-mass spectrometry, respectively, after ingestion of micronized progesterone by eight postmenopausal women. One subject received 400 mg of micronized progesterone orally that induced a hypnotic state that lasted for approximately 2 hours. Blood samples were drawn periodically from all subjects for measurement of progesterone and its metabolites in serum. Levels of serum progesterone and its metabolites increased significantly from baseline values and reached a peak between 2 and 6 hours after oral progesterone administration. Significant quantities of five compounds (progesterone, 5 alpha-pregnan-3 alpha-ol-20-one, 5 beta-pregnan-3 alpha-ol-20-one, 5 beta-pregnan-3 alpha,20 beta-diol, and 5 beta-pregnan-3 alpha-ol-11,20-dione) that have been reported to possess anesthetic qualities were identified. The sedative and hypnotic effects of oral administration of progesterone may be mediated through those compounds.

Related research

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.

Endometrial Assessment · Luteal Phase Biopsy

Endometrial biopsy findings in infertility: analysis of 12,949 cases

Sahmay S et al., 1995 Int J Fertil Menopausal Stud

Endometrial biopsy has been an important way of assessing infertile couples for several years. In this review of a wide-ranging series of endometrial biopsies of infertile couples in the Turkish population it was our aim to find the distribution of results according to the years 1956-1966, 1967-1980, 1981-1992. University hospital. 12,949 endometrial biopsies, referred to our gynecological pathology laboratory for infertility investigation between 1956 and 1992. Patient report files from pathology laboratory data, analyzed retrospectively. The assessment of the biopsies is made by the same pathologist. 78.8% of cases had primary infertility, 21.2% secondary. Most of them were in the age group 26-35 years (48.8%). 37.58% of cases were found to show normal secretory endometrium, 20.95% proliferative endometrial changes, and 28.22% signs of luteal phase defect (LPD). Other local endometrial factors were also encountered, but in 1.79% the sample was considered insufficient for diagnosis. Moreover, in nine cases, malignancy was diagnosed with the help of endometrial biopsy. During the study period, cases of normal secretory endometrium and tuberculous endometritis were observed to decrease and LPD to increase significantly. It is worthy to note that in only 28 (0.21%) cases had endometrial biopsies been performed during a pregnancy cycle. We conclude that endometrial biopsy not only shows the hormonal response of endometrium but gives additional information about the local factors of endometrium concerning atrophy, specific and non-specific infections, and malignancy.

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

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

Cumming DC et al., 1985 Fertil Steril

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.

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

PMID 7353687 7353687 DOI 10.1016/s0015-0282(16)44530-9 10.1016/s0015-0282(16)44530-9 Wentz et al. 1980, Wentz 1980

Cite this article

Wentz, A. C. (1980). Endometrial biopsy in the evaluation of infertility. Fertility and sterility, 33(2), 121-124. https://doi.org/10.1016/s0015-0282(16)44530-9

Keywords

Biopsy, Clomiphene/pharmacology, Endometrium/pathology, Female, Humans, Infertility, Female/diagnosis, Luteal Phase/drug Effects, Menstruation Disturbances/diagnosis, Time Factors, Clomiphene