Glock, J. L., & Brumsted JR (1995). Color flow pulsed Doppler ultrasound in diagnosing luteal phase defect. Fertility and Sterility, 64(3), 500-504. https://doi.org/10.1016/s0015-0282(16)57783-8
Glock JL, Brumsted JR. Color flow pulsed Doppler ultrasound in diagnosing luteal phase defect. Fertil Steril. 1995;64(3):500-504. doi:10.1016/s0015-0282(16)57783-8
Glock, Jacob L., and John R. Brumsted. "Color flow pulsed Doppler ultrasound in diagnosing luteal phase defect." Fertility and sterility, vol. 64, no. 3, 1995, pp. 500-504.
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Corpus luteum blood flow resistance was higher in 3 women with LPD
In a 1995 prospective pilot of 10 women at risk for luteal phase defect (LPD), blood flow to the corpus luteum met higher resistance in the 3 women with LPD than in the 6 with normal cycles. One woman did not ovulate and was excluded. The authors suggest Doppler may help assess luteal phase adequacy.
Key Findings
Of 9 women who ovulated, 3 (33.3%) had LPD by endometrial biopsy and 6 (66.7%) had a normal cycle. One further woman did not ovulate.
Mean resistance index was significantly higher in LPD than in normal women across the follicular and luteal phases (P = 0.02).
Peak systolic and end diastolic velocities generally ran lower in LPD, but the differences were not statistically significant (P = 0.54 and P = 0.11).
Resistance index and serum progesterone were strongly correlated at each luteal time point, strongest in the midluteal phase (r = -0.80, P < 0.01).
In normal women the dominant ovary had lower resistance than the other ovary (0.50 versus 0.65, P = 0.001). Women with LPD showed no such difference (0.60 versus 0.66, P = 0.37).
Interpretation
This is a small single-center prospective study of one natural cycle per woman. Only 3 women had LPD, diagnosed when the endometrial biopsy was more than 3 days out of phase. The authors report an association between blood-flow resistance and luteal function in 3 women with LPD and 6 with normal cycles. They do not test whether impaired blood flow causes LPD. The authors state that the sample is too small to set a cutoff value for diagnosis. The women had regular cycles and were at risk for LPD, so the findings do not describe women in general.
RRM Context
Restorative reproductive medicine evaluates luteal function in relation to ovulation, so timing matters. The study anchored its exams to the LH surge. Doppler adds an imaging marker to the progesterone and biopsy measures. The authors raise the possibility of using it as an adjunct to progesterone measurement.
Our editorial summary of this paper, not the article's abstract.
Abstract
Objective
To determine whether color flow pulsed Doppler analysis of corpus luteum blood flow in normal cycles differs from cycles with a luteal phase defect.
Design
A prospective study of natural ovarian cycles.
Setting
The University of Vermont Reproductive Endocrinology and Infertility Service.
Patients
Ten women with regular menstrual cycles and at risk for luteal phase defect (LPD) four with unexplained infertility, two with recurrent abortion, and four with age > 35 years.
Interventions
All women were examined by transvaginal color flow pulsed Doppler during the early follicular, late follicular, early luteal, midluteal, and late luteal phase of the menstrual cycle. Venous blood for P concentration was drawn on each day of Doppler exam. Urine testing for LH surge and endometrial biopsy during the late luteal phase were performed on each patient.
Main Outcome Measures
Lowest resistance index associated with the highest amplitude signal from intraovarian vessels of each ovary, dated endometrial biopsies, serum P.
Results
Mean resistance indexes in LPD patients (n = 3) were significantly higher compared with normal women (n = 6) throughout the follicular and luteal phases. One patient remained anovulatory and was excluded from statistical analysis. Although systolic and diastolic velocities generally were observed to be lower in LPD patients compared with normal women, these differences were not statistically significant. High correlations were observed between P and resistance index within each luteal time point, achieving its highest value during the midluteal phase.
Conclusions
This initial study provides evidence that color flow pulsed Doppler analysis of blood flow impedance to the corpus luteum may aid in assessing luteal phase adequacy.
Proximal tubal obstruction, either unilateral or bilateral, is a frequent finding on hysterosalpingogram (HSG). Approximately two-thirds of the fallopian tubes resected for proximal tubal obstruction reveal an absence of luminal occlusion. The distinction between true pathologic occlusion and either spasm or plugging is crucial in determining therapy. We combined hysteroscopic cannulation of the proximal fallopian tube with laparoscopy in 11 patients with proximal tubal obstruction diagnosed by HSG and confirmed at laparoscopy. Hysteroscopic cannulation was able to be performed in 72% of the fallopian tubes attempted, and there was a postcannulation patency rate by HSG of 73%. Six of the 11 patients became pregnant after tubal cannulation and adjunctive distal tubal surgery. Hysteroscopic cannulation of the fallopian tube is a safe diagnostic procedure that can be used to identify those patients with true proximal occlusion, and may also serve as a therapeutic procedure in some of these patients.
Evidence from our laboratory with the use of cultured (primary and passaged) cells has extended our initial observation that human uterine fibroid is an extrapituitary source of prolactin. Fibroid prolactin antigen in conditioned medium reacted specifically in radioimmunoassay for human pituitary prolactin. Control experiments demonstrated that the radioimmunoassay results were not spurious due to degradation of tracer 125I-labeled prolactin. Immunoparallel dilution curves indicated antigenic relatedness of pituitary and fibroid prolactin. In a calibrated Sephadex G-100 column, fibroid prolactin eluted in the same region (20.3 to 20.9 kd) as purified pituitary prolactin. Glycosylated prolactin, detected by concanavalin A affinity column chromatography, appeared to constitute only a small percentage of fibroid prolactin made in culture. The ratio of fibroid prolactin bioactivity (lactogen Nb2 lymphoma bioassay) to antigen (radioimmunoassay) was 0.77. These data indicate that human uterine fibroid tissue produces a molecule similar to or, perhaps, identical with pituitary prolactin.
Kupesic S et al., 1997·Eur J Obstet Gynecol Reprod Biol
To evaluate intraovarian resistance index (RI) in 47 healthy fertile volunteers with ovulatory cycles, 28 patients with luteal phase defect (LPD) and four patients with luteinized unruptured follicle (LUF Sy). Transvaginal color Doppler assessment of the follicular and corpus luteum blood flow and plasma progesterone (P) levels were obtained in each patient. Significantly higher intraovarian artery RI (< 0.001) was obtained for LPD group than for controls during the luteal phase. In the control group both follicular and corpus luteum RI were significantly lower (P < 0.001) on the dominant side, while in LPD group no difference (P > 0.05) between the sides occurred. Mean P levels were significantly lower (P < 0.001) in the LPD group (6.9 +/- 2.3 ng/ml) than in controls (24.1 +/- 11.4 ng/ml). In all the LPD patients histopathology revealed delayed endometrial pattern, while normal endometrial dating was found in all the evaluated patients form the control group (n = 15). In the patients with LUF Sy (n = 4) similar RI values were obtained in the follicular and corpus luteum phase. There was no difference between the sides in terms of the intraovarian RI, while subnormal values of P were obtained in all the examined patients (14.1 +/- 6.2 ng/ml). Transvaginal color Doppler may predict the function capacity of the corpus luteum.
To assess the sensitivity and specificity of common clinical tests used for the diagnosis of luteal phase defect (LPD). The sensitivity and specificity of these tests for predicting low integrated P levels over the luteal phase were calculated. Outpatient reproductive endocrinology and infertility clinic at a university medical center. Fifty-eight strictly defined normal women were used to determine normal integrated luteal phase P levels. The study population was a separate 34 women who either were normal (n = 15) or were being evaluated for infertility or recurrent abortion (n = 19). These 34 study subjects all had the following tests performed in the same menstrual cycle: daily reproductive hormone levels, daily assessment of preovulatory follicle size, late luteal endometrial biopsies, and BBT charts. Basal body temperature, maximum preovulatory follicle size, dated endometrial biopsies, and serum P levels (single and multiple) were used in an attempt to predict which patients had low integrated P levels. Unacceptably low sensitivity and/or specificity levels were found for the following tests: appearance of BBT charts, luteal phase length, and preovulatory follicle diameter. Timed endometrial biopsy was found to have marginally acceptable sensitivity and specificity levels whether dated by next menstrual period or midcycle events. The best test for the prediction of low integrated P was a single serum P level from the midluteal phase that was < 10 ng/mL (31.8 nmol/L) or a sum of three random serum P measurements that was < 30 ng/mL (95.4 nmol/L) (also obtained in the midluteal phase). Luteal phase defect is a relatively uncommon but important cause of infertility and/or habitual abortion. The recommended test for the determination of LPD is a midluteal phase single serum P level < 10 ng/mL or the sum of three serum P levels that is < 30 ng/mL. The endometrial biopsy is a second line test that is only recommended when LPD needs to be evaluated in a treated cycle (ovulation induction or supplemental P).
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.
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.
PMID 7641901 7641901 DOI 10.1016/s0015-0282(16)57783-8 10.1016/s0015-0282(16)57783-8 Glock et al. 1995, Glock 1995
Cite this article
Glock, J. L., & Brumsted JR (1995). Color flow pulsed Doppler ultrasound in diagnosing luteal phase defect. Fertility and Sterility, 64(3), 500-504. https://doi.org/10.1016/s0015-0282(16)57783-8
Glock JL, Brumsted JR. Color flow pulsed Doppler ultrasound in diagnosing luteal phase defect. Fertil Steril. 1995;64(3):500-504. doi:10.1016/s0015-0282(16)57783-8
Glock, Jacob L., and John R. Brumsted. "Color flow pulsed Doppler ultrasound in diagnosing luteal phase defect." Fertility and sterility, vol. 64, no. 3, 1995, pp. 500-504.
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