| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
ORIGINAL RESEARCH |
From the Departments of Obstetrics and Gynecology, Radiology, and Medical Biostatistics, University of Vermont College of Medicine and Fletcher Allen Health Care, Burlington, Vermont.
Address reprint requests to: Ira M. Bernstein, MD, University of Vermont College of Medicine, Department of Obstetrics and Gynecology, Burgess 217, FAHC, 111 Colchester Avenue, Burlington, VT 05401-1435; E-mail: ibernste{at}zoo.uvm.edu.
 |
ABSTRACT |
|---|
TOP
 ABSTRACT MATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
METHODS: We prospectively measured the uterine artery pulsatility index, peak systolic velocity, and volumetric blood flow during the menstrual cycle and at 4, 6, and 12 weeks of pregnancy in women who conceived. Upper extremity radial artery hemodynamic changes were examined as a control vessel. Ten subjects conceived within 12 months of menstrual cycle studies. Analyses were performed using repeated measures analysis of variance with P < .05 accepted for significance.
RESULTS: In women who conceived, uterine artery peak systolic velocity demonstrated a significant increase during the period of observation, which began after cycle day 10 (0.36 x 0.02 meters per second) of the menstrual cycle and continued though 12 menstrual weeks (1.05 ± 0.10 meters per second, P < .001). Uterine artery pulsatility index decreased significantly during the observation window from 3.0 ± 0.2 in the follicular phase to 1.6 ± 0.2 at 12 menstrual weeks (P < .001). Blood flow in the uterine artery increased significantly from cycle day 10 (22.2 ± 1.8 mL per minute) to 12 menstrual weeks’ gestation (150.2 ± 40.3 mL per minute, P < .001). These patterns were significantly different from the patterns observed for the radial artery.
CONCLUSION: Uterine artery hemodynamic adaptation in early pregnancy follows a continuum established during the menstrual cycle. These adaptations result in decreased uterine artery impedance and increased blood flow. These changes differ from those observed in the upper extremity radial artery (control vessel) suggesting independence of regional pelvic and systemic hemodynamic adaptations.
Uterine vascular relaxation and increase in uterine blood flow in early pregnancy appear to be important determinants of pregnancy outcome.1–8 Failure of uterine vascular adaptation in the form of reduced uterine artery resistance and increased blood flow during the luteal phase of the menstrual cycle has been associated with both infertility and reduced assisted reproductive success.9 Specifically, reduced pregnancy rates with in vitro fertilization10,11 are observed when increased luteal phase uterine vascular resistance is present. Failure of the uterine vasculature to undergo further modification, as reflected by increased impedance measured using Doppler-acquired velocity waveforms from the uterine artery, has been associated with an increased risk for the development of both fetal growth restriction and pre-eclampsia. These vascular patterns have been identified as early as the first trimester of pregnancy.12
The primary goal of this project was to prospectively describe the time course of human uterine artery vascular adaptation through the menstrual cycle and into early pregnancy. We were interested in the specific pattern of the uterine artery adaptation when compared with a control vessel. We intended to examine the timing and size of the uterine artery vascular adaptation as distinct from the systemic adaptation represented by a nonpelvic control artery. In addition, although not a primary goal of this research, we also examined the differences in uterine artery hemodynamic profile in those women who conceived within 1 year of initiating attempts at conception and those who did not to consider the hypothesis that alterations on uterine artery hemodynamics influence fertility.
|
MATERIALS AND METHODS |
|---|
|
TOP
ABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
We examined women prospectively beginning during the menstrual phase of the menstrual cycle. The study design called for examination of subjects at three time points in each of two spontaneous ovulatory cycles. This was followed by up to 12 months of observation as couples attempted to conceive with the aid urinary luteinizing hormone (LH) detection kits (OvuQuick OneStep, Quidel, San Diego, CA). After confirmation of conception, repeated hemodynamic studies were performed and timed according to the urinary detection of LH. Visits were timed to coincide with LH surge + 16 days, LH surge + 28 days, and LH surge + 70 days corresponding roughly to 4, 6, and 12 menstrual weeks’ gestation. The actual timing of pregnancy visits was LH surge + 16.8 ± 1.1 (mean ± standard deviation) days, LH surge +27.3 ± 0.8 days, and LH surge +70.3 ± 1.8 days. Demographic characteristics for the group of ten women achieving pregnancy are outlined in Table 1
.
|
r2)] x average pulse rate}. We have previously evaluated both intra- and interobserver reproducibility and found these estimates of blood flow to be reproducible.14
As in the menstrual phase studies before each study visit, participants abstained from vigorous exercise for a 24-hour period and fasted for 12 hours before each evaluation. Conceiving and nonconceiving subjects were compared on demographic characteristics using t tests and Fisher exact test. Comparisons between groups with respect to uterine hemodynamics during the menstrual cycle were done using repeated measures analysis of variance. The model consisted of one across-subject factor group (conceiving and nonconceiving) and one within-subject factor group (phase) and their interaction. Tests for differences in uterine and radial artery hemodynamic responses over the menstrual cycle were performed using repeated measures analyses of variance. The statistical model consisted of within-subject factors, type of artery (uterine or radial), and phase of measurement (menses through LH + 70 days) and their potential interaction. The significance of the interaction term was used to test whether hemodynamic changes across the six phases were artery specific (ie, whether uterine and radial arteries displayed parallel patterns). If evidence of an interaction was observed, separate one-factor repeated measures were done, comparing the six phases within the uterine and radial arteries. Comparisons among phase means were performed using Fisher least significant difference procedure. All statistical analyses were done using SAS Statistical Software (SAS Institute Inc., Cary, NC). Statistical significance was determined based on 
< .05.
This study was approved by the University of Vermont/Fletcher Allen Health Care Committee on Human Research in the Medical Sciences. All subjects provided written informed consent before participation.
|
RESULTS |
|---|
|
TOP
ABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
). We found no difference in uterine artery pulsatility index (PI), peak systolic velocity (PSV), or volumetric blood flow during the menstrual cycle comparing women who conceived within 1 year of attempts with those who did not conceive at each phase of observation (Table 2). In addition, there was no difference in the pattern of any of the measured parameters (ie, PI, PSV, and volumetric blood flow) over the course of the menstrual cycle when the conceiving and nonconceiving groups were compared.
|
demonstrates the pattern of uterine and radial artery PI and PSV through the menstrual cycle and into early pregnancy in the ten women who conceived. There were significant differences in the overall pattern of adaptation when these vessels were compared (repeated measures analysis of variance, P < .05). Uterine artery PI demonstrated a steady and progressive decrease beginning after day 10 of the menstrual cycle during the follicular to luteal phase menstrual transition and continuing through 12 menstrual weeks. In contrast, radial artery PI demonstrated an increase during this same study observation window. Uterine PSV demonstrated an increase through the period of observation also originating during the follicular to luteal transition. Radial artery PSV demonstrated no significant change over time.
|
illustrates the changes in volumetric blood flow associated with the progression through the menstrual cycle and into early pregnancy. The uterine arteries demonstrate a progressive increase in blood flow beginning after menstrual day 10, which becomes significant at 12 menstrual weeks’ gestation. In contrast, the radial artery blood flow demonstrates no significant change over the period of observation. Of note, uterine blood flow for the twin gestation was 23 mL per minute at 4 weeks, 21 mL per minute at 6 weeks, and 168 mL per minute at 12 weeks. These values are below the mean at 4 and 6 weeks and within one standard deviation of the mean at 12 weeks (Figure 1).
|
|
DISCUSSION |
|---|
|
TOP
ABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
The specific patterns in the uterine arterial PI and PSV closely match the findings of Jurkovic et al,16 where the uteroplacental circulation was evaluated in 45 women in early pregnancy. In that study, the mean PI was approximately 2.6 at 4 weeks and 1.5 at 12 weeks, closely paralleling our findings. Similarly, the changes in PSV identified in that study closely match the findings reported here. Jurkovic et al16 found a mean PSV of 0.4 meters per second at 4 weeks accelerating to 0.80 meters per second at 12 weeks. Finally, they identified an acceleration in uterine hemodynamic adaptations towards the end of the first trimester, a pattern that is matched in the current study. We chose to examine the radial artery for comparison with the uterine artery because of the similarity in nonpregnant size and the ease with which the radial artery could be studied. We presumed that the radial artery would be a good representative for the systemic circulation, but this is uncertain as we do not know if the changes in total peripheral resistance are accurately represented by the changes we have observed in the radial artery in early pregnancy.
We were interested in the observation that although hemodynamic parameters in the uterine vasculature change significantly during the menstrual cycle, the next significant adaptation in women achieving pregnancy occurs between 6 and 12 menstrual weeks’ gestation coinciding with the luteoplacental shift. It appears that although the corpus luteum provides some stimulus for the initial transitions associated with an adaptive uterine circulation, a more complete and dramatic adaptation requires specific placental signals. It appears that these signals are not present until beyond the 6th week of gestation and that they are responsible for the bulk of the change in uterine artery blood flow that attends early pregnancy adaptation.
As noted earlier, the subjects in this study also participated in a research project examining plasma volume expansion in early pregnancy. In contrast to the hemodynamic findings of the current study, we identified no increase in plasma volume during the luteal phase of the menstrual cycle, and the plasma volume expansion of pregnancy was first identified after 6 menstrual weeks. This combination of observations supports an "underfill hypothesis" of maternal vascular adaptation in pregnancy, at least with regard to the specific findings of the uterine vasculature.17 The question of whether the uterine or radial vessels better represent the totality of the maternal vascular response to pregnancy is uncertain, and further observations will be necessary to confirm that the underfill hypothesis is consistent with the changes in total vascular resistance rather than specific to the uterine vasculature alone.
In this study, we compared the uterine vascular adaptations across the menstrual cycle between women achieving spontaneous conception within 1 year of initiating attempts and those who did not conceive. Overall, there was little difference between the groups, and the only significant difference noted was of a higher follicular phase PI in subjects who conceived. In general, there was a tendency for women who conceived to have higher estimates of uterine artery impedance in all phases of the cycle and a smaller incremental rise in uterine blood flow during the luteal phase compared with those who did not conceive. These findings do not support previous publications suggesting a role for increased luteal phase uterine artery impedance and decreased luteal phase blood flow as contributors to infertility. Although this prospective study did not have sufficient power to conclusively identify the lack of a relationship between menstrual phase changes in uterine arterial hemodynamics and infertility, the results suggest that they are unlikely to be major factors.
|
Footnotes |
|---|
Received August 3, 2001. Received in revised form November 14, 2001. Accepted November 29, 2001.
|
REFERENCES |
|---|
|
TOP
ABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
2. Campbell S, Pearce JMF, Hackett G, Cohen-Overbeek T, Hernandez C. Qualitative assessment of uteroplacental blood flow: Early screening test for high-risk pregnancies. Obstet Gynecol 1986;68:649–53.[Medline]
3. North RA, Ferrier C, Long D, Townend K, Kincaid-Smith P. Uterine artery Doppler flow velocity waveforms in the second trimester for the prediction of preeclampsia and fetal growth retardation. Obstet Gynecol 1994;83: 378–86.
4. Frusca T, Soregaroli M, Valcamonico A, Guandalini F, Danti L. Doppler velocimetry of the uterine arteries in nulliparous women. Early Hum Develop 1997;48: 177–85.
5. Bewley S, Cooper D, Campbell S. Doppler investigation of uteroplacental blood flow resistance in the second trimester: A screening study for pre-eclampsia and intrauterine growth retardation. Br J Obstet Gynaecol 1991;98:871–9.[Medline]
6. Konchak PS, Bernstein IM, Capeless EL. Uterine artery Doppler velocimetry in the detection of adverse obstetric outcomes in women with unexplained elevated maternal serum alpha-fetoprotein. Am J Obstet Gynecol 1995;173: 1115–9.[Medline]
7. Bower S, Bewley S, Campbell S. Improved prediction of pre-eclampsia by two-stage screening of uterine arteries using early diastolic notch and color Doppler imaging Obstet Gynecol 1993;82:78–83.
8. Zimmermann P, Eirio V, Joskinen J, Kujansuu E, Ranta T. Doppler assessment of the uterine and uteroplacental circulation in the second trimester in pregnancies at high risk for pre-eclampsia and/or intrauterine growth retardation: Comparison and correlation between different Doppler parameters. Ultrasound Obstet Gynecol 1997;9:330–8.[Medline]
9. Coulam CB, Bustillo M, Soenksen DM, Britten S. Ultrasonographic predictors of implantation after assisted reproduction. Fertil Steril 1994;62:1004–10.[Medline]
10. Steer CV, Campbell S, Tan SL, Crayford T, Mills C, Mason BA, et al. The use of transvaginal color flow imaging after in vitro fertilization to identify optimum uterine conditions before embryo transfer. Fertil Steril 1992;57:372–6.[Medline]
11. Bassil S, Magritte JP, Roth J, Nisolle M, Donnez J, Gordts S. Uterine vascularity during stimulation and its correlation with implantation in in-vitro fertilization. Hum Reprod 1995;10:1497–501.
12. Harrington K, Carpenter RG, Goldfrad C, Campbell S. Transvaginal Doppler ultrasound of the uteroplacental circulation in the early prediction of pre-eclampsia and intrauterine growth retardation. Br J Obstet Gynaecol 1997;104:674–81.[Medline]
13. Bernstein IM, Ziegler W, Badger GJ. Plasma volume expansion in early pregnancy. Obstet Gynecol 2001;97: 669–72.
14. Ziegler WF, Bernstein I, Badger G, Leavitt T, Cerrero ML. Regional hemodynamic adaptation during the menstrual cycle. Obstet Gynecol 1999;94:965–9.
15. Fisher SJ, Roberts JM. Defects in placentation and perfusion. In: Lindheimer M, Roberts J, Cunningham FG, eds. Chesley’s hypertensive disorders in pregnancy. Stamford, CT: Appleton & Lange; 1999:377–94.
16. Jurkovic D, Jauniaux E, Kurjak A, Hustin J, Campbell S, Nicolaides KH. Transvaginal color Doppler assessment of the uteroplacental circulation in early pregnancy. Obstet Gynecol 1991;77:365–9.
17. Schrier RW, Durr JA. Pregnancy: An overfill or underfill state. Am J Kidney Dis 1987;9:284–9.[Medline]
This article has been cited by other articles:
|
|
 |
|
  H. Tamura, I. Miwa, K. Taniguchi, R. Maekawa, H. Asada, T. Taketani, A. Matsuoka, Y. Yamagata, H. Ishikawa, and N. Sugino Different changes in resistance index between uterine artery and uterine radial artery during early pregnancy Hum. Reprod., February 1, 2008; 23(2): 285 - 289. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Wilson, M. Lopez, M. Vargas, C. Julian, W. Tellez, A. Rodriguez, A. Bigham, J. F. Armaza, S. Niermeyer, M. Shriver, et al. Greater uterine artery blood flow during pregnancy in multigenerational (Andean) than shorter-term (European) high-altitude residents Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2007; 293(3): R1313 - R1324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Zamudio, L. Postigo, N. P. Illsley, C. Rodriguez, G. Heredia, M. Brimacombe, L. Echalar, T. Torricos, W. Tellez, I. Maldonado, et al. Maternal oxygen delivery is not related to altitude- and ancestry-associated differences in human fetal growth J. Physiol., July 15, 2007; 582(2): 883 - 895. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Mu and S. L. Adamson Developmental changes in hemodynamics of uterine artery, utero- and umbilicoplacental, and vitelline circulations in mouse throughout gestation Am J Physiol Heart Circ Physiol, September 1, 2006; 291(3): H1421 - H1428. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Aardenburg, M. E. Spaanderman, D. A. Courtar, H. W. van Eijndhoven, P. W. de Leeuw, and L. L. Peeters A Subnormal Plasma Volume in Formerly Preeclamptic Women is Associated with a Low Venous Capacitance Reproductive Sciences, February 1, 2005; 12(2): 107 - 111. [Abstract] [PDF]
|
|
|
|
|
|
D. P. Damron, I. M. Bernstein, R. E. Shapiro, and A. Schonberg Uterine Blood Flow Response to Alpha-Adrenergic Blockade in Nulligravid Women of Reproductive Age Reproductive Sciences, September 1, 2004; 11(6): 388 - 392. [Abstract] [PDF]
|
|
|
|
 |
|
 R. P. Dickey and I. M. Bernstein Uterine Artery Hemodynamic Adaptations Through the Menstrual Cycle Into Early Pregnancy Obstet. Gynecol., August 1, 2002; 100(2): 379 - 380. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
