| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Original Studies |
Research Institute for Endocrinology, Reproduction, and Metabolism, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Fertility, and the IVF Center (M.W.E., J.K., R.S., J.S.), Department of Clinical Epidemiology and Biostatistics (L.T.M.R.M.), Vrije Universiteit Medical Center, 1007 MB Amsterdam, The Netherlands
Address all correspondence and requests for reprints to: Mariet W. Elting, M.D., Vrije Universiteit Medical Center, IVF Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. E-mail: m.elting{at}azvu.nl
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
The morphological aspect of polycystic ovaries is explained histologically by the fact that polycystic ovaries contain a double number of antral follicles and have a thickened ovarian cortex and an increased stroma compared with normal ovaries (1). Van der Meer et al. (2) confirmed the existence of an enlarged follicle cohort in polycystic ovary syndrome patients during controlled ovarian hyperstimulation by measuring significantly larger FSH-sensitive follicle cohorts than in regularly menstruating women. Recently, we found that PCOS patients frequently gain regular menstrual cycles when aging (3). We theorized that this might be explained by a decrease in the size of the follicle cohort due to ovarian aging. An easy way to determine the size of the cohort at any given time might not only be of benefit in predicting the outcome of ovarian hyperstimulation in in vitro fertilization (IVF), but also might be useful for the further study of changes in cohort size with age. The method used by Van der Meer et al. (2) is very labor intensive.
Fanchin et al. (4) measured estradiol (E2) levels before and 24 h after administering a fixed dose of 300 IU FSH on cycle day 3 to detect a possible poor response among patients scheduled to undergo IVF. This test, called the EFORT (exogenous FSH ovarian reserve test), might not only determine poor responders, but might be a predictor for the cohort size as well.
It has recently been shown that inhibin B increases in the early follicular phase simultaneously with the FSH rise; it is possibly produced by the small antral follicles (5). A low inhibin B concentration on cycle day 3 can predict a poor response in IVF hyperstimulation (6). A high inhibin B in combination with a low FSH in the early follicular phase was found to be associated with a greater chance for a successful IVF outcome, and the gonadotropin-stimulated inhibin B level was found to correlate with the number of oocytes (7). The inhibin B levels 4 days after FSH stimulation in a down-regulated IVF cycle were recently reported to be an early indicator for the number of stimulated follicles (8).
A measurement of ovarian volume by transvaginal ultrasound also might be able to predict the cohort size. Several studies reported that the ovarian volume in the early follicular phase correlated with the number of follicles or the number of oocytes in an IVF stimulation (9, 10, 11, 12).
The primary aim of this study was to test the hypothesis that the FSH-induced E2 increment, the FSH-induced inhibin B increment, and the ovarian volume, all measured in the early follicular phase, can predict the follicle cohort size in polycystic ovaries as well as in normal ovaries. The secondary aim of the study was to investigate whether we could explain the heterogeneity of the PCOS by differences in follicle cohort sizes.
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Subjects
We defined three groups of subjects.
Group 1: women with PCOS. As in previous studies of PCOS patients by our research group, we classified our PCOS patients as patients with oligo- or amenorrhea (nine or fewer cycles a year), elevated LH (>6.5 IU/L), determined at least 2 weeks after and 3 weeks before a menstrual bleeding, and a normal FSH value (<10 IU/L). Hirsutism and/or hyperandrogenemia, although usually present, were not obligatory for the diagnosis.
Group 2: women with regular menstrual cycles and polycystic ovaries (PCO) detected by ultrasound. Ultrasound appearance of polycystic ovaries was defined as 10 or more follicles of 2–8 mm, in a generally cystic pattern or in a peripheral cystic pattern around a dense core of stroma, in both ovaries. Regular menstrual cycles were defined as an average cycle length of 26–32 days, with no more variation than ±3 days from the average.
Group 3: women with regular menstrual cycles without polycystic ovaries. These women had regular menstrual cycles, as defined in group 2, and normal ovaries as detected by ultrasound.
In each group we included 10 patients. Of the 10 PCOS patients, 5 women had elevated androstenedione and/or testosterone levels, and a sixth patient had a borderline elevated androstenedione level (8.5 nmol/L) at the time of PCOS diagnosis. Hirsutism was present, in a more or less pronounced form, in 6 women. Hirsutism and/or hyperandrogenemia was found in 8 of the 10 PCOS patients.
All 30 patients were under treatment for infertility in the out-patient clinic of the IVF center when asked to participate in the study. All had an indication for IVF in the second treatment cycle, such as idiopathic infertility for more than 3 yr, a minor tubal factor, a male factor, or unsuccessful treatment with intrauterine inseminations. Weight (kilograms) and height (meters) were measured to calculate the body mass index (kilograms per meters squared). We obtained written informed consent from all participating patients.
Study design
In this study we defined the follicle cohort as all FSH-sensitive antral follicles of 2 mm or more located in both ovaries that were capable of follicle growth in reaction to an exogenous or endogenous FSH increase. To determine the correlation of the predictors (E2 increment, inhibin B increment, and ovarian volume) with the follicle cohort size and to compare cohort sizes in the different groups, the stimulation of the cohort in each patient had to be standardized. The stimulated cohort was defined as the cohort stimulated by the individual FSH threshold dose plus one ampule. Therefore, it was necessary to determine the individual FSH threshold of each patient and subsequently calculate the dose for stimulating the follicle cohort (2).
First cycle: determination of the FSH threshold
The FSH threshold was determined by a low dose step-up regimen of recombinant FSH (recFSH; 75 IU/ampule Gonal-F, Ares Serono, Geneva, Switzerland) given iv after pituitary desensitization with triptorelin acetate (0.1 mg/day Decapeptyl, Ferring Pharmaceuticals Ltd., Hoofddorp, The Netherlands). In women with regular cycles, sc triptorelin was started in the midluteal phase. In the case of oligo- or amenorrhea in PCOS patients, triptorelin was started on the first day of a withdrawal bleeding induced by progesterone administration (100 mg, im, Progestine, Organon, Oss, The Netherlands). Desensitization was defined as an E2 concentration below 100 pmol/L, which was tested for the first time after 2 weeks of triptorelin administration. Stimulation started when desensitization was achieved. RecFSH was administered iv by a portable infusion pump (Autosyringe, Travenol Laboratories, Hooksett, NH) starting with a half-ampule daily. When after 7 days of stimulation no follicle larger than 10 mm was measured by ultrasound and/or the E2 level was below 200 pmol/L, we increased the FSH dose by one quarter ampule per day (which approximately equals a rise in the FSH level of 1 IU/L). We repeated this procedure every 5 days until a follicle had grown to more than 10 mm, and/or a rise of E2 above 200 pmol/L was achieved. This dose was continued until the largest follicle reached a diameter of 18 mm. To induce actual ovulation, we administered 10,000 IU hCG, sc (Profasi, Ares Serono). We canceled a cycle when more than three follicles 16 mm or larger or six 14-mm follicles were present. Forty-one hours after hCG administration we performed an intrauterine insemination. The patients used progesterone (100-mg tablets, Progestan, Nourypharma, Oss, The Netherlands) three times daily vaginally for luteal support.
Second cycle: measurement of ovarian volume
Day 1 of the second cycle was the first day of menstrual
bleeding in women with regular cycles or the first day of withdrawal
bleeding in patients with oligo- or amenorrhea. On day 3, a
transvaginal ultrasound was performed using an Aloka SSD-1700
ultrasound apparatus (5.0-MHz probe) to check for ovarian cysts and to
calculate the ovarian volume by measuring the ovarian diameter in three
directions (formula: 
/6 x D1 x D2 x D3). The
volumes of the right and left ovaries were measured once in each
patient. All measurements were performed by one author (M.W.E.). The
total ovarian volume was defined as the average of the right and left
ovarian volumes.
Second cycle: administration of 300 IU FSH and measurement of the follicle cohort size after ovarian hyperstimulation for IVF
After the ultrasound on cycle day 3, blood was taken for measurements of E2, FSH, LH, inhibin B, androstenedione (A), and testosterone (T) concentrations. Subsequently, a fixed dose of four ampules of recFSH (Gonal-F, 300 IU) was given sc. Twenty-four hours later, E2 and inhibin B were measured again. Norethisterone (5 mg, orally, three times daily, Primolut N, Schering AG, Weesp, The Netherlands) was started on day 5 and continued for 10 days. Two days later, desensitization was started by triptorelin (0.1 mg, sc, daily). When desensitization was achieved (E2, <100 pmol/L), controlled ovarian hyperstimulation was started with recFSH (75 IU, iv). We calculated the dose of FSH as the threshold dose (determined in cycle I) plus one ampule per day. Ovarian hyperstimulation continued until the day the largest follicle reached a diameter of 18 mm. We then measured the follicle cohort by ultrasound as the total number of follicles 10 mm or larger. At that time we discontinued FSH and triptorelin and administered 10,000 IU hCG (Profasi) 36 h before transvaginal follicle aspiration. From the day of oocyte retrieval until 15 days later the patient used progesterone (Progestan, 100 mg, three times daily, two tablets vaginally) for luteal support. On the second or third day after oocyte retrieval, two or three embryos were transferred.
Assays
Serum E2, FSH, and LH were determined by commercially available immunometric assays (Amerlite, Amersham Pharmacia Biotech, Aylesbury, UK). For E2, the interassay coefficient of variation (CV) was 11% at 250 pmol/L and 8% at 8000 pmol/L; the intraassay CV was 13% at 350 pmol/L, 9% at 1100 pmol/L, and 9% at 5000 pmol/L. The lower limit of detection for E2 was 90 pmol/L. In the EFORT we measured E2 with a sensitive RIA (Sorin, Biomedica, Saluggia, Italy). This measurement of E2 was abbreviated as EE. For EE, the interassay CV was 11% at 60 pmol/L, 8% at 200 pmol/L, 11% at 550 pmol/L, and 8% at 900 pmol/L. The intraassay CV was 4% at 110 pmol/L and 5% at 1000 pmol/L. The lower limit of detection for EE was 18 pmol/L. For FSH, the interassay CV was 9% at 3 IU/L and 5% at 35 IU/L; the intraassay CV was 9% at 5 IU/L, 8% at 15 IU/L, and 6% at 40 IU/L. The lower limit of detection for FSH was 0.5 IU/L. For LH, the interassay CV was 9% at 3 IU/L and 5% at 50 IU/L; the intraassay CV was 5% at 10 IU/L, 3% at 20 IU/L, and 3% at 40 IU/L. The lower limit of detection for LH was 0.3 IU/L. A and T were determined by commercially available RIAs (Coat-a-Count, Diagnostic Products, Los Angeles, CA). For A, the interassay CV was 15% at 1 nmol/L and 5% at 20 nmol/L; the intraassay CV was 14% at 1 nmol/L, 6% at 3 nmol/L, and 4% at 10 nmol/L. The lower limit of detection for A was 0.5 nmol/L. For T, the interassay CV was 10% at 3 nmol/L and 7% at 10 nmol/L; the intraassay CV was 6% at 4 nmol/L and 5% at 10 nmol/L. The lower limit of detection for T was 0.4 nmol/L. Inhibin B was determined immunometrically by a commercially available assay (Serotec, Oxford, UK). For inhibin B, the interassay CV was 17% at 25 ng/L, 14% at 55 ng/L, and 9% at 120 ng/L. The lower limit of detection for inhibin B was 13 ng/L. Values below the detection limit of an assay were assigned a value equal to the detection limit of that assay.
Statistical analysis
Differences between the patient groups were tested by a simple one-way ANOVA for comparison of the normally distributed variables. The only variable with a skewed distribution (the E2 concentration measured on cycle day 3) was tested nonparametrically by the Kruskal-Wallis test. An ANOVA test for linearity was used to find any trend in the groups. The correlation between the independent variables (the E2 increment, the inhibin B increment, and the total ovarian volume) and the dependent variable (the total number of follicles obtained after stimulation) was established by linear regression analysis. First, the slopes of the regression lines of these variables for each patient group were tested for similarity by creating two new binary variables (dummy variables) and performing t tests for the coefficients of the dummy variables. Second, for the total group of patients, linear regression analysis was used to find a prediction model for the dependent variable. Comparison of regression coefficients was performed using a Fisher Z transformation and calculation of confidence intervals of Z. Multiple regression analysis was performed with variables that were significantly correlated to the number of follicles to test whether there were confounding variables and to find the best prediction model. For all tests the significance level was 0.05.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
. In one patient
from the control group, the ovarian volume was not measured on cycle
day 3 previous to the test with FSH. In the PCOS group, inhibin B was
measured in nine patients.
|
Although the control group seemed to be somewhat older, this was not statistically significant from the other two groups (P = 0.11). There appeared to be a trend for a higher body mass index in the PCOS group, but when testing for linearity in the groups this could not be established with certainty (P = 0.07). The FSH concentration measured on cycle day 3 in the control group was significantly higher than the FSH level in the PCOS group (P < 0.05). There was a linear trend for a lower FSH in the PCOS group (P < 0.05). LH, measured on cycle day 3, was not significantly different among the groups, but there was a linear trend for a higher LH level in the PCOS group (P < 0.05). Basal concentrations of E2, inhibin B, A, and T were not significantly different among the groups. The total ovarian volumes of the PCO and PCOS groups were significantly different from that in the control group (P < 0.05) and showed a linear trend for a higher volume in the PCOS group (P < 0.01).
Treatment cycle characteristics
The total numbers of follicles (
10 mm) in the PCO group and the
PCOS group were significantly different from that in the control group
(both P < 0.01), and there was a linear trend for a
higher number of follicles in the PCOS group (P <
0.01). The mean size of the follicle cohort was 2 times larger in the
PCO group as well as in the PCOS group (see Fig. 1). We calculated the
E2-increment in 24 h as the EE level from
day 4 minus the EE level from day 3 for each patient. The
E2 increments were not statistically different
(P = 0.09) among the groups, but we found a linear
trend for a higher E2 increment from the control
group toward the PCOS group (P < 0.05). The inhibin B
increment (measured as the increase in inhibin B from day 3 to day 4)
showed a significant difference between the PCOS group and the control
group (P < 0.05), but not between the PCO group and
the control group. There was a trend for a higher increase in inhibin B
in the PCOS group (P < 0.05).
|
The slopes of the regression lines of the E2
increment vs. the number of follicles for the three patient
groups were not significantly different (Fig. 2A). The line of the control group was
located significantly lower than the other two lines (P
< 0.05). Expressed by the dependent variable (y), the line
of the control group was located ±10 follicles lower. Also, for
the inhibin B increment the slopes of the regression lines for the
three groups were not significantly different (Fig. 2B). However, it
appeared that the regression line for the ovarian volume of the PCO
group had a different slope (Fig. 2C) than those of the PCOS group and
the control group. Although the slopes of these lines were not
significantly different, we preferred not to use the total population
of the three groups in one model for linear regression analysis of
ovarian volume. The regression lines for the inhibin B increment and
the ovarian volume of the control group also were located significantly
lower than the lines of the PCOS and PCO groups (P <
0.05).
|
Univariate regression analysis. In a prediction model of the
total population, the correlation coefficients of the
E2 increment and the inhibin B increment for
predicting the total number of follicles were 0.617 and 0.665,
respectively (Table 2). The regression
line of the E2 increment on the number of
follicles was drawn by the regression equation: y =
13.1 + 0.055 x E2 increment; with a 95%
confidence interval of 0.028 - 0.082, meaning that each
E2 increment of 100 pmol/L predicts 5.5 follicles
(95% confidence interval, 2.8–8.2). The regression equation for the
inhibin B increment shows that an increase of 100 ng/L inhibin B
predicts 6.2 follicles (95% confidence interval, 3.5–9.0). When
comparing the two correlation coefficients of these variables, they
were not significantly different (P = 0.67; z =
0.43).
|
). When including independent variables that
were significantly (P < 0.05) correlated with the
number of follicles [T, r = 0.494; A, r = 0.462; LH, r
= 0.548; FSH, r = -0.528 (all measured on cycle day 3); age,
r = 0.457], both prediction models were improved by the variables
LH and FSH. A stepwise regression analysis showed that the
E2 increment or the inhibin B increment was
selected as the first significant variable (P < 0.01)
in their model, LH as the second (P < 0.05), and FSH
as the third (P < 0.05) in both models (Table 2). The
models did not improve if the variable group was added. T and A were
probably not selected because of their correlation to LH (T, r =
0.683; A, r = 0.514). When excluding LH as a variable, A and FSH
were chosen successively as significant variables (P <
0.05) in the prediction model with E2 (r =
0.754; r2 = 0.519; P < 0.001),
and T and FSH were used in the model with inhibin B (r = 0.782;
r2 = 0.564; P < 0.001). |
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Our study shows that the FSH-induced E2 increment and the FSH-induced inhibin B increment after administration of 300 IU recFSH on day 3 of spontaneous or withdrawal bleeding can predict the follicle cohort size in PCOS patients as well as in regularly menstruating PCO patients and control women. For these two variables, the regression lines of the three separate groups are approximately parallel, which suggests that granulosa cells (GCs) of polycystic ovaries produce E2 and inhibin B in the same amount as GCs of normal ovaries. This finding is in agreement with studies of the aromatase activity of the GCs of polycystic ovaries by Jakimiuk et al. (13), Erickson et al. (14, 15), and Mason et al. (16), who all concluded that GCs of polycystic ovaries are intrinsically normal. In these in vitro studies (14, 15, 16), a higher E2 production at the same FSH concentration of the GCs of PCOS patients compared with GCs of control patients was found. This increased sensitivity for FSH could not be confirmed in our in vivo study. Also, for inhibin B we were not able to find an increased production per follicle in the PCOS group. This is in line with the report by Magoffin et al. (17), who compared the inhibin A, inhibin B, and activin A concentrations in follicular fluid from size-matched follicles of 4–7 mm in women with PCOS and control women. They found no differences in inhibin B concentrations. It was concluded that the production of inhibin B must be the same in size-matched antral follicles of PCOS and control women.
In our study the E2 increment and inhibin B increment have equivalent strength in predicting the follicle cohort size because the correlation coefficients of their prediction models are not significantly different. The fact that the FSH-induced E2 increment is strongly correlated to the FSH- induced inhibin B increment suggests that both are produced by the same ovarian structure. It has been established that antral follicles of 2 mm and larger can exhibit aromatase activity in the GCs and also show follicle growth under the influence of FSH. E2 production precedes follicular growth (18, 19). In the early follicular phase of the normal menstrual cycle, inhibin B increases simultaneously with FSH, with a preovulatory decline (5). Expression of messenger ribonucleic acid for all subunits of inhibin was found in the GCs of small antral follicles from normal and PCOS ovaries (20, 21). The findings of our in vivo study strongly suggest that inhibin B as well as E2 are produced by the GCs of small antral follicles under the influence of FSH. Therefore, their FSH-induced increase in the early follicular phase is a measure of the size of the antral follicle cohort.
Improvement of both prediction models occurred when LH, FSH, A, and T, measured on the third day of the cycle, were included in the multivariate analysis. LH and FSH were selected successively and seem to represent the differences between the control and PCOS groups, namely the trend for higher LH and lower FSH in the PCOS group. When excluding LH, as it is the inclusion criterion for our PCOS patients, A and T were chosen before FSH in both models. Although hyperandrogenemia seems to be related to the number of follicles, LH is a stronger predictor in our study population.
In conclusion, we found a test that is easy to perform and estimates the FSH-sensitive follicle cohort in PCOS, regularly menstruating PCO, or control women. The rise in FSH- induced E2 and inhibin B in the early follicular phase can be used before the start of an IVF hyperstimulation and predict the number of stimulated follicles in all kinds of patients (low or high responders).
Heterogeneity of PCOS
The regression lines for the E2 increment and the inhibin B increment of the PCO group and the PCOS group are located significantly higher than the line of the control group for both variables. Although age did not differ significantly in the groups, the control group might show some biological age difference compared with the other two groups. However, the mean number of follicles (14.1 ± 7.8), being a normal response to ovarian hyperstimulation for IVF, does not suggest an older ovarian age of the control group.
It is remarkable that PCOS as well as PCO patients have a follicle
cohort twice as big as the size of the cohort in regularly menstruating
control women. However, the SD and the 95% confidence
interval of the mean number of follicles are much larger in the PCOS
group than in the PCO group. Apparently, some of the patients with
oligo- or amenorrhea and elevated LH did have a follicle cohort size
comparable to the largest cohorts of the control group. This can be
explained by the fact that a small number of PCOS patients do not show
polycystic ovaries on ultrasonography (22, 23, 24). The fact
that the PCO group has a smaller confidence interval for the number of
follicles obtained is probably due to our inclusion criteria for the
two PCO groups. For the PCO group, a transvaginal ultrasound, counting
the visible antral follicles, was performed, and for the PCOS group
oligo- or amenorrhea together with elevated LH were required. The
inclusion criteria for the PCO group (10 follicles of 2–8 mm in each
ovary measured by transvaginal ultrasound) is also responsible for the
different slope of the regression line of the ovarian volume for
predicting the number of follicles in this group compared with the
other two groups. All patients in the PCO group had a large follicle
cohort by definition even if the ovarian volume was relatively small.
It seems that the antral follicle count in the early follicular phase
for this group is a better predictor than the ovarian volume, as was
found in several other studies (25, 26). These results
again show that PCOS is highly heterogeneous, and division into
subgroups based on different characteristics may lead to difficulties
in interpreting the data.
We believe that the cycle irregularity in PCOS is caused by the enlarged follicle cohort. Too many small antral follicles make too much inhibin B and E2, thus causing too great a suppression of FSH for follicles to continue to grow (3). However, this theory cannot explain the difference in cycle regularity between the PCO and PCOS groups in this study, because the cohorts in the groups are of similar size. The two groups differ in LH, because the PCOS group was selected on the basis of high LH levels. Therefore, the difference between the PCOS and PCO groups might be explained by the elevated LH level in the PCOS group. The role of LH in causing cycle disturbances is supported by the report of Willis et al. (27), who cultured GCs of anovulatory PCOS patients, ovulatory PCO patients, and control patients in the presence of LH. The GCs from anovulatory PCOS patients responded much earlier with E2 secretion to LH (at 4 mm instead of 9.5/10 mm) than those of the other two patient categories. They theorized that this might also lead in vivo to premature GC differentiation, stagnation of follicle growth, and anovulation. Androgens and insulin were both mentioned to be candidates for influencing this process (28).
However, another explanation of the difference in cycle regularity might be that women with PCO and women with PCOS differ in their pituitary feedback of inhibin B in suppressing FSH. Our study shows no significant differences in basal inhibin B and E2 concentrations among the three groups. Yet, a linear trend for a lower FSH in the PCOS group was found. This lower FSH in combination with a similar inhibin B concentration might point in the direction of increased inhibin B sensitivity of the pituitary in the PCOS group. Although we realize that this is highly speculative, we suggest that in addition to the enlarged follicle cohort, the possibly different pituitary sensitivity might contribute to the development of cycle irregularity in PCOS. Theoretically, the decreased FSH in the PCOS group might be based on the local autocrine or paracrine role of follistatin in the pituitary (29). Follistatin binds to activin (30) and as such inhibits FSH secretion. An elevated follistatin level in the pituitary might explain the lower FSH in the PCOS group when basal inhibin B and E2 levels are similar in the PCO and PCOS groups. This in line with the findings of Urbanek et al. (31), who recently showed that the follistatin gene is the gene with the highest linkage with PCOS found to date.
In conclusion, the results of our study confirm the hypothesis that the FSH-induced E2 increment and the FSH-induced inhibin B increment can predict the size of the follicle cohort in patients with PCOS, regularly menstruating women with polycystic ovaries, and regularly menstruating women with normal ovaries. The follicle cohort sizes of the PCO group and the PCOS group are twice as big as the cohort size of the control group. The difference in menstrual cycle pattern between the two PCO groups of this study cannot be explained by differences in follicle cohort sizes.
|
Acknowledgments |
|---|
|
Footnotes |
|---|
Received January 22, 2000.
Revised August 21, 2000.
Revised November 16, 2000.
Accepted December 12, 2000.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
This article has been cited by other articles:
 |
|
 |
|
  S.A. Amer, S. Laird, W.L. Ledger, and T.C. Li Effect of laparoscopic ovarian diathermy on circulating inhibin B in women with anovulatory polycystic ovary syndrome Hum. Reprod., February 1, 2007; 22(2): 389 - 394. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. S. Wachs, M. S. Coffler, P. J. Malcom, and R. J. Chang Comparison of Follicle-Stimulating-Hormone-Stimulated Dimeric Inhibin and Estradiol Responses as Indicators of Granulosa Cell Function in Polycystic Ovary Syndrome and Normal Women J. Clin. Endocrinol. Metab., August 1, 2006; 91(8): 2920 - 2925. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Eldar-Geva, A. Ben-Chetrit, I. M. Spitz, R. Rabinowitz, E. Markowitz, T. Mimoni, M. Gal, E. Zylber-Haran, and E. J. Margalioth Dynamic assays of inhibin B, anti-Mullerian hormone and estradiol following FSH stimulation and ovarian ultrasonography as predictors of IVF outcome Hum. Reprod., November 1, 2005; 20(11): 3178 - 3183. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. K. Welt, A. E. Taylor, J. Fox, G. M. Messerlian, J. M. Adams, and A. L. Schneyer Follicular Arrest in Polycystic Ovary Syndrome Is Associated with Deficient Inhibin A and B Biosynthesis J. Clin. Endocrinol. Metab., October 1, 2005; 90(10): 5582 - 5587. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Lutchman Singh, M. Davies, and R. Chatterjee Fertility in female cancer survivors: pathophysiology, preservation and the role of ovarian reserve testing Hum. Reprod. Update, January 1, 2005; 11(1): 69 - 89. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Nikolaou and C. Gilling-Smith Early ovarian ageing: are women with polycystic ovaries protected? Hum. Reprod., October 1, 2004; 19(10): 2175 - 2179. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G.J. Scheffer, F.J.M. Broekmans, C.W.N. Looman, M. Blankenstein, B.C.J.M. Fauser, F.H. de Jong, and E.R. te Velde The number of antral follicles in normal women with proven fertility is the best reflection of reproductive age Hum. Reprod., April 1, 2003; 18(4): 700 - 706. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Y.K. Yong, D. T. Baird, K.J. Thong, A. S. McNeilly, and R. A. Anderson Prospective analysis of the relationships between the ovarian follicle cohort and basal FSH concentration, the inhibin response to exogenous FSH and ovarian follicle number at different stages of the normal menstrual cycle and after pituitary down-regulation Hum. Reprod., January 1, 2003; 18(1): 35 - 44. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. K. Welt, A. E. Taylor, K. A. Martin, and J. E. Hall Serum Inhibin B in Polycystic Ovary Syndrome: Regulation by Insulin and Luteinizing Hormone J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5559 - 5565. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I.A.J. van Rooij, F.J.M. Broekmans, E.R. te Velde, B.C.J.M. Fauser, L.F.J.M.M. Bancsi, F.H.d. Jong, and A.P.N. Themmen Serum anti-Mullerian hormone levels: a novel measure of ovarian reserve Hum. Reprod., December 1, 2002; 17(12): 3065 - 3071. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Welt, Y. Sidis, H. Keutmann, and A. Schneyer Activins, Inhibins, and Follistatins: From Endocrinology to Signaling. A Paradigm for the New Millennium Experimental Biology and Medicine, October 1, 2002; 227(9): 724 - 752. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Eldar-Geva, E.J. Margalioth, A. Ben-Chetrit, M. Gal, D.M. Robertson, D.L. Healy, Y.Z. Diamant, and I.M. Spitz Serum inhibin B levels measured early during FSH administration for IVF may be of value in predicting the number of oocytes to be retrieved in normal and low responders Hum. Reprod., September 1, 2002; 17(9): 2331 - 2337. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
