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1.
PROBLEM: To measure and compare concentrations of inhibin A, inhibin B, activin A and oestradiol in the follicular fluid of women with endometriosis, tubal damage and unexplained infertility with oocyte quality and fertilising capacity. Also, to assess whether impaired follicular function in women with endometriosis might be related to altered inhibin or activin concentrations and whether this correlated. METHOD OF STUDY: Follicular fluids were collected from individual follicles during oocyte retrieval for in vitro fertilisation (IVF) in natural cycles. Inhibin A, inhibin B and activin A were measured using two-site enzyme immunoassay, and oestradiol was assayed by fluoro-immunometric method. RESULTS: Follicular fluid inhibin A levels were found to be significantly higher in women with endometriosis. Inhibin A was directly correlated with follicle size. There was no correlation between the levels of inhibin A, inhibin B, activin A and oocyte quality or fertilising capacity in the three groups of women. CONCLUSIONS: Follicular fluid concentration of inhibin A is elevated in follicles of women with endometriosis and is positively correlated with follicle maturation. However, we were unable to demonstrate any association between the follicular fluid concentrations of inhibin A, inhibin B, activin A or oestradiol and the quality and fertilisation capacity of oocytes in women with tubal damage, unexplained infertility or endometriosis.  相似文献   

2.
BACKGROUND: The aim of this study was to investigate the changes in circulating levels and the clinical use of inhibin A, activin A and follistatin as endocrine markers of early pregnancy loss. METHODS: Blood samples were collected from women presenting with a sporadic missed miscarriage (n = 10), and controls having pregnancy termination at 8-12 weeks (n = 15) and from women with a history of unexplained recurrent miscarriages (n = 12) at 6-12 weeks gestation. All samples were assayed for inhibin A, inhibin B, activin A, follistatin, hCG, estradiol and progesterone. RESULTS: Serum inhibin A, hCG, estradiol and progesterone levels were significantly ( approximately 2-3 fold) decreased in sporadic miscarriages compared with controls. In the recurrent miscarriage group, time dependent changes in plasma inhibin A and hCG levels were significantly (P < 0.05) altered in the group that had a subsequent miscarriage compared with those who had a live birth. At 6-7 weeks gestation, plasma inhibin A ( approximately 4 fold, P < 0.01), hCG ( approximately 4 fold, P < 0.01) and estradiol ( approximately 2 fold, P < 0.001) levels were significantly lower in women who went on to have another miscarriage than those with a live birth. Inhibin B levels were near the detection limit of the assay. CONCLUSIONS: Our findings suggest that inhibin A is a specific marker of early pregnancy loss before the onset of the clinical symptoms of recurrent miscarriage. There is a high degree of association between levels of inhibin A and hCG in cases of miscarriage, indicating that these two proteins could be used in combination to predict future pregnancy outcome.  相似文献   

3.
Serum inhibin A and activin A concentrations increase in pre-eclampsia. We investigated the time courses of the changes in relation to the onset of the maternal syndrome and if their measurement could be useful for clinical prediction particularly in relation to early onset disease, the most severe of the clinical presentations. Serial samples were taken from 1496 healthy nulliparae. Changes in activin A and inhibin A were analysed in women with: early onset pre-eclampsia (n = 11), pre-eclampsia delivering at 34-36 weeks (n = 14), term pre-eclampsia (n = 25) and gestational hypertension (n = 25); and in a subset with uncomplicated pregnancies (n = 25). Serum inhibin A and activin A were increased in all groups prior to pre-eclampsia, before 20 weeks in those with early onset pre-eclampsia. Screening efficacy was determined at 15-19 and 21-25 weeks in all women who developed pre-eclampsia (n = 70) and randomly selected controls (n = 240). Predictive sensitivities were low (16-59%) but much better for early onset pre-eclampsia: 67 and 44% at 15-19 weeks and 89 and 89% at 21-25 weeks for inhibin A and activin A respectively. Hence, serum inhibin A and activin A concentrations increase before the onset of pre-eclampsia at gestational ages that depend on when pre-eclampsia develops. On their own such measures are unlikely to prove efficient for screening.  相似文献   

4.
Polycystic ovary syndrome (PCOS) is characterized by arrestedfollicle development at the early antral stage. Alterationsin inhibin production by developing follicles could be involvedin PCOS by suppressing follicle stimulating hormone concentrationsduring the follicular phase of the menstrual cycle as well asby increasing thecal androgen production. Inhibin B appearsto be more important than inhibin A during the follicular phase;however, there are no data regarding the follicular fluid concentrationsof inhibin B in PCOS. The purpose of this study was to compareinhibin A, inhibin B and activin A concentrations in the follicularfluid from regularly cycling women and women with PCOS. InhibinA, inhibin B and activin A were measured in the follicular fluidof 4–7 mm follicles from PCOS ovaries and size-matchedfollicles from normally cycling women by specific and sensitivetwo-site enzyme-linked immunosorbent assays. In both controland polycystic ovaries, inhibin B was approximately 10-foldhigher than activin A and more than 100-fold higher than inhibinA. There was no difference in activin A concentrations betweenPCOS and control follicles. In control ovaries, the inhibinB and inhibin A concentrations in dominant follicles were significantlyhigher than in cohort follicles. While inhibin A concentrationswere lower in PCOS follicles than in normal cohort follicles,there was no difference in inhibin B concentrations betweenPCOS follicles and normal cohort follicles. These data are consistentwith the concept that inhibin B is the physiologically mostimportant form of inhibin during the follicular phase of themenstrual cycle and indicate that PCOS is not associated withincreased inhibin B concentrations in follicular fluid.  相似文献   

5.
Serum concentrations of inhibin A, inhibin B, activin A and follistatin were determined using two-site enzyme-linked immunosorbent assays (ELISA) during pubertal ovarian development in 28 girls and five follicular phase women. Blood obtained every 15 to 20 min overnight was pooled for peptide determination. Serum inhibin A concentrations increased in mid puberty, exhibiting positive correlations with bone age (r = 0.527, P = 0.0016) and oestradiol concentrations (r = 0.581, P = 0.0005). Inhibin B concentrations peaked in mid puberty and declined thereafter, but remained greater than concentrations seen in prepubertal girls, and correlating positively with oestradiol (r = 0.362, P = 0.046) and follicle stimulating hormone (FSH) concentrations (r = 0.369, P = 0.038). Total activin A concentrations did not vary significantly across pubertal stages. Total follistatin concentrations, determined by radioimmunoassay, decreased with advancing puberty, exhibiting negative correlations with bone age (r = -0.634, P = 0.0001) and oestradiol concentration (r = -0.687, P = 0.0001). Follistatin concentrations determined by an ELISA specific for follistatin 288 were greatest in mid-pubertal girls, but concentrations in late puberty were less than those in early puberty. The free follistatin assay indicated that all circulating follistatin was activin-bound. These results suggest that significant changes in serum concentrations of FSH-regulatory peptides accompany the onset of puberty.  相似文献   

6.
The purpose of this study was to evaluate whether maternal serum (MS) and amniotic fluid (AF) inhibin A levels are elevated in patients who subsequently develop severe preecalmpsia, and to investigate the correlation between MS and AF inhibin A levels in the second trimester. The study included 40 patients who subsequently developed severe preecalmpsia and 80 normal pregnant women. Inhibin A levels in MS and AF were measured with enzyme-linked immunosorbent assay (ELISA). The MS and AF inhibin A levels in patients who developed severe preeclampsia were significantly higher than those in the control group (both for p<0.001). There was a positive correlation between MS and AF inhibin A levels in patients who developed severe preeclampsia (r=0.397, p=0.011), but not in the control group (r=0.185, p=0.126). The best cutoff values of MS and AF inhibin A levels for the prediction of severe preeclampsia were 427 pg/mL and 599 pg/mL, respectively; the estimated ORs that were associated with these cut-off values were 9.95 (95% CI 3.8-25.9, p<0.001) and 6.0 (95% CI 2.3-15.8, p<0.001). An elevated level of inhibin A in MS and AF at the time of second trimester amniocentesis may be a risk factor for the subsequent development of severe preeclampsia.  相似文献   

7.
BACKGROUND: In a previous study we have found that in normal ovulatory women, serum inhibin B levels on days 4-6 of FSH administration correlated with the number of oocytes retrieved. In the current study we examined the significance of earlier inhibin B measurements in predicting the oocyte number, in both normal and low responders. METHODS: Study A consisted of 19 patients undergoing their first IVF cycle (n = 10) or had a normal response ( vertical line 6 oocytes retrieved, n = 9), while study B consisted of 15 patients with a previous low ovarian response (16. Study B: oocyte number correlated significantly with inhibin B and inhibin A on all days of FSH treatment, even on day 2 (r = 0.90, P < 0.001 and r = 0.65, P < 0.05 for inhibin B and A respectively). No significant correlation was found with E(2) levels. In both studies, all patients with inhibin B >100 pg/ml on treatment day 2 had >6 oocytes. CONCLUSIONS: Our data suggest that serum inhibin B measured early during FSH stimulation may indicate whether sufficient oocytes will be retrieved, in both normal and low responders. Serum inhibin B measured during early FSH treatment may be of predictive value in monitoring ovarian stimulation treatment for IVF.  相似文献   

8.
Inhibin A, inhibin B, and activin A are growth factors which play local autocrine/paracrine roles in reproductive tissues. Since peritoneal fluid hormone content may reflect in part ovarian and endometrial secretory activities, the present study aimed to evaluate: (i) whether inhibin alpha-, activin betaA- and betaB-subunits, and activin receptor type II and type IIB mRNA are expressed in peritoneal tissues; (ii) expression and secretion of inhibin A and B, and activin A in cultured endometriotic cells; and (iii) concentrations of inhibin A and B, and activin A in serum and in peritoneal fluid in healthy women and in patients with endometriosis throughout the menstrual cycle. A group of women (n = 72) was recruited at laparoscopy for infertility investigation and divided into two groups: (i) control healthy women (n = 35), (ii) women with endometriosis (n = 37). Both groups were subdivided according to the follicular and luteal phase of the menstrual cycle. At the time of laparoscopy, specimens of peritoneal tissues were collected from three healthy women, while endometriotic tissue samples were collected and cultured from three women with endometriosis. Peritoneal tissues and cultured endometriotic cells expressed inhibin alpha-, activin betaA-, and betaB-subunits, and activin receptors mRNAs; in addition, inhibin-related proteins were measurable in culture medium. In healthy women, inhibin A and B, and activin A concentrations in peritoneal fluid were significantly higher than in serum (P < 0.001), at both phases of the menstrual cycle. Peritoneal inhibin A and B, and activin A concentrations were not significantly different between healthy women and patients with endometriosis, either when evaluated according to the degree of the disease and/or to the phase of the menstrual cycle. In conclusion, the findings that high concentrations are present in peritoneal fluid and that menstrual cycle-related changes occur suggest that reproductive organs may contribute to inhibin-related proteins in peritoneal fluid.   相似文献   

9.
The concentrations of inhibin A, inhibin B and activin A in follicular fluid and oocyte culture medium were analysed to investigate the production of these peptide hormones by ovarian granulosa cells and oocyte-cumulus complexes, as well as their potential as possible biochemical markers for oocyte quality and fertilizing capacity. Follicular fluids were collected from individual follicles during oocyte retrieval for in-vitro fertilization (IVF). Oocyte-cumulus culture media were collected after in-vitro insemination. The concentrations of dimeric inhibin A, inhibin B and activin A were measured using two-site enzyme-linked immunosorbent assays in the follicular fluid and matched oocyte culture medium. Hormone concentrations were compared with oocyte quality and fertilizing capacity. The concentration of inhibin A in follicular fluid increased while that of inhibin B decreased with increasing follicle size. Follicular fluid concentrations of inhibin A inhibin B and activin A were not significantly different in follicles with differing oocyte quality. Oocyte culture medium concentrations of activin A were significantly higher in morphologically good quality oocytes. There was no relationship between the concentrations of the three hormones and oocyte fertilizing capacity. This study confirms that follicular fluid concentrations of inhibin A may prove to be a marker of follicular growth and maturation. Higher concentrations of activin A produced by good quality oocyte-cumulus complexes suggest that activin A may play a role in oocyte maturation.  相似文献   

10.
BACKGROUND: A nucleotide substitution in the inhibin alpha subunit (INHA 769G>A, A257T) has been associated with premature ovarian failure (POF). We hypothesize this mutation causes a reduction in inhibin bioactivity, removing its suppression on the pituitary FSH secretion. The aim of this study is to establish if A257T inhibin has reduced bioactivity. METHODS: Mouse LbetaT2 pituitary gonadotrope, human granulosa (COV434) and human embryonic kidney (HEK293) cells were co-transfected with an activin-responsive reporter and increasing amounts of wild-type or variant A257T inhibin alpha subunit, and the degree of inhibin antagonism of activin signalling determined. RESULTS: A 5-fold inhibition was observed with wild-type inhibin alpha subunit overexpression (P < 0.001) (confirmed in HEK293 cells), while the A257T inhibin showed no inhibitory activity. In human ovarian COV434 transfected cells, while wild-type and A257T inhibin A had similar bioactivities, there was a significant reduction in the bioactivity of A257T inhibin B compared with wild-type inhibin B (P < 0.005). In all the three cell systems, overexpression of wild-type and A257T alpha subunit resulted in a 2- to 6-fold increase in secretion of dimeric inhibin indicating the reduced inhibin response was not due to a failure of dimerization. CONCLUSIONS: This study supports the hypothesis that the INHA 769G>A variant may increase susceptibility to POF with impaired inhibin B bioactivity and provides insight into the complex aetiology of POF.  相似文献   

11.
12.
Day 5 inhibin B levels in a treatment cycle are predictive of IVF outcome   总被引:24,自引:0,他引:24  
BACKGROUND: Day 5 serum inhibin B during IVF treatment has been investigated as a predictor of outcome. METHODS: A total of 54 women (< or = 39 years, normal menses and endocrine profiles) were treated with urinary gonadotrophins or recombinant FSH following pituitary down-regulation. Serum day 3 FSH in a preceding cycle was <8.5 IU/l. Plasma inhibin B, inhibin A and estradiol were determined after 4 days of gonadotrophin administration (day 5). RESULTS: Day 5 inhibin B was the most highly correlated with the number of mature follicles (>14 mm), oocytes retrieved and fertilized. Receiver operating characteristic analysis gave high accuracy for day 5 inhibin B in predicting ovarian response and indicated that a threshold of 400 pg/ml may be helpful in the decision as to whether to continue treatment. Women with <400 pg/ml (n = 16) had lower numbers of follicles, mature follicles, oocytes retrieved, fertilized and cleaved compared with those >400 pg/ml (n = 36) and this threshold gave a positive likelihood ratio of 30, 92.9% sensitivity, 95.0% specificity and 86.7% positive predictive value to detect poor ovarian response. Day 5 inhibin B was the best predictor of pregnancy (no live births and four cycles cancelled, low inhibin group; nine live births and no cancelled cycles, high inhibin group). CONCLUSIONS: Normogonadotrophic, normogonadal women with day 5 inhibin B <400 pg/ml in down-regulated cycles have a poor response to ovarian stimulation and are less likely to conceive compared with women with higher day 5 inhibin B.  相似文献   

13.
14.
15.
BACKGROUND: The objective of the present study was to investigate the correlation between inhibin B and estradiol levels in follicular fluid (FF) with the quality of subsequent embryo development from in-vitro fertilized oocytes aspirated from the same follicle. METHODS: A total of 156 infertile women undergoing controlled ovarian stimulation for IVF and embryo transfer was recruited to the present study. Prospectively, 233 FF samples and matched mature oocytes were studied. Concentrations of inhibin B and estradiol were determined by enzyme-linked immunosorbent assay (ELISA) and immunofluorometric assay (IFMA) respectively. RESULTS: Inhibin B levels in FF were significantly correlated with embryo scores on days 2 and 3 (48 and 72 h after oocyte retrieval). In contrast, both inhibin B and estradiol levels in FF were inversely related to age. Furthermore, FF inhibin B levels were inversely associated with serum FSH levels on day 3 of the menstrual cycle, which was believed to reflect the ovarian reserve. CONCLUSION: Inhibin B in FF may serve as an effective marker of follicular development and a useful predictor of quality of embryo. In addition, quality of oocyte is age-related and declines as age increases.  相似文献   

16.
The roles of oestradiol, inhibin A and inhibin B in the luteal-follicular transition were assessed by means of specific assays. Six premenopausal women were studied during a control and then a cycle treated with percutaneous oestradiol 0.1 mg/day from day 10 after the luteinizing hormone (LH) surge until day 4 of the following cycle. Inhibin A concentrations decreased similarly in control and treated cycles from day -5 to day 2, then increased in control cycle to 23.3 +/- 3.4 pg/ml on day 10 (mean +/- SEM). They remained low until day 5 in treated cycles and were lower than controls on day 10 (P < 0.01). Follicle stimulating hormone (FSH) concentrations increased on day 1 in controls and on day 5 in treated cycles when oestradiol concentration fell abruptly. Inhibin B concentrations remained low until day 1 in controls and day 4 in treated cycles. In both, inhibin B concentrations increased 1 day after FSH, peaking at 160 pg/ml. FSH concentrations began to plateau when inhibin B concentrations were >100 pg/ml and oestradiol concentrations below 200 pmol/l. These data suggest that inhibin A is not responsible for FSH suppression in the luteal phase and that the negative control of FSH shifts from oestradiol in the luteal phase to inhibin B in the mid-follicular phase.  相似文献   

17.
The present study investigates the usefulness of inhibin A, inhibin B and serum oestradiol concentrations obtained in the fifth day of gonadotrophin therapy in predicting ovarian response and assisted reproductive treatment outcome in women undergoing ovarian stimulation under pituitary desensitization. A total of 80 women undergoing their first cycle of in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment were studied. Twenty consecutive cycles which were cancelled because of a poor follicular response were initially selected. As a control group, 60 women were randomly selected from our assisted reproductive treatment programme matching by race, age, body mass index, and indication for IVF/ICSI to those in the cancelled group. For each cancelled cycle, three IVF/ICSI women who met the matching criteria were included. Basal follicle stimulating hormone (FSH) concentrations were significantly higher in the cancelled than in the control group, whereas basal inhibin B was significantly higher in the latter. Basal oestradiol concentrations were similar in both groups of patients. On day 5 of gonadotrophin therapy serum concentrations of oestradiol, inhibin A and inhibin B were significantly lower in the cancelled group as compared with controls. Logistic regression analysis showed that the association for day 5 inhibin B (with a predictive value of ovarian response of 91.03%) with cancellation rate was significant, independent of, and stronger than, the effects of any other hormone variable investigated. In addition, day 5 inhibin B concentrations were correlated directly with parameters of ovarian response, ovum retrieval and oocyte and fertilization outcome. However, day 5 inhibin B was not a better predictor of pregnancy than the other hormone variables studied on this day. It is concluded that inhibin B concentrations obtained early in the follicular phase during ovarian stimulation under pituitary suppression for assisted reproductive treatment are highly predictive of ovarian response.  相似文献   

18.
BACKGROUND: Serum FSH elevations and decreases in inhibin B have been consistently demonstrated in the early follicular phase of cycles in women of advanced reproductive age. However, secretory products of the dominant follicle (estradiol and inhibin A) in the serum of older ovulatory women are maintained at levels similar to those of their younger counterparts. The goal of this investigation was to determine if ovarian secretory capacity is dependent on relative FSH levels and if basal measures of ovarian reserve reflect ovarian secretory capacity. METHODS: We administered equivalent low, but effective doses of recombinant FSH for 5 days to a group of older subjects (40-45 years, n=9) and younger controls (20-25 years, n=10) after pituitary suppression with a GnRH agonist. Outcome measures included follicular development as determined by serial transvaginal ultrasound examinations and serum levels of estradiol, inhibin A and inhibin B. RESULTS: Serum levels of estradiol and inhibin A were not statistically different between the two groups, while the number of large follicles formed was greater in the younger subjects. Basal parameters of ovarian reserve were not significantly correlated with ovarian secretory capacity, but did correlate with the number of follicles recruited in response to low-dose FSH. CONCLUSIONS: By providing equivalent serum levels of FSH in older and younger reproductive aged women, this study demonstrates that the secretory capacity of recruited follicles is maintained in older reproductive aged women.  相似文献   

19.
Inhibins are regulators of paracrine and endocrine function during pregnancy, but their intrauterine sites of secretion are not well established. In amniotic fluid, inhibin A-, inhibin B- and inhibin pro-alphaC-containing isoforms were present in high concentrations, whereas in maternal serum, inhibin A and pro-alphaC forms were present in high amounts, with low concentrations of inhibin B. In fetal cord serum, inhibin pro-alphaC was present in all samples, inhibin B was detectable in male but not female fetuses, with no detectable inhibin A in either sex. From cultured explants, both inhibin A and B were secreted by chorion laeve, whereas only inhibin A was secreted by placenta, with both tissues secreting inhibin pro-alphaC. Only low concentrations of both dimeric inhibins and pro-alphaC forms were secreted by decidua parietalis and amnion. The dual perfused placental cotyledon secreted both inhibin A and pro-alphaC into maternal perfusate, but only inhibin pro-alphaC into the fetal circulation and less than to the maternal side. We conclude that trophoblast is the predominant source of dimeric inhibins, but with markedly different secretion depending on its intrauterine location. There was a significant decrease in inhibin A and pro-alphaC in amniotic fluid collected at term active labour compared to elective Caesarean section (P < 0.001). This may reflect a local change in inhibin/activin processing at labour, likely in chorion laeve trophoblast cells, which may be important in the paracrine control of the feto-maternal communication required to maintain pregnancy and initiate labour.  相似文献   

20.
To test the hypothesis that dimeric inhibin A and/or inhibin B concentrations represent improved markers of in-vitro fertilization (IVF) outcome over follicle stimulating hormone (FSH), 78 women who achieved pregnancy within three assisted reproduction treatment cycles were matched to 78 women who underwent at least three assisted reproductive treatment cycles and failed to achieve pregnancy. Baseline serum inhibin B and FSH were obtained between days 1 and 4 in a cycle prior to ovarian stimulation, and inhibin A and B were measured immediately before the ovulatory stimulus and in follicular fluid from the lead follicle. Comparing pregnant and non-pregnant subjects at baseline, younger age (34.0 +/- 0.5 versus 36.0 +/- 0.5 years; P < 0.003) and a combination of FSH lower than the median value (11.2 IU/l) and inhibin B higher than the median value (76.5 pg/ml) were associated with pregnancy (P < 0.03), but FSH (11.7 +/- 0.5 versus 12.9 +/- 0.9 IU/ml) and inhibin B (89.0 +/- 10.2 versus 79.7 +/- 7.7 pg/ml) were not independently associated. At the time of the ovulatory stimulus, serum inhibin A (52.8 +/- 3.8 versus 40.0 +/- 2.7 IU/ml; P < 0.004), inhibin B (1623.8 +/- 165.1 versus 859.2 +/- 94.8 pg/ml; P < 0.0009) and the number of oocytes retrieved (14.6 +/- 0.8 versus 10.1 +/- 0.6; P < 0.0001) were predictive of pregnancy when controlled for age. Inhibin A was correlated with the number of embryos (r = 0.4; P < 0.0001). However, neither inhibin A nor inhibin B provided additional information in predicting successful outcome over age and number of oocytes. We conclude that: (i) in patients undergoing assisted reproductive technology, age and number of oocytes retrieved are the strongest predictors of success; (ii) of the parameters available prior to cycle initiation, a combination of lower FSH and higher inhibin B was associated with a greater chance for a successful outcome but an absolute cut-off could not be defined; and (iii) during ovarian stimulation, higher concentrations of inhibin A and inhibin B in serum are associated with successful IVF and mark ovarian reserve as a measure of oocyte number and quality.  相似文献   

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