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1.
Human granulosa cells, from women undergoing ovum collection for in-vitro fertilization (IVF), will luteinize in vitro and provide a model for investigating the antigonadotrophic action of a prostaglandin F2 alpha (PGF2 alpha) analogue, cloprostenol, on granulosa-derived luteal cells. The granulosa cells were cultured in a defined medium and exposed to treatments during a preincubation period of 0 to 3 days and a final incubation with low density lipoprotein (LDL) from days 3 to 4. In the absence of human chorionic gonadotrophin (HCG), progesterone production was low, whereas exposure to HCG in the final incubation resulted in a 10-fold increase in progesterone concentrations. The inclusion of cloprostenol with HCG in the final incubation significantly (P less than 0.05) inhibited HCG-stimulated progesterone production. Exposure to HCG during the preincubation prevented the antigonadotrophic action of cloprostenol in the final incubation. The antigonadotrophic action of cloprostenol was retained when the granulosa cells were exposed to cloprostenol during the preincubation. Omission of LDL from the final incubation lowered the production of progesterone but the pattern of responses to HCG and cloprostenol were similar. Prevention of the antigonadotrophic action of cloprostenol after exposure to HCG may be a mechanism through which chorionic gonadotrophin can prevent regression of the corpus luteum in early pregnancy. Cloprostenol does not appear to inhibit LDL-stimulated steroidogenesis in human granulosa cells. 相似文献
2.
Vascular endothelial growth factor production by human luteinized granulosa cells in vitro 总被引:10,自引:2,他引:10
Lee A; Christenson LK; Patton PE; Burry KA; Stouffer RL 《Human reproduction (Oxford, England)》1997,12(12):2756-2761
Vascular endothelial growth factor/vascular permeability factor (VEGF/VPF)
originating from the follicle or corpus luteum may be a physiological
regulator of ovulation and neovascularization of luteinizing tissue, as
well as a pathological factor in the development of ovarian
hyperstimulation syndrome (OHSS). The objective of this study was to
quantify VEGF production by human luteinized granulosa cells in vitro and
to determine if gonadotrophin stimulates VEGF production directly and/or
indirectly via enhanced synthesis of progesterone. In study 1, luteinized
granulosa cells collected from women undergoing ovarian stimulation for
in-vitro fertilization were cultured in the presence and absence of human
chorionic gonadotrophin (HCG; 100 ng/ml) and/or low density lipoprotein
(LDL; 100 microg protein/ml). In study 2, the progesterone synthesis
inhibitor trilostane (250 ng/ml) and/or a progesterone receptor antagonist
ZK137.316 (3.2 microM) were also added. Medium was harvested on days 1, 3,
5, 7 and 9 of culture and assayed for VEGF and progesterone. Results of
study 1 were divided into two categories based on control concentrations of
VEGF on day 1: 'low producers' (n = 6; <750 pg VEGF/ml) and 'high
producers' (n = 5; >1000 pg VEGF/ml; P < 0.01). VEGF concentrations
in cultures of both low and high producers increased (P < 0.01) from day
1 to maximal values on day 3, then steadily declined through to day 9.
Chronic exposure to LDL or HCG increased (P < 0.05) VEGF concentrations
in cultures of low producers by day 3 and day 5 respectively. In contrast,
LDL did not alter VEGF concentrations in cultures of high producers and HCG
did not increase VEGF concentrations until day 7. Nevertheless, acute
exposure to HCG beginning on day 7 increased (P < 0.05) VEGF
concentrations 3-fold in cultures of low or high producers. In study 2,
trilostane treatment decreased (P < 0.05) progesterone concentrations by
91% on day 1 of culture but had no effect on VEGF concentrations on any
day. ZK137.316 alone or with trilostane did not affect VEGF synthesis.
These results suggest that VEGF production by luteinized granulosa cells is
enhanced by gonadotrophin (HCG) independent of gonadotrophin-stimulated
progesterone synthesis. These data are consistent with the hypothesis that
the exacerbation of OHSS in early pregnancy is mediated by the CG
stimulation of luteal VEGF production.
相似文献
3.
Kranen Roland W.; Overes Hannie W.T.M.; Kloosterboer Helenius J.; Poels Lambert G. 《Human reproduction (Oxford, England)》1993,8(1):24-29
This report examines the relationship between aromatase activityand progesterone production and the expression of actin andvinculin in rat granulosa cells, exposed to insulin, folliclestimulating hormone (FSH) and human chorionic gonadotrophin(HCG). Granulosa cells of pre-antral follicles from juvenilerats treated with diethylstilbestrol (DES) were cultured oncollagen A-coated plastic coverslips in serum-free medium. Ata moderate or low level of steroidogenesis (FSH alone), theexpression of vinculin was diminished while vinculin plaquesdisappeared completely. At a high level of steroidogenesis (bothFSH and insulin), actin in stress fibre form was also decreasedconsiderably. Under conditions of progesterone production (pretreatmentwith FSH and subsequent incubation with HCG), a concomitantincrease of actin in soluble form was found. It is concludedfrom these studies that the higher the steroidogenesis levelof the granulosa cells, the lower the organization of the microfilamentsvinculin and actin, which are regulated independently of eachother. 相似文献
4.
Murata M; Tamura A; Kodama H; Hirano H; Takahashi O; Tanaka T 《Molecular human reproduction》1998,4(8):797-801
To determine whether human luteal cells can utilize very low density
lipoproteins (VLDL)-carried cholesterol for steroidogenesis, we
investigated the expression of VLDL receptor mRNA in human ovarian tissues
and progesterone production by human luteinized granulosa cells after the
addition of VLDL. The production of progesterone in the presence of human
chorionic gonadotrophin (HCG) was increased significantly (P < 0.05) by
VLDL (2479 +/- 1477 ng/10(5) cells, mean +/- SD, n = 6) and low density
lipoproteins (LDL) (2726 +/- 1287), in comparison with the level in the
absence of these lipoproteins (1350 +/- 739). Northern blot analysis
revealed that the levels of expression of VLDL and LDL receptor mRNA in
granulosa cells were almost equal to those in whole ovarian tissue. VLDL
receptor mRNA was abundant in granulosa cells of preovulatory follicles and
cells of the corpus luteum. Preovulatory thecal cells and stromal cells
expressed lower amounts of VLDL receptor mRNA than granulosa cells of
preovulatory follicles and cells of the corpus luteum. From the present
study, it might be suggested that VLDL is utilized for steroidogenesis in
human luteinized granulosa cells.
相似文献
5.
Takao Y; Honda T; Ueda M; Hattori N; Yamada S; Maeda M; Fujiwara H; Mori T; Wimalasena J 《Molecular human reproduction》1997,3(7):569-578
We examined the immunohistochemical localization of luteinizing hormone
(LH)/human chorionic gonadotrophin (HCG) receptor (LH-R) in the human ovary
using the anti-human LH-R monoclonal antibody, 3B5. In the antral
follicles, LH-R was detected on theca interna cells. In pre-ovulatory
follicles, granulosa cells also expressed LH-R. During corpus luteum
formation, granulosa cells seemed to increase the expression of LH-R, and
in corpus luteum of mid-luteal phase, large luteal cells expressed LH-R
more intensely than small luteal cells. In the regressing corpus luteum,
LH-R was almost undetectable on both luteal cells, whereas in the corpus
luteum of early pregnancy, LH-R continued to be expressed on large luteal
cells. The granulosa cells obtained from the patients undergoing in-vitro
fertilization therapy were cultured for 3 days in serum-free medium,
without or with HCG (10 IU/ml) and tumour necrosis factor (TNF)alpha (10
ng/ml). Flow cytometry showed that the expression of LH-R on the cell
surface of luteinizing granulosa cells was enhanced by HCG, but was
unaffected by TNFalpha. These results suggest that the main target cells
for LH/HCG change from theca interna cells/small luteal cells to granulosa
cells/large luteal cells during ovulation, corpus luteum formation, and
differentiation into the corpus luteum of pregnancy, probably under the
influence of LH/HCG.
相似文献
6.
Human granulosa cells were maintained in culture with extracellular matrix
in the presence or absence of human chorionic gonadotrophin (HCG) using a
defined culture medium. Such cultures are maintained by gonadotrophin in a
manner suggesting that features of 'luteal rescue' may be occurring in
vitro. Western analysis of culture medium demonstrated that the granulosa
cells produced tissue inhibitor of metalloproteinases (TIMP)-1 but not
TIMP-2. The presence of TIMP-1 in cultured cells was also detected
immunocytochemically. Immunoassay of TIMP-1 output revealed that HCG
exposure for 7 days caused a 2-fold increase in TIMP-1 production versus
control reaching maximum at approximately 1 ng HCG/ml. The sensitivity of
this response to HCG was similar to that observed for stimulation of
progesterone production. Delayed addition of HCG, from day 4 of culture,
elicited increases in TIMP-1 which were evident within 24 hours, and were
not explained by changes in cell replication or survival. Removal of HCG
from cultures previously luteinized with HCG for 6 days resulted in a fall
in TIMP-1 production. Thus TIMP-1 production by luteinized granulosa cells
in culture is gonadotrophin dependent. We speculate that prolonged cellular
function associated with 'luteal rescue' may result from increased
extracellular matrix stability mediated by up-regulation of TIMP-1
production.
相似文献
7.
There is evidence that insulin-like growth factor I (IGF-I) is a potent regulator of oestradiol synthesis by human granulosa and luteal cells; however, the question of whether IGF-I regulates progesterone synthesis by these cell types has yet to be answered. As a first step towards this goal, we have compared the effects of IGF-I, follicle stimulating hormone (FSH), and human chorionic gonadotrophin (HCG) on progesterone production by human granulosa cells obtained from individual dominant and cohort follicles, and granulosa luteal cells from preovulatory follicles of patients undergoing in-vitro fertilization (IVF). Granulosa cells from normal, unstimulated follicles cultured in serum-free medium as controls (no additions) produced some progesterone spontaneously. In all cases, FSH stimulated basal progesterone levels (10-fold average increase) and the effect was dose-dependent (ED50 of FSH = 9.1 +/- 3.9 ng/ml). Similar effects were observed when granulosa cells from large follicles were incubated with HCG (ED50 of HCG = 6.9 +/- 2.8 ng/ml). By comparison, the effects of IGF-I on progesterone production were not marked, being absent in 80% of the follicles tested. However, granulosa cells from healthy follicles co-incubated with IGF-I and FSH or HCG produced more progesterone compared with cells treated with the gonadotrophins alone; this effect of IGF-I was dose dependent (ED50 of IGF-I = 10 ng/ml). When the effect of each agonist was tested on IVF granulosa luteal cells, HCG but not FSH or IGF-I stimulated basal progesterone levels but the HCG effect required a two-day lag phase.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
8.
D H Edgar K M Whalley J A Gemmell G B James J A Mills 《Human reproduction (Oxford, England)》1991,6(2):198-202
The pregnancy rate in patients undergoing assisted conception treatment following pituitary desensitization with GnRH analogue and ovarian stimulation with gonadotrophins has been reported to be higher when ovarian function is supported in the luteal phase by exogenous human chorionic gonadotrophin (HCG). In the present study, we have examined the effects of culturing monolayers of granulosa cells, collected from such patients at oocyte retrieval, for various time intervals in the presence or absence of HCG on their subsequent ability to secrete progesterone (P4) either spontaneously or in response to further challenge with HCG. When cultured in the absence of HCG, granulosa cells demonstrated a rapid decline in both the spontaneous P4 secretion rate and the ability to secrete P4 in response to HCG. Maintenance in the presence of HCG inhibited the rapid decline in ability to secrete P4 spontaneously and also significantly enhanced the ability to respond to subsequent HCG stimulation. These results suggest that HCG support in the luteal phase in GnRH analogue-treated patients may have a cellular basis for its action both in maintenance of P4 secretion and also in rendering the corpus luteum more sensitive to rescue by conceptus-derived HCG. 相似文献
9.
M Fukuoka K Yasuda H Fujiwara H Kanzaki T Mori 《Human reproduction (Oxford, England)》1992,7(10):1361-1364
We have reported that the cytokines, interleukin-1 (IL-1), tumour necrosis factor alpha (TNF alpha), and interferon (IFN) alpha, beta, and gamma modulate the steroidogenic function of human luteinized granulosa cells in culture. In the present study we examined the interactions between these cytokines in modulating progesterone and oestradiol production by these cells. Neither IL-1 nor TNF alpha had significant effects on human chorionic gonadotrophin (HCG)-stimulated progesterone production, whereas IFN gamma (1-10 ng/ml) significantly reduced HCG-stimulated progesterone production by 26-37%. Concomitant treatment with IL-1 (1 ng/ml) did not further enhance the inhibitory effect of IFN gamma on HCG-stimulated progesterone production. In contrast, the combination of TNF alpha (1 ng/ml) and IFN gamma (10 ng/ml) acted synergistically to markedly inhibit HCG-stimulated progesterone production by 81%. In addition, IL-1 and TNF alpha, neither of which was effective alone, acted synergistically to reduce significantly HCG-stimulated progesterone production by 30%. The combination of TNF alpha and IFN gamma also markedly inhibited follicle stimulating hormone (FSH)-stimulated oestradiol production by 97%, a significantly greater inhibition than that obtained with either cytokine alone. These results suggest that the cytokines may interact to modulate the steroidogenic function of luteal cells in the developing corpus luteum. 相似文献
10.
Gonadotrophin-releasing hormone (GnRH) regulates gonadotrophin release. It has been shown that GnRH may have a direct effect on the ovary, as the addition of GnRH to granulosa cell cultures inhibits the production of progesterone and oestradiol. Specific GnRH receptors have been found to be present in rat and human granulosa cells. Desensitization of the pituitary by GnRH agonist has become common in in-vitro fertilization (IVF) treatment, usually by a long protocol of 2-3 weeks. With the introduction of GnRH antagonists, which produce an immediate blockage of the GnRH receptors, a much shorter exposure is needed of 3-6 days. The aim of this study was to evaluate the effect of a GnRH agonist (buserelin) and a GnRH antagonist (cetrorelix) on the function of granulosa cells cultured in vitro from IVF patients. Women were treated by IVF randomized either to have buserelin nasal spray from the luteal phase in the previous cycle or cetrorelix from day 6 of the cycle. Both groups had ovarian stimulation with human menopausal gonadotrophin (HMG) 150 IU daily, i.e. HCG was administered when the follicles were larger than 17 mm, and aspirated 36 h later. Granulosa cells, separated and washed from large follicles containing ova, were pooled. After 48 h of pre-incubation, the granulosa cells were cultured for 4 days in medium with either added testosterone or cAMP with or without HCG, with change of medium after 2 days. The progesterone and oestradiol concentrations in the culture medium were measured by immunological assay, and cellular protein was measured by microprotein assay. The results showed that granulosa cells from women treated with GnRH antagonist (cetrorelix) responded earlier to the in-vitro hormone stimulation in terms of progesterone accumulation than women treated with the GnRH agonist (buserelin). This may have been due to difference in time of exposure to the analogue. The results may indicate that the luteal function is less impaired in GnRH antagonist treatment than in GnRH agonist treatment. 相似文献
11.
Johnson M.R.; Abbas A.A.; Irvine R.; Riddle A.F.; Norman-Taylor J.Q.; Grudzinskas J.G.; Collins W.P.; Nicolaides K.H. 《Human reproduction (Oxford, England)》1994,9(1):41-48
The effects have been studied of different ovulation inductionregimens [either domiphene citrate or buserelin in combinationwith human menopausal gonadotrophin (HMG)] on the circulatingconcentrations of progesterone, oestradiol, relaxin and humanchorionic gonadotrophin (HCG) during the first trimester ofpregnancy. Ovulation induction with clomiphene resulted in elevatedconcentrations of gonadotrophins in both phases of the cycle,while during ovulation induction with buserelin, gonadotrophinconcentrations were elevated in the follicular phase only. Theconcentrations of all corpus luteum products were greater inclomiphene pregnancies compared with spontaneous pregnancies,but only oestradiol and relaxin concentrations were greaterin clomiphene pregnancies compared with buserelin pregnancies.The concentrations of HCG were significantly reduced in clomiphenepregnancies compared to natural pregnancies. Relaxin concentrationswere significantly higher from 7 weeks gestation in buserelincompared with spontaneous pregnancies, while progesterone, oestradioland HCG concentrations were not consistently different. Consistentassociations were found between relaxin and HCG concentrationsin spontaneous pregnancies and between the concentrations ofrelaxin and both progesterone and oestradiol in pregnanciesachieved after ovulation induction. These data suggest that(i) given the similarity in the circulating concentrations ofHCG, the relatively lower circulating gonadotrophin concentrationsduring the luteal phase of the cycle of conception result inreduced circulating concentrations of oestradiol and relaxin;while in the case of relaxin this effect is partially reversible,there is no evidence that this is so for oestradiol; (ii) synthesisof progesterone in the corpus luteum is less affected by lowerconcentrations of gonadotrophins during the luteal phase; (iii)ovulation induction with clomiphene results in pregnancies withlower concentrations of HCG, suggesting that trophoblast functionmay be impaired; and (iv) corpus luteum function is linked withplacental steroidogenesis. 相似文献
12.
Zelinski-Wooten MB; Hutchison JS; Hess DL; Wolf DP; Stouffer RL 《Human reproduction (Oxford, England)》1998,13(3):554-560
The efficacy of follicle stimulating hormone (FSH) as an alternative to
luteinizing hormone (LH)/human chorionic gonadotrophin (HCG) for the
initiation of periovulatory events in primate follicles is unknown. A
single bolus of 2500 IU recombinant (r)-hFSH was compared to 1000 IU r- HCG
for its ability to promote oocyte nuclear maturation and fertilization,
granulosa cell luteinization and corpus luteum function following r-hFSH
(60 IU/day) induction of multiple follicular development in rhesus monkeys.
Following the r-hFSH bolus, bioactive luteinizing hormone concentrations
were <3 ng/ml. Peak concentrations of serum FSH (1455+/-314 mIU/ml;
mean+/-SEM) were attained 2-8 h after r-hFSH, and declined by 96 h.
Bioactive HCG concentrations peaked between 2-8 h after r-HCG and remained
> or = 100 ng/ml for >48 h, while immunoreactive FSH concentrations
were at baseline. The proportion of oocytes resuming meiosis and undergoing
in-vitro fertilization (IVF) were comparable for r-hFSH (89%; 47+/-19%) and
r- HCG (88%; 50+/-17%). In-vitro progesterone production and expression of
progesterone receptors in granulosa cells did not differ between groups.
Peak concentrations of serum progesterone in the luteal phase were similar,
but were lower 6-9 days post-FSH relative to HCG. Thus, a bolus of r-hFSH
was equivalent to r-HCG for the reinitiation of oocyte meiosis,
fertilization and granulosa cell luteinization, but a midcycle FSH surge
did not sustain normal luteal function in primates.
相似文献
13.
Neulen J; Raczek S; Pogorzelski M; Grunwald K; Yeo TK; Dvorak HF; Weich HA; Breckwoldt M 《Molecular human reproduction》1998,4(3):203-206
Vascularization is a prominent event during corpus luteum formation,
providing low density lipoproteins for steroid biosynthesis and enabling
transport of secreted steroids. The process of vascularization is
controlled by specific regulators. Vascular endothelial growth factor
(VEGF), otherwise named vascular permeability factor (VPF), induces
endothelial cell proliferation as well as angiogenesis in vivo and
increases capillary permeability. Here we report the expression of VEGF/VPF
mRNA by cultured human luteinized granulosa cells (GC) for at least 10
days. Without HCG VEGF/VPF expression declined after day 4 and by day 10
was reduced to approximately 30% of the value at day 4. However, after
culture in the presence of 1 U/ml human chorionic gonadotrophin (HCG),
expression of VEGF/VPF mRNA by GC was four times greater than control
experiments by day 10, and increased 100% from day 4 to day 10.
Simultaneously, HCG supplementation increased VEGF/VPF secretion by GC.
Medium VEGF/VPF on day 3 was 13 pM without and 11 pM with HCG. Medium
VEGF/VPF on day 10 was 6 pM without HCG and 29 pM with HCG. These results
suggest that vascularization of the corpus luteum is induced by
HCG-mediated effects of VEGF/VPF.
相似文献
14.
The precise mechanisms by which corpus luteum (CL) function is modulated during early pregnancy are not known. Evidence in failed pregnancies (ectopic, abortions), shows that factors other than human chorionic gonadotrophin (HCG) could be involved in its regulation. The objective of this study was to investigate the dynamics of beta-HCG, progesterone and oestradiol production in early pregnancy and its relation to embryonic quality and topographic localization. Plasma concentrations of progesterone, oestradiol and beta-HCG were studied between days +12 and +21 after an in-vitro fertilization (IVF) embryo transfer in 11 intrauterine pregnancies, 10 intrauterine abortions and seven tubal pregnancies. Tubal pregnancies and abortions were grouped according to doubling time (DT) of HCG. Results showed that oestradiol concentrations were apparently reduced in both ectopic pregnancies and abortions compared with normal pregnancies. The fall in oestradiol concentrations was seen in ectopic pregnancies with an abnormal DT for HCG and in all abortions. When the ectopic pregnancy had a normal DT, oestradiol and progesterone concentrations were normal. In abortions, the fall in oestradiol and progesterone concentrations was less influenced by the DT of HCG. These findings suggest that corpus luteum function depends on an adequate DT of HCG more than an absolute value, and with normal trophoblastic tissue the site of implantation does not affect CL function. 相似文献
15.
Regulatory role of angiotensin II on progesterone production by cultured human granulosa cells. Expression of angiotensin II type-2 receptor 总被引:1,自引:1,他引:0
Johnson MC; Vega M; Vantman D; Troncoso JL; Devoto L 《Molecular human reproduction》1997,3(8):663-668
The role of angiotensin II (AngII) in ovarian steroidogenesis is not
clearly understood. In order to study its action on progesterone synthesis
and to determine which receptor subtype is involve, granulosa cells
obtained from women undergoing in-vitro fertilization were cultured for 2
or 4 days and then incubated in the presence of AngII (10(-7) M) with or
without human chorionic gonadotrophin (HCG, 10 IU/ml) for 3 or 18 h. In
cells cultured for 2 days, incubation with AngII decreased progesterone
secretion by 36%, and inhibited activity of 3 beta-hydroxysteroid
dehydrogenase (3 beta-HSD) by 87% (P < 0.05), although its expression
was not significantly reduced. However, in cells cultured for 4 days,
progesterone production was enhanced by incubation with AngII (38%), and no
change was observed in 3 beta-HSD expression. Both inhibitory and
stimulatory effects were dose- dependent. Progesterone secretion was
increased (93%) by incubation with HCG of cells cultured for 4, but not for
2 days, and no potentiation was observed with AngII. Treatment with
PD123177 completely blocked the action of AngII and decreased the
HCG-stimulated secretion of progesterone by 27%. Angiotensin type-2 (AT2)
receptor mRNA was expressed in cells cultured for 4 days. In conclusion,
AngII showed a regulatory role in in-vitro progesterone production by human
granulosa luteinized cells, modulating the activity of 3 beta-HSD. It is
likely that these actions may be mediated via membrane receptors, possibly
of the AT2 receptor family.
相似文献
16.
It has been reported that success at in-vitro fertilization/embryo transfer (IVF/ET) treatment is increased by follicular fluid (FF) re-injected into the abdomen. In the present study a possible direct effect of FF on human granulosa cell (GC) progesterone (P4) secretion and LH/human chorionic gonadotrophin (HCG) receptor content was studied in the presence and absence of FSH. Human GC cultured for 8 days in medium alone showed a 40-fold decrease in P4 secretion. Addition of human FSH increased P4 secretion and [125I]HCG specific binding by 12- and 8-fold, respectively, compared to human GC cultured in medium alone. The effect of FF was evaluated in a heterologous system by the addition of FF from large antral porcine follicles (LFF) to human GC in culture. The decline in human GC-P4 secretion after 8 days of culture was not altered by either porcine serum alone or porcine LFF alone. However, the concomitant addition of FSH and LFF significantly increased [125I]HCG specific binding, but did not alter the FSH-induced P4 secretion when both parameters were compared to GC cultured in FSH + porcine serum. Furthermore, the addition of HCG alone significantly increased P4 secretion 33- and 70-fold in GC pre-cultured with either FSH alone or FSH + LFF respectively compared with the stimulatory effect of HCG on GC pre-cultured in medium alone. These results may suggest that FSH and LFF increase the functional content of LH/HCG receptor in luteinized human GC. 相似文献
17.
Herman Arie; Raziel Arie; Strassburger Debora; Soffer Yigal; Bukovsky Ian; Ron-El Raphael 《Human reproduction (Oxford, England)》1996,11(7):1552-1557
Luteal support is essential in in-vitro fertilization (IVF)when long-acting gonadotrophin-releasing hormone agonist (GnRHa)is used. Because progesterone lacks luteotrophic stimulation,it seems to be the drug of choice in cases with an increasedrisk of ovarian hyperstimulation syndrome (OHSS). The aim ofthis study was to assess the beneficial effect of the mid-lutealaddition of human choriomc gonadotrophin (HCG) in IVF, usinga down-regulation protocol and luteal support with progesterone,in a prospective randomized study. The study included 170 IVFcycles down-regulated with long-acting GnRHa which were supportedwith 50 mg/day progesterone i.m. during the luteal phase. Patientswere evaluated in the mid-luteal period. Those without clinicalsigns of OHSS, oestradiol concentrations <1000 pg/ml andprogesterone concentrations <50 mg/ml were randomly allocatedto either the addition of 2500 IU HCG (HCG+ group) or no HCG(HCG group). End luteal phase progesterone concentrationsamong non-pregnant patients were used to assess the contributionof exogenous progesterone and to categorize pregnancies accordingto their corpus luteum function. Similar low OHSS (2.7 and 1.8%)and pregnancy (30 and 29%) rates were observed in the HCG+ andHCG groups respectively. Of the 26 pregnancies in theHCG+ cases, there was only one case with reduced corpus luteumfunction, compared with 12 of the 25 pregnancies among HCGpatients. Cases with reduced corpus luteum function requiredcontinuous progesterone support and presented lower HCG concentrationsand a higher rate of adverse pregnancy outcome. We concludethat mid-luteal HCG addition does not affect pregnancy rate,but in fact helps to preserve corpus luteum function and avoidsthe need for further supplementation during early pregnancy. 相似文献
18.
Peri-ovulatory progesterone plays an indispensable role in ovulation and luteinization, possibly by controlling tissue remodelling of the ovulatory follicle. This study was designed to evaluate gonadotrophin- versus progestin-mediated changes to the morphology of the follicle wall during luteinization. Ovaries were obtained from macaques undergoing ovarian stimulation either before (0 h) or up to 36 h following administration of an ovulatory human chorionic gonadotrophin (HCG) bolus with or without a 3beta-hydroxysteroid dehydrogenase inhibitor and a non-metabolisable progestin. Morphological changes occurred within 12 h of HCG in the theca, and around 24 h in the granulosa layer and basement membrane. Steroid depletion resulted in follicles that did not luteinize during the 36 h interval, or alternatively, those that exhibited premature luteinization by 12 h post-HCG. Progestin replacement restored normal morphology, although the presence of antral blood suggested acceleration of normal tissue remodelling. A proportion of pre-ovulatory follicles became atretic after the HCG bolus, although progestin treatment reduced the percentage of atretic follicles. Ovarian stimulation resulted in the development of multiple pre-ovulatory follicles which are heterogeneous in their response to the HCG bolus and local progestin action. Nevertheless, this model supports both anti-atretic and pro-differentiative actions of progesterone in promoting follicular health and remodelling during the development of the corpus luteum. 相似文献
19.
N McClure J Leya E Radwanska R Rawlins R V Haning 《Human reproduction (Oxford, England)》1992,7(6):758-764
The incidence and statistical associations of the ovarian hyperstimulation syndrome (OHSS) were studied in 304 egg retrievals with gonadotrophin-releasing hormone agonist suppression, gonadotrophin administration and follicular aspiration. In addition to preserving corpus luteum function, the luteal phase administration of human chorionic gonadotrophin (HCG) was associated with a higher incidence of severe OHSS than was supplementation with progesterone alone (12 versus 0%, P less than 0.001). Severe OHSS occurred in 3.7% and 12% of retrievals without and with pregnancy respectively (P less than 0.01). Stepwise logistic regression showed that the occurrence of moderate or severe OHSS was statistically predicted by the log of the serum oestradiol on the day the initial HCG was given (P less than 0.0001), treatment with luteal phase HCG (P less than 0.0003), and fetal number (P less than 0.0079). In the late luteal phase of cycles without luteal HCG, the serum oestradiol concentration was one-tenth and the serum progesterone concentration was one-fifth of the luteal phase value with HCG support (P less than 0.001). Without luteal phase HCG, oestradiol was two-fold higher (P less than 0.001) and progesterone was 1.4-fold higher (P less than 0.005) in pregnant than in non-pregnant women. With luteal phase HCG, oestradiol was 1.4-fold higher in pregnant than in non-pregnant women (P less than 0.05), and progesterone was 1.7-fold higher (P less than 0.001). Oestradiol upper limits of 4400 and 14,700 pmol/l (1200 and 4000 pg/ml) for cycles with and without luteal phase HCG respectively correspond to approximately 5% risk of moderate or severe OHSS with a singleton pregnancy under these conditions. 相似文献