Period Of Progesterone Treatment Research Articles

Claudin 5 as a marker of endometrial receptivity in patients with previous implantation failure

To evaluate endometrial functionality in relation to embryo receptivity in order to find markers that might improve the success rate, analyzing two key aspects of this process. First, the vascular function determined by claudin expression and, secondly, the expression of integrins as a marker of endometrial receptivity. Prospective study. 14 patients with implantation failure as defined by Alex Simon etal 2012 criteria were included. All patients had a Mock cycle before IVF cycle. Cld-1, -2, -5 and integrin aVb3 expression was evaluated in the biopsies using specific monoclonal antibodies by immunohistochemistry. Patients with asynchronic endometrium received a five day period of progesterone treatment. Cld 5 was diferentially expressed in 11 out of 14 patients. Integrin aVb3 was expressed in 11. Nine patients expressed both. Cld1 and 2 were poorly expressed and unrelated to clinical pregnancy. All the patients were tadalafil-treated, but only six of them received progesterone for a five day period before embryo transfer independently of embryo stage. Interestingly, five out of the six patients cld5+ and integrin aVb3+ that were treated with progesterone for five days achieved a clinical pregnancy. Cld5 and Integrin aVb3 endometrial expression was related to tadalafil treatment and facilitated clinical pregnancy. Adjustment of progesterone treatment period favored clinical pregnancy.

Allopregnanolone concentration and mood—a bimodal association in postmenopausal women treated with oral progesterone

Allopregnanolone effects on mood in postmenopausal women are unclear thus far. Allopregnanolone is a neuroactive steroid with contradictory effects. Anaesthetic, sedative, and anxiolytic as well as aggressive and anxiogenic properties have been reported. The aim of this study is to compare severity of negative mood between women receiving different serum allopregnanolone concentrations during progesterone treatment. A randomized, placebo-controlled, double-blind, crossover study of postmenopausal women (n=43) treated with 2 mg estradiol daily during four treatment cycles. Oral micronized progesterone at 30, 60, and 200 mg/day, and placebo were added sequentially to each cycle. Participants kept daily symptom ratings using a validated rating scale. Blood samples for progesterone and allopregnanolone analyses were collected during each treatment cycle. During progesterone treatment, women had significantly higher negative mood scores when allopregnanolone serum concentration was in the range of 1.5-2 nmol/l compared to lower and higher concentrations. In addition, women displayed a significant increase in negative mood during the progesterone treatment period, compared to the estradiol-only period when 30 mg progesterone daily was used. On the other hand, treatment with higher doses of progesterone had no influence on negative mood. Mood effects during progesterone treatment seem to be related to allopregnanolone concentration, and a bimodal association between allopregnanolone and adverse mood is evident.

Effect of exogenous progesterone and eCG treatment on ovarian follicular dynamics in vicunas ( Vicugna vicugna)

The aim of the present study was two-fold. First, to evaluate the effect of exogenous progesterone on ovarian follicular dynamics in order to assess its ability to synchronize ovarian activity in the vicuna. Secondly, to evaluate the ovarian response to the treatment with eCG through the observation of the structures developed in the ovaries. Follicular dynamics was monitored daily by transrectal ultrasonography in 12 adult, non-pregnant vicunas. Plasma progesterone and estradiol-17β concentrations were measured in blood samples collected daily. In experiment 1, intravaginal devices containing 0.33 g of progesterone were inserted into the vagina and kept in place for 5 days (treatment group, n = 8). After progesterone withdrawal, five animals were further monitored in order to evaluate the efficacy of the CIDR ® to synchronize the emergence of a dominant follicle. In experiment 2, four females received 750 IU of eCG IM. Two were previously monitored ultrasonographically to confirm the absence of a dominant follicle at the beginning of the superstimulatory treatment (group A). The other two animals had a CIDR ® inserted into the vagina for 5 days and the superstimulatory treatment was applied 24 h after device withdrawal (group B). Females from both groups were surgically explored 96 h after eCG injection; the ovaries were exposed and the number of newly formed structures produced by each ovary was counted. Peak progesterone concentrations (25.9 ± 5.29 nmol l −1, mean ± S.E.M.) were attained on day 1 after device insertion, remained high until the day of device withdrawal (9.7 ± 1.98 nmol l −1) and decreased to 5.5 ± 1.13 nmol l −1 the day after. There was no follicle development to the state of dominance after device insertion. Moreover, mean follicle diameter steadily decreased after insertion of the device until the minimum mean value (1.85 ± 0.17 mm) was recorded on day 5 ( P = 0.006). Similarly, plasma concentrations of estradiol-17β remained below 35 pmol l −1 during the period of progesterone treatment in all animals and the mean estradiol-17β declined with the lowest value (22.1 ± 2.19 pmol l −1) being recorded on day 4 after device insertion. After superstimulation of follicular development with eCG, the total number of follicles that developed was 33 in group A and 58 in group B and the mean number of newly developed ovarian structures per female was 22.75 ± 4.26. In conclusion, progesterone released by the CIDR ® exerts a negative effect on ovarian follicular development and function suggesting intravaginal devices could be used to synchronize the beginning of follicular waves during a superstimulatory treatment. There was also a tendency for greater ovarian follicular development when the animals were previously treated with progesterone.

Behavioral Dominance and Corpus Luteum Function in Red DeerCervus elaphus

Times of the ovulatory LH surge and characteristics of the rise in circulating progesterone concentrations after ovulation in red deer hinds were investigated in relation to each animal's dominance status. Observations were made during the 1992 (experiment 1) and 1993 (experiment 2) breeding seasons, while the same 12 hinds were held in a pen in the absence of a stag. Ovulation was synchronized by administration of progesterone followed by luteolytic prostaglandin F2αanalogue. Social status was determined for each hind by noting dyadic agonistic interactions during the period of progesterone treatment. Hinds were weighed before and after the experiments. Time of onset of estrus (lordosis) was recorded while handling at 3-hr intervals (for 81 hr in experiment 1; 96 hr in experiment 2) after progesterone withdrawal, and blood samples were collected at these times to characterize the preovulatory LH surge. Subsequently, daily blood samples were collected for up to 11 days for measurement of progesterone concentrations. There was a tendency for weight change to be related to dominance status in experiment 1 and this was significant in experiment 2 (p< 0.01). The rate of increase in circulating progesterone concentration after ovulation was related to status (data of experiments 1 and 2 combined;p< 0.02), but was not correlated with the time of estrus or with the time or height of the LH surge. A third experiment (carried out in 1993), when the same hinds were kept with a stag after induced ovulation, showed that time of estrus (mating) was not related to dominance status. The data suggest that corpus luteum function is affected by social status. The results are discussed in the context of mechanisms by which dominance status influences the sex of a hind's calves.

Progesterone up-regulates vasodilator effects of calcitonin gene–related peptide in N G-nitro- l-arginine methyl ester–induced hypertension

OBJECTIVE: We recently reported that calcitonin gene–related peptide can reverse the hypertension produced by N G-nitro- l-arginine methyl ester in pregnant rats. In the current study we investigated whether these vasodilator effects of calcitonin gene–related peptide were progesterone dependent. STUDY DESIGN: Calcitonin gene–related peptide or N G-nitro- l-arginine methyl ester was infused through osmotic minipumps, either separately or in combination, to groups of five pregnant rats from day 17 of gestation until day 8 post partum or to nonpregnant ovariectomized rats for 8 days. Progesterone was injected during days 1 to 6 post partum and for 6 days after ovariectomy. Systolic blood pressure was measured daily. RESULTS: Animals receiving N G-nitro- l-arginine methyl ester exhibited significant elevations of blood pressure during pregnancy and post partum. Coadministration of calcitonin gene–related peptide to these rats reversed the hypertension during pregnancy but not during the postpartum period. At the dose used in this study calcitonin gene–related peptide administered alone was without significant effects on blood pressure. However, it reduced both the mortality and growth restriction of the fetus associated with N G-nitro- l-arginine methyl ester in these animals. Calcitonin gene–related peptide reversed the hypertension in N G-nitro- l-arginine methyl ester–infused postpartum rats during the periods of progesterone treatment only, and these effects were lost when progesterone treatment was stopped. Neither progesterone nor calcitonin gene–related peptide alone were effective. To further confirm these observations, progesterone effects were tested in ovariectomized adult rats. Similar to the findings in postpartum rats, calcitonin gene–related peptide completely reversed the elevation in blood pressure in N G-nitro- l-arginine methyl ester–treated rats receiving progesterone injections. The effects of calcitonin gene–related peptide were apparent only during the progesterone treatment period, and these effects were lost when progesterone treatment was stopped. Again, at these doses calcitonin gene–related peptide and progesterone were each ineffective alone. Conclusions: Calcitonin gene–related peptide reverses the N G-nitro- l-arginine methyl ester–induced hypertension during pregnancy, when progesterone levels are elevated, but not post partum or in ovariectomized nonpregnant rats. The blood pressure–lowering effects of calcitonin gene–related peptide were restored in both postpartum and ovariectomized rats with progesterone treatment. Therefore we conclude that progesterone modulates vasodilator effects of calcitonin gene–related peptide in hypertensive rats. (Am J Obstet Gynecol 1997;176:894-900.)

Effect of alteration of maternal plasma progesterone concentrations on fetal behavioural state during late gestation.

Placental progesterone synthesis exposes the fetus to high levels of progesterone and progesterone metabolites during late gestation which may influence fetal behaviour. To determine the role of maternal progesterone synthesis in the control of fetal arousal state and fetal breathing movements (FBM), the effect of raising and lowering maternal progesterone concentrations was examined in chronically catheterised fetal sheep. Fetal and maternal vascular catheters, fetal tracheal and amniotic fluid catheters as well as electrodes for recording fetal electrocortical (ECoG), electro-ocular (EOG) and nuchal muscle electromyographic (EMG) activity were implanted between 118 and 122 days gestational age (GA). Progesterone, 100 mg, administered twice daily i.m. for 3 days (130-133 days GA) resulted in a marked elevation in maternal plasma progesterone concentrations (370 +/- 121%, n = 5, P < 0.05), but had no effect on fetal plasma concentrations. Fetal EOG episodes and the duration of fetal behavioural arousal were significantly suppressed throughout the progesterone treatment period (74.4-81.1% and 58-65% respectively, P < 0.05, n = 5). Four ewes received Trilostane (25 mg i.v.), a 3 beta-hydroxysteroid dehydrogenase inhibitor, between 136 and 140 days GA. Maternal and fetal progesterone concentrations were significantly lowered by 60 min after treatment (19.8 +/- 8.0% and 39.5 +/- 24.3% respectively, P < 0.05). The incidence of fetal EOG activity increased from a pretreatment level of 26.8 +/- 1.5 min/h to 30.3 +/- 2.8 min/h at 1-6 h and to 35.0 +/- 1.7 min/h (P < 0.05) during the 7-12 h after Trilostane treatment. The duration of FBM episodes was significantly higher at 1-6 h and 7-12 h after Trilostane treatment (19.5 +/- 3.0 and 23.6 +/- 5.5 min/h respectively, P < 0.05) compared with pretreatment levels (11.2 +/- 1.2 min/h). We conclude that increasing maternal progesterone levels suppresses fetal EOG activity and behavioural arousal, whereas reducing maternal progesterone synthesis leads to an elevation of EOG activity and FBM.

Effect of Feeding Calcium Soaps to Early Postpartum Dairy Cows on Plasma Prostaglandin F2α, Luteinizing Hormone, and Follicular Growth

Multiparous Holstein cows (n=18) were fed a total mixed ration containing corn silage, corn grain, whole cottonseed, soybean meal, dried distillers grains, and chopped bermudagrass hay (control) or same diet plus Ca salts of long-chain fatty acids (2.2% of diet DM) for the first 60 d postpartum. Predicted energy balance was calculated from DM intake, milk yield and composition, and BW. On d 25 postpartum, cows were injected with 25mg of prostaglandin F2α and treated for 15 d with an intravaginal device containing 1.9g progesterone. Profiles of 15-keto-13,14-dihydro-prostaglandin F2α (d 1 to 21) and plasma triglycerides (d 7 to 60) were similar between groups. Average number of follicles, determined by ultrasonography prior to d 25, tended to differ between groups; controls had more 3- to 5-mm and fewer 6- to 9-mm follicles than the group of fat-fed cows. Basal, smoothed mean concentration, and average luteinizing hormone amplitude, determined by 10-min samples for 8h on d 10, were not significantly different between groups. Increasing predicted energy balance was associated with increased pulse amplitude and diameter of the largest follicle on d 10. During the progesterone treatment period and the postprogesterone treatment estrous cycle, cows fed fat had greater numbers of 3- to 5-mm and >15-mm follicles. In conclusion, feeding fat did not influence 15-keto-13,14-dihydro-prostaglandin F2α or luteinizing hormone dynamics but did alter the average number of follicles within different size classes and the diameter of largest and second largest follicle after progesterone treatment.

Embryo transfer in the Angora goat

A total of 711 embryos was collected from 121 Angora does mated to Angora bucks. They were transferred to 667 feral recipient does, of which 361 kidded, producing 378 kids. Donors were treated with 36, 40 or 45 mg of an equine anterior pituitary extract (HAP) or 1500 i.u. pregnant mare serum gonadotrophin (PMSG) given at the end of a period of progesterone treatment (12 mg/day by intramuscular injection), while the recipients were either untreated, or their time of oestrus was controlled by progestagen-impregnated intravaginal pessaries or by the prostaglandin analogue 'Estrumate' (I.C.I.). All 121 donors exhibited oestrus after treatment, and 104 (86%) were in oestrus 48–60 h after the final injection of progesterone. Donors were naturally mated by allowing them free access to bucks, hand-mated at 12-h intervals, surgically inseminated into the uterus, or inseminated into the cervix; and in does treated with HAP the proportion of recovered eggs fertilized were respectively 88, 79, 65 and 32%. Seven does received PMSG. They were all hand-mated, and 46% of eggs recovered were fertilized. The mean numbers of corpora lutea in does treated with HAP and PMSG were 10.4 ± 0.9 and 13.7 ± 2.2, and it is suggested that the low rate of fertilization following PMSG was due to an excessive ovulatory response. Treatment with pessaries and Estrumate effectively controlled the time of oestrus in recipients and, overall, there was little difference between the proportions of treated and untreated recipients which kidded (58 v. 50% recipients kidded). Embryos were recovered from donors 3½–5½ days after they were first observed in oestrus, and they were transferred to recipients first observed in oestrus 48 h before to 48 h after their respective donors. The kidding rate of does which received day 3½ embryos was less than that of those which received older embryos (28 v. 55%), but the degree of asynchrony between respective donors and recipients had no effect upon survival.

Seasonal variation in the reactivity to oestrogen of the ovariectomized ewe

Fifteen tests carried out at an average interval of 4 weeks for 14 months showed an annual rhythm in the proportion of spayed crossbred ewes which exhibited oestrus after an injection of 15.6 µg oestradiol benzoate (ODB) following a 12 day period of progesterone treatment. Reactivity was highest in late summer and early autumn and lowest in winter and early spring. The periods of minimum reactivity coincided with the periods of low environmental temperatures and low body weights. The significance of the annual rhythm is discussed with particular relation to the phenomenon of "silent oestrus". No similar rhythm was detected in the 7-aginal response to oestrogen.

The behavioural and vaginal response of the spayed ewe to oestrogen injected at various times relative to the injection of progesterone.

SUMMARY Three trials, each using seventy-two ovariectomized Suffolk cross-bred ewes, were conducted to determine the interaction on the behavioural and vaginal response of varying the time of injection of oestradiol benzoate (ODB; dose levels 16, 20 and 25 μg in oil) relative to that of progesterone (six injections each of 6 mg in oil, spread over 3 days). When ODB was injected before or during the period of progesterone treatment no ewe was served, and the vaginal response was partially suppressed. Maximal behavioural responses were observed when ODB was injected 24–48 hr after the final injection of progesterone. Responses decreased as this interval increased. Maximal vaginal responses were observed when ODB was injected 48 hr or more after the final injection of progesterone. Vaginal sensitivity did not decline with increase in this interval. For assay purposes, using both criteria, it is necessary to inject oestrogen 48 hr after cessation of progesterone treatment in order to obtain a maximal response.