Search PubMed⌕ Search

Biomedical subjects

I E Messinis

Publications and source records attributed to I E Messinis.

At least 91 records · Page 5Linked to original sources

Relationship between intrafollicular levels of prolactin and sex steroids and in-vitro fertilization of human oocytes.

In this study the importance of intrafollicular prolactin (PRL) and sex steroid levels, as indices of the potential in-vitro fertilization and development of human oocytes, was investigated. Oocytes were recovered from 20 normal female volunteers treated with a fixed schedule including norethisterone and clomiphene. The embryos which developed after in-vitro fertilization were graded on a scale of 0 to 10 using morphological criteria. Intrafollicular PRL, oestradiol, progesterone and androstenedione levels did not differ significantly between follicles containing oocytes which fertilized and those which did not fertilize in vitro. Nor did these hormones differ significantly between follicles giving rise to embryos with a bad score (0-5) and those with a good score (6-10). No significant correlation was found between serum and follicular fluid PRL levels. It is suggested that fertilization and developmental potential of human oocytes in vitro cannot be predicted by the intrafollicular levels of PRL and sex steroids at the time of laparoscopic egg recovery.

Androstenedione↗

Effect of high dose exogenous oestrogen on midcycle luteinizing hormone surge in human spontaneous cycles.

Induction of multiple follicular development in women results in supraphysiological serum oestradiol (E2) levels and marked reduction of the endogenous LH surge. To examine whether high serum E2 levels at midcycle can suppress gonadotrophin secretion during the LH surge, five normally ovulating women were given an intramuscular injection of 10 mg oestradiol benzoate 6-42 h before the expected endogenous LH surge. The results were compared with the preceding untreated control cycle. Serum E2 levels at the onset of the LH surge (mean +/- SEM) were significantly higher in the oestrogen-treated cycles (13,600 +/- 1963 pmol/l) than in the control cycles (1012 +/- 116 pmol/l) (P less than 0.001). The duration of the LH surge (64.8 +/- 2.2 h) and LH peak levels (136 +/- 9.6 mIU/ml) in the oestrogen treated cycles were similar to those in the control cycles (61.2 +/- 3.9 and 119 +/- 9.4 mIU/ml respectively) (mean +/- SEM). The cycle day on which the LH surge started and the size of the dominant follicle, as assessed by ultrasound, did not differ significantly between the two groups of cycles. These results show that in spontaneous cycles the endogenous LH surge is neither reduced nor amplified by the induction of supraphysiological serum E2 levels during the immediate pre-ovulatory stage.

Estradiol↗

Luteal phase after ovarian hyperstimulation.

The luteal phase was investigated in 17 women with normal menstrual cycles and tubal infertility who were superovulated with clomiphene (9 cycles), clomiphene plus pulsatile human menopausal gonadotrophin (hMG) (12 cycles) and clomiphene plus pulsatile follicle stimulating hormone (FSH) (11 cycles) during an in-vitro fertilization programme. Follicles were aspirated 34-36 h after the onset of the endogenous LH surge. Urinary total oestrogen levels during the first 6 days of the luteal phase were significantly higher, the duration of the luteal phase was significantly shorter and the luteal levels of urinary pregnanediol were significantly lower in the two combination treatment cycles than in the clomiphene only cycles. When the three treatment groups were combined the mid-luteal peak pregnanediol levels and the duration of the luteal phase showed significant negative correlations with plasma or urinary oestrogen levels during the follicular and the luteal phase. It is suggested that the luteal function in cycles superovulated with clomiphene/hMG or clomiphene/FSH is disrupted and this is related to the high amounts of circulating oestrogen.

Clomiphene↗

Disparate effects of endogenous and exogenous oestradiol on luteal phase function in women.

Five normally ovulating women were induced to superovulate with pulsatile 'pure' FSH (28 i.u. every 3 h by a s.c. pump), and another 5 women were given an i.m. injection of 10 mg oestradiol benzoate in the late follicular phase. Serum oestradiol concentrations in the luteal phase were similar in both groups and significantly higher than in corresponding control cycles. The luteal phase was of shorter duration in the FSH (11.2 +/- 0.7 days) than in the control (13.4 +/- 0.2 days) and the oestrogen-treatment cycles (13.4 +/- 0.7 days) (P less than 0.05, mean +/- s.e.m.). FSH cycles had significantly lower early luteal serum LH (Day 1: 5.3 +/- 1.5 mi.u./ml) and mid-luteal serum progesterone values (35.4 +/- 3.5 nmol/l) compared with the control (27.8 +/- 5.8 mi.u./ml and 65.4 +/- 5.7 nmol/l, respectively) and oestrogen treatment cycles (25.3 +/- 8.3 mi.u./ml and 59.1 +/- 8.4 nmol/l, respectively) (P less than 0.05, mean +/- s.e.m.). These results suggest that, in hyperstimulated cycles, the luteal phase can be disrupted even without follicle aspiration, and that suppression of endogenous LH secretion may be responsible.

Corpus Luteum↗

Characteristics of ovarian follicles in spontaneous and stimulated cycles in which there was an endogenous luteinizing hormone surge.

The growth of ovarian follicles was assessed with the use of ultrasound in spontaneous cycles and in cycles stimulated with clomiphene citrate (CC) alone, CC plus pulsatile human menopausal gonadotropin, and CC plus pulsatile follicle-stimulating hormone (FSH). At the time of the onset of the luteinizing hormone surge (LH), the size of the leading follicle did not differ significantly between the spontaneous and the stimulated cycles, although it was larger in the CC/FSH cycles. During the two days before the LH surge onset, the growth rate was faster in the stimulated than the spontaneous cycles. It is suggested that despite the provocation of extremely high plasma-estradiol levels and multiple follicular development, the leading follicle in stimulated cycles ovulated at a size equal to or greater than that in spontaneous cycles. The reason for the higher follicle size in the CC/FSH cycles is, as yet, unclear.

Clomiphene↗

Comparison between clomiphene plus pulsatile human menopausal gonadotrophin and clomiphene plus pulsatile follicle stimulating hormone in induction of multiple follicular development in women.

Eighteen normally cycling women with tubal infertility undergoing in-vitro fertilization and embryo transfer were treated with clomiphene only (nine cycles), clomiphene plus human menopausal gonadotrophin (HMG) (18 cycles) and clomiphene plus follicle-stimulating hormone (FSH) (12 cycles). Clomiphene was given from day 2 to 6 (150 mg daily). HMG and FSH were injected s.c. in a pulsatile manner via a pump (28 IU every 3 h). Plasma FSH and oestradiol levels and the number of follicles greater than or equal to 16 mm in diameter were similar in the clomiphene/HMG and the clomiphene/FSH cycles, but significantly higher than in the clomiphene-only cycles. In contrast, luteinizing hormone and progesterone levels during the treatment did not differ significantly among the three regimens. Twelve of the 18 women were treated with clomiphene/HMG in one cycle and clomiphene/FSH in another and eight of them with clomiphene only in a third cycle (a total of 32 cycles). In the clomiphene/HMG cycle seven of these 12 women (58%) had plasma FSH levels during treatment similar to those in the clomiphene/FSH cycle and six of them (86%) had the same number of follicles in both cycles. A significant, but not very strong correlation was found between FSH treatment levels and the number of follicles greater than or equal to 16 mm when all 32 cycles were combined (r = 0.40). It is suggested that pulsatile HMG and FSH in combination with clomiphene are in general equally effective in inducing multiple follicular development in normal women. However, individual responses show great variability.

Clomiphene↗

Endogenous luteinizing hormone surge in women during induction of multiple follicular development with pulsatile follicle stimulating hormone.

In this study nine consecutive normally cycling women undergoing in-vitro fertilization (IVF) were superovulated with clomiphene citrate followed by pulsatile 'pure' FSH injected s.c. via a pump (28 IU every 3 h). All women displayed an endogenous LH surge, which was markedly attenuated in most of the cases (peak value 44.5 +/- 5.9 U/l, duration 29.2 +/- 1.2 h, mean +/- SEM) as compared to spontaneous cycles. An increase in serum progesterone levels before the onset of the LH surge was seen in only one woman at a time when the LH values were low. During the LH surge serum progesterone levels increased significantly in all patients (12.7 +/- 1.90 nmol/l vs 4.74 +/- 1.57 nmol/l at the onset of the surge, mean +/- SEM, P less than 0.05) indicating follicular luteinization. Very high oestradiol levels in serum were found at the onset of the LH surge (7504 +/- 898 pmol/l, mean +/- SEM). Preovulatory oocytes were recovered from all women through a laparoscope 34-36 h after the beginning of the LH surge and embryos were replaced to them after IVF. One ongoing clinical pregnancy occurred. In contrast to results in monkeys, these results demonstrate for the first time that normally cycling women superovulated with clomiphene pulsatile 'pure' FSH will display an endogenous LH surge. Although the surge is attenuated implantation can occur.

Clomiphene↗

Relationships between the characteristics of endogenous luteinizing hormone surge and the degree of ovarian hyperstimulation during superovulation induction in women.

Ovarian hyperstimulation was induced in 17 normally cycling women undergoing in-vitro fertilization (IVF) and embryo transfer with clomiphene (9 cycles), clomiphene followed by pulsatile hMG (12 cycles) or clomiphene followed by pulsatile FSH (11 cycles). Hyperstimulation was greater with the combined treatments than with clomiphene alone. In all 32 cycles an endogenous LH surge occurred. The peak values and the duration of the LH surge showed significant negative correlations with the plasma oestradiol levels, the number of the follicles and the total follicular fluid volume aspirated at laparoscopy. We suggest that during superovulation induction for IVF, the endogenous LH surge is attenuated by factors which are related to the degree of ovarian hyperstimulation.

Clomiphene↗

The effect of pulsatile follicle stimulating hormone on the endogenous luteinizing hormone surge in women.

The effect of pulsatile administration of 'pure' FSH on the endogenous LH surge was investigated in 10 infertile but otherwise normal women. In each woman the LH surge in the spontaneous cycle preceding the treatment cycle was characterized in blood samples taken every 6 h. FSH was injected s.c. via a pump (28 IU every 3 h) starting on cycle day 2. Only five of the FSH-treated women displayed an endogenous LH surge, and this was markedly attenuated in four of them. The LH surge occurred significantly earlier in the FSH-treated than in the corresponding spontaneous cycle (cycle day 10.2 +/- 0.5 vs 13.6 +/- 0.8 mean- +/- SEM, P less than 0.05), although it tended to occur later in the FSH-treated cycles with a higher total follicular fluid volume of follicles 12-15 mm in diameter. This volume was even greater in the FSH-treated cycles without an endogenous LH surge. Serum progesterone levels increased significantly in all five FSH-treated cycles after the onset of the LH surge and ovulation was confirmed by ultrasound in four of them. These results suggest that the LH surge during superovulation induction with pulsatile FSH in normally cycling women is a variable event. We postulate that unknown inhibitory substances secreted be small growing follicles antagonize the positive feedback effect of E2 on LH secretion.

Animals↗

A comparison of fixed regimens for obtaining human cleaving oocytes for research purposes.

A fixed schedule for ovarian stimulation and follicular aspiration, previously used in our department for research purposes, was modified in an attempt to increase the recovery and cleavage rates of the oocytes. Three different clomiphene regimens were used to stimulate the ovaries of normal volunteer women requesting laparoscopic sterilization (50 mg and 150 mg daily for 5 days, and 50 mg daily for 10 days). Oocytes were recovered from 83% of the aspirated follicles, i.e. 1.6 oocytes/patient: 65% of the oocytes cleaved after in-vitro fertilization and, on average, 1.0 cleaving egg was obtained per patient. There were no differences in the recovery and cleavage rates between the three clomiphene regimens. It is concluded that a sufficient number of cleaving embryos for research purposes can be generated with the present fixed regimen, which offers little inconvenience to the volunteers as the day of egg recovery can be predicted some time in advance.

Adult↗

Urinary oestrogen levels and follicle ultrasound measurements in clomiphene induced cycles with an endogenous luteinizing hormone surge.

Total oestrogen in urine and the ultrasonic size of the follicles were measured in relation to the onset of the endogenous luteinizing hormone (LH) surge (day 0) in 18 cycles induced with clomiphene citrate in an in-vitro fertilization programme. Oestrogen values in urine (microgram/24 h) increased progressively during the late follicular phase up to the day of the onset of the surge. The mean maximum follicle diameter (22.3, SD 4.7 mm) estimated by ultrasound was measured on day 0. At the onset of the LH surge, the values of urinary total oestrogen showed a better relation with the total volume of the first three follicles in order estimated by ultrasound (r = 0.71) than with the mean ultrasonic diameter of the leading follicle (r = 0.56). A wide range of individual values for both urinary oestrogen and follicle size was found. In another group of 32 women treated with clomiphene for recovery of oocytes used for research purposes, a good correlation was found between the mean ultrasonic follicle diameter 16 h before the laparoscopy and the follicle diameter calculated from the fluid volume at aspiration (r = 0.80). These results suggest that the decision when to give human chorionic gonadotrophin (hCG) in an in-vitro fertilization programme remains arbitrary in many individual cases. Apart from the oestrogen levels, the calculation of the size of all follicles, instead of only the leading one, may give further help in timing the hCG.

Clomiphene↗

Consequences of polyspermy in man.

Polyspermy occurs with a frequency of about 12% under some hormonal regimens currently being used for in vitro fertilization and embryo transfer. Oocytes with three pronuclei usually show normal cleavage and are morphologically indistinguishable from embryos produced by normal fertilization. Chromosome studies and DNA measurements on dispermic embryos show that about one-half are triploid, the others having either a normal diploid chromosome complement or a severely depleted chromosome complement. The evidence suggests that these errors must arise at the first mitotic division of the oocyte. Aberrant spindle formation is implicated.

Cell Nucleus↗

Histamine H1 receptor participation in the control of prolactin secretion in postpartum.

It has been reported that cimetidine, an H2-receptor antagonist, stimulates PRL secretion in postpartum. In the present study, the PRL response to two H1-receptor antagonists, promethazine and d-chlorpheniramine, was studied in 38 normal puerperal women on day 1 after delivery. Serum PRL levels decreased significantly after a single dose of promethazine (100 mg) given im (5 women) or d-chlorpheniramine (20 mg) given iv (6 women). In contrast, no significant change in PRL levels was observed after only saline infusion (6 women). Promethazine, given concomitantly to an iv bolus injection of TRH (200 micrograms) (6 women) and d-chlorpheniramine, given at the onset of suckling (6 women), did not alter stimulation of PRL release induced by these challenges. These results suggest the involvement of histamine H1 receptors in the regulation of basal PRL secretion in postpartum and would indicate that they do not participate in the mechanisms underlying suckling-induced PRL release.

Adolescent↗

Endogenous luteinizing hormone surge during superovulation induction with sequential use of clomiphene citrate and pulsatile human menopausal gonadotropin.

There is dispute as to whether an endogenous LH surge occurs in women during follicle stimulation with human menopausal gonadotropin (hMG) for in vitro fertilization (IVF). In this study, 12 consecutive normally cycling women with tubal infertility were treated with clomiphene citrate and hMG for ovulation induction and subsequent IVF. Beginning on the fifth day of clomiphene administration (150 mg daily for 5 days), 225 IU hMG were given daily sc in a pulsatile manner (28 IU/3 h). All women had an endogenous LH surge which started on the seventh to ninth day of hMG administration. The mean duration [25.5 +/- 1.0 (+/- sem) h] and the mean peak value (38.9 +/- 4.7 U/liter) of the LH surge were less than those in spontaneous cycles. However, luteinization of at least some of the follicles occurred, based on findings of supraphysiological levels of serum progesterone during the surge and subsequent increase in urinary pregnanediol levels (luteal phase). Preovulatory oocytes were recovered via laparoscopy 34-35 h after the onset of the surge, and these oocytes cleaved after IVF. One pregnancy was achieved after embryo transfer, which resulted in abortion. These results represent the first demonstration that an attenuated LH surge is obtained in normally cycling women during superovulation induction with sequential clomiphene/pulsatile hMG treatment.

Clomiphene↗

Carcinoembryonic antigen in high risk pregnancies.

The significance of carcinoembryonic antigen (CEA) measurement was evaluated in 25 pregnant women with diabetes mellitus, 15 Rh negative sensitized and nine prolonged pregnancies. Another 114 women with normal pregnancy served as controls. Values in maternal and umbilical cord serum and in amniotic fluid did not change appreciably through 24-42 weeks' gestation. No significant difference in maternal serum, cord serum and amniotic fluid CEA values was found between diabetic, Rh negative sensitized and normal pregnancies at the corresponding weeks. Similar findings were obtained in prolonged pregnancies, except the values in amniotic fluid which were significantly higher than in normal pregnancies due to the presence of meconium. These results suggest that the measurement of CEA in high risk pregnancies is not useful in predicting fetal condition.

Amniotic Fluid↗

Relationships between serum prolactin levels and follicle stimulating hormone response to luteinizing hormone-releasing hormone during early puerperium.

The effect of serum prolactin (Prl) levels on pituitary response to iv luteinizing hormone-releasing hormone (LRH) (100 micrograms) was studied in 23 normal puerperal women on day 1 post-partum. All women had an uneventful full-term pregnancy and delivery. The LRH test was repeated in 8 of the women on day 3 and in the remaining 15 on day 6 post-partum. Serum Prl levels were high on days 1 and 3, but decreased significantly on day 6 (P less than 0.01). No pituitary FSH response to LRH stimulus was found on day 1 post-partum in all 23 women. In those who were given placebo, FSH levels in serum did not change in response to LRH on day 3 (4 women), but increased significantly on day 6 (5 women) in all subjects (P less than 0.05). Conversely, when oral metoclopramide was given from day 1 to 6 (10 women) the responsiveness of FSH to LRH on day 6, found in the placebo group, was not observed. Early reduction of serum Prl values on day 3 post-partum by bromocriptine treatment from day 1 to 3 (4 women) did not accelerate the FSH response to LRH. These results suggest an inhibitory effect of elevated serum Prl on the pituitary FSH response to LRH in women during early puerperium.

Adult↗

Effect of estrogen and progesterone treatment on the depressor response to prostaglandin E2 in ovariectomized women.

The effect of exogenous estrogen and progesterone on the response of the systemic arterial pressure to prostaglandin E2 (PGE2) was studied in 15 ovariectomized women. All experiments were performed on the 7th postoperative day. Arterial blood pressure was measured in all women in supine position at one minute intervals by an automatic recorder. PGE2 infused intravenously in all subjects for 10 minutes. Ten of the women who were given intramuscular injections of either estradiol benzoate (10 mg) or inert vehicle 60-65 hours before the experiment, showed a significant decline in both systolic and diastolic blood pressure during the PGE2 infusion. In contrast, the remaining of the women who were injected with progesterone intramuscularly also 60-65 hours before the experiment, did not present any significant alterations in blood pressure during or after the infusion of PGE2. These results suggest that, in ovariectomized women, progesterone treatment prevents the depressor response to PGE2. This may be due to increased inactivation of PGE2 by various tissues.

Adult↗