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Biomedical subjects

H B Croxatto

Publications and source records attributed to H B Croxatto.

At least 145 records · Page 8Linked to original sources

Endocrine response and ovum transport in women treated with D-Trp6-luteinizing hormone-releasing hormone in the postovulatory period.

Possible alterations in ovum transport during increased activity of the hypothalamic-pituitary-ovarian axis were investigated in women. D-Trp6-luteinizing hormone (LH)-releasing hormone, a synthetic peptide with potent gonadotropin-releasing activity, was used to induce a gonadotropin surge and stimulate ovarian steroid secretion in the postovulatory phase. The compound was administered intramuscularly or intravenously 24, 48, or 72 hours following the maximum preovulatory LH level in plasma in seven women. An immediate and pronounced gonadotropin surge accompanied by a moderate increase in the estradiol and progesterone level was obtained in all cases. Ova were recovered from the fallopian tubes in four of the seven women 24 hours following treatment. The rate of recovery and the location of ova within the genital tract indicate that the treatment and the resulting endocrine changes failed to accelerate migration of the ova toward the uterus. This observation, taken together with other negative findings previously reported, suggests that in comparison with other mammals transport of the ovum in the woman is relatively insensitive to endocrine changes occurring in the postovulatory phase.

Adult↗

A five-year clinical trial of levonorgestrel silastic implants (Norplant TM).

Silastic implants containing the progestin, levonorgestrel, were tested as a long-term contraceptive system in 101 women. During five full years of use, no pregnancies occurred. The 5-year continuation rate was 54%. Menstrual irregularities were the most frequent reason for termination of use but only during the first year. More than half of the terminations for this reason were in the first year. Some of the subjects elected to continue use of the implants beyond 5 years, allowing release rate data to be obtained through 6 years. From the second through the sixth year of use, the implants delivered a constant 30 micrograms per day of levonorgestrel to the subjects, and even after six years 57% of the original steroid content remained in the capsules. Return of fertility following removal was essentially immediate and not related to time of use. Medical reasons for removal were infrequent and no pattern was discernible.

Adult↗

Changes in nuclear estrogen receptor level in the rat oviduct during ovum transport.

The purpose of this study was to assess variations in the concentration of nuclear estrogen receptor in the oviduct during normal embryo transport and to determine its temporal relationship with the passage of eggs to the uterus. Groups of 6--8 rats were sacrificed at different intervals from 0800 h on Day 1 to 1700 h on Day 4 of pregnancy to determine the concentration of nuclear estrogen receptor in the oviduct, the plasmatic estrogen level and the location of eggs in the genital tract. No significant variations in the amount of nuclear estrogen receptor were observed throughout the first 3 days. However, on Day 4 of pregnancy, concomitant with an elevation of plasma estrogen level there was a significant increase in nuclear estrogen receptor which started 4 to 5 h before the first ova began to reach the uterus. The receptor concentration attained a 3-fold elevation over previous days and returned to basal levels when 30% of the ova had been transferred to the uterus. These results provide evidence that estrogen exerts a direct action on the oviduct during embryo transport and that the passage of embryos to the uterus is preceded by a well-defined increment of estrogenic action on the oviduct. This temporal relationship is in keeping with the concept that estrogen receptor mediated events taking place in the oviduct may be involved in timing the transport of ova through the tubouterine junction.

Animals↗

Role of ovarian and adrenal progesterone in the regulation of ovum transport in pregnant rats.

This study was designed to assess the role of postovulatory ovarian and adrenal progesterone secretion in the regulation of ovum transport in pregnant rats. The number and distribution of embryos in the genital tract and the plasma progesterone levels were determined during the first 5 days of pregnancy in ovariectomized (OVX), adrenalectomized (ADX), ovariectomized and adrenalectomized (OVX + ADX), intact control (IC), or sham-operated control (SOC) rats. Some OVX or OVX + ADX rats received subdermal implants of progesterone pellets following surgery. The day of insemination was designated Day 1 of pregnancy. Transport of embryos from the oviduct to the uterus was essentially complete by the morning of Day 5 in IC and SOC. Neither adrenalectomy performed on Day 1, nor ovariectomy done on Day 4 of pregnancy modified the time of passage of ova from the oviduct to the uterus. Retention of some eggs in the oviduct, accompanied by rapid transport of others into the uterus and expulsion through the vagina, was observed when ovariectomy was performed on Days 1, 2 or 3, or when ovariectomy plus adrenalectomy were performed on Day 1. Following ovariectomy plus adrenalectomy or ovariectomy but not adrenalectomy alone, there was a marked and sustained decline in serum progesterone concentration. Subdermal implants of progesterone supplied on Day 1 restored progesterone levels and improved the pattern of ovum transport in OVX or OVX + ADX. It is concluded that postcoital secretion of progesterone by the ovary plays a major role in the physiologic regulation of oviductal embryo transport in the rat. Progesterone secreted by the adrenal is neither essential nor can it substitute for the ovarian source in the regulation of this process.

Adrenal Glands↗

Plasma progesterone levels following subdermal implantation of progesterone pellets in lactating women.

The magnitude and duration of elevated plasma progesterone levels resulting from subdermal implantation of progesterone pellets were investigated in full nursing women. This condition was chosen because it is associated with a low rate of ovulation and minimal endogenous progesterone production. In addition, treatment with progesterone pellets was intended to be a substitute for oral or parenteral administration of synthetic progestogens to nursing mothers. A control group of full nursing women receiving no hormones provided blood samples so that basal plasma progesterone levels from the second to the sixth post-partum month could be assessed. Progesterone pellets were implanted subdermally on day 30-35 after delivery. Insertion of 2, 4 or 6 pellets each containing 100 mg of progesterone caused an initial elevation of plasma progesterone to 5.9, 9.9 and 13.5 nmol/l, respectively. This initial elevation was followed by a gradual decline, so that basal levels were attained at 70, 100 and 150 days after insertion of 2, 4 or 6 pellets. Implantation of 6 progesterone pellets led to a significant decrease in the ovulation rate of nursing women. These results indicate that subdermal implantation of 6 progesterone pellets can provide biologically effective levels of the hormone for up to 5 months.

Adolescent↗

Plasma progesterone levels during long-term treatment with levonorgestrel silastic implants.

Plasma progesterone levels were measured in 113 women using a subdermal implant containing 200 mg levonorgestrel (NORPLANT) in an attempt to assess the roles of anovulation and inadequate luteal function in the contraceptive action of this method. Twenty-two women using an IUD (Copper T 200) served as a control group. Blood samples were taken twice a week for 6 consecutive weeks. This was done one to four times in each subject during the first 7 years after insertion of NORPLANT. Plasma progesterone was measured by a specific RIA and criteria based upon normal values in this laboratory were used to define each set of samples as ovulatory, uncertain or anovulatory. The rate of anovulation varied between 25 and 80% throughout the 7 years. The highest rate was observed during the first year of treatment of treatment. The rate of anovulation was significantly correlated with the plasma levels of levonorgestrel. Varying degrees of inadequate corpus luteum function were detected among NORPLANT users. All sets of samples in the control group were ovulatory and compatible with normal luteal function. These results clearly show that continuous administration of levonorgestrel by means of NORPLANT interferes with ovulation and/or luteal function in a significant proportion of cycles throughout the first 7 years of use.

Adult↗

Plasma levels of levonorgestrel in women during longterm use of norplant.

Levonorgestrel plasma levels were determined by a specific radioimmunoassay in a group of 110 women at various intervals between 1 and 60 months following implantation of six silastic capsules containing levonorgestrel (Norplant). The implants were placed subdermally in the volar aspect of the forearm. Blood samples were taken twice a week for six consecutive weeks in each subject. Blood drawn from the antecubital vein ipsilateral to the implant site contained two to three times more levonorgestrel than contralateral samples. Average systemic plasma levels represented by contralateral samples ranged from 0.35 +/- 0.03 to 0.29 +/- 0.02 ng/ml (Mean +/- S.E.) in the first and fifth year, respectively. The difference between these values is statistically significant at the 5% level. The results of the regression analysis of individual levels suggest that the decline observed throughout the first five years is mainly due to an early decrease taking place in the first two years. When the sampling period was repeated in the same subjects two or three times 10 to 24 months apart, no significant difference was found. A significant negative correlation was found between plasma levonorgestrel levels and body weight and body surface. The data indicate that the contraceptive efficacy of Norplant during the first five years of use is associated with sustained release of levonorgestrel and is in keeping with the estimated life span of Norplant of seven years.

Female↗

Studies on the duration of ovum transport by the human oviduct. III. Time interval between the luteinizing hormone peak and recovery of ova by transcervical flushing of the uterus in normal women.

This article deals with attempts to time the onset and duration of the ovum's sojourn in the endometrial cavity of women. Recovery of the ovum from the uterus was attempted by means of transcervical flushing of the cavity 48 to 216 hours after the luteinizing hormone (LH) peak in plasma. A single flushing or repetitive flushings done at 24-hour intervals in the same cycle were performed in different subjects. With both modalities, the adverse effects were mild and few. Of 132 flushings done in 76 subjects, 90 were considered to be technically adequate from the point of view of recovering over 50% of the flushing volume. Twenty ova were recovered. Technically adequate flushings and adequate timing of the LH peak were accomplished in 39 cycles. In this group, 13 ova were recovered between 96 and 168 hours after the LH peak. The highest yield of ova per flushing was obtained from 120 to 168 hours with an average of 37% and a range of 25% to 50%. Limitations of the technique are discussed. Some uncertainties persist which prevent the drawing of definitive conclusions about how soon after the LH peak the egg enters the uterine cavity, how long it stays there, and what is the extent of individual variation. However, recovery rates at various times after ovulation agree with previous data derived from transfundal flushing and indicate that the ovum is usually transferred to the uterus between 96 and 120 hours after the LH peak is retained there for several days.

Adult↗

Correlation between histologic dating of human corpus luteum and the luteinizing hormone peak--biopsy interval.

The purpose of this study was to assess the accuracy of retrospective dating of ovulation in women based on the histologic dating of the corpus luteum. Corpora lutea enucleated from the ovary of 39 women between one and six days following the LH peak in plasma were examined by routine histologic techniques and dated according to Corner's criteria. The correlation between the luteinizing hormone (LH) peak--biopsy interval and histologic dating was assessed. Linear regression analysis of the data gave a correlation coefficient of 0.76. However, the dating of different corpora lutea obtained at the same LH peak--biopsy interval can differ by as much as four days. In addition, it was found that the stages named by Corner as days 1 and 2 seem to develop within the first 24 hours following the LH peak, while stages corresponding to days 4 and 5 each take two days to develop. It is concluded that the use of corpus luteum morphologic features for retrospective timing of ovulation is subject to an error of variable magnitude due to unequal duration of each stage, as well as considerable individual variation.

Corpus Luteum↗

Plasma levels of levonorgestrel in women during longterm use of Norplants.

Levonorgestrel plasma levels were determined by a specific radioimmunoassay in a group of 110 women at various intervals between 1 and 60 months following implantation of six silastic capsules containing levonorgestrel (Norplant). The implants were placed subdermally in the anterior aspect of the forearm. Blood samples were taken twice a week for six consecutive weeks in each subject. Blood drawn from the antecubital vein ipsilateral to the implant site contained two to three times more levonorgestrel than contralateral samples. Average systemic plasma levels represented by contralateral samples ranged from 0.35 +/- 0.03 to 0.29 +/- 0.02 ng/ml (Mean +/- S.E.) in the first and fifth year, respectively. The difference between these values is statistically significant at the 6% level. The results of the regression analysis of individual levels suggest that the decline observed throughout the first five years is mainly due to an early decrease taking place in the first two years. When the sampling period was repeated in the same subjects two or three times 10 to 24 months apart, no significant difference was found. A significant negative correlation was found between plasma levonorgestrel levels and body weight and body surface. The data indicate that the contraceptive efficacy of Norplants during the first five years of use is associated with sustained release of levonorgestrel and is in keeping with the estimated life span of Norplants of seven years.

Adult↗

Ectopic pregnancies associated with low dose progestagen-releasing IUDs.

Dimethyl-polysiloxane capsules containing pure progestagens were attached to Tatum's T IUDs and tested in 594 fertile women for contraceptive performance. The control group was represented by 71 women who received identical devices containing barium sulphate instead of steroid and 100 women who received a Copper T-200. The progestagens and the doses tested were megestrol acetate (4.8, 19.2, 26 and 32 micrograms/day; levonorgestrel (2.1, 3.4 and 8.5 micrograms/day); norethindrone (18 micrograms/day); R2323 (28.6 and 45 micrograms/day); and norgestrienone (26 micrograms/day). Twelve pregnancies were diagnosed during 5201 woman-months of exposure accumulated within the first year of use among users of the steroid-bearing IUDs. Five of these were ectopic gestations. Ten pregnancies, all uterine, were detected during 1701 woman-months of exposure in the control group. Intrauterine delivery of progestagens by means of a carrier IUD is effective in decreasing the pregnancy rate but it might effect postovulatory events in a way which increases the rate of tubal implantation. Because of this property, progestagen-releasing IUDs should be limited to doses that assure maximal effectiveness to avoid increasing the risk of ectopic pregnancy.

Adolescent↗

Ovum transport in women treated with methyl ergonovine.

The location of ova in the genital tract was studied between 24 and 120 hours after the luteinizing hormone (LH) surge in 32 women who had been treated with methyl ergonovine in doses known to stimulate tubal contractility. Thirteen eggs were found in the fallopian tubes, between 48 and 120 hours after th LH peak, and no eggs were recovered from the endoemtrial cavity. No significant difference in tubal ovum recovery or in tubal segmental distribution of ova was found in comparison with these parameters in an untreated control group. These results indicate that stimulation of tubal contractility with methyl ergonovine does not accelerate ovum transport through the fallopian tubes in the human.

Ergonovine↗