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Biomedical subjects

H B Croxatto

Publications and source records attributed to H B Croxatto.

At least 109 records · Page 6Linked to original sources
PubMed1988

Effects of delayed transfer and treatment with oestrogen on the transport of microspheres by the rat oviduct.

Starch or dextran blue microspheres were transferred microsurgically to the infundibulum of the oviduct on Days 1, 2, or 3 of pregnancy of control and oestradiol-treated rats. The animals were killed a few hours to several days after transfer to assess the number and distribution of ova and microspheres in the tract. After transfer on Day 1 of pregnancy, microspheres and eggs crossed the ampullary-isthmic junction (AIJ) 18 h after ovulation. After transfer on Day 2 of pregnancy, more than 50% of microspheres were retained in the ampulla, indicating that the AIJ changes again 34 h after ovulation. Treatment with oestradiol did not advance the passage of eggs or microspheres across the AIJ but caused accelerated transport through the isthmus as soon as the eggs or microspheres reached this segment. Dextran blue microspheres were seen to move back and forth in the isthmus of control anaesthetized rats at a frequency of 5-6 times/min. Between 7 and 20 h after treatment with oestradiol the frequency of these movements was significantly augmented, indicating that increased frequency of contractions of the smooth muscle of the isthmus precedes and accompanies accelerated transport of ova through this segment.

Animals↗
PubMed1988

Effects of 4-hydroxyandrostenedione and exogenous testosterone on blood concentrations of oestradiol and oviducal embryo transport in the rat.

The effect of decreasing oestrogen secretion on the oviducal migration of embryos was investigated in pregnant rats. The reduction of oestradiol production was achieved by administration of the aromatase inhibitor 4-hydroxy-4-androstene-3,17-dione (4-OH-A) at various times after coitus. When 4-OH-A was administered from days 2 to 5, nearly half the embryos were retained in the oviducts at midday on day 5 of pregnancy, in contrast with control animals in which all embryos were transferred to the uterus. Shorter treatments were less effective. The rate of secretion of oestradiol from the ovary on days 2-5 of pregnancy in control rats was low in the morning and high in the afternoon. Treatment with 4-OH-A from days 2 to 5 reduced the secretory surges of oestradiol in the afternoon by 77% without significantly changing the progesterone output. Systemic testosterone levels were significantly increased by this treatment. To assess whether changes in the transport of ova were due to an increase in testosterone concentrations the influence of exogenous testosterone on embryo transport and oestradiol production was tested. Testosterone administered by subdermal implants from days 2 or 3 to day 5 disturbed embryo transport in a manner similar to that of 4-OH-A. The longest period of testosterone administration decreased ovarian oestradiol production by 82% without changing the secretion of progesterone.(ABSTRACT TRUNCATED AT 250 WORDS)

Androstenedione↗
PubMed1988

On the rate of tubal pregnancy contralateral to the corpus luteum.

Ectopic implantation of the embryo in the tube opposite to the ovary containing the corpus luteum constitutes evidence of peritoneal or uterine transmigration of the egg. The frequency of this phenomenon was reinvestigated utilizing histopathologic confirmation of the side of the corpus luteum. A tubal pregnancy contralateral to the ovulating ovary was found in 28% of 67 cases, indicating that either the oocyte, the zygote or the embryo had entered the tube in which implantation took place from a medial site such as the peritoneal or the uterine cavity rather than directly from the ovulating ovary. Assuming that once in the medial site there is equal chance of entering either tube, it follows that in 56% of tubal pregnancies the egg has entered the tube from a midline location. Attempts to recover the oocyte from the tubes in normal women were successful in fewer than 5% of cases contralateral to the corpus luteum. It is concluded that tubal pregnancy is associated with a significant increase in the occurrence of transmigration of the egg.

Adult↗
PubMed1988

Breastfeeding pattern and the duration of lactational amenorrhea in urban Chilean women.

The influence of the breastfeeding pattern and several clinical variables upon the duration of postpartum amenorrhea was assessed in a group of healthy women selected for having had a normal pregnancy and delivery and being highly motivated for prolonged breastfeeding on demand. 676 women who were fully nursing at the second month postpartum entered the study. Supplements were administered to 11% and 48% of the infants by the end of the 3rd and 6th month, respectively. The first bleeding was experienced before the end of the sixth month postpartum by 57% of the cases. Supplementation had a strong negative influence while nursing frequency had a significant positive influence upon the length of amenorrhea. Notwithstanding, a frequency of 8+ suckling episodes per 24 h could not maintain amenorrhea in around half of the subjects. Age and parity had a moderate negative influence upon the risk of experiencing the first postpartum bleeding. Maternal weight and ponderal index, infant sex, birth weight and growth rate showed no significant influence upon the length of amenorrhea. In this urban population selected for having the highest motivation and best breastfeeding performance, the association of breastfeeding with amenorrhea was weak in comparison with what has been described for other populations. The risk of experiencing the first bleeding was reduced while fully breastfeeding with a high number of nursing episodes per day and night, particularly in older women with higher parity. But even in such situation 25% and 50% of the women had started to cycle by the end of the fifth and eight postpartum month.

Adult↗
PubMed1987

The effect of RU486 on transport, development and implantation of mouse embryos.

Pregnancy was interrupted in Swiss-Rockefeller mice by a single subcutaneous injection of the antiprogesterone RU486 given postcoitally. A dose of 0.1 mg/animal injected on day 1, produced partial inhibition of pregnancy, a notable delay in embryonic development and a slight retention of embryos in the oviducts. When the same dose was injected on day 2, 3 or 4, no implantation sites were seen at autopsy performed on day 12 of pregnancy. Treatment with 0.5 or 1 mg/animal on day 1 produced the loss of a large proportion of the embryos from the genital tract by day 4 of pregnancy and suppressed implantation completely. These observations indicate that preimplantation phenomena in mice are highly dependent on progesterone action.

Animals↗
PubMed1987

Treatment with Norplant subdermal implants inhibits sperm penetration through cervical mucus in vitro.

Attempts were made to collect several samples of cervical mucus in each of thirty-three cycles of women using NORPLANT subdermal implants, in seven cycles from NORPLANT-2 rod users, and in 33 control cycles. The attempts to collect a mucus sample were successful on 20 of 77 and 7 of 14 occasions in NORPLANT capsule and rod users, respectively, due to the scanty amount and stickiness found in the majority. All 59 attempts in control subjects were successful. The distance travelled by the fastest sperm and by the bulk of spermatozoa through the cervical mucus in vitro was assessed after 10 min of incubation with a normal semen sample. The best score for each cycle was considered for the comparison between treated and control cases. Sperm penetration was greatly impaired in mucus samples of implant users with penetration by the fastest sperm exceeding 10 mm in only two instances and exceeding 20 mm in none. In 30 of 33 control samples, the fastest sperm travelled 21 mm or more and in 28, the bulk of spermatozoa travelled further than 10 mm. Unsuccessful attempts to collect mucus and poor sperm migration were observed in NORPLANT implant users even when circulating estradiol levels were comparable to those seen in the late follicular phase of the normal menstrual cycle. These results suggest that the principal mechanism by which NORPLANT implants prevent pregnancy is by interference of sperm migration through cervical mucus.

Adult↗
PubMed1987

The mode of action of IUDs.

In women, IUDs produce alterations of the uterine environment in terms of a pronounced foreign body reaction. This biological response may interfere with steps of the reproductive process that normally take place before the ovum reaches the uterine cavity. In order to discuss this hypothesis on the mechanism of action of IUDs, this review is focussed on 1) detection in urine and blood of substances alleged to be specifically produced by the embryo, 2) migration of gametes in the female genital tract, and 3) microscopic features of ova recovered from the genital tract.

Embryo Implantation↗
PubMed1987

The place of progesterone in human contraception.

Progesterone, the natural hormone produced by the corpus luteum and other steroid-secreting glands, is endowed with antiestrogenic action and has a fundamental role in the initiation and maintenance of pregnancy and in the regulation of gonadotropin secretion. Although it was discovered half a century ago, it has found little clinical use as a therapeutic agent due to its low potency and extensive degradation following oral administration in comparison with a variety of highly potent synthetic analogs that became available in the last three decades. When delivered systemically, a large proportion of the dose bypasses degradation in the gut and liver, and progesterone can achieve effective levels in target tissues for clinical use. Sustained administration via compressed pellets implanted subdermally or silicone rubber rings placed in the vagina produced circulating levels of progesterone within the lower third of those found in the luteal phase of the human menstrual cycle. Those levels were shown to delay the recovery of fertility in nursing women without adverse effects to the mother or the infant. Progesterone transferred to the babies via the breast milk did not change their rate of pregnandiol-3-alpha glucuronide excretion. It is concluded that sustained administration of the natural hormone progesterone may be an effective and safe contraceptive method for nursing women.

Administration, Intravaginal↗
PubMed1987

Long-term follow-up of women treated with Norplant implants.

This report describes the long-term follow-up of 376 women who received NORPLANT implants in the period October 1974 through May 1979. One-hundred-and-ten subjects received replacement implants after variable lengths of use of the first set. The average levonorgestrel plasma levels declined steadily through eight years of use of NORPLANT capsules (r = -.937). Values were 0.35 ng/ml, 0.29 ng/ml and 0.22 ng/ml at treatment years 1, 5 and 8, respectively. Levonorgestrel plasma levels after replacement with a second set of implants were similar to those observed after the first insertion, either when placed in the same site as the first set or in a different area. Nineteen pregnancies occurred during 18,530 woman-months of use of the first set of implants, eleven of them during years 6 through 8 of treatment. The Pearl Index for the first 5 years of NORPLANT implants use was 0.63. No pregnancy has occurred in 4194 woman-months observed during treatment with a second set of capsules. Fifty-six women (14.9%) out of 376 acceptors of the first implant and 10 (9.1%) out of 110 acceptors of the replacement implants were terminated for other medical reasons, mainly bleeding problems and side effects commonly associated with hormonal contraception. Two women died while using NORPLANT implants, one of a cardiac arrest after surgery for a gallbladder disease and one because of endocranial hypertension originating from the rupture of an aneurism of the median cerebral artery. The bleeding pattern observed in the three months after NORPLANT capsules replacement was similar to that observed in the 90 days before replacement and different from that experienced by the same women in the first 90 days of implant use. This finding can be interpreted as an indicator of adaptive changes experienced by the target organs during long-term continuous administration of levonorgestrel. The prompt recovery of fertility after removal of NORPLANT implants suggests that these changes are reversible.

Adult↗
PubMed1987

Recovery of fertility and outcome of planned pregnancies after the removal of Norplant subdermal implants or Copper-T IUDs.

The recovery of fertility after discontinuation of NORPLANT implant use was assessed in ninety women who stated a desire for a new child at the time of removal. Three subjects were lost to follow-up after removal. The cumulative probability of conception in the remaining 87 women was 25, 49, 73 and 86 percent at one, three, six and twelve months after removal, respectively. Nine observations were censored either because of the use of a contraceptive method soon after removal of the implants (n = 7) or separation (n = 2). All other cases were pregnant at the end of two years with exception of three subjects where a male factor for infertility was present. There was no significant correlation between the length of NORPLANT use and the length of the interval from removal to conception. A significantly higher frequency of intervals longer than 6 months was observed among women older than 30 years as compared to younger women. Pathology during pregnancy was cholestasia (n = 5), hypertension (n = 1) and gestational diabetes (n = 1). The outcome was term delivery in 59 cases, premature delivery in 4 cases, and spontaneous abortion in 7 cases. One woman is still pregnant and the outcome is unknown in 4 cases. One premature infant died. A contemporary control group of Copper T users enrolled under the same criteria as NORPLANT implant users provided 44 women who had the device removed to become pregnant. The cumulative probability of pregnancy was 27, 69, 84 and 89 at one, three, six and twelve months and all were pregnant by the end of the second year. Six censored observations occurred because of the use of another contraceptive method after removal (n = 3) or loss to follow-up (n = 3). The outcome of pregnancy was term delivery in 23 cases and abortion in 7 cases. Recovery of fertility occurred at a normal rate after NORPLANT implant removal and the incidence of problems detected in the ensuing pregnancy were within the expected range for Chilean women.

Age Factors↗
PubMed1987

Ovum transport in pregnant rats is little affected by RU486 and exogenous progesterone as compared to cycling rats.

In cycling and pregnant rats, the eggs stay in the oviduct for approximately 66 and 90 h, respectively. The influence of progesterone in these timings was investigated. An excess or a simulated deficit of progesterone was induced with exogenous progesterone or the antiprogesterone RU486, respectively, beginning on the day of ovulation. The effect of these treatments on egg transport in cycling and pregnant rats was assessed in detail and complemented with determinations of estradiol and progesterone circulating levels and progesterone receptor levels in the oviduct. Accelerated transport of ova followed treatment with RU486 in cycling and pregnant rats but with different features. In cycling rats, acceleration began 24 h after the onset of treatment and was not associated with changes in estradiol levels; in pregnant rats, it started 72 h after treatment and was associated with a 5-fold increase in estradiol circulating levels. Thus, RU486 failed to accelerate ovum transport during the first three days of treatment in pregnant rats, in spite of the fact that no progesterone receptors were available in the oviduct as early as 24 h of treatment. Progesterone administration caused egg retention in the oviducts and a 50% reduction in circulating estradiol levels in cycling rats, whereas in pregnant rats progesterone excess did not change estradiol circulating levels and had no effect on the location of embryos on Days 4 and 5. These results demonstrate a different physiological importance of endogenous progesterone in slowing down oviductal ovum transport in cycling and pregnant rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Late luteal phase administration of RU486 for three successive cycles does not disrupt bleeding patterns or ovulation.

RU486, a 19-nor steroid, binds with high affinity to the receptors for progesterone and glucocorticoids, blocking the actions of these hormones on their target tissues. We conducted studies to determine whether RU486 administered at the end of the luteal phase would disturb the menstrual rhythm, ovulation, or hormonal parameters in the treatment and post-treatment cycles. The first study was done in six surgically sterilized women during two consecutive cycles. RU486 [17 beta-hydroxy-11 beta-(4-dimethylaminophenyl)17 alpha-(1-propynyl)estra-4,9-dien-3-one; 100 mg/day] was given for 4 consecutive days, commencing on days 23-27 of the first cycle. Menstrual bleeding occurred by the second day of RU486 administration in all women and was indistinguishable from their usual bleeding pattern. The onset of this bleeding was advanced by RU486 administration, since it entailed shortening of the luteal phase with prolongation of the following follicular phase. Serum LH, FSH, estradiol, and progesterone levels were normal in five of the six women in both the treatment and posttreatment cycles. The second study was conducted in 10 women who were not exposed to the risk of pregnancy. RU486 (100 mg/day) was given for 4 consecutive days, commencing 4 days before their expected menses for 3 successive cycles, preceded and followed by 2 placebo-treated cycles. Bleeding patterns were indistinguishable during the RU486 and placebo cycles. Late luteal phase administration of RU486 consistently produced menstrual bleeding within 1-3 days of drug administration. Daily early morning urinary LH excretion in 6 women and estrone glucuronide and pregnanediol glucuronide excretion in 5 women during both placebo and RU486 cycles were consistent with luteinization, suggesting ovulation and appropriate corpus luteum function. We conclude that RU486 has no major effect on menstrual cycle events if given at the time of the natural progesterone withdrawal that occurs before menses in nonpregnant women.

Adult↗
PubMed1986

Bleeding pattern, outcome of accidental pregnancies and levonorgestrel plasma levels associated with method failure in Norplant implants users.

The aim of this study was to characterize the bleeding pattern, the outcome of pregnancies and the levonorgestrel plasma levels associated with method failures in Norplant implants users. Nineteen pregnancies are reported in 458 woman and 21,589 woman-months observed during the first eight years of Norplant use. Pregnancy rates increased slightly during the first six years of use, attaining a Pearl Index above three thereafter. All women who became pregnant had experienced a regular bleeding pattern in the six months preceding conception. Levonorgestrel plasma levels observed at different intervals before conception and during the conceptional cycle were similar to those observed in non-pregnant women at comparable intervals after Norplant insertion. The nineteen pregnancies ended in thirteen term deliveries, one premature delivery, three abortions and two ectopic pregnancies. No abnormalities were found in the infants. The two ectopic pregnancies are the only ones reported for Norplant users in The Population Council studies. The overall incidence is less than 0.8 per 1000 woman-years.

Abortion, Spontaneous↗
PubMed1986

Fertilized and unfertilized ova are transported at different rates by the hamster oviduct.

To determine if the egg provides any clues for the regulation of ovum transport in the hamster, oocyte and embryo transport were compared. On the evening preceding ovulation, the animals were randomly assigned to one of five groups. They were caged overnight with a male of proven fertility (Group 1) or they were isolated (Group 2). Other females were artificially inseminated in both uterine horns at 2200 h either with fertile epididymal spermatozoa (Group 3), spermatozoa rendered infertile by freezing and thawing (Group 4), or with fertile spermatozoa in one uterine horn and infertile spermatozoa in the contralateral horn (Group 5). The number, condition, and distribution of ova in the genital tract were assessed at various intervals during the next 4 days. The rate of fertilization and normal development in females or sides inseminated with fertile or infertile spermatozoa was over 90% and 0% respectively. Embryos in Groups 1 and 3 reached the uterus 1 day earlier than unfertilized oocytes in Groups 2 and 4. In group 5, the transport of embryos resulting from insemination with fertile spermatozoa followed a pattern similar to those in Groups 1 and 3; the oocytes in the contralateral tract resembled those of Groups 2 and 4. The different transport rates of embryos and oocytes were not associated with the reproductive state of the female but with the condition of the ova. Moreover, the different transport rates were observed in animals transporting the two types of eggs simultaneously on different sides indicating that there is a local recognition of some unidentified factor unequally present in fertilized and unfertilized eggs.

Animals↗
PubMed1986

Two satisfactory methods for purification of human acrosin.

Acrosin has been purified from human sperm cells by two alternative procedures which give purer products and in higher yields than could be achieved previously. The products were characterized by their molecular weight, catalytic action, sensitivity to inhibitors, and reaction with a polyclonal anti-acrosin antibody. After acid extraction of the cells, one method involves removal of acrosin inhibitors by vacuum dialysis, followed by affinity chromatography on a soybean trypsin inhibitor (SBTI) column, and therefore requires that the acrosin be in an active form capable of binding to the inhibitor. The other method involves affinity chromatography on a column of a monoclonal anti-acrosin antibody (MAb) and can be used to provide either active or proenzyme forms of acrosin, by choice of extraction conditions and inclusion of appropriate inhibitors. The yield of human acrosin from the SBTI method was 104% and from the MAb column was 75%. It is hoped that these procedures will make the very scarce human acrosin more readily available for further study.

Acrosin↗
PubMed1986

Monoclonal antibodies to bovine and human acrosin.

Monoclonal antibodies to human acrosin were required for studies of immunological interference with fertilization. Since human acrosin was not available in adequate amounts, monoclonal antibodies have been raised in mice against purified bovine acrosin and screened for cross-reaction with human sperm cells. Two of these antibodies are described, B4F6 and C2E5. Data from enzyme-linked immunosorbent assays, immunoblots, immunoprecipitation, and indirect immunofluorescence on sperm cells indicate that B4F6 binds only to bovine acrosin, and that C2E5 binds both to bovine and to human acrosin at a conformationally determined epitope. The antibodies do not inhibit the hydrolysis of benzoylarginine ethyl ester by acrosin, but C2E5 did inhibit the dissolution of the hamster zona pellucida by purified human acrosin. The antibodies have also been used for affinity purification of acrosin and proacrosin.

Acrosin↗
PubMed1986

Effectiveness of different estrogen pulses in plasma for accelerating ovum transport and their relation to estradiol levels in the rat oviduct.

Elevations of circulating estradiol (E2) levels due to administration of exogenous E2 accelerate embryo transport through the genital tract in pregnant rats. This study relates oviductal embryo transport to tissue E2 levels associated with blood E2 oscillations of differing profiles. Plasma E2 pulses differing in rate of increase, amplitude, and duration were achieved through various schedules of iv and sc E2 administration. Rats on the first day of pregnancy received a total dose of 5 micrograms 17 beta-E2 by short (10-15 min) or long (200-300 min) term iv infusions. Some animals were used to monitor blood and tissue levels of E2 (oviduct and diaphragm). Others were killed 24 h after treatment to assess number of embryos recovered. Fast iv infusions caused brief, high amplitude (greater than 1000 pg/ml) E2 oscillations which were ineffective in eliciting accelerated embryo transport. The longer iv infusions produced lower but sustained elevations of circulating E2 levels comparable to those achieved by sc administration and were associated with accelerated embryo transport. The oviductal E2 concentration during and after a short iv infusion was never lower than that associated with a sc injection. The lack of response to a brief, high amplitude increase in circulating E2, therefore, could not be accounted for by decreased tissue content of the hormone. These results indicate that when the total mass of E2 administered is kept constant, the magnitude of embryo transport acceleration is positively correlated with the duration and negatively correlated with the amplitude and/or slope of increase in circulating estrogen. Since different tissue content of E2 does not account for the response or no response observed it follows that the geometry of E2 oscillations in plasma has a signal value for the target cells which acts independently from the bioavailability of the hormone.

Animals↗