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Biomedical subjects

L Westergaard

Publications and source records attributed to L Westergaard.

At least 19 recordsLinked to original sources

GnRH agonist (buserelin) or hCG for ovulation induction in GnRH antagonist IVF/ICSI cycles: a prospective randomized study.

BACKGROUND: We aimed to determine the efficacy of ovarian hyperstimulation protocols employing a GnRH antagonist to prevent a premature LH rise allowing final oocyte maturation and ovulation to be induced by a single bolus of either a GnRH agonist or hCG. METHODS: A total of 122 normogonadotrophic patients following a flexible antagonist protocol was stimulated with recombinant human FSH and prospectively randomized (sealed envelopes) to ovulation induction with a single bolus of either 0.5 mg buserelin s.c. (n = 55) or 10,000 IU of hCG (n = 67). A maximum of two embryos was transferred. Luteal support consisted of micronized progesterone vaginally, 90 mg a day, and estradiol, 4 mg a day per os. RESULTS: Ovulation was induced with GnRH agonist in 55 patients and hCG in 67 patients. Significantly more metaphase II (MII) oocytes were retrieved in the GnRH agonist group (P < 0.02). Significantly higher levels of LH and FSH (P < 0.001) and significantly lower levels of progesterone and estradiol (P < 0.001) were seen in the GnRH agonist group during the luteal phase. The implantation rate, 33/97 versus 3/89 (P < 0.001), clinical pregnancy rate, 36 versus 6% (P = 0.002), and rate of early pregnancy loss, 4% versus 79% (P = 0.005), were significantly in favour of hCG. CONCLUSIONS: Ovulation induction with a GnRH agonist resulted in significantly more MII oocytes. However, a significantly lower implantation rate and clinical pregnancy rate in addition to a significantly higher rate of early pregnancy loss was seen in the GnRH agonist group, most probably due to a luteal phase deficiency.

Adult↗

Effect of 4-octylphenol on germ cell number in cultured human fetal gonads.

This study evaluates whether a hormone disruptor found in environment, 4-octylphenol, affects the rate of proliferation of germ cells from human fetal gonads during a 3 week culture period. Five testis and five ovaries were obtained from fetuses of women undergoing legal abortions between the 6th and 9th week of fetal life, representing the period where early gonadal differentiation takes place. Each gonad was divided into equal sized test and control tissue. The test tissue was exposed to a continued presence of 10 micromol/l 4-octylphenol in the culture medium. The cultures were terminated by fixation of the tissues, which where then processed for histology and serially sectioned. The mitotic index of the germ cells (i.e. number of mitosis per 100 germ cells) and the number of germ cells per area was determined. Each of the five testes cultured in 4-octylphenol exhibited a significantly reduced mitotic index and number of pre-spermatogonia compared to the control, whereas none of the five ovaries exposed to 4-octylphenol revealed any difference compared to the control. It is concluded that 4-octylphenol exerts a sex-specific effect on male germ cells.

Cell Count↗

Prognostic factors in oligodendrogliomas.

An outcome analysis was performed on 96 patients with pure cerebral oligodendrogliomas operated in the 30-year period 1962 to 1991. The most important predictive prognostic factors were youth and no neurological deficit, demonstrated as a median survival for the group younger than 20 years of 17.5 years and for the group older than 60 years of 13 months. The group without neurological deficits had a 5-years survival of 43 per cent while the group with deficits had a 5-years survival of 5 per cent. The 5-years survival for oligodendroglioma of grade II was 46 per cent and for grade III 10 per cent. We found no effect of radiotherapy on survival, neither in the whole material or in any subgroup.

Adolescent↗

Forskolin and the meiosis inducing substance synergistically initiate meiosis in fetal male germ cells.

We have shown that Meiosis Inducing Substance (MIS) and forskolin synergistically and dose dependently induce meiosis in germ cells of cultured fetal mouse testes. We used a bioassay which consists of fetal mouse testes and ovaries cultured for 6 days. In this study MIS media are spent culture media from 24 hour cultures of minced adult mouse testes. In the bioassay one gonad of each fetus is cultured either in MIS medium, in control medium with forskolin, or in MIS medium with forskolin. The other gonad serves as the control and is cultured in control medium. After culture the gonads are fixed, squashed, and DNA-stained. In these preparations germ cells and somatic cells can be distinguished, and the number of germ cells in the different stages of meiosis is counted as is the number of somatic cells in mitosis. MIS activity is defined to be present in a medium when meiosis is induced in male germ cells during culture. We found that MIS media as well as forskolin induced meiosis in fetal male germ cells in a dose-dependent manner. In addition, MIS media and forskolin acted synergistically by inducing meiosis. Female germ cells seem to be unaffected by the various culture media. These findings indicate that receptors for stimuli of meiotic initiation may exist in germ cells or neighbouring somatic cells. In addition to induction of meiosis, MIS media and forskolin also dose dependently increase the number of male germ cells compared to controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Prognostic parameters in benign astrocytomas.

To elucidate the prognosis of different types of benign astrocytomas and to ascertain whether patients with partially resected benign astrocytomas, or any subtype of these, would benefit from postoperative radiotherapy, we studied retrospectively material comprising 300 patients with benign astrocytomas treated in the period 1956 to 1991. The pilocytic type of astrocytoma was found to have an outstandingly good prognosis and should be regarded as a distinct nosological entity. For the non-pilocytic supratentorial astrocytomas, a multivariate regression analysis showed that age, tumour site, Kernohan grade and lymphocytic perivascular cuffing influenced survival. The proportion of gemistocytes increased with age. After correction for age, the proportion of gemistocytes had no significant influence on survival. It was not possible to demonstrate any influence of radiotherapy on median survival time of patients with non-pilocytic supratentorial benign astrocytomas. The study emphasizes the necessity of a prospective combined multicenter analysis of the effect of radiation on benign astrocytomas.

Adolescent↗

[Cervix factors as a cause of infertility].

The uterine cervix plays an important role in the natural fertilization process and, consequently, it is also a significant factor in infertility. In about 6% of infertile couples, the infertility is caused by the cervical factor. The post coital test (PCT) is the most essential diagnostic procedure. A good PCT result excludes the cervical factor as the cause of infertility. A poor or negative PCT result, on the other hand, only indicates that the cervical tract is the cause in the case of women with verified ovulation and in whom other causes have been excluded. Treatment of the cervical factor has always been difficult. Intrauterine insemination is the best documented treatment method with a pregnancy rate of about 30%. In future, gamete intrafallopian transfer (GIFT) and in vitro fertilization (IVF) may be alternatives in the treatment of infertility owing to the cervical factor.

Cervix Mucus↗

Post-operative infections of osteoplastic compared with free bone flaps.

A retrospective study was performed to evaluate the rate of infection in free and osteoplastic bone flaps after craniotomy. Two hundred and two craniotomies were performed in 98 cases of tumour, 35 cases of trauma and 69 cases of vascular disease. The overall incidence of infection was 6.4% (13 cases). The infectious agents were Staphylococcus aureus in four cases; Pneumococcus and gram-positive rods each in one case. In seven cases no infectious agent was identified. In 127 cases with free bone flaps eight (6.3%) were infected, and in 75 cases with osteoplastic bone flaps five (6.7%) were infected. One of five (20%) osteoplastic and four of eight (50%) free bone flaps had to be removed in order to accomplish healing, suggesting that an osteoplastic bone flap may be preserved more often in cases of infection.

Adolescent↗

Initiation of oogenesis in the human fetal ovary: ultrastructural and squash preparation study.

Ovaries from 27 human fetuses at less than or equal to 12 weeks' gestational age were examined with electron microscopy and squash preparation studies. The findings demonstrated that meiosis begins in the fetal ovary between 11 and 12 weeks of age. This is several weeks after gonadal sex differentiation, which can be recognized in the testis at 6 weeks. Ovaries at earlier ages included primitive germ cells and oogonia. With advancing fetal age, mitotic activity and germ cell degeneration became increasingly evident. Preleptotene cells were found as early as 9 to 10 weeks, suggesting that meiotic capacity is present soon after gonadal sex differentiation but further progression into meiosis is delayed until some specific inductive influence is exerted.

Female↗

Ultrastructure of human cumulus-oocyte complexes from healthy and atretic follicles.

Follicular fluids with cumulus-oocyte complexes and granulosa cells were aspirated from antral follicles in healthy women at different stages of the normal menstrual cycle. The cumulus-oocyte complexes were processed for light and electron microscopy and classified as pre-ovulatory, healthy non-pre-ovulatory and atretic by certain light microscopical criteria, i.e. degree of expansion, number of layers and pycnotic nuclei in the cumulus investment, size of the peri-vitelline space and oocyte nuclear morphology. Their follicles were similarly classified by follicular steroid measurements and/or flow cytometric DNA analyses of the aspirated granulosa cells. A high degree of correlation between these classifications was found. Moreover, pre-ovulatory and atretic cumulus-oocyte complexes showed particular fine morphological characteristics, some of which were different while others appeared to be identical. Similarities were increased number of lipid droplets in the cumulus cells, widened peri-vitelline space, peripheral displacement or breakdown of the oocyte nucleus and disconnection of the junctions between cumulus cell projections and the oolemma. In addition to the criteria used for the light microscopical classification, pre-ovulatory complexes were characterized by release of the content of cortical granules while atretic ones displayed cumulus cells with pseudopodia-like projections, cumulus cells in the perivitelline space and lipid droplets in the ooplasm.

Androsterone↗

Steroid levels in ovarian follicular fluid related to follicle size and health status during the normal menstrual cycle in women.

Steroid levels in 308 follicular fluid (FF) aspirates obtained during laparotomy from 116 women with normal ovarian function were related to the size (greater than 1 mm diameter) and health of the aspirated follicles and the phase of the menstrual cycle in which the FF sampling was done. The percentage of granulosa cells (g.c.) in the DNA S phase (S fraction) in each FF aspirate was determined by flow cytometry and used to classify non-pre-ovulatory follicles as healthy or atretic. A significant correlation between g.c. DNA S fraction and concentration of oestradiol (E2) in FF (FF-E2) was found, restricted to non-pre-ovulatory follicles with diameter greater than 6 mm. This evidence supports the notion that E2 acts as a local g.c. mitogen in these follicles, but also indicates that other factors may be required to stimulate g.c. proliferation in the smaller antral follicles (less than or equal to 6 mm diameter). The pattern of steroids in FF of healthy follicles was related to the stage of follicular development, being predominantly 'androgenic' in small follicles (less than or equal to 6 mm diameter), 'oestrogenic' in larger non-pre-ovulatory follicles (greater than 6 mm diameter) and 'progestagenic' in pre-ovulatory follicles. In contrast, atretic follicles of all sizes (2-13 mm diameter) exhibited an 'androgenic' pattern of steroids in FF. The intrafollicular hormonal milieu in the larger healthy non-pre-ovulatory and in pre-ovulatory follicles varied as a function of menstrual cycle phase, whereas that in small follicles (healthy as well as atretic) and in larger atretic follicles remained 'androgenic' through all the phases of the cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Meiosis-inducing substances in human preovulatory follicular fluid related to time of follicle aspiration and to the potential of the oocyte to fertilize and cleave in vitro.

Meiosis-inducing substance (MIS) and steroid and gonadotropic hormones were investigated in 41 preovulatory follicular fluids (FFs) aspirated at either 0, 12, or 36 hours after human chorionic gonadotropin (hCG) administration in 25 women with clomiphene citrate-stimulated cycles. Twenty-one oocytes were recovered from these FFs and subjected to in vitro fertilization. MIS activity was present in 25 (61%) of the FFs. The frequency of MIS-active FFs increased from 11% (1 of 9) at 0 hours and 40% (2 of 5) at 12 hours to 81% (22 of 27) at 36 hours after hCG administration (P less than 0.001). The concentration of hormones in MIS-active FFs was not significantly different from that of MIS-inactive FFs. Twelve (86%) of 14 oocytes that fertilized and cleaved in vitro were recovered from MIS-active FFs. By contrast, all seven oocytes that remained unfertilized in vitro were recovered from MIS-inactive FFs. These findings support the notion that resumption of meiosis in the preovulatory oocyte is triggered by MIS in FF and suggest that follicular MIS production may be one of the factors that determines the success of in vitro fertilization and early embryonic development.

Androstenedione↗

Follicular atresia in relation to oocyte morphology in non-pregnant and pregnant women.

Antral follicles from normally menstruating women and women in the third trimester of pregnancy were classified as healthy or atretic by flow cytometric DNA measurements on aspirated granulosa cells and by the concentration of steroids in the follicular fluid. The oocytes contained in these follicles were characterized as healthy or degenerating by their morphology at the light microscopic level. In 98% of the cases (61/62) morphologically healthy or degenerating oocytes were found in follicles which were classified as healthy or atretic respectively. In the normally menstruating women degenerative changes in the oocyte and the remainder of the follicle appeared to occur in synchrony. In pregnant women asynchrony was noted between the oocyte and the remainder of the follicle as follicular atresia progressed. The present study demonstrated the usefulness of flow cytometric DNA measurement in characterizing antral follicles of all sizes as healthy or more or less atretic.

Adult↗

Origin and differentiation of the endocrine cells of the ovary.

A large proportion of the somatic cells of the developing ovaries of mouse, human and rabbit stems from the mesonephric tissue. In the immature mouse ovary and in the 19-day-old fetal rabbit ovary, the first steroid-producing cells differentiate among the mesonephric-derived cells within the ovary. In the fetal human ovary, the first steroid-producing cells arise in the inner part of the cortex and differentiate concomitantly with the formation of small follicles. The origin of the early steroid-producing cells in the human ovary is still uncertain. During early ovarian development, formation and further differentiation of the steroid-producing interstitial cells seem to continue only in areas devoid of free viable germ cells.

Animals↗

Steroid concentrations in fluid from human ovarian antral follicles during pregnancy.

Steroid concentrations in fluid from 138 ovarian antral follicles obtained from 30 pregnant women were measured and compared with those in aspirates of 151 follicles of similar size (i.e. diameter 2-6 mm) from 61 non-pregnant women who had normal regular menstruations. The follicles were classified as healthy or atretic by flow cytometric DNA measurement of the granulosa cells contained in the follicular fluid aspirate. Nine (7%) of the follicles from pregnant women and 21 (14%) of those from non-pregnant women were healthy, and the remainder atretic (P greater than 0.05). Androstenedione was the most abundant steroid in all follicles. Mean progesterone levels in follicular fluid from pregnant women were significantly (P less than 0.05) higher than in follicular fluid from non-pregnant women. In pregnant women progesterone levels were significantly (P less than 0.01) higher in fluid from healthy than from atretic follicles. In contrast, no significant differences in steroid concentrations were found between fluid from healthy and atretic follicles in non-pregnant women. We conclude that antral ovarian follicles may develop normally to a diameter of around 6 mm during the third trimester of human pregnancy. We also conclude that these follicles accumulate steroids in the follicular fluid in amounts which equal those found in follicles of similar size in the ovaries of non-pregnant women, but that the composition of intrafollicular steroids during pregnancy is modified towards higher concentration of progesterone. The reason for this increased intrafollicular progesterone level is unclear.

Adult↗

The precision and accuracy of symphysis--fundus distance measurements during pregnancy.

We studied the precision and accuracy of SF measurements. Five trained obstetricians made three measurements of SF on each of 33 patients in the third trimester. The intraobserver variation varied from 0 cm to 8 cm, and comprised on average 1.5 to 2 cm (95th centiles 2.5 to 4 cm). The interobserver variation varied from 1 to 13 cm, and comprised on average 4 cm (95th centile 8 cm). The accuracy of SF measurements was estimated by comparison with ultrasound-guided measurements, which showed a very high precision. Two of the investigators differed significantly, by -1.56 cm and -1.97 cm, from the other 3.

Clinical Competence↗

Is resumption of meiosis in the human preovulatory oocyte triggered by a meiosis-inducing substance (MIS) in the follicular fluid?

Aspirates from 31 ovarian follicles and 2 corpora lutea of 26 women at different stages of the menstrual cycle were investigated for activity of meiosis-inducing substance (MIS) and meiosis-preventing substance (MPS). The aspirated follicles were classified as dominant (i.e., preovulatory), healthy, or atretic according to their size, steroid hormone content, and stage of the menstrual cycle. To test for MIS and MPS activity, gonads of sexually undifferentiated fetal mice were cultured in media containing either 15% follicular fluid aspirate (test gonads) or 15% human blood serum (control gonads). MIS activity is present in follicular fluid if the test testes contain more meiotic germ cells than the control testes. MPS activity is present if the test ovaries have less meiotic germ cells than their controls. MIS activity was present only in healthy follicles of the late follicular phase (12 of 15 follicles). No MIS activity was seen in healthy or atretic follicles from other phases of the menstrual cycle. The MIS activity is apparently unrelated to the composition of steroids in the follicular fluid. MPS activity was not found in any of the follicles. It is proposed that the preovulatory resumption of meiosis may be triggered by a MIS in the follicular fluid.

Adolescent↗