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In vitro effects of inhibin on apoptosis and apoptosis related proteins in human ovarian granulosa cells.

OBJECTIVE: To clarify the in vitro effects of inhibin A (I) on apoptotic cell death and its mechanisms in ovarian granulosa cells the immunoexpression patterns of the apoptosis markers caspase-3 and pro- and anti-apoptotic proteins (Bcl-2, Bcl-xl, Bak) were evaluated in ovarian granulosa cells collected from women with different hormonal status. MATERIALS AND METHODS: Granulosa cells were isolated from follicles of women participating in an in vitro fertilization (IVF) program, normally cyclic (NC) and premenopausal women (PrM). The obtained cells were cultured for 72 h with inhibin A (Sigma, USA)--10 ng/ml. The concentration of estradiol in the culture medium was determined by radioimmunoassay using the Coat-A-Count kit (Nippon, Japan), whose intra- and interassay coefficients of variations were 6,8% and 6,2% respectively. The expression of caspase-3, Bak, Bcl-2, Bcl-xl was investigated immunohistochemically. The percentages of immunopositive cells were calculated and Student's t-test was used for statistical analysis. RESULTS: Addition of inhibin A (10 ng/ml) to granulosa cells cultures resulted in increased estradiol production. Maximal stimulation was observed in granulosa cells collected from women participating in IVF whereas minimal effect of inhibin treatment on estradiol production was demonstrated in premenopausal women. Inhibin A exposition enhanced the immunoexpression of prooncogenes (Bcl-2, Bcl-xl) and reduced the expression of caspase-3 and pro-apoptotic protein Bak in ovarian granulosa cells from the three experimental groups. CONCLUSIONS: Our findings suggest that inhibin A in vitro stimulates the estradiol secretion by granulosa cells dependently of the woman hormonal status, while it inhibits apoptotic process in granulosa cells independently of the hormonal status.

Adult↗

Beliefs about Norplant implants among low income urban women.

This study documents the counseling experiences and beliefs about Norplant implants that are held by an ethnically diverse sample of low income clinic patients in the United States. Virtually all implant acceptors, but only about half of those choosing other contraceptives, receive information about the Norplant system during clinic-based counseling. Exposure to group counseling and to a film regarding Norplant implants are associated with high levels of knowledge among acceptors. Several important patterns emerge in comparing the beliefs of patients choosing the Norplant system with those of patients choosing other methods of birth control. Substantial proportions of the latter group adhere to several inaccurate beliefs about the method, associating its use with: long-term health problems, problems for future babies, future fertility problems, infection, and high cost. These outcomes in particular, as well as several others described, should be systematically addressed and reviewed in contraceptive counseling.

Adult↗

Ethnography of fertility and menstruation in rural Mexico.

In rural populations in Mexico, the system of ideas in relation to the reproductive cycle is built on a mestizo base, with pre-Colombian and Western elements. The objective of the study was the analysis of concepts and resources related to human reproduction in Morelos, in order to design a primary reproductive health care program. The use of ethnographic methods helped identify bio-cultural constructs on which the communities base their reproductive patterns. Our main research results reveal that these populations attribute great value to the extension of the family through descendants. Women's sexuality is directly linked to reproduction and blood is the supremely feminine substance. Great importance is consistently attributed to menstruation about which well-defined concepts exist in the community, where as pre-menarche changes are perceived as a state of bio-psychosocial maturity. Menarche beyond 14 years of age is considered abnormal and is attributed to an 'excess of cold' in the body, therapy is usually administered by traditional birth attendants. In the mythical explanations given for bleeding, the moon plays a fundamental role, as the first rupture of the hymen is attributed to it. A general lack of knowledge about ovulation and its relation to reproduction was observed, resulting in incorrect contraceptive practices.

Adolescent↗

Measuring sterility from incomplete birth histories.

In this article, methods are presented for measuring the level and age pattern of sterility from incomplete birth histories, such as those that can be collected in demographic surveys of women who may not yet have reached the end of their reproductive span. The characteristics of the methods are examined in a simulation study that demonstrates that estimates based on information about fertility subsequent to a given age are more robust to variations in reproductive determinants, sample size, and sampling variation than the other measures, which include the frequently employed length of the open birth interval. In an illustrative analysis of World Fertility Survey data from sub-Saharan Africa, sterility was found to be high in Cameroon, intermediate in Lesotho and Sudan, and low in Ghana and Kenya relative to an English historical population.

Adult↗

RETRACTED: A pilot efficacy study with a single-rod contraceptive implant (Implanon) in 200 Indonesian women treated for < or = 4 years.

In this 4-year open-label, noncomparative, single-center pilot efficacy study, the contraceptive efficacy, safety, bleeding pattern and acceptability of Implanon was studied in 200 sexually active women of proven fertility in Indonesia. All subjects received the single-rod subdermal implant Implanon, which contains 68 mg etonogestrel (3-keto-desogestrel), with an initial release rate of 67 micrograms etonogestrel/day. Contraceptive efficacy was analyzed by calculation of the pregnancy rate, bleeding patterns were determined by the 90-day reference period method, and acceptability by the discontinuation rate. No in-treatment pregnancies were reported during 658.4 women-years of exposure, resulting in a Pearl Index of 0.0 (95% CI 0.0-0.6). The overall bleeding pattern was acceptable, with no discontinuations because of irregular bleeding. Incidence of irregular bleeding was highest during the first two reference periods and decreased thereafter. Amenorrhea was experienced by 7%-12% of subjects during years 1 and 2, by 5%-7% during year 3, and by 2%-5% during year 4, with one discontinuation because of amenorrhea. No clinically significant changes were reported for systolic and diastolic blood pressure, body mass index, and hemoglobin level. Three adverse experiences were related to treatment and resulted in discontinuation (two headaches and one dyspnea). One difficult implant removal was reported. In conclusion, this pilot efficacy study indicates that Implanon provides excellent contraceptive reliability and an acceptable bleeding pattern. Overall safety and acceptability are good, as suggested by the low incidence of adverse experiences and the low discontinuation rate.

Adolescent↗

Enhanced production of monoclonal antibodies against zona pellucida-free, unfertilized mouse oocytes by intrasplenic immunization.

Monoclonal antibodies were obtained by intrasplenic insertion of a total of 40-50 zona pellucida-free, unfertilized mouse oocytes into each mouse. The oocytes were prepared by a combined enzyme-mechanical method without impairing the fertility of the oocyte or inducing parthenogenesis. Of a total of 1063 hybrids obtained, 15 yielded supernatants with positive reactions to unfertilized oocytes. Tests for preimplantation stage specificity demonstrated that 9 of the supernatants detected antigen epitopes in unfertilized oocytes only. The other supernatants showed positive reaction patterns to various embryonal stages of the preimplantation period. Two supernatants recognized materials in the culture medium shedded by zona pellucida-free oocytes. Thus, by applying intrasplenic immunization, the production of antibodies against zona pellucida-free mouse oocytes is enhanced. The procedures described outline a rational way of selecting antibodies of interest for research in the mechanism of fertilization.

Animals↗

Characteristics of human ovulation in natural cycles correlated with age and achievement of pregnancy.

BACKGROUND: The aim of this study was to evaluate whether characteristics of human ovulation correlate with age and pregnancy potential. METHODS: Two groups of women with regular menstrual cycles were included (i.e. one fertile and one infertile group), which were divided into four age groups (< or =29, 30-34, 35-39, > or = 40 years). Monitoring included observations of follicular phase length, whether ovulations occurred from the left or right ovary, the pattern of ovulations in succeeding natural cycles and, in a subset of women, early follicular phase FSH concentrations. RESULTS: Ovulation moving from one ovary to the other in two consecutive cycles (i.e. contralateral ovulation) was inversely correlated with age, showing a ratio of contralateral ovulation per contra plus ipsilateral ovulations (C/C+I) of 62% in women <29 years, gradually decreasing to 42% in women >40 years. The ratio of right-sided ovulation per right plus left-sided ovulations (R/R+L) was unrelated to age and remained almost constant at a level of approximately 55%. The follicular phase length was inversely correlated with age, being 16.2 +/- 2.9, 15.4 +/- 2.9, 14.8 +/- 2.8 and 13.7 +/- 1.3 days in women < 29, 30-34, 35-39 and >40 years of age respectively. The follicular phase length was similar when comparing ovulations occurring from the right and left ovary, but comparing two successive cycles, the length of the follicular phase of the second cycle, showing contralateral ovulation, was shorter than ipsilateral ovulation with two consecutive ovulations in the same ovary. The pregnancy rate of the four groups decreased with age, being 14, 12, 5 and 3% respectively. The C/C+I ratio correlates with pregnancy rate and follicular phase length, and inversely correlates with basal FSH, whereas R/R+L is unrelated to age and pregnancy rate. CONCLUSIONS: Human ovulation shows characteristics related to age. The interaction between the two ovaries seems to be most pronounced in the younger years, where ovulations jump from one ovary to the other more frequently than later on in life. The C/C+I ratio shows a clear correlation with age and pregnancy rate.

Adult↗

Benefit-risk assessment of the levonorgestrel intrauterine system in contraception.

The levonorgestrel-releasing intrauterine system (IUS) is a long-acting, fully reversible method of contraception. It is one of the most effective forms of contraception available, and combines the advantages of both hormonal and intrauterine contraception. The levonorgestrel-releasing IUS also gives the users many non-contraceptive benefits: the amount of menstrual bleeding and the number of days of menstrual bleeding are reduced, which makes it suitable for the treatment of menorrhagia (heavy menstrual blood loss). Dysmenorrhoea (painful menstruation) and premenstrual symptoms are also relieved. In addition, the levonorgestrel-releasing IUS provides protection for the endometrium during hormone replacement therapy. The local release of levonorgestrel into the uterine cavity results in a strong uniform suppression of the endometrial epithelium as the epithelium becomes insensitive to estradiol released from the ovaries. This accounts for the reduction in menstrual blood loss. All possible patterns of bleeding are seen among users of the levonorgestrel-releasing IUS; however, most of the women who experience total amenorrhoea continue to ovulate. The first months of use are often characterised by irregular, scanty bleeding, which in most cases resolves spontaneously. The menstrual pattern and fertility return to normal soon after the levonorgestrel-releasing IUS is removed. The contraceptive efficacy is high with 5-year failure rates of 0.5-1.1 per 100 users. The absolute number of ectopic pregnancies is low, as is the rate per 1000 users. The levonorgestrel-releasing IUS is equally effective in all age groups and the bodyweight of the user is not associated with failure of the method. In Western cultures continuance rates among users of the levonorgestrel-releasing IUS are comparable with those of other long-term methods of contraception. Premature removal of the device is most often associated with heavy menstrual bleeding and pain, as with other long-term methods of contraception, and is most common in the youngest age group. When adequately counselled about the benign nature of oligo- or amenorrhoea, most women are very willing to accept life without menstruation. The risk of premature removal can be markedly diminished with good pre-insertion counselling, which also markedly increases user satisfaction. User satisfaction is strongly associated with the information given at the time of the levonorgestrel-releasing IUS insertion. Thus, the benefits of the levonorgestrel-releasing IUS make it a very suitable method of contraception for most women.

Administration, Intravaginal↗

Vitrification of mouse oocytes using closed pulled straws (CPS) achieves a high survival and preserves good patterns of meiotic spindles, compared with conventional straws, open pulled straws (OPS) and grids.

BACKGROUND: We modified the loading of pulled straws into a new closed system, called closed pulled straws (CPS) for holding oocytes for vitrification. The morphological survival, dynamics of meiotic spindles, and fertilization in vitro of vitrified oocytes using CPS were compared with conventional straws, open pulled straws (OPS), and grids. METHODS: Surviving oocytes were stained for spindles and chromosomes after 1, 2 and 3 h incubations, and compared with controls. The capacity of fertilization and embryonic cleavage were examined in vitro. RESULTS: The survival rates of the CPS (79%) and straw (77%) groups were significantly higher (P < 0.05) than the OPS (63%) and grid (39%) groups. At a 1h incubation, vitrified oocytes of four groups had significantly fewer normal spindles than controls (P < 0.05). The straw group was inferior to the others in spindle morphology (P < 0.05). After a 3 h incubation, recovery of vitrified oocytes with normal spindles was significantly improved in all groups (P < 0.05). The percentages of fertilization and blastocyst formation of vitrified oocytes after a 1 h incubation was significantly lower than controls (P < 0.05), but they were improved after 2 or 3 h incubations (P < 0.05). CONCLUSIONS: Oocytes vitrified using CPS, OPS or grids could lessen spindle injuries and expedite recuperation. The survival using OPS or grids is lower. Sufficient culture time for recovery of meiotic spindle would be imperative for fertilization events of vitrified oocytes. CPS has the advantages of achieving a high survival and preserving good spindles.

Animals↗

The causes of stalling fertility transitions.

An examination of fertility trends in countries with multiple DHS surveys found that in the 1990s fertility stalled in midtransition in seven countries: Bangladesh, Colombia, Dominican Republic, Ghana, Kenya, Peru, and Turkey. In each of these countries fertility was high (more than six births per woman) in the 1950s and declined to fewer than five births per woman in the early or mid-1990s, before stalling. The level of stalling varied from 4.7 births per woman in Kenya to 2.5 births per woman in Turkey. An analysis of trends in the determinants of fertility revealed a systematic pattern of leveling off or near leveling in a number of determinants, including contraceptive use, the demand for contraception, and number of wanted births. The stalling countries did not experience significant increases in unwanted births or in the unmet need for contraception during the late 1990s, and program effort scores improved slightly, except in the Dominican Republic. These findings suggest no major deterioration in contraceptive access during the stall, but levels of unmet need and unwanted births are relatively high, and improvements in access to family planning methods would, therefore, be desirable. No significant link was found between the presence of a stall and trends in socioeconomic development, but at the onset of the stall the level of fertility was low relative to the level of development in all but one of the stalling countries.

Birth Rate↗

Evidence of fertility regulation among rural French villagers, 1749-1789: a sequential econometric model of birth-spacing behavior (Part 2).

This is the second part of a two-part paper in which the authors examine statistical models of marital fertility regulation in rural France from 1749 to 1789. They create a case against the "natural fertility" characterization of the period by presenting "clear indications that marital fertility was being regulated in congruence with the differential valuations placed upon children, according to their gender and age. A complex pattern is found in the non-biological responses of couples' fertility to both non-familial and familial experience of infant deaths, which take the form of 'hoarding' and 'replacement effects', respectively. Evidence is present bearing upon the suspected endogeneity of infant deaths, and its relationship to the adoption of preventive methods of limiting family size." (SUMMARY IN FRE)

Birth Intervals↗

A C. elegans mutant screen based on antibody or histochemical staining.

A method has been developed for isolating mutations in Caenorhabditis elegans that alter antibody or histochemical staining patterns. The basis for this method is a new procedure for making C. elegans permeable that does not kill the eggs contained within the uterus of gravid adult hermaphrodites. A mutagenized population of gravid hermaphrodites is made permeable and then stained with either an antibody or a histochemical stain. Animals that stain aberrantly are picked to individual petri plates and the eggs within the uterus of the stained mother hatch and establish a new genetic line. Antibody and histochemical stains are especially useful phenotypes because the staining pattern will usually directly reflect the gene expression pattern of the gene that codes for the antigen or enzyme. This method was used to isolate mutants that alter the expression of a mec-7lacZ fusion gene. Transgenic animals that contained the mec-7lacZ gene integrated into chromosome I were treated with the mutagen ethylmethanesulfonate, allowed to self-fertilize for two generations and then stained with X-gal or antibodies against beta-galactosidase. Gravid animals that stained abnormally were picked to fresh petri plates and their offspring were used to establish new mutant lines.

Animals↗

Human chorionic gonadotropin and growth factors at the embryonic-endometrial interface control leukemia inhibitory factor (LIF) and interleukin 6 (IL-6) secretion by human endometrial epithelium.

BACKGROUND: The elucidation of the molecular mechanisms by which the embryo contributes to its implantation is an area of extensive research. The main objective of this study was to investigate the pattern of leukemia inhibitory factor (LIF) and interleukin-6 (IL-6) secretion by human endometrial epithelium, and their regulation by human chorionic gonadotropin (hCG) and other growth factors present at the embryonic-endometrial interface. METHODS: Endometrial epithelial cells (EEC) were isolated from biopsies collected at both proliferative and secretory phases of fertile women. RESULTS: HCG (1-50 IU/ml) increased LIF secretion by EEC cultures derived from follicular phase (up to 285+/-75%) or from secretory phase (up to 212+/-16%). In contrast, hCG reduced IL-6 secretion by EEC in both phases. The hCG/LH receptor gene was transcribed by EEC as evidenced by RT-PCR. Insulin-like growth factors 1 and 2 increased LIF secretion by EEC. Transforming growth factor beta1 stimulated LIF and reduced IL-6 secretion. CONCLUSIONS: Through hCG, the blastocyst may be involved in the control of its implantation (via an increase of proimplantatory LIF) and tolerance (via an inhibition of proinflammatory IL-6). Other growth factors present at the embryonic-endometrial interface are also involved in the control of LIF and IL-6 endometrial secretion.

Adolescent↗

Return of fertility in nulliparous women after discontinuation of the intrauterine device: comparison with women discontinuing other methods of contraception.

OBJECTIVE: To clarify the effect of the using the intrauterine device on fertility in nulliparous women. DESIGN: Prospective cohort study of two groups of nulliparous women, one recruited while using an intrauterine device and the other while using an oral contraceptive. SETTING: Seventeen family planning clinics in England and Scotland. SAMPLE: 1,071 nulliparous, married women, aged 18-40 years, 558 of whom contributed information to the main objective of the study. METHODS: The women were recruited between 1982 and 1985 and followed up annually to 1994. Dates and reasons for any contraceptive method changes (which were most frequently to barrier methods) were recorded, together with the outcome of any pregnancies, at each follow up. MAIN OUTCOME MEASURES: The number of nulliparous women giving birth at term after stopping contraception (oral contraceptive, intrauterine device or barrier method) in order to conceive. RESULTS: Women who stopped using a barrier method to achieve a planned pregnancy conceived most quickly: 54% were delivered after one year vs 39% of intrauterine device and 32% of oral contraceptive users (log rank P = 0.002). There was no association between fertility and duration of oral contraceptive use: However, short term intrauterine device users (< 42 months) showed a fertility pattern more favourable than seen in those discontinuing oral contraceptives, with increasing duration of intrauterine device use being associated with decreasing fertility (linear trend P = 0.005); the fertility of women who had used the intrauterine device for 78 + months was the most impaired (28% were delivered by 12 months vs 46% of short term users; at 36 months the corresponding figures were 79% vs 91%). This association remained after adjusting for potential confounding factors, including maternal age, husband's social class, and history of gynaecological illnesses, factors which themselves had independent associations with fertility. CONCLUSIONS: Long term intrauterine device use in nulliparous women appears to be associated with an increased risk of fertility impairment.

Adolescent↗

Assessing the effects of mortality reduction on population ageing.

"This article presents a new method for decomposing age distribution changes into changes in the number of births and changes in age-specific rates of mortality and migration. The method is developed on the basis of the equation for the age-specific growth rate proposed by Horiuchi and Preston (1988). Using this method, it is shown that the increase in the proportion of women in Japan during 1970-1980 is mainly due to the reduction of mortality, particularly at old ages. The results lend support to the proposed idea that the pattern of age structure changes in developed countries is now shifting from fertility-dominated to mortality-dominated ageing." This is a revised version of a paper originally presented at the 1989 Annual Meeting of the Population Association of America.

Age Distribution↗

The pattern of changes in ovarian stromal and uterine artery blood flow velocities during in vitro fertilization treatment and its relationship with outcome of the cycle.

OBJECTIVES: To assess the effect of short-term (2-3 weeks) pituitary suppression and controlled ovarian stimulation on ovarian and uterine artery Doppler measurements during the in vitro fertilization (IVF) treatment cycle and to compare the pattern of these changes between conception and non-conception cycles as well as between patients with normal and those with polycystic ovaries. DESIGN: Prospective observational study of women undergoing IVF treatment. SUBJECTS: Women using the long-treatment buserelin protocol who did not have uterine fibroids, ovarian cysts or endometrioma. METHODS: Serial transvaginal color and pulsed Doppler measurements of ovarian stromal and uterine artery blood flow velocity were carried out in the early follicular phase of the menstrual cycle, on the day of pituitary suppression and on the day of administration of human chorionic gonadotropin (hCG). The main outcome measures were the ovarian stromal and uterine artery blood flow peak systolic velocity (PSV) and pulsatility index (PI). RESULTS: A total of 105 patients were recruited but six patients were excluded from the analysis because they had only one stage of the measurements performed. There was a significant decline in mean ovarian stromal artery PSV after 2-3 weeks of gonadotropin releasing hormone (GnRH) agonist therapy but no effect on ovarian stromal artery PI. The mean uterine artery PSV or PI did not change significantly after 2-3 weeks of GnRH agonist therapy. There was a significantly higher mean ovarian stromal artery PSV in conception cycles compared to non-conception cycles in the early follicular phase and on the day of pituitary suppression, but not on the day of hCG administration. There were no differences between conception and non-conception cycles in the mean uterine artery PSV or PI. Women with polycystic ovaries had a higher mean ovarian artery PSV on all the three occasions of measurement. CONCLUSION: These data suggest that assessment of ovarian blood flow before commencement of gonadotropin stimulation may play a role in assessing cycles likely to result in pregnancy.

Adult↗

Dermal ridge patterns and fertility in a Polish rural sample.

The relationship between ridge counts and pattern intensities on fingers, palms and soles, and number of pregnancies, number of surviving children, maternal age at birth of first child, and miscarriages was investigated in a rural Polish sample of 273 females. All subjects had completed their reproduction by the time of investigation and the use of contraceptives was negligible. Results show that females with a history of miscarriage have lower mean ridge counts on all fingers and lower pattern intensity on all fingers except V, with statistically significant differences for fingers III and IV. The results also suggest a relationship between the intensity of patterns on fingers II and V and in thenar areas, with the number of pregnancies and/or surviving offspring. The limitations of the present data and a need for more specific investigations are discussed.

Abortion, Spontaneous↗