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Clinical evaluation of the therapeutic effectiveness of ethinyl oestradiol and oestrone sulphate on prolonged bleeding in women using depot medroxyprogesterone acetate for contraception. World Health Organization, Special Programme of Research, Development and Research Training in Human Reproduction, Task Force on Long-acting Systemic Agents for Fertility Regulation.

A placebo-controlled randomized clinical trial was conducted in six centres to compare the effects of a 14 day treatment with either 50 micrograms ethinyl oestradiol daily or 2.5 mg oestrone sulphate daily, on depot medroxyprogesterone acetate (DMPA)-induced prolonged bleeding. Out of 1035 women admitted to the study, 278 requested treatment and were given ethinyl oestradiol (n = 90), oestrone sulphate (n = 91) or placebo (n = 97). Ethinyl oestradiol was successful in stopping the bleeding episode in 93% of cases, compared with oestrone sulphate and placebo which had success rates of 76 and 74% respectively. However, the relative advantage of ethinyl oestradiol was marginal, with an average reduction of 1 bleeding day and 3 spotting days compared with the other two groups. Immediately after treatment, women given ethinyl oestradiol had less bleeding but a more unpredictable pattern than the other two groups. In the long term, there were no differences between the bleeding patterns or the discontinuation rates for any reason in the three groups, and the most important single reason for discontinuation in those groups remained 'menstrual problems'. In summary, the study showed that treatment of DMPA-induced prolonged bleeding with ethinyl oestradiol had a limited short-term effect but no beneficial effect on the acceptability of DMPA as a contraceptive method. Treatment with oestrone sulphate was no different from placebo.

Adolescent↗

The analysis of menstrual bleeding patterns: a review.

Patterns of vaginal bleeding are an important factor in the acceptability of contraceptive methods. The analysis of data obtained from daily menstrual diary records is a major methodological problem to which no satisfactory solution exists. This review describes approaches to the analysis of bleeding patterns among contracepting and non-contracepting women and reviews the difficulties involved. The reference period method, introduced to avoid the arbitrary rules and definitions required for an analysis based on the concept of a menstrual cycle, is discussed and its limitations presented. The review draws on reports of meetings convened by the World Health Organization and the University of Exeter Family Planning Unit to discuss issues in the analysis. Previously unpublished methods are summarized and areas of controversy and topics for further research are identified.

Contraception↗

Effect of ovule position within the pod on the probability of seed production in Bauhinia ungulata (Fabaceae).

BACKGROUND AND AIMS: It has been claimed that ovules linearly ordered within a fruit differ in their probabilities of reaching maturity. This was investigated by studying the effect the position of an ovule within the pod has on seed abortion and seed production in Bauhinia ungulata. METHODS: Fruits collected during the dry seasons of 1999, 2000 and 2001 were opened, and the number, position and status of each ovule within the fruit were recorded. A GLM model was used to assess the effects of population, tree identity and ovule position within the pod on ovule fertilization, seed abortion, seed damage and seed maturation in two populations of B. ungulata. KEY RESULTS: Nearly 30% of the ovules were not fertilized in 1999; this percentage dropped to 5% the following two years. Seed abortion (50%) and seed damage (15%) were the same every year during the study period. Only 15% of the initial ovules developed into mature seeds in 1999; this value increased to 35% in 2000 and 2001. However, seed survivorship was dependent on the position of the ovule within the pod; non-fertilized and early aborted ovules were found more often near the basal end of the ovary. The frequency of seed damage was not affected by position. Mature seeds were found mainly in the stylar half of fruits, where ovules are likely to be fertilized by fast pollen tubes. CONCLUSIONS: The pattern of seed production in B. ungulata is non-random but is dependent upon the position of the ovule within the pod. The results suggest that the seeds produced within a fruit might differ in their vigour.

Bauhinia↗

Genetic evaluations of dairy bulls for daughter energy balance profiles using linear type scores and body condition score analyzed using random regression.

The difference in body lipid between the start and end of lactation represents the body energy lost (or gained) in support of maintaining lactation including the nonproduction components of lactation. This source of energy is ignored in current genetic evaluations for production for dairy sires. The depletion and accretion of body tissue creates a pattern of body energy content over time that is, in part, under genetic control. Using random regression and field data, we modeled changes in body condition score (BCS) and liveweight, predicted from linear type traits, on first parity cows to produce daily breeding values of their sires for energy balance. These curves show that sires differ in the way their daughters lose and regain body energy throughout lactation. For all sires, the overall mean maximum daughter body energy loss was 1499 MJ (SD = 144 MJ) and occurred at d 99 (SD = 12.8 d) of lactation and the mean total daughter body energy loss at d 305 of lactation was 779 MJ (SD = 224 MJ). In this study, the profiles of body energy loss indicate that daughters of most sires lost body energy before d 150 and then recovered body energy, whereas the daughters of a few sires continued to lose body energy through to the end of lactation. Some sires with high merit for production may have daughters with body tissue mobilization profiles associated with poorer health and fertility leading to higher costs. A method of accounting for this cost could be to correct yield for body tissue mobilization. Deducting kilograms of milk from the breeding value for milk for each sire, equivalent in energy content to the body energy lost, resulted in a correlation of 0.98 between the ranking of sires for milk kilograms before and after adjustment. However, some sires changed rank bylarge amounts, the largest being +355 positions. Breeding values for energy balance can be calculated from single observations of BCS and linear type traits on daughters of a sire; data that can routinely be collected in national conformation assessment schemes.

Animals↗

Changes in gonadotrophin secretion during childhood and puberty.

The changes in gonadotrophin secretion in childhood and puberty involve changes in the pulsatile pattern as well as mean concentration. We have examined pulsatile secretion using 24-h LH profiles in 78 children aged 4.2-15.6 years and six adult men. The profiles were analysed by a method which gives an estimate of peak and baseline levels and by spectral analysis. Prepubertal children were divided into groups by age and pubertal children by pubertal stage. Baseline LH levels in children aged 4.2-6.9 years were higher than in those aged 7.1-9.8 years. Pulse frequency in both groups was slow (periodicities 140-200 min). In the oldest prepubertal group there was an increase in peak levels with increased spectral power at periodicities of 100-120 min. Pulse frequency did not change in puberty (periodicity 120-160 min). Girls demonstrated an increase in both peak and baseline LH concentrations in early puberty. Boys had an increase in only peak levels in early puberty; there was no increase in baseline concentrations until a testicular volume of 10 ml was attained. In conclusion, these data show that LH levels do not reach a nadir until 8 years of age. We have detected a sex difference in the pattern of LH secretion seen in early puberty, and this mirrors clinical findings. The mature pattern attained by the end of puberty in both sexes is probably important for fertility.

Adolescent↗

A possible mechanism of action of danazol and an ethinylestradiol/norgestrel combination used as postcoital contraceptive agents.

Twenty-seven women requesting postcoital contraception were randomly allocated to take an ethinylestradiol/dl-norgestrel combination or danazol. Urine specimens were assayed for luteinising hormone (LH) and pregnanediol-3-glucuronide (P3G) levels from the day of the postcoital treatment to the next period. In addition, the urine samples of these recruits and 12 additional women were assayed for the Beta-subunit of human chorionic gonadotropin (B-hCG). A consistent pattern of alteration in urinary steroids was lacking, indicating a heterogeneous effect on ovarian function. There was no evidence of early pregnancy in successfully treated cases. We suggest that the main mechanism of action of these drugs is at the endometrial level.

Chorionic Gonadotropin↗

Time to pregnancy as a function of male and female serum concentrations of 2,2'4,4'5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE).

BACKGROUND: Persistent organochlorine pollutants (POP) may affect both the female and male reproductive system in animals as well as in humans. METHODS: Blood samples were collected from pregnant women and their partners from Greenland, Warsaw and Kharkiv, and from a cohort of Swedish fishermen's wives. Blood samples were analysed for 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE). Information on the participants' fertility, measured as time to pregnancy (TTP), was collected. In total, 778 men and 1505 women were included in the analyses. RESULTS: The data from Warsaw, Kharkiv and the Swedish fishermen's wives indicated no effect of either male or female exposure to POP on TTP. However, among men and women from Greenland, there seemed to be an association between serum concentrations of CB-153 and p,p'-DDE and prolonged TTP. Due to the strong intra-individual correlation between CB-153 and p,p'-DDE in the Greenlandic population, it was not possible to determine whether the risk was associated with CB-153 or p, p'-DDE or was an interaction between the two compounds. CONCLUSIONS: The overall results of the present study create a somewhat ambiguous pattern, but give some support to the idea that dietary POP exposure might be harmful for couple fertility.

Dichlorodiphenyl Dichloroethylene↗

Isolation and partial characterization of Urechis caupo egg envelopes.

Eggs of Urechis caupo are surrounded by a congruent to 0.9 micrometer thick egg envelope and, attached to that, a peripheral jelly layer about 3 micrometers thick. Before fertilization, the sperm undergoes the acrosome reaction and binds to the egg envelope. As part of a study of the induction of the acrosome reaction and sperm binding in Urechis, we have developed a method to prepare an egg envelope fraction by differential centrifugation. The isolation procedure removes much of the jelly layer, but does not alter the fine structure of the envelope. When a sperm contacts an isolated envelope, it undergoes a normal acrosome reaction and binds to the envelope's outer face. Electrophoresis of the envelope fraction on sodium dodecyl sulphate (SDS)/polyacrylamide gels revealed six major components stained by Coomassie Blue, of which four are stained by the periodic acid-Schiff reagents (PAS). To measure the degree of enrichment of the envelope fraction, envelopes were isolated from eggs that had been externally radio-iodinated; the specific activity of the envelope fraction was 17 +/- 3 times greater than that of intact eggs. The amino acid composition of the envelope fraction is dominated by Gly (19 mole %), Asx (11%), Thr (11%), Ser (8%), Ala (8%) and Glx (8%). The sugars fucose, xylose, mannose, galactose, glucose, N-acetylglucosamine and N-acetylgalactosamine were detected by gas-liquid chromatography. We also investigated whether the egg envelope changes at fertilization. No change was detected in the electrophoretic 125I pattern of externally radio-iodinated eggs, and the envelope fractions prepared from unfertilized and fertilized eggs produced the same Coomassie Blue pattern on SDS/polyacrylamide gels.

Amino Acids↗

Medicinal plants: historical and cross-cultural usage patterns.

PURPOSE: An attempt is made to review the prevalence of medicinal herb use in different societies and the various lines of evidence for its effectiveness for particular health needs and the alleviation of disease conditions. METHODS: Published scientifically collected data and anecdotal reports representing numerous populations are compiled and evaluated. Original research findings from Caribbean, American, and Caribbean-American samples are included in the comparisons. RESULTS: Medicinal plant products have been successfully administered both externally and internally in several different forms for a wide range of health problems cross-culturally since prehistoric times. Certain toxic effects and contraindications have also been recorded. CONCLUSIONS: Many botanical medications contain curative bioactive chemical ingredients which have proven to be valuable as primary or supplemental therapies when carefully applied. Further research will ultimately clarify their appropriate roles in the treatment of diseases and injuries as well as in preventive health maintenance.

Adult↗

Pollen-stigma interference in two gynodioecious species of Lamiaceae with intermediate individuals.

BACKGROUND AND AIMS: Intermediate individuals (perfect flowers with very high degree of pollen abortion) in a gynodioecious plant species are very rare. A study is made of male-female relationships in each flower type and how floral characters can enhance the avoidance of 'pollen discounting' and 'self-pollination' in two gynodioecious species, Teucrium capitatum and Origanum syriacum. METHODS: The relationship between stigma receptivity and pollen viability was studied in two gynodioecious protandrous species of Lamiaceae, in addition to measuring some floral morphological characters over the life span of the flowers. KEY RESULTS: Three plant types in each species were found: plants bearing hermaphrodite (or male fertile) flowers (MF), female (or male sterile) flowers (MS) and intermediate flowers (INT). Plant types differed in flower size, with MS types being shorter than the other two types. There was no difference in style length among plant types in T. capitatum. Stigma receptivity decayed with floral age and was negative and significantly correlated with pollen viability in the two species, and positive and significantly correlated with style length in O. syriacum but only in MS flowers of T. capitatum. CONCLUSIONS: Reduction in size of floral characters is associated with male sterility, except style length in T. capitatum. MF flowers have two successive reproductive impediments: self-pollination and pollen-stigma interference. In both species, self-pollination is avoided by dichogamy (negative correlation between stigma receptivity and pollen viability), and pollen-stigma interference shows two different patterns: (1) style elongation in O. syriacum is characterized by a significant length increase, final MF dimensions are greater than those of MS dimensions, and style length is positively and significantly correlated with stigma receptivity; and (2) style movement in T. capitatum is characterized by a non-significant increase in style length, final MF floral dimensions are similar to those of MS dimensions, and there is no correlation between style length and stigma receptivity.

Flowers↗

Polymorphism of human leukocyte antigen-E gene in the Japanese population with or without recurrent abortion.

PROBLEM: The aim of this study was to investigate the gene frequencies and shared alleles of human leukocyte antigen (HLA)-E gene in Japanese couples with or without recurrent abortion. METHOD OF STUDY: Polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis was carried out to detect polymorphism in exon 3 of the HLA-E gene in 30 Japanese couples with recurrent abortion and 38 normal Japanese couples with proven fertility. RESULTS: No point mutation was detected in exon 3 of HLA-E in both recurrent aborters and normal controls. HLA-EG and HLA-ER alleles were detected with frequencies of 66.7% and 33.3% in couples with recurrent abortion and 69.2% and 30.8 in normal couples, respectively. The gene frequency of HLA-EG was higher than that of HLA-ER, which is contrary to that found in Caucasian, African-American and Hispanic people but similar to Chinese people. The frequency of each allele was not significantly different between recurrent aborters and normal controls. The number of shared alleles between each couple with recurrent abortion is not significantly different from that with normal controls. CONCLUSION: Allele frequencies of HLA-E were suggested to be different in Asian people from those in other ethnic people. In light of no specific distribution pattern in recurrent aborters, HLA-E polymorphism does not seem to play a role in the pathogenesis of recurrent abortion.

Abortion, Habitual↗

Evaluation of the acrosome reaction and viability in buffalo spermatozoa using two staining methods: the effects of heparin and calcium ionophore A23187.

In this study, we investigated the effect of heparin and calcium ionophore A23187 on in vitro induction of buffalo sperm acrosome reaction (AR). Two methods for detection of the AR and viability were employed. Fluorescein isothiocyanate-conjugated Arachis hypogea agglutinin (FITC-PNA) was used as a vital stain in combination with ethidium homodimer-1 (EthD-1) to determine the acrosome status of viable spermatozoa. In another experiment, trypan blue replaced EthD-1 to differentiate live and dead spermatozoa having undergone AR. The results from the two methods were significantly correlated (r > 0.9). Four different staining patterns were found in both methods. The FITC-PNA intensely labels the acrosome region of acrosome-intact spermatozoa. EthD-1 and trypan blue stained red and blue at the post-acrosomal region of dead spermatozoa, respectively. Spermatozoa incubated with heparin showed a significant increase ( p < 0.05) in the percentage of live acrosome-reacted sperm after 30 min incubation period. This trend continued and was significantly different over the entire incubation period when compared with the control group at the same interval. In the ionophore-treated group, the proportion of changes in live acrosome-intact and live acrosome-reacted spermatozoa was statistically significantly different ( p < 0.001) when compared with those treated with heparin at the same interval. The AR occurred sooner and to a greater extent when incubated with the ionophore but at 5 h of incubation the percentage of false acrosomal reaction was significantly higher than those in the control and heparin-treated groups. The results in this study indicated that the in vitro induction of AR by heparin and calcium ionophore evaluated by both methods could be used to assess sperm fertilizing capacity for in vitro fertilization of this species.

Acrosome Reaction↗

Calcium-binding proteins and calcium-release channels in human maturing oocytes, pronuclear zygotes and early preimplantation embryos.

BACKGROUND: The study aim was to investigate the presence and localization of Ca2+-binding proteins and Ca2+-release receptor channels in human maturing oocytes, pronuclear zygotes and preimplantation embryos. METHODS: Immunocytochemical analysis, using specific antibodies against the proteins being studied, followed with confocal laser microscopy, was performed on human oocytes and embryos. RESULTS: Calreticulin and calsequestrin (the two major calcium storage proteins of somatic cells), two types of calcium release receptors, the inositol trisphosphate and ryanodine receptors (InsP(3)R-2, RyRs-1,2,3), and the molecular chaperone, calnexin, were identified in all investigated cell types. Calreticulin was predominant in the cell cortex and in the nuclear envelope, while calsequestrin was distributed throughout the entire cytoplasm. Generally, localization of the InsP(3)R-2 and RyRs was similar to that of calreticulin and calsequestrin respectively. Both types of receptor were enriched in the subplasmalemmal region of meiotic oocytes. In addition, the InsP(3)R was detected in the nuclear structures of oocytes and blastomeres. Calnexin distribution overlapped with that of calreticulin but appeared to be present in distinct subcompartments. CONCLUSIONS: Human oocytes and embryos express the calcium sequestration and release proteins in highly organized and developmentally regulated patterns. Fine-tuning of these proteins may play a crucial role in regulation of Ca2+ transience during oocyte maturation, fertilization and early embryo development.

Blastocyst↗

Male infertility in Kuwait. Etiologic and therapeutic aspects.

OBJECTIVE: To evaluate the pathological patterns associated with male infertility in Kuwait and to characterize treatment outcome after varicocele repair using percutaneous varicocele embolization. METHODS: We carried out a prospective study of 64 infertile men in Kuwait between 2001 and 2005. All patients included had proven non-obstructive azoospermia or oligospermia (sperm count <20 million/ml). All patients underwent ultrasonographic evaluation of the scrotum. Fine needle aspiration of the testes was performed on all azoospermic patients. RESULTS: A total of 24 (38%) patients were azoospermic while 40 (62%) were oligospermic. Sertoli- cell-only pattern was the most common cytopathology associated with primary testicular failure. Among the oligospermic patients, 50% had small to moderate varicocele. Spermatic vein embolization resulted in a significant rise in the mean sperm count from 10.6 +/- 3.8 million/ml to 30.2 +/- 6.8 million/ml (p<0.05) in 5 treated oligospermic patients, followed by spontaneous pregnancy in 2 couples. No effect was seen on azoospermic patients. CONCLUSION: From an etiological point of view, we believe that the high incidence of Sertoli cell-only-syndrome among nationals and residents of a country that underwent a major environmental insult strengthens the chances of an environmental role in the development of this syndrome. From a management point of view, in cultures where in vitro fertilization is either still not widely acceptable or is unaffordable, oligospermia with clinical or subclinical varicocele deserves a trial of a low risk, out patient procedure, namely, spermatic vein embolization that could improve fertility.

Adult↗

Does contraceptive method change the Pap smear finding?

The aim of the present study was to investigate the effect of various types of contraceptives on morphological finding of Pap smear results. Pap smear results of 7,753 fertile women who presented to 15 different family planning services in Fars Province (south of Iran) were analyzed according to their methods of contraception. The population consisted of 2241 women who used intrauterine device (IUD) as a contraceptive method (Group 1), 2521 women who were oral contraceptive (OCP) users (Group 2), and the control group, which consisted of women who used other methods of contraceptive. Comparison between the Pap smear results showed a higher number of benign cellular changes among Group 1 (22.4%) than Group 2 (19.3%), and the differences were statistically significant (p = 0.009). In addition, 80.6% women who used oral contraceptive pill (OCP) as contraceptive showed cellular changes within normal limits, while it were 77.6% for intrauterine device (IUD) users. Compared with Group 2, Group 1 had a significantly higher percentage of metaplastic cells in their Pap smear results (G1 7.4%, G2 5.8%, p < 0.05). No epithelial abnormalities were reported in Pap smears. Trichomonas vaginalis was higher in G1 than the other groups (p < 0.005), but the difference was not statistically significant for candidiasis. It may be concluded that in this population, IUD and OCP had no effect on morphological pattern of the Pap smears, but there was a significant increased rate of trichomonas infection in IUD users.

Adult↗

Are there adverse effects of periconceptional spermicide use?

Recent studies have suggested that spermicide exposure around conception may cause congenital malformations, reduced birth weight, or spontaneous abortion. This large, prospective study examined the risk for multiple malformation, patterns of malformations, low birth weight, preterm delivery, and spontaneous abortion in infants whose mothers used spermicides only before or after their last menstrual period, compared with a control group using other contraceptive methods. The multiple malformation rates in women using spermicides only before or after their last menstrual period were 3.8 and 4.8 per thousand, respectively. For the control groups, the corresponding rates were 5.4 and 6.4 (not significant). No pattern of malformations was found in spermicide-exposed infants. The risk of preterm delivery, the risk for producing a low-birth-weight (less than 2500 gm) infant, and the risk of spontaneous abortion were no higher in women exposed to spermicides than in women using other methods of contraception. This study finds no evidence that spermicide exposure around the time of conception is dangerous to the fetus.

Abnormalities, Drug-Induced↗

Computerized sperm motility and application of sperm cryopreservation.

An objective method for measuring sperm motion characteristics was developed on an Intellect 100 Quantel Image Analysis System suitable for various image cytometric applications. It provided overall analysis of percent motility (% MS) as well as individual and mean measurements of motion characteristics, including vigor characteristics such as curvilinear velocity (Vc), straight line velocity (Vsl), and trajectory pattern characteristics, that is, progressiveness ratio (PR) and amplitude of lateral head displacement (Alh). Evaluation of the method for reproducibility and accuracy showed reliable measurements of these parameters measured on a minimum of 70 motile sperm, sufficient to describe adequately the sperm population. A study was performed comparing motion characteristics of 30 semen samples falling in a normal range before and after cryopreservation in cryoprotector medium (CM). A mean motility rate of recovery (MRR) of 45% was obtained. Only sperm count and concentration in motile forms among initial semen variables correlated weakly with MRR. Velocity recovery rate (VRR) approached 1 with a marked variability among ejaculates. Distribution profile of Vc was highly modified by freezing in CM: spermatozoa that were initially fast and progressive were the most resistant to cryoaggression. PR and Alh values were little affected by freezing in CM. The tolerance of various samples from a given patient was highly variable for % MS and Alh and less variable for Vc and PR. This illustrates the difficulty in predicting the effect of freezing on motility characteristics and, therefore, of extrapolating from semen variables the ability of frozen-thawed samples to fertilize.

Freezing↗