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Biomedical subjects

A M Flynn

Publications and source records attributed to A M Flynn.

At least 19 recordsLinked to original sources

Fertility of fully breast-feeding women in the early postpartum period.

OBJECTIVE: To examine bleeding between 6 and 8 weeks postpartum in fully breast-feeding women and its association with fertility as assessed by hormone analysis. METHODS: Seventy-two fully breast-feeding women were followed prospectively from 42 days postpartum. Vaginal bleeding was recorded daily. Women who experienced bleeding were compared with women who did not with respect to time of ovulation and time of first menses. RESULTS: Nearly half of the women experienced some vaginal bleeding or spotting between 6 and 8 weeks postpartum. These women eventually menstruated and ovulated earlier than the women who did not bleed, but the differences were not significant. The study had 34% and 45% power to detect a 20% difference in the proportion menstruating and ovulating, respectively, at 6 months postpartum, and 10% and 16% power to detect the same differences at 1 year. Seven women experienced ovarian follicular development before day 56, but neither bleeding nor follicular development was associated with ovulation in any woman in the first 8 weeks postpartum. CONCLUSIONS: It is unlikely that vaginal bleeding in fully breast-feeding women in the first 8 weeks postpartum represents a return to fertility.

Female↗

Volumetric self-sampling of cervicovaginal fluid to determine potential fertility: a multicentre pre-effectiveness study of the Rovumeter.

The aim of this study was to assess how effectively the Rovumeter, designed for the volumetric self-sampling of cervicovaginal fluid (CVF), can be used to locate the minimum period of potential fertility (PPF) during ovulatory cycles. A multicentre, prospective study was undertaken of volunteers (attending natural family planning clinics) over three consecutive, apparently normal, menstrual cycles. All women collected daily samples of early morning urine and CVF and recorded the volumes (to the nearest 1.0 and 0.1 ml respectively). The concentrations of oestrone glucuronide (EG), luteinizing hormone (LH) and pregnanediol glucuronide (PG) were measured in all samples of early morning urine by immunoassay. A preliminary data set was used to optimize an algorithm to detect the start and end of potential fertility from the volumes of CVF. The end-points used were the normality of each menstrual cycle from its length, the length of luteal phase, and concentrations of EG, LH and PG, the start and end days of potential fertility from CVF volumes, and the minimum PPF, which was defined as the day of the LH peak minus 3 to day plus 2 inclusive. Overall, 72 women (median age 30 years, range 24-38) were recruited from three centres (23 from Birmingham, 24 from Milan, 25 from Santiago) and contributed data from 235 menstrual cycles (median length 28 days, range 23-44). The urinary LH peak was identified in 228 cycles (97%; median time, day 15 from day 1 of last menses, with range day 10 to day 35). The use of the Rovumeter gave start and end signals of potential fertility during 138 cycles (59%). The median length of the derived PPF was 8 days (range 4-18). The signals covered the defined, minimum PPF in 113 cycles [i.e. 50% of those with an LH peak; range 28% (Milan) to 62% (Birmingham)]. Overall 16/72 women (22%) had successful tests over three consecutive menstrual cycles [range 2/24 (8%; Milan) to 8/23 (35%; Birmingham)]. We conclude that signals from daily changes in the volume of CVF as determined by the use of the Rovumeter consistently locate the minimum period of potential fertility in only a small proportion of women.

Adult↗

Symptothermal and hormonal markers of potential fertility in climacteric women.

One hundred seventy-seven menstrual cycles in 36 women between 45 and 53 years of age were studied prospectively. All the women were experienced in the symptothermal method of natural family planning. The objective was to determine the symptothermal and hormonal indices of potential fertility by measuring urinary estrone glucuronide and pregnanediol glucuronide. Thirty-three percent had regular cycles consistent with potential fertility, 19% had cycles consistent with infertility, and 47% had a mixture of both types of cycle.

Biomarkers↗

Ultrasonographic patterns of ovarian activity during breastfeeding.

In this study, ultrasonography was used to detect follicular activity in lactating women, and these findings were related to the underlying hormonal profiles and to the mucus symptom. A number of different patterns of follicular development were seen before the women returned to normal fertile cycles during the period that was previously considered to be characterized by ovarian quiescence. Some of the transitory patterns of follicular activity were reflected in rising hormone levels and patterns of fertile mucus that were sometimes confusing for these lactating women who were using natural family planning.

Breast Feeding↗

The temporal relationship between vaginal fluid volumes obtained with the Rovumeter vaginal aspirator and the fertile phase of the cycle.

Recent trends in family planning demonstrate an increasing interest in natural methods of birth regulation. In their present form, however, these methods are highly subjective and individualistic. A further trend in fertility programmes has been a very rapid development of technological methods to detect fertility in the female cycle, some of which could possibly benefit natural family planning users. One such technique--that of changing volumes of cervico-vaginal fluid (CVF), which is a mixture of cervical mucus and vaginal transudate--has been tested in a pilot study to ascertain its reliability to demarcate the fertile phase of the cycle. Results show that in all cycles tested, it is possible using the Rovumeter aspirator to detect the beginning of the fertile phase by rapidly increasing volumes of CVF; this volume reaches a peak approximately 1 day before ovulation detected by ultrasound and demonstrates an abrupt fall after ovulation and the onset of the infertile phase. From the results of this pilot study, we believe that, by the use of suitable algorithms and larger studies, it should be possible to develop a CVF volume method which could be offered as an objective alternative method for users of natural family planning and programmes.

Adult↗

Detection of the fertile phase from changes in cervico-vaginal fluid volume.

Characteristic changes in cervico-vaginal fluid (CVF) volume which occur during the menstrual cycle might be used to detect the fertile phase. Twenty-five normal women were asked to withdraw CVF and measure its volume at home using a small, disposable, graduated vaginal aspirator. In 16 cycles day 0 (ovulation) was defined as the day of maximum follicular diameter according to serial ultrasound examination. A rise in CVF volume occurred between day -9 and -2 and a peak between day -4 and 0. In these sixteen, and in a further 72 cycles, day 0 (time of maximum fertility) was taken as the day of peak cervical mucus secretion. CVF volume rose, on the average, on day -6.2 (range -17 to -2) and peaked on day -0.8 (range -5 to +2). In two cycles, no rise and peak were identified. Changes in CVF volume were easy to recognise and could be useful to couples wishing to achieve pregnancy.

Adult↗

Structural requirements for the neutralization of heparin-like saccharides by complement S protein/vitronectin.

S protein, a major inhibitor of the assembly of the membrane attack complex of complement, has recently been shown to be identical to the serum spreading factor vitronectin. It also neutralizes the anticoagulant activities of heparin. We have studied the structural requirements for the heparin neutralizing properties of S protein/vitronectin using heparin, heparan sulfate, and heparin oligosaccharides with well defined anticoagulant specificities. The abilities of heparin fractions, Mr 7,800-18,800, with high affinity for antithrombin, and of the International Heparin Standard, to accelerate the inactivation of thrombin and Factor Xa by antithrombin were readily neutralized by S protein/vitronectin. Binding and neutralization of heparin by S protein/vitronectin was inhibited by heparin with low affinity for antithrombin, indicating that S protein/vitronectin can interact with a region on the heparin chain that might serve as a proteinase binding site. S protein/vitronectin efficiently neutralized oligosaccharides of Mr 2,400-7,200, unlike the two other physiologically occurring heparin neutralizing proteins histidine-rich glycoprotein and platelet factor 4. Furthermore, S protein/vitronectin neutralized the anti-Factor Xa activity of a synthetic pentasaccharide comprising the antithrombin-binding sequence of heparin. High molar excess of a synthetic tridecapeptide corresponding to part (amino acids 374-359) of the proposed glycosaminoglycan binding domain of S protein/vitronectin neutralized high affinity heparin and some oligosaccharides, but failed to neutralize the synthetic antithrombin-binding pentasaccharide. Like platelet factor 4, but unlike histidine-rich glycoprotein, S protein/vitronectin readily neutralized the anticoagulant activities of heparan sulfate of Mr approximately 20,000. These findings suggest that S protein/vitronectin may interact through its glycosaminoglycan binding domain(s) with various functional domains of the heparin (heparan sulfate) molecule, including the antithrombin-binding pentasaccharide sequence. Furthermore, the results suggest that S protein/vitronectin may be a physiologically important modulator of the anticoagulant activity of heparin-like material on or near the vascular endothelium.

Antithrombins↗

Neutralization of heparin-related saccharides by histidine-rich glycoprotein and platelet factor 4.

Heparin and heparin oligosaccharides prepared by nitrous acid depolymerization were fractionated by affinity chromatography on immobilized antithrombin and by gel chromatography. The anticoagulant activities of high affinity heparin of Mr greater than or equal to 7,800 could be readily neutralized by the plasma protein histidine-rich glycoprotein (see also Lijnen, H.R., Hoylaerts, M., and Collen, D. (1983) J. Biol. Chem. 258, 3803-3808), whereas oligosaccharides falling below 18 saccharide units (Mr 5,400) became increasingly resistant to neutralization. An octasaccharide with characteristic marked ability to accelerate the inactivation of Factor Xa by antithrombin retained greater than 50% of its activity even at a histidine-rich glycoprotein/oligosaccharide molar ratio of 500:1. Histidine-rich glycoprotein, like the platelet-derived heparin neutralizing protein platelet factor 4 (Lane, D.A., Denton, J., Flynn, A.M., Thunberg, L. and Lindahl, U. (1984) Biochem J. 218, 725-732), therefore requires interaction with saccharide sequences in addition to the antithrombin-binding pentasaccharide of heparin in order to efficiently express its antiheparin activity. Heparan sulfate isolated from pig intestinal mucosa (HS I, Mr approximately 20,000) and from human aorta (HS II, Mr approximately 40,000) exhibited anti-Factor Xa activities of 180 and 20 units/micromol [corrected], respectively. A fraction corresponding to about 5% of HS I bound with high affinity to immobilized antithrombin and contained all of the anticoagulant activity of the starting material. While these heparan sulfates were readily neutralized by platelet factor 4, they were relatively resistant to neutralization by histidine-rich glycoprotein, although complete neutralization could be attained in the presence of molar excess of this protein. These findings may be of importance in relation (a) to the functional role of endogenous anticoagulant polysaccharides at the vascular wall and (b) to clinical situations in which heparin or heparin-related compounds are administered as exogenous anticoagulants.

Heparin↗

Anticoagulant activities of heparin oligosaccharides and their neutralization by platelet factor 4.

Oligosaccharides of well-defined molecular size were prepared from heparin by nitrous acid depolymerization, affinity chromatography on immobilized antithrombin III (see footnote on Nomenclature) and gel chromatography on Sephadex G-50. High affinity (for antithrombin III) octa-, deca-, dodeca-, tetradeca-, hexadeca- and octadeca-saccharides were prepared, as well as oligosaccharides of larger size than octadecasaccharide. The inhibition of Factor Xa by antithrombin III was greatly accelerated by all of these oligosaccharides, the specific anti-Factor Xa activity being invariably greater than 1300 units/mumol. The anti-Factor Xa activity of the decasaccharide was not significantly decreased in the presence of platelet factor 4, even at high platelet factor 4/oligosaccharide ratios. Measurable but incomplete neutralization of the anti-Factor Xa activities of the tetradeca- and hexadeca-saccharides was observed, and complete neutralization of octadeca- and larger oligo-saccharides was achieved with excess platelet factor 4. The octa-, deca-, dodeca-, tetradeca- and hexadeca-saccharides had negligible effect on the inhibition of thrombin by antithrombin III, whereas specific anti-thrombin activity was expressed by the octadeca-saccharide and by the larger oligosaccharides. An octadecasaccharide is therefore the smallest heparin fragment (prepared by nitrous acid depolymerization) that can accelerate thrombin inhibition by antithrombin III. The anti-thrombin activities of the octadecasaccharide and larger oligosaccharides were more readily neutralized by platelet factor 4 than were their anti-Factor Xa activities. These findings are compatible with two alternative mechanisms for the action of platelet factor 4, both involving the binding of the protein molecule adjacent to the antithrombin III-binding site. Such binding results in either steric interference with the formation of antithrombin III-proteinase complexes or in displacement of the antithrombin III molecule from the heparin chain.

Anticoagulants↗

[Natural family planning (symptothermal method) and objective ovulation parameters--a pilot study].

This pilot study involved 20 cycles contributed by six apparently healthy women. They were all experienced users of the symptothermal method of NFP and trained as NFP-teachers. In a double-blind study NFP-parameters like S-19 = F1, appearance of any mucus = F2 and appearance of fertil mucus = F3 also peak mucus symptom +4 = L1 and 3. day of high basal body temperature = L2 are related to ovulation detected by ultrasonic measurement of follicular growth and hormonal values (LH, total Oestrogen in urine). We have focused on the calculation of the first day and the end of the fertile phase. In relation to the maximal follicular diameter (mfd = day 0) the LH-peak was located at day -0,7. The peak mucus symptom was observed at day -0,58. F1 was seen 10,4 +/- 2,6 days, F2 6,2 +/- 2,6 days, F3 2,8 +/- 1,4 days before day 0. L1 was located at 3,37 +/- 1,74 days, L2 4,1 +/- 1,95 days after day 0. Using at least 2 indicators as recommended with the symptothermal method none of 19 cycles failed to detect the beginning of the fertile phase, but 3 out of 20 failed to detect the end. In 19 out of 20 cycles natural signals observed by the participants indicated ovulation. It must be mentioned that all our women were highly motivated persons.

Body Temperature↗

An automatic electronic device (Rite Time) to detect the onset of the infertile period by basal body temperature measurements.

Two trials of an electronic thermometer (Rite Time), designed to record and interpret basal body temperature (BBT) patterns in normal ovulating women, are described. A total of 140 menstrual cycles from 34 women, who used the thermal or symptothermal methods of natural family planning, were studied. Rite Time gave a signal for the start of the infertile period in 117 cycles, of which 114 (97%) appeared to have occurred at appropriate times. Further studies using hormonal and ultrasound reference points for ovulation were carried out in 21 cycles. Rite Time generally produced BBT patterns of quality acceptable for interpretation of the periovulatory BBT shift. About one-half of the volunteers said that they would be willing to replace their conventional charting methods with Rite Time.

Body Temperature↗

Natural methods of family planning.

Reliable indicators to detect the fertile and infertile phases in the menstrual cycle are now available, largely due to the intensive scientific research into fertility over the past decade. This means that couples who follow the rules of the different NFP methodologies have a highly effective means of birth control, without the introduction of hormones, chemicals or devices into the body. New scientific techniques can be expected within the next couple of years which will simplify the detection of the fertile phase and hopefully help to elucidate the grey area of the early fertile days, where most of the unplanned pregnancies occur. Fertility awareness by both partners is an important positive contribution to the whole sexual relationship and emphasizes that NFP is an educational delivery system rather than a technological one. The modification of sexual behaviour and the motivation of both partners for the successful use of NFP may initially present a problem to some couples. On the other hand, many partners find the discipline enhances their sexual relationship and dialogue. Whatever the motivation, today more and more couples are happier to be in autonomous control of their bodies and their fertility.

Body Temperature↗

A randomized controlled trial of non-stress antepartum cardiotocography.

In a prospective randomized controlled study of non-stress antepartum cardiotocography (CTG), involving 569 tracings in 300 patients, "non-reactive' traces showed a significant association with still-births and neonatal deaths, intrauterine growth retardation, admission to special care baby unit for conditions associated with intrauterine hypoxia, and low Apgar scores at 1 and 5 min. The report of the CTG was made available to the clinician in 144 patients and withheld in 156 patients. With the report available, significantly more patients were allowed to continue their antenatal care as out-patients, and significantly more antenatal in-patients were allowed home. There were no other significant differences in management, or outcome in the two groups.

Clinical Trials as Topic↗