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ABSTRACT: The aim of this study was to investigate the prevalence of infertility and the use of infertility treatment among women aged 40-55 years.
Population-based postal questionnaire survey of UK women. Over 60,000 women randomly sampled from the 2001 electoral roll were sent a questionnaire, and those aged 55 years and under who had ever been pregnant or tried to achieve a pregnancy (n = 6584) were asked to provide a reproductive history.
Overall, 2.4% of women aged 40-55 years had unresolved infertility with no pregnancies, and a further 1.9% had been pregnant but not achieved a live birth. The prevalence of unresolved fertility did not differ among birth cohorts. Sixteen percent of women reported ever consulting a doctor because of infertility and 8% reported receiving treatment to conceive. Across the whole sample, 4.2% of women reported that they had achieved at least one pregnancy as a result of treatment. Compared with earlier birth cohorts, women born later were more likely to report consultations (18% versus 13%) and treatment (9% versus 6%) for infertility, and pregnancies as a result of infertility treatment (6.7% versus 2.7%). Among those who reported medical consultations, women born more recently first consulted at a later age compared with those born earlier.
Although both the number of women seeking medical care for infertility and the proportion reporting pregnancies as a result of infertility treatment has increased, there is no evidence to support an overall increase in unresolved infertility over the past 15 years. The vast majority of women aged 40-55 who reported difficulties conceiving did have a child, or children, at some point in their lives.
Human Reproduction 03/2008; 23(2):447-50. · 4.47 Impact Factor
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ABSTRACT: The aim of this study was to examine the association between biological, behavioural and lifestyle risk factors and risk of miscarriage.
Population-based case-control study.
Case-control study nested within a population-based, two-stage postal survey of reproductive histories of women randomly sampled from the UK electoral register.
Six hundred and three women aged 18-55 years whose most recent pregnancy had ended in first trimester miscarriage (<13 weeks of gestation; cases) and 6116 women aged 18-55 years whose most recent pregnancy had progressed beyond 12 weeks (controls).
Women were questioned about socio-demographic, behavioural and other factors in their most recent pregnancy.
First trimester miscarriage.
After adjustment for confounding, the following were independently associated with increased risk: high maternal age; previous miscarriage, termination and infertility; assisted conception; low pre-pregnancy body mass index; regular or high alcohol consumption; feeling stressed (including trend with number of stressful or traumatic events); high paternal age and changing partner. Previous live birth, nausea, vitamin supplementation and eating fresh fruits and vegetables daily were associated with reduced risk, as were feeling well enough to fly or to have sex. After adjustment for nausea, we did not confirm an association with caffeine consumption, smoking or moderate or occasional alcohol consumption; nor did we find an association with educational level, socio-economic circumstances or working during pregnancy.
The results confirm that advice to encourage a healthy diet, reduce stress and promote emotional wellbeing might help women in early pregnancy (or planning a pregnancy) reduce their risk of miscarriage. Findings of increased risk associated with previous termination, stress, change of partner and low pre-pregnancy weight are noteworthy, and we recommend further work to confirm these findings in other study populations.
BJOG An International Journal of Obstetrics & Gynaecology 02/2007; 114(2):170-86. · 3.41 Impact Factor
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ABSTRACT: There has been much debate about paternal pre-conceptual exposure to low level ionising radiation and possible increased risk of ill health among the children subsequently conceived. The prevalence of reported learning difficulties was examined in over 16000 children born to UK nuclear industry workers, using fathers' information on exposure from the workers' individual employment and dosimetry records. There was no evidence that paternal exposure to low level ionising radiation at work influences the prevalence of learning difficulties in otherwise healthy children conceived after exposure.
Occupational and environmental medicine 10/2004; 61(9):786-9. · 3.64 Impact Factor
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ABSTRACT: We aimed to review trends in the probability of birth and multiple birth before and after the legal restriction limiting the maximum allowable number of embryos transferred, and to examine factors that determine the probability of multiple birth following IVF treatment.
We analysed data relating to 7170 IVF and 530 intracytoplasmic sperm injection cycles reaching embryo transfer undertaken by 4417 women at a single tertiary referral assisted conception centre in the UK between 1984 and 1997. Probability of birth, and of proportion of multiple births among those who gave birth, was explored using logistic regression analysis.
Between 1984 and 1997 there was a significant increase in probability of birth but no change in the probability of multiple birth. The trend in probability of birth was almost wholly explained by the significant increase in number of embryos created per cycle. Pooling all the data, risk factors for increased chance of birth and multiple birth were: younger age (<35 years), diagnoses other than tubal infertility, fewer than three previous unsuccessful cycles, previous IVF live birth and a large number of embryos created. Given these factors, increasing the number of embryos transferred did not increase the chance of a birth, but did increase the chance of a multiple birth.
The probability of birth has increased and the probability of multiple birth has remained unchanged, despite legislation limiting the number of embryos transferred in the UK. Efforts should be made to reduce the incidence of multiple births by transferring fewer embryos, especially in the presence of good prognostic factors for birth.
Human Reproduction 12/2001; 16(12):2598-605. · 4.47 Impact Factor
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ABSTRACT: To determine whether men and women who are occupationally exposed to ionising radiation are at increased risk of primary infertility.
A cross sectional analysis of reproductive outcome was reported in an occupational cohort of nuclear industry workers from the Atomic Energy Authority, Atomic Weapons Establishment, and British Nuclear Fuels in the United Kingdom. Data on employment and radiation monitoring supplied by employers were linked to data obtained from self administered questionnaires sent to all current employees and a sample of past workers. A total of 5353 men and 603 women aged 40 years or more at the time of survey whose first pregnancy, or attempt at pregnancy, had occurred after first employment in the nuclear industry were recruited to the study. Primary infertility was defined as consultation with a doctor about the failure to achieve at least one viable (24 weeks gestational age or more) pregnancy.
2.6% Of men and 3.7% of women reported primary infertility. For men, this proportion did not differ by amount of radiation monitored or by dose received. The prevalence of infertility was higher among monitored women than non-monitored women, but not significantly so and the numbers were too small to draw any firm conclusions.
No support was found for a hypothesis linking exposure to low level ionising radiation among men with primary infertility. There was weak evidence of an association in women, but the relatively few monitored women prevented detailed examination of these data.
Occupational and Environmental Medicine 09/2001; 58(8):535-9. · 3.02 Impact Factor
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ABSTRACT: Does preconceptional exposure to ionising radiation before conception affect the health of offspring? Some studies have suggested that radiation exposure might influence the sex ratio at birth, potentially indicating genetic damage. We examined the sex ratio of over 46000 children born to UK nuclear industry workers, using information on exposure from the workers' individual employment and dosimetry records. We found no statistically significant alterations of the sex ratio, and no evidence that exposure to low-level ionising radiation at work influences the sex ratio of children conceived after exposure.
The Lancet 06/2001; 357(9268):1589-91. · 38.28 Impact Factor
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ABSTRACT: There is some concern about the genetic effects of exposure to low-level ionising radiation, but the evidence is sparse and conflicting. Most work has concentrated on cancer in offspring and little has been done on adverse reproductive outcome. We aimed to assess whether the offspring of men and women who are occupationally exposed to ionising radiation are at increased risk of fetal death and congenital malformation.
We analysed pregnancies reported by an occupational cohort of nuclear industry workers in the UK, employed at establishments operated by the Atomic Energy Authority, Atomic Weapons Establishment, and British Nuclear Fuels. Employment and radiation monitoring data supplied by employers was linked to each pregnancy.
11,697 men and 1903 women reported one or more singleton pregnancy conceived after first employment within the nuclear industry, the men reporting a total of 23,676 singleton pregnancies and the women 3585. The risks of fetal death and congenital malformation were not related to whether the father had been monitored before conception or to the dose of radiation received. Among pregnancies reported by women, the risk of early (<13 weeks of gestation) miscarriage was higher if the mother had been monitored before conception (odds ratio [OR] 1.3, 95% CI 1.0-1.6), but there was no trend with dose. The risk of stillbirth was also higher if the mother had been monitored before conception (OR 2.2, 95% CI 1.0-4.6), but the finding was based on only 29 cases (13 exposed). The risk of any major malformation, or of specific groups of malformations, was not associated with maternal monitoring, or dose received, before conception.
We found no evidence of a link between exposure to low-level ionising radiation before conception and increased risk of adverse reproductive outcome in men working in the nuclear industry. Similarly for women there was no evidence of an association between monitoring before conception and malformation in offspring. The findings relating maternal preconceptual monitoring to increased risk of fetal death are equivocal and require further investigation.
The Lancet 11/2000; 356(9238):1293-9. · 38.28 Impact Factor
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The Lancet 03/2000; 355(9202):492; author reply 493. · 38.28 Impact Factor
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ABSTRACT: To describe the methods used in the nuclear industry family study for which a comprehensive database has been assembled that links employment in the nuclear industry and dosimetry records to information on employees' reproductive health and the health of their children. To discuss the response rates and characteristics of the study population.
Occupational cohort design leading to a retrospective cohort study of reproductive outcomes reported by 46 396 current and former employees of both sexes in the nuclear industry. Employees of nuclear establishments in the United Kingdom operated by the Atomic Energy Authority, the Atomic Weapons Establishment, and British Nuclear Fuels were surveyed with postal questionnaires ot collect information on pregnancies, children,and periods of infertility. Information on employment and monitoring for ionising radiation was supplied by the employing nuclear authority and was linked to pregnancies and periods of infertility with unique personal identification numbers.
The design and completion of this study resulted in high quality data on a representative population of the Atomic Energy Authority, Atomic Weapons Establishment, and British Nuclear Fuels workforces. The response to the survey was extremely good (82% for male workers and 88% for female workers, excluding undelivered questionnaires), and a unique relational database has been created which will enable infertility, pregnancy, and child health outcomes to be examined with respect to the employment and radiation monitoring characteristics of parents.
This is the first United Kingdom study to link detailed reproductive history data to occupational information held by employers. The methods developed for the study were found to be feasible and successful. The design can be adapted for other investigations of reproductive hazards to men and women in the workplace and is currently in use to survey over 100 000 armed forces personnel in an investigation of reproductive outcome among veterans of the Gulf war.
Occupational and Environmental Medicine 01/2000; 56(12):798-808. · 3.02 Impact Factor
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ABSTRACT: We sought to assess whether the use of norethindrone and gonadotropin-releasing hormone agonist therapy in the early follicular phase reduces the occurrence of functional ovarian cysts and shortens the duration of pituitary desensitization. We also assessed whether the use of norethindrone impairs implantation rates after in vitro fertilization treatment.
We performed a prospective, randomized, single-blind study involving 117 patients who were randomized to receive norethindrone 24 hours before gonadotropin-releasing hormone agonist therapy (n = 63, treatment group) or gonadotropin-releasing hormone agonist alone (n = 54, control group) for pituitary desensitization.
The incidence of functional ovarian cyst formation after 1 week of gonadotropin-releasing hormone agonist therapy was significantly lower in the treatment group compared with the control group. Furthermore, the duration of pituitary suppression was significantly shorter in the treatment group than in the control group. There were no significant differences between the 2 groups in the follicular response and embryo quality. Adjusted for age, the implantation rate (22% vs 9%, P =.02) and clinical pregnancy rate (34% vs 18%, P =.04) were significantly higher in the treatment group than in the control group.
A combination of norethindrone and gonadotropin-releasing hormone agonist therapy is therefore more effective in achieving prompt pituitary suppression and should be considered for routine use during in vitro fertilization cycles.
American Journal of Obstetrics and Gynecology 10/1999; 181(3):576-82. · 3.47 Impact Factor
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ABSTRACT: To determine whether children of men and women occupationally exposed to ionising radiation are at increased risk of developing leukaemia or other cancers before their 25th birthday.
Cohort study of children of nuclear industry employees.
Nuclear establishments operated by the Atomic Energy Authority, Atomic Weapons Establishment, and British Nuclear Fuels.
39 557 children of male employees and 8883 children of female employees.
Cancer incidence in offspring reported by parents. Employment and radiation monitoring data (including annual external dose) supplied by the nuclear authorities.
111 cancers were reported, of which 28 were leukaemia. The estimated standardised incidence ratios for children of male and female employees who were born in 1965 or later were 98 (95% confidence interval 73 to 129) and 96 (50 to 168) for all malignancies and 109 (61 to 180) and 95 (20 to 277) for leukaemia. The leukaemia rate in children whose fathers had accumulated a preconceptual dose of >/=100 mSv was 5.8 times that in children conceived before their fathers' employment in the nuclear industry (95% confidence interval 1.3 to 24.8) but this was based on only three exposed cases. Two of these cases were included in the west Cumbrian ("Gardner") case-control study. No significant trends were found between increasing dose and leukaemia.
Cancer in young people is rare, and our results are based on small numbers of events. Overall, the findings suggest that the incidence of cancer and leukaemia among children of nuclear industry employees is similar to that in the general population. The possibility that exposure of fathers to relatively high doses of ionising radiation before their child's conception might be related to an increased risk of leukaemia in their offspring could not be disproved, but this result was based on only three cases, two of which have been previously reported. High conceptual doses are rare, and even if the occupational association were causal, the number of leukaemias involved would be small; in this study of over 46 000 children, fewer than three leukaemias could potentially be attributed to such an exposure.
BMJ 06/1999; 318(7196):1443-50. · 14.09 Impact Factor
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BMJ 06/1999; 318(7196):1453-4. · 14.09 Impact Factor
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ABSTRACT: To describe trends in HIV prevalence among female injecting drug users (IDU) in London between 1990 and 1996.
HIV prevalence and risk behaviour were measured yearly between 1990 and 1993, and in 1996, in point prevalence HIV surveys of IDU recruited from both drug-treatment and community-based settings within Greater London. Sample sizes were 173 in 1990, 111 in 1991, 128 in 1992, 146 in 1993 and 200 in 1996.
Each survey used structured questionnaires and common sampling and interview strategies. Oral fluid specimens were collected for testing for antibodies to HIV (anti-HIV). Multiple logistic regression was used to assess the trend in HIV prevalence.
The percentage of female IDU testing positive for antibodies to HIV showed a marked decline over the study period, from 15.0% in 1990 to 1.0% in 1996 (P < 0.001). This trend was independent of all other variables examined. Each year, higher HIV prevalences were found among IDU recruited from community settings compared with treatment agencies.
These results concur with those of IDU recruited from treatment sites, although the yearly estimates in this study are higher. London benefits from low prevalence of HIV infection among IDU, coupled with behaviour change facilitated by early intervention. Continued surveillance of injectors recruited from both community and treatment settings is necessary in order properly to assess HIV prevalence among IDU.
AIDS 05/1999; 13(7):833-7. · 6.24 Impact Factor
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ABSTRACT: To provide an assessment of pregnancy and live birth probabilities for women presenting for in vitro fertilisation treatment for the first time, when committed in advance to have up to three cycles of treatment in one year.
Up to three cycles of in vitro fertilisation within one year, committed in advance.
A tertiary referral centre for assisted reproduction.
Two hundred and thirty-two women, undergoing a total of 536 cycles of in vitro fertilisation or intracytoplasmic sperm injection between August 1993 and December 1995.
Analysis of cumulative clinical pregnancy and live birth rates for women having IVF treatment for the first time and undertaking a three-cycle package, using the life-table approach.
Cumulative clinical pregnancy and live birth rates.
The cumulative probabilities of clinical pregnancy and live birth after two cycles of treatment were 38.2% and 33.2%, respectively, compared with 54.2% and 48.2%, respectively, after three cycles of treatment. Cumulative clinical pregnancy and live birth rates after three cycles of treatment for women up to the age of 40 years were 57.8% and 51.3%, respectively. Cumulative clinical pregnancy and live birth rates declined with increasing age (P = 0.02 and P= 0.01, respectively).
The three-cycle package encourages couples to have multiple treatment cycles, thereby improving their ultimate chances of a live birth. The cumulative clinical pregnancy and live birth rates after such a package provide a more realistic assessment of overall and age-specific success rates after multiple treatment cycles.
British Journal of Obstetrics and Gynaecology 03/1999; 106(2):165-70.
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ABSTRACT: This study compared the outcome of a course of up to three cycles of in-vitro fertilization (IVF) treatment in 46 women (97 cycles) who had polycystic ovaries (PCO) seen on ultrasound scan, but who had no clinical symptomatology associated with polycystic ovary syndrome, with that of 145 women (332 cycles) who had normal ovarian morphology on ultrasound examination. All 191 women had normal early follicular phase serum follicle stimulating hormone (FSH) concentrations, were less than 40 years of age and used the long protocol of pituitary suppression with gonadotrophin-releasing hormone agonist therapy. On average, the women with PCO produced more follicles, oocytes and embryos than the women with normal ovaries, but the fertilization, cleavage and miscarriage rates were similar. Adjusted for age, the odds of achieving a pregnancy within three cycles of treatment in a woman with PCO were 69% higher than those of a woman with normal ovaries [odds ratio (OR): 1.69, 95% confidence interval (CI) 0.99-2.90, P = 0.05)] and the odds of achieving a live birth were 82% higher (OR: 1.82, 95% CI 1.05-3.16, P = 0.03). There is, therefore, evidence that outcome of IVF treatment for women with PCO seen on ultrasound examination may be better than that for women with normal ovaries.
Human Reproduction 02/1999; 14(1):167-71. · 4.47 Impact Factor
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New England Journal of Medicine 11/1997; 337(16):1175-6. · 53.30 Impact Factor
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ABSTRACT: To investigate on a population basis the suggestion that certain factors naturally alter the odds of having a boy or a girl, and that some women are predisposed towards having children of one particular gender.
Routine data analysis.
Routinely collected data on singleton infants born in Scotland from 1975 to 1988, linked so that births (live and still) to the same mother could be identified. The analyses relate to 549,048 first to fifth order births occurring to 330,088 women whose records were complete from the first delivery onwards.
Gender of infant.
Of 549,048 births, 51.4% were male. Apart from random variation, the sex ratio of 1.06 remained constant at all birth orders (P = 0.18). The probability of a male infant appeared unrelated to the genders of the preceding siblings (P > 0.20 in second to fifth deliveries), and there was no evidence of variation with maternal age (P = 0.31), maternal height (P = 0.69), paternal social class (P = 0.12), maternal social class (P = 0.57), year of delivery (P = 0.84) or season of birth (P = 0.41). Whilst mothers whose children were all the same gender were more likely to continue childbearing than those with children of different genders, there was no evidence that those with daughters were more likely to continue than those with sons.
The suggestion that some women have a natural predisposition towards having children of a particular gender is not supported by these data. On a population basis there is no evidence to suggest that gender determination is anything other than a chance process.
British Journal of Obstetrics and Gynaecology 09/1997; 104(9):1050-3.
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ABSTRACT: To assess the reproducibility of ovarian and endometrial volume measurements obtained using transvaginal three-dimensional (3D) ultrasound (US).
Prospective clinical study.
A tertiary referral center for assisted reproduction.
Forty women undergoing ovarian stimulation for IVF-ET using the long protocol of GnRH agonist.
Three observers independently measured 20 stored ovarian scanned volumes and 20 endometrial volumes. Also, ovarian volume was calculated from three diameters obtained by two-dimensional (2D) US.
Analysis of variance, the paired Student's t-test, and calculation of intraclass and interclass correlation coefficients were used for statistical analysis.
Three-dimensional ovarian volume measurements were not significantly different from ovarian volume calculated from three diameters (7.98 versus 7.58 mL). The mean endometrial volume measurement was 3.56 mL. The intraobserver coefficient of variation for both ovarian and endometrial volume was 8%. The interobserver coefficient of variation was 9% for ovarian volume and 11% for endometrial volume. Intraclass and interclass correlation coefficients were 0.95 and 0.95 for ovarian volume and 0.90 and 0.82, respectively, for endometrial volume.
Transvaginal 3D US produces highly reproducible ovarian and endometrial volume measurements.
Fertility and Sterility 12/1996; 66(5):718-22. · 3.56 Impact Factor
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ABSTRACT: One thousand and sixty-three twins with cancer whose co-twin was born alive were identified among patients born since September 1939 with cancers incident in England and Wales during 1971-1984 at childhood and young adult ages. Site-specific risks of cancer were analysed in relation to birth order within the twinship and sexes of the twin pair, using adjusted national birth data to give control distributions of these variables. Risk of leukaemia was increased in first-born twins, risk of testicular cancer was increased in second-born twins with female co-twins but decreased in second-born twins with male co-twins and lung cancer risk was increased in first-born twins with same-sex co-twins. Cutaneous melanoma risk was increased in persons with opposite-sex co-twins, nervous system cancer risk was increased in females with opposite-sex co-twins and Hodgkin's disease risk was increased in persons with same-sex co-twins. For most of the findings, no previous comparable analyses are available, so interpretation of the results must be provisional until the analyses can be repeated on other data. The result for leukaemia would accord with previous suggestions that leukaemia may be of prenatal origin and may sometimes lead to intrauterine death. The Hodgkin's disease result would fit with theories of an infectious aetiology, and this view is strengthened by reanalysis of previous data on paralytic poliomyelitis in twins, which show a pattern similar to that for the Hodgkin's disease patients. Cancer risk in relation to birth order and sex of twins can give novel, objective data relating to prenatal and infectious disease aetiology of cancers.
International Journal of Cancer 09/1996; 67(4):472-8. · 5.44 Impact Factor
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ABSTRACT: Our purpose was to compare cumulative conception and live-birth rates after in vitro fertilization with and without the use of the long, short, and ultrashort regimens of the gonadotropin-releasing hormone agonist buserelin.
Life-table analysis of conception and live-birth rates in relation to ovarian stimulation regimen used in 2893 women who had one of five stimulation regimens exclusively throughout all treatment cycles, namely, human menopausal gonadotropin with or without clomiphene citrate; follicle-stimulating hormone with or without clomiphene citrate; and long, short, and ultrashort protocols of buserelin, plus follicle-stimulating hormone or human menopausal gonadotropin; and in an additional 347 women who had been administered both human menopausal gonadotropin and follicle-stimulating hormone with or without clomiphene citrate.
The cumulative conception rate and cumulative live-birth rate were significantly higher in those women treated exclusively with the long buserelin regimen (59% and 55%, respectively, after three cycles) compared with those who only had human menopausal gonadotropin or follicle-stimulating hormone with or without clomiphene citrate (39% and 29%, respectively, after three cycles) (p = 0.001 and p = 0.0001) or compared with those who had only short or ultrashort buserelin regimens (22% and 17% after two cycles) (p = 0.0001 and p = 0.005). The pregnancy failure rate in patients on the long buserelin regimen was 22.4% (95% confidence interval 14.8% to 30.0%) compared with 33.3% (95% confidence interval 29.6% to 37.0%) in those who had human menopausal gonadotropin or follicle-stimulating hormone with or without clomiphene citrate (p = 0.03). When the probabilities of first conception and first live birth were examined by treatment regimen, after we allowed for the effects of age, cause of infertility, calendar year of treatment, and treatment cycle number (with a multiple logistic regression model), it was found that, relative to human menopausal gonadotropin or follicle-stimulating hormone with or without clomiphene citrate, the odds of conceiving with the long buserelin regimen was 1.63 (95% confidence interval 1.31 to 2.03) (p < 0.001) and the odds of a live birth was 1.97 (95% confidence interval 1.53 to 2.54) (p < 0.001). Similarly, relative to short or ultrashort buserelin the odds of conceiving with long bureselin was 1.88 (95% confidence interval 1.39 to 2.55) (p < 0.001) and the odds of a live birth was 1.79 (95% confidence interval 1.25 to 2.56) (p = 0.001).
Pituitary desensitization with the long protocol of buserelin significantly increases the probabilities of conception and live birth after in vitro fertilization.
American Journal of Obstetrics and Gynecology 09/1994; 171(2):513-20. · 3.47 Impact Factor
