Fiona Bruinsma

Risk of cancer after use of fertility drugs with in-vitro fertilisation

BACKGROUNDnWe investigated the incidence of invasive cancer of the breast, ovary, and uterus in a cohort of patients who had undergone in-vitro-fertilisation (IVF) treatment and examined whether cause of infertility or exposure to fertility drugs to induce superovulation was associated with an increased cancer risk.nnnMETHODnTen Australian IVF clinics provided data for women who had been referred for IVF before Jan 1, 1994. The frequencies of invasive breast, ovarian, and uterine cancer were assessed by record linkage to population-based cancer registries and the national death index. The observed number of cancers was compared with the expected number calculated by application of age-standardised general-population cancer rates to the cohort. Standardised incidence ratios (SIRs) were derived from the ratio of observed to expected cases.nnnFINDINGSnThe cohort consisted of 29,700 women: 20,656 were exposed to fertility drugs and 9044 were not. 143 breast cancers, 13 ovarian cancers, and 12 cancers of the uterus occurred among these women. For breast and ovarian cancer the incidence was no greater than expected (SIR 0.91 [95% CI 0.74-1.13] for breast cancer and 0.88 [0.42-1.84] for ovarian cancer in the exposed group and 0.95 [0.73-1.23] for breast cancer and 1.16 [0.52-2.59] for ovarian cancer in the unexposed group). The incidence of uterine cancer was no higher than expected in the exposed group (1.09 [0.45-2.61]) but was significantly higher in the unexposed group (2.47 [1.18-5.18]). Women with unexplained infertility had significantly more cancers of the ovary and uterus than expected (2.64 [1.10-6.35] and 4.59 [1.91-11.0], whole cohort). Analysis of cancer incidence within 12 months of exposure to fertility drugs with IVF showed that incidence was significantly higher than expected for breast and uterine cancer (1.96 [1.22-3.15] and 4.96 [1.24-19.8]).nnnINTERPRETATIONnWomen who have been exposed to fertility drugs with IVF seem to have a transient increase in the risk of having breast or uterine cancer diagnosed in the first year after treatment, though the incidence overall is no greater than expected. Unexplained infertility was associated with an increased risk of a diagnosis of ovarian or uterine cancer.

The risk of preterm birth following treatment for precancerous changes in the cervix: a systematic review and meta-analysis.

Please cite this paper as: Bruinsma F, Quinn M. The risk of preterm birth following treatment for precancerous changes in the cervix: a systematic review and meta‐analysis. BJOG 2011;118:1031–1041.

Precancerous changes in the cervix and risk of subsequent preterm birth

Objectiveu2002 The aims of this study were (i) to examine whether women referred for assessment of precancerous changes in the cervix had higher rates of preterm birth compared with those in the general population and (ii) to compare preterm birth rates for treated and untreated women adjusting for possible confounding factors.

Oestrogen treatment to reduce the adult height of tall girls: long-term effects on fertility

BACKGROUNDnTreatment with oestrogen to reduce the adult height of tall girls has been available since the 1950s. We undertook a retrospective cohort study to assess the long-term effects of this treatment on fertility.nnnMETHODSnEligible participants were identified from the records of Australian paediatric endocrinologists who assessed tall girls from 1959 to 1993, and from self-referrals. Individuals included girls who had received oestrogen treatment (diethylstilboestrol or ethinyl oestradiol) (treated group) and those who were assessed but not treated (untreated group). Information about reproductive history was sought by telephone interview.nnnFINDINGSn1432 eligible individuals were identified, of whom 1243 (87%) could be traced. Of these, 780 (63%) completed interviews: 651 were identified from endocrinologists records, 129 were self-referred. Treated (n=371) and untreated (n=409) women were similar in socioeconomic and other characteristics. After adjustment for age, treated women were more likely to have ever tried for 12 months or more to become pregnant without success (relative risk [RR] 1.80, 95% CI 1.40-2.30); more likely to have seen a doctor because they were having difficulty becoming pregnant (RR 1.80, 1.39-2.32); and more likely to have ever taken fertility drugs (RR 2.05, 1.39-3.04). Time to first pregnancy analysis showed that the treated group was 40% less likely to conceive in any given menstrual cycle of unprotected intercourse (age-adjusted fecundability ratio 0.59, 95% CI 0.46-0.76). These associations persisted when self-referred women were excluded.nnnINTERPRETATIONnHigh-dose oestrogen treatment in adolescence seems to reduce female fertility in later life. This finding has implications for current treatment practices and for our understanding of reproductive biology.

Having a baby in Victoria 1989–2000: continuity and change in the decade following the Victorian Ministerial Review of Birthing Services

Objective: To investigate changing patterns in the provision of maternity care in Victoria based on data collected in three statewide surveys conducted in 1989, 1994 and 2000.

Having a baby in Victoria 1989–2000: women's views of public and private models of care

Objective: To assess and contrast womens views of antenatal, intrapartum and postnatal care based on data collected in three state‐wide surveys of recent mothers conducted in 1989, 1994 and 2000.

Oestrogen treatment for tall stature in girls: estimating the effect on height and the error in height prediction

Objectiveu2002 To determine the effect of oestrogen treatment on attenuating the growth of tall girls after adjusting for error in height prediction.

Treatment of cervical cancer precursors: influence of age, completeness of excision and cone depth on therapeutic failure, and on adverse obstetric outcomes.

Sir, We agree with Professor Westgate that umbilical cord compression is one of the possible causes of fetal hypoxia during shoulder dystocia, and that the cord pH may reflect the fetal condition before shoulder dystocia, as we have demonstrated that the presence of a nonreassuring fetal heart rate pattern is one of the factors independent of the pH values. We also agree with Professor Westgate that umbilical cord compression may explain the ‘dissociation’ between cord gas values and the occurrence of hypoxic ischaemic encephalopathy (HIE) in some of the cases. Having said that, we believe that the pathophysiological mechanism could be multiple, and premature separation of placenta is one of the possibilities, as the rate of decline of pH of 0.011 per minute is very similar to women with placental abruption or cord prolapse. Furthermore, we postulate that the compression of the fetal neck and carotid vessels by the maternal tissue at the pelvic outlet level may contribute to the development of HIE, as well as explain the ‘dissociation’ between cord gas values and the occurrence of HIE. When the neck vessels are compressed, not only is there impairment of the supply of oxygenated blood to the brain, but the elimination of products of anaerobic metabolism by brain hypoxia is also delayed. Therefore the cord blood pH, which reflects the systemic circulation, may fail to reflect the degree of cerebral hypoxia and acidosis. This hypothesis may also explain why the Zavanelli manoeuvre may help to improve neonatal outcome even after a long head-to-body delivery interval, as the circulation to the head may be improved after replacement of the fetal head back into the vagina. Nonetheless, we suggest that Apgar score at 5 minutes may be a more robust indicator of brain hypoxia in shoulder dystocia, as it reflects not only the cardiorespiratory status (colour and pulse rate), but also the central neurological responses (breathing, muscle tone and reflex). j

Looking back in time: conducting a cohort study of the long-term effects of treatment of adolescent tall girls with synthetic hormones

ObjectivePublic health research is an endeavour that often involves multiple relationships, far-reaching collaborations, divergent expectations and various outcomes. Using the Tall Girls Study as a case study, this paper will present and discuss a number of methodological, ethical and legal challenges that have implications for other public health research.ApproachThe Tall Girls Study was the first study to examine the long-term health and psychosocial effects of oestrogen treatment for tall stature.ResultsIn undertaking this study the research team overcame many hurdles: in maintaining collaboration with treating clinicians and with the women they had treated as girls - groups with opposing points of view and different expectations; using private practice medical records to trace women who had been patients up to forty years earlier; and exploring potential legal issues arising from the collection of data related to treatment.ConclusionWhile faced with complex challenges, the Tall Girls Study demonstrated that forward planning, ongoing dialogue between all stakeholders, transparency of processes, and the strict adherence to group-developed protocols were keys to maintaining rigour while undertaking pragmatic research.ImplicationsPublic health research often occurs within political and social contexts that need to be considered in the planning and conduct of studies. The quality and acceptability of research findings is enhanced when stakeholders are engaged in all aspects of the research process.

Adverse pregnancy outcomes after treatment for cervical intraepithelial neoplasia.

Ablation is safer than excision, but any unnecessary treatment should be avoided