Clomiphene Citrate and Pregnancy Outcome

Summary: Data from Australia and elsewhere have shown consistently that adverse perinatal outcomes such as preterm birth and perinatal mortality are more common in pregnancies resulting from assisted conception with IVF and GIFT than normally conceived pregnancies. Factors that may contribute to the excess of poor outcomes include maternal factors, the assisted conception procedures themselves and possibly the influence of drugs used to induce superovulation. This review examines the medical literature describing pregnancies following ovulation induction with one of the drugs used to induce superovulation, clomiphene citrate, and compares their outcomes with Australian IVF and GIFT pregnancy outcomes.
The review shows that whilst some studies have suggested higher rates of ectopic pregnancy, spontaneous abortion and congenital malformations in clomiphene citrate induced pregnancies, the findings are inconsistent and the data are flawed. There are only very poor data available on the incidence of preterm birth. Multiple pregnancy is a well-recognized adverse outcome of clomiphene citrate induced pregnancies. Attempts to improve perinatal outcomes of pregnancies following assisted conception will be helped by a better understanding of the relative contributions of maternal and treatment factors and further studies of pregnancy outcome after ovulation induction are needed.     

Malnutrition as a prognostic factor in lymphoblastic leukaemia: a multivariate analysis

One hundred and twenty eight Brazilian children with lymphoblastic leukaemia were intensively treated with a Berlin-Frankfurt-Munich based protocol. More children had a white cell count above 50 x 10(9)/l (31%) then observed in developed countries. After a median follow up of 31 months (11-58 months), the estimated probability of relapse free survival was 41% (7%) for the whole group. After adjustment in the Cox's multivariate model, malnutrition was the most significant adverse factor affecting duration of complete remission. Age above 8 years and high peripheral white cell count were also significant adverse factors. Among the nutritional indices, the height for age and weight for age z scores were both significant, whether the cut off points of z-2 or z = -1.28 were chosen to define malnutrition. A strong statistical association between the two indices was found; the contribution of height for age z score to the prediction of relapse free survival was more significant. Children with height for age z score < -2 had a relapse risk of 8.2 (95% confidence interval 3.1 to 21.9) relative to children with z score > -2. The results of this study suggest that socioeconomic and nutritional factors should be considered in the prognostic evaluation of children with leukaemia in developing countries.     

Ultrasonographic measurement of subarachnoid space in normal infants and children

This study was undertaken to evaluate the sonographic measurement of subarachnoid spaces in normal children and its relationship with age and to define a normal range in a Chinese population and to differentiate normal variant findings from pathologic dilatation. The subarachnoid spaces in 278 normal term neonates, infants, and children were studied with real-time ultrasound using a 7.5-MHz vector transducer. The craniocortical width, sinocortical width, and interhemispheric width were measured in the coronal plane at the level of the foramen of Monro, on either side of the hemispheres. Correlation of sonographic measurements with age was made. The mean widths were plotted against age. A correlation with age was found in all three spaces, with an increasing trend with age until 28 weeks of gestation. Thereafter, a decreasing trend was noted. The normal upper limit of subarachnoid spaces for children is proposed to be the values on the ninety-fifth percentile of the regression curve. Correlation of measurement with age must be considered to decide whether an increase in subarachnoid space is pathologic or not.     

Second Twin: Quality of Survival if Born by Breech Extraction Following Internal Podalic Version

The intrapartum management of the vertex-breech and vertex-transverse twin gestation is controversial. The fall in perinatal mortality rate to a low level has resulted in this parameter failing to be an adequate gauge of the safety of breech extraction and the answer lies in the quality of survival of the infants. Fifty-one twin pairs, collected over 12 years at the Mercy Hospital for Women, Melbourne, occurred where twin 2 was born by breech extraction following internal inversion and the control (twin 1) did not have this procedure performed. In 8 pairs either a stillbirth or neonatal death occurred; in one pair childhood death due to an accident (fire) occurred; in 4 pairs the parents refused entrance to the study as they perceived both twins to be similar; in 2 sets the assessment was incomplete; 11 sets were untraceable leaving 25 sets fully assessed as children ranging in age from 2 to 12 years. Growth, and psychological scores were not significantly different between twins 1 and 2 but 2 children had cerebral palsy and both were born by breech extraction following internal version at 29.2 and 30.1 weeks' gestation, respectively. Because of small numbers the results failed to achieve statistical significance and this study was unable to answer the question regarding the safety of breech extraction following internal version but did show that the majority of infants so born do well.     

A Clinicopathological Study of Adenocarcinoma in Situ of the Cervix. The Influence of Cervical HPV Infection and Other Factors, and the Role of Conservative Surgery

Adenocarcinoma in situ (ACIS) of the uterine cervix is an increasingly recognized disease. Thirty-seven cases were reviewed to determine the effect of HPV, marital status, parity, smoking habit and age on the topography and behaviour of this lesion. Using a commercial probe, 25% of 28 lesions tested were positive for HPV 16/18. The presence of HPV and a history of smoking appeared to exert no significant influence upon the topography and behaviour of ACIS. Nulliparity and a history of never being married was associated with a significant reduction in the incidence of coexisting CIN lesions. Age less than 36 years was associated with a significant reduction in the proximal linear extent of ACIS. While hysterectomy is probably the definitive treatment for ACIS of the cervix, there is an important place for conservative management by conization alone. Patients younger than 36 years are most likely to be desirous of retained fertility and appear to have the lesions most amenable to conservative surgery.     

Presacral Neurectomy - A Reappraisal

Between April 1984 and April 1990, 20 patients with a mean age of 27.9 years underwent presacral neurectomy at The Royal Women's Hospital, Melbourne, Australia. Overall, 11 of the 19 patients (58%) assessable for follow-up were totally cured of pain and 8 (42%) were partially cured. The most common indication for presacral neurectomy was secondary dysmenorrhoea, usually in association with endometriosis or pelvic adhesions. In 4 patients with uterine dysmenorrhoea not associated with pelvic pathology the operation produced a complete cure. The general consensus of gynaecological opinion is that presacral neurectomy should still be reserved for a limited number of carefully selected patients in whom other methods of treatment have been exhausted. It is imperative that a prior psychological assessment should be undertaken whenever a functional component is suspected. Whilst pain of uterine origin may be cured by presacral neurectomy, lateral pelvic pain of adnexal origin requires ovarian sympathectomy.     

A survey of 22 individuals with Prader-Willi Syndrome in New South Wales

Abstract Twenty-two individuals with Prader-Willi Syndrome in New South Wales were surveyed. The results show that males were diagnosed at a significantly earlier age than females and suggest a recent trend towards earlier diagnosis. The advantages of early diagnosis are discussed. In those in whom cytogenetic studies had been performed, 47% were found to have a deletion involving chromosome 15q11–13. Profound neonatal hypotonia had been present in all cases. Obesity became apparent between 1.5 and 10 years (mean = 3.8 years). Facial dysmorphism was reported in 83% and acromicria in 100%. Sixty-two per cent of subjects were regarded as less pigmented than first degree relatives. Cognitive assessments were performed on nine subjects. Two (22%) were functioning in the normal range of intelligence. Behaviour problems, both food-related and non-food-related, were present in the majority and placed considerable stress on the family caring for the individual with Prader-Willi Syndrome.     

Comparison of preservative-free and preservative-containing ipratropium bromide

Abstract A double-blind crossover study was performed on 33 children with asthma to compare the effectiveness of nebulized solutions of preservative-containing and preservative-free ipratropium bromide. Both solutions produced bronchodilation. No significant differences were found between the two solutions at any time after nebulization in minimum and maximum changes from baseline value or in the areas under the lung function time curves. The presently formulated preservative-containing ipratropium bromide solution was not shown to be inferior to a preservative-free compound.