A comparison of endometrial thickness following augmentation of ovulation with clomifene citrate or letrozole in women with ovulatory infertility.

OBJECTIVES: To compare endometrial thickness following augmentation of ovulation with clomifene (CC) and letrozole and to assess the rate of multi-follicle development and the FSH fluctuations during the stimulated cycles. METHODS: A comparative study was carried out at the infertility clinic of Faculty of Medicine, University of Kelaniya, Sri Lanka. Each arm included 25 participants. They received either 100 mg of CC or 2.5 mg of letrozole per day for 5 days starting from 2nd day of the cycle. The fluctuation of FSH in the follicular phase of the cycle, the endometrial thickness and the number of pre-ovulatory follicles on the day of detecting a mature follicle, were measured. RESULTS: Treatment with letrozole resulted in a smaller rise in the follicular phase FSH, which was shorter in duration than with CC. Also it resulted in a higher mean endometrial thickness at the time of detecting a mature follicle [9.89 (SD=2.02) mm vs. 8.58 (SD=1.32) mm; p=0.021]. Augmentation of ovulation with CC showed a trend towards multi-follicle development compared to letrozole. CONCLUSIONS: This study suggests that letrozole is superior to CC in augmentation of ovulation in terms of endometrial growth and mono-follicle development. However more studies are needed to assess how these differences affect the treatment outcome before it is recommended for clinical use.

Aetiology of infertility among females seeking treatment at a tertiary care hospital in Sri Lanka.

OBJECTIVES: Aim of this study was to describe the proportion of contributory factors of female infertility in a population that sought fertility treatment. Furthermore, the clinical findings and underlying pathologies associated with ovulatory dysfunction were also sought. METHODS: A cross-sectional study was carried out at the infertility clinic of the North Colombo Teaching Hospital. New clinic attendees were recruited and both partners had a detailed clinical interview. The women underwent a baseline pelvic ultrasound scan, assessment of ovulation and a hormone profile. Tests for tubal patency were carried out when clinically indicated. RESULTS: Ovulatory dysfunction was noted in 53% (n=218). Clinical and investigatory findings associated with ovulatory dysfunction included irregular menstrual cycles, acanthosis nigricans, hirsutism, polycystic ovary syndrome, a LH:FSH ratio of >1, and increased TSH or testosterone levels. Unilateral tubal occlusion was seen in 9.1 % (n=18) while it was bilateral in 1% (n=2). Abnormalities in sexual function were noted in 10.8% (n=56). CONCLUSIONS: Abnormalities in ovulation were common. Clinical findings that could be used to recognise women at risk of ovulatory dysfunction were identified. Abnormalities in sexual function, which are often overlooked in the clinical management of infertility, were seen in over 10% of patients. Tubal factor infertility is rare.

Serum insulin patterns and the relationship between insulin sensitivity and glycaemic profile in women with polycystic ovary syndrome.

OBJECTIVE: To evaluate serum insulin levels and insulin sensitivity in women with polycystic ovary syndrome (PCOS) in relation to their glycaemic status. DESIGN: An observational study. SETTING: A tertiary-level reproductive health centre in Sri Lanka. SAMPLE: Infertile women diagnosed as having PCOS (n=168) on the basis of the Rotterdam criteria were included in the study. METHODS: Glycaemic status and serum insulin values were assessed at fasting and at 2 hours after a 75-g oral glucose load and stratified as diabetes mellitus (DM) (10.12%), impaired glucose tolerance (IGT) (23.21%) and normoglycaemia (66.67%). The normoglycaemic group was restratified as groups A (10.7%), B (79.5%) and C (9.8%) on the basis of serum insulin levels, with group A having the lowest and group C the highest values. The Quantitative Insulin Sensitivity Check Index (QUICKI) scores of women with DM and IGT and those in groups A, B and C in the normoglycaemic category were compared. MAIN OUTCOME MEASURES: Insulin sensitivity in these groups of women. RESULTS: Body mass index (BMI) exceeded 23 kg/m(2) in 77.38% of the women. In normoglycaemic women with PCOS, insulin sensitivity was highest in group A. In groups B and C, insulin sensitivities corresponded to those found for women with IGT and DM respectively. This pattern was also reflected in the BMI. CONCLUSIONS: Normoglycaemic women with PCOS are heterogeneous regarding insulin sensitivity. The treatment offered to those with DM and IGT could be extended to subgroups B and C of normoglycaemic subjects. Normoglycaemic women with PCOS with high insulin sensitivity (group A) would not qualify for this treatment.

An outbreak of Aspergillus meningitis following spinal anaesthesia for caesarean section in Sri Lanka: a post-tsunami effect?

An outbreak of Aspergillus fumigatus meningitis occurred in 5 women following spinal anaesthesia, performed between 21 June and 17 July 2005 for caesarean section, in Colombo, Sri Lanka. The patients' median age was 27 years. Different teams in 2 maternity hospitals gave spinal anaesthesia. Mean incubation period was 11.2 days. Fever, headache and nuchal rigidity were common presentations. Remittent fever continued despite broad-spectrum intravenous antibiotics. Papilloedema, lateral rectus palsy, cerebral infarction and haemorrhage developed later. Three patients died. Cerebrospinal fluid pleocytosis with low glucose yielded negative PCR for fungi. Fungal cultures subsequently grew Aspergillus fumigatus. A post-mortem of the first patient confirmed Aspergillus meningitis, followed by treatment with amphotericin B and voriconazole, that saved the lives of others. Visual and hearing impairment in one and complete recovery in the other were observed a year after treatment. Examination of unused plastic syringes, needles, cannulae, and ampoules of anaesthetic agents confirmed that 43 syringes from three different manufactures were contaminated with Aspergillus fumigatus. The stores for drugs and devices of the Ministry of Health were examined and found to be full of tsunami donations, while regular procurements of the Ministry were kept in a poorly maintained humid warehouse. Inadequate space for tsunami donations was identified as the most plausible explanation for sub-optimal storage. Withdrawal and incineration of all unused syringes controlled the outbreak. The survival of those aggressively treated for Aspergillus meningitis suggests in hindsight that the availability of diagnostic tests and specific treatment, and early recognition of the outbreak could have saved the lives of victims who died. Early life-threatening side-effects and permanent long term sequelae of antifungal medication stress the need to be cautious with empirical treatment in immuno-competent low-risk individuals.

Effect of skim milk supplementation of the maternal diet on lactational amenorrhea, maternal prolactin, and lactational behavior.

Effect of skim milk supplementation of the maternal diet on lactational amenorrhea was studied in 30 pairs of healthy lactating women matched for parity, body mass index, and previous experience of lactational amenorrhea. Supplementation of the maternal diet had no significant effect on the time of resumption of regular menstruation or ovulation, maternal prolactin concentrations, breast-feeding pattern, maternal body mass index, or infant weight. However, the supplemented group breast-fed nearly exclusively (supplemental feeds were introduced but did not exceed 20% of total feeds) for a significantly longer duration (P < 0.05) than did the control group. Previous experience of lactational amenorrhea was significantly positively correlated with the time of resumption of menstruation in the supplemented (P < 0.01) and control (P < 0.05) groups when frequency of breast-feeding, maternal body mass index, and supplementary feeds to the infant were controlled for. Thus, maternal nutritional supplementation does not appear to affect the contraceptive benefit of lactation when the frequency of breast-feeding is not compromised but apparently lengthens the duration of nearly full breast-feeding.

Safe motherhood in Sri Lanka: a 100-year march.

The present safe motherhood status in Sri Lanka has been achieved by a series of activities for health and social development during the past century. While ancient and traditional religious, as well as cultural concepts provided a sound foundation, it was the policies that focused on human development that resulted in reducing the maternal mortality rate to 2.4 per 10000 live births, and the infant mortality rate to 16.5 per (1000) live births. Maternal and Child Health (MCH) services were initially closely linked to improvements in the healthcare infrastructure and social development, while family planning introduced in 1953 enhanced its progress further. With MCH integrated into reproductive health, the march towards a safer motherhood in Sri Lanka will require the implementation of new policies and strategies.

Econazole and clotrimazole in the treatment of vaginal candidiasis: a double blind comparative study.

OBJECTIVES: To compare the efficacy of treatment with econazole and clotrimazole in patients with vaginal candidiasis. DESIGN: A double blind study. Patients with vaginal candidiasis were randomly treated with vaginal depot preparations of econazole and clotrimazole. Efficacy after treatment by reduction of symptoms, a gynaecological examination and microbiological analysis of vaginal fluid. Adverse reactions were noted. SETTING: University gynaecological clinic at the de Soysa Hospital for Women, Colombo. PATIENTS: 102 patients microbiologically confirmed as having vaginal candidiasis. RESULTS: Two weeks after econazole treatment 19% still complained of a discharge and 7.5% had pruritus. The respective values for clotrimazole were 18% and 12%. The finding on gynaecological examination generally supported the reduction of symptoms. Microbiological assessment showed that 90.5% in the econazole group and 96% in the clotrimazole group became culture negative at two weeks after treatment. Adverse effects were similar in incidence and number for both treatment groups. Econazole was less acceptable to patients than clotrimazole. CONCLUSIONS: Econazole and clotrimazole are of equal efficacy for treatment of vaginal candidiasis. Econazole was less acceptable to patients.

Pregnancy following renal transplantation in Sri Lanka.

OBJECTIVE: To assess the outcome and complications of pregnancy following renal transplantation in Sri Lanka. METHODS: Ten pregnancies following transplantation managed between January 1993 and July 1999 by the University Obstetrics and Gynaecology Unit, De Soysa Hospital for Women, Colombo were reviewed. RESULTS: Five women had planned pregnancy with an average duration from transplantation to conception of 2.3 (+/- 0.2) years; five had an unplanned pregnancy within 12 months of transplantation. All were treated with immunosuppressives, with none developing rejection. In the planned pregnancy group, 3 developed pregnancy induced hypertension and 3 impaired glucose tolerance. All delivered mature healthy babies with an average birth weight of 2.6 (+/- 0.3) kg. In the unplanned group, 1 developed cholestatic jaundice and delivered a growth retarded baby at 36 weeks. Another developed severe pulmonary oedema at 34 weeks (due to a past myocardial infarction) resulting in a fresh stillbirth. Two others has mid-trimester foetal deaths complicating severe diabetes mellitus. The conception at 3 months after transplantation developed diabetes mellitus and pregnancy induced hypertension, and delivered a live growth retarded baby. None had deterioration of renal function. CONCLUSION: Although a successful outcome is possible with stringent pre-pregnancy selection, maternal morbidity and foetal wastage can be high in those without.

Obstetric performance, perinatal outcome and risk of infection to the newborn in spontaneous and artificial rupture of membranes during labour.

OBJECTIVE: To compare the obstetric performance, perinatal outcome and risk of neonatal infection in labour following spontaneous (SROM) and artificial (AROM) rupture of membranes. DESIGN: Prospective, non-randomised, comparative study during a one-month period in 1995. The study was approved by the ethics committee of the Faculty of Medicine, University of Colombo. SETTING: University Obstetrics Unit at De Soysa Hospital for Women, Colombo. PATIENTS: 324 women who were in early established labour after 37 weeks of gestation. 151 of these had SROM and 173 AROM. The AROM and SROM groups among primigravidae and multigravidae were considered separately. RESULTS: Oxytocin use in multigravidae was significantly higher in the AROM group than in the SROM group (p < 0.001). The emergency caesarean section (LSCS) rate in primigravidae was significantly higher in the AROM group than the SROM group (p < 0.001). A significantly larger number of primigravid AROM women had abnormal fetal heart rate changes on auscultation (p < 0.05) and cardiotopographic (CTG) patterns (p < 0.001) when compared with primigravid SROM women. Choreoamnionitis and funisitis were commoner in the AROM group although the difference was not statistically significant. CONCLUSIONS: AROM appears to be associated with a higher chance of fetal distress particularly in primigravidae. Both AROM and SROM are associated with a potential risk of infection at intrauterine sites.

PIP: Artificial rupture of the membranes during established labor is believed to augment labor progression, but this practice carries the risk of maternal and neonatal infection. A prospective study conducted at De Soysa Hospital for Women in Colombo, Ceylon, in 1995 compared the obstetric performance, perinatal outcome, and risk of neonatal infection in 151 women with spontaneous rupture of membranes (SROM) and 173 women with artificial rupture of membranes (AROM). The need for oxytocin was higher in both primi- and multigravidae in the AROM group (37.5% and 38.8%, respectively) than the SROM group (24.7% and 18.9%, respectively), but this association reached statistical significance only among multigravidae. Also higher in the AROM group than the SROM group, but not significantly, were the rates of instrumental delivery and emergency cesarean section. Compared with primigravid AROM women, a significantly larger number of primigravid AROM women had abnormal auscultated fetal heart rates and cardiotopographic patterns. The appearance of meconium in liquor and the occurrence of low Apgar scores were similar in both groups. There were no clinical maternal or neonatal infections, but the intrauterine sites showed evidence of inflammation soon after membrane rupture. 36.1% of women in the SROM group and 24.0% of those in the AROM group whose cord and membranes were evaluated had histologic evidence of inflammation. Choreoamnionitis and funisitis were slightly more common in the AROM group. The potential for infection at intrauterine sites had no linear relationship to the mean membrane rupture-delivery interval or the number of vaginal examinations.

Polymorphism in the epidermal growth factor gene is associated with birthweight in Sinhalese and white Western Europeans.

Birthweight predicts health later in life and is influenced by inherited factors. We investigated the association of the c.61G > A, and c.2566G > A polymorphisms in the epidermal growth factor (EGF) gene [GenBank NM_001963] with birthweight in three groups of healthy pregnant women, and in women with pregnancies affected by fetal growth restriction (FGR). Subjects comprised 171 Sinhalese women with normal pregnancies (Group A), 64 white Western European women with normal pregnancies (Group B), 101 white Western European women with normal pregnancies and their babies (Group C) and 107 women with pregnancies affected by FGR, their partners and their babies (Group D). Maternal EGF genotypes were associated with birthweight of healthy babies of women in Groups A (P = 0.03), B (P = 0.001) and C (P = 0.01). The association persisted following adjustment for confounding by gestational age, sex, maternal weight, parity and smoking habit. The trend from heaviest to lightest birthweights in all these groups was c.61AA > c.61GA > c.61GG and c.2566GG > c.2566GA > c.2566AA. The EGF haplotype associated with lower birthweight (c.61G, c.2566A) was transmitted at increased frequency from heterozygous parents to babies affected by FGR in Group D (P = 0.02). These findings support the hypothesis that growth factors expressed by the feto-maternal unit affect birthweight, and implicates polymorphism in the EGF gene in the aetiology of birthweight variability.

Vaginal breech delivery or cesarean section.

In 579 singleton breech deliveries the total perinatal mortality rate was 10.4% and the corrected perinatal mortality rate was 0.67%. There were 452 babies delivered vaginally (78.1%) and 127 delivered by cesarean section (21.9%). The perinatal mortality rate was very high in the premature breech delivery and in the low-birth-weight infant. Cesarean section should be used to avoid a traumatic vaginal delivery and it should be used more liberally in the mature breech, but it is unlikely that cesarean section rates in excess of 50% will significantly reduce the perinatal mortality mortality rate. More information is required as to whether extending the indications for cesarean section in the low-birth-weight infant will further reduce the perinatal mortality rate.

Vitamin A status of pregnant women in five districts of Sri Lanka.

Vitamin A status was assessed in early and late stages of pregnancy in 496 pregnant women living in Colombo, Kurunegala, Kegalle, Badulla and Galle districts, using clinical, dietary and biochemical parameters. Serum vitamin A concentration was determined by a fluorometric method and the retinol binding protein concentration by radial immunodiffusion. The serum vitamin A levels of subjects in the lowest socioeconomic group in Galle and Kegalle districts were significantly lower than those living in Colombo. The percentage of subjects having serum vitamin A levels less than 20 micrograms/dl, increased in late pregnancy in all areas, with the highest value (27.8%) in the Galle district. None of the subjects had severe ocular manifestations of vitamin A deficiency. The higher incidence of subclinical vitamin A deficiency noted among subjects in Galle and Kegalle districts could be attributed at least in part to a low dietary intake of vitamin A and carotenoids.