Effect of GnRH antagonist on follicular development and uterine biophysical profile in controlled ovarian stimulation

Background: Objective of current study was to assess the effect of GnRH antagonist on follicular development, premature luteinization, uterine biophysical profile and pregnancy rate in controlled ovarian stimulation with clomiphene and gonadotropins for intrauterine insemination in women with unexplained infertility.Methods: Randomised controlled trial. Minimal stimulation protocol with or without GnRH antagonist was compared. Setting: Infertility clinic, PGIMER, Chandigarh. Patients: Couples with unexplained infertility, age of female partner between 20-39 years. Intervention: GnRH antagonist 0.25 mg since follicle size 14 mm till hCG administration. Main outcome measures: Follicle characteristics, premature luteinisation, uterine biophysical profile and pregnancy rate.  Results: The mean number of follicles recruited in group A was 2.32 ± 1.01 while that in group B (receiving GnRH antagonist) it was 4.10 ± 1.69. Statistically significant increase in total biophysical profile score was observed in periovulatory phase in the antagonist group. 40% women in group A had premature luteinization whereas only 4% women in group B suffered from premature luteinization. 20% women who received GnRH antagonist conceived against only 6% in group A, this difference however was not statistically significantConclusions: GnRH antagonist has a role in increasing the number of follicles recruited. Furthermore, GnRH antagonist can improve the total uterine biophysical profile score by improving the endometrial thickness, endometrial pattern, blood flow and decreasing the impedance to the blood flow in uterine artery. The drug can potentially help in improving pregnancy rates by decreasing the rate of premature luteinisation. 

Clinical significance of ovarian stromal blood flow in assessment of ovarian response in stimulated cycle for in vitro fertilization

Background: Several ultrasound parameters have been examined to predict the ovarian response to gonadotropins. The only parameter that has been conclusively proven to predict ovarian response is the antral follicle count. It has been suggested that ovarian blood flow may play a crucial role in the development of ovarian follicles. The present study was planned to prospectively analyse the effect of ovarian stromal blood flow on ovarian responsiveness in terms of number of oocytes retrieved in stimulated cycle for IVF.Methods: Fifty subjects between 22 to 37 years of age with male factor, tubal factor or unexplained infertility underwent controlled ovarian stimulation by the standard “Long protocol”. Ovarian stromal blood flow was recorded on baseline transvaginal sonography on day 2 or 3 of cycle and was correlated with number of oocytes retrieved in IVF cycle.Results: The ovarian stromal blood flow was found to be negatively correlated with age. The number of follicles formed in a subject after stimulation with gonadotropins was negatively correlated with ovarian stromal resistance index and pulsatility index.Conclusions: Ovarian blood flow predicts ovarian responsiveness and hence provides a non-invasive and cost effective prognostic factor of IVF outcome

Disseminated peritoneal leiomyomatosis: a rare entity with diagnostic conundrum

Disseminated peritoneal leiomyomatosis (DPL) is a rare, usually benign disease primarily affecting premenopausal women. It is signalized by multiple smooth muscle nodules which grossly or radiologically may simulate peritoneal carcinomatosis or disseminated intraabdominal malignancies. A case study of 45 year female who presented with DPL after 8 years of hysterectomy is reported here

Weekly iron folic acid supplementation plays differential role in maintaining iron markers level in non-anaemic and anaemic primigravida: A randomized controlled study

AbstractAnaemia during pregnancy is most commonly observed and highly prevalent in South-East Asia. Various effective programmes have been laid down for its management, mainly daily supplementation of iron folic acid (IFA) tablets. Following the same, standard obstetrical practice has included the IFA supplementation without requiring the determination of iron deficiency. In this study, a total of 120 primigravida (N=60; non-anaemic (Hb>11g/dl) and N=60 anaemic (Hb=8–11g/dl)) were selected among those attending the Antenatal Clinic in Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India. They were supplemented with daily and weekly IFA tablets till 6weeks postpartum. Corresponding changes in haemoglobin level on advance of pregnancy, side effects and compliance associated with daily and weekly IFA supplementation and its associations with iron status markers were studied. The inflammatory markers were also estimated. The statistical significance level (p<0.05) between the groups were assessed by applying unpaired t-test using SPSS (version 16.0). The obtained results publicized the salutary role of daily IFA supplementation in improving the haemoglobin level and iron status markers in anaemic pregnant women though the levels could not reach up to the non-anaemic haemoglobin levels. However, weekly IFA supplementation seems to be a better approach in non-anaemic pregnant women where almost comparable results were obtained in terms of haematological parameters, gestation length and birth weight.ConclusionWeekly IFA supplementation found to be as effective as daily supplementation in iron sufficient non-anaemic pregnant women whereas anaemic pregnant women should be prescribed daily IFA supplementation irrespective of iron replete/deplete state

Ovulation induction using clomiphene citrate using stair – Step regimen versus traditional regimen in polycystic ovary syndrome women – A randomized control trial

Objective: To determine the efficacy of the stair-step protocol (SSP) using clomiphene citrate (CC) in patients with polycystic ovary syndrome (PCOS) and compare it with traditional regimen. Design: This was randomized control trial. Setting: Infertility Clinic. Patient(s): Sixty infertile PCOS women. Intervention(s): Patients were randomized into the study (SSP – 30 patients) and control group (traditional protocol – 30 patients). In the SSP, patients were treated with CC 50 mg/day for 5 days and in nonresponsive patients, the dosage was increased to 100 mg/day for 5 days in the same cycle. Maximum dose of 150 mg was given until the dominant follicle was generated. In control group, the dose increment in nonovulatory cases was done in subsequent cycle. Ultrasonography follow-up was done to detect ovulation. Main Outcome Measure(s): Ovulation rate and duration of treatment. Results: Ovulation (66.7% vs. 50% respectively) and pregnancy rates (26.7% vs. 15.7%) were similar between the stair step and the control group. The duration of treatment was significantly shorter in stair step compared to traditional protocol (17.23 vs. 53 days). CC 100 mg was the most effective dose for ovulation in either group. There were no significant differences in the systemic side effect. Conclusions: By using SSP, effective treatment is provided in significantly shorter time period without any detrimental effect on the ovulation and pregnancy rates

Tamoxifen: An alternative to clomiphene in women with polycystic ovary syndrome

Background : Clomiphene citrate is commonly used for ovulation induction in women with anovulatory infertility. However, pregnancy rates with this drug are not as good as ovulation rates. Tamoxifen may be a better choice in some patients who fail to either ovulate or conceive with clomiphene due to its favorable effect on the cervical mucus and endometrium. This study was conducted to evaluate the role of tamoxifen in women with anovulatory infertility and find out the optimum dose needed for achieving the best outcome. Materials and Methods : 160 women attending the infertility clinic and suffering from anovulatory infertility were recruited for the study. Tamoxifen was administered in the dose of 40 mg daily and ovulation monitored. In case of anovulation, the dose was increased to 80 mg daily. Ovulation and pregnancy rates were calculated. Results : Twenty-three out of 160 women who received 40 mg of tamoxifen conceived, giving a pregnancy rate of 14.38% and pregnancy rate per ovulatory cycle as 14.94%. 32 out of 80 women who received 80 mg of tamoxifen conceived, giving a pregnancy rate of 40% and pregnancy rate per cycle as 33.68%. This difference in the pregnancy rate between the two groups was statistically significant. 35 women out of 90 with polycystic ovary syndrome (PCOS) became pregnant with a pregnancy rate of 38.8% and 20 out of 70 women with clomiphene citrate failure conceived, giving a pregnancy rate of 28.5%. Conclusions : Tamoxifen is a good alternative to clomiphene in women with PCOS and clomiphene-resistant cases

Chemoradiation therapy induces in vivo changes in gene promoter methylation & gene transcript expression in patients with invasive cervical cancer

Background & objectives: Invasive cervical cancer patients are primarily treated with chemoradiation therapy. The overall and disease-free survival in these patients is variable and depends on the tumoral response apart from the tumour stage. This study was undertaken to assess whether in vivo changes in gene promoter methylation and transcript expression in invasive cervical cancer were induced by chemoradiation. Hence, paired pre- and post-treatment biopsy samples were evaluated for in vivo changes in promoter methylation and transcript expression of 10 genes (ESR1, BRCA1, RASSF1A, MYOD1, MLH1, hTERT, MGMT, DAPK1, BAX and BCL2L1) in response to chemoradiation therapy. Methods: In patients with locally advanced invasive cervical cancer, paired pre- and post-treatment biopsies after 10 Gy chemoradiation were obtained. DNA/RNA was extracted and gene promoter methylation status was evaluated by custom-synthesized methylation PCR arrays, and the corresponding gene transcript expression was determined by absolute quantification method using quantitative reverse transcription PCR. Results: Changes in the gene promoter methylation as well as gene expression following chemoradiation therapy were observed. BAX promoter methylation showed a significant increase (P< 0.01) following treatment. There was a significant increase in the gene transcript expression of BRCA1 (P< 0.01), DAPK1 and ESR1 (P< 0.05), whereas MYOD1 and MLH1 gene transcript expression was significantly decreased (P< 0.05) following treatment. Interpretation & conclusions: The findings of our study show that chemoradiation therapy can induce epigenetic alterations as well as affect gene expression in tissues of invasive cervical cancer which may have implications in determining radiation response