• Acute herpes simplex encephalitis in pregnancy.

      Dobson, Samuel; Muppala, H (2015-03)
    • Aetiology of recurrent miscarriage and the role of adjuvant treatment in its management: a retrospective cohort review.

      Jayaprakasan, Kanna (2018-03)
      We conducted a retrospective review into the role of commonly prescribed conventional adjuvant treatments in improving live birth rates after recurrent miscarriage (RM). Data from 301 couples attending the RM clinic in two Tertiary teaching hospitals were analysed with their live birth rate following a further pregnancy and a prevalence of conditions investigated in RM being the main outcomes measured. We found that 26% of women had explained RM and 74% had unexplained RM. Adjuvant versus conservative management did not improve the live birth rates in those with unexplained RM (68.4% vs. 76.6%, respectively; p = .28). The prevalence of anti-phospholipid syndrome, inherited thrombophilia, thyroid disease, parental karyotype abnormalities and structural uterine abnormalities were 7.4%, 4.5%, 6.6%, 2.9% and 6.6%, respectively. In conclusion, empirical adjuvant treatment for the management of women with unexplained RM does not appear to offer any benefit as they have a good prognosis with early pregnancy support alone. Impact statement What is already known on this subject? Does the adjuvant treatment in the management of unexplained recurrent miscarriage (RM) improve successful pregnancy outcomes? High-quality data regarding the management and outcomes of RM is very limited, with many clinicians prescribing adjuvant treatments for unexplained RM with very little good quality evidence of their benefit or risk. What do the results of this study add? We carried out a retrospective cohort study of all patients attending a recurrent miscarriage clinic over a two-year period at specialist clinics in two tertiary referral centres to evaluate the prevalence of associated diseases, the treatments given and the outcomes in subsequent pregnancies. This study will help clinicians counsel their patients about management options in RM and help them reassure their patients that the prognosis with conservative management alone is good. This will help to avoid any unnecessary use of adjuvant treatment and its associated risks and cost. What are the implications of these findings for clinical practice and/or further research? This study demonstrates that adjuvant treatments in unexplained RM have no significant benefit on future live birth rates. Despite this finding, high quality, prospective, randomised controlled trials looking at both adverse outcomes and benefits of adjuvant treatment in RM are needed.
    • An audit of outpatient hysteroscopy in Royal Derby Hospital

      Kolhe, Shilpa; Shittu, SA; Petipiece, L (2014-04)
      Introduction Hysteroscopy offers an extension of the gynaecologists' armamentarium as it improves the diagnostic accuracy and permits better treatment of abnormal intra-uterine conditions. All gynaecological units should provide dedicated outpatient hysteroscopy service as it is associated with clinical and economic benefits. The objective was to assess the compliance of our practice with the standards in the RCOG/BSGE guideline and to assess correlation between our hysteroscopic and histological findings. The auditable standards of the RCOG that were assessed include success rate and reasons for failures, rate of cervical dilatation, and percentage of women with written information leaflet and informed consent. Methods We retrospectively reviewed the medical notes of 114 patients who had hysteroscopy over 3 months period in Royal Derby Hospital. Data obtained were analysed using Microsoft excel software. Result The result showed that postmenopausal bleeding (48%) was the commonest indication for the referral to the outpatient clinic. Success rate was 90.4%. All the patients were given information leaflets prior to consent. Recommended vaginoscopy approach was used in 63.2%, cervical dilation was done in 15%. Success rate of outpatient polypectomy was 84.4%. Documentation was considered standard in 84.2% of patients. The correlation between histology and hysteroscopic findings was satisfactory with sensitivity of 100% and specificity of 75% for endometrial carcinoma. Hysteroscopy could not differentiate between endometrial hyperplasia and carcinoma. Where no sample was available for histology, hysteroscopy was significantly helpful. Conclusion We recommended expansion of the outpatient operative service to include endometrial ablation, sterilisation and removal of submucous fibroids and use of a standardised proforma for documentation of procedure in all patients. The audit revealed good compliance with guideline and that outpatient hysteroscopy service in the hospital was efficient. Hysteroscopy is invaluable where sample is not available for histology.
    • Assessment of Circulating Anti-Müllerian Hormone in Women Using Hormonal Contraception: A Systematic Review.

      Ahmed, Mohamed; James, Cathryn (2019-07)
      Background: The status of ovarian reserve markers during hormonal contraception (HC) remains uncertain with conflicting literature data. The purpose of this study was to assess the impact of HC on circulating anti-Müllerian hormone (AMH) and other ovarian reserve markers. Materials and Methods: A systematic review was conducted, including all cohort, cross-sectional, and randomized controlled studies assessing serum anti Müllerian hormone concentration in women using HC. Data sources included MEDLINE, EMBASE, DynaMed Plus, ScienceDirect, TRIP database, ClinicalTrials.gov, and the Cochrane Library from January 2000 to October 2018. Results: A total of 366 studies were identified, of which 15 were eligible, including 3280 women, mostly using combined HC (CHC). Articles were divided according to duration of HC into short- (2-3 weeks), medium- (2-6 months), long- (>1 year), and varied-term studies. Two study designs were identified, including studies comparing AMH before and during/after CHC and studies comparing CHC users versus nonusers. Short- and medium-term studies (n = 284) reported no change in circulating AMH in women using cyclical CHC for one to six cycles. Apart from one study, all long- and varied-term studies (six studies, n = 1601) consistently showed a marked decline in AMH, antral follicle count, and ovarian volume. Three long-term studies (n = 1324) provided evidence of AMH recovery after discontinuation of HC. Conclusion: Circulating AMH seems to remain unchanged in women using cyclical CHC for up to 6 months, but appears to markedly decline in long-term users with recovery after discontinuation.
    • A case of caesarean scar ectopic pregnancy-successful treatment with intra-amniotic methotrexate followed by a systemic course of intramuscular methotrexate

      Robertson, C; Pettipiece, L; Tamizian, Onnig; Allsop, J (2013-12)
      Case: A 34-year-old woman, G5 P2 was seen at the Royal Derby Hospital in early pregnancy. Previous deliveries were by emergency caesarean section, the first at 30 weeks of gestation for a ruptured uterus and the second at 34 weeks for placenta praevia. Ultrasound scan showed a live pregnancy of 6+1 weeks with the gestation sac deeply embedded in the caesarean section scar. Myometrium could not be seen on the outer surface of the uterus and the pregnancy was closely applied to the bladder wall. A complete pregnancy percreta through the old scar was diagnosed. Although asymptomatic, the patient was offered termination of the pregnancy and a review of the literature was undertaken to decide how to safely manage the case. The patient initially underwent uterine artery methotrexate infusion via femoral catheters and embolization, however this was unsuccessful and a fetal heart was still present 7 days following treatment. After further counselling, the patient underwent intra-amniotic methotrexate and intra-cardiac lignocaine into the pregnancy, followed by alternate day intra-muscular methotrexate over 1 week, with alternate day folic acid. The treatment was successful and the patient went home 8 days after the initial treatment with falling beta-hCG levels. Discussion: The diagnosis of a complete pregnancy percreta through an old scar highlighted considerable risks for this patient. These included severe retro-vesical bleeding that would most likely require surgical resolution with the loss of the uterus and possible bladder damage. A number of problems may have been encountered if the pregnancy had continued, for example, severe placental insufficiency due to abnormal vascular supply, very pre-term delivery or intra-uterine demise. There was the risk of retro- or intra-vesical severe haemorrhage, and the likelihood of caesarean hysterectomy with bladder involvement as well as the risk of maternal loss of life due to uncontrollable haemorrhage, particularly after 20 weeks of gestation.
    • Case report of eclampsia complicated with spontaneous splenic rupture

      Mishra, Ritu; Pope, Nicole; Bevington, Laura (2018-04)
      Objectives We present a case report of eclampsia complicated with spontaneous rupture of spleen. Design A case report and literature search. Setting Queens hospital Burton on Trent. A 33 year old primigravida under low risk care presented to A&E at 38 weeks of gestation after suffering two eclamptic fits. On presentation her G. C. S was 8, B. P was 177/109 mmHg and she was oliguric. The fetal heart rate was 125 beats /min and her bishops score was 2. Magnesium sulphate and labetalol infusion was commenced. Blood results showed Hb 11.7 g/dl, Platelets -134 109/ l, mmol/l, ALT 399 IU/l and raised urea and creatinine. On maternal stabilisation category 1 caesarean section was called for fetal bradycardia. On delivery of sadly a pale stillborn baby, the blood pressure crashed leading to a peri-arrest situation. Profuse bleeding was noted from a large laceration on the dorsal surface of the spleen and a splenectomy was performed by the surgical team. Result The parturient's recovery was complicated with effects of massive blood transfusion, coagulopathy and acute renal failure. Three hepatic sub capsular haematomas were discovered on further imaging which resolved spontaneously. She recovered fully and was discharged home after 4 weeks in hospital. Conclusion Spontaneous splenic rupture in pregnancy without antecedent trauma is rare and is lethal complication of preeclampsia. The first case was reported by saxtroph in 1803. A previous study by Denehy et al, demonstrates that only 2.2% of 89 cases of splenic rupture in pregnancy were documented to be spontaneous in the puerperium.
    • Chemotherapy improves survival rate in Stage 1 ovarian cancers

      Dewick, Laura; Asher, Viren (2018)
      Purpose of Investigation: The role of adjuvant chemotherapy in Stage 1 ovarian cancer is conflicting with no clear evidence to support adjuvant chemotherapy versus observation alone. The authors sought to establish the survival benefit of adjuvant chemotherapy in all Stage 1 ovarian cancers. Materials and Methods: Retrospective data including age, stage, grade, histology, RMI, and chemotherapy status on all patients undergoing treatment for Stage 1 ovarian cancer between May 2003 and November 2013 at Royal Derby Hospital was collected. Results: Eighty-nine cases of Stage 1 ovarian cancer were included. A total of 73 patients (84.88%) received adjuvant chemotherapy while 13 (15.12%) did not. The patients receiving adjuvant chemotherapy had a median overall survival (OS) of 108 months (CI 99.07-118.33) while the median OS for the patients who did not receive any adjuvant treatment was 63.71 months (CI 43.06-83.35) p = 0.003. Conclusion: Adjuvant chemotherapy significantly improves OS in Stage 1 ovarian cancer patients.
    • Comparing the experience of enhanced recovery programme for gynaecological patients undergoing laparoscopic versus open gynaecological surgery: a prospective study.

      Lee, Joanne; Asher, Viren; Nair, Arun; White, Victoria; Brocklehurst, Catherine; Traves, Martyn; Bali, Anish (2018-06)
      Background: Enhanced recovery has been shown to improve patients' experience after surgery. There are no previous studies comparing patients' experience between those undergoing laparoscopic and open gynaecological surgery. Therefore, the aim of this prospective study is to compare patients' functional recovery based on milestones set by the enhanced recovery programme and patients' satisfaction between the two groups. Methods: All eligible patients undergoing gynaecological surgery within an enhanced recovery after surgery (ERAS) programme from March to August 2014 were involved in this study. All patients received the questionnaires on admission which were then collected prior to discharge. They were followed up by telephone within 7 days. Results: Two hundred sixty-three patients were involved. One hundred forty-four questionnaires were returned (54% response rate). Fifty-one percent (n = 74) were from the laparoscopic group and 49% (n = 70) were from the laparotomy group. In terms of achieving milestones, more patients in the laparotomy group performed the deep breathing exercises (laparoscopic versus open; 66.2% versus 87.1% (p = 0.003). The laparoscopic group were more able to eat on day 0, but by day 1, there was no difference between the groups. Both groups were similar in their ability to drink (p = 0.98), mobilise (p = 0.123) and sit out in a chair (p = 0.511). In the laparoscopic group, the patients' experience was better for pain control (p < 0.0001) and nausea control (p = 0.003) from recovery to day 1, and they were more able to put on their own clothes (p = 0.001) and were more confident in mobilising (p < 0.0001) and in going home (p < 0.0001). The laparoscopic group had greater patient satisfaction with their pain always being well controlled (p < 0.0001) whilst more patients in the laparotomy group reported being satisfied to very satisfied with their overall care on the gynaecology ward (p = 0.04). Both groups were equally satisfied with their care from nursing staff (p = 0.709) and doctors (p = 0.431). Conclusion: The two groups were in general equally able to achieve the majority of the milestones despite differences in symptoms such as pain, nausea and confidence in mobilising and going home. Pre-operative education can empower patients to engage in their recovery. There is a high level of patient satisfaction in both groups.
    • Complete cytoreduction after five or more cycles of neo-adjuvant chemotherapy confers a survival benefit in advanced ovarian cancer.

      Phillips, A (2018-01)
      OBJECTIVES: To assess the impact of 5 or more cycles of neoadjuvant chemotherapy (NACT) and cytoreductive outcomes on overall survival (OS) in patients undergoing interval debulking surgery (IDS) for advanced ovarian cancer. METHODS: A retrospective review of patients receiving NACT followed by IDS between 2007 and 2017. Patients were analysed according to number of NACT cycles received: group 1 consisted of patients receiving ≤4 cycles and group 2 consisted of those receiving ≥5 cycles. Outcomes were stratified by cytoreductive outcome, surgical complexity, stage and chemotherapy exposure. RESULTS: 231 patients in group 1 and 167 in group 2 were identified. In group 1, the OS for those achieving Complete (R0), Optimal<1 cm (R1) and Suboptimal (R2) was 51.1, 36.1, and 34.3 months respectively. Statistically significant differences in survival were seen in patients achieving R0vR2 (p < 0.019) but not in R0vR1 (p = 0.125) or R1vR2 (p = 0.358). In group 2, the OS for those achieving R0, R1 and R2 was 53.0, 24.7, and 22.1 months respectively. Statistically significant differences were seen between R0vR1 and R0vR2 (p < 0.00001) but not between R1vR2 (p = 0.917). No difference in OS was seen between groups 1 and 2. In patients achieving R1, there was a trend towards decreasing OS with increasing exposure to NACT from 36.1 (95%CI 32.0-40.2)months with 3 cycles to 24.3 (95%CI 14.4-34.2)months with ≥6 cycles. CONCLUSIONS: Surgery with utilisation of cytoreductive procedures to achieve complete clearance should be offered to all patients even after ≥5 cycles if R0 can be achieved. R1 cytoreduction has questionable value in those receiving ≤4 cycles and no value in those receiving ≥5 cycles.
    • Dehydroepiandrosterone (DHEA) role in enhancement and maintenance of implantation (DREAM): randomised double-blind placebo-controlled trial-study protocol.

      Jayaprakasan, Kanna (BMJ, 2021)
      INTRODUCTION: Dehydroepiandrosterone (DHEA) is an important precursor of androgen and has been studied and researched extensively for improving the various outcome measures of ovarian stimulation in women with advanced age or poor ovarian response. Androgens also play an important role in the enhancement of endometrial and decidual function by regulating both the transcriptome and secretome of the endometrial stromal cells and have a positive effect on various factors like insulin-like growth factor binding protein 1, homeobox genes (HOXA10, HOXA11), secreted phosphoprotein 1, prolactin which are necessary for implantation. It is well-known that the circulating 'precursor pool' of DHEA declines with age more so in poor ovarian reserve patients and exogenous supplementation may be beneficial in such cases. This double-blinded randomised controlled trial (RCT) aims to test the hypothesis whether transient targeted supplementation of DHEA as an adjuvant to progesterone in frozen embryo transfer (FET) cycles, for women with low serum testosterone, helps in improving live birth rate. METHODS AND ANALYSIS: This study is planned as a double-blinded, placebo-controlled randomised trial and the sample size, calculated for the primary outcome measure-live birth rate, is 140. All participants will be having a flexible antagonist protocol for controlled ovarian stimulation and an elective freeze-all policy for the embryos as per the hospital protocol after written informed consent. For FET, the endometrium will be prepared by hormone replacement treatment protocol. During the FET cycle, the intervention group will be receiving DHEA 25 mg two times a day for 15 days from the day of starting progesterone supplementation and the control group will be receiving a placebo. ETHICS AND DISSEMINATION: The approval of the study was granted by the Clinical Trials Registry-India and the Institutional Ethical Committee of CRAFT Hospital and Research Center. All participants will provide written informed consent before being randomised into allocated treatment groups. The results will be disseminated to doctors and patients through conference presentations, peer-reviewed publications, social media and patient information booklets. TRIAL REGISTRATION NUMBERS: CTRI/2020/06/025918; ECR/1044/Inst/KL/2018.
    • Diaphragm disease in advanced ovarian cancer: Predictability of pre-operative imaging and safety of surgical intervention.

      Phillips, A (2018-05)
      OBJECTIVES: To establish the positive predictive values of pre-operative identification with CT imaging of metastatic diaphragm disease in surgically managed cases of advanced ovarian cancer (AOC). Additionally, we have assessed the post-operative morbidity and survival following diaphragmatic surgical intervention in a large regional cancer centre in the United Kingdom. STUDY DESIGN: A retrospective review of all cases of AOC with metastatic diaphragm disease surgically treated at the Pan-Birmingham Gynaecological Cancer Centre, UK between 1st August 2007 and 29th February 2016. RESULTS: A total of 536 women underwent surgery for primary AOC. Diaphragm disease was evident intra-operatively in 215/536 (40.1%) and 85/536 women (15.9%) underwent a procedure involving their diaphragm. Of these 85 cases, 38 peritoneal strippings (38/85, 44.7%), 31 partial diaphragmatic resections (31/85, 35.6%) and 16 electro-surgical ablations (16/85, 18.9%) were performed. There were no significant differences in post-operative complications between the three different diaphragmatic surgical groups. Of those patients who underwent peritoneal stripping or partial diaphragm resection, 12% were upstaged to stage 4A by virtue of pleural invasion. The positive predictive value for pre-operative radiological identification of diaphragmatic disease was 78.6%. CT imaging failed to detect diaphragmatic involvement despite obvious diaphragm disease during surgery in 29.4% of cases, giving a low negative predictive value of 64.8%. The sensitivity and specificity for CT imaging in detecting diaphragm disease was 44.3% and 93.8%, respectively. CONCLUSIONS: Diaphragmatic disease is often discovered in AOC. However, pre-operative assessment with CT imaging is not reliable in accurately detecting diaphragm involvement. Therefore, all patients with AOC should be regarded as in potential need for diaphragm surgery and their operation undertaken in cancer centres with adequate expertise in upper abdominal surgery. If there is a suspicion of diaphragm muscle invasion during diaphragmatic peritonectomy, the muscle should be partially resected. This will lead to potential upstaging of disease to stage 4A and therefore, to suitability for targeted therapy. In our Centre, the surgical removal of diaphragmatic disease did not significantly increase surgical morbidity.
    • Does sites of recurrence impact survival in secondary cytoreduction surgery for recurrent epithelial ovarian cancer?

      Phillips, A (2020-01)
      Outcomes of secondary cytoreduction surgery (SCS) were evaluated for morbidity, progression free survival (PFS) and overall survival (OS) and factors influencing results were explored. Retrospective analysis of all cases of SCS for epithelial ovarian cancer (EOC) was performed from October 2010 to December 2017. 62 patients were prospectively identified as candidates for SCS and 57 underwent SCS. 20(35%) patients required bowel resection/s, 24(42%) had nodal resections and 11(19%) had extensive upper abdominal surgery. 51(89%) achieved complete cytoreduction. After a median follow-up of 30 months (range 9-95 months), median PFS was 32 months (CI 17-76 months) and median OS has not reached. Seventeen patients have died and 32 have progressed. Three patients had Clavien-Dindo grade-3 and two had grade-4 morbidity. Patients who had multi-site recurrence had shorter median PFS (p = 0.04) and patients who required bowel resections had blower median OS (p = 0.009) compared to rest of the cohort.IMPACT STATEMENT What is already known on this subject? Retrospective studies have confirmed survival advantage for recurrence in epithelial ovarian cancer and recommend SCS for carefully selected patients. This finding is being evaluated in randomised control trials currently.What do the results of this study add? This study presents excellent results for survival outcomes after SCS and highlights importance of careful selection of patients with a goal to achieve complete cytoreduction. In addition, for the first time in literature, this study also explores various factors that may influence results and finds that there are no differences in survival outcomes whether these patients had early stage or advanced stage disease earlier. Patients who have multisite recurrence tend to have shorter PFS but no difference were noted for overall survival. Patients who have recurrence in bowels necessitating resection/s have a shorter median OS compared to rest of cohorts, however, still achieving a good survival time. What are the implications of these findings for clinical practice and/or further research? These findings will raise awareness for the clinicians and patients while discussing surgical outcomes and would set an achievable standard to improve cancer services. The pattern of recurrence and associated outcomes also point towards difference in biological nature of recurrent disease and could provide an opportunity for scientists to study the biological makeup of these recurrent tumours.
    • Double-blind randomized controlled trial of letrozole versus clomiphene citrate in subfertile women with polycystic ovarian syndrome

      Amer, Saad; Smith, J; Mahran, A; Fox, Peter; Fakis, Apostolos (2017-06)
      STUDY QUESTION: Would letrozole as a primary ovulation induction agent generate better pregnancy rates than clomiphene citrate (CC) in subfertile women with anovulatory polycystic ovarian syndrome (PCOS)? SUMMARY ANSWER: Participants receiving letrozole as a primary treatment achieved a significantly (P =0.022) higher clinical pregnancy rate per patient (61.2%) compared to CC (43.0%). WHAT IS KNOWN ALREADY: According to a recent Cochrane systematic review (2014), letrozole appears to improve live-birth (LB) and pregnancy rates in anovulatory women with PCOS, compared to CC. However, the review concluded that the quality of evidence was low due to poor reporting of study methods and possible publication bias. STUDY DESIGN, SIZE, DURATION: This double-blind randomized controlled trial (RCT) included 159 participants between April 2007 and June 2014. Subjects were randomly allocated to either CC (n = 79) or letrozole (n = 80) in a 1:1 ratio. Both drugs were encapsulated to look identical. Randomization was performed in mixed blocks and stratified by patients’ BMI (<30 and 30–35 kg/m2). PARTICIPANTS/MATERIALS, SETTING, METHODS: The trial included subfertile women diagnosed with PCOS. Treatment started with one tablet (CC 50 mg, letrozole 2.5 mg) increasing to two in non-responders and continuing until pregnancy or for up to six ovulatory cycles. Non-responders were crossed over to the other treatment after a 6-week break. Cycles were initially monitored with ultrasound follicle tracking then mid-luteal serum progesterone measurement in subsequent cycles. MAIN RESULTS AND THE ROLE OF CHANCE: Amongst the 159 participants included in the intention-to-treat analysis, four women conceived before treatment and six were lost-to-follow-up. The remaining 149 participants (74 on CC and 75 on letrozole) completed at least the first treatment. Women receiving letrozole achieved a significantly (P = 0.022; absolute difference [95% confidence interval] 18% [3–33%]) higher pregnancy rate (61.%) than those on CC (43%). The median number of treatment cycles received until pregnancy was significantly (log rank P = 0.038) smaller with letrozole (4[3–5] cycles) compared to CC (6[4–7] cycles). LB rates were not statistically (P = 0.089) different between the two groups, although there was a trend towards higher rates on letrozole (48.8%) compared to CC (35.4%). After the crossover, pregnancy and LB rates on letrozole (n = 45; 28.9 and 24.4%, respectively) were not statistically (P = 0.539 and P = 0.601) different from CC (n = 31; 22.6 and 19.4%). LIMITATIONS, REASONS FOR CAUTION: One possible limitation of this trial may be the exclusion of PCOS women with BMI > 35 kg/m2, which would limit the applicability of the results in this subgroup of PCOS. However, this group of women are generally excluded from treatment in the majority of fertility centres, especially in Europe, due to the associated challenges and risks.
    • Eag and HERG potassium channels as novel therapeutic targets in cancer.

      Asher, Viren; Bali, Anish (2010-12)
      Voltage gated potassium channels have been extensively studied in relation to cancer. In this review, we will focus on the role of two potassium channels, Ether à-go-go (Eag), Human ether à-go-go related gene (HERG), in cancer and their potential therapeutic utility in the treatment of cancer. Eag and HERG are expressed in cancers of various organs and have been implicated in cell cycle progression and proliferation of cancer cells. Inhibition of these channels has been shown to reduce proliferation both in vitro and vivo studies identifying potassium channel modulators as putative inhibitors of tumour progression. Eag channels in view of their restricted expression in normal tissue may emerge as novel tumour biomarkers.
    • Effect of antipsychotics on mitochondrial bioenergetics of rat ovarian theca cells

      Amer, Saad (2017)
      Background: Antipsychotics (APs) are widely prescribed drugs, which are well known to cause reproductive adverse effects through mechanisms yet to be determined. The purpose of this study was to investigate the effect of antipsychotics on mitochondrial bioenergetics of rat ovarian theca cells as a possible mechanism of reproductive toxicity. Methods: Isolated rat’s theca interstitial cells (TICs) were treated with two typical (chlorpromazine [CPZ] and haloperidol [HAL]) and two atypical APs (risperidone [RIS] and clozapine [CLZ]). The effects of these APs on TICs bioenergetics (ATP content, mitochondrial complexes I and III activities, oxygen consumption rates (OCRs), mitochondrial membrane potential (MPP) and lactate production) and on steroidogenesis (androstenedione and progesterone synthesis) were investigated. Results: All Aps resulted in a concentration-dependent decrease in the ATP content of TICs. All APs in their estimated IC50s (6 μM, 21 μM, 35 μM and 37μM for CPZ, HAL, CLZ and RIS respectively) significantly decreased TICs OCRs (p<0.0001), MPP (p<0.0001) and significantly (p =0.0003) inhibited mitochondrial complex I activity. Only typical APs inhibited complex III (p=0.005). Also, APs in IC50s increased TICs lactate production to varying degrees. All Aps used at their IC50s significantly inhibited progesterone (p=0.0022) and androstenedione (p=0.0027) production. Only CPZ was found to inhibit these hormones in the low concentration (1μM). Conclusion: All four antipsychotics seem to inhibit mitochondrial bioenergetics and steroidogenesis in rat’s ovarian theca cells. These findings support the hypothesis that APs-induced reproductive toxicity may be through mechanisms involving mitochondrial insult. Further research is required to establish the link between APs-induced mitochondrial dysfunction and disordered steroidogenesis.
    • Effect of ethnicity on live birth rates after in vitro fertilisation/intracytoplasmic sperm injection treatment: analysis of UK national database.

      Jayaprakasan, Kanna (2016-08)
      OBJECTIVE: To evaluate the effect of ethnicity of women on the outcome of in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) treatment. DESIGN: Observational cohort study. SETTING: UK National Database. POPULATION: Data from 2000 to 2010 involving 38 709 women undergoing their first IVF/ICSI cycle were analysed. METHODS: Anonymous data were obtained from the Human Fertilization and Embryology Authority (HFEA), the statutory regulator of IVF and ICSI treatment in the UK. Data analysis was performed by regression analysis with adjustment for age, cause and type of infertility and treatment type (IVF or ICSI) to express results as odds ratio (OR) and 95% confidence intervals (95% CI). METHODS: Live birth rate per cycle of IVF or ICSI treatment. RESULTS: While white Irish (OR 0.73; 95% CI 0.60-0.90), Indian (0.85; 0.75-0.97), Bangladeshi (0.53: 0.33-0.85), Pakistani (0.68; 0.58-0.80), Black African (0.60; 0.51-0.72), and other non-Caucasian Asian (0.86; 0.73-0.99) had a significantly lower odds of live birth rates per fresh IVF/ICSI cycle than White British women, ethnic groups of White European (1.04; 0.96-1.13), Chinese (1.12; 0.77-1.64), Black Caribbean (0.76; 0.51-1.13), Middle Eastern (0.73; 0.51-1.04), Mediterranean European (1.18; 0.83-1.70) and Mixed race population (0.94; 0.73-1.19) had live birth rates that did not differ significantly. The cumulative live birth rates showed similar patterns across different ethnic groups. CONCLUSION: Ethnicity is a major determinant of IVF/ICSI treatment outcome as indicated by significantly lower live birth rates in some of the ethnic minority groups compared with white British women. TWEETABLE ABSTRACT: Ethnicity affects IVF outcome with lower live birth rates in some ethnic groups more than in white British.
    • Effect of transfer of a poor quality embryo along with a top quality embryo on the outcome during fresh and frozen in vitro fertilization cycles.

      Dobson, Samuel (2018-09)
      OBJECTIVE: To evaluate the impact of a poor quality embryo (PQE) during double E (DET) with a top quality embryo (TQE) on IVF outcome. DESIGN: A review of prospectively collected data. SETTING: Tertiary level fertility clinic. PATIENT(S): All patients undergoing blastocyst transfers as part of fresh IVF (n = 939) and frozen ET (n = 1,009) cycles performed between 2010 and 2016. INTERVENTION(S): Single ET (SET) with TQE (group 1) was set as control and compared with outcomes for SET with PQE (group 2), DET with 2 TQEs (group 3), PQE plus TQE (group 4), and 2 PQE (group 5). MAIN OUTCOME MEASURE(S): Live births and multiple births. RESULT(S): The live birth rates for group 4 were statistically similar to group 1 during fresh IVF (26.5% vs. 33.7%; odds ratio [OR], 0.95; 95% confidence interval [CI] 0.53-1.7) and frozen ET (24.2% vs. 32.7%; OR, 0.75; 95% CI 0.48-1.2), although there was a trend for lower success. Conversely, multiple births were higher in group 4 for fresh IVF (19% vs. 4.7%; OR, 2.9; 95% CI 1.3-6.6) and frozen ET (10.3% vs. 2.6%; OR, 2.4; 95% CI 1.2-4.9). The live birth rates for group 2 (12.2% for fresh IVF and 14.6% for frozen ET) and group 5 (21.2% for fresh IVF and 14% for frozen ET) were lower and for group 3 were higher (40.8% for fresh IVF and 40.3% for frozen ET) when compared with group 1. Multiple births were significantly higher with DET. CONCLUSION(S): This study does not support DET with one PQE along with a TQE, when there is only one TQE and one or more PQEs available for fresh IVF or frozen ET.
    • Effect of transfer of a poor quality embryo along with a top quality embryo on the outcome during fresh and frozen in vitro fertilization cycles.

      Dobson, Samuel (2018-09)
      OBJECTIVE: To evaluate the impact of a poor quality embryo (PQE) during double ET (DET) with a top quality embryo (TQE) on IVF outcome. DESIGN: A review of prospectively collected data. SETTING: Tertiary level fertility clinic. PATIENT(S): All patients undergoing blastocyst transfers as part of fresh IVF (n = 939) and frozen ET (n = 1,009) cycles performed between 2010 and 2016. INTERVENTION(S): Single ET (SET) with TQE (group 1) was set as control and compared with outcomes for SET with PQE (group 2), DET with 2 TQEs (group 3), PQE plus TQE (group 4), and 2 PQE (group 5). MAIN OUTCOME MEASURE(S): Live births and multiple births. RESULT(S): The live birth rates for group 4 were statistically similar to group 1 during fresh IVF (26.5% vs. 33.7%; odds ratio [OR], 0.95; 95% confidence interval [CI] 0.53-1.7) and frozen ET (24.2% vs. 32.7%; OR, 0.75; 95% CI 0.48-1.2), although there was a trend for lower success. Conversely, multiple births were higher in group 4 for fresh IVF (19% vs. 4.7%; OR, 2.9; 95% CI 1.3-6.6) and frozen ET (10.3% vs. 2.6%; OR, 2.4; 95% CI 1.2-4.9). The live birth rates for group 2 (12.2% for fresh IVF and 14.6% for frozen ET) and group 5 (21.2% for fresh IVF and 14% for frozen ET) were lower and for group 3 were higher (40.8% for fresh IVF and 40.3% for frozen ET) when compared with group 1. Multiple births were significantly higher with DET. CONCLUSION(S): This study does not support DET with one PQE along with a TQE, when there is only one TQE and one or more PQEs available for fresh IVF or frozen ET.
    • Enigma of urethral pain syndrome: why are there so many ascribed etiologies and therapeutic approaches?

      Chilaka, Victor; Okewole, I; Phillip, H (2014-06)
      Urethral pain syndrome has had several sobriquets, which have led to much confusion over the existence of this pathological condition and the useful options in the care of the afflicted patient. Our aim was to explore the proposed etiologies of this syndrome, and to provide a critical analysis of each proposed etiology and present a balanced argument on the plausibility of the proposed etiology and therapeutic approaches. We carried out an English language electronic search in the following databases: Medline, Embase, Amed, Cinahl, Pubmed, Cochrane Library, Trip Database and SUMSearch using the following search terms: urethral syndrome, urethral diseases, urethra, urologic diseases etiology/etiology, presentation, treatment, outcome, therapeutics and treatment from 1951 to 2011. In excess of 200 articles were recovered. With the clearly defined objectives of analyzing the proposed etiologies and therapeutic regimes, two author(s) (HP and IO) perused the abstracts of all the recovered articles, selecting those that addressed the etiologies and therapeutic approaches to treating the urethral pain syndrome. The number of articles was reduced to 25. The full text of all 25 articles were retrieved and reviewed. Through the present article, we hope to elucidate the most probable etiology of this condition whilst simultaneously, advance a logical explanation for the apparent success in the treatment of this condition using a range of different therapeutic modalities. We have carried out a narrative review, which we hope will reduce some of the confusion around this clinical entity by combining the known facts about the disease.
    • Evidence-Based Management of Recurrent Miscarriages

      James, Cathryn; Tahseen, Samina (2017-03)