Effect of Berberine Phytosome on reproductive, dermatologic, and metabolic characteristics in women with polycystic ovary syndrome: a controlled, randomized, multi-centric, open-label clinical trial.

Background: Berberine is a poorly absorbed natural alkaloid widely used as nutraceutical to counteract diarrhoea and to lower cholesterol and hyperglycaemia. It has also been reported to reduce signs and symptoms of polycystic ovary syndrome (PCOS). Objective: To explore, through a multi-centric, randomized, controlled and prospective study, the possible role played by a form berberine that is more easily absorbed (Berberine Phytosome®, BP) in 130 Pakistani women with a diagnosis of PCOS and fertility problems due to menstrual and ovary abnormalities. Results: Ninety days of supplementation with BP, administered at 550 mg x2/die, determined (i) resumption of regular menstruation in about 70% of women (versus 16% in the control group; p < 0.0001), (ii) normalization of the ovaries anatomy in more than 60% of women (versus 13% in the control group; p < 0.0001), (iii) acne improvement in 50% of women (versus 16% in the control group; p = 0.0409) and (iv) hirsutism reduction in 14% of women (versus 0% in the control group; p = 0.0152). The metabolic and the hormonal profiles of the women in the two groups did not significantly differentiate at the end of the study. BP was well-tolerated and no specific side-effects were registered. Respectively after one, two and 8 years of trying, three women supplemented with BP became and are currently pregnant. Conclusion: Our study showed the positive effects of BP supplementation in women with PCOS and confirmed the high safety profile of this nutraceutical. Clinical Trial Registration: https://clinicaltrials.gov/, identifier NCT05480670.

A comparative absorption study of sucrosomial® orodispersible vitamin D3 supplementation vs. a reference chewable tablet and soft gel capsule vitamin D3 in improving circulatory 25(OH)D levels in healthy adults with vitamin D deficiency-Results from a prospective randomized clinical trial.

Background: Vitamin D (Vit D) deficiency (VDD), associated with diverse health conditions, is commonly treated with Vit D3 supplements. However, the gastrointestinal (GI) absorption of Vit D3 in different formulations has not been well studied. Objective: We aimed to compare the absorption of an innovative phospholipids-sucrester matrix biodelivery vehicle-based (sucrosomial®) orodispersible Vit D3 preparation against a reference chewable tablet and soft gel capsule (SGC) Vit D3 formulations in Vit D-deficient healthy adults. Methods: In study 1, 25 subjects were randomized to receive a weekly single dose of 200,000 IU of sucrosomial® Vit D3 (n = 12) or chewable tablet Vit D3 (n = 13) for 3 weeks. In study 2, 20 subjects were randomized to receive a single dose of 200,000 IU every other week of sucrosomial® Vit D3 (n = 10) or SGC Vit D3 (n = 10) for 6 weeks. Circulatory 25-hydroxyvitamin D3 [25(OH)D] levels were reassessed after 2, 3, and 6 weeks in study 1 and after 4 and 6 weeks in study 2. Results: In study 1, after 2 weeks, circulatory 25(OH)D levels increased significantly in both Vit D3 treatment groups (p < 0.0001) but improved markedly in the sucrosomial® Vit D3 group, with no further considerable change after 3 and 6 weeks in both groups. Overall, at all three follow-ups, sucrosomial® Vit D3 treatment achieved significantly higher and sustained 25(OH)D levels (p < 0.001). In study 2, after 4 weeks, both Vit D3 treatment groups showed significant improvement in circulatory 25(OH)D levels (p < 0.0001) but substantially higher in the sucrosomial® group with statistically significant differences between the two treatment groups (p = 0.02). At the 6-week follow-up, only subjects in the sucrosomial® Vit D3 group showed a further increase in circulatory 25(OH)D levels (p = 0.049), but no further significant changes in the levels of the SGC Vit D3 group (p = 0.062), showing a statistically significant difference between the two treatment groups (p = 0.002). The Vit D3 treatment was well tolerated by all participants, and no treatment-emergent effects or serious adverse events were reported. Conclusion: Our results suggest that the sucrosomial® Vit D3 preparation absorbs efficiently in the GI system, achieving adequately higher and sustained circulatory Vit D levels in VDD, and thus can effectively contribute to the body protection against VDD-associated health conditions. Clinical trial registration: clinicaltrials.gov, identifier: NCT05706259.

Female Urinary Incontinence: Frequency, Risk Factors, and Impact on the Quality of Life of Pregnant Pakistani Women.

Objectives: To determine the frequency and associated risk factors of urinary incontinence (UI), and its effect on the quality of life (QOL) of pregnant Pakistani women. Methods: This was a cross-sectional study of 309 pregnant women, 16-40 weeks gestation, age 18- 45 years, at the Aga Khan University Hospital Karachi, between August 2019 and February 2020. Data were obtained using the International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short form (ICIQ-UI-SF). Results: The frequency of UI was 63.1%. Stress UI was the commonest type (53.0%) followed by urgency (17.5%) and mixed UI (11.7%). In majority of women, it occurred in small amounts, once a week with a very severe impact on QoL in 24.91% of women, affecting sexual relation the most. Risk factors for UI in pregnancy were age > 35 years (p < 0.02), gestation > 37 weeks (p< 0.00), higher body mass index and family history of UI (p< 0.00), previous instrumental vaginal delivery (P < 0.002), cough, constipation and strenuous job (p< 0.00), and lack of pelvic floor muscle exercises (p <0.03). Conclusions: UI is a common problem in pregnant women in Pakistan. It affects sexual functions the most, with a severe impact on the QOL, however, it commonly remains unreported. Thus the health care providers need to enquire all pregnant women on this issue, especially those at risk, and educate them on the available management options.

Vaginal Reconstruction in Patients with vaginal agenesis: Options and Outcome: A single-center experience.

Objectives: To assess the postoperative functional, anatomical outcome and complications of various surgical procedures of vaginoplasty performed for patients with vaginal agenesis at our institution. Methods: This was a cross-sectional study of 14 patients (age range 17-40 years), who underwent vaginoplasty at the Aga Khan University Hospital, Karachi, Pakistan between January 2008 to December 2018. We aimed to assess the anatomical outcomes in terms of vaginal depth, axis and functional outcome as painless and satisfactory vaginal intercourse. Results: The mean age and mean body mass index (BMI) of the cases were 26.8 ± 8.1 years and 27.7143 ± 4.6 respectively. All were phenotypically female, with only two cases of XY genotype. Two patients were married on presentation. On evaluation, four cases had Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome, three had androgen insensitivity syndrome (AIS), one case had congenital adrenal hyperplasia and six cases did not fit into any diagnosis. Associated renal anomalies were diagnosed in 14.3% of cases. The performed procedures were; Singaporean flap vaginoplasty (in four patients), Lee's, modified McIndoe and pull-through vaginoplasty (in three each patients), and Davydov vaginoplasty (in one patient). One patient was complicated by intraoperative bladder injury (p<0.63) and two cases by vaginal stenosis (p<0.43). The mean operative time was 120 minutes and the mean estimated blood loss was 200mls. Postoperatively, the vaginal length varied from 6-10 cm with a normal vaginal axis and satisfactory sexual activity. Conclusions: Vaginal agenesis is associated with several sexual disorders and despite the various surgical options available, the best procedure in terms of fewer complications and best surgical outcome is yet to be determined.

Causative factors, social and surgical outcomes of vesicovaginal fistulas treated via an abdominal transvesical approach: A single-center experience.

OBJECTIVE: To study the demographics, and surgical and social outcomes of patients with fistula repair performed at our hospital. METHODS: This cross-sectional study included 120 patients with fistula repair performed between 2014 and 2019 in the Urology Department of Lady Reading Hospital, Peshawar using an open transvesical repair method without omental interposition. Data were collected on patients' demographics, and social and surgical outcomes. Fistula severity was assessed using the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). RESULTS: About 80 (66.6%) fistulas were iatrogenic and 40 (33.3%) were ischemic, with 36 (90%) due to obstructed labor. The median age of patients was 36 years (29-40 years). The majority of the patients were multiparous and premenopausal (99; 82.5%). Fifty (56.5%) of the iatrogenic fistulas were due to non-obstetric hysterectomy, and 20 (25%) were due to cesarean hysterectomy. Women had the fistulas for 4-49 weeks before seeking treatment with an average ICIQ score of 18. In all, 73 (73%) of the fistula caused by delivery had involved stillbirths, 4 (3.96%) were early neonatal deaths, and nearly 25 (21%) of patients were divorced. About 114 (95%) of patients were completely cured on discharge. CONCLUSION: Vesicovaginal fistula is a devastating condition, with a rising trend in iatrogenic fistulas in low-income countries. In the hands of experienced surgeons, trans-abdominal repair without omental interposition shows a high success rate.

Ruptured uterus: Frequency, risk factors and feto-maternal outcome: Current scenario in a low-resource setup.

INTRODUCTION: Pakistan is among the countries with the highest maternal death rates. Obstetric hemorrhage accounts for 41% of these deaths. Uterine rupture is a grave obstetric emergency with high maternal and neonatal morbidity and mortality. It is important to identify its frequency and associated risk factors to formulate programs for its prevention and management. This study aimed to assess the frequency, associated risk factors, fetomaternal outcomes, and management of women with the ruptured uterus at our hospital. MATERIAL AND METHODS: It was a retrospective study of 206 women to review data collected from cases of uterine rupture managed at the WCTH Bannu, Pakistan from October 2016 to October 2018. A structured proforma was designed and used to extract data from operating theatre registers and the hospital medical records. In our hospital, there is a strong system of maintaining all information of the patients related to demographics, obstetric information, operative notes, and postoperative course during their hospital stay in the patient's charts. Detailed information on operative procedures is further maintained in the operation theater register and all these registers are checked in the weekly statistical meetings to ensure proper documentation. Data was entered and analyzed in SPSS package version 21 (IBM Corp.; Armonk, NY, USA). Frequency and percentages were calculated for the categorical variables. For inferential statistics, chi-square or Fischer exact tests were used. A p-value of < 0.05 was considered statistically significant. RESULTS: The overall incidence of the ruptured uterus was 1.71%. The important etiological factors were grand multiparity 62 (35.2%), obstructed/neglected labour 58 (32.9%), injudicious use of Oxytocin 56 (31.8%) and prostaglandins 26 (14.7%), previous cesarean section 35 (19.8%) and previous pelvic surgery (0.5%). Hysterectomy was done in 80.6% of cases, 34 (19.2%) patients underwent uterine repair and 4.5% had bladder repair. The mortality rate was 21%, mainly due to irreversible shock or disseminated intravascular coagulation. Perinatal mortality was 91.4%. Duration of surgery more than two hours and presentation to the hospital at night time was significantly associated with poor maternal outcome (p = 0.00). CONCLUSION: Uterine rupture is a preventable obstetric emergency associated with high fetomaternal morbidity and mortality. The main causes were grand multigravidity, obstructed labour, previous C-sections and injudicious use of oxytocin and prostaglandins. Women with prolonged surgery and admission at night time had a poor maternal outcome.

Vaginal Leiomyoma Presenting as Pelvic Organ Prolapse in Pregnancy.

Vaginal leiomyomas are extremely rare in pregnancy. These can present in a variety of ways. They can cause mechanical obstruction leading to maternal and perinatal morbidity. Herein, we describe a patient with a vaginal leiomyoma misdiagnosed and operated as pelvic organ prolapse during the second trimester of pregnancy. She presented with a huge vaginal mass, foul-smelling vaginal discharge, difficulty in urination and defecation and septicemia. On examination, she had a large foul-smelling and necrotic mass protruding from the vagina with urethra lying outside the vagina, and sutures visible just above the mass on the anterior vaginal wall. She was admitted and a  lower segment caesarian section was done followed by transvaginal resection of the mass, and cystoscopy was done. Vaginal leiomyomas require surgical removal and it is usually curative and recommended as the initial treatment of choice, especially when the tumour is large enough to cause a potential obstacle to normal labour. Key Words: Vaginal leiomyoma, Pelvic organ prolapse, Pregnancy.

The practice of Burch Colposuspension versus Mid Urethral Slings for the treatment of Stress Urinary Incontinence in developing country.

OBJECTIVES: To compare the effectiveness and complications of Burch colposuspension and Mid Urethral Slings (MUS) for the treatment of Stress Urinary Incontinence (SUI). METHODS: We conducted a cross-sectional study of 162 patients who underwent surgery for SUI with Burch colposuspension (n=40), tension free vaginal tape (TVT) (n= 59) or transobturator tape (TOT) (n=63), from 2006 to 2014 at the Aga Khan University Hospital- Karachi. All three groups were assessed in terms of demographics, cure rates, intraoperative and postoperative complications at one and five years using incontinence impact questionnaire-short form-7 (IIQ-7) and urogenital distress inventory -short form-6 (UDI-6). RESULTS: Mean age of the participants in Burch, TVT and TOT group was 44.1 ± 7.4, 48.3 ± 8.9, 53.0 ± 9.4 respectively. Majority of patients in TVT group were premenopausal (59.3%) and postmenopausal in TOT group (53.9%). Most abdominal hysterectomies were done in Burch group (40) while vaginal hysterectomies and anterior and posterior colporrhaphy in TOT group (55). All the procedures had both subjective and objective cure rate of more than 82% at one year, with TVT having the highest success rate of 96.61%. The objective cure rate in Burch, TVT and TOT group at five years was 74.19%, 90.30% and 81.25% respectively. Intraoperative complications included hemorrhage in one patient during Burch procedure and bladder perforation in two cases of TVT, with no significant difference in short or long-term complications with either procedure. CONCLUSIONS: All the three procedures have equal efficacy and complication rates. Even though TVT is the new gold standard but in view of current debate regarding mesh related complications, there is a need to readdress Burch colposuspension for treatment of SUI.

Surgery for pelvic organ prolapse and stress urinary incontinence and female sexual functions: A quasi-experimental study.

OBJECTIVES: To assess the effect of pelvic organ prolapse (POP) and/or stress urinary incontinence (SUI) on various domains of female sexual functions in patients before and after reconstructive surgery for these pelvic floor disorders. METHODS: We conducted a quasi-experimental study of 126 women aged 25-65 years, presenting with POP / SUI, from January 1st 2019 to December 31st 2019 at Aga Khan University Hospital. POP surgery was performed only in patients with symptomatic POP ≥ stage 2 according to POP-Q (quantification). Sexual functions were assessed using Female Sexual Function Index (FSFI) questionnaire, among sexually active women at baseline and 18 months after surgery. RESULTS: Mean age of the participants was 51.6, with a mean parity of four. Out of 126 patients, 31 patients underwent vaginal hysterectomy, pelvic floor repair and mid-urethral sling (MUS), 55 had vaginal hysterectomy with pelvic floor repair, 12 women had only pelvic floor repair and 10 patients had uterine suspension surgery for prolapse, while 18 patients underwent MUS operation alone for SUI. There was a statistically significant difference in female sexual functions after surgery for POP and/or SUI (p<0.01). This improvement was observed in both total and individual scores of each domain of FSFI with an overall improvement in sexual function from a mean of 18.5 pre-surgery to 20.8 post-surgery. CONCLUSIONS: This study reveals that women sexual functions are affected by POP and SUI and improve remarkably after reconstructive surgeries for these pelvic floor disorders.

The association of symptoms of overactive bladder with pelvic organ prolapse and its improvement after pelvic reconstructive surgery.

OBJECTIVES: This study asseses the association of overactive bladder symptoms and pelvic organ prolapse severity and evaluates the effect of pelvic reconstructive surgery on overactive bladder (OAB) symptoms in women with pelvic organ prolapse (POP). It also looks into any pre and post-operative factors responsible for persistent postoperative OAB symptoms. METHODS: This was a retrospective cross-sectional study conducted at the Aga Khan University Hospital, Karachi between 1st January 2014 and 31st December 2018. In this study women presenting with POP and concommitent OAB who underwent surgery for site specific defects, measured using Pelvic Organ Prolapse Quantification (POP-Q) staging system. OAB was defined as presence of urinary frequency, urinary urgency incontinence (UUI) and an affirmative response to item #15 and/or item #16 of the Pelvic Floor Distress Inventory (PFDI), which was used both pre and postoperatively. Primary outcome of the study was to find complete resolution or improvement of urinary frequency and UUI on the PFDI, 24 months after surgery. The secondary outcome was to see persistent OAB postoperatively and the factors associated with it. RESULTS: Overactive bladder (OAB) symptoms improved significantly regardless of the severity of prolapse at 24 months postoperative period. Body mass index (BMI) and postoperative constipation were the only statistically significant variables associated with persistent OAB symptoms postoperatively. CONCLUSIONS: Surgical correction of POP results in significant improvement in symptoms of OAB, in all stages of POP and co-existing OAB. However women with high BMI and post-operative constipation may be prone to persistent frequency and/or UUI.

A clinical audit of management of third and fourth degree perineal tears.

OBJECTIVE: To perform a clinical audit of the practices related to the management of third and fourth degree perineal tears. METHODS: The retrorspective study was conducted in 2019 at the Aga Khan University Hospital, Karachi, and comprised medical records from January 2008 to December 2018 of women having singleton term vaginal delivery and sustaining obstetric anal sphincter injuries. The change in practices regarding tear management was compared with a previous audit done at the same institution in 2008. Data was analysed using SPSS 20. RESULTS: Of the 25,370 deliveries, 142(0.56%) sustained obstetric anal sphincter injuries. There was a significant increase compared to the previous audit in terms of documentation of the method of repair, use of delayed absorbable suture material for the repair of external anal sphincter and follow-up at 6 weeks to see the success of repair and plan the next delivery (p<0.05). The use of vacuum vaginal delivery increased to 27(19%) from 5(4%), but there was decrease in injuries complicated by instrumental vaginal deliveries (p<0.05). CONCLUSIONS: Despite the increase in the number of deliveries, the frequency of obstetric anal sphincter injuries remained similar to the previous audit, indicating that regular clinical audits are integral to keeping clinical practice in accordance with the established standards.