Effect of vitamin D in addition to letrozole on the ovulation rate of women with polycystic ovary syndrome: protocol of a multicentre randomised double-blind controlled trial.

INTRODUCTION: Low vitamin D status is prevalent among women with polycystic ovary syndrome (PCOS). The objective of the study is to assess the effect of vitamin D supplementation on (1) the ovulation rate to letrozole and (2) other reproductive, endocrine and metabolic outcomes after 1 year of supplementation in women with PCOS. METHODS AND ANALYSIS: This is a multicentre, randomised, double-blind, controlled clinical trial. A total of 220 anovulatory women with PCOS diagnosed by the Rotterdam criteria will be recruited. They will be randomly assigned to either the (1) vitamin D supplementation group or (2) placebo group. Those in the vitamin D group will take oral Vitamin D3 50 000 IU/week for 4 weeks, followed by 50 000 IU once every 2 weeks for 52 weeks. Those who remain anovulatory after 6 months will be treated with a 6-month course of letrozole (2.5 mg to 7.5 mg for 5 days per cycle titrated according to response) for ovulation induction. The primary outcome is the ovulation rate. All statistical analyses will be performed using intention-to-treat and per protocol analyses. ETHICS AND DISSEMINATION: Ethics approval was sought from the Institutional Review Board of the participating units. All participants will provide written informed consent before joining the study. The results of the study will be submitted to scientific conferences and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04650880.

Knowledge, attitudes and intention on fertility preservation among breast cancer patients.

Breast cancer is the most common cancer in reproductive age women. The aim of this study is to assess the knowledge, attitude and intention on fertility preservation among women diagnosed to have breast cancer. This is a multi-centre cross-sectional questionnaire study. Reproductive age women diagnosed with breast cancer attending Oncology, Breast Surgery and Gynaecology Clinics and support groups were invited to participate. Women filled in paper or electronic form of the questionnaire. 461 women were recruited and 421 women returned the questionnaire. Overall, 181/410 (44.1%) women had heard of fertility preservation. Younger age and higher education level were significantly associated with increased awareness of fertility preservation. Awareness and acceptance of the different fertility preservation methods in reproductive age women with breast cancer was suboptimal. However, 46.1% women felt that their fertility concerns affected their decision for cancer treatment in some way.

Comparison of the number of oocytes obtained after ovarian stimulation between Chinese and Caucasian women undergoing in vitro fertilization using a standardized stimulation regime.

BACKGROUND: In vitro fertilization (IVF) is a well-established method to treat various causes of infertility. Some previous retrospective studies suggested a lower ovarian response in Asian women compared to Caucasian women. However, the ovarian stimulation regimens were not standardized, potentially confounding the findings. The objective of this study is to compare the number of oocytes obtained after ovarian stimulation between Chinese and Caucasian women undergoing IVF using a standardized stimulation regimen. METHODS: This is a prospective cohort study conducted in two tertiary IVF units in Hong Kong, China and Sydney, Australia from October 2016 to August 2019. A total of 192 women aged 18-42 years with a body weight > 60 kg underwent IVF with a standard ovarian stimulation regimen of 150 micrograms corifollitropin alfa (Elonva®) followed by 200 IU follitropin beta (Puregon®) per day. The number of oocytes retrieved in Chinese women treated in the Hong Kong center was compared to that of Caucasian women treated in the Australian center. RESULTS: Serum AMH levels were similar between the two groups. Although women in the Chinese cohort were older and had a higher body mass index (BMI), longer duration of infertility and lower antral follicle count (AFC) than those in the Caucasian cohort in this study, no differences in the number of oocytes retrieved [11 (8-17) vs. 11 (6-17), p=0.29], total dosage and duration of stimulation and number of follicles aspirated were noted between the two ethnic cohorts. The peak estradiol level was greater in Chinese women than in Caucasian women. After controlling for age, BMI and AFC, ethnicity was a significant independent determinant of the number of oocytes obtained. CONCLUSIONS: Chinese women had a higher number of oocytes after ovarian stimulation using a standardized stimulation regimen compared with Caucasian women undergoing IVF after controlling for age, BMI, AFC and AMH despite presenting later after a longer duration of infertility. TRIAL REGISTRATION NUMBER: NCT02748278.

A Randomized Controlled Trial Comparing Trainee-Directed Virtual Reality Simulation Training and Box Trainer on the Acquisition of Laparoscopic Suturing Skills.

OBJECTIVE: To compare the proficiency of novices in acquiring laparoscopic suturing skills following training in a virtual reality simulator or box trainer compared to no training. METHODS: This was a RCT in a university-affiliated teaching hospital recruiting participants who had no laparoscopic suturing experience to have suturing skill training in the virtual reality simulator, box trainer, or no training as control. Trainees were allowed to terminate training when they perceived competence in the procedure. Suturing skills were tested in the box trainer and scored using a modified Global Operative Assessment of Laparoscopic Skills questionnaire by their own self-evaluation and two experienced gynaecological laparoscopists. RESULTS: Of the 36 participants recruited, 27 (75%) had no laparoscopic experience. Participants with no laparoscopic experience took longer to complete training than those with experience (median 90 minutes [interquartile range (IQR) 80-115] vs. 55 min [IQR 40-65], respectively; P = 0.044). There were no differences in successful completion of the task (7/12 [58.3%], 10/12 [83.3%], 7/12 [58.3%]; P = 0.325), median suturing time in seconds (628 [IQR 460-835], 611 [IQR 434-691], 609 [IQR 540-837]; P = 0.702), mean subjective (mean ± SD 9.8 ± 1.8, 10.4 ± 2.8, 9.3 ± 2.4; P = 0.710), and objective (7.2 ± 1.8, 8.2 ± 2.1, 7.6 ± 1.7; P = 0.426) modified Global Operative Assessment of Laparoscopic Skills score in the simulator, pelvic trainer, and control groups, respectively. The intraclass correlation coefficient of the two reviewers was 0.422 (95% CI 0.159-0.717). CONCLUSION: Trainees were unable to accurately assess themselves as to skill level in laparoscopic suturing. A longer training time is required for novices to master laparoscopic suturing using a simulator or box trainer.

Sperm fucosyltransferase-5 mediates spermatozoa-oviductal epithelial cell interaction to protect human spermatozoa from oxidative damage.

Oxidative damage by reactive oxygen species (ROS) is a major cause of sperm dysfunction. Excessive ROS generation reduces fertilization and enhances DNA damage of spermatozoa. Interaction between spermatozoa and oviductal epithelial cells improves the fertilizing ability of and reduces chromatin damage in spermatozoa. Our previous data showed that oviductal epithelial cell membrane proteins interact with the human spermatozoa and protect them from ROS-induced reduction in sperm motility, membrane integrity and DNA integrity. Sperm fucosyltransferase-5 (sFUT5) is a membrane carbohydrate-binding protein on human spermatozoa. In this study, we demonstrate for the first time that sFUT5 is involved in human spermatozoa-oviduct interaction and the beneficial effects of such interaction on the fertilizing ability of human spermatozoa. Anti-sFUT5 antibody-treated spermatozoa had reduced binding to oviductal membrane proteins. It is consistent with the result that affinity-purified sFUT5 is bound to the epithelial lining of human oviduct and to the immortalized human oviductal epithelial cell line, OE-E6/E7. Pretreatment of spermatozoa with anti-sFUT5 antibody and oviductal membrane proteins with sFUT5 suppressed the protective action of oviductal membrane proteins against ROS/cryopreservation-induced oxidative damage in spermatozoa. Asialofetuin, a reported sFUT5 substrate, can partly mimic the protective effect of oviductal epithelial cell membrane proteins on sperm motility, membrane and DNA integrity. The results enhance our understanding on the protective mechanism of oviduct on sperm functions.

Two-dimensional versus three-dimensional laparoscopy: evaluation of physicians' performance and preference using a pelvic trainer.

STUDY OBJECTIVE: To compare the proficiency and preference of physicians in performing standard tasks in a box trainer using 2-dimensional (2D) versus 3-dimensional (3D) laparoscopy. DESIGN: Prospective randomized controlled trial. DESIGN CLASSIFICATION: Prospective, randomized controlled trial (Canadian Task Force classification I). SETTING: Tertiary care teaching hospital. PARTICIPANTS: Thirty physicians from the Department of Obstetrics and Gynecology. INTERVENTION: Participants were randomly assigned to perform a set of 3 to 4 tasks in a pelvic trainer using 2D laparoscopy first and then 3D laparoscopy, and vice versa. MAIN RESULTS AND MEASUREMENTS: The time taken to complete the tasks and side effects experienced were noted. Participants were asked to complete a modified Global Operative Assessment of Laparoscopic Skills (GOALS) form at the end of their tasks to evaluate their experiences and to assess their own proficiency with both visual modalities. RESULTS: The time taken for peg transfer, duct cannulation, and suturing was significantly faster using 3D laparoscopy compared with 2D laparoscopy. There were no significant differences in the time taken for pattern cutting with both visual modalities. Participants experienced more dizziness using 3D laparoscopy (6.9% vs 37.9%; p = .004). The GOALS self-evaluation score was significantly higher for 3D compared with 2D laparoscopy. After the study, 11 of 29 (37.9%) participants preferred 2D, 16 of 29 (55.2%) preferred 3D, and 1 of 29 (8.3%) had no preference. CONCLUSION: Although 3D laparoscopy scored higher on self-evaluation and was preferred by more participants, it only gave better objective performance in the completion of some selected tasks by participants with intermediate skill levels and was associated with more dizziness. Further studies are needed to determine the value of 3D laparoscopy, especially when used in the clinical setting.

Time to revisit the human chorionic gonadotropin discriminatory level in the management of pregnancy of unknown location.

OBJECTIVES: The purpose of this study was to review the management and outcomes of all patients with pregnancy of unknown location who had serum human chorionic gonadotropin (hCG) levels greater than 1000 mIU/mL in our institution and to determine the likelihood of a subsequent normal intrauterine pregnancy at different hCG discriminatory levels. METHODS: A retrospective review was performed on all women admitted with the diagnosis of pregnancy of unknown location and an hCG level greater than 1000 mIU/mL over a 5-year period (July 2007 to June 2012). Patients were identified from a computerized hCG result database. The medical records, including sonographic findings, hCG levels, and outcomes, were reviewed. RESULTS: A total of 113 patients were identified. There were 23 viable intrauterine pregnancies (20.4%) and 22 visualized ectopic pregnancies (19.5%). The highest hCG level associated with a subsequent normal intrauterine pregnancy was 9083 mIU/mL in a patient with triplet pregnancy. Possible factors associated with nonvisualization of a normal intrauterine pregnancy included uterine fibroids, adenomyosis, endometrial polyps, and obesity. The negative laparoscopy rate was 48.8%. CONCLUSIONS: Viable intrauterine pregnancy is possible in patients with pregnancy of unknown location and hCG levels above the generally accepted discriminatory zone, strict adherence to which can potentially disrupt a normal pregnancy. We support the need for judicious use of the hCG discriminatory level in hemodynamically stable patients with pregnancy of unknown location, and the decision to intervene should not be based solely on a single hCG level.

Cell membrane proteins from oviductal epithelial cell line protect human spermatozoa from oxidative damage.

OBJECTIVE: To study the potential protective action in vitro of oviductal epithelial cell membrane proteins against oxidative damage in human spermatozoa. DESIGN: Prospective in vitro study. SETTING: University research laboratory and infertility clinic. PATIENT(S): Semen from men attending the infertility clinic at the Queen Mary Hospital with normal semen parameters (World Health Organization, 2010). INTERVENTION(S): We studied the effect of oviductal epithelial cell membrane proteins on the sperm functions and endogenous antioxidant enzyme activities. MAIN OUTCOME MEASURE(S): Sperm motility, lipid peroxidation, DNA fragmentation, intracellular reactive oxygen species (ROS) level, superoxide dismutase, and glutathione peroxidase activities. RESULT(S): Oviductal epithelial cell membrane proteins bind to the human spermatozoa and protect them from ROS-induced damages in terms of sperm motility, membrane integrity, DNA integrity, and intracellular ROS level. Spermatozoa-oviduct epithelial cell interaction also enhances the antioxidant defenses in spermatozoa. CONCLUSION(S): Our results demonstrated the protective effects of spermatozoon-oviductal epithelial cell interaction against oxidative stress in human spermatozoa. The results enhance our understanding of the protective mechanism of oviduct on sperm functions.

Cesarean scar molar pregnancy.

BACKGROUND: Molar pregnancy found in a cesarean scar is exceedingly rare. It can be challenging to manage and can have potentially catastrophic consequences. CASE: A 34-year-old multigravid woman presented with persistent symptoms of pregnancy after a surgical termination of pregnancy. Cesarean scar molar pregnancy was suspected on ultrasonography, and suction evacuation was performed under ultrasound guidance. This was followed by bimanual compression, oxytocin, and uterine artery embolization to reduce bleeding. CONCLUSION: A high index of suspicion is needed for early diagnosis and management of cesarean scar molar pregnancy.