Raymond Hang Wun Li

A randomized, controlled, pilot trial on the effect of dehydroepiandrosterone on ovarian response markers, ovarian response, and in vitro fertilization outcomes in poor responders

OBJECTIVE To evaluate whether pretreatment dehydroepiandrosterone (DHEA) supplementation improves ovarian response markers, ovarian response to standard low-dose gonadotropin stimulation, and in vitro fertilization (IVF) outcomes in poor responders. DESIGN Randomized, double-blind, placebo-controlled pilot study. SETTING Tertiary reproductive medicine unit. PATIENT(S) Thirty-two women with anticipated poor ovarian response. INTERVENTION(S) Randomization into DHEA group (n=16) receiving GNC (25 mg three times a day) or placebo (n=16) starting from at least 12 weeks before the scheduled IVF treatment according to a computer-generated randomization list. MAIN OUTCOME MEASURE(S) Measurement of monthly ovarian response markers, including antral follicle count (AFC), serum antimüllerian hormone (AMH), and follicle-stimulating hormone (FSH) levels; comparison of ovarian response to a standard dose of gonadotropin stimulation at week 8 and IVF outcomes; and AFC after 12 weeks (primary outcome). RESULT(S) The DHEA supplementation resulted in statistically significantly higher serum DHEA-S, free androgen index, and follicular DHEA-S levels. No statistically significant differences in the ovarian response markers (AFC, AMH, or FSH), the ovarian response to standard-dose gonadotropin stimulation, or IVF outcomes were found between the two groups. CONCLUSION(S) No statistically significant improvement in ovarian response markers, ovarian response to standard dose gonadotropin stimulation, or IVF outcomes was found in poor responders receiving pretreatment DHEA. CLINICAL TRIAL REGISTRATION NUMBER HKCTR-1149 (www.hkclinicaltrials.com) and NCT01915186 (www.ClinicalTrials.org).

A Randomized Double-Blinded Placebo-Controlled Trial on the Effect of Dehydroepiandrosterone for 16 Weeks on Ovarian Response Markers in Women with Primary Ovarian Insufficiency

CONTEXT Preliminary reports have shown encouraging effects of dehydroepiandrosterone (DHEA) in women with poor ovarian reserve undergoing assisted reproduction and primary ovarian insufficiency (POI), although data from randomized controlled trials are limited. The present study assesses the effect of DHEA on ovarian response markers in women with POI. OBJECTIVE The objective of the study was to evaluate whether DHEA for 16 wk would improve ovarian response markers in women with POI. DESIGN This was a randomized, double-blinded, placebo-controlled study. SETTING The study was conducted at a tertiary reproductive unit. PATIENTS Twenty-two women with unexplained POI participated in the study. INTERVENTIONS Eligible subjects were randomized into the DHEA group (n = 10), who received DHEA (LiveWell, 25 mg three times a day), or the placebo group (n = 12), who received placebo for 16 wk according to a computer-generated randomization list. Ovarian response markers included serum anti-mullerian hormone (AMH), FSH levels, and antral follicle count (AFC) as well as follicles of 10 mm or greater in diameter, and hormonal profiles were measured at 4-wk intervals until 4 wk after completion of treatment. Any returns of menses and side effects from treatment were recorded. MAIN OUTCOME MEASURES The primary outcome was serum AMH level. RESULTS No significant change in serum AMH and FSH levels had been detected throughout the study. AFC and ovarian volume were significantly higher at wk 12 and 20, respectively, in the DHEA group. Significantly more women having at least one follicle of 10 mm or greater at wk 12, 16, and 20 were found in the DHEA group. Serum testosterone and DHEA sulfate levels along with higher estradiol levels were significantly higher in the DHEA group. CONCLUSION This randomized, double-blinded, placebo-controlled trial found higher AFC and ovarian volume at wk 12 and 20, respectively, in the DHEA group, although there were no significant changes in serum AMH and FSH levels. Further trials using a longer duration of DHEA should be considered to evaluate the long-term effect of DHEA in women with POI.

Effect of preovulatory progesterone elevation and duration of progesterone elevation on the pregnancy rate of frozen–thawed embryo transfer in natural cycles

OBJECTIVE To assess the incidence of P elevation (PE) in natural cycles and evaluate its effect on frozen-thawed embryo transfer cycles performed in natural cycles (FET-NC). STUDY DESIGN Retrospective analysis. SETTING A tertiary assisted reproductive unit. PATIENT(S) Subfertile woman who did not conceive in their stimulated IVF cycle and underwent the first FET-NC cycle. INTERVENTION(S) Achieved serum samples were assayed for P concentrations from the day of LH surge up to 3 days before the surge. The cutoff level of PE was defined as 5 nmol/L. MAIN OUTCOME MEASURE(S) Clinical and ongoing pregnancy rates. RESULT(S) The incidence of PE in natural cycles was 173 of 610 (28.4%). There were no significant differences in both clinical and ongoing pregnancy rates (39.0% vs. 37.3% and 32.5% vs. 31.7%) between those with vs. without PE on the day of LH surge. If PE lasted for 2 days or more, there was a significant reduction in the clinical pregnancy rate (39.4% vs. 20.7%). Using multivariate logistic regression, womens age, PE for 2 days or more, and the number of top-quality embryos were the significant factors for clinical pregnancy rates in FET-NC. CONCLUSION(S) The incidence of PE in FET-NC was similar to that in stimulated cycles. Progesterone elevation for 2 days or more before the LH surge impaired the clinical pregnancy rate of FET-NC, whereas PE on the day of LH surge only did not have such an adverse effect.

A randomized double blind comparison of atosiban in patients undergoing IVF treatment

STUDY QUESTION Does atosiban (oxytocin/vasopressin V1A receptor antagonist), given around embryo transfer improve the live birth rate of women undergoing IVF treatment? SUMMARY ANSWER The use of atosiban around embryo transfer did not improve the live birth rate in a general population of IVF patients. WHAT IS KNOWN ALREADY Uterine contractions in IVF cycles were significantly increased following ovarian stimulation and women with frequent uterine contractions had a lower pregnancy rates. A few observational studies suggested that the use of atosiban around embryo transfer resulted in higher pregnancy rates in women with repeated implantation failure (RIF). A non-randomized trial of IVF patients also reported higher implantation and clinical pregnancy rates after the use of atosiban. STUDY DESIGN, SIZE, DURATION This multi-centre randomized double blind study recruited 800 general subfertile women undergoing IVF treatment between November 2011 and March 2013. Subjects were randomized into the atosiban (n = 400) and placebo (n = 400) groups according to a computer-generated randomization list. PARTICIPANTS/MATERIALS, SETTING, METHODS Subjects were recruited and randomized in the three IVF units in Guangzhou, Hong Kong and Ho Chi Minh City. Women in the atosiban group received i.v. atosiban 30 min before embryo transfer with a bolus dose of 6.75 mg, and the infusion was continued at 18 mg/h for ∼1 h. The dose of atosiban was then reduced to 6 mg/h continued for another 2 h. Those in the placebo group received i.v. normal saline only. The primary outcome measure was the live birth rate. MAIN RESULTS AND THE ROLE OF CHANCE There was no significant difference in the live birth rate between the atosiban and placebo groups (39.8 versus 38.0%, P = 0.612, rate ratio 1.051, 95% confidence interval: 0.884-1.251). No significant differences were found between the two groups in the positive pregnancy test, clinical pregnancy, ongoing pregnancy, miscarriage, multiple pregnancy, ectopic pregnancy rates and implantation rate per woman. Similar results were found between the groups at different IVF centres, with a repeated cycle, presence of uterine fibroids or a serum estradiol level on the day of hCG above the median level. LIMITATIONS, REASONS FOR CAUTION Limitations include the transfer of early cleavage embryos, no measurement of uterine contractions, no documentation of adenomyosis and incomplete tracking of congenital abnormalities in newborns. WIDER IMPLICATIONS OF THE FINDINGS This randomized double blind study demonstrated that the use of atosiban given around embryo transfer did not improve the live birth rate in a general population of IVF patients; therefore atosiban should be given only in the context of clinical research. STUDY FUNDING/COMPETING INTERESTS Centres in Hong Kong and Vietnam received research funding from Ferring, which was not involved in study design, execution, data analysis and manuscript preparation. There are no conflicts of interest. TRIAL REGISTRATION NUMBER ClinicalTrials.gov Identifier: NCT01501214.

Luteal phase support does not improve the clinical pregnancy rate of natural cycle frozen-thawed embryo transfer: a retrospective analysis

OBJECTIVE To evaluate pregnancy outcomes with and without use of luteal phase support (LPS) in frozen-thawed embryo transfer (FET) performed in natural cycles (NC). STUDY DESIGN Retrospective analysis. Before 1st July 2009, two doses of 1500 IU intramuscular human chorionic gonadotrophin were given on the day of FET and 6 days after the transfer. Such practice was stopped after 1st July 2009. The pregnancy outcomes of NC FET with and without LPS were compared. RESULTS A total of 408 NC FET cycles were analysed. Demographic data, embryo quality, clinical pregnancy rates and miscarriage rates were comparable with and without LPS. By univariate logistic regression, the only significant factors predicting the clinical pregnancy rate were the womens age, the number of embryos transferred, the number of top quality embryos before and after cryopreservation, and the average number of blastomeres after thawing. Only the womens age (OR 0.944, 95%C.I. 0.893-0.998, p=0.044) remained to be a significant predictor of clinical pregnancy rate by multivariate logistic regression. CONCLUSION The pregnancy outcomes of NC FET were similar with or without LPS. The womens age was the significant factor affecting the clinical pregnancy rate. A randomised trial should be carried out to confirm the results.

Caesarean scar pregnancy: a 10-year experience.

To review the management and outcome of all women with caesarean scar pregnancy (CSP) at a single centre.

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.

Human chorionic gonadotropin stimulates spheroid attachment on fallopian tube epithelial cells through the mitogen-activated protein kinase pathway and down-regulation of olfactomedin-1

OBJECTIVE To study the effect of human chorionic gonadotropin (hCG) on olfactomedin-1 (Olfm1) expression and spheroid attachment in human fallopian tube epithelial cells in vitro. DESIGN Experimental study. SETTING Reproductive biology laboratory. PATIENT(S) Healthy nonpregnant women. INTERVENTION(S) No patient interventions. MAIN OUTCOME MEASURE(S) Luteinizing hormone/chorionic gonadotropin receptor (LHCGR) and Olfm1 expression in fallopian tube epithelium cell line (OE-E6/E7 cells). OE-E6/E7 cells treated with hCG, U0126 extracellular signal-regulated kinase (ERK) inhibitor, or XAV939 Wnt/β-catenin inhibitor were analyzed by Western blotting, real-time polymerase chain reaction, and in vitro spheroid attachment assay. RESULT(S) Human chorionic gonadotropin increased spheroid attachment on OE-E6/E7 cells through down-regulation of Olfm1 and activation of Wnt and mitogen-activated protein kinase (MAPK) signaling pathways. U0126 down-regulated both MAPK and Wnt/β-catenin signaling pathways and up-regulated Olfm1 expression. XAV939 down-regulated only the Wnt/β-catenin signaling pathway but up-regulated Olfm1 expression. CONCLUSION(S) Human chorionic gonadotropin activated both ERK and Wnt/β-catenin signaling pathways and enhanced spheroid attachment on fallopian tube epithelial cells through down-regulation of Olfm1 expression.

A randomized comparison of pharmacokinetics of a single vaginal dose of dry misoprostol or misoprostol moistened with normal saline or with acetic acid

BACKGROUND The pharmacokinetics of vaginal misoprostol as a dry tablet or as a tablet moistened with normal saline or with acetic acid were studied. METHODS For this study, 42 women requesting termination of pregnancy at gestational age of <12 weeks were recruited and received 400 µg vaginal misoprostol tablets. They were randomized into three groups: (i) dry tablets, (ii) tablets moistened with 3 ml of normal saline and (iii) tablets moistened with 3 ml of 5% acetic acid. Venous blood samples were taken at 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330 and 360 min after misoprostol administration. Misoprostol acid (MPA) was determined in serum samples using gas chromatography/tandem mass spectrometry. RESULTS The serum peak MPA concentration (C(max)) was significantly higher and the time-to-peak concentration (T(max)) was significantly shorter in the normal saline and acetic acid groups, when compared with the dry tablet group. Both areas under the curve at 240 and 360 min (AUC(240) and AUC(360)) of the normal saline and acetic acid groups were also significantly greater than that of the dry tablet group. The coefficients of variation in C(max) and T(max) were highest in the normal saline group, while that of AUC(240) and AUC(360) were highest in the dry tablet group. The C(max) was significantly higher in subjects in the dry tablet group with vaginal pH < 5 than in those with pH 5. There were no significant differences in other pharmacokinetic parameters between subjects with vaginal pH < 5 and those with vaginal pH 5 in all three groups. CONCLUSIONS Vaginal misoprostol tablets moistened with normal saline or 5% acetic acid achieved better absorption than the dry tablet. The use of vaginal misoprostol tablets moistened with normal saline or 5% acetic acid would potentially improve the clinical efficacy of misoprostol. HKClinicalTrials.com registration: HKCTR-821.

A randomized, controlled, double‐blinded trial of local lidocaine gel and intrauterine lidocaine infusion for pain relief during saline infusion sonogram

To evaluate the efficacy of topical lidocaine gel and intrauterine lidocaine infusion administered prior to saline contrast sonohysterography (SCSH) in reducing pain level during the procedure.