The success rate of in vitro fertilisation (IVF) treatment for couples with infertility remains low due to lack of a reliable tool in selecting euploid embryos for transfer. This study aims to ...compare the efficacy in embryo selection based on morphology alone compared with non-invasive preimplantation genetic testing for aneuploidy (niPGT-A) and morphology in infertile women undergoing IVF.
This is a randomised double-blind controlled trial conducted in two tertiary assisted reproduction centres. A total of 500 infertile women will be recruited and undergo IVF as indicated. They will be randomly assigned on day 6 after oocyte retrieval into two groups: the intervention group using morphology and niPGT-A and the control group based on morphology alone. In the control group, blastocysts with the best quality morphology will be replaced first. In the intervention group, blastocysts with the best morphology and euploid result of spent culture medium will be replaced first. The primary outcome is a live birth per the first embryo transfer. The statistical analysis will be performed with the intention to treat and per protocol.
Ethics approval was sought from the institutional review board of the two 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.
NCT04474522.
IntroductionLow 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 analysisThis 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 disseminationEthics 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.
Abstract
STUDY QUESTION
Will use of oral progestogen in women with threatened miscarriage in the first trimester reduce the miscarriage rate when compared with placebo?
SUMMARY ANSWER
Use of oral ...progestogen in women with threatened miscarriage in the first trimester did not reduce miscarriage before 20 weeks when compared with placebo.
WHAT IS KNOWN ALREADY
Miscarriage is a common complication of pregnancy and occurs in 15–20% of clinically recognized pregnancies. Use of vaginal progestogens is not effective in reducing miscarriage but there is still no good evidence to support use of oral progestogen for the treatment of threatened miscarriage.
STUDY DESIGN, SIZE, DURATION
This was a randomized double-blind controlled trial. A total of 406 women presenting with threatened miscarriage in the first trimester were recruited from 30 March 2016 to May 2018.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Women attending Early Pregnancy Assessment Clinics because of vaginal bleeding during the first trimester were recruited and randomly assigned to use dydrogesterone 40 mg orally, followed by 10 mg orally three times a day or placebo until 12 completed weeks of gestation or 1 week after the bleeding stopped, whichever was later. The primary outcome was the miscarriage rate before 20 weeks of gestation.
MAIN RESULTS AND THE ROLE OF CHANCE
The two groups of women had comparable age, BMI, number of previous miscarriages, gestation and ultrasound findings at presentation. The miscarriage rate before 20 weeks of gestation was similar in both groups, being 12.8% (26/203) in the progestogen group and 14.3% (29/203) in the placebo group (relative risk 0.897, 95% CI 0.548–1.467; P = 0.772). The live birth rate was 81.3% in the progestogen group versus 83.3% in the placebo group (P = 0.697). No significant differences were found between the two groups in terms of obstetric outcomes and side effects.
LIMITATIONS, REASONS FOR CAUTION
The primary outcome was the miscarriage rate, rather than the live birth rate. Women were recruited from Early Pregnancy Assessment Clinics and those with heavy vaginal bleeding might be admitted into wards directly instead of attending Early Pregnancy Assessment Clinic. The severity of vaginal bleeding was subjectively graded by women themselves. The sample size was not adequate to demonstrate a smaller difference in the miscarriage rate between the progestogen and placebo groups. We did not exclude women with multiple pregnancy, which increased the risk of miscarriage although there was only one set of twin pregnancy in the placebo group.
WIDER IMPLICATIONS OF THE FINDINGS
Use of oral progestogen is not recommended in women with threatened miscarriage in the first trimester.
STUDY FUNDING/COMPETING INTEREST(S)
This study was funded by the Health and Medical Research Fund, HKSAR (reference number 12132341). All authors declared no conflict of interest.
TRIAL REGISTRATION NUMBER
ClinicalTrials.gov with an identifier NCT02128685.
TRIAL REGISTRATION DATE
1 May 2014.
DATE OF FIRST PATIENT'S ENROLMENT
30 March 2016.
To compare the effects of hyaluronic acid (HA)–enriched transfer medium versus standard medium on live birth rate after frozen embryo transfer (FET).
Randomized, double-blind, controlled trial.
Two ...tertiary fertility centers.
Infertile women aged <43 years at the time of in vitro fertilization undergoing FET.
The women were randomly assigned to 2 groups in a 1:1 ratio. The HA group used EmbryoGlue (Vitrolife, Gothenburg, Sweden) with an HA concentration of 0.5 mg/mL, while the control group used supplemented G-2 (Vitrolife) medium with an HA concentration of 0.125 mg/mL.
Live birth rate.
Five hundred fifty women were recruited from April 2016 to April 2018 and included in the intention-to-treat analysis. Eight women in the HA group and 5 women in the control group did not undergo FET because the embryos did not survive on thawing. One woman in the HA group cancelled FET because of fever. One woman in the HA group withdrew and received conventional medium. The 2 groups were similar in demographic characteristics. The live birth rates in the HA group and the control group were comparable (25.5% vs. 25.8%; relative risk 0.99; 95% confidence interval 0.74–1.31). The other clinical outcomes were also similar between the 2 groups. Logistic regression showed that the type of transfer medium was not associated with live birth.
The use of HA-enriched transfer medium does not improve the live birth rate of FET compared with standard medium.
NCT02725827 (ClinicalTrials.gov)
Medio de transferencia enriquecido con ácido hialurónico para transferencia de embriones congelados: Un estudio aleatorizado controlado doble ciego.
Comparar los efectos del medio de transferencia enriquecido con ácido hialurónico (HA) versus el medio convencional en la tasa de nacido vivo con transferencia de embriones congelados (FET).
Estudio aleatorizado controlado doble ciego.
Dos centros terciarios de fertilidad.
Mujeres infértiles de < 43 años al momento de la fertilización in vitro sometidas a FET.
Las mujeres se aleatorizaron a dos grupos en una relación 1:1. El grupo HA utilizó EmbryoGlue (Vitrolife, Gothenburg, Suecia) con una concentración de HA de 0.5 mg/mL, mientras el grupo control utilizó medio G-2 suplementado (Vitrolife) con una concentración de HA de 0.125 mg/mL.
Tasa de nacido vivo.
Quinientas cincuenta mujeres fueron reclutadas entre Abril de 2016 y Abril de 2018 y fueron incluidas en el análisis con intención de tratar. Ocho mujeres en el grupo HA y 5 en el grupo control no fueron sometidas a FET puesto que los embriones no sobrevivieron a la descongelación. Una mujer del grupo HA canceló el FET por fiebre. Una paciente del grupo HA se retiró y recibió medio convencional. Los dos grupos fueron similares en sus características demográficas. Las tasas de nacido vivo en los grupos HA y control fueron comparables (25.5% vs 25.8%; riesgo relativo 0.99; intervalo de confianza del 95% 0.74-1.31). Los demás resultados clínicos también fueron similares entre los 2 grupos. La regresión logística mostró que el tipo de medio de transferencia no estaba asociado con la tasa de nacido vivo.
El uso de medio de transferencia enriquecido con HA no mejora la tasa de nacido vivo de FET comparado con el medio convencional.
Is fentanyl and midazolam non-inferior to pethidine and diazepam in pain relief during oocyte retrieval under conscious sedation?
A randomized double-blinded non-inferiority trial of 170 infertile ...women undergoing oocyte retrieval under conscious sedation in an assisted reproduction centre. The women were randomized to receive intravenously either 0.1 mg fentanyl and 5 mg midazolam or 25 mg pethidine and 5 mg diazepam, plus paracervical block with 10 ml 1% lignocaine. The primary outcome was abdominal pain level during retrieval assessed by linear visual analogue scale from 0–10. Secondary outcomes included vaginal pain levels during and after retrieval and postoperative abdominal pain levels and side-effects, satisfaction level, clinical pregnancy and ongoing pregnancy rates. A pre-defined non-inferiority margin of 1 for the difference in pain levels between two groups was set.
Vaginal and abdominal pain levels during retrieval were significantly lower in the fentanyl and midazolam group compared with the pethidine and diazepam group (per-protocol analysis, vaginal pain: 1.6 versus 4.3; mean difference: –2.7, 95% CI –3.7, –1.8; P < 0.001; abdominal pain: 2.9 versus 5.2; mean difference: –2.3, 95% CI –3.3 to –1.3; P < 0.001 for non-inferiority). No differences were observed in these pain levels after retrieval. Most women experienced no postoperative side-effects. The fentanyl and midazolam group had better sedation level, satisfaction level on pain relief and satisfaction on the overall retrieval procedure than the pethidine and diazepam group. No significant differences were found in clinical pregnancy and ongoing pregnancy rates between the two groups.
The fentanyl and midazolam group had significantly lower vaginal and abdominal pain levels during oocyte retrieval than the pethidine and diazepam group.
Purpose
This study aimed to optimize the non-invasive preimplantation genetic testing for aneuploidy (niPGT-A) in the laboratory by comparing two collection timing of the spent culture medium (SCM), ...two embryo rinsing protocols, and the use of conventional insemination instead of intracytoplasmic sperm injection (ICSI).
Methods
Results of two embryo rinsing methods (one-step vs sequential) and SCM collected on day 5 vs day 6 after retrieval were compared against trophectoderm (TE) biopsies as reference. Results from day 6 SCM in cycles fertilized by conventional insemination were compared with PGT-A using ICSI.
Results
The rate of concordance was higher in day 6 samples than in day 5 samples when the sequential method was used, in terms of total concordance (TC; day 6 vs day 5: 85.0% vs 60.0%,
p
= 0.0228), total concordance with same sex (TCS, 82.5% vs 28,0%,
p
< 0.0001), and full concordance with same sex (FCS, 62.5% vs 24.0%,
p
= 0.0025). The sequential method significantly out-performed the one-step method when SCM were collected on day 6 (sequential vs one-step, TC: 85.0% vs 64.5%,
p
= 0.0449; TCS: 82.5% vs 54.8%,
p
= 0.0113; FCS: 62.5% vs 25.8%,
p
= 0.0021). There was no significant difference in niPGT-A results between cycles fertilized by the conventional insemination and ICSI.
Conclusion
We have shown a higher concordance rate when SCM was collected on day 6 and the embryos were rinsed in a sequential manner. Comparable results of niPGT-A when oocytes were fertilized by conventional insemination or ICSI. These optimization steps are important prior to commencement of a randomized trial in niPGT-A.
Objectives: To compare the maternal characteristics and neonatal outcomes of clavicular fractures in the newborns with diagnosis made in the same admission after delivery versus that made in ...readmission; and to provide reassurance to parents and public that clavicular fracture in the newborn is a self-limiting condition with good prognosis. Methods: All cases of newborns with fractured clavicles in a regional hospital during a 5-year period from 1 January 2006 to 31 December 2010. Results: A total of 188 cases of newborns with clavicular fractures were identified. The overall rate of fractured clavicles in the newborns was 0.65%. The respective rates of fractured clavicles in the newborns after instrumental deliveries and Caesarean section were 3.41% (38/1116) and 0.05% (3/6140). Overall, 68% and 90% of the cases were diagnosed in the first 3 days and within 7 days after birth, respectively; 28% of the cases were diagnosed upon readmission; 20% did not have any physical signs. In our cohort, 6.4% (12/188) of the cases were complicated with Erb’s palsy; all these recovered completely within 6 months. There was no statistically significant difference in the maternal characteristics (except use of oxytocin) between the group diagnosed in the same admission versus that diagnosed at readmission. There were statistically significant differences in the mean gestational age, mean birth weight, proportion of newborns with birth weight of 4000-4999 g, body length, Apgar score <7 at first minute, meconium-stained liquor, incidental diagnosis of fractures, physical signs of fractured clavicles, neonatal jaundice (NNJ), treatment for NNJ, sepsis, and duration of hospitalisation between the two groups. Almost all cases were assessed by orthopaedic surgeons. All cases recovered completely without any neurological deficits. Conclusion: Clavicular fracture in the newborn is not an uncommon condition. Infants delivered by Caesarean section are not ‘immune’ to this birth trauma. The condition has good prognosis, regardless of whether the diagnosis is made in the same admission after delivery or at readmission. Parents should be reassured of the self-limiting nature of this condition.
Combined en bloc liver/pancreas transplantation （CLPT） was used primarily in the treal~nent of otherwise non- resectable upper abdominal malignancy. In fact, a more appropriate indication is in ...patients with liver disease and insulin-dependent diabetes mellitus （IDDM）. Here, we report on two successful cases of CLPT at our hospital. One was a patient with non-resectable advanced liver cancer. The recipient survived for 23 mo and finally died of recurrent tumor. The other was a patient with severe biliary complication after orthotopic liver transplantation and preoperative IDDM. We performed CLPT with a modified surgical technique of preserving the native pancreas. He is currently liver-disease- and insulin-free more than 27 mo post-transplant. Based on our experience in two cases of abdominal cluster transplantation, we describe the technical details of CLPT and a modification of the surgical procedure.
Sarcopenic obesity is associated with higher rates of morbidity and mortality than seen with either sarcopenia or obesity alone. We aimed to define sarcopenic visceral obesity (SVO) using ...CT-quantified skeletal muscle index and visceral-to-subcutaneous adipose tissue ratio and to examine its association with waitlist mortality in patients with cirrhosis. Included were 326 adults with cirrhosis awaiting liver transplantation in the ambulatory setting with available abdominal CT within 6 months from enrollment between February 2015 and January 2018. SVO was defined as patients with sarcopenia (skeletal muscle index <50 cm 2 /m 2 in men and <39 cm 2 /m 2 in women) and visceral obesity (visceral-to-subcutaneous adipose tissue ratio ≥1.21 in men and ≥0.48 in women). The percentage who met criteria for sarcopenia, visceral obesity, and SVO were 44%, 29%, and 13%, respectively. Cumulative incidence of waitlist mortality was higher in patients with SVO compared to patients with sarcopenia without visceral obesity or visceral obesity without sarcopenia at 12 months (40% vs. 21% vs. 12%) (overall logrank p =0.003). In univariable Cox regression, SVO was associated with waitlist mortality (HR: 3.42, 95% CI: 1.58-7.39), which remained significant after adjusting for age, sex, diabetes, ascites, encephalopathy, MELDNa, liver frailty index, and different body compositions (HR: 2.64, 95% CI: 1.11-6.30). SVO was associated with increase waitlist mortality in patients with cirrhosis in the ambulatory setting awaiting liver transplantation. Concurrent loss of skeletal muscle and gain of adipose tissue seen in SVO quantified by CT may be a useful and objective measurement to identify patients at risk for suboptimal pretransplant outcomes.
