scholarly journals Effect of vitamin D supplementation on assisted reproduction technology (ART) outcomes and underlying biological mechanisms: protocol of a randomized clinical controlled trial. The “supplementation of vitamin D and reproductive outcome” (SUNDRO) study

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Alessio Paffoni ◽  
Edgardo Somigliana ◽  
Veronica Sarais ◽  
Stefania Ferrari ◽  
Marco Reschini ◽  
...  
Keyword(s):  
Vitamin D ◽  
Pregnancy Rate ◽  
Causal Relation ◽  
Controlled Trial ◽  
Competent Authority ◽  
Vitamin D Supplementation ◽  
Clinical Pregnancy ◽  
Clinical Pregnancy Rate ◽  
Female Fertility ◽  
Controlled Study

Abstract Background Vitamin D plays an important role in human physiology and pathology. The receptor for vitamin D regulates 0.5–5% of the human genome. Accordingly, vitamin D insufficiency has been shown to increase the risk of several diseases. In recent years, based on growing evidence, on a role of vitamin D has been also postulated in reproductive health both in animals and humans, especially in female fertility female fertility. In vitro fertilization success was shown to be higher in women with appropriate reserves of vitamin D. However a causal relation has not been demonstrated and randomized controlled trials testing the effectiveness of vitamin D supplementation in IVF are warranted. Methods This is a multicenter randomized double blinded placebo controlled study aimed at determining the benefits of vitamin D [25(OH)D] supplementation in improving clinical pregnancy rate in women undergoing IVF. Eligible women with a serum level of 25-hydroxyvitamin D [25(OH)D] < 30 ng/ml will be randomized. Recruited women will be given the drug (either 600,000 IU of 25(OH) D or placebo in a single oral administration) at the time of randomization. Two centres will participate and the sample size (700 women) is foreseen to be equally distributed between the two. Patients will be treated according to standard IVF protocols. Discussion The primary aim of the study is the cumulative clinical pregnancy rate per oocyte retrieval. Clinical pregnancy is defined as the presence of at least one intrauterine gestational sac with viable foetus at first ultrasound assessment (3 weeks after a positive human chorionic gonadotropin [hCG] assessment). Secondary outcomes include: 1) clinical and embryological variables; 2) oocyte and endometrium quality at a molecular level. To investigate this latter aspect, samples of cumulus cells, follicular and endometrial fluids will be obtained from a subgroup of 50 age-matched good-prognosis cases and controls. Trial registration The protocol was included in EudraCT on 22nd September 2015 with the registration number assigned ‘2015-004233-27’; it was submitted through the database of the Italian “Osservatorio Nazionale della Sperimentazione Clinica (OsSC)” - (National Monitoring Centre of Clinical Trials) to the National Competent Authority on 8th March 2016 and approved on 23rd June 2016.

scholarly journals Antioxidant pretreatment for male partner before ART for male factor subfertility: a randomized controlled trial

2020 ◽  
Vol 2020 (4) ◽  
Author(s):  
Treasa Joseph ◽  
Mariano Mascarenhas ◽  
Reka Karuppusami ◽  
Muthukumar Karthikeyan ◽  
Aleyamma T Kunjummen ◽  
...  
Keyword(s):  
Pregnancy Rate ◽  
Embryo Transfer ◽  
Controlled Trial ◽  
Male Partner ◽  
Clinical Pregnancy ◽  
Clinical Pregnancy Rate ◽  
Semen Parameters ◽  
Male Factor ◽  
Sperm Dna ◽  
Significant Difference

Abstract STUDY QUESTION Does oral antioxidant pretreatment for the male partner improve clinical pregnancy rate in couples undergoing ART for male factor subfertility? SUMMARY ANSWER There was no significant difference in clinical pregnancy rate following oral antioxidant pretreatment for male partner in couples undergoing ART for male factor subfertility compared to no pretreatment. WHAT IS KNOWN ALREADY Damage to sperm mediated by reactive oxygen species (ROS) contributes significantly to male factor infertility. The ROS-related injury reduces fertilization potential and adversely affects the sperm DNA integrity. Antioxidants act as free radical scavengers to protect spermatozoa against ROS induced damage. During ART, use of sperms which have been exposed to ROS-mediated damage may affect the treatment outcome. Pretreatment with antioxidants may reduce the ROS-mediated sperm DNA damage. Currently, antioxidants are commonly prescribed to men who require ART for male factor subfertility but there is ambiguity regarding their role. STUDY DESIGN, SIZE, DURATION This was an open label, randomized controlled trial conducted at a tertiary level infertility clinic between February 2013 and October 2019. The trial included 200 subfertile couples who were undergoing ART treatment for male factor subfertility. PARTICIPANTS/MATERIALS, SETTING, METHODS Couples were randomized into treatment arm (n = 100) and control arm (n = 100). In the treatment arm, the male partner received oral antioxidants (Vitamin C, Vitamin E and Zinc) for 3 months just prior to the ART cycle. In the control arm, no antioxidant was given to the male partner. The primary outcome was clinical pregnancy rate, while live birth rate (LBR), miscarriage rate and changes in semen parameters were the secondary outcomes. MAIN RESULTS AND THE ROLE OF CHANCE Out of 200 women randomized, 135 underwent embryo transfer as per protocol. Following intention to treat analysis, no significant difference was noted in clinical pregnancy (36/100, 36% vs 26/100, 26%; odds ratio (OR) 1.60, 95% CI 0.87 to 2.93) and LBR (25/100, 25% vs 22/100, 22%; OR 1.18, 95% CI 0.61 to 2.27) between antioxidant and no pretreatment arms. The clinical pregnancy rate per embryo transfer was significantly higher following antioxidant pretreatment (35/64, 54.7% vs 26/71, 36.6%; OR 2.09, 95% CI 1.05 to 4.16) compared to no pretreatment. There was no significant difference in LBR per embryo transfer (25/64, 39.1%, vs 22/71, 31.0%; OR 1.43, 95% CI 0.70 to 2.91) after antioxidant pretreatment versus no pretreatment. The semen parameters of sperm concentration (median, interquartile range, IQR) (18.2, 8.6 to 37.5 vs 20.5, 8.0 to 52.5, million/ml; P = 0.97), motility (median, IQR) (34, 20 to 45 vs 31, 18 to 45%; P = 0.38) and morphology (mean ± SD) (2.0 ± 1.4 vs 2.2 ± 1.5%; P = 0.69) did not show any significant improvement after intake of antioxidant compared to no treatment, respectively. LIMITATIONS, REASONS FOR CAUTION The objective assessment of sperm DNA damage was not carried out before and after the antioxidant pretreatment. Since the clinicians were aware of the group allotment, performance bias cannot be ruled out. WIDER IMPLICATIONS OF THE FINDINGS The current study did not show any significant difference in clinical pregnancy and LBR following antioxidant pretreatment for the male partner in couples undergoing ART for male subfertility. The findings need further validation in a larger placebo-controlled randomized trial. STUDY FUNDING/COMPETING INTEREST(S) This trial has been funded by Fluid Research grant of Christian Medical College, Vellore (internal funding). The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER CTRI/2013/02/003431 TRIAL REGISTRATION DATE 26 February 2013 DATE OF FIRST PATIENT’S ENROLMENT 11 February 2013

scholarly journals Randomized Controlled Study of the Effects of DHEA on the Outcome of IVF in Endometriosis

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Yanxia Zhang ◽  
Meiqing Li ◽  
Lian Li ◽  
Jianghua Xiao ◽  
Zhe Chen
Keyword(s):  
Pregnancy Rate ◽  
Live Birth ◽  
Birth Rate ◽  
Implantation Rate ◽  
Live Birth Rate ◽  
Clinical Pregnancy ◽  
Clinical Pregnancy Rate ◽  
Synthesis Process ◽  
Controlled Study ◽  
Control Group

Objective. To investigate the effect of dehydroepiandrosterone (DHEA) on the outcome of in vitro fertilization (IVF) in patients with endometriosis (EMT). Methods. Female patients diagnosed with EMT in our hospital from May 2018 to May 2019 were selected. The patients were divided into the control group (n = 22) and the DHEA group (n = 22) according to the random number table. Patients in the control group received placebo and patients in the DHEA group received DHEA. Patients in both groups received either DHEA (25 mg) or placebo orally 3 times a day for 90 days from the first day of menstruation. Patients were subsequently treated with an IVF cycle. In the control group, 22 patients completed the first cycle and 13 patients completed the second cycle. In the DHEA group, 22 patients completed the first cycle and 11 patients completed the second cycle. Serum sex hormone levels including serum E2 on hCG day, mean progesterone on hCG day, FSH on day 2, AMH on day 2, and gonadotropin dose were determined using a chemiluminescent immunoassay kit. The number of antral follicles of the bilateral ovaries was counted by transvaginal B-ultrasound, and the maximum length and transverse diameter of the ovaries were measured at the same time, to calculate the average diameter of the ovaries, observe the morphology of endometrium, and measure the thickness of the endometrium. The implantation rate, clinical pregnancy rate, persistent pregnancy rate, and live birth rate were compared between the two groups. Results. There were no significant differences in serum E2, progesterone, endometrial thickness, recovered oocytes, mean number of transferred embryos, and mean score of leading embryo transfer between the DHEA group and the women who completed the first and second cycles ( P > 0.05 ). The AMH, antral follicle count, serum E2 on hCG day, the number of recovered oocytes, fertilized oocytes, and the fertilization rate in the DHEA group were higher than those in the control group ( P < 0.05 ). The doses of FSH on day 2, COH on day 3, and gonadotropin were lower than those in the control group ( P < 0.05 ). There was no significant difference in the total number of embryos, the number of high-quality embryos, and the number of transplanted embryos between the two groups ( P > 0.05 ). The implantation rate, clinical pregnancy rate, persistent pregnancy rate, and live birth rate in the DHEA group were higher than those in the control group ( P < 0.05 ). Conclusion. DHEA can significantly increase serum E2 level and improve IVF outcome by regulating the hormone synthesis process, thus improving oocyte and embryo quality.

P–612 Transdermal testosterone vs. Placebo (lubricant gel) pre-treatment in improving IVF outcomes in diminished ovarian reserve patients (POSEIDON group 3 and 4): a randomised controlled trial

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
K D Nayar ◽  
S Gupta ◽  
R Bhattacharya ◽  
P Mehra ◽  
J Mishra ◽  
...  
Keyword(s):  
Pregnancy Rate ◽  
Controlled Trial ◽  
Implantation Rate ◽  
Clinical Pregnancy ◽  
Clinical Pregnancy Rate ◽  
Miscarriage Rate ◽  
Ongoing Pregnancy Rate ◽  
Testosterone Gel ◽  
Group 3 ◽  
Pre Treatment

Abstract Study question To compare the efficacy of transdermal testosterone with placebo (lubricant gel) in improving IVF outcomes using GnRH antagonist protocol in POSEIDON group 3 and 4 patients. Summary answer Patients receiving pre-treatment with testosterone gel had higher mean number of oocytes retrieved and grade A embryos as compared to the patients receiving lubricant gel. What is known already Diminished ovarian reserve (DOR) is associated with suboptimal ovarian response, higher cycle cancellation rate and lower clinical pregnancy rate following IVF cycles. Various treatment regimens have been devised for management of such patients and use of adjuvants in the form of oral or transdermal androgen is one of them. Androgens improves follicular response to gonadotropin stimulation as well as increase FSH receptor expression in granulosa cells, in turn leading to better oocyte yield and pregnancy rate. Aim was to compare the effect of transdermal testosterone gel with placebo gel on ART outcome in DOR patients (POSEIDON Group 3 and 4). Study design, size, duration A prospective, randomised controlled trial was carried out from 1st September 2019 to 31st October 2020 at a tertiary infertility centre in India. 50 patients fulfilling the criteria of Group 3 and Group 4 of POSEIDON classification were included in the study. Patients with endocrine disorders (thyroid, prolactin), endometrioma, history of surgery on the ovaries, sensitivity to testosterone gel, male factor infertility and deranged liver and renal function tests were excluded. Participants/materials, setting, methods Enrolled patients were randomised into two groups of 25 patients each, one group was pretreated (TTG group) with transdermal testosterone gel, 12.5 mg/day from day 6th of previous cycle to day 2nd of stimulation cycle while patients in other group took lubricant gel for the same duration before stimulation with GnRH antagonist fixed protocol followed by fresh Day 3 transfer. Main results and the role of chance The baseline characteristics of the two groups were comparable. The primary outcome measures were the number of oocytes retrieved and number of grade A embryos formed (according to Istanbul consensus). The secondary outcome measures were implantation rate, clinical pregnancy rate, miscarriage rate and ongoing pregnancy rate. The mean number of oocytes retrieved in TTG group was 5±1.02 which was significantly higher than placebo group–3.5±1.2, (p &lt; 0.001). The mean number of Grade A embryos were also significantly higher (4.78±0.54 vs 3.00±0.23, p &lt; 0.001) in TTG group. The TTG group had higher implantation rate (28% vs 20%, p = 0.49), clinical pregnancy rate (32% vs 18%, p = 0.41), ongoing pregnancy rate (32% vs 16%, p = 0.38) and lower miscarriage rate (0% vs 20%, p = 0.38), however, these differences were not statistically significant. Limitations, reasons for caution The study was done at a single centre with small sample size, replication with more subjects and in different centers is needed. Wider implications of the findings: Pre-treatment with testosterone gel in DOR patients improves ovarian response to stimulation and results in higher number of oocytes retrieved and good quality embryos resulting in improved clinical pregnancy rates. Transdermal testosterone is advantageous because of better bioavailability, easy application, patient friendly and less adverse effects. Trial registration number MCDH/2019/54

scholarly journals Vitamin D supplementation in people with IBS has no effect on symptom severity and quality of life: results of a randomised controlled trial

2021 ◽  
Author(s):  
Claire E. Williams ◽  
Elizabeth A. Williams ◽  
Bernard M. Corfe
Keyword(s):  
Quality Of Life ◽  
Vitamin D ◽  
Symptom Severity ◽  
Controlled Trial ◽  
Community Setting ◽  
Vitamin D Supplementation ◽  
Controlled Study ◽  
Double Blind ◽  
Vitamin D Levels

Abstract Purpose Several small trials suggest a benefit of vitamin D supplementation in irritable bowel syndrome (IBS). The generalisability of these reports is limited by their design and scale. This study aimed to assess whether vitamin D supplementation improved IBS symptoms in a UK community setting. Methods This was a randomised, double-blind, placebo-controlled study. Participants were recruited from the community in winter months between December 2017 and March 2019. 135 participants received either vitamin D (3,000 IU p.d.) or placebo for 12 weeks. The primary outcome measure was change in IBS symptom severity; secondary outcomes included change in IBS-related quality of life. Results The participants were analysed on an intent-to-treat basis. 60% of participants were vitamin D deficient or insufficient at baseline. Although vitamin D levels increased in the intervention arm relative to placebo (45.1 ± 32.88 nmol/L vs 3.1 ± 26.15 nmol/L; p < 0.001). There was no difference in the change of IBS symptom severity between the active and placebo trial arms (− 62.5 ± 91.57 vs – 75.2 ± 84.35, p = 0.426) over time. Similarly there was no difference between trial arms in τhe change in quality of life (− 7.7 ± 25.36 vs – 11.31 ± 25.02, p = 0.427). Conclusions There is no case for advocating use of vitamin D in the management of IBS symptoms. The prevalence of vitamin D insufficiency suggests routine screening and supplementation should be implemented in this population for general health reasons. This trial was retrospectively registered with ISRCTN (ISRCTN13277340) on 24th April 2018 after recruiting had been initiated.

P–375 Intralipid supplementation in women with unexplained recurrent implantation failure and elevated uterine natural killer cell levels - A randomized placebo controlled trial

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Y Dogra ◽  
N Singh ◽  
S Mathur
Keyword(s):  
Pregnancy Rate ◽  
Controlled Trial ◽  
Killer Cell ◽  
Live Birth Rate ◽  
Clinical Pregnancy ◽  
Clinical Pregnancy Rate ◽  
Unk Cells ◽  
Group A ◽  
Group B ◽  
Unk Cell

Abstract Study question Does intralipid supplementation in women with unexplained recurrent implantation failure (RIF) with elevated uterine natural killer cell (uNK) levels improve pregnancy outcomes during IVF? Summary answer Intralipid supplementation appears to improve clinical pregnancy rate in women with unexplained RIF with elevated uNK cell levels. What is known already The increased numbers of uNK cells in peri-implantation endometrium have been reported in women with recurrent miscarriage (RM) and RIF after IVF. However, reports are contradictory when it comes to correlation of increased numbers of uNK cells with pregnancy outcome. Current opinion suggests there is a potential for intralipid therapy in improving reproductive outcome, although data on live birth rate is very limited. No studies have assessed the effect of intralipid on IVF outcomes in RIF women based on elevated uNK cells. Identified studies have all used pNK cell testing as preferred diagnostic tool for analysis of NK cell levels. Study design, size, duration A randomized placebo controlled trial was conducted at Division of Reproductive Medicine at tertiary care institute. Thirty women with RIF and fifty fertile controls with age &lt;35 years having regular menstrual cycles and no hormonal treatment in last 3 months were enrolled in the study from January 2019 to December 2020 for uNK cell testing. Randomization was done using random numbers and sealed envelopes. Only the subjects were masked and allocation concealment was done. Participants/materials, setting, methods Subjects included RIF 20–35 years, normal ovarian reserve, unexplained and tubal factors, normal karyotype and normal uterine cavity. Cut off for uNK cells was derived from fertile controls by immunohistochemical staining of CD56+ cells from midluteal endometrial biopsy sample. Subjects with elevated uNK cell levels were randomized during IVF to group A (Intralipid) or group B ( saline ). The infusion was repeated within one week of positive pregnancy test and then every 2 weeks. Main results and the role of chance The mean age and BMI were comparable between fertile control and study group(29.45±3.3 vs 31.17±3.3 years, 22.97±1.89 vs 23.21±2.2 kg/m2 ;p&gt;0.05). The median uNK cell levels was 7%(used as cut off) in fertile controls and 13.5% in RIF. 18 women (60%, 18/30) with RIF who had elevated uNK cell level (&gt;7%) were randomized. Four women were lost to follow up. The median age, BMI, number of previous failed cycles and duration of infertility were comparable between Group A(n = 7) and Group B(n = 7){30(IQR:27–31) vs 33(IQR:30–34)years, 22.7(IQR:21.08–24.4) vs 22.6(IQR:21.37–24.2)kg/m2, 2(IQR:2–3) vs 2(IQR:2–3), 8(IQR:7–8) vs 8(IQR:7–10)years}. The median FSH, AMH and AFC were 5.86(IQR:5.13–7.67)mIU/l, 2.4(IQR:2.16–6.12)ng/ml, 10(IQR:8–12) in Group A which were comparable with Group B {6.2(IQR:4.78–6.5)mIU/l, 4.8(IQR:2.67–6.25)ng/ml, 12(IQR:12–16) }. All patients underwent antagonist protocol. The clinical pregnancy rate was 57.14%(4/7) in group A which was significantly higher as compared to 28.6%(2/7) in group B(p &lt; 0.05). None of the patients reported any side effects due to intralipid. Limitations, reasons for caution The limitation of present study is its small sample size. However, the study is currently recruiting more RIF patients, and these are the interim results of the same. More RCTs with larger sample size are required to assess the efficacy of intralipid in this specific subset of population. Wider implications of the findings: The present study suggests the beneficial effect of intralipid in women with unexplained RIF with elevated uNK cell levels in increasing the chemical and clinical pregnancy rate. However, ongoing pregnancy rate and live birth rate should be investigated further in this subset of population. Trial registration number CTRI/2019/01/017213

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