scholarly journals Dehydroepiandrosterone (DHEA) role in enhancement and maintenance of implantation (DREAM): randomised double-blind placebo-controlled trial—study protocol

BMJ Open ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. e054251
Author(s):  
Majiyd Abdul Noushin ◽  
Apeksha Sahu ◽  
Swati Singh ◽  
Sankalp Singh ◽  
Kannamannadiar Jayaprakasan ◽  
...  
Keyword(s):  
Informed Consent ◽  
Live Birth ◽  
Ovarian Stimulation ◽  
Birth Rate ◽  
Controlled Trial ◽  
Randomised Trial ◽  
Live Birth Rate ◽  
Control Group ◽  
Double Blinded ◽  
Written Informed Consent

IntroductionDehydroepiandrosterone (DHEA) is an important precursor of androgen and has been studied and researched extensively for improving the various outcome measures of ovarian stimulation in women with advanced age or poor ovarian response. Androgens also play an important role in the enhancement of endometrial and decidual function by regulating both the transcriptome and secretome of the endometrial stromal cells and have a positive effect on various factors like insulin-like growth factor binding protein 1, homeobox genes (HOXA10, HOXA11), secreted phosphoprotein 1, prolactin which are necessary for implantation. It is well-known that the circulating ‘precursor pool’ of DHEA declines with age more so in poor ovarian reserve patients and exogenous supplementation may be beneficial in such cases. This double-blinded randomised controlled trial (RCT) aims to test the hypothesis whether transient targeted supplementation of DHEA as an adjuvant to progesterone in frozen embryo transfer (FET) cycles, for women with low serum testosterone, helps in improving live birth rate.Methods and analysisThis study is planned as a double-blinded, placebo-controlled randomised trial and the sample size, calculated for the primary outcome measure—live birth rate, is 140. All participants will be having a flexible antagonist protocol for controlled ovarian stimulation and an elective freeze-all policy for the embryos as per the hospital protocol after written informed consent. For FET, the endometrium will be prepared by hormone replacement treatment protocol. During the FET cycle, the intervention group will be receiving DHEA 25 mg two times a day for 15 days from the day of starting progesterone supplementation and the control group will be receiving a placebo.Ethics and disseminationThe approval of the study was granted by the Clinical Trials Registry—India and the Institutional Ethical Committee of CRAFT Hospital and Research Center. All participants will provide written informed consent before being randomised into allocated treatment groups. The results will be disseminated to doctors and patients through conference presentations, peer-reviewed publications, social media and patient information booklets.Trial registration numbersCTRI/2020/06/025918; ECR/1044/Inst/KL/2018.

P–586 Clinical outcome in frozen cycles using cryopreserved blastocysts derived from ovarian stimulation with follitropin delta

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
J Havelock ◽  
J C Arce ◽  
X ESTHER-. an. ESTHER
Keyword(s):  
Clinical Outcome ◽  
Live Birth ◽  
Ovarian Stimulation ◽  
Birth Rate ◽  
Clinical Performance ◽  
Randomised Trial ◽  
Survival Rates ◽  
Implantation Rate ◽  
Live Birth Rate ◽  
Follitropin Alfa

Abstract Study question To compare the live birth rate using frozen-thawed blastocysts obtained from ovarian stimulation with individualised follitropin delta dosing to conventional follitropin alfa dosing. Summary answer The live birth rate in cryo cycles conducted within 1 year after ovarian stimulation was comparable for individualised follitropin delta and conventional follitropin alfa treatment. What is known already It has been demonstrated that the follitropin delta (Rekovelle, Ferring Pharmaceuticals) in an individualised dosing regimen based on anti-Müllerian hormone (AMH) level and body weight is non-inferior to conventional follitropin alfa (Gonal-f, Merck Serono) dosing with respect to ongoing pregnancy and ongoing implantation rates in fresh cycles. The individualised approach also reduced the risk of ovarian hyperstimulation syndrome (OHSS) versus the conventional approach. Furthermore, treatment with follitropin delta and follitropin alfa gave comparable pregnancy rates in repeated fresh cycles. Study design, size, duration Analysis of frozen cycles using blastocysts obtained from a randomised trial comparing follitropin delta versus follitropin alfa in 1,326 IVF/ICSI patients (18–40 years) and a subsequent trial of up to two additional ovarian stimulation cycles. The clinical outcome includes women with cryopreserved blastocysts following ovarian stimulation and who underwent frozen cycles within 1 year after starting stimulation in their last cycle. Participants/materials, setting, methods A total of 917 women had at least one Day 5 blastocyst which was vitrified and stored following up to three ovarian stimulation cycles. A started cryo cycle was defined as warming of a blastocyst. After warming, 1–2 blastocysts were transferred in cryo cycles, using natural cycle or programmed regimens. Treatment differences and 95% confidence intervals (CI) were calculated with adjustment for age strata and accounting for repeated cycles within patient. Main results and the role of chance The proportion of women with frozen blastocysts was similar in the two treatment groups, with 69.5% in the follitropin delta group and 68.8% in the follitropin alfa group. Similar postwarming blastocyst survival rates were observed for the two groups, with 87.4% of the warmed blastocysts proceeding to transfer in the follitropin delta group and 88.8% in the follitropin alfa group. About half of the women (48.1% in each treatment group) with frozen blastocysts underwent at least one frozen cycle with transfer within the 1-year period, with an average of 1.5 cycles per woman in the follitropin delta group and 1.6 cycles per woman in the follitropin alfa group. The ongoing implantation rate was 27.6% in the follitropin delta group and 27.8% in the follitropin alfa group (adjusted difference 0.5% [95% CI: –7.1%; 8.2%]). The live birth rate per started cryo cycle was 32.0% in the follitropin delta group and 31.3% in the follitropin alfa group (adjusted difference 1.2% [95% CI: –6.8%; 9.3%]), while the live birth rate per cryo cycle with transfer was 33.2% and 31.9% (adjusted difference 1.9% [95% CI: –6.2%; 10.0%]), respectively. Limitations, reasons for caution The number of blastocysts to be transferred in the frozen cycles as well as the protocol for endometrial preparation was based on local centre practices. Wider implications of the findings: These findings suggest that the follitropin delta and follitropin alfa dosing regimens are equally effective in terms of live birth rate in frozen replacement cycles and add reassuring information to the clinical performance of cryopreserved blastocysts derived from ovarian stimulation with follitropin delta. Trial registration number NCT01956110, NCT01956123.

scholarly journals Endometrial scratching in women with one failed IVF/ICSI cycle—outcomes of a randomised controlled trial (SCRaTCH)

2020 ◽  
Author(s):  
N E van Hoogenhuijze ◽  
F Mol ◽  
J S E Laven ◽  
E R Groenewoud ◽  
M A F Traas ◽  
...  
Keyword(s):  
The Netherlands ◽  
Live Birth ◽  
Birth Rate ◽  
Controlled Trial ◽  
Live Birth Rate ◽  
Control Group ◽  
Live Births ◽  
Icsi Cycle ◽  
Endometrial Scratching ◽  
Randomised Controlled

Abstract STUDY QUESTION Does endometrial scratching in women with one failed IVF/ICSI treatment affect the chance of a live birth of the subsequent fresh IVF/ICSI cycle? SUMMARY ANSWER In this study, 4.6% more live births were observed in the scratch group, with a likely certainty range between −0.7% and +9.9%. WHAT IS KNOWN ALREADY Since the first suggestion that endometrial scratching might improve embryo implantation during IVF/ICSI, many clinical trials have been conducted. However, due to limitations in sample size and study quality, it remains unclear whether endometrial scratching improves IVF/ICSI outcomes. STUDY DESIGN, SIZE, DURATION The SCRaTCH trial was a non-blinded randomised controlled trial in women with one unsuccessful IVF/ICSI cycle and assessed whether a single endometrial scratch using an endometrial biopsy catheter would lead to a higher live birth rate after the subsequent IVF/ICSI treatment compared to no scratch. The study took place in 8 academic and 24 general hospitals. Participants were randomised between January 2016 and July 2018 by a web-based randomisation programme. Secondary outcomes included cumulative 12-month ongoing pregnancy leading to live birth rate. PARTICIPANTS/MATERIALS, SETTING, METHODS Women with one previous failed IVF/ICSI treatment and planning a second fresh IVF/ICSI treatment were eligible. In total, 933 participants out of 1065 eligibles were included (participation rate 88%). MAIN RESULTS AND THE ROLE OF CHANCE After the fresh transfer, 4.6% more live births were observed in the scratch compared to control group (110/465 versus 88/461, respectively, risk ratio (RR) 1.24 [95% CI 0.96–1.59]). These data are consistent with a true difference of between −0.7% and +9.9% (95% CI), indicating that while the largest proportion of the 95% CI is positive, scratching could have no or even a small negative effect. Biochemical pregnancy loss and miscarriage rate did not differ between the two groups: in the scratch group 27/153 biochemical pregnancy losses and 14/126 miscarriages occurred, while this was 19/130 and 17/111 for the control group (RR 1.21 (95% CI 0.71–2.07) and RR 0.73 (95% CI 0.38–1.40), respectively). After 12 months of follow-up, 5.1% more live births were observed in the scratch group (202/467 versus 178/466), of which the true difference most likely lies between −1.2% and +11.4% (95% CI). LIMITATIONS, REASONS FOR CAUTION This study was not blinded. Knowledge of allocation may have been an incentive for participants allocated to the scratch group to continue treatment in situations where they may otherwise have cancelled or stopped. In addition, this study was powered to detect a difference in live birth rate of 9%. WIDER IMPLICATIONS OF THE FINDINGS The results of this study are an incentive for further assessment of the efficacy and clinical implications of endometrial scratching. If a true effect exists, it may be smaller than previously anticipated or may be limited to specific groups of women undergoing IVF/ICSI. Studying this will require larger sample sizes, which will be provided by the ongoing international individual participant data-analysis (PROSPERO CRD42017079120). At present, endometrial scratching should not be performed outside of clinical trials. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by ZonMW, the Dutch organisation for funding healthcare research. J.S.E. Laven reports grants and personal fees from AnshLabs (Webster, Tx, USA), Ferring (Hoofddorp, The Netherlands) and Ministry of Health (CIBG, The Hague, The Netherlands) outside the submitted work. A.E.P. Cantineau reports ‘other’ from Ferring BV, personal fees from Up to date Hyperthecosis, ‘other’ from Theramex BV, outside the submitted work. E.R. Groenewoud reports grants from Titus Health Care during the conduct of the study. A.M. van Heusden reports personal fees from Merck Serono, personal fees from Ferring, personal fees from Goodlife, outside the submitted work. F.J.M. Broekmans reports personal fees as Member of the external advisory board for Ferring BV, The Netherlands, personal fees as Member of the external advisory board for Merck Serono, The Netherlands, personal fees as Member of the external advisory for Gedeon Richter, Belgium, personal fees from Educational activities for Ferring BV, The Netherlands, grants from Research support grant Merck Serono, grants from Research support grant Ferring, personal fees from Advisory and consultancy work Roche, outside the submitted work. C.B. Lambalk reports grants from Ferring, grants from Merck, grants from Guerbet, outside the submitted work. TRIAL REGISTRATION NUMBER Registered in the Netherlands Trial Register (NL5193/NTR 5342). TRIAL REGISTRATION DATE 31 July 2015. DATE OF FIRST PATIENT’S ENROLMENT 26 January 2016.

scholarly journals A randomized triple blind controlled trial comparing the live birth rate of IVF following brief incubation versus standard incubation of gametes

2018 ◽  
Vol 34 (1) ◽  
pp. 100-108 ◽  
Author(s):  
Zhi Qin Chen ◽  
Yu Wang ◽  
Ernest Hung Yu Ng ◽  
Mei Zhao ◽  
Jia Ping Pan ◽  
...  
Keyword(s):  
Live Birth ◽  
Birth Rate ◽  
Controlled Trial ◽  
Live Birth Rate

scholarly journals Ovulation Rate after Metformin and Clomiphene vs Clomiphene Alone in Polycystic Ovary Syndrome (PCOS): A Randomized, Double-Blind, Placebo-Controlled Trial

2020 ◽  
Vol 02 (01) ◽  
pp. 32-36 ◽  
Author(s):  
Georgia Heathcote ◽  
Clare Boothroyd ◽  
Kevin Forbes ◽  
Alan Lee ◽  
Margaret Gregor ◽  
...  
Keyword(s):  
Live Birth ◽  
Birth Rate ◽  
Polycystic Ovary ◽  
Controlled Trial ◽  
Live Birth Rate ◽  
Ovulation Rate ◽  
Miscarriage Rate ◽  
Ovary Syndrome ◽  
Double Blind ◽  
Double Blind Placebo

Background: Polycystic ovary syndrome (PCOS) affects 5%-15% of women of reproductive age and has a negative impact on their fertility. The primary outcome of this study is ovulation rate when standard (immediate release) metformin (MF) is added to clomiphene citrate (CC) in oligoovulatory and anovulatory women with PCOS. Methods: This is a randomized, double-blind, placebo-controlled trial. Twenty-seven women with PCOS (according to the Rotterdam consensus), desiring pregnancy and without another cause of subfertility were recruited from a public hospital outpatient gynecology clinic. Up to six cycles of CC (25-150 mg) plus either MF 500 mg tds (CC+MF) or placebo (CC+Pl) were offered. Student’s t-test, Chi-squared test, and Fisher’s exact test were used for analysis. Results: Thirteen women with up to six cycles each were included in the final analysis. The rate of ovulation and ovulation rate per cycle was similar between women in the CC+MF and CC+Pl groups RR 1.09 (95% CI 0.80-1.49) and RR 0.88 (95% CI 0.63-1.22), respectively as was chemical pregnancy rate RR 1.77 (95% CI 0.58-5.38). The live birth rate was higher in CC+MF RR 6.83 (95% CI 0.83-56.27) and miscarriage rate was lower RR 0.21 (95% CI 0.002-1.07). The number needed to treat for live birth was 10. Conclusion: Use of standard MF, 500 mg tds, when given with CC results in an increase in live birth rate, and a decrease in miscarriage rate.

scholarly journals Trapa bispinosa Roxb. extract lowers advanced glycation end-products and increases live births in older patients with assisted reproductive technology: a randomized controlled trial

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Masao Jinno ◽  
Ryoji Nagai ◽  
Masayoshi Takeuchi ◽  
Aiko Watanabe ◽  
Koji Teruya ◽  
...  
Keyword(s):  
Live Birth ◽  
Birth Rate ◽  
Controlled Trial ◽  
Live Birth Rate ◽  
Endometrial Receptivity ◽  
Developmental Potential ◽  
Live Births ◽  
Cumulative Live Birth ◽  
Glycation End Products

Abstract Background Advanced glycation end-products (AGE), which accumulate with insulin resistance and aging, impair folliculogenesis and may decrease endometrial receptivity. Hishi (Trapa bispinosa Roxb.) extract, a safe herbal medicine, strongly inhibits AGE formation in vitro. We determined whether Hishi lowers AGE and increases live births in older assisted reproductive technology (ART) patients. Methods This prospective randomized open-label controlled trial included 64 patients 38 to 42 years old undergoing ART with or without Hishi extract between June 11, 2015 and July 12, 2019. None had over 2 ART failures, diabetes, uterine anomalies, or exhausted ovarian reserve. After allocation, the Hishi group received Hishi extract (100 mg/day) until late pregnancy or failure. The control group received no extract. Both groups underwent 1 cycle of conventional infertility treatment; 1 long-protocol cycle of ovarian stimulation, oocyte retrieval, in vitro fertilization/intracytoplasmic sperm injection, and fresh embryo transfer (ET); and, if needed, cryopreserved ET until live birth or embryo depletion. Serum AGE were measured before and during ART, as were AGE in follicular fluid (FF). Results Cumulative live birth rate among 32 Hishi patients was 47%, significantly higher than 16% among 31 controls (p<0.01; RR, 4.6; 95% CI, 1.4 – 15.0; 1 control dropped out). Live birth rate per ET, including fresh and cryopreserved, was significantly higher with Hishi (28% in 47 ET vs. 10% in 49 ET; p<0.05; RR, 3.4; 95% CI, 1.1-10.4). Among variables including age, day-3 FSH, anti-Müllerian hormone, and Hishi, logistic regression identified only Hishi as significantly associated with increased cumulative live birth (p<0.05; OR, 5.1; 95% CI, 1.4 - 18.3). Hishi significantly enhanced oocyte developmental potential, improved endometrial receptivity in natural cycles, and decreased AGE in serum and FF. Larger serum AGE decreases with Hishi were associated with more oocytes becoming day-2 embryos. Conclusions Hishi decreased AGE in serum and FF and improved oocyte developmental potential and endometrial receptivity, increasing live births in older patients. Treatment of infertility by AGE reduction represents a new addition to infertility treatment. Therapeutic trials of Hishi for other AGE-associated diseases might be considered. Trial registration UMIN registration in Japan (UMIN000017758) on June 1, 2015. https://www.umin.ac.jp/ctr/index.htm

scholarly journals Comparison of the C Umulative Live Birth Rates After One ART Cycle Including All Subsequent Frozen–thaw Cycles in Women Undergoing IVF Using Progestin Primed Ovarian Stimulation Versus Long GnRH Agonist Protocol

2021 ◽  
Author(s):  
Hong Chen ◽  
Zhi qin Chen ◽  
Ernest Hung Yu Ng ◽  
zili sun ◽  
Zheng wang ◽  
...  
Keyword(s):  
Live Birth ◽  
Gnrh Agonist ◽  
Ovarian Reserve ◽  
Ovarian Stimulation ◽  
Birth Rate ◽  
Live Birth Rate ◽  
Stimulation Protocol ◽  
Birth Rates ◽  
Live Birth Rates ◽  
Cumulative Live Birth

Abstract Background: The efficacy and reproductive outcomes of progestin primed ovarian stimulation protocol (PPOS) were previously compared to rarely used ovarian stimulation protocol and also the live birth rate were reported by per embryo transfer rather than cumulative live birth rates (CLBRs). Does the use of PPOS improve the cumulative live birth rates (CLBRs) and shorten time to live birth when compared to long GnRH agonist protocol in women with normal ovarian reserve?Methods: A retrospective cohort study was designed to include women aged<40 with normal ovarian reserve (regular menstrual cycles, FSH <10 IU/L, antral follicle count >5) undergoing IVF from January 2017 to December 2019. The primary outcome was cumulative live birth rates (CLBRs) within 18 months from the day of ovarian stimulation.Results: A total of 995 patients were analyzed. They used either PPOS (n=509) or long GnRH agonist (n=486) protocol at the discretion of the attending physicians. Both groups had almost comparable demographic and cycle stimulation characteristics except for duration of infertility which was shorter in the PPOS group. In the GnRH agonist group 372 cases (77%) completed fresh embryo transfer, resulting into 218 clinical pregnancies and 179 live birth. The clinical pregnancy rate, ongoing pregnancy, and live birth per transfer were 58.6%, 54.0%, 53.0% respectively. In the PPOS, no fresh transfer was carried out. During the study period, the total number of initiated FET cycles with thawed embryos was 665 in the PPOS group and 259 in the long agonist group. Of all FET cycles, a total of 206/662 (31.1%) cycles resulted in a live birth in the PPOS group versus 110/257 (42.8%) in the long agonist group (OR: 0.727; 95% CI: 0.607–0.871; p<0.001) .The implantation rate of total FET cycles was also lower in the PPOS group compared with that in the agonist group 293/1004 (29.2%) and 157/455 (34.5%) (OR: 0.846; 95% CI: 0.721–0.992; p= 0.041). Cumulative live birth rates after one complete IVF cycle including fresh and subsequent frozen embryo cycles within 18 months follow up were significantly lower in the PPOS group compared that in the long agonist group 206/509 (40.5%) and 307/486 (63.2%), respectively (OR: 0.641; 95% CI: 0.565-0.726). The average time from ovarian stimulation to pregnancy and live birth was significantly shorter in the long agonist group compared to the PPOS group (p<0.01) In Kaplan-Meier analysis, the cumulative incidence of ongoing pregnancy leading to live birth was significantly higher in the long agonist compared in the PPOS group(Log rank test, p<0.001). Cox regression analysis revealed stimulation protocol adopted was strongly associated with the cumulative live birth rate after adjusting other confounding factors (OR =1.917 (1.152-3.190), p=0.012) .Conclusion: Progestin primed ovarian stimulation was associated with a lower cumulative live birth rates and a longer time to pregnancy / live birth than the long agonist protocol in women with a normal ovarian reserve.

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