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

INTRODUCTION: Dehydroepiandrosterone (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 ANALYSIS: This 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 DISSEMINATION: The 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 NUMBERS: CTRI/2020/06/025918; ECR/1044/Inst/KL/2018.

A comparative evaluation of subendometrial and intrauterine platelet-rich plasma treatment for women with recurrent implantation failure.

OBJECTIVE: To compare the effectiveness of treatment with autologous activated platelet-rich plasma (PRP), administered to either the subendometrium (SE-PRP) or endometrial surface (intrauterine; IU-PRP), against controls. DESIGN: Prospective observational cohort study. SETTING: Tertiary fertility unit. PATIENTS: Women aged <40 years with a history of recurrent implantation failure undergoing frozen embryo transfer (FET) (n = 318). INTERVENTIONS: In SE-PRP, PRP was injected into the subendometrial space transvaginally in the luteal phase of the previous cycle of embryo transfer under ultrasound guidance (n = 55). In IU-PRP, PRP was administered during the index FET cycle when the endometrium was approximately 7 mm (n = 109). Both SE-PRP and IU-PRP groups were administered 300 µg of granulocyte colony-stimulating factor (G-CSF) subcutaneously once a day for 3 days to boost white blood cells (WBC) and growth factor production in the PRP sample. The control group consisted of women who did not choose PRP treatment and underwent standard FET with no intervention (n = 154). MAIN OUTCOME MEASURES: Ongoing pregnancy rate or live birth rate (OPR/LBR) per transfer cycle, clinical pregnancy rate (CPR) per transfer cycle, and miscarriage rate. RESULTS: As a result, OPR/LBR was higher in the SE-PRP (22/55, 40%) and IU-PRP (45/109, 41.3%) groups than that in the control group (34/154, 22.1%). It was similar between the SE-PRP and IU-PRP groups. Moreover, CPR showed a similar trend with a higher rate in the SE-PRP (28/55, 51%) and IU-PRP (57/109, 52.3%) groups than that in the controls (52/154, 33.8%). No statistical difference in the CPR was noted between the SE-PRP and IU-PRP groups. The miscarriage rate was similar in all three groups (14/55, 25.45%; 25/109, 22.23%; and 34/154, 22.07%, respectively). CONCLUSION: In women with a history of recurrent implantation failure, PRP treatment appears to improve FET outcome with an increase in OPR/LBR. However, SE-PRP treatment does not offer any advantage over lesser invasive IU-PRP treatment.