Co-administration of GnRH agonists with vaginal progesterone compared to vaginal progesterone in luteal phase support of the frozen-thawed embryo transfer cycle: An RCT

Background: Since progesterone alone does not seem to be enough for luteal phase support (LPS), especially in frozen embryo transfer (FET) cycles, so gonadotropin-releasing hormone agonist (GnRH-a) is suggested as an adjuvant therapy in combination with progesterone for LPS. Objective: To evaluate the effects of the administration of GnRH agonists with vaginal progesterone compared to vaginal progesterone alone in luteal phase support of the frozen-thawed embryo transfer cycles. Materials and Methods: In this randomized controlled clinical trial, 240 infertile women who were candidates for FET were evaluated into two groups (n = 120/each). Group I received 400 mg vaginal progesterone twice a day from the time of transfer. The second group received vaginal progesterone and also 0.1 mg diphereline on days 0, 3, and 6 of FET for LPS. Finally, the clinical and ongoing pregnancy rates, and the implantation, and spontaneous abortion rates were compared in two groups. Results: Results showed that there was no significant difference between the mean age of women and the duration of infertility (p = 0.78, p = 0.58, respectively). There were no significant differences between groups in the terms of implantation and spontaneous abortion rates (p = 0.19, p = 0.31, respectively). However, in terms of clinical and ongoing pregnancy rates, the significant differences were seen between groups (p = 0.008 and p = 0.005, respectively). Conclusion: Co-administration of GnRH-a and vaginal progesterone in LPS may be superior to vaginal progesterone alone in women who underwent a frozen-selected embryo transfer cycle. Key words: Luteal phase, Fertilization in vitro, Embryo transfer.

Exploring the Association Between Prostate Cancer Diagnosis per se and use of GnRH Agonists and Diabetes Control in Men with type 2 Diabetes Mellitus: A Nationwide, Population-Based Cohort Study

Background: Gonadotropin Releasing Hormones agonists (GnRH), which are first line treatment for metastatic prostate cancer (PCa), increase risk of type 2 diabetes mellitus (T2DM). This study aims to quantify the association of use of GnRH with diabetes control in PCa men with T2DM.Methods: Nationwide population-based cohort study in the Swedish National Diabetes Register and Prostate Cancer data Base Sweden 4.1, on the association between GnRH and diabetes control in T2DM men with PCa by comparing T2DM men with PCa vs. without PCa, as well as comparing T2DM men with PCa on or not on GnRH. The primary exposure was use of GnRH. Worsening diabetes control was the primary outcome, defined as: 1) increase of HbA1c to 58 mmol/mol or higher; 2) HbA1c increase by 10 mmol/mol or more; 3) Start of antidiabetic drugs or switch to insulin; 4) combine all definitions above. Cox proportional hazards regression was used to analyze the association. Results: There were 5,714 T2DM men with PCa of whom 692 were on GnRH and 28,445 PCa-free men with T2DM with similar baseline characteristics. Diabetes control was worse in men with GnRH vs. PCa-free men (HR: 1.24, 95% CI: 1.13-1.34) as well as compared with PCa men without GnRH (HR:1.58, 95% CI: 1.39-1.80). Conclusion: Use of GnRH in T2DM men with PCa was associated with worse glycemic control. The findings highlight the need to closely monitor diabetes control in men with T2DM and PCa starting GnRH agonists and to limit the duration of their use when possible.

Luteal phase support for in vitro fertilization/intracytoplasmic sperm injection fresh cycles: a systematic review and network meta-analysis

Background Various luteal phase supports (LPSs) have been proven to increase the pregnancy rate in fresh cycles of in vitro fertilization or intracytoplasmic sperm injection; however, there is still significant debate regarding the optimal use of LPS. Methods A systematic review with the use of a network meta-analysis was performed via electronic searching of Ovid MEDLINE, the Cochrane Library, Embase, Web of Science, ClinicalTrials.gov and Google Scholar (up to January 2021) to compare the effectiveness and safety of various LPSs, as well as to evaluate the effects of different initiations of LPSs on pregnancy outcomes. The primary outcomes included live birth and ongoing pregnancy, with the results presented as odds ratios (ORs) with 95% confidence intervals (CIs). Results Eighty-nine randomized controlled trials with 29,625 women comparing 14 interventions or placebo/no LPS treatments were included in the meta-analyses. No significant differences were found in terms of the pregnancy outcomes when LPS was started within 48 h after oocyte retrieval versus a delayed initiation between 48 h and 96 h after oocyte retrieval. The addition of gonadotropin-releasing hormone (GnRH) agonists to progesterone vaginal pessaries showed a significant benefit in terms of live birth (OR 1.39, 95% CI 1.08 to 1.78). Only human chorionic gonadotropin (HCG) was found to be more efficacious than the placebo/no LPS treatment in terms of live birth (OR 15.43, 95% CI 2.03 to 117.12, low evidence). Any active LPSs (except for rectal or subcutaneous progesterone) was significantly more efficacious than the placebo/no LPS treatment in terms of ongoing pregnancy, with ORs ranging between 1.77 (95% CI 1.08 to 2.90) for the vaginal progesterone pessary and 2.14 (1.23 to 3.70) for the intramuscular progesterone treatment. Among the comparisons of efficacy and tolerability between the active treatments, the differences were small and very uncertain. Conclusion Delays in progesterone supplementation until 96 h after oocyte retrieval does not affect pregnancy outcomes. The safety of GnRH agonists during the luteal phase needs to be evaluated in future studies before the applications of these agonists in clinical practice. With comparable efficacy and acceptability, there may be several viable clinical options for LPS.

Retrospective cohort study of androgen deprivation therapy and the risk of diabetes in men with prostate cancer in Lithuania

ObjectivesTo examine the risk of type 2 diabetes in patients with prostate cancer and its association with androgen deprivation therapy (ADT).Design and participantsWe performed a retrospective cohort study of patients diagnosed with prostate cancer in the Lithuanian male population between 1 January 2003 and 31 December 2012 who were identified through the Lithuanian Cancer registry. All prostate cancer cases were linked to the National Health Insurance Fund database to obtain information regarding the diagnosis of diabetes mellitus and information on prescriptions of antiandrogens and gonadotropin-releasing hormone (GnRH) agonists. Patients with prostate cancer were followed up until the diagnosis of type 2 diabetes, or 31 December 2017, or date of death, whichever came first. Cox proportional hazard models were used to estimate the risk of type 2 diabetes in patients with prostate cancer with or without ADT exposure.Results27 580 men were diagnosed with prostate cancer, out of whom 14 502 (52.6%) did not receive ADT and 13 078 (47.4%) were treated with ADT. The incidence of type 2 diabetes for all patients with prostate cancer was 7.4/1000 person-years, for men on GnRH agonists 9.0/1000 person-years and 5.8/1000 person-years for men on antiandrogens. There was an increased risk of developing type 2 diabetes comparing ADT users and non-users (HR=1.49, 95% CI 1.34 to 1.66).ConclusionThis study showed an increased risk of diabetes in patients with prostate cancer treated with ADT in comparison to ADT-free patient cohort. GnRH agonist users showed higher susceptibility, while the group on antiandrogen monotherapy showed no such increase.