Intrauterine injection of HCG before embryo transfer: a parallel, double-blind randomized trial.

RESEARCH QUESTION: Does intrauterine administration of HCG before embryo transfer improve live birth rate during IVF cycles? DESIGN: A parallel, randomized controlled trial conducted between July 2018 and February 2020. Infertile women (n = 181) scheduled for fresh or vitrified-warmed embryo transfer after IVF carried out for any indication were randomized in a 1:1 ratio to receive either HCG (500 IU in 0.1 ml of tissue culture media) or culture media (0.1 ml of tissue culture media) via intrauterine injection 4 min before embryo transfer. In both groups, an intrauterine insemination catheter was used for administering the medication. Primary outcome was live birth, with ongoing pregnancy and clinical pregnancy as secondary outcomes. Analysis was based on intention-to-treat principle. RESULTS: Baseline and cycle characteristics were comparable between the two groups. In the control group, one woman with a confirmed clinical pregnancy was lost to follow-up. Live birth rates were 24% (22/90) in the HCG group versus 19% (17/90) in the control group (RR 1.29, 95% CI 0.74 to 2.27). Clinical pregnancy and ongoing pregnancy rates were 34% versus 26% (RR 1.31, 95% CI 0.84 to 2.04) and 24% versus 19% (RR 1.29, 95% CI 0.74 to 2.27) in the HCG and the control groups, respectively. CONCLUSION: Intrauterine injection of HCG before embryo transfer did not improve live birth rates in women undergoing IVF. As the study was designed to detect a 20% difference between groups, a smaller, clinically important difference could not be ruled out. Treatment outcomes were lower than expected in the control group.

Progesterone/Oestradiol ratio can Better Predict Intracytoplasmic Sperm Injection Outcomes than Absolute Progesterone Level.

BACKGROUND: Several parameters were proposed to predict the impact of premature luteinization on intracytoplasmic sperm injection (ICSI) outcomes such as isolated progesterone (P) level, progesterone to oocyte ratio, and progesterone/estradiol ratio (P/E2). AIM: The aim of this study is to compare the predictive value of P/E2 ratio and isolated P level on the ovulation triggering day for pregnancy outcomes in fresh GnRH antagonist ICSI cycles. SETTINGS AND DESIGN: A retrospective cohort study conducted in a university-affiliated in vitro fertilization center between January 2017 and April 2019. METHODS: The study included women who underwent their first- or second-ranked GnRH antagonist ICSI cycles with day-3 embryo transfer. P/E2 ratio was calculated as (P [ng/mL] × 1000)/E2 (pg/mL). Cutoff values of ≥1.5 ng/ml for high P (HP) and ≥0.55 for HP/E2 ratio were chosen based on the literature. STATISTICAL ANALYSIS: A receiver operating curve was performed to detect the predictability of serum P/E2 and P for the ongoing pregnancy rate. First, patients were divided according to either P level (low P < 1.5 ng/mL and HP ≥1.5 ng/mL) or P/E2 ratio (low P/E2 <0.55 and HP/E2 ≥ 0.55). Patients were further divided into four subgroups: (Group A: HP and HP/E2 ratio, Group B: low P and low P/E2 ratio, Group C: HP only, and Group D: HP/E2 only). A multivariate regression analysis models were used to account for the effect of the cycle confounders on the likelihood of pregnancy. RESULTS: A total of 402 ICSI cycles were analyzed. The area under the curve was 0.67 and 0.59 for P/E2 and P, respectively. P/E2 showed a significant association with ongoing pregnancy (adjusted odds ratios [aOR]: 0.409, 95% confidence interval [CI] 0.222-0.753, P = 0.004) while HP revealed no significant predictive value (aOR: 0.542, 95% CI 0.284-1.036, P = 0.064) after the multivariate analysis. CONCLUSIONS: P elevation may not present as an independent predictor for cycle outcomes. P/E2 ratio has a better prognostic value than P alone in predicting pregnancy of GnRH antagonist cycles.

Effect of Metformin on Premature Luteinization and Pregnancy Outcomes in Intracytoplasmic Sperm Injection-Fresh Embryo Transfer Cycles: A Randomized Double-Blind Controlled Trial.

BACKGROUND: Premature luteinization (PL) is not unusual in in vitro fertilization (IVF) and could not be wholly avoided by using either gonadotropin-releasing hormone (GnRH) agonists or GnRH antagonist regimens. The study aims to evaluate metformin's efficacy in preventing PL in fresh GnRH antagonist intracytoplasmic sperm injection (ICSI) cycles with cleavage-stage embryo transfer. MATERIALS AND METHODS: This randomized, double-blind, placebo-controlled trial was conducted in a tertiary university IVF center. We recruited infertile women who were scheduled to perform their first or second ICSI trial. Eligible women were recruited and randomized in a 1:1 ratio into two groups. Metformin was administered in a dose of 1500 mg per day since the start of contraceptive pills in the cycle antecedent to stimulation cycle until the day of ovulation triggering, while women in the placebo group received a placebo for the same regimen and duration. The primary outcome was the incidence of PL, defined as serum progesterone (P) on the triggering day ≥1.5 ng/mL. Secondary outcomes comprised the live birth, ongoing pregnancy, implantation, and good-quality embryos rates. RESULTS: The trial involved 320 eligible participants (n=160 in each group). Both groups had comparable stimulation days, endometrial thickness, peak estradiol levels, number of oocytes retrieved, and number of mature oocytes. Metformin group experienced lower level of serum P (P<0.001) and incidence of PL (10 vs. 23.6%, P=0.001). Moreover, lower progesterone/estradiol (P/E) ratio and progesterone to mature oocyte index (PMOI) (P=0.002 and P=0.002, respectively) were demonstrated in women receiving metformin. Metformin group generated a better rate of goodquality embryos (P=0.005) and ongoing pregnancy (43.8 vs. 31.8%, P=0.026). A similar trend, though of borderline significance, was observed in the live birth rate in favor of metformin administration (38.15 vs. 27.5%, P=0.04). CONCLUSION: Metformin could be used in patients with potential PL to improve fresh cycle outcomes by preventing PL (Registration number: NCT03088631).

Effect of adjunctive vaginal progesterone after McDonald cerclage on the rate of second-trimester abortion in singleton pregnancy: a randomized controlled trial.

OBJECTIVE: To evaluate the effect of adjunctive use of vaginal progesterone after McDonald cerclage on the rate of second-trimester abortion in singleton pregnancy. METHODS: A randomized controlled trial at Woman's Health Hospital, Assiut University, Egypt, between April 2017 and March 2019 enrolled women eligible for McDonald cerclage. After cerclage, participants were randomly assigned to receive progesterone (400 mg pessary) once daily until 37 weeks or no progesterone. The primary outcome was rate of abortion before 28 weeks. Secondary outcomes included gestational age at delivery, preterm delivery, mean birthweight, Apgar score, and admission to the neonatal intensive care unit (NICU). RESULTS: The rate of spontaneous abortion was higher in the no-progesterone group (P=0.016). Mean gestational age and mean birthweight was higher in the progesterone group (P<0.001 and P=0.002, respectively). The frequency of preterm neonates, neonates with Apgar score less than 7, and admission to NICU was higher in the progesterone group than in the no-progesterone group (P=0.005, P=0.008, and P=0.044, respectively). CONCLUSION: Adjunctive use of vaginal progesterone after McDonald cerclage was found to decrease the frequency of second-trimester abortion and to improve perinatal outcomes in singleton pregnancy. Clinicaltrials.gov: NCT02846909.

Dual trigger using recombinant HCG and gonadotropin-releasing hormone agonist improve oocyte maturity and embryo grading for normal responders in GnRH antagonist cycles: Randomized controlled trial.

OBJECTIVES: To evaluate the effectiveness of dual trigger using gonadotropin-releasing hormone (GnRH) agonist and recombinant human chorionic gonadotropin (rHCG) versus rHCG alone for normal responders in GnRH antagonist intracytoplasmic sperm injection (ICSI) cycles. PATIENTS AND METHODS: The current study was a registered open-labeled randomized controlled trial (clinical trial.gov: NCT02916173) conducted in the ART Unit of a tertiary University hospital between October 2016 and October 2018. The study participants were randomized to either group I (HCG group) or group II (dual trigger group). The primary outcome was the number of mature (MII) oocytes in both groups. RESULTS: Both groups were similar regarding the baseline demographic and clinical characteristics. Women in the dual trigger group had a statistically significant higher number of retrieved oocytes (p = 0.001), MII oocytes (p = 0.01) and the number of grade one embryos (p = 0.04). Both groups were similar regarding the fertilization, implantation, clinical pregnancy and live birth rates in a fresh cycle. Dual trigger group was significantly higher in the clinical pregnancy rate and live birth rate after frozen embryo transfer (p = 0.04, 0.03, respectively). CONCLUSION: Dual trigger by GnRH agonist and rHCG improve the oocyte maturity and embryo grading for normal responders in GnRH antagonist ICSI cycles.

The role of levonorgestrel intra-uterine system in the management of adenomyosis: A systematic review and meta-analysis of prospective studies.

INTRODUCTION: The levonorgestrel intrauterine system (LNG-IUS) is a long-acting hormone-releasing uterine device that has many non-contraceptive benefits. The study aims to assess the safety and efficacy of LNG-IUS in the management of adenomyosis. MATERIAL AND METHODS: We searched the following bibliographic databases: MEDLINE via PubMed, SCOPUS, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE and Google Scholar for the relevant studies which used LNG-IUS in management of patients with clinically or ultrasonographic diagnosed adenomyosis.The main outcome measures are pain score at the end of follow-up, bleeding, symptomatic relief, uterine volume (mL), endometrial thickness (mm) and/or hemoglobin level. RESULTS: Ten prospective studies (patients n = 551) were included. The overall effect estimates showed that the LNG-IUS led to significant reductions in pain score after 12 months (standardized mean difference [SMD[ -3.87, 95% confidence interval [CI] -5.51 to -2.23, P < .001), 24 months (SMD -5.56, 95% CI -9.80 to -1.32, P = .01) and 36 months of insertion (SMD -3.81, 95% CI -4.27 to -3.36, P < .001). Similarly, the Pictorial Blood Assessment Chart (PBAC) showed significant reduction up to 36 months after LNG-IUS insertion (SMD -2.32, 95% CI -2.91 to -1.73, P < .001). The LNG-IUS led to significant reductions in the uterine volume 12 months (SMD -.60, 95% CI -0.88 to -.31, P < .001) and 36 months after insertion (SMD -0.42, 95% CI -0.69 to -0.14, P = .003). CONCLUSIONS: LNG-IUS is a promising and effective option for the management of adenomyosis. Its use effectively reduced the severity of symptoms, uterine volume and endometrial thickness, and improved laboratory outcomes.

The effect of initiating intravenous oxytocin infusion before uterine incision on the blood loss during elective cesarean section: a randomized clinical trial.

Objective: This study compares the effect of starting intravenous oxytocin infusion early before uterine incision versus late after umbilical cord clamping on the blood loss during elective cesarean section (CS). Methods: A single-blinded randomized clinical trial conducted on 200 pregnant women at term (>37 weeks) gestation scheduled for elective CS were assigned to either IV infusion of 30 IU of oxytocin started before uterine incision (Group I) or started immediately after clamping the umbilical cord (Group II). The primary outcome was the mean volume of blood loss during CS. The secondary outcomes included the mean volume of postoperative blood loss, the mean reduction in the hemoglobin and hematocrit levels, the need for additional uterotonics, blood transfusion and additional surgical procedures. Results: The baseline characteristics of both groups are quiet similar. No statistical significant difference between both groups as regard to pre- and postpartum hemoglobin levels (p = .06 and 0.24 respectively) and hematocrit values (p = .12 and .51 respectively). There was a significant reduction in the intraoperative blood loss in group I compared with group II (432.7 ± 90.6 versus 588.9 ± 96.3 mL respectively, p = .001). The need for additional uterotonics was more frequent in the group II (19 women) than in group I (seven women) with statistical significance (p = .002). No differences between both groups regarding the need for blood transfusion or additional surgical procedures. Conclusions: Initiating intravenous oxytocin infusion before uterine incision during elective CS could be associated with reduction in the intraoperative blood loss and the need for additional uterotonics.