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).

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 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.

Impact of Metformin on IVF Outcomes in Overweight and Obese Women With Polycystic Ovary Syndrome: A Randomized Double-Blind Controlled Trial.

OBJECTIVES: To evaluate the impact of metformin on in vitro fertilization (IVF) outcomes in overweight and obese women with polycystic ovary syndrome (PCOS). METHODS: This was a randomized double-blind placebo-controlled study ( ClinicalTrials.gov : NCT02910817) carried out in a University IVF Center. The study included 102 overweight and obese women (body mass index [BMI] >24 kg/m2) with PCOS who underwent their first fresh autologous IVF-embryo transfer cycle and agreed to participate in the study. The study participants were randomized into 2 groups: metformin group received metformin (1000 mg per day) at the start of controlled ovarian stimulation (COH) until the day of the pregnancy check, and placebo group received placebo tablets in the same duration. The primary outcome measure was the total number of retrieved oocytes. RESULTS: Both groups were homogenous in baseline demographic characteristics. Metformin group versus the placebo group demonstrated decrease in the mean number of the retrieved oocytes (9.06 ± 4.23 vs 16.86 ± 8.3, P < .01) and similar live birth rate (LBR; 25.5% vs 17.6%, P = .34). The number of fertilized oocytes was lower in the metformin group (5.65 ± 2.66 vs 9 ± 4.55, P < .01). However, the fertilization rate was similar in both groups (62.3% vs 53.4%, P = .10). There was no difference in the implantation rate (15.7% vs 11.8%, P = .32), multiple pregnancy rate (13.4% vs 3.9%, P = .08), or miscarriage rate (23.5% vs 35.7%, P = .46). No cases of ovarian hyperstimulation syndrome (OHSS) were observed in both groups. CONCLUSION: Short-term administration of metformin to overweight or obese women with PCOS undergoing IVF decreased number of the retrieved oocytes but did not improve the LBR. SYNOPSIS: Metformin use could decrease the number of retrieved oocytes in overweight and obese women with polycystic ovary syndrome undergoing IVF.

The effect of follicullar fluid pesticides and polychlorinated biphenyls concentrations on intracytoplasmic sperm injection (ICSI) embryological and clinical outcome.

OBJECTIVES: The present study evaluated the correlation between the concentrations of polychlorinated biphenyls (PCBs) and pesticides in the follicular fluid (FF) obtained during intracytoplasmic sperm injection (ICSI) with the ovarian response, endometrial thickness, and embryological and clinical outcomes. DESIGN: Cross-sectional observational study. MATERIALS AND METHODS: Women aged 20 to 38 years (300 infertile couples) presenting to a university-affiliated fertility center were approached to participate in the study. Only 150 couples that underwent ICSI for male factor infertility agreed to participate, and 94 of them had retrieved enough FF samples suitable for laboratory testing. The FF sample was obtained, centrifuged, and stored in liquid nitrogen. Two organochlorine pesticides (OCPs), Lindane and DDT;three organophosphates (OPs);chlorpyrifos;Diazinon; malathion; one Chloroacetanilide (Pretilachlor);two pyrethroids(Bioallethrin and ß-cyfluthrin); and the concentrations of four PCBs, 28, 52, 138, 180, were estimated in the obtained FF samples by using gas chromatography/mass spectrometry. SPSS statistical analysis program (version 17) was used for analysis. Multiple regression analysis was used to correlate the PCBs and pesticides with ICSI outcomes. RESULTS: There were significant negative correlations between FF concentrations of the eight examined pesticides and the four PCBs on the endometrial thickness. However, Pretilachlor, chlorpyrifos, ß-cyfluthrin, and Diazinon were the only toxic agents that negatively correlated with the number of the oocytes retrieved. Fertilization and early embryo cleavage rates were negatively correlated with Pretilachlor and ß-cyfluthrin. Moreover, high concentrations of Lindane,DDT, Diazinon,and chlorpyrifos were significantly associated lower implantation rate. PCB 28 and 180 concentration in the FF was associated with a lower number of retrieved oocytes and fertilization rate, respectively. The number of implanted embryos was negatively correlated with PCB 52 FF concentration. However, the clinical pregnancy rate did not reach the level of significance. CONCLUSION: Higher concentrations of any studied PCBs and pesticides are associated with thinner endometrial thickness. The higher the level of Pretilachlor, ß-cyfluthrin, PCB 28 and 180, the lower the retrieval, fertilization, and embryo cleavage rates. High PCB and pesticide concentrations in the FF adversely affected embryological ICSI outcomes. However, more data are needed to evaluate their effect on the clinical outcome.