Eman A. Elgindy

Gonadatrophin suppression to prevent chemotherapy-induced ovarian damage: a randomized controlled trial.

OBJECTIVE: To estimate the effectiveness of gonadotropin-releasing hormone (GnRH) analogues cotreatment in preventing chemotherapy-induced amenorrhea in young breast cancer patients undergoing cyclophosphamide-based chemotherapy. METHODS: One hundred hormone-insensitive breast cancer participants (aged 18-40 years) were recruited from two university-affiliated oncology centers in Egypt. Opting for type of cotreatment was based on available timeframe until start of chemotherapy. Fifty women ready for early chemotherapy were randomized to receive either chemotherapy alone (arm I) or chemotherapy after downregulation (estradiol less than 50 pg/mL) by GnRH antagonist and agonist (arm II). Then, GnRH antagonist was discontinued and agonist was continued until the end of chemotherapy. When chemotherapy was to start later than 10 days after study inclusion, 50 women were randomized to receive either chemotherapy alone (arm III) or chemotherapy after downregulation with GnRH agonist (arm IV). Resumption of menstruation at 12 months after end of chemotherapy was the primary outcome. Postchemotherapy hormonal and ultrasound changes were secondary outcomes. RESULTS: Twelve months after termination of chemotherapy, there were no differences in menstruation resumption rates between GnRH-treated patients and control group individuals in either early (80% in arms I and II, risk ratio 1, 95% confidence interval 0.7-.32; P=1.00) or delayed chemotherapy groups (80% and 84% in arms III and IV, risk ratio 0.95, 95% confidence interval 0.73-1.235; P=.71). There were no differences in hormonal and ultrasound markers between GnRH analogue users and control group individuals. The use of GnRH analogue cotreatment did not predict independently the odds of menstruating at 12 months. CONCLUSION: GnRH analogue cotreatment does not offer a significant protective effect on ovarian function in patients treated by cyclophosphamide-based chemotherapy. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry. www.anzctr.org.au, ACTRN12609001059257. LEVEL OF EVIDENCE: I

Progesterone level and progesterone/estradiol ratio on the day of hCG administration: detrimental cutoff levels and new treatment strategy

OBJECTIVE To identify if there are certain cutoff levels for P and or the P/E(2) ratio on the day of hCG that would be defined as detrimental for occurrence of pregnancy in women with normal ovarian reserve undergoing cleavage-stage embryo transfer (ET). Secondarily, to determine if these same cutoffs might have the same potential negative effect in women undergoing blastocyst ET. DESIGN Prospective cohort study including two randomized cohorts. SETTING Private and university fertility centers. PARTICIPANT(S) A total of 240 women undergoing long agonist protocol with at least four grade 1 day 3 embryos. INTERVENTION(S) Women were randomized in a 1:1 ratio to undergo day 3 or day 5 embryo transfer. MAIN OUTCOME MEASURE(S) Clinical pregnancy rate (CPR) was the primary outcome. RESULT(S) Using receiver operator characteristics, cutoffs for P and P/E(2) ratio were 1.5 ng/mL and 0.55, respectively. Patients with P ≤ 1.5 ng/mL and P/E(2) ≤ 0.55 undergoing cleavage-stage ET had higher CPR. Using multiple regression, P/E(2) ratio was the only independent predictor for pregnancy. The P and P/E(2) cutoffs were not correlated with CPR in blastocyst transfers. CONCLUSION(S) Progesterone >1.5 ng/mL and P/E(2) >0.55 affect the CPR in women undergoing cleavage-stage, but not blastocyst ET. P/E(2) ratio is the only independent prognosticator for cycle outcome in women undergoing cleavage-stage ET.

Blastocyst-stage versus cleavage-stage embryo transfer in women with high oestradiol concentrations: randomized controlled trial

This prospective, randomized, controlled trial tested the hypothesis that delaying embryo transfer to the blastocyst stage can increase the probability of clinical pregnancy and live birth in women with high oestradiol concentrations on the day of human chorionic gonadotrophin (HCG) undergoing intracytoplasmic sperm injection using the long protocol. A total of 200 women with oestradiol >3000 pg/ml on the HCG day with four or more good-quality, day-3 embryos were randomized in a 1:1 ratio to undergo day-3 or day-5 embryo transfer. Clinical pregnancy rates (CPR; 41% versus 59%; relative risk 0.70, 95% CI 0.52–0.93) and ongoing pregnancy/live-birth rates (35% versus 52%; relative risk 0.67, 95% CI 0.46–0.93) were lower in women undergoing cleavage-stage than blastocyst-stage embryo transfer. Using receiver operating characteristic curves, among women undergoing cleavage-stage embryo transfer, a detrimental cut-off value for not achieving pregnancy for oestradiol was 4200 pg/ml, with lower CPR and ongoing pregnancy/live-birth rates (P = 0.006 and 0.02, respectively). No detrimental cut-off value for oestradiol was identified among women undergoing blastocyst-stage embryo transfer. Delaying embryo transfer to the blastocyst stage can increase the probability of pregnancy in women with high oestradiol on the HCG day

Does luteal estradiol supplementation have a role in long agonist cycles

OBJECTIVE To test the hypothesis that the addition of 6 mg estradiol (E2) valerate either orally or vaginally to progesterone (P) for luteal support, can increase the probability of pregnancy in intracytoplasmic sperm injection (ICSI) cycles using the long agonist protocol. DESIGN Prospective open-labeled randomized controlled trial. SETTING Private and university fertility centers. PARTICIPANT(S) Women undergoing ICSI cycles, with controlled ovarian hyperstimulation using long agonist protocol. INTERVENTION(S) On embryo transfer day, participants were randomized to receive, only P (group A, n = 90), P along with 6 mg E(2) valerate either orally (group B, n = 90), or vaginally (group C, n = 90) for luteal support. MAIN OUTCOME MEASURE(S) Clinical pregnancy was the main outcome. luteal serum E(2) and P profiles were the secondary outcomes. RESULT(S) Highest pregnancy rate was achieved in group C (45.56%), it was significantly higher than A (relative risk 1.52, 95% CI: 1.03 to 2.24). Day 0 (hCG day) E2 levels were similar in the three groups. Group A had lower E2 levels on days 7, 10, and 13 and a higher magnitude of E2 decline on days 7 and 10. Similar levels of luteal E2 were documented in groups B and C. P levels were similar in the three groups. CONCLUSIONS(S) Addition of 6 mg E(2) valerate to P support may encumber the sharp decline in luteal E(2) level. It may enhance the probability of pregnancy if administered vaginally.

Towards an optimal luteal support modality in agonist triggered cycles: a randomized clinical trial

STUDY QUESTION In ICSI patients with high risk of ovarian hyperstimulation syndrome (OHSS), are antagonist cycles triggered by gonadotropin releasing hormone (GNRH) agonist with a specialized luteal support regimen associated with comparable ongoing pregnancy rate (OPR) and less OHSS than those triggered by hCG? SUMMARY ANSWER In antagonist ICSI cycles, GnRH agonist triggering with a specialized luteal support regimen is associated with comparable OPR to those triggered by hCG but may be less likely to be associated with OHSS. WHAT IS KNOWN ALREADY In IVF/ICSI protocols, exogenous hCG was used for years as a substitute of the endogenous LH surge. However, because of its longer half life, hCG is associated with more risk of OHSS, especially in high risk women. For this reason, GnRH agonist triggering was introduced. There is, however, no consensus on the best protocol for luteal support on agonist triggered cycles. STUDY DESIGN, SIZE, DURATION Randomized controlled open label trial including 190 participants recruited from June 2015 to March 2016 in a private fertility center. Participants were divided into 2 equal groups; GnRH agonist trigger and hCG trigger. Randomization was done using identical sealed envelope technique. PARTICIPANTS/MATERIALS, SETTING, METHODS One hundred ninety women, predicted to have high response, were randomized on the day of final oocyte maturation into two equal groups: group (A), GnRH agonist trigger followed by specialized regimen (1500 IU hCG) at time of oocyte retrieval plus oral estradiol and intramuscular progesterone during luteal phase; and group (B), 5000 IU of hCG with luteal support (oral estradiol and vaginal progesterone). MAIN RESULTS AND THE ROLE OF CHANCE The 2 groups were comparable in baseline characteristics. OPR per randomized patient was comparable in the 2 groups {49/95 (51.6%) in group A, and 50/95 (52.6%) in group B ((P = 0.88); RR = 0.980, 95% CI: 0.75-1.29)}. Considerable (moderate + severe) OHSS was higher in group B (13/95 [14%] versus 5/95 [5%] P = 0.047; uncorrected Chi-square test). Upon performing multivariate regression analysis for predicting OHSS, number of follicles ≥11 mm on trigger day was the only independent predictor (P = 0.0004). LIMITATIONS, REASONS FOR CAUTION Strict selection criteria limit generalization of results. The study was powered for pregnancy rate not OHSS, so that the strength of evidence on OHSS prediction is weak. WIDER IMPLICATIONS OF THE FINDINGS We recommend the use of GnRH agonist plus the specialized luteal phase support in high responders with high risk of OHSS undergoing IVF/ICSI cycles. This protocol achieved a similar ongoing pregnancy to hCG triggering and may be less likely to result in moderate to severe OHSS. STUDY FUNDING/COMPETING INTEREST(S) None. TRIAL REGISTRATION NUMBER PACTR 201506001132105. TRIAL REGISTRATION DATE 24/6/2015. DATE OF FIRST PATIENT’S ENROLLMENT 26/6/2015.