IVF/ICSI outcomes between cycles with luteal estradiol (E2) pre-treatment before GnRH antagonist protocol and standard long GnRH agonist protocol: a prospective and randomized study

Objective

To study if luteal E₂ pre-treatment before GnRH antagonist protocol improves IVF/ICSI outcomes compared with standard long GnRH agonist protocol.

Design

A prospective, randomized and controlled study.

Setting

ART center of a state public hospital

Patient(s)

Two hundred twenty infertile women underwent IVF/ICSI treatments.

Intervention(s)

Participants received oral Estradiol Valerate 4 mg/day preceding the IVF cycle from day 21 until day 2 of next cycle before GnRH antagonist protocol (E₂ pre-treatment group n?=?109) or received standard long GnRH agonist protocol as control group (n?=?111).

Main outcome measure(s)

Number of oocytes collected, MII oocytes, fertilization, implantation, live birth and early pregnancy rate, and hormone profiles.

Result(s)

E₂ pre-treatment exerted a significant suppressive effect on FSH but not LH secretion compared with basal FSH and LH levels. In E₂ pre-treatment group serum LH level was significantly higher during COH and serum P was also significantly higher on the day of HCG injection compared with control group. Five patients from E₂ pre-treatment group had elevated LH at all time (≥10 IU/L) and also a concomitantly high P (>1 ng/mL). Two of the five women achieved pregnancy but had early pregnancy loss. Overall, IVF/ICSI outcomes such as implantation, clinical pregnancy and live birth rates were similar between E₂ pre-treatment and control groups.

Conclusion(s)

Luteal E₂ pre-treatment before GnRH antagonist protocol significantly increases serum LH level and incidence rate of premature LH but no significant effect is observed on implantation, clinical pregnancy, live birth and early pregnancy loss rates compared with long GnRH agonist protocol. However, more studies in large numbers of cycles are needed to confirm that increased serum LH level by E₂ pre-treatment during COH has no negative effect on the IVF/ICSI outcomes.     

IVF/ICSI outcomes of the OCP plus GnRH agonist protocol versus the OCP plus GnRH antagonist fixed protocol in women with PCOS: a randomized trial

Objective

To compare the IVF/ICSI outcomes of the long GnRH agonist and the fixed GnRH antagonist protocol in women with PCOS.

Design

Randomized controlled trial.

Setting

Baskent University Department of Obstetrics and Gynecology.

Patients

Three hundred women with PCOS.

Interventions

IVF/ICSI following the long GnRH agonist down-regulation or the fixed GnRH antagonist protocols.

Main outcome measures

Ongoing pregnancy rates.

Results

Ongoing pregnancy rates were 36.4?% in the OCP?+?GnRH agonist group and 35.9?% in the OCP?+?GnRH antagonist group (p?>?0.05). Progesterone levels on the day of hCG (0.76?±?0.71 vs. 0.58?±?0.50), endometrial thickness on the day of hCG (11.57?±?2.50 vs. 10.50?±?2.01), total gonadotropin used (1388.71?±?482.39 vs. 1253.25?±?415.81), and duration of COH (9.07?±?1.96 vs. 8.39?±?1.75) were significantly lower in the OCP?+?GnRH antagonist group.

Conclusion

The OCP?+?long GnRH agonist and the OCP?+?fixed GnRH antagonist protocols yield similar ongoing pregnancy rates in women with PCOS. Although this study consisting three hundred patients, seems to be large enough in a single center, we were not able to reach to the actual size of power analysis which was approximately 3,000.     

GnRH antagonist versus long GnRH agonist protocol in poor IVF responders: a randomized clinical trial

Objective

To compare the efficacy of the long GnRH agonist and the fixed GnRH antagonist protocols in IVF poor responders.

Study design

This was a randomized controlled trial performed in the Iakentro IVF centre, Thessaloniki, from January 2007 to December 2011, concerning women characterised as poor responders after having 0–4 oocytes retrieved at a previous IVF cycle. They were assigned at random, using sealed envelopes, to either a long GnRH agonist protocol (group I) or a GnRH antagonist protocol (group II).

Results

Overall 364 women fulfilled the inclusion criteria and were allocated to the two groups: finally 330 participated in our trial. Of these, 162 were treated with the long GnRH agonist protocol (group I), and 168 with the fixed GnRH antagonist protocol (group II). Numbers of embryos transferred and implantation rates were similar between the two groups (P = NS). The overall cancellation rate was higher in the antagonist group compared to the agonist group, but the difference was not significant (22.15% vs. 15.2%, P = NS). Although clinical pregnancy rates per transfer cycle were not different between the two groups (42.3% vs. 33.1%, P = NS), the clinical pregnancy rate per cycle initiated was significantly higher in the agonist compared to the antagonist group (35.8% vs. 25.6%, P = 0.03).

Conclusions

Although long GnRH agonist and fixed GnRH antagonist protocols seem to have comparable pregnancy rates per transfer in poor responders undergoing IVF, the higher cancellation rate observed in the antagonist group suggests the long GnRH agonist protocol as the first choice for ovarian stimulation in these patients.     

Dual triggering with GnRH agonist plus hCG versus triggering with hCG alone for IVF/ICSI outcome in GnRH antagonist cycles: a systematic review and meta-analysis

Purpose

To summarize available evidence from randomized-controlled trials which have evaluated triggering of final oocyte maturation with concomitant GnRH agonists and hCG in patients undergoing IVF, and to analyze whether dual triggering is as efficacious as hCG triggering in terms of oocyte and pregnancy outcomes.

Methods

A comprehensive literature search was performed to identify randomized-controlled trials comparing IVF outcomes between women receiving combined administration of hCG with GnRH agonists and those receiving hCG alone for triggering of final oocyte maturation.

Results

Four studies including 527 patients eligible for inclusion in meta-analysis were identified. No significant difference in the number of mature oocytes or fertilized oocytes retrieved was found between groups. Clinical pregnancy rate with dual triggering was significantly higher as compared with hCG-alone triggering (pooled OR?=?0.48, 95% CI 0.31–0.77, P?=?0.002), but there was no significant difference in the ongoing pregnancy rate between groups.

Conclusion

Results of meta-analysis indicate comparable or significantly improved outcomes with the use of GnRH agonists plus hCG as compared with hCG alone for triggering of final oocyte maturation.

     

Ovulation triggering with GnRH agonist vs. hCG in the same egg donor population undergoing donor oocyte cycles with GnRH antagonist: a prospective randomized cross-over trial

Objective  To compare fertilization, implantation and pregnancy rates in donor oocyte cycles triggered for final oocyte maturation with either human chorionic gonadotropin (hCG) or gonadotropin releasing hormone (GnRH) agonist in the same donor population in two sequential stimulation cycles. Design  Prospective randomized cross-over trial. Setting  Private infertility clinic. Patient(s)  Eighty-eight stimulation cycles in 44 egg donors. Interventions  Controlled ovarian hyperstimulation (COH) with GnRH antagonist protocol triggered with hCG or GnRH agonist (leuprolide acetate 0.15 mg) in the same egg donors in two consecutive cycles. Main outcome measure(s)  The primary outcome measure was the proportion of mature and fertilized oocytes per donor cycle. Secondary outcome measures were implantation and pregnancy rates in the recipients and incidence of ovarian hyperstimulation syndrome (OHSS) in oocyte donors. Result(s)  The proportion of mature oocytes, fertilized oocytes and mean embryo scores were comparable between the two triggering agents. While implantation (36.53% vs, 32.93%), pregnancy (69.08% vs. 68.81%) and clinical pregnancy (41.3% vs. 40.2%) rates were comparable for the groups, the incidence of OHSS was significantly lower in GnRH than in hCG triggered cycles. Conclusion(s)  Fertilization, implantation and pregnancy rates from donor oocytes stimulated with GnRH antagonist protocol were identical for donor cycles triggered with hCG and GnRH agonist. GnRH antagonist triggering in egg donors was associated with lower rates of OHSS. This is the first prospective randomized cross-over study supporting the hypothesis that GnRH agonist is an effective alternative to hCG for the final oocyte maturation in oocyte donor cycles and should be the method of choice, especially for donors with evident risk factors for OHSS.     

Perinatal outcomes in 521 gestations after fresh and frozen cycles: a secondary outcome of a randomized controlled trial comparing GnRH antagonist versus GnRH agonist protocols

Research questionAre perinatal outcomes different after treatment with the gonadotrophin-releasing hormone (GnRH) antagonist versus the long GnRH agonist protocol for IVF?DesignPerinatal outcomes were secondary outcomes in a large Phase IV, dual-centre, open-label, randomized controlled trial to compare GnRH antagonist and long GnRH agonist protocols in women <40 years undergoing their first assisted reproductive technology treatment. Women (n = 1050) were randomized in a ratio 1:1 from January 2009 to December 2013 and followed until December 2016. All fresh and frozen embryo transfer (FET) cycles from a single oocyte aspiration, resulting in a gestation (human chorionic gonadotrophin >10 IU/l) were included (n = 521). Data were analysed to compare preterm birth [PTB] (<37 weeks), very PTB (<32 weeks), low birthweight [LBW] (<2500 g) and very LBW (<1500 g) rates among singleton live births in GnRH antagonist versus agonist protocol.ResultsSimilar perinatal outcomes were found after both protocols. In singletons after fresh embryo transfer, mean gestational age at delivery was 39.1 ± 2.49 versus 39.3 ± 1.90 (P = 0.67) and very PTB rates 1.9% versus 0% (P = 0.17). Mean birthweight was 3264 ± 662 g in the antagonist and 3341 ± 562 g in the agonist group (P = 0.37). LBW was found in 12.4% versus 7% (P = 0.19) and very LBW in 2.9% versus 1% (P = 0.34). In FET cycles, the perinatal outcomes were similar. Small for gestational age and large for gestational age rates were similar in both protocols for singleton live births after fresh and FET.ConclusionsPerinatal outcomes are similar after the GnRH antagonist versus GnRH agonist protocols for IVF. The choice of the GnRH analogue in ovarian stimulation should be based solely on optimizing the chance of pregnancy and not on risks in perinatal outcomes.     

Injection of embryo culture supernatant to the endometrial cavity does not affect outcomes in IVF/ICSI or oocyte donation cycles: a randomized clinical trial

Objective

To evaluate whether intrauterine injection of embryo culture supernatant before embryo transfer has any impact on pregnancy and implantation rates.

Study design

A total of 400 cycles, of which 200 IVF/ICSI and 200 oocyte donor (OD), were randomly assigned to have their uterine cavity injected (group I) or not (group II). Primary endpoints to be studied were pregnancy and implantation rates.

Results

Clinical pregnancy rate per transfer (47.87%, 90/188 versus 48.45%, 94/194) based on transvaginal scan findings at 7 weeks of gestation and implantation rate (25.6% versus 26.5%) were similar in the two groups. The day of embryo transfer, day 3 or day 5, did not affect the final outcome.

Conclusion

Injection of embryo culture supernatant into the uterine cavity, 30 min before the embryo transfer on either day 3 or 5, neither improves nor adversely affects the pregnancy rate in IVF/ICSI or oocyte donation cycles.