Dydrogesterone supplementation in addition to routine micronized progesterone administration for luteal support in cycles triggered with lone GnRH agonist results in an acceptable pregnancy rate and avoids the need to freeze embryos

2021 ◽  
Author(s):  
Myriam SAFRAI ◽  
Shmuel HERTSBERG ◽  
Assaf BEN-MEIR ◽  
Benjamin REUBINOFF ◽  
Tal IMBAR ◽  
...  
Keyword(s):  
Pregnancy Rate ◽  
Gnrh Agonist ◽  
Luteal Support ◽  
Micronized Progesterone

P–667 Dydrogesterone supplementation in cycles triggered with lone GnRH agonist for final oocyte maturation resulted in an acceptable pregnancy rate

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M Safrai ◽  
S Hertsberg ◽  
A Be Meir ◽  
B Reubinoff ◽  
T Imbar ◽  
...  
Keyword(s):  
Pregnancy Rate ◽  
Embryo Transfer ◽  
Gnrh Agonist ◽  
Luteal Phase ◽  
Fresh Embryo Transfer ◽  
Luteal Support ◽  
Luteal Phase Support ◽  
Gnrh Agonist Trigger ◽  
The Mean ◽  
Agonist Trigger

Abstract Study question Can luteal oral Dydrogesterone (Duphaston) supplementation in an antagonist cycle after a lone GnRH agonist trigger rescue the luteal phase, allowing the possibility to peruse with fresh embryo transfer? Summary answer Functionality of the luteal phase in an antagonist cycle after a lone GnRH agonist trigger can be restored by adding Duphaston to conventional luteal support. What is known already Ovarian hyperstimulation syndrome (OHSS) is dramatically reduced when using antagonist cycle with lone GnRH agonist trigger before ovum pick up. This trigger induces short luteinizing hormone (LH) and follicle-stimulating hormone (FSH) peaks, associated with reduced progesterone and estrogen levels during the luteal phase. They cause an inadequate luteal phase and a significantly reduced implantation rate leading to a freeze all practice in those cycles. Study design, size, duration A retrospective cohort study. The study group (n = 123) included women that underwent in vitro fertilization cycles from January 2017 to May 2020. Patients received a GnRH-antagonist with a lone GnRH-agonist trigger due to imminent OSHH. The control group (n = 374) included patients under 35 years old that, during the same time period, underwent a standard antagonist protocol with a dual trigger of a GnRH-agonist and hCG. Participants/materials, setting, methods Study patients were given Dydrogesterone (Duphaston) in addition to micronized progesterone vaginal pills (Utrogestan) for luteal support (Duphaston group). Controls were treated conventionally with Utrogestan for luteal phase support (hCG group). The outcomes measured were pregnancy rate and OHSS events. Main results and the role of chance Our study was the first to evaluate the addition of Duphaston to standard luteal phase support in an antagonist cycle triggered by a lone GnRH agonist before a fresh embryo transfer. The mean number of oocytes retrieved and estradiol plasma levels were significantly higher in the Duphaston group than in the hCG group (16.9 ±7.7 vs. 10.8 ± 5.3 and 11658 ± 5280 pmol/L vs. 6048 ± 3059 pmol/L, respectively). The fertilization rate was comparable between the two groups. The mean number of embryos transferred and the clinical pregnancy rate were also comparable between groups (1.5 ± 0.6 vs 1.5 ± 0.5 and 46.3% vs 40.9%, respectively). No OHSS event was reported in either group. Limitations, reasons for caution This retrospective study may carry an inherent selection and information bias, derived from medical record coding. An additional limitation was the choice of physician for the lone GnRH trigger, which may have introduced a selection bias and another potential caveat was the relatively small sample size of our study groups. Wider implications of the findings: The addition of Duphaston to conventional luteal support could effectively salvage the luteal phase without increasing the risk for OHSS. This enables, to peruse in those cycle, with fresh embryo transfer, avoiding the need to freeze all the embryos and postponed embryo transfer. Leading to lower psychological burden and costs. Trial registration number 0632–20-HMO

scholarly journals Luteal Support with very Low Daily Dose of Human Chorionic Gonadotropin after Fresh Embryo Transfer as an Alternative to Cycle Segmentation for High Responders Patients Undergoing Gonadotropin-Releasing Hormone Agonist-Triggered IVF

2021 ◽  
Vol 14 (3) ◽  
pp. 228
Author(s):  
Andrea Roberto Carosso ◽  
Stefano Canosa ◽  
Gianluca Gennarelli ◽  
Marta Sestero ◽  
Bernadette Evangelisti ◽  
...  
Keyword(s):  
Embryo Transfer ◽  
Chorionic Gonadotropin ◽  
Gnrh Agonist ◽  
Human Chorionic Gonadotropin ◽  
Luteal Phase ◽  
Real Life ◽  
Luteal Support ◽  
Gnrh Agonist Trigger ◽  
High Responders ◽  
Agonist Trigger

The segmentation of the in vitro fertilization (IVF) cycle, consisting of the freezing of all embryos and the postponement of embryo transfer (ET), has become popular in recent years, with the main purpose of preventing ovarian hyperstimulation syndrome (OHSS) in patients with high response to controlled ovarian stimulation (COS). Indeed cycle segmentation (CS), especially when coupled to a GnRH-agonist trigger, was shown to reduce the incidence of OHSS in high-risk patients. However, CS increases the economic costs and the work amount for IVF laboratories. An alternative strategy is to perform a fresh ET in association with intensive luteal phase pharmacological support, able to overcome the negative effects of the GnRH-agonist trigger on the luteal phase and on endometrial receptivity. In order to compare these two strategies, we performed a retrospective, real-life cohort study including 240 non-polycystic ovarian syndrome (PCO) women with expected high responsiveness to COS (AMH >2.5 ng/mL), who received either fresh ET plus 100 IU daily human chorionic gonadotropin (hCG) as luteal support (FRESH group, n = 133), or cycle segmentation with freezing of all embryos and postponed ET (CS group, n = 107). The primary outcomes were: implantation rate (IR), live birth rate (LBR) after the first ET, and incidence of OHSS. Overall, significantly higher IR and LBR were observed in the CS group than in the FRESH group (42.9% vs. 27.8%, p < 0.05 and 32.7% vs. 19.5%, p < 0.05, respectively); the superiority of CS strategy was particularly evident when 16–19 oocytes were retrieved (LBR 42.2% vs. 9.5%, p = 0.01). Mild OHSS appeared with the same incidence in the two groups, whereas moderate and severe OHSS forms were observed only in the FRESH group (1.5% and 0.8%, respectively). In conclusion, in non-PCO women, high responders submitted to COS with the GnRH-antagonist protocol and GnRH-agonist trigger, CS strategy was associated with higher IR and LBR than the strategy including fresh ET followed by luteal phase support with a low daily hCG dose. CS appears to be advisable, especially when >15 oocytes are retrieved.

scholarly journals GnRH agonist and hCG (dual trigger) versus hCG trigger for follicular maturation: a systematic review and meta-analysis of randomized trials

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Kai-Lun Hu ◽  
Siwen Wang ◽  
Xiaohang Ye ◽  
Dan Zhang ◽  
Sarah Hunt
Keyword(s):  
Systematic Review ◽  
Pregnancy Rate ◽  
Live Birth ◽  
Gnrh Agonist ◽  
Birth Rate ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Live Birth Rate ◽  
Follicular Maturation ◽  
Hcg Trigger

Abstract Background Traditionally, final follicular maturation is triggered by a single bolus of human chorionic gonadotropin (hCG). This acts as a surrogate to the naturally occurring luteinizing hormone (LH) surge to induce luteinization of the granulosa cells, resumption of meiosis and final oocyte maturation. More recently, a bolus of gonadotropin-releasing hormone (GnRH) agonist in combination with hCG (dual trigger) has been suggested as an alternative regimen to achieve final follicular maturation. Methods This study was a systematic review and meta-analysis of randomized trials evaluating the effect of dual trigger versus hCG trigger for follicular maturation on pregnancy outcomes in women undergoing in vitro fertilization (IVF). The primary outcome was the live birth rate (LBR) per started cycle. Results A total of 1048 participants were included in the analysis, with 519 in the dual trigger group and 529 in the hCG trigger group. Dual trigger treatment was associated with a significantly higher LBR per started cycle compared with the hCG trigger treatment (risk ratio (RR) = 1.37 [1.07, 1.76], I2 = 0%, moderate evidence). There was a trend towards an increase in both ongoing pregnancy rate (RR = 1.34 [0.96, 1.89], I2 = 0%, low evidence) and implantation rate (RR = 1.31 [0.90, 1.91], I2 = 76%, low evidence) with dual trigger treatment compared with hCG trigger treatment. Dual trigger treatment was associated with a significant increase in clinical pregnancy rate (RR = 1.29 [1.10, 1.52], I2 = 13%, low evidence), number of oocytes collected (mean difference (MD) = 1.52 [0.59, 2.46), I2 = 53%, low evidence), number of mature oocytes collected (MD = 1.01 [0.43, 1.58], I2 = 18%, low evidence), number of fertilized oocytes (MD = 0.73 [0.16, 1.30], I2 = 7%, low evidence) and significantly more usable embryos (MD = 0.90 [0.42, 1.38], I2 = 0%, low evidence). Conclusion Dual trigger treatment with GnRH agonist and HCG is associated with an increased live birth rate compared with conventional hCG trigger. Trial registration CRD42020204452.

scholarly journals Effect of Individualized Progesterone Supplementation for Luteal Support in Frozen-Thawed Cycles on Pregnancy Outcomes

2021 ◽  
pp. 1-6
Author(s):  
Gülşen Doğan Durdağ ◽  
Gizem Bektaş ◽  
Esengül Türkyılmaz ◽  
Halime Göktepe ◽  
Meltem Sönmezer ◽  
...  
Keyword(s):  
Embryo Transfer ◽  
Pregnancy Outcomes ◽  
University Hospital ◽  
Serum Progesterone ◽  
Luteal Support ◽  
Significant Difference ◽  
Lower Limits ◽  
Micronized Progesterone ◽  
Frozen Thawed Embryo Transfer ◽  
Thawed Embryo Transfer

Objective: In frozen-thawed embryo transfer (FET) cycles, preparing a synchronous endometrium for the embryo is essential. Aim of this study is to provide individualized luteal support in hormonally replaced FET cycles, and to evaluate mid-luteal serum progesterone levels and pregnancy outcomes.Study Design: In this prospective cohort study, 30 patients were included in a university hospital in six month-period. Serum progesterone level on embryo transfer day was monitored, and if it was found to be below the lower limits defined by previous studies (10 ng/mL), additional 100 mg intramuscular micronized progesterone was administered once.Mid-luteal progesterone levels and pregnancy outcomes were recorded.Results: There was no significant difference between mid-luteal progesterone levels of the patients whose transfer day progesterone was above and below 10 ng/mL (p=0.481). Although clinical pregnancy rate tended to be higher in patients whose mid-luteal progesterone was above 10 ng/mL, it was also not statistically significant.Conclusion: This is the first study in which vaginal progesterone treatment was supported by intramuscular progesterone according to serum progesterone values for the purpose of individualized progesterone support. Significant difference was not found in pregnancy outcomes. However, further studies are required to optimize management and improve pregnancy rates in hormonally treated FET cycles.

O-109 A first dose-response trial investigating the effects of adding choriogonadotropin beta to follitropin delta in women undergoing ovarian stimulation in a long GnRH agonist protocol

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M Fernandez Sanchez ◽  
H Višnová ◽  
C Blockeel ◽  
A Pinborg ◽  
Y Khalaf ◽  
...  
Keyword(s):  
Pregnancy Rate ◽  
Cell Line ◽  
Gnrh Agonist ◽  
Ovarian Stimulation ◽  
Randomised Trial ◽  
Chinese Hamster ◽  
Ongoing Pregnancy ◽  
Cho Cell ◽  
Ongoing Pregnancy Rate ◽  
Cho Cell Line

Abstract Study question Does addition of choriogonadotropin beta (CG beta) to follitropin delta increase the number of good-quality blastocysts following ovarian stimulation in a long GnRH agonist protocol? Summary answer At the doses investigated, the addition of CG beta reduced the number of intermediate follicles and decreased the number of oocytes and blastocysts. What is known already CG beta is a new recombinant hCG (rhCG) molecule expressed by a human cell line (PER.C6â) with a different glycosylation profile compared to urinary hCG or rhCG derived from a Chinese Hamster Ovary (CHO) cell-line. In the first-in-human trial, the CG beta pharmacokinetics were similar between men and women. In women, the area under the curve (AUC) and the peak serum concentration (Cmax) increased dose proportionally following single and multiple daily doses. In men, a single dose of CG beta provided higher exposure with a longer half-life and proportionately higher testosterone production than rhCG derived from a CHO cell line. Study design, size, duration Placebo-controlled, double-blind, randomised trial (RAINBOW) to explore the efficacy and safety of CG beta as add-on treatment to follitropin delta in women undergoing COS in a long GnRH agonist protocol. The primary endpoint was the number of good-quality blastocysts (grade 3 BB or higher, Gardner and Schoolcraft, 1999). Subjects were randomised to receive either placebo or 1, 2, 4, 8, or 12 µg CG beta added to the daily individualised follitropin delta dose during COS. Participants/materials, setting, methods In total 619 women (30-42 years) with AMH levels between 5 and 35 pmol/L were randomized in equal proportions to the six treatment groups. All subjects were treated with an individualised dose of follitropin delta determined based on AMH (Elecsys AMH Plus Immunoassay) and body weight. Triggering was performed when 3 follicles were ≥17 mm but no more than 25 follicles ≥12 mm were reached Main results and the role of chance The incidence of cycle cancellation (range 0%-2.9%), total follitropin delta dose (mean 112 µg) and duration of stimulation (mean 10 days) were similar across the groups. A reduced number of intermediate follicles (12 to 17 mm) and fewer oocytes (mean range 9.7 to 11.2) were observed for all doses of CG beta compared to the follitropin delta only group (mean 12.5). The mean number of goodquality blastocysts was 3.3 in the follitropin delta group and ranged between 2.1 and 3.0 across the CG beta groups. The incidence of transfer cancellation was higher in the 4, 8 and 12 µg group, mostly as no blastocyst was available for transfer. In the group receiving only follitropin delta, the ongoing pregnancy rate (10-11 weeks after transfer) was high i.e. 43% per started cycle vs 28-39% in CG beta groups and 49% per transfer vs 38-50% in the CG beta groups. In line with the number of collected oocytes, the OHSS incidence was overall lower following follitropin delta with CG beta than following follitropin delta only treatment. Regardless of the dose, CG beta was safe and well-tolerated with low risk of immunogenicity. Limitations, reasons for caution The effect of the unique glycosylation of CG beta and the associated potency implications in women were not known prior to this trial. Further studies will be needed to evaluate potentially lower doses of CG beta for this and/or different indications. Wider implications of the findings The high ongoing pregnancy rate in the follitropin delta group supports the use of individualised follitropin delta dosing in a long GnRH agonist protocol. The differential potency of CG beta may have impaired the growth of intermediate follicles with the investigated doses without affecting the ongoing pregnancy rates per transfer. Trial registration number NCT03564509

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