Additional luteal support might improve IVF outcomes in patients with low progesterone level in middle luteal phase following a GnRH agonist protocol

Author(s):  
Jiongjiong Tu ◽  
Ge Lin ◽  
Fei Gong
2021 ◽  
Vol 14 (3) ◽  
pp. 228
Author(s):  
Andrea Roberto Carosso ◽  
Stefano Canosa ◽  
Gianluca Gennarelli ◽  
Marta Sestero ◽  
Bernadette Evangelisti ◽  
...  

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.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M Safrai ◽  
S Hertsberg ◽  
A Be Meir ◽  
B Reubinoff ◽  
T Imbar ◽  
...  

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


2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Céline Pirard ◽  
Ernest Loumaye ◽  
Pascale Laurent ◽  
Christine Wyns

Background. The aim of this pilot study was to evaluate intranasal buserelin for luteal phase support and compare its efficacy with standard vaginal progesterone in IVF/ICSI antagonist cycles.Methods. This is a prospective, randomized, open, parallel group study. Forty patients underwent ovarian hyperstimulation with human menopausal gonadotropin under pituitary inhibition with gonadotropin-releasing hormone antagonist, while ovulation trigger and luteal support were achieved using intranasal GnRH agonist (group A). Twenty patients had their cycle downregulated with buserelin and stimulated with hMG, while ovulation trigger was achieved using 10,000 IU human chorionic gonadotropin with luteal support by intravaginal progesterone (group B).Results. No difference was observed in estradiol levels. Progesterone levels on day 5 were significantly lower in group A. However, significantly higher levels of luteinizing hormone were observed in group A during the entire luteal phase. Pregnancy rates (31.4% versus 22.2%), implantation rates (22% versus 15.4%), and clinical pregnancy rates (25.7% versus 16.7%) were not statistically different between groups, although a trend towards higher rates was observed in group A. No luteal phase lasting less than 10 days was recorded in either group.Conclusion. Intranasal administration of buserelin is effective for providing luteal phase support in IVF/ICSI antagonist protocols.


Author(s):  
Nathalie F. Wang ◽  
Leif Bungum ◽  
Sven O. Skouby

Abstract The need for luteal phase support in IVF/ICSI is well established. A large effort has been made in the attempt to identify the optimal type, start, route, dosage and duration of luteal phase support for IVF/ICSI and frozen embryo transfer. These questions are further complicated by the different types of stimulation protocols and ovulation triggers used in ART. The aim of this review is to supply a comprehensive overview of the available types of luteal phase support, and the indications for their use. A review of the literature was carried out in the effort to find the optimal luteal phase support regimen with regards to pregnancy related outcomes and short and long term safety. The results demonstrate that vaginal, intramuscular, subcutaneous and rectal progesterone are equally effective as luteal phase support in IVF/ICSI. GnRH agonists and oral dydrogesterone are new and promising treatment modalities but more research is needed. hCG and estradiol are not recommended for luteal phase support. More research is needed to establish the most optimal luteal phase support in frozen embryo transfer cycles, but progesterone has been shown to improve live birth rate in some studies. Luteal phase support should be commenced between the evening of the day of oocyte retrieval, and day three after oocyte retrieval and it should be continued at least until the day of positive pregnancy test. So, in conclusion still more large and well-designed RCT’s are needed to establish the most optimal luteal phase support in each stimulation protocol, and especially in frozen embryo transfer.


1990 ◽  
Vol 2 (4) ◽  
pp. 351 ◽  
Author(s):  
YF Wong ◽  
EP Loong ◽  
KR Mao ◽  
PP Tam ◽  
NS Panesar ◽  
...  

Salivary oestradiol (E2) and progesterone (P) levels have been shown to reflect the biologically active fractions in the serum. The luteal-phase status of stimulated cycles was investigated after in vitro fertilization and embryo transfer (IVF-ET). Thirty patients were randomly allocated to one of three luteal therapy groups: group A had no support, group B had intramuscular P and group C had intramuscular P and human chorionic gonadotrophin (hCG). One pregnancy was achieved in group A, two in group B and three in group C. Significant correlations between salivary and serum levels of E2 and of P in matched samples during luteal phase were found. Salivary E2 levels from luteal day 8 through day 14 and P levels from day 3 through day 14 were significantly higher in the pregnant than in the nonpregnant cycles. Among the nonpregnant cycles, salivary E2 and P levels were significantly higher in group C than in group A or B. These findings suggest that, in stimulated cycles for IVF-ET, determination of salivary E2 and P levels may be used as reliable alternatives to serum concentrations for assessing the luteal phase. Also, the additional hCG has an enhanced luteotrophic effect, as reflected by the higher salivary E2 and P levels, which may lead to a better pregnancy rate.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
B Biscaro ◽  
A R Lorenzon ◽  
E L Motta ◽  
C Gomes

Abstract Study question Is there a difference between IVF outcomes in patients undergoing follicular versus luteal phase ovarian stimulation in different menstrual cycles? Summary answer Number of euploid blastocyst were higher in luteal phase ovarian stimulation IVF cycles. All other outcomes were similar between follicular and luteal phase IVF cycles. What is known already It has been published that human beings can have two or three follicular recruitment waves as observed in animals studies a long time ago. From these findings, several recent studies showed that two egg retrievals at the same menstrual cycle, named as Duo Stim, optimize time and IVF outcomes in women with low ovarian reserve due to more eggs retrieved in a shorter period with consequently higher probability of having good embryos to transfer. However, there is no knowledge about diferences concerning IVF outcomes between folicular and luteal ovarian stimulation, performed at the same women in different menstrual cycles. Study design, size, duration Retrospective, case-control study in a single IVF center. One-hundred-two patients who had two IVF treatments – the first cycle initiating ovarian stimulation at follicular phase (FPS) and the second cycle initiating after a spontaneous ovulation at luteal phase (LPS) – in different menstrual cycles (until 6 months apart) between 2014 and 2020, were included. Statistical analysis was performed with Mann-Whitney test and was considered significant when p ≤ 0.05. Data is represented as mean±SD. Participants/materials, setting, methods Patients underwent two IVF treatments in different menstrual cycles; the FPS IVF treatment was initiating at D2/D3 of menstrual cycle and the LPS treatment started three or four days after spontaneous ovulation, if at least 4 antral follicles were detected. Both IVF treatments were performed with and antagonist protocol and freeze all strategy. The majority of patients presents low ovarian reserve/Ovarian age as primary infertility factor (84.3%). Main results and the role of chance Patient’s mean age was 39.30±3.15 years, BMI (22.66±3.16) and AMH levels (0.85±0.85 ng/mL). Comparison of hormonal levels at the beginning of ovarian stimulation showed differences for FPS vs LPS, as expected: E2 (39.69±31,10 pg/mL vs 177.33±214.26 pg/mL,p&lt; 0.0001) and P4 (0.76±2.47ng/mL vs 3,00±5.00 ng/mL,p&lt; 0.0001). However, E2 and P4 at the day of oocyte maturation trigger were not different between FPS and LPS (1355.24±895.73 pg/mL vs 1133.14±973.01 ng/mL,p=0.0883 and 1.12±1.49 ng/mL vs 2.94±6.51,p=0.0972 respectively). There was no difference for total dose of gonadotrofins (FPS 2786.43±1102.39.01UI vs LPS 2824.12±1188.87UI, p = 0,8578), FSH (FPS 9.50±4.98 vs LPS 11.90±12.99,p=0.7502) and AFC (FPS 7.13±4.25 vs LPS 6.42±4.65,p=0,0944). From 102 patients that started ovarian stimulation, 78 had 1 or more oocyte collect in FPS group and 75 in LPS group: OPU (FPS 4.78±4.93 vs LPS 4.65±5.54,p=0.7889), number of MII (FPS 3.21±3.52 vs LPS 3.40±4.53,p=0.7889). From those, 52 patients performed ICSI in both cycles; fertilization rate 64.9%±28.6% for FPS vs 62.1%±32.4% for LPS,p=0.7899) and blastocyst formation 2.15±2.15 for FPS vs 2.54±2.35,p=0.3496). Data from 25 patients who had embryo biopsy for PGT-A showed similar number of blastocyst biopsed (2.12±1.72 FPS vs 2.48±1.71 LPS,p=0.3101) and a statistically significant difference regarding number of euploid blastocyst (0,20±0,41 FPS vs 0,96±0,93 LPS,p=0,0008). Limitations, reasons for caution This is a retrospective study in a limited number of patients. Therefore, it is not possible to make a definitive conclusion that LPS proportionate higher number of euploid than FPS. More studies are necessary to investigate not only IVF outcomes but also the impact on pregnancy rates. Wider implications of the findings: In our study, LPS protocol after spontaneous ovulation, presents similar IVF outcomes compared to routinely FPS protocol. Intriguingly, the number of euploid blastocyst was significant higher in LPS, which may be further investigated. In this way, LPS is another option of IVF treatment, and may optimize time and treatment results. Trial registration number Not applicable


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