luteal support
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2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ziqi Jin ◽  
Jingdi Li ◽  
EnTong Yang ◽  
Hao Shi ◽  
Zhiqin Bu ◽  
...  

Abstract Background To investigate whether the endometrial thickness change ratio from the progesterone administration day to the blastocyst transfer day is associated with pregnancy outcomes in a single frozen-thawed euploid blastocyst transfer cycle. Methods All patients used natural cycles with luteal support for endometrial preparation and selected a single euploid blastocyst for transfer after a biopsy for preimplantation genetic testing. The endometrial thickness was measured by transvaginal ultrasound on the progesterone administration day and the transfer day, the change in endometrial thickness was measured, and the endometrial thickness change ratio was calculated. According to the change rate of endometrial thickness, the patients were divided into three groups: the endometrial thickness compaction group, endometrial thickness non-change group and endometrial thickness expansion group. Among them, the endometrial thickness non-change and expansion groups were combined into the endometrial thickness noncompaction group. Results Ultrasound images of the endometrium in 219 frozen-thawed euploid blastocyst transfer cycles were evaluated. The clinical pregnancy rate increased with the increase in endometrial thickness change ratio, while the miscarriage rate and live birth rate were comparable among the groups. The multiple logistic regression results showed that in the fully adjusted model a higher endometrial thickness change ratio (per 10%) was associated with a higher clinical pregnancy rate (adjusted odds ratio [aOR] 1.29; 95% confidence interval [CI], 1.01–1.64; P = .040). Similarly, when the patients were divided into three groups according to the change rate of endometrial thickness, the endometrial thickness noncompaction group had a significant positive effect on the clinical pregnancy rate compared with the endometrial thickness compaction group after adjusting for all covariates. Conclusions In frozen-thawed euploid blastocyst transfer cycles in which the endometrium was prepared by natural cycles with luteal support, the clinical pregnancy rate was higher in cycles without endometrial compaction after progesterone administration.


2021 ◽  
Vol 116 (3) ◽  
pp. e109-e110
Author(s):  
Marianne Dreyer Holt ◽  
Sven Olaf Skouby ◽  
Agnieszka Warzecha ◽  
Nathalie Søderhamn Bülow ◽  
Anne Lis Englund Mikkelsen ◽  
...  

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


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
R Toikkanen ◽  
A Terho ◽  
S Pelkonen ◽  
H Martikainen

Abstract Study question Is the treatment outcome compromised after superovulation for fresh IVF/ICSI in comparison to frozen cycle with spontaneous ovulation and luteal support with progesterone? Summary answer Live birth rate (LBR) is dependent on embryo quality both in the fresh and frozen cycles with no sign of harmful effect of the superovulation. What is known already Freeze-all strategy has been advocated in recent years based on the assumption that luteal phase after superovulation is not optimal for embryo implantation. The effects of variable hormonal treatments, given in association with ART, on the endometrium, are still largely unknown. Therefore, more data is needed in order to optimize the treatment policies. Study design, size, duration This is an observational retrospective single-center cohort study. Data were collected from Oulu University Hospital’s ART-database including a total of 5647 single embryo transfer cycles from years 1995–2020. Patients stimulated with long agonist protocol for IVF/ICSI and day 2–3 transfer were included. Frozen embryo transfer was performed in a natural cycle with an ovulation test used for timing of transfer. Luteal support with progesterone was given for two weeks in all cycles. Participants/materials, setting, methods There were 3053 IVF/ICSI fresh cycles (2237 top and 816 N-top) and 2594 frozen cycles (806 top and 1788 N-top). The main outcome measure was LBR compared between fresh and frozen cycles when either a top or a N-top embryo was transferred. As a secondary outcome, clinical pregnancy rate was investigated. Data on the age and body mass index (BMI) of the patients was available. Student’s T-test was used to compare continuous variables. Main results and the role of chance The groups did not differ regarding the age and BMI of the patients. After the transfer of a top quality embryo the clinical pregnancy rate (35.4 vs. 30.8%; p < 0.05) and LBR (29.4 vs. 25.5%; p not significant) was slightly higher in the fresh cycle. After the transfer of a N-top quality embryo the clinical pregnancy rate (19.9 vs. 19.4%) and LBR (15.9 vs. 15.4%) were similar both in the fresh and frozen cycles. Limitations, reasons for caution This study only represents cleavage stage embryo transfers, and all FETs were performed in a natural cycle. In a retrospective study there may also be residual confounding that could not be excluded. Wider implications of the findings: This study provides further evidence that treatment outcome regarding LBR is not affected by superovulation therapy. Hence, the use of freeze-all strategy is warranted only in cases with a risk of ovarian hyperstimulation syndrome. Trial registration number Not applicable


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
E Riviello ◽  
A Riva ◽  
A Bottai ◽  
G Buzzaccarini ◽  
L Marin ◽  
...  

Abstract Study question Does adjuvant therapy after frozen-thawed embryo-transfer (FRET) with CardioAspirin and Prednisone enhance clinical pregnancy rate (CPR) and live birth rate (LBR)? Summary answer Adjuvant therapy enhanced CPR and LBR in study-group. A significant correlation was found confronting blastocyst FRET in study-group versus controls. What is known already Embryo implantation is a rate-limiting step of FRET cycles. It’s a complex process resulting from a balance between inflammation pathways and maternal immune tolerance. Low-dose aspirin unlocks Prostaglandin-F2 synthesis by Cyclooxygenase–1, thus increasing uterine vascular permeability and attachment reaction while reducing vasoconstriction. Pregnancy results from a balance between helper and regulatory T-cells (Treg), the latter protect the embryo from maternal immune attack. Treg cells’ immunosuppressive function is pivotal in pregnancy establishment. Prednisone increases the proportion of Treg cells thus inhibiting inflammation. Many therapy schedules for implantation enhancement are currently used worldwide, although there is no consistent shared evidence. Study design, size, duration Retrospective cohort-control study including 237 subjects who underwent FRET after artificial endometrial-preparation from January 2018 to March 2020. Estrogenic stimulation was either oral or transdermic. The study-group received luteal support (vaginal Progesterone 600 mg/die) and adjuvant therapy (CardioAspirin and Prednisone 25–5 mg); the control-group received luteal support only. Pregnancy test (PT) was scheduled 10–14 days post-transfer (blastocysts or cleavage stage embryos). Second PT and ultrasound were performed 7 days later if the first was positive. Participants/materials, setting, methods Patients referred to Padua University Hospital’s Human Reproduction Pathophysiology Unit. Exclusion criteria: >50/<18 years, fresh embryo-transfer cycles, oocyte-thawing cycles, natural/natural-modified cycles. Male factor was the prevalent fertility issue. Single embryo-transfer was performed in both groups. Mean endometrial thickness was 9 mm trilaminar in both groups. Statistical analysis were carried out using JMP Pro 14 software. Categorical variables were analyzed using Chi-square test or Fisher’s exact test where appropriate. Main results and the role of chance In the study-group, 87 subjects were given luteal support and adjuvant therapy, while in the control-group, 150 subjects received luteal support only. Groups were homogeneous for age, number of embryos transferred, endometrial thickness, endometrial features (trilaminarity) and fertilization tecniques (108 IVF/ 127 ICSI). CPR and LBR were significantly higher in the study-group. CPR was 31.4% in study-group versus 14.8% in controls (p = 0.002), LBR was 27.4% in study-group versus 11.6% in controls (p = 0.002). Since heterogeneity between groups was found regarding the type of embryo transferred (55.3% cleavage-stage versus 44.7% blastocyst, p < 0.01), the groups were split analyzed basing upon the type if embryo transferred. In the cleavage-stage FRET condition no relevant correlation was found between groups. However in blastocyst-FRET group CPR (34.5% study-group versus 18% controls, p = 0.04) and LBR (30.9% study-group versus 12% controls, p = 0.017) were significantly higher in the study-group, thus showing that adjuvant therapy could improve CPR and LBR. Limitations, reasons for caution Limited sample size negatively impacts the study’s power. It would be appropriate to expand the sample to obtain more reliable results. Wider implications of the findings: Although no unanimous consent exists for tout-court adjuvant therapy administration, scientific literature shows that such therapy can help patients with repeated implantation failures or anti-nuclear-antibodies positivity. Assuming that a single-therapy-regimen could perfectly fit all patients is not realistic. We have to move towards patient-tailored adjuvant therapy thinking. Trial registration number Not applicable


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
D Chowdhury ◽  
Y Kopeika

Abstract Study question Can modified luteal support in fresh cycle “rescue” the cumulative live birth rate (CLBR) in high responders who receive agonist trigger? Summary answer Live birth rate in high responders who had agonist trigger in fresh cycle was significantly reduced despite modified luteal support. What is known already Previous studies, including small randomised controlled trials, claimed that good live birth rate could be achieved at fresh transfer in “high responders” who had GnRHa trigger with modified luteal phase support. However, majority of these studies exclude the true high responders (patients with 20 and above oocytes) and average number of collected eggs reported in many of these studies in the range of 9 to 12. The data on outcome of fresh transfer in true high responders is very limited. Study design, size, duration A prospective observational study was conducted in 407 patients, aged 23–42 years who were expected to be at risk of high response (AFC>18, AMH>20 pmol/l) undergoing controlled ovarian stimulation between 2014–2019 triggered either with HCG or GnRH agonist. Live birth rate (LBR) in a fresh and subsequent 3 frozen transfers were compared in groups with different triggers and freeze all. Participants/materials, setting, methods Patients were stimulated in short antagonist protocol. The trigger was chosen based on the background characteristics, peak oestradiol and clinician discretion. Triggering was achieved either with 0.5 mg buserelin (GnRHa) 0.5mgin 230 patients (A) or with 250 mcg of hCG(H) in 177 patients. Modified luteal support included vaginal progesterone, oral oestrogen and 1500 iu of hCG on the day of egg retrieval. The later was omitted with more than 20 oocytes. Main results and the role of chance The mean age, AFC, number of previous cycles, number of embryos transferred were 33.3, 22.4, 0.26 and 1.2 respectively and did not have significant difference between different triggers. Whereas AMH (53 pmol/l (A) vs 43.1 pmol/l (H), P = 0.003), peak oestradiol (15140.74 (A) vs 9738.59 (H), P = 5.59X10–14), and number of oocytes collected (21 vs.17, P = 5.63X10–7) were significantly higher in GnRHa group. Seventeen patients in buserelin group had elective freeze all. Ovarian Hyperstimulation Syndrome (OHSS) rate was 3.9% in buserelin group (more then half of these cases had a bolus of hCG at egg collection; most were mild/moderate). On the other hand, hCG group had 2.5% of OHSS (all severe). Live birth rate in fresh cycle was 31% in hCG and 21% in GnRHa groups. If freeze all was undertaken in fresh cycle after GnRHa trigger, then LBR in the first frozen cycle of this group was 53% (P = 0.003, fresh vs frozen GnRHa group). CLBR was not different between GnRHa and hCG groups (51%). However, this was significantly lower than CLBR in GnRHa trigger freeze all group 76% (P = 0.03) Limitations, reasons for caution The limitation of this study is its non-randomised nature. However, since it is one of the biggest studies for high responders it has a power to minimise bias by adjusting for multiple variables. Wider implications of the findings: Proceeding with fresh transfer in high responders after GnRHa trigger with modified luteal support not only maintains the risk of OHSS (equivalent to hCG group) but also significantly impairs the LBR not compensated even after 3 subsequent frozen embryo transfers. Therefore, freeze-all approach should be preferred in this group. Trial registration number NA


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Y Mizrachi ◽  
E Horowitz ◽  
H Gane. Herman ◽  
J Farhi ◽  
A Raziel ◽  
...  

Abstract Study question Should women receive luteal phase support (LPS) following natural cycle frozen embryo transfer (NC-FET)? Summary answer Progesterone LPS following NC-FET increases the live birth rate. There is no evidence to support the administration of hCG for LPS in these cases. What is known already Whether or not women should receive LPS following NC-FET is highly controversial. Previous studies have shown conflicting results. Study design, size, duration We conducted a systematic search of the literature published in Medline/PubMed, Embase and the Cochrane Library, from January 2000 until December 2020. We included all original English, peer-reviewed articles, irrespective of study-design. The search strategy included keywords related to natural cycle frozen embryo transfer and luteal phase support. Studies reporting the results of artificial or stimulated FET cycles were excluded. Participants/materials, setting, methods Our systematic search generated 395 records. After screening, eight studies were included in the review and seven studies were included in the meta-analysis. Two studies (n = 858) used hCG, and 6 studies (n = 1507) used progesterone for luteal support. Four studies were randomized controlled trials (RCTs), whereas the other four were historic cohort studies. Main results and the role of chance In a meta-analysis using random effects model, hCG administration for LPS did not increase the clinical pregnancy rate (two studies, OR 0.85, 95% CI 0.64–1.14). On the other hand, progesterone LPS was associated with a higher clinical pregnancy rate (five studies, OR 1.48, 95% CI 1.14–1.94), and a higher live birth rate (three studies, OR 1.67, 95% CI 1.19–2.36). Limitations, reasons for caution There was large heterogeneity in progesterone dose and route of administration, as well as the methods used for ovulation detection and triggering. Moreover, only four studies were randomized. Finally, both studies examining the use of hCG for LPS were performed by the same group of researchers in a single center. Wider implications of the findings: The available evidence indicates that progesterone administration for LPS is beneficial following natural cycle frozen embryo transfer. There is no evidence to support the administration of hCG for LPS in these cases. Additional Large RCTs are necessary in order to improve the quality of evidence and validate our findings. Trial registration number PROSPERO ID: CRD42020199045


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Maren Shapiro ◽  
Phillip Romanski ◽  
Ann Thomas ◽  
Andrea Lanes ◽  
Elena Yanushpolsky

Abstract Background A number of studies have looked at dual triggers with hCG and GnRH agonist (GnRHa) in varying doses, but the question remains: what is the optimal dose of hCG to minimize ovarian hyperstimulation syndrome (OHSS) and still offer adequate pregnancy rates? The purpose of this study was to compare pregnancy and OHSS rates following dual trigger for oocyte maturation with GnRHa and a low-dose hCG versus hCG alone. A secondary objective was the assess pregnancy outcomes in subsequent frozen cycles for the same population. Methods A total of 963 women < 41 years old, with a BMI 18–40 kg/m2 and an AMH > 2 ng/mL who underwent fresh autologous in vitro fertilization (IVF) with GnRH antagonist protocol at a University-based fertility center were included in this retrospective cohort study. Those who received a low dose dual trigger with hCG (1000u) and GnRHa (2 mg) were compared to those who received hCG alone (10,000u hCG/250-500 μg Ovidrel). Differences in implantation rates, pregnancy, live birth, and OHSS were investigated. Results The dual trigger group was younger (mean 33.6 vs 34.1 years), had a higher AMH (6.3 vs 4.9 ng/mL,) more oocytes retrieved (18.1 vs 14.9) and a higher fertilized oocyte rate (80% vs 77%) compared with the hCG only group. Yet, the dual trigger group had a lower probability of clinical pregnancy (gestational sac, 43.4% vs 52.8%) and live birth (33.4% vs 45.8%), all of which were statistically significant. There were 3 cases of OHSS, all in the hCG-only trigger group. In subsequent frozen cycles, pregnancy rates were comparable between the two groups. Conclusions The dual trigger group had a better prognosis based on age and AMH levels and had better stimulation outcomes, but significantly worse pregnancy outcomes, suggesting the low dose hCG (1000u) in the dual trigger may not have provided adequate luteal support, compared to an hCG-only trigger (10,000u hCG/250-500 μg Ovidrel). Interestingly, the pregnancy rates were comparable in subsequent frozen cycles, further supporting the hypothesis that the issue lies in inadequate luteal phase support, rather than embryo quality. Based on these findings, our program has changed the protocol to 1500u of hCG in a dual trigger.


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