Progesterone levels on the human chorionic gonadotropin trigger day affect the pregnancy rates for embryos transferred at different stages of development in both general and selected IVF/ICSI populations

2020 ◽  
Author(s):  
Philippe Merviel ◽  
Sarah Bouée ◽  
Anne-Solenn Jacamon ◽  
Jean-Jacques Chabaud ◽  
Marie-Thérèse Le Martelot ◽  
...  

Abstract Background Two meta-analyses have shown that pregnancy and birth rates are significantly higher after blastocyst transfer than after cleaved embryo transfer. Other studies have revealed that a serum progesterone level > 1.5 ng/ml on the trigger day is responsible for premature luteinization and is associated with a low pregnancy rate. The objectives of the present study were to determine whether blastocyst transfer gave higher pregnancy rates than cleaved embryo transfer at day 3 in both the general and selected IVF/ICSI populations, and whether the serum progesterone level influenced the pregnancy rate. Method : We studied IVF/ICSI cycles with GnRH antagonist - FSH/hMG protocols in a general population (n = 1210) and a selected “top cycle” population (n = 677), after blastocyst transfer on D5 or cleaved embryo transfer on D3. The selected cycles had to meet the following criteria: female age < 35, first or second cycle, and one or two embryos transferred. We recorded predictive factors for pregnancy and calculated the serum progesterone to oocyte ratio (P/Ooc), the serum progesterone to serum estradiol ratio (P/E2), and the serum progesterone to follicle (> 14 mm) index (PFI). Results In the general population, the clinical pregnancy rate was significantly higher after blastocyst transfer (33.3%) than after cleaved embryo transfer (25.3%; p < 0.01). The differences between blastocyst and embryo transfer groups were not significant in the selected population (respectively 35.7% vs. 35.8% for the clinical pregnancy rate). The only predictive factors common to the general and selected populations were the serum progesterone levels on the eve of the trigger day and on the day itself, which were significantly lower in the subgroups of women who became pregnant (p < 0.01). We found a serum progesterone threshold of 0.9 ng/ml, as also reported by other studies. The P/Ooc ratio and the PFI appear to have predictive value for cleaved embryos transfers. Conclusions Blastocyst transfers were associated with higher clinical pregnancy rate than cleaved embryo transfers in a general population but not in a selected population. The serum progesterone levels on the eve of the trigger day and on the day itself predicted the likelihood of pregnancy.

Author(s):  
Akshaya Kumar Mahapatro ◽  
Abhishek Radhakrishan

Background: Purpose of this study was to evaluate the in vitro fertilisation outcome in patients having normal or elevated day-2 serum progesterone level undergone IVF by using GnRH antagonist.Methods: A retrospective study conducted in Institute of Reproductive Medicine, Chennai during January 2013 to March 2014. According to patient’s Day-2 serum progesterone level the total no of cases (N=151) were divided into two groups group-1 (N=116) with progesterone value ≤1.5ng/ml and group-2 (N=35) with progesterone value>1.5ng/ml. Ovarian stimulation was started with recombinant FSH on day 2 and GnRH antagonist injections started from day 6 of stimulation. Total dose of gonadotropins, days of gonadotrophin injections, no of eggs collected, Clinical pregnancy rate and live birth rate were compared between two groups.Results: Two groups were similar with regards to age, BMI, days of gonadotrophins and total doses of gonadotrophins. Incidence of elevated P level was 23.17%. Total pregnancy rate was 36.42%. A non-statistically-significant difference was observed in clinical pregnancy (37.06% vs 34.28%) and live birth (32.75% vs 28.57%) between the normal and elevated progesterone groups.Conclusions: Elevated day-2 serum progesterone level   was associated with lower clinical pregnancy rate but it was not statistically-significant.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
C Maignien ◽  
B Mathilde ◽  
B Valérie ◽  
C Ahmed ◽  
C Charles ◽  
...  

Abstract Study question Is there a relationship between progesterone levels on the day of frozen blastocyst transfer and ongoing pregnancy rate (OPR), in hormonal replacement therapy (HRT) cycles? Summary answer Women undergoing HRT-frozen embryo transfer with progesterone levels≤9.76ng/ml on the day of blastocyst transfer had a significantly lower OPR than those with progesterone levels&gt;9.76 ng/ml. What is known already The importance of serum progesterone levels around the time of frozen embryo transfer (FET) is a burning issue, in view of the growing number of FET worldwide. However, the optimal range of serum progesterone levels is not clearly determined and discrepancies arise from the current literature. Study design, size, duration: Observational cohort study with 915 patients undergoing HRT-FET at a tertiary care university hospital, between January 2019 and March 2020. Participants/materials, setting, methods Patients undergoing single autologous blastocyst FET under HRT using exogenous estradiol and vaginal micronized progesterone for endometrial preparation. Women were only included once during the study period. The serum progesterone level was measured in the morning of the FET, in a single laboratory. The primary endpoint was OPR beyond pregnancy week 12. Statistical analysis was conducted using univariate and multivariate logistic regression models. Main results and the role of chance Mean serum progesterone level on the day of FET was 12.90 ± 4.89 ng/ml). The OPR was 35.5% (325/915) in the overall population. Patients with a progesterone level ≤ 25th percentile (≤9.76ng/ml) had a significantly lower OPR and a higher miscarriage rate (MR) compared with women with progesterone level over Centile 25 (29.6% versus 37.4%; p = 0.033 and 34.8% versus 21.3%; p = 0.008, respectively). After adjustment for the potential confounders in a multivariate analysis, a serum progesterone level ≤ 9.76 ng/ml on the day of FETand FET of a Day 6-blastocyst (versus Day 5-blastocyst) were found as independent risks factor of lower OPR. Limitations, reasons for caution The main limitation of our study is linked to its observational design. Extrapolation of our results to other laboratories, or other routes and/or doses of administering progesterone also needs to be validated. Wider implications of the findings: This study suggests that a minimum serum progesterone level is needed to optimize reproductive outcomes in autologous blastocyst FET, in HRT-cycles. Further studies are needed to evaluate if modifications of progesterone routes and/or doses may improve pregnancy chances, in an approach to individualize the management of ART patients. Trial registration number NA


Author(s):  
Raksha K. Shetty ◽  
Purnima K. Nadkarni ◽  
Pooja P. Singh ◽  
Prabhakar Singh ◽  
Aditi A. Nadkarni ◽  
...  

Background: Elective frozen embryo transfer (FET), has recently increased significantly with improvements in cryopreservation techniques. Observational studies and randomized controlled trials suggested that the endometrium in stimulated cycles is not optimally prepared for implantation; risk of ovarian hyperstimulation syndrome reduced and pregnancy rates increased following FET and perinatal outcomes are less affected after FET. However, the evidence is not unequivocal and recent randomised control trials challenge the use of elective FET for the general IVF population. Pregnancy rates were analysed in a cohort of patients undergoing embryo transfers.Methods: This was a retrospective cohort study of patients who underwent embryo transfers from April 2018 to March 2019 at study centre in Surat.175 cycles of embryo transfers (119 fresh and 56 frozen) were included in the study. Outcomes measured were positive pregnancy, clinical pregnancy and ongoing clinical pregnancy rates achieved in the IVF-ET cycles.Results: There were no statistically significant differences between positive pregnancy rate (54.6% versus 60.7%, Odds ratio (OR) 0.78; 95% Confidence Interval (CI) 0.41-1.49), clinical pregnancy rate (48.73% versus 57.14%, OR 0.52; 95% CI 0.1- 2.64) and ongoing clinical pregnancy rate  (45.38% versus 51.78% OR 1.4; 95% CI 0.29 - 6.67) in fresh ET and FET cycles, respectively, p < 0.05 was considered statistically significant for all measures.Conclusions: Despite the observed higher rates of positive biochemical, clinical and ongoing clinical pregnancy per transfer in the FET cohort, these did not reach statistical significance. Thus, both transfer strategies are reasonable options, although there is a trend favouring the freeze-all strategy.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Ahmad Mahran ◽  
Mohammed Khairy ◽  
Reham Elkhateeb ◽  
Abdel Rahman Hegazy ◽  
Ayman Abdelmeged ◽  
...  

Abstract Background The clinical implication of the increased serum progesterone level on the day of HCG administration in assisted reproduction treatment (ART) is still controversial. The current study aimed to compare the predictive value of serum progesterone on day of HCG administration / metaphase II oocyte (P/MII) ratio on IVF/ ICSI outcome to serum progesterone (P) level alone and the ratio of serum progesterone/estradiol level (P/E2) ratio in prediction of pregnancy rates after ART. Material & methods Two hundred patients admitted to the IVF/ICSI program at Minia IVF center in Egypt in the period from October 2016 to May 2018 were included in this study. Serum Progesterone (P) and Estradiol (E2) levels were estimated on the day of HCG administration. The ratio between serum P and the number of MII oocytes (P/MII ratio) was calculated and the predictive values of the three parameters (P, P/E2 ratio and P/MII ratio) in prediction of cycle outcomes were measured. Results P/ MII oocyte ratio was significantly lower in patients who attained clinical pregnancy (n = 97) as compared with those who couldn’t whilst there was no significant difference in P and P/E2 ratio between the two groups. Using a cut off value of 0.125, the sensitivity and specificity of progesterone/ MII ratio in prediction of no pregnancy in IVF/ICSI were 75.7 and 77.1% respectively with the area under The Receiver operating curve (ROC-AUC) = 0.808. The respective values of the ROC-AUC for the P and P/E2 ratio were 0.651 and 0.712 with sensitivity and specificity of 71.2 and 73.5%for P level and of 72.5 and 75.3% for P/E2 ratio. Implantation or clinical pregnancy rates were significantly different between patients with high and low P/MII ratio irrespective of day of embryo transfer (day 3 or 5). Conclusions In patients with normal ovarian response, serum progesterone on day of HCG / MII oocyte ratio can be a useful predictor of pregnancy outcomes and in deciding on freezing of all embryos for later transfer instead of high progesterone level alone.


2021 ◽  
Author(s):  
Tingting Yang ◽  
Bo Chen ◽  
Xiaoyan Sun ◽  
Qingyang Li ◽  
Qiumei Li ◽  
...  

Abstract Background So far, only few literatures have studied the relationship between blastocyst transfer position and ART outcomes, and the conclusions are still controversial. Our study is to evaluate the effect of air bubble position on ART outcome and to find the optimal embryo transfer position in frozen-thawed blastocyst transfer. Methods This study included a retrospective cohort analysis of 399 frozen-thawed single blastocyst transfers ultrasound-guided performed between June 1, 2017 and November 30, 2020. All of the women scheduled for frozen-thawed single blastocyst transfers ultrasound-guided. The primary outcome is clinical pregnancy rate and the secondary outcome is live birth rate. Statistical analyses were conducted using One-way Anova, Kruscal Whallis H test, chi-square test and Smooth curve fitting. Results When BFD was less than 19 mm, there was no significant change in clinical pregnancy rate as BFD increased (OR = 0.95, 95% CI: 0.89 to 1.02, P = 0.1373); when BFD was more than 19 mm, the clinical pregnancy rate decreased by 16% for every 1 mm increase in BFD (OR = 0.84, 95% CI: 0.72 to 0.98, P = 0.0363). The effect of BFD on live birth rate were similar to that on clinical pregnancy rate, the inflection point was 19mm, when BFD was more than 19 mm, the live birth rate decreases by 58% for every 1 mm increase in BFD (OR = 0.42, 95% CI: 0.21 to 0.86, P = 0.0174) Conclusions The ideal pregnancy outcome can be achieved within 19mm from uterus fundus after single blastocyst transfer, The clinical pregnancy and live birth at a distance of more 19mm from the uterus fundus have a cliff-like downward trend.


Author(s):  
Robab Davar ◽  
Soheila Pourmasumi ◽  
Banafsheh Mohammadi ◽  
Maryam Mortazavi Lahijani

Background: The results of previous studies on the effect of low-dose aspirin in frozenthawed embryo transfer (FET) cycles are limited and controversial. Objective: To evaluate the effect of low-dose aspirin on the clinical pregnancy in the FET cycles. Materials and Methods: This study was performed as a randomized clinical trial from May 2018 to February 2019; 128 women who were candidates for the FET were randomly assigned to two groups receiving either 80 mg oral aspirin (n = 64) or no treatment. The primary outcome was clinical pregnancy rate and secondary outcome measures were the implantation rate, miscarriage rate, and endometrial thickness. Results: The endometrial thickness was lower in patients who received aspirin in comparison to the control group. There were statistically significant differences between the two groups (p = 0.018). Chemical and clinical pregnancy rates and abortion rate was similar in the two groups and there was no statistically significant difference. Conclusion: The administration of aspirin in FET cycles had no positive effect on the implantation and the chemical and clinical pregnancy rates, which is in accordance with current Cochrane review that does not recommend aspirin administration as a routine in assisted reproductive technology cycles. Key words: Aspirin, Embryo transfer, Pregnancy rates.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M J Zamora ◽  
I Katsouni ◽  
D Garcia ◽  
R Vassena ◽  
A Rodríguez

Abstract Study question What is the live birth rate after frozen embryo transfer (FET) of slow-growing embryos frozen on day 5 (D5) or on day 6 (D6)? Summary answer The live birth rate after single FET is significantly higher for slow-growing embryos frozen on D5 compared to those frozen on D6. What is known already Most data on the outcomes of blastocyst transfer stem from studies that evaluate fresh transfer from normal growing D5 blastocyst ET. However not all embryos will begin blastulation nor reach the fully expanded stage by D5; those are the slow-growing embryos. Studies that compare D5 to D6 embryos in FET cycles show contradictory results. Some have reported higher clinical pregnancy rates after D5 FET, while others have reported similar outcomes for D5 and D6 cryopreserved blastocyst transfers. There is a lack of evidence regarding the best approach for vitrifying embryos that exhibit a slow developmental kinetic. Study design, size, duration This retrospective cohort study included 821 single FET of slow-growing embryos frozen on D5 or D6, belonging to patients undergoing in vitro fertilization with donor oocytes between January 2011 and October 2019, in a single fertility center. The origin of blastocysts was either supernumerary embryos after fresh embryo transfer or blastocysts from freeze-all cycles. All embryos were transferred 2- 4h after thawing. Participants/materials, setting, methods We compared reproductive outcomes of slow-growing embryos frozen on D5 versus (n = 442) slow-growing embryos frozen on D6 (n = 379). D5 group consisted in embryos graded 0, 1, 2 of Gardner scale and frozen on D5. Similarly, D6 group consisted in embryos graded 3, 4, 5 of Gardner scale (blastocyst stage) and frozen on D6. Differences in pregnancy rates between study groups were compared using a Chi2 test. A p-value &lt;0.05 was considered statistically significant. Main results and the role of chance Baseline characteristics were comparable between study groups. Overall, mean age of the woman was 42.3±5.4 years old; donor sperm was used in 25% of cycles, and it was frozen in 73.2% of cycles. Pregnancy rates were significantly higher when transferring slow D5 embryos compared to D6 for all the pregnancy outcomes analyzed: biochemical pregnancy rate was 27.7% vs 20.2%, p &lt; 0.016; clinical pregnancy rate was 17.5% vs 10.2%, p &lt; 0.004); ongoing pregnancy rate was: 15.7% vs 7.8% (p &lt; 0.001); live birth rate was: 15.4% vs 7.5%, (p &lt; 0.001). These results suggest that when embryos exhibit a slow development behavior (not reaching full blastocysts at D5), waiting until D6 for blastulation and expansion does not improve clinical outcomes. Vitrification at D5 will should the preferred option in cases where the oocyte is assumed of high quality Limitations, reasons for caution The retrospective design of the study is its main limitation. Also, morphology as sole selection criterion for transfer. However, blastocyst morphology is a very good predictor of implantation and pregnancy, and a good indicator of the embryo’s chromosomal status (higher euploidy rate in higher morphological quality blastocysts). Wider implications of the findings: These results can help to the standardization of laboratory protocols. As the decision of vitrifying slow developing embryos on D5 or D6 is made by the laboratory team or by the gynaecologist in agreement with the patient, having an evidence based strategy simplifies patient counselling and decision making. Trial registration number Not applicable


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
K Neumann ◽  
G Griesinger

Abstract Study question Does the administration of an oxytocin-receptor antagonist around time of embryo transfer in IVF impact the likelihood to achieve a clinical pregnancy? Summary answer Administration of oxytocin-receptor antagonists around embryo transfer increases the likelihood of clinical pregnancy achievement. What is known already Uterine contractions occurring around time of embryo transfer have been described as one possible mechanism of failure of implantation of an embryo in the context of in-vitro fertilization (IVF). Hence the utilization of oxytocin-receptor antagonists was evaluated in randomized clinical trials (RCT) as a therapeutic approach. The compound Atosiban was studied by most RCTs (summarized in Huang et al. 2017). Recently further studies have become available which also investigated the novel agents Barusiban and Nolasiban. This systematic review collates the evidence of all drugs functioning as oxytocin-receptor antagonists which have been investigated in RCTs on IVF treatment so far. Study design, size, duration Multiple literature databases were searched for randomized controlled studies comparing the outcome of IVF cycles with administration of an oxytocin-receptor antagonist in the time period before, during or after embryo transfer versus placebo or nil in IVF patients. Meta-analyses were performed using standard procedures in the software program RevMan v.5.4. All analyses were done per randomized patient, wherever feasible. Participants/materials, setting, methods Eleven RCTs were identified and included in the meta-analysis. Seven utilized the agent Atosiban, one Barusiban and three Nolasiban. These drugs were administered either intravenously, subcutaneously or orally. The patient populations were heterogenous (fresh cycle, frozen-thawed cycle, endometriosis, implantation failure or general IVF-population) between trials. Only four studies reported live birth rates whereas all RCTs reported clinical pregnancy rate. Main results and the role of chance Administration of an oxytocin-receptor antagonist around embryo transfer increases the likelihood of live birth (relative risk: 1.1, 95% CI: 0.99-1.22, p = 0.06, I2=31%, four RCTs, n = 2,510). Accordingly, the ongoing pregnancy rate is increased (relative risk: 1.14, 95% CI: 1.03-1.26, p = 0.01, I2=18%, four RCTs, n = 2,510) as well as the clinical pregnancy rate (relative risk: 1.31, 95% CI: 1.13-1.51, p = 0.0002, I2=61%, eleven RCTs, n = 3,611) by administration of an oxytocin-receptor antagonist. The risk to suffer a miscarriage, however, is not influenced by an oxytocin-receptor antagonist administration (relative risk: 0.90, 95% CI: 0.72-1.12, p = 0.35, I2=0%, seven RCTs, n = 2,936). The risk of multiple pregnancy is not different between groups (relative risk: 1.05 95% CI: 0.81-1.36, p = 0.73, I2=5%, seven RCTs, n = 3,014) as is the risk for an ectopic pregnancy (relative risk: 0.88 95% CI: 0.43-1.8, p = 0.73, I2=0%, four RCTs, n = 2,714). Limitations, reasons for caution Methodological rigor is heterogenous between trials and some of the evidence is of poor quality. Evaluation of included studies is still ongoing and queries are pending. Additionally, there is heterogeneity between patient populations and definition of outcomes; only four RCTs report ongoing pregnancies and live births. Wider implications of the findings The administration of oxytocin-receptor antagonists around embryo transfer increases the pregnancy rate and may be a promising approach to enhance the likelihood to achieve a live birth per embryo transfer. Trial registration number n.a.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
P C Jindal ◽  
M Singh

Abstract Study question Does GCSF by intrauterine route leads to better result in the treatment of thin endometrium as compared to GCSF by the subcutaneous route, in IVF-ICSI Cycles? Summary answer Yes, GCSF by intrauterine route leads to better result in the treatment of thin endometrium as compared to subcutaneous-GCSF, in ART Cycles? What is known already GCSF, is a member of the colony stimulating factor family of cytokines and growth factors. GCSF receptors are expressed in high concentration on dominant follicle, particularly at preovulatory stage.The endometrium also shows an increased expression of these receptors. GCSF concentration rises in the follicular fluid at the same time. Serum levels of GCSF are found to be in direct correlation with levels of GCSF in follicular fluid. Serum levels increase progressively from the day the embryo-transfer to the day of implantation. GCSF has been found to be beneficial in patients with thin endometrium and recurrent implantation failure. Study design, size, duration This was a RCT conducted between 2018–2019. 30 patients with thin endometrium were enrolled in each group. In either group, GCSF was given if endometrium was less than 7mm on day 14, maximum of two doses were administered. Patients undergoing frozen embryo transfer were recruited in the study, after meeting the inclusion and exclusion criteria. Primary outcome measured was increase in endometrium thickness and the secondary outcome was the clinical pregnancy rate and abortion-rate. Participants/materials, setting, methods 60 patients with thin endometrium were randomly divided into two groups. Group A: Inj. GCSF (300 mcg/1 ml) subcutaneously on Day 14 onwards alternate days for two doses. Group B: Inj. GCSF (300 mcg/1 ml) instilled slowly into the uterine cavity using an intrauterine insemination (IUI) catheter under USG guidance. Endometrial thickness was assessed after 48 h. If endometrial thickness was found to be &lt; 7 mm, a second infusion of GCSF was carried out. Main results and the role of chance In the subcutaneous group (group-A) the mean endometrial thickness before GCSF injection was 5.8 ± 0.6 mm and, after injection it increased to 6.9 ± 0.4 mm. Similarly, in the intrauterine group (group-B) the mean endometrial thickness before GCSF was 5.9 ± 0.7 which increased to a mean of 7.9 ± 0.5 after GCSF instillation. The difference between endometrial thickness before and after intrauterine infusion of GCSF was more than that in the subcutaneous group. In group-A, 08 patients conceived out of 30 patients ( clinical pregnancy rate 26.6%) and in group B 11 conceived out of 30 patients in whom GCSF was instilled intrauterine (pregnancy rate 36.6%). Thus, there was a difference in the clinical pregnancy rate in the two groups, the intrauterine group yielding a higher clinical pregnancy rate, but it was not statistically significant. Because of the thin endometrium, we found an abortion rate of 25% (2/8) in the subcutaneous-GCSF group, and an abortion rate of 18% (2/11) in the intrauterine GCSF group. Limitations, reasons for caution There are few potential limitations because of the small sample size. Confounders such as obesity, smoking and alcohol intake, presence of adenomyosis and endometriosis, were not taken into consideration. Though prevalence of obesity is usually low in Indian women. Habits of smoking and alcohol are exceedingly uncommon in Indian women. Wider implications of the findings: Use of GCSF plays an important role in management of patients of thin endometrium undergoing embryo transfer. It is an easily available and economical preparation in developing countries and the intrauterine instillation of GCSF can be easily practiced in an ART unit with good results in resistant thin endometrium patients. Trial registration number Not applicable


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