Increase In Clinical Pregnancy Rate Research Articles

The effect of gonadotropin-releasing hormone agonist downregulation in conjunction with hormone replacement therapy on endometrial preparation in patients for frozen–thawed embryo transfer

ObjectiveTo investigate the effects of combining gonadotropin-releasing hormone agonist (GnRHa) downregulation with hormone replacement therapy (HRT, GnRHa-HRT) on the clinical outcomes of patients undergoing frozen–thawed embryo transfer (FET).MethodsIn this retrospective study, we included patients who had FET between January 2018 and December 2022. They were categorized into HRT and GnRHa-HRT groups based on the endometrial preparation protocol. The study compared the clinical outcomes of patients in two groups. Possible factors affecting clinical outcomes were analyzed using univariate analysis. To analyze the impact of two endometrial preparation methods on clinical outcomes, multifactorial logistic regression was performed.ResultsThe rates of clinical pregnancy (47.31% vs. 59.60%), embryo implantation (37.58% vs. 49.65%), biochemical pregnancy (52.36% vs. 64.31%), and early abortion (7.07% vs. 10.77%) were statistically different between the two groups (p < 0.05). Analysis using multifactorial logistic regression showed that there was a 1.65-fold increase in clinical pregnancy rates (OR = 1.65, 95% CI: 1.29–2.12, p < 0.001) and a 1.55-fold increase in embryo implantation rates (OR = 1.55, 95% CI: 1.27–1.90, p < 0.001) in the GnRHa-HRT group when compared to the HRT group. For blastocyst transfer, the clinical pregnancy and implantation rates of the GnRHa-HRT group were significantly higher than those of the HRT group (OR = 1.75, 95% CI: 1.30–2.37, p < 0.001; OR = 1.73, 95% CI: 1.35–2.21, p < 0.001).ConclusionIn FET cycles, leuprorelin (as a GnRHa) downregulation combined with HRT may improve the clinical outcome of patients compared to the HRT cycle, especially for the clinical pregnancy and embryo implantation rates of patients with blastocyst transfer.

P-433 Endometrial cavity fluid and clinical pregnancy outcomes in assisted reproduction cycles. A systematic review and meta-analysis

Abstract Study question Does Endometrial cavity fluid (ECF) presence affect clinical pregnancy rates in assisted reproduction (ART) cycles? Does ECF aspiration improve clinical pregnancy outcomes? Summary answer ECF aspiration appears to improve clinical pregnancy outcomes by 56%. What is known already Accumulation of ECF has been a notable finding in ART cycles. The origin of ECF is up to debate; nonetheless, it is frequently associated with a concurrent diagnosis of hydrosalpinx, gonadotropin therapy, subclinical uterine infections, polycystic ovary syndrome amongst other causes. A recent meta-analysis of nine studies highlighted that the presence of ECF substantially diminishes the rates of implantation and clinical pregnancy following embryo transfer, particularly when exceeding 3.5 mm. However, the benefit of ECF aspiration upon clinical pregnancy remains obscure. Study design, size, duration The present meta-analysis aimed to compare clinical pregnancy rates between patients with ECF on the day of embryo transfer undergoing ECF aspiration vs. those who did not. The study was conducted according to the PRISMA guidelines. Six databases (Embase, MEDLINE®, APA PsycInfo, Global Health, HMIC Health Management Information Consortium and Google Scholar) and two additional sources were searched from inception to 23rd November 2023. Participants/materials, setting, methods Observational and Randomized Control Trials meeting inclusion criteria underwent analysis. Quality assessment for observational studies utilised the ROBINS-I Risk of Bias (RoB) tool, and Cochrane RoB V2 tool was used to assess RCTs. Certainty of evidence was evaluated through the GRADE framework. The Meta-analysis was conducted by computing Odds Ratio (OR), Random Effects (RE) using the Haensel-Mantel method. Summative and subgroup data were analysed via the web-based Cochrane RevMan platform. Main results and the role of chance A total of 3 studies were deemed eligible for inclusion, of which 2 were observational (Hou et al., 2022; Hussaini et al., 2018) and a single RCT (Saad et al., 2019). Observational studies were deemed of moderate RoB while the RCT of low RoB. Certainty in overall evidence (GRADE) was deemed moderate. A total of 379 patients were included in the meta-analysis, of a median age 29 [IQR 24.45, 34]. Previous diagnoses of endometriosis, adenomyosis or uterine surgery were not reported in any of the included studies, while only two studies reported the percentage of tubal factor infertile patients in their respective included sample (73% and 25%, Ntotal=125). When aggregately analysed, ECF aspiration resulted in a significant increase in clinical pregnancy rates, OR 1.56 [95% CI 1.04, 2.33], I2= 1%, P = 0.03. Additionally, subgroup analysis of low RoB studies, OR 1.61 [95% CI 1.08, 2.40], I2= 0%, P = 0.02, successfully controlled for heterogeneity whilst also yielding statistically significant results. Limitations, reasons for caution Inherent to the nature of observational studies, our meta-analysis suffers from the scarcity of robust randomized control studies and adequately powered observational evidence. Wider implications of the findings Our study suggests that ECF aspiration at embryo transfer may improve clinical pregnancy outcomes. However, robust RCTs are required to assess the degree of clinical impact as well as the patient subgroups and their clinical characteristics that may benefit more from such an intervention. Trial registration number not applicable

P-195 Euploid embryo transfer in a hyaluronic acid-enriched media results in a higher ongoing pregnancy rate than euploid embryo transfer in media not containing hyaluronic acid

Abstract Study question Will using a hyaluronan-rich transfer medium increase the ongoing pregnancy rate and live birth rate when transferring euploid embryos cultivated in a dry incubator? Summary answer Transferring euploid embryos in a media with high concentrations of hyaluronic acid increases the ongoing pregnancy rate compared with media with no hyaluronic acid. What is known already Cochrane Review found that solutions with high concentrations of hyaluronic acid increase the chance of live birth by adding probably 1 additional live birth for every 14 embryos transferred in a high-concentration hyaluronic acid solution for patients aged 27 to 35. A study involving 85 frozen embryo transfer cycles showed a positive effect of high concentrations of hyaluronic acid on the results of transfer of morphologically poor euploid blastocysts. Previous studies were conducted in humidified incubators where hyaluronic acid-rich media was equilibrated without oil overlay. Our clinic uses dry incubators, necessitating oil overlay with all media, including hyaluronic acid-rich media. Study design, size, duration A randomized prospective study involving 255 patients aged 19-44 undergoing a transfer of a single euploid embryo between June 2023 and November 2023. Patients were randomly assigned to the study and control groups. Blastocysts were incubated after thawing for 3 hours either in a hyaluronic acid-enriched medium or in a medium without hyaluronic acid. Participants/materials, setting, methods Embryos underwent PGT-A at the blastocyst stage on either day 5 or day 6, using the EmbryoMap method. Trophectoderm biopsy was performed using the Flicking technique without a laser. 5-7 cells were removed for analysis. Blastocysts were vitrified following biopsy. Hyaluronic acid-enriched media was equilibrated for 16-18 hours in a 5%O2 6%CO2 atmosphere in a well of 4-well culture dish under oil overlay (600 microliters of media and 500 microliters of oil). Main results and the role of chance In this ongoing study, 127 transfers of euploid blastocysts in a hyaluronic acid-rich media resulted in 70 ongoing pregnancies, with a 55.1% ongoing pregnancy rate. In comparison, 128 transfers of euploid blastocysts in a media with no hyaluronic acid resulted in 65 ongoing pregnancies, with a 50.8% ongoing pregnancy rate. The relative improvement in the ongoing pregnancy rate is 8.5%. Our data suggests that using a hyaluronic acid-rich medium for the transfer of euploid blastocysts of good morphology can improve clinical pregnancy rates, although the effect is less dramatic than was shown in a 2023 study by Nakagawa et al. for morphologically poor euploid blastocysts, where more than twofold increase in clinical pregnancy rates was detected. Limitations, reasons for caution Specific media equilibration protocol is required for the incubation and transfer of embryos in a hyaluronan-rich transfer medium for IVF clinics utilizing dry incubators. Further research is required to confirm results and to establish whether transferring embryos in hyaluronic acid-enriched media increases the live birth rate after euploid embryo transfer. Wider implications of the findings Our results show that it is feasible to use a hyaluronic acid-enriched medium in a dry incubator with an oil overlay and that using it according to described protocol could increase the ongoing pregnancy rate after a single euploid blastocyst transfer. Trial registration number not applicable

P-386 The effect of intravenous immunoglobulin versus placebo in patients with recurrent pregnancy loss: a systematic review and meta-analysis of randomized trials

Abstract Study question In women with recurrent pregnancy loss (RPL), how does intravenous immunoglobulin (IVIg) compared with placebo affect live birth rate (LBR) in the first subsequent pregnancy? Summary answer IVIg significantly improved LBR in the per protocol (PP), but not the intention to treat (ITT) analysis. LBR increased significantly with number of pregnancy losses. What is known already RPL is defined as two or more pregnancy losses before 24 weeks of gestation, impacting 1-2% of fertile couples. It results from diverse causes, and immunological factors are increasingly implicated in unexplained RPL cases. IVIg has been studied as a treatment with various proposed mechanisms. Existing research on IVIg in RPL has shown conflicting results, but a recent Japanese randomized controlled trial (RCT) reported a significantly increased LBR when IVIg was administered early and in high-dose. Study design, size, duration We conducted a systematic review and meta-analysis of relevant (RCTs, incorporating individual patient data (IPD) to evaluate IVIg’s impact on LBR in RPL patients. Participants/materials, setting, methods This study adhered to PRISMA guidelines and was registered in PROSPERO (ID CRD42023375788). We searched PubMed, Embase, and Cochrane libraries for relevant RCTs up to March 20, 2023. We conducted a meta-analysis with predefined primary (live birth and clinical pregnancy rates) and secondary outcomes. Risk ratios with 95% confidence intervals were calculated for dichotomous outcomes, and mean and standard deviation for continuous variables. We contacted the original authors to perform subgroup analyses based on IPD. Main results and the role of chance A total of 10 RCTs comprising 594 women were included in the meta-analysis, and IPD were retrieved from six RCTs including 354 women. No statistically significant results in LBR between IVIg and placebo treated women were found in the ITT analysis (RR: 1.02 [95% CI 0.86-1.22] p = 0.78). In the PP analysis, LBR was increased in the IVIg group compared with placebo (RR: 1.23 [1.00-1-50]). A statistically significant increase in clinical pregnancy rate was found in the IVIg group compared with placebo among women receiving high dose (median ³ 77.5 g) IVIg (RR: 1.79, [95% CI 1.21-2.65], p = 0.004). Furthermore, a statistically significant decrease in pregnancy loss rate was found in patients receiving high doses of IVIg (RR: 0.76 [95% CI 0.60-0.96], p = 0.02) compared to placebo. In the IPD analysis, RRs for live birth in the IVIg group compared with placebo increased steadily with the number of previous pregnancy losses. RRs for live birth in patients receiving IVIg compared with placebo were 5.26 (1.58-17.53) and 7.50 [1.20-47.05) in patients with ≥6 and ≥7 consecutive pregnancy losses, respectively. In analyses of IPD data adjusted for maternal age, the RRs for live birth were almost similar. Limitations, reasons for caution Limitations in the systematic review include potential bias due to financial support from pharmaceutical companies in half of the studies; potential confounding in subgroup analysis, missing individual patient data; and clinical and methodological heterogeneity among the included RCTs, which all may impact the overall reliability of results. Wider implications of the findings The findings highlight the importance of patient selection and personalized treatment. The PP analysis favored IVIg, emphasizing importance of protocol adherence. Secondly, the effectiveness of IVIg seems to increase with number of previous consecutive pregnancy losses. Thirdly, the dose of IVIg seem to impact its effectiveness. Trial registration number CRD42023375788

#390 : Why Our Clinical Pregnancy Rates Have Improved Over the Past Two Years: Exploring Key Points of Gonadotropin-Releasing Hormone Antagonist Protocol in Fresh Embryo Transfer Cycles

Background and Aims: GnRH-ant protocol is effective in preventing a surge of pituitary luteinising hormone during controlled ovarian stimulation. In recent years, GnRH-ant protocol has been optimised to improve in vitro fertilisation outcomes. However, firstly, the success rate of frozen embryo transfer is consistently better than that of fresh embryo transfer and secondly, the success rate of GnRH-ant protocol on fresh embryo transfer is lower than that of the long protocol. This study aims to draw out a comparison of before and after data from our own centre to find the reasons for the gradual maturation of GnRH-ant protocol on fresh embryo transfer. Our study proposed to investigate the determinants affecting fresh embryo transfer in gonadotropin-releasing hormone antagonist (GnRH-ant) protocols. Method: We reviewed 2464 fresh embryo transfer cycles for IVF/ICSI-ET assisted reproduction techniques performed at our centre from 1 January 2015 to 31 December 2019. The exclusion criteria were as follows: endometriosis grade III to IV (American Fertility Society classification of endometriosis); adenomyosis; severe male oligospermia or obstructive azoospermia. Firstly, we compared the single-cycle clinical pregnancy rates between 2015 to 2017 and 2018 to 2019. Next, we performed a multifactorial regression analysis to understand what changes our centre had made between the five years in terms of years. Finally, data from 2015 to 2019 were grouped as a whole and then subjected to understand exactly where the differences in clinical pregnancy rates were affecting the GnRH-ant protocol for fresh embryo transfer. Results: A total of 1,388 cycles were included from 2015 to 2017, with a clinical pregnancy rate of 51.42% (688/1388). 1,076 cycles were included from 2018 to 2019, with a clinical pregnancy rate of 57.43% (618/1076). 2018 to 2019 compared to 2015 to 2017 for first-time IVF/ICSI. There was a 6.01% increase in clinical pregnancy rate for women who had assisted conception and performed GnRH-ant protocol with fresh embryo transfer. The results of the univariate analysis conducted suggested that the factors influencing the classification of clinical pregnancy included female basal E2 base, LH base, FSH base, P base, female Gn initiation date E2 start, LH start, FSH start, P start, Gn initiation volume and number of Gn days, antagonist addition date E2 add, LH add, FSH add, P add, plate machine day E2 trigger, LH trigger, P trigger, plate machine day number of different follicles in the meridian follicles 10-14 mm, follicles 14-16 mm, follicles 16-18 mm, follicles 18mm or more. Multifactorial regression analysis after correction suggested that age, BMI, endometrial thickness on the day of transfer, number of embryos transferred and progesterone level on HCG Day were independent influencing factors for successful pregnancy with antagonist regimen and fresh embryo transfer. Conclusion: Age, BMI, endometrial thickness on the day of transfer, number of embryos transferred and progesterone levels on HCG Day were independent influences.

P-621 Machine learning software significantly increase clinical pregnancy rates in natural frozen-thawed embryo transfer cycles

Abstract Study question To study the effect of physician support software for determining ovulation time on pregnancy outcomes in natural cycle frozen embryo transfers (NC-FET) Summary answer Match between the physician and the algorithm regarding the time of ovulation in NC-FET cycles resulted in significant 14.4% increase in clinical pregnancy rates. What is known already Today the preferred method for frozen embryo transfer is natural cycle based on ovulation detection. As of today, an algorithm for predicting ovulation has not been developed and its use and its effect on success rates have not been tested. The aim of this study was to test a physician support artificial intelligence (AI) software for determining ovulation time and to study the effect of its use on pregnancy outcomes in frozen-thawed embryo transfers (NC-FET). Study design, size, duration NC-FET cycles from September 2018 to June 2021 were used to develop ovulation detection algorithm. Next, the effect of the selection of the ovulation date by the algorithm on pregnancy rates was tested by retrospective analysis on NC-FET cycles performed between July 2021 to June 2022. Cycles were divided into two groups: The Matched group in which there was a match between the ovulation date set by the physician and the algorithm and Mismatched group. Participants/materials, setting, methods Study group included 349 single embryo transfer patients after applying strict inclusion criteria. The Matched group included 198 patients and 151 patients in the Mismatched group. Patient's age, BMI, smoking, number of past retrievals and past embryo transfers, endometrium thickness, embryos age and quality, number of tests per cycle and pregnancy rates were compared. Statistical analysis included multivariable logistic regression to study the association between Match/Mismatch and clinical pregnancy rates while controlling for potential confounders Main results and the role of chance Matched group and Mismatched group had similar characteristics. Mean patients age at oocyte retrieval were 34.5 + 5.5 vs. 34.7 + 5.5 respectively (p=0.72). Clinical pregnancy rate in the Matched group were 38.9% compared to 24.4% in the Mismatched group (p =0.006). The difference was particularly noticeable when day 3 embryos were transferred (39.8% vs. 17.6% respectively p=0.009), and was also observed on day 5 embryos transfer, although non-significant (39.1% vs. 30.0% respectively, p=0.197). In the Matched group the chance of pregnancy actually almost doubled (OR = 1.97, CI 95% 1.23-3.17, p=0.005) while controlling potential confounders. Further analysis of the Mismatch group found that in 120 cycles (%) the doctor set the ovulation date one day or more before the date set by the algorithm and in 31(%) cases the date was a day or more after the ovulation date according to the algorithm. Logistic regression showed that the chance of pregnancy was significantly affected when the doctor determines the day of ovulation earlier than the algorithm (OR = 0.42, CI 95% 0.29-1.43, p=0.005) Limitations, reasons for caution Although cycles selected for comparison were controlled for key factors that affect pregnancy outcomes, The main drawback is the retrospective analysis. Further prospective randomized trials are needed to study the effectiveness of the algorithm and its effect on treatment results. Wider implications of the findings This is the first AI algorithm designed to predict ovulation. Using AI algorithms in NC-FET can help in identifying ovulation accurately and reliably and may increase pregnancy rate Trial registration number Not applicable

ART outcomes of patients in women with Isolated Hypogonadotropic Hypogonadism: a retrospective study in China

BackgroundIsolated Hypogonadotropic Hypogonadism (IHH) is a rare reproductive disorder caused by the dysfunction of the gonadotropin-releasing hormone axis. Patients with IHH typically fail to enter or develop through puberty and retain infertile without an exogenous hormone supplement. This study aimed to investigate the population characteristics and reproductive outcomes in IHH patients undergoing assisted reproductive technology (ART) treatment, and evaluate the best-performed predictor for ovarian response and clinical pregnancy in patients with IHH.MethodsThis retrospective cohort study included 83 women with IHH who underwent fresh ART cycles and non-diagnosed controls (n = 676). The receiver operating characteristic curves were generated to assess the predictor for the ovarian response. Logistic regression analyses were performed to investigate the independent factors for clinical pregnancy in IHH.ResultsThe basal hormone levels were significantly lower in the IHH group compared to the control group. The fertilization rate and 2PN rate were significantly higher in IHH groups, as was the number of transferable embryos. The study identified that AMH was the best predictor of high ovarian response in IHH, with an AUC of 0.767 (0.573, 0.961). Conversely, the follicle-to-oocyte index (FOI) exhibited the highest AUC of 0.814 (0.642, 0.985) for predicting low ovarian response. Based on FOI values, the IHH patients were divided into two groups, and the study found a significant increase in clinical pregnancy rate (43.8%, 58%; P < 0.001) and live birth rate (37.5%, 58%; P < 0.001) from the low FOI to the normal FOI groups. Moreover, the number of oocytes retrieved, fertilized embryos/rate, 2PN embryos/rate, and number of excellent quality embryos were significantly higher in the normal FOI group (P < 0.001 or P = 0.005) than in the low FOI group. Logistic regression analyses revealed FOI to be the independent factor affecting clinical pregnancy in IHH patients.ConclusionsThe study findings suggest that patients with IHH were good responders to IVF treatment. Although AMH was the best-performed predictor for the high ovarian response, FOI had the best capability in predicting the low ovarian response. FOI was an independent factor affecting clinical pregnancy in IHH undergoing IVF/ICSI.

To curette or not to curette; efficiency of oocyte retrieval technique.

Follicular curetting is the gentle and rapidly rotating movement of the aspiration needle in a clockwise and counterclockwise fashion. The aim of our study is to assess this retrieval technique comparing cycle and pregnancy outcomes between curetting and non-curetting. This was a retrospective review of 817 patients that underwent oocyte retrieval at our fertility center from January 1st, 2016 until August 31st, 2019. All patients enrolled in the study underwent standard ovarian stimulation protocols. Three physicians routinely utilized follicle curetting during oocyte retrieval, while a fourth physician did not curette. Retrievals and embryo transfers were performed based on a rotating physician schedule. Retrievals that were performed using a curetting technique had a significantly higher number of total oocytes retrieved 12.4 ± 8.1 vs 10.7 ± 7.5 (p = 0.01), and number of M2 oocytes retrieved 8.1 ± 6.4 vs 6.9 ± 6.0 (p = 0.03), resulting in an increased M2 oocyte yield 63.7% ± 41.3 vs 50.9% ± 30.6 (p = 0.0001). These patients also had a significant increase in clinical pregnancy rate per retrieval 55 vs 41% (p = 0.0016), live birth rate per retrieval 42 vs 34% (p = 0.04) and with no significant difference in multiple gestations or OHSS. A significant improvement in clinical pregnancy rates and live birth per retrieval was detected in patients undergoing curetting. These patients had more embryos frozen, leading to more transfers and more successful pregnancies.

Does endometrial thickness affect pregnancy outcomes in isolated male infertility IVF cycles? A retrospective cohort study

In our retrospective cohort study, we aimed to determine the role of endometrial thickness (ET) in isolated male factor infertile women in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) fresh embryo cycles. The patients were classified as having an endometrial thickness of <7 mm (n: 80), 7–9.9 mm (n: 335), 10–14 mm (n: 579) and >14 mm (n: 50) according to their ETs on the human chorionic gonadotropin (hCG) day. The overall clinical pregnancy rate was 37.4%, and no significant difference was found between the groups (p = .262). There was no significant difference between live birth rates (p = .094), but the highest pregnancy (46%) and live birth (34%) rates were found in the group with >14 mm ET. The increase in ET in IVF cycles increases pregnancy rates, albeit partially. When it is desired to determine a cut-off value, it can be said that pregnancy rates increase significantly in thicknesses of 14 mm and above. Impact Statement What is already known on this subject? When the literature is examined, many studies conclude that clinical pregnancy rates increase with the increase in endometrial thickness (ET) in IVF cycles, but there are also studies that argue the opposite. There is no study in the literature investigating the effect of ET on clinical pregnancy rates in patients with isolated male factor infertility. What do the results of this study add? In support of the literature, an increase in ET was found to be associated with an increase in clinical pregnancy rates, regardless of male and female factors. Although pregnancy occurs in thin endometriums, abortion rates are undesirably high. What are the implications of these findings for clinical practice and/or further research? Although the risk of abortion is high in thin endometriums, live birth rates are satisfactory. As a result, thin endometrium does not require cycle cancellation.

P-120 Microfluidic sperm selection device increases clinical pregnancy rate in IVF/ PGT-A cycles

Abstract Study question Evaluate the influence of sperm selection according to the sorting technique, and its effects in clinical and laboratory parameters in IVF/PGT-A cycles. Summary answer Cycles that used microfluidic sperm selection device presented an increase in clinical pregnancy rates. What is known already A common genomic anomaly detected in subfertile men is the Sperm DNA fragmentation. It is resulted of a high concentation of free radicals produced causing oxidative stress in sperm cells. In order to achieve a normal embryonic development is necessary good spermatozoa with intact genetic material. In fact, embryonic quality parameters as lower fertilization, blastocyst formation and pregnancy rates has been related with Sperm DNA fragmentation increased cases. The microfluidic sperm selection device has been commercialized promising to select spermatozoa with a low level of DNA fragmentation and suggest a relationship between embryo quality, euploidy and pregnancy rates. Study design, size, duration A case-control study involving 494 IVF/PGT-A cycles that resulted in embryo biopsy between June, 2020 and November, 2021 at a Brazilian private practice unit (Instituto Ideia Fertil) were included in this analysis. Participants/materials, setting, methods All cycles that would perform PGT-A were splitted in two groups considering the sperm sorting technique: case - Microfluidic sperm selection device (245 cycles) and control - Density gradient centrifugation + swim-up (249 cycles) were included. The variables considered in this analysis were patient age, sperm concentration, fertilization, D3 top quality, blastocyst top quality, blastulation, ploidy and pregnancy rates. This data were analysed between groups and female age (until 37; 38-40 and over 41). Main results and the role of chance The mean age of the female and male patients found were 38.05 and 38.2 respectively and there was not statistically significant different between groups. Fertilization rate compared between case (72.4%) and control (76.5%) groups (p &amp;lt; 0.05) demonstrated statistically significant difference, but when stratified accordingly to the age, only the female age until 37 years old group showed significant difference (73.25%; 76.43%; p &amp;lt; 0.05). The variables analyzed as D3 Top Quality, Blastocyst Top Quality, blastulation and ploidy did not present difference (p = 0.552; 0.699; 0.378). The clinical pregnancy rate analyzed revealed in case group 65.33% and control 56.38% (p &amp;lt; 0.05), demonstrating statistically significant difference. When groups were splitted according to the female age (until 37 years old; 38-40 and over 41) the findings behaved in the same characteristics, increasing only the clinical pregnancy rate. The tests used was Mann-Whitney and Kruskal-wallis. Limitations, reasons for caution The DNA fragmentation test was not evaluated because not all patients had this test performed. Besides that, another parameter that will be analysed is live birth rate. Wider implications of the findings Microfluidic sperm sorting device made possible to select high quality spermatozoa according to motility, morphology, and low rates of fragmentation, showing the importance of having a good sperm in clinical pregnancy rate. Trial registration number none

Blastocyst versus cleavage transfers: who benefits?

This retrospective cohort study determined the relative efficacy of blastocyst and cleavage-stage transfers in patients with differing numbers of zygotes. A total of 1116 women whose embryo transfers were planned independently of patient characteristics were included. Cleavage-stage (D3) and blastocyst-stage (D5) transfer outcomes were analyzed per number of zygotes. The D5 group included transfer cancellations as the intention-to-treat population. The effect of the embryo transfer date on the clinical outcomes (clinical pregnancy and implantation rates) was analyzed using multivariate logistic regression. Among the patients, 584 and 532 underwent D3 and D5 embryo transfers, respectively. The clinical pregnancy rates were significantly higher in D5 patients with ≥ 6 zygotes (25.7% vs 48.3%). The multivariate logistic regression analysis for clinical pregnancy did not show significant differences between the blastocyst and cleavage-stage transfers in patients with ≤ 5 zygotes (0.874[0.635-1.204]). Compared to the cleavage-stage, blastocyst-stage transfers for patients with ≥ 6 zygotes resulted in a three-fold increase in clinical pregnancy rates (3.122[1.797-5.425]). Blastocyst transfers were not inferior to cleavage-stage embryo transfers among patients with few zygotes and were preferable for patients with several zygotes.

ORAL SUPPLEMENTATION WITH A COMBINATION ANTIOXIDANT FORMULATION IMPROVES CLINICAL PREGNANCY RATE

The role of oxidative stress in female infertility has been well established from, numerous studies in the literature. A recent study has suggested an increase in clinical pregnancy rates after supplementation of the culture media with antioxidants. We designed this pilot study to investigate the potential of oral antioxidant supplementation on clinical pregnancy rates, blastulation rate and fertilization rate in assisted reproductive technology (ART).

P–325 The impact of letrozole on endometrial thickness in IVF cycles

Abstract Study question Does daily administration of letrozole during IVF stimulation affect endometrial thickness ? Summary answer Patients treated with letrozole during fresh IVF cycles had a thinner endometrium on the day of trigger compared to patients who did not receive letrozole. What is known already Letrozole supplementation is commonly used during fertility preservation for breast cancer patients to reduce peak estrogen levels with no adverse effects on embryo outcomes. Studies in poor responders have found that letrozole use resulted in a shorter duration of stimulation and a lower total dose of gonadotropin, with no detrimental effect on IVF outcomes. In normal responders, studies have shown an increase in blastocysts obtained, but have not yet shown an increase in clinical pregnancy rates. There is concern that when a fresh embryo transfer is planned letrozole use may negatively affect endometrial thickness and subsequently diminish pregnancy rates. Study design, size, duration In a retrospective cohort study between January 2009 and June 2019 at a single academic fertility center, we compared the endometrial thickness in 97 cancer patients who underwent IVF-fertility preservation with daily letrozole use to 158 cancer patients who underwent IVF-fertility preservation without letrozole. Participants/materials, setting, methods All women diagnosed with cancer were referred for fertility preservation prior to gonadotoxic treatment exposure and were less than 40 years old at the time of oocyte retrieval. All patients who received letrozole started on day one of stimulation and continued until the day of oocyte retrieval. The primary outcome was endometrial thickness on the day of trigger. The secondary outcomes were number of oocytes retrieved, number of MII retrieved, and maximal estradiol level. Main results and the role of chance During the study period, 336 cancer patients underwent fertility preservation. Eighty-one patients were excluded; 50 because they had an intrauterine device or were on long term oral contraceptives and 31 because endometrial thickness was not documented. Of the remaining 255 patients, 86 had breast cancer, 95 had a hematological cancer and 74 had various other cancers. Ninety-seven cancer patients treated with letrozole were compared to 158 cancer patients who did not receive letrozole. Patients who received letrozole were significantly older (34 vs 28yrs, P &amp;lt; 0.0001). There were no significant differences in baseline characteristics such as BMI, AFC nor in the total duration for stimulation. Endometrial thickness on the day of trigger was significantly less in letrozole treated patients (8 vs 9mm, P &amp;lt; 0.003). There were no significant differences in total number of oocytes retrieved (12.5 vs 11, P = 0.126) nor in the number of mature oocytes (8 vs 8, P = 0.312). Patients in the letrozole group received a higher total gonadotropin dose (2680IU vs 1980IU, P = 0.016). The maximum estradiol level was significantly lower in patients treated with letrozole (1068 vs 3838ml/dl, P = &amp;lt;0.0001). A regression analysis showed that using letrozole during stimulation decreased the endometrial thickness by 0.81mm (CI –1.37 to –0.253, P = 0.005). Limitations, reasons for caution The retrospective nature of this study could have introduced selection and misinformation bias. We report on cancer patients where all oocytes or embryos were vitrified. Without fresh embryo transfer data, it is unclear if a thinner endometrium due to letrozole will effect the implantation or pregnancy rate. Wider implications of the findings: As the use of letrozole expands beyond cancer patients and poor responders, it is important to understand the impact on the endometrium. This study shows that letrozole reduces endometrial thickness. However, the effect on endometrial function remains unknown. Further study is needed before letrozole can be used with fresh transfers. Trial registration number 2020–6370

Experience of our clinic in intrauterine insemination cycles made with microfluidic sperm sorting chips

Objective: Determination of the clinical pregnancy rate in intrauterine insemination (IUI) cycles performed with microfluidic sperm sorting chips.&#x0D; Material and Methods: In Giresun University Obstetrics and Pediatrics Hospital Infertility Clinic, 133 patients who underwent IUI after ovarian stimulation with gonadotropins in unexplained infertility, mild to moderate male factor, ovulatory dysfunction, mild endometriosis were retrospectively analyzed between January 2016-January 2020. Microfluidic sperm sorting chip was used for sperm preparation.&#x0D; Results: The number of cycles was found to be 133. Mean female age was; 29.9±4.7 years, mean total motile sperm count was; 72.9±63.7 million, mean antral follicle count was; 18.1±10.1, the mean total gonadotropin dose used was 897.6±366 IU. Considering the causes of infertility; 54.1% unexplained, 8.3% mild male factor, 31.6% polycystic ovary syndrome (PCOS) and 6% endometriosis. The clinical pregnancy rate was found to be 19.5% (26/133).&#x0D; Conclusion: Microfluidic sperm sorting chips provide an increase in clinical pregnancy rates compared to conventional methods in IUI cycles and allow for a practical and rapid sperm preparation.&#x0D; Key Words: IUI, microfluidic sperm sorting chip, clinical pregnancy rate.

Effect of Human Chorionic Gonadotropin Injection Before Frozen Embryo Transfer on Pregnancy Outcomes in Endometriosis-Associated Infertility.

Purpose: The aim of this study was to investigate the effect of human chorionic gonadotropin (hCG) in hormone replacement (HT) regime for frozen thawed embryo transfer in women with endometriosis (EM).Methods: We performed a retrospective, database-search, cohort study and included data on EM patients who underwent frozen embryo transfer (FET) between January 1, 2009 and August 31, 2018. According to the protocols for FET cycle, the patients were divided into two groups: control group (n = 296) and hCG group (n = 355). Clinical pregnancy rate, live birth rate, early abortion rate, late abortion rate, and ectopic pregnancy rate were compared between the two groups.Results: There was a significant increase in clinical pregnancy rate in the hCG group (57.7 vs. 49%, p = 0.027) compared with the control group. The live birth rate in the hCG group (45.6 vs. 38.5%, p = 0.080) was also elevated, but this difference was not statistically significant.Conclusion: hCG administration in HT regime for FET increases the pregnancy rate in women with EM.

Therapeutic endometrial scratching and implantation after in vitro fertilization: a multicenter randomized controlled trial

To study whether endometrial scratching in the luteal phase before ovarian stimulation increases clinical pregnancy rates in women with one or more previous implantation failures. A nonblinded multicenter randomized clinical trial. Fertility clinics. Three hundred four eligible patients scheduled for IVF/intracytoplasmic sperm injection were randomized. The intervention group (n = 151) underwent endometrial scratching in the luteal phase before controlled ovarian stimulation, while no intervention was performed in the control group (n = 153). Endometrial scratching with a Pipelle de Cornier catheter in the luteal phase before ovarian stimulation. Clinical pregnancy rate and prenatal and birth data. There was no overall significant improvement in clinical pregnancy rates between the control and intervention groups (38.5% vs. 44.4%; relative risk = 1.15; confidence interval [0.86-1.55]). However, subgroup analyses revealed that women with three or more previous implantation failures had a significant increase in clinical pregnancy rate (31.1% vs. 53.6%; relative risk = 1.72; confidence interval [1.05-2.83]) after scratching. No difference was seen as regards prenatal and birth data between the two groups. Endometrial scratching in the luteal phase before ovarian stimulation significantly enhances the clinical pregnancy rate in women with three or more prior implantation failures. This result seems to corroborate previous reports, which found that particularly women with repeated implantation failure seem to gain a positive effect from endometrial scratching. Importantly, there were no significant differences in prenatal data and birth data between the groups. NCT01963819.

Intrauterine administration of peripheral mononuclear cells in recurrent implantation failure: a systematic review and meta-analysis

It has been proposed that intrauterine administration of peripheral blood mononuclear cells (PBMCs) modulates maternal immune response through a cascade of cytokines, chemokines and growth factors to favor implantation. We conducted a meta-analysis to verify the effect of intrauterine PBMC administration on the outcome of embryo transfer in women with recurrent implantation failure (RIF). All relevant trials published in PubMed, Web of Science and Cochrane library databases were searched. Two randomized controlled trials and three cohort studies (1173 patients in total) matched the inclusion criteria. No differences in live birth rates were seen between the PBMC-treated patients and controls (OR: 1.65, 95% CI: 0.84–3.25; p = 0.14; I2: 66.3%). The clinical pregnancy rate was significantly higher in women who received intrauterine PBMCs before embryo transfer compared with those who did not (OR: 1.65, 95% CI: 1.30–2.10; p = 0.001, heterogeneity; I2: 60.6%). Subgroup analyses revealed a significant increase in clinical pregnancy rates with the administration of PBMCs in women with ≥3 previous failures compared with controls (OR: 2.69, 95% CI: 1.53–4.72; p = 0.001, I2: 38.3%). In summary, the data did not demonstrate an association between the administration of PBMCs into the uterine cavity before fresh or frozen-thawed embryo transfer and live birth rates in women with RIF. Whether intrauterine PBMC administration significantly changes live birth and miscarriage rates requires further investigation.

Intrauterine administration of human chorionic gonadotropin (hCG) for subfertile women undergoing assisted reproduction.

Intrauterine administration of human chorionic gonadotropin (hCG) for subfertile women undergoing assisted reproduction.

A comparison of treatment results of the different treatment protocols in patients with poor ovarian response

To compare the effect of the different protocols in patients receiving in vitro fertilization treatment due to poor ovarian response. Seventy-seven of the patients included in the study were treated with gonadotropin (450 IU) + GnRH antagonist (group 1), 84 of the patients were treated with gonadotropin (450 IU) + microdose GnRH analog (group 2), and 53 of the patients were treated with clomiphene citrate (100 mg/day) + gonadotropin (300 IU) + GnRH antagonist (Group 3). In assessing total gonadotropin dosage, patients in Group 3 detected significantly less gonadotropin as compared to the other two groups (p < .001). Group 1 were superior to the other two groups with respect to retrieved oocytes, meiosis II oocytes and number of embryos obtained at the end of the treatment. As for the evaluation of clinical pregnancy, although the highest pregnancy rate was in Group 3, this finding was not of statistical significance. Although increasing the dosage of gonadotropins for ovarian hyper stimulation treatment in patients with poor ovarian response is beneficial with respect to retrieved oocytes, meiosis II oocytes and number of embryos, the increased dosage does not provide a statistically significant increase in clinical pregnancy rates.

A randomized controlled trial with addition of letrozole as an adjunct to FSH in high responders in stimulated IVF cycles show negative impact of ovarian stimulation on the endomterium

Can letrozole reduces the incidence of premature progesterone rises late follicular phase, and thus impact positively on endometrial receptivity to high responders in stimulated in vitro fertilization (IVF) cycles? A randomized parallel controlled trial This randomized parallel controlled trial was conducted in from the Hospital from October 2015 to August 2016.Altogether 133 women undergoing IVF treatment were randomized into two groups using computer-generated randomization plan, to one of the following two treatment regimens: A standard GnRH-a protocol and 100 IU-225IU recFSH were applied from stimulation day 1 and letrozole 2.5 mg/day from cycle day 5 to the day before hCG administration (Letrozole group, n=69) or none (control group, n=64).Standard luteal phase support with progesterone were provided. While estradiol levels were significantly lower in the letrozole group (P < 0.001), the progesterone levels (1.09±0.40,0.93±0.38)ng/ml and P/E2(0.74,0.30) (P < 0.05) on the day of hCG administration were increased in the letrozole group. RecFSH , the recovery rate of eggs, Fertilization rate, high-quality embryo rate,thickness of endometrium,were similar between the letrozole and control groups. Clinical pregnancy rate: 58.5%(31/53),72.9%(35/48) was lower in the letrozole group, although there was no statistical significance by T test( P=0.128 ). The results suggest that co-treatment with letrozole can not reduce the incidence of premature progesterone rise at the late follicular phase,thus show negative impact on endometrial receptivityin in stimulated IVF cycles.With no increase in clinical pregnancy rates compared with control group in high responders undergoing assisted reproductive technology.