Frozen-thawed Embryo Transfer Research Articles

A repeated gonadotropin-releasing hormone agonist trigger improves pregnancy outcomes of frozen-thawed embryo transfer in GnRH antagonist cycles: a retrospective propensity-matched score analysis.

To evaluate whether co-treatment of repeated GnRHa triggers with GnRH antagonist protocols can improve the clinical outcomes in in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) procedures. In this retrospective study, 712 Chinese Han women aged 20-42 undergoing autologous IVF/ICSI-ET with a flexible GnRH antagonist protocol were analyzed. The 735 cycles were split into the single (n = 238) and the repeated (n = 497) GnRHa groups. In the single GnRHa group, 0.2mg of triptorelin was given for oocyte maturation, whereas in the repeated GnRHa group, two doses of 0.2mg were administered 12h apart. PSM design was used for a fair comparison. The main study outcomes included the clinical pregnancy rate (CPR), live birth rate (LBR), good-quality embryo rate, and fertilization rate. Multivariate logistic regression analyses were used to identify all potential factors affecting clinical outcomes. Post-PSM, analysis of 159 cycles per group showed the repeated GnRHa group outperforming the single GnRHa group in IVF fertilization rates (71.5% vs. 67.7%, P < 0.05) and good-quality embryo rate (47.1% vs. 43.7%, P < 0.05). Furthermore, the repeated GnRHa group achieved higher CPR (72.6% vs. 53.4%, P < 0.05) and LBR (59.7% vs. 43.8%, P < 0.05) in FET cycles. Multivariate logistic regression indicated a significant negative correlation between the use of a single GnRHa trigger and both clinical pregnancy (OR = 0.382, P < 0.05) and live birth (OR = 0.518, P < 0.05). Our study reported that individuals who received a repeated GnRHa trigger exhibited higher CPR and LBR during FET cycles compared to those who received a single dose GnRHa trigger.

The role of Letrozole in IVF treatment: new remedy or old mirage?

Aromatase inhibitors, particularly letrozole, are now established as first-line ovulation induction agents, offering an effective ovarian stimulation strategy to enhance outcomes of intrauterine insemination. In recent years, they have also emerged as potentially valuable adjuvants to gonadotropin ovarian stimulation for IVF, particularly in fertility preservation in women with estrogen-responsive cancers. Their primary mechanism of action is to reduce circulating estrogen levels by inhibiting androgen aromatization. Recent studies have provided evidence that this property may confer therapeutic advantages in other patients undergoing IVF. In this article, evidence supporting the role of adjuvant letrozole in poor responders, as a moderator of OHSS symptoms, and an agent for improving the luteal phase after ovarian stimulation is reviewed. The use of letrozole for endometrial preparation in the frozen-thawed embryo transfer cycle is also considered.

The effects of fresh embryo transfer and frozen-thawed embryo transfer on the perinatal outcomes of single fetuses from mothers with PCOS.

To investigate the effects of fresh embryo transfer and frozen-thawed embryo transfer on perinatal outcomes among patients with PCOS. Patients who underwent in vitro fertilization and embryo transfer at the reproductive medicine center of the Affiliated Hospital of Guangdong Medical University from February 2013 to March 2021 were retrospectively analyzed. Patients were divided into the fresh embryo transfer group and frozen-thawed embryo transfer group according to whether fresh embryo transfer was performed. According to their conditions, patients were further classified into the ET-PCOS group (group A, n = 104), ET-non-PCOS group (group B, n = 212), FET-PCOS group (group C, n = 102), or FET-non-PCOS group (group D, n = 148); the general data, laboratory indicators and pregnancy outcomes of the patients were statistically analyzed, and the perinatal outcomes and related factors between the groups were compared and analyzed. The level of E2 on the HCG test day in the ET group was lower than that in the FET group. The natural birth rate of group D was lower than that of group A and group B, and the cesarean section rate was higher than that of group A and group B; the clinical pregnancy rate of group A was higher than that of group B and group D, and the difference was statistically significant (P < 0.05). There was no significant difference in the total abortion rate, early abortion rate or late abortion rate between the groups (P > 0.05). There was no significant difference in gestational age, neonatal sex or neonatal weight between the groups (P > 0.05). The incidence of placenta previa in Group B was significantly lower than that in Group D, and the difference was significant (P < 0.05). The incidence of fetal distress in Group B was significantly lower than that in Groups C and D, and the incidence of neonatal jaundice in Group D was significantly higher than that in Groups A and B (P < 0.05). In the multivariate analysis, the number of high-quality embryos was independent factors affecting clinical pregnancy, and the embryo transfer method was an independent factor affecting fetal distress and neonatal jaundice. Young PCOS patients without risk of OHSS have a high clinical pregnancy rate with fresh transplant cycles. PCOS disease itself has no significant effect on the perinatal outcomes of the mother or singleton infant. Frozen-thawed embryo transfer may increase the incidence of low placenta, fetal distress and neonatal jaundice.

Improving pregnancy outcomes in patients with recurrent implantation failure: The power of RNA-seq-based endometrial receptivity testing.

To evaluate whether RNA-seq-based endometrial receptivity testing (rsERT) can improve pregnancy outcomes in personalized frozen-thawed embryo transfer (pFET) during hormone replacement therapy (HRT) cycles among patients with recurrent implantation failure (RIF). We conducted a retrospective cohort study involving 98 RIF patients undergoing HRT for FET. The experimental group consisted of 58 patients who underwent pFET after rsERT, while the control group included 40 patients who refused rsERT and underwent conventional ET. We recorded and examined the subsequent pregnancy outcomes from all cycles. The results of rsERT revealed that 67.24% of the experimental group were out of the "window of implantation" (WOI), with all cases showing a delay. The HCG-positive rate, implantation rate, and clinical pregnancy rate (CPR) in the experimental group were significantly higher than those in the control group, at 75.86% versus 50.00% (P = .030), 56.38% versus 31.43% (P = .002), and 68.97% versus 47.50% (P = .033), respectively. Our study demonstrated that utilizing rsERT technology to guide pFET in HRT cycles significantly enhances implantation and CPRs in RIF patients. Importantly, our findings confirm the effectiveness of rsERT technology and establish a scientific rationale for personalized reproductive medical interventions.

Does hCG-trigger in the mild stimulation protocol for endometrial preparation have any effect on pregnancy outcome in frozen-thawed embryo transfer?

BackgroundRecent literature has explored the role of human chorionic gonadotropin (hCG) triggering in frozen embryo transfer (FET) cycles with natural endometrial preparation. Despite this, the impact of hCG triggering on pregnancy outcomes following endometrial preparation with mild stimulation (mST) using Letrozole and Gonadotropins remains inadequately characterized. This study aimed to elucidate the effects of hCG-trigger on pregnancy outcomes in mST-FET cycles.MethodsIn the present retrospective cohort study, the pregnancy outcomes of 409 eligible patients who underwent FET cycles with endometrial preparation using a mild ovarian stimulation protocol by letrozole plus low dose gonadotropins at the Royan Institute between 2020 and 2022, were investigated. The study population were segregated into two distinct groups according to type of ovulation: the spontaneous ovulation group (n = 138) and the hCG-trigger group (n = 271). The pregnancy outcomes including implantation and clinical pregnancy rates (CPR) and live birth rates (LBR) were compared between two groups. The multivariable logistic regression was performed to detect the most significant variables related to the LBR in the mST-FET cycles.ResultsDemographic and baseline characteristics were comparable between groups. No significant difference was found in terms of implantation rate (0.65 ± 0.32 vs. 0.60 ± 0.30, P-value: 0.31), CPR (37% vs. 39.7%, P-value: 0.53), and LBR (35.5% vs. 37.3%, P-value: 0.74) in the spontaneous ovulation and hCG-trigger groups, respectively. The logistic regression analysis revealed that only the stage of the transferred embryo exhibited a significant relationship with LBR (blastocyst vs. cleavage: odds ratio (OR); 2.33, 95% confidence interval (CI):1.41–3.86, P-value = 0.001).ConclusionPregnancy outcomes in the mST-FET cycles, including implantation rate, CPR, and LBR are comparable in cycles with or without hCG triggering. Based on the findings from multivariate regression analysis, the sole significant predictive factor for the LBR was the transfer of blastocyst embryos. It is recommended that these results be examined and discussed in future prospective studies with a larger sample size, considering the lack of comparable research in this field.

Comparison of fresh and frozen-thawed embryo transfer cycles in patients with low oocyte retrieval

Objective: To explore the choice of embryo transfer schemes for patients with low oocyte retrieval (≤ 3 oocytes). Methods: A retrospective analysis was conducted on patients with oocyte yields ≤ 3 undergoing in vitro fertilization and embryo transfer (IVF-ET) and frozen embryo transfer (FET) at the Maternity &amp; Child Care Center of Qinhuangdao Reproductive Medicine Department from January 2018 to December 2022. The data included 202 fresh cycles, with 104 cycles in Group-A and 98 cycles in Group-B. Additionally, 87 cycles involved the transfer of frozen embryos from fresh cycles that could not be transplanted for various reasons, with 31 cycles in Group-C and 56 cycles in Group-D. General patient information, embryo transfer details, and clinical pregnancy outcomes in both fresh and frozen cycles were statistically analyzed. Results: No significant differences were observed between Groups A and C in age, anti-Müllerian hormone (AMH), basal follicle-stimulating hormone (bFSH), body mass index (BMI), duration of infertility, the proportion of patients with diminished ovarian reserve (DOR), oocyte retrieval count, usable embryo count, or the number of transplanted embryos (all p&gt; 0.05). Advanced age was a risk factor for a decreased pregnancy rate, and FET significantly increased the pregnancy rate (p&lt; 0.05, respectively). Conclusion: For patients under 35 years old with low oocyte retrieval, it is recommended to freeze all embryos when available and then proceed with FET. For patients aged 35 and above, without reducing the pregnancy rate, fresh embryo transfer is recommended to minimize treatment cycle frequency and economic expenses. doi: https://doi.org/10.12669/pjms.40.10.9269 How to cite this: Shi H, Song Q, Liu J, Li C, Liu R. Comparison of fresh and frozen-thawed embryo transfer cycles in patients with low oocyte retrieval. Pak J Med Sci. 2024;40(10):2251-2255. doi: https://doi.org/10.12669/pjms.40.10.9269 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Comparison of efficacy of long follicular phase regimen and antagonist regimen on pregnancy outcome of fresh cycle or freeze-thawed cycle embryo transfer

Objective: To compare the pregnancy outcome of the fresh cycle or freeze-thaw cycle embryo transfer of patients treated with a long follicular phase regimen and antagonist regimen, and explore the clinical therapeutic effect of the two regimens. Methods: This was a retrospective study. The data of a total of 543 patients who underwent in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) or frozen-thawed embryo transfer (FET) in Baoding Maternal and Child Health Care Hospital from January 2020 to December 2022 were retrospectively analyzed in this study and were divided into four group to analyze the basic conditions, medication, laboratory indicators and clinical outcomes after embryo transfer of patients in each group. Results: The pregnancy rate and implantation rate in Groups A, B and C were higher than those in Group-D, and the differences were statistically significant (p&lt;0.05). The difference in multiple pregnancy rate and abortion rate among groups was not statistically significant (p&gt;0.05). The influencing factors of clinical pregnancy rate were identified by binary Logistic regression analysis. Advanced age was found to be a risk factor for improving the pregnancy rate, while the increase in the number of oocytes retrieved is a protective factor for improving the pregnancy rate. The differences were statistically significant (p&lt;0.05). Conclusion: The antagonist regimen has a low dosage and short medication time and can achieve a high embryo utilization rate and blastula formation rate, saving time and cost for patients. doi: https://doi.org/10.12669/pjms.40.10.9050 How to cite this: Li P, Zhai J, Liu T, Guo M, Wang Y. Comparison of efficacy of long follicular phase regimen and antagonist regimen on pregnancy outcome of fresh cycle or freeze-thawed cycle embryo transfer. Pak J Med Sci. 2024;40(10):2170-2175. doi: https://doi.org/10.12669/pjms.40.10.9050 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Contribution of cervical incompetence to occurrence of second trimester abortion in patients with polycystic ovary syndrome during the frozen embryo transfer cycle.

Second-trimester abortion is a critical issue in infertile women with polycystic ovary syndrome (PCOS) treated with assisted reproductive technology (ART), cervical incompetence (CI) may play a role. Although previous studies have revealed an association between PCOS and CI in women undergoing ART with fresh embryo transfer, the associated risk factors in frozen embryo transfer cycles are still unknown. The primary objective of this study is to examine the impact of CI on the occurrence of second-trimester abortion in women with PCOS undergoing frozen embryo transfer. This retrospective cohort study included patients who underwent frozen-thawed embryo transfer and experienced second-trimester abortion between January 2012 and January 2020 from the Reproductive Medical Center of the First Affiliated Hospital of Zhengzhou University. Logit-transformed propensity score matching (PSM) was used to assess covariates. Patients were classified into the PCOS and non-PCOS groups. The PCOS group was further divided into two subgroups: the CI group and non-CI group. After case matching with PSM, 278 patients were included: 139 each in the PCOS group and non-PCOS groups. More miscarriages were attributed to CI in the PCOS group compared with the control group (20.14% vs. 10.07%). Subsequently, in the PCOS group, CI and non-CI subgroup analyses revealed a higher transfer cleavage-stage embryo incidence in the CI group than in the blastocysts group (p=0.001). Moreover, the between-group miscarriage-related gestational age varied significantly (p=0.039). Binary logistic regression analysis revealed that cleavage embryo transfer (p= 0.047) was associated with increased CI risk in the PCOS group, besides, increasing the number of transferred embryos did not impact the occurrence of CI in patients with PCOS. CI independently predicted a higher risk of second-trimester abortion in patients with PCOS during the frozen embryo transfer cycle. What's more, increasing the number of transferred embryos did not affect the incidence of CI in the PCOS group.

Additional Daily Intramuscular Progesterone for Luteal Phase Support does not Improve Live Birth Rates of Programmed Frozen-Thawed Embryo Transfer Cycles

This retrospective cohort study aims to investigate whether additional daily intramuscular progesterone (IMP) for luteal phase support improves live birth rates of programmed frozen-thawed embryo transfer (FET) cycles. The study was conducted at a tertiary level university hospital assisted reproductive technology (ART) center between January 2014 and Jan 2021. Six hundred four infertile patients with single-day 5-6 frozen-thawed blastocyst embryo transfer were enrolled in the study. All patients received either 8% micronized vaginal gel or vaginal progesterone capsules for luteal phase support. Intramuscular progesterone was added to vaginal progesterone depending on the in vitro fertilization (IVF) specialist’s choice. Luteal phase support (LPS) was started 6 days before transfer in frozen-thawed cycles and continued until the end of the first trimester. Cycles were compared depending on vaginal progesterone types (8% gel vs. capsule) and the presence of intramuscular progesterone. The primary outcome was the live birth rate. A total of 604 FET cycles were enrolled. Using 8% micronized progesterone or progesterone capsules did not change the live birth rates (24% vs. 25.9%). As the main result, intramuscular progesterone support with vaginal progesterone compared with only vaginal progesterone did not improve the live birth results (22% vs. 24%). In conclusion, this study demonstrated that routine IMP progesterone given in combination with vaginal progesterone does not improve ART outcomes. This combination may be beneficial in a selective population with a monitored luteal phase. Using any form of vaginal progesterone alone is adequate for LPS.

High androgen level during controlled ovarian stimulation cycle impairs endometrial receptivity in PCOS patients

PCOS is one of the most common endocrine disorders among women of reproductive age. While the mechanism involved is not yet fully characterized. Our study aims to examine the pregnancy outcomes of embryo transfers in women with PCOS after pretreatment, and to explore the possible effect of high androgen levels on endometrial receptivity. Retrospective cohort study was conducted to analyze pregnancy outcomes among 2714 infertile women with tubal factor and 452 PCOS women. Endometrium samples were collected from 6 controls and 6 PCOS patients to detect the expression of endometrial receptivity marks. The implantation rate, clinical and ongoing pregnancy rates and live birth rate in women with PCOS followed fresh embryo transfers were obviously decreased even after the pretreatment. Similar pregnancy outcomes were found in frozen-thawed embryo transfer cycles between women with or without PCOS. Strikingly, serum total testosterone (TT) levels on trigger day were significantly higher in PCOS women. Women with high TT levels presented significantly lower clinical and ongoing pregnancy rates, and the expression of insulin-like growth factor binding protein 1 (IGFBP-1), and leukemia inhibitory factor (LIF) in the endometria decreased significantly as well. High doses of testosterone significantly down-regulated the expression of IGFBP-1 and LIF in Ishikawa cells. Although endocrine abnormalities had been improved before the controlled ovarian stimulation (COS) cycle started, higher serum TT levels were detected on the trigger day of the COS cycle in PCOS patients, which may contribute to the decreased fresh embryo implantation by impairing endometrial receptivity.

Differences in perinatal complications and serum hormone levels due to uterine endometrial preparation methods in frozen-thawed embryo transfer.

In frozen-thawed embryo transfer (FET), differences in endometrial preparation methods affect the incidence of perinatal complications. However, the underlying causes are unclear. We aimed to investigate whether serum E2, P4 levels are associated with perinatal complications. This is a retrospective cohort study, involving 306 successful FET pregnancies from 2017 to 2022. Participants were divided into Natural Cycle (NC) and Hormone Replacement Cycle (HRC) group. We compared serum hormone levels, maternal backgrounds, and perinatal outcomes and complications. Furthermore, within the HRC group, serum hormone levels were compared for perinatal complications previously reported to show differences in incidence rates depending on the method of endometrial preparation. HRC exhibited significantly higher serum E2 levels during the implantation period, but lower P4 levels during ovulation, implantation, and pregnancy test period compared with NC. HRC also had significantly higher rates of postpartum hemorrhage (PPH) and placenta accreta spectrum (PAS). There was no association found between perinatal complications more likely to occur in HRC and serum E2, P4 levels. In HRC, there were more occurrences of PPH and PAS. Although serum E2, P4 levels during FET did not correlate with perinatal complications.

Effects of the Zishen Yutai Pill on live births compared with placebo among infertile women with frozen-thawed embryo transfer cycle: A multicentre double-blind randomized controlled trial

BackgroundZishen Yutai Pill exhibited clinical benefit to infertile women undergoing fresh embryo transfer cycles, improving their pregnancy outcomes. However, as the endometrial environment in frozen embryo transfer (FET) is different from fresh cycles, the effects of ZYP on fresh embryo transfer could not be generalized to FET. ObjectiveWe aimed to explore the effects of ZYP on live birth rate in women's FET cycles. MethodsThis multicentre, double-blind, placebo-controlled, randomized study was conducted at 11 reproductive medical centres in China. Women were recruited and randomly assigned to ZYP or placebo intervention (5 g once, 3 times per day) around the time of FET. The live birth rate was set as the primary outcome. Secondary outcomes included implantation rate, biochemical pregnancy rate, clinical pregnancy rate, pregnancy loss rates. Data was analyzed based on the intention-to-treat principle, with per protocol analysis as sensitivity analysis. ResultsBetween December 2017 and April 2019, 934 women were screened, of whom 880 met all eligibility criteria and were allocated to ZYP (n=441) or placebo (n=439). In ITT analysis, the live birth rates were 38.32% (169/441) in ZYP group and 32.57% (143/439) (absolute difference 5.75%, 95%CI [−0.57%, 12.00%], OR 1.29, 95%CI [0.98, 1.70], P=0.08). The intervention of ZYP did not result in significantly differences in all secondary outcomes compared with placebo (all P>0.05). Similar trends were observed in PP analysis. In post hoc analysis, ZYP resulted in higher rates of live birth than placebo among women in specific subgroups, i.e., with miscarriage history (39.23% vs. 26.45%, P=0.01) or advanced maternal age (33.93% vs. 21.85%, P=0.04). ConclusionIn infertile women undergoing FET cycle, intervention with ZYP led to a trend of live birth rate increment compared with placebo, but without statistical significance. However, women with miscarriage history and advanced age could experience possible benefits from ZYP intervention. RegistrationChiCTR-INR-17010809 (http://www.chictr.org.cn).

Cumulative live birth rate of a blastocyst versus cleavage stage embryo transfer policy during in vitro fertilisation in women with a good prognosis: multicentre randomised controlled trial

ObjectivesTo evaluate whether embryo transfers at blastocyst stage improve the cumulative live birth rate after oocyte retrieval, including both fresh and frozen-thawed transfers, and whether the risk of obstetric and...

Effects of intrauterine infusion of autologous platelet-rich plasma gel on endometrial thickness and outcomes of frozen-thawed embryo transfer in women with thin endometrium.

The purpose of this study is to determine whether intrauterine infusion of autologous platelet-rich plasma (PRP) gel increases endometrial thickness (EMT) and improves the outcomes of frozen-thawed embryo transfer (FET) in women with thin endometrium. This study included 111 women (aged 25-44years) who had thin endometrium. All patients had at least one previous cycle canceled because of thin endometrium or previous embryo transfer cycles and an EMT < 7mm. Forty-seven women underwent intrauterine infusion of autologous PRP gel on three occasions during endometrial preparation and the remaining women served as controls. The final EMT was measured by ultrasound before the start of the luteal phase, and FET-related outcome parameters were monitored. Mean EMT was greater in women who received PRP gel than in those who did not (6.7mm vs. 6.3mm, respectively, p < 0.05). FET was attempted in all women. The 47 women who underwent infusion of PRP had a significantly higher pregnancy rate (18 pregnancies (38.3%), with 17 (36.2%) ongoing) compared with 64 control women (ten pregnancies (18.5%), nine (16.7%) ongoing). However, there was no significant reduction in the miscarriage rate. Intrauterine infusion of autologous PRP gel during endometrial preparation for FET cycles can improve the EMT, clinical pregnancy rate, and ongoing pregnancy rate in women with thin endometrium.

Single-cell RNA-sequencing analysis of the effects of frozen-thawed embryo transfer on the transcriptome of trophoblasts

Objectives: Frozen-thawed embryo transfer (FET) is widely used in in vitro fertilization (IVF) clinics but is associated with an increased risk of several pregnancy complications, including large-for-gestational age and placenta-related diseases. However, the effects of FET on placentation remain unclear. Therefore, we used single-cell RNA-sequencing (scRNA-seq) technology to investigate the impact of FET on placental gene expression in different subtypes of trophoblasts. Methods: A mouse model of IVF and FET was constructed to collect placenta tissues. scRNA-seq was performed on placentas from two dams undergoing IVF-embryo transfer and two dams undergoing IVF-FET. Differentially expressed gene (DEG) analyses were performed in different subtypes of trophoblasts. Identified DEGs were PCR validated. Results: The fetal weights and placental efficiency were higher in the FET group than those on the IVF group at E18.5, with no significant difference in placental weights. Subsequently, 55,406 placental cells were captured and annotated. Upregulated DEGs in the FET group in syncytiotrophoblasts (SynTs) and sinusoidal trophoblast giant cells (S-TGCs) within the placental labyrinth were enriched in pathways related to vascular development and oxidative stress, respectively. The expression of the imprinted gene Igf2 in SynTs, S-TGCs, and spongiotrophoblasts was significantly increased. In the junctional zone, FET upregulated the expression of prolactin genes such as Prl3b1 in glycogen trophoblasts (GlyTs) while the downregulated expression of GlyT genes following FET was associated with mesenchyme development. Conclusion: This study first identifies DEGs and enriched pathways in different subtypes of trophoblasts following FET. These genes and pathways may contribute to the increased placental efficiency and fetal weights. Future studies are required to confirm these results and further explore the key mechanisms in placental pathologies.

Comparison of ultra-long gonadotropin releasing hormone agonist versus standard downregulation in women with adenomyosis undergoing frozen-thawed embryo transfer: a randomized clinical trial

BackgroundAdenomyosis can lead to infertility and failure of in vitro fertilization. Limited evidence suggests that the use of long-term treatment with gonadotropin-releasing hormone (GnRH) agonists followed by frozen-thawed embryo transfer (FET) may be the preferred approach for women with adenomyosis.ObjectiveThe aim of this randomized controlled trial is to compare the efficacy of an ultra-long GnRH agonist with standard downregulation in women with adenomyosis undergoing FET.Materials and methodsThis randomized controlled trial enrolled 72 women with adenomyosis diagnosed by sonographic criteria who underwent FET cycles at the Avicenna Infertility Center. These women were randomly assigned to two equal groups: one received GnRH agonist treatment for three months before the FET cycle and the other served as the standard downregulation group. Results were reported as chemical and clinical pregnancy rates.ResultsThe two groups were similar in age, body mass index, anti-Müllerian hormone levels, number of previous pregnancies and miscarriages, presence of uterine myomas, and endometriosis. However, the total dose of estradiol used until embryo transfer was significantly higher in the ultra-long GnRH agonist group than in the standard group (96.14 mg vs. 80.52 mg, p-value = 0.004). Nevertheless, chemical and clinical pregnancy rates did not differ significantly between the two groups.ConclusionsUltra-long GnRH agonist downregulation did not improve the chemical and clinical pregnancy rate in the FET cycle in women with adenomyosis compared with standard GnRH agonist downregulation in the other words, ultra-long GnRH agonist downregulation is not superior to standard protocol. In women with adenomyosis (without history of endometriosis), downregulation of standard GnRH agonists prior to frozen-thawed embryo transfer may be the preferred embryo transfer protocol to gain higher clinical/chemical pregnancy rate.Trial registrationClinical trial registry: IRCT20160717028967N9, available at: https://irct.behdasht.gov.ir/trial/36103.

Evaluating the effectiveness and adverse effects of oral versus transdermal estradiol for endometrial preparation in frozen-thawed embryo transfer: a randomized controlled trial

BackgroundEndometrial preparation significantly influences the success of embryo transfer procedures. Although both oral and transdermal estradiol are common methods for endometrial priming, their efficacy and potential side effects remain uncertain. This randomized controlled trial aims to compare the effectiveness of oral and transdermal estradiol in endometrial preparation, while also evaluating their respective side effects in patients undergoing assisted reproduction treatments.MethodThis randomized clinical trial (ISRCTN15301227) was conducted at Hung Vuong Hospital between July 2020 and March 2022. Among 550 eligible patients undergoing frozen embryo transfer cycles, we included 380 patients for the study. The study protocol and all materials received approval from the Ethics Committee of Hung Vuong Hospital (1315/CN-HĐĐĐ). Participants were randomly assigned to one of two groups: Group A (n =190) received oral estradiol at an initial dose of 4 mg per day for 7 days, with the dose increased according to clinical response. Group B (n =190) received transdermal estradiol at an initial dose of 2 measures of 2.5 g estradiol gel per day for 7 days, with the dose similarly increased according to clinical response. Treatment in both groups began on days 2–3 of the menstrual cycle, with the maximum duration of estradiol administration being 27 days. We compared estradiol levels on the day of progesterone administration, duration of treatment, total estradiol dose, endometrial thickness, pregnancy outcomes, and any observed side effects between the two groups.ResultsGroup A exhibited significantly higher estradiol levels on the day of progesterone administration compared to Group B (270.5 pg/ml versus 186.5 pg/ml, p < 0.001). However, the comparison revealed no significant difference in endometrial thickness between the two groups (10.5 mm versus 10.6 mm, p = 0.85). Furthermore, pregnancy rates including positive human chorionic gonadotropin, clinical pregnancy, ongoing pregnancy, live birth, and pregnancy failure were also found to be similar between the two groups. Notably, a greater proportion of patients in Group A experienced mild side effects compared to those in Group B (20.3% versus 10.1%, respectively; n =37 versus n =18), and this discrepancy was found to be statistically significant (p = 0.007).ConclusionTransdermal estradiol offers comparable endometrial thickness and pregnancy outcomes, along with improved patient compliance and fewer side effects compared to oral estradiol.

Effects of pretreatment with long-acting gonadotropin-releasing hormone agonists on pregnancy outcomes in patients with minimal and mild peritoneal endometriosis: A retrospective study of 274 frozen-thawed embryo transfer cycles.

To investigate the effects of pretreatment with long-acting gonadotropin-releasing hormone agonist (GnRH-a) before frozen-thawed embryo transfer (FET) on pregnancy outcomes in patients after minimal-mild (stages I-II) peritoneal endometriosis surgery. A retrospective cohort study was performed from March 2018 to May 2019. Overall, 274 patients met inclusion criteria of undergoing FET after minimal/mild peritoneal endometriosis surgery. For the FET protocol, patients were divided into 2 groups: GnRH-a plus hormone replacement therapy (HRT) (group A, n = 154) and HRT-only (group B, n = 120), with the former divided into 2 subgroups receiving 1 (group A1, n = 80) or 2 doses (group A2, n = 74) of GnRH-a. Basic characteristics and pregnancy outcomes of groups A and B and groups A1 and A2 were compared. Clinical pregnancy rate (CPR) and live birth rate (LBR) were the primary outcomes and logistic regression was used to analyze independent correlation factors. The CPR and LBR in group A were 58.4% and 50.0%, respectively, and were not significantly higher than in group B (49.2% and 40.0%; respectively, χ2 = 2.339, P = .126 and χ2 = 2.719, P = .099, respectively). CPR and LBR in group A1 were not significantly lower than those in group A2 (52.5% and 45.0% vs 64.9% and 55.4%, respectively; χ2 = 2.420, P = .120 and χ2 = 1.665, P = .197, respectively). However, group A2's CPR and LBR were significantly higher than group B's (64.9% and 55.4% vs 49.2% and 40.0%, respectively; χ2 = 4.560, P = .023 and χ2 = 4.375, P = .026, respectively). Logistic regression analysis showed that GnRH-a pretreatment (1 or 2 doses) had no significant effect on CPR and LBR compared with the HRT-only group. Patients with minimal-mild (stages I-II) peritoneal endometriosis surgery may not require GnRH-a pretreatment before FET.

Automated endometrial identification and volume calculation in normal uteri using a novel smart ERA technique

To evaluate the repeatability of a novel automated technique called Smart ERA (Smart Endometrial Receptivity Analysis) for the automated segmentation and volume calculation of the endometrium in patients with normal uteri,, and to compare the agreement of endometrial volume measurements between Smart ERA, the semi-automated Virtual Organ Computer-aided Analysis (VOCAL) technique and manual segmentation. This retrospective study evaluated endometrial volume measurement in infertile patients who underwent frozen-thawed embryo transfer (FET). Transvaginal three-dimensional ultrasound scans were performed using a Resona R9 ultrasound machine. Data was collected from patients between 2021 and 2022. Patients with normal uteri and optimal ultrasound images were included. Endometrial volumes were measured using Smart ERA, VOCAL at 15° rotation, and manual segmentation. Intra-observer repeatability and agreement between techniques were assessed using the intraclass correlation coefficient (ICC) and Bland–Altman analysis. A total of 407 female patients were evaluated (mean age 33.2 ± 4.7 years). The repeatability of Smart ERA showed an ICC of 0.983 (95% CI 0.984–0.991). The agreement between Smart ERA and the manual method, Smart ERA and VOCAL, and VOCAL and the manual method, as assessed by ICC, were 0.986 (95% CI 0.977–0.990), 0.943 (95% CI 0.934–0.963), and 0.951 (95% CI 0.918–0.969), respectively. The Smart ERA technique required approximately 3 s for endometrial volume calculation, while VOCAL took around 5 min and the manual segmentation method took approximately 50 min. The Smart-ERA software, which employs a novel three-dimensional segmentation algorithm, demonstrated excellent intra-observer repeatability and high agreement with both VOCAL and manual segmentation for endometrial volume measurement in women with normal uteri. However, these findings should be interpreted with caution, as the algorithm's performance may not be generalizable to populations with different uterine characteristic. Additionally, Smart ERA required significantly less time compared to VOCAL and manual segmentation.

The impact of intracytoplasmic sperm injection versus conventional in vitro fertilization on the reproductive outcomes of couples with non-male factor infertility and frozen-thawed embryo transfer cycles

This study was aimed to investigate the impact of intracytoplasmic sperm injection (ICSI) on reproductive outcomes in couples with non-male factor infertility and frozen-thawed embryo transfer (FET) treatment. This retrospective cohort study involved a total of 10,143 cycles from 6206 couples who underwent FET at the Third Affiliated Hospital of Zhengzhou University between January 2016 and September 2022. Patients were categorized into two groups based on the insemination methods of transferred embryos. Clinical and neonatal outcomes were compared between ICSI and conventional in vitro fertilization (cIVF) groups. The results showed that ICSI was not associated with improved clinical outcomes compared to cIVF. However, ICSI was associated with lower birthweight when twins were born. In conclusion, although subgroup analysis showed that ICSI was associated with slightly improved live birth rate for infertile couples with non-male factor infertility compared to cIVF, the regression analysis showed that ICSI did not demonstrate any improvement of the reproductive outcomes. The infertile women with twin pregnancies should be further informed of the lower birthweight and lower birth length when their oocytes were inseminated with ICSI. The findings of this study provide valuable insights for clinicians when discussing the benefits and risks of ICSI in patients with non-male factor infertility.