Gonadotropin-releasing Hormone Agonist Pretreatment Research Articles

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.

Pretreatment with long-acting gonadotropin-releasing hormone agonists improved pregnancy outcomes after hysteroscopic multiple polypectomies: A retrospective study of 660 frozen–thawed embryo transfer cycles

ObjectiveTo compare the reproductive pregnancy outcomes of pretreatment with long-acting gonadotropin-releasing hormone agonist (GnRH-a) plus hormone replacement therapy (HRT) with HRT-only cycles, and investigate differences between single polypectomy and multiple polypectomies, and between one or two doses of GnRH-a. Materials and methodsThis was a retrospective cohort study on patients undergoing polypectomy who underwent frozen–thawed embryo transfer (FET) from March 2018 to May 2019. They were divided into GnRH-a pretreatment and HRT-only groups. Each group was divided into single polypectomy or multiple polypectomies (in a single hysteroscopic session) subgroups. Clinical pregnancy rate and live birth rate (LBR) were the main outcomes. The effect of GnRH-a dosage was further analysed. ResultsThere were 212 GnRH-a pretreatment cases (45 single and 167 multiple polyps) and 448 HRT-only cases (228 single and 220 multiple polyps). The LBR of the GnRH-a pretreatment group (53.3%) was significantly higher than the HRT group (43.3%; P = 0.016). Logistic regression analysis showed that GnRH-a pretreatment significantly affected the LBR (odds ratio, OR 1.470, 95% confidence interval, Cl 1.046–2.065; P = 0.026). In the multiple polypectomy subgroup, the LBR with GnRH-a pretreatment was higher than with HRT-only (54.5% vs 43.6%; P = 0.034). However, the LBR was not different between the respective single polypectomy subgroups (48.9% vs 43.0%; P = 0.466). For patients with multiple polyps, two GnRH-a pretreatments produced a higher LBR than a single GnRH-a pretreatment (62.7% vs 47.8%), but without significant difference (P = 0.055). ConclusionGnRH-a pretreatment improved the LBR for FET cycles after hysteroscopic multiple polypectomies, independent of dose.

Pretreatment with a long-acting GnRH agonist for frozen-thawed embryo transfer cycles: how to improve live birth?

BackgroundWhether pretreatment with gonadotropin-releasing hormone agonist (GnRHa) can improve the pregnancy outcomes in frozen-thawed embryo transfer (FET) cycles is controversial. The inconsistencies in the results of different studies would be related to the characteristics of the included patients and the protocol of GnRHa use. In this study, we investigated the efficacy of pretreatment with a long-acting GnRH agonist in the early follicular phase of FET cycles and determined which population was suitable for the protocol.ResultsWe retrospectively included 630 and 1141 patients in the GnRHa FET and hormone replacement treatment (HRT) FET without GnRHa groups respectively, between October 2017 and March 2019 at a university-affiliated in vitro fertilization center. On the second or third day of menstruation, 3.75 mg of leuprorelin was administered. After 14 days, HRT was initiated for endometrial preparation. No significant differences were observed between the two groups in terms of patient characteristics. However, the GnRHa FET group showed a higher percentage of endometrium with a triple line pattern (94.8% vs 89.6%, p < 0.001) on the day of progesterone administration, with increased implantation (35.6% vs 29.8%, p = 0.005), clinical pregnancy (49.8% vs 43.3%, p = 0.008), and live birth rate (39.4% vs 33.7%, p = 0.016), than the HRT FET cycles with similar endometrial thickness, ectopic pregnancy and early miscarriage rates. Binary logistic regression analysis showed the GnRHa FET group to be associated with an increased chance of clinical pregnancy (P=0.028, odds ratio [OR] 1.32, 95% confidence interval [CI] 1.03–1.70) and live birth (P=0.013, odds ratio [OR] 1.34, 95% confidence interval [CI] 1.06–1.70) compared to the HRT FET without GnRHa group. After subgroup analysis, we found that the GnRHa FET group showed a significantly higher live birth rate in the subgroups of age < 40 years, primary infertility, with polycystic ovary syndrome (PCOS), and irregular menstruation.ConclusionsPretreatment with a long-acting GnRHa during the early follicular phase improved the live birth rate in FET cycles. Age < 40 years, primary infertility, PCOS, and irregular menstruation are effective indications for endometrial preparation with GnRHa pretreatment in FET cycles. However, further randomized controlled trials are required to verify these results.

Evaluation of the efficacy of GnRH-a pretreatment before total hysterectomy for adenomyosis patients: a propensity score matching analysis

Objective: To evaluate the efficacy of gonadotropin-releasing hormone agonist (GnRH-a) pretreatment before total hysterectomy for adenomyosis patients with uterine volume ≥12 gestational weeks and moderate or severe anemia. Methods: From January 2018 to March 2023, 689 patients who underwent total hysterectomy for adenomyosis in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. According to the preoperative medication, they were divided into study group (127 cases) and control group (562 cases). Patients in the study group underwent GnRH-a pretreatment for 3 cycles before surgery, and the control group received operation directly. SPSS 26.0 software was used to perform 1∶1 matching for the two groups of patients through the propensity score matching method. Matching variables included age, body mass index, gravidity, parity, history of pelvic and abdominal surgery, menstrual cycle, menstrual period, dysmenorrhea score, initial diagnosis of cancer antigen 125 (CA125), uterine volume and hemoglobin value. The dysmenorrhea score, uterine volume, hemoglobin value and CA125 level before and after GnRH-a pretreatment in the study group were compared. And the duration of operation, intraoperative blood loss, postoperative white blood cell count, perioperative blood transfusion cases, postoperative disease rate, duration of hospitalization, total hospitalization cost between the two groups were compared. Results: With propensity score matching, 119 patients in the study group and 119 patients in the control group were finally enrolled in this study. In the study group, before and after the treatment with GnRH-a, the dysmenorrhea score (7.4±1.7 vs 5.6±1.8), uterine volume [(362±160) vs (233±126) cm3], hemoglobin value [(74.1±10.7) vs (102.5±13.5) g/L], and CA125 level [(104±76) vs (64±51) kU/L] were statistically different (all P<0.05). There were statistical differences of operation time [(86±18) vs (116±31) minutes], intraoperative blood loss [(24±9) vs (43±22) ml], white blood cell count after 1 day of operation [(9.80±0.10)×109/L vs (9.90±0.10)×109/L], number of perioperative blood transfusion case [5.9% (7/119) vs 61.3% (73/119)], postoperative disease rate [5.0% (6/119) vs 16.0% (19/119)], hospitalization duration [(7.1±1.6) vs (7.9±1.6) days], and total hospitalization cost [(35 323±5 275) vs (37 159±5 640) yuan] between the study group and the control group (all P<0.05). Conclusion: The pretreatment of using GnRH-a before total hysterectomy for adenomyosis patients with uterine volume ≥12 gestational weeks and moderate or severe anemia is not only conducive to improving dysmenorrhea, signs of anemia, reducing uterine volume, but also conducive to the implementation of surgery, reducing intraoperative and postoperative complications, and reducing hospital costs.

Pregnancy outcomes in women with adenomyosis, undergoing artificial endometrial preparation with and without gonadotropin-releasing hormone agonist pretreatment in frozen embryo transfer cycles: An RCT.

Selecting a suitable and preferable method for endometrial preparation in frozen embryo transfer (FET) cycles for women with adenomyosis is still challenging in infertility treatment. To compare 2 artificial endometrial preparation regimens with and without gonadotropin-releasing hormone agonist (GnRHa) pretreatment in women with adenomyosis undergoing FET cycles. This randomized clinical trial study was conducted on 140 adenomyosis cases who underwent FET cycles at Arash Women's hospital, Tehran, Iran from May 2020 to March 2021. Participants were randomly allocated into hormonal replacement therapy (HRT) and HRT+GnRHa pretreatment groups (n = 70/each). Endometrial preparation with 2-6 mg daily estradiol was started in the HRT+GnRHa group, taking after down-regulation with the GnRHa. Within the HRT group, the same dose of estradiol was commenced within the early follicular stage. The main (chemical and clinical pregnancy rates) and auxiliary results (twin pregnancy, miscarriage, and live birth rates) were compared between groups. The demographic characteristics and severity of adenomyosis, endometrial thickness, and pattern at starting progesterone administration were similar in the 2 groups, and triple-line endometrium was found to be the dominant pattern in both groups (p = 0.65). No significant differences were observed in chemical, clinical, and twin pregnancy rates as well as miscarriage and live birth rates between groups (p = 0.71, p = 0.81, p = 0.11, and p = 0.84, respectively). However, the total estrogen dose and duration of estrogen consumption were significantly higher in the pretreatment group (p = 0.001, and p = 0.003). These results indicated that the hormonal endometrial preparation with estrogen and progestin for FET cycles is as efficacious as a protocol involving preceding pituitary suppression with a GnRHa. Further large randomized clinical studies are required to confirm these findings.

Obstetric and neonatal outcomes after programmed frozen embryo transfer with or without GnRH agonist for polycystic ovary syndrome: secondary analysis results from a randomized controlled trial

Recent studies have reported higher risks of adverse maternal and neonatal outcomes, such as hypertensive disorders of pregnancy, after programmed frozen embryo transfer, especially in cycles with gonadotropin-releasing hormone agonist pretreatment. It remains unclear if GnRH agonist pretreatment before programmed frozen embryo transfer further increases the risk for obstetrical complications among women with polycystic ovary syndrome. This study aimed to compare the obstetrical and neonatal complications of singleton and twin pregnancies after programmed frozen embryo transfer with or without gonadotropin-releasing hormone-a pretreatment among women with polycystic ovary syndrome. This was a secondary analysis of a single-center, randomized controlled trial comparing the live birth rate and cost-effectiveness of programmed cycle-prepared frozen embryo transfers with or without gonadotropin-releasing hormone agonist pretreatment among women with polycystic ovary syndrome. The analysis was restricted to women with polycystic ovary syndrome, aged 24 to 40 years, who delivered live neonates after frozen-thawed blastocyst transfer. The obstetrical and neonatal outcomes were compared between programmed cycles with and those without gonadotropin-releasing hormone agonist pretreatment. The adjusted odds ratios with 95% confidence intervals were calculated and adjustments were made for relevant confounders. The maternal and neonatal complications associated with 177 live single births and 38 twin births (253 newborns in total) were analyzed. There were no significant differences in the frequencies of obstetrical complications, including hypertensive disorders of pregnancy, between the gonadotropin-releasing hormone agonist pretreatment and no pretreatment group for both singleton and twin pregnancies. However, there was a significantly greater incidence of having a low birthweight neonate among singleton infants born after gonadotropin-releasing hormone agonist pretreatment when compared with no pretreatment (10.2% vs 1.3%; P=0.042), and a low birthweight among singleton infants was still more likely after adjusting for confounders (relative ratio, 3.85; 95% confidence interval, 1.13-7.11; P=.024). Other neonatal complications were all comparable between the pretreatment and no pretreatment groups for both singleton and twin pregnancies. For women with polycystic ovary syndrome, programmed frozen embryo transfer cycles with gonadotropin-releasing hormone agonist pretreatment could lead to a greater risk of having a low birthweight singleton neonate.

Gonadotropin-Releasing Hormone agonist (GnRH-a) Pretreatment before Hormone Replacement Therapy Does Not Improve Reproductive Outcomes of Frozen–Thawed Embryo Transfer Cycle in Older Patients with Intrauterine Fibroid: A Retrospective Cohort Study

Surgery in elder patients with intermural fibroids delays pregnancy, and GnRH-a can shrink uterine fibroids to a certain extent; therefore, for geriatric patients with fibroids, determining whether GnRH-a pretreatment before frozen-thawed embryo transfer (FET) can improve its success rate remains to be studied. We conducted this study to research whether GnRH-a pretreatment before hormone replacement treatment (HRT) could optimize the reproductive outcomes compared with others preparations in geriatric patients with intramural fibroids. According to the endometrial preparation, patients were divided into a GnRH-a-HRT group, a HRT group and a natural cycle (NC) group. The live birth rate (LBR) was the first outcome, and the clinical pregnancy outcome (CPR), the miscarriage rate, the first trimester abortion rate and the ectopic pregnancy rate were the secondary outcomes. A total of 769 patients (aged 35 years or older) were included in this study. No significant difference was observed in the live birth rate (25.3% vs. 17.4% vs. 23.5%, p = 0.200) and the clinical pregnancy rate (46.3% vs. 46.1% vs. 55.4%, p = 0.052) among the three endometrial preparation regimens. In this study, for the geriatric patient with the intramural myoma, the pretreatment with GnRH-a did not show any advantage over the NC and HRT preparation groups before the FET, and the LBR was not significantly increased.

Effects of gonadotropin-releasing hormone agonist pretreatment on frozen embryo transfer outcomes in artificial cycles: a meta-analysis.

Gonadotropin-releasing hormone agonist (GnRHa) before artificial cycle (AC) is expected to improve pregnancy outcomes in frozen-thawed embryo transfer (FET). Many studies have explored the impact of GnRHa pretreatment of AC in FET, but the results were inconsistent. This meta-analysis was performed to systematically evaluate the effect of GnRHa pretreatment on AC in FET. The last search was January 31, 2022. Randomized controlled trials and cohort studies aiming to assess the effect of GnRHa as the pretreatment of AC for endometrial preparation in FET were included. GnRHa was used before AC in the treatment group. In the control group, no pretreatment was used before AC. The eligible studies included at least one of the following outcomes: implantation, clinical pregnancy, and live birth. We calculated the odds ratio (OR) or mean difference (MD) and 95% confidence interval (CI) for each study and used a random-effects or fixed model to estimate the results. 27 articles (10 RCTs and 17 non-RCTs) and 14152 patients were included. AC + GnRHa improved the implantation rate (OR = 1.31, 95% CI 1.03-1.66, I2 = 79%), clinical pregnancy rate (OR = 1.27, 95% CI 1.10-1.45, I2 = 53%), and live birth rate (OR = 1.16, 95% CI 1.05-1.29, I2 = 39%). We also found that AC + GnRHa increased the implantation rate (OR = 1.35, 95% CI 1.07-1.69, I2 = 53%) and clinical pregnancy rate (OR = 1.50, 95% CI 1.12-2.01, I2 = 50%) in repeated implantation failure. In addition, AC + GnRHa was positively associated with preterm birth (OR = 1.5, 95% CI 1.15-1.94, I2 = 0%). GnRHa pretreatment in FET can improve implantation, clinical pregnancy, and live birth rates, especially in patients with repeated implantation failure. GnRHa pretreatment seems to improve FET outcomes, though with a higher preterm birth rate.

Administration of depot GnRH agonist prior to programmed frozen-thawed embryo transfer does not improve the live birth rate in ovulatory women: A large, multi-center retrospective study.

Despite that gonadotropin-releasing hormone (GnRH) agonist pretreatment has been widely used before programmed frozen-thawed transfer (FET), its impact on live birth rates in ovulatory women remains uncertain. In the present study, we aim to determine if GnRH agonists pretreatment before FET improves live birth rates in women undergoing in vitro fertilization with FET. Programmed FET cycles conducted in four infertility centers were retrospectively collected and reviewed for eligibility from January 2016 and December 2017. Patient’s demographics, ovarian stimulation parameters, and pregnancy outcomes were compared between those given GnRH agonist pretreatment versus no pretreatment in ovulatory women undergoing FET cycles. A total of 6397 programmed cycles were screened for eligibility, of which 5049 cycles were included in the study for analysis. Compared with the group of no GnRH agonist pretreatment (n = 4143), women in the GnRH agonist group (n = 906) were older (33.0 vs 34.0, P < .001), had a higher proportion of subjects with previous transfer attempts and had a higher number of embryos transferred. After controlling for confounders, the logistic regression results showed that GnRH agonist pretreatment did not increase the odds of both clinical pregnancy (OR 0.92, 95% CI [0.70–1.20]), ongoing pregnancy (OR 0.91, 95% CI [0.69–1.19]) and live birth rates (OR 0.84, 95% CI [0.64–1.10]). However, when restricted to women who had no previous transfer attempts, women in the GnRH pretreatment group had lower odds of achieving live birth (OR 0.49, 95% CI [0.30–0.79]). Sensitivity analysis performed in patients with male factor infertility causes showed GnRH agonist pretreated group had lower live birth rates compared to no GnRH agonist pretreatment group (OR = 0.65, 95% CI [0.43–0.97]). Our findings suggested that GnRH agonist pretreatment does not bring additional benefits in live birth rate improvements for ovulatory women undergoing FET cycles. Therefore, the pros of using GnRH agonist to reduce premature ovulation should be weighed against the cons of prolonged time to pregnancy, discomforts resulting from pituitary suppression, and increased medical costs associated with GnRH agonist use.

GnRH-agonist pretreatment in hormone replacement therapy improves pregnancy outcomes in women with male-factor infertility.

ObjectiveThis study aimed to examine the efficacy of HRT with gonadotropin-releasing hormone agonist (GnRH-a) pre-treatment in women with male-factor infertility who underwent a frozen embryo transfer (FET) programme.DesignBetween January 2016 and October 2020, 2733 women with male-factor infertility who underwent the HRT protocol as the endometrial preparation method were enrolled at two Reproductive Medicine Centres. Patients were divided into two groups based on whether they had GnRH-a pre-treatment before HRTs: the GnRHa-HRT group and the HRT group. The inverse probability of treatment weighting (IPTW) method was conducted to balance patient baseline characteristics between treatment cohorts to reduce selection bias. The live birth rate was considered regarded as the primary pregnancy outcome.ResultsMultivariate logistic regression adjusted for confounding factors, the GnRHa-HRT group showed a notably higher rate of live birth (OR 2.154, 95% CI 1.636~2.835, P<0.001) when compared to the HRT group. Additionally, the rate of miscarriage was significantly lower in the GnRHa-HRT group. The GnRHa-HRT group had significantly higher rates of biochemical pregnancy, clinical pregnancy, multiple pregnancy, and term birth.ConclusionThe endometrial preparation protocol of HRT with GnRH-a pre-treatment could obviously increase the live birth rate for women with male-factor infertility undergoing the FET programme.

Hormone replacement therapy with GnRH agonist pretreatment improves pregnancy outcomes in patients with previous intrauterine adhesions

PurposeTo explore the optimal cycle regimen for frozen-thawed embryo transfer (FET) in women with previous intrauterine adhesions (IUAs). MethodsIn this retrospective cohort study, a total of 1,002 FET cycles for patients with previous IUAs from January 2015 to December 2020 were included. Among them, 294 conventional hormone replacement therapy (HRT) cycles were matched with 155 HRT with gonadotropin releasing hormone agonist pretreatment (HRT+GnRH-a) cycles using propensity score matching. Multivariate logistic regression analysis was performed to further investigate the impact of cycle regimen on pregnancy outcomes. ResultsAfter propensity score matching, baseline characteristics were consistent between HRT and HRT+GnRH-a group. Logistic regression analysis revealed that there was a significant superiority of HRT+GnRH-a over the conventional HRT group regarding the incidences of live birth (aOR=1.966, 95%CI: 1.212-3.188, P=0.006) and ongoing pregnancy (aOR=1.710, 95%CI: 1.057-2.767, P=0.029). HRT+GnRHa also had a higher odd of clinical pregnancy (aOR=1.414, 95%CI: 0.903-2.216, P=0.130), and lower odd of early miscarriage (aOR=0.511, 95%CI: 0.219-1.195, P=0.121) compared to HRT, yet not reached statistical significance. ConclusionHRT with GnRH-a pretreatment improves pregnancy outcomes in women with previous IUAs. GnRH-a may restore the endometrial receptivity in the FET cycles of IUAs. Synopsis: HRT with GnRH-a pretreatment may promote pregnancy prognosis of FET in women with history of IUAs by restoring endometrial receptivity.

Effect of artificial cycle with or without GnRH-a pretreatment on pregnancy and neonatal outcomes in women with PCOS after frozen embryo transfer: a propensity score matching study

BackgroundIn frozen embryo transfer (FET), there is limited consensus on the best means of endometrial preparation in terms of the reproductive outcomes in women with polycystic ovary syndrome (PCOS). The present study aimed to compare the pregnancy and neonatal outcomes following artificial cycle FET (AC-FET) with or without gonadotropin-releasing hormone agonist (GnRH-a) pretreatment among women with PCOS.MethodsA total of 4503 FET cycles that satisfied the inclusion criteria were enrolled in this retrospective cohort study between 2015 and 2020. The GnRH-a group received GnRH-a pretreatment while the AC-FET group did not. Propensity score matching (PSM) method and multivariate logistic regression analysis were performed to adjust for potential confounding factors.ResultsAfter PSM, women in the GnRH-a group suffered a significantly lower miscarriage rate (11.2% vs. 17.1%, P = 0.033) and a higher live birth rate (LBR) compared with those in the AC-FET group (63.1% vs. 56.8%, P = 0.043). No differences were observed in the rates of biochemical pregnancy, clinical pregnancy and ectopic pregnancy between the two groups. A higher mean gestational age at birth was observed in the GnRH-a group than in the AC-FET group (39.80 ± 2.01 vs. 38.17 ± 2.13, P = 0.009). The incidence of neonatal preterm birth (PTB) in the GnRH-a group was lower than that in the AC-FET group (7.4% vs. 14.9%, P = 0.009). Singleton newborns conceived after GnRH-a group were more likely to be small for gestational age (SGA) than those born after AC-FET group (16.4% vs. 6.8%, P = 0.009). However, no significant differences were found between the two groups in terms of mean birthweight, apgar score, the rates of macrosomia, large for gestational age and low birth weight.Conclusion(s)In women with PCOS who underwent AC-FET, GnRH-a pretreatment was significantly associated with a higher live birth rate and a reduced risk of neonatal PTB. However, there was a concomitant increase in the risk of developing SGA babies.

GnRH agonist treatment regulates IL-6 and IL-11 expression in endometrial stromal cells for patients with HRT regiment in frozen embryo transfer cycles

To evaluate the effect of gonadotropin-releasing hormone agonist (GnRHa) pretreatment time on clinical outcomes of patients who underwent endometrial preparation in HRT cycles and the molecular mechanism in frozen-thawed embryo transfer (FET) cycles, we retrospectively chose 1143 cycles and separated four groups. Endometrial tissues were collected from 44 patients who were cancelled on the day of embryo transfer (there were 10 patients refused to collect endometrium) and were tested for endometrial receptivity marker mRNA and miR-124-3p expression. Furthermore, endometrial stromal cells (ESCs) were transfected to investigate the molecular mechanism. The clinical pregnancy rate and live birth rate were significantly high in group B. The endometrial expression of the IL-6 and IL-11 mRNAs was significantly increased in groups with GnRHa pretreatment compared with group A without the GnRHa pretreatment. Similar results were obtained for the endometrial receptivity markers LIF and integrin αvβ3. The groups treated with GnRHa exhibited a progressive and significant time-dependent decrease in the IL-6 and IL-11 mRNA. In contrast, the levels of LIF and integrin αvβ3 expression remained unaltered among group B-D. In addition, transfection of ESCs with miR-124-3p mimics significantly reduced levels of the IL-6 and IL-11 mRNAs and proteins. The luciferase report assay demonstrated that IL-6 and IL-11 is a target gene of miR-124-3p. The results showed that ultra-long GnRHa administration can improve outcomes, especially after 3 cycles of GnRHa pretreatment, and endometrial receptivity through IL-6 and IL-11 expression levels of ESC regulated by the miR-124-3p for patients with HRT, who underwent FET cycles.

Hormonal Replacement Treatment for Frozen-Thawed Embryo Transfer With or Without GnRH Agonist Pretreatment: A Retrospective Cohort Study Stratified by Times of Embryo Implantation Failures.

ObjectiveTo evaluate the efficacy of the long-acting gonadotropin-releasing hormone agonist (GnRH-a) administration before hormone replacement treatment for frozen-thawed embryo transfer in women with different times of embryo implantation failures.MethodsA retrospective cohort study was performed between January 2015 and December 2019. A total of 9263 women who underwent frozen-thawed embryo transfer were included in the study. The study is divided into three parts based on the times of embryo implantation failures. The sample sizes were 4611 for no implantation failure, 3565 for one failure and 1087 for multiple failures. Two endometrium preparation protocols, HRT and HRT with GnRH-a pretreatment (G-HRT), were compared. Confounding factors were treated by propensity score matching and generalized estimation equation.ResultsFor women with no failure of embryo implantation, the live birth rate was not statistically different when they underwent HRT and G-HRT (HRT: 42.75% [498/1165], G-HRT: 45.24% [527/1165], P=0.2261). Similar outcome also appeared in women with one failure of embryo implantation (HRT: 47.22% [535/1133], G-HRT: 50.31% [570/1131], P=0.1413). For women with multiple failures of embryo implantation, the live birth rate was significantly difference (HRT: 38.74% [117/302], G-HRT: 45.48% [357/785], P=0.0449). When stratified by age, the live birth rate is similar for women older than 37 years. Generalized estimation equation showed that GnRH agonist pretreatment was independently associated with the live birth rate for women with multiple failures (adjust OR: 1.5, 95%CI: [1.12-2.00]).ConclusionFor women with no/one failure of embryo implantation, the live birth rate is similar between HRT and G-HRT protocols. For women with multiple failure of embryo implantation, GnRH agonist pretreatment is beneficial to raise the live birth rate.

Pretreatment with a GnRH agonist and hormone replacement treatment protocol could not improve live birth rate for PCOS women undergoing frozen-thawed embryo transfer cycles

BackgroundThe ideal protocols of endometrial preparation for polycystic ovary syndrome (PCOS) patients are lacking and need further declaration. Our objective was to compare the clinical outcomes of frozen-thawed embryo transfer (FET) with and without pretreatment gonadotropin-releasing hormone agonist (GnRHa) in PCOS patients.MethodsIn this retrospective cohort study, we used propensity score matching (PSM) to compare the live birth rate between patients who underwent FET with hormone replacement treatment (HRT) and patients with GnRHa pretreatment (GnRHa + HRT). Patients using GnRHa + HRT (n = 514) were matched with 514 patients using HRT.ResultsThe live birth rate was higher in the GnRHa + HRT group compared with the HRT group with no significant difference (60.12% vs 56.03%, p = 0.073). The clinical pregnancy rate (75.29% vs 70.62%), miscarriage rate (14.20% vs 13.81%) and ectopic pregnancy rate (0.39% vs 0.19%) were similar between the two groups. The preterm birth rate in GnRHa + HRT was higher than HRT (20.23% vs 13.04%). No difference was found in live birth between GnRHa +HRT and HRT before adjusting for covariates (crude OR 1.22, 95%CI, 0.99–1.51, p = 0.062) and after PSM (OR 1.47, 95%CI, 0.99–2.83, p = 0.068). In addition, there is a marginally difference after adjusting for covariates (aOR 1.56, 95%CI, 1.001–2.41, p = 0.048), this finding with p-value close to 0.05 represent insufficient empirical evidence. Similar results were obtained after propensity score matching in the entire cohort.ConclusionsGnRHa pretreatment could not improve the live birth rate in women with PCOS.

Endometrial Preparation for Frozen-Thawed Embryo Transfer With or Without Pretreatment With GnRH Agonist: A Randomized Controlled Trial at Two Centers.

ObjectiveThis prospective randomized controlled trial compared the reproductive outcomes of frozen embryo transfer (FET) with hormone replacement treatment (HRT) with or without gonadotropin-releasing hormone agonist (GnRHa) pretreatment.MethodsA total of 133 patients scheduled for HRT-FET mainly because of tubal and/or male factors who received two high-quality cleavage-stage embryos were enrolled at two participating centers. The GnRHa group (n = 65) received GnRHa pretreatment, while the control group (n = 68) did not. Analysis was based on the intention-to-treat (ITT) principle.ResultsAmong the 133 participants, 130 (97.7%) underwent embryo transfer and 127 (95.5%) completed the protocol. The clinical pregnancy rate according to ITT did not differ between the GnRHa and control groups [39/65 (60.0%) vs. 41/68 (60.3%), p = 0.887]. The implantation rate (47.6% vs. 45.3%, p = 0.713), early pregnancy loss rate (5.1% vs. 19.5%, p = 0.09), and live birth rate (49.2% vs. 50.0%, p = 0.920) were also comparable between groups.ConclusionPretreatment with GnRHa does not improve the reproductive outcomes for women receiving HRT-FET.Clinical Trial RegistrationThe study was registered with the Chinese Clinical Trial Registry (ChiCTR-IOR-17014170; http://www.chictr.org.cn).

Effects of artificial cycles with and without gonadotropin-releasing hormone agonist pretreatment on frozen embryo transfer outcomes in patients with adenomyosis

Gonadotropin-releasing hormone agonist (GnRH-a) is generally added to the improve pregnancy outcomes of hormone replacement therapy cycles among patients with adenomyosis. We aimed to investigate whether adding GnRH-a can result in better pregnancy outcomes. This retrospective analysis included 341 patients with adenomyosis who underwent frozen embryo transfer (FET) after in vitro fertilization (IVF). The control group was treated only with hormone replacement therapy cycles to prepare the endometrium, and GnRH-a was added to the study group before hormone administration to adjust the menstruation cycle. Based on the similar baseline values and embryological data, there was no significant difference in the clinical pregnancy rates (40.63% vs. 42.54%, P = 0.72) and live birth rates (23.75% vs. 23.75%, P = 0.74) of the control and study groups. Other secondary outcomes, including the rates of clinical miscarriage, ectopic pregnancy, preterm birth and term birth, were not significantly different between the two groups. Compared with the hormone replacement therapy cycle alone, GnRH-a downregulation based on a hormone replacement therapy cycle may not increase the rate of clinical pregnancy or live birth of IVF-ET with FET among infertile patients with adenomyosis.

Role of suppression of endometriosis with progestins before IVF-ET: a non-inferiority randomized controlled trial

BackgroundEndometriosis affects the responsiveness to ovarian stimulation. This study aimed to assess the role of Dienogest pretreatment for endometriosis suppression as compared to Gonadotropin-releasing hormone agonist (GnRHa) in patients with endometriosis pursuing IVF treatment.MethodsIn this randomized controlled trial, 134 women with endometriosis-related infertility were randomly allocated to group A (n = 67) who had monthly depot GnRHa for 3 months before ovarian stimulation in IVF treatment (Ultra-long protocol), and Group B (n = 67) who had daily oral Dienogest 2 mg/d for 3 months before starting standard long protocol for IVF. The primary outcome measure was the number of oocytes retrieved. The secondary outcome measures included the number of mature oocytes, fertilization rate, quality of life assessed by FertiQoL scores, cost of treatment, and pregnancy outcomes.ResultsAlthough there was no statistically significant difference between both groups regarding ovarian stimulation, response parameters, and pregnancy outcomes, the Dienogest group had a lower cost of treatment (2773 vs. 3664 EGP, P < 0.001), lower side effects (29.9% vs. 59.7%, P < 0.001), higher FertiQoL treatment scores (33.2 vs. 25.1, P < 0.001) and higher tolerability scores (14.1 vs. 9.4, P < 0.001 < 0.001).ConclusionOur study indicates that Dienogest is a suitable and safe substitute for GnRHa pretreatment in endometriosis patients.Trial registrationNCT04500743 “Retrospectively registered on August 5, 2020”.

Effects of artificial cycles with and without gonadotropin-releasing hormone agonist pretreatment on frozen embryo transfer outcomes.

ObjectiveThis study aimed to compare the pregnancy outcomes between women receiving frozen embryo transfer (FET) with hormone replacement treatment (HRT) with and without gonadotropin-releasing hormone agonist (GnRHa) pretreatment.MethodsAll consecutive women undergoing HRT cycles (2936 cycles) or HRT with GnRHa pretreatment (HRT + GnRHa, 303 cycles) at our reproductive center between January 2015 and December 2017 were analyzed retrospectively.ResultsThe average age was higher in the HRT + GnRHa compared with the HRT group (34.0 ± 4.8 vs. 31.3 ± 4.4). However, the pregnancy outcomes were comparable between the two groups. The clinical pregnancy rate was significantly increased in younger women (≤35 years) in the HRT + GnRHa group compared with the HRT group (56.8% vs. 48.7%), but the live birth rates were similar in the two groups (44.2% vs. 38.4%). The HRT + GnRHa protocol significantly increased the clinical pregnancy rate (55.6% vs. 43.2%) and live birth rate (43.5% vs. 33.5%) compared with the HRT group among women with endometriosis, and significantly decreased the abortion rate in women with polycystic ovarian syndrome (3.1% vs. 16.4%).ConclusionsGnRHa pretreatment may improve pregnancy outcomes in women with endometriosis and polycystic ovarian syndrome.

Impact of Gonadotropin-Releasing Hormone Agonist Pre-treatment on the Cumulative Live Birth Rate in Infertile Women With Adenomyosis Treated With IVF/ICSI: A Retrospective Cohort Study.

Introduction: Although pre-treatment with a GnRH agonist can reduce the size of adenomyosis lesions, the supra-physiological hormone level induced by controlled ovarian hyperstimulation (COH) may negate the usefulness of the GnRH agonist in patients with adenomyosis lesions, leading to continued poor outcomes in fresh embryo transfer cycles during in vitro fertilization (IVF). It is unclear whether GnRH agonist pre-treatment before starting the long GnRH agonist protocol for IVF/ICSI (intracytoplasmic sperm injection) can improve cumulative live birth rate (CLBR) of infertile women with adenomyosis.Method: In this retrospective cohort study, a total of 374 patients diagnosed as adenomyosis (477 cycles) underwent IVF/ICSI with long GnRH agonist protocol with or without GnRH agonist pre-treatment between January 2009 and June 2018. Logistic regression was used to assess the association between GnRH agonist pre-treatment and pregnancy outcome after adjusting for confounding factors.Results: The live birth rate in fresh embryo transfer cycles was higher in the non-pre-treatment group than in the GnRH agonist pre-treatment group (37.7 vs. 21.2%, P = 0.028); the adjusted odds ratio (OR) for the long agonist protocol without pre-treatment was 1.966 (95% CI: 0.9–4.296, P = 0.09). The CLBR was higher in the non-pre-treatment group than in the GnRH agonist pre-treatment group (40.50 vs. 27.90%, P = 0.019); the adjusted OR for the long agonist protocol without pre-treatment was 1.361 (95% CI: 0.802–2.309, P = 0.254).Conclusion: Our results indicated that GnRH agonist pre-treatment before starting the long GnRH agonist protocol does not improve the live birth rate in fresh embryo transfer cycles or CLBR in infertile women with adenomyosis after IVF/ICSI treatment when compared to that in non-pre-treated patients. A subsequent prospective randomized controlled study is needed to confirm these results.