Gonadotropin-releasing Hormone Agonist Group Research Articles

P-597 The effects of triple trigger on IVF outcomes and pregnancy rates in poor responder patients

Abstract Study question Are there any positive effects of triple trigger on oocyte morphology, embryo quality and pregnancy rates in poor responder (POR) patients? Summary answer The trigger with human chorionic gonadotropin (hCG), gonadotropin-releasing hormone agonist (GnRHa) and human menopausal gonadotropin (hMG) may improve embryo quality and pregnancy rates in POR. What is known already The ESHRE consensus criteria define a poor ovarian response (POR) as less than four oocytes retrieved. Advanced female age and severe sperm disorder were associated fertilization failure after intracytoplasmic sperm injection (ICSI). Also, oocyte quality is pivotal to determine the fertilization of the oocyte. Hence there is no study to evaluate triple trigger on the embryo quality in POR and severe male infertility are excluded. Study design, size, duration In this prospective randomized study, we analyzed poor responder patients that have history of fertilization failure and cleavage arrest embryo, including 100 patients with only hCG trigger (group 1), 100 patients with dual trigger hCG + GnRHa (Group 2), and 100 patients with triple trigger hCG + GnRHa + hMG (Group 3). Patients who have the POR criteria according to MII oocytes lower than 4 were included in the analysis. Participants/materials, setting, methods Mean age, body mass index (BMI), AMH levels, day-2 FSH and E2, duration of infertility, LH and E2 levels on trigger day, duration of stimulation, total dose of gonadotropins used, number of previous trials, MII oocytes were examined and compared between the groups. Sperm concentration under 5 x 106 mL was not included to exclude severe male factor. Embryo quality, pregnancy rates evaluation was performed for each patient that has been performed GnRH antagonist protocols. Main results and the role of chance Age, Body Mass Index (BMI), AMH levels, day 2 FSH and E2, duration of infertility, duration of stimulation, E2 levels on trigger day, and total dose of gonadotropins usage between the three groups were similar. Number of MII oocytes, fertilization (2PN), and D5 (blastocyst) embryo transfer were significantly higher in Group 3 (Table 1). Pregnancy rates are higher in group 3 however significantly not significant. Limitations, reasons for caution The study is limited by its sample size and a higher sample size might be used in the future studies to corroborate the current findings. hMG trigger dosage may be arranged in another study. Wider implications of the findings Our results showed that the number of MII oocytes 2PN levels, D5 ET were higher in DOR patients triggered with hCG + GnRHa + hMG. Trial registration number 28012022

Ovulation triggering with hCG alone, GnRH agonist alone or in combination? A randomized controlled trial in advanced-age women undergoing IVF/ICSI cycles.

Is a dual ovulation trigger with a combination of GnRH agonist (GnRHa) and hCG superior to single hCG and/or single GnRHa trigger in improving treatment outcomes in advanced-age women (aged ≥ 35 years) undergoing IVF/ICSI treatment? Co-administration of GnRHa and hCG as a dual trigger increases the number of good-quality embryos but it is not associated with a higher number of oocytes retrieved, compared with single hCG or GnRHa trigger. Many studies have demonstrated that a dual trigger has positive impact on oocyte maturation, retrieval rate and pregnancy rate without increasing the risk of ovarian hyperstimulation syndrome (OHSS) in some groups of IVF patients, when compared with single hCG trigger. Few studies have however been conducted to compare a dual trigger with a single GnRHa trigger, and insufficient evidence exists to support which trigger can achieve the best outcomes in IVF patients aged ≥35 years. This was an open-label randomized controlled trial of 510 participants conducted at single reproductive medical center from January 2019 to December 2021. After a sample size calculation performed by retrospectively analyzing our previous clinical data, we planned to recruit 170 patients in each group and 510 patients in total for the study. Women aged ≥35 years undergoing IVF/ICSI treatment, receiving a non-pituitary down-regulation protocol, and with low risk of OHSS, were enrolled in this trial. On the trigger day, patients were randomized into three groups: hCG alone (who received 6000 IU of hCG), GnRHa alone (who received 0.2 mg of triptorelin) and dual trigger (who received 0.2 mg of triptorelin plus 2000 IU of hCG) groups. The primary outcome parameter was the number of retrieved oocytes. The secondary outcome parameters included, among others, the number and rates of mature oocytes, two pronuclei (2PN) embryos and good-quality embryos, as the rates of OHSS, clinical pregnancy, miscarriage and live birth. There were no significant differences in the baseline demographic characteristics among the three groups. The dual trigger was associated with a higher retrieval rate (87.9% vs 84.1% in the hCG group, P = 0.031; 87.9% vs 83.6% in the GnRHa group, P = 0.014). However, the number of retrieved oocytes in the dual trigger group was comparable with those in the hCG group (4.08 ± 2.79 vs 3.60 ± 2.71, P = 0.080) and the GnRHa group (4.08 ± 2.79 vs 3.81 ± 3.38, P = 0.101); comparable data between the groups were also found when analyzing the number of 2PN embryos and the 2PN rate. In the dual trigger group, the numbers of good-quality embryos and viable embryos were both significantly higher than in the hCG group (1.74 ± 1.90 vs 1.19 ± 1.45, P = 0.016 and 2.19 ± 2.11 vs 1.56 ± 1.66, P = 0.008, respectively) and the GnRHa group (1.74 ± 1.90 vs 1.20 ± 1.67, P = 0.003 and 2.19 ± 2.11 vs 1.45 ± 1.75, P = 0.001, respectively). Pregnancy outcomes after fresh embryo transfer (ET) were comparable between the groups. The live birth rate and ongoing pregnancy rate after frozen ET in the dual trigger group were significantly higher than those in the GnRHa group (32.6% vs 14.1%, P = 0.007 and 34.8% vs 17.6%, P = 0.013, respectively), but not superior to those in the hCG group (32.6% vs 27.9%, P = 0.537 and 34.8% vs 27.9%, P = 0.358, respectively). Women of advanced age are quite a heterogeneous population and overlap with poor ovarian responders or patients with diminished ovarian reserve. We therefore could not entirely exclude selection biases or confounding factors. This study was also not a double-blinded trial; the patients in the GnRHa and dual trigger groups could have been affected by the placebo effect. The results of this study suggest that in advanced-age women with low risk of OHSS, a dual trigger or even a single hCG trigger may be a better choice than a single GnRHa trigger. This study was supported by the Shanghai Municipal Health Commission of Science and Research Fund (20184Y0289). The authors declare no conflict of interest. This trial was registered in the Chinese Clinical Trial Registry (ChiCTR-1800016285). 24 May 2018. 2 January 2019.

Reproductive Outcome After GnRH Agonist Triggering With Co-Administration of 1500 IU hCG on the Day of Oocyte Retrieval in High Responders: A Long-Term Retrospective Cohort Study

While triggering oocyte maturation with GnRH agonist (GnRHa) seems to be safe and effective in terms of the risk of developing OHSS and the number of metaphase II oocytes, it nevertheless results in luteal phase deficiency. To date, strategies have been developed in order to rescue defective luteal phase of GnRHa triggered cycles. Our study aimed to assess the reproductive outcome of GnRHa triggered cycles combined with modified luteal support (1500 IU hCG at the day of oocyte retrieval) in women with high ovarian response and to compare the outcome with hCG triggered cycles in GnRH antagonist IVF-ICSI procedures. A retrospective cohort database review of the results of GnRH antagonist IVF-ICSI cycles was conducted at a tertiary-care IVF center in Ljubljana, Slovenia. A total of 6126 cycles, performed from January 1, 2014, to December 31, 2020, were included in the final analysis. Final oocyte maturation was performed with either 5000, 6500, or 10,000 IU hCG (women with normal ovarian response) or 0.6 mg GnRHa (buserelin), supplemented with 1500 IU hCG on the day of oocyte retrieval (in women with high ovarian response). In cases of excessive ovarian response and/or high risk of OHSS luteal support was not introduced and all good quality blastocysts were frozen. According to significant differences in patients’ age and the number of oocytes in the two groups, matching by age and number of oocytes was performed. No significant differences were observed regarding pregnancy rate per embryo transfer, rate of early pregnancy loss, and livebirth rate per pregnancy between the GnRHa and hCG trigger groups, respectively. A significant difference in the number of developed embryos and blastocysts, as well as the number of frozen blastocysts, was seen in favor of the GnRHa trigger. However, the birth weight in the GnRHa trigger group was significantly lower.ConclusionThe results of our study support the use of GnRHa for final oocyte maturation in GnRH antagonist IVF cycles in women with high ovarian response. Luteal phase rescue was performed by co-administration of 1500 IU hCG on the day of oocyte retrieval and estradiol and progesterone supplementation. In our experience, such an approach results in a comparable reproductive outcome with hCG trigger group.

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.

Salvia miltiorrhiza-Containing Chinese Herbal Medicine Combined With GnRH Agonist for Postoperative Treatment of Endometriosis: A Systematic Review and meta-Analysis.

Background: Endometriosis is an estrogen-dependent gynecological inflammatory condition that may lead to infertility and recurrent pelvic pain. The purpose of this research was to determine the efficacy and safety of Salvia miltiorrhiza-containing Chinese herbal medicine (CHM) combined with gonadotropin-releasing hormone agonist (GnRH-a) for postoperative endometriosis management. Methods:Eight databases were systematically searched before October 2021, including PubMed, Embase, Cochrane Library, Scopus, Web of Sceince, CNKI, VIP, and Wanfang. Finally, all randomized controlled studies comparing Salvia miltiorrhiza-containing CHM paired with GnRH-a to GnRH-a alone for postoperative endometriosis management were included. Results: A total of 10 trials involving 836 patients were reported and analyzed. Compared with the control group, the Salvia miltiorrhiza-containing CHM combined with GnRH-a group showed significant superiority in decreasing endometriosis recurrence (risk ratio [RR] = 0.26; 95% confidence intervals [CI]: 0.16–0.41) and increasing the pregnancy rate ([RR] = 1.96; 95% CI: 1.58–2.44). Similarly, the effect of the Salvia miltiorrhiza-containing CHM combined with GnRH-a on CA-125 serum levels was positive (standardized mean difference [SMD] = -0.79; 95% CI: −1.11 to −0.47). Furthermore, this group showed a significant reduction in adverse effects. Conclusion: The results indicate that Salvia miltiorrhiza-containing CHM may be a viable choice for postoperative endometriosis therapy, with the potential to enhance pregnancy while decreasing recurrence and adverse effects.

Abstract P2-12-16: Use of ovarian function suppression to preserve fertility during neoadjuvant chemotherapy oncologically safe in women under age 40: An inverse probability weighting adjusted analysis

Abstract Backgrounds Ovarian function suppression by gonadotropin releasing hormone agonist (GnRHa) is used to preserve fertility during neoadjuvant chemotherapy (NCT) in breast cancer especially in young women. Some results showed that patients with hormone-receptor (HR) negative breast cancer treated with NCT concurrent with GnRHa to preserve fertility had better outcome than without GnRHa. Methods From 2011 to 2014, 296 women aged under 40 years old with stage I to IIIA breast cancer, treated with NCT before surgery were analyzed. Primary endpoint was rate of pathologic complete response (pCR). Secondary endpoint was disease free survival (DFS) and overall survival (OS) between two groups categorized by concurrent with GnRHa during NCT to preserve fertility. Subgroup analysis was done with different HR status. Results Ninety-eight patients (33.1%) received concurrent GnRHa with NCT. Baseline characteristic showed no different between two groups except younger age with GnRHa group (p<0.001) and more use of GnRHa in HR+/HER2- subtype (p=0.023). pCR rate was higher with GnRHa group (8.08% vs 20.41%, p=0.002). However there was no significant difference in 5yr DFS between without GnRHa and with GnRHa (HR 1.4 95% CI 0.60 2-3.582) in entire cohort. In HR positive subcohort, 5yr DFS was not different between without GnRHa and with GnRH a group (80.9% and 87.7% respectively,p=0.643). In HR negative subcohort, 5yr DFS was 71.6% vs 70.6% (p=0.931). There were no overall survival difference between two group in entire and subcohort (p>0.05). Multivariable analysis also did not show survival improvement after use of GnRHa in HR- subtype (hazard ratio 2.166, (95% CI 0.746-6.292), p=0.155) and HR+ subtype (hazard ratio 1.231, (95% CI 0.205-7.411), p=0.820). Conclusion Among young women with breast cancer with negative hormone receptor treated with concomitant GnRHa achieved more pCR com compared with no GnRHa during chemotherapy. This result did not reach out to better survival outcome at this point. Trend to better outcome seen in survival curve implies further evaluation in this particular population. Citation Format: Young Joo Lee, Seonok Kim, Hee J Kim. Use of ovarian function suppression to preserve fertility during neoadjuvant chemotherapy oncologically safe in women under age 40: An inverse probability weighting adjusted analysis [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-12-16.

Oral Gonadotropin-Releasing Hormone Antagonist Relugolix Has the Same Effect as Gonadotropin-Releasing Hormone Agonist Injections in Terms of Preparation for Transcervical Resection Myomectomy.

For preparing the optimal condition in transcervical resection (TCR) surgery, gonadotropin-releasing hormone (GnRH) agonist has been utilized. Recently, an oral GnRH antagonist (relugolix) is available and acts directly on GnRH receptor, avoiding flare up and reducing blood E2 levels rapidly. We retrospectively compared the oral GnRH antagonist (n = 14) effect to that of subcutaneous GnRH agonist (n = 19) for the pretreatment of endometrium in TCR myomectomy. Endometrial thickening was determined by intraoperative videos. The color tone of the endometrium in the normal part was assessed by digital image processing. The median duration of the first GnRH agonist injection and the surgery was 67 days (21-136 days), which is significantly longer than that of the oral GnRH antagonist group, 18.5 days (7-157 days P < 0.01). Both the GnRH agonist and antagonist groups did not exhibit prominence in the endometrium. The GnRH antagonist group showed the same degree of whiteness in the normal endometrium as the GnRH agonist group. The oral GnRH antagonist administration could rapidly atrophy the endometrium and create an optimal surgical field for TCR in a short period.

Efficacy of Post-Operative Medication to Prevent Recurrence of Endometrioma: Cyclic Oral Contraceptive (OC) After Gonadotropin-Releasing Hormone (GnRH) Agonist Versus Dienogest.

BackgroundThere are several medical treatment options for endometrioma. Progestin, especially dienogest, is an effective drug for preventing recurrence of endometrioma after surgery. Additionally, oral contraceptive (OC) use after conservative surgery has been reported to reduce significantly the risk of endometrioma recurrence. The aim of this study was to compare the long-term effects of gonadotropin-releasing hormone (GnRH) agonist followed by OC to those of dienogest alone to prevent recurrence of endometrioma after laparoscopic surgery.MethodsA retrospective cohort study was performed on patients who underwent conservative laparoscopic surgery for endometrioma between January 2000 and December 2020, in the Endometriosis Clinic, Department of Gynecology, Samsung Medical Center. A total of 624 patients who received medical treatment at least six months after laparoscopic conservative surgery for endometrioma was included. Among them, 372 patients used OC after GnRH agonist therapy, and 252 patients used dienogest. Within the OC group, 148 used a 21/7 regiment and 224 used a 24/4 regimen. A cumulative endometrioma recurrence curve was presented using the Kaplan-Meier method to compare the recurrence of those groups.ResultsThe cumulative recurrence rate of endometrioma for 60 months was 2.08% (n = 4) in the OC after GnRH agonist group and 0.40% (n = 1) in the dienogest group. There was no statistical difference in cumulative recurrence of endometrioma between the two groups. In subgroup analysis, the cumulative recurrence rate of endometrioma over 60 months was 4.21% (n = 2) in the 21/7 OC group and 1.09% (n = 2) in the 24/4 OC group and showed no significant difference.ConclusionLong-term use of OC after GnRH agonist as well as that of dienogest treatment are effective postoperative medical therapies for preventing endometrioma recurrence. Thus, the choice of regimen can be individualized or used interchangeably depending on patient condition, need for contraception, and compliance with drug therapy.

Impact of perioperative use of GnRH agonist or dienogest on ovarian reserve after cystectomy for endometriomas: a randomized controlled trial

BackgroundOvarian endometrioma is a common gynecological disease that is often treated with surgery or hormonal treatment. Ovarian cystectomy, a surgical procedure for ovarian endometrioma, can result in impaired ovarian reserve.MethodsWe conducted a randomized controlled trial to evaluate the efficacy of hormonal treatment [gonadotropin-releasing hormone agonist (GnRHa) or dienogest (DNG)] for preserving ovarian reserve after cystectomy for ovarian endometrioma. The primary endpoint was the level of serum Anti-Müllerian hormone (AMH) as a marker of ovarian reserve.ResultsBefore and after laparoscopic surgery, 22 patients in the GnRHa group and 27 patients in the DNG group were administered hormonal treatment for a total of 4 months. After 1-year follow-up, >60% of the patients in the DNG group retained over 70% of their pretreatment AMH levels, whereas no patient in the GnRHa group retained their AMH levels after cystectomy (P < 0.01). Interleukin-6 (IL-6) is a key cytokine involved in inflammation. Compared with the GnRHa group, patients in the DNG group had lower IL-6 levels at the end of treatment.ConclusionsOur data revealed that DNG is more effective than GnRHa in preserving ovarian reserve after cystectomy of ovarian endometrioma. This is achieved through the reduction of the inflammatory response during the perioperative period and other endometriosis-related inflammatory reactions.Trial registrationThe registration number of this trial is UMIN-CTR, UMIN000018569, registered 6 August 2015, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000021492, and Japan Registry of Clinical Trials, jRCTs041180140, registered 29 March 2019, https://jrct.niph.go.jp/en-latest-detail/jRCTs041180140. This randomized controlled trial was conducted in accordance with the CONSORT guidelines.

GnRH agonist supplementation in hormone replacement therapy–frozen embryo transfer cycles: a randomized controlled trial

Research questionWill two boluses of gonadotrophin-releasing hormone agonist (GnRHa) during hormone replacement therapy–frozen embryo transfer (HRT–FET) cycles reduce the total pregnancy loss rate? DesignRandomized controlled trial including a total of 287 HRT–FET cycles performed between 2013 and 2019. After randomization participants allocated to the GnRHa group (n = 144) underwent a standard HRT protocol, supplemented with a total of two boluses of triptorelin 0.1 mg; one bolus 2 days before starting vaginal progesterone and one bolus on the 7th day of progesterone. The control group (n = 143) underwent a standard HRT–FET protocol only. ResultsThe intention-to-treat analysis showed no significant difference in total pregnancy loss between the GnRHa group and the control group (21% versus 33%; relative risk [RR] 0.63, 95% confidence interval [CI] 0.35–1.11), nor was the biochemical pregnancy loss per positive human chorionic gonadotrophin (HCG) significantly lower in the GnRHa group (12%, 8/67) compared with the control group (25%, 18/72) (RR 0.48, 95% CI 0.22–1.02). Participants with a live birth had a significantly higher mean progesterone concentration compared with participants without a live birth (25.0 ± 12.2 versus 23.8 ± 8.9 nmol/l; P = 0.001). Furthermore, a trend for a higher live birth rate (LBR) correlated with the highest oestradiol quartile concentration (oestradiol >0.957 nmol/l). ConclusionsAlthough a difference of 14% in biochemical loss and 12% in total pregnancy loss in favour of GnRHa supplementation was seen this did not reach statistical difference. Luteal progesterone and oestradiol concentrations correlate with LBR in the HRT–FET cycle, emphasizing the importance of luteal serum progesterone and oestradiol monitoring.

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).

Efficacy of High-Intensity Focused Ultrasound Combined With GnRH-a for Adenomyosis: A Systematic Review and Meta-Analysis.

Objective: High-intensity focused ultrasound (HIFU) is an innovative non-invasive technology used for adenomyosis. Gonadotropin-releasing hormone agonist (GnRH-a) is a hormone commonly used for adenomyosis. We investigated and assessed the efficacy of HIFU combined with GnRH-a for adenomyosis.Methods: For this systematic review and meta-analysis, we searched Pubmed, Cochrane Library, Web of Science, Embase, CNKI, WanFang, and VIP databases for relevant articles published in Chinese or English that compared HIFU combined with GnRH-a vs. HIFU alone in patients with adenomyosis. The last literature search was completed on January 31, 2021. Two reviewers independently assessed study eligibility and assessed risk of bias. Another two reviewers extracted the data. The RevMan5.3 software was used for the data analysis. Changes in volume of the uterine and adenomyotic lesion were defined as the primary outcomes. The secondary outcomes were visual analog scale (VAS) scores for dysmenorrhea, menstrual volume scores, serum CA125 levels, and recurrence rate. This study is registered with PROSPERO (CRD42021234301).Results: Three hundred and ninety potentially relevant articles were screened. Nine studies with data for 766 patients were finally included. Compared with the HIFU alone group, the HIFU combined with GnRH-a group had a higher rate of uterine volume reduction (MD 7.51, 95% CI 5.84–9.17, p < 0.00001), smaller adenomyotic lesion volume (MD 4.11, 95% CI 2.93–5.30, p < 0.00001), lower VAS score for dysmenorrhea (MD 1.27, 95% CI 0.54–2.01, p = 0.0007) and menstrual volume score (MD 0.88, 95% CI 0.73–1.04, p < 0.00001), and lower CA125 level (SMD 0.31, 95% CI 0.05–0.56, p = 0.02) after the procedure. The recurrence rate in the HIFU combined with GnRH-a group was lower than that in the HIFU alone group (RR 0.28, 95% CI 0.10–0.82, p = 0.02).Conclusions: Compared with HIFU treatment alone, HIFU combined with GnRH-a for the treatment of adenomyosis has greater efficacy in decreasing the volumes of the uterine and adenomyotic lesions and alleviating symptoms. However, since the number of the included studies was too small and most of them were written in Chinese, this conclusion needs to be referenced with caution. And the long-term evidence of its efficacy is still insufficient.Systematic Review Registration: https://www.crd.york.ac.uk/prospero/ identifier [CRD42021234].

P–273 Effects of ovulation induction with GnRH Agonist (GnRHa) on oocyte and embryo quality at the mitochondrial level: A retrospective and experimental study

Abstract Study question Does the GnRHa trigger improve oocyte and embryo quality in patients younger than 40, and do mtUPPR have a role? Summary answer GnRHa trigger improves oocyte nuclear/cytoplasmic maturation, blastocyst utilization and downregulates HSP60 levels and upregulates ATF5 levels compared to hCG trigger. GnRHa trigger suppresses mitochondrial stress. What is known already hCG has been used for decades to achieve final oocyte maturation and, thereby, correct oocyte retrieval timing in connection with ovarian hyperstimulation protocols. As an alternative to hCG, a GnRH agonist has been used to trigger the endogenous release of LH (and FSH) in a fashion resembling the mid-cycle surge of gonadotrophins. GnRHa is as effective as hCG for the induction of ovulation. It has been very well known that the GnRHa trigger improves oocyte nuclear maturation, embryo quality, and implantation rate, but the underlying mechanism remains unknown. Study design, size, duration 3054 women younger than 40; oocytes retrieved more than 10 (up to 20) analyzed. Male infertility was excluded. Ovulation triggered either by hCG (n = 1368) or GnRHa (1668). Female mice were divided into three groups as control, hCG-treated and GnRHa-treated group. Superovulation was performed by FSH + hCG or GnRHa. Oocytes were collected 13 hours after hCG/GnRHa injection. ATF5, BiP, and HSP60 levels were analyzed by Western blot. Statistical analysis was performed using Student’s t-test. Participants/materials, setting, methods This study has two parts. i) RCT and ii) Experimental. In the experimental part, three months old female BALB/C mice (25–30 g) were used and divided into three groups (n = 20/group) as control, hCG-treated and GnRHa-treated group. Superovulation was performed by administering an injection of 5 IU FSH (i.p.) and hCG (i.p.) or GnRHa (20 mg/kg) i.m. Oocytes were collected 13 hours after hCG/GnRHa injection. ATF5, BiP, and HSP60 levels were analyzed by Western blot. Main results and the role of chance The mean age (34.8 vs. 35.2 years), total gonadotropin dose (2176 vs. 2230 IU), and the number of oocytes picked up (14.9 vs. 13.4) were not statistically different among GnRHa and hCG group, respectively. No LH rise or any OHSS was noticed in any groups. Oocyte maturation (79.8% vs. 75.9%), oocyte diameter (as a marker of cytoplasmic maturity) (10198 µm2 and 9474 µm2), fertilization rate (78% vs. 72%), and embryo utilization rate (52% vs. 47.2%) were significantly higher in GnRHa group compared to hCG group, respectively. HSP60 level (activated by mtUPR) was statistically higher in the hCG group compared to the GnRHa group (55% vs. 22%, p &amp;lt; 0.05 respectively). On the other hand, the ATF5 level was significantly higher in the GnRHa group than the hCG group (p &amp;lt; 0.0001). Limitations, reasons for caution The limitation is that this is a proof-of-concept study to reveal the mechanism of good embryo quality with GnRHa trigger. Wider implications of the findings: This application offers convenience and simplifies the IVF protocol with a better oocyte and embryo quality while reducing Ovarian Hyperstimulation Syndrome (OHSS) risk during IVF care Trial registration number Not applicable

Endometrial preparation for vitrified–warmed embryo transfer with or without GnRH-agonist pre-treatment in patients with polycystic ovary syndrome: a randomized controlled trial

Research questionWhat are the effects on pregnancy outcome in patients with polycystic ovary syndrome (PCOS) in endometrial preparation cycles for vitrified–warmed embryo transfer with or without gonadotrophin releasing hormone (GnRH) agonist pre-treatment? DesignA total of 212 patients with PCOS referred to Royan Institute, Tehran, Iran, between 20 August 2017 to 20 June 2018 were included. The patients were randomly assigned to receive oestradiol after downregulation with GnRH agonist (group A) or without GnRH agonist down-regulation (group B). ResultsA total of 188 patients with PCOS completed the trial, 93 patients in group A and 95 patients in group B. Basal oestradiol and LH levels were significantly higher in group B (26.66 versus 41.61, P = 0.01 and 0.93 versus 5.33, P < 0.0001, respectively). Clinical pregnancy rates were not significantly different in both groups (31.2% versus 33.7%). Similarly, no significant differences were found between groups A and B in miscarriage (9.7% versus 11.6%), implantation (0.58 versus 0.51) and live birth (21.7% versus 22.1%) rates and for medical complications during pregnancy and neonatal anomalies. ConclusionsOur findings indicate that endometrial preparation for frozen–thawed embryo transfer with and without ovarian suppression by GnRH agonist provides similar results.

Comparison of clinical outcomes between the depot gonadotrophin-releasing hormone agonist protocol and gonadotrophin-releasing hormone antagonist protocol in normal ovarian responders

BackgroundThe gonadotrophin-releasing hormone (GnRH) antagonist protocol has some advantages, such as a simple method, short medication duration, and low incidence of ovarian hyperstimulation syndrome, but whether the GnRH antagonist protocol is suitable for normal ovarian responders has been controversial. We compared the clinical outcomes of fresh and frozen-thawed transfer cycles between the depot GnRH agonist protocol and GnRH antagonist protocol in normal ovarian responders.MethodsData of normal ovarian responders who underwent in vitro fertilization-embryo transfer (IVF-ET) or intracytoplasmic sperm injection-embryo transfer (ICSI-ET) between January 2017 and December 2018 in our hospital were retrospectively analysed. In this study, there were 1119 fresh transfer cycles, including 502 GnRH antagonist cycles (GnRH antagonist group) and 617 depot GnRH agonist cycles (depot GnRH agonist group), as well as 468 frozen-thawed transfer cycles, includng 191 GnRH antagonist cycles (GnRH antagonist group) and 277 depot GnRH agonist cycles (depot GnRH agonist group). The clinical outcomes were compared between the GnRH antagonist group and the depot GnRH agonist group.ResultsWith the fresh transfer cycles, there were no statistically significant differences in the anti-Mullerian hormone level, number of transferred embryos or high-quality embryo rate between the two groups. The total dosage of gonadotropin (Gn), duration of Gn stimulation, number of oocytes retrieved, clinical pregnancy rate and incidences of moderate and severe ovarian hyperstimulation syndrome (OHSS) were significantly lower but the abortion rate was significantly higher in the GnRH antagonist group than in the depot GnRH agonist group (all P < 0.05). With the frozen-thawed transfer cycles, there were no statistically significant differences in the number of transferred embryos, clinical pregnancy rate or abortion rate between the two groups (all P > 0.05).ConclusionsWith the fresh transfer cycles, the GnRH antagonist protocol had a lower clinical pregnancy rate and lower incidences of moderate and severe OHSS than the depot GnRH agonist protocol, but with the frozen-thawed transfer cycles, both protocols had similar clinical pregnancy rates. These results remain to be further confirmed through large-sample, prospective, randomized and controlled studies.

IVF Outcomes of Microdose Flare-up, GnRH Antagonist, and Long Protocols in Patients having a Poor Ovarian Response in the First Treatment Cycle.

To compare the IVF outcome of patients assumed to be poor responders before their first cycle treated by microdose flare-up or GnRH antagonist protocols with patients who had a poor ovarian response after their first cycle stimulated with long GnRH protocol. Observational cohort study. Department of Obstetrics and Gynecology, IVF Unit of Gazi University Faculty of Medicine, from September 2014 to February 2019. Patients treated with the first cycle of IVF and diagnosed as poor responders after ovarian stimulation were evaluated according to the treatment protocol, including microdose flare-up (Group 1: 136 patients), GnRH antagonist (Group 2: 105 patients), and long GnRH agonist (Group 3: 77 patients). Basal FSH level was significantly lower in group 3 compared to other groups (p<0.05). The number of oocytes retrieved, the number of metaphase II oocytes were similar between groups, although the mean AFC was significantly higher in group 3 than in group1 and 2 (p<0.05). Clinical pregnancy rates per patient were higher in group 3 (20.8%) than in group 1 (12.5%) and group 2 (13.3%), but the difference was not statistically significant (p=0.230). The live birth rate per patient was statistically higher in group 3 (19.5%) as compared to other groups (8.8%, 9.5%, respectively; p<0.05). Long protocol may be an option in poor responders undergoing IVF. Ovarian reserve markers are essential factors with stimulation protocol for the success of IVF in poor responder patients. Key Words: Infertility, Ovulation ınduction, Ovarian reserve, Fertilisation in-vitro, Oocyte retrieval, Pregnancy outcome, Reproductive techniques, Assisted.

The exogenous progesterone-free luteal phase: two pilot randomized controlled trials in IVF patients

Research questionIs the reproductive outcome similar after gonadotrophin-releasing hormone agonist (GnRHa) trigger followed by luteal human chorionic gonadotrophin (HCG) boluses compared with HCG trigger and a standard luteal phase support (LPS)? DesignTwo open-label pilot randomized controlled trials (RCT) with 250 patients from 2014 to 2019, with a primary outcome of ongoing pregnancy per embryo transfer. Patients with ≤13 follicles on the trigger day were randomized (RCT 1) to: Group A (n = 65): GnRHa trigger followed by a bolus of 1500 IU HCG s.c. on the oocyte retrieval day (ORD) and 1000 IU HCG s.c. 4 days later, and no vaginal LPS; or Group B (n = 65): 6500 IU HCG trigger, followed by a standard vaginal progesterone LPS. Patients with 14–25 follicles on the trigger day were randomized (RCT 2) to Group C (n = 60): GnRHa trigger followed by 1000 IU HCG s.c. on ORD and 500 IU HCG s.c. 4 days later, and no vaginal LPS; or Group D (n = 60): 6500 IU HCG trigger and a standard vaginal LPS. ResultsIn RCT 1, the ongoing pregnancy rate was 44% (22/50) in the GnRHa group versus 46% (25/54) in the HCG trigger group (RR 0.95, 95% CI 0.62–1.45). No ovarian hyperstimulation syndrome (OHSS) was seen in Groups A or B. In RCT 2, the ongoing pregnancy rate was 51% (25/49) in the GnRHa group versus 60% (31/52) in the HCG trigger group (RR 0.86, 95% CI 0.60–1.22). The OHSS rates were 3.3% and 6.7%, respectively. ConclusionsAlthough a larger-scale study is needed before standard clinical implementation, the present study supports that the exogenous progesterone-free LPS is efficacious, simple and patient-friendly.

Use of Ulipristal Acetate and Risk of Liver Disease: A Nationwide Cohort Study.

Large-scale clinical trials on the hepatotoxicity of ulipristal acetate (UPA) are lacking. This work aimed to determine the incidence of liver disease with UPA vs gonadotropin-releasing hormone (GnRH) agonists. A retrospective cohort study was conducted in South Korea of women with uterine fibroids from the Korean Health Insurance Data 2010 to 2018. Women with uterine fibroids were divided into 2 treatment groups: the UPA (5 mg/day) and GnRH agonist groups. Main outcome measures included the presence or absence of severe liver disease, mild liver disease, and liver transplantation. Among the patients with uterine fibroids,17 207 patients were treated with GnRH agonists and 20 926 patients with UPA. After 1:1 propensity score matching for each group, there were 11 445 individuals. Neither group had a liver transplantation case. In the conditional logistic regression analysis, the incidence of total liver diseases (relative risk [RR] 1.111; 95% CI, 1.015-1.216) and mild liver diseases (RR 1.094; 95% CI, 1-1.196) was higher in the UPA group than in the GnRH agonist group, but that of severe liver diseases (RR 0.07; 95% CI, 0.001-4.412) and toxic liver disease (RR 1.256; 95% CI, 0.845-1.867) did not differ between the groups. The incidence of severe liver disease, hepatic failure, and toxic liver disease was not different between the UPA and GnRH agonist groups. However, the incidence of mild liver disease was higher in the UPA group than in the GnRH agonist group. The incidence of hepatic damage with UPA was very low.

Dual trigger in normally-responding assisted reproductive technology patients increases the number of top-quality embryos.

ObjectiveThe feasibility of a gonadotropin-releasing hormone agonist (GnRHa) trigger in normal responders is still a matter of debate. The aim of this study was to compare the number of mature oocytes, the number of good-quality embryos, and the live birth rate in normal responders triggered by GnRHa alone, GnRHa and human chorionic gonadotropin (hCG; a dual trigger), and hCG alone.MethodsA retrospective cohort study was conducted at the infertility clinic of a university hospital. Data from 200 normal responders who underwent controlled ovarian hyperstimulation and intracytoplasmic sperm injection with a GnRH antagonist protocol between January 2016 and January 2017 were reviewed. The first study group consisted of patients with cycles triggered by GnRHa alone. The second study group consisted of patients with cycles triggered by both GnRHa and low-dose hCG (a dual trigger). The control group consisted of patients with cycles triggered by hCG alone.ResultsThe groups were comparable in terms of demographics and cycle characteristics. The numbers of total oocytes retrieved and metaphase II oocytes were similar between the groups. The total numbers of top-quality embryos were 3.2±2.9 in the GnRHa group, 4.4±3.2 in the dual-trigger group, and 2.9±2.1 in the hCG group (p=0.014). The live birth rates were 21.4%, 30.5%, and 28.2% in those groups, respectively (p=0.126).ConclusionIn normal responders, a dual-trigger approach appears superior to an hCG trigger alone with regard to the number of top-quality embryos produced. However, no clinical benefit was apparent in terms of live birth rates.

Cardiac biomarkers in patients with prostate cancer and cardiovascular disease receiving gonadotrophin releasing hormone agonist vs antagonist

BackgroundGonadotrophin releasing hormone (GnRH) agonists and antagonists reduce testosterone levels for the treatment of advanced and metastatic prostate cancer. Androgen deprivation therapy (ADT) is associated with increased risk of cardiovascular (CV) events and CV disease (CVD), especially in patients with preexisting CVD treated with GnRH agonists. Here, we investigated the potential relationship between serum levels of the cardiac biomarkers N-terminal pro-B-type natriuretic peptide (NTproBNP), D-dimer, C-reactive protein (CRP), and high-sensitivity troponin (hsTn) and the risk of new CV events in prostate cancer patients with a history of CVD receiving a GnRH agonist or antagonist.MethodsPost-hoc analyses were performed of a phase II randomized study that prospectively assessed CV events in patients with prostate cancer and preexisting CVD, receiving GnRH agonist or antagonist. Cox proportional hazards models were used to determine whether the selected biomarkers had any predictive effect on CV events at baseline and across a 12-month treatment period.ResultsBaseline and disease characteristics of the 80 patients who took part in the study were well balanced between treatment arms. Ischemic heart disease (66%) and myocardial infarction (37%) were the most common prior CVD and the majority (92%) of patients received CV medication. We found that high levels of NTproBNP (p = 0.008), and hsTn (p = 0.004) at baseline were associated with the development of new CV events in the GnRH agonist group but not in the antagonist. In addition, a nonsignificant trend was observed between higher levels of NTproBNP over time and the development of new CV events in the GnRH agonist group.ConclusionsThe use of cardiac biomarkers may be worthy of further study as tools in the prediction of CV risk in prostate cancer patients receiving ADT. Analysis was limited by the small sample size; larger studies are required to validate biomarker use to predict CV events among patients receiving ADT.