Hormone Antagonist Research Articles

Effectiveness and safety of GnRH antagonist originator and generic in real-world clinical practice: a retrospective cohort study.

This study aims to determine whether the live birth rates were similar between GnRH antagonist original reference product Cetrotide® and generic Ferpront®, in gonadotropin-releasing hormone (GnRH) antagonist protocol for controlled ovarian stimulation (COS). This retrospective cohort study investigates COS cycles utilizing GnRH antagonist protocols. The research was conducted at a specialized reproductive medicine center within a tertiary care hospital, spanning the period from October 2019 to October 2021. Within this timeframe, a total of 924 cycles were administered utilizing the GnRH antagonist originator, Cetrotide® (Group A), whereas 1984 cycles were undertaken using the generic, Ferpront® (Group B). Ovarian reserve markers, including anti-Mullerian hormone, antral follicle number, and basal follicular stimulating hormone, were lower in Group A compared to Group B. Propensity score matching (PSM) was performed to balance these markers between the groups. After PSM, baseline clinical features were similar, except for a slightly longer infertile duration in Group A versus Group B (4.43 ± 2.92 years vs. 4.14 ± 2.84 years, P = 0.029). The duration of GnRH antagonist usage was slightly longer in Group B than in Group A (6.02 ± 1.41 vs. 5.71 ± 1.48 days, P < 0.001). Group B had a slightly lower number of retrieved oocytes compared to Group A (14.17 ± 7.30 vs. 14.96 ± 7.75, P = 0.024). However, comparable numbers of usable embryos on day 3 and good-quality embryos were found between the groups. Reproductive outcomes, including biochemical pregnancy loss, clinical pregnancy, miscarriage, and live birth rate, did not differ significantly between the groups. Multivariate logistic regression analyses suggested that the type of GnRH antagonist did not independently impact the number of oocytes retrieved, usable embryos, good-quality embryos, moderate to severe OHSS rate, clinical pregnancy, miscarriage, or live birth rate. The retrospective analysis revealed no clinically significant differences in reproductive outcomes between Cetrotide® and Ferpront® when used in women undergoing their first and second COS cycles utilizing the GnRH antagonist protocol.

Oral medroxyprogesterone acetate for the use of ovulation suppression in in vitro fertilization: a cohort trial

To broadly assess the efficacy of medroxyprogesterone acetate (MPA) for ovulatory suppression during in vitro stimulation (IVF) when compared to gonadotropin releasing hormone (GnRH) antagonist cycles DESIGN: Cohort Trial SETTING: A single academic-affiliated private fertility practice SUBJECTS: Patients of all diagnoses aged 18-44 years undergoing autologous IVF for fertility treatment between 2020-2023 EXPOSURE: Comparison of MPA vs. antagonist IVF stimulation cycles MAIN OUTCOME MEASURES: Rates of premature ovulation, oocyte and embryo yield, embryo quality, pregnancy rates, and logistical benefits RESULTS: Prospective data was collected on 418 patients who underwent MPA-protocol ovarian stimulation (MPA group) which was compared to 419 historical control GnRH antagonist cycles (control group). Age was similar between groups (35.6 +/- 4.6 vs. 35.7 +/- 4.8 years; p = 0.75). There were no cases of premature ovulation in the MPA group compared to a total of five cases in the control group (0% vs. 1.2%; RR 0.09, 95% CI 0.01-1.66). No differences were seen between number of oocytes retrieved (14.3 +/- 10.2 vs. 14.3 +/- 9.7; p = 0.83), blastocysts (4.9 +/- 4.6 vs. 5.0 +/- 4.6; p = 0.89), or euploid blastocysts (2.4 +/- 2.6 vs. 2.2 +/- 2.4; p = 0.18) in the MPA vs. control group respectively. Clinical pregnancy rate was similar between groups (70.4% vs. 64.2%; RR 0.92, 95% CI 0.72 - 1.18). There was no difference in length of IVF stimulation or dose of stimulation medications. Patients in the MPA group saved an average of $491 +/- $119 on medications, had an average of one less monitoring visit (4.4 +/- 0.9 vs. 5.6 +/- 1.1; p < 0.01), and 5.0 +/- 1.2 less injections per cycle. When adjusting for age and ovarian reserve, protocol group (MPA vs. control) did not influence having an embryo available for transfer (76.6% vs. 73.4%; adjusted RR 1.05, 95% CI 0.94 - 1.14). For ovulatory suppression during IVF cycles, MPA was effective at preventing ovulation while demonstrating similar cycle and reproductive outcomes, with the additional benefits of patient cost savings, increased convenience with decreased number of visits, and fewer injections.

Unlocking estrogen receptor: Structural insights into agonists and antagonists for glioblastoma therapy.

Glioblastoma(GBM), a malignant brain tumor originating in glial cells, is one of the most common primary brain malignancies, affecting one in 100,000 people, typically in the frontal lobe. Estrogens, like estradiol-17 (E2), significantly influence GBMprogression, metastasis, and angiogenesis. Estrogen receptors (ERs) are crucial in signal transduction and physiology, making them potential therapeutic targets. However, their roles in GBM pathogenesis remain unclear. This review explores ERs in GBM, focusing on their involvement in tumor immune evasion, modulation of the tumor microenvironment, and the mechanisms underlying GBM progression. Additionally, therapeutic opportunities targeting ERs for GBM treatment are discussed. Estrogen, synthesized primarily in ovaries and in smaller amounts by adrenal glands and fat tissues, regulates reproductive systems, bone density, skin health, and cardiovascular function. The invasive nature and heterogeneity of GBM complicate therapy development. Preclinical findings suggest that endocrine therapy with hormone receptor agonists or antagonists can extend patient survival and improve post-treatment quality of life. The ERβ pathway, in particular, shows tumor-suppressive potential, limiting glioma progression with fewer side effects. ERβ agonists could become a novel drug class for GBM treatment. Identifying biomarkers and specific therapeutic targets is crucial for early detection and improved prognosis. Estrogen and its receptors are advantageous for GBM treatment due to their regulation of numerous biological processes, ability to penetrate the blood-brain barrier, and genomic and non-genomic control of transcription, making them promising targets for GBM therapy.

Relationship between CCL25/CCR9 Levels in Follicular Fluid and High Ovarian Response in Patients with Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is one of the prevalent gynecological endocrine disorders encountered in clinical practice. Women diagnosed with PCOS demonstrate increased ovarian responsiveness, rendering them more prone to ovarian hyperstimulation syndrome (OHSS) during controlled ovarian stimulation (COS) procedures. The current study aimed at investigating whether CCL25/CCR9 plays a role in the pathological process of high ovarian response (HOR) during COS procedures. Single-center retrospective cohort study. Patients. A total of 200 PCOS patients who received a fixed regimen of gonadotropin-releasing hormone (GnRH) antagonist were enrolled in this study. The cohort comprised 118 patients exhibiting HOR and 82 patients demonstrating a normal ovarian response (NOR). The age and body mass index (BMI) variances across the two groups did not differ significantly. Similarly, the two groups observed no statistically significant differences in the baseline levels of luteinizing hormone (LH), progesterone (P), estradiol (E2), basal prolactin (PRL), and testosterone (T). Compared to the NOR group, HOR patients exhibit markedly elevated levels of anti-Müllerian hormone (AMH), antral follicle count (AFC), basal follicle-stimulating hormone (FSH), and HOMA-IR (all p < 0.05). Conversely, no statistically significant differences were observed between the two groups with respect to COS parameters, encompassing initial gonadotropin (Gn) dose, stimulation duration, and total Gn dose. During COS, the number of oocytes with diameter ≥14 mm, the levels of E2 on the HCG day, and the number of retrieved oocytes were significantly higher in the HOR group than in the NOR group (all p < 0.001). Additionally, the levels of CCL25/CCR9, matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMPs), TNF-α, and IL-6 were significantly higher in the FF of the HOR group than in the NOR group (all p < 0. 001), while the variance in IL-1β levels between the two cohorts did not reach statistical significance. The relevance analysis results indicated that the levels of CCL25/CCR9 in the FF of the HOR group are positively correlated with the number of retrieved oocytes and oocytes with diameters ≥14 mm during COS, AMH levels, and AFC. Concurrently, the CCL25 levels in the FF of the HOR group were positively correlated with HOMA-IR. Multivariable linear regression analysis revealed that the elevated AFC and HOMA-IR independently increase the CCL25 levels. The CCL25/CCR9 levels in FF are positively correlated with the clinical indicators of HOR, suggesting that CCL25/CCR9 may play a role in the pathogenesis of HOR in patients with PCOS.

Effect of Gonadotropin-Releasing Hormone Antagonist on the Expression Patterns of Insulin-Like Growth Factor 1, Androgen Receptor, and Luteinizing Hormone Receptor in an Experimental Rat Model of Functional Ovarian Cysts.

We studied the expression of insulin-like growth factor 1 (IGF-1), androgen receptor (AR) and luteinizing hormone receptor (LHR) in the ovaries under the conditions of the modeling and subsequent treatment of functional ovarian cysts with gonadotropin-releasing hormone antagonist (ant-GnRH). The intensity of IGF-1, LHR, and AR expression in the generative elements of rat ovaries changed under conditions of functional ovarian cysts simulation, as well as during treatment with ant-GnRH. In both experimental groups, the expression levels of the studied markers in preantral follicles and epithelial lining of cysts were found to be related to the number of growing follicles and cysts. A divergence of LHR and AR expression indices and a more pronounced decrease in the number of cystic cavities were observed in the group receiving ant-GnRH. These changes demonstrate a positive effect of ant-GnRH on intra-ovarian regulatory factors and a therapeutic effect in functional ovarian cysts.

Identification of specific reference gene for normalization of RT-qPCR data in rhythmic gene expression studies of the effect of developmental hormone antagonist in postembryonic development in Bombyx mori.

Bombyx mori is a lepidopteran holometabolous insect with distinct developmental stages: egg, larvae, pupae, and adult. The lepidopteran insect undergoes major modifications in the central nervous system (CNS) so as to adapt to the lifestyle of these distinct stages with specific habitats and functions from voraciously feeding larval stages to flying reproductive adults via dormant pupal stages. Such transitions are linked to transcriptional, epigenetic, and translational complexities. Therefore, studying rhythmic gene expression in CNS of various developmental stages and the effects of antagonists on developmental hormones requires a very stable reference gene (RG). To facilitate rhythmic gene expression studies using reverse transcription quantitative polymerase chain reaction (RT-qPCR) in B. mori and the effect of developmental hormone juvenile hormone (JH) and 20-hydroxy ecdysone hormone (20 HE), antagonists Precocene 1 and testosterone, respectively, were used. Eight candidate RGs, namely, Translational initiation factor 3 subunit 4 (TI3S4), Translational initiation factor 3 subunit 5 (TI3S5), Ribosomal protein subunit 7 (RPs7), TATA-binding protein association factor (TAF13), Translational initiation factor 4 A (TI4A), Ribosomal protein (RPL32), Elongation factor 1 (EF1), and Arginine kinase (AK), were assessed in the CNS of B. mori. The postembryonic developmental (PED) stages used were the fifth late larval instar, early pupa, mid pupa, late pupa, and adult. The assessments were done at four different time points, Zeitgeber time (ZT) 0, 6, 12, and 18, to find stability towards 24-h rhythmic expression. RefFinder, geNorm, and Ct value analysis were performed. RefFinder and geNORM studies suggested stability order as TI3S4 > TI3S5 > RPs7, but Ct value evaluation showed stability order as TI3S5 > TI3S4 > RPs7. We therefore demonstrated that TI3S4, TI3S5, and RPs7 can be used as RG in various PED stages in CNS of B. mori (Strain: CB-hybrid, PM×CSR2) towards studies with effects of JH and 20 HE antagonists.

Morphofunctional State of the Ovaries in Rats with Experimental Model of Functional Cysts and Their Treatment with Gonadotropin-Releasing Hormone Antagonist.

The morphofunctional features of the ovaries were evaluated in rats with functional ovarian cysts model treated with gonadotropin-releasing hormone antagonist. Administration of the antagonist significantly (p=0.009) reduced the number of cysts and the growth of follicles in the ovaries. The obtained results attest to a possibility of successful treatment of functional ovarian cysts with gonadotropin-releasing hormone antagonist.

Reproductive Outcomes of Dual Trigger versus hCG Alone in Women Undergoing In Vitro Fertilization with Fresh Embryo Transfer Cycles.

To investigate the effect of the triggering method on the results of fresh embryo transfer in patients who underwent gonadotropin-releasing hormone antagonist cycles. The study was conducted retrospectively at a university-based tertiary reproductive center. The sample consisted of a total of 295 patients, of whom 111 were in the human chorionic gonadotropin (hCG) trigger group and 184 were in the dual trigger group. The main outcome measure of this study was the live birth rate, and secondary outcomes were the implantation rate, clinical pregnancy rate, miscarriage rate, and good-quality embryo rate. Patient demographics and baseline characteristics did not significantly differ between the dual and hCG trigger groups. The results also indicated statistically nonsignificant differences between the two groups in terms of the number of oocytes retrieved (p > 0.05), the number of mature oocytes (p > 0.05), and the fertilization rate (p > 0.05). The number of good-quality embryos (p=0.002) was higher in the dual trigger group compared with the hCG trigger group. However, the rates of clinical pregnancy and live births did not significantly differ between the groups (p > 0.05). Although the number of total and high-quality embryos obtained was higher in the dual trigger group, there were no significant differences between the two groups in terms of pregnancy outcomes. The fresh embryo transfer yielded similar rates of implantation and live births in both trigger groups.

GnRH antagonist monotherapy versus a GnRH agonist plus bicalutamide for advanced hormone-sensitive prostate cancer; KYUCOG-1401.

To compare the effectiveness and safety of gonadotropin-releasing hormone (GnRH) antagonist monotherapy to combined androgen blockade (CAB) with a GnRH agonist and bicalutamide in patients with advanced hormone-sensitive prostate cancer (HSPC). The study was conducted as KYUCOG-1401 trial (UMIN000014243) and enrolled 200 patients who were randomly assigned to either group A (GnRH antagonist monotherapy followed by the addition of bicalutamide) or group B (CAB by a GnRH agonist and bicalutamide). The primary endpoint was PSA progression-free survival. The secondary endpoints were the time to CAB treatment failure, radiographic progression-free survival, overall survival, changes in serum parameters, including PSA, hormones, and bone and lipid metabolic markers, and adverse events. PSA progression-free survival was significantly longer in group B (hazard ratio [HR], 95% confidence interval [CI]; 1.40, 1.01-1.95, p = 0.041). The time to CAB treatment failure was slightly longer in group A (HR, 95% CI; 0.80, 0.59-1.08, p = 0.146). No significant differences were observed in radiographic progression-free survival or overall survival. The percentage of patients with serum testosterone that did not reach the castration level was higher at 60 weeks (p = 0.046) in group A. No significant differences were noted in the serum levels of bone metabolic or lipid markers between the two groups. An injection site reaction was more frequent in group A. The present results support the potential of CAB using a GnRH agonist and bicalutamide as a more effective treatment for advanced HSPC than GnRH antagonist monotherapy.

Ovarian response determines the luteinizing hormone suppression threshold for patients following the gonadotrophin releasing hormone antagonist protocol: A retrospective cohort study

BackgroundOvarian reactivity to gonadotrophin stimulation varies, and individual adjustments to the timing and dose of gonadotrophin-releasing hormone (GnRH) antagonist administration are necessary to prevent excessive increases and decreases in luteinizing hormone (LH) levels in patients with different ovarian response following the GnRH antagonist (GnRH-A) protocol. The present study aims to investigate optimal LH suppression thresholds for patients with normal ovarian response (NOR), high ovarian response (HOR), and poor ovarian response (POR) following the GnRH-A protocol respectively. MethodsA total of 865 in vitro fertilization (IVF) cycles using a flexible or fixed GnRH-A protocol were included. Patients were categorized into the HOR, NOR, or POR group according to their anti-Müllerian hormone (AMH) levels. Then, patients in each group were stratified into one of four subgroups according to the quartile (Q1-Q4) of the basal LH level to LH on triggering day ratio (bLH/hLH). The primary outcomes were the clinical pregnancy and live birth rates, and the secondary outcomes were the number of oocytes retrieved, MII oocytes, two pronucleus (2PN) embryos, and good-quality embryos. ResultsThere were 526 patients with NOR, 180 with HOR, and 159 with POR. Basal LH level, LH on triggering day and bLH/hLH were identified as independent predictors of clinical pregnancy rate and live birth rate by logistics regression analysis. Compared to those with NOR, patients with POR had the lowest embryo implantation rate (22.6% vs. 32.8%, P < 0.05), clinical pregnancy rate (32.3% vs. 47.3%, P < 0.05) and live birth rate (22.6 vs. 37.8%, P < 0.05) of fresh embryo transfer (ET). The embryo implantation, clinical pregnancy and live birth rates of frozen embryo transfer (FET) were not significantly different among the three groups. In the subgroup analysis, patients with HOR had the highest embryo implantation rate (51.6%, P < 0.05), clinical pregnancy rate (68.4%, P < 0.05) and live birth rate (52.6%, P < 0.05) of ET in Q3, with a bLH/hLH ratio of 2.40–3.69. In the NOR group, the embryo implantation rate (41.9%, P < 0.05), clinical pregnancy rate (61.5%, P < 0.05) and live birth rate (50.8%, P < 0.05) of ET and live birth rate (53.1%, P < 0.05) of FET were highest in Q2, with a bLH/hLH ratio of 1.29–2.05. Patients with POR had the highest clinical pregnancy rate (57.1%, P < 0.05) and live birth rate (42.9%, P < 0.05) of ET in Q2, with a bLH/hLH ratio of 0.86–1.35. ConclusionsIn the present study, the bLH/hLH ratio represented the LH suppression threshold. The subgroup analysis of HOR, NOR and POR showed that, the LH suppression threshold varies according to ovarian response. We recommend LH suppression thresholds of 2.40–3.69 for HOR, 1.29–2.05 for NOR, and 0.86–1.35 for POR to obtain the highest clinical pregnancy rate and live birth rate. This study provides comprehensive and precise references for clinicians to monitor LH levels individually during controlled ovarian stimulation (COS) according to the patient’s ovarian response following the GnRH-A protocol.

Follicle-Stimulating Hormone Exacerbates Cardiovascular Disease in the Presence of Low or Castrate Testosterone Levels

Low testosterone (T), common in aging men, associates with cardiovascular disease. We investigated whether follicle-stimulating hormone (FSH), which is affected by T, modulates the cardiovascular effects associated withlow T or castration. FSHβ-/-:low-density lipoprotein receptor (LDLR)-/- mice, untreated or castrated (orchiectomy, gonadotropin-releasing hormone agonist or antagonist), demonstrated significantly less atherogenesis compared with similarly treated LDLR-/- mice, but not following FSH delivery. Smaller plaque burden in LDLR-/- mice receiving gonadotropin-releasing hormone antagonists vs agonists were nullified in FSHβ-/-:LDLR-/- mice. Atherosclerotic and necrotic plaque size and macrophage infiltration correlated with serum FSH/T. In patients with prostate cancer, FSH/T following androgen-deprivation therapy initiation predicted cardiovascular events. FSH facilitates cardiovascular disease when T is low or eliminated.

Association between the systemic immune-inflammation index and GnRH antagonist protocol IVF outcomes: a cohort study

Research questionWhat is the relationship between the systemic immune-inflammation index (SII) and IVF outcomes in women undergoing a gonadotrophin-releasing hormone (GnRH) antagonist protocol? DesignThis retrospective cohort study analysed clinical data and blood samples collected before oocyte retrieval from participants undergoing IVF with the GnRH antagonist protocol. Logistic regression and generalized additive models were used to examine the association between SII quartiles and continuous SII values and IVF outcomes. ResultsHigher SII values correlated negatively with biochemical pregnancy, clinical pregnancy, live birth and implantation rates, and positively with early pregnancy loss, independent of age, body mass index, anti-Müllerian hormone and stimulation parameters. The most significant adverse outcomes were observed in the highest SII quartile. A non-linear relationship was identified between log-transformed SII and IVF outcomes, with an inflection point at an SII of approximately 6.72, indicating a threshold effect. ConclusionsElevated SII is associated with poorer IVF outcomes in women after the GnRH antagonist protocol, suggesting its potential as a predictive marker in IVF treatments. Further research is needed to confirm these findings and explore the underlying mechanisms.

Live birth rate of gonadotropin-releasing hormone antagonist versus luteal phase gonadotropin-releasing hormone agonist protocol in IVF/ICSI: a systematic review and meta-analysis.

In vitro fertilization (IVF) and embryo transfer and intracytoplasmic sperm injection (ICSI) have allowed millions of infertile couples to achieve pregnancy. As an essential part of IVF/ICSI enabling the retrieval of a high number of oocytes in one cycle, controlled ovarian stimulation (COS) treatment mainly composes of the standard long gonadotrophin-releasing hormone agonist (GnRH-a) protocol and the gonadotrophin-releasing hormone antagonist (GnRH-ant) protocol. However, the effectiveness of GnRH-ant protocol is still debated because of inconsistent conclusions and insufficient subgroup analyses. This systematic review and meta-analysis included a total of 52 studies, encompassing 5193 participants in the GnRH-ant group and 4757 in the GnRH-a group. The findings of this study revealed that the GnRH-ant protocol is comparable with the long GnRH-a protocol when considering live birth as the primary outcome, and it is a favourable protocol with evidence reducing the incidence of ovarian hyperstimulation syndrome in women undergoing IVF/ICSI, especially in women with polycystic ovary syndrome. Further research is needed to compare the subsequent cumulative live birth rate between the two protocols among the general and poor ovarian response patients since those patients have a lower clinical pregnancy rate, fewer oocytes retrieved or fewer high-grade embryos in the GnRH-ant protocol.

The effect of laparoscopic ovarian drilling on pregnancy outcomes in polycystic ovary syndrome women with more than 2 in-vitro fertilization cycle failures: A pilot RCT.

Background: The effect of laparoscopic ovarian drilling (LOD) before in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI) cycles on pregnancy outcomes is an unclear and challenging subject. Objective: To evaluate the impact of LOD before IVF/ICSI cycles on controlled ovarian stimulation and pregnancy outcomes in polycystic ovary syndrome (PCOS) women with a history of more than 2 IVF failures. Materials and Methods: In this randomized clinical trial, women with PCOS diagnosis who referred to Arash Women's hospital, Tehran, Iran for IVF/ICSI cycle from August 2015-January 2018 were evaluated. Eligible participants were allocated into 2 groups randomly (n = 17/each group). The participants in the LOD group (intervention) were treated with laparoscopic couture, and after one month, they underwent IVF/ICSI cycles using the gonadotropin-releasing hormone antagonist protocol. The control group had no intervention. The oocyte and embryo qualities, ovarian hyperstimulation syndrome rate, the rates of chemical and clinical pregnancy and early miscarriage, live birth, and pregnancy complications, were compared between groups. Results: Finally, 34 participants were evaluated. The controlled ovarian stimulation outcomes were similar between groups. The ovarian hyperstimulation syndrome rate in the LOD group was significantly lower than in the control group (p = 0.04). One case of spontaneous pregnancy was reported in the LOD group. No significant difference was observed between groups in clinical pregnancy, miscarriage, and live birth rates. The rates of pregnancy complications (gestational diabetes mellitus, preeclampsia, and preterm birth) were similar between groups. Conclusion: Performing LOD before IVF/ICSI cycles did not improve the pregnancy outcomes in PCOS women, a clinical trial with a larger sample size is needed to prove these results.

Progesterone-primed cycles result in slower embryos without compromising implantation potential and with the advantages of oral administration and potential cost reduction

To study the impact of the use of progesterone on embryo morphokinetics and on the outcomes of intracytoplasmic sperm injection cycles. Cohort study. Private university-affiliated invitro fertilization center. This study included 236 freeze-all intracytoplasmic sperm injection cycles and the resultant 2,768 injected oocytes cultured in a time-lapse imaging incubation system. Patients were matched by age and divided into groups depending on the protocol used to prevent the luteinizing hormone surge: progestin-primed (144 cycles and 1,360 embryos) and gonadotropin hormone-releasing hormone (GnRH) antagonist (144 cycles and 1,408 embryos) groups. The kinetic recorded markers were time to pronuclear appearance and fading, time to 2-8 cells, time to morulation, time to start of blastulation, and time to blastulation. The durations of cell cycles and time to complete synchronous divisions were calculated. The Known Implantation Data Score ranking was recorded. Morphokinetics and clinical outcomes were compared between the groups. Embryo morphokinetics and clinical outcomes. Slower time to pronuclear appearance, time to 2 cells, time to 7 cells, time to start of blastulation, and time to blastulation were observed in embryos derived from progestin-primed cycles than in those from the GnRH antagonist group. No significant differences were noted in any other morphokinetic milestone. Significantly higher cancellation and implantation rates were observed in the progestin-primed group. However, no significant differences were noted in the pregnancy and miscarriage rates. The expenses for treatment using premature GnRH antagonist and progestins were US$318.18 and US$11.05, respectively. Exogenous progesterone replaces the GnRH antagonist for the prevention of premature luteinizing hormone surge, in freeze-all cycles, with the advantage of oral administration and potential cost reduction.

The effects of flexible short protocol with gonadotropin-releasing hormone antagonist on preventing premature ovulation in poor responders

PurposeThe proportion of patients with poor ovarian response (POR) is increasing, but effective treatment remains a challenge. To control the hidden peaks of luteinizing hormone (LH) and premature ovulation for poor responders, this study investigated the efficacy of flexible short protocol (FSP) with gonadotropin-releasing hormone antagonist (GnRH-ant) on trigger day.MethodsThe 662 cycles of POR patients were retrospectively analyzed. The cohort was divided into control and intervention groups. The intervention group (group A) with 169 cycles received a GnRH-ant given on trigger day. The control (group B) with 493 cycles received only FSP. The clinical outcomes of the two groups were compared.ResultsCompared with group B, with gonadotropin-releasing hormone antagonist (GnRH-ant) on trigger day in group A the incidences of spontaneous premature ovulation decreased significantly (2.37% vs. 8.72%, P < 0.05). The number of fresh embryo-transfer cycles was 45 in group A and 117 in group B. There were no significant differences in clinical outcomes, including implantation rate, clinical pregnancy rate, live birth rate and the cumulative live birth rate (12.0% vs. 9.34%; 22.22% vs. 21.93%; 17.78% vs. 14.91%; 20.51% vs. 20%, respectively; P > 0.05) between the two group.ConclusionFSP with GnRH-ant addition on trigger day had no effect on clinical outcomes, but could effectively inhibit the hidden peaks of luteinizing hormone (LH) and spontaneous premature ovulation in POR. Therefore, it is an advantageous option for POR women.

#21 : Letrozole Can Be a Good Adjuvant for In Vitro Fertilization (IVF) Procedure in Patient with Ovarian Endometriosis

Background and Aims: To evaluation the pregnancy rate in IVF procedure with letrozole in patient with ovarian endometrioma. Method: Prospective study performed by single physician at primary fertility center. From August 2016 to November 2019, 109 cycles of IVF were performed from couples who were diagnosed as endometrioma. 40 women were diagnosed during ovarian cystectomy, 69 were by transvaginal ultrasonography. In 64 cycles, gonadotrophic releasing hormone (GnRH) antagonist protocol was used, and in another 45 cycles, gonadotrophin releasing hormone agonist (GnRHa) protocol were applied. In every cycle, 10 mg of letrozole was added from the start of gonadotrophin till the end of ovarian stimulation. Results: Women’s age was 36.10±3.67, and the number of their previous IVF cycle was 2.66±1.63. AMH was 2.30±2.31, follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) on the third day of menstruation were 9.40±5.26, 7.81±4.60 and 54.1±44.2. Start dosages and total dosages of recombinant FSH were 314.32±74.99 and 2541.37±992.77, and serum E2 and progesterone on trigger day were 1220.06±1072.49 and 0.92±0.79. The endometrial thickness was 9.20±1.46. The number of obtained oocytes was 9.05±5.94 and metaphase II(M2) oocytes were 6.71±4.12. 1.91±0.42 embryos were transferred to the uterine cavity and 2.68±2.58 surplus embryos were cryopreserved. Pregnancy rate was diagnosed if serum beta human chorionic gonadotrophin (hCG) level was above 5 ng/ml on 14th day after oocyte retrieval, and the result was 44.95% (49/109). Clinical pregnancy rate which was defined if gestational sac was visualized by transvaginal ultrasonography after at least 21st days after oocyte retrieval, and the result was 24.77% (27/109). Conclusion: In IVF procedure for the patients with ovarian endometrioma, just adding letrozole to conventional controlled ovarian hyperstimulation protocol can reduce serum peak E2 level without make harmful effect on uterine endometrium, and result in comparable pregnancy rate.

Prevention of OHSS

Ovarian hyperstimulation syndrome (OHSS), perhaps the most serious complication arising from in vitro fertilization (IVF), is rare but life-threatening in some cases. In this lecture, we will first delve into the pathophysiology of OHSS and hallmark features such as hemoconcentration, hypercoagulability, electrolyte imbalances, fluid loss into third space, and renal insufficiency. In addition, clinical vignettes will illustrate some of the most severe cases of OHSS. Next, various methods for identifying patients at high risk of OHSS will be discussed. Available literature indicates that younger age and polycystic ovarian syndrome (PCOS) may be associated with the incidence of OHSS. Ovarian reserve markers such as anti-müllerian hormone (AMH) and antral follicle counts (AFC) have been suggested as useful screening tools. Also, stimulation cycle profiles, such as developing multiple follicles, peak serum estradiol levels, and the number of retrieved oocytes, may aid in identifying those at high risk. To lower the incidence of OHSS, modifying controlled ovarian stimulation (COS) protocols is essential. Evidence suggests that gonadotropin-releasing hormone (GnRH) antagonist protocol is beneficial in reducing the risk of OHSS. Medications such as dopamine agonists, aspirin, and metformin may be associated with lower risk while using clomiphene citrate remains controversial. “Coasting,” which is holding gonadotropins for several days to decrease the OHSS risk, has been suggested as another strategy. Triggering could be done differently using a GnRH agonist. Cycle segmentation by cryopreserving oocytes and embryos is also a feasible option. Close monitoring and early detection of symptoms are essential for prompt intervention and management of OHSS. By implementing preventative measures and closely monitoring patients, physicians may reduce the incidence and severity of OHSS and ensure safer fertility treatments.

#20 : Follitropin Delta Can Play a Good Role in Both Patients with High Serum AMH Level and Patients with Low Serum AMH Level in IVF

Background and Aims: To evaluation clinical efficacy of follitropin delta in IVF procedure for Korean. Method: This is a prospective study performed by single physician at primary fertility center. From December 2020 to November 2021, total 82 cycles of IVF were performed. 70% of total cycles was performed using gonadotrophic releasing hormone (GnRH) antagonist protocol, and another 30% of cycles were gonadotrophin releasing hormone agonist (GnRHa) protocol. Results: Average duration of infertility was 2.2± 1.5 years. AMH levels were 2.4± 2.4 ng/ml. The number of obtained oocytes were 8.9± 5.0. Mean daily dose of follitropin delta were 10.3± 2.5 mcg, and total dosage were 121.8± 25.5 mcg. Duration of stimulation were 9.9± 2.0 days. Biochemical pregnancy rate was 38% and clinical pregnancy rate was 27%. No cases of severe ovarian hyperstimulation syndrome were developed. Conclusion: For both patients with good ovarian reserve, and the patients with poor ovarian reserve, follitropin delta can play a good role. With its discriminative fixed dosing protocol, follitropin delta gives more convenient way for both physicians and patients with minimal risk of OHSS, without having detrimental effect on pregnancy rate.

#304 : Comparing GnRH Agonist and GnRH Antagonist Protocols for IVF-ET Outcomes in Patients with Endometriosis: A Meta-Analysis

Background and Aims: Endometriosis is known to have detrimental effects on fertility, but there is no consensus on the optimal stimulation protocol for IVF-ET in patients with endometriosis. The study aimed to compare the IVF outcomes of gonadotropin-releasing hormone (GnRH) agonist protocols versus antagonist protocols in patients diagnosed with endometriosis. Method: We performed a meta-analysis of studies that compared IVF outcomes of GnRH agonist versus antagonist protocols in patients with endometriosis. Through literature search, we retrieved 222 articles, and the last search date was April 7, 2023. Among them, six studies which met inclusion criteria were eligible for final analysis. The primary outcome was clinical pregnancy. Random effects and fixed effects models were applied according to I2 statistics. Results: The use of GnRH agonist was associated with higher clinical pregnancy rate (Odds ratio (OR) 1.61, 95% CI 1.35–1.93, 6 studies, [Formula: see text]&lt;0.00001, I2=16%), higher live birth rate (OR 1.75, 95% CI 1.32–2.33, 3 studies, [Formula: see text]&lt;0.0001, I2=12%), and similar miscarriage rate. The total dose of gonadotropin did not differ between the two methods, but the GnRH agonist protocol had a longer duration of stimulation (WMD 1.34, 95% CI 0.44–2.24, 5 studies, I2=98%), retrieved more oocytes (WMD 2.23, 95% CI 0.58–3.88, 3 studies, [Formula: see text]=0.0008, I2=97%), more MII oocytes (WMD 2.81, 95% CI 2.34–3.28, 3 studies, [Formula: see text]&lt;0.00001, I2=0), and more embryos (WMD 1.90, 95%CI 1.13–2.67, 3 studies, [Formula: see text]&lt;0.00001, I2=68%). Conclusion: Patients with endometriosis may benefit from using GnRH agonist protocol in the IVF-ET cycle, as it may be associated with a higher clinical pregnancy rate and live birth rate. Even though the stimulation duration is longer, more oocytes, mature oocytes, and embryos may be expected. Although the findings of this study may be potentially beneficial for clinicians, it is crucial to conduct additional randomized prospective trials with larger cohorts to further validate the results.