GnRH Antagonist Research Articles

Innovative Medical Treatments for Endometriosis

This presentation will focus on the following innovative areas in medical treatments for endometriosis. Where were we, say, a decade ago compared to where we are now? What diagnostic techniques should we employ to define the population we should treat? Does gold standard surgical treatment help patients avoid unwanted medical treatment - or should it now be the other way round? Do we still believe that medical treatment is not indicated for infertility related to endometriosis? What are the genuinely evidence-based innovative medical treatments for endometriosis? Consensus statements and guidelines represent a clear line in the sand of what may be considered gold standard practice of the time – the World Endometriosis Society’s consensus on current management of endometriosis (2013) 1 provides a good perspective on where we were around a decade ago; the ESHRE Guideline (2022) 2 reflects best practice today. There is growing consensus that a laparoscopic (+/- histological) diagnosis is no longer practical, or indeed needed, in most cases to implement the whole gamut of medical treatment, even though the entire evidence base for treating endometriosis hinges on laparoscopic diagnosis. Hence, “in 2023, there is a strong case for treatment of endometriosis to be based on a clinical diagnosis of ‘likely endometriosis’ supported by imaging findings, when appropriate, in lieu of a traditional diagnosis by laparoscopy +/- histology”. Following laparoscopic surgery, those not intending to conceive should consider the levonorgestrel intrauterine system or combined oral contraceptive pill for at least 18-24 months to reduce the recurrence of endometriosis-related pain symptoms; 2 following surgery for either endometriomas or deep endometriosis, long term hormone therapy should be considered to reduce the chance of recurrence.2 Given the respective evidence bases, progestin hormone therapy may be preferable to the combined oral contraceptive pill to turn the tide of increasing prevalence of endometriosis. 3 While medical treatment has not been recommended to improve fertility, indeed a delaying effect on fertility through medical treatment has traditionally been highlighted, innovative analysis methods, including network meta-analysis, have raised the question whether some medical treatments (dydrogesterone and GnRH agonists) might benefit fertility – and this is merit-worthy of further investigation. GnRH antagonists and aromatase inhibitors are the innovative medical treatments that have shifted from ‘showing potential’ to ‘recommended’, so we will delve into the data supporting this to discover that, for aromatase inhibitors, this remains far from convincing, but for GnRH antagonists, these present a genuine innovative medical treatment option for those suffering from endometriosis.

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.

Non-inferiority of progestin-primed ovarian stimulation versus GnRH antagonist protocol: A propensity score-weighted analysis

PurposeTo evaluate the effectiveness of the progestin-primed ovarian stimulation (PPOS) protocol versus the gonadotropin-releasing hormone antagonist (GnRH-ant) protocol in ovarian stimulation. MethodsIn this retrospective cohort study, we included 804 patients who were treated between January 1st, 2022, and July 1st, 2023. Outcomes of ovarian stimulation were compared between the PPOS (n = 206) and GnRH-ant (n = 598). The primary outcome was the number of good cleavage embryos. ResultsBaseline characteristics were comparable in both groups. In both unadjusted and adjusted analysis, the mean number of good cleavage embryos in PPOS (6.33) was non-inferior to GnRH-ant (6.44; unadjusted ratio of two means 1.02, 95%CI 0.92, 1.13). The trigger-day estradiol level in patients with PPOS was higher than in patients with GnRH-ant (4,420 vs 3,830 pg/ml, respectively) despite similar total follicle stimulating hormone dose and fewer days of ovarian stimulation. The number of oocytes, MII oocytes, cleavage and blastocyst embryos were comparable between the two protocols. After the first transfer of embryos, the clinical pregnancy rate and implantation rate were higher in the PPOS group, while the pregnancy rate and ongoing pregnancy were not significantly different. None of the PPOS patients had an unexpected LH surge, and serum LH levels decreased slightly during ovarian stimulation. ConclusionsThe PPOS protocol with dydrogesterone provided similar embryo outcomes to the GnRH-ant protocol, with notable distinctions in clinical pregnancy and implantation rate. The serum LH concentration during ovarian stimulation using PPOS was well-controlled.

#325 : A Comparison of Three Different IVF FSH Dosing Strategies for PCOS Patients; A Retrospective Analysis of 855 IVF Cycles

Background and Aims: IVF responses to gonadotrophins may be difficult to predict in patients with PCOS. Nowadays there are various options including using the strategy of GnRH agonist trigger and freeze all embryos. The follitropin delta dosing algorithm has been used to predict an ovarian response that reduces the effects of ovarian hyperstimulation syndrome. The aim of this study was to compare the outcomes of three different FSH dosing strategies in PCOS patients. Methods: This retrospective multi-centre trial enrolled 626 PCOS women. They underwent 855 stimulated IVF cycles using a GnRH antagonist protocol and 634 frozen embryo transfers with embryos from the original stimulated cycles. Patients were classified into 3 groups: Group 1 (underdosing), Group 2 (algorithm dosing) and group 3 (overdosing). The algorithmic dose was based on the follitropin delta algorithm using AMH and body weight. The main outcome measure was the live birth rate per cycle started. Results: The live birth rate per cycle was 40.8% for group 1, 42.1% for group 2 and 45.5% for group 3. Group 3 had the greatest average number of embryos frozen (1.55 embryos in group 1, 2.45 group 2 and 2.96 group 3). The average number of eggs collected was greatest in group 3 (8.7 eggs in group 1, 11.9 group 2 and 14.2 group 3). The most frozen of all cycles occurred in group 3 (45.6%). Conclusions: Higher FSH dosing resulted in more eggs and more live births per cycle started. It also resulted in less fresh embryo transfers. These results could be used when choosing an FSH dosing strategy for PCOS patients.

#162 : Effect of r-LH Supplementation in Controlled Ovarian Stimulation in Antagonist Protocol of IVF

Background and Aims: Adding LH to FSH can increase the mean of retrieved oocytes and cumulative embryos. LH stimulates the theca cells to secrete androgens, which are converted to estrogens during folliculogenesis. Women with long GnRH agonist downregulation, GnRH antagonist protocol, poor ovarian reserve, and patients with hypogonadotropic hypogonadism may have advantages in using exogenous LH. Here we show our experience using r-LH in our clinic concerning oocyte retrieval and maturity rates. Methods: We retrospectively took data from patients who underwent antagonist protocol from January 2021- January 2023 in Mbrio IVF Clinic Jakarta. Forty-three patients were stimulated by r-FSH (n=9) and a combination of r-FSH and r-LH (co-treatment) (n = 34) for 9-11 days and triggered by r-HCG or dual trigger (r-HCG and GnRHa). We statistically analyzed the retrieval rate, maturation rate, and OSI (ovarian sensitivity index) by independent-T and Mann-Whitney U tests. The level of significance was set at p < 0.05. Results: The mean age (33 vs. 35 yo), estrogen level, and trigger treatment were similar in both groups. The median AMH level in group r-FSH was higher than the co-treatment group (p 0.012; 4.44 vs. 1.75). The median retrieval and mean maturation rates were equivalent in both groups (100% vs. 90.9%; 78.5% vs. 80%). The OSI was higher in r-FSH than the second group but statistically insignificant. (p 0.20; 5.42 vs. 3.29). Conclusions: Adding LH to FSH in antagonist protocol gives both groups the same retrieval and maturity rate. Although they had comparable OSI, the AMH level in the co-treatment was lower than in the first group. The lower AMH level group gets advantages from the co-treatment in this data. We need larger data and complex analysis to validate the result.

Optimising Ovulation Induction in PCOS

Biochemical, Metabolic and Endocrine changes in PCOS result in reproductive impairment in women with PCOS. Controlled ovarian stimulation (COS) may be associated with • Unpredictable response • Response may be slow • Hyper-response - OHSS • Risk of Cyst Formation • Poor oocyte quality • Miscarriage • Cycle cancellation So, the ovulation induction protocol should be efficacious and safe resulting in a singleton live birth, minimising complications, and risks like ovarian hyperstimulation syndrome (OHSS), multiple pregnancies and cancellation of cycles. For this special consideration should be given to prediction of response, pre-treatment, choosing the right ovulation induction (OI) protocol with right dose and analogue, using GnRH agonist trigger instead of hCG, preventing late follicular phase rise in progesterone, or following the segmentation protocol. We can maximize the success rates by stimulation individualization based on age, AMH, AFC and amended further for BMI. AMH is considered as more sensitive marker to define follicle excess than AFC as it appraises more follicle classes - preantral and early antral. One should probably use mild stimulation protocols where gonadotropins are given in combination with oral ovulogens or the low dose step up protocol. It is essential that we use GnRH antagonist protocol and administer GnRH agonist if there is risk of OHSS. If segmentation protocol is used one could also use the progesterone primed ovarian stimulation instead of GnRG antagonist. One could reduce the incidence of OHSS by laparoscopic ovarian drilling and use of Metformin and aspirin before assisted reproduction. If the patient is at risk of developing OHSS during stimulation then one could administer cabergoline, intravenous infusion of calcium gluconate or albumin and methylprednisolone. But freezing all embryos and transferring them in a subsequent cycle increase the efficacy and reduce complications of ART in PCOS women. Elective single embryo transfer(eSET) should be the norm to reduce the multiple pregnancy rate. Conclusion Thus, in all ART cycles individualised COS with freeze all and eSET could help in increasing the success of ART and reducing stress and anxiety and complications in these women.

#314 : Comparison of Dual-Trigger and Human Chorionic Gonadotropin-Only Trigger Among Diminished Ovarian Reserve Who Underwent Intracytoplasmic Sperm Injection: A Retrospective Cohort Study

Background and Aims: Diminished ovarian reserve (DOR) remains one of the greatest challenges for ART treatment. The objective of this study was to compare the laboratory outcomes of dual trigger and human chorionic gonadotropin (HCG) trigger alone in the final oocyte maturation for DOR patients. Methods: In this retrospective study,we evaluated 130 DOR women (dual group, n=75 and HCG group, n=45) underwent intracytoplasmic sperm injection (ICSI) between July 2020 and February 2023 at the Assisted Reproductive Department, Hung Vuong Hospital. DOR was defined as antral follicle count [Formula: see text]5 and serum anti-Müllerian hormone level [Formula: see text]1.2ng/mL. All patients using the GnRH antagonist protocolwith frozen embryo transfer. Baseline characteristics and cycle parameters, as well as IVF outcomes of both groups were compared. Generalized linear model (GLM) with negative binomial distribution for retrieved oocytes outcome and binomial distribution for other outcomes such as maturation rate, fertilization rate, rate of successfully achieving blastocytes and day-3 embryos. Results: Baseline characteristics were similar between the dual trigger group and the HCG group for age (p=0.2), AFC (p=0.44), AMH (p=0.76), BMI (p = 0.12), indication and number of priorARTcycles. The dual-trigger group had a significantly higher number of retrieved oocytes (95% CI 0.125–2.437, p=0.03), metaphase oocyterate (OR = 1.90, 95% CI 1.05–3.43; p=0.033). Fertilized oocyte rate (OR 1.42, 95% CI 2.015–0.795, p=0.967) andday-3 embryos (OR = 1.42, 95% CI 2.70–.73, p=0.294) were comparable in two groups. Conclusions: Our data suggests that dual trigger for final oocyte maturation might improve laboratory outcomes of IVF cycles in DOR patients.

The Impact of Growth Hormone Co-Treatment Duration on Outcomes in IVF/ICSI Cycles Among Poor Ovarian Responders.

The efficiency of in vitro fertilization is improved by growth hormone (GH) during ovarian stimulation. Additionally, patients with diabetes experience impaired insulin resistance and compromised glucose tolerance, which further exacerbate their condition. Due to these side effects, in this study, the duration of GH treatment was compared in IVF/ICSI cycles among poor ovarian responders. In this study, POSEIDON criteria were used to choose patients. Subcutaneous administration of gonadotropin-releasing hormone (GnRH) antagonist was done beginning on the sixth day of the cycle and continuing through the day of human chorionic gonadotropin (hCG) injection. In one group, GH was administered 4 units/day from the 2nd day of the cycle until hCG injection, and in another group, the first dose was administered on the 6th day of the cycle. Following the administration of hCG, which lasted from 24 to 36 hr, oocytes were retrieved with the support of B-mode sonography. In our analysis, no significant differences were observed between the two groups in terms of the number of retrieved oocytes, metaphase II oocytes, and quality of grade A and B embryos. The results show that the treatment or conditions did not have a significant impact on the outcomes among the studied groups. Our findings indicate that a shorter duration of GH administration can yield similar outcomes compared to a longer duration in IVF/ICSI cycles involving poor ovarian responders. This result holds the potential for a more cost-effective and patient-friendly approach in managing assisted reproductive technology procedures. It may lead to reduced side effects and improved adherence to medication regimens in patients.

Analysis of controlled ovarian hyperstimulation protocols in women over 35 years old with poor ovarian response: a real-world study

The objective of this study was to investigate the optimal controlled ovarian hyperstimulation (COH) protocol for patients aged 35 and above with poor ovarian response (POR), utilizing real-world data. This retrospective cohort study examined clinical information from a total of 4256 patients between January 2017 and November 2022. The patients were categorized into three groups: modified GnRH agonist protocol (2116 patients), GnRH antagonist protocol (1628 patients), and Mild stimulation protocol (512 patients). Comparative analysis was conducted on clinical variables and pregnancy outcomes across the three groups. The GnRH agonist protocol was associated with a higher number of oocyte number (4.02 ± 2.25 vs. 3.15 ± 1.52 vs. 2.40 ± 1.26, p < 0.001), higher number of transferable embryos (1.73 ± 1.02 vs. 1.35 ± 1.22 vs. 1.10 ± 0.86, p = 0.016), higher cumulative live birth rate 28.50(603/2116) vs. 24.94(406/1628) vs. 20.51(105/512), p < 0.001) than GnRH antagonist protocol and Mild stimulation protocol, the Mild stimulation protocol was associated with a higher miscarriage rates 16.27(62/381) vs. 16.61(48/289) vs. 32.22(29/90), p = 0.001) than the other two groups. Therefore, it can be concluded that all three protocols can be used in patients over 35 years old with poor ovarian response. However, if patients require more frozen-thawed embryo transfers to achieve better cumulative live birth rates, the modified GnRH agonist protocol may be the preferable option.

Retrospective Analysis of Fresh Single Blastocyst Transfer versus Two Cleavage-Stage Fresh Day-3 Embryo Transfer with High-Quality Embryos during Gonadotropin-Releasing Hormone Antagonist Cycles in High Responders

Retrospective Analysis of Fresh Single Blastocyst Transfer versus Two Cleavage-Stage Fresh Day-3 Embryo Transfer with High-Quality Embryos during Gonadotropin-Releasing Hormone Antagonist Cycles in High Responders

Duphaston as a suitable medication for women taking intracytoplasmic sperm injection to treat infertility

Objective: Duphaston is used as an alternative to gonadotropin-releasing hormone (GnRH) antagonists for suppressing premature luteinizing hormone (LH) surges. This study aimed to compare the efficacy of Duphaston protocols with that of Cetrotide in suppressing the LH surge. Methods: In this retrospective cross-sectional study, 669 infertile women (aged 25–40 years) were administered recombinant follicle-stimulating hormone (rFSH) from the third day of their menstrual cycle. After the follicular diameter reached 13 to 14 mm, Cetrotide was prescribed orally to the control subjects, also case subjects took Duphaston orally. The retrieved oocytes were fertilized by an intracytoplasmic sperm injection (ICSI). Results: The levels of FSH, LH, and estradiol did not differ significantly between the groups (P &gt;0.05). However, the findings indicated that Duphaston led to greater oocyte retrieval than Cetrotide (P = 0.006). However, the number of mature oocytes and viable embryos in the case subjects did not reach a significant difference compared to that in the control subjects (P &gt;0.05). The number of good-quality embryos (stage 1) was significantly higher in the case subjects (P = 0.04). In addition, there is no significant difference in the chemical, clinical pregnancy, implantation rate, and miscarriage rate between both groups (P &gt;0.05). Conclusion: Duphaston could be utilized as a suitable medication rather than a GnRH antagonist in women subjected to controlled ovarian hyperstimulation.

Progestin primed ovarian stimulation using dydrogesterone from day 7 of the cycle onwards in oocyte donation cycles: a longitudinal study

Does a progestin-primed ovarian stimulation (PPOS) protocol with dydrogesterone from cycle day 7 yield similar outcomes compared with a gonadotrophin-releasing hormone (GnRH) antagonist protocol in the same oocyte donors? This retrospective longitudinal study included 128 cycles from 64 oocyte donors. All oocyte donors had the same type of gonadotrophin and daily dose in both stimulation cycles. The primary outcome was the number of cumulus-oocyte complexes (COC) retrieved. The number of COC retrieved (mean ± SD 19.7 ± 10.8 versus 19.2 ± 8.3; P = 0.5) and the number of metaphase II oocytes (15.5 ± 8.4 versus 16.2 ± 7.0; P = 0.19) were similar for the PPOS and GnRH antagonist protocols, respectively. The duration of stimulation (10.5 ± 1.5 days versus 10.8 ± 1.5 days; P = 0.14) and consumption of gonadotrophins (2271.9 ± 429.7 IU versus 2321.5 ± 403.4 IU; P = 0.2) were also comparable, without any cases of premature ovulation. Nevertheless, there was a significant difference in the total cost of medication per cycle: €898.3 ± 169.9 for the PPOS protocol versus €1196.4 ± 207.5 (P < 0.001) for the GnRH antagonist protocol. The number of oocytes retrieved and number of metaphase II oocytes were comparable in both stimulation protocols, with the advantage of significant cost reduction in favour of the PPOS protocol compared with the GnRH antagonist protocol. No cases of premature ovulation were observed, even when progestin was started later in the stimulation.

A prediction model for high ovarian response in the GnRH antagonist protocol.

The present study was designed to establish and validate a prediction model for high ovarian response (HOR) in the GnRH antagonist protocol. In this retrospective study, the data of 4160 cycles were analyzed following the in vitro fertilization (IVF) at our reproductive medical center from June 2018 to May 2022. The cycles were divided into a training cohort (n=3121) and a validation cohort (n=1039) using a random sampling method. Univariate and multivariate logistic regression analyses were used to screen out the risk factors for HOR, and the nomogram was established based on the regression coefficient of the relevant variables. The area under the receiver operating characteristic curve (AUC), the calibration curve, and the decision curve analysis were used to evaluate the performance of the prediction model. Multivariate logistic regression analysis revealed that age, body mass index (BMI), follicle-stimulating hormone (FSH), antral follicle count (AFC), and anti-mullerian hormone (AMH) were independent risk factors for HOR (all P< 0.05). The prediction model for HOR was constructed based on these factors. The AUC of the training cohort was 0.884 (95% CI: 0.869-0.899), and the AUC of the validation cohort was 0.884 (95% CI:0.863-0.905). The prediction model can predict the probability of high ovarian response prior to IVF treatment, enabling clinicians to better predict the risk of HOR and guide treatment strategies.

GnRH antagonist protocol versus progestin-primed ovarian stimulation in patients with polycystic ovary syndrome: a systematic review and meta-analysis.

The aim of this meta-analysis was comparing the efficacy of GnRH antagonist (GnRH-ant) protocol and progestin-primed ovarian stimulation (PPOS) in polycystic ovarian syndrome (PCOS) women. A search was conducted from PubMed, Embase, The Cochrane library, Web of Science, and Scopus databases to collect clinical papers regarding GnRH-ant protocol and PPOS protocol from inception to September 2023. Subsequently, the retrieved documents were screened, and the content of the documents that conformed to the requirements was extracted. Moreover, statistical meta-analyses were conducted using the RevMan 5.4 software. Furthermore, with the use of a star-based system and the Cochrane handbook, the methodological quality of the covered papers was evaluated on the Ottawa-Newcastle scale. A total of eight papers were covered in the meta-analysis, with 2156 PCOS women enrolled (i.e., 1085 patients in the GnRH-ant protocol group and 1071 patients in the PPOS group). As indicated by the meta-analysis results, the PPOS group was correlated with a lower risk of ovarian hyperstimulation syndrome (OHSS) (SMD = 9.24, [95% CI: (2.50, 34.21)], P = 0.0009), more gonadotropin (Gn) dose (SMD = - 0.34, [95% CI: (- 0.56, - 0.13)], P = 0.002) compared with GnRH-ant group. No statistical difference was identified on the oocytes condition and pregnancy outcomes. As revealed by the data of this study, the progesterone protocol is comparable with the GnRH-ant protocol in oocytes condition and clinical outcomes. The progestin-primed ovarian stimulation could serve as an alternative for polycystic ovarian syndrome women who have failed in GnRH antagonist protocol. The above-described conclusions should be verified by more high-quality papers due to the limitation of the number and quality of included papers. PROSPERO registration: CRD42023411284.

Luteinizing Hormone Levels as an Indicator of the Timing of Antagonist Administration in a Gonadotropin-Releasing Hormone Antagonist Protocol

Luteinizing Hormone Levels as an Indicator of the Timing of Antagonist Administration in a Gonadotropin-Releasing Hormone Antagonist Protocol

Impact of 2.5 mg versus 5 mg letrozole co-treatment in an antagonist protocol for IVF: a retrospective study.

The present study aimed to compare the effectiveness of two different doses of letrozole (2.5 mg and 5 mg daily) in an antagonist protocol for infertile women with normal ovarian reserve. This retrospective cohort study included infertile women who underwent in vitro fertilization treatment with letrozole co-treatment at doses of 2.5 mg and 5 mg from 2007 - 2021 at Shanghai Ninth People's Hospital (Shanghai, China). The control group comprised infertile women who received gonadotropin-releasing hormone antagonist alone. The primary outcome was the cumulative live birth rate, while secondary outcomes included follicular phase endocrine parameters, ovarian stimulation outcomes, pregnancy outcomes, and the incidences of maternal and neonatal complications. Baseline and follow-up data were compared between the groups using ANOVA for normally distributed variables, the Kruskal-Wallis test for non-normally distributed variables, and the Chi-square test for categorical variables. A total of 422 participants were enrolled in the study, with 211 women in the antagonist group, 109 women in the 2.5 mg letrozole co-treatment group, and 102 women in the 5 mg letrozole co-treatment group. Letrozole co-treatment significantly suppressed oestradiol and follicle-stimulating hormone concentrations from stimulation day 5 and onwards, while increasing luteinizing hormone levels on stimulation day 5 and trigger day. The effect was more pronounced with a 5 mg dose of letrozole compared to a 2.5 mg dose (P < 0.05). Administration of 5 mg letrozole reduced the gonadotropin dose (P < 0.05) without negatively affecting the number of oocytes retrieved and subsequent embryo parameters (P > 0.05). The analysis of cumulative live birth rates showed rates of 29.4% in the letrozole 5 mg group, 27.5% in the letrozole 2.5 mg group, and 33.6% in the control group, with no statistically significant difference (P > 0.05). There were no reported pregnancy complications in the two letrozole groups. Additionally, there were no significant differences among the three groups in terms of gestational age and birth weight for both singleton and twin births. This study indicates that the administration of letrozole in an antagonist protocol, at both 2.5 mg and 5 mg dosages, results in comparable clinical outcomes.

Progestin-Primed Ovarian Stimulation versus GnRH Antagonist Protocol for Ovarian Stimulation in IVF: A Prospective Pilot Study

Background: Progestin-primed ovarian stimulation (PPOS) has been proposed as an alternative to conventional gonadotropin-releasing hormone (GnRH) antagonist protocol for ovarian stimulation in in vitro fertilization (IVF). The aim of PPOS is to provide an effective, patient-friendly treatment. However, studies comparing outcomes after the use of PPOS and GnRH antagonist protocol in IVF have shown mixed results. This study compared ongoing pregnancy rates after the use of PPOS versus GnRH antagonist protocol for ovarian stimulation in IVF. Methods: This prospective pilot study was conducted at a single IVF center. Women aged 18–35 years old with an anti-Müllerian hormone (AMH) level greater than or equal to 1.2[Formula: see text]ng/mL or an antral follicle count (AFC) greater than or equal to 5 who were undergoing their first IVF cycle were allocated to undergoing ovarian stimulation using PPOS (dydrogesterone 20[Formula: see text]mg/day started on the day of gonadotropin) or a GnRH antagonist protocol (fixed regimen from stimulation day 5). The primary outcome was the ongoing pregnancy rate (at 12 weeks’ gestation). Results: The study included 30 women (15 in each treatment group). Baseline characteristics were similar between groups. The ongoing pregnancy rate was 7/15 (46.7%) in the PPOS group and 8/15 (53.3%) in the GnRH antagonist group ([Formula: see text]); the number of oocytes retrieved and fertilization rates were also comparable between groups. One case of mild ovarian hyperstimulation syndrome (OHSS) occurred in the GnRH antagonist group. Conclusions: This pilot study showed similar ongoing pregnancy rates after the use of a PPOS protocol and a conventional GnRH antagonist protocol for ovarian stimulation in IVF. Additional studies with larger sample sizes are needed to confirm these findings.

Abstract 12107: Cardiovascular Outcomes Associated With Gonadotropin-Releasing Hormone Antagonists vs Gonadotropin-Releasing Hormone Agonists for Prostate Cancer Treatment: A Meta-Analysis of Randomized Controlled Trials

Background: Androgen deprivation therapy (ADT), comprising the administration of Gonadotropin-releasing hormone (GnRH) agonists and antagonists, is a widely utilized treatment for prostate cancer patients and has been universally accepted as the first-line treatment for symptomatic metastatic prostatic cancer. While ADT has proven effective, concerns about its impact on cardiovascular health have emerged. Conflicting results regarding the association between ADT and cardiovascular events have been reported in the most recent PRONOUNCE trial hence a meta-analysis to systematically evaluate the evidence is desired. Aim: The primary objective of this meta-analysis was to investigate and compare the effects of GnRH agonists and antagonists on cardiovascular events in patients with prostate cancer. Methods: A comprehensive search was conducted in major electronic databases to identify relevant RCTs. Studies published from inception to April 2023 were scrutinized. Results: 9 studies met the eligibility criteria and were included in the final analysis. A total of 3648 patients were randomized to receive either an agonist (n=1375) or an antagonist (n=2273). The pooled results revealed a significant reduction in the risk of adverse cardiovascular events by 48% with the use of GnRH agonists compared to GnRH antagonists (RR=0.52; 95% CI=0.39-0.71; p&lt;0.01). Furthermore, GnRH agonists also decreased the risk of all-cause mortality by 46% (RR=0.54; 95% CI= 0.33-0.88; p=0.01) and cardiovascular mortality by 78% (RR= 0.22; 95% CI= 0.07-0.76; p=0.02) compared to GnRH antagonists. Conclusion: The findings of this meta-analysis reveal the favorable cardiovascular risk profile associated with GnRH agonists, supporting their role as a preferred treatment option over GnRH antagonists.

Clinical evidence of growth hormone for infertile women with diminished ovarian reserve undergoing IVF: a systematic review and meta-analysis.

To appraise the current randomized clinical trials (RCTs) for evidence of the association of growth hormone (GH) with improved outcomes in infertile women with diminished ovarian reserve (DOR) undergoing in vitro fertilization (IVF). Relevant RCTs published in Chinese or English were identified through a comprehensive search of nine databases from the period of database inception to April 20, 2023. We included trials investigating adjuvant GH during ovarian stimulation and reported the subsequent outcomes. The group with adjuvant GH treatment and the group without adjuvant GH treatment were set up as the trial and control groups, respectively. The quality of RCTs was measured according to the Cochrane Collaboration Handbook. Of the 579 studies initially identified, 10 RCTs comprising 852 infertile women with DOR were included. The GH dose of individual trials ranged between 3 and 5 IU/day. Overall, we judged the trials to be at high risk of bias in the blinding domain. Pooled results showed that GH was associated with an increased clinical pregnancy rate (RR = 1.63, 95%CI [1.31, 2.03], p < 0.0001) and a greater number of oocytes retrieved (MD = 0.91, 95%CI [0.47, 1.35], p < 0.0001). Favorable associations were also observed when ovarian stimulation was combined with GH therapy for improving the optimal embryos rate (RR = 1.84, 95%CI [1.30, 2.59], p = 0.0005) and the number of optimal embryos (MD = 0.28, 95%CI [0.08, 0.48], p = 0.005) along with reducing the cycle cancellation rate (RR = 0.46, 95%CI [0.24, 0.89], p = 0.02). Moreover, GH resulted in an increase in the fertilization rate (RR = 1.33, 95%CI [1.18, 1.50], p < 0.00001) and the embryo implantation rate (RR = 1.56, 95%CI [1.21, 2.01], p = 0.0006). In addition, there was a significant enhancement in estradiol levels (SMD = 1.18, 95%CI [0.46, 1.91], p = 0.001) and endometrial thickness (MD = 0.75, 95%CI [0.41, 1.09], p < 0.0001) on the day of hCG. With regard to the total number of days and total dose of gonadotrophins used, GH treatment was correlated with shorter days (MD = -0.26, 95%CI [-0.46, -0.06], p = 0.01) and lower dose (MD = -460.97, 95%CI [-617.20, -304.73], p < 0.00001) of gonadotrophins applied during ovarian stimulation. Furthermore, GH in conjunction with the GnRH antagonist protocol was more conducive to improving the number of oocytes retrieved when compared with the GnRH agonist protocol (p < 0.0001). Moreover, a notable association was also seen in IVF combined with GH more than or equal to 4.5 IU/day to increase the number of optimal embryos and estradiol levels on the day of hCG (p < 0.05). For infertile women with DOR undergoing IVF, adjuvant treatment with GH during ovarian stimulation protocols showed better clinical outcomes, shorter days and lower dosages of gonadotrophin required. Furthermore, well-designed RCTs are needed to verify our results in the future. https://www.crd.york.ac.uk PROSPERO (CRD42023421739).

Perception and Comfort with Endometriosis Management Among OB/GYN Residents.

The diagnosis of endometriosis often takes several years, delaying appropriate care while patients suffer from pelvic pain, dysmenorrhea, and dyspareunia. Understanding whether residents in obstetrics and gynecology (OB/GYN) are being adequately exposed to and trained in the diagnosis and management of the disease is important for improving care. We conducted an online cross-sectional survey of OB/GYN residents to investigate their comfort level and familiarity with endometriosis diagnosis and management. Residency program directors and coordinators of 20 OB/GYN residency programs in California, USA were emailed to disseminate the 31-question, anonymous survey in January to February 2023. Responses were collected using Redcap and analysis was conducted using STATA. 67 residents answered at least one non-demographic question and were included. A resident response rate was not calculated because we were unable to determine how many programs distributed the survey. 84% of residents felt they could recognise symptoms of endometriosis but over 30% of senior residents were not comfortable with sonographic diagnosis of endometrioma. Approximately one third of residents felt comfortable managing hypoestrogenic symptoms, osteoporotic risks, and add-back progestin for certain hormonal therapies. Academic-hospital based residents had significantly more exposure to attendings prescribing long-acting reversible contraception, GnRH antagonists, and GnRH agonists but there were no significant differences in trainee prescribing practices or comfort. More respondents would feel comfortable medically managing endometriosis (52%) than surgically managing the disease (26%) if they were in practice today, with only 39% of PGY3-4 residents feeling comfortable surgically managing endometriosis. There is considerable room for improvement in the education of residents in the diagnosis and medical and surgical management of endometriosis.