GNRH AGONIST TRIGGERing in ivf cycle

The presentation discusses GnRH agonist (GnRHa) as an alternative to hCG for triggering oocyte maturation in IVF, focusing on reducing OHSS risk. It compares GnRHa with hCG, covering its mechanism, clinical indications, and effectiveness. The presentation highlights the need for optimized luteal phase support post-GnRHa trigger and discusses dual trigger strategies for better outcomes. Special considerations for specific patient populations are also addressed.

1. GnRH Agonist Triggering in IVF Cycles Dr Reha Rakholia mbbs , ms obgy , mch reproductive medicine and surgery

2. Overview Substitute to hCG for oocyte maturation and prevention of OHSS. Introduced in the late 1980s to early 90s. Use limited due to widespread pituitary downregulation by GnRH Agonist protocol . Reintroduced after GnRH antagonists were used to prevent premature LH surge. GnRH trigger is for those that utilizes GnRH antagonist or PPOS (Progestin Primed Ovarian Stimulation )for LH surge suppression Activates receptors to promote release of gonadotropins.

3. Effectiveness in inducing oocyte maturation and ideal luteal phase protocol remains under discussion.

4. Literature suggests luteolytic properties of GnRHa effectively prevent OHSS but may lower pregnancy rates. Optimizing luteal phase profile after GnRHa trigger can yield pregnancy rates comparable to hCG trigger.

5. Indications for GnRHa Trigger High risk for OHSS development. Suitable for oocyte donors E lective cryopreservation. Used in fertility preservation for medical or social reasons. Applicable in trophoectoderm biopsy for PGT . P remature serum progesterone rise prior to induction of oocyte maturation .

6. GnRHa Trigger Limitations Hypothalamic Dysfunction. Long-term Suppression

7. Physiology: Natural vs GnRHa -induced Mid-cycle Surge GnRHa interacts with GnRH receptors causing a 'flare' of gonadotropins. LH and FSH surge resembles natural mid-cycle surge before ovulation. Natural surge lasts approximately 48 hours with distinct phases. GnRHa -triggered surge is shorter, potentially affecting corpus luteum formation.

8. FSH surge role (not fully understood) important in oocyte maturation and resumption of meiosis. Supports the function of the oocyte–cumulus complex and its detachment from the follicle wall. Aids in the generation of LH receptors on granulosa cells.

9. Comparison: Natural Ovulatory Surge vs. GnRHa -Triggered Surge Natural Ovulatory Surge: Traditionally consists of three phases: abrupt onset (14h), LH peak/plateau (14h), and gradual descent (20h), lasting 48 hours. GnRHa -Triggered Surge: Occurs in two phases: rapid ascent and moderate descent, lasting 24–36 hours. Short duration of LH surge can induce oocyte maturation and ovulation but may result in defective corpus luteum formation.

10. Advanced Insights into Follicular Fluid Dynamics and Granulosa/Luteal Cell Functionality Post-GnRHa Trigger

11. Comparative Dynamics of Follicular Fluid after GnRHa and hCG Triggers Post- GnRHa trigger, follicular fluid shows significantly higher levels of LH and FSH, akin to the natural mid-cycle surge. Progesterone levels decrease by approximately 25% post- GnRHa trigger, affecting luteal phase support requirements. Oestrogen , inhibin-A, and inhibin-B levels remain consistent across both triggers, suggesting similar follicular maturity and development.

12. The GnRHa trigger's ability to closely replicate the natural surge leads to efficient oocyte maturation. However, decreased luteal phase progesterone in follicular fluid and circulation may affect pregnancy rates.

13. Molecular Mediators of Oocyte Maturation: The Role of Amphiregulin • Amphiregulin and EGF-like family members surge in follicular fluid after LH/ hCG exposure, facilitating oocyte maturation by enhancing LH's follicular effects. . • Levels of amphiregulin are significantly lower in follicular fluid post- GnRHa trigger as compared to HCG , resembling those in a natural cycle. • This differential expression suggests a nuanced role of LH/ hCG in follicular development, influencing IVF strategies.

14. VEGF, Ang-2, and Their Roles in OHSS Pathophysiology • VEGF significantly contributes to vascular permeability and is implicated in the development of OHSS. • GnRHa triggers lead to decreased VEGF and Ang-2 levels in follicular fluid, directly impacting the pathophysiology of OHSS.

15. Luteal Cell Functionality after GnRHa vs. hCG Trigger • Despite rapid luteolysis post- GnRHa trigger, granulosa/luteal cells exhibit comparable functionality and viability to hCG -triggered cells within the initial 48 hours. • After both trigger hCG exposure to i n vitro post-trigger shows that luteal cells can still enhance progesterone production, critical for supporting the luteal phase and early pregnancy. • This resilience in luteal cell functionality suggests that with appropriate luteal phase support, IVF outcomes post- GnRHa trigger can be optimized.

16. GnRHa Administration: Dosage and Delivery Methods • Available for subcutaneous injection: triptorelin, buserelin , leuprorelin, nafarelin . • Buserelin and nafarelin can also be administered via intranasal spray . .

17. Optimal dosing is crucial: too low may fail to induce sufficient LH surge for oocyte maturation; too high could risk unnecessary side effects or diminished efficacy. Studies have shown varied dosing efficacy, with 0.2 mg triptorelin and 1 mg leuprorelin commonly used, indicating the need for personalized dosing strategies based on patient response and IVF protocol requirements.

18. Influence of Body Mass Index on GnRHa Efficacy • The efficacy of GnRHa triggering may be influenced by the patient's BMI, with emerging evidence suggesting a potential need for dose adjustment in patients with higher BMI. • Research indicates varied responses in oocyte maturity and quality in patients with BMI ≥25 kg/m^2, highlighting the importance of considering patient-specific factors in dosing decisions.

19. Optimizing the Timing of GnRHa Administration • The timing of GnRHa administration relative to the final dose of GnRH antagonist is crucial for maximizing the efficacy of the trigger. • Recent studies suggest that the window between the last antagonist dose and the GnRHa trigger can significantly impact the number of mature oocytes retrieved and their fertilization potential.

20. Timing of GnRHa Administration After GnRH Antagonist Research on GnRHa Timing: • Importance of displacing GnRH antagonist at pituitary receptors for LH surge trigger. • Horowitz et al. study: Comparable oocytes retrieved, MII oocytes, and fertilization rates with GnRHa trigger <2.5 hours and >7 hours after last GnRH antagonist dose. • Need for further research to determine optimal timing for GnRHa trigger post-GnRH antagonist

21. GnRHa triggers present a viable alternative to hCG , with benefits including reduced OHSS risk and mimicking the natural LH surge for oocyte maturation.

22. Oocyte Yield after GnRHa Trigger: An Overview Understanding the Efficiency and Outcomes

23. Effectiveness of GnRHa Trigger in Oocyte Yield • Studies show GnRHa trigger's efficacy is on par with hCG for oocyte yield in autologous and donor cycles. • Some research indicates GnRHa may lead to a higher proportion of mature oocytes . • Key findings from literature: Humaidan et al.'s study highlighted 16% more MII oocytes with GnRHa AND 11% more mature embryos .

24. 1 study :Post-trigger LH and progesterone levels strongly correlate with total and mature oocytes retrieved. EFS cases had an LH <15 IU/L and progesterone ≤3.5 ng/mL post-trigger, with an 18.8% probability of EFS at LH <15 IU/L. Another study :An LH ≤15 IU/L post-trigger is associated with lower oocyte yield , yet no impact on oocyte maturity was observed. Monitoring LH levels post-trigger.

25. Kummer et al.  Chen et al

26. Advantages of GnRHa Trigger Over hCG • Enhanced maturity and quality of oocytes. • Early embryo development benefits. • Hormonal milieu differences at oocyte maturation with GnRHa may contribute to improved outcomes.

27. Predicting successful oocyte retrieval post- GnRHa is critical for deciding on retrieval or rescue hCG dose.

28. Meyer et al. identified low post-trigger LH (≤15 IU/L) is linked with suboptimal retrieval. Suboptimal response correlates with initial low serum FSH (<0.1 mIU /mL) and LH levels (<0.1 mIU /mL), and low LH (<0.5 mIU /mL) on the trigger day. Long-term oral contraceptive use may contribute to low serum LH and FSH. Herman et al.'s review and Popovic- Todorovic et al.'s study support low LH at stimulation start as a risk for poor oocyte yield. Low body mass index and baseline LH also pose a risk for inadequate response to GnRHa trigger.

29. Step Action Next Steps Retrigger Protocol No oocytes retrieved? - Retrigger with hCG . - Schedule repeat oocyte retrieval for the contralateral ovary 34 hours later. Post-Trigger Serum Level Monitoring (Approx. 12 hours post-trigger) Check LH and Progesterone Intervention Based on Serum Levels No LH/Progesterone Surge? - Retrigger with hCG - Schedule oocyte retrieval 35 hours later. Suboptimal LH Rise (<15 IU/L)? Option A: Retrigger with hCG ASAP & proceed as planned. Option B: Consider canceling the cycle.

30. Managing EFS and Suboptimal Responses • Criteria for identifying at-risk patients include low LH levels post-trigger. • Strategies include retriggering protocols and the use of dual triggers for intervention.

31. The Dual Trigger Strategy: Clinical Implications Concept of dual trigger combines GnRHa with hCG . Clinical trials show benefits like improved oocyte yield ,more mature oocytes, higher-quality embryos, reduced EFS risk. RCT comparing hCG 10,000 IU vs. GnRHa + hCG 10,000 IU showed better outcomes in dual trigger group.( higher numbers of oocytes and mature oocytes as well as clinical pregnancy and live birth rates ) Systematic review and meta-analysis support higher live birth rates with dual trigger.

32. Optimizing Dual Trigger Strategy Zilberberg et al.'s study on dual trigger timing: 40 hours ( GnRHa ) and 34 hours ( hCG ) before retrieval in women with previous high immature oocyte proportion.. Findings: Higher MII oocytes, proportion of MII oocytes per retrieval, high-quality embryos. Caution advised for patients at high risk of OHSS with adjuvant hCG .

33. Luteal Phase Steroid Profile: Natural Cycle vs. GnRHa Trigger Implications for IVF Outcomes and Strategies to Optimize Pregnancy Rates

34. Luteal Phase in Natural Cycle LH acts as a luteotropic hormone supporting the corpus luteum and steroidogenesis. Increases growth factors and cytokines necessary for implantation: VEGF, fibroblast growth factor 2.

35. LH's regulatory roles include synthesis of prostaglandins, stimulation of embryonic growth, and maintenance of pregnancy. Beyond the ovary, LH via LH receptor influences the endometrium, fallopian tubes, early fetal cells, placenta, etc., affecting prostaglandin synthesis, tubal glycoprotein stimulation, embryonic growth, and pregnancy initiation/maintenance.

36. Impact of GnRHa Trigger on the Luteal Phase • Median duration of luteal phase: 9 days post- GnRHa vs. 13 days post- hCG . • LH secretion is pulsatile. • Similar number of pulses on day of retrieval and 48 hours later. • Trend towards decreasing amplitude. • Basal LH secretory rate significantly lower 48 hours after retrieval with GnRHa . • Shortened LH surge leads to decreased progesterone production and early luteolysis .

37. LH Pulse: LH is secreted by the pituitary gland in a pulsatile manner, meaning it is released in bursts or spikes at regular or irregular intervals. Basal LH Secretory Rate: The basal LH secretory rate refers to the underlying, continuous rate of LH secretion by the pituitary gland, outside of the pulses. It is a measure of the background level of LH secretion, not including the spikes or pulses.

38. Impact on Progesterone and Estrogen Shortened LH surge post- GnRHa trigger correlates with decreased progesterone production. Serum levels of progesterone and estrogen are significantly lower throughout the luteal phase with GnRHa trigger than after an hCG trigger.

39. GnRHa Trigger and Luteal Phase Support in IVF The GnRHa trigger induces oocyte maturation but does not sufficiently support the natural luteal phase. Mechanisms Inhibiting LH Release GnRHa may downregulate the pituitary, inhibiting endogenous LH release. Supra-physiologic levels of progesterone and oestrogen also suppress LH release. Resultant early luteolysis impacts pregnancy outcomes ; even early pregnancy may not rescue the corpora lutea function.

40. Markers of Corpus Luteum Function Nevo et al discovered that even when a woman becomes pregnant after Gnrh agonist trigger , the levels inhibin A and pro- α C , don't go up during the later part of the menstrual cycle. These substances are usually indicators that the corpus luteum is working well. This finding suggests that the usual signs of a healthy corpus luteum may not be present even if a pregnancy has begun.

41. Endometrial Gene Expression Changes Significant alterations in endometrial gene expression have been observed after GnRHa trigger, affecting the uterine environment for implantation.

42. Indicators of Initial Corpus Luteum Function Kaye et al. demonstrated that prorenin and 17 α- hydroxyprogesterone, indicators of corpus luteum function, peak at five days and two days, respectively, after GnRHa trigger, but decline by the ninth day. This finding demonstrates that corpus luteum function continues, at least initially, despite administration of GnRHa  

43. Luteal Phase Considerations in Special Populations PCOS patients may have elevated serum LH and decreased sensitivity at the hypothalamus to inhibition by ovarian steroids such as progesterone The differences in hormonal responses, like higher LH levels in PCOS, can enhance the effectiveness of GnRHa triggers. Recognizing these variations is key to customizing treatment for infertility, suggesting a need for tailored approaches to improve success rates.

44. Modifying Luteal Phase Support to Enhance Pregnancy Rates • Strategies include intensive exogenous steroid support and monitoring of hormone levels. • An adjuvant low dose of hCG or recombinant LH administration can modify standard luteal support. • Aimed at increasing pregnancy rates after fresh embryo transfer without raising OHSS risk.

45. Gnrh agonist trigger

46. Standard Luteal Support Protocols vs Intensive luteal support

47. Standard Luteal Support Protocols P rogesterone alone or in combination with oestrogen supplementation O ften involve vaginal micronized progesterone (200 mg tid daily) and may include oral estrogen supplementation (up to 6 mg daily). These regimens aim to mimic the natural luteal phase environment to a basic extent, supporting early pregnancy until placental takeover.

48. Transition to Intensive Luteal Support Intensive luteal support addresses the shortfall of standard support, especially post-GnRHa trigger, by aggressively supplementing estrogen and progesterone to mimic natural levels closely, aiming to improve implantation rates and pregnancy outcomes.

49. Aspect Standard Luteal Support Intensive Luteal Support Basis for Need Supra-physiologic levels of steroid hormones during stimulated cycles cause a decrease in endogenous LH, risking early luteolysis . Significant decrease in serum levels of oestrogen and progesterone after GnRHa trigger, necessitating more aggressive support to prevent luteal phase dysfunction. Methods Employed progesterone alone or in combination with oestrogen supplementation. Primarily involves vaginal micronized progesterone with or without oral oestrogen, starting after transfer and discontinued by seven weeks of gestation. supplementation with both oestrogen and progesterone in addition to close monitoring of serum steroid levels to adjust doses as necessary.  Begins with 50 mg IM progesterone daily and three 0.1 mg oestradiol transdermal patches every other day, with adjustments based on serum steroid levels. Supplementation continues until about 10 weeks gestational age. Or 50 mg IM progesterone in oil and 6 mg oral oestradiol from the day of retrieval until 10 weeks of gestation.

50. IMBAR et al Engmann et al.

51. Standard Luteal Support Intensive Luteal Support Outcome Studies & Results A meta-analysis showed a clinical pregnancy rate of 7.9% in the GnRHa group compared to 30.14% in the hCG group, with higher early pregnancy loss rates in the GnRHa group. Engmann et al. study reported a 53% ongoing pregnancy rate, comparable to 48.3% in the hCG group. Imbar et al. found a 37% clinical pregnancy rate and a 27.1% live birth rate. Shapiro et al. reported a 50% ongoing pregnancy rate, significantly improved over standard support. Considerations - The availability of IM progesterone is not universal. Studies suggest no superiority of IM progesterone over vaginal progesterone after an hCG trigger, but it may be essential after GnRHa trigger.

52. Protocol Details by Engmann et al.

53. Parameter Details Start of Supplementation Day after oocyte retrieval Progesterone Supplementation 50 mg IM (intramuscular) daily, can be increased to 75 mg daily. Additional micronized vaginal progesterone may be added as needed to maintain serum progesterone above 20 ng/mL. Oestradiol Supplementation Three 0.1 mg transdermal patches every other day, can be increased to four 0.1 mg patches. Oral micronized oestradiol (2 mg to 8 mg daily) may be added to maintain serum oestradiol above 200 pg/mL. Monitoring Schedule Serum levels of oestradiol and progesterone evaluated on days 3 and 7 after oocyte retrieval, and weekly thereafter. Duration of Supplementation Until approximately 10 weeks gestational age. Outcome 53% ongoing pregnancy rate in the study group compared to 48.3% in the hCG trigger group.

54. Comparative Studies on Intensive Support Studies have demonstrated that intensive support, including IM progesterone and adjusted estrogen supplementation, significantly improves pregnancy outcomes, with ongoing pregnancy rates comparable to or better than those seen with standard hCG trigger support.

55. Effectiveness of Intensive Support Comparative analysis and graphical representation of success rates underline the effectiveness of intensive luteal support, highlighting significantly improved ongoing pregnancy rates in IVF cycles post-GnRHa trigger with this approach.

56. Dosing and Monitoring in Intensive Support Critical to the success of intensive support is the careful monitoring of serum hormone levels and the adjustment of dosages to maintain optimal conditions for implantation and early pregnancy, requiring a personalized approach to each patient's regimen.

57. Adjuvant Low-Dose hCG in Fertility Treatments

58. Supporting steroidogenesis in the luteal phase is essential, typically done by LH. After a GnRHa trigger, strategies focus on restoring or replacing LH's function, often in addition to providing the luteal phase steroids exogenously. Use of hCG with GnRHa trigger should be cautious to minimize OHSS risk.

59. Dual Trigger with hCG

60. Dual trigger with low-dose hCG and GnRH agonist enhances luteinization. Studies by Shapiro et al. show promising pregnancy rates with hCG dose (ranging between 1000 and 2500 IU) ≤33 IU/kg body weight Griffin et al. recommend 1000 IU hCG + GnRHa for higher live birth rates. Dual trigger serves as a backup for GnRHa failure. Potential for more mature oocytes and better embryos. Balance benefits and risks, closely monitor OHSS for optimal outcomes.

61. Adjuvant hCG in IVF at the time of Oocyte Retrieval

62. Study Study Design Intervention Outcome Humaidan et al. Multiple studies Single bolus of 1500 IU hCG at oocyte retrieval + standard luteal-phase support Delivery rates: 24% (hCG after GnRHa trigger) vs. 31% (hCG trigger) [24] Karacan et al. Retrospective cohort study GnRHa trigger + 1500 IU hCG at oocyte retrieval vs. GnRHa trigger + cryopreserved embryos Live birth rates: 45.9% vs. 43.8% Prospective randomized double-blind trial Prospective randomized trial hCG at GnRHa trigger vs. hCG at oocyte retrieval Live birth rates similar, higher incidence of OHSS with hCG at oocyte retrieval (9.7% vs 3.8%)

63. OHSS Risks with Adjuvant hCG Slight increase in OHSS incidence Reports of severe OHSS in high-risk populations Importance of patient selection and monitoring

64. H CG Bolus Two Days After Oocyte Retrieval

65. Study Intervention Results Proof-of-concept study 1500 IU hCG bolus 2 days after retrieval without progesterone supplementation Similar progesterone levels, pregnancy outcomes, and no OHSS compared to hCG trigger + progesterone group. Kol et al. 1500 IU hCG bolus 2 days after retrieval Similar pregnancy rates, higher estradiol levels compared to hCG trigger group.

66. This suggests administration of hCG two days following oocyte retrieval may rescue the corpora lutea and allow for ongoing steroidogenesis at sufficient levels to support an early pregnancy

67. Very Low Dose hCG in IVF Aspect Details Protocol Recombinant hCG, 125 IU daily Start Time Day 2 or Day 6 of stimulation Duration Throughout the luteal phase Main Benefit Increases luteal progesterone without external supplements comparable to standard luteal phase Clinical Pregnancy Rates Comparable to standard luteal support Study Type Proof-of-concept with normal responders Findings Effective in rescuing corpora lutea function Further Research Needed before widespread clinical adoption Availability Very low doses not widely commercially available

68. Recombinant LH in Luteal Phase Alternative for luteal support with potential OHSS risk reduction Single study overview: Comparable delivery rates, no OHSS cases Further evidence required for routine use

69. Luteal GnRHa Triptorelin 0.1 mg every other day, alternating with progesterone in oil , beginning on the day of embryo transfer. Recurrent LH surges to support corpus luteum Comparable pregnancy outcomes, lower OHSS rates vs hCG trigger Further research needed

70. Alternating with progesterone in oil

71. Luteal Coasting

72. Study Details Kol et al. - Utilized luteal coasting after trigger in a case series of 21 high-responder patients. No luteal phase steroid supplementation was provided unless serum progesterone levels dropped, then a 1500 IU hCG bolus was administered. - Aimed to individualize luteal supplementation, minimizing the risk of OHSS. Lawrenz et al. (1st series) - Advocated for individualized luteal support in a case series. - Observed luteal progesterone levels ranged from 14 to 43.69 ng/mL in patients with 20 oocytes retrieved after GnRHa trigger, indicating variable luteolysis . Lawrenz et al. (2nd series) - In a small case series, it was demonstrated that ongoing pregnancies could be achieved with early luteal progesterone levels <15 ng/mL if a 1500 IU hCG bolus is administered with Ongoing pregnancy rate was 66.7% (2/3 patients).

73. Considerations Individual serum progesterone levels can vary significantly, making it essential to interpret them cautiously. Previous studies show endogenous progesterone levels can vary eightfold within 90 minutes in the same individual. The strategy requires further studies for efficacy confirmation.

74. Cycle Segmentation: Cryopreservation of All Oocytes or Embryos Enhancing IVF Success Rates

75. Why Consider a Freeze-All Policy?

76. Study Patient Group Freeze-All Strategy Clinical Pregnancy Rate Manzanares et al. PCOS patients with previous cycle cancellations Freeze all embryos with subsequent thaw and transfer cycle 33% Garcia-Velasco High-risk OHSS patients Freeze all oocytes with subsequent thaw and transfer cycle 50%compared to 29.5% in those who underwent coasting and fresh embryo transfer. Makhijani et al. Patients receiving GnRH agonist or hCG trigger Freeze all embryos with subsequent thaw and transfer cycle Similar Implantation rates Clinical pregnancy rates Clinical loss rates Live birth rates Research Insights on Freeze-All Strategy

77. Segmentation of the IVF process has become a feasible option due to excellent pregnancy rates observed in freeze-all cycles. While the cycle segmentation approach yields positive results, factors related to the cost of additional frozen embryo transfer cycles should be considered, making it most suitable for specific clinical situations.

78. Tailoring Protocols for Higher Success Rates • Importance of individualizing luteal phase management. • Predictors of success: Peak E2 levels and LH on day of trigger. • Dual trigger strategy: Enhanced live birth rates in specific cases.

79. Study Findings Study - Peak E2 ≥4000 pg/mL and elevated LH at trigger are predictors of higher pregnancy success rates after GnRHa trigger and intensive luteal support. - Clinical pregnancy rate was significantly higher (53.6%) in women with peak E2 ≥4000 pg/mL compared to those with peak E2 <4000 pg/mL (38.1%). Study by Griffin et al. - Use of dual trigger GnRHa with low dose hCG (1000 IU) resulted in significantly higher live birth rates compared to GnRHa trigger alone in women with peak E2 <4000 pg/mL. Study by Engmann et al. - Similar live birth rates were observed between patients receiving GnRHa trigger and 1000 IU hCG at trigger versus 1500 IU hCG at oocyte retrieval.

80. Conclusion Individualized approach crucial for optimizing conception rates while mitigating OHSS risk. Peak E2 and LH levels on the day of trigger are predictive of pregnancy success after GnRHa trigger. Dual trigger with low-dose hCG enhances live birth rates in women with peak E2 <4000 pg / mL. Criteria such as follicle count help decide between hCG bolus and freeze-all strategy to prevent OHSS.

81. Ovarian Hyperstimulation Syndrome (OHSS) Prevention • Effective OHSS prevention with GnRHa trigger due to the short LH surge and inadequate corpus luteum formation. • Overall elimination of OHSS after GnRHa trigger, supported by a Cochrane review. • Few cases of moderate to severe OHSS persist, possibly due to low-dose hCG supplementation or genetic factors. • Genetic factors, such as mutations in the GnRH, FSH, or LH receptors, or variations in the genes for VEGF and its receptor, are implicated in these cases.

82. Use of GnRHa Trigger in Specific Clinical Situations • GnRHa trigger in freeze-all cycles for PGT demonstrates comparable euploidy and live birth rates to hCG trigger. • Not of concern for luteolysis in current cycle with a subsequent thaw and transfer cycle planned. • GnRHa trigger does not adversely affect oocyte/embryo quality, leading to comparable live birth rates as hCG -triggered cycles.

83. Oocyte donation cycle : GnRHa vs. hCG No significant differences in oocytes retrieved, proportion of mature oocytes, fertilization rates, implantation rates, pregnancy rates, and live birth rates . Similar p regnancy and miscarriage rates in recipient patients. Use of gnrh agonist trigger prevent OHSS

84. GnRHa Trigger in Breast Cancer Patients • Benefits for patients undergoing cryopreservation before cancer treatment specially with oestrogen receptor-positive breast cancer . • Significantly lower serum oestradiol levels and minimized OHSS risk.

85. Safety of GnRHa Trigger • Comparable maternal and neonatal outcomes to hCG trigger. • No significant differences in congenital anomalies or complications.

86. Additional Benefits of GnRHa Trigger • Improvements in patient comfort and satisfaction. • Reduced abdominal bloating, pain, and ovarian torsion risk. • Shorter luteal phase duration with earlier menses.

87. Dual Trigger Strategy for Improved Outcomes • Combining GnRHa with hCG for cases with history of immature oocytes , empty follicle syndromes, or low fertilization . • Benefits of mimicking the natural cycle's LH and FSH surge.

88. Towards Safer and More Effective ART Practices • Evolution in ART practices with the introduction of GnRHa trigger. • Success in assisted reproductive technology defined as achieving pregnancy without OHSS, resulting in a healthy singleton live birth at term. • Proposal to modify reporting systems to include OHSS rates, encouraging practices to avoid OHSS. • This is particularly important for high responders like women with PCOS, those undergoing elective cryopreservation, and oocyte donors, where safety is paramount.

89. Thank you