Abstract

Abstract Study question Is patients’ BMI associated with oocyte yield and maturation following different trigger strategies with r-hCG, GnRH agonist (GnRHa) or dual trigger? Summary answer Patients’ BMI is not associated with oocyte yield and oocyte maturation following triggering with rhCG, GnRHa or dual trigger. What is known already Triggering final oocyte maturation is a key step of ovarian stimulation for IVF/ICSI treatment. Although hCG has traditionally been the gold standard for final oocyte maturation, GnRHa is increasingly used as optimal trigger in “freeze-all” era. Recent evidence has demonstrated excellent results with dual-trigger, a combination of hCG and GnRHa. Despite this swift in clinical practice, early studies demonstrated that hCG plasma levels depend on hCG trigger dose and BMI. Furthermore, although dose-finding studies following for GnRHa trigger demonstrated equal efficacy of triptorelin doses ranging from 0.1-0.4mg, these studies pertained only to low BMI patients. Study design, size, duration This is a retrospective observational study including 5190 consecutive cycles ovarian stimulation cycles (OS) performed between January 2019 -September 2022 in a tertiary Fertility Unit within a University Affiliated Hospital. Overall 5190 ovarian stimulation cycles were analyzed: 2691 cycles triggered with subcutaneous administration of 0.2 mg of GnRHa (triptorelin), 1110 with 250 mcg of r-hCG and 1389 with a dual trigger (combination of both 0.2 mg triptorelin+ 250 mcg of r-hCG). Participants/materials, setting, methods Ovarian stimulation was performed with recombinant FSH or HMG at a starting dose 150-300IU depending on patients’ ovarian reserve and BMI. Control of LH surge was accomplished by a flexible GnRH antagonist or PPOS protocol. The primary outcome measures were oocyte maturation rate (MII/oocytes) and FOI (oocytes/AFC); secondary outcomes were oocyte and MII yield. Multivariable regression models were performed to evaluate the interaction between BMI and type of trigger in relation to study’s outcomes. Main results and the role of chance Overall, oocyte and MII yield was significantly different between different types of trigger mainly due the fact that GnRHa was primary used in freeze-all cases, with excellent ovarian reserve. This resulted in a higher number of oocytes (15.95 ± 8.88) and MIIs (12.31 ± 7.27) as compared with cycles triggered with in rhCG (7.83 ± 5.42 and 5.86 ± 4.22 respectively) or dual trigger (8.51 ± 5.70 and 6.44 ± 4.54 respectively) was utilized. Nonetheless, when oocyte maturation rate was comparable between trigger groups (% [95% CI]): GnRHa 77.2 [76.6; 77.8] vs rhCG 74.9 [73.3; 76] vs dual 75.6 [74.5; 76.7]. Multivariable regression analysis, adjusting for confounding factors, demonstrated that BMI was not associated with oocyte maturation rate (OR:1.00 [95% CI: 0.99;1.01]) and FOI (Beta 0.52 [95% CI: -0.49;1.54]). Similarly BMI was not associated number oocytes (Beta 0.02 [95% CI: -0.08; 0.13]) or on the number of MIIs (Beta 0.01 [95% CI: -0.08; 0.10]) retrieved. Interactions between BMI and trigger groups were considered in each model. All analyses were conducted considering patients’ weight, but no association was revealed. Limitations, reasons for caution This is a retrospective study, and we cannot exclude the presence of residual bias despite the large series, the multiple regression models and the indexes like maturation rate and FOI we adopted to account for confounding factors. Wider implications of the findings Although previous small observational studies supported an association between BMI and hCG levels, our large analysis of > 5000 cycles clearly shows that the efficiency of r-hCG, triptorelin or dual trigger is not associated with the patient's BMI and weight, as no significant differences were found in maturation rate and FOI. Trial registration number Not applicable

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