GnRH agonist trigger in poor prognosis patients undergoing a multicycle approach through DuoStim or consecutive stimulations: a SWOT analysis.

PURPOSE OF REVIEW: Identify the most recent and significant evidence regarding the ovulation trigger within the framework of a multicycle approach through DuoStim, providing valuable insights for improving treatment strategies in patients with a poor prognosis. RECENT FINDINGS: The trigger method plays a pivotal role in optimizing in-vitro fertilization (IVF) stimulation, influencing oocyte retrieval and maturation rates, as well as follicle recruitment in consecutive ovarian stimulations such as double stimulation. Decision-making involves multiple factors and, while guidelines exist for conventional stimulation, specific recommendations for the multicycle approach are not well established. SUMMARY: The different methods for inducing oocyte maturation underscore the need for personalization of IVF protocols. The GnRH agonist trigger induces rapid luteolysis and establishes favorable hormonal conditions that do not adversely affect the recruitment of consecutive follicular waves in the context of DuoStim. It serves as a valid alternative to hCG in freeze-all cycles. This strategy might enhance the safety and flexibility of ovarian stimulations with no impact on oocyte competence and IVF efficacy.

Oocyte competence is comparable between progestin primed ovarian stimulation with Norethisterone acetate (NETA-PPOS) and GnRH-antagonist protocols: A matched case-control study in PGT-A cycles.

OBJECTIVE: To outline oocyte competence after progestin primed ovarian stimulation with Norethisterone acetate (NETA-PPOS) compared to conventional GnRH-antagonist protocol. STUDY DESIGN: Retrospective matched case-control study involving advanced-maternal-age women undergoing ICSI with PGT-A. 89 NETA-PPOS were matched with 178 control patients based on maternal age and ovarian reserve biomarkers. Both groups underwent recombinant-FSH OS with GnRH-agonist ovulation trigger and collected ≥1 MII. In the study group, NETA (10 mg/day) was administered orally starting from day2 of the menstrual cycle. Euploid blastocyst rate per cohort of metaphase-II oocytes (EBR per MII) was the primary outcome. All other embryological and clinical outcomes were reported. Gestational age, birthweight and length were also assessed. RESULTS: The EBR per MII was comparable among PPOS and control (13.9 % ± 19.3 % versus 13.3 % ± 17.9 %; the sample size allowed to exclude up to a 10 % difference). Blastocysts morphology and developmental rate were similar. No difference was reported for all clinical outcomes among the 61 and 107 vitrified-warmed euploid single blastocyst transfers respectively conducted. The cumulative live birth delivery rate per concluded cycles was also comparable (24.7 % versus 21.9 %). Neonatal outcomes were analogous. CONCLUSIONS: Oocyte competence after NETA-PPOS and standard OS is comparable. This evidence is reassuring and, because of its lower cost and possibly higher patients' compliance, supports PPOS administration whenever the patients are indicated to freeze-all (e.g., fertility preservation, PGT-A, oocyte donation). More data are required about follicle recruitment, oocyte yield, gestational and perinatal outcomes. Randomized-controlled-trials are advisable to confirm our evidence.

Concomitant Autoimmunity in Endometriosis Impairs Endometrium-Embryo Crosstalk at the Implantation Site: A Multicenter Case-Control Study.

Endometriosis and autoimmune diseases share a hyper-inflammatory state that might negatively impact the embryo-endometrium crosstalk. Inflammatory and immune deregulatory mechanisms have been shown to impair both endometrial receptivity and embryo competence at the implantation site. The aim of this study was to investigate the potential additional impact of co-existing autoimmunity in women affected by endometriosis on the early stages of reproduction. This was a retrospective, multicenter case-control study enrolling N = 600 women with endometriosis who underwent in vitro fertilization-embryo transfer cycles between 2007 and 2021. Cases were women with endometriosis and concomitant autoimmunity matched based on age and body mass index to controls with endometriosis only in a 1:3 ratio. The primary outcome was the cumulative clinical pregnancy rate (cCPR). The study found significantly lower cleavage (p = 0.042) and implantation (p = 0.029) rates among cases. Autoimmunity (p = 0.018), age (p = 0.007), and expected poor response (p = 0.014) were significant negative predictors of cCPR, with an adjusted odds ratio of 0.54 (95% CI, 0.33-0.90) for autoimmunity. These results suggest that the presence of concomitant autoimmunity in endometriosis has a significant additive negative impact on embryo implantation. This effect might be due to several immunological and inflammatory mechanisms that interfere with both endometrial receptivity and embryo development and deserves further consideration.

Effect of rLH Supplementation during Controlled Ovarian Stimulation for IVF: Evidence from a Retrospective Analysis of 1470 Poor/Suboptimal/Normal Responders Receiving Either rFSH plus rLH or rFSH Alone.

We retrospectively studied a real-life population of 1470 women undergoing IVF, with poor/suboptimal/normal ovarian responsiveness to controlled ovarian stimulation (COS), comparing the cumulative live birth rate (cLBR) when COS was performed using rFSH alone or rFSH + rLH in a 2:1 ratio. Overall, we observed significantly higher cLBR in the rFSH alone group than in the rFSH + rLH group (29.3% vs. 22.2%, p < 0.01). However, considering only suboptimal/poor responders (n = 309), we observed comparable cLBR (15.6% vs. 15.2%, p = 0.95) despite the fact that patients receiving rFSH + rLH had significantly higher ages and worse ovarian reserve markers. The equivalent effectiveness of rFSH + rLH and rFSH alone was further confirmed after stratification according to the number of oocytes retrieved: despite basal characteristics were still in favor of rFSH alone group, the cLBR always resulted comparable. Even subdividing patients according to the POSEIDON classification, irrespective of differences in the baseline clinical characteristics in favor of FSH alone group, the cLBR resulted comparable in all subgroups. Despite the retrospective, real-life analysis, our data suggest that rLH supplementation in COS may represent a reasonable option for patients with predictable or unexpected poor/suboptimal ovarian responsiveness to FSH, those matching the Bologna criteria for poor responsiveness, and those included in the POSEIDON classification.